bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral manifestations in Kindler syndrome: case report and discussion of literature findings
Authors: Barbosa Nathalia Mocellin , Visioli Fernanda , Martins Manoela Domingues , Martins Marco Antônio Trevizani , Munerato Maria Cristina 
Published: January 2016

ABSTRACTKindler syndrome is a rare genetic disorder showing some predominant clinical manifestations, for example, trauma‐induced blisters, progressive poikiloderma, skin atrophy, and photosensitivity. Oral manifestations are not commonly described and can be often misdiagnosed. This report describes the case of a female patient diagnosed with Kindler syndrome showing the classical clinical features affecting the skin, in addition to oral lesions manifesting as keratotic plaques and ulcers affecting the buccal mucosa, floor of the mouth, alveolar ridge, hard palate, and soft palate. An incisional biopsy was performed to confirm the diagnostic hypothesis of an autoimmune lesion possibly related with the syndrome. Knowledge about the possible manifestations of the Kindler syndrome is important to improve its management.
Do Frames Emphasizing Harm to Age and Racial‐Ethnic Groups Reduce Support for Voter ID Laws?*
Authors: Wilson David C. , Brewer Paul R. 
Published: January 2016

ObjectivesResearch suggests that issue frames emphasizing how voter ID laws might harm eligible voters can influence opinions toward the laws. This study examines the effects of frames emphasizing harm to specific groups of eligible voters—namely, elderly, college‐aged, African‐American, and Hispanic voters—on public support for such laws.MethodsWe analyze data from question wording experiments included in two state polls.ResultsWe replicate the finding that emphasizing the harmful effects of the laws on eligible voters reduces support. We also find that a frame emphasizing harm to African Americans produces an additional reduction in support. Emphasizing harm to other specific groups (the elderly, college‐aged, or Hispanics) does not produce discernible effects beyond the general framing effect. Within group analyses by race, age and political predispositions reveal additional patterns of effects.ConclusionThe results suggest political communication about specific groups can shift public opinion for voter ID laws.
Variation in intraoperative and postoperative red blood cell transfusion in pediatric surgery
Authors: Stey Anne M. , Vinocur Charles D. , Moss R. Lawrence , Hall Bruce L. , Cohen Mark E. , Kraemer Kari , Ko Clifford Y. , Kenney Brian D. 
Published: January 2016

BACKGROUNDIntraoperative and postoperative red blood cell (RBC) transfusions are relatively frequent events tracked in the American College of Surgeons' National Surgical Quality Improvement Program‐Pediatric (ACS‐NSQIP‐P). This study sought to quantify variation in RBC transfusion practices among hospitals.STUDY DESIGN AND METHODSThis is an observational study of children older than 28 days who underwent a general, neurologic, urologic, otolaryngologic, plastic, or orthopedic operation at 50 hospitals in participating in the ACS‐NSQIP‐P during 2011 to 2012. The primary outcome was whether or not a RBC transfusion was administered from incision time to 72 hours postoperatively. Transfusions of fresh‐frozen plasma, cryoprecipitate, and platelets were excluded from data abstraction due the rarity of their administration. A multivariate hierarchical risk‐adjustment model estimated the risk‐adjusted hospital RBC transfusion odds ratio (OR) and designated hospitals by transfusion practice.RESULTSThe mean RBC transfusion rate was 1.5%. Five preoperative variables were associated with greater than threefold increased odds of having an intraoperative or postoperative RBC transfusion; young age; 29 days to 1 year (OR, 5.9; p < 0.001) and 1 to 2 years (OR, 3.4; p < 0.001); American Society of Anesthesiologists Class IV (OR, 3.2; p < 0.001); procedure linear risk (OR, 3.1; p < 0.001); preoperative septic shock (OR, 14.5; p < 0.001); and preoperative cardiopulmonary resuscitation (OR, 8.1; p < 0.001). Twenty‐five hospitals had RBC transfusion practices significantly different than risk‐adjusted mean (17 higher and eight lower).CONCLUSIONIntraoperative and postoperative RBC transfusion practices vary widely among hospitals after controlling for patient and procedural characteristics.
Supernatant protein biomarkers of red blood cell storage hemolysis as determined through an absolute quantification proteomics technology
Authors: D'Alessandro Angelo , Dzieciatkowska Monika , Hill Ryan C. , Hansen Kirk C. 
Published: January 2016

BACKGROUNDLaboratory technologies have highlighted the progressive accumulation of the so‐called “storage lesion,” a wide series of alterations to stored red blood cells (RBCs) that may affect the safety and effectiveness of the transfusion therapy. New improvements in the field are awaited to ameliorate this lesion, such as the introduction of washing technologies in the cell processing pipeline. Laboratory studies that have tested such technologies so far rely on observational qualitative or semiquantitative techniques.STUDY DESIGN AND METHODSA state‐of‐the‐art quantitative proteomics approach utilizing quantitative concatamers (QconCAT) was used to simultaneously monitor fluctuations in the abundance of 114 proteins in AS‐3 RBC supernatants (n = 5; 11 time points, including before and after leukoreduction, at 3 hours, on Days 1 and 2, and weekly sampling from Day 7 through Day 42).RESULTSLeukoreduction‐dependent depletion of plasma proteins was observed at the earliest time points. A subset of proteins showed very high linear correlation (r2 > 0.9) not only with storage time, but also with absolute levels of hemoglobin α1 and β, a proxy for RBC hemolysis and vesiculation. Linear regression was performed to describe the temporal relationship between these proteins. Our findings suggest a role for supernatant glyceraldehyde‐3‐phosphate dehydrogenase; peroxiredoxin‐1, ‐2, and ‐6; carbonic anhydrase‐1 and ‐2; selenium binding protein‐1; biliverdin reductase; aminolevulinate dehydratase; and catalase as potential biomarkers of RBC quality during storage.CONCLUSIONA targeted proteomics technology revealed novel biomarkers of the RBC storage lesion and promises to become a key analytical readout for the development and testing of alternative cell processing strategies.
Triplets with neonatal alloimmune thrombocytopenia due to antibodies against human platelet antigen 1a
Authors: Solh Ziad , Breakey Vicky , Murthy Prashanth , Smith James W. , Arnold Donald M. 
Published: January 2016

BACKGROUNDNeonatal alloimmune thrombocytopenia (NAIT) has been reported only rarely in twins and not at all, to our knowledge, in triplets.CASE REPORTNonidentical triplets were born with severe thrombocytopenia. Nadir platelet (PLT) counts were 17 × 109, 12 × 109, and 10 × 109/L. NAIT was confirmed by an incompatibility for human PLT antigen (HPA)−1a and the presence of maternal anti‐HPA‐1a. The maternal genotype was HPA‐1bb and the paternal genotype was HPA‐1aa; thus, all children were affected.RESULTSPLT counts for each infant improved with the administration of random‐donor PLT transfusions. All three infants also received intravenous immunoglobulin. None had major bleeding. A small isolated subependymal hemorrhage was found incidentally in one infant; this remained stable on repeat imaging.CONCLUSIONSThis is the first report of triplets with NAIT. Anti‐HPA‐1a is sufficiently potent to affect three infants simultaneously. Random‐donor PLTs were effective in improving PLT counts in all three infants.
Fighting the Monster: Applying the Host Damage Framework to Human Central Nervous System Infections
Authors: Panackal Anil A. , Williamson Kim C. , van de Beek Diederik , Boulware David R. , Williamson Peter R. 
Published: January 2016

ABSTRACT
The host damage-response framework states that microbial pathogenesis is a product of microbial virulence factors and collateral damage from host immune responses. Immune-mediated host damage is particularly important within the size-restricted central nervous system (CNS), where immune responses may exacerbate cerebral edema and neurological damage, leading to coma and death. In this review, we compare human host and therapeutic responses in representative nonviral generalized CNS infections that induce archetypal host damage responses: cryptococcal menigoencephalitis and tuberculous meningitis in HIV-infected and non-HIV-infected patients, pneumococcal meningitis, and cerebral malaria. Consideration of the underlying patterns of host responses provides critical insights into host damage and may suggest tailored adjunctive therapeutics to improve disease outcome.
Human Mesenchymal Stem Cells of Diverse Origins Support Persistent Infection with Kaposi’s Sarcoma-Associated Herpesvirus and Manifest Distinct Angiogenic, Invasive, and Transforming Phenotypes
Authors: Lee Myung-Shin , Yuan Hongfeng , Jeon Hyungtaek , Zhu Ying , Yoo Seungmin , Shi Songtao , Krueger Brian , Renne Rolf , Lu Chun , Jung Jae U. , Gao Shou-Jiang 
Published: January 2016

ABSTRACT

Kaposi’s sarcoma (KS), a highly angiogenic and invasive tumor often involving different organ sites, including the oral cavity, is caused by infection with Kaposi’s sarcoma-associated herpesvirus (KSHV). Diverse cell markers have been identified on KS tumor cells, but their origin remains an enigma. We previously showed that KSHV could efficiently infect, transform, and reprogram rat primary mesenchymal stem cells (MSCs) into KS-like tumor cells. In this study, we showed that human primary MSCs derived from diverse organs, including bone marrow (MSCbm), adipose tissue (MSCa), dental pulp, gingiva tissue (GMSC), and exfoliated deciduous teeth, were permissive to KSHV infection. We successfully established long-term cultures of KSHV-infected MSCa, MSCbm, and GMSC (LTC-KMSCs). While LTC-KMSCs had lower proliferation rates than the uninfected cells, they expressed mixtures of KS markers and displayed differential angiogenic, invasive, and transforming phenotypes. Genetic analysis identified KSHV-derived microRNAs that mediated KSHV-induced angiogenic activity by activating the AKT pathway. These results indicated that human MSCs could be the KSHV target cells
in vivo
and established valid models for delineating the mechanism of KSHV infection, replication, and malignant transformation in biologically relevant cell types.

IMPORTANCE
Kaposi’s sarcoma is the most common cancer in AIDS patients. While KSHV infection is required for the development of Kaposi’s sarcoma, the origin of KSHV target cells remains unclear. We show that KSHV can efficiently infect human primary mesenchymal stem cells of diverse origins and reprogram them to acquire various degrees of Kaposi’s sarcoma-like cell makers and angiogenic, invasive, and transforming phenotypes. These results indicate that human mesenchymal stem cells might be the KSHV target cells and establish models for delineating the mechanism of KSHV-induced malignant transformation.
The Adenovirus E4-ORF3 Protein Stimulates SUMOylation of General Transcription Factor TFII-I to Direct Proteasomal Degradation
Authors: Bridges Rebecca G. , Sohn Sook-Young , Wright Jordan , Leppard Keith N. , Hearing Patrick 
Published: January 2016

ABSTRACT
Modulation of host cell transcription, translation, and posttranslational modification processes is critical for the ability of many viruses to replicate efficiently within host cells. The human adenovirus (Ad) early region 4 open reading frame 3 (E4-ORF3) protein forms unique inclusions throughout the nuclei of infected cells and inhibits the antiviral Mre11-Rad50-Nbs1 DNA repair complex through relocalization. E4-ORF3 also induces SUMOylation of Mre11 and Nbs1. We recently identified additional cellular targets of E4-ORF3 and found that E4-ORF3 stimulates ubiquitin-like modification of 41 cellular proteins involved in a wide variety of processes. Among the proteins most abundantly modified in an E4-ORF3-dependent manner was the general transcription factor II–I (TFII-I). Analysis of Ad-infected cells revealed that E4-ORF3 induces TFII-I relocalization and SUMOylation early during infection. In the present study, we explored the relationship between E4-ORF3 and TFII-I. We found that Ad infection or ectopic E4-ORF3 expression leads to SUMOylation of TFII-I that precedes a rapid decline in TFII-I protein levels. We also show that E4-ORF3 is required for ubiquitination of TFII-I and subsequent proteasomal degradation. This is the first evidence that E4-ORF3 regulates ubiquitination. Interestingly, we found that E4-ORF3 modulation of TFII-I occurs in diverse cell types but only E4-ORF3 of Ad species C regulates TFII-I, providing critical insight into the mechanism by which E4-ORF3 targets TFII-I. Finally, we show that E4-ORF3 stimulates the activity of a TFII-I-repressed viral promoter during infection. Our results characterize a novel mechanism of TFII-I regulation by Ad and highlight how a viral protein can modulate a critical cellular transcription factor during infection.

IMPORTANCE
Adenovirus has evolved a number of mechanisms to target host signaling pathways in order to optimize the cellular environment during infection. E4-ORF3 is a small viral protein made early during infection, and it is critical for inactivating host antiviral responses. In addition to its ability to capture and reorganize cellular proteins, E4-ORF3 also regulates posttranslational modifications of target proteins, but little is known about the functional consequences of these modifications. We recently identified TFII-I as a novel target of E4-ORF3 that is relocalized into dynamic E4-ORF3 nuclear structures and subjected to E4-ORF3-mediated SUMO modification. Here, we show that TFII-I is targeted by E4-ORF3 for ubiquitination and proteasomal degradation and that E4-ORF3 stimulates gene expression from a TFII-I-repressed viral promoter. Our findings suggest that the specific targeting of TFII-I by E4-ORF3 is a mechanism to inactivate its antiviral properties. These studies provide further insight into how E4-ORF3 functions to counteract host antiviral responses.
Expression and Role of the ErbB3-Binding Protein 1 in Acute Myelogenous Leukemic Cells
Authors: Nguyen Le Xuan Truong , Zhu Li , Lee Yunqin , Ta Lynn , Mitchell Beverly S. 
Published: January 2016

Abstract
Purpose: The ErbB3-binding protein 1 (Ebp1) has been implicated in diverse cancers as having either oncogenic or tumor suppressor activities. The present study was undertaken to determine the effects of Ebp1 expression in AML cells and to determine the mechanisms by which Ebp1 promotes cell proliferation in these cells.
Experimental Design: The expression of Ebp1 was studied in mononuclear cells obtained from the peripheral blood of 54 patients with AML by Western blot analysis. The effects of Ebp1 expression on proliferating cell nuclear antigen (PCNA) expression and cell proliferation was measured using Western blot analysis, immunoprecipitation, in vitro ubiquitination, and colony-forming assays. The role of Ebp1 in promoting rRNA synthesis and cell proliferation was evaluated by measuring the level of pre-rRNA and the recruitment of Pol I to rDNA.
Results: Ebp1 is highly expressed in acute myelogenous leukemia (AML) cells and regulates the level of ribosomal RNA (rRNA) synthesis by binding to RNA Polymerase I (Pol I) and enhancing the formation of the Pol I initiation complex. Ebp1 also increases the stability of PCNA protein by preventing its interaction with Mdm2, for which it is a substrate.
Conclusions: These results demonstrate an important role of Ebp1 in promoting cell proliferation in AML cells through the regulation of both rRNA synthesis and PCNA expression. Clin Cancer Res; 22(13); 3320–7. ©2016 AACR.
Dabigatran Versus Warfarin for Atrial Fibrillation in Real-World Clinical Practice
Authors: Romanelli Robert J. , Nolting Laura , Dolginsky Marina , Kym Eunice , Orrico Kathleen B. 
Published: January 2016

Background—
Trial data for the benefits and risks of dabigatran versus warfarin in the treatment of nonvalvular atrial fibrillation are lacking. We sought to review real-world observational evidence for the comparative effectiveness and safety of these agents.

Methods and Results—

A systematic search of multiple databases was conducted from first available date to March 10, 2015 for longitudinal, observational studies comparing dabigatran with warfarin. Two reviewers evaluated studies for eligibility and extracted hazard ratios for ischemic stroke and gastrointestinal and intracranial bleeding. hazard ratios were pooled using random-effects meta-analysis. Metaregression was performed to assess treatment-effect heterogeneity. We identified 232 unique citations. Seven retrospective cohort studies met study eligibility criteria, with 348 750 patients and a mean follow-up of 2.2 years. In pooled analyses, dabigatran-150 mg was not superior to warfarin in preventing stroke (hazard ratio, 0.92; 95% confidence interval, 0.84–1.01;
P
=0.066), but had a significantly lower hazard of intracranial bleeding (0.44; 0.34–0.59;
P
<0.001). Dabigatran-150 mg had a significantly greater hazard of gastrointestinal bleeding than warfarin (1.23; 1.01–1.50;
P
=0.041), which was potentiated in studies of older (elderly) versus younger populations (median/mean age, ≥75 versus <75 years; β=1.53; 95% confidence interval, 1.10–2.14;
P
=0.020).

Conclusions—
In real-world clinical practice, dabigatran is comparable with warfarin in preventing ischemic stroke among patients with nonvalvular atrial fibrillation. However, dabigatran is associated with a lower risk for intracranial bleeding relative to warfarin, but—particularly among the elderly—a greater risk for gastrointestinal bleeding. Bleeding outcomes from observational studies are consistent with those from the pivotal Randomized Evaluation of Long-Term Anticoagulation Therapy trial.
Herpesvirus Infections and Childhood Arterial Ischemic Stroke
Authors: Elkind Mitchell S. V. , Hills Nancy K. , Glaser Carol A. , Lo Warren D. , Amlie-Lefond Catherine , Dlamini Nomazulu , Kneen Rachel , Hod Eldad A. , Wintermark Max , deVeber Gabrielle A. , Fullerton Heather J. 
Published: January 2016

Background—
Epidemiological studies demonstrate that childhood infections, including varicella zoster virus, are associated with an increased risk of arterial ischemic stroke (AIS). Other herpesviruses have been linked to childhood AIS in case reports. We sought to determine whether herpesvirus infections, which are potentially treatable, increase the risk of childhood AIS.

Methods and Results—

We enrolled 326 centrally confirmed cases of AIS and 115 stroke-free controls with trauma (29 days to 18 years of age) with acute blood samples (≤3 weeks after stroke/trauma); cases had convalescent samples (7–28 days later) when feasible. Samples were tested by commercial enzyme-linked immunosorbent assay kits for immunoglobulin M/immunoglobulin G antibodies to herpes simplex virus 1 and 2, cytomegalovirus, Epstein-Barr virus, and varicella zoster virus. An algorithm developed a priori classified serological evidence of past and acute herpesvirus infection as dichotomous variables. The median (quartiles) age was 7.7 (3.1–14.3) years for cases and 10.7 (6.9–13.2) years for controls (
P
=0.03). Serological evidence of past infection did not differ between cases and controls. However, serological evidence of acute herpesvirus infection doubled the odds of childhood AIS, even after adjusting for age, race, and socioeconomic status (odds ratio, 2.2; 95% confidence interval, 1.2–4.0;
P
=0.007). Among 187 cases with acute and convalescent blood samples, 85 (45%) showed evidence of acute herpesvirus infection; herpes simplex virus 1 was found most often. Most infections were asymptomatic.

Conclusions—
Herpesviruses may act as a trigger for childhood AIS, even if the infection is subclinical. Antivirals like acyclovir might have a role in the prevention of recurrent stroke if further studies confirm a causal relationship.
Consumption of Caffeinated Products and Cardiac Ectopy
Authors: Dixit Shalini , Stein Phyllis K. , Dewland Thomas A. , Dukes Jonathan W. , Vittinghoff Eric , Heckbert Susan R. , Marcus Gregory M. 
Published: January 2016

Background

Premature cardiac contractions are associated with increased morbidity and mortality. Though experts associate premature atrial contractions (
PAC
s) and premature ventricular contractions (
PVC
s) with caffeine, there are no data to support this relationship in the general population. As certain caffeinated products may have cardiovascular benefits, recommendations against them may be detrimental.

Methods and Results

We studied Cardiovascular Health Study participants with a baseline food frequency assessment, 24‐hour ambulatory electrocardiography (Holter) monitoring, and without persistent atrial fibrillation. Frequencies of habitual coffee, tea, and chocolate consumption were assessed using a picture‐sort food frequency survey. The main outcomes were
PAC
s/h and
PVC
s/hour. Among 1388 participants (46% male, mean age 72 years), 840 (61%) consumed ≥1 caffeinated product per day. The median numbers of
PAC
s and
PVC
s/h and interquartile ranges were 3 (1–12) and 1 (0–7), respectively. There were no differences in the number of
PAC
s or
PVC
s/h across levels of coffee, tea, and chocolate consumption. After adjustment for potential confounders, more frequent consumption of these products was not associated with ectopy. In examining combined dietary intake of coffee, tea, and chocolate as a continuous measure, no relationships were observed after multivariable adjustment: 0.48% fewer
PAC
s/h (95%
CI
−4.60 to 3.64) and 2.87% fewer
PVC
s/h (95%
CI
−8.18 to 2.43) per 1‐serving/week increase in consumption.

Conclusions
In the largest study to evaluate dietary patterns and quantify cardiac ectopy using 24‐hour Holter monitoring, we found no relationship between chronic consumption of caffeinated products and ectopy.
Prognostic Significance of Hyperglycemia in Acute Intracerebral Hemorrhage
Authors: Saxena Anubhav , Anderson Craig S. , Wang Xia , Sato Shoichiro , Arima Hisatomi , Chan Edward , Muñoz-Venturelli Paula , Delcourt Candice , Robinson Thompson , Stapf Christian , Lavados Pablo M. , Wang Jiguang , Neal Bruce , Chalmers John , Heeley Emma ,   for the INTERACT2 Investigators
Published: January 2016

Background and Purpose—
We aimed to determine associations of baseline blood glucose and diabetes mellitus with clinical outcomes in participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2).

Methods—
INTERACT2 was an international prospective, open, blinded end point, randomized controlled trial of 2839 patients with spontaneous intracerebral hemorrhage (<6 hours) and elevated systolic blood pressure randomly assigned to intensive (target systolic blood pressure <140 mm Hg) or guideline-based (systolic blood pressure <180 mm Hg) BP management. Associations of hyperglycemia at presentation (>6.5 mmol/L) and combined and separate poor outcomes of death and major disability (scores of 3–6, 3–5, and 6, respectively, on the modified Rankin scale) at 90 days were determined in logistic regression models.

Results—

In 2653 patients with available data, there were 1348 (61%) with hyperglycemia and 292 (11%) with diabetes mellitus. Associations of baseline blood glucose and poor outcome were strong and near continuous. After adjustment for baseline variables, the highest fourth (7.9–25.0 mmol/L) of blood glucose was significantly associated with combined poor outcome (adjusted odds ratio 1.35, 95% confidence interval 1.01–1.80;
P
trend 0.015). Diabetes mellitus also predicted poor outcome (adjusted odds ratio 1.46, 95% confidence interval 1.05–2.02;
P
=0.023), though more important for residual disability than death on separate analysis.

Conclusions—
Hyperglycemia and diabetes mellitus are independent predictors of poor outcome in patients with predominantly mild to moderate severity of intracerebral hemorrhage. These data support guideline recommendations for good glycemic control in patients with intracerebral hemorrhage.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00716079.