bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultra-Protective Ventilation Reduces Biotrauma in Patients on Venovenous Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome*
Authors: Rozencwajg Sacha , Guihot Amélie , Franchineau Guillaume , Lescroat Mickael , Bréchot Nicolas , Hékimian Guillaume , Lebreton Guillaume , Autran Brigitte , Luyt Charles-Edouard , Combes Alain , Schmidt Matthieu 
Published: August 2019

Introduction:
Ventilator settings for patients with severe acute respiratory distress syndrome supported by venovenous extracorporeal membrane oxygenation are currently set arbitrarily. The impact on serum and pulmonary biotrauma markers of the transition to ultra-protective ventilation settings following extracorporeal membrane oxygenation implantation, and different mechanical ventilation strategies while on extracorporeal membrane oxygenation were investigated.

Design:
Randomized clinical trial.

Settings:
Nine-month monocentric study.

Patients:
Severe acute respiratory distress syndrome patients on venovenous extracorporeal membrane oxygenation.

Interventions:
After starting extracorporeal membrane oxygenation, patients were switched to the bi-level positive airway pressure mode with 1 second of 24 cm H2O high pressure and 2 seconds of 12 cm H2O low pressure for 24 hours. A computer-generated allocation sequence randomized patients to receive each of the following three experimental steps: 1) high pressure 24 cm H2O and low pressure 20 cm H2O (very high positive end-expiratory pressure–very low driving pressure); 2) high pressure 24 cm H2O and low pressure 5 cm H2O (low positive end-expiratory pressure–high driving pressure); and 3) high pressure 17 cm H2O and low pressure 5 cm H2O (low positive end-expiratory pressure–low driving pressure). Plasma and bronchoalveolar lavage soluble receptor for advanced glycation end-products, plasma interleukin-6, and monocyte chemotactic protein-1 were sampled preextracorporeal membrane oxygenation and after 12 hours at each step.

Measurements and Main Results:
Sixteen patients on ECMO after 7 days (1–11 d) of mechanical ventilation were included. “Ultra-protective” mechanical ventilation settings following ECMO initiation were associated with significantly lower plasma sRAGE, interleukin-6, and monocyte chemotactic protein-1 concentrations. Plasma sRAGE and cytokines were comparable within each on-ECMO experimental step, but the lowest bronchoalveolar lavage sRAGE levels were obtained at minimal driving pressure.

Conclusions:
ECMO allows ultra- protective ventilation, which combines significantly lower plateau pressure, tidalvolume, and driving pressure. This ventilation strategy significantly limited pulmonary biotrauma, which couldtherefore decrease ventilator-induced lung injury. However, the optimal ultra-protective ventilation strategy once ECMO is initiated remains undetermined and warrants further investigations. (Crit Care Med 2019; 47:1505–1512)
Outcomes of Micropulse Transscleral Cyclophotocoagulation in Eyes With Good Central Vision
Authors: Varikuti Venkata N.V. , Shah Parth , Rai Oshin , Chaves Ariel C. , Miranda Alex , Lim Boon-Ang , Dorairaj Syril K. , Sieminski Sandra F. 
Published: August 2019

Precis:
This study is the first to report micropulse transscleral cyclophotocoagulation (MP-TSCPC) use in only good vision patients. MP-TSCPC significantly reduced intraocular pressure (IOP) and glaucoma medication use without any significant reduction in visual acuity at every postoperative follow-up point.

Purpose:
To evaluate outcomes of MP-TSCPC in eyes with baseline best-corrected visual acuity (BCVA) of ≥20/60.

Methods:
A retrospective review of patients who underwent MP-TSCPC at Mayo Clinic and Ross Eye Institute from July 2016 to August 2017 with BCVA of ≥20/60, and a minimum of 3 months follow-up.

Results:
A total of 61 eyes of 46 patients (68.80±17.12 y) underwent MP-TSCPC with a mean follow-up of 10.2±3.1 months. Mean IOP and mean number of glaucoma medications used were significantly reduced from baseline at every follow-up time point (P<0.0001). At month 12, mean IOP was reduced 40.2% from baseline with 85.4% of the patients having an IOP reduction of ≥20%, and mean glaucoma medication use reduced by 0.82±0.53 with 79.6% of the patients having a reduction of ≥1 medication. There was no significant reduction in BCVA from baseline at any follow-up point (P>0.05), except for 10 eyes with a vision loss of ≥2 lines and 5 out of 10 eyes had cataract progression. The probability of complete success (IOP range, 6 to 21 mm Hg or ≥20% IOP reduction; BCVA loss ≤2 lines, no reoperation for glaucoma) was 74.14%, 83.61%, 84.21%, and 75.0% at months 1, 3, 6, 12, respectively. The probability of qualified success (above criteria for IOP, no reoperation and BCVA loss >2 lines) was 81.03%, 91.80%, 94.74%, and 93.75% at months 1, 3, 6, 12, respectively.

Conclusions:
MP-TSCPC should be considered earlier in the management of glaucoma and can possibly be offered as an alternative to incisional glaucoma surgeries.
Video Technology to BOOST Preceptor Recruitment: A Mixed Methods Study
Authors: Nunes D'Aquila Mitzi , Richter Lagha Regina , Tramel Janice , Lie Désirée A. 
Published: August 2019

Purpose
This study's aim was to examine the impact of a brief video presentation for changing clinician knowledge and attitude about precepting physician assistant (PA) students.

Methods
In this mixed methods study, we developed a 12-minute video and made presentations to potential preceptors. Change in knowledge and attitudes was assessed with a pre/post survey. We conducted focus groups (FGs) to elicit barriers and motivators for precepting PA students and assessed acceptability and impact of the video.

Results
Twenty-three preceptors participated in three 45-minute presentations. Participants showed significant knowledge increase in 7 of 10 survey questions. After the presentation, willingness to precept PA students was high. Major FG themes were: teaching is motivating, need clarity about PA students' needs, need support to teach, prefer video presentation to email, and similarities with medical student teaching is positive.

Conclusions
A brief in-person video presentation is acceptable and is associated with increased knowledge and comfort in precepting PA students.
Role of ultrafast-acting insulin analogues in the management of diabetes
Authors: Kruger Davida F. , Novak Lucia M. 
Published: August 2019

ABSTRACT
To control both fasting and prandial plasma glucose levels in people with diabetes, insulin therapy must mimic “normal” physiological insulin secretion as much as possible. This is achieved with a long-acting insulin injected once or twice daily and a bolus of insulin injected before every meal. Prandial (bolus) insulin can either be regular human insulin (RHI) or a rapid-acting insulin analogue (RAIA). Although the efficacy of RHI has been established over approximately 35 years of clinical use, RAIAs offer several clinical advantages over RHI, namely that they have been engineered with a reduced tendency to aggregate as hexamers, which allows for rapid dissociation and absorption after a subcutaneous injection. Conventional RAIAs include insulin lispro, insulin aspart, and insulin glulisine. The more recently developed fast-acting insulin aspart (faster aspart) is an ultrafast-acting mealtime insulin that contains the conventional insulin aspart in a new formulation with the excipients niacinamide and l-arginine to achieve faster insulin absorption than RHI and the conventional insulin aspart formulation. This article reviews the clinical evidence supporting the use of RAIAs as part of a basal–bolus regimen in patients with diabetes, with a focus on new formulations whose pharmacological profiles more closely mimic the endogenous prandial insulin secretion pattern that is seen in individuals without diabetes. This review also provides a clinical perspective to help guide health care professionals in the use of RAIAs.
Blood-sparing removal technique of extracorporeal membrane oxygenation circuit in a Jehovah Witness patient
Authors: Park Sang Min , Lee Bom , Kim Christopher Y. 
Published: August 2019

Abstract

Rationale:
Percutaneous cardiopulmonary support (PCPS) using extracorporeal membrane oxygenation (ECMO) is widely used in the critical patients with cardiopulmonary collapse. It is a representative blood-consuming procedure. In limited situations in which the option of blood transfusion is unavailable, there is no general agreement as to whether ECMO is contraindicated.

Patient concerns:
A 61-year-old male Jehovah Witness with acute respiratory collapse and loss of consciousness was rushed to our emergency room. Throughout his hospital course, the patient's family refused any type of blood transfusion even at the risk of death.

Diagnosis:
The clinical situations were secondary to a massive pulmonary thromboembolism

Interventions:
The patient underwent veno-venous ECMO via both femoral veins. The patient was recovered by intensive medical care although the level of hemoglobin (Hb) and hematocrit (Hct) was gradually decreased from 15.8 g/dl and 46.8% to 11.7 g/dl and 36.5%, respectively.

Outcomes:
On hospital day 3, ECMO was successfully removed using a blood-sparing ECMO removal technique involving the recycling of blood within the circuit by continuous saline infusion. There was no significant change in level of Hb/Hct and hemodynamic profile. At 2 days after ECMO removal, the level of Hb/Hct was elevated up to 9.2 g/dl and 30.0%, respectively without any transfusion.

Lessons:
Our blood-sparing removal technique of ECMO appears to be feasible and led to no significant adverse impact on hemodynamic status. The technique might be helpful for critical patients who cannot receive blood transfusion due to any cause.
Infection in xenotransplantation: opportunities and challenges
Authors: Fishman Jay A. 
Published: August 2019

Purpose of review
Posttransplantation infections are common. It is anticipated that infection will be no less common in xenotransplantation recipients. Prolonged xenograft survivals have resulted from advances in immunosuppressive strategies and development of swine that decrease host immune responses via genetic manipulation, notably CRISPR/cas9 manipulation. As prospects for clinical trials improve, consideration of the unique infectious risks posed by xenotransplantation reemerge.

Recent findings
Organisms likely to cause infection in human recipients of porcine xenografts are unknown in advance of clinical trials. Microbiological screening of swine intended as xenograft donors can be more intensive than is currently feasible for human allograft donors. Monitoring infection in recipients will also be more intensive. Key opportunities in infectious diseases of xenotransplantation include major technological advances in evaluation of the microbiome by unbiased metagenomic sequencing, assessments of some risks posed by porcine endogenous retroviruses (PERVs) including antiretroviral susceptibilities, availability of swine with deletion of genomic PERVs, and recognition of the rapidly changing epidemiology of infection in swine worldwide.

Summary
Unknown infectious risks in xenotransplantation requires application of advanced microbiological techniques to discern and prevent infection in graft recipients. Clinical trials will provide an opportunity to advance the safety of all of organ transplantation.
The potential role of 3D-bioprinting in xenotransplantation
Authors: Li Ping , Zhang Wenjun , Smith Lester J. , Ayares David , Cooper David K.C. , Ekser Burcin 
Published: August 2019

Purpose of review
To review the impact of a new technology, 3D-bioprinting, in xenotransplantation research.

Recent findings
Genetically engineered pigs, beginning with human (h) CD55-transgenic and Gal-knockout pigs, have improved the outcomes of xenotransplantation research. Today, there are more than 30 different genetically engineered pigs either expressing human gene(s) or lacking pig gene(s). CRIPSR/cas9 technology has facilitated the production of multigene pigs (up to nine genes in a single pig), which lack multiple pig xenoantigens, and express human transgenes, such as hCD46, hCD55, hThrombomodulin, hCD39, etc. Although recent studies in nonhuman primates (NHPs) have demonstrated prolonged survival after life-supporting pig kidney, heart, and islet xenotransplantation, researchers have difficulty determining the best genetic combination to test in NHPs because of a potential greater than 100 000 genetic combinations. 3D-bioprinting of genetically engineered pig cells: is superior to 2D in-vitro testing, enables organ-specific testing, helps to understand differences in immunogenicity between organs, and is faster and cheaper than testing in NHPs. Moreover, 3D-bioprinted cells can be continuously perfused in a bioreactor, controlling for all variables, except the studied variable.

Summary
3D-bioprinting can help in the study of the impact of specific genes (human or pig) in xenotransplantation in a rapid, inexpensive, and reliable way.
Letermovir for Difficult to Treat Cytomegalovirus Infection in Lung Transplant Recipients
Authors: Veit Tobias , Munker Dieter , Kauke Teresa , Zoller Michael , Michel Sebastian , Ceelen Felix , Schiopu Sanziana , Barton Jürgen , Arnold Paola , Milger Katrin , Behr Jürgen , Kneidinger Nikolaus 
Published: August 2019

Background.
Cytomegalovirus (CMV)-infection remains a major cause of morbidity and mortality after lung transplantation. Treatment with currently available drugs poses treatment difficulties in some patients due to drug resistance or intolerability.

Methods.
We report a series of 4 lung transplant recipients with CMV-infection and treatment failure upon standard care due to antiviral drug resistance and treatment-limiting side effects. As rescue therapy letermovir recently approved for the prophylaxis of CMV-infection in patients after hematopoietic stem cell transplantation was initiated. Patients received 480 mg/day for a follow up of 36.1 ± 12.9 weeks. Efficacy and tolerability were assessed retrospectively.

Results.
Mild nausea, vomiting, and diarrhea were the only side effects of letermovir reported by a single patient. A small adjustment of the tacrolimus dose was mandatory upon treatment initiation with letermovir. CMV viral load could be decreased and cleared subsequently in all patients. CMV clearance was observed after 17.7 ± 12.6 weeks despite lack of CMV-immunity.

Conclusions.
CMV-infection and -disease were successfully managed with letermovir. Letermovir was well tolerated and effective in treating CMV-infections in lung transplant recipients failing on currently available antiviral agents.
Impact of Tocilizumab (Anti–IL-6R) Treatment on Immunoglobulins and Anti-HLA Antibodies in Kidney Transplant Patients With Chronic Antibody-mediated Rejection
Authors: Shin Bong-Ha , Everly Matthew J. , Zhang Hao , Choi J. , Vo Ashley , Zhang Xiaohai , Huang Edmund , Jordan Stanley C. , Toyoda Mieko 
Published: August 2019

Background.
Chronic antibody-mediated rejection (cAMR) results in the majority of renal allograft losses. Currently, there are no approved therapies. We recently reported on clinical use of tocilizumab (TCZ) for treatment of cAMR in HLA-sensitized kidney transplant patients. IgG1 and IgG3 subclasses of IgG are potent effectors of complement- and antibody-dependent cellular cytotoxicity, which are critical mediators of AMR. Here, we examined the impact of TCZ treatment for cAMR on total IgG, IgG1-4 subclasses, and anti–HLA-IgG (total and subclasses).

Methods.
Archived plasma obtained pre- and post-TCZ treatment (8 mg/kg, 6×, monthly) from 12 cAMR patients who failed standard of care treatment with intravenous immune globulin + rituximab with or without plasma exchange were tested for total IgG and IgG1-4 by ELISA, anti–HLA-total IgG, IgG3 and IgG4, and donor-specific antibody by Luminex assay. Archived plasma from 14 cAMR patients treated with the standard of care were included as controls.

Results.
Total IgG and IgG1-3 were significantly reduced post-TCZ, whereas no reduction was seen post-treatment in the control group. Of 11 patients, 8 (73%) showed reduction of anti–HLA-total IgG and IgG3 post-TCZ, but this was not statistically significant.

Conclusions.
TCZ reduced total IgG and IgG1-3 and anti–HLA-total IgG and IgG3 levels, suggesting that TCZ suppresses Ig production in B cells nonspecifically, likely through inhibition of interleukin 6–mediated signaling to B cells and plasma cells. This may be a contributing factor for the beneficial effect of TCZ on cAMR observed in this patient population.
H
3
+
, the ideal probe for
in situ
measurement of the Galactic cosmic rays
Authors: Oka Takeshi 
Published: August 2019

The reason why

H

3

+

is an ideal probe for
in situ
measurement of cosmic ray energy density in the Galaxy is discussed. The variation of measured values of cosmic ray ionization rate
ζ
of H
2
since the theoretical prediction by Spitzer & Tomasko (Spitzer & Tomasko 1968
Astrophys. J.
152
, 971–986) is reviewed. How the measurements by

H

3

+

established
ζ
as of the order of 10
−17
s
−1
for dense clouds, 10
−16
s
−1
for diffuse clouds in the Galactic disc, and 10
−14
s
−1
for warm and diffuse gas in the Galactic centre is discussed.

This article is part of a discussion meeting issue ‘Advances in hydrogen molecular ions: H
3
+
, H
5
+
and beyond’.
Mental Health in UK Biobank Revised – development, implementation and results from an online questionnaire completed by 157,366 participants
Authors: Davis Katrina A. S. , Coleman Jonathan R. I. , Adams Mark , Allen Naomi , Breen Gerome , Cullen Breda , Dickens Chris , Fox Elaine , Graham Nick , Holliday Jo , Howard Louise M , John Ann , Lee William , McCabe Rose , McIntosh Andrew , Pearsall Robert , Smith Daniel J. , Sudlow Cathie , Ward Joey , Zammit Stan , Hotopf Matthew 
Published: August 2019

AbstractThis paper corrects and updates a paper published in BJPsych Open 2018 “Mental Health in UK Biobank” (https://doi.org/10.1192/bjo.2018.12) that was voluntarily retracted following the finding of errors in the coding of the variable for alcohol use disorder. Notably, the percentage of participants reaching threshold for alcohol use disorder on the Alcohol Use Disorder Identification Tool increased from 7% to 21%.BackgroundUK Biobank is a well-characterised cohort of over 500,000 participants that offers unique opportunities to investigate multiple diseases and risk factors. An online mental health questionnaire completed by UK Biobank participants expands the potential for research into mental disorders.MethodsAn expert working group designed the questionnaire, using established measures where possible, and consulting with a service user group regarding acceptability. Operational criteria were agreed for defining likely disorder and risk states, including lifetime depression, mania/hypomania, generalised anxiety disorder, unusual experiences and self-harm, and current post-traumatic stress and alcohol use disorders.Results157,366 completed online questionnaires were available by August 2017. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status. Lifetime depression was the most common finding in 24% of participants (37,434), with current alcohol use disorder criteria met by 21% (32,602), while other criteria were met by less than 8% of the participants. There was extensive comorbidity among the syndromes. Mental disorders were associated with a high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.ConclusionsThe questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed due to selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
How Top-Down and Bottom-Up Regulation in Fronto-Amygdalar Network Changes over Time during Drug Cue-Exposure: An fMRI Study among Abstinent Heroin User
Authors: Zare-Sadeghi Arash , Oghabian Mohammad Ali , Zare-Bidoky Mehran , Batouli Seyed Amir Hossein , Ekhtiari Hamed 
Published: August 2019

AbstractTop-down regulation is one of the major neural cores in drug-craving management and relapse prevention. The dynamic temporal behavior of top-down regulation between the dorso-lateral and ventro-medial prefrontal cortices (DLPFC and VMPFC) and amygdala during drug cue-exposure has not been studied yet. Fifteen abstinent participants with heroin use disorder were scanned using drug cue-induced craving fMRI task. Using Dynamic Causal Modelling (DCM), the winning model showed a significant reciprocal connection between the VMPFC and DLPFC while there was a one-way effect of the VMPFC on the amygdala. There is also a top-down modulation by DLPFC on the VMPFC-Amygdala connection. Craving contrast input only modulated amygdala directly. Using sliding-window for temporal evaluation, craving input to amygdala increased over time, simultaneously, DLPFC top-down modulatory effect on VMPFC-amygdala connection decreased. Temporal changes in the network connectivity during cue exposure with enhancement in craving input to amygdala and reduction in top-down modulatory effects of DLPFC, could provide us with new insights towards the dynamic nature of the cue-reactivity and failure to control its motivational consequences. Dynamic response of top-down regulatory networks during cue exposure can be considered as a new potential biomarker in the future addiction fMRI studies.
Differential expression of soluble receptor for advanced glycation end-products (sRAGE) in mice susceptible or resistant to chronic colitis
Authors: Bramhall Michael , Rich Kevin , Chakraborty Ajanta , Logunova Larisa , Han Namshik , Wilson James , Booth Catherine , Mclaughlin John , Brass Andy , Cruickshank Sheena M. 
Published: August 2019

AbstractAimsIdentifying the factors that contribute to chronicity in inflamed colitic tissue is not trivial. However, in mouse models of colitis, we can investigate at preclinical timepoints. We sought to validate murine Trichuris muris infection as a model for identification of factors that promote development of chronic colitis.MethodsWe compared preclinical changes in mice with a resolving immune response to T. muris (resistant) versus mice that fail to expel the worms and develop chronic colitis (susceptible). Findings were then validated in healthy controls and patients with suspected or confirmed IBD.ResultsThe Receptor for Advanced Glycation End Products (Rage) was highly dysregulated between resistant and susceptible mice prior to the onset of any pathological signs. Increased soluble RAGE (sRAGE) in the serum and faeces of resistant mice correlated with reduced colitis scores. Mouse model findings were validated in a preliminary clinical study: faecal sRAGE was differentially expressed in patients with active IBD compared with IBD in remission, patients with IBD excluded or healthy controls.ConclusionPre-clinical changes in mouse models can identify early pathways in the development of chronic inflammation that human studies cannot. We identified the decoy receptor sRAGE as a potential mechanism for protection against chronic inflammation in colitis in mice and humans. We propose that the RAGE pathway is clinically relevant in the onset of chronic colitis, and that further study of sRAGE in IBD may provide a novel diagnostic and therapeutic target.