bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral and Intravenous Amoxicillin Dosing Recommendations in Neonates: A Pooled Population Pharmacokinetic Study
Authors: Keij Fleur M , Schouwenburg Stef , Kornelisse René F , Preijers Tim , Mir Fatima , Degraeuwe Pieter , Stolk Leo M , van Driel Arianne , Kenter Sandra , van der Sluijs Jacqueline , Heidema Jojanneke , den Butter Paul C P , Reiss Irwin K M , Allegaert Karel , Tramper-Stranders Gerdien A , Koch Birgit C P , Flint Robert B 
Published: September 2023

Abstract

Background
There is a lack of evidence on oral amoxicillin pharmacokinetics and exposure in neonates with possible serious bacterial infection (pSBI). We aimed to describe amoxicillin disposition following oral and intravenous administration and to provide dosing recommendations for preterm and term neonates treated for pSBI.

Methods
In this pooled-population pharmacokinetic study, 3 datasets were combined for nonlinear mixed-effects modeling. In order to evaluate amoxicillin exposure following oral and intravenous administration, pharmacokinetic profiles for different dosing regimens were simulated with the developed population pharmacokinetic model. A target of 50% time of the free fraction above the minimal inhibitory concentration (MIC) with an MICECOFF of 8 mg/L (to cover gram-negative bacteria such as Escherichia coli) was used.

Results
The cohort consisted of 261 (79 oral, 182 intravenous) neonates with a median (range) gestational age of 35.8 weeks (range, 24.9–42.4) and bodyweight of 2.6 kg (range, 0.5–5). A 1-compartment model with first-order absorption best described amoxicillin pharmacokinetics. Clearance (L/h/kg) in neonates born after 30 weeks’ gestation increased with increasing postnatal age (PNA day 10, 1.25-fold; PNA day 20, 1.43-fold vs PNA day 3). Oral bioavailability was 87%. We found that a twice-daily regimen of 50 mg/kg/day is superior to a 3- or 4-times daily schedule in the first week of life for both oral and intravenous administration.

Conclusions
This pooled population pharmacokinetic description of intravenous and oral amoxicillin in neonates provides age-specific dosing recommendations. We conclude that neonates treated with oral amoxicillin in the first weeks of life reach adequate amoxicillin levels following a twice-daily dosing regimen. Oral amoxicillin therapy could therefore be an adequate, cost-effective, and more patient-friendly alternative for neonates worldwide.
Study of the association between serum levels of kynurenine and cardiovascular outcomes and overall mortality in chronic kidney disease
Authors: El Chamieh Carolla , Larabi Islam Amine , Alencar De Pinho Natalia , Lambert Oriane , Combe Christian , Fouque Denis , Frimat Luc , Jacquelinet Christian , Laville Maurice , Laville Solène , Lange Céline , Alvarez Jean-Claude , Massy Ziad A , Liabeuf Sophie ,   the Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) Study Group, Hannedouche T , Moulin B , Klein A , Combe C , Bourdenx J P , Keller A , Delclaux C , Vendrely B , Deroure B , Lacraz A , Lobbedez T , Landru I , Massy Z , Lang P , Belenfant X , Thervet E , Urena P , Delahousse M , Vela C , Essig M , Clément D , Sekhri H , Smati M , Jamali M , Hacq B , Panescu V , Bellou M , Frimat Luc , Kamar N , Noël C , Glowacki F , Maisonneuve N , Azar R , Hoffmann M , Hourmant M , Testa A , Besnier D , Choukroun G , Lambrey G , Burtey S , Lebrun G , Magnant E , Laville M , Fouque D , Juillard L , Chazot C , Zaoui P , Kuentz F 
Published: September 2023

ABSTRACT

Background
Kynurenine is a protein-bound uremic toxin. Its circulating levels are increased in chronic kidney disease (CKD). Experimental studies showed that it exerted deleterious cardiovascular effects. We sought to evaluate an association between serum kynurenine levels and adverse fatal or nonfatal cardiovascular events and all-cause mortality in CKD patients.

Methods
The CKD-REIN study is a prospective cohort of people with CKD having an estimated glomerular filtration rate (eGFR) &lt;60 ml/min/1.73 m². Baseline frozen samples of total and free fractions of kynurenine and tryptophan were measured using a validated liquid chromatography tandem mass spectrometry technique. Cause-specific Cox models were used to estimate hazard ratios (HRs) for each outcome.

Results
Of the 2406 included patients (median age: 68 years; median eGFR: 25 ml/min/1.73 m2), 52% had a history of cardiovascular disease. A doubling of serum-free kynurenine levels was associated with an 18% increased hazard of cardiovascular events [466 events, HR (95%CI):1.18(1.02,1.33)], independently of eGFR, serum-free tryptophan level or other uremic toxins, cardioprotective drugs, and traditional cardiovascular risk factors. Serum-free kynurenine was significantly associated with non-atheromatous cardiovascular events [HR(95%CI):1.26(1.03,1.50)], but not with atheromatous cardiovascular events [HR(95%CI):1.15(0.89,1.50)]. The association of serum-free kynurenine with cardiovascular mortality was also independently significant [87 events; adjusted HR(95%CI):1.64(1.10,2.40)]. However, the association of serum-free kynurenine with all-cause mortality was no more significant after adjustment on serum-free tryptophan [311 events, HR(95%CI):1.12(0.90, 1.40)].

Conclusions
Our findings imply that serum-free kynurenine, independently of other cardiovascular risk factors (including eGFR), is associated with fatal or nonfatal cardiovascular outcomes, particularly non-atheromatous cardiovascular events; in patients with CKD. Strategies to reduce serum kynurenine levels should be evaluated in further studies.
A-192 Cause and Departmental Origin of Errors—An Investigation of Questionable Patient Test Results
Authors: Brady A L , Hayden M , Elkins M B , Nasr M R , Reyes A , Cao Z T 
Published: September 2023

Abstract

Introduction
Reliable patient test results are crucial for quality patient care, involving pre-, post- and analytical phases. Questionable Patient test Results (QPRs), either not matching patient clinical presentation or apparent outliers for the patient population, are often encountered. We aimed to investigate the source and nature of possible errors that cause QPRs.

Methods
960 QPRs were identified during July-December 2022 at our institution. We examined the nature of the QPRs, the corresponding patient clinical records, the procedures involved in pre-, post- and analytical phases, and quality control systems.

Results
The QPRs were found to be originated from 31 departments and medical specialty units. Of those, 5 departments/units had &gt;50 QPRs (accounting for 64% of total QPRs) and are listed in the table provided. The table also lists the information on 7 types of errors identified by our analysis. Of all errors, 78% occurred at pre-analytical phase, with the majority of errors occurring during sample collection.

Discussion
The most common types of errors were either diluted or contaminated samples accounting for 38% and 34%, respectively. Such errors often occur during sample drawing from an existing I.V. access port if not adequately flushed after saline solution infusion (causing sample dilution) or dextrose solution (causing glucose contamination). Many errors were due to samples drawn in the wrong collection tube type. Sample integrity issues included hemolysis, lack of sufficient sample volume, or clotting. For those QPRs that we did not find apparent errors, they were either due to random errors or the results fit the patient’s true medical condition.

Conclusions
Our findings highlight the importance of pre-analytical quality control measures and the need for regular staff education/training. This study pinpointed the errors that require targeted education materials, as well as the hospital units that would benefit most from this focus on error prevention.
Phenology of Leucotaraxis argenticollis, a specialist predator of the invasive hemlock woolly adelgid, in the eastern United States
Authors: Preston Carrie E , Dietschler Nicholas J , Whitmore Mark C , Salom Scott M 
Published: September 2023

Abstract
In hemlock stands within eastern US forests, classical biological control has been one of the main strategies used to manage the hemlock woolly adelgid, Adelges tsugae Annand. Specialist predator species may offer a management solution to help regulate A. tsugae populations. In the Pacific Northwest, a suite of specialist predators has been a focus of research and includes 2 species of silver fly, Leucotaraxis argenticollis (Zetterstedt) and Leucotaraxis piniperda (Malloch) (Diptera: Chamaemyiidae). Leucotaraxis spp. phenology has been documented in the Pacific Northwest, but the phenology of either western Leucotaraxis species is unknown in the eastern United States. This study sought to document the phenology of Le. argenticollis in NY in 2021 and in VA in 2021 and 2022. Nylon mesh cages were applied over eastern hemlock branches infested with A. tsugae to contain Le. argenticollis adults. Biweekly and monthly branch samples were taken in 2021 and 2022, documenting all life stages of A. tsugae and of Le. argenticollis that were observed. In 2021 and 2022, Le. argenticollis adults and eggs were present during the oviposition stage of the 2 generations of A. tsugae. In addition, Le. argenticollis larvae were present when A. tsugae ovisacs had eggs and while A. tsugae nymphs of both generations were present. These observations indicate that Le. argenticollis phenology is well synchronized with A. tsugae in the eastern United States.
Sequential transplantation of the liver–kidney–heart from different donors: a case report
Authors: Wang Liaoran , Zhang Yu , Yu Hang , Song Jiangping , Wang Yi 
Published: September 2023

Abstract

Background
Multi-organ transplantation has emerged as a viable treatment strategy for patients afflicted with multiple organ failure or significant organ dysfunctions. Despite the promising therapeutic outcomes, this approach also amplifies the risk of organ rejection, infection, or neoplastic growth. We present a unique case of a patient who sequentially underwent liver, kidney, and heart transplantation, all sourced from different donors. This case brings forth intriguing possibilities about the interplay between cardiovascular diseases and complications arising post-transplantation, thereby enriching our understanding of comprehensive transplant immunomodulation and cardiovascular disease prevention.

Case summary
A 59-year-old male with chronic alcohol misuse developed liver cirrhosis in 2012 and subsequent kidney failure in 2018 due to alcoholic liver disease, type II diabetes, hyperlipidaemia, and severe hypertension. Subsequently, an incident of extensive transmural myocardial infarction (Killip III) warranted a heart transplant in 2022. Post-transplant, the patient was maintained on a standard immunosuppression regimen with regular post-operative follow-ups. No signs of rejection were noted 1-year post-final transplantation under standard immunosuppression.

Discussion
The presented case exemplifies the potential and feasibility of sequential multi-organ transplantation. The multifaceted interplay between the transplanted organs and the immunosuppressive pharmaceuticals likely exert distinct influences on transplantation immune regulation, possibly diverging from the dynamics observed in single-organ transplantation. A comprehensive exploration of the mechanisms governing immune responses in the context of multi-organ transplantation could yield valuable insights for mitigating graft dysfunction. Furthermore, the rapid progression of atherosclerosis observed after liver and kidney transplantation necessitates further scrutiny to elucidate potential correlations with the post-transplantation state.
Revisiting aortic valve prosthesis choice in patients younger than 50 years: 10 years results of the AUTHEARTVISIT study
Authors: Traxler Denise , Krotka Pavla , Reichardt Berthold , Copic Dragan , Veraar Cecilia , Mildner Michael , Wendt Ralph , Auer Johann , Mascherbauer Julia , Ankersmit Hendrik Jan , Graf Alexandra 
Published: September 2023

Abstract

OBJECTIVES
This population-based cohort study investigated mid-term outcome after surgical aortic valve replacement with a bioprosthetic or mechanical valve prosthesis in patients aged &lt;50 years in a European social welfare state.

METHODS
We analysed patient data from the main social insurance carriers in Austria (2010–2020). Subsequent patient-level record linkage with national health data provided patient characteristics and clinical outcome. Survival, reoperation, myocardial infarction, heart failure, embolic stroke or intracerebral haemorrhage, bleeding other than intracerebral haemorrhage and major adverse cardiac events were evaluated as outcomes.

RESULTS
A total of 991 patients were analysed. Regarding demographics, no major differences between groups were observed. Multivariable Cox regression revealed no significant difference in overall survival (P = 0.352) with a median follow-up time of 6.2 years. Reoperation-free survival was decreased (hazard ratio = 1.560 [95% CI: 1.076–2.262], P = 0.019) and the risk for reoperation was increased (hazard ratio = 2.770 [95% CI: 1.402–5.472], P = 0.003) in patients who received bioprostheses. Estimated probability of death after reoperation was 0.23 (CL: 0.08–0.35) after 2 years and 0.34 (CL: 0.06–0.53) after 10 years over both groups. Regarding further outcomes, no significant differences between the two groups were observed.

CONCLUSIONS
In patients below 50 years of age receiving aortic valve replacement, implantation of bioprostheses when compared to mechanical heart valve prostheses was associated with a significantly higher rate of reoperations and reduced reoperation-free survival. Nevertheless, we could not observe a difference in overall survival. However, long-term follow-up has to evaluate that a significantly lower rate of reoperations may translate in consistently improved long-term survival.
SynLight: a bicistronic strategy for simultaneous active zone and cell labeling in the Drosophila nervous system
Authors: Aimino Michael A , Humenik Jesse , Parisi Michael J , Duhart Juan Carlos , Mosca Timothy J 
Published: September 2023

Abstract
At synapses, chemical neurotransmission mediates the exchange of information between neurons, leading to complex movement, behaviors, and stimulus processing. The immense number and variety of neurons within the nervous system make discerning individual neuron populations difficult, necessitating the development of advanced neuronal labeling techniques. In Drosophila, Bruchpilot-Short and mCD8-GFP, which label presynaptic active zones and neuronal membranes, respectively, have been widely used to study synapse development and organization. This labeling is often achieved via the expression of 2 independent constructs by a single binary expression system, but expression can weaken when multiple transgenes are expressed by a single driver. Recent work has sought to circumvent these drawbacks by developing methods that encode multiple proteins from a single transcript. Self-cleaving peptides, specifically 2A peptides, have emerged as effective sequences for accomplishing this task. We leveraged 2A ribosomal skipping peptides to engineer a construct that produces both Bruchpilot-Short-mStraw and mCD8-GFP from the same mRNA, which we named SynLight. Using SynLight, we visualized the putative synaptic active zones and membranes of multiple classes of olfactory, visual, and motor neurons and observed the correct separation of signal, confirming that both proteins are being generated separately. Furthermore, we demonstrate proof of principle by quantifying synaptic puncta number and neurite volume in olfactory neurons and finding no difference between the synapse densities of neurons expressing SynLight or neurons expressing both transgenes separately. At the neuromuscular junction, we determined that the synaptic puncta number labeled by SynLight was comparable to the endogenous puncta labeled by antibody staining. Overall, SynLight is a versatile tool for examining synapse density in any nervous system region of interest and allows new questions to be answered about synaptic development and organization.
Adult Age Differences in Evoked Emotional Responses to Dynamic Facial Expressions
Authors: Abiodun Sade J , Salerno Joanna M , McAllister Galen A , Samanez-Larkin Gregory R , Seaman Kendra L 
Published: September 2023

Abstract

Objectives
Facial expressions are powerful social signals that motivate feelings and actions in the observer. Research on face processing has overwhelmingly used static facial images, which have limited ecological validity. Previous research on the age-related positivity effect and age differences in social motivation suggest that older adults might experience different evoked emotional responses to facial expressions than younger adults. Here, we introduce a new method to explore age-related differences in evoked responses to dynamic facial expressions across adulthood.

Methods
We used dynamic facial expressions which varied by expression type (happy, sad, and angry) and expression magnitude (low, medium, and full) to gather participant ratings on their evoked emotional response to these stimuli along the dimensions of valence (positive vs negative) and arousal.

Results
As predicted, older adults rated the emotions evoked by positive facial expressions (happy) more positively than younger adults. Furthermore, older adults rated the emotion evoked by negative facial expressions (angry and sad) more negatively than younger adults. Contrary to our predictions, older adults did not differ significantly in arousal to negative expressions compared with younger adults. Across all ages, individuals rated positive expressions as more arousing than negative expressions.

Discussion
The findings provide some evidence that older adults may be more sensitive to variations in dynamic facial expressions than younger adults, particularly in terms of their estimates of valence. These dynamic facial stimuli that vary in magnitude are promising for future studies of more naturalistic affect elicitation, studies of social incentive processing, and use in incentive-driven choice tasks.
Very Early-Life Risk Factors for Developing Dementia: Evidence From Full Population Registers
Authors: Fischer Martin , Lövdén Martin , Nilsson Therese , Seblova Dominika 
Published: September 2023

Abstract

Objectives
Very early-life conditions are recognized as critical for healthy brain development. This study assesses early-life risk factors for developing dementia. In the absence of historical medical birth records, we leverage an alternative full population approach using demographic characteristics obtained from administrative data to derive proxy indicators for birth complications and unfavorable birth outcomes. We use proxy variables to investigate the impact of early-life risk factors on dementia risk.

Methods
We use administrative individual-level data for full cohorts born 1932–1950 in Sweden with multigenerational linkages. Records on hospitalization and mortality are used to identify dementia cases. We derive 3 birth risk factors based on demographic characteristics: advanced maternal age, narrow sibling spacing, and twin births, and apply survival analysis to evaluate long-term effects on dementia risk. We control for confounding using multiple indicators for socio-economic status (SES), including parental surnames, and by implementing a sibling design. As comparison exposure, we add low education from the 1970 Census.

Results
The presence of at least 1 birth risk factor increases dementia risk (HR = 1.059; 95% CI: 1.034, 1.085). The occurrence of twin births poses a particularly heightened risk (HR = 1.166; 95% CI: 1.084, 1.255).

Discussion
Improvements to the very early-life environment hold significant potential to mitigate dementia risk. A comparison to the influence of low education on dementia (the largest known modifiable risk factor) suggests that demographic birth characteristics are of relevant effect sizes. Our findings underscore the relevance of providing assistance for births experiencing complications and adverse health outcomes to reduce dementia cases.
Combining atmospheric and non-tidal ocean loading effects to correct high precision gravity time-series
Authors: Antokoletz E D , Wziontek H , Dobslaw H , Balidakis K , Klügel T , Oreiro F A , Tocho C N 
Published: September 2023

SUMMARY
In modelling atmospheric loading effects for terrestrial gravimetry, state-of-the-art approaches take advantage of numerical weather models to account for the global 3-D distribution of air masses. Deformation effects are often computed assuming the Inverse Barometer (IB) hypothesis to be generally valid over the oceans. By a revision of the IB assumption and its consequences we show that although the seafloor is not deformed by atmospheric pressure changes, there exists a fraction of ocean mass that current modelling schemes are usually not accounting for. This causes an overestimation of the atmospheric attraction effect over oceans, even when the dynamic response of the ocean to atmospheric pressure and wind is accounted through dynamic ocean models. This signal can reach a root mean square variability of a few nm s−2, depending on the location of the station. We therefore test atmospheric and non-tidal ocean loading effects at five superconducting gravimeter (SG) stations, showing that a better representation of the residual gravity variations is found when Newtonian attraction effects due to the IB response of the ocean are correctly considered. A sliding window variance analysis shows that the main reduction takes place for periods between 5 and 10 d, even for stations far away from the oceans. Since periods of non-tidal ocean mass variability closely resemble atmospheric signals recorded by SGs, we recommend to directly incorporate both an ocean component together with the IB into services that provide weather-related corrections for terrestrial gravimetry.
3D mapping challenges in hybrid video-assisted thoracoscopic surgical ablation of Brugada syndrome
Authors: Eltsov Ivan , Pannone Luigi , Ramak Robbert , Monaco Cinzia , Della Rocca Domenico Giovanni , Bala Gezim , Kronenberger Rani , Overeinder Ingrid , Almorad Alexander , Stroker Erwin , Sieira Juan , Brugada Pedro , Sarkozy Andrea , Chierchia Gian-Battista , de Asmundis Carlo , La Meir Mark 
Published: September 2023

Abstract

OBJECTIVES
Brugada syndrome is a life-threatening disease with an arrhythmogenic substrate located in the epicardium of right ventricle outflow tract. Therefore, the correct region identification is crucial for a successful ablation procedure. Various mapping techniques can be adopted to elaborate this issue, but they were all initially developed for endovascular use.

METHODS
In this study, we analysed 21 consecutive hybrid video-assisted thoracoscopic ablation of Brugada syndrome, performed using different mapping systems to identify the ablation target and confirm the elimination of arrhythmogenic substrate; 35 maps have been analysed.

RESULTS
Acute success of epicardial right ventricle outflow tract ablation has been achieved in 100% of procedures, no periprocedural complications have been observed; HD Grid catheter showed higher area identification speed and faster fractionated potentials visualization; Rhythmia system has demonstrated the best map density; Carto 3 system showed a significant advantage in patient preparation time, but mapping speed was reduced due to focal catheter use only.

CONCLUSIONS
All tested electro anatomical mapping systems can be used for hybrid video-assisted thoracoscopic ablation with same clinical success; however, accuracy and efficacy of mapping systems are heterogenous and highly dependent on proper patient preparation, mapping system and physician skills.