bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA splicing during terminal erythropoiesis
Authors: Conboy John G. 
Published: January 2017

Purpose of review
Erythroid progenitors must accurately and efficiently splice thousands of pre-mRNAs as the cells undergo extensive changes in gene expression and cellular remodeling during terminal erythropoiesis. Alternative splicing choices are governed by interactions between RNA binding proteins and cis-regulatory binding motifs in the RNA. This review will focus on recent studies that define the genome-wide scope of splicing in erythroblasts and discuss what is known about its regulation.

Recent findings
RNA-seq analysis of highly purified erythroblast populations has revealed an extensive program of alternative splicing of both exons and introns. During normal erythropoiesis, stage-specific splicing transitions alter the structure and abundance of protein isoforms required for optimized red cell production. Mutation or deficiency of splicing regulators underlies hematopoietic disease in myelopdysplasia syndrome patients via disrupting the splicing program.

Summary
Erythroid progenitors execute an elaborate alternative splicing program that modulates gene expression posttranscriptionally, ultimately regulating the structure and function of the proteome in a differentiation stage-specific manner during terminal erythropoiesis. This program helps drive differentiation and ensure synthesis of the proper protein isoforms required to produce mechanically stable red cells. Mutation or deficiency of key splicing regulatory proteins disrupts the splicing program to cause disease.
Can Human Papillomavirus DNA Self-sampling be an Acceptable and Reliable Option for Cervical Cancer Screening in Female Sex Workers?
Authors: Wong Eliza L.Y. , Cheung Annie W.L. , Huang Fenwei , Chor Josette S.Y. 
Published: January 2017

Background:
The causal relation between human papillomavirus (HPV) and cervical cancer has enabled HPV self-sampling to be envisaged as a possible screening method.

Objectives:
The aim of this study is to explore the acceptability and reliability of HPV DNA self-sampling as an alternative option for cervical screening among female sex workers.

Methods:
Sixty-eight participants carried out self-sampling for HPV testing, gave a clinician-obtained sample for HPV testing, and a Papanicolaou test. After the samplings, the participants were questioned on the acceptability of the tests.

Results:
Most participants (65.6%) preferred to adopt HPV DNA self-sampling in the future; in particular, those without previous experience of Papanicolaou tests marginally significantly preferred self-sampling (86.7%, P = .055). The overall crude agreement in HPV detection rates between clinician and HPV DNA self-sampling was 85.3% (58/68), with a κ of 0.69 (95% confidence interval, 0.51–0.87). The sensitivity and specificity of self-collected samples were 66.7% and 66.1%, respectively, and the positive and negative predicted values were 24.0% and 92.5%, respectively. The prevalence of HPV was slightly higher in self-collected samples (39.7%, 27/68) than in clinician-collected samples (36.8%, 25/68). The participants expressed positive attitudes toward self-sampling but were less confident in their skills of self-sampling compared with clinicians (70.6% versus 91.2%).

Conclusions:
The findings showed that self-sampling could be incorporated into current cervical cancer screening approaches.

Implications for Practice:
Self-sampling could potentially increase compliance to cervical cancer screening and thus reduce the morbidity and mortality from cervical cancer. Further research and education on self-sampling will be required for women of diverse backgrounds.
Case Report
Authors: Blumenthal Ryan , Saayman Gert 
Published: January 2017

AbstractWe present the case of a 41-year-old woman who was fatally injured during a witnessed lightning strike event and in whom autopsy revealed the unusual keraunopathological finding of overt pneumomediastinum. The possible pathophysiological mechanism(s) of causation of this phenomenon are discussed, with specific reference also to the “Macklin” effect and the role of blast overpressures associated with lightning strike. It is suggested that the latter may lead to sudden alveolar rupture, with subsequent rapid tracking of air along bronchovascular sheaths in a centripetal manner toward the hilum of the lung and thus into the mediastinum. A review of the blast literature suggests that this victim would have been exposed to a blast pressure wave of approximately 29-psi (200 kPa) to 72-psi (500 kPa) magnitude.
Suspected Cerebral Edema in Diabetic Ketoacidosis: Is There Still a Role for Head CT in Treatment Decisions?*
Authors: Soto-Rivera Carmen L. , Asaro Lisa A. , Agus Michael S. D. , DeCourcey Danielle D. 
Published: January 2017

Objectives:
Neurologic deterioration associated with cerebral edema in diabetic ketoacidosis is typically sudden in onset, progresses rapidly, and requires emergent treatment. The utility of brain imaging by head CT in decisions to treat for cerebral edema has not been previously studied. The objective of this study was to describe the characteristics of pediatric patients with diabetic ketoacidosis who develop altered mental status and evaluate the role of head CT in this cohort.

Design:
Retrospective analysis of clinical, biochemical, and radiologic data.

Setting:
Tertiary care children’s hospital (2004–2010).

Patients:
Six hundred eighty-six admissions of patients (< 26 yr) with diabetic ketoacidosis.

Interventions:
None.

Measurements and Main Results:
Altered mental status was documented during 96 of 686 diabetic ketoacidosis admissions (14%). Compared with alert patients, those with altered mental status were younger (median, 12.0 vs 13.1 yr; p = 0.007) and more acidotic (pH, 7.04 vs 7.19; p < 0.001), with higher serum osmolality (328 vs 315 mOsm/kg; p < 0.001) and longer hospital length of stay (4.5 vs 3 d; p = 0.002). Head CT was performed during 60 of 96 diabetic ketoacidosis admissions with altered mental status (63%), 16 (27%) of which had abnormal results. Hyperosmolar therapy for cerebral edema was given during 23 of the 60 admissions (38%), during which 12 (52%) had normal head CT results, eight of these 12 (67%) after cerebral edema treatment and four (33%) before. Of the 11 admissions with abnormal head CT results that received hyperosmolar therapy, four head CT scan (36%) occurred after hyperosmolar treatment and seven (64%) before. For the 11 admissions with head CT before cerebral edema treatment, there was a median 2-hour delay between head CT and hyperosmolar therapy.

Conclusions:
In this single-center retrospective study, there was no evidence that decisions about treatment of patients with diabetic ketoacidosis and suspected cerebral edema were enhanced by head CT, and head CT may have led to a significant delay in hyperosmolar therapy.
Long-Term Function After Pediatric Critical Illness: Results From the Survivor Outcomes Study*
Authors: Pinto Neethi P. , Rhinesmith Elizabeth W. , Kim Tae Yeon , Ladner Peter H. , Pollack Murray M. 
Published: January 2017

Objective:
Knowledge of the long-term outcomes of survivors of pediatric critical illness is sparse but important. The aim of this study was to evaluate morbidity and mortality 6 months and 3 years after hospital discharge.

Design:
Prospective cohort study.

Setting:
Urban, inner city, academic PICU.

Patients:
Consecutive patients admitted to the PICU from June 2012 to August 2012.

Interventions:
None.

Measurements and Main Results:
We collected descriptive and demographic information and functional status assessments at baseline, admission, hospital discharge, 6 months and 3 years following discharge. Functional status was measured with the Functional Status Scale. New morbidity was defined as a change in Functional Status Scale score of greater than or equal to 3. Postdischarge assessments utilized scripted telephone surveys. Of 303 consecutive PICU patients, 253 were eligible and 129 parents consented. Follow-up outcomes were obtained for 77 patients (59.7%) at 6 months and 70 of these patients (54.2%) at 3 years. Both mortality and morbidity increased after discharge. Cumulative mortality increased from 3.9% (n = 3) at discharge to 7.8% (n = 6) at 6 months (p = 0.08) and 10.4% (n = 8) at 3 years (p = 0.03). New morbidity increased cumulatively from 5.2% (n = 4) at discharge to 6.5% (n = 5) at 6 months (p = 0.65) and 10.4% (n = 8) at 3 years (p = 0.16). Almost as many children demonstrated worsening of their functional status or died (38%) as children who survived without a change in functional status (44%). Less than 10% of children exhibited functional gains over time. Long-term functional outcome was associated with PICU variables including the need for invasive therapies and indicators of severity of illness such as use of mechanical ventilation, ventilator days, use of vasoactive medications, and PICU length of stay. The combined poor outcomes of new morbidity and mortality increased cumulatively from 9.1% (n = 7) at discharge to 14.3% (n = 11) at 6 months (p = 0.16) and 20.8% (n = 16) by 3 years (p = 0.01).

Conclusions:
Mortality and new morbidity appear to substantially increase after discharge. Critical illness is associated with a sustained impact on survival and functional status.
Impact of Viral Respiratory Pathogens on Outcomes After Pediatric Cardiac Surgery
Authors: Moynihan Katie , Barlow Andrew , Alphonso Nelson , Anderson Ben , Johnson Janelle , Nourse Clare , Schlebusch Sanmarié , Karl Tom R. , Schlapbach Luregn J. 
Published: January 2017

Objectives:
Viral respiratory infection is commonly considered a relative contraindication to elective cardiac surgery. We aimed to determine the frequency and outcomes of symptomatic viral respiratory infection in pediatric cardiac surgical patients.

Design:
Retrospective cohort study of children undergoing cardiac surgery. Symptomatic children were tested using a multiplex Polymerase Chain Reaction (respiratory virus polymerase chain reaction) panel capturing nine respiratory viruses. Tests performed between 72 prior to and 48 hours after PICU admission were included. Mortality, length of stay in PICU, and intubation duration were investigated as outcomes.

Setting:
Tertiary PICU providing state-wide pediatric cardiac services.

Patients:
Children less than 18 years admitted January 1, 2008 to November 29, 2014 for cardiac surgery.

Measurements and Main Results:
Respiratory virus polymerase chain reaction was positive in 73 (4.2%) of 1,737 pediatric cardiac surgical admissions, including 13 children with multiple viruses detected. Commonly detected viruses included rhino/enterovirus (48%), adenovirus (32%), parainfluenza virus 3 (10%), and respiratory syncytial virus (3%). Pediatric Index of Mortality 2, Aristotle scores, and cardiopulmonary bypass times were similar between virus positive and negative/untested cohorts. Respiratory virus polymerase chain reaction positive patients had a median 2.0 days greater PICU length of stay (p < 0.001) and longer intubation duration (p < 0.001). Multivariate analysis adjusting for age, Aristotle score, cardiopulmonary bypass duration, and need for preoperative PICU admission confirmed that virus positive patients had significantly greater intubation duration and PICU length of stay (p < 0.001). Virus positive patients were more likely to require PICU admission greater than 4 days (odds ratio, 3.5; 95% CI, 1.9–6.2) and more likely to require intubation greater than 48 hours (odds ratio, 2.5; 95% CI, 1.4–4.7). There was no difference in mortality. No association was found between coinfection and outcomes.

Conclusions:
Pediatric cardiac surgical patients with a respiratory virus detected at PICU admission had prolonged postoperative recovery with increased length of stay and duration of intubation. Our results suggest that postponing cardiac surgery in children with symptomatic viral respiratory infection is appropriate, unless the benefits of early surgery outweigh the risk of prolonged ventilation and PICU stay.
Doppler Ultrasonography of the Central Retinal Vessels in Children With Brain Death*
Authors: Riggs Becky J. , Cohen Joanna S. , Shivakumar Bhavana , Trimboli-Heidler Carmelina , Patregnani Jason T. , Miller Marijean M. , Spaeder Michael C. , Dean Nathan P. 
Published: January 2017

Objective:
The purpose of this observational study is to explore if bedside Doppler ultrasonography of the central retinal vessels has the potential to become an ancillary study to support the timely diagnosis of brain death in children.

Design:
Seventeen-month prospective observational cohort.

Setting:
Forty-four bed pediatric medical and surgical ICU in an academic teaching hospital.

Patients:
All children 0–18 years old who were clinically evaluated for brain death at Children’s National Health Systems were enrolled and followed until discharge or death.

Interventions:
None.

Measurements and Main Results:
All patients had at least one ophthalmic ultrasound within 30 minutes of each brain death examination. The central retinal artery peak systolic blood flow velocity, resistive index, pulsatility index, and Doppler waveforms were evaluated in each patient. Thirty-five ophthalmic ultrasounds were obtained on 13 patients, 3 months to 15 years old, who each had two clinical examinations consistent with brain death. The average systolic blood pressure during the ultrasound examinations was 102 mm Hg (± 28), diastolic blood pressure 65 mm Hg (± 24), mean arterial pressure 79 mm Hg (± 23), heart rate 133 beats/min (± 27), temperature 36°C (± 0.96), arterial Co
2 35 mm Hg (± 9), and end-tidal Co
2 23 mm Hg (± 6). For all examinations, the average peak systolic velocity of the central retinal artery was significantly decreased at 4.66 cm/s (± 3.2). Twelve of 13 patients had both resistive indexes greater than or equal to 1, average pulsatility indexes of 3.6 (± 3.5) with transcranial Doppler waveforms consistent with brain death. Waveform analysis of the 35 ultrasound examinations revealed 11% with tall systolic peaks without diastolic flow, 17% with oscillatory flow, 29% showed short systolic spikes, and 23% had no Doppler movement detected. A rippling “tardus-parvus” waveform was present in 20% of examinations.

Conclusion:
This study supports that the combination of qualitative waveform analysis and quantitative blood flow variables of the central retinal vessels may have the potential to be developed as an ancillary study for supporting the diagnosis of brain death in children.
From Vitality to Vital Exhaustion and Other States of “Tense Tiredness”: A New Biopsychosocial Risk Domain
Authors: Rozanski Alan , Cohen Randy 
Published: January 2017

ABSTRACTFatigue is a common prodromal symptom for various medical conditions, including acute myocardial infarction. Fatigue is also the core component of vital exhaustion, which consists of a specific triad: excessive fatigue, increased irritability, and feelings of demoralization. In this issue ofPsychosomatic Medicine, Frestad and Prescott present a meta-analysis of 16 studies, involving 53,337 participants, which found vital exhaustion to be associated with an increased risk of incident coronary heart disease (CHD) and recurrent cardiac events among individuals with established CHD. After discussing methodological limitations of the studies included in this meta-analysis, we describe these findings in terms of a larger genre of risk that is biopsychosocial in origin and tied to two types of tiredness: “calm tiredness” and “tense tiredness.” The former is regenerative, while the latter enhances disease risk. We propose that besides vital exhaustion, other symptoms of negative affect may combine with tiredness to produce increased clinical risk, such as the presence of depressed mood, an inability to relax or recover after work, and symptoms of burnout. We further propose that vital exhaustion can be considered as part of a larger paradigm, ranging from a positive state of vitality to a negative state of exhaustion of vitality. We conclude this editorial by emphasizing the importance of improving vitality and the need to clarify biobehavioral mechanisms that play a role in the association between vital exhaustion and adverse CHD outcomes. New interventions are needed that target reducing exhaustion and improving vitality for individuals at high risk of CHD.
Prevention of ventilator-associated pneumonia
Authors: Li Bassi Gianluigi , Senussi Tarek , Aguilera Xiol Eli 
Published: January 2017

Purpose of review
Ventilator-associated pneumonia (VAP) is an iatrogenic disease. Here we appraise recent advancements in the development and testing of strategies to prevent VAP. We also provide recommendations on the most promising interventions that should be applied.

Recent findings
In the last year, preventive bundles have consistently let to a reduction of VAP. A few trials on endotracheal tubes (ETTs) with novel cuffs failed to translate positive bench findings into clinical settings. In addition, meta-analyses confirmed the primary role of subglottic secretion aspiration in VAP prevention. A relatively new ETT, with an innovative cuff design, has been tested in clinical trials confirming potential value. Meta-analyses confirmed reduction of VAP with the use of chlorhexidine for oropharyngeal decontamination. However, prophylactic inhaled or oral antibiotics are ineffective. Finally, there is growing interest in orally ingested probiotics to prevent VAP. The results of ongoing studies on probiotics are much-awaited.

Summary
In conclusion, in the past year, new evidence elucidated limitations of new ETT cuffs in the prevention of VAP; whereas, subglottic secretion aspiration proved consistent benefits. Modulation of oropharyngeal colonization with chlorhexidine decreases risks of VAP and should be widely implemented. Finally, preventive measures with proven preventive value should be grouped into bundles.
Modifiers of Response to Treatment With Fesoterodine for Urgency-Predominant Urinary Incontinence in a Randomized Controlled Trial
Authors: Winkelman William D. , Huang Alison J. , Schembri Michael , Rogers Rebecca G. , Richter Holly , Myers Deborah L. , Kraus Stephen R. , Johnson Karen C. , Hess Rachel , Gregory Tomas , Bradley Catherine S. , Arya Lily , Brown Janette S. , Subak Leslee L. 
Published: January 2017

ObjectiveThe aim of this study was to identify clinical and demographic characteristics that moderate response to treatment with fesoterodine among women with a diagnosis of urgency-predominant urinary incontinence.MethodsA multicenter, double-blinded, 12-week randomized controlled trial of pharmacologic therapy for urgency-predominant urinary incontinence in community-dwelling women diagnosed by the 3-item Incontinence Questionnaire (3IQ) was previously performed. Participants (N = 645) were randomized to fesoterodine therapy (4–8 mg daily; n = 322) or placebo (n = 323). Urinary incontinence was assessed by 3-day voiding diaries. In this secondary analysis, a “responder” was defined as reduction of 50% or greater in overall incontinence episode frequency compared with baseline. Clinical and demographic characteristics that may moderate treatment response were assessed by testing for interaction between characteristics and intervention in logit models of responders, adjusting for clinical site.ResultsParticipants’ ages were a mean of 56 (SD, 14) years, 68% were white race, and they had a mean of 3.9 (SD, 3.0) urgency incontinence episodes per day. There were no baseline differences in demographic, clinical, or incontinence characteristics between treatment and placebo groups or between responders and nonresponders. There was an increase in the proportion of responders to fesoterodine with increasing age (P= 0.04) and parity (0.04) and among married women (P= 0.03), but no effect modification was observed by race/ethnicity, body mass index, education, employment status, or alcohol or tobacco use.ConclusionsIn ambulatory women with urgency-predominant urinary incontinence, older age, being married, and higher parity significantly moderated and potentiated the effects of pharmacologic therapy on incontinence frequency. This study identifies certain populations who may have increased responsiveness to treatment with antimuscarinic therapy and may be used to inform and guide future therapy.
Cerebellar mutism syndrome: cause and rehabilitation
Authors: Catsman-Berrevoets Coriene E. 
Published: January 2017

Purpose of review
Mutism of cerebellar origin may occur in the context of various causes but is most frequent in children after resection of a large midline cerebellar tumour. In this review, the endeavour to reach a consensus on name and definition of postoperative mutism of cerebellar origin and associated symptoms is highlighted. In addition, progress in understanding of cause and risk factors for the syndrome is discussed as well as the rehabilitation issues.

Recent findings
Consensus on the term cerebellar mutism syndrome (CMS) has been reached. The exact pathogenesis of CMS remains unclear. Recently, attention was drawn to the hypothesis that thermal injury might be an important mechanism in the pathogenesis of CMS. Diffusion tensor imaging tractography was found to visualize the damage to relevant pathways that are associated with persistent impairments after recovery of CMS. There is still no established treatment for CMS to date.

Summary
By reaching a consensus on terminology and description of CMS, a firm basis has been created for future research. The pathogenesis of CMS seems multifactorial and important risk factors have been found. However, CMS cannot be effectively prevented yet and no established or specific treatment is available, apart from very general rehabilitation and cognitive interventions.
A forward-looking review of seizure prediction
Authors: Freestone Dean R. , Karoly Philippa J. , Cook Mark J. 
Published: January 2017

Purpose of review
Seizure prediction has made important advances over the last decade, with the recent demonstration that prospective seizure prediction is possible, though there remain significant obstacles to broader application. In this review, we will describe insights gained from long-term trials, with the aim of identifying research goals for the next decade.

Recent findings
Unexpected results from these studies, including strong and highly individual relationships between spikes and seizures, diurnal patterns of seizure activity, and the coexistence of different seizure populations within individual patients exhibiting distinctive dynamics, have caused us to re-evaluate many prior assumptions in seizure prediction studies and suggest alternative strategies that could be employed in the search for algorithms providing greater clinical utility. Advances in analytical approaches, particularly deep-learning techniques, harbour great promise and in combination with less-invasive systems with sufficiently power-efficient computational capacity will bring broader clinical application within reach.

Summary
We conclude the review with an exercise in wishful thinking, which asks what the ideal seizure prediction dataset would look like and how these data should be manipulated to maximize benefits for patients. The motivation for structuring the review in this way is to create a forward-looking, optimistic critique of the existing methodologies.