bluuebunny/crossref_metadata_2025_split huggingface dataset:
Airborne laser scanning reveals increased growth and complexity of boreal forest canopies across a network of ungulate exclosures in Norway
Authors: Kolstad Anders L. , Snøan Ingrid Bekken , Austrheim Gunnar , Bollandsås Ole Martin , Solberg Erling J. , Speed James D. M. 
Published: August 2021

AbstractLarge herbivores are often classed as ecosystem engineers, and when they become scarce or overabundant, this can alter ecosystem states and influence climate forcing potentials. This realization has spurred a call to integrate large herbivores in earth system models. However, we lack a good understanding of their net effects on climate forcing, including carbon and energy exchange. A possible solution to this lies in harmonizing data across the myriad of large herbivore exclosure experiments around the world. This is challenging due to differences in experimental designs and field protocols. We used airborne laser scanning (ALS) to describe the effect of herbivore removal across 43 young boreal forest stands in Norway and found that exclusion caused the canopy height to increase from 1.7 ± 0.2 to 2.5 ± 0.2 m (means ± se), and also causing a marked increase in vertical complexity and above‐ground biomass. We then go on to discuss some of the issues with using ALS; we propose ALS as an approach for studying the effects of multiple large herbivore exclosure experiments simultaneously, and producing area‐based estimates on canopy structure and forest biomass in a cheap, efficient, standardized and reproducible way. We suggest that this is a vital next step towards generating biome‐wide predictions for the effects of large herbivores on forest ecosystem structure which can both inform both local management goals and earth system models.
Challenges and opportunities of gender mainstreaming strategy implementation in public sectors: The case of Women and Children Affairs Office, Bahir Dar City Administration, Amhara Region, Ethiopia
Authors: Mihrete Alemeneh G. , Bayu Eyayu K. 
Published: August 2021

AbstractGender Mainstreaming is an organizational strategy to bring a gender perspective to all aspects of an institution's policy. This research aimed to investigate the challenges and opportunities of gender mainstreaming implementation by taking women, children, and youth affairs office of Bahir Dar City administration as a case. To do so, a qualitative research method with a case study research design was employed. To select the participants, purposive and availability sampling techniques were employed. Interview, focus group discussion, and document review were used as major data collection instruments. The data were analyzed thematically. The findings revealed that, absence of gender focal person, compartmentalization, lack of commitments, lack of training, lack of theoretical and technical skills about gender, and insufficient budget were the identified challenges. The presence of evaluation among heads at the council, existence of policies, and cooperative leadership were identified as an opportunity. To sum up, there are numerous challenges that hinder its monitoring and evaluation activities to mainstream gender even if there were a few opportunities that facilitate their activities. Based on the findings, the regional government should support and monitor the respective office challenges.
Palynology of a short sequence of the Lower Devonian Beartooth Butte Formation at Cottonwood Canyon (Wyoming): age, depositional environments and plant diversity
Authors: Noetinger Sol , Bippus Alexander C. , Tomescu Alexandru M.F. 
Published: August 2021

AbstractThe Beartooth Butte Formation hosts the most extensive Early Devonian macroflora of western North America. The age of the flora at Cottonwood Canyon (Wyoming) has been constrained to the Lochkovian–Pragian interval, based on fish biostratigraphy and unpublished palynological data. We present a detailed palynological analysis of the plant‐bearing layers at Cottonwood Canyon. The palynomorphs consist of 32 spore, five cryptospore, two prasinophycean algae and an acritarch species. The stratigraphic ranges of these palynomorphs indicate a late Lochkovian or Pragian age, confirming previous age assignments. Analysis of samples from three different depositional environments of the plant‐bearing sequence (layers within situlycophyte populations, flood layers that buried those populations and an organic matter accumulation zone within a flood layer) demonstrate distinct palynofacies. Comparisons between palynomorph and plant macrofossil diversity reveal some discrepancies. Whereas zosterophylls and lycophytes, most diverse and abundant among the macrofossils, have only one known corresponding spore type (assignable to zosterophylls) in the palynomorph assemblage, the trimerophytes, rare in the macrofossil assemblage, are represented by three spore types. Some of these discrepancies reflect taphonomic differences between the macrofossils and palynomorphs, while others could be due to the fact that the parent plants of most palynomorph types in the Cottonwood Canyon assemblage are unknown. These observations emphasize the need for concerted efforts to bring together the knowledge of macro‐ and microfloras within Early Devonian localities. Nevertheless, given the palaeophytogeographic significance of the Beartooth Butte Formation flora, its palynofossil and macrofossil assemblages, taken together, provide new data relevant to future discussions of Early Devonian biogeography.
AdS3 gravity and RCFT ensembles with multiple invariants
Authors: Meruliya Viraj , Mukhi Sunil 
Published: August 2021

Abstract
We use the Poincaré series method to compute gravity partition functions associated to SU(N)1 WZW models with arbitrarily large numbers of modular invariants. The result is an average over these invariants, with the weights being given by inverting a matrix whose size is of order the number of invariants. For the chosen models, this matrix takes a special form that allows us to invert it for arbitrary size and thereby explicitly calculate the weights of this average. For the identity seed we find that the weights are positive for all N, consistent with each model being dual to an ensemble average over CFT’s.
Different mechanisms of magnitude and spatial representation for tactile and auditory modalities
Authors: Bollini Alice , Esposito Davide , Campus Claudio , Gori Monica 
Published: August 2021

AbstractThe human brain creates an external world representation based on magnitude judgments by estimating distance, numerosity, or size. The magnitude and spatial representation are hypothesized to rely on common mechanisms shared by different sensory modalities. We explored the relationship between magnitude and spatial representation using two different sensory systems. We hypothesize that the interaction between space and magnitude is combined differently depending on sensory modalities. Furthermore, we aimed to understand the role of the spatial reference frame in magnitude representation. We used stimulus–response compatibility (SRC) to investigate these processes assuming that performance is improved if stimulus and response share common features. We designed an auditory and tactile SRC task with conflicting spatial and magnitude mapping. Our results showed that sensory modality modulates the relationship between space and magnitude. A larger effect of magnitude over spatial congruency occurred in a tactile task. However, magnitude and space showed similar weight in the auditory task, with neither spatial congruency nor magnitude congruency having a significant effect. Moreover, we observed that the spatial frame activated during tasks was elicited by the sensory inputs. The participants' performance was reversed in the tactile task between uncrossed and crossed hands posture, suggesting an internal coordinate system. In contrast, crossing the hands did not alter performance (i.e., using an allocentric frame of reference). Overall, these results suggest that space and magnitude interaction differ in auditory and tactile modalities, supporting the idea that these sensory modalities use different magnitude and spatial representation mechanisms.
Physiologically based pharmacokinetic modelling to predict the clinical effect of CYP3A inhibitors/inducers on esaxerenone pharmacokinetics in healthy subjects and subjects with hepatic impairment
Authors: Watanabe Akiko , Ishizuka Tomoko , Yamada Makiko , Igawa Yoshiyuki , Shimizu Takako , Ishizuka Hitoshi 
Published: August 2021

Abstract
Purpose
Esaxerenone is a novel, oral, nonsteroidal treatment for hypertension. Physiologically based pharmacokinetic (PBPK) modelling was performed to predict the drug–drug interaction (DDI) effect of cytochrome P450 (CYP)3A modulators on esaxerenone pharmacokinetics in healthy subjects and subjects with hepatic impairment.

Methods
In our PBPK model, the fraction of esaxerenone metabolised by CYP3A was estimated from mass-balance data and verified and optimised by clinical DDI study results with strong CYP3A modulators. The model was also verified by the observed pharmacokinetics after multiple oral dosing and by the effect of hepatic impairment on esaxerenone pharmacokinetics. The model was applied to predict the DDI effects on esaxerenone pharmacokinetics with untested CYP3A modulators in healthy subjects and with strong CYP3A modulators in subjects with hepatic impairment.

Results
The PBPK model well described esaxerenone pharmacokinetics after multiple oral dosing. The predicted fold changes in esaxerenone plasma exposure after coadministration with strong CYP3A modulators were comparable with the observed data (1.53-fold with itraconazole and 0.31-fold with rifampicin). Predicted DDIs with untested moderate CYP3A modulators were less than the observed DDI with strong CYP3A modulators. The PBPK model also described the effect of hepatic impairment on esaxerenone plasma exposure. The predicted DDI results with strong CYP3A modulators in subjects with hepatic impairment indicate that, for concomitant use of CYP3A modulators, caution is advised for subjects with hepatic impairment, as is for healthy subjects.

Conclusion
The PBPK model developed predicted esaxerenone pharmacokinetics and DDIs and informed concurrent use of esaxerenone with CYP3A modulators.
Results from a PI-RADS-based MRI-directed diagnostic pathway for biopsy-naive patients in a non-university hospital
Authors: Reijnen Jeroen S. , Marthinsen Jon B. , Tysland Alf O. , Müller Christoph , Schönhardt Irina , Andersen Erlend , Seierstad Therese , Hole Knut H. 
Published: August 2021

Abstract
Purpose
To assess the safety and performance of a MRI-directed diagnostic pathway for patients with first-time suspicion of prostate cancer in a non-university hospital.

Methods
Between May 2017 and December 2018 all biopsy-naive patients examined in our hospital followed a MRI-directed diagnostic work-up algorithm based on PI-RADS score. In short, PI-RADS 1–2 was generally not biopsied and PI-RADS 3–5 was reviewed by a multidisciplinary team. Patients with PI-RADS 4-5 were all referred to biopsy, either transrectal ultrasound-guided biopsy or MRI in-bore biopsy for small tumors and for sites difficult to access. PI-RADS scores were compared to the histopathology from biopsies and surgical specimens for patients who had prostatectomy. Non-biopsied patients were referred to a safety net monitoring regimen.

Results
Two hundred and ninety-eight men were enrolled. 97 (33%) had PI-RADS 1–2, 44 (15%) had PI-RADS 3, and 157 (53%) had PI-RADS 4–5. 116 (39%) of the patients avoided biopsy. None of these were diagnosed with significant cancer within 2–3.5 years of safety net monitoring. Almost all high ISUP grade groups (≥ 3) were in the PI-RADS 4–5 category (98%). Prostatectomy specimens and systematic biopsies from MRI-negative areas indicated that very few clinically significant cancers were missed by the MRI-directed diagnostic pathway.

Conclusion
Our findings add to evidence that a MRI-directed diagnostic pathway can be safely established in a non-university hospital. The pathway reduced the number of biopsies and reliably detected the site of the most aggressive cancers.

Graphic abstract
The additional value of ONEST (Observers Needed to Evaluate Subjective Tests) in assessing reproducibility of oestrogen receptor, progesterone receptor, and Ki67 classification in breast cancer
Authors: Cserni Bálint , Bori Rita , Csörgő Erika , Oláh-Németh Orsolya , Pancsa Tamás , Sejben Anita , Sejben István , Vörös András , Zombori Tamás , Nyári Tibor , Cserni Gábor 
Published: August 2021

AbstractThe reproducibility of assessing potential biomarkers is crucial for their implementation. ONEST (Observers Needed to Evaluate Subjective Tests) has been recently introduced as a new additive evaluation method for the assessment of reliability, by demonstrating how the number of observers impact on interobserver agreement. Oestrogen receptor (ER), progesterone receptor (PR), and Ki67 proliferation marker immunohistochemical stainings were assessed on 50 core needle biopsy and 50 excision samples from breast cancers by 9 pathologists according to daily practice. ER and PR statuses based on the percentages of stained nuclei were the most consistently assessed parameters (intraclass correlation coefficients, ICC 0.918–0.996), whereas Ki67 with 5 different theoretical or St Gallen Consensus Conference–proposed cut-off values demonstrated moderate to good reproducibility (ICC: 0.625–0.760). ONEST highlighted that consistent tests like ER and PR assessment needed only 2 or 3 observers for optimal evaluation of reproducibility, and the width between plots of the best and worst overall percent agreement values for 100 randomly selected permutations of observers was narrow. In contrast, with less consistently evaluated tests of Ki67 categorization, ONEST suggested at least 5 observers required for more trustful assessment of reliability, and the bandwidth of the best and worst plots was wider (up to 34% difference between two observers). ONEST has additional value to traditional calculations of the interobserver agreement by not only highlighting the number of observers needed to trustfully evaluate reproducibility but also by highlighting the rate of agreement with an increasing number of observers and disagreement between the better and worse ratings.
Surgical outcome of percutaneous transhepatic gallbladder drainage in acute cholecystitis: Ten years’ experience at a tertiary care centre
Authors: Ábrahám Szabolcs , Tóth Illés , Benkő Ria , Matuz Mária , Kovács Gabriella , Morvay Zita , Nagy András , Ottlakán Aurél , Czakó László , Szepes Zoltán , Váczi Dániel , Négyessy András , Paszt Attila , Simonka Zsolt , Petri András , Lázár György 
Published: August 2021

Abstract
Background
Percutaneous transhepatic gallbladder drainage (PTGBD) plays an important role in the treatment of elderly patients and/or patients in poor health with acute cholecystitis (AC). The primary aim of this study is to determine how these factors influence the clinical outcome of PTGBD. Moreover, we assessed the timing and results of subsequent cholecystectomies.

Patients and Methods
We retrospectively examined the results of 162 patients undergoing PTGBD between 2010 and 2020 (male–female ratio: 51.23% vs. 48.77%; mean age: 71.43 ± 13.22 years). Patient’s performance status and intervention outcomes were assessed with clinical success rates (CSR) and in-hospital mortality. The conversion rate (CR) of possible urgent or delayed, elective laparoscopic cholecystectomies (LC) after PTGBD were analysed.

Results
PTGBD was the definitive treatment in 42.18% of patients, while it was a bridging therapy prior to cholecystectomy (CCY) for the other patients. CSR was 87.97%, it was only 64.29% in grade III AC. In 9.87% of the cases, urgent LC was necessary after PTGBD, and its conversion rate was approximately equal to that of elective LC (18.18 vs. 17.46%, respectively, p = 0.2217). Overall, the post-PTGBD in-hospital mortality was 11.72%, while the same figure was 0% for grade I AC, 7.41% for grade II and 40.91% for grade III. Based on logistic regression analyses, in-hospital mortality (OR 6.07; CI 1.79–20.56), clinical progression (OR 7.62; CI 2.64–22.05) and the need for emergency CCY (OR 14.75; CI 3.07–70.81) were mostly determined by AC severity grade.

Conclusion
PTGBD is an easy-to-perform intervention with promising clinical success rates in the treatment of acute cholecystitis. After PTGBD, the level of gallbladder inflammation played a decisive role in the course of AC. In a severe, grade III inflammation, we have to consider low CSR and high mortality.
Prospective clinical evaluation of chairside-fabricated zirconia-reinforced lithium silicate ceramic partial crowns—5-year results
Authors: Rinke Sven , Zuck Tanja , Hausdörfer Tim , Leha Andreas , Wassmann Torsten , Ziebolz Dirk 
Published: August 2021

Abstract
Objectives
A university-based randomized clinical study evaluated the 5-year performance of chairside-fabricated zirconia-reinforced lithium silicate (ZLS)-ceramic partial crowns.

Material and methods
Forty-five patients were restored with 61 chairside-fabricated ZLS-restorations (Cerec SW 4.2, Dentsply Sirona, Germany; Vita Suprinity, Vita Zahnfabrik, Germany). Deviating from the manufacturers’ recommendations, restorations with reduced minimum material thicknesses (MMT) were fabricated: group 1, MMT = 0.5–0.74 mm (n = 31); group 2, MMT = 0.75–1.0 mm (n = 30). For luting, a self-adhesive cement (SAC) or a total-etch technique with a composite cement (TEC) was applied. Statistical evaluation was performed by time-to-event analysis (Kaplan–Meier). Possible covariates of the survival (SVR) and success rates (SCR), evaluated in a Cox regression model, were MMT, restoration position (premolar/molar), and cementation technique (SAC vs. TEC).

Results
Forty patients (54 restorations, premolars, n = 23; molars, n = 31) participated in the 5-year follow-up. Five losses due to ceramic fractures occurred in group 1 (n = 28) (SVR: 83.0% [95% confidence interval (CI): 0.71–0.96]). Group 2 (n = 26) showed no losses (SVR: 100%). The success rate for partial crowns placed on premolars was 100% and 69% (95% CI: 0.54–0.84) for molar restorations. Recementation was required in 4 restorations with SAC (SCR: 86% [95% CI: 0.73–0.99]; SCR-DC: 100%). Restorations in group 2 showed a significantly reduced risk of material fracture hazard ratio (HR) = 0.09, p = 0.0292) compared with the restorations in group 1. Molar partial crowns showed an increased risk for a clinical intervention (HR = 5.26, p = 0.0222) compared to premolar restorations.

Conclusions
Material thickness and position of the restoration are risk factors influencing the survival and success rate of ZLS-ceramic partial crowns.

Clinical relevance
Observation of an MMT of at least 0.75–1.0 mm for ZLS-ceramics is essential to avoid material-related fractures.
Clinical trial registration: German Clinical Trails Register (trial number: DRKS00005611)
Long-term glucocorticoid treatment and high relapse rate remain unresolved issues in the real-life management of polymyalgia rheumatica: a systematic literature review and meta-analysis
Authors: Floris Alberto , Piga Matteo , Chessa Elisabetta , Congia Mattia , Erre Gian Luca , Angioni Maria Maddalena , Mathieu Alessandro , Cauli Alberto 
Published: August 2021

AbstractA systematic review and meta-analysis were conducted, according to the PRISMA methodology, to summarize current evidence on the prevalence and predictors of long-term glucocorticoid (GC) treatment and disease relapses in the real-life management of polymyalgia rheumatica (PMR).Out of 5442 retrieved studies, 21 were eligible for meta-analysis and 24 for qualitative analysis. The pooled proportions of patients still taking GCs at 1, 2, and 5 years were respectively 77% (95%CI 71–83%), 51% (95%CI 41–61%), and 25% (95CI% 15–36%). No significant difference was recorded by distinguishing study cohorts recruited before and after the issue of the international recommendations in 2010. The pooled proportion of patients experiencing at least one relapse at 1 year from treatment initiation was 43% (95%CI 29–56%). Female gender, acute-phase reactants levels, peripheral arthritis, starting GCs dosage, and tapering speed were the most frequently investigated potential predictors of prolonged GC treatment and relapse, but with inconsistent results. Only a few studies and with conflicting results evaluated the potential role of early treatment with methotrexate in reducing the GC exposure and the risk of relapse in PMR.This study showed that a high rate of prolonged GC treatment is still recorded in the management of PMR. The relapse rate, even remarkable, can only partially explain the long-term GC treatment, suggesting that other and not yet identified factors may be involved. Additional research is needed to profile patients with a higher risk of long-term GC treatment and relapse and identify more effective steroid-sparing strategies.Key Points:• High rate of long-term glucocorticoid (GC) treatment is recorded in polymyalgia rheumatica (PMR), being 77%, 51%, and 25% of patients still on GCs after respectively 1, 2, and 5 years.• A pooled relapse rate of 43% at 1 year, even remarkable, can only partially explain the long-term GC treatment in PMR.• Several studies have attempted to identify potential predictors of prolonged treatment with GCs and relapse, but with inconsistent results.• Additional research is needed to profile patients with a higher risk of long-term GC treatment and relapse and identify more effective steroid-sparing strategies.
A Novel Mutation in COL4A1 Gene in a Chinese Family with Pontine Autosomal Dominant Microangiopathy and Leukoencephalopathy
Authors: Li Qing , Wang Chengfeng , Li Wei , Zhang Zaiqiang , Wang Shanshan , Wupuer Autongsha , Hu Xiao , Wumaier Kalibinuer , Zhu Yi , Li Hongyan , Yu Wengui 
Published: August 2021

AbstractPontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL) is a rare hereditary cerebral small vessel disease. We report a novel collagen type IV alpha 1 (COL4A1) gene mutation in a Chinese family with PADMAL. The index case was followed up for 6 years. Neuroimaging, whole-exome sequencing, skin biopsy, and pedigree analysis were performed. She initially presented with minor head injury at age 38. MRI brain showed chronic lacunar infarcts in the pons, left thalamus, and right centrum semiovale. Extensive workup was unremarkable except for a patent foramen ovale (PFO). Despite anticoagulation, PFO closure, and antiplatelet therapy, the patient had recurrent lacunar infarcts in the pons and deep white matter, as well as subcortical microhemorrhages. Whole-exome sequencing demonstrated a novel c.*34G > T mutation in the 3′ untranslated region of COL4A1 gene. Skin biopsy subsequently demonstrated thickening of vascular basement membrane, proliferation of endothelial cells, and stenosis of vascular lumen. Three additional family members had gene testing and 2 of them were found to have the same heterozygous mutation. Of the 18 individuals in the pedigree of 3 generations, 12 had clinical and MRI evidence of PADMAL. The mechanisms of both ischemic and hemorrhagic stroke are likely the overexpression of COLT4A1 in the basement membrane and frugality of the vessel walls. Our findings suggest that the novel c.*34G > T mutation appears to have the same functional consequences as the previously reported COL4A1 gene mutations in patients with PADMAL and multi-infarct dementia of Swedish type.