bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide screening of genes associated with momilactone B sensitivity in the fission yeast Schizosaccharomyces pombe
Authors: Tomita Keisuke , Yashiroda Yoko , Matsuo Yasuhiro , Piotrowski Jeff S , Li Sheena C , Okamoto Reika , Yoshimura Mami , Kimura Hiromi , Kawamura Yumi , Kawamukai Makoto , Boone Charles , Yoshida Minoru , Nojiri Hideaki , Okada Kazunori 
Published: May 2021

Abstract
Momilactone B is a natural product with dual biological activities, including antimicrobial and allelopathic properties, and plays a major role in plant chemical defense against competitive plants and pathogens. The pharmacological effects of momilactone B on mammalian cells have also been reported. However, little is known about the molecular and cellular mechanisms underlying its broad bioactivity. In this study, the genetic determinants of momilactone B sensitivity in yeast were explored to gain insight into its mode of action. We screened fission yeast mutants resistant to momilactone B from a pooled culture containing genome-wide gene-overexpressing strains in a drug-hypersensitive genetic background. Overexpression of pmd1, bfr1, pap1, arp9, or SPAC9E9.06c conferred resistance to momilactone B. In addition, a drug-hypersensitive, barcoded deletion library was newly constructed and the genes that imparted altered sensitivity to momilactone B upon deletion were identified. Gene Ontology and fission yeast phenotype ontology enrichment analyses predicted the biological pathways related to the mode of action of momilactone B. The validation of predictions revealed that momilactone B induced abnormal phenotypes such as multiseptated cells and disrupted organization of the microtubule structure. This is the first investigation of the mechanism underlying the antifungal activity of momilactone B against yeast. The results and datasets obtained in this study narrow the possible targets of momilactone B and facilitate further studies regarding its mode of action.
Maternal Factors Predicting Loss to Follow-Up from Newborn Hearing Screenings in New Jersey
Authors: Zeitlin Wendy , McInerney MaryRose , Aveni Kathryn , Scheperle Rachel , DeCristofano Angela 
Published: May 2021

Abstract
Because hearing loss in children can result in developmental deficits, early detection and intervention are critical. This article identifies a constellation of maternal factors that predict loss to follow-up (LTF) at the point of rescreening—the first follow-up for babies who did not pass the hearing screening performed at birth—through New Jersey’s early hearing detection and intervention program. Maternal factors are critical to consider, as mothers are often the primary decision makers around children’s health care. All data were obtained from the state’s department of health and included babies born between June 2015 and June 2017. Logistic regression was used to predict LTF. Findings indicate that non-Hispanic Black mothers, younger mothers, mothers with previous live births, and mothers with obesity were more likely to be LTF. Hispanic mothers and those enrolled in the state’s Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) program were less likely to be LTF. Mothers most at risk for LTF should be targeted for intervention to help children with hearing loss achieve the benefits from early intervention. Being a WIC recipient is a protective factor for LTF; therefore, elements of WIC could be used to reduce the state’s LTF rate.
Spatially varying phytoplankton seasonality on the Northwest Atlantic Shelf: a model-based assessment of patterns, drivers, and implications
Authors: Zang Zhengchen , Ji Rubao , Feng Zhixuan , Chen Changsheng , Li Siqi , Davis Cabell S 
Published: May 2021

Abstract
The signal of phytoplankton responses to climate-related forcing can be obscured by the heterogeneity of shelf seascapes, making them difficult to detect from fragmented observations. In this study, a physical–biological model was applied to the Northwest Atlantic Shelf to capture the seasonality of phytoplankton. The difference in phytoplankton seasonality between the Mid-Atlantic Bight (MAB) and the Gulf of Maine (GoM) is a result of the interplay between nutrients and temperature: In the MAB, relatively high temperature in the cold season and longer oligotrophic environment in the warm season contribute to an earlier winter bloom and a later fall bloom; in the GoM, low temperature and strong mixing limit phytoplankton growth from late fall to early spring, resulting in a later spring bloom and an earlier fall bloom. Although the temperature difference between the GoM and the MAB might decrease in the future, stratification and surface nutrient regimes in these two regions will remain different owing to distinct thermohaline structures and deep-water intrusion. The spatial heterogeneity of phytoplankton dynamics affects pelagic and benthic production through connections with zooplankton and benthic–pelagic coupling.
A worst-case approach for interest rate stresses and stock crashes
Authors: Beißer Marcel , Geisinger Leander , Korn Ralf 
Published: May 2021

Abstract
In the current low interest rate environment even sovereign bonds cannot be considered as risk-free investments. To care for this aspect we introduce a worst-case continuous-time portfolio problem with combined stresses, that is, both stocks and the money market account can experience shocks in the form of unpredictable downward jumps in their values. We characterize the worst-case optimal portfolio strategy as an indifference strategy that is the solution of a constrained optimization problem. Our results generalize existing results in a multi-asset setting. Numerical examples demonstrate new effects in the presence of interest rate shocks. These insights can be used for risk management in the presence of crash risks.
Vaccine Effectiveness Following Routine Immunization With Bivalent Human Papillomavirus (HPV) Vaccine: Protection Against Incident Genital HPV Infections From a Reduced-Dosing Schedule
Authors: Hoes Joske , King Audrey J , Klooster Tessa M Schurink van’t , Berkhof Johannes , Bogaards Johannes A , de Melker Hester E 
Published: May 2021

Abstract

Background
In the Netherlands, the bivalent human papillomavirus (HPV) vaccine has been offered to preadolescent girls via the National Immunization Program in a 2-dose schedule since 2014. The current study estimates vaccine effectiveness (VE) against HPV infections up to 4 years postvaccination among girls eligible for routine 2-dose immunization.

Methods
A cohort study (HAVANA2) was used in which participants annually filled out an online questionnaire and provided a vaginal self-sample for determination of HPV by the SPF10-LiPA25 assay, able to detect 25 HPV types. VE against incident type-specific infections and pooled outcomes was estimated by a Cox proportional hazards model with shared frailty between the HPV types.

Results
In total, 2027 girls were included in the study, 1098 (54.2%) of whom were vaccinated with 2 doses. Highest incidence rate was 5.0/1000 person-years (HPV-51) among vaccinated participants and 9.1/1000 person-years (HPV-74) among unvaccinated participants. Adjusted pooled VE was 84.0% (95% confidence interval [CI], 27.0%–96.5%) against incident HPV-16/18 infections and 86.5% (95% CI, 39.5%–97.08%) against cross-protective types HPV-31/33/45.

Conclusions
Four years postvaccination, 2 doses of bivalent HPV vaccine were effective in the prevention of incident HPV-16/18 infections and provided cross-protection to HPV-31/33/45. Our VE estimates rival those from 3-dose schedules, indicating comparable protection by 2-dose schedules.
Ocular transmission and manifestation for coronavirus disease: a systematic review
Authors: Almazroa Ahmed , Alamri Suhailah , Alabdulkader Balsam , Alkozi Hanan , Khan Altaf , Alghamdi Walead 
Published: May 2021

AbstractBackgroundThere is currently a lack of information regarding ocular tropism and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Globally, the cumulative number of coronavirus disease 2019 (COVID-19) cases is increasing daily. Thus the potential for ocular transmission and manifestations of SARS-CoV-2 requires more investigation.MethodsA systematic search of electronic databases for ocular transmission and manifestations of SARS-CoV-2 was performed. Pooled cross-sectional studies were used for conducting a meta-analysis to estimate the prevalence of ocular transmission of SARS-CoV-2 to the respiratory system and ocular manifestations (associated symptoms) of SARS-CoV-2.ResultsThe highest prevalence of SARS-CoV-2-positive tears using reverse transcription polymerase chain reaction was found to be 7.5%. However, the highest prevalence of ocular conjunctivitis associated with SARS-CoV-2 was 32%. Thus, SARS-CoV-2 can evidently infect the eye, as revealed in the conjunctival secretions of COVID-19 patients.ConclusionThe available data reflect the influence of the ocular structure on SARS-CoV-2. The analysis showed that ocular manifestation is an indication for SARS-CoV-2, particularly conjunctivitis. Moreover, there is no evidence that the ocular structure can be an additional path of transmission for SARS-CoV-2, however, it warrants further investigation.
Green and Cost-Effective Extraction Techniques of Quercetin from Mixture of Nutraceuticals with Yield Analysis via Spectrophotometry and High-Performance Liquid Chromatography Methods
Authors: Gamal Mohammed , Abd-ElSalam Heba-Alla H , Naguib Ibrahim A , Al-Ghobashy Medhat A , Zaazaa Hala E , Abdelkawy M 
Published: May 2021

Abstract

Background
Extraction is the leading critical stage in the analysis of nutraceuticals. Ginkgo biloba (GB) has gained interest because of its therapeutic usages.

Objectives
The aim was to develop four cost-effective extraction techniques for the extraction of quercetin from GB in a sachet containing a mixture of nutraceuticals. These techniques are solid-phase extraction (SPE), liquid–liquid extraction, inverted dispersive liquid–liquid microextraction, and the QuEChERS (quick, easy, cheap, effective, rugged, and safe) method.

Method
Direct spectrophotometry was used to monitor the recovery of the standard quercetin throughout the optimization steps. The HPLC–UV method of analysis was optimized to quantify the yields from the extracts present in the complicated contents of the sachets. The present study was assessed by analytical Eco-Scale assessment (ESA) and the National Environmental Method Index (NEMI) for greenness in comparison with the literature.

Results
SPE showed the best cleanup outcomes. ESA and NEMI showed an adequate greenness of the proposed extraction protocol.

Conclusions
Quercetin (marker for GB) extraction from market nutraceutical sachets is considered an exemplar for analysis in the QC of nutraceuticals. Regarding the greenness results, the proposed method of extraction is better even with adequate greenness as the extraction was a one-step process, in comparison with multistep processes of previously published protocols. Accordingly, it is recommended for use in routine extraction and analysis of such nutraceuticals.

Highlights
Four extraction protocols have been developed. For GB ternary-mixture sachets, proper recovery was obtained using C18 SPE. The assessment of greenness of the proposed protocol guaranteed the superiority of the presented method. Safer sorbents and chemicals are favored for use in routine extraction of nutraceuticals.
The Development of an Organizational Safety Culture in the United States Forest Service
Authors: Flores David , Haire Emily 
Published: May 2021

AbstractFor over 100 years, the US Forest Service (USFS) has developed initiatives to improve safety outcomes. Herein we discuss the engineered solutions used from 1910 through 1994, when the agency relied on physical science to address the hazards of wildland fire suppression. We then interpret safety initiatives of the subsequent 25 years, as the USFS incorporated social science perspectives both into its understanding of emergency fire incidents and its mitigation of vulnerabilities across all fields of work. Tracing the safety programs using a historical sociology approach, we identify, within the agency’s narrative, three recent developments in its organizational safety culture: cultural awareness, cultural management, and cultural reorganization. This article describes how the development of top-down safety initiatives are questioned and shaped by employees who actively influence the trajectory of a safety culture in the USFS.
Cultural evolution leads to vocal iconicity in an experimental iterated learning task
Authors: Erben Johansson Niklas , Carr Jon W , Kirby Simon 
Published: May 2021

Abstract
Experimental and cross-linguistic studies have shown that vocal iconicity is prevalent in words that carry meanings related to size and shape. Although these studies demonstrate the importance of vocal iconicity and reveal the cognitive biases underpinning it, there is less work demonstrating how these biases lead to the evolution of a sound symbolic lexicon in the first place. In this study, we show how words can be shaped by cognitive biases through cultural evolution. Using a simple experimental setup resembling the game telephone, we examined how a single word form changed as it was passed from one participant to the next by a process of immediate iterated learning. About 1,500 naïve participants were recruited online and divided into five condition groups. The participants in the control-group received no information about the meaning of the word they were about to hear, while the participants in the remaining four groups were informed that the word meant either big or small (with the meaning being presented in text), or round or pointy (with the meaning being presented as a picture). The first participant in a transmission chain was presented with a phonetically diverse word and asked to repeat it. Thereafter, the recording of the repeated word was played for the next participant in the same chain. The sounds of the audio recordings were then transcribed and categorized according to six binary sound parameters. By modelling the proportion of vowels or consonants for each sound parameter, the small-condition showed increases of front unrounded vowels and the pointy-condition increases of acute consonants. The results show that linguistic transmission is sufficient for vocal iconicity to emerge, which demonstrates the role non-arbitrary associations play in the evolution of language.
Sequence-dependent recruitment of SRSF1 and SRSF7 to intronless lncRNA NKILA promotes nuclear export via the TREX/TAP pathway
Authors: Khan Misbah , Hou Shuai , Azam Sikandar , Lei Haixin 
Published: May 2021

Abstract
The TREX-TAP pathway is vital for mRNA export. For spliced mRNA, the TREX complex is recruited during splicing; however, for intronless mRNA, recruitment is sequence dependent. However, the export of cytoplasmic long noncoding RNA (lncRNA) is poorly characterized. We report the identification of a cytoplasmic accumulation region (CAR-N) in the intronless lncRNA, NKILA. CAR-N removal led to strong nuclear retention of NKILA, and CAR-N insertion promoted the export of cDNA transcripts. In vitro RNP purification via CAR-N, mass spectrometry, and siRNA screening revealed that SRSF1 and SRSF7 were vital to NKILA export, and identified a cluster of SRSF1/7 binding sites within a 55 nucleotide sequence in CAR-N. Significant nuclear enrichment of NKILA was observed for NKILA lacking CAR-N or the cluster of binding sites in knock-in models. Depletion of TREX-TAP pathway components resulted in strong nuclear retention of NKILA. RNA and protein immunoprecipitation verified that SRSF1/7 were bound to NKILA and interacted with UAP56 and ALYREF. Moreover, NKILA lacking CAR-N was unable to inhibit breast cancer cell migration. We concluded that the binding of SRSF1/7 to clustered motifs in CAR-N facilitated TREX recruitment, promoting the export of NKILA, and confirmed the importance of NKILA localization to its function.
The Miracle of Mercy
Authors: Campagna Giordana 
Published: May 2021

Abstract
Many states governed by the rule of law provide for mercy powers, most prominently the power to grant pardons. This raises a potential conflict: the rule of law requires that like cases be treated alike. Mercy, on the other hand, is usually understood as being unfettered by legal principles, including the principle of treating like cases alike. Focusing on state officials’ pardon powers as an example of mercy, this article argues that we should conceive of pardons as miracles. Like miracles which suspend individual laws of nature, pardons suspend legal rules on an individual and discretionary basis. Once suspended, the legal rules no longer apply to the given case, and consequently there is no conflict between pardons and the rule of law. As I will show, this discretionary suspension of legal rules is a prerequisite for pardons to fulfil their function as a corrective to undesirable legal results.
Development of a Novel Mentorship Platform to Foster Relational Mentoring, Empowered Vulnerability, and Professional Identity Formation in Undergraduate Medical Education
Authors: Chen Jie Jane , Kusner Jonathan J. , Saldaña Fidencio , Potter Jennifer 
Published: May 2021

Problem
Mentorship is valuable to medical students undergoing professional identity formation. Many institutions lack infrastructure to facilitate the personalized mentoring that supports students’ integration of new professional identities with their personal identities and values.

Approach
The authors developed a novel mentorship platform called Weave via a multistep, iterative design process, incorporating in-person and survey-based student and faculty feedback. Features of Weave include clear communication of mentorship offerings and expectations, plus opportunities to engage mentors based on professional and personal (identity-based) attributes. Faculty at Harvard Medical School who created a mentor profile within the first 3 months of launch and students who visited the website within the same period were invited to complete usability surveys in February 2019; students were invited to complete impact surveys in August 2020.

Outcomes
Fifty-two of 132 invited faculty members (39.4%) and 80 of 185 students (43.2%) completed the usability surveys. Most of these faculty (86.5%) and students (73.8%) reported navigating the website was easy/very easy; 36 faculty (69.2%) created a mentor profile within 10 minutes. Key innovations highlighted by faculty and students were the listing of personal attributes and identities of diverse faculty; centralized, increased access to faculty mentors; ease of use; and provision of clear expectations. Nearly all students who completed the impact surveys agreed that Weave allowed them to connect with a faculty mentor whom they would not have found through other sources and to learn about the dimensions of diverse faculty.

Next Steps
Weave is a customizable online mentorship platform that fosters empowered vulnerability and increases dialogue between medical students and faculty based on professional and personal interests and identities. Weave may be expanded to other mentoring contexts and adapted for implementation at other institutions to help cultivate an institutional culture that values mentoring and to strengthen broader diversity and inclusion efforts.
Tryptanthrin Regulates Vascular Smooth Muscle Cell Phenotypic Switching in Atherosclerosis by AMP-Activated Protein Kinase/Acetyl-CoA Carboxylase Signaling Pathway
Authors: Shi Xiujin , Zhang Yi , Han Jialun , Peng Wenxing , Fang Zhenwei , Qin Ying , Xu Xiaoyu , Lin Jie , Xiao Fucheng , Zhao Limin , Lin Yang 
Published: May 2021

Abstract:
Atherosclerosis (AS) is one of the most severe cardiovascular diseases involved in the phenotypic switching of vascular smooth muscle cells (VSMCs). Tryptanthrin is a natural product with broad biological activities. However, the effect of tryptanthrin on atherosclerotic progression is unclear. The aim of this study was to determine the role of tryptanthrin in AS and explore the potential mechanism. In vitro, primary VSMCs were stimulated with platelet-derived growth factor-BB (PDGF) to induce cell dedifferentiation. Treatment with tryptanthrin (5 μM or 10 μM) suppressed the proliferation and recovered the contractility of VSMCs in the presence of PDGF. The contractile proteins (α-smooth muscle actin, calponin, and SM22α) were increased, and the synthetic protein vimentin was decreased by tryptanthrin in PDGF-induced VSMCs. ApoE−/− mice fed with high-fat diet were used as an in vivo model of AS. Similarly, gavage administration of tryptanthrin (50 mg/kg or 100 mg/kg) attenuated VSMC phenotypic changes from a contractile to a synthetic state in aortic tissues of AS mice. The serum lipid level, atherosclerotic plaque formation, and arterial intimal hyperplasia were attenuated by tryptanthrin. Furthermore, tryptanthrin increased the expression levels of phosphorylated AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) both in vitro and in vivo. Administration of compound C, an AMPK inhibitor, reversed the inhibitory effect of tryptanthrin on VSMC dedifferentiation in vitro. Thus, we demonstrate that tryptanthrin protects against AS progression through the inhibition of VSMC switching from a contractile to a pathological synthetic phenotype by the activation of AMPK/ACC pathway. It provides novel insights into AS prevention and treatment.
Population Pharmacokinetic Analysis of Dexmedetomidine in Children using Real World Data from Electronic Health Records and Remnant Specimens
Authors: James Nathan T. , Breeyear Joseph H. , Caprioli Richard , Edwards Todd , Hachey Brian , Kannankeril Prince J. , Keaton Jacob M. , Marshall Matthew D. , Van Driest Sara L. , Choi Leena 
Published: May 2021

AbstractAimOur objectives were to perform a population pharmacokinetic analysis of dexmedetomidine in children using remnant specimens and data from electronic health records (EHRs) and explore the impact of patient’s characteristics and pharmacogenetics on dexmedetomidine clearance.MethodsDexmedetomidine dosing and patient data were gathered from EHRs and combined with opportunistically sampled remnant specimens. Population pharmacokinetic models were developed using nonlinear mixed-effects modeling. The first stage developed a model without genotype variables; the second stage added pharmacogenetic effects.ResultsOur final study population included 354 post-cardiac surgery patients age 0 to 22 years (median 16 months). The final two-compartment model included allometric weight scaling and age maturation. Population parameter estimates and 95% confidence intervals were 27.3 L/hr (24.0 – 31.1 L/hr) for total clearance (CL), 161 L (139 – 187 L) for central compartment volume of distribution (V1), 26.0 L/hr (22.5 – 30.0 L/hr) for intercompartmental clearance (Q), and 7903 L (5617 – 11119 L) for peripheral compartment volume of distribution (V2). The estimate for postmenstrual age when 50% of adult clearance is achieved was 42.0 weeks (41.5 – 42.5 weeks) and the Hill coefficient estimate was 7.04 (6.99 – 7.08). Genotype was not statistically or clinically significant.ConclusionOur study demonstrates the use of real-world EHR data and remnant specimens to perform a population PK analysis and investigate covariate effects in a large pediatric population. Weight and age were important predictors of clearance. We did not find evidence for pharmacogenetic effects ofUGT1A4orUGT2B10genotype orCYP2A6risk score.What is already known about this subject∘Previous dexmedetomidine pharmacokinetic (PK) studies in pediatric populations have limited sample size.∘Smaller studies present a challenge for identifying covariates that may impact individual PK profiles.What this study adds∘We performed a dexmedetomidine population PK study with a large pediatric cohort using data obtained from electronic health records and remnant plasma specimens to enable increased sample size.∘xsDifferences in PK due toUGT1A4orUGT2B10variants orCYP2A6risk score are not clinically impactful for this population.