bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noninvasive Blood Pressure Monitoring and Electrocardiography
Authors: Langhan Melissa , Wolf Seth 
Published: January 2019

Abstract
There is a lack of data about the benefits of cardiovascular monitoring with continuous 3-lead electrocardiography (ECG) and intermittent noninvasive cuff blood pressure (BP) during procedural sedation and analgesia (PSA) in the pediatric population. However, these two safe modalities are important for patients during higher levels of PSA because of the risk of rare life-threatening conditions and to help identify possible medication side effects and drug interactions of common sedative medications. These monitoring modalities can also aid in determining the adequacy of sedation. It is generally accepted that a baseline determination of heart rate and BP should be obtained prior to any sedative administration. With deeper levels of sedation and throughout recovery, continuous 3-lead ECG and intermittent BP monitoring are recommended, in addition to other modalities such as pulse oximetry and capnography, to monitor the safety of the patient.
Some Implications for Policy
Authors: Dohrenwend Bruce P. 
Published: January 2019

Abstract
This chapter underlines research findings from previous chapters that provide useful background for developing future policies for post-Vietnam wars. A major policy recommendation is prioritizing procedures for reducing harm by the U.S. military to civilians and prisoners when fighting wars amongst the people. Research findings point to the importance of keeping the most vulnerable soldiers out of severe combat and other highly stressful assignments. This chapter supports policies designed to provide returning veterans with programs that increase the relative importance of their post-war activities compared to their war-time experiences. Other recommendations advocate equalizing the assignment to combat units of individuals from majority and minority racial-ethnic groups and providing help to the family members of veterans with chronic PTSD. For the benefit of individuals serving in our military, it urges policy makers to commit our military forces to fight only in just wars that merit popular support.
Attitudes matter—welfare work and migration in Sweden
Authors: Schütze Carolin 
Published: January 2019

AbstractThis paper investigates the factors that influence Swedish welfare workers’ attitudes towards migrants and how these attitudes are associated with their encounters with migrant users. Due to increased migration over the last decade, Sweden is now considered an immigrant nation. Migrants with the right to reside in Sweden are included within the larger welfare system. This paper argues that preconceived notions about migrants can affect the welfare services that they receive. Results from an online survey with a sample of 1,319 welfare practitioners reveal that welfare workers’ attitudes play a significant role when it comes to how they perceive their encounters with migrant users. The findings demonstrate that more favourable attitudes towards migrants were predicted mainly by personal contact with migrants and that different organisational contexts result in different experiences of encounters with migrant users. Less favourable attitudes towards migrants were primarily predicted by a strong ethnic national identity. Most importantly, the findings show that welfare workers’ who have more favourable attitudes towards migrants are less likely to perceive their encounters with migrant users as difficult. This paper contributes to welfare and migration research in two ways. First, this study provides additional support for previous claims from qualitative research by supporting the assumptions that preconceived negative ideas about migrants have meaning for practical welfare work. Second, this paper integrates two streams of research—attitude formation theory and street-level bureaucracy theory—thus expanding existing assumptions about what determines welfare practices with migrants.
Skull Base Manifestations of Erdheim-Chester Disease: A Case Series and Systematic Review
Authors: Marinelli John P , Peters Pierce A , Vaglio Augusto , Van Gompel Jamie J , Lane John I , Carlson Matthew L 
Published: January 2019

Abstract

BACKGROUND
Erdheim-Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis. Up to 50% of patients develop central nervous system involvement, and a subset of these patients can present with isolated tumor-like masses.

OBJECTIVE
To describe the skull base manifestations of ECD with an emphasis on aspects most pertinent to surgeons who may be referred such patients for primary evaluation.

METHODS
Scopus, Web of Science, and PubMed were searched from database inception to May 1, 2018 for articles reporting skull base ECD. An institutional retrospective analysis of all patients treated at the authors’ institution since January 1, 1996 was also performed to supplement these data.

RESULTS
Of 465 retrieved articles, 18 studies totaling 20 patients met inclusion criteria. Institutional review identified an additional 7 patients. Collectively, the median age at diagnosis was 49 yr (interquartile range, 42-58) with a 4:1 male-to-female ratio. Patients frequently presented with diplopia (48%), headache (30%), dysarthria (22%), and vertigo or imbalance (22%), though trigeminal hypesthesia (11%), facial nerve paresis (7%), hearing loss (7%), and trigeminal neuralgia (7%) were also observed. ECD commonly mimicked meningioma (33%), trigeminal schwannoma (8%), neurosarcoidosis (8%), and skull base lymphoma (8%).

CONCLUSION
Discrete skull base lesions frequently mimic more common pathology such as meningioma or cranial nerve schwannomas. Medical therapy comprises the initial treatment for symptomatic skull base disease. Surgical resection is not curative and the utility of surgical intervention is largely limited to biopsy to establish diagnosis and/or surgical debulking to relieve mass effect.
Safety and immunogenicity of tetanus/diphtheria vaccination in patients with rheumatic diseases—a prospective multi-centre cohort study
Authors: Bühler Silja , Jaeger Veronika Katharina , Adler Sabine , Bannert Bettina , Brümmerhoff Carolin , Ciurea Adrian , Distler Oliver , Franz Juliane , Gabay Cem , Hagenbuch Niels , Herzog Christian , Hasler Paul , Kling Kerstin , Kyburz Diego , Müller Rüdiger , Nissen Michael John , Siegrist Claire-Anne , Villiger Peter Matthias , Walker Ulrich A. , Hatz Christoph 
Published: January 2019

Abstract

Objectives
We aimed to assess the safety and immunogenicity of a diphtheria/tetanus vaccine booster dose in three different patient groups with rheumatic diseases on a variety of immunosuppressive/immunomodulatory medications compared with healthy controls (HCs).

Methods
We conducted a multi-centre prospective cohort study in Switzerland. We enrolled patients with RA, axial SpA/PsA, vasculitis (Behçet’s disease, ANCA-associated vasculitis) and HCs. Diphtheria/tetanus vaccination was administered according to the Swiss vaccination recommendations. Blood samples were drawn before vaccination, and 1 month and 3 months afterwards. Antibody concentrations against vaccine antigens were measured by ELISA. Immunogenicity was compared between patient and medication groups. A mixed model was applied for multivariate analysis. Missing data were dealt with using multiple imputation.

Results
Between January 2014 and December 2015, we enrolled 284 patients with rheumatic diseases (131 RA, 114 SpA/PsA, 39 vasculitis) and 253 HCs. Of the patients, 89% were on immunosuppressive/immunomodulatory medication. Three months post-vaccination 100% of HCs vs 98% of patients were protected against tetanus and 84% vs 73% against diphtheria. HCs and SpA/PsA patients had significantly higher responses than RA and vasculitis patients. Assessing underlying diseases and medications in a multivariate model, rituximab was the only factor negatively influencing tetanus immunogenicity, whereas only MTX treatment had a negative influence on diphtheria antibody responses. No vaccine-related serious adverse events were recorded.

Conclusion
Diphtheria/tetanus booster vaccination was safe. Tetanus vaccination was immunogenic; the diphtheria component was less immunogenic. Vaccine responses were blunted by rituximab and MTX.

Trial registration
ClinicalTrials.gov, http://clinicaltrials.gov, Identifier: NCT01947465.
Overcoming ibrutinib resistance by targeting phosphatidylinositol-3-kinase signaling in diffuse large B-cell lymphoma
Authors: Jain Neeraj , Havranek Ondrej , Singh Ram Kumar , Khashab Tamer , Shirazi Fazal , Sehgal Lalit , Samaniego Felipe 
Published: January 2019

AbstractDiffuse large B-cell lymphoma is the most common subtype of non-Hodgkin lymphoma; 40% of patients relapse following a complete response or are refractory to therapy. The activated subtype of diffuse large B-cell lymphoma relies upon B-cell receptor signaling for survival; this signaling can be modulated by the activity of Bruton’s tyrosine kinase. Targeting that kinase with its inhibitor ibrutinib provides a potential therapeutic approach for the activated B-cell subtype of diffuse large B-cell lymphoma. However, non-Hodgkin lymphoma is often resistant to ibrutinib or soon develops resistance after exposure to it. In this study, we explored the development of acquired ibrutinib resistance. After generating three isogenic ibrutinib-resistant diffuse large B-cell lymphoma cell lines, we investigated the deregulated pathways that are associated with colony formation, growth rates, and tumorigenic properties. We found that reduced levels of Bruton’s tyrosine kinase and enhanced phosphatidylinositol 3-kinase/AKT signaling were hallmarks of these ibrutinib-resistant cells. Upregulation of phosphatidylinositol-3-kinase-beta expression in those cells drove resistance and was reversed by the blocking activity of phosphatidylinositol-3-kinase-beta/delta. Treatment with the selective phosphatidylinositol-3-kinase-beta/delta dual inhibitor KA2237 reduced both tumorigenic properties and survival-based phosphatidylinositol-3-kinase/AKT/mTOR signaling of these ibrutinib-resistant cells. Additionally, combining KA2237 with currently available chemotherapeutic agents synergistically inhibited the metabolic growth of these ibrutinib-resistant cells. This study elucidates the compensatory upregulated phosphatidylinositol-3-kinase/AKT axis that emerges in ibrutinib-resistant cells.
Necrotizing Soft Tissue Infections Staphylococcus aureus - but not Streptococcus pyogenes-isolates display high rate of internalization and cytotoxicity toward human myoblasts
Authors: Baude Jessica , Bastien Sylvère , Gillet Yves , Leblanc Pascal , Itzek Andreas , Tristan Anne , Bes Michèle , Duguez Stephanie , Moreau Karen , Diep Binh An , Norrby-Teglund Anna , Henry Thomas , Vandenesch François ,   and INFECT Study Group
Published: January 2019

AbstractNecrotizing Soft Tissue Infections (NSTIs), often reaching the deep fascia and muscle, are mainly caused by group A Streptococcus (GAS) and to a lesser extent by Staphylococcus aureus (SA). Conversely SA is a leading etiologic agent of pyomyositis suggesting that SA could have a specific tropism for the muscle. To assess the pathogenicity of these two bacterial species for muscles cells in comparison to keratinocytes, adhesion and invasion of NSTI-GAS and NSTI-SA were assessed on these cells. Bloodstream infections (BSI) SA isolates and non-invasive coagulase negative Staphylococci (CNS) isolates were used as controls.SA isolates from NSTI and from BSI exhibited stronger internalization into human keratinocytes and myoblasts than CNS or NSTI-GAS. While the median level of SA internalization culminated at 2% in human keratinocytes, it reached over 30% in human myoblasts due to a higher percentage of infected myoblasts (>11%) as compared to keratinocytes (<3%) assessed by transmission electron microscopy. Higher cytotoxicity for myoblasts of NSTI-SA as compared to BSI-SA, was attributed to higher levels of psmα and RNAIII transcripts in NSTI group as compared to hematogenous group. However, the two groups were not discriminated at the genomic level. The cellular basis of high internalization rate in myoblasts was attributed to higher expression of α5β1 integrin in myoblasts as compared to keratinocytes. Major contribution of FnbpAB-integrin α5β1 pathway to internalization was confirmed by isogenic mutants.Our findings suggest the contribution of NSTI-SA severity by its unique propensity to invade and kill myoblasts, a property not shared by NSTI-GAS.ImportanceNecrotizing Soft Tissue Infection (NSTI) is a severe infection caused mainly by group A Streptococcus (GAS) and occasionally by S. aureus (SA); the latter being more often associated with pyomyositis. NSTIs frequently involve the deep fascia and may provoke muscle necrosis. The goal of this study was to determine the tropism and pathogenicity of these two bacterial species for muscle cells. The results revealed a high tropism of SA for myoblasts and myotubes followed by cytotoxicity as opposed to GAS that did not invade these cells. This study uncover a novel mechanism of SA contribution to NSTI with a direct muscle involvement, while in GAS NSTI this is likely indirect, for instance, secondary to vascular occlusion.
The mutational constraint spectrum quantified from variation in 141,456 humans
Authors: Karczewski Konrad J. , Francioli Laurent C. , Tiao Grace , Cummings Beryl B. , Alföldi Jessica , Wang Qingbo , Collins Ryan L. , Laricchia Kristen M. , Ganna Andrea , Birnbaum Daniel P. , Gauthier Laura D. , Brand Harrison , Solomonson Matthew , Watts Nicholas A. , Rhodes Daniel , Singer-Berk Moriel , England Eleina M. , Seaby Eleanor G. , Kosmicki Jack A. , Walters Raymond K. , Tashman Katherine , Farjoun Yossi , Banks Eric , Poterba Timothy , Wang Arcturus , Seed Cotton , Whiffin Nicola , Chong Jessica X. , Samocha Kaitlin E. , Pierce-Hoffman Emma , Zappala Zachary , O’Donnell-Luria Anne H. , Minikel Eric Vallabh , Weisburd Ben , Lek Monkol , Ware James S. , Vittal Christopher , Armean Irina M. , Bergelson Louis , Cibulskis Kristian , Connolly Kristen M. , Covarrubias Miguel , Donnelly Stacey , Ferriera Steven , Gabriel Stacey , Gentry Jeff , Gupta Namrata , Jeandet Thibault , Kaplan Diane , Llanwarne Christopher , Munshi Ruchi , Novod Sam , Petrillo Nikelle , Roazen David , Ruano-Rubio Valentin , Saltzman Andrea , Schleicher Molly , Soto Jose , Tibbetts Kathleen , Tolonen Charlotte , Wade Gordon , Talkowski Michael E. ,   Genome Aggregation Database (gnomAD) Consortium, Neale Benjamin M. , Daly Mark J. , MacArthur Daniel G. 
Published: January 2019

SummaryGenetic variants that inactivate protein-coding genes are a powerful source of information about the phenotypic consequences of gene disruption: genes critical for an organism’s function will be depleted for such variants in natural populations, while non-essential genes will tolerate their accumulation. However, predicted loss-of-function (pLoF) variants are enriched for annotation errors, and tend to be found at extremely low frequencies, so their analysis requires careful variant annotation and very large sample sizes1. Here, we describe the aggregation of 125,748 exomes and 15,708 genomes from human sequencing studies into the Genome Aggregation Database (gnomAD). We identify 443,769 high-confidence pLoF variants in this cohort after filtering for sequencing and annotation artifacts. Using an improved human mutation rate model, we classify human protein-coding genes along a spectrum representing tolerance to inactivation, validate this classification using data from model organisms and engineered human cells, and show that it can be used to improve gene discovery power for both common and rare diseases.
Multicenter Analysis of Dosing Protocols for Sotalol Initiation
Authors: Biswas Minakshi , Levy Andrew , Weber Rachel , Tarakji Khaldoun , Chung Mina , Noseworthy Peter A. , Newton-Cheh Christopher , Rosenberg Michael A. 
Published: January 2019

AbstractSotalol is a Vaughan-Williams Class III antiarrhythmic medication that is commonly used in the management of both atrial and ventricular arrhythmias. Like others in this class, sotalol carries a risk of the potentially lethal arrhythmia torsade de pointes due to its effect of prolonging the QT interval on ECG. For this reason, many centers admit patients for telemetry monitoring during the initial 2-3 days of dosing. However, despite its widespread use, little information is available about the dosing protocols used during this initiation process. In this multicenter investigation, we examine the characteristics of various dose protocols in 213 patients who initiated sotalol over a 4-year period. Of these patients, over 90% were able to successfully complete the dosing regimen (i.e., were discharged on the medication). Significant bradycardia, excessive QT prolongation, and ineffectiveness were the main reasons for failed completion. We found that any dose adjustment was one of the strongest univariate predictors of successful initiation (OR 6.6, 95%CI 1.3 – 32.7, p = 0.021), while initial dose, indication, and resting heart rate or QT interval on baseline ECG did not predict successful initiation. Several predictors of any dose adjustment were identified, and included diabetes, hypertension, presence of pacemaker, heart failure diagnosis, and depressed LV ejection fraction. Using marginal structural models (i.e., inverse probability weighting based on probability of a dose adjustment), we verified that these factors also predicted successful initiation via preventing any dose adjustment, and suggests that consideration of these factors may result in higher likelihood of successful initiation in future investigations. In conclusion, we found that the majority of patients admitted for sotalol initiation are successfully discharged on the medication, often without a single adjustment in the dose. Our findings suggest that several factors predicting lack of dose adjustment could be used clinically to identify patients who could potentially undergo outpatient initiation, although prospective studies are needed to verify this approach.
How lucky was the genetic investigation in the Golden State Killer case?
Authors: Edge Michael (Doc) , Coop Graham 
Published: January 2019

AbstractLong-range forensic familial searching is a new method in forensic genetics. In long-range search, a sample of interest is genotyped at single-nucleotide polymorphism (SNP) markers, and the genotype is compared with a large database in order to find relatives. Here, we perform some simple calculations that explore the basic phenomena that govern long-range searching. Two opposing phenomena—one genealogical and one genetic—govern the success of the search in a database of a given size. As one considers more distant genealogical relationships, any target sample is likely to have more relatives—on average, one has more second cousins than first cousins, and so on. But more distant relatives are also harder to detect genetically. Starting with third cousins, there is an appreciable chance that a given genealogical relationship will not be detectable genetically. Given the balance of these genealogical and genetic phenomena and the size of databases currently queryable by law enforcement, it is likely that most people with substantial recent ancestry in the United States are accessible via long-range search.NoteThis material was originally posted on the Coop lab site on May 7th, 2018, soon after the reporting of the arrest of Joseph DeAngelo in the Golden State Killer case, one of the first high-profile uses of long-range familial search. Subsequently, Erlich et al. (2018) published a detailed analysis in a large empirical dataset along with a theoretical analysis of a model similar to the one we use here, obtaining results broadly consistent with the ones presented here. Because Erlich and colleagues kindly cited this work when describing their model, we thought it would be appropriate to post this material in a venue where it is more easily cited.
Neuroinflammation and functional connectivity in Alzheimer’s disease: interactive influences on cognitive performance
Authors: Passamonti L. , Tsvetanov K.A. , Jones P.S. , Bevan-Jones W.R. , Arnold R. , Borchert R.J. , Mak E. , Su L. , O’Brien J.T. , Rowe J.B. 
Published: January 2019

AbstractNeuroinflammation is a key part of the etio-pathogenesis of Alzheimer’s disease. We test the relationship between neuroinflammation and the disruption of functional connectivity in large-scale networks, and their joint influence on cognitive impairment.We combined [11C]PK11195 positron emission tomography (PET) and resting-state functional magnetic resonance imaging (rs-fMRI) in 28 humans (13 females/15 males) with clinical diagnosis of probable Alzheimer’s disease or mild cognitive impairment with positive PET biomarker for amyloid, and 14 age-, sex-, and education-matched healthy humans (8 females/6 males). Source-based ‘inflammetry’ was used to extract principal components of [11C]PK11195 PET signal variance across all participants. rs-fMRI data were pre-processed via independent component analyses to classify neuronal and non-neuronal signals. Multiple linear regression models identified sources of signal co-variance between neuroinflammation and brain connectivity profiles, in relation to group and cognitive status.Patients showed significantly higher [11C]PK11195 binding relative to controls, in a distributed spatial pattern including the hippocampus, medial, and inferior temporal cortex. Patients with enhanced loading on this [11C]PK11195 binding distribution displayed diffuse abnormal functional connectivity. The expression of a stronger association between such abnormal connectivity and higher levels of neuroinflammation correlated with worse cognitive deficits.Our study suggests that neuroinflammation relates to the pathophysiological changes in network function that underlie cognitive deficits in Alzheimer’s disease. Neuroinflammation, and its association with functionally-relevant reorganisation of brain networks, is proposed as a target for emerging immuno-therapeutic strategies aimed at preventing or slowing the emergence of dementia.Significance StatementNeuroinflammation is an important aspect of Alzheimer’s disease (AD), but it was not known whether the influence of neuroinflammation on brain network function in humans was important for cognitive deficit.Our study provides clear evidence that in vivo neuroinflammation in AD impairs large-scale network connectivity; and that the link between inflammation and functional network connectivity is relevant to cognitive impairment.We suggest that future studies should address how neuroinflammation relates to network function as AD progresses; and whether the neuroinflammation in AD is reversible, as the basis of immunotherapeutic strategies to slow the progression of AD.