bluuebunny/crossref_metadata_2025_split huggingface dataset:
Injections and infections: understanding syringe service program utilization in a rural state
Authors: Thakarar Kinna , Sankar Nitysari , Murray Kimberly , Lucas Frances L. , Burris Debra , Smith Robert P. 
Published: July 2021

Abstract
Background
Increasing rates of injection drug use (IDU) associated-infections suggest significant syringe service program (SSP) underutilization. Our study objective was to assess practices of safe injection techniques and to determine predictors of SSP utilization in a rural state.

Patients and methods
This was a fifteen-month cross-sectional study of participants hospitalized with IDU-associated infections in Maine. Data were collected through Audio Computer-Assisted Self-Interview survey and medical record review. Descriptive analyses were performed to characterize demographics, health characteristics, and injection practices. The primary outcome was SSP utilization, and the main independent variable was self-reported distance to SSP. Logistic regression analyses were performed to identify factors associated SSP utilization, controlling for gender, homelessness, history of overdose, having a primary care physician and distance to SSP.

Results
Of the 101 study participants, 65 participants (64%) reported past 3 month SSP utilization, though only 33% used SSPs frequently. Many participants (57%) lived more than 10 miles from an SSP. Participants who lived less than 10 miles of an SSP were more likely to use an SSP (adjusted odds ratio 5.4; 95% CI 1.9–15.7).

Conclusions
Our study highlights unsafe injection practices and lack of frequent SSP utilization among people admitted with IDU-associated infections in a rural state. Especially given increasing stimulant use, these results also highlight the need for SSP access. Particularly in rural areas where patients may live more than 10 miles from an SSP, expansion of harm reduction services, including mobile units, should be a priority.
Lead thrombus under standard-dose edoxaban in a patient with normal to high creatinine clearance and protein S deficiency
Authors: Lee Wei-Chieh , Huang Min-Ping 
Published: July 2021

Abstract
Background
Non-vitamin K antagonist oral anticoagulants (NOACs) are as effective and safe as warfarin for thromboembolic prevention and treatment. The efficacy of NOACs lacks evidence from large and randomized studies in patients with inherited severe thrombophilia, including protein S deficiency. Further, some concerns still exist regarding the relative efficacy of edoxaban in preventing arterial thromboembolism in patients with normal to high creatinine clearance (CrCl). We present a case of a rare complication of lead thrombus under standard-dose edoxaban in a patient with protein S deficiency and supernormal renal function.

Case presentation
A 65-year-old man experienced persistent chest tightness and a high level of D-dimer. Chest computed tomography (CT) showed a lead thrombus at the superior vena cava. He had a medical history including, paroxysmal atrial fibrillation (PAf), sick sinus syndrome after permanent pacemaker implantation, and transient ischemic attack. He received standard-dose edoxaban (60 mg daily) after PAf was diagnosed. His estimated CrCl was 98.6–102.1 mL/min. However, protein S deficiency (22.8%; normal range: 55–130%) was diagnosed. After switching to dabigatran (150 mg twice daily) for 3 months, the chest CT showed lead thrombus resolution and no symptoms were seen during the follow-up period.

Conclusions
This case was a rare complication of lead thrombus in a protein S deficient patient with normal renal function receiving standard-dose edoxaban. Edoxaban efficacy is uncertain in patients with protein S deficiency, and intracardiac devices also increase the risk of thromboembolic events.
Regional inequalities and substitutability of health resources in the Czech Republic: a five methods of evaluation
Authors: Dlouhý Martin 
Published: July 2021

Abstract
Background
An analysis of the regional distribution of health resources is one of the tools for evaluating equal geographic access to health care. The usual analytical approach to an assessment of regional differences is to evaluate each health resource separately. This is a sensible approach, because there may be systematic reasons for any differences, for example, higher salaries in urban areas. However, a separate evaluation of the regional distribution of health resource capacities may be misleading. We should evaluate all health resource capacities as a whole and consider the substitutability of resources.

Objective
This study aims to measure regional inequalities in the Czech Republic with the help of alternative approaches to the evaluation of regional inequalities in the case of several substitutable health resources.

Methods
Five alternative evaluation methods (models) are described and applied: the separate evaluation, expert model, market model, common weights model, and production frontier model.

Results
The regional distribution of physicians and nurses in the Czech Republic in 2017 was evaluated. In spite of many regulations at the national and regional levels, we have found inequalities in regional resource distribution. The models that consider all health resources and the possibility of a resource substitution show lower inequalities between regional health resource capacities.

Conclusion
Both researchers and policy-makers should always consider the possibility of resource substitutions in the assessment of regional inequalities.
Validity, reliability, and calibration of the physical activity unit 7 item screener (PAU-7S) at population scale
Authors: Schröder Helmut , Subirana Isaac , Wärnberg Julia , Medrano María , González-Gross Marcela , Gusi Narcis , Aznar Susana , Alcaraz Pedro E. , González-Valeiro Miguel A. , Serra-Majem Lluis , Terrados Nicolás , Tur Josep A. , Segú Marta , Homs Clara , Garcia-Álvarez Alicia , Benavente-Marín Juan C. , Barón-López F. Javier , Labayen Idoia , Zapico Augusto G. , Sánchez-Gómez Jesús , Jiménez-Zazo Fabio , Marín-Cascales Elena , Sevilla-Sanchez Marta , Herrera-Ramos Estefanía , Pulgar Susana , del Mar Bibiloni María , Sistac-Sorigué Clara , Gómez Santiago F. 
Published: July 2021

AbstractBackgroundValidation of self-reported tools, such as physical activity (PA) questionnaires, is crucial. The aim of this study was to determine test-retest reliability, internal consistency, and the concurrent, construct, and predictive validity of the short semi-quantitative Physical Activity Unit 7 item Screener (PAU-7S), using accelerometry as the reference measurement. The effect of linear calibration on PAU-7S validity was tested.MethodsA randomized sample of 321 healthy children aged 8–16 years (149 boys, 172 girls) from the nationwide representative PASOS study completed the PAU-7S before and after wearing an accelerometer for at least 7 consecutive days. Weight, height, and waist circumference were measured. Cronbach alpha was calculated for internal consistency. Test-retest reliability was determined by intra-class correlation (ICC). Concurrent validity was assessed by ICC and Spearman correlation coefficient between moderate to vigorous PA (MVPA) derived by the PAU-7S and by accelerometer. Concordance between both methods was analyzed by absolute agreement, weighted kappa, and Bland-Altman statistics. Multiple linear regression models were fitted for construct validity and predictive validity was determined by leave-one-out cross-validation.ResultsThe PAU-7S overestimated MVPA by 18%, compared to accelerometers (106.5 ± 77.0 vs 95.2 ± 33.2 min/day, respectively). A Cronbach alpha of 0.76 showed an acceptable internal consistency of the PAU-7S. Test-retest reliability was good (ICC 0.71p < 0.001). Spearman correlation and ICC coefficients of MVPA derived by the PAU-7S and accelerometers increased from 0.31 to 0.62 and 0.20 to 0.62, respectively, after calibration of the PAU-7S. Between-methods concordance improved from a weighted kappa of 0.24 to 0.50 after calibration. A slight reduction in ICC, from 0.62 to 0.60, yielded good predictive validity. Multiple linear regression models showed an inverse association of MVPA with standardized body mass index (β − 0.162;p < 0.077) and waist to height ratio (β − 0.010;p < 0.014). All validity dimensions were somewhat stronger in boys compared to girls.ConclusionThe PAU-7S shows a good test-retest reliability and acceptable internal consistency. All dimensions of validity increased from poor/fair to moderate/good after calibration. The PAU-7S is a valid instrument for measuring MVPA in children and adolescents.Trial registrationTrial registration numberISRCTN34251612.
GPR110 ligands reduce chronic optic tract gliosis and visual deficit following repetitive mild traumatic brain injury in mice
Authors: Chen Huazhen , Kevala Karl , Aflaki Elma , Marugan Juan , Kim Hee-Yong 
Published: July 2021

Abstract
Background
Repetitive mild traumatic brain injury (mTBI) can result in chronic visual dysfunction. G-protein receptor 110 (GPR110, ADGRF1) is the target receptor of N-docosahexaenoylethanolamine (synaptamide) mediating the anti-neuroinflammatory function of synaptamide. In this study, we evaluated the effect of an endogenous and a synthetic ligand of GPR110, synaptamide and (4Z,7Z,10Z,13Z,16Z,19Z)-N-(2-hydroxy-2-methylpropyl) docosa-4,7,10,13,16,19-hexaenamide (dimethylsynaptamide, A8), on the mTBI-induced long-term optic tract histopathology and visual dysfunction using Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA), a clinically relevant model of mTBI.

Methods
The brain injury in wild-type (WT) and GPR110 knockout (KO) mice was induced by CHIMERA applied daily for 3 days, and GPR110 ligands were intraperitoneally injected immediately following each impact. The expression of GPR110 and proinflammatory mediator tumor necrosis factor (TNF) in the brain was measured by using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) in an acute phase. Chronic inflammatory responses in the optic tract and visual dysfunction were assessed by immunostaining for Iba-1 and GFAP and visual evoked potential (VEP), respectively. The effect of GPR110 ligands in vitro was evaluated by the cyclic adenosine monophosphate (cAMP) production in primary microglia isolated from adult WT or KO mouse brains.

Results
CHIMERA injury acutely upregulated the GPR110 and TNF gene level in mouse brain. Repetitive CHIMERA (rCHIMERA) increased the GFAP and Iba-1 immunostaining of glia cells and silver staining of degenerating axons in the optic tract with significant reduction of N1 amplitude of visual evoked potential at up to 3.5 months after injury. Both GPR110 ligands dose- and GPR110-dependently increased cAMP in cultured primary microglia with A8, a ligand with improved stability, being more effective than synaptamide. Intraperitoneal injection of A8 at 1 mg/kg or synaptamide at 5 mg/kg significantly reduced the acute expression of TNF mRNA in the brain and ameliorated chronic optic tract microgliosis, astrogliosis, and axonal degeneration as well as visual deficit caused by injury in WT but not in GPR110 KO mice.

Conclusion
Our data demonstrate that ligand-induced activation of the GPR110/cAMP system upregulated after injury ameliorates the long-term optic tract histopathology and visual impairment caused by rCHIMERA. Based on the anti-inflammatory nature of GPR110 activation, we suggest that GPR110 ligands may have therapeutic potential for chronic visual dysfunction associated with mTBI.
Intravenous administration of LPS activates the kynurenine pathway in healthy male human subjects: a prospective placebo-controlled cross-over trial
Authors: Millischer Vincent , Heinzl Matthias , Faka Anthi , Resl Michael , Trepci Ada , Klammer Carmen , Egger Margot , Dieplinger Benjamin , Clodi Martin , Schwieler Lilly 
Published: July 2021

AbstractBackgroundAdministration of lipopolysaccharide (LPS) from Gram-negative bacteria, also known as the human endotoxemia model, is a standardized and safe model of human inflammation. Experimental studies have revealed that peripheral administration of LPS leads to induction of the kynurenine pathway followed by depressive-like behavior and cognitive dysfunction in animals. The aim of the present study is to investigate how acute intravenous LPS administration affects the kynurenine pathway in healthy male human subjects.MethodsThe present study is a prospective, single-blinded, randomized, placebo-controlled cross-over study to investigate the effects of intravenously administered LPS (Escherichia coli O113, 2 ng/kg) on tryptophan and kynurenine metabolites over 48 h and their association with interleukin-6 (IL-6) and C-reactive protein (CRP). The study included 10 healthy, non-smoking men (18–40 years) free from medication. Statistical differences in tryptophan and kynurenine metabolites as well as associations with IL-6 and CRP in LPS and placebo treated subjects were assessed with linear mixed-effects models.ResultsSystemic injection of LPS was associated with significantly lower concentrations of plasma tryptophan and kynurenine after 4 h, as well as higher concentrations of quinolinic acid (QUIN) after 48 h compared to the placebo injection. No differences were found in kynurenic acid (KYNA) or picolinic acid plasma concentrations between LPS or placebo treatment. The KYNA/kynurenine ratio peaked at 6 h post LPS injection while QUIN/kynurenine maintained significantly higher from 3 h post LPS injection until 24 h. The kynurenine/tryptophan ratio was higher at 24 h and 48 h post LPS treatment. Finally, we report an association between the kynurenine/tryptophan ratio and CRP.ConclusionsOur findings strongly support the concept that an inflammatory challenge with LPS induces the kynurenine pathway in humans, activating both the neurotoxic (QUIN) and neuroprotective (KYNA) branch of the kynurenine pathway.Trial registrationThis study is based on a study registered at ClinicalTrials.gov,NCT03392701. Registered 21 December 2017.
Calcium channel blockers do not protect against saturated fatty acid-induced ER stress and apoptosis in human pancreatic β-cells
Authors: Šrámek Jan , Němcová Vlasta , Kovář Jan 
Published: July 2021

AbstractIt was evidenced that saturated fatty acids (FAs) have a detrimental effect on pancreatic β-cells function and survival, leading to endoplasmic reticulum (ER) calcium release, ER stress, and apoptosis. In the present study, we have tested the effect of three calcium influx inhibitors, i.e., diazoxide, nifedipine, and verapamil, on the apoptosis-inducing effect of saturated stearic acid (SA) in the human pancreatic β-cell lines NES2Y and 1.1B4. We have demonstrated that the application of all three calcium influx inhibitors tested has no inhibitory effect on SA-induced ER stress and apoptosis in both tested cell lines. Moreover, these inhibitors have pro-apoptotic potential per se at higher concentrations. Interestingly, these findings are in contradiction with those obtained with rodent cell lines and islets. Thus our data obtained with human β-cell lines suggest that the prospective usage of calcium channel blockers for prevention and therapy of type 2 diabetes mellitus, developed with the contribution of the saturated FA-induced apoptosis of β-cells, seems rather unlikely.
Exploring perceived effects from loss of PEPFAR support for outreach in Kenya and Uganda
Authors: Qiu Mary , Paina Ligia , Rodríguez Daniela C. , Wilhelm Jess A. , Eze-Ajoku Ezinne , Searle Alexandra , Zakumumpa Henry , Ssengooba Freddie , MacKenzie Caroline , Bennett Sara 
Published: July 2021

Abstract
Introduction
In 2015, the President’s Emergency Plan for AIDS Relief undertook policy shifts to increase efficiencies in its programming, including transitioning HIV/AIDS funding away from low burden areas. We examine the impact of these changes on HIV outreach in Kenya and Uganda.

Methods
Qualitative data collection was conducted as a part of a broader mixed-methods evaluation. Two rounds of facility-level case studies and national-level interviews were conducted in Kenya and Uganda, with health facility, sub-national and central Ministry of Health staff, HIV clients, and implementing partners.

Results
In both countries, the loss of outreach support affected community-based HIV/AIDS education, testing, peer support, and defaulter tracing.

Discussion
Loss of external support for outreach raises concerns for countries’ ability to reach the 90–90-90 UNAIDS target, as key linkages between vulnerable communities and health systems can be adversely affected.

Conclusion
Development partners should consider how to mitigate potential consequences of transition policies to prevent negative effects at the community level.
A large consanguineous family with a homozygous Metabotropic Glutamate Receptor 7 (mGlu7) variant and developmental epileptic encephalopathy: Effect on protein structure and ligand affinity
Authors: Jdila Marwa Ben , Mignon-Ravix Cécile , Ncir Sihem Ben , Kammoun Fatma , Fakhfakh Faiza , Villard Laurent , Triki Chahnez 
Published: July 2021

AbstractBackgroundDevelopmental and epileptic encephalopathies (DEE) are chronic neurological conditions where epileptic activity contributes to the progressive disruption of brain function, frequently leading to impaired motor, cognitive and sensory development.Patients and methodsThe present study reports a clinical investigation and a molecular analysis by Next Generation Sequencing (NGS) of a large consanguineous family comprising several cases of developmental and epileptic encephalopathy. Bioinformatic prediction and molecular docking analysis were also carried out.ResultsThe majority of patients in our studied family had severe developmental impairments, early-onset seizures, brain malformations such as cortical atrophy and microcephaly, developmental delays and intellectual disabilities. The molecular investigations revealed a novel homozygous variant c.1411G>A (p.Gly471Arg) in theGRM7gene which was segregating with the disease in the family. Bioinformatic tools predicted its pathogenicity and docking analysis revealed its potential effects on mGlu7 protein binding to its ligand.ConclusionOur results contribute to a better understanding of the impact ofGRM7variants for the newly described associated phenotype.
Selection of CT variables and prognostic models for outcome prediction in patients with traumatic brain injury
Authors: Khaki Djino , Hietanen Virpi , Corell Alba , Hergès Helena Odenstedt , Ljungqvist Johan 
Published: July 2021

Abstract
Background
Traumatic brain injuries (TBI) are associated with high risk of morbidity and mortality. Early outcome prediction in patients with TBI require reliable data input and stable prognostic models. The aim of this investigation was to analyze different CT classification systems and prognostic calculators in a representative population of TBI-patients, with known outcomes, in a neurointensive care unit (NICU), to identify the most suitable CT scoring system for continued research.

Materials and methods
We retrospectively included 158 consecutive patients with TBI admitted to the NICU at a level 1 trauma center in Sweden from 2012 to 2016. Baseline data on admission was recorded, CT scans were reviewed, and patient outcome one year after trauma was assessed according to Glasgow Outcome Scale (GOS). The Marshall classification, Rotterdam scoring system, Helsinki CT score and Stockholm CT score were tested, in addition to the IMPACT and CRASH prognostic calculators. The results were then compared with the actual outcomes.

Results
Glasgow Coma Scale score on admission was 3–8 in 38%, 9–13 in 27.2%, and 14–15 in 34.8% of the patients. GOS after one year showed good recovery in 15.8%, moderate disability in 27.2%, severe disability in 24.7%, vegetative state in 1.3% and death in 29.7%. When adding the variables from the IMPACT base model to the CT scoring systems, the Stockholm CT score yielded the strongest relationship to actual outcome. The results from the prognostic calculators IMPACT and CRASH were divided into two subgroups of mortality (percentages); ≤50% (favorable outcome) and > 50% (unfavorable outcome). This yielded favorable IMPACT and CRASH scores in 54.4 and 38.0% respectively.

Conclusion
The Stockholm CT score and the Helsinki score yielded the closest relationship between the models and the actual outcomes in this consecutive patient series, representative of a NICU TBI-population. Furthermore, the Stockholm CT score yielded the strongest overall relationship when adding variables from the IMPACT base model and would be our method of choice for continued research when using any of the current available CT score models.
Panton-valentine leukocidin Staphylococcus aureus severe infection in an infant: a case report and a review of the literature
Authors: Castellazzi Massimo Luca , Bosis Samantha , Borzani Irene , Tagliabue Claudia , Pinzani Raffaella , Marchisio Paola , di Pietro Giada Maria 
Published: July 2021

Abstract
Background
Panton-Valentine leukocidin (PVL) is one of the major virulence factor of Staphylococcus aureus (SA) that might be associated with invasive life-threating infections. A prompt diagnosis and adequate treatment are essential in achieving the best outcome and avoiding serious sequelae. We describe a case of severe invasive PVL-SA infection in an infant. A literature review starting from 2010 was also performed in order to discuss clinical presentations, radiological findings, treatment and outcome.

Case presentation
This is a case of a 6-month-old boy who rapidly developed high fever and poor general condition. He was diagnosed as having multiple muscular abscesses, multiple foci of osteomyelitis and bloodstream infections caused by Panton-Valentine leukocidin Methicillin-resistant Staphylococcus aureus. He received intravenous antibiotics and surgical drainage of the abscess with progressive recovery.

Conclusion
Our report highlights the importance of improving awareness of this severe infection, as a prompt diagnosis and adequate manage is essential in order to save life and to prevent serious complications.