bluuebunny/crossref_metadata_2025_split huggingface dataset:
The specific ex vivo released cytokine profile is associated with ischemic stroke outcome and improves its prediction
Authors: Klimiec-Moskal Elzbieta , Piechota Marcin , Pera Joanna , Weglarczyk Kazimierz , Slowik Agnieszka , Siedlar Maciej , Dziedzic Tomasz 
Published: January 2020

AbstractBackgroundInflammation is associated with poor outcome after stroke. A relationship between ex vivo cytokine synthesis and stroke outcome remains unclear. We explored an association between ex vivo cytokine release, circulating interleukin (IL)-6 as a marker of systemic inflammation, and stroke prognosis. We assessed the utility of ex vivo synthesized cytokines for predicting stroke outcome.MethodsWe collected blood from 248 ischemic stroke patients and stimulated it ex vivo with lipopolysaccharide. We measured concentration of synthesized cytokines (TNFα, IP-10, IL-1β, IL-6, IL-8, IL-10, and IL-12) and plasma IL-6. We assessed functional outcome 3 months after stroke using the modified Rankin Scale. To assess the prognostic ability of cytokines, we applied multivariate logistic regression, cluster analysis, and construction of multimarker score.ResultsDecreased release of IP-10, TNFα, IL-1β, and IL-12; increased release of IL-10 and IL-8; and higher plasma IL-6 level were associated with poor outcome. Cluster analysis identified three groups of patients with distinct cytokine profiles. The group with the worst outcome demonstrated high synthesis of IL-10, IL-8, IL-1β, and IL-6 and low synthesis of IL-12, IP-10, and TNFα accompanied by high circulating IL-6 level. The group with the best prognosis showed high synthesis of TNFα, IP-10, IL-12, IL-1β, and IL-6; low synthesis of IL-10 and IL-8; and low plasma IL-6. Patients with intermediate outcome had low synthesis of all cytokines accompanied by low circulating IL-6. We constructed a multimarker score composed of ex vivo released IL-12, IL-10, TNFα, and plasma IL-6. Addition of this score to clinical variables led to significant increase in c-statistic (0.81 vs 0.73,p= 0.02) and net reclassification improvement.ConclusionThe decreased ex vivo release of pro-inflammatory cytokines and increased release of IL-10 and IL-8 are related to poor outcome after stroke. Cytokine-based multimarker score adds prognostic value to clinical model for predicting stroke outcome.
Does the frontal sensory organ in adults of the hoplonemertean Quasitetrastemma stimpsoni originate from the larval apical organ?
Authors: Magarlamov Timur Yu , Dyachuk Vyacheslav , Chernyshev Alexey V. 
Published: January 2020

Abstract
Background
The apical organ is the most prominent neural structure in spiralian larvae. Although it has been thoroughly investigated in larvae of the class Pilidiophora in phylum Nemertea, studies on its structure in other nemertean larvae are limited. Most adult hoplonemertean worms have a frontal organ located in a position corresponding to that of the larval apical organ. The development and sensory function of the frontal organ has not been thoroughly characterized to date.

Results
The apical organ in the early rudiment stage of Quasitetrastemma stimpsoni larvae consists of an apical plate enclosed by ducts of frontal gland cells and eight apical neurons. The apical plate is abundantly innervated by neurites of apical neurons. During the late rudiment stage, the larval apical organ has external innervation from below by two subapical-plate neurons, along with 11 apical neurons, and its plate contains serotonin-like immunoreactive (5-HT-lir) cells. In the vermicular stage (free-swimming juvenile), the number of apical neurons is reduced, and their processes are resorbed. Serotonin is detected in the apical plate with no visible connection to apical neurons. In adult worms, the frontal organ has a small apical pit with openings for the frontal gland ducts. The organ consists of 8 to 10 densely packed 5-HT-lir cells that form the roundish pit.

Conclusions
Although the ultrastructure of the Q. stimpsoni larval apical organ closely resembles that of the apical organ of Polycladida larvae, the former differs in the presence of flask-shaped neurons typical of Spiralia. Significant differences in the structure of the apical organs of hoplonemertean and pilidia larvae point to two different paths in the evolutionary transformation of the ancestral apical organ. Ultrastructural and immunoreactive analyses of the apical organ of a hoplonemertean larva in the late rudiment and vermicular stages and the frontal organ of the adult worms identified common morphological and functional features. Thus, we hypothesize that the larval apical organ is modified during morphogenesis to form the adult frontal organ, which fulfills a sensory function in the hoplonemertean worm. This unique developmental trait distinguishes the Hoplonemertea from other nemertean groups.
Decay of infectious adenovirus and coliphages in freshwater habitats is differentially affected by ambient sunlight and the presence of indigenous protozoa communities
Authors: McMinn Brian R. , Rhodes Eric R. , Huff Emma M. , Korajkic Asja 
Published: January 2020

AbstractBackgroundSanitary quality of recreational waters worldwide is assessed using fecal indicator bacteria (FIB), such asEscherichia coliand enterococci. However, fate and transport characteristics of FIB in aquatic habitats can differ from those of viral pathogens which have been identified as main etiologic agents of recreational waterborne illness. Coliphages (bacteriophages infectingE. coli) are an attractive alternative to FIB because of their many morphological and structural similarities to viral pathogens.MethodsIn this in situ field study, we used a submersible aquatic mesocosm to compare decay characteristics of somatic and F+ coliphages to those of infectious human adenovirus 2 in a freshwater lake. In addition, we also evaluated the effect of ambient sunlight (and associated UV irradiation) and indigenous protozoan communities on decay of somatic and F+ coliphage, as well as infectious adenovirus.ResultsOur results show that decay of coliphages and adenovirus was similar (p = 0.0794), indicating that both of these bacteriophage groups are adequate surrogates for decay of human adenoviruses. Overall, after 8 days the greatest log10reductions were observed when viruses were exposed to a combination of biotic and abiotic factors (2.92 ± 0.39, 4.48 ± 0.38, 3.40 ± 0.19 for somatic coliphages, F+ coliphages and adenovirus, respectively). Both, indigenous protozoa and ambient sunlight, were important contributors to decay of all three viruses, although the magnitude of that effect differed over time and across viral targets.ConclusionsWhile all viruses studied decayed significantly faster (p < 0.0001) when exposed to ambient sunlight, somatic coliphages were particularly susceptible to sunlight irradiation suggesting a potentially different mechanism of UV damage compared to F+ coliphages and adenoviruses. Presence of indigenous protozoan communities was also a significant contributor (pvalue range: 0.0016 to < 0.0001) to decay of coliphages and adenovirus suggesting that this rarely studied biotic factor is an important driver of viral reductions in freshwater aquatic habitats.
The ABCA1 blocking agent probucol decreases capacitation in ejaculated dog spermatozoa
Authors: Schäfer-Somi Sabine , Budik Sven 
Published: January 2020

Abstract
Background
The ATP binding cassette (ABC) transporters participate in the cholesterol and phospholipid transport within and through cell membranes of many cells including spermatozoa. Cholesterol efflux is important for capacitation of spermatozoa. ABCA1 expression has been assessed in canine spermatozoa previously but its role in capacitation still has to be determined. The aim of the study was to test whether inhibition of ABCA1 (1) decreases capacitation in ejaculated and epididymal canine sperm samples and (2) decreases cholesterol efflux in the same samples. Twenty-one ejaculates and sperm from 22 epididymal tails were collected from healthy dogs. Motility was measured by CASA and viability assessed after staining with SYBR-14/PI. Samples from ejaculated sperm and sperm from epididymal tails were aliquoted. One part was incubated with the ABCA1 inhibitor probucol, the other served as a negative control. In all samples, capacitation was evaluated by chlortetracyclin (CTC) assay and cholesterol was measured by cholesterol efflux assay and colorimetric enzymatic assay.

Results
In ejaculated sperm, blockade of ABCA1 with 100 µM of probucol/mL of sample resulted in a significantly higher percentage of uncapacitated and acrosome reacted spermatozoa (P < 0.001 and P = 0.031), capacitation was significantly decreased (35% in probucol samples vs 54.2% in controls, P < 0.001). In probucol inhibited sperm samples from epididymal tails, the percentage of capacitated spermatozoa did not differ between groups but the percentage of acrosome reacted spermatozoa increased significantly (P = 0.014). The cholesterol measurement revealed significantly lower cholesterol concentration in the probucol group when compared to the controls (P = 0.035), however only in ejaculated sperm samples.

Conclusions
CTC assay and cholesterol measurement revealed significant differences between groups; we conclude that inhibition of ABCA1 significantly decreased capacitation and cholesterol efflux in ejaculated canine spermatozoa. The inhibition was not complete but ABCA1 is supposed to contribute to capacitation in canine ejaculated spermatozoa. ABCA1 is probably not important for capacitation of epididymal spermatozoa but might exert other functions during spermatozoa ripening.
The refugee post-migration stress scale (RPMS) – development and validation among refugees from Syria recently resettled in Sweden
Authors: Malm Andreas , Tinghög Petter , Narusyte Jurgita , Saboonchi Fredrik 
Published: January 2020

Abstract
Background
Despite the growing recognition of the impact of post-resettlement factors on the mental health of refugees, a clear definition of the concept of post-migration stress, as well as an updated, valid instrument for assessing the construct, are still lacking. The aim of the current study was to develop and validate the Refugee Post-Migration Stress Scale (RPMS), a concise, multi-dimensional instrument for assessing post-migration stress among refugees.

Results
Based on a review of previous research and observations from a refugee trauma clinic, a preliminary 24-item instrument was developed, covering seven hypothesized domains of post-migration stress: perceived discrimination, lack of host country specific competences, material and economic strain, loss of home country, family and home country concerns, social strain, and family conflicts.
In the context of a population-based survey of mental health among refugees from Syria recently resettled in Sweden (n = 1215), the factorial structure of the RPMS was investigated. Confirmatory Factor Analysis revealed slightly insufficient fit for the initial theorized multi-domain model. Exploratory Factor Analysis in four iterations resulted in the omission of three items and an adequate fit of a 7-factor model, corresponding to the seven hypothesized domains of post-migration stress. To assess concurrent validity, correlational analyses with measures of anxiety, depression, post-traumatic stress disorder (PTSD), and mental wellbeing were carried out. All domains of post-migration stress showed significant correlations with anxiety, depression, and PTSD scores, and significant negative correlations with mental wellbeing scores.

Conclusions
The newly developed RPMS appears to be a valid instrument for assessing refugee post-migration stress. Our findings that post-migration stress primarily relating to social and economic factors seems to be associated with mental ill health among refugees is in line with previous research.
The effect of discharge destination and primary insurance provider on hospital discharge delays among patients with traumatic brain injury: a multicenter study of 1,543 patients
Authors: Sorensen Melissa , Sercy Erica , Salottolo Kristin , Waxman Michael , West Thomas A. , Tanner Allen , Bar-Or David 
Published: January 2020

Abstract
Background
Hospital length of stay (HLOS) is a commonly used measure of hospital quality and is influenced by clinical and non-clinical factors. To reduce HLOS, it is key to identify factors placing patients at increased risk of lengthy HLOS and discharge delays.

Methods
This was a retrospective cohort study of patients age ≥ 18 admitted to four level 1 trauma centers between 1/1/2015 and 3/31/2018 with traumatic brain injury (TBI). The primary outcome was discharge delay, defined as discharge ≥24 h after case management notes indicated the patient was ready for discharge. The independent variables of interest were primary insurance provider and discharge destination. Chi-square, Fisher exact, and unadjusted and adjusted logistic regression analyses were used to assess associations between discharge delay and the two primary independent variables, as well as other patient demographic and clinical characteristics. Complications developing during the delay period were also examined.

Results
A total of 1543 patients with TBI were included. The median age was 61 years, and the median HLOS was 5 days. Approximately half of patients were discharged home (54%). The most common insurance providers were Medicare (35%) and commercial/private (35%). Two-hundred ten (14%) patients experienced a discharge delay. The median delay period was 3 days, and the most common reasons for delay were insurance authorization (52%) and lack of accepting bed (41%). Compared to being discharged home, patients discharged to a skilled nursing facility (adjusted odds ratio (AOR) = 10.35) or intermediate care facility (AOR = 10.64) had the highest odds of discharge delay. Compared to Medicare patients, uninsured/self-pay patients (AOR = 2.98) and those with Medicaid (AOR = 2.83) or commercial/private insurance (AOR = 2.22) had higher odds of delay. Thirty-two patients (15% of those delayed) experienced at least one complication during the delay, some of which were clinically severe.

Conclusions
A substantial portion of TBI patients in this study experienced discharge delays, and discharge destination and primary insurance provider were significant drivers of these delays. Evaluation of a facility’s quality of care should consider the specific causes of these delays.
Brainstem dysfunction in critically ill patients
Authors: Benghanem Sarah , Mazeraud Aurélien , Azabou Eric , Chhor Vibol , Shinotsuka Cassia Righy , Claassen Jan , Rohaut Benjamin , Sharshar Tarek 
Published: January 2020

AbstractThe brainstem conveys sensory and motor inputs between the spinal cord and the brain, and contains nuclei of the cranial nerves. It controls the sleep-wake cycle and vital functions via the ascending reticular activating system and the autonomic nuclei, respectively. Brainstem dysfunction may lead to sensory and motor deficits, cranial nerve palsies, impairment of consciousness, dysautonomia, and respiratory failure. The brainstem is prone to various primary and secondary insults, resulting in acute or chronic dysfunction. Of particular importance for characterizing brainstem dysfunction and identifying the underlying etiology are a detailed clinical examination, MRI, neurophysiologic tests such as brainstem auditory evoked potentials, and an analysis of the cerebrospinal fluid. Detection of brainstem dysfunction is challenging but of utmost importance in comatose and deeply sedated patients both to guide therapy and to support outcome prediction. In the present review, we summarize the neuroanatomy, clinical syndromes, and diagnostic techniques of critical illness-associated brainstem dysfunction for the critical care setting.
Therapeutic drug monitoring of infliximab compared to standard clinical treatment with infliximab: study protocol for a randomised, controlled, open, parallel-group, phase IV study (the NOR-DRUM study)
Authors: Syversen Silje W , Goll Guro L , Jørgensen Kristin K , Olsen Inge C , Sandanger Øystein , Gehin Johanna E , Warren David J , Sexton Joseph , Mørk Cato , Jahnsen Jørgen , Kvien Tore K , Bolstad Nils , Haavardsholm Espen A 
Published: January 2020

Abstract
Background
Infliximab (INX) and other tumour necrosis factor inhibitors (TNFi) have revolutionised the treatment of several immune mediated inflammatory diseases. Still, many patients do not respond sufficiently to therapy or lose efficacy over time. The large interindividual variation in serum drug concentrations on standard doses and the development of anti-drug antibodies are thought to be major reasons for treatment failures. Therapeutic drug monitoring (TDM), an individualised treatment strategy based on systematic assessments of serum drug concentrations, has been proposed as a clinical tool to optimise efficacy of INX treatment. TDM seems reasonable both from a clinical and an economical point of view, but the effectiveness of this treatment strategy has not yet been demonstrated in randomised clinical trials. The NORwegian DRUg Monitoring study (NOR-DRUM) aims to assess the effectiveness of TDM, both with regard to the achievement of remission in patients starting INX treatment (part A) as well as to maintain disease control in patients on INX treatment (part B).

Methods
The NOR-DRUM study is a randomised, open, controlled, parallel-group, comparative, multi-centre, national, superiority, phase IV study with two separate parts, NOR-DRUM A and NOR-DRUM B. Patients with rheumatoid arthritis, psoriatic arthritis, spondyloarthritis, ulcerative colitis, Crohn’s disease and psoriasis are included. In both study parts participants are randomised 1:1 to either TDM of infliximab (intervention group) or to standard treatment with infliximab without knowledge of drug levels or ADAb status (control group). NOR-DRUM A will include 400 patients starting INX therapy. The primary outcome is remission at 30 weeks. In NOR-DRUM B, 450 patients on maintenance treatment with INX will be included. The primary endpoint is occurrence of disease worsening during the 52-week study period.

Discussion
As the first trial to assess the effectiveness, safety and cost-effectiveness of TDM in patients receiving TNFi for a range of immune mediated inflammatory diseases, we hope that the NOR-DRUM study will contribute to the advancement of evidence based personalised treatment with biological medicines.

Trial registration
Clinicaltrials.gov, NCT03074656. Registered on 090317.
Vitamin D supplementation compared to placebo in people with First Episode psychosis - Neuroprotection Design (DFEND): a protocol for a randomised, double-blind, placebo-controlled, parallel-group trial
Authors: Gaughran Fiona , Stringer Dominic , Berk Michael , Smith Shubulade , Taylor David , Whiskey Eromona , Landau Sabine , Murray Robin , McGuire Philip , Gardner-Sood Poonam , Wojewodka Gabriella , Ciufolini Simone , Jordan Harriet , Clarke Jessie , Allen Lauren , Krivoy Amir , Stubbs Brendon , Lowe Philippa , Arbuthnott Maurice , Rathod Shanaya , Boardman Andrew , Firdosi Mudasir , McGrath John J. 
Published: January 2020

Abstract
Background
People experiencing their first episode of psychosis are often deficient in vitamin D. Observational studies have reported an association between low vitamin D concentrations and poorer subsequent health outcomes in psychosis. A vitamin D deficiency in neonates and children has been linked to a later increased risk of schizophrenia and psychotic-like experiences. This trial aims to examine the effect of high-dose vitamin D supplementation on outcomes in early psychosis. We hypothesise that vitamin D supplementation will be associated with better mental health outcomes.

Methods/design
The DFEND study is a multicentre double-blind placebo-controlled parallel-group trial of vitamin D supplementation in people with early psychosis. Patients with an ICD-10 diagnosis of functional psychosis will be randomised in a 1:1 ratio to receive either 120,000 IU/month of vitamin D (cholecalciferol) or a matched placebo for 6 months. The primary outcome is the total Positive and Negative Syndrome Scale (PANSS) score at the 6-month follow-up for all patients. Secondary outcomes include assessment of mood (Calgary Depression Scale), general function (Global Assessment of Functioning), cardiovascular risk (body mass index, waist circumference, C-reactive protein, cholesterol and HbA1c) and vitamin D levels at the 6-month follow-up. Additionally, 3- and 6-month total PANSS scores will be analysed for those with inadequate vitamin D levels at the baseline.

Discussion
The DFEND study is the first trial to examine whether vitamin D supplementation in early psychosis is associated with better mental health outcomes. The findings of this study may help to resolve the clinical equipoise regarding the benefits and cost-effectiveness of routine vitamin D supplementation in people with psychosis.

Trial registration
ISRCTN, ISRCTN12424842. Registered on 25 February 2015.
Health Pregnancy, Healthy Baby: testing the added benefits of pregnancy ultrasound scan for child development in a randomised control trial
Authors: Richter Linda , Slemming Wiedaad , Norris Shane A. , Stein Alan , Poston Lucilla , Pasupathy Dharmintra 
Published: January 2020

AbstractBackgroundThe 2016 World Health Organization Antenatal Guidelines and the 2015 South African Maternal and Child Health Guidelines recommend one early antenatal ultrasound scan to establish gestational age and to detect multiple pregnancies and fetal abnormalities. Prior research indicates that ultrasound scan can also increase parental–fetal attachment. We aim to establish whether, compared to routine care, messages to promote parental attachment and healthy child development, conducted during one or two pregnancy ultrasound scans, improve early child development and growth, exclusive breastfeeding, parental–child interactions and prenatal and postnatal clinic attendance.MethodsThe effect of messages to sensitise mothers and fathers to fetal development will be tested in a three-armed randomised trial with 100 mothers and their partners from Soweto, Johannesburg in each arm. The primary outcome is child development at 6 months postnatally. Secondary outcomes include infant feeding, parental attachment and interaction, parental mental health and infant growth, assessed at 6 weeks and 6 months. Parents in Arm 1 receive a fetal ultrasound scan < 25 weeks during routine antenatal care at tertiary hospitals, and a second standard ultrasound scan at the research site within 2 weeks. Arm 2 participants receive the routine antenatal ultrasound scan and an additional ultrasound scan < 25 weeks at the research site, together with messages to promote parental attachment and healthy child development. Arm 3 participants receive the routine ultrasound scan and two additional ultrasound scans at the research site, < 25 weeks and < 36 weeks, together with messages to promote parental attachment and healthy child development.DiscussionEvidence from high-income countries suggests that first-time prospective mothers and fathers enjoy seeing their fetus during ultrasound scan and that it is an emotional experience. A number of studies have found that ultrasound scan increases maternal attachment during pregnancy, a predictor of positive parent–infant interactions which, in turn, promotes healthy infant development. It is generally agreed that studies are needed which follow up parental–child behaviour and healthy child development postnatally, include fathers and examine the construct in a wider diversity of settings, especially in low and middle-income countries. Testing the added benefits of pregnancy ultrasound scan for child development is a gap that the proposed trial in South Africa seeks to address.Trial registrationPan African Clinical Trials Registry,PACTR201808107241133. Registered on 15 August 2018.