bluuebunny/crossref_metadata_2025_split huggingface dataset:
How the dual process model of human cognition can inform efforts to de‐implement ineffective and harmful clinical practices: A preliminary model of unlearning and substitution
Authors: Helfrich Christian D. , Rose Adam J. , Hartmann Christine W. , van Bodegom‐Vos Leti , Graham Ian D. , Wood Suzanne J. , Majerczyk Barbara R. , Good Chester B. , Pogach Leonard M. , Ball Sherry L. , Au David H. , Aron David C. 
Published: January 2018

AbstractRationale and objectivesOne way to understand medical overuse at the clinician level is in terms of clinical decision‐making processes that are normally adaptive but become maladaptive. In psychology, dual process models of cognition propose 2 decision‐making processes. Reflective cognition is a conscious process of evaluating options based on some combination of utility, risk, capabilities, and/or social influences. Automatic cognition is a largely unconscious process occurring in response to environmental or emotive cues based on previously learned, ingrained heuristics. De‐implementation strategies directed at clinicians may be conceptualized as corresponding to cognition: (1) a process of unlearning based on reflective cognition and (2) a process of substitution based on automatic cognition.ResultsWe define unlearning as a process in which clinicians consciously change their knowledge, beliefs, and intentions about an ineffective practice and alter their behaviour accordingly. Unlearning has been described as “the questioning of established knowledge, habits, beliefs and assumptions as a prerequisite to identifying inappropriate or obsolete knowledge underpinning and/or embedded in existing practices and routines.” We hypothesize that as an unintended consequence of unlearning strategies clinicians may experience “reactance,” ie, feel their professional prerogative is being violated and, consequently, increase their commitment to the ineffective practice.We define substitution as replacing the ineffective practice with one or more alternatives. A substitute is a specific alternative action or decision that either precludes the ineffective practice or makes it less likely to occur.Both approaches may work independently, eg, a substitute could displace an ineffective practice without changing clinicians' knowledge, and unlearning could occur even if no alternative exists. For some clinical practice, unlearning and substitution strategies may be most effectively used together.ConclusionsBy taking into account the dual process model of cognition, we may be able to design de‐implementation strategies matched to clinicians' decision‐making processes and avoid unintended consequence.
Identifying behavioral states and habitat use of acoustically tracked humpback whales in Hawaii
Authors: Elizabeth Henderson E. , Helble Tyler A. , Ierley Glenn , Martin Steve 
Published: January 2018

AbstractAlthough humpback whales have been well‐studied on their Hawaiian breeding grounds, it is difficult to track individual animals over long distances without tags, particularly when they move offshore. Here, singing humpback whales were localized in three dimensions on the Pacific Missile Range Facility off Kauai, Hawaii, located between 20 km and 80 km offshore, from January 2011 through June 2014. Detailed behavioral analyses were conducted on the resulting tracks. One hundred and eight individual tracks were identified and metrics of these tracks were examined. Using these metrics, the tracks were classified into four behavior categories, described herein as Directed Travel, Repeated Stationary Dives, Mill, and tracks with Combinations of behavioral states. Some diel and seasonal patterns were identified, with Mill tracks occurring more at night than the other behaviors, Repeated Stationary Dive tracks occurring more during the day, and Directed Travel occurring only at the start and end of the breeding season. These results provide detailed insights into the movement of singing humpback whales, particularly in offshore waters where they may be migrating into or out of breeding grounds. This also contributes valuable information on the baseline behavior of humpback whales on a US Navy training range.
Pediatric psoriasis: Evolving perspectives
Authors: Eichenfield Lawrence F. , Paller Amy S. , Tom Wynnis L. , Sugarman Jeffrey , Hebert Adelaide A. , Friedlander Sheila Fallon , Siegfried Elaine , Silverberg Nanette , Cordoro Kelly M. 
Published: January 2018

AbstractBackground/ObjectivesChildhood‐onset psoriasis is a common skin disorder that has recently received increasing attention, particularly because of its significant medical, social, financial, and psychological burdens and its associated comorbidities. With limited data available and lack of standardized management guidelines for pediatric psoriasis, an expert panel desired to provide an updated critical overview and practical guidance for management of the affected population.MethodsA panel of pediatric dermatologists with extensive experience in pediatric psoriasis defined and prioritized a core set of topics, performed an English‐language literature review, prepared critical evaluations and presentations of topic areas, and carried out a consensus meeting and follow‐up consensus manuscript.ResultsThe summation of evolving perspectives in pediatric psoriasis includes epidemiology and natural history of the disease, precipitating factors and comorbidities, quality of life and burden of disease, clinical features and disease presentation, differential diagnosis, pathogenesis and treatment, including topical, photo, and systemic therapies.ConclusionPediatric psoriasis is an important immune‐mediated inflammatory skin disease with potential for significant impact on affected individuals and their caregivers. Current state‐of‐the‐art care is based primarily on experience and expert consensus, but pediatric data are accumulating and therapeutic options are rapidly evolving.
Regulating factory safety in the Bangladeshi garment industry
Authors: James Philip , Miles Lilian , Croucher Richard , Houssart Mark 
Published: January 2018

AbstractThis paper examines how far the workplace inspection program established under the 2013 Accord on Fire and Building Safety has served to improve safety in Bangladesh garment factories, and the extent to which its operation has been influenced by factors that the literature suggests are important in shaping the outcomes of private regulatory initiatives. The findings suggest that such regulation can generate positive outcomes, even in the absence of strong public regulatory support. They also caution against discounting the role of compliance‐based enforcement strategies, while highlighting the importance of their adequate resourcing and transparency. Some support is also offered for the argument that such regulatory initiatives could directly influence the market dynamics that shape supplier working conditions.
‘She is looking at me! Shall I share?’ How Chinese and American preschoolers respond to eye gaze during sharing
Authors: Wu Zhen , Chen Xi , Gros‐Louis Julie , Su Yanjie 
Published: January 2018

AbstractPrevious research shows that the recipient's verbal communication about desires increases young children's sharing behavior. The current study examined how an adult partner's non‐verbal communication through eye gaze influenced sharing behavior in children from different cultures. We presented one hundred forty‐six 3‐ to 5‐year‐old American and Chinese children with a Dictator Game, in which they were asked to distribute resources between themselves and an experimenter. Children were randomly assigned to three conditions, in which the experimenter alternated her gaze between the child and the items that she wanted, or looked randomly around the room, or left when the child made decisions about sharing but claimed to come back later. Results showed that Chinese children shared more than American children did in the alternating‐gaze condition, but not in the other two conditions; furthermore, the experimenter's alternating gaze influenced Chinese children to be more generous, but had no significant effect on American children. This suggests that compared to American children, Chinese children may be more compliant with others’ requests communicated through a subtle cue of eye gaze. The study demonstrates important differences in sharing behaviors between American and Chinese preschoolers, and these differences are consistent with the cultural constructs of individualism and collectivism.
Characterization of the Preclinical Pharmacology of the New 2-Aminomethylphenol, JPC-3210, for Malaria Treatment and Prevention
Authors: Birrell Geoffrey W. , Heffernan Gavin D. , Schiehser Guy A. , Anderson John , Ager Arba L. , Morales Pablo , MacKenzie Donna , van Breda Karin , Chavchich Marina , Jacobus Laura R. , Shanks G. Dennis , Jacobus David P. , Edstein Michael D. 
Published: January 2018

ABSTRACT

The new 2-aminomethylphenol, JPC-3210, has potent
in vitro
antimalarial activity against multidrug-resistant
Plasmodium falciparum
lines, low cytotoxicity, and high
in vivo
efficacy against murine malaria. Here we report on the pharmacokinetics of JPC-3210 in mice and monkeys and the results of
in vitro
screening assays, including the inhibition of cytochrome P450 (CYP450) isozymes. In mice, JPC-3210 was rapidly absorbed and had an extensive tissue distribution, with a brain tissue-to-plasma concentration ratio of about 5.4. JPC-3210 had a lengthy plasma elimination half-life of about 4.5 days in mice and 11.8 days in monkeys. JPC-3210 exhibited linear single-oral-dose pharmacokinetics across the dose range of 5 to 40 mg/kg of body weight with high oral bioavailability (∼86%) in mice. Systemic blood exposure of JPC-3210 was 16.6% higher in
P. berghei
-infected mice than in healthy mice.
In vitro
studies with mice and human hepatocytes revealed little metabolism and the high metabolic stability of JPC-3210. The abundance of human metabolites from oxidation and glucuronidation was 2.0% and 2.5%, respectively. CYP450 studies in human liver microsomes showed JPC-3210 to be an inhibitor of CYP2D6 and, to a lesser extent, CYP3A4 isozymes, suggesting the possibility of a metabolic drug-drug interaction with drugs that are metabolized by these isozymes.
In vitro
studies showed that JPC-3210 is highly protein bound to human plasma (97%). These desirable pharmacological findings of a lengthy blood elimination half-life, high oral bioavailability, and low metabolism as well as high
in vivo
potency have led the Medicines for Malaria Venture to select JPC-3210 (MMV892646) for further advanced preclinical development.
Diaphorina citri Nymphs Are Resistant to Morphological Changes Induced by “Candidatus Liberibacter asiaticus” in Midgut Epithelial Cells
Authors: Mann Marina , Fattah-Hosseini Somayeh , Ammar El-Desouky , Stange Richard , Warrick EricaRose , Sturgeon Kasie , Shatters Robert , Heck Michelle 
Published: January 2018

ABSTRACT

“
Candidatus
Liberibacter asiaticus” is the causative bacterium associated with citrus greening disease. “
Ca
. Liberibacter asiaticus” is transmitted by
Diaphorina citri
more efficiently when it is acquired by nymphs rather than adults. Why this occurs is not known. We compared midguts of
D. citri
insects reared on healthy or “
Ca
. Liberibacter asiaticus”-infected citrus trees using quantitative PCR, confocal microscopy, and mitochondrial superoxide staining for evidence of oxidative stress. Consistent with its classification as propagative, “
Ca
. Liberibacter asiaticus” titers were higher in adults than in nymphs. Our previous work showed that adult
D. citri
insects have basal levels of karyorrhexis (fragmentation of the nucleus) in midgut epithelial cells, which is increased in severity and frequency in response to “
Ca
. Liberibacter asiaticus.” Here, we show that nymphs exhibit lower levels of early-stage karyorrhexis than adults and are refractory to the induction of advanced karyorrhexis by “
Ca
. Liberibacter asiaticus” in the midgut epithelium. MitoSox Red staining showed that guts of infected adults, particularly males, experienced oxidative stress in response to “
Ca
. Liberibacter asiaticus.” A positive correlation between the titers of “
Ca
. Liberibacter asiaticus” and the
Wolbachia
endosymbiont was observed in adult and nymph midguts, suggesting an interplay between these bacteria during development. We hypothesize that the resistance of the nymph midgut to late-stage karyorrhexis through as yet unknown molecular mechanisms benefits “
Ca
. Liberibacter asiaticus” for efficient invasion of midgut epithelial cells, which may be a factor explaining the developmental dependency of “
Ca
. Liberibacter asiaticus” acquisition by the vector.
Herpes Simplex Virus 1 Mutant with Point Mutations in
UL39
Is Impaired for Acute Viral Replication in Mice, Establishment of Latency, and Explant-Induced Reactivation
Authors: Mostafa Heba H. , Thompson Thornton W. , Konen Adam J. , Haenchen Steve D. , Hilliard Joshua G. , Macdonald Stuart J. , Morrison Lynda A. , Davido David J. 
Published: January 2018

ABSTRACT

In the process of generating herpes simplex virus 1 (HSV-1) mutations in the viral regulatory gene encoding infected cell protein 0 (ICP0), we isolated a viral mutant, termed KOS-NA, that was severely impaired for acute replication in the eyes and trigeminal ganglia (TG) of mice, defective in establishing a latent infection, and reactivated poorly from explanted TG. To identify the secondary mutation(s) responsible for the impaired phenotypes of this mutant, we sequenced the KOS-NA genome and noted that it contained two nonsynonymous mutations in
UL39
, which encodes the large subunit of ribonucleotide reductase, ICP6. These mutations resulted in lysine-to-proline (residue 393) and arginine-to-histidine (residue 950) substitutions in ICP6. To determine whether alteration of these amino acids was responsible for the KOS-NA phenotypes
in vivo
, we recombined the wild-type UL39 gene into the KOS-NA genome and rescued its acute replication phenotypes in mice. To further establish the role of
UL39
in KOS-NA's decreased pathogenicity, the
UL39
mutations were recombined into HSV-1 (generating UL39
mut
), and this mutant virus showed reduced ocular and TG replication in mice comparable to that of KOS-NA. Interestingly, ICP6 protein levels were reduced in KOS-NA-infected cells relative to the wild-type protein. Moreover, we observed that KOS-NA does not counteract caspase 8-induced apoptosis, unlike wild-type strain KOS. Based on alignment studies with other HSV-1 ICP6 homologs, our data suggest that amino acid 950 of ICP6 likely plays an important role in ICP6 accumulation and inhibition of apoptosis, consequently impairing HSV-1 pathogenesis in a mouse model of HSV-1 infection.

IMPORTANCE
HSV-1 is a major human pathogen that infects ∼80% of the human population and can be life threatening to infected neonates or immunocompromised individuals. Effective therapies for treatment of recurrent HSV-1 infections are limited, which emphasizes a critical need to understand in greater detail the events that modulate HSV-1 replication and pathogenesis. In the current study, we identified a neuroattenuated HSV-1 mutant (i.e., KOS-NA) that contains novel mutations in the UL39 gene, which codes for the large subunit of ribonucleotide reductase (also known as ICP6). This mutant form of ICP6 was responsible for the attenuation of KOS-NA
in vivo
and resulted in diminished ICP6 protein levels and antiapoptotic effect. Thus, we have determined that subtle alteration of the UL39 gene regulates expression and functions of ICP6 and severely impacts HSV-1 pathogenesis, potentially making KOS-NA a promising vaccine candidate against HSV-1.
Functional Analysis of the Dengue Virus Genome Using an Insertional Mutagenesis Screen
Authors: Perry Jeffrey W. , Chen Yanhua , Speliotes Elizabeth , Tai Andrew W. 
Published: January 2018

ABSTRACT
In the last few decades, dengue virus, an arbovirus, has spread to over 120 countries. Although a vaccine has been approved in some countries, limitations on its effectiveness and a lack of effective antiviral treatments reinforce the need for additional research. The functions of several viral nonstructural proteins are essentially unknown. To better understand the functions of these proteins and thus dengue virus pathogenesis, we embarked on a genomewide transposon mutagenesis screen with next-generation sequencing to determine sites in the viral genome that tolerate 15-nucleotide insertions. Using this approach, we generated support for several published predicted transmembrane and enzymatic domains. Next, we created 7 mutants containing the 15-nucleotide insertion from the original selection and found 6 of them were capable of replication in both mammalian and mosquito tissue culture cells. Interestingly, one mutation had a significant impairment of viral assembly, and this mutation may lead to a better understanding of viral assembly and release. In addition, we created a fully infectious virus expressing a functionally tagged NS4B protein, which will provide a much-needed tool to elucidate the role of NS4B in viral pathogenesis.

IMPORTANCE
Dengue virus is a mosquito-borne virus distributed in tropical and subtropical regions globally that can result in hospitalization and even death in some cases. Although a vaccine exists, its limitations and a lack of approved antiviral treatments highlight our limited understanding of dengue virus pathogenesis and host immunity. The functions of many viral proteins are poorly understood. We used a previously published approach using transposon mutagenesis to develop tools to study these proteins' functions by adding insertions randomly throughout the viral genomes. These genomes were transferred into cells, and infectious progeny were recovered to determine sites that tolerated insertions, as only the genomes that tolerated insertions would be able to propagate. Using these results, we created viruses with epitope tags, one in the viral structural protein Capsid and one in the viral nonstructural protein NS4B. Further investigation of these mutants may elucidate the roles of Capsid and NS4B during dengue virus infections.
Transradial cerebral angiography: techniques and outcomes
Authors: Snelling Brian M , Sur Samir , Shah Sumedh S , Khandelwal Priyank , Caplan Justin , Haniff Rianna , Starke Robert M , Yavagal Dileep R , Peterson Eric C 
Published: January 2018

BackgroundDespite several retrospective studies analyzing the safety and efficacy of transradial access (TRA) versus transfemoral access (TFA) for cerebral angiography, this transition for neurointerventional procedures has been gradual. Nonetheless, based on our positive initial institutional experience with TRA for mechanical thrombectomy in acute ischemic stroke patients, we have started transitioning more of our cerebral angiography cases to TRA. Here we present our single institution experience.MethodsWe performed a retrospective review of patients receiving TRA cerebral angiography at our institution between January 2016 and February 2017. We present our experience transitioning from TFA to TRA, including our criteria for patient selection, technical nuances, patient experience, complications, and operator learning curve.ResultsWe included 148 angiograms performed in 141 people by one of four operators. No major complications were observed, and the technical success of the procedures was consistent with those of TFA. Marked improvement in operator efficiency was achieved in a short number of cases during this transition when looking at operator proficiency as a function of angiograms performed and days of exposure to TRA (4.3 vs 3.6 min/vessel, P<0.05).ConclusionsSafety and efficiency can be preserved while transitioning to TRA. While further investigation is necessary to support transition to TRA, these findings should call for a re-evaluation of the role of TRA in catheter cerebral angiography.
Investigating Low-Velocity Fluid Flow in Tumors with Convection-MRI
Authors: Walker-Samuel Simon , Roberts Thomas A. , Ramasawmy Rajiv , Burrell Jake S. , Johnson Sean Peter , Siow Bernard M. , Richardson Simon , Gonçalves Miguel R. , Pendse Douglas , Robinson Simon P. , Pedley R. Barbara , Lythgoe Mark F. 
Published: January 2018

Abstract
Several distinct fluid flow phenomena occur in solid tumors, including intravascular blood flow and interstitial convection. Interstitial fluid pressure is often raised in solid tumors, which can limit drug delivery. To probe low-velocity flow in tumors resulting from raised interstitial fluid pressure, we developed a novel MRI technique named convection-MRI, which uses a phase-contrast acquisition with a dual-inversion vascular nulling preparation to separate intra- and extravascular flow. Here, we report the results of experiments in flow phantoms, numerical simulations, and tumor xenograft models to investigate the technical feasibility of convection-MRI. We observed a significant correlation between estimates of effective fluid pressure from convection-MRI with gold-standard, invasive measurements of interstitial fluid pressure in mouse models of human colorectal carcinoma. Our results show how convection-MRI can provide insights into the growth and responsiveness to vascular-targeting therapy in colorectal cancers.
Significance: A noninvasive method for measuring low-velocity fluid flow caused by raised fluid pressure can be used to assess changes caused by therapy. Cancer Res; 78(7); 1859–72. ©2018 AACR.
In Silico Evaluation of Pharmacokinetic Optimization for Antimitogram-Based Clinical Trials
Authors: Haviari Skerdi , You Benoît , Tod Michel 
Published: January 2018

Abstract
Antimitograms are prototype in vitro tests for evaluating chemotherapeutic efficacy using patient-derived primary cancer cells. These tests might help optimize treatment from a pharmacodynamic standpoint by guiding treatment selection. However, they are technically challenging and require refinements and trials to demonstrate benefit to be widely used. In this study, we performed simulations aimed at exploring how to validate antimitograms and how to complement them by pharmacokinetic optimization. A generic model of advanced cancer, including pharmacokinetic–pharmacodynamic monitoring, was used to link dosing schedules with progression-free survival (PFS), as built from previously validated modules. This model was used to explore different possible situations in terms of pharmacokinetic variability, pharmacodynamic variability, and antimitogram performance. The model recapitulated tumor dynamics and standalone therapeutic drug monitoring efficacy consistent with published clinical results. Simulations showed that combining pharmacokinetic and pharmacodynamic optimization should increase PFS in a synergistic fashion. Simulated data were then used to compute required clinical trial sizes, which were 30% to 90% smaller when pharmacokinetic optimization was added to pharmacodynamic optimization. This improvement was observed even when pharmacokinetic optimization alone exhibited only modest benefit. Overall, our work illustrates the synergy derived from combining antimitograms with therapeutic drug monitoring, permitting a disproportionate reduction of the trial size required to prove a benefit on PFS. Accordingly, we suggest that strategies with benefits too small for standalone clinical trials could be validated in combination in a similar manner.
Significance: This work offers a method to reduce the number of patients needed for a clinical trial to prove the hypothesized benefit of a drug to progression-free survival, possibly easing opportunities to evaluate combinations. Cancer Res; 78(7); 1873–82. ©2018 AACR.