bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracranial Pulsatility in Relation to Severity and Progression of Cerebral White Matter Hyperintensities
Authors: Kneihsl Markus , Hofer Edith , Enzinger Christian , Niederkorn Kurt , Horner Susanna , Pinter Daniela , Fandler-Höfler Simon , Eppinger Sebastian , Haidegger Melanie , Schmidt Reinhold , Gattringer Thomas 
Published: September 2020

Background and Purpose:
Previous studies suggested an association between increased intracranial arterial pulsatility and the severity of microangiopathic white matter hyperintensities (WMH). However, possible confounders such as age and hypertension were seldomly considered and longitudinal data are lacking. We here aimed to explore whether increased middle cerebral artery pulsatility is associated with baseline severity and progression of cerebral small vessel disease–related WMH in elderly individuals.

Methods:
The study population consisted of elderly participants from the community-based ASPS (Austrian Stroke Prevention Study). Baseline and follow-up assessment comprised transcranial Doppler sonography, brain magnetic resonance imaging, and clinical/laboratory examination of vascular risk factors. Pulsatility index on transcranial Doppler sonography was averaged from baseline indices of both middle cerebral arteries and was correlated with baseline WMH severity and WMH progression over a median follow-up period of 5 years in uni- and multivariable analyses. WMH severity was graded according to the Fazekas scale, and WMH load was quantified by semiautomated volumetric assessment.

Results:

The study cohort comprised 491 participants (mean age: 60.7±6.9 years; female: 48.5%). Pulsatility index was increased in participants with more severe WMH at baseline (
P
<0.001) but was not associated with WMH progression during follow-up (r
s
: 0.097,
P
=0.099). In multivariable analyses, only arterial hypertension remained significantly associated with baseline severity (
P
=0.04) and progression (
P
=0.008) of WMH, although transcranial Doppler sonography pulsatility index was not predictive (
P
>0.1, respectively).

Conclusions:
This community-based cohort study of elderly individuals does not support the pulsatility index of the middle cerebral artery on transcranial Doppler sonography as an independent marker of microangiopathic WMH severity and progression over time.
Regional High Wall Shear Stress Associated With Stenosis Regression in Symptomatic Intracranial Atherosclerotic Disease
Authors: Lan Linfang , Liu Haipeng , Ip Vincent , Soo Yannie , Abrigo Jill , Fan Florence , Ma Sze Ho , Ma Karen , Ip Bonaventure , Liu Jia , Fan Yuhua , Zeng Jinsheng , Mok Vincent , Wong Lawrence , Liebeskind David , Leung Thomas , Leng Xinyi 
Published: September 2020

Background and Purpose:
Understanding the mechanisms underlying progression/regression of symptomatic intracranial atherosclerotic stenosis (sICAS) will inform secondary prevention of the patients. Focal wall shear stress (WSS) may play an important role, which, however, had seldom been investigated.

Methods:
Patients with acute ischemic stroke or transient ischemic attack (TIA) attributed to 50% to 99% intracranial atherosclerotic stenosis were recruited. All patients underwent cerebral computed tomography angiography at baseline, and a computational fluid dynamics model was built based on computed tomography angiography to simulate blood flow and quantify WSS in the vicinity of the sICAS lesion. All patients received optimal medical treatment and a second computed tomography angiography at 1 year. The change in the luminal stenosis from baseline to 1 year in sICAS was defined as progression (increased >10%), quiescence (±10%), or regression (decreased >10%). Associations between baseline WSS metrics and sICAS regression were analyzed.

Results:
Among 39 patients (median age 62 years; 27 males), sICAS luminal stenosis progressed, remained quiescent and regressed in 6 (15.4%), 15 (38.5%), and 18 (46.2%) cases, respectively. A higher maximum WSS and larger high-WSS area, throughout the sICAS lesion or obtained separately in the proximal and distal parts of the lesion, were independently associated with regression of luminal stenosis in sICAS over 1 year.

Conclusions:
A majority of sICAS lesions regress or stay quiescent in the luminal stenosis over 1 year after stroke under optimal medical treatment, when higher focal WSS may facilitate stenosis regression. Further studies of the effects of hemodynamics including WSS in altering plaque vulnerability and stroke risks are needed.
Incidence and Mortality of Cerebral Venous Thrombosis in a Norwegian Population
Authors: Kristoffersen Espen Saxhaug , Harper Charlotte Elena , Vetvik Kjersti Grøtta , Zarnovicky Svetozar , Hansen Jakob Møller , Faiz Kashif Waqar 
Published: September 2020

Background and Purpose:
There are conflicting figures of the incidence of cerebral venous thrombosis (CVT). The incidence was previously estimated to around 0.5/100 000/y, but more recent studies have suggested 1 to 1.5/100 000/y. The purpose of this study was to explore the incidence and mortality of CVT in a Norwegian population.

Methods:

A retrospective cross-sectional hospital population-based study conducted at Akershus University Hospital serving roughly 10% of the total Norwegian population. Patients were identified through chart reviews based on the relevant
International Classification of Diseases
(
Tenth Revision
) codes for new CVT cases in a 7-year period between January 1, 2011, and December 31, 2017. Only inhabitants living in the hospital’s catchment area were included.

Results:
Sixty-two patients aged 0 to 80 years were identified and included. The median age was 46 years and 53% were females. The overall incidence of CVT was 1.75 (95% CI, 1.36–2.23) per 100 000/y with no significant sex differences. The incidence for children and adolescents (<18 years, n=9) was lower than for adults (≥18 years, n=53); 1.08 (0.52–1.97) versus 1.96 (1.49–2.55) per 100 000/y per year, with the highest incidence for those >50 years with 2.10 (1.38–3.07)/100 000/y. Headache was the most prevalent symptom, reported in 83%, followed by nausea, motor deficits, and seizures observed in 45%, 32%, and 32% of the patients. Transverse sinuses and the jugular vein were the most frequent sites of thrombosis. In most patients (61%), thrombosis occurred in multiple sinuses/veins. Risk factors were found in 73% of the patients, and most of the patients had a combination of 2 or more risk factors. The 30-day and 1-year mortality rates were 3% and 6%.

Conclusions:
The incidence of CVT in this population was higher than previously reported. The mortality rate was similar to previous studies.
Association of anti-NR2 and U1RNP antibodies with neurotoxic inflammatory mediators in cerebrospinal fluid from patients with neuropsychiatric systemic lupus erythematosus
Authors: Kondo-Ishikawa Seiko , Fujii Takao , Ishigooka Nozomi , Murakami Kosaku , Nakashima Ran , Hashimoto Motomu , Yoshifuji Hajime , Tanaka Masao , Ohmura Koichiro , Mimori Tsuneyo 
Published: September 2020

Background Autoantibodies (auto Abs) and inflammatory mediators (IMs) in cerebrospinal fluid (CSF) may be involved in the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE). It is suggested that anti- N-methyl D-aspartate receptor NR2 subunit (NR2) Ab can develop NP manifestation after blood–brain barrier (BBB) abruption. We also reported the association between NPSLE and CSF anti-U1RNP Ab. In the present study, combined effects of CSF anti-NR2 and anti-U1RNP Abs on IMs in patients with NPSLE were examined. Methods CSF samples were collected from 69 patients with NPSLE and 13 non-NPSLE controls. CSF anti-NR2 and anti-U1RNP Abs were determined using ELISA. Levels of IL-6, IL-8, and monokine induced by IFN-γ (MIG) in CSF were measured by quantitative multiplex cytokine analysis. Results CSF IL-6 levels were higher in CSF anti-NR2-positive than in CSF anti-NR2-negative patients ( p = 0.003) and non-NPSLE controls ( p = 0.015) and were positively correlated with anti-NR2 titer ( r = 0.42). CSF IL-8 levels were higher in CSF anti-U1RNP-positive than in CSF anti-U1RNP-negative patients ( p = 0.041). CSF MIG levels were more elevated in CSF anti-NR2-positive ( p = 0.043) and anti-U1RNP-positive patients ( p = 0.029) than in non-NPSLE controls. Additionally, in double positive (DP; both anti-NR2 and U1RNP Ab positive) group, CSF IL-6 and MIG levels were significantly higher than in the double negative (DN; both anti-NR2 and U1RNP Ab negative) group. However, combined effect of both Abs on IM elevation and clinical manifestation was not clear. Conclusions CSF anti-NR2 and anti-U1RNP Abs have different effects on the elevation of CSF IM levels in patients with NPSLE. Additional effect of anti-U1RNP Abs on anti-NR2 Ab-mediated NP manifestation, however, was not recognized in our study.
Patient Characteristics Associated With Readmission to 3 Neurology Services at an Urban Academic Center
Authors: Bondi Steven , Yang Dixon , Croll Leah , Torres Jose 
Published: September 2020

Background and Purpose: Hospital 30-day readmissions in patients with primary neurological problems are not well characterized. We sought to determine patient characteristics associated with readmission across 3 different inpatient neurology services at New York University Langone Hospital. Methods: We retrospectively reviewed all 30-day readmissions from the General Neurology, Epilepsy, and Stroke services at NYULH Brooklyn and Manhattan campuses from 2016-2017 and compared them to a random sample of non-readmitted neurology patients. We used univariate analyses to compare demographics, clinical characteristics, disease specific metrics, and discharge factors of non-readmitted and readmitted groups and binomial logistic regression to examine specific variables with adjustment for confounders. Results: We included 284 patients with 30-day readmissions and 306 control patients without readmissions matched by discharge location and service. After adjusting for confounders, we found that the following factors were associated with increased readmission risk: a recent hospital encounter increased risk for all services, increased number of medications at discharge, intensive care unit stay, higher length of stay, and prior history of seizure for the General Neurology Service, increased number of medications at discharge for the Epilepsy Service, and active malignancy and higher discharge modified Rankin Scale score for the Stroke Service. Conclusion: This study identifies potential risk factors for readmission in patients across multiple neurology services. Further research is needed to establish whether these risk factors hold across multiple institutions.
Plazomicin: a new aminoglycoside in the fight against antimicrobial resistance
Authors: Clark Justin A. , Burgess David S. 
Published: September 2020

Objective: To review the mechanism of action, mechanisms of resistance, in vitro activity, pharmacokinetics, pharmacodynamics, and clinical data for a novel aminoglycoside. Data sources: A PubMed search was performed from January 2006 to August 2019 using the following search terms: plazomicin and ACHN-490. Another search was conducted on clinicaltrials.gov for published clinical data. References from selected studies were also used to find additional literature. Study selection and data extraction: All English-language studies presenting original research ( in vitro, in vivo, pharmacokinetic, and clinical) were evaluated. Data synthesis: Plazomicin has in vitro activity against several multi-drug-resistant organisms, including carbapenem-resistant Enterobacteriaceae. It was Food and Drug Administration (FDA) approved to treat complicated urinary tract infections (cUTIs), including acute pyelonephritis, following phase II and III trials compared with levofloxacin and meropenem, respectively. Despite the FDA Black Box Warning for aminoglycoside class effects (nephrotoxicity, ototoxicity, neuromuscular blockade, and pregnancy risk), it exhibited a favorable safety profile with the most common adverse effects being decreased renal function (3.7%), diarrhea (2.3%), hypertension (2.3%), headache (1.3%), nausea (1.3%), vomiting (1.3%), and hypotension (1.0%) in the largest in-human trial. Relevance to patient care and clinical practice: Plazomicin will likely be used in the treatment of multi-drug-resistant cUTIs or in combination to treat serious carbapenem-resistant Enterobacteriaceae infections. Conclusions: Plazomicin appears poised to help fill the need for new agents to treat infections caused by multi-drug-resistant Enterobacteriaceae.
STudy of Antithrombotic Treatment after IntraCerebral Haemorrhage: Protocol for a randomised controlled trial
Authors: Larsen Kristin Tveitan , Forfang Elisabeth , Pennlert Johanna , Glader Eva-Lotta , Kruuse Christina , Wester Per , Ihle-Hansen Hege , Carlsson Maria , Berge Eivind , Al-Shahi Salman Rustam , Bruun Wyller Torgeir , Rønning Ole Morten 
Published: September 2020

Background and aims Many patients with prior intracerebral haemorrhage have indications for antithrombotic treatment with antiplatelet or anticoagulant drugs for prevention of ischaemic events, but it is uncertain whether such treatment is beneficial after intracerebral haemorrhage. STudy of Antithrombotic Treatment after IntraCerebral Haemorrhage will assess (i) the effects of long-term antithrombotic treatment on the risk of recurrent intracerebral haemorrhage and occlusive vascular events after intracerebral haemorrhage and (ii) whether imaging findings, like cerebral microbleeds, modify these effects. Methods STudy of Antithrombotic Treatment after IntraCerebral Haemorrhage is a multicentre, randomised controlled, open trial of starting versus avoiding antithrombotic treatment after non-traumatic intracerebral haemorrhage, in patients with an indication for antithrombotic treatment. Participants with vascular disease as an indication for antiplatelet treatment are randomly allocated to antiplatelet treatment or no antithrombotic treatment. Participants with atrial fibrillation as an indication for anticoagulant treatment are randomly allocated to anticoagulant treatment or no anticoagulant treatment. Cerebral CT or MRI is performed before randomisation. Duration of follow-up is at least two years. The primary outcome is recurrent intracerebral haemorrhage. Secondary outcomes include occlusive vascular events and death. Assessment of clinical outcomes is performed blinded to treatment allocation. Target recruitment is 500 participants. Trial status: Recruitment to STudy of Antithrombotic Treatment after IntraCerebral Haemorrhage is on-going. On 30 April 2020, 44 participants had been enrolled in 31 participating hospitals. An individual patient–data meta-analysis is planned with similar randomised trials.
Cord blood CD8+ T-cell expansion following granulocyte transfusions eradicates refractory leukemia
Authors: Hiwarkar Prashant , Adams Stuart , Gilmour Kimberly , Nataraj Ramya , Bonney Denise , Poulton Kay , Wynn Robert 
Published: September 2020

AbstractThe action of hematopoietic cell transplantation in controlling leukemia is principally mediated by donor T cells directed against residual recipient malignant cells. However, its utility is limited by graft-versus-host disease (GVHD), where alloreactivity is extended beyond leukemic and marrow cells. In a human/murine chimeric model, we previously showed that the preferential infiltration of cord blood (CB) CD8+ T cells eradicates an Epstein-Barr virus–driven lymphoblastoid tumor without causing xenogeneic GVHD. In the clinic, however, cord blood CD8+ T-cell reconstitution is significantly delayed, and the observation of such a robust antileukemia effect mediated by cord blood CD8+ T cells has not been reported. We describe an observation of very early T-cell expansion in 4 high-risk pediatric leukemia patients receiving third-party, pooled granulocytes after T cell–replete CB transplantation (CBT). The T-cell expansion was transient but robust, including expansion of CD8+ T cells, in contrast to the delayed CD8+ T-cell expansion ordinarily observed after T cell–replete CBT. The CD8+ T cells were polyclonal, rapidly switched to memory phenotype, and had the ability to mediate cytotoxicity. This phenomenon is reproducible, and each patient remains in long-term remission without GVHD. The results suggest that fetal-derived CB CD8+ T cells can be exploited to generate robust antileukemia effects without GVHD.
AMG 701 induces cytotoxicity of multiple myeloma cells and depletes plasma cells in cynomolgus monkeys
Authors: Goldstein Rebecca L. , Goyos Ana , Li Chi-Ming , Deegen Petra , Bogner Pamela , Sternjak Alexander , Thomas Oliver , Klinger Matthias , Wahl Joachim , Friedrich Matthias , Rattel Benno , Lamas Edwin , Min Xiaoshan , Sudom Athena , Farshbaf Mozhgan , Coxon Angela , Balazs Mercedesz , Arvedson Tara 
Published: September 2020

AbstractMultiple myeloma (MM) is a hematologic malignancy that is characterized by the accumulation of abnormal plasma cells (PCs) in the bone marrow (BM). Patient outcome may be improved with BiTE (bispecific T-cell engager) molecules, which redirect T cells to lyse tumor cells. B-cell maturation antigen (BCMA) supports PC survival and is highly expressed on MM cells. A half-life extended anti-BCMA BiTE molecule (AMG 701) induced selective cytotoxicity against BCMA-expressing MM cells (average half-maximal effective concentration, 18.8 ± 14.8 pM), T-cell activation, and cytokine release in vitro. In a subcutaneous mouse xenograft model, at all doses tested, AMG 701 completely inhibited tumor formation (P &lt; .001), as well as inhibited growth of established tumors (P ≤ .001) and extended survival in an orthotopic MM model (P ≤ .01). To evaluate AMG 701 bioactivity in cynomolgus monkeys, a PC surface phenotype and specific genes were defined to enable a quantitative digital droplet polymerase chain reaction assay (sensitivity, 0.1%). Dose-dependent pharmacokinetic and pharmacodynamic behavior was observed, with depletion of PC-specific genes reaching 93% in blood and 85% in BM. Combination with a programmed cell death protein 1 (PD-1)–blocking antibody significantly increased AMG 701 potency in vitro. A model of AMG 701 binding to BCMA and CD3 indicates that the distance between the T-cell and target cell membranes (ie, the immunological synapse) is similar to that of the major histocompatibility complex class I molecule binding to a T-cell receptor and suggests that the synapse would not be disrupted by the half-life extending Fc domain. These data support the clinical development of AMG 701.
Leishmania infection induces a limited differential gene expression in the sand fly midgut
Authors: Coutinho-Abreu Iliano V. , Serafim Tiago Donatelli , Meneses Claudio , Kamhawi Shaden , Oliveira Fabiano , Valenzuela Jesus G. 
Published: September 2020

Abstract
Background
Sand flies are the vectors of Leishmania parasites. To develop in the sand fly midgut, Leishmania multiplies and undergoes various stage differentiations giving rise to the infective form, the metacyclic promastigotes. To determine the changes in sand fly midgut gene expression caused by the presence of Leishmania, we performed RNA-Seq of uninfected and Leishmania infantum-infected Lutzomyia longipalpis midguts from seven different libraries corresponding to time points which cover the various Leishmania developmental stages.

Results
The combined transcriptomes resulted in the de novo assembly of 13,841 sand fly midgut transcripts. Importantly, only 113 sand fly transcripts, about 1%, were differentially expressed in the presence of Leishmania parasites. Further, we observed distinct differentially expressed sand fly midgut transcripts corresponding to the presence of each of the various Leishmania stages suggesting that each parasite stage influences midgut gene expression in a specific manner. Two main patterns of sand fly gene expression modulation were noted. At early time points (days 1–4), more transcripts were down-regulated by Leishmania infection at large fold changes (> 32 fold). Among the down-regulated genes, the transcription factor Forkhead/HNF-3 and hormone degradation enzymes were differentially regulated on day 2 and appear to be the upstream regulators of nutrient transport, digestive enzymes, and peritrophic matrix proteins. Conversely, at later time points (days 6 onwards), most of the differentially expressed transcripts were up-regulated by Leishmania infection with small fold changes (< 32 fold). The molecular functions of these genes have been associated with the metabolism of lipids and detoxification of xenobiotics.

Conclusion
Overall, our data suggest that the presence of Leishmania produces a limited change in the midgut transcript expression profile in sand flies. Further, Leishmania modulates sand fly gene expression early on in the developmental cycle in order to overcome the barriers imposed by the midgut, yet it behaves like a commensal at later time points where a massive number of parasites in the anterior midgut results only in modest changes in midgut gene expression.
Gel-based proteomic map of Arabidopsis thaliana root plastids and mitochondria
Authors: Grabsztunowicz Magda , Rokka Anne , Farooq Irum , Aro Eva-Mari , Mulo Paula 
Published: September 2020

Abstract
Background
Non-photosynthetic plastids of plants are known to be involved in a range of metabolic and biosynthetic reactions, even if they have been difficult to study due to their small size and lack of color. The morphology of root plastids is heterogeneous and also the plastid size, density and subcellular distribution varies depending on the cell type and developmental stage, and therefore the functional features have remained obscure. Although the root plastid proteome is likely to reveal specific functional features, Arabidopsis thaliana root plastid proteome has not been studied to date.

Results
In the present study, we separated Arabidopsis root protein fraction enriched with plastids and mitochondria by 2D-PAGE and identified 84 plastid-targeted and 77 mitochondrion-targeted proteins using LC-MS/MS. The most prevalent root plastid protein categories represented amino acid biosynthesis, carbohydrate metabolism and lipid biosynthesis pathways, while the enzymes involved in starch and sucrose metabolism were not detected. Mitochondrion-targeted proteins were classified mainly into the energetics category.

Conclusions
This is the first study presenting gel-based map of Arabidopsis thaliana root plastid and mitochondrial proteome. Our findings suggest that Arabidopsis root plastids have broad biosynthetic capacity, and that they do not play a major role in a long-term storage of carbohydrates. The proteomic map provides a tool for further studies to compare changes in the proteome, e.g. in response to environmental cues, and emphasizes the role of root plastids in nitrogen and sulfur metabolism as well as in amino acid and fatty acid biosynthesis. The results enable taking a first step towards an integrated view of root plastid/mitochondrial proteome and metabolic functions in Arabidopsis thaliana roots.