bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the Class I MHC Peptidome Resulting From DNCB Exposure of HaCaT Cells
Authors: Bailey Alistair , Nicholas Ben , Darley Rachel , Parkinson Erika , Teo Ying , Aleksic Maja , Maxwell Gavin , Elliott Tim , Ardern-Jones Michael , Skipp Paul 
Published: December 2020

AbstractSkin sensitization following the covalent modification of proteins by low molecular weight chemicals (haptenation) is mediated by cytotoxic T lymphocyte (CTL) recognition of human leukocyte antigen (HLA) molecules presented on the surface of almost all nucleated cells. There exist 3 nonmutually exclusive hypotheses for how haptens mediate CTL recognition: direct stimulation by haptenated peptides, hapten modification of HLA leading to an altered HLA-peptide repertoire, or a hapten altered proteome leading to an altered HLA-peptide repertoire. To shed light on the mechanism underpinning skin sensitization, we set out to utilize proteomic analysis of keratinocyte presented antigens following exposure to 2,4-dinitrochlorobenzene (DNCB). We show that the following DNCB exposure, cultured keratinocytes present cysteine haptenated (dinitrophenylated) peptides in multiple HLA molecules. In addition, we find that one of the DNCB modified peptides derives from the active site of cytosolic glutathione-S transferase-ω. These results support the current view that a key mechanism of skin sensitization is stimulation of CTLs by haptenated peptides. Data are available via ProteomeXchange with identifier PXD021373.
Synonymous mutations and the molecular evolution of SARS-CoV-2 origins
Authors: Wang Hongru , Pipes Lenore , Nielsen Rasmus 
Published: December 2020

AbstractHuman severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is most closely related, by average genetic distance, to two coronaviruses isolated from bats, RaTG13 and RmYN02. However, there is a segment of high amino acid similarity between human SARS-CoV-2 and a pangolin-isolated strain, GD410721, in the receptor-binding domain (RBD) of the spike protein, a pattern that can be caused by either recombination or by convergent amino acid evolution driven by natural selection. We perform a detailed analysis of the synonymous divergence, which is less likely to be affected by selection than amino acid divergence, between human SARS-CoV-2 and related strains. We show that the synonymous divergence between the bat-derived viruses and SARS-CoV-2 is larger than between GD410721 and SARS-CoV-2 in the RBD, providing strong additional support for the recombination hypothesis. However, the synonymous divergence between pangolin strain and SARS-CoV-2 is also relatively high, which is not consistent with a recent recombination between them, instead, it suggests a recombination into RaTG13. We also find a 14-fold increase in the dN/dS ratio from the lineage leading to SARS-CoV-2 to the strains of the current pandemic, suggesting that the vast majority of nonsynonymous mutations currently segregating within the human strains have a negative impact on viral fitness. Finally, we estimate that the time to the most recent common ancestor of SARS-CoV-2 and RaTG13 or RmYN02 based on synonymous divergence is 51.71 years (95% CI, 28.11–75.31) and 37.02 years (95% CI, 18.19–55.85), respectively.
Optimal Crash Cart Configuration for a Surgical NICU
Authors: Lefebvre Maria S. , Milloy Shaunna , Joynt Chloe 
Published: December 2020

Background:
Neonates admitted to cardiac and surgical neonatal intensive care units (NICUs) are at an increased risk of requiring emergency lifesaving interventions that require the use of both Neonatal Resuscitation Program (NRP) and Pediatric Advanced Life Support (PALS) algorithms. Clinicians working within the surgical NICU must be able to access emergency equipment and medications quickly in order to respond to critical situations. A crash cart that integrates human factors principles and supports both the NRP and PALS algorithms is necessary to promote patient safety for this high-risk population.

Purpose:
A multidisciplinary quality improvement project constructed an optimal crash cart configuration that embedded human factors principles and supported clinical workflow by reflecting both the NRP and the PALS algorithms in an NICU that cares for cardiac and surgical patients.

Methods:
A crash cart working group including frontline NICU staff, simulation experts, and a human factors specialist was formed within a surgical NICU. Human factors principles were utilized to align the organization of the cart with the NRP and PALS algorithms to increase the efficiency and intuitiveness of the cart. The new crash cart configuration was usability tested through simulation, revised on the basis of clinical feedback, and then implemented in a clinical setting. Data were collected following implementation of the new crash cart to validate that the new configuration was viewed as a significant improvement. The Plan-Do-Study-Act cycle was used to make improvements and capture outcome indicators.

Results:
Evaluation data collected both during usability simulation testing and in situ within the NICU clinical environment indicated that the revised crash cart scored higher on Likert scale response questions than the previous crash cart.

Implications for Practice:
Human factors science, in combination with frontline user engagement, should be utilized to create intuitive crash cart configurations, which are then tested in a simulation environment and evaluated in situ in the NICU.

Implications for Research:
Further research around crash cart design within NICUs that use multiple lifesaving algorithms would add to the paucity of research around the impact of human factors theory in the utilization of lifesaving equipment and medications within this specific population.
Abuse-Deterrent Opioid Formulations and the Opioid Crisis: A Pharmacist's Perspective
Authors: Gadd Shannon , Cox Nicholas , Samuelson James , Kenney Amy , Turner Kyle , Cochran Gerald 
Published: December 2020

Background:
For over 20 years, the United States has suffered the detrimental effects of an opioid epidemic. Extended-release opioid products are particularly prone to abuse due to the high amount of opioid present. By bypassing the controlled-release mechanisms and nonoral administration, individuals experience intense and dangerous “highs.” Abuse-deterrent opioid formulations have been recommended as a potential solution to the crisis, but widespread utilization has been stunted and their role in therapy remains unclear owing to limited real-world efficacy data and affordability issues. This review discusses abuse-deterrent opioid formulations, the mechanisms and data underlying available products, and a pharmacist's perspective of their role in the opioid crisis.

Methods:
The authors reviewed PubMed, MEDLINE, and Google Scholar electronic databases for premarketing and postmarketing studies on OxyContin, Xtampza ER, and Hysingla ER.

Results:
Studies showed lower rates of abuse (19% reduction), opioid use disorder (27%), overdose (34%), and fatalities (85%) with the reformulated OxyContin when compared with the original product and comparator opioids. However, these studies revealed the potential for bypassing abuse-deterrent mechanisms and diverting abuse to other drugs. Postmarketing studies are unavailable for Xtampza ER or Hysingla ER, although premarketing studies suggested that some controlled-release properties persist when the product is manipulated, indicating that abuse may be more difficult and less rewarding.

Conclusions:
Abuse-deterrent opioid products may lead to reductions in abuse, overdose, and overdose fatalities. However, cost, loopholes in deterrence mechanism, and possible diversion to other substances hinder their role in the opioid crisis. Multiple approaches must be used to improve opioid safety, and further postmarketing and real-world analyses should be performed on available opioid formulations to assess their impact on abuse-related adverse events.
Microsampling Assays for Pharmacokinetic Analysis and Therapeutic Drug Monitoring of Antimicrobial Drugs in Children: A Critical Review
Authors: Moorthy Ganesh S. , Vedar Christina , Downes Kevin J. , Fitzgerald Julie C. , Scheetz Marc H. , Zuppa Athena F. 
Published: December 2020

Background:
With the increasing prevalence of multidrug resistant organisms, therapeutic drug monitoring (TDM) has become a common tool for assuring the safety and efficacy of antimicrobial drugs at higher doses. Microsampling techniques, including dried blood spotting (DBS) and volumetric absorptive microsampling (VAMS), are attractive tools for TDM and pediatric clinical research. For microsampling techniques to be a useful tool for TDM, it is necessary to establish the blood–plasma correlation and the therapeutic window of antimicrobial drugs in the blood.

Methods:
DBS involves the collection of small volumes of blood (30–50 µL per spot) on a filter paper, whereas VAMS allows the accurate and precise collection of a fixed volume of blood (10–30 µL) with microsampling devices. One of the major advantages of VAMS is that it reduces or eliminates the volumetric blood hematocrit (HCT) bias associated with DBS. Liquid chromatography with tandem mass spectrometry is a powerful tool for the accurate quantification of antimicrobial drugs from small volumes of blood specimens.

Results:
This review summarizes the recent liquid chromatography with tandem mass spectrometry assays that have used DBS and VAMS approaches for quantifying antimicrobial drugs. Sample collection, extraction, validation outcomes, including the interassay and intra-assay accuracy and precision, recovery, stability, and matrix effect, as well as the clinical application of these assays and their potential as tools of TDM are discussed herein.

Conclusions:
Microsampling techniques, such as VAMS, provide an alternative approach to traditional plasma sample collection for TDM.
Validation of a Capillary Dry Blood Sample MITRA-Based Assay for the Quantitative Determination of Systemic Tacrolimus Concentrations in Transplant Recipients
Authors: Undre Nasrullah , Dawson Ian , Aluvihare Varuna , Kamar Nassim , Saliba Faouzi , Torpey Nicholas , Anaokar Swapneel , Kazeem Gbenga , Hussain Imran 
Published: December 2020

Background:
Tacrolimus is a narrow therapeutic index medication, which requires therapeutic drug monitoring to optimize dosing based on systemic exposure. MITRA microsampling offers a convenient, minimally invasive approach for the collection of capillary blood samples from a finger prick versus conventional venous blood sampling for quantitation of tacrolimus blood concentrations. However, the suitability of MITRA microsampling for the determination of tacrolimus concentrations requires assessment in clinical settings.

Methods:
Paired venous (2 mL) and capillary (10 μL) blood samples were collected pre–tacrolimus dose and 1 and 3 hours postdose during routine outpatient visits from stable adult liver or kidney transplant patients receiving prolonged-release tacrolimus. Tacrolimus concentrations were determined by liquid chromatography–tandem mass spectrometry, and the concentrations obtained by the 2 sampling methods were compared by linear regression and Bland–Altman agreement analyses.

Results:
Samples were available for 82 transplant recipients (kidney, n = 41; liver, n = 41). A high correlation was observed between tacrolimus concentrations in capillary and venous blood samples (Pearson correlation coefficient, 0.97; Lin concordance coefficient, 0.87; slope of the fitted line, >1.0). Tacrolimus concentrations in capillary samples were 22.5% higher on average than in the corresponding venous blood samples (95% limits of agreement, 0.5%–44.6%). Similar results were observed in both transplant subgroups.

Conclusions:
MITRA finger prick sampling provides a convenient alternative to venipuncture for therapeutic drug monitoring in transplant recipients maintained on prolonged-release tacrolimus. When using the finger prick MITRA method, the positive bias in tacrolimus concentrations observed with this technique, when compared with venipuncture, needs to be taken into consideration.
Accuracy of new-generation intraocular lens calculation formulas in eyes undergoing combined silicone oil removal and cataract surgery
Authors: Zhang Jiaqing , Wang Wei , Liu Zhenzhen , Yang Guangyao , Qiu Xiaozhang , Xu Jingmin , Jin Guangming , Li Yonghao , Zhang Shaochong , Tan Xuhua , Luo Lixia , Liu Yizhi 
Published: December 2020

Purpose:
To compare the performance of new-generation and traditional intraocular lens (IOL) calculation formulas in eyes undergoing combined silicone oil (SO) removal and cataract surgery and to evaluate the prediction accuracy of Wang-Koch (WK) adjustment in SO-filled long eyes.

Setting:
Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Design:
Retrospective consecutive case-series study.

Methods:
New-generation formulas (Barrett Universal II, Emmetropia Verifying Optical, Kane, and Ladas Super formulas) and traditional formulas (Haigis, Hoffer Q, Holladay 1, and SRK/T formulas) were compared. The performance of WK adjustment was assessed in eyes with axial length more than 26 mm. The median absolute error (MedAE) was the main parameter to evaluate the accuracy of formulas.

Results:
A total of 211 participants (211 eyes) who underwent combined SO removal and phacoemulsification with IOL implantation were included. Four new-generation formulas displayed statistically significant lower MedAE (0.32 to 0.35 diopter [D]) and higher percentage of eyes within ±1.00 D of prediction error (85.31% to 87.20%) compared with those of the traditional formulas (MedAE: 0.39 to 0.50 D; ±1.00 D: 81.04% to 81.99%, P < .05). For SO-filled long eyes, all traditional formulas showed hyperopic bias (0.36 to 0.65 D, P < .05), except for Haigis formula (0.28 D, P = .083), and this bias could be corrected by WK adjustment (P > .05). EVO formula displayed the lowest MedAE both in total (0.32 D) and in long eyes (0.33 D).

Conclusions:
New-generation formulas and traditional formulas with WK adjustment showed satisfactory prediction accuracy in eyes undergoing combined SO removal and cataract surgery. EVO formula displayed the highest accuracy.
Clinical evaluation of the effectiveness of asymmetric intracorneal ring with variable thickness and width for the management of keratoconus
Authors: Cuiña Sardiña Ricardo , Arango Alexandra , Alfonso Jose F. , Álvarez de Toledo Juan , Piñero David P. 
Published: December 2020

Purpose:
To evaluate the short-term clinical outcomes obtained with a new model of asymmetric intracorneal ring segments (ICRS) with variable thickness and base width in keratoconus.

Setting:
Four ophthalmologic centers in Spain.

Design:
Prospective multicenter longitudinal noncomparative clinical trial.

Methods:
Thirty-one keratoconus eyes of 25 patients (aged 15 to 50 years) that underwent implantation of ICRS of variable thickness and base (AJL-pro+) in 4 Spanish centers were enrolled. Visual, refractive, topographic, aberrometric, and pachymetric changes were evaluated during a 3-month follow-up. Complications were also recorded.

Results:
Statistically significant changes after surgery were observed in uncorrected distance visual acuity (P = .002) and corrected distance visual acuity (CDVA) (P = .005), as well as in spherical equivalent (P = .006). At 3 months postoperatively, no loss of 2 or more lines of CDVA was observed, whereas 48.4% (15) of eyes gained ≥1 line. Statistically significant changes were observed in the steepest and mean keratometric values (P ≤ .047) and in the magnitude of astigmatism (P < .001) of both anterior and posterior corneal surfaces. Likewise, a change to a less prolate shape of the anterior surface was found (P = .011). Primary coma was also reduced significantly at 1 month postoperatively (P = .001, mean reduction 40.1%). No serious implant-related complications occurred during the follow-up.

Conclusions:
The implantation of intrastromal asymmetric ring segments of variable thickness and base width in keratoconus corneas induces a significant anterior corneal flattening, leading to refractive changes, a significant reduction of its prolate shape and irregularity, and improvement in patient CDVA.
Quantifying the Degree of Bruise Visibility Observed Under White Light and an Alternate Light Source
Authors: Scafide Katherine N. , Downing Nancy R. , Kutahyalioglu Nesibe S. , Sebeh Yesser , Sheridan Daniel J. , Hayat Matthew J. 
Published: December 2020

ABSTRACT

Background
Documentation of injuries associated with abuse and assault has pivotal impacts on clinical and legal outcomes. Before this study, no reliable and valid tools to consistently document the clinical visibility of bruises existed. The purpose of this study was to systematically evaluate reliability and validity of the Bruise Visibility Scale for documenting bruises visualized in normal (white) light and the Absorption Visibility Scale for documenting bruises visualized using an alternate light source (ALS).

Methods
Bruises were induced using a paintball on the upper arms of 157 participants stratified into six skin color categories. Bruises were visualized 21 times over 4 weeks under white light and 10 ALS wavelength/goggle color combinations. Bruise size was measured using a metric ruler; bruise color was measured using a spectrophotometer. Interrater reliability was calculated using kappa and intraclass correlations coefficients. Construct validity was evaluated using generalized linear mixed modeling of associations between bruise size and color with both visibility scales.

Results
Interrater agreement for bruise detection was over 90% for all but two ALS wavelength/goggle combinations. Kappa values indicated adequate interrater agreement under white light (κ = 0.76) and ALS (κ = 0.78). The visibility scale intraclass correlation coefficients were .91 for normal light and .93 for ALS. Statistical modeling showed greater bruise size was associated with higher visibility using either scale, and greater contrast in color or lightness was associated with higher Bruise Visibility Scale values.

Implications for Practice
Both visibility scales showed satisfactory reliability and validity. Forensic nurses can use the scales to consistently document bruises.
Adrenal insufficiency updates in children
Authors: Ramirez Alcantara Jonanlis , Halper Alyssa 
Published: December 2020

Purpose of review
The current article will review the newest diagnostic tools, genetic causes, and treatment of adrenal insufficiency in children.

Recent findings
It is common practice to perform an adrenocorticotropin hormone (ACTH) stimulation test when adrenal insufficiency is suspected. The indications for use of a high-dose or low-dose of synthetic ACTH in children have been refined. In addition, newer studies propose adding 15 and 30-min serum or salivary cortisol levels to the low-dose ACTH stimulation test to correctly identify adrenal insufficiency. Recent identification of genetic mutations in children with non-classic steroidogenic acute regulatory protein and other mutations associated with primary and secondary adrenal insufficiency have expanded the cause and pathophysiology of monogenic adrenal insufficiency. In addition, newer hydrocortisone formulations and delivery methods and medications to use in combination with hydrocortisone are being explored to improve treatment for children with adrenal insufficiency.

Summary
Improved diagnostic aids, detection of newer genetic mutations, and better treatment options and delivery systems will help correctly identify and manage children with adrenal insufficiency to improve health outcomes and quality of life.

Video abstract

http://links.lww.com/COE/A21
The role of endoscopic medial maxillectomy in sinus disease
Authors: Govindaraju Revadi , Prepageran Narayanan 
Published: December 2020

Purpose of review
The endoscopic medial maxillectomy (EMM) has remained a relevant procedure for certain sinus diseases and at the same time reemerged as a salvage technique or even as a primary procedure for other diseases. Several mucosal-sparing techniques have also been described and the outcome of the surgeries is available for review.

Recent findings
Modifications of the EMM technique in the last two decades, aimed at mucosal preservation of the inferior turbinate, nasolacrimal duct, and medial maxillary wall have been successful in addressing a multitude of diseases. There are also evidences to support adjunct procedures/methods to improve access, healing, and to address associated dysfunction such as impaired mucociliary clearance. Tailored approaches have shown favourable outcomes with a low rate of adverse effects.

Summary
The EMM is appropriate for selected indications, in particular lesions causing medial wall destruction or extensive tumour involving the anterior wall or the prelacrimal recess. As for other maxillary sinus diseases including those identified to a limited site, a modified EMM is a reasonable consideration. The choice is appropriate provided instrument access, visualization, the ability for complete resection, postoperative care, and the requirement for surveillance is not compromised. A tailored approach with or without adjunct procedures is recommended.
Treatment of persistent/recurrent nodal disease in nasopharyngeal cancer
Authors: Tsang Raymond K. , Ng Wai-Tong 
Published: December 2020

Purpose of review
Persistent or recurrent disease in the neck lymphatics is an unusual pattern of failure in nasopharyngeal carcinoma (NPC) after definitive radiotherapy or chemoradiotherapy. The purpose of this review is to critically synthesize the current knowledge regarding salvage treatment of this unique form of failure in NPC.

Recent findings
Surgery in the form of radical neck dissection has been established as the standard salvage treatment with 5-year regional control of 60--86%. Recent shift in paradigm has resulted in the use of modified or selective neck dissection as salvage surgery in some centers. Risk factors for poor survival outcome include recurrent nodal disease, number of involved lymph nodes, extracapsular extension, high lymph node ratio, and positive resection margin. There are no well controlled studies on the role of additional radiotherapy or chemotherapy to improve local control or survival after salvage neck dissection in this group of patients with regional failure.

Summary
There is limited literature regarding the extent of surgical dissection in treating nodal persistent or recurrent disease. Prospective studies are also needed to determine whether adjuvant therapy improves treatment outcomes.
Diagnostic testing for SARS-CoV-2/COVID19
Authors: Spearman Paul 
Published: December 2020

Purpose of review
SARS-CoV-2 is the novel human coronavirus responsible for the COVID19 pandemic. Accurate detection of infection with SARS-CoV-2 is an essential component of efforts to treat individual patients and to contain spread of the virus in the community. The purpose of this review is to describe current diagnostic modalities for SARS-CoV-2 and outline their use. Special considerations for pediatric age groups are included.

Recent findings
RNA PCR from the upper respiratory tract remains the gold standard for detection of infection with SARS-CoV-2. Antigen testing is being widely deployed as a faster and more convenient alternative to PCR, but is less sensitive and should only be used for diagnosis early after symptom onset. Serologic assays can document prior infection and are helpful in diagnosing multisystem inflammatory syndrome in children. Serologic testing should not be used to diagnose acute or active infection. Immune assays are likely to provide a useful measure of protection against COVID19 in the future as knowledge of protective responses improves.

Summary
A variety of SARS-CoV-2 diagnostics have recently been developed and deployed. Clinicians should understand the appropriate use and interpretation of RNA PCR, antigen testing and immune assays for SARS-CoV-2 in order to diagnose and treat patients in this evolving pandemic.