bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics of Oral Nirmatrelvir/Ritonavir, a Protease Inhibitor for Treatment of COVID‐19, in Subjects With Renal Impairment
Authors: Toussi Sima S. , Neutel Joel Michael , Navarro Jesus , Preston Richard Alfred , Shi Haihong , Kavetska Olga , LaBadie Robert R. , Binks Michael , Chan Phylinda L.S. , Demers Neil , Corrigan Brian , Damle Bharat 
Published: June 2022

Nirmatrelvir coadministered with ritonavir is highly efficacious in reducing the risk of coronavirus disease 2019 (COVID‐19) adverse outcomes among patients at increased risk of progression to severe disease, including patients with chronic kidney disease. Because nirmatrelvir is eliminated by the kidneys when given with ritonavir, this phase I study evaluated the effects of renal impairment on pharmacokinetics, safety, and tolerability of nirmatrelvir/ritonavir. Participants with normal renal function (n = 10) or mild, moderate, or severe renal impairment (n = 8 each) were administered a single 100‐mg nirmatrelvir dose with 100 mg ritonavir given 12 hours before, together with and 12 and 24 hours after the nirmatrelvir dose. Systemic nirmatrelvir exposure increased with increasing renal impairment, with mild, moderate, and severe renal impairment groups having respective adjusted geometric mean ratio areas under the plasma concentration‐time profile from time 0 extrapolated to infinite time of 124%, 187%, and 304% vs. the normal renal function group. Corresponding ratios for maximum plasma concentration were 130%, 138%, and 148%. Apparent clearance was positively correlated with estimated glomerular filtration rate, and geometric mean renal clearance values were particularly lower for the moderate (47% decrease) and severe (80% decrease) renal impairment groups vs. the normal renal function group. Nirmatrelvir/ritonavir exhibited an acceptable safety profile; treatment‐related adverse events were mild in severity, and there were no significant findings regarding laboratory measurements, vital signs, or electrocardiogram assessments. These findings led to a dose reduction recommendation for nirmatrelvir/ritonavir in patients with moderate renal impairment (150/100 mg nirmatrelvir/ritonavir instead of 300/100 mg twice daily for 5 days). NCT04909853.
Durum wheat Teosinte Branched1 null mutations increase tillering
Authors: Volkman McKenna M. , Martin John M. , Hogg Andrew C. , Wright Lucas , Hale Caleb , Carr Patrick M. , Giroux Michael J. 
Published: June 2022

AbstractWheat (Triticum spp.) yield is increased by either producing and testing variants of yield‐limiting genes or crossing to create new allelic combinations. Tiller number and seeds per tiller influence wheat yield, and both are impacted by the Teosinte Branched1 (TB1) gene. We screened 16 hard red spring wheat (Triticum aestivum L.) cultivars, 15 hard red winter wheat cultivars and lines, and 10 durum wheat [Triticum turgidum L. subsp. durum (Desf.) van Slageren] cultivars and lines commonly grown in Montana and found several previously reported TB1 missense alleles along with one new silent and a missense TB1‐A1 allele among the 16 hard red spring wheat cultivars but no TB1 null alleles. Among the 10 durum cultivars, five carried a TB1‐B1‐S184G missense allele and all winter wheat cultivars carried wild‐type TB1 alleles. To determine the impact of TB1 null alleles, this study examined durum wheat genotypes varying for TB1 null alleles created by ethyl methanesulfonate (EMS) mutagenesis. The goal was to determine the impact of TB1 null alleles on tillering, agronomic, and seed traits. The impact of TB1 null alleles was studied alone and together in field trials. The TB1 single‐ and double‐null mutants produced up to 15% more tillers and 18% with positive trends toward increased plant biomass. The results of this research demonstrate that the integration of EMS‐derived TB1 null alleles may prove useful in increasing small‐grain tillering to optimize plant biomass and yield under different growing conditions.
Short‐term outcomes of patients undergoing endoscopic submucosal dissection for colorectal lesions
Authors: Nakajima Yuki , Nemoto Daiki , Nemoto Tetsutaro , Takahata Yosuke , Aizawa Masato , Utano Kenichi , Isohata Noriyuki , Endo Shungo , Lefor Alan Kawarai , Togashi Kazutomo 
Published: June 2022

AbstractObjectivesEndoscopic submucosal dissection (ESD) of colorectal lesions was invented in Japan, but postoperative management including hospital stay has not been reconsidered due to the Japanese insurance system. To explore appropriate postoperative management after colorectal ESD, we reviewed short‐term outcomes after ESD in non‐selected consecutive patients.MethodsPatients who underwent colorectal ESD from April 2013 to September 2020 in one institution were reviewed. The primary outcome measure was the occurrence of adverse events stratified by the Clavien‐Dindo classification with five grades. A logistic regression model with the Firth procedure was applied to investigate predictors of severe (grade III or greater) adverse events.ResultsA total of 330 patients (female 40%, male 60%; median 72 years; IQR 65–80 years) with colorectal lesions (median 30 mm, IQR 23–40 mm; colon 77%, rectum 23%; serrated lesion 4%, adenoma 47%, mucosal cancer 30%, invasive cancer 18%) was evaluated. The en bloc resection rate was 97%. The median dissection time was 58 min (IQR: 38–86). Intraprocedural perforation occurred in 3%, all successfully treated by endoscopic clipping. No delayed perforations occurred. Postprocedural bleeding occurred in 3% on days 1–10 (median day 2); all were controlled endoscopically. Severe adverse events included only delayed bleeding. In analyzing severe adverse events in a multivariate logistic regression model with the Firth procedure, antithrombotic agent use (p = 0.016) and rectal lesions (p = 0.0010) were both significant predictors.ConclusionsNo serious adverse events occurred in this series. Four days of hospitalization may be too long for the majority of patients after ESD.
The Marinoan cap carbonate of Svalbard: Syngenetic marine dolomite with 17O‐anomalous carbonate‐associated sulphate
Authors: Fairchild Ian J. , Bao Huiming , Windmill Richard J. , Boomer Ian 
Published: June 2022

AbstractTwo cap carbonates overlying Cryogenian panglacial deposits are found in North‐East Svalbard of which the younger (635 Ma) forms the base of the Ediacaran Period. It is represented by a transgressive succession in which laminated dolostone, typically around 20 m thick (Member D1), is succeeded transitionally by a similar thickness of impure carbonates (Member D2). In Spitsbergen, there is evidence of microbially influenced sediment stabilisation and carbonate precipitation in the lower part of D1, whilst the upper part of D1 and D2 show centimetre‐decimetre‐scale graded units with undulatory lamination interpreted as evidence of storm activity. Carbonate originated as possible freshwater whitings, as well as microbial precipitates. Exhumed and eroded hardgrounds display replacive 10–30 μm dolomite crystals with cathodoluminescence characteristics consistent with early diagenetic manganese and iron reduction. Regionally, carbon isotope values consistently decrease by around 2‰ from around −3‰ over 30 m of section which is both a temporal and a bathymetric signal, but not a global one. An exponential decline in carbonate production predicted by box models is fitted by a semi‐quantitative sedimentation model. A mass‐anomalous 17O depletion in carbonate‐associated sulphate in dolomite, inherited from precursor calcite, decreases from −0.6 to −0.3‰ in the basal 15 m of section and then approaches background values. The post‐glacial anomalous 17O depletion in carbonate‐associated sulphate and barite elsewhere has been interpreted in terms of ultra‐high pCO2 at the onset of deglaciation. Such anomalies, with larger amplitude, have been reported in Svalbard from underlying lacustrine and tufaceous limestones representing a hyperarid glacial environment. The anomalous sulphate could be produced contemporarily, or the internally drained landscape may have continued to release 17O‐anomalous sulphate as it was transgressed during cap carbonate deposition. The late Cryogenian to earliest Ediacaran record in Svalbard provides the most complete record of the basal 17O‐depletion event in the world.
Retinoic acid signaling regulates late stages of semicircular canal morphogenesis and otolith maintenance in the zebrafish inner ear
Authors: Mackowetzky Kacey , Dicipulo Renée , Fox Sabrina C. , Philibert Danielle A. , Todesco Hayley , Doshi Jainil D. , Kawakami Koichi , Tierney Keith , Waskiewicz Andrew J. 
Published: June 2022

AbstractBackgroundThe vitamin A derivative all‐trans retinoic acid (RA) regulates early stages of inner ear development. As the early disruption of the RA pathway results in profound mispatterning of the developing inner ear, this confounds analyses of specific roles in later stages. Therefore, we used the temporal‐specific exposure of all‐trans RA or diethylaminobenzaldehyde to evaluate RA functions in late otic development.ResultsPerturbing late RA signaling causes behavioral defects analogous to those expected in larvae suffering from vestibular dysfunction. These larvae also demonstrate malformations of the semi‐circular canals, as visualized through (a) use of the transgenic strain nkhspdmc12a, a fluorescent reporter expressed in otic epithelium; and (b) injection of the fluorescent lipophilic dye DiI. We also noted the altered expression of genes encoding ECM proteins or modifying enzymes. Other malformations of the inner ear observed in our work include the loss or reduced size of the utricular and saccular otoliths, suggesting a role for RA in otolith maintenance.ConclusionOur work has identified a previously undescribed late phase of RA activity in otic development, demonstrating that vestibular defects observed in human patients in relation to perturbed RA signaling are not solely due to its early disruption in otic development.
A machine learning method for estimating the probability of presence using presence‐background data
Authors: Wang Yan , Samarasekara Chathuri L. , Stone Lewi 
Published: June 2022

AbstractEstimating the prevalence or the absolute probability of the presence of a species from presence‐background data has become a controversial topic in species distribution modelling. In this paper, we propose a new method by combining both statistics and machine learning algorithms that helps overcome some of the known existing problems. We have also revisited the popular but highly controversial Lele and Keim (LK) method by evaluating its performance and assessing the RSPF condition it relies on. Simulations show that the LK method with the RSPF assumptions would render fragile estimation/prediction of the desired probabilities. Rather, we propose the local knowledge condition, which relaxes the predetermined population prevalence condition that has so often been used in much of the existing literature. Simulations demonstrate the performance of the new method utilizing the local knowledge assumption to successfully estimate the probability of presence. The local knowledge extends the local certainty or the prototypical presence location assumption, and has significant implications for demonstrating the necessary condition for identifying absolute (rather than relative) probability of presence from presence background without absence data in species distribution modelling.
Estimating survival and adoption rates of dependent juveniles
Authors: Street Phillip A. , Riecke Thomas V. , Williams Perry J. , Behnke Tessa L. , Sedinger James S. 
Published: June 2022

AbstractPopulation growth and fitness are typically most sensitive to adult survival in long‐lived species, but variation in recruitment often explains most of the variation in fitness, as past selection has canalized adult survival. Estimating juvenile survival until age of independence has proven challenging, because marking individuals in this age class may directly affect survival. For Greater Sage‐grouse, uniquely marking juveniles in the first days of life likely results in adverse effects to survival, detection of juveniles is not perfect, and females adopt juveniles from other parents. These challenges are encountered by researchers studying avian and mammalian species with similar life histories, yet methods do not exist that explicitly estimate all these components of the recruitment process. We propose a novel data collection method and demographic model to simultaneously estimate rates of detection, survival, and adoption of juvenile individuals. Using multiple cameras to film the beginning of juvenile activity on specific days, we obtained counts of juveniles associated with marked females. Increases of juveniles to broods provided information that enabled us to estimate rates of adoption that can be applied at the population level. Losses from broods informed apparent survival. These losses could be attributed to death, or they could be chicks that were adopted by other females. We found evidence that apparent survival of juveniles was influenced by localized weather patterns when chicks were young. Similarly, we found that young chicks were more susceptible to the adverse effect of attending females being flushed by an observer. Both of these patterns diminished quickly as chicks aged. We provide the first‐ever estimates of interval‐specific adoption rates. Our results suggest that researchers should be cautious when designing studies to estimate juvenile survival. More importantly, they provide insight into adoption, a behavior that has been known to exist for decades.
Growth and development of an invasive forest insect under current and future projected temperature regimes
Authors: Walter Jonathan A. , Thompson Lily M. , Powers Sean D. , Parry Dylan , Agosta Salvatore J. , Grayson Kristine L. 
Published: June 2022

AbstractTemperature and its impact on fitness are fundamental for understanding range shifts and population dynamics under climate change. Geographic climate heterogeneity, behavioral and physiological plasticity, and thermal adaptation to local climates make predicting the responses of species to climate change complex. Using larvae from seven geographically distinct wild populations in the eastern United States of the non‐native forest pest Lymantria dispar dispar (L.), we conducted a simulated reciprocal transplant experiment in environmental chambers using six custom temperature regimes representing contemporary conditions near the southern and northern extremes of the US invasion front and projections under two climate change scenarios for the year 2050. Larval growth and development rates increased with climate warming compared with current thermal regimes and tended to be greater for individuals originally sourced from southern rather than northern populations. Although increases in growth and development rates with warming varied somewhat by region of the source population, there was not strong evidence of local adaptation, southern populations tended to outperform those from northern populations in all thermal regimes. Our study demonstrates the utility of simulating thermal regimes under climate change in environmental chambers and emphasizes how the impacts from future increases in temperature can vary based on geographic differences in climate‐related performance among populations.
Land‐use change shifts and magnifies seasonal variations of the decomposer system in lowland tropical landscapes
Authors: Krashevska Valentyna , Stiegler Christian , June Tania , Widyastuti Rahayu , Knohl Alexander , Scheu Stefan , Potapov Anton 
Published: June 2022

AbstractDeforestation and agricultural expansion in the tropics affect local and regional climatic conditions, leading to synergistic negative impacts on land ecosystems. Climatic changes manifest in increased inter‐ and intraseasonal variations and frequency of extreme climatic events (i.e., droughts and floods), which have evident consequences for aboveground biodiversity. However, until today, there have been no studies on how land use affects seasonal variations below ground in tropical ecosystems, which may be more buffered against climatic variation. Here, we analyzed seasonal variations in soil parameters, basal respiration, microbial communities, and abundances of soil invertebrates along with microclimatic conditions in rainforest and monocultures of oil palm and rubber in Sumatra, Indonesia. About 75% (20 out of 26) of the measured litter and soil, microbial, and animal parameters varied with season, with seasonal changes in 50% of the parameters depending on land use. Land use affected seasonal variations in microbial indicators associated with carbon availability and cycling rate. The magnitude of seasonal variations in microbial parameters in the soil of monocultures was almost 40% higher than in the soil of rainforest. Measured parameters were associated with short‐term climatic conditions (3‐day period air humidity) in plantations, but not in rainforest, confirming a reduced soil buffering ability in plantations. Overall, our findings suggest that land use temporally shifts and increases the magnitude of seasonal variations of the belowground ecosystem compartment, with microbial communities responding most strongly. The increased seasonal variations in soil biota in plantations likely translate into more pronounced fluctuations in essential ecosystem functions such as nutrient cycling and carbon sequestration, and these ramifications ultimately may compromise the stability of tropical ecosystems in the long term. As the observed seasonal dynamics is likely to increase with both local and global climate change, these shifts need closer attention for the long‐term sustainable management of plantation systems in the tropics.
Forecasting the combined effects of future climate and land use change on the suitable habitat of Davidia involucrata Baill
Authors: Tang Junfeng , Zhao Xuzhe 
Published: June 2022

AbstractAccurately predicting the future distribution of species is crucial for understanding how species will response to global environmental change and for evaluating the effectiveness of current protected areas (PAs). Here, we assessed the effect of climate and land use change on the projected suitable habitats of Davidia involucrata Baill under different future scenarios using the following two types of models: (a) only climate covariates (climate SDMs) and (b) climate and land use covariates (full SDMs). We found that full SDMs perform significantly better than climate SDMs in terms of both AUC (p < .001) and TSS (p < .001) and also projected more suitable habitat than climate SDMs both in the whole study area and in its current suitable range, although D. involucrate is predicted to loss at least 26.96% of its suitable area under all future scenarios. Similarly, we found that these range contractions projected by climate SDMs would negate the effectiveness of current PAs to a greater extent relative to full SDMs. These results suggest that although D. involucrate is extremely vulnerability to future climate change, conservation intervention to manage habitat may be an effective option to offset some of the negative effects of a changing climate on D. involucrate and can improve the effectiveness of current PAs. Overall, this study highlights the necessity of integrating climate and land use change to project the future distribution of species.
Creating practices and strategies towards persistence for undeclared, Black males at Predominately White Institutions (PWIs)
Authors: McElderry Jonathan A. 
Published: June 2022

AbstractThe majority of research on Black males highlights the problems or barriers faced by this demographic due to the low retention and completion rates. A factor that is often not discussed when students enter college is their decision around initially declaring a major and its future impact on their persistence and college completion. This chapter explores practices and strategies for senior administrators in higher education to assist undeclared, Black male students at Predominately White Institutions (PWIs) toward persistence and ultimately college completion. The recommendations for practice in this chapter offer tangible tools to create a positive campus experience for Black male collegians, as well as educate and hold members of the campus community accountable.
Circulating TREM2 as a noninvasive diagnostic biomarker for NASH in patients with elevated liver stiffness
Authors: Indira Chandran Vineesh , Wernberg Charlotte Wilhelmina , Lauridsen Mette Munk , Skytthe Maria Kløjgaard , Bendixen Sofie Marchsteiner , Larsen Frederik Tibert , Hansen Camilla Dalby , Grønkjær Lea Ladegaard , Siersbæk Majken Storm , Caterino Tina Di , Detlefsen Sönke , Møller Holger Jon , Grøntved Lars , Ravnskjaer Kim , Moestrup Søren Kragh , Thiele Maja Sofie , Krag Aleksander , Graversen Jonas Heilskov 
Published: June 2022

Background and Aims:
Reliable noninvasive biomarkers are an unmet clinical need for the diagnosis of NASH. This study investigates the diagnostic accuracy of the circulating triggering receptor expressed on myeloid cells 2 (plasma TREM2) as a biomarker for NASH in patients with NAFLD and elevated liver stiffness.

Approach and Results:
We collected cross‐sectional, clinical data including liver biopsies from a derivation (n = 48) and a validation cohort (n = 170) of patients with elevated liver stiffness measurement (LSM ≥ 8.0 kPa). Patients with NAFLD activity scores (NAS) ≥4 were defined as having NASH. Plasma TREM2 levels were significantly elevated in patients with NASH of the derivation cohort, with an area under the receiver operating characteristics curve (AUROC) of 0.92 (95% confidence interval [CI], 0.84–0.99). In the validation cohort, plasma TREM2 level increased approximately two‐fold in patients with NASH, and a strong diagnostic accuracy was confirmed (AUROC, 0.83; 95% CI, 0.77–0.89; p < 0.0001). Plasma TREM2 levels were associated with the individual histologic features of NAS: steatosis, lobular inflammation, and ballooning (p < 0.0001), but only weakly with fibrosis stages. Dual cutoffs for rule‐in and rule‐out were explored: a plasma TREM2 level of ≤38 ng/ml was found to be an optimal NASH rule‐out cutoff (sensitivity 90%; specificity 52%), whereas a plasma TREM2 level of ≥65 ng/ml was an optimal NASH rule‐in cutoff (specificity 89%; sensitivity 54%).

Conclusions:
Plasma TREM2 is a plausible individual biomarker that can rule‐in or rule‐out the presence of NASH with high accuracy and thus has the potential to reduce the need for liver biopsies and to identify patients who are eligible for clinical trials in NASH.