bluuebunny/crossref_metadata_2025_split huggingface dataset:
Technical advancements in epigenomics and applications in transplantation
Authors: Kuscu Canan , Eason James D. , Kuscu Cem 
Published: December 2020

Purpose of review
To summarize recently developed next generation sequencing-based methods to study epigenomics and epitranscriptomics. To elucidate the potential applications of these recently developed methods in transplantation research.

Recent findings
There are several methods established with the collaborative efforts from different consortiums, such as ENCODE, Human Cell Atlas, and exRNA consortium to study role of epigenetics in human health. Rapid development in the sequencing technology also enabled the establishment of these genome-wide studies. This review specifically focuses on these techniques, such as EM-seq to study DNA methylation, CUT&RUN, and CUT&Tag to study histone/transcription factor--DNA interactions, ATAC-seq to study chromatin accessibility, Hi-C to explore 3D genome architecture and several methods to study epigenetics at single-cell level. In addition, we briefly mentioned recent efforts to study lncRNAs and extracellular miRNAs.

Summary
Technical advancements in genomics, particularly epigenomics, shed light on the role of epigenetics and recently epitranscriptomics in different fields. Application of those techniques to transplantation research is still very limited because of technical limitations. On the other hand, there are a lot of promising studies showing that these new techniques can be adapted to study the molecular biology of transplant-related problems.
Dissecting the human kidney allograft transcriptome: single-cell RNA sequencing
Authors: Varma Elly , Luo Xunrong , Muthukumar Thangamani 
Published: December 2020

Purpose of review
Single-cell RNA sequencing (scRNA-seq) has provided opportunities to interrogate kidney allografts at a hitherto unavailable molecular level of resolution. Understanding of this technology is essential to better appreciate the relevant biomedical literature.

Recent findings
Sequencing is a technique to determine the order of nucleotides in a segment of RNA or DNA. RNA-seq of kidney allograft tissues has revealed novel mechanistic insights but does not provide information on individual cell types and cell states. scRNA-seq enables to study the transcriptome of individual cells and assess the transcriptional differences and similarities within a population of cells. Initial studies on rejecting kidney allograft tissues in humans have identified the transcriptional profile of the active players of the innate and adaptive immune system. Application of scRNA-seq in a preclinical model of kidney transplantation has revealed that allograft-infiltrating myeloid cells follow a trajectory of differentiation from monocytes to proinflammatory macrophages and exhibit distinct interactions with kidney allograft parenchymal cells; myeloid cell expression of Axl played a major role in promoting intragraft myeloid cell and T-cell differentiation.

Summary
The current review discusses the technical aspects of scRNA-seq and summarizes the application of this technology to dissect the human kidney allograft transcriptome.
Nurses' Experiences with Implementation of a Postcesarean Birth Opioid-Sparing Protocol
Authors: Jun Jin , Sturza Marisa , Maguire Sarah , Waljee Jennifer , Smith Roger , Peahl Alex 
Published: December 2020

Abstract

Purpose:
Opioid-sparing protocols have significantly reduced opioid use postcesarean birth through maximizing nonpharmacologic and nonopioid pain management tools. This study explored nurses' experiences with an opioid-sparing protocol at a single institution, where inpatient opioid prescribing was reduced by over half.

Method:
Focus groups were used to identify key facilitators and barriers to implementation of the opioid-sparing protocol. The Consolidated Framework for Implementation Research (CFIR) guided data collection and analysis. Focus groups were recorded, transcribed, thematically coded, and analyzed for barriers and facilitators using predetermined CFIR domains.

Results:
Three focus groups of nurses who care for women during postpartum were conducted in March and April 2019. Fourteen nurses participated. They were all women, with an average of 9.3 years (SD = 5.4) of maternity nursing experience. Facilitators of implementation were: 1) high satisfaction with the intervention's efficacy; 2) awareness of opioid harms promoting readiness for opioid-sparing efforts; 3) adequate staffing and the culture of evidence-based practice; and 4) bedside skills in pain management to identify patients' needs. The most significant barrier was a lack of nurse engagement with protocol development and implementation.

Clinical Implications:
An increased partnership among the interprofessional team members through all stages of implementation is necessary for the success and sustainability of best patient care practices.
The Dotson Bridge and Mentoring Program
Authors: Christian LaDonna , Cater Gloria , Dieujuste Colette 
Published: December 2020

Background
Even though the Institute of Medicine released a report on the importance of ethnic diversity in the health care workforce to reduce health disparities, there has been little progress in increasing diversity in nursing.

Problem
Nationally, health care systems do not have adequate representation of Black/African American, Asian, and Latino RNs.

Approach
The Dotson Bridge and Mentoring Program is an innovative mentoring program for African American, Latino, Asian, and Native American (ALANA) students.

Conclusion
Mentoring programs that support ALANA students can lead to an increase in retention, graduation, and NCLEX pass rates and should be an integral part of nursing programs. The outcomes of the program included improving the course pass rates from 50% to 92%, improving the first-time NCLEX pass rate from 74% to 94% and decreasing the attrition rate from 23% to 1%.
Treating Paroxysmal Sympathetic Hyperactivity With Enteral Baclofen in Anoxic Brain Injury
Authors: O’Keefe Lena M. , Mui Gracia 
Published: December 2020

Introduction:
Paroxysmal sympathetic hypersensitivity (PSH) has become more frequently recognized in patients with severe neurological brain injury. Left untreated, PSH has been associated with poor neurological outcomes. Currently, most therapeutic options are circumstantial with evidence stemming from subjective case reports.

Case Series:
Two young females were admitted after cardiac arrest and found to have anoxic brain injury with subsequent PSH. Initial treatment was targeted at relief of the hyperadrenergic symptoms, which included bromocriptine, propranolol, opioids and benzodiazepines. These therapies were minimally effective, and the patients remained comatose. After initiation of enteral baclofen treatment, they exhibited drastic reduction of PSH symptoms and became alert and interactive. After a 6-week hospital stay, they were both discharged to long-term rehabilitation centers.

Conclusion:
This case series reviews the current therapies used for PSH and discusses 2 patients with uncontrolled PSH secondary to anoxic brain injury. Both patients arose from coma and had significant symptomatic improvement with enteral baclofen treatment. Thus, enteral baclofen should be considered as a primary treatment for PSH to prevent sustained symptoms and prolonged hospitalizations.
Thrombolysis for Acute Ischemic Stroke Following Transcatheter Aortic Valve Replacement
Authors: Malhotra Ashwin , Segal Alan Z. 
Published: December 2020

Introduction:
Intravenous thrombolytic therapy with recombinant tissue type plasminogen activator (IV-tPA) is the first-line treatment option for acute ischemic stroke (AIS). The tPA exclusion criteria, defined decades ago, require updates as new technologies emerge. Transcatheter aortic valve replacement (TAVR), which has begun to replace open surgery, poses a risk for acute stroke and falls outside of prior tPA guidelines.

Case Report:
Here we describe a post-TAVR patient treated safely with IV-tPA for presumed AIS.

Conclusion:
Previously undescribed, we suggest that tPA should be considered for post-TAVR AIS patients who otherwise satisfy inclusion and exclusion criteria.
Elevated Serum IgG4 Was Found in Eosinophilic Granulomatosis With Polyangiitis
Authors: Wu Ziyan , Zhang Shulan , Li Ping , Song Ning , Zhang Fengchun , Li Yongzhe 
Published: December 2020

Objective
The aim was to determine the levels and clinical impact of immunoglobulin G4 (IgG4) and other IgG subclasses in a Chinese population with eosinophilic granulomatosis with polyangiitis (EGPA).

Methods
We enrolled 49 patients who had EGPA, 27 who had granulomatosis with polyangiitis (GPA), 31 who had microscopic polyangiitis (MPA), and 30 healthy controls (HCs). Serum IgG subclasses were measured using commercial immunonephelometric assays and compared among different groups.

Results
Fifteen EGPA patients (30.61%) had elevated IgG4 levels, based on a cutoff value of 135 mg/dL. In addition, 2 GPA patients (7.40%) and 1 MPA patient (3.33%) had elevated IgG4 levels. The EPGA group had a higher IgG4 level (65.60 mg/dL) than the GPA group (32.70 mg/dL, p = 0.0021), the MPA group (30 mg/dL, p = 0.0021), and the HC group (28.55 mg/dL, p = 0.0002). The EPGA group also had a higher IgG4/IgG ratio (0.0644) than the GPA group (0.0322, p = 0.13), the MPA group (0.0289, p = 0.0055), and the HC group (0.0212, p < 0.0001).

Conclusions
Our results indicate that Chinese patients with EGPA have increased levels of serum IgG4. Further study is needed to determine the pathogenic role of IgG4 and IgG4 antineutrophil cytoplasmic antibodies in EGPA.
18F-Fluciclovine PET/CT in Therapeutic Decision Making for Prostate Cancer
Authors: Dreyfuss Alexandra D. , Ahn Grace S. , Barsky Andrew R. , Gillman Jennifer A. , Vapiwala Neha , Pantel Austin R. 
Published: December 2020

Purpose
This practice-based analysis examined the performance and clinical impact of 18F-fluciclovine PET/CT in patients with biochemical recurrence (BR) of prostate cancer (PC).

Methods
We carried out a retrospective cohort study of patients with BR after primary treatment of PC who received imaging with 18F-fluciclovine PET/CT at our institution between January 2010 and January 2019. PET/CT results were compared with biopsy, conventional imaging results, and/or response to PC therapy. 18F-Fluciclovine PET/CT performance statistics and effects on treatment planning were calculated.

Results
A total of 328 patients with a median age of 71 years (range, 47–90 years) and median serum prostate-specific antigen level of 1.6 ng/mL (0.02–186.7 ng/mL) were included. Three hundred thirty-six 18F-fluciclovine PET/CT scans were analyzed and classified as positive (65%), negative (25%), or equivocal (10%) based on radiology reports. Sensitivity was 93% (95% confidence interval, 86%–96%) and specificity was 63% (95% confidence interval, 45%–77%). Of patients with known management recommendations post-PET/CT, scan results changed or influenced pre-PET/CT management plans in 73%, and 58% of recommendations involved treatment modality decisions. Overall, 82% of patients’ actual management was concordant with post-PET/CT recommendations. Of evaluable patients, 116 (35%) had some form of post-PET radiotherapy included in their care plans, with 95% receiving radiotherapy at a PET-avid target.

Conclusions
In the largest single-institutional cohort to date, 18F-fluciclovine PET/CT showed value in the workup of PC in the setting of BR, with noteworthy influence over clinical management decisions. Further studies are needed to evaluate whether PET/CT-based changes in management are associated with improved outcomes.
111In-Labeled White Blood Cell Uptake in the Urinary Bladder in Occult Urinary Tract Infection
Authors: Ullman Henrik , Viragh Karoly , Thomas Mariam , Ni Chiayi 
Published: December 2020

Abstract
A 55-year-old woman with multiple medical problems, including anuric, dialysis-dependent, end-stage renal disease, presented with persistent fever of unknown origin. Despite extensive workup with cross-sectional imaging and panculture, the etiology was not found. Eventually, an 111In-labeled WBC scan was performed to evaluate for occult infection, which revealed intense heterogeneous uptake in the urinary bladder. Subsequent bladder catheterization showed pus and blood, which grew Klebsiella pneumoniae. The fevers resolved with adjustment of the therapy. Although urinary analysis and culture are standard practice in the workup of fever of unknown origin, anuria may obscure this common source of infection.
Regorafenib-Associated Acute Pancreatitis Diagnosed on 18F-FDG PET/CT
Authors: Pereira Melvika , Prakash Anjali , Puranik Ameya D. , Purandare Nilendu , Shah Sneha , Agrawal Archi , Rangarajan Venkatesh 
Published: December 2020

Abstract
A 23-year-old man with metastatic osteosarcoma, with disease progression on conventional chemotherapy, was treated with regorafenib, a multikinase inhibitor. After treatment for 6 months with regorafenib, 18F-FDG PET/CT scan demonstrated FDG uptake in a necrotic space-occupying lesion involving tail of pancreas. After imaging, patient described symptoms of epigastric pain with elevated serum amylase and lipase levels, confirming diagnosis of regorafenib-induced pancreatitis, because patient had no other causative factors of pancreatitis. Physicians should be aware of rare and possibly clinically silent adverse effects of tyrosine kinase inhibitors, like acute pancreatitis, and recognize the 18F-FDG PET/CT findings to guide appropriate clinical management.
Head-to-Head Comparison of 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT in Patients With Midgut Neuroendocrine Tumors
Authors: Ansquer Catherine , Touchefeu Yann , Faivre-Chauvet Alain , Leux Christophe , Le Bras Maëlle , Régenet Nicolas , Fleury Vincent , Maucherat Bruno , Senellart Hélène , Guyetant Serge , Carlier Thomas , Scotet-Cérato Evelyne , Rauscher Aurore , Frampas Eric , Kraeber-Bodéré Françoise 
Published: December 2020

Purpose
The aim of this study was to compare retrospectively 18F-DOPA PET/CT versus 68Ga-DOTANOC PET/CT in a group of patients affected by midgut NET.

Patients and Methods
Patients with histologically proven grade 1 or grade 2 midgut NET were explored after injection of 150 MBq of 68Ga-DOTANOC and 210 MBq of 18F-DOPA. The PET/CTs were analyzed visually and semiquantitatively at the patient level, regional level (7 defined regions), and lesion level (maximum of 5 lesions/organ). The criterion standard was determined on the basis of histology and imaging follow-up.

Results
Thirty patients (17 males and 13 females; median age, 63.5 years [37–82 years]) were included. Both PET/CTs were negative in 3 patients and positive in 25 patients. PET/CTs were discordant in 2 patients, with 18F-DOPA positive and 68Ga-DOTANOC negative. 18F-DOPA PET/CT detected more involved regions and more metastatic lesions than 68Ga-DOTANOC PET/CT in 6 (20%) and 10 (33.3%) patients, respectively. Of the 81 confirmed affected regions, 77 (95%) were detected by 18F-DOPA PET/CT and 71 (87.7%) by 68Ga-DOTANOC PET/CT (P < 0.0001). 18F-DOPA PET/CT detected significantly more lesions (211/221) than 68Ga-DOTANOC PET/CT (195/221), corresponding to a sensitivity of 95.5% and 88.2%, respectively (P < 0.0001). Tumor-to-background ratios were more favorable in liver for 18F-DOPA than for 68Ga-DOTANOC. Interestingly, a correlation was found between 18F-DOPA SUVmax and tumor burden and especially with the number of regions involved by the disease (P = 0.019).

Conclusions

18F-DOPA PET/CT is superior to 68Ga-DOTANOC PET/CT for the detection of lesions, and when available, this tracer may be recommended as the first-line examination for an accurate staging of midgut NET.
68Ga-Fibroblast Activation Protein Inhibitor, a Promising Radiopharmaceutical in PET/CT to Detect the Primary and Metastatic Lesions of Chromophobe Renal Cell Carcinoma
Authors: Pang Yizhen , Wei Jihong , Shang Qihang , Zhao Liang , Chen Haojun 
Published: December 2020

Abstract

18F-FDG PET/CT was performed to locate the primary lesion in a 71-year-old man with bone metastasis. However, no abnormal 18F-FDG activity likely presenting the primary tumor was observed. 68Ga-fibroblast activation protein inhibitor PET/CT was then performed for further detecting the primary tumor, which showed a higher activity in lesions of bone metastases than 18F-FDG. Additionally, another lesion with intense uptake was observed in the inferior pole of right kidney, likely presenting the primary tumor. A renal biopsy revealed the diagnosis of chromophobe renal cell carcinoma. This case highlighted that 68Ga-fibroblast activation protein inhibitor could be a promising radiopharmaceutical in the diagnosis of renal cell carcinoma.
Out of the blue: understanding abrupt and wayward transitions in thought using probability and predictive processing
Authors: Mills Caitlin , Zamani Andre , White Rebecca , Christoff Kalina 
Published: December 2020

Thoughts that appear to come to us ‘out of the blue’ or ‘out of nowhere’ are a familiar aspect of mental experience. Such thoughts tend to elicit feelings of surprise and spontaneity. Although we are beginning to understand the neural processes that underlie the arising of such thoughts, little is known about what accounts for their peculiar phenomenology. Here, we focus on one central aspect of this phenomenology—the experience of surprise at their occurrence, as it relates to internal probabilistic predictions regarding mental states. We introduce a distinction between two phenomenologically different types of transitions in thought content: (i)abrupt transitions, which occur at surprising times but lead to unsurprising thought content, and (ii)wayward transitions, which occur at surprising times and also lead to surprising thought content. We examine these two types of transitions using a novel approach that combines probabilistic and predictive processing concepts and principles. We employ two different probability metrics—transition and occurrence probability—to characterize and differentiate between abrupt and wayward transitions. We close by discussing some potentially beneficial ways in which these two kinds of transitions in thought content may contribute to mental function, and how they may be implemented at the neural level.This article is part of the theme issue ‘Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation’.
How deep is the rift between conscious states in sleep and wakefulness? Spontaneous experience over the sleep–wake cycle
Authors: Windt Jennifer M. 
Published: December 2020

Whether we are awake or asleep is believed to mark a sharp divide between the types of conscious states we undergo in either behavioural state. Consciousness in sleep is often equated with dreaming and thought to be characteristically different from waking consciousness. Conversely, recent research shows that we spend a substantial amount of our waking lives mind wandering, or lost in spontaneous thoughts. Dreaming has been described as intensified mind wandering, suggesting that there is a continuum of spontaneous experience that reaches from waking into sleep. This challenges how we conceive of the behavioural states of sleep and wakefulness in relation to conscious states. I propose a conceptual framework that distinguishes different subtypes of spontaneous thoughts and experiences independently of their occurrence in sleep or waking. I apply this framework to selected findings from dream and mind-wandering research. I argue that to assess the relationship between spontaneous thoughts and experiences and the behavioural states of sleep and wakefulness, we need to look beyond dreams to consider kinds of sleep-related experience that qualify as dreamless. I conclude that if we consider the entire range of spontaneous thoughts and experiences, there appears to be variation in subtypes both within as well as across behavioural states. Whether we are sleeping or waking does not appear to strongly constrain which subtypes of spontaneous thoughts and experiences we undergo in those states. This challenges the conventional and coarse-grained distinction between sleep and waking and their putative relation to conscious states.This article is part of the theme issue ‘Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation’.
Hallucinations on demand: the utility of experimentally induced phenomena in hallucination research
Authors: Rogers Sebastian , Keogh Rebecca , Pearson Joel 
Published: December 2020

Despite the desire to delve deeper into hallucinations of all types, methodological obstacles have frustrated development of more rigorous quantitative experimental techniques, thereby hampering research progress. Here, we discuss these obstacles and, with reference to visual phenomena, argue that experimentally induced phenomena (e.g. hallucinations induced by flickering light and classical conditioning) can bring hallucinations within reach of more objective behavioural and neural measurement. Expanding the scope of hallucination research raises questions about which phenomena qualify as hallucinations, and how to identify phenomena suitable for use as laboratory models of hallucination. Due to the ambiguity inherent in current hallucination definitions, we suggest that the utility of phenomena for use as laboratory hallucination models should be represented on a continuous spectrum, where suitability varies with the degree to which external sensory information constrains conscious experience. We suggest that existing strategies that group pathological hallucinations into meaningful subtypes based on hallucination characteristics (including phenomenology, disorder and neural activity) can guide extrapolation from hallucination models to other hallucinatory phenomena. Using a spectrum of phenomena to guide scientific hallucination research should help unite the historically separate fields of psychophysics, cognitive neuroscience and clinical research to better understand and treat hallucinations, and inform models of consciousness.This article is part of the theme issue ‘Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation’.
The Alzheimer risk factor CD2AP causes dysfunction of the brain vascular network
Authors: Vandal Milène , Institoris Adam , Korin Ben , Gunn Colin , Lee Suzie , Lee Jiyeon , Bourassa Philippe , Mishra Ramesh C. , Peringod Govind , Jiang Yulan , Hirai Sotaro , Belzil Camille , Reveret Louise , Tremblay Cyntia , Hashem Mada , Elias Esteban , Meilandt Bill , Foreman Oded , Rouse-Girma Meron , Muruve Daniel , Nicola Wilten , Körbelin Jakob , Dunn Jeff F. , Braun Andrew P. , Bennett David A. , Gordon Grant R.J. , Calon Frédéric , Shaw Andrey S. , Nguyen Minh Dang 
Published: December 2020

SummaryGenetic variations in CD2-associated protein (CD2AP) predispose to Alzheimer’s disease (AD) but the underlying mechanisms remain unknown. Here, we show that a cerebrovascular loss of CD2AP is associated with cognitive decline in AD and that genetic downregulation of CD2AP in brain endothelial cells impairs memory function in two distinct mouse models. Mice with reduced CD2AP in brain microvessels display decreased resting cerebral blood flow, impaired functional hyperemia and vasomotion. In brain endothelial cells, CD2AP regulates the levels and signaling of ApoE receptor 2 elicited by Reelin glycoprotein. Activation of the CD2AP-ApoER2 pathway with Reelin mitigates the toxic effects of Aβ on resting blood flow and vasomotion of brain vessels depleted of CD2AP. Thus, we demonstrate that deregulation of CD2AP perturbs specific functions and segments of the cerebral microvasculature and propose that targeting CD2AP molecular partners may offer refined therapeutic strategies for the treatment of AD.