bluuebunny/crossref_metadata_2025_split huggingface dataset:
CIRCINATE PARTITION-LIKE FINDINGS ON CONE MOSAIC IMAGED BY ADAPTIVE OPTICS SCANNING LASER OPHTHALMOSCOPY IN EYES WITH INNER NUCLEAR LAYER MICROCYSTIC CHANGES
Authors: Hasegawa Tomoko , Ooto Sotaro , Makiyama Yukiko , Hata Masayuki , Miyamoto Kazuaki , Yoshimura Nagahisa 
Published: March 2017

Purpose:
To report cases that showed partition-like, dark areas in the cone mosaic on adaptive optics scanning laser ophthalmoscopy (AO-SLO) images in eyes with inner nuclear layer (INL) microcystic changes.

Methods:
Eyes with INL microcystic changes were imaged by prototype AO-SLO.

Results:
An eye with Leber hereditary optic neuropathy, an eye with traumatic optic neuropathy, and an eye with retinitis pigmentosa that showed microcystic lesions in the INL were imaged by AO-SLO. The images revealed characteristic, dark, partition-like lesions in the cone mosaic of all the eyes in areas where microcystic changes in the INL were shown by spectral domain optical coherence tomography. The AO-SLO findings in eyes with optic neuropathy were quite similar in shape and size to those seen in eyes with retinitis pigmentosa.

Conclusion:
We report cases that manifest dark, partition-like areas in the cone mosaic on AO-SLO images. Microcystic lesions in the INL may affect the images of the cone mosaic.
TWO CASES OF ACUTE RETINAL NECROSIS DUE TO VARICELLA ZOSTER DESPITE PRIOR SHINGLES VACCINATION
Authors: Weinlander Eric J. , Wang Angeline L. , Jaru-ampornpan Pimkwan , Altaweel Michael M. , Nork T. Michael 
Published: March 2017

Purpose:
To review two cases of acute retinal necrosis in adults due to varicella zoster virus despite prior shingles vaccination.

Methods:
Retrospective chart review.

Patients:
A 62-year-old man and a 64-year-old man with unilateral acute retinal necrosis who had shingles vaccinations 16 and 7 months before their ocular symptoms.

Results:
Polymerase chain reaction confirmation of varicella zoster virus in the anterior chambers of both patients. Both patients had good responses to oral antiviral therapy and topical and/or oral steroids.

Discussion:
These two cases demonstrate that singles vaccination is not an absolute protection against varicella zoster virus–related acute retinal necrosis. However, such vaccination may reduce the severity of the acute retinal necrosis.
Severity and Outcome of Acute-on-Chronic Liver Failure is Dependent on the Etiology of Acute Hepatic Insults
Authors: Shalimar  , Kedia Saurabh , Mahapatra Soumya J. , Nayak Baibaswata , Gunjan Deepak , Thakur Bhaskar , Acharya Subrat K. 
Published: March 2017

Background:
Acute-on-chronic liver failure (ACLF) may be precipitated by various hepatic insults. The present study evaluated the outcomes of ACLF with different acute insults.

Patients and Methods:
A total of 368 ACLF patients were included. Data collected included etiologies of acute hepatic insult and underlying chronic liver disease, and organ failure. Model for end-stage liver disease (MELD), chronic liver failure consortium (CLIF)-C ACLF, and acute physiology and chronic health evaluation (APACHE) II scores were calculated. Predictors of survival were assessed by the Cox proportional hazard model.

Results:
The most frequent acute insult was active alcohol consumption [150 (40.8%) patients], followed by hepatitis B virus (HBV) [71 (19.3%) patients], hepatitis E virus (HEV) superinfection [45 (12.2%) patients], autoimmune hepatitis flare [17 (4.6%) patients], antituberculosis drugs [16 (4.3%) patients], and hepatitis A virus superinfection [2 (0.5%) patients]; 67 (18.2%) cases were cryptogenic. Alcohol-ACLF and cryptogenic-ACLF were more severe. Median CLIF-C, MELD, and APACHE II scores in alcohol-ACLF and cryptogenic-ACLF were significantly higher than those in HBV-ACLF and HEV-ACLF (CLIF-C: 47.1, 47.4 vs. 42.9, 42.0, P=0.002; MELD: 29, 29.9 vs. 28.9, 25.2, P=0.02; APACHE II: 16.5, 18.0 vs. 12, 14, P<0.001, respectively). Frequencies of kidney and brain failures were also higher in alcohol/cryptogenic-ACLF than in HBV/HEV-ACLF (kidney failure: 35.3%/34.3% vs. 23.9%/11.1%, P=0.009; brain failure: 26.0%/22.4% vs. 15.5%/4.4%, P=0.01, respectively). Mortality in the alcohol-ACLF group was the highest (64.0%), followed by that in the cryptogenic-ACLF (62.7%), HBV-ACLF (45.1%), and HEV-ACLF (17.8%) groups (P<0.001). In multivariable analysis, alcohol-ACLF had significantly higher mortality compared with HEV-ACLF (hazard ratio, 3.06; 95% confidence interval, 1.10-8.49, P=0.03).

Conclusions:
Alcohol/cryptogenic-ACLF had more severe phenotypic presentation, more incidence of organ failures, and higher mortality compared with HEV/HBV-ACLF. Alcohol-ACLF had the highest mortality, whereas HEV-ACLF had the best survival.
Research Interest in Pediatric Emergency Medicine Fellows
Authors: Michelson Kenneth A. , Nigrovic Lise E. , Nagler Joshua , McAneney Constance M. , Mistry Rakesh D. 
Published: March 2017

Objective
Factors predictive of research career interest among pediatric emergency medicine (PEM) fellows are not known. We sought to determine the prevalence and determinants of interest in research careers among PEM fellows.

Methods
We performed an electronically distributed national survey of current PEM fellows. We assessed demographics, barriers to successful research, and beliefs about research using 4-point ordinal scales. The primary outcome was the fellow-reported predicted percentage of time devoted to clinical research 5 years after graduation. We measured the association between barriers and beliefs and the predicted future clinical research time using the Spearman correlation coefficient.

Results
Of 458 current fellows, 231 (50.4%) submitted complete responses to the survey. The median predicted future clinical research time was 10% (interquartile range, 5%–20%). We identified no association between sex, residency type, and previous research exposure and predicted future research time. The barrier that most correlated with decreased predicted clinical research time was difficulty designing a feasible fellowship research project (Spearman coefficient [ρ], 0.20; P = 0.002). The belief that most correlated with increased predicted clinical research time was excitement about research (ρ = 0.69, P < 0.001).

Conclusions
Most fellows expect to devote a minority of their career to clinical research. Excitement about research was strongly correlated with career research interest.
Assessing Suicide Risk: What is Commonly Missed in the Emergency Room?
Authors: ALAVI NAZANIN , RESHETUKHA TARAS , PROST ERIC , ANTONIAK KRISTEN , GROLL DIANNE 
Published: March 2017

Objective:
Although risk assessment for suicide has been extensively studied, it is still an inexact process. The current study determined how busy emergency clinicians actually assessed and documented suicide risk, while also examining the differences between psychiatric and emergency medicine opinions on the importance of various suicide predictors.

Method:
Phase 1 of the study involved the administration of a survey on the relative importance of various suicide predictors for the specialties of psychiatry and emergency medicine. In phase 2 of the study, a chart review of psychiatric emergency room patients was conducted to determine the actual documentation rates of the suicide predictors.

Results:
Several predictors that were deemed to be important, including suicidal plan, intent for suicide, having means available for suicide, and practicing suicide (taking different steps leading up to suicide but not actually attempting suicide), had low documentation rates.

Conclusions:
Medical specialties have different opinions on the importance of various suicide predictors. Also, some predictors deemed important had low documentation rates. Educational interventions and simple assessment tools may help to increase documentation rates of several suicide predictors in busy clinical settings.
Repetitive Transcranial Magnetic Stimulation and Treatment-emergent Mania and Hypomania: A Review of the Literature
Authors: RACHID FADY 
Published: March 2017

Background:
This review focuses on treatment-emergent mania/hypomania (TEM) associated with repetitive transcranial magnetic stimulation (rTMS).

Methods:
English-language studies involving possible rTMS-induced mania/hypomania published between 1966 and 2015 were retrieved through a Medline search using the search terms mania, hypomania, mixed affective state, treatment-emergent, repetitive transcranial magnetic stimulation, and rTMS. Fifteen case series and controlled studies describing TEM associated with rTMS treatment have been published involving 24 individuals, most of whom were diagnosed with either bipolar I or II disorder or major depressive disorder.

Results:
rTMS has been shown to possibly induce manic or hypomanic episodes in patients with depression, who are sometimes also taking antidepressants. Both high-frequency and low-frequency rTMS with different stimulus parameters may be associated with TEM in both males and females.

Conclusions:
Given these findings, it is highly recommended that patients with bipolar disorder who are experiencing a depressive episode be prescribed a mood stabilizer and that patients diagnosed with major depressive disorder be reevaluated to consider the possibility that they might have bipolar disorder, before rTMS treatment is initiated. If TEM occurs, discontinuation of rTMS should be considered, while continuing mood-stabilizing medications. Further research is needed concerning the underlying neurobiological mechanisms and epidemiologic characteristics of TEM associated with rTMS.
Brief Report: Progression of Atherosclerosis in HIV-Infected Individuals—Prospective Data From an Asian Cohort
Authors: Lui Grace , Ma Ronald C. W. , Chook Ping , Wong Chun-Kwok , Tam Claudia H. T. , Chan Michael H. M. , Lee Shui-Shan , Wong Rity Y. K. , Cheung Catherine S. K. , Choi Kin-Wing , Leung Ping-Chung , Wong Ka-Hing , Chan Kenny C. W. , Lee Nelson 
Published: March 2017

Background:
The magnitude and risk factors of progression of atherosclerosis in Asian HIV-infected individuals were unknown. This study aimed to evaluate: (1) the rate of progression of atherosclerosis in HIV-infected individuals, and (2) metabolic and inflammatory parameters that may predict atherosclerosis progression in HIV-infected individuals in an Asian cohort.

Setting:
A prospective, longitudinal study was performed among adults attending an HIV Metabolic clinic in Hong Kong.

Methods:
Carotid intima media thickness (cIMT) was measured at baseline and 24 months. Body composition, metabolic, and inflammatory biomarkers [including homeostasis model assessment of insulin resistance, LDL (low-density lipoprotein) cholesterol particle size, high-sensitive C reactive protein, adiponectin] associated with cIMT change were analyzed; their predictive performances were estimated using receiver operating characteristic analyses.

Results:
Sixty-one HIV-infected individuals (mean ± SD age 49.8 ± 11.4 years, 89% men, 97% Chinese, diabetes 39%, hypertension 30%, and dyslipidemia 85%) were recruited. Annual rate of change of cIMT was +0.0075 (0.0000–0.0163) mm/yr, and 19% developed new plaque at 24 months. Two patients died during the study period, 1 because of sudden cardiac death. Using receiver operating characteristic analyses, combination of lower limb fat percentage, LDL cholesterol subclass pattern B, and lower adiponectin level, but not Framingham score, predicted greater cIMT progression in HIV-infected individuals.

Conclusions:
Asian HIV-infected individuals had atherosclerosis progression. Limb fat percentage, LDL cholesterol particle size, and adiponectin level may identify at-risk Asian HIV-infected individuals for early intervention.
Temporal Trends and Rural-Urban Differences in Hospital Length of Stay for Alzheimer Disease and Related Disorders
Authors: Opoku Samuel T.Y. , Apenteng Bettye A. , Lin Ge 
Published: March 2017

Objectives:
The aim of this study was to assess rural-urban differences and temporal trends in length of inpatient stay among patients diagnosed with Alzheimer disease and related dementia (ADRD).

Materials and Methods:
The study sample comprised 27,313 ADRD and 27,313 matched non-ADRD inpatient discharges from Nebraska hospitals from 2005 to 2011. Descriptive statistics and multivariable regression models were used to assess rural-urban variations and temporal trends in length of stay (LOS).

Results:
LOS was found to be similar for ADRD and non–ADRD-related hospitalizations. No rural-urban differences in LOS were observed for ADRD-related hospitalizations. However, there was a temporal decline in LOS for ADRD-related hospitalizations.

Conclusions:
LOS for ADRD-related hospitalizations was found to be influenced mostly by patient-level demographic and clinical factors. Hospital-level factors were not associated with LOS.
What is a vector?
Authors: Wilson Anthony James , Morgan Eric René , Booth Mark , Norman Rachel , Perkins Sarah Elizabeth , Hauffe Heidi Christine , Mideo Nicole , Antonovics Janis , McCallum Hamish , Fenton Andy 
Published: March 2017

Many important and rapidly emerging pathogens of humans, livestock and wildlife are ‘vector-borne’. However, the term ‘vector’ has been applied to diverse agents in a broad range of epidemiological systems. In this perspective, we briefly review some common definitions, identify the strengths and weaknesses of each and consider the functional differences between vectors and other hosts from a range of ecological, evolutionary and public health perspectives. We then consider how the use of designations can afford insights into our understanding of epidemiological and evolutionary processes that are not otherwise apparent. We conclude that from a medical and veterinary perspective, a combination of the ‘haematophagous arthropod’ and ‘mobility’ definitions is most useful because it offers important insights into contact structure and control and emphasizes the opportunities for pathogen shifts among taxonomically similar species with similar feeding modes and internal environments. From a population dynamics and evolutionary perspective, we suggest that a combination of the ‘micropredator’ and ‘sequential’ definition is most appropriate because it captures the key aspects of transmission biology and fitness consequences for the pathogen and vector itself. However, we explicitly recognize that the value of a definition always depends on the research question under study.This article is part of the themed issue ‘Opening the black box: re-examining the ecology and evolution of parasite transmission’.
Host species exploitation and discrimination by animal parasites
Authors: Forbes Mark R. , Morrill André , Schellinck Jennifer 
Published: March 2017

Parasite species often show differential fitness on different host species. We developed an equation-based model to explore conditions favouring host species exploitation and discrimination. In our model, diploid infective stages randomly encountered hosts of two species; the parasite's relative fitness in exploiting each host species, and its ability to discriminate between them, was determined by the parasite's genotype at two independent diallelic loci. Relative host species frequency determined allele frequencies at the exploitation locus, whereas differential fitness and combined host density determined frequency of discrimination alleles. The model predicts instances where populations contain mixes of discriminatory and non-discriminatory infective stages. Also, non-discriminatory parasites should evolve when differential fitness is low to moderate and when combined host densities are low, but not so low as to cause parasite extinction. A corollary is that parasite discrimination (and host-specificity) increases with higher combined host densities. Instances in nature where parasites fail to discriminate when differential fitness is extreme could be explained by one host species evolving resistance, following from earlier selection for parasite non-discrimination. Similar results overall were obtained for haploid extensions of the model. Our model emulates multi-host associations and has implications for understanding broadening of host species ranges by parasites.
This article is part of the themed issue ‘Opening the black box: re-examining the ecology and evolution of parasite transmission’.
Fast-killing parasites can be favoured in spatially structured populations
Authors: Leggett Helen C. , Wild Geoff , West Stuart A. , Buckling Angus 
Published: March 2017

It is becoming increasingly clear that the evolution of infectious disease is influenced by host population structure. Theory predicts that parasites should be more ‘prudent’—less transmissible—in spatially structured host populations. However, here we (i) highlight how low transmission, the phenotype being selected for in this in context, may also be achieved by rapacious host exploitation, if fast host exploitation confers a local, within-host competitive advantage and (ii) test this novel concept in a bacteria–virus system. We found that limited host availability and, to a lesser extent, low relatedness favour faster-killing parasites with reduced transmission. By contrast, high host availability and high relatedness favour slower-killing, more transmissible parasites. Our results suggest high, rather than low, virulence may be selected in spatially structured host–parasite communities where local competition and hence selection for a within-host fitness advantage is high.This article is part of the themed issue ‘Opening the black box: re-examining the ecology and evolution of parasite transmission’.
De novomutations in regulatory elements cause neurodevelopmental disorders
Authors: Short Patrick J. , McRae Jeremy F. , Gallone Giuseppe , Sifrim Alejandro , Won Hyejung , Geschwind Daniel H. , Wright Caroline F. , Firth Helen V. , FitzPatrick David R. , Barrett Jeffrey C. , Hurles Matthew E. ,   on behalf of the DDD study
Published: March 2017

SummaryDe novomutations in hundreds of different genes collectively cause 25-42% of severe developmental disorders (DD). The cause in the remaining cases is largely unknown. The role ofde novomutations in regulatory elements affecting known DD associated genes or other genes is essentially unexplored. We identifiedde novomutations in three classes of putative regulatory elements in almost 8,000 DD patients. Here we show thatde novomutations in highly conserved fetal-brain active elements are significantly and specifically enriched in neurodevelopmental disorders. We identified a significant two-fold enrichment of recurrently mutated elements. We estimate that, genome-wide,de novomutations in fetaLbrain active elements are likely to be causal for 1-3% of patients without a diagnostic coding variant and that only a small fraction (<2%) ofde novomutations in these elements are pathogenic. Our findings represent a robust estimate of the contribution ofde novomutations in regulatory elements to this genetically heterogeneous set of disorders, and emphasise the importance of combining functional and evolutionary evidence to delineate regulatory causes of genetic disorders.
Inferring Within-Host Bottleneck Size: A Bayesian Approach
Authors: Dybowski R. , Restif O. , Price D.J. , Mastroeni P. 
Published: March 2017

AbstractA number of approaches exist for bottleneck-size estimation with respect to within-host bacterial infections; however, some are more appropriate than others under certain circumstances. A Bayesian comparison of several approaches is made in terms of the availability of isogenic multitype bacteria (e.g., WITS), knowledge of post-bottleneck dynamics, and the suitability of dilution with monotype bacteria. The results are summarised by a guiding flowchart.A sampling approach to bottleneck-size estimation is also introduced.
Heterosubtypic cross-reactivity of HA1 antibodies to influenza A, with emphasis on nonhuman subtypes (H5N1, H7N7, H9N2)
Authors: te Beest Dennis E. , Bruin Erwin de , Imholz Sandra , Koopmans Marion , Boven Michiel van 
Published: March 2017

AbstractEpidemics of influenza A vary greatly in size and age distribution of cases, and this variation i attributed to varying levels of pre-existing immunity. Recent studies have shown that antibody mediated immune responses are more cross-reactive than previously believed, and shape patterns of humoral immunity to influenza A viruses over long periods. Here we quantify antibody responses to the hemagglutinin subunit 1 (HA1) across a range of subtypes using protein microarray analysis of cross-sectional serological surveys carried out in the Netherlanc before and after the A/2009 (H1N1) pandemic. We find significant associations of responses, both within and between subtypes. Interestingly, substantial overall reactivity is observed to HA1 of avian H7N7 and H9N2 viruses. Seroprevalence of H7N7 correlates with antibody titer to A/1968 (H3N2), and is highest in persons born between 1954 and 1969. Seroprevalence of H9N2 is high across all ages, and correlates strongly with A/1957 (H2N2). This correlation is most pronounced in A/2009 (H1N1) infected persons born after 1968 who have never encountered A/1957 (H2N2)-like viruses. We conclude that heterosubtypic antibody crossreactivity, both between human subtypes and between human and nonhuman subtypes, is common in the human population.
Deep brain fluorescence imaging with minimally invasive ultra-thin optical fibers
Authors: Ohayon Shay , Caravaca-Aguirre Antonio M. , Piestun Rafael , DiCarlo James J. 
Published: March 2017

AbstractA major open challenge in neuroscience is the ability to measure and perturb neural activity in vivo from well-defined neural sub-populations at cellular resolution anywhere in the brain. However, limitations posed by scattering and absorption prohibit non-invasive (surface) multiphoton approaches1,2for deep (>2mm) structures, while Gradient Refreactive Index (GRIN) endoscopes2–4are thick and cause significant damage upon insertion. Here, we demonstrate a novel microendoscope to image neural activity at arbitrary depths via an ultrathin multimode optical fiber (MMF) probe that is 5-10X thinner than commercially available microendoscopes. We demonstrate micron-scale resolution, multispectral and volumetric imaging. In contrast to previous approaches1,5–8we show that this method has an improved acquisition speed that is sufficient to capture rapid neuronal dynamics in-vivo in rodents expressing a genetically encoded calcium indicator. Our results emphasize the potential of this technology in neuroscience applications and open up possibilities for cellular resolution imaging in previously unreachable brain regions.