bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic and transcriptome identification of fluconazole-resistant genes for Trichosporon asahii
Authors: Xia Zhikuan , Yu Haiying , Wang Congmin , Ding Xiao , Zhang Dequan , Tan Xinyu , Chen Jianghan , Hu Songnian , Yang Rongya 
Published: August 2019

Abstract
Trichosporon asahii infection is difficult to control clinically. This study identified a case with over 15 years of T. asahii infection-related systemic dissemination disease and conducted genome and transcriptome sequencing to identify fluconazole-resistant genes in fluconazole-resistant versus susceptible strains isolated from this patient's facial skin lesions. The data revealed mutations of the ergosterol biosynthetic pathway-related genes in the T. asahii genome of the fluconazole-resistant strain, that is, there were 36 novel mutations of the ERG11 gene, three point mutations (V458L, D457V, and D334S) in the ERG3, and a missense mutation (E349D) in ERG5 in the fluconazole-resistant strain of the T. asahii genome. To ensure that ERG11 is responsible for the fluconazole resistance, we thus simultaneously cultured the strains in vitro and cloned the ERG11 CDS sequences of both fluconazole-susceptible and -resistant strains into the Saccharomyces cerevisiae. These experiments confirmed that these mutations of ERG11 gene affected fluconazole resistance (&gt; 64 μg/ml vs. &lt;8 μg/ml of the MIC value between fluconazole-resistant and -susceptible strains) in Saccharomyces cerevisiae. In addition, expression of ergosterol biosynthesis pathway genes and drug transporter was upregulated in the fluconazole-resistant strain of T. asahii. Collectively, the fluconazole resistance in this female patient was associated with mutations of ERG11, ERG3, and ERG5 and the differential expression of drug transporter and fatty acid metabolic genes.
Global approaches to promoting whole grain consumption
Authors: Toups Kelly E 
Published: August 2019

Abstract
There is wide global consensus that whole grains are an important component of a healthy diet, yet in many countries around the globe populations continue to fall short of recommended intakes for whole grains. This article aims to evaluate whole grain promotional strategies of various stakeholders across 4 countries with diverse culinary and cultural norms: the United States, Singapore, the Philippines, and Denmark. To do this, information was collected on regulations, NGO (nongovernmental organization) activities, and promotional campaigns across each of the target countries. The effort led to the identification of best practices for promoting whole grain consumption in both the public and private spheres.
Decision-making for active living infrastructure in new communities: a qualitative study in England
Authors: Le Gouais A , Foley L , Ogilvie D , Guell C 
Published: August 2019

ABSTRACT

Background
Urban design can influence population levels of physical activity and subsequent health impacts. This qualitative study investigates local level decision-making for ‘active living’ infrastructure (ALI)—walking and cycling infrastructure and open spaces in new communities.

Methods
Thirty-five semi-structured interviews with stakeholders, and limited ethnographic observations, were conducted with local government and private sector stakeholders including urban and transport planners, public health practitioners, elected councillors and developers. Interview transcripts were coded and analysed thematically.

Results
Public health practitioners in local government could act as knowledge brokers and leaders to motivate non-health stakeholders such as urban and transport planners to consider health when designing and building new communities. They needed to engage at the earliest stages and be adequately resourced to build relationships across sectors, supporting non-health outcomes such as tackling congestion, which often had greater political traction. ‘Evidence’ for decision-making identified problems (going beyond health), informed solutions, and also justified decisions post hoc, although case study examples were not always convincing if not considered contextually relevant.

Conclusion
We have developed a conceptual model with three factors needed to bridge the gap between evidence and ALI being built: influential public health practitioners; supportive policies in non-health sectors; and adequate resources.
Extreme morning chronotypes are often familial and not exceedingly rare: the estimated prevalence of advanced sleep phase, familial advanced sleep phase, and advanced sleep–wake phase disorder in a sleep clinic population
Authors: Curtis Brian John , Ashbrook Liza H , Young Terry , Finn Laurel A , Fu Ying-Hui , Ptáček Louis J , Jones Christopher R 
Published: August 2019

AbstractStudy ObjectivesReport the first prevalence estimates of advanced sleep phase (ASP), familial advanced sleep phase (FASP), and advanced sleep–wake phase disorder (ASWPD). This can guide clinicians on the utility of screening for extreme chronotypes both for clinical decision-making and to flag prospective participants in the study of the genetics and biology of FASP.MethodsData on morning or evening sleep schedule preference (chronotype) were collected from 2422 new patients presenting to a North American sleep center over 9.8 years. FASP was determined using a severity criterion that has previously identified dominant circadian mutations in humans. All patients were personally seen and evaluated by one of the authors (C.R.J.).ResultsOur results demonstrate an ASP prevalence of 0.33%, an FASP prevalence of 0.21%, and an ASWPD prevalence of at least 0.04%. Most cases of young-onset ASP were familial.ConclusionsAmong patients presenting to a sleep clinic, conservatively 1 out of every 300 patients will have ASP, 1 out of every 475 will have FASP, and 1 out of every 2500 will have ASWPD. This supports obtaining a routine circadian history and, for those with extreme chronotypes, obtaining a family history of circadian preference. This can optimize treatment for evening sleepiness and early morning awakening and lead to additional circadian gene discovery. We hope these findings will lead to improved treatment options for a wide range of sleep and medical disorders in the future.
MiRNA-target pairs regulate adventitious rooting in Populus: a functional role for miR167a and its target Auxin response factor 8
Authors: Cai Heng , Yang Chunxia , Liu Sian , Qi Haoran , Wu Ling , Xu Li-An , Xu Meng 
Published: August 2019

Abstract
The ability of a plant to form roots from its non-root tissues is ecologically advantageous during rapid adaptation to a changing environment. Although this biological phenomenon has been widely utilized for cuttings in many economically important agronomic and tree species, its genetic and developmental mechanisms have been poorly understood. In this study, we conducted an association analysis of small RNAs, the degradome and the transcriptome of adventitious rooting in poplar softwood cuttings, which revealed that 373 miRNA-target pairs were detected. Of these, 72 significantly differentially expressed targets were screened as likely to modulate adventitious root (AR) development, in conjunction with plant hormone signal transduction. Poplar miR167a and its targets PeARF6s and PeARF8s were subjected to functional verification of their ability to mediate plant growth and hormone signal transduction. Overexpression of miR167a inhibited target transcripts and improved lateral root (LR) development in poplar, while overexpressing PeARF8.1mut increased AR numbers and slightly inhibited LR development. Taken together, these results suggest that miR167a-PeARF8.1 modules play crucial roles in regulating AR and LR development in poplar and improve the adaptation of poplar to more complex environments.
Productivity Losses and Firm Responses to Electricity Shortages: Evidence from Ghana
Authors: Abeberese Ama Baafra , Ackah Charles Godfred , Asuming Patrick Opoku 
Published: August 2019

Abstract
One of the commonly cited obstacles to firms’ operations in developing economies is inadequate access to electricity. This paper explores the impact of electricity outages on firm productivity using arguably exogenous variation in outages, induced by an electricity rationing program, across small and medium-sized Ghanaian manufacturing firms. The results indicate that eliminating outages in this setting could lead to an increase in firm productivity. Further analyses of the strategies firms use to cope with outages show that changing the firm's product mix to favor less electricity-intensive products mitigates the negative impacts of outages on productivity. However, using a generator, a common strategy in many parts of the world, is unable to insulate firms from the negative impacts of outages on productivity.
Association Between Sepsis and Microvascular Brain Injury*
Authors: Ehlenbach William J. , Sonnen Joshua A. , Montine Thomas J. , Larson Eric B. 
Published: August 2019

Objectives:Many survivors of sepsis suffer long-term cognitive impairment, but the mechanisms of this association remain unknown. The objective of this study was to determine whether sepsis is associated with cerebral microinfarcts on brain autopsy.Design:Retrospective cohort study.Setting and Subjects:Five-hundred twenty-nine participants of the Adult Changes in Thought, a population-based prospective cohort study of older adults carried out in Kaiser Permanente Washington greater than or equal to 65 years old without dementia at study entry and who underwent brain autopsy.Measurements and Main Results:Late-life sepsis hospitalization was identified using administrative data. We identified 89 individuals with greater than or equal to 1 sepsis hospitalization during study participation, 80 of whom survived hospitalization and died a median of 169 days after discharge. Thirty percent of participants with one or more sepsis hospitalization had greater than two microinfarcts, compared with 19% participants without (χ2p= 0.02); 20% of those with sepsis hospitalization had greater than two microinfarcts in the cerebral cortex, compared with 10% of those without (χ2p= 0.01). The adjusted relative risk of greater than two microinfarcts was 1.61 (95% CI, 1.01–2.57;p= 0.04); the relative risk for having greater than two microinfarcts in the cerebral cortex was 2.12 (95% CI, 1.12–4.02;p= 0.02). There was no difference in Braak stage for neurofibrillary tangles or consortium to establish a registry for Alzheimer’s disease score for neuritic plaques between, but Lewy bodies were less significantly common in those with sepsis.Conclusions:Sepsis was specifically associated with moderate to severe vascular brain injury as assessed by microvascular infarcts. This association was stronger for microinfarcts within the cerebral cortex, with those who experienced severe sepsis hospitalization being more than twice as likely to have evidence of moderate to severe cerebral cortical injury in adjusted analyses. Further study to identify mechanisms for the association of sepsis and microinfarcts is needed.
Old Mice Demonstrate Organ Dysfunction as well as Prolonged Inflammation, Immunosuppression, and Weight Loss in a Modified Surgical Sepsis Model*
Authors: Stortz Julie A. , Hollen McKenzie K. , Nacionales Dina C. , Horiguchi Hiroyuki , Ungaro Ricardo , Dirain Marvin L. , Wang Zhongkai , Wu Quran , Wu Kevin K. , Kumar Ashok , Foster Thomas C. , Stewart Brian D. , Ross Julia A. , Segal Marc , Bihorac Azra , Brakenridge Scott , Moore Frederick A. , Wohlgemuth Stephanie E. , Leeuwenburgh Christiaan , Mohr Alicia M. , Moldawer Lyle L. , Efron Philip A. 
Published: August 2019

Objectives:
Our goal was to “reverse translate” the human response to surgical sepsis into the mouse by modifying a widely adopted murine intra-abdominal sepsis model to engender a phenotype that conforms to current sepsis definitions and follows the most recent expert recommendations for animal preclinical sepsis research. Furthermore, we aimed to create a model that allows the study of aging on the long-term host response to sepsis.

Design:
Experimental study.

Setting:
Research laboratory.

Subjects:
Young (3–5 mo) and old (18–22 mo) C57BL/6j mice.

Interventions:
Mice received no intervention or were subjected to polymicrobial sepsis with cecal ligation and puncture followed by fluid resuscitation, analgesia, and antibiotics. Subsets of mice received daily chronic stress after cecal ligation and puncture for 14 days. Additionally, modifications were made to ensure that “Minimum Quality Threshold in Pre-Clinical Sepsis Studies” recommendations were followed.

Measurements and Main Results:
Old mice exhibited increased mortality following both cecal ligation and puncture and cecal ligation and puncture + daily chronic stress when compared with young mice. Old mice developed marked hepatic and/or renal dysfunction, supported by elevations in plasma aspartate aminotransferase, blood urea nitrogen, and creatinine, 8 and 24 hours following cecal ligation and puncture. Similar to human sepsis, old mice demonstrated low-grade systemic inflammation 14 days after cecal ligation and puncture + daily chronic stress and evidence of immunosuppression, as determined by increased serum concentrations of multiple pro- and anti-inflammatory cytokines and chemokines when compared with young septic mice. In addition, old mice demonstrated expansion of myeloid-derived suppressor cell populations and sustained weight loss following cecal ligation and puncture + daily chronic stress, again similar to the human condition.

Conclusions:
The results indicate that this murine cecal ligation and puncture + daily chronic stress model of surgical sepsis in old mice adhered to current Minimum Quality Threshold in Pre-Clinical Sepsis Studies guidelines and met Sepsis-3 criteria. In addition, it effectively created a state of persistent inflammation, immunosuppression, and weight loss, thought to be a key aspect of chronic sepsis pathobiology and increasingly more prevalent after human sepsis.
Core Outcome Measures for Research in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation for Acute Respiratory or Cardiac Failure: An International, Multidisciplinary, Modified Delphi Consensus Study*
Authors: Hodgson Carol L. , Burrell Aidan J. C. , Engeler Daniel M. , Pellegrino Vincent A. , Brodie Daniel , Fan Eddy 
Published: August 2019

Objectives:
Research evaluating outcomes in critically ill patients with acute respiratory and cardiac failure supported with extracorporeal membrane oxygenation has increased significantly. The objective was to identify a core set of outcomes that are essential to include in all clinical research evaluating the use of either venoarterial or venovenous extracorporeal membrane oxygenation in critically ill patients, particularly regarding safety and adverse events.

Design:
A three-round modified Delphi process.

Subjects:
Patients, caregivers, multidisciplinary clinicians, researchers, industry partners, and research funders were included.

Setting:
Participants represented key extracorporeal membrane oxygenation organizations, including the Extracorporeal Life Support Organization, the International Extracorporeal Membrane Oxygenation Network, clinicians from high volume extracorporeal membrane oxygenation centers, and extracorporeal membrane oxygenation researchers or former extracorporeal membrane oxygenation patients from five continents.

Interventions:
We used recommended standards for the development of a core outcome set. Outcome measures identified from systematic reviews of the literature and from qualitative studies of survivors were mapped to the domains identified by the Core Outcome Measures in Effectiveness Trials initiative separately for venovenous extracorporeal membrane oxygenation and venoarterial extracorporeal membrane oxygenation.

Measurements and Main Results:
Participant response rates were 40 of 47 (85%), 35 of 37 (95%), and 64 of 69 (93%) for survey rounds 1, 2, and 3, respectively, with participants representing 10 different countries on five continents. After the third round survey, 8 outcome measures met consensus for both venovenous extracorporeal membrane oxygenation and venoarterial extracorporeal membrane oxygenation.

Conclusions:
This study identified core outcomes to assess in all research evaluating the use of extracorporeal membrane oxygenation, including adverse events specific to this intervention, permitting standardization of outcome reporting for the first time. Identifying appropriate measurement instruments to evaluate these outcomes is an important next step to enable synthesis of extracorporeal membrane oxygenation research.
Impact of Therapeutic Drug Monitoring of Antiretroviral Drugs in Routine Clinical Management of People Living With HIV: A Narrative Review
Authors: Cattaneo Dario , Baldelli Sara , Cozzi Valeria , Clementi Emilio , Marriott Deborah J. E. , Gervasoni Cristina ,   on behalf of the IATDMCT Anti-Infective Committee
Published: August 2019

Background:
The treatment of HIV infection has evolved significantly since the advent of highly active antiretroviral therapy. As a result, a response rate of 90%–95% now represents a realistically achievable target. Given this background, it is difficult to imagine the additional benefits that therapeutic drug monitoring (TDM) could provide in the management of HIV infection.

Methods:
This article is not intended to provide a systematic literature review on TDM of antiretroviral agents; rather, the authors aim to discuss the potential added value of TDM in the optimal management of people living with HIV (PLWH) in selected real-life clinical scenarios based on data collected over 10 years by their TDM service.

Results:
Some clinical situations, in which the selection of the optimal antiretroviral therapy is challenging, have been identified. These include poorly compliant patients, suboptimal antiretroviral therapies (in terms of both efficacy and toxicity), polypharmacy with a high risk of drug–drug interactions, and different patient populations, such as pregnant women.

Conclusions:
The transformation of HIV infection from a near-universally fatal illness to a lifelong chronic disease has resulted in an HIV population that is growing and aging, placing new and increasing demands on public programs and health services. Increasingly, the management of comorbidities, polypharmacy, and drug–drug interaction, and their impact on antiretroviral therapy will have to be undertaken. These clinical settings represent some of the new frontiers for the use of TDM with the goal of achieving optimal prescription and outcome for PLWH.
Graves’ hyperthyroidism in pregnancy
Authors: Nguyen Caroline T. , Mestman Jorge H. 
Published: August 2019

Purpose of review
Graves’ hyperthyroidism is associated with significant obstetric, maternal, fetal, and neonatal complications. Early diagnosis and an understanding of the management of Graves’ hyperthyroidism in pregnancy can help to prevent these complications. Antithyroid drugs (ATD) should be avoided in early pregnancy, given their association with congenital malformations.

Recent findings
TSH-receptor antibodies (TRAb) are integral in the management of Graves’ hyperthyroidism in pregnancy and in the preconception period. TRAb are indicative of the current activity of Graves’ hyperthyroidism and the likelihood of relapse. Furthermore, TRAb predicts the risk of fetal and neonatal hyperthyroidism.
The incidence of congenital malformations is roughly the same for propylthiouracil (PTU) and methimazole (MMZ). Exposure to both ATDs in early pregnancy has been associated with increased incidence of congenital malformations compared with exposure to either ATD alone.

Summary
The goal of the physician is maintaining euthyroidism throughout pregnancy and delivery of a healthy, euthyroid baby. An understanding of the natural progression of Graves’ hyperthyroidism in pregnancy and the proper utilization of TRAb enables the physician to minimize the risks associated with Graves’ hyperthyroidism and side effects of ATDs unique to pregnancy. The physician should prioritize preconception counseling in women with Graves’ hyperthyroidism in order to avoid hyperthyroidism and having to use ATDs in pregnancy.
Use of multiple free flaps in head and neck reconstruction
Authors: Hsieh Tsung-yen , Bewley Arnaud 
Published: August 2019

Purpose of review
To review the recent literature on the use of multiple flaps in head and neck reconstruction with attention to form, function, outcomes, and complications.

Recent findings
Multiple free flap reconstructions are technically feasible with high flap survival rates, tolerable complication rates, and overall adequate functional and aesthetic outcomes, given the large extent of the defects and the high surgical complexity of these cases.

Summary
Multiple free flap reconstructions should be considered in cases of large defects involving multiple functional regions and tissue types, which most often arises following resection of advanced malignancies. As there is mortality benefit with clear surgical margins and eradication of malignant lymph nodes, larger resections should be pursued if necessary, followed by a multiple flap reconstruction.
Oculocardiac Reflex: An Underrecognized But Important Association With Orbital Trap Door Fractures
Authors: Mehmood Noormah , Hasan Ali 
Published: August 2019

Abstract
Blowout fractures of the floor of the orbit can serve as a “trap door” for extraocular muscles. Presentation of inferior orbital muscle entrapment classically involves an upward gaze restriction. Diplopia and exophthalmos can also be present. Rarely, orbital fractures can result in an oculocardiac reflex, which is a triad of bradycardia, syncope, and nausea. The purpose of this study was to describe a patient who had orbital floor fracture with symptoms highly suggestive for oculocardiac reflex after a traumatic injury. Although entrapment of extraocular muscles does require early intervention to prevent ischemia and tissue necrosis, the presence of oculocardiac reflex warrants emergent evaluation and management by an ophthalmologist due to the risk of developing arrhythmias. Frequently, there may be none or very subtle clinical findings present, and abnormal motility may be the only apparent clinical sign, which can be difficult to assess in very young and uncooperative children; therefore, a high index of suspicion must be maintained for early identification and management as well as a reduction of complications.