bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pepsin and pH of Gastric Juice in Patients With Gastrointestinal Reflux Disease and Subgroups
Authors: Ergun Pelin , Kipcak Sezgi , Dettmar Peter W. , Fisher Jeanine , Woodcock Andrew D. , Bor Serhat 
Published: May 2021

Goal:
The aim of this study was to investigate the pepsin values and pH results of gastric juice among the subtypes of gastroesophageal reflux disease (GERD) and functional heartburn.

Background:
The major destructive agents of GERD on the esophageal epithelium are gastric acid and pepsin. No precise information about pepsin concentration in gastric juice exists.

Study:
Ninety patients with GERD, 39 erosive reflux disease (ERD) Los Angeles (LA) grade A/B, 13 ERD LA grade C/D, 19 nonerosive reflux disease (NERD), 8 esophageal hypersensitivity, 11 functional heartburn, and 24 healthy controls were included in the study. During endoscopy gastric juices from the patients were aspirated and their pH readings immediately recorded. Gastric juice samples were analyzed using Peptest, a lateral flow device containing 2 unique human monoclonal antibodies to detect any pepsin present in the gastric juice sample.

Results:
The highest mean gastric pepsin concentration (0.865 mg/mL) and the lowest median gastric pH (1.4) was observed in the LA grade C/D group compared with the lowest mean gastric pepsin concentration (0.576 mg/mL) and the highest median gastric pH (2.5) seen in the NERD group. Comparing pH, the NERD patient group was significantly higher (P=0.0018 to P=0.0233) when compared with all other GERD patient groups.

Conclusions:
The basal gastric pepsin level in the healthy control group was comparable to literature values. There was good correlation and a significant linear relationship between the gastric pepsin level and gastric pH within the patient groups. The severity of the GERD disease is related to the lowest pH and the highest pepsin concentration in gastric juice.
Gluten-induced Neurocognitive Impairment
Authors: Edwards George Jessica B. , Aideyan Babatunde , Yates Kayla , Voorhees Kristin N. , O’Flynn Jennifer , Sweet Kristen , Avery Kate , Ehrlich Alan , Bast Alice , Leffler Daniel A. 
Published: May 2021

Goals:
This study aimed to understand the neurocognitive symptoms associated with gluten exposure in individuals with self-reported celiac disease (CD) and nonceliac gluten sensitivity (NCGS).

Background:
While gluten-induced neurocognitive impairment (GINI; eg, “celiac fog” or “brain fog”) is commonly described by individuals with CD and NCGS, there are little data regarding the prevalence and symptoms associated with these experiences.

Study:
A 9-question online survey was accessed by 1396 individuals (1143 with CD; 253 with NCGS). Forced choice and free-response questions were asked of participants to obtain a description of neurocognitive symptoms experienced after gluten ingestion. Free-response answers were coded using a coding structure developed based on the Health-Related Quality of Life Instrument.

Results:
The majority of survey participants (89% of CD and 95% of NCGS) reported having GINI symptoms. When describing symptoms, the most common word descriptors for both groups were difficulty concentrating, forgetfulness, and grogginess. Timing of symptoms, including onset and symptom peak, were similar across the 2 groups. Coding of free responses found the most common references were to cognitive, physical, psychological, and overall quality of life impacts.

Conclusions:
This survey suggests that GINI is common and may be severe in both individuals with CD and NCGS. Cognitive impairment and decline in physical functioning may be similar to that occurring in other illnesses, such as lupus. Clinical follow-up with both individuals with CD and NCGS should include assessment of GINI symptoms. Further research is warranted, including the development of a patient-reported outcome measure including neurocognitive effects of gluten exposure.
Proton Pump Inhibitors Versus Histamine-2-Receptor Antagonists for Stress Ulcer Prophylaxis in Critically Ill Patients
Authors: Deliwala Smit S. , Hamid Kewan , Goyal Hemant , Ponnapalli Anoosha , Zayed Yazan , Bala Areeg , Lakshman Harini , Malladi Shrikanth , Jones Shane , Santana Maria , Leon Brianna , An Minh T. , Chawla Saurabh 
Published: May 2021

Goals and Background:
Stress ulcer prophylaxis has been shown to lower gastrointestinal bleeding (GIB) rates. Various agents have been studied, and the optimal strategy continues to be contested. This study evaluates the efficacy between proton pump inhibitors (PPIs) and histamine-2-receptor antagonists. Small sample sizes and methodology flaws limited prior studies.

Study:
A systematic search of MEDLINE, EMBASE, CENTRAL, Web of Science, and ClinicalTrials.gov for randomized controlled trials reporting the use of PPI and histamine-2-receptor antagonist reporting rates of GIB and standardized intensive care outcomes. Risk ratios (RR) and standardized mean difference (SMD) with 95% confidence intervals (CIs). A trial sequential analysis was performed to guard against errors.

Results:
A total of 14 randomized controlled trials of 28,526 patients with a mean age of 57.83±17.35 years and 30.82% females. In our pooled analysis, PPI outperformed its comparator (RR: 0.68; 95% CI: 0.57-0.82) in clinically significant GIB. PPI re-demonstrated significant reduction in overt GIB (RR: 0.61; 95% CI: 0.39-0.97). No differences between groups was noted toward all-cause mortality (RR: 1.05; 95% CI: 1.00-1.10) or incidence of pneumonia (RR: 1.11; 95% CI: 0.82-1.51). Duration of stay (SMD: 0.07; 95% CI: −0.04-0.17) and ventilator days (SMD: 0.01; 95% CI: −0.01-0.04) were indifferent between the groups.

Conclusions:
Among critically ill patients, PPI was associated with reduced clinically significant or overt GIB. No differences in pneumonia were seen with the use of either agent. Trial sequential analysis for clinically significant GIB ruled out the risk for false-positive results, and thereby it is unlikely that future trials will affect our conclusions.
Interassessor agreement of portfolio-based competency assessment for orthotists/prosthetists in Australia: a mixed method study
Authors: Dillon Michael P. , Puli Louise , Ridgewell Emily , Anderson Sarah P , Chiavaroli Neville , Clarke Leigh 
Published: May 2021

Background:
Internationally qualified orthotists/prosthetists who want to practice in Australia must pass a portfolio-based competency assessment. Testing the agreement between independent assessors is important to engender confidence in the assessment, and continually improve the processes.

Objectives:
To quantify interassessor agreement for all 68 performance indicators in the Australian Orthotic Prosthetic Association's Entry Level Competency Standards and where there was significant disagreement between assessors, to explore the reasons why.

Study design:
Mixed methods: explanatory sequential.

Method:
Fifteen portfolios were assigned to independent assessors. Assessors determined whether the evidence presented met the requirements of each performance indicator. Interassessor agreement was calculated using Gwet's Agreement Coefficient 1 (AC1), and these data informed semistructured interviews to explore the reasons for disagreement.

Results:
Most performance indicators (87%) had moderate to substantial agreement (AC1 > 0.71), which could be attributed to a variety of factors including the use of a simple assessment rubric with supporting guidelines and assessor training to establish shared expectations. The remaining performance indicators (13%) had fair to slight agreement (AC1 ≤ 0.7). Interviews with assessors suggested that disagreement could be attributed to the complexity of some performance indicators, unconscious bias, and the appropriateness of the evidence presented.

Conclusions:
Although most performance indicators in Australian Orthotic Prosthetic Association's Entry Level Competency Standard were associated with moderate to substantial interassessor agreement, there are opportunities to improve agreement by simplifying the wording of some performance indicators and revising guidelines to help applicants curate the most appropriate evidence for each performance indicator.
Chemical exchange saturation transfer for detection of antiretroviral drugs in brain tissue
Authors: Bade Aditya N. , Gendelman Howard E. , McMillan JoEllyn , Liu Yutong 
Published: May 2021

Objective:
Antiretroviral drug theranostics facilitates the monitoring of biodistribution and efficacy of therapies designed to target HIV type-1 (HIV-1) reservoirs. To this end, we have now deployed intrinsic drug chemical exchange saturation transfer (CEST) contrasts to detect antiretroviral drugs within the central nervous system (CNS).

Design and methods:
CEST effects for lamivudine (3TC) and emtricitabine (FTC) were measured by asymmetric magnetization transfer ratio analyses. The biodistribution of 3TC in different brain sub-regions of C57BL/6 mice treated with lipopolysaccharides was determined using MRI. CEST effects of 3TC protons were quantitated by Lorentzian fitting analysis. 3TC levels in plasma and brain regions were measured using ultraperformance liquid chromatography tandem mass spectrometry to affirm the CEST test results.

Results:
CEST effects of the hydroxyl and amino protons in 3TC and FTC linearly correlated to drug concentrations. 3TC was successfully detected in vivo in brain sub-regions by MRI. The imaging results were validated by measurements of CNS drug concentrations.

Conclusion:
CEST contrasts can be used to detect antiretroviral drugs using MRI. Such detection can be used to assess spatial--temporal drug biodistribution. This is most notable within the CNS where drug biodistribution may be more limited with the final goal of better understanding antiretroviral drug-associated efficacy and potential toxicity.
Phase2Phase
Authors: Eldeniz Cihat , Gan Weijie , Chen Sihao , Fraum Tyler J. , Ludwig Daniel R. , Yan Yan , Liu Jiaming , Vahle Thomas , Krishnamurthy Uday , Kamilov Ulugbek S. , An Hongyu 
Published: May 2021

Objectives
Respiratory binning of free-breathing magnetic resonance imaging data reduces motion blurring; however, it exacerbates noise and introduces severe artifacts due to undersampling. Deep neural networks can remove artifacts and noise but usually require high-quality ground truth images for training. This study aimed to develop a network that can be trained without this requirement.

Materials and Methods
This retrospective study was conducted on 33 participants enrolled between November 2016 and June 2019. Free-breathing magnetic resonance imaging was performed using a radial acquisition. Self-navigation was used to bin the k-space data into 10 respiratory phases. To simulate short acquisitions, subsets of radial spokes were used in reconstructing images with multicoil nonuniform fast Fourier transform (MCNUFFT), compressed sensing (CS), and 2 deep learning methods: UNet3DPhase and Phase2Phase (P2P). UNet3DPhase was trained using a high-quality ground truth, whereas P2P was trained using noisy images with streaking artifacts. Two radiologists blinded to the reconstruction methods independently reviewed the sharpness, contrast, and artifact-freeness of the end-expiration images reconstructed from data collected at 16% of the Nyquist sampling rate. The generalized estimating equation method was used for statistical comparison. Motion vector fields were derived to examine the respiratory motion range of 4-dimensional images reconstructed using different methods.

Results
A total of 15 healthy participants and 18 patients with hepatic malignancy (50 ± 15 years, 6 women) were enrolled. Both reviewers found that the UNet3DPhase and P2P images had higher contrast (P < 0.01) and fewer artifacts (P < 0.01) than the CS images. The UNet3DPhase and P2P images were reported to be sharper than the CS images by 1 reviewer (P < 0.01) but not by the other reviewer (P = 0.22, P = 0.18). UNet3DPhase and P2P were similar in sharpness and contrast, whereas UNet3DPhase had fewer artifacts (P < 0.01). The motion vector lengths for the MCNUFFT800 and P2P800 images were comparable (10.5 ± 4.2 mm and 9.9 ± 4.0 mm, respectively), whereas both were significantly larger than CS2000 (7.0 ± 3.9 mm; P < 0.0001) and UNnet3DPhase800 (6.9 ± 3.2; P < 0.0001) images.

Conclusions
Without a ground truth, P2P can reconstruct sharp, artifact-free, and high-contrast respiratory motion-resolved images from highly undersampled data. Unlike the CS and UNet3DPhase methods, P2P did not artificially reduce the respiratory motion range.
Real-Time Deformability Cytometry Detects Leukocyte Stiffening After Gadolinium-Based Contrast Agent Exposure
Authors: Jacobi Angela , Ariza de Schellenberger Angela , Uca Yavuz Oguz , Herbig Maik , Guck Jochen , Sack Ingolf 
Published: May 2021

Objectives
Reports on gadolinium (Gd) retention in soft tissues after administration of Gd-based contrast agents (GBCAs) raise concerns about Gd-induced changes in the biophysical properties of cells and tissues. Here, we investigate if clinical GBCAs of both classes of linear and macrocyclic structure cause changes in the mechanical properties of leukocytes in human blood samples.

Material and Methods
Real-time deformability cytometry was applied to human blood samples from 6 donors. The samples were treated with 1 mM gadoteric acid (Dotarem), gadopentetic acid (Magnevist), gadobutrol (Gadovist), or Gd trichloride at 37°C for 1 hour to mimic clinical doses of GBCAs and exposure times. Leukocyte subtypes—lymphocytes, monocytes, and neutrophils—were identified based on their size and brightness and analyzed for deformability, which is inversely correlated with cellular stiffness.

Results
We observed significant stiffening (3%–13%, P < 0.01) of all investigated leukocyte subtypes, which was most pronounced for lymphocytes, followed by neutrophils and monocytes, and the effects were independent of the charge and steric structure of the GBCA applied. In contrast, no changes in cell size and brightness were observed, suggesting that deformability and cell stiffness measured by real-time deformability cytometry are sensitive to changes in the physical phenotypes of leukocytes after GBCA exposure.

Conclusions
Real-time deformability cytometry might provide a quantitative blood marker for critical changes in the physical properties of blood cells in patients undergoing GBCA-enhanced magnetic resonance imaging.
The Discriminative Power and Stability of Radiomics Features With Computed Tomography Variations
Authors: Jimenez-del-Toro Oscar , Aberle Christoph , Bach Michael , Schaer Roger , Obmann Markus M. , Flouris Kyriakos , Konukoglu Ender , Stieltjes Bram , Müller Henning , Depeursinge Adrien 
Published: May 2021

Objectives
The aims of this study were to determine the stability of radiomics features against computed tomography (CT) parameter variations and to study their discriminative power concerning tissue classification using a 3D-printed CT phantom based on real patient data.

Materials and Methods
A radiopaque 3D phantom was developed using real patient data and a potassium iodide solution paper-printing technique. Normal liver tissue and 3 lesion types (benign cyst, hemangioma, and metastasis) were manually annotated in the phantom. The stability and discriminative power of 86 radiomics features were assessed in measurements taken from 240 CT series with 8 parameter variations of reconstruction algorithms, reconstruction kernels, slice thickness, and slice spacing. Pairwise parameter group and pairwise tissue class comparisons were performed using Wilcoxon signed rank tests.

Results
In total, 19,264 feature stability tests and 8256 discriminative power tests were performed. The 8 CT parameter variation pairwise group comparisons had statistically significant differences on average in 78/86 radiomics features. On the other hand, 84% of the univariate radiomics feature tests had a successful and statistically significant differentiation of the 4 classes of liver tissue. The 86 radiomics features were ranked according to the cumulative sum of successful stability and discriminative power tests.

Conclusions
The differences in radiomics feature values obtained from different types of liver tissue are generally greater than the intraclass differences resulting from CT parameter variations.
Diagnostic Performance of 9 Quantitative Ultrasound Parameters for Detection and Classification of Hepatic Steatosis in Nonalcoholic Fatty Liver Disease
Authors: Pirmoazen Amir M. , Khurana Aman , Loening Andreas M. , Liang Tie , Shamdasani Vijay , Xie Hua , El Kaffas Ahmed , Kamaya Aya 
Published: May 2021

Background
Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide. Quantitative ultrasound (QUS) parameters based on radiofrequency raw data show promise in quantifying liver fat.

Purpose
The aim of this study was to evaluate the diagnostic performance of 9 QUS parameters compared with magnetic resonance imaging (MRI)–estimated proton density fat fraction (PDFF) in detecting and staging hepatic steatosis in patients with or suspected of NAFLD.

Materials and Methods
In this Health Insurance Portability and Accountability Act–compliant institutional review board–approved prospective study, 31 participants with or suspected of NAFLD, without other underlying chronic liver diseases (13 men, 18 women; average age, 52 years [range, 26–90 years]), were examined. The following parameters were obtained: acoustic attenuation coefficient (AC); hepatorenal index (HRI); Nakagami parameter; shear wave elastography measures such as shear wave elasticity, viscosity, and dispersion; and spectroscopy-derived parameters including spectral intercept (SI), spectral slope (SS), and midband fit (MBF). The diagnostic ability (area under the receiver operating characteristic curves and accuracy) of QUS parameters was assessed against different MRI-PDFF cutoffs (the reference standard): 6.4%, 17.4%, and 22.1%. Linearity with MRI-PDFF was evaluated with Spearman correlation coefficients (p).

Results
The AC, SI, Nakagami, SS, HRI, and MBF strongly correlated with MRI-PDFF (P = 0.89, 0.89, 0.88, −0.87, 0.81, and 0.71, respectively [P < 0.01]), with highest area under the receiver operating characteristic curves (ranging from 0.85 to 1) for identifying hepatic steatosis using 6.4%, 17.4%, and 22.1% MRI-PDFF cutoffs. In contrast, shear wave elasticity, shear wave viscosity, and shear wave dispersion did not strongly correlate to MRI-PDFF (P = 0.45, 0.38, and 0.07, respectively) and had poor diagnostic performance.

Conclusion
The AC, Nakagami, SI, SS, MBF, and HRI best correlate with MRI-PDFF and show high diagnostic performance for detecting and classifying hepatic steatosis in our study population.

Summary Statement
Quantitative ultrasound is an accurate alternative to MRI-based techniques for evaluating hepatic steatosis in patients with or at risk of NAFLD.

Key Findings
Our preliminary results show that specific quantitative ultrasound parameters accurately detect different degrees of hepatic steatosis in NAFLD.
Laparoscopic Appendectomy in the Days of COVID-19
Authors: Abramov Roi , Neymark Mariya , Harbi Asaf , Gilshtein Hayim 
Published: May 2021

Background:
Acute appendicitis is one of the most common emergencies treated by general surgeons. The treatment of choice in the majority of cases is laparoscopic appendectomy. In the era of the COVID-19 pandemic, there is a concern for a delayed referral of patients and thus a more advanced presentation of the disease leading to a prolonged and complicated course.

Methods:
Retrospective review of a computerized database of patients who were admitted with acute appendicitis and underwent laparoscopic appendectomy during the COVID pandemic in a single tertiary center in Israel. Patients were compared with those who were admitted and operated for appendicitis in the same period in the previous year.

Results:
One hundred twenty-three patients underwent laparoscopic appendectomy in the study period in 2020, compared with 109 who had surgery in 2019. During the COVID pandemic 41 patients presented with complicated appendicitis versus 22 patients in 2019 (P=0.0174). The placement of peritoneal drains was more prevalent during the pandemic, 5.5% versus 11.4%, and the use of stapler device for appendicular stump closure (P=0.0105).

Conclusions:
During the first stage of the COVID-19 pandemic, there was a significant increase in the rate of complicated appendicitis. Patients should be strongly encouraged not to refrain from medical treatment and go to the emergency room with the persistence of symptoms.
Keratinocyte Cancer Mortality in Kidney Transplant Recipients
Authors: Shao Emily Ximin , Betz-Stablein Brigid , Khosrotehrani Kiarash , Campbell Scott , Isbel Nicole , Green Adele C. 
Published: May 2021

Background.
Kidney transplant recipients are at increased risk of developing and dying from keratinocyte cancer. Risk factors for keratinocyte cancer death have not been previously described.

Methods.
In a cohort of kidney transplant recipients transplanted in Queensland from 1995 to 2014, we identified keratinocyte cancer deaths by searching national transplant and state death registries to March 2020. Standardized keratinocyte cancer mortality rates and mortality ratios were calculated. We used a competing risks model to identify factors associated with keratinocyte cancer death and calculated relative risks (RRs) and 95% confidence intervals (CIs).

Results.
There were 562 deaths in 1866 kidney transplant recipients (62% male individuals; 86% Caucasian) with 25 934 person-y of follow-up, of which 36 were due to squamous cell carcinoma and 1 to basal cell carcinoma with standardized mortality rates of 78 (95% CI, 53-111) and 2 (95% CI, 0.1-11) per 100 000 person-y, respectively. The standardized mortality ratio for keratinocyte cancer was 23 (95% CI, 23-24). Besides Caucasian ethnicity (associated with 100% of keratinocyte cancer deaths), male sex (RR, 3.24; 95% CI, 1.26-8.33), and older age at transplantation (≥50 versus <50 y; RR, 3.09; 95% CI, 1.38-6.89) were associated with increased risk of keratinocyte cancer death.

Conclusions.
Keratinocyte cancer mortality in kidney transplant recipients is over 20 times higher than in the general population. Most keratinocyte cancer deaths are due to cutaneous squamous cell carcinoma, however, basal cell carcinoma can be fatal. Education in skin cancer prevention is essential to avoid unnecessary deaths from keratinocyte cancer among kidney transplant recipients.