bluuebunny/crossref_metadata_2025_split huggingface dataset:
B cells and food allergy
Authors: Udemgba Chioma , Lin Adora 
Published: August 2021

Purpose of review
B cells are known in food allergy pathogenesis for their production of IgE but their roles in the development of tolerance to foods are not well understood. Further understanding of B-cell biology in the context of food allergy is essential for the creation of effective prevention strategies and therapies.

Recent findings
The majority of allergen-specific IgE in humans appears to arise from antigen-experienced B cells that have already undergone class switch recombination to other antibody isotypes, such as IgG1, and can also be produced by cells class switching to IgE locally in the gastrointestinal tract. Allergen-specific IgG4 can have protective effects in individuals and is associated with tolerance. Regulatory B cells, which can produce allergen-specific IgG4, are reduced in food-allergic individuals and may also be an important component of tolerance. Therapeutic approaches that block the generation and action of IgE and that enhance tolerizing immune responses are being evaluated for the treatment of food allergy.

Summary
B cells play several roles in the development of food allergy versus tolerance. Their functions may translate into the care of food allergy as biomarkers or therapeutic targets and can be employed in other atopic diseases to better understand their pathogenesis and create new avenues for treatment.
Accuracy of Noncycloplegic Refraction for Detecting Refractive Errors in School-aged African Children
Authors: Ilechie Alex Azuka , Addo Naa Adjeley , Abraham Carl Halladay , Owusu-Ansah Andrew , Annan-Prah Alex 
Published: August 2021

SIGNIFICANCE
Cycloplegia is often restricted in screening settings. Previous studies have evaluated noncycloplegic refraction for screening, but their data are not fully applicable to school-aged African children. This article adds to the literature by investigating this in school-aged African children.

PURPOSE
The purpose of this study was to evaluate the ability of noncycloplegic autorefraction (NCA) and noncycloplegic retinoscopy (NCR) to detect refractive errors in school-aged African children and quantify differences between noncycloplegic and cycloplegic refraction measures.

METHODS
Autorefraction and retinoscopy were performed on 150 children aged 6 to 15 years before and after cyclopentolate cycloplegia. Subjective refraction was performed by the same examiner after cycloplegia. Noncycloplegic and cycloplegic measurements were compared, and the data were assessed with receiver operating characteristic curves and Bland-Altman plots.

RESULTS
With the exception of cylindrical vector J0 (P = .17) and J45 (P = .08) obtained with NCR, all mean measures of NCA and NCR significantly differed from mean cycloplegic subjective refraction measurements by −0.71 ± 0.67 (P ≤ .001; 95% confidence interval, −2.02 to +0.60) and −0.75 ± 0.68 (P ≤ .001; 95% confidence interval, −2.08 to +0.58), respectively. Mean spherical power between the two tests did not differ (NCA −NCR, mean bias of −0.037 ± 0.675 and 95% limits of agreement of −1.36 to 1.286; P = .51). The sensitivities for detecting any refractive error for NCR and NCA were 86.8 and 82.9%, respectively, and the specificities were 82.0% for NCR and 82.4% for NCA. Performance of both tests was excellent for myopia (area under the curve, >0.90; sensitivity, ≥90%) and similar (P = .13), but the specificities for detecting hyperopia were 78.0% for NCR and 80.0% for NCA.

CONCLUSIONS
Noncycloplegic refraction may accurately detect astigmatism and myopia in this population but may elicit higher myopic values and lower hyperopic values than using cycloplegic refraction.
Validation of the International Reading Speed Texts in a Sample of Older (60+) Canadian Adults
Authors: Morrice Elliott , Soldano Vanessa , Addona Cynthia , Murphy Caitlin Elizabeth , Johnson Aaron P. 
Published: August 2021

SIGNIFICANCE
On average, older adults (60+) with normal vision read the International Reading Speed Texts (IReST) 37.8 words per minute slower than the standardized values provided by the IReST manufacturer. When assessing reading speed in older adults, clinicians should bear in mind that the IReST norms do not account for these age-related differences.

PURPOSE
The purpose of this study was to validate the IReST in an English-speaking Canadian sample of older adults (60+).

METHODS
Canadian English-speaking older adults (n = 25) read all 10 IReST aloud using the same protocol from the original IReST validation study.

RESULTS
There were significant differences between the older adult sample and the published IReST values for each text (mean difference, −37.84; 95% confidence interval, −41.34 to −34.34).

CONCLUSIONS
Reading speeds of older (60+) Canadian adults fell outside of the standardized values of the English language IReST. Researchers/clinicians who wish to assess older adults' reading speed using the IReST ought to take this discrepancy into account.
Photophobia Associated with Traumatic Brain Injury: A Systematic Review and Meta-analysis
Authors: Merezhinskaya Natalya , Mallia Rita K. , Park DoHwan , Millian-Morell Lymarie , Barker Felix M. 
Published: August 2021

SIGNIFICANCE
This study reports the prevalence and relative risk of photophobia in patients with traumatic brain injury (TBI).

OBJECTIVES
This study aimed to conduct a systematic review and meta-analysis to determine the prevalence and relative risk of photophobia in patients with TBI.

DATA SOURCES
Three databases were used for literature search: PubMed, EMBASE, and Cochrane Library.

STUDY APPRAISAL AND SYNTHESIS METHODS
Publications reporting the prevalence of photophobia after TBI in patients of any age were included. A series of meta-regression analyses based on a generalized linear mixed model was performed to identify potential sources of heterogeneity in the prevalence estimates.

RESULTS
Seventy-five eligible publications were identified. The prevalence of photophobia was 30.46% (95% confidence interval [CI], 20.05 to 40.88%) at 1 week after the injury. Prevalence decreased to 19.34% (95% CI, 10.40 to 28.27%) between 1 week and 1 month after TBI and to 13.51% (95% CI, 5.77 to 21.24%) between 1 and 3 months after the injury. The rapid decrease in the prevalence of photophobia in the first 3 months after a TBI injury was significant (P < .001). Three months post-TBI, the prevalence of photophobia leveled off to a near plateau with nonsignificant variability, increasing between 3 and 6 months (17.68%; 95% CI, 9.05 to 26.32%) and decreasing between 6 and 12 months since TBI (14.85%; 95% CI, 6.80 to 22.90%). Subgroup analysis of 14 publications that contained control data showed that the estimated risk ratio for photophobia was significantly higher in the TBI than in the control group during the entire 12 months after TBI.

CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
This study demonstrates that photophobia is a frequent complaint after TBI, which largely resolves for many individuals within 3 months after the injury. For some patients, however, photophobia can last up to 12 months and possibly longer. Developing an objective quantitative methodology for measuring photophobia, validating a dedicated photophobia questionnaire, and having a specific photophobia International Classification of Diseases, Tenth Revision code would greatly improve data gathering and analysis.
Trends in the Number and Characteristics of HIV Pre-Exposure Prophylaxis Providers in the United States, 2014–2019
Authors: Zhu Weiming , Huang Ya-Lin A. , Kourtis Athena P. , Hoover Karen W. 
Published: August 2021

Background:
The number and characteristics of pre-exposure prophylaxis (PrEP) health care providers in the United States have not been reported.

Methods:
We analyzed a national pharmacy database that included >90% of all prescriptions dispensed by retail pharmacies and 60%–86% dispensed by mail-order outlets. We estimated the number of PrEP providers by year, provider type, physician specialty, and geographic location. We also measured the Gini coefficients for the distribution of PrEP patients among providers.

Results:
The number of PrEP providers increased from 9621 in 2014 to 65,822 in 2019. In 2019, 68.1% of PrEP providers were physicians. The proportion of nurse practitioners or physician assistants increased from 18.0% in 2014 to 29.7% in 2019. Among all the US health care providers, those who prescribed PrEP increased from 0.7% in 2014 to 4.3% in 2019. Among all general practice/family medicine physicians, the percentage of who prescribed PrEP increased from 1.8% in 2014 to 13.6% in 2019 and from 14.2% to 34.2% among infectious disease physicians. The ratio of PrEP providers to 100 persons with PrEP indications was lowest in the South with 4.4. The Gini coefficient for the distribution of PrEP patients among providers was 0.75 in 2019, with 50% of the PrEP patients prescribed PrEP by 2.2% of PrEP providers.

Conclusions:
An increasing number of providers prescribed PrEP during 2014–2019. The South had the largest number of new HIV diagnoses and greatest need for HIV prevention but had less PrEP service capacity compared with other regions. Expanded access to PrEP services is needed in the United States.
Population Impact and Efficiency of Improvements to HIV PrEP Under Conditions of High ART Coverage Among San Francisco Men Who Have Sex With Men
Authors: Le Guillou Adrien , Buchbinder Susan , Scott Hyman , Liu Albert , Havlir Diane , Scheer Susan , Jenness Samuel M. 
Published: August 2021

Background:
Key components of Ending the HIV Epidemic (EHE) plan include increasing HIV antiretroviral therapy (ART) and HIV pre-exposure prophylaxis (PrEP) coverage. One complication to addressing this service delivery challenge is the wide heterogeneity of HIV burden and health care access across the United States. It is unclear how the effectiveness and efficiency of expanded PrEP will depend on different baseline ART coverage.

Methods:
We used a network-based model of HIV transmission for men who have sex with men (MSM) in San Francisco. Model scenarios increased varying levels of PrEP coverage relative under current empirical levels of baseline ART coverage and 2 counterfactual levels. We assessed the effectiveness of PrEP with the cumulative percentage of infections averted (PIA) over the next decade and efficiency with the number of additional person-years needed to treat (NNT) by PrEP required to avert one HIV infection.

Results:
In our projections, only the highest levels of combined PrEP and ART coverage achieved the EHE goals. Increasing PrEP coverage up to 75% showed that PrEP effectiveness was higher at higher baseline ART coverage. Indeed, the PIA was 61% in the lowest baseline ART coverage population and 75% in the highest. The efficiency declined with increasing ART (NNT range from 41 to 113).

Conclusions:
Improving both PrEP and ART coverage would have a synergistic impact on HIV prevention even in a high baseline coverage city such as San Francisco. Efforts should focus on narrowing the implementation gaps to achieve higher levels of PrEP retention and ART sustained viral suppression.
“Evolving Trends in Pancreatic Cystic Tumors: A 3-Decade Single-Center Experience With 1290 Resections”
Authors: Roldán Jorge , Harrison Jon M. , Qadan Motaz , Bolm Louisa , Baba Taisuke , Brugge William R. , Casey Brenna W. , Krishnan Kumar , Mino-Kenudson Mari , Pitman Martha B. , Kambadakone Avinash , Ferrone Cristina R. , Warshaw Andrew L. , Lillemoe Keith D. , Fernández-del Castillo Carlos 
Published: August 2021

Objective:
The aim of this study was to describe our institutional experience with resected cystic tumors of the pancreas with emphasis on changes in clinical presentation and accuracy of preoperative diagnosis.

Summary Background Data:
Incidental discovery of pancreatic cystic lesions has increased and has led to a rise in pancreatic resections. It is important to analyze surgical outcomes from these procedures, and the prevalence of malignancy, pre-malignancy and resections for purely benign lesions, some of which may be unintended.

Methods:
Retrospective review of a prospective database spanning 3 decades. Presence of symptoms, incidental discovery, diagnostic studies, type of surgery, postoperative outcomes, and concordance between presumptive diagnosis and final histopathology were recorded.

Results:
A total of 1290 patients were identified, 62% female with mean age of 60 years. Fifty-seven percent of tumors were incidentally discovered. Ninety-day operative mortality was 0.9% and major morbidity 14.4%. There were 23 different diagnosis, but IPMN, MCN, and serous cystadenoma comprised 80% of cases. Concordance between preoperative and final histopathological diagnosis increased by decade from 45%, to 68%, and is presently 80%, rising in parallel with the use of endoscopic ultrasound, cytology, and molecular analysis. The addition of molecular analysis improved accuracy to 91%. Of misdiagnosed cases, half were purely benign and taken to surgery with the presumption of malignancy or premalignancy. The majority of these were serous cystadenomas.

Conclusions:
Indications and diagnostic work-up of cystic tumors of the pancreas have changed over time. Surgical resection can be performed with very low mortality and acceptable morbidity and diagnostic accuracy is presently 80%. About 10% of patients are still undergoing surgery for purely benign lesions that were presumed to be malignant or premalignant. Further refinements in diagnostic tests are required to improve accuracy.
Quantifying bias from dependent left truncation in survival analyses of real world data
Authors: Sondhi Arjun , Humblet Olivier , Swaminathan Akshay 
Published: August 2021

AbstractIn real world data (RWD) studies, observed datasets are often subject to left truncation, which can bias estimates of survival parameters. Standard methods can only suitably account for left truncation when survival and entry time are independent. Therefore, in the dependent left truncation setting, it is important to quantify the magnitude and direction of estimator bias to determine whether an analysis provides valid results. We conduct simulation studies of common RWD analytic settings in order to determine when standard analysis provides reliable estimates, and to identify factors that contribute most to estimator bias. We also outline a procedure for conducting a simulation-based sensitivity analysis for an arbitrary dataset subject to dependent left truncation. Our simulation results show that when comparing a truncated real-world arm to a non-truncated arm, we observe the estimated hazard ratio biased upwards, providing conservative inference. The most important data-generating parameter contributing to bias is the proportion of left truncated patients, given any level of dependence between survival and entry time. For specific datasets and analyses that may differ from our example, we recommend applying our sensitivity analysis approach to determine how results would change given varying proportions of truncation.
Impact of different diagnostic measures on drug class association with dementia progression risk: a longitudinal prospective cohort study
Authors: Kaur Daman , Bucholc Magda , Finn David P. , Todd Stephen , Wong-Lin KongFatt , McClean Paula L. 
Published: August 2021

AbstractBackgroundClinical Dementia Rating Sum of Boxes (CDRSOB) scale is known to be highly indicative of cognitive-functional status, but it is unclear whether it is consistent with clinical diagnosis in evaluating drug class associations with risk of progression to mild cognitive impairment (MCI) and dementia.MethodsWe employed multivariable logistic regression on longitudinal NACC data, to identify drug classes associated with disease progression risk, using clinical diagnosis and CDRSOB as the outcome.ResultsAnticoagulants, non-steroidal anti-inflammatory drugs, antihypertensives, antidepressants, and Parkinson’s medications were significantly associated with decreased progression to mild cognitive impairment (MCI)/dementia, and antipsychotics, antidiabetics, hypolipidemic drugs, and Alzheimer’s disease (AD) medications were significantly associated with increased progression risk. Associations were however dependant on the diagnostic measure used, e.g., levodopa was associated with reduced MCI-to-AD risk using CDRSOB as the outcome (OR:0.28, FDR p<0.002), but not with clinical diagnosis. Additionally, some associations appear to be gender specific; for instance, antiadrenergic agents had lower MCI-to-Dementia risk only for men (OR:0.67, FDR p<0.001) using CDRSOB.ConclusionsOverall, we demonstrate that choice of diagnostic measure can influence the magnitude and significance of risk or protection attributed to drug classes. A consensus must be reached within the research community with respect to the most accurate diagnostic outcome to identify risk and improve reproducibility.
Helmet noninvasive ventilation for COVID-19 patients “Helmet-COVID”: study protocol for a multicenter randomized controlled trial
Authors: Arabi Yaseen , Tlayjeh Haytham , Aldekhyl Sara , Al-Dorzi Hasan M , Abdukahil Sheryl Ann , Al Harbi Mohammad Khulaif , Haji Husain Al , Mutairi Mohammed Al , Zumai Omar Al , Qasim Eman Al , Wehaibi Wedyan Al , Qahtani Saad Al , Al-Hameed Fahad , Chalabi Jamal , Alshahrani Mohammed , Alharthy Abdulrahman , Mady Ahmed , Eshaq Abdulhadi Bin , Bshabshe Ali Al , Aseri Zohair Al , Duhailib Zainab Al , Kharaba Ayman , Alqahtani Rakan , Ghamdi Adnan Al , Altalag Ali , Alghamdi Khalid , Almaani Mohammed , Algethamy Haifa , Aqeily Ahmad Al , Baseet Faisal Al , Samannoudi Hashem Al , Obaidi Mohammed Al , Ismaiel Yassin , Al-Fares Abdulrahman A 
Published: August 2021

AbstractIntroductionNoninvasive ventilation delivered by helmet is has been used for respiratory support of patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. The aim of this study is to compare helmet noninvasive ventilation with usual care versus usual care alone to reduce the mortality.Methods and analysisThis is a multicenter, pragmatic, parallel, randomized controlled trial that compares helmet noninvasive ventilation with usual care to usual care alone in 1:1 ratio. A total of 320 patients will be enrolled in this study. The primary outcome is 28-day all-cause mortality. The primary outcome will be compared between the two study groups in the intention-to-treat and per-protocol cohorts. An interim analysis will be conducted for both safety and effectiveness.Ethics and disseminationApprovals are obtained from the Institutional Review Boards (IRBs) of each participating institution. Our findings will be published in peer-review journals and presented at relevant conferences and meetings.Trial registration numberNCT04477668 registered on July 20, 2020Article SummaryStrengths and limitations of this studyThis trial compares helmet NIV to usual care for respiratory support of patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia.The trial is a multi-center, pragmatic, parallel randomized controlled trial.The main limitation is the unblinded design due to the nature of the intervention.
Phenolic profiles and antioxidant activities of Saskatchewan (Canada) bred haskap (Lonicera caerulea)berries
Authors: Zehfus Lily R. , Eskiw Christopher , Low Nicholas H. 
Published: August 2021

AbstractPhenolic extracts from five Saskatoon, Saskatchewan, bred and grown haskap berry varieties (Aurora, Blizzard, Honey Bee, Indigo Gem, and Tundra) were characterized via liquid chromatography with photodiode array detection (HPLC-PDA) and mass spectrometry (HPLC-MS/MS). Tundra had the highest phenolic content (727.0 mg/100 g FW) while Indigo Gem had the highest anthocyanin content (447.8 mg/100 g FW). HPLC-MS/MS identified two previously unreported anthocyanins (Tundra variety): delphinidin-sambubioside and a peonidin-pentoside. Fruit extracts were fractionated to produce an anthocyanin rich (40% ethanol) and flavanol/flavonol rich (100% ethanol) fraction. This process affords the ability to isolate/concentrate specific subclasses for nutraceutical applications. Highin vitroradical scavenging was observed for all haskap phenolic extracts. An extract from the Tundra variety delayed borage oil oxidation more effectively than commercial antioxidants (BHT and Rosamox). These results show the high phenolic content of these haskaps along with their capacity for radical scavenging/delaying lipid oxidation, indicating potential commercial value.
Direct focus sensing and shaping for high-resolution multi-photon imaging in deep tissue
Authors: Qin Zhongya , She Zhentao , Chen Congping , Wu Wanjie , Lau Jackie K.Y. , Ip Nancy Y. , Qu Jianan Y. 
Published: August 2021

AbstractHigh-resolution optical imaging of deep tissue in-situ such as the living brain is fundamentally challenging because of the aberration and scattering of light. In this work, we develop an innovative adaptive optics three-photon microscope based on direct focus sensing and shaping that can accurately measure and effectively compensate for both low- and high-order specimen-induced aberrations and recover near-diffraction-limited performance at depth. A conjugate adaptive optics configuration with remote focusing enables in vivo imaging of fine neuronal structures in the mouse cortex through the intact skull up to a depth of 750 µm below pia, making high-resolution microscopy in cortex near non-invasive. Functional calcium imaging with high sensitivity and accuracy, and high-precision laser-mediated microsurgery through the intact skull were demonstrated. Moreover, we also achieved in vivo high-resolution imaging of the deep cortex and subcortical hippocampus up to 1.1 mm below pia within the intact brain.
Structural insights into recognition of chemokine receptors by Staphylococcus aureus leukotoxins
Authors: Lambey Paul , Otun Omolade , Cong Xiaojing , Hoh François , Brunel Luc , Verdié Pascal , Grison Claire , Peysson Fanny , Jeannot Sylvain , Durroux Thierry , Bechara Cherine , Granier Sébastien , Leyrat Cédric 
Published: August 2021

AbstractStaphylococcus aureus (SA) leukocidin LukED belongs to a family of bicomponent pore forming toxins that play important roles in SA immune evasion and nutrient acquisition. LukED targets specific G protein-coupled chemokine receptors to lyse human erythrocytes and leukocytes. The first recognition step of receptors is critical for specific cell targeting and lysis. The structural and molecular bases for this mechanism are not well understood but could constitute essential information to guide antibiotic development. Here, we characterized the interaction of LukE with chemokine receptors ACKR1, CCR2 and CCR5 using a combination of structural, pharmacological and computational approaches. First, crystal structures of LukE in complex with a small molecule mimicking sulfotyrosine side chain (p-cresyl sulfate) and with peptides containing sulfotyrosines issued from receptor sequences revealed the location of receptor sulfotyrosine binding sites in the toxins. Then, by combining the available experimental information with protein docking, classical and accelerated weight histogram (AWH) molecular dynamics we propose models of the ACKR1-LukE and CCR5-LukE complexes. This work provides novel insights into chemokine receptor recognition by leukotoxins and suggests that the conserved sulfotyrosine binding pocket could be a target of choice for future drug development.