bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of proton pump inhibitor or rebamipide use on gut microbiota of rheumatoid arthritis patients
Authors: Kim Ji-Won , Jeong Yunju , Park Sang-Jun , Jin Hui , Lee Jennifer , Ju Ji Hyeon , Ji Geun Eog , Park Sung-Hwan 
Published: May 2020

AbstractObjectivePatients with RA commonly use gastrointestinal (GI) protective drugs for treatment and prevention of drug-associated GI injuries. However, how these drugs affect the gut microbiota in RA patients remains unknown. The objective of this study was to examine the gut microbiota of RA patients according to use of GI protective drugs such as proton pump inhibitors (PPIs), histamine 2-receptor antagonists and rebamipide.MethodsFaecal samples were obtained from 15 healthy controls and 32 RA patients who were receiving PPI, histamine 2-receptor antagonist or rebamipide. Bacterial DNA was extracted from the faecal samples and 16S rRNA sequencing was performed. Microbial composition and function were analysed using Quantitative Insights Into Microbial Ecology and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States.ResultsRA patients exhibited reduced diversity and altered composition of the gut microbiota compared with healthy controls. The gut microbiota of RA patients receiving acid-suppressing drugs, particularly PPIs, was distinct from that of RA patients receiving rebamipide (PPI vs rebamipide, P = 0.005). Streptococcus was enriched in RA patients receiving PPI, while Clostridium bolteae was enriched in RA patients receiving rebamipide. The gut microbiota of PPI users was abundant with microbial functional pathway involved in the production of virulence factors. This featured microbial function was positively correlated with relative abundance of Streptococcus, the differentially abundant taxa of PPI users.ConclusionThe gut microbiota of RA patients receiving PPIs was distinguishable from that of those receiving rebamipide. The enriched virulent function in the gut microbiota of PPI users suggests that inappropriate PPI use may be harmful in RA patients.
Markov-Modulated Continuous-Time Markov Chains to Identify Site- and Branch-Specific Evolutionary Variation in BEAST
Authors: Baele Guy , Gill Mandev S , Bastide Paul , Lemey Philippe , Suchard Marc A 
Published: May 2020

AbstractMarkov models of character substitution on phylogenies form the foundation of phylogenetic inference frameworks. Early models made the simplifying assumption that the substitution process is homogeneous over time and across sites in the molecular sequence alignment. While standard practice adopts extensions that accommodate heterogeneity of substitution rates across sites, heterogeneity in the process over time in a site-specific manner remains frequently overlooked. This is problematic, as evolutionary processes that act at the molecular level are highly variable, subjecting different sites to different selective constraints over time, impacting their substitution behavior. We propose incorporating time variability through Markov-modulated models (MMMs), which extend covarion-like models and allow the substitution process (including relative character exchange rates as well as the overall substitution rate) at individual sites to vary across lineages. We implement a general MMM framework in BEAST, a popular Bayesian phylogenetic inference software package, allowing researchers to compose a wide range of MMMs through flexible XML specification. Using examples from bacterial, viral, and plastid genome evolution, we show that MMMs impact phylogenetic tree estimation and can substantially improve model fit compared to standard substitution models. Through simulations, we show that marginal likelihood estimation accurately identifies the generative model and does not systematically prefer the more parameter-rich MMMs. To mitigate the increased computational demands associated with MMMs, our implementation exploits recent developments in BEAGLE, a high-performance computational library for phylogenetic inference. [Bayesian inference; BEAGLE; BEAST; covarion, heterotachy; Markov-modulated models; phylogenetics.]
Omalizumab and other biologics in drug desensitization
Authors: Fernandez Javier , Ruano-Zaragoza María , Blanca-Lopez Natalia 
Published: May 2020

Purpose of reviewOmalizumab has been proposed for controlling adverse reactions during drug desensitization. Our aim is to know the current evidence involving the use of omalizumab in drug-allergy desensitization.Recent findingsDrug-allergy desensitization is not risk free, but it is a useful procedure and has been applied for drug hypersensitivity reactions with mast cells degranulation through IgE and non-IgE mechanisms. Since 2007, omalizumab has been considered as a potential strategy to prevent adverse reactions.Our review found few case reports and only one randomized double-blind, placebo-controlled study, using different omalizumab regimens prior to drug desensitization. This scarce evidence is insufficient to predict the effectiveness of omalizumab in rapid drug desensitization procedures, but it may be useful in future studies of omalizumab or related next-generation antibodies.SummaryOmalizumab or other IgE-targeting biologics, either a fixed dose of 300 mg omalizumab or a dose-related total IgE level and body mass weight may be an option for patients with IgE-mediated or mast cell drug reactions in troublesome desensitization.
Critical Care Clinician Reports on Coronavirus Disease 2019: Results From a National Survey of 4,875 ICU Providers
Authors: Kaplan Lewis J. , Kleinpell Ruth , Maves Ryan C. , Doersam Jennifer K. , Raman Rameela , Ferraro David M. 
Published: May 2020

Importance:
Global cases of coronavirus disease 2019 infection continue to increase, and significant numbers of patients are critically ill, placing an immense burden on ICU resources. Understanding baseline resource needs and surge capacity in the ICU will be essential to meet current and projected healthcare needs. Continued appraisal of the state of readiness for healthcare systems at individual, regional and national levels will be paramount to ensure we are poised to continue the fight against coronavirus disease 2019.

Objectives:
This study queried U.S. ICU clinician perspectives on ICU preparedness and concerns regarding delivering coronavirus disease 2019 patient care.

Design, Setting, and Participants:
An anonymous web-based survey administered from March 18, 2020, to March 25, 2020 (email and newsletter) used survey methodology to query members of U.S. national critical care organizations.

Main Outcomes and Measures:
Through a 12-item descriptive questionnaire, ICU clinicians were assessed regarding preparedness, techniques employed to augment critical care capacity, and concerns related to caring for coronavirus disease 2019 patients.

Results:
A total of 4,875 ICU clinicians responded to the survey. Respondents included ICU nurses (n = 3,470, 71.3%), physicians (n = 664, 13.6%), advanced practice providers (nurse practitioners and physician assistants; n = 334, 6.9%), respiratory therapists (n = 236, 4.9%), and pharmacists (n = 79, 1.6%). Over half (n = 2,552, 52.5%) reported having cared for a presumed or confirmed coronavirus disease 2019 patient. The majority (n = 4,010, 82.9%) identified that their hospital was employing techniques to augment critical care capacity. However, 64.5% (n = 3,125) believed that their ICU facility and team were inadequately prepared to treat coronavirus disease 2019 patients. The majority (n = 4,547, 93.9%) anticipated ICU personal protective equipment shortages based upon their current use profile. The chief reported concerns include ICU resource shortages such as supplies, medications, beds, ICU staffing shortages, and patient surge leading to overcrowding.

Conclusions and Relevance:
This national ICU clinician survey indicates that hospitals are expanding ICU bed capacity to prepare for coronavirus disease 2019 patient surge. Importantly, amid this preparation, ICU clinicians harbor concerns regarding preparedness, staffing, and common use resources that merit specific education as well as resource allocation and utilization planning.
Targeted molecular imaging of head and neck squamous cell carcinoma: a window into precision medicine
Authors: Wu Jun , Yuan Ying , Tao Xiao-Feng 
Published: May 2020

Abstract
Tumor biomarkers play important roles in tumor growth, invasion, and metastasis. Imaging of specific biomarkers will help to understand different biological activities, thereby achieving precise medicine for each head and neck squamous cell carcinoma (HNSCC) patient. Here, we describe various molecular targets and molecular imaging modalities for HNSCC imaging. An extensive search was undertaken in the PubMed database with the keywords including “HNSCC,” “molecular imaging,” “biomarker,” and “multimodal imaging.” Imaging targets in HNSCC consist of the epidermal growth factor receptor, cluster of differentiation 44 variant 6 (CD44v6), and mesenchymal-epithelial transition factor and integrins. Targeted molecular imaging modalities in HNSCC include optical imaging, ultrasound, magnetic resonance imaging, positron emission tomography, and single-photon emission computed tomography. Making the most of each single imaging method, targeted multimodal imaging has a great potential in the accurate diagnosis and therapy of HNSCC. By visualizing tumor biomarkers at cellular and molecular levels in vivo, targeted molecular imaging can be used to identify specific genetic and metabolic aberrations, thereby accelerating personalized treatment development for HNSCC patients.
Age and menopausal status are important factors influencing the serum human epididymis secretory protein 4 level: a prospective cross-sectional study in healthy Chinese people
Authors: Cheng Hong-Yan , Zeng Lin , Ye Xue , Ma Rui-Qiong , Tang Zhi-Jian , Chu Hong-Ling , Zhao Yi-Ming , Zhu Li-Rong , Gao Yu-Nong , Chang Xiao-Hong , Cui Heng 
Published: May 2020

Abstract

Background:
Human epididymis secretory protein 4 (HE4) is a new ovarian cancer biomarker. The factors influencing HE4 levels are not clear, and the reference data in China are limited. Here, we aim to evaluate the effects of menopause and age on HE4 levels and to provide a possible reference value for HE4 in healthy Chinese people.

Methods:
A total of 2493 healthy females aged 40 years or older were recruited from March 2013 to March 2017 with the cooperation of four medical institutions across Beijing, China. The serum levels of HE4 and cancer antigen 125 (CA125) were measured by enzyme-linked immunosorbent assay. The Wilcoxon rank-sum test of variance and a stratified analysis were used to analyze the relationships among age, menopausal status, and levels of HE4 or CA125. Confidence intervals (5%–95%) were determined for reference ranges in different populations.

Results:
There was a statistically significant difference in median HE4 levels between the post-menopausal (n = 2168) and pre-menopausal groups (n = 325) (36.46 vs. 24.04 pmol/L, Z = −14.41, P < 0.001). HE4 increased significantly with age in the post-menopausal groups (H = 408.18, P < 0.001) but not in the pre-menopausal subjects (Z = −0.43, P = 0.67). The upper 95th percentile of HE4 levels were 44.63 pmol/L for pre-menopausal women, 78.17 pmol/L for post-menopausal women, and 73.3 pmol/L for all women. In the post-menopausal population, the HE4 reference ranges were 13.15 to 47.31, 14.31 to 58.04, 17.06 to 73.51, 24.50 to 115.25, and 35.71 to 212.37 pmol/L for different age groups from forty divided by decade. The CA125 level was affected mainly by menopausal status and not age.

Conclusions:
Menopausal status and age were both important factors influencing the level of HE4, and age affected HE4 levels mainly in post-menopausal women. The HE4 level was higher in the post-menopausal population than in the pre-menopausal population and increased with age.
Positron emission computed tomography/single photon emission computed tomography in Parkinson disease
Authors: Yao Nian-Ting , Zheng Qian , Xu Zi-Qian , Yin Jian-Hong , Lu Lin-Guang , Zuo Qi , Yang Su , Zhang Chun-Lin , Jiao Ling 
Published: May 2020

Abstract
Parkinson disease (PD) is the second-most common neurodegenerative disorder. Its main pathological mechanism is the selective degeneration and deletion of dopaminergic neurons in the dense part of the substantia nigra and the damage of dopaminergic neurons caused by the abnormal deposition of a Lewy body, leading to a decreased dopamine level. Positron emission computed tomography (PET)/single photon emission computed tomography (SPECT) is a molecular imaging technology that can directly or indirectly reflect changes in molecular levels by using a specific tracer. With the research and development on the tracers of related enzymes for labeling dopamine transporter and dopamine receptor and for being involved in dopamine formation, this imaging technology has been applied to all aspects of PD research. It not only contributes to clinical work but also provides an important theoretical basis for exploring the pathological mechanism of PD at a molecular level. Therefore, this review discusses the application value of PET/SPECT in PD in terms of early diagnosis, disease severity evaluation, clinical manifestations, differential diagnosis, and pathological mechanism.
Cardiac output estimation by pulse wave analysis using the pressure recording analytical method and intermittent pulmonary artery thermodilution
Authors: Greiwe Gillis , Luehsen Katharina , Hapfelmeier Alexander , Rogge Dorothea , Kubik Mathias , Schulte-Uentrop Leonie , Saugel Bernd 
Published: May 2020

BACKGROUND
Invasive pulse wave analysis is used in peri-operative settings to estimate cardiac output (CO). The ‘pressure recording analytical method’ (PRAM) implemented in the MostCareUp CO monitor is an invasive pulse wave analysis method using high-frequency sampling and analysis of the pulse wave to directly estimate the arterial impedance as a key variable of the proprietary CO estimation algorithm.

OBJECTIVE
To compare CO estimated by PRAM (PRAM-CO; test method) with CO measured by pulmonary artery thermodilution (PATD-CO; reference method).

DESIGN
Prospective observational method comparison study. PRAM-CO and PATD-CO were assessed simultaneously at five time points with at least 20 min between measurements. Arterial pressure waveforms were carefully checked for damping artefacts and a proprietary electronic filter of the MostCareUp CO monitor was used to optimise waveform quality.

SETTING
ICU of a German university hospital from August 2018 until April 2019.

PATIENTS
We included adult patients admitted to the ICU after elective off-pump coronary artery bypass surgery who were monitored with a radial arterial catheter and a pulmonary artery catheter. Patients with severe heart valve insufficiency or persistent arrhythmia were excluded.

MAIN OUTCOME MEASURES AND ANALYSIS
PATD-CO and PRAM-CO were compared using Bland-Altman analysis accounting for repeated measurements, the percentage error and trending analysis (four-quadrant plot, concordance rate).

RESULTS
We analysed 195 paired CO values of 41 patients. Mean PATD-CO and PRAM-CO were 4.99 ± 1.02 and 4.92 ± 1.05 l min−1, respectively. PATD-CO and PRAM-CO ranged from 3.04 to 8.74 and 2.79 to 8.01 l min−1, respectively. The mean of the differences between PATD-CO and PRAM-CO was −0.08 ± 0.74 l min−1 with 95% limits of agreement of −1.55 to +1.40 l min−1. The percentage error was 29.8%. The concordance rate in four-quadrant plot analysis was 92%.

CONCLUSION
Using the system's electronic waveform filter PRAM-CO shows good agreement and trending ability compared with PATD-CO in adults after off-pump coronary artery bypass surgery.
Prophylactic norepinephrine infusion or leg wrapping for postspinal hypotension in elective caesarean delivery
Authors: Sundararajan Monisha , Ravindran Charulatha , Ponnusamy Rani , Murugesan Ravishankar 
Published: May 2020

BACKGROUND
Because of its alpha and beta agonist properties, norepinephrine infusion is currently being studied for the prevention of spinal hypotension during caesarean delivery. Vasopressor infusions are not always possible if there is an unavailability of infusion pumps. Leg wrapping with crepe bandage is an effective technique for prevention of postspinal hypotension and could be useful in resource-poor settings.

OBJECTIVE
The aim of this study was to compare the incidence of hypotension with norepinephrine infusion or leg wrapping with a control group in women undergoing caesarean delivery with spinal anaesthesia.

DESIGN
Randomised, double-blind, controlled trial.

SETTING
Single centre, tertiary level institute, India.
Study period 3 April 2018 to 31 March 2019.

PATIENTS
One hundred and forty-four women aged 19 to 40 years with a singleton pregnancy.

INTERVENTION
In group Leg Wrapping, crepe bandage was applied tightly from metatarsus to groin. Group Norepinephrine and the control group received sham leg wrapping. In group Norepinephrine, the women received a norepinephrine infusion according to their body weight, while group Leg Wrapping and the control group received a 0.9% normal saline infusion at a similar rate. All three groups received a 500 ml co-load of Ringer's solution over 15 min. Noninvasive SBP was monitored every 2 min until delivery, and every 5 min thereafter. Any hypotensive event (SBP < 20% of baseline) was treated with an intravenous bolus of norepinephrine (7.5 μg).

MAIN OUTCOME MEASURES
The primary outcome was the incidence of hypotension. The secondary outcomes were performance error measurements, and the incidences of hypertension, bradycardia, norepinephrine rescue bolus and neonatal outcomes.

RESULTS
The incidences of hypotension were significantly lower in the norepinephrine infusion group and the leg wrapping groups than the control group (P values 0.021 for both). Performance error calculations showed that SBP was maintained closer to baseline with the norepinephrine infusion.

CONCLUSION
Norepinephrine infusion and leg wrapping can both reduce the incidence of postspinal hypotension during elective caesarean delivery compared with saline infusion alone.

TRIAL REGISTRATION
Clinical trial number and registry URL: CTRI/2018/04/012917 registered at Clinical Trial Registry of India http://www.ctri.nic.in/Clinicaltrials/login.php.
Pharmacokinetics of Oral Treprostinil in Children With Pulmonary Arterial Hypertension
Authors: Hopper Rachel K. , Ivy D. Dunbar , Yung Delphine , Mullen Mary P. , Hanna Brian D. , Kirkpatrick Edward , Hirsch Russel , Austin Eric D. , Fineman Jeffrey , Solum Derek , Deng C. Q. , Feinstein Jeffrey A. 
Published: May 2020

Abstract:
As part of a clinical trial, this study examined the pharmacokinetics (PK) of oral treprostinil (TRE) in children with pulmonary arterial hypertension. The trial consisted of the following 3 cohorts: transition from parenteral (cohort 1) or inhaled (cohort 2) TRE, or de novo addition (cohort 3). Oral TRE was dosed 3 times daily. PK samples were obtained before an oral TRE dose, and at 2, 4, 6, and 8 hours thereafter. The PK parameters were calculated using noncompartmental analysis. Thirty-two children (n = 10 in cohorts 1 and 2, n = 12 in cohort 3) were enrolled; the median age was 12 years (range 7–17 years), and the median weight was 42.2 kg (range 19.3–78 kg). The median oral TRE dose for all subjects was 3.8 mg (5.9, 3.5, and 4.0 mg for cohorts 1, 2, and 3, respectively). The TRE concentration versus time profile demonstrated a peak concentration at a median of 3.8 hours with wide variability. In cohort 1, oral dosing led to higher peak (5.9 ng/mL) and lower trough (1 ng/mL) concentrations than parenteral (peak 5.4 ng/mL and trough 4.2 ng/mL), but a lower mean concentration (3.61 vs. 4.46 ng/mL), likely due to variable metabolism and noncomparable dosing. Both the area under the curve and average concentration were linearly correlated with oral TRE dose and dose normalized to body weight, but not with weight or age alone. In pediatric patients, an increased oral TRE dose or dose frequency may be required to minimize PK variability and achieve greater correlation with parenteral dosing.
Acute Effects of Interleukin-1 Blockade Using Anakinra in Patients With Acute Pericarditis
Authors: Wohlford George F. , Buckley Leo F. , Vecchié Alessandra , Kadariya Dinesh , Markley Roshanak , Trankle Cory R. , Chiabrando Juan Guido , de Chazal Horacio Medina , Van Tassell Benjamin , Abbate Antonio 
Published: May 2020

Abstract:
Interleukin-1 (IL-1) receptor antagonist (anakinra) has been shown to be effective in steroid-dependent recurrent pericarditis resistant to nonsteroidal anti-inflammatory drugs (NSAIDs) and colchicine. We sought to evaluate the acute efficacy of anakinra given early in patients with acute pericarditis. We enrolled patients within 24 hours of presentation of a first or recurrent episode of acute pericarditis who were experiencing severe pain (≥6 in 11-point Likert scale), despite treatment with at least one dose of NSAIDs and of colchicine. The primary outcome was pain relief at 24 hours. Subcutaneous anakinra 100 mg was administered in all patients, whereas NSAIDs and colchicine were suspended for 24 hours. Serum levels of interleukin-6 (IL-6) were measured at baseline and 24 hours. Data are reported as median (interquartile range). We treated 5 patients (4 male and 1 female; 38 [31–54] years old). Anakinra significantly reduced pain from 6.0 (6.0–7.5) to 4.0 (2.5–4.0) at 6 hours (P = 0.012 vs. baseline) and to 2.0 (1.5–2.5) at 24 hours (P = 0.0025 vs. baseline). No patients required rescue pain medication. IL-6 levels were also significantly reduced from 95.3 (24.2–155.1) to 23.9 (4.5–71.9) pg/mL at 24 hours (P = 0.037). The reduction in pain intensity paralleled the reduction in IL-6 serum levels (R = +0.966, P = 0.007). No adverse events related to treatment occurred. The administration of anakinra given early in acute pericarditis treatment course rapidly and significantly improved chest pain from acute pericarditis. The improvement is correlated with a reduction in IL-6 levels.
Hypertension and race/ethnicity
Authors: Deere Bradley P. , Ferdinand Keith C. 
Published: May 2020

Purpose of review
United States racial/ethnic minorities may experience disproportionate hypertension (HTN) morbidity and mortality. This review discusses recent literature regarding the differential impact of HTN, especially among African Americans and Hispanics.

Recent findings
Although disparities in HTN prevalence, control, and outcomes persist in racial/ethnic minorities relative to non-Hispanic Whites, racial/ethnic minorities are frequently underrepresented in genetic and clinical studies. Genomics have improved our understanding of HTN, but with no clinically useful application, the role of social determinants of health in HTN disparities is increasingly recognized. Team-based approaches with targeted, multilevel interventions may overcome barriers that uniquely impact racial/ethnic minorities.

Summary
Despite extensive epidemiological research, racial/ethnic minorities remain at higher risk HTN-related morbidity and mortality. Translational efforts may address the differential impact of HTN in racial/ethnic minorities. This review highlights recent research and concepts related to HTN and race/ethnicity.