bluuebunny/crossref_metadata_2025_split huggingface dataset:
Offsite primary care providers using telehealth to support a sustainable workforce in rural and remote general practice: A rapid review of the literature
Authors: Calleja Zoe , Job Jennifer , Jackson Claire 
Published: August 2022

AbstractIntroductionRural and remote general practices face increasing demands for care without the workforce required to meet patient needs. The coronavirus pandemic has created an opportunity to explore sustainable, telehealth‐driven solutions to this chronic and complex problem.ObjectiveThis review examined interventions using offsite primary care providers to deliver ongoing patient care via telehealth to support rural and remote general practices. We aimed to understand the impact of such interventions on the Quadruple Aim (patient experience, provider experience, health care costs, and health outcomes).DesignA rapid review of studies published from 2011 and grey literature published from 2016.FindingsSix studies met the eligibility criteria. No eligible Australian studies were identified. Most studies investigated ongoing primary care services provided via telehealth by offsite pharmacists. Patients and rural primary care staff reported positive experiences with the interventions. One study demonstrated potential return on investment for rural practices. While one study reported clinically and statistically significant improvements in health outcomes over time, two studies did not observe statistically significant differences in health outcomes between intervention and control cohorts.DiscussionThe Quadruple Aim should be carefully considered when designing, implementing, and evaluating interventions that involve offsite primary care providers using telehealth to support a sustainable workforce in rural and remote general practice.ConclusionSustainable solutions to workforce shortages in rural and remote general practice are needed urgently. Using offsite primary care providers to deliver telehealth and support practices in these regions is one possible solution that warrants further investigation, particularly in Australia.
Common and rare genetic risk variants in age‐related macular degeneration and genetic risk score in the Coimbra eye study
Authors: Farinha Cláudia , Barreto Patricia , Coimbra Rita , Cachulo Maria Luz , Melo Joana Barbosa , Cunha‐Vaz José , Lechanteur Yara , Hoyng Carel B. , Silva Rufino 
Published: August 2022

AbstractPurposeTo determine the contribution of common and rare genetic variants in age‐related macular degeneration (AMD) in a Portuguese population from the Coimbra Eye Study (CES), and the genetic risk score (GRS).MethodsParticipants underwent ophthalmologic examination and imaging. A centralized reading centre performed AMD staging. Genetic sequencing was carried out with the EYE‐RISK assay. Sixty‐nine single nucleotide polymorphisms (SNPs) were genotyped and tested for association with AMD. Case–control and progression‐to‐AMD analyses were performed using logistic regression to assess allelic odds ratio (OR) at a 95% confidence interval (CI) for each variant. GRS was calculated for cases/controls and progressors/non‐progressors. Cumulative impact of rare variants was compared between cases/controls using logistic regression.ResultsIn case–control analysis (237 cases/640 controls) variants associated with risk of disease were: ARMS2 rs10490924, ARMS2_HTRA1 rs3750846, CFH rs35292876, SLC16A8 rs8135665, TGFBR1 rs1626340. Major risk variants ARMS2/HTRA1 rs3750846, CFH rs570618 and C3 rs2230199 had unexpected lower allele frequency (AF), and the highest risk‐conferring variant was a rare variant, CFH rs35292876 (OR, 2.668; p‐value = 0.021). In progression‐to‐AMD analysis (137 progressors/630 non‐progressors), variants associated with risk of progression were ARMS2 rs10490924, ARMS2_HTRA1 rs3750846, CFH rs35292876. GRS of cases/controls was 1.124 ± 1.187 and 0.645 ± 1.124 (p‐value < 0.001), and of progressors/non‐progressors was 1.190 ± 1.178 and 0.669 ± 1.141 (p‐value < 0.001). Higher proportion of pathogenic rare CFH variants was observed in cases (OR, 9.661; p‐value < 0.001).ConclusionsBoth common and rare variants were associated with AMD, but a CFH rare variant conferred the highest risk of disease while three major risk variants had a lower‐than‐expected AF in our population originary from a geographic region with lower prevalence of AMD. GRS was still significantly higher in AMD patients. Damaging CFH rare variants were cumulatively more common in AMD cases.
Association between structural and functional treatment outcomes in neovascular age‐related macular degeneration
Authors: Haji Hauraz , Gianniou Christina , Brynskov Troels , Sørensen Torben L. , Olsen Rasmus , Krogh Nielsen Marie 
Published: August 2022

AbstractPurposeThe administration frequency of intravitreal anti‐vascular endothelial growth factor (anti‐VEGF) in neovascular age‐related macular degeneration (AMD) have been widely discussed. The primary objective of the study was to explore the association between anatomical outcomes and changes in functional outcome.MethodsThis was a retrospective cohort study of patients with newly diagnosed neovascular AMD with a minimum of 12 months of follow‐up. Only one eye per patient was included. Patients were treated according to the observe‐and‐plan or the pro‐re‐nata regimen. All patients were regularly examined from the time of diagnosis up to 24 months. The effect of intraretinal fluid (IRF), subretinal fluid (SRF) and pigment epithelium detachment (PED) at any time point on visual acuity (VA) was tested, as well as the long‐term effect and the risk of losing VA. Further, the variability of central retinal thickness (CRT) was calculated for each eyes' individual measures during the observation period, excluding the monthly loading phase. The prognostic effect of each factor on VA was estimated by regression analysis. The primary outcome measure was VA, which was correlated with the presence or absence of fluid, seen as IRF, SRF or PED.ResultsA total of 504 treatment naïve eyes from 504 patients was included. The presence of IRF was associated with lower VA at all visits (p < 0.001). However, the presence of SRF or PED was not significantly associated with worse VA at any time point during the observation period. Patients in the upper quartile of CRT variance had a greater loss in VA after 12 and 24 months (p < 0.001).ConclusionsIn this retrospective cohort study, the presence of intraretinal fluid was associated with poorer visual outcome in neovascular AMD patients treated with anti‐VEGF, but the presence of subretinal fluid and PEDs was not. This suggests that IRF is worse than subretinal fluid and PEDs for AMD outcomes and therefore requires the most intensive treatment. Further, we found that patients with the highest CRT variability during the study period had poorer visual outcomes after 12 and 24 months, indicating that stringent control of retinal fluid volume fluctuations is important to prevent visual acuity decline over time.
The safety of paternal and maternal use of 5‐aminosalicylic acid during conception and pregnancy: a nationwide cohort study
Authors: Nørgård Bente Mertz , Friedman Sonia , Kjeldsen Jens , Nielsen Jan 
Published: August 2022

SummaryBackgroundData on the safety of paternal use of 5‐aminosalicylic acid (5‐ASA) prior to conception are lacking, and the safety of maternal use of 5‐ASA during pregnancy has not been examined in nationwide data.AimsTo examine offspring outcomes after paternal pre‐conception use of 5‐ASA, and after maternal use during pregnancyMethodsThis nationwide cohort study was based on Danish health registries. The study population included live born singletons of patients with ulcerative colitis (UC) or Crohn's disease (CD). Paternal exposure included 2168 children fathered by men treated with 5‐ASA, and 7732 unexposed. Maternal exposure included 3618 children exposed in utero to 5‐ASA, and 7128 unexposed. The outcomes were pre‐term birth, small for gestational age (SGA), low Apgar score and major congenital abnormalities (CAs) according to EUROCAT guidelines.ResultsThe vast majority of fathers and mothers used mesalazine. In children fathered by men with UC using 5‐ASA, we found no increased risk of pre‐term birth, SGA or low Apgar score. The hazard ratio (HR) of CAs was 1.30 (95% CI 0.92–1.85). In children of fathers with CD, the odds ratio (OR) of SGA was 1.52 (95% CI 0.65–3.55). After maternal 5‐ASA exposure, the OR of SGA in children of women with UC was 1.46 (95% CI: 0.93–2.30); for CAs in children of women with CD, HR was 1.44 (95% CI 0.84–2.47).ConclusionsPaternal and maternal use of 5‐ASA was safe across offspring outcomes; none of the findings reached statistical significance. The safety of 5‐ASA formulations that are used infrequently cannot be settled here.
Meta‐analysis: diagnostic accuracy of hepatitis C core antigen detection during therapy with direct‐acting antivirals
Authors: Sepúlveda‐Crespo Daniel , Treviño‐Nakoura Ana , Bellon José M. , Ardizone Jiménez Beatriz , Jiménez‐Sousa María A. , Fernández‐Rodríguez Amanda , Martínez Isidoro , Resino Salvador 
Published: August 2022

SummaryBackgroundTreatment of hepatitis C virus (HCV) infection with direct‐acting antivirals (DAAs) is monitored by assessing plasma HCV‐RNA load. However, detection of HCV core antigen (HCVcAg) may be an alternative.AimTo evaluate the diagnostic performance of the HCVcAg assay to monitor the efficacy of DAAs in HCV‐infected patientsMethodsWe performed searches in multiple electronic databases until 6 July 2022, of studies evaluating the HCVcAg detection in plasma or serum compared with the HCV‐RNA test (gold standard). We calculated pooled measurement at 2 and 4 weeks of treatment, and at end‐of‐treatment (EOT), as well as sustained virological response (SVR; 12 weeks after EOT).ResultsWe selected 16 studies from 2016 to 2022, with 3237 patients and 8958 samples. Overall, the diagnostic performance and clinical utility of the HCVcAg assay were poor at week 2 (sensitivity = 0.40, specificity = 0.96, positive likelihood ratio (PLR) = 9.16, negative likelihood ratio (NLR) = 0.63, and area under the summary receiver operating curve (SROC) = 0.57), fair at week 4 (sensitivity = 0.30, specificity = 0.90, PLR = 3.18, NLR = 0.77, and AUC = 0.79), acceptable at EOT (sensitivity = 0.40, specificity =0.98, PLR = 16.54, NLR = 0.62, and AUC = 0.97) and excellent for SVR (sensitivity = 0.94, specificity = 0.99, PLR = 107.54, NLR = 0.06, and AUC = 0.99).ConclusionsThe HCVcAg assay may be helpful for monitoring the efficacy of HCV treatment with DAAs in HCV‐infected patients at EOT and for documenting SVR, but not at weeks 2 and 4 of treatment due to poor diagnostic performance.
An Early Pleistocene interglacial deposit at Pingorsuit, North‐West Greenland
Authors: Bennike Ole , Colgan William , Hedenäs Lars , Heiri Oliver , Lemdahl Geoffrey , Wiberg‐Larsen Peter , Ribeiro Sofia , Pronzato Roberto , Manconi Renata , Bjørk Anders A. 
Published: August 2022

At the Pingorsuit Glacier in North‐West Greenland, an organic‐rich deposit that had recently emerged from the retreating ice cap was discovered at an elevation of 480 m above sea level. This paper reports on macrofossil analyses of a coarse detritus gyttja and peaty soil, which occurred beneath a thin cover of till and glacifluvial deposits. The sediments contained remains of vascular plants, mosses, beetles, caddisflies, midges, bryozoans, sponges and other invertebrates. The flora includes black spruce, tree birch, boreal shrubs and wetland and aquatic taxa, which shows that mires, lakes and ponds were present in the area. We describe a new extinct waterwort speciesElatine odgaardii. The fossils were deposited in a boreal environment with a mean July air temperature that was at least 9 °C higher than at present. The fossil assemblages show strong similarities with others from Greenland that have been assigned an Early Pleistocene age, and we suggest a similar age for the sediments found at the margin of the Pingorsuit Glacier.At the Pingorsuit Glacier in North‐West Greenland, an organic‐rich deposit was discovered at an elevation of 480 m above sea level. The sediments contained remains of vascular plants, mosses, beetles, caddisflies, midges, bryozoans, sponges and other invertebrates. The fossils were deposited in a boreal environment with a mean July air temperature that was at least 9 °C higher than at present.
The interplay between basement fabric, rifting, syn‐rift folding, and inversion in the Rio do Peixe Basin, NE Brazil
Authors: Pichel Leonardo M. , Antunes Alex F. , Fossen Haakon , Rapozo Barbara F. , Finch Emma , Córdoba Valeria C. 
Published: August 2022

AbstractThe Rio do Peixe Basin is part of a series of aborted Cretaceous rifts formed within the Proterozoic Borborema Province, onshore NE Brazil in response to rifting between Africa and South America. The basin is remarkably well‐imaged and comprises fault‐bounded depocentres, the main ones being the NE‐oriented Brejo das Freiras and the E–W‐oriented Sousa half‐grabens. These grabens and their bounding faults are influenced by Neoproterozoic basement shear zones and present a complex framework of secondary normal faults and folds. Recent workers also interpret large reverse faults and regional post‐rift shortening driven by far‐field stresses from the Andes. For those reasons, the basin represents an ideal setting to investigate the multiphase history of rift basins. We thus combine borehole‐calibrated 2D and 3D seismic and magnetic data with section restoration and numerical modelling to investigate the architecture and evolution of this basin. We aim to understand: (i) the controls of the basement fabric in 3D fault architecture and kinematics and (ii) how syn‐rift faults controlled the geometry and development of fault‐related folds. By doing this, we also investigate the timing, kinematics, and magnitude of inversion in the basin to explore its multiphase history. We demonstrate that (i) the basement fabric controlled not only the strike of faults but also their geometry and polarity at depth, (ii) folds in the syn‐rift sequence are attributed simply to syn‐rift extension along stepped and/or curved faults, and (iii) inverted and/or reverse faults occur within the basin, but these are minor and appear to have formed during rifting. We explain this minor inversion by a change in plate kinematics related to the onset of the nearby transform margin to the north. These results have implications for understanding the 3D evolution of oblique grabens, the role of structural inheritance, and the recognition of inversion‐ versus extension‐related folds in rift basins worldwide.
Robust Processing Advantage for Binomial Phrases with Variant Conjunctions
Authors: Chantavarin Suphasiree , Morgan Emily , Ferreira Fernanda 
Published: August 2022

AbstractPrior research has shown that various types of conventional multiword chunks are processed faster than matched novel strings, but it is unclear whether this processing advantage extends to variant multiword chunks that are less formulaic. To determine whether the processing advantage of multiword chunks accommodates variations in the canonical phrasal template, we examined the robustness of the processing advantage (i.e., predictability) of binomial phrases with non‐canonical conjunctions (e.g.,salt and also pepper; salt as well as pepper). Results from the cloze study (Experiment 1) showed that there was a high tendency of producing the canonical conjunct (pepper), even in the binomials that contained non‐formulaic conjunctions. Consistent with these findings, results from two eye tracking studies (Experiments 2a and 2b) showed that canonical conjuncts were read faster than novel conjuncts that were matched on word length (e.g.,paprika), even in the binomials with variant conjunctions. This robust online processing advantage was replicated in a self‐paced reading study that compared all three conjunction types (Experiment 3). Taken together, these findings show that binomials with variant function words also receive facilitated processing relative to matched novel strings, even though both types of strings are neither conventional nor relatively frequent. Exploratory analyses revealed that this processing speed advantage was driven by the lexical–semantic association between the canonical conjuncts (salt–pepper), rather than lexical and phrasal frequency. Overall, these results highlight flexibility in the processing of multiword chunks that current models of multiword storage and processing must take into account.
Standardizing submaximal exercise intensities for use of supine push–pull exercise during cardiovascular magnetic resonance
Authors: Steenhorst Jarno J. , Hirsch Alexander , van den Berg Linda E. M. , Kamphuis Lieke S. , Merkus Daphne , Boersma Eric , Helbing Willem A. 
Published: August 2022

AbstractBackgroundCardiovascular magnetic resonance (CMR) imaging during supine exercise at (sub)maximal oxygen consumption (VO2) offers unique diagnostic insights. However, maximal VO2 is not achievable in the supine position and standardizing submaximal exercise intensities remains challenging. Using heart rate or workload could be a viable option to translate VO2‐based submaximal exercise intensities.AimTo translate submaximal exercise intensities upright cycling exercise (UCE) to supine push–pull exercise (SPPE), by comparing heart rate or workload determined during UCE, with heart rate and workload during SPPE at similar exercise intensities.Methods and ResultsSixteen healthy young adults (20.4 ± 2.2 years; 8 female) underwent cardiopulmonary UCE and SPPE testing [mean ± standard deviation maximal VO2: 3.2 ± 0.6 vs. 5 ± 0.3 L min−1, p < 0.001 and median (interquartile range) of the maximum workload: 310 (244, 361) vs. 98 (98, 100), p < 0.001, respectively]. Heart rate at 40% and 60% of maximal VO2, as determined by UCE, showed low bias (−3 and 0 bpm, respectively) and wide limits of agreement (±26 and ±28 bpm, respectively), in Bland–Altman analysis. VO2/Workload relation was exponential and less efficient during SPPE compared to UCE. Generalized estimated equation analysis predicted model‐based mean workload during SPPE, with acceptable 95% confidence interval.ConclusionHeart rate during UCE at submaximal exercise intensities can reasonably well be used to for SPPE in healthy subjects. Using workload, an ergometer specific, model‐based mean can be used to determine exercise intensities during SPPE. Individual variations in response to posture and movement change are high. During clinical interpretation of exercise CMR, individual exercise intensity has to be considered.
Evaluating the efficacy of prototype antiseizure drugs using a preclinical pharmacokinetic approach
Authors: Mensah Jeffrey A. , Johnson Kristina , Reilly Christopher A. , Wilcox Karen S. , Rower Joseph E. , Metcalf Cameron S. 
Published: August 2022

AbstractObjectivePharmacokinetics (PK) of a drug drive its exposure, efficacy, and tolerability. A thorough preclinical PK assessment of antiseizure medications (ASMs) is therefore essential to evaluate the clinical potential. We tested protection against evoked seizures of prototype ASMs in conjunction with analysis of plasma and brain PK as a proof‐of‐principle study to enhance our understanding of drug efficacy and duration of action using rodent seizure models.MethodsIn vivo seizure protection assays were performed in adult male CF‐1 mice and Sprague Dawley rats. Clobazam (CLB), N‐desmethyl CLB (NCLB), carbamazepine (CBZ), CBZ‐10,11‐epoxide (CBZE), sodium valproate (VPA), and levetiracetam (LEV) concentrations were quantified in plasma and brain using liquid chromatography–tandem mass spectrometry. Mean concentrations of each analyte were calculated and used to determine PK parameters via noncompartmental analysis in Phoenix WinNonLin.ResultsNCLB concentrations were approximately 10‐fold greater than CLB in mice. The antiseizure profile of CLB was partially sustained by NCLB in mice. CLB concentrations were lower in rats than in mice. CBZE plasma exposures were approximately 70% of CBZ in both mice and rats, likely contributing to the antiseizure effect of CBZ. VPA showed a relatively short half‐life in both mice and rats, which correlated with a sharp decline in efficacy. LEV had a prolonged brain and plasma half‐life, associated with a prolonged duration of action in mice.SignificanceThe study demonstrates the utility of PK analyses for understanding the seizure protection time course in mice and rats. The data indicate that distinct PK profiles of ASMs between mice and rats likely drive differences in drug efficacy between rodent models.
Landscape determinants of pelagic and benthic primary production in northern lakes
Authors: Puts Isolde Callisto , Ask Jenny , Siewert Matthias B. , Sponseller Ryan A. , Hessen Dag O. , Bergström Ann‐Kristin 
Published: August 2022

AbstractGlobal change affects gross primary production (GPP) in benthic and pelagic habitats of northern lakes by influencing catchment characteristics and lake water biogeochemistry. However, how changes in key environmental drivers manifest and impact total (i.e., benthic + pelagic) GPP and the partitioning of total GPP between habitats represented by the benthic share (autotrophic structuring) is unclear. Using a dataset from 26 shallow lakes located across Arctic, subarctic, and boreal northern Sweden, we investigate how catchment properties (air temperature, land cover, hydrology) affect lake physico‐chemistry and patterns of total GPP and autotrophic structuring. We find that total GPP was mostly light limited, due to high dissolved organic carbon (DOC) concentrations originating from catchment soils with coniferous vegetation and wetlands, which is further promoted by high catchment runoff. In contrast, autotrophic structuring related mostly to the relative size of the benthic habitat, and was potentially modified by CO2 fertilization in the subarctic, resulting in significantly higher total GPP relative to the other biomes. Across Arctic and subarctic sites, DIC and CO2 were unrelated to DOC, indicating that external inputs of inorganic carbon can influence lake productivity patterns independent of terrestrial DOC supply. By comparison, DOC and CO2 were correlated across boreal lakes, suggesting that DOC mineralization acts as an important CO2 source for these sites. Our results underline that GPP as a resource is regulated by landscape properties, and is sensitive to large‐scale global changes (warming, hydrological intensification, recovery of acidification) that promote changes in catchment characteristics and aquatic physico‐chemistry. Our findings aid in predicting global change impacts on autotrophic structuring, and thus community structure and resource use of aquatic consumers in general. Given the similarities of global changes across the Northern hemisphere, our findings are likely relevant for northern lakes globally.