bluuebunny/crossref_metadata_2025_split huggingface dataset:
Octyl gallate triggers dysfunctional mitochondria leading to ROS driven membrane damage and metabolic inflexibility along with attenuated virulence in Candida albicans
Authors: Saibabu Venkata , Fatima Zeeshan , Ahmad Kamal , Khan Luqman Ahmad , Hameed Saif 
Published: May 2019

Abstract
Recently the high incidence of worldwide Candida infections has substantially increased. The growing problem about toxicity of antifungal drugs and multidrug resistance aggravates the need for the development of new effective strategies. Natural compounds in this context represent promising alternatives having potential to be exploited for improving human health. The present study was therefore designed to evaluate the antifungal effect of a naturally occurring phenolic, octyl gallate (OG), on Candida albicans and to investigate the underlying mechanisms involved. We demonstrated that OG at 25 μg/ml could effectively inhibit C. albicans. Mechanistic insights revealed that OG affects mitochondrial functioning as Candida cells exposed to OG did not grow on non-fermentable carbon sources. Dysfunctional mitochondria triggered generation of reactive oxygen species (ROS), which led to membrane damage mediated by lipid peroxidation. We explored that OG inhibited glucose-induced reduction in external pH and causes decrement in ergosterol levels by 45%. Furthermore, OG impedes the metabolic flexibility of C. albicans by inhibiting the glyoxylate enzyme isocitrate lyase, which was also confirmed by docking analysis. Additionally, OG affected virulence traits such as morphological transition and cell adherence. Furthermore, we depicted that OG not only prevented biofilm formation but eliminates the preformed biofilms. In vivo studies with Caenorhabditis elegans nematode model confirmed that OG could enhance the survival of C. elegans after infection with Candida. Toxicity assay using red blood cells showed only 27.5% haemolytic activity. Taken together, OG is a potent inhibitor of C. albicans that warrants further structural optimization and pharmacological investigations.
Chromatin remodeler Ep400 ensures oligodendrocyte survival and is required for myelination in the vertebrate central nervous system
Authors: Elsesser Olga , Fröb Franziska , Küspert Melanie , Tamm Ernst R , Fujii Toshihiro , Fukunaga Rikiro , Wegner Michael 
Published: May 2019

Abstract
Differentiating oligodendrocytes generate myelin to ensure rapid saltatory conduction in the vertebrate central nervous system. Although oligodendroglial differentiation and myelination are accompanied by dramatic chromatin reorganizations, previously studied chromatin remodelers had only limited direct effects on the process. To study the functional significance of chromatin changes for myelination and identify relevant remodelers, we deleted Ep400, the central ATP-hydrolyzing subunit of the TIP60/EP400 complex, at defined times of mouse oligodendrocyte development. Whereas Ep400-deficient oligodendrocyte precursors develop normally, terminal differentiation and myelination are dramatically impaired. Mechanistically, Ep400 interacts with transcription factor Sox10, binds to regulatory regions of the Myrf gene and is required to induce this central transcriptional regulator of the myelination program. In addition to reduced and aberrant myelin formation, oligodendrocytes exhibit increased DNA damage and apoptosis so that numbers never reach wildtype levels during the short lifespan of Ep400-deficient mice. Ep400 deletion in already mature oligodendrocytes remains phenotypically inapparent arguing that Ep400 is dispensable for myelin maintenance. Given its essential function in myelin formation, modulation of Ep400 activity may be beneficial in conditions such as multiple sclerosis where this process is compromised.
PSICA: a fast and accurate web service for protein model quality analysis
Authors: Wang Wenbo , Li Zhaoyu , Wang Junlin , Xu Dong , Shang Yi 
Published: May 2019

AbstractThis paper presents a new fast and accurate web service for protein model quality analysis, called PSICA (Protein Structural Information Conformity Analysis). It is designed to evaluate how much a tertiary model of a given protein primary sequence conforms to the known protein structures of similar protein sequences, and to evaluate the quality of predicted protein models. PSICA implements the MUfoldQA_S method, an efficient state-of-the-art protein model quality assessment (QA) method. In CASP12, MUfoldQA_S ranked No. 1 in the protein model QA select-20 category in terms of the difference between the predicted and true GDT-TS value of each model. For a given predicted 3D model, PSICA generates (i) predicted global GDT-TS value; (ii) interactive comparison between the model and other known protein structures; (iii) visualization of the predicted local quality of the model; and (iv) JSmol rendering of the model. Additionally, PSICA implements MUfoldQA_C, a new consensus method based on MUfoldQA_S. In CASP12, MUfoldQA_C ranked No. 1 in top 1 model GDT-TS loss on the select-20 QA category and No. 2 in the average difference between the predicted and true GDT-TS value of each model for both select-20 and best-150 QA categories. The PSICA server is freely available at http://qas.wangwb.com/∼wwr34/mufoldqa/index.html.
VOLPES: an interactive web-based tool for visualizing and comparing physicochemical properties of biological sequences
Authors: Bartonek Lukas , Zagrovic Bojan 
Published: May 2019

Abstract
The structure, dynamics and, ultimately, biological function of proteins and nucleic acids are determined by the physicochemical properties of their primary sequences. Such properties are frequently captured via one-dimensional profile plots depicting a given physicochemical variable as a function of sequence position. Hydrophobicity, charge or structural disorder in proteins or nucleobase-density in nucleic acids are routinely visualized in this manner to analyze sequences at a glance. Such visualizations, however, are typically created case-by-case in a purely static manner, employ fixed visualization parameters only and do not enable a quantitative comparison between different sequences. Here, we present VOLPES (volpes.univie.ac.at), a user-friendly web server and the corresponding JavaScript library that enable a fully interactive, multifunctional visualization, analysis and comparison of the physicochemical properties of protein and nucleic-acid sequences, allowing unprecedented insight into biological sequence data and creating a starting point for further in-depth exploration.
Against Moral Responsibilisation of Health: Prudential Responsibility and Health Promotion
Authors: Brown Rebecca C H , Maslen Hannah , Savulescu Julian 
Published: May 2019

Abstract
In this article, we outline a novel approach to understanding the role of responsibility in health promotion. Efforts to tackle chronic disease have led to an emphasis on personal responsibility and the identification of ways in which people can ‘take responsibility’ for their health by avoiding risk factors such as smoking and over-eating. We argue that the extent to which agents can be considered responsible for their health-related behaviour is limited, and as such, state health promotion which assumes certain forms of moral responsibility should (in general) be avoided. This indicates that some approaches to health promotion ought not to be employed. We suggest, however, that another form of responsibility might be more appropriately identified. This is based on the claim that agents (in general) have prudential reasons to maintain their health, in order to pursue those things which make their lives go well—i.e. that maintenance of a certain level of health is (all-things-considered) rational for many agents, given their pleasures and plans. On this basis, we propose that agents have a self-regarding prudential responsibility to maintain their health. We outline the implications of a prudential responsibility approach to health promotion.
Calculating History: A Mid-Seventeenth-Century Reader of Robert Persons’ A Conference about the Next Succession (1594/1595)
Authors: Archibald Christopher 
Published: May 2019

Abstract
This article examines one of the Bodleian Library’s copies of Robert Persons’ Elizabethan succession tract A Conference about the Next Succession that a 1650s reader has heavily annotated and used to compile a miscellany of poems and extracts from religious, political and historical works. The annotations and miscellany are concerned primarily with recent religious and political history. The reader compiles copies of popular ballads and poems, quotations from religious polemic by Catholic authors and a set of calculations of the dates of recent events in English Catholic history. This marked book serves as a case study through which to explore historical consciousness and the production of particularly Catholic forms of history and memory in the early modern period. This article seeks to query critical narratives concerning apparently combative seventeenth-century political reading practice by extending the remit of the ‘political’ to encompass different generic forms and approaches. It argues that by combining chronological and analogical perspectives this reader constructs a distinctively recusant history. An appendix identifies all of the works used by the annotator and all of the known editions or manuscripts they may have used.
Estimating Exposome Score for Schizophrenia Using Predictive Modeling Approach in Two Independent Samples: The Results From the EUGEI Study
Authors: Pries Lotta-Katrin , Lage-Castellanos Agustin , Delespaul Philippe , Kenis Gunter , Luykx Jurjen J , Lin Bochao D , Richards Alexander L , Akdede Berna , Binbay Tolga , Altinyazar Vesile , Yalinçetin Berna , Gümüş-Akay Güvem , Cihan Burçin , Soygür Haldun , Ulaş Halis , Cankurtaran Eylem Şahin , Kaymak Semra Ulusoy , Mihaljevic Marina M , Petrovic Sanja Andric , Mirjanic Tijana , Bernardo Miguel , Cabrera Bibiana , Bobes Julio , Saiz Pilar A , García-Portilla María Paz , Sanjuan Julio , Aguilar Eduardo J , Santos José Luis , Jiménez-López Estela , Arrojo Manuel , Carracedo Angel , López Gonzalo , González-Peñas Javier , Parellada Mara , Maric Nadja P , Atbaşoğlu Cem , Ucok Alp , Alptekin Köksal , Saka Meram Can ,   Genetic Risk and Outcome of Psychosis (GROUP) investigators, Alizadeh Behrooz Z , van Amelsvoort Therese , Bruggeman Richard , Cahn Wiepke , de Haan Lieuwe , Luykx Jurjen J , van Winkel Ruud , Rutten Bart P F , van Os Jim , Arango Celso , O’Donovan Michael , Rutten Bart P F , van Os Jim , Guloksuz Sinan 
Published: May 2019

Abstract
Exposures constitute a dense network of the environment: exposome. Here, we argue for embracing the exposome paradigm to investigate the sum of nongenetic “risk” and show how predictive modeling approaches can be used to construct an exposome score (ES; an aggregated score of exposures) for schizophrenia. The training dataset consisted of patients with schizophrenia and controls, whereas the independent validation dataset consisted of patients, their unaffected siblings, and controls. Binary exposures were cannabis use, hearing impairment, winter birth, bullying, and emotional, physical, and sexual abuse along with physical and emotional neglect. We applied logistic regression (LR), Gaussian Naive Bayes (GNB), the least absolute shrinkage and selection operator (LASSO), and Ridge penalized classification models to the training dataset. ESs, the sum of weighted exposures based on coefficients from each model, were calculated in the validation dataset. In addition, we estimated ES based on meta-analyses and a simple sum score of exposures. Accuracy, sensitivity, specificity, area under the receiver operating characteristic, and Nagelkerke’s R2 were compared. The ESMeta-analyses performed the worst, whereas the sum score and the ESGNB were worse than the ESLR that performed similar to the ESLASSO and ESRIDGE. The ESLR distinguished patients from controls (odds ratio [OR] = 1.94, P < .001), patients from siblings (OR = 1.58, P < .001), and siblings from controls (OR = 1.21, P = .001). An increase in ESLR was associated with a gradient increase of schizophrenia risk. In reference to the remaining fractions, the ESLR at top 30%, 20%, and 10% of the control distribution yielded ORs of 3.72, 3.74, and 4.77, respectively. Our findings demonstrate that predictive modeling approaches can be harnessed to evaluate the exposome.
Partnered Educational Governance: Rethinking Student Agency in Undergraduate Medical Education
Authors: Bilodeau Philippe Antoine , Liu Xin Mei , Cummings Beth-Ann 
Published: May 2019

Historically, students have been “consumers” of undergraduate medical education (UME) rather than stakeholders in its design and implementation. Student input has been retrospective, and although UME leaders have been open to feedback, matters most important to students have often been overlooked, leaving students feeling largely unheard. Student representation has also lacked structure and unity of feedback.
A vision for effective student representation drove the creation of a partnered educational governance (PEG) model at McGill University in Montreal, Quebec, Canada, where sharing of expertise between student representatives and UME leadership has improved the UME program and the educational experience of students.
The PEG model is grounded in the literature on student government, the student-as-partner framework, and theories of accountability. As part of the model, the student Medical Education Committee, an organized structure for discussion and reporting to student constituents, was established. This structure allows student representatives, entrusted by their peers and faculty, to proactively provide input to UME committees in the development of policies and curricula. The partnership between students and faculty facilitates a shared understanding of educational challenges and potential solutions.
Within the first year, meaningful changes associated with the PEG model included increased student engagement in key program decisions, such as the redesign of a research course and an update to the absences and leaves policy. The PEG model enables unified student representation that is accountable and representative—and has a significant impact on outcomes—while maintaining the UME program’s ownership of and responsibility for the curriculum and policies.
Qualitative Research Methods in Medical Education
Authors: Sawatsky Adam P. , Ratelle John T. , Beckman Thomas J. 
Published: May 2019

Abstract
Qualitative research was originally developed within the social sciences. Medical education is a field that comprises multiple disciplines, including the social sciences, and utilizes qualitative research to gain a broader understanding of key phenomena within the field. Many clinician educators are unfamiliar with qualitative research. This article provides a primer for clinician educators who want to appraise or conduct qualitative research in medical education. This article discusses a definition and the philosophical underpinnings for qualitative research. Using the Standards for Reporting Qualitative Research as a guide, this article provides a step-wise approach for conducting and evaluating qualitative research in medical education. This review will enable the reader to understand when to utilize qualitative research in medical education and how to interpret reports using qualitative approaches.
The Effect of Hearing-Protection Devices on Auditory Situational Awareness and Listening Effort
Authors: Smalt Christopher J. , Calamia Paul T. , Dumas Andrew P. , Perricone Joseph P. , Patel Tejash , Bobrow Johanna , Collins Paula P. , Markey Michelle L. , Quatieri Thomas F. 
Published: May 2019

Objectives:
Hearing-protection devices (HPDs) are made available, and often are required, for industrial use as well as military training exercises and operational duties. However, these devices often are disliked, and consequently not worn, in part because they compromise situational awareness through reduced sound detection and localization performance as well as degraded speech intelligibility. In this study, we carried out a series of tests, involving normal-hearing subjects and multiple background-noise conditions, designed to evaluate the performance of four HPDs in terms of their modifications of auditory-detection thresholds, sound-localization accuracy, and speech intelligibility. In addition, we assessed their impact on listening effort to understand how the additional effort required to perceive and process auditory signals while wearing an HPD reduces available cognitive resources for other tasks.

Design:
Thirteen normal-hearing subjects participated in a protocol, which included auditory tasks designed to measure detection and localization performance, speech intelligibility, and cognitive load. Each participant repeated the battery of tests with unoccluded ears and four hearing protectors, two active (electronic) and two passive. The tasks were performed both in quiet and in background noise.

Results:
Our findings indicate that, in variable degrees, all of the tested HPDs induce performance degradation on most of the conducted tasks as compared to the open ear. Of particular note in this study is the finding of increased cognitive load or listening effort, as measured by visual reaction time, for some hearing protectors during a dual-task, which added working-memory demands to the speech-intelligibility task.

Conclusions:
These results indicate that situational awareness can vary greatly across the spectrum of HPDs, and that listening effort is another aspect of performance that should be considered in future studies. The increased listening effort induced by hearing protectors may lead to earlier cognitive fatigue in noisy environments. Further study is required to characterize how auditory performance is limited by the combination of hearing impairment and the use of HPDs, and how the effects of such limitations can be linked to safe and effective use of hearing protection to maximize job performance.
New insights into human prolactin pathophysiology: genomics and beyond
Authors: Chang Sydney , Copperman Alan B. 
Published: May 2019

Purpose of review
To briefly summarize what is known regarding hyperprolactinemia and prolactin-secreting tumors, and review recent findings.

Recent findings
Prolactin was previously thought to inhibit secretion of gonadotropin-releasing hormone (GnRH) by directly inhibiting the firing of GnRH neurons, resulting in hypogonadotropic hypogonadism and infertility. However, kisspeptin has recently been implicated as the mediator of hyperprolactinemia-induced infertility, by acting upstream of the GnRH neurons as an integrator of endocrine signals.
Macroprolactin is generally considered to be inactive and clinically insignificant, but new studies have suggested that patients with macroprolactinemia may have reproductive manifestations as well as sexual dysfunction.
Several mutations and polymorphisms in the prolactin receptor have been described, which could describe a genetic cause for prolactinomas and characterize cases of isolated familial hyperprolactinemia.
Kisspeptin and tyrosine kinase inhibitors have emerged as potential new therapeutic targets for the treatment of hyperprolactinemia and dopamine-resistant prolactinomas.

Summary
Molecular studies are shedding light on the pathophysiology of hyperprolactinemia and the effects of excess prolactin production on the reproductive system. Similarly, genetic studies have begun to reveal how differences in prolactin receptor function may account for some of the previously ‘idiopathic’ cases of hyperprolactinemia and bring to light new causes of prolactinomas. Further elucidation of the transcriptional pathways affected by these genetic changes may help to create new therapeutic targets.
Informed consent in gynecologic surgery
Authors: Overcarsh Patricia , Arvizo Cynthia , Harvey Lara 
Published: May 2019

Purpose of review
Informed consent is frequently used interchangeably with obtaining a signature on a form. This oversimplification shifts the value from the process of informed consent to the documentation. This review focuses on the recommended components of the consent process, barriers encountered, factors influencing patient satisfaction, attempts to improve the consent practice, and considerations in special populations.

Recent findings
The process of informed consent is key to promoting shared decision-making and patient autonomy. Several barriers exist to providing optimal consent including time constraints as well as educational, cultural, and language barriers. Innovative approaches such as audiovisual aids show promise in overcoming barriers and improving the consent process.

Summary
Patients seek expertise and knowledge to aid in making decisions that align with their care goals. Providers have an obligation to provide individualized and accessible counseling. Ongoing research is needed to optimize this process.
Central Corneal Thickness in Childhood Cataract
Authors: Thau Avrey , Dawodu Oseluese , Mireskandari Kamiar , Ali Asim , Tehrani Nasrin , DeBenedictis Caroline , Bhoiwala Devang , Aultman William , Alnabi Waleed A. , Leiby Benjamin E. , Levin Alex V. 
Published: May 2019

Purpose:
We explored elevated central corneal thickness (CCT) in children with cataracts as possibly reflecting preexisting corneal malformation related to specific cataract morphology.

Methods:
All children consecutively seen during the study periods who had cataracts and corneal pachymetry as part of their routine care were enrolled at academic centers in large cities of Canada and the United States. Study data collected included age, sex, CCT, and cataract morphology. Differences among cataract morphology groups with respect to mean CCT measurements were evaluated and compared with a historical control thickness of 558 μm.

Results:
A total of 96 children were enrolled in this study. The average subject age was 5.1 years, and 55 children (57%) were female. The mean CCT value for all subjects was 566.1 μm. There was little evidence to conclude that the cataract morphology groups differed from each other (P = 0.65) or from controls with respect to CCT.

Conclusions:
In children, CCT is likely independent of cataract morphology. This implies that factors other than preoperative malformation are more likely related to elevated CCT observed in children with aphakia and pseudophakia.