bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection and management of acute myeloid leukemia measurable residual disease: is it standard of care?
Authors: Paterno Giovangiacinto , Del Principe Maria Ilaria , Venditti Adriano 
Published: December 2019

Purpose of review
In the present manuscript, we will review the current approaches to investigate measurable residual disease (MRD) and its clinical applications in AML management.

Recent findings
Over the last decades, several methods have been developed to trace MRD, with flow cytometry and polymerase chain reaction (PCR) being the most reliable. However, new technologies, such as digital PCR and Next-Generation Sequencing are emerging as particularly useful in AML. The 2017 European LeukemiaNet (ELN) recommendations have incorporated MRD assessment to define the response criteria to therapy, and more recently, the ELN MRD Working Party has published guidelines for the use of MRD in clinical practice.

Summary
Morphologic complete remission (mCR) after induction therapy, has been consistently shown not only to have a critical prognostic role but also to fail in predicting relapse on an individual basis. Major attempts to improve our prediction capability have been made by measuring the residual levels of leukemic cells that persist in the bone marrow after chemotherapy. This number of cells, also called MRD, harbors in the bone marrow below the threshold of morphology and is responsible for leukemia recurrence. Therefore, the detection of MRD promises to help predict the risk of relapse, allowing a more proper patients’ risk-stratification and the use of risk-tailored therapeutic strategy.
Lasers for stone treatment: how safe are they?
Authors: Noureldin Yasser A. , Kallidonis Panagiotis , Liatsikos Evangelos N. 
Published: December 2019

Purpose of reviewTo update laser lithotripsy advances in regard to new laser types and technologies as well as review contemporary laser safety concerns.Recent findingsThe high prevalence of urolithiasis and the continuing miniaturization of scopes has encouraged the growth of laser lithotripsy technology. The holmium:yttrium-aluminum-garnet (Ho:YAG) laser has been used for over 20 years in endourology and has been extensively studied. Holmium laser power output is affected by a number of factors, including pulse energy, pulse frequency, and pulse width. Several recent experimental studies suggest that the new dual-phase Moses ‘pulse modulation’ technology, introduced in high-power laser machines, carries a potential to increase stone ablation efficiency and decrease stone retropulsion. A newly introduced thulium fiber laser (TFL) has been adapted to a very small laser fiber size and is able to generate very low pulse energy and very high pulse frequency. Both of these technologies promise to play a larger role in laser lithotripsy in the near future. However, more experimental and clinical studies are needed to expand on these early experimental findings. Even though laser lithotripsy is considered safe, precautions should be taken to avoid harmful or even catastrophic adverse events to the patient or the operating room staff.SummaryThe Ho:YAG laser remains the clinical gold standard for laser lithotripsy for over the last two decades. High-power Ho:YAG laser machines with Moses technology have the potential to decrease stone retropulsion and enhance efficiency of laser ablation. The new TFL has a potential to compete with and perhaps even replace the Ho:YAG laser for laser lithotripsy. Safety precautions should be taken into consideration during laser lithotripsy.
Risk factors and molecular characterization of penile cancer: impact on prognosis and potential targets for systemic therapy
Authors: Thomas Anita , Vanthoor Joren , Vos Gigi , Tsaur Igor , Albersen Maarten 
Published: December 2019

Purpose of review
To provide a comprehensive summary of risk factors, molecular machinery as well as potential therapeutic targets with a particular focus on literature published in the last 2 years on prognosis and treatment of penile cancer (PeCa).

Recent findings
E2F, LAMC2, MAML2, ID1 and IGFBP2 proteins were demonstrated to play a critical role for aggressive tumor behavior and might predict poor survival in PeCa. PD-L1 axis was confirmed as a promising pathway to serve as a therapeutic target. A number of genetic alterations were illuminated. In clinical testing, pan-HER tyrosine kinase inhibitor dacomitinib provided promising results in chemo-naïve and EGFR monoantibody nimotuzumab in chemotherapy-failed PeCa patients.

Summary
Knowledge of prognosis-relevant altered molecular pathways in PeCa is expanding paving the way for identification of potential therapeutic targets. Multicenter clinical trials in the setting of centralized PeCa care are warranted to foster effective marker-based individualized treatment strategies.
Evaluating Dimensions of Fatigue in Men With Prostate Cancer Receiving Radiation Therapy
Authors: Dickinson Kristin , Kupzyk Kevin , Saligan Leorey 
Published: December 2019

Background
Cancer-related fatigue (CRF) is a complex multidimensional symptom. Identifying the fatigue dimension that may be most bothersome can guide in the development of individualized management strategies.

Objective
The purpose of this article is to describe the multidimensional fatigue experience of men with prostate cancer.

Methods
Data for this study were obtained from an ongoing descriptive longitudinal study at the National Institutes of Health, involving men diagnosed with nonmetastatic prostate cancer scheduled to receive external beam radiation therapy. Data were analyzed at 7 time points: baseline, before treatment initiation (T1), treatment midpoint (T2), treatment completion (T3), and 1 month (T4), 3 months (T5), 6 months (T6), and 12 months (T7) after treatment completion. Study data were obtained from medical records and self-report (fatigue, depressive symptoms, and sleep disturbance) questionnaires.

Results
Scores for total fatigue peaked at T2 and remained significantly different from baseline at T3. After T3, total fatigue scores were not significantly different from baseline. Affective fatigue had the highest scores (worst fatigue) reported during treatment, sensory fatigue scores were highest from T4 to T6, and cognitive fatigue scores were highest at T7. Affective and sensory fatigue scores peaked at T2, whereas behavioral and cognitive fatigue scores peaked at T3.

Conclusion
Independent changes in specific dimensions of CRF were observed during and post treatment.

Implications for Practice
Understanding the specific dimensions of CRF and how they change during and post treatment can help guide clinicians to recommend targeted and personalized management strategies.
Sublingual Versus Swallowed Morphine
Authors: Dyal Brenda W. , Powell-Roach Keesha L. , Robison Jeanne , Campbell Bethaney , Yoon Saunjoo L. , Wilkie Diana J. 
Published: December 2019

Background
The optimal route for immediate-release morphine administration is controversial. The known physical characteristics of morphine that allow absorption are counter to the unproven belief that sublingual morphine is absorbed more quickly.

Objective
The aim of this study was to compare swallowed and sublingual morphine for effects on plasma morphine concentrations (PMCs), pain relief, and taste.

Methods
Ten participants with cancer (mean age, 50 ± 12 years) received a 10-mg morphine tablet in a randomized crossover design with repeated premeasure and postmeasure for 60 minutes. Measures included PMC and visual analog scale (100 mm) scores for pain relief and taste.

Results
Interindividual variability in maximum PMC was 25-fold (2.2–55 ng/mL). At 60 minutes, sublingual and swallowed routes were not significantly different for mean area under the curve for PMC (swallowed, 329 ± 314 ng/mL; sublingual, 314 ± 299 ng/mL) or for mean pain relief scores (swallowed, 81 ± 32; sublingual, 78 ± 31). Taste scores at 5 (P < .05), 10 (P < .04), 15 (P < .02), and 20 (P < .04) minutes after swallowed doses were significantly less unpleasant than after sublingual doses.

Conclusion
In this crossover design, between-group PMCs were similar for sublingual and swallowed morphine and resulted in a similar level of pain relief. Given the 25-fold across-participant differences in PMC after the same dose, additional research is warranted to identify the sources of this tremendous variability in PMC.

Implications for Practice
Because of unpleasant taste, which could influence adherence and subsequent analgesia, clinicians should encourage patients to swallow their morphine doses and restrict use of sublingual morphine to individuals who are unable to swallow.
Understanding Infection Prevention Practices in Optometry Clinics
Authors: Fernandes Priyanka , OYong Kelsey , Terashita Dawn 
Published: December 2019

SIGNIFICANCE
The Los Angeles County Department of Public Health investigated an outbreak of epidemic keratoconjunctivitis secondary to adenovirus linked to a single optometry clinic between June and July 2017. Suboptimal infection prevention practices were identified in the implicated clinic.

PURPOSE
The purpose of this study was to determine infection prevention practices in optometry clinics within Los Angeles County.

METHODS
A 17-question survey on infection prevention practices among a sample of optometry providers in the county was conducted by the Los Angeles County Department of Public Health. The survey was administered via e-mails sent to a local optometric society's Listserv and in person at a local continuing education event for optometrists. The results were analyzed and are represented as percentages.

RESULTS
There were 42 responses, 20 via the online survey (response rate, 15%) and 22 via the in-person survey (response rate, 22%). More than half had no written hand-hygiene policy (58.5%, n = 24/41), 46.2% (n = 18/39) did not wear gloves while examining patients with eye drainage, and about half (48.6%, n = 18/37) did not use droplet precautions for patients with respiratory symptoms. The vast majority used multidose eye-drop vials (92.5%, n = 37/40), but 41.6% (n = 15/36) did not discard the vial if the tip came into contact with conjunctiva/skin/environmental surface. To ensure a clean tonometer for each patient, the majority (68.4%, n = 26/38) used 70% isopropyl alcohol, 47.4% (n = 18/38) used noncontact tonometers, and 23.6% (n = 9/38) used disposable tips (answers not mutually exclusive); none used bleach.

CONCLUSIONS
Our data highlight several areas of concern in the practice of standard or transmission-based precautions in the sampled population. First, hand-hygiene policies are not well enforced. Second, personal protective equipment is not appropriately used while examining potentially infectious patients. Third, eye-drop vials are not consistently discarded if contaminated with eye secretions. Lastly, a large proportion of surveyed practices use inadequate disinfection techniques of tonometers.
Randomized Crossover Trial Evaluating the Impact of Senofilcon A Photochromic Lens on Driving Performance
Authors: Buch John R. , Toubouti Youssef , Cannon Jessica 
Published: December 2019

SIGNIFICANCE
The first contact lens to incorporate a photochromic additive was cleared by the U.S. Food and Drug Administration last year. Because any ophthalmic lens that absorbs visible wavelengths will reduce retinal illuminance, it is important to understand the impact of this new photochromic contact lens on vision and both daytime and nighttime driving performance.

PURPOSE
The purpose of this study was to evaluate the effect of senofilcon A photochromic contact lens wear on vision and driving performance under real-world conditions by comparison with a nonphotochromic contact lens and plano photochromic spectacles.

METHODS
In this randomized four-visit bilateral crossover study, 24 licensed regular drivers and established wearers of soft contact lenses were enrolled. Subjects wore in random order each of three study lens types: the investigational photochromic soft contact lens (test), a nonphotochromic soft contact lens (control 1), and plano photochromic spectacle lenses (control 2). Driver performance was assessed on a closed-circuit driving track under challenging controlled conditions. The primary endpoint was overall driving performance score calculated as a composite Z score of six objective metrics.

RESULTS
All 24 subjects (mean age, 29.8 years) completed the study. For nighttime driving, the adjusted mean differences in Z score (95% confidence interval) between test and control 1 and between test and control 2 were 0.069 (−0.045 to +0.183) and 0.117 (0.003 to 0.231), respectively. For daytime driving, mean differences were 0.101 (−0.013 to +0.216) between test and control 1 and 0.044 (−0.070 to +0.158) between test and control 2. Results demonstrated noninferiority of the test lens relative to controls for nighttime and daytime driving performance using a noninferiority margin of −0.25 Z score. Noninferiority was also demonstrated on all logMAR and contrast threshold testing. No adverse events were reported during the study.

CONCLUSIONS
Study results revealed no evidence of concerns with either driving performance or vision while wearing photochromic contact lenses.
Therapeutic Uses of Cannabis on Sleep Disorders and Related Conditions
Authors: Choi Seulah , Huang Barry C. , Gamaldo Charlene E. 
Published: December 2019

Summary:
Marijuana generally refers to the dried mixture of leaves and flowers of the cannabis plant, and the term cannabis is a commonly used to refer to products derived from the Cannabis sativa L. plant. There has been an increasing interest in the potential medicinal use of cannabis to treat a variety of diseases and conditions. This review will provide the latest evidence regarding the medical risks and potential therapeutic benefits of cannabis in managing patients with sleep disorders or those with other medical conditions who commonly suffer with sleep disturbance as an associated comorbidity. Published data regarding the effects of cannabis compounds on sleep in the general population, as well as in patients with insomnia, chronic pain, posttraumatic stress disorder, and other neurological conditions, will be presented. Current trends for marijuana use and its effects on the economy and the implications that those trends and effects have on future research into medical cannabis are also presented.
Cannabis for Pediatric Epilepsy
Authors: Huntsman Richard J. , Tang-Wai Richard , Shackelford Alan E. 
Published: December 2019

Summary:
Epilepsy is a chronic disease characterized by recurrent unprovoked seizures. Up to 30% of children with epilepsy will be refractory to standard anticonvulsant therapy, and those with epileptic encephalopathy can be particularly challenging to treat. The endocannabinoid system can modulate the physiologic processes underlying epileptogenesis. The anticonvulsant properties of several cannabinoids, namely Δ9-tetrahydrocannabinol and cannabidiol (CBD), have been demonstrated in both in vitro and in vivo studies. Cannabis-based therapies have been used for millennia to treat a variety of diseases including epilepsy. Several studies have shown that CBD, both in isolation as a pharmaceutical-grade preparation or as part of a CBD-enriched cannabis herbal extract, is beneficial in decreasing seizure frequency in children with treatment-resistant epilepsy. Overall, cannabis herbal extracts appear to provide greater efficacy in decreasing seizure frequency, but the studies assessing cannabis herbal extract are either retrospective or small-scale observational studies. The two large randomized controlled studies assessing the efficacy of pharmaceutical-grade CBD in children with Dravet and Lennox–Gastaut syndromes showed similar efficacy to other anticonvulsants. Lack of data regarding appropriate dosing and pediatric pharmacokinetics continues to make authorization of cannabis-based therapies to children with treatment-resistant epilepsy challenging.
Developing robust biomarkers for vascular cognitive disorders: adding ‘V’ to the AT(N) research framework
Authors: Sachdev Perminder S. 
Published: December 2019

Purpose of review
The AT(N) research framework was introduced in 2018 to define Alzheimer's disease as a biological entity. It is recognized that Alzheimer's disease lesions rarely occur in isolation in older brains, with cerebrovascular disease (CVD) being a common comorbidity. To fully characterize the disorder of dementia, the AT(N) framework needs to be extended with biomarkers for other disorders. The present review examines some of the requirements for adding a ‘V’ to the AT(N), and examines the currently available biomarkers as definitive markers of CVD.

Recent findings
Neuroimaging biomarkers of CVD have received the greatest attention, with rapid advances in MRI techniques showing the greatest promise. Challenges remain in standardization of techniques, validation of some of the results and assessing total CVD burden from diverse lesion types. Retinal imaging shows promise as a window to cerebral vasculature. Biochemical markers are advancing rapidly, but their specificity for CVD is not established.

Summary
Biomarkers of CVD have seen rapid advances but further validation and determination of their specificity are needed before they can be reliably used to delineate a V in the AT(N) framework as definitive indicators of significant CVD.
Hydroxide Ion Carrier for Proton Pump in Bacteriorhodopsin: Primary Proton Transfer
Authors: Imai M. , Ono J. , Nishimura Y. , Nakai H. 
Published: December 2019

ABSTRACTBacteriorhodopsin (BR) is a model protein for light-driven proton pumps, where the vectorial active proton transport results in light-energy conversion. To clarify the microscopic mechanism of primary proton transfer from retinal Schiff base (SB) to Asp85 in BR, herein we performed quantum-mechanical metadynamics simulations of the whole BR system (∼3800 atoms). The simulations showed a novel proton transfer mechanism, viz. hydroxide ion mechanism, in which the deprotonation of specific internal water (Wat452) yields the protonation of Asp85 via Thr89, after which the resulting hydroxide ion accepts the remaining proton from retinal SB. Furthermore, systematic investigations adopting four sequential snapshots obtained by the time-resolved serial femtosecond crystallography revealed that proton transfer took 2–5.25 μs on the photocycle. The presence of Wat401, which is the main difference between snapshots at 2 and 5.25 μs, is found to be essential in assisting the primary proton transfer.SIGNIFICANCEBacteriorhodopsin (BR), the benchmark of light-driven proton pumps, has attracted much attention from diverse areas in terms of energy conversion. Despite the significant experimental and theoretical efforts, the microscopic mechanism of the proton transfers in BR is not completely unveiled. In this study, quantum-mechanical molecular dynamics simulations of whole BR system were performed to elucidate the primary proton transfer in the L intermediate state with the latest snapshots obtained from X-ray free electron laser. As a result, it is found that the hydroxide ion originating from the specific internal water, which appears at the active site only in the L state, acts as a carrier for the primary proton transfer, demonstrating the importance of hydroxide ions in proton pumps.
The Ocular Glymphatic Clearance System
Authors: Wang Xiaowei , Lou Nanhong , Eberhardt Allison , Kusk Peter , Xu Qiwu , Förstera Benjamin , Peng Sisi , Yang Yujia , Shi Meng , Xavier Anna L. R. , Ertürk Ali , Libby Richard T. , Chen Lu , Thrane Alexander S. , Nedergaard Maiken 
Published: December 2019

AbstractDespite high metabolic activity, the retina and optic nerve head lack traditional lymphatic drainage. We here identified a novel ocular glymphatic clearance route for fluid and wastes via the proximal optic nerve. Amyloid-β (Aβ) was cleared from the vitreous via a pathway driven by the ocular-cranial pressure difference. After traversing the lamina barrier, intra-axonal Aβ was cleared via the perivenous space and subsequently drained to lymphatic vessels. Light-induced pupil constriction enhanced, while atropine or raising intracranial pressure blocked efflux. In two distinct murine models of glaucoma, Aβ leaked from the eye via defects in the lamina barrier instead of directional axonal efflux. The discovery of a novel pathway for removal of fluid and metabolites from the intraocular space prompts a reevaluation of the core principles governing eye physiology and provides a framework for new therapeutic approaches to treat common eye diseases, including glaucoma.One Sentence SummaryGlymphatic pathway clears ocular amyloid-β via optic nerve and fails in glaucoma.
CAP-MAP: Cap Analysis Protocol with Minimal Analyte Processing, a rapid and sensitive approach to analysing mRNA cap structures
Authors: Galloway Alison , Atrih Abdelmadjid , Grzela Renata , Darzynkiewicz Edward , Ferguson Michael A. J. , Cowling Victoria H. 
Published: December 2019

AbstractEukaryotic messenger RNA (mRNA) is modified by the addition of an inverted guanosine cap to the triphosphate at the 5’ end. The cap guanosine and initial transcribed nucleotides are further methylated by a series of cap methyltransferases to generate the mature cap structures which protect RNA from degradation and recruit proteins involved in RNA processing and translation. Research demonstrating that the cap methyltransferases are regulated has generated interest in determining the methylation status of the mRNA cap structures present in cells. Here we present CAP-MAP: Cap Analysis Protocol with Minimal Analyte Processing, a rapid and sensitive method for detecting cap structures present in mRNA isolated from tissues or cell cultures.