bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of benzodiazepines and benzodiazepine‐related drugs in the Nordic countries between 2000 and 2020
Authors: Højlund Mikkel , Gudmundsson Larus S. , Andersen Jacob H. , Saastamoinen Leena K. , Zoega Helga , Skurtveit Svetlana O. , Wastesson Jonas W. , Hallas Jesper , Pottegård Anton 
Published: October 2022

AbstractUse of benzodiazepines (BZ) and related drugs is subject to considerable debate due to problems with dependency and adverse events. We aimed to describe and compare their use across the Nordic countries. Data on the use of clonazepam, BZ‐sedatives, BZ‐hypnotics, and benzodiazepine‐related drugs (BZRD) in adults (≥20 years) were obtained from nationwide registers in Denmark, Finland, Iceland, Norway, and Sweden, 2000–2020. Main measures were therapeutic intensity (TI:DDD/1000 inhabitants [inhab.]/day) and annual prevalence (users/1000 inhab./year). Overall, TI of BZ and related drugs decreased in all Nordic countries from 2004 to 2020. However, there were considerable differences between countries in TI. In 2020, the TI of BZ and related drugs ranged from 17 DDD/1000 inhab./day in Denmark to 93 DDD/1000 inhab./day in Iceland. BZRD accounted for 55–78% of BZ use in 2020, followed by BZ sedatives at 20–44%, BZ‐hypnotics at <1–5%, and clonazepam at <1–2%. Annual prevalence of BZ use increased with age in all countries, and the highest annual prevalence was observed among people ≥80 years. Overall, the use of BZ and related drugs has decreased in all Nordic countries from 2004 to 2020, however, with considerable differences in their use between countries. The highest prevalence was observed among the oldest age groups—despite warnings against their use in this population.
Serum untargeted metabolomics reveal metabolic alteration of non‐small cell lung cancer and refine disease detection
Authors: Li Jiaoyuan , Liu Ke , Ji Zhi , Wang Yi , Yin Tongxin , Long Tingting , Shen Ying , Cheng Liming 
Published: October 2022

AbstractThis study was performed to characterize the metabolic alteration of non–small‐cell lung cancer (NSCLC) and discover blood‐based metabolic biomarkers relevant to lung cancer detection. An untargeted metabolomics‐based approach was applied in a case–control study with 193 NSCLC patients and 243 healthy controls. Serum metabolomics were determined by using an ultra high performance liquid chromatography–tandem mass spectrometry (UHPLC‐MS/MS) method. We screened differential metabolites based on univariate and multivariate analysis, followed by identification of the metabolites and related pathways. For NSCLC detection, machine learning was employed to develop and validate the model based on the altered serum metabolite features. The serum metabolic pattern of NSCLC was definitely different from the healthy condition. In total, 278 altered features were found in the serum of NSCLC patients comparing with healthy people. About one‐fifth of the abundant differential features were identified successfully. The altered metabolites were enriched in metabolic pathways such as phenylalanine metabolism, linoleic acid metabolism, and biosynthesis of bile acids. We demonstrated a panel of 10 metabolic biomarkers which representing excellent discriminating capability for NSCLC discrimination, with a combined area under the curve (AUC) in the validation set of 0.95 (95% CI: 0.91–0.98). Moreover, this model showed a desirable performance for the detection of NSCLC at an early stage (AUC = 0.95, 95% CI: 0.92–0.97). Our study offers a perspective on NSCLC metabolic alteration. The finding of the biomarkers might shed light on the clinical detection of lung cancer, especially for those cancers in an early stage in Chinese population.
Dynamic interplay of microRNA in diseases and therapeutic
Authors: Kargutkar Neha , Hariharan Priya , Nadkarni Anita 
Published: October 2022

AbstractMicroRNAs are the major class of small non‐coding RNAs, evolutionary conserved post‐transcriptional regulators of gene expression. Since their discovery in 1993, they have been implicated as master regulators in numerous cellular processes. MicroRNA (miRNA)s regulate gene expression by attenuation and/or mRNA degradation and are commonly associated with cell development, differentiation, and homeostasis. Extensive research in past two decades has provided new insights into the potential implications of miRNA in the onset, progression, and therapeutic nature of miRNAs in disease manifestation. Owing to the novel discoveries, “miRNAs” would probably pave a new direction in therapeutic research. However, “micro” in length miRNAs have attracted considerable attention in numerous other fields. Understanding the functionality of miRNAs, in this review article, we discussed the mechanistic role of miRNAs in human diseases and have outlined most of the recent published work in clinical therapeutics. We have constructed different network models for miRNA and its targets which made us understand their interrelationship and association with diseases. Future research would surely overcome challenges and would introduce new strategies for the utility of miRNAs in a broader setting.
Enhanced osteogenesis by addition of cancellous bone chips at xenogenic bone augmentation: In vitro and in vivo experiments
Authors: Chen Xiaofan , Wang Haicheng , Wang Yuning , Shi Ying , Wang Zuolin 
Published: October 2022

AbstractObjectivesTo investigate and compare the influence of deproteinized bovine bone mineral (DBBM) combined with autologous cortical (CorBC) or cancellous bone chips (CanBC) as bone grafts on guided bone regeneration (GBR) in vivo and in vitro.Materials and MethodsDefects were created in the mandibular buccal alveolar ridges in dogs and randomly filled with 3 groups of bone grafts: DBBM, DBBM + CorBC, or DBBM + CanBC. Osteogenesis was evaluated by sequential fluorescent labeling and histological analysis. Moreover, rat bilateral calvaria defects were randomly grafted with DBBM, DBBM + CorBC, or DBBM + CanBC. A blank group was included as control. Defect healing was assessed by histological staining, micro‐CT, and quantitative polymerase chain reaction. In vitro migration, proliferation, and osteogenic differentiation assays were performed by stimulating rat bone marrow mesenchymal stem cells (rBMSCs) with cortical (CorBCM) or cancellous bone conditioned medium (CanBCM) to unveil the cellular mechanism.ResultsIn the canine model, the augmented sites of DBBM + CanBC exhibited higher mineralized tissue proportion than the other two groups (DBBM: 0.61 ± 0.03 versus DBBM + CorBC: 0.69 ± 0.07 versus DBBM + CanBC: 0.86 ± 0.06; p < .05). In the rat model, the BV/TV value of DBBM + CanBC (0.51 ± 0.01) was higher than those of DBBM + CorBC (0.41 ± 0.02), DBBM (0.31 ± 0.01), and Control (0.10 ± 0.01; p < .01). Further radiological, histological and transcriptional results showed similar trends. In vitro experiments revealed that CorBCM and especially CanBCM could enhance rBMSCs migration, proliferation, and osteogenic differentiation.ConclusionIn vivo and in vitro experiments verified favorable synergistic effect of mixing autologous bone chips with DBBM on osteogenesis. Furthermore, CanBC presented more powerful osteogenic effect than CorBC.
Early division of the paramedian forehead interpolated flap using cutaneous ultrasound
Authors: González Jose Castiñeiras , Argüero Eduardo Zorita , Canga Paula Fernández , Prieto Manuel Ángel Rodríguez 
Published: October 2022

SummaryBackground and objectivesThe paramedian forehead flap is an interpolated flap, consisting of the transfer of tissue from the forehead region to the nasal area, irrigated by the supratrochlear artery. Traditionally, the vascular pedicle is divided at between 14 and 21 days. However, this time could be overestimated. Our objective is to demonstrate that the paramedian forehead flap can be divided before that set out in the literature and to demonstrate the usefulness of cutaneous ultrasound to determine the optimal time for division.Patients and methodsA prospective observational study, including patients who required nasal defect reconstruction with a paramedian forehead flap, was designed. The inclusion criteria were: nasal tip, dorsum or alar skin defects following oncological surgery, larger than 2 cm. Twelve patients were included. A retrospective cohort was used to perform a cost reduction analysis.ResultsThe average time to flow, measured by ultrasound, was 6.6 days. The average number of days to division of the pedicle was 6.9 days. No serious complications were reported.ConclusionsThe paramedian forehead flap can be divided before the traditional reported time. Ultrasound is a reliable and cost‐effective technique to determine and individualize pedicle division time.
Vegetation structure derived from airborne laser scanning to assess species distribution and habitat suitability: The way forward
Authors: Moudrý Vítězslav , Cord Anna F. , Gábor Lukáš , Laurin Gaia Vaglio , Barták Vojtěch , Gdulová Kateřina , Malavasi Marco , Rocchini Duccio , Stereńczak Krzysztof , Prošek Jiří , Klápště Petr , Wild Jan 
Published: October 2022

AbstractEcosystem structure, especially vertical vegetation structure, is one of the six essential biodiversity variable classes and is an important aspect of habitat heterogeneity, affecting species distributions and diversity by providing shelter, foraging, and nesting sites. Point clouds from airborne laser scanning (ALS) can be used to derive such detailed information on vegetation structure. However, public agencies usually only provide digital elevation models, which do not provide information on vertical vegetation structure. Calculating vertical structure variables from ALS point clouds requires extensive data processing and remote sensing skills that most ecologists do not have. However, such information on vegetation structure is extremely valuable for many analyses of habitat use and species distribution. We here propose 10 variables that should be easily accessible to researchers and stakeholders through national data portals. In addition, we argue for a consistent selection of variables and their systematic testing, which would allow for continuous improvement of such a list to keep it up‐to‐date with the latest evidence. This initiative is particularly needed not only to advance ecological and biodiversity research by providing valuable open datasets but also to guide potential users in the face of increasing availability of global vegetation structure products.
Gestational diabetes mellitus in early pregnancy amongst Asian Indian women: Evidence for poor pregnancy outcomes despite treatment
Authors: Punnose John , Malhotra Rajeev Kumar , Sukhija Komal , M Rashika Rijhwani , Choudhary Naimaa , Sharma Asha , Vij Prassan , Bahl Pinky 
Published: October 2022

AbstractAimTo compare the pregnancy outcomes in women with gestational diabetes (GDM) based on the timing of diagnosis.MethodsThis retrospective cohort study was conducted between January 2011 and September 2017 amongst 2638 Asian Indian pregnant women. The inclusion criteria included; singleton pregnancies having HbA1c <48 mmols/mol (6.5%) in the first trimester, GDM screening by 75 g OGTT using IADPSG criteria and delivery at our centre. The cohort was divided into 3 groups: Early GDM (E‐GDM)‐diagnosis <24 gestational weeks (Gw), Standard GDM (S‐GDM)–diagnosis ≥24Gw, Non‐GDM‐ No GDM ≥24 Gw. Multivariable logistic regression models compared the pregnancy outcomes between Non‐GDM, S‐GDM and E‐GDM groups. A sub‐group multivariable analysis was done amongst GDM women using gestational age at diagnosis both as a categorical and continuous variable.ResultsCompared to Non‐GDM women, the odds were higher for premature birth, large for gestational age (LGA) babies, macrosomia, Neonatal ICU(NICU) admission and lower for normal vaginal delivery in the E‐GDM group, but for the S‐GDM group, the risk was higher for premature birth, LGA babies, NICU admission and induction of labour. Compared to GDM women in the 24–28 Gw category significantly higher odds for premature birth and LGA babies were observed in the <14 Gw category. A continuous increase of 19% odds for premature birth with every 4 weeks decrease in gestational age at GDM diagnosis was observed.ConclusionsAsian Indian women having a GDM diagnosis before 24Gw are at higher risk for adverse pregnancy events than those having diagnosis ≥24Gw or not having GDM.
Weight management in young adults with type 1 diabetes: The advancing care for type 1 diabetes and obesity network sequential multiple assignment randomized trial pilot results
Authors: Igudesman Daria , Crandell Jamie , Corbin Karen D. , Zaharieva Dessi P. , Addala Ananta , Thomas Joan M. , Casu Anna , Kirkman M. Sue , Pokaprakarn Teeranan , Riddell Michael C. , Burger Kyle , Pratley Richard E. , Kosorok Michael R. , Maahs David M. , Mayer‐Davis Elizabeth J. ,   for the ACTION Study Group
Published: October 2022

AbstractAimsCo‐management of weight and glycaemia is critical yet challenging in type 1 diabetes (T1D). We evaluated the effect of a hypocaloric low carbohydrate, hypocaloric moderate low fat, and Mediterranean diet without calorie restriction on weight and glycaemia in young adults with T1D and overweight or obesity.Materials and MethodsWe implemented a 9‐month Sequential, Multiple Assignment, Randomized Trial pilot among adults aged 19‐30 years with T1D for ≥1 year and body mass index 27‐39.9 kg/m2. Re‐randomization occurred at 3 and 6 months if the assigned diet was not acceptable or not effective. We report results from the initial 3‐month diet period and re‐randomization statistics before shutdowns due to COVID‐19 for primary [weight, haemoglobin A1c (HbA1c), percentage of time below range <70 mg/dl] and secondary outcomes [body fat percentage, percentage of time in range (70‐180 mg/dl), and percentage of time below range <54 mg/dl]. Models adjusted for design, demographic and clinical covariates tested changes in outcomes and diet differences.ResultsAdjusted weight and HbA1c (n = 38) changed by −2.7 kg (95% CI −3.8, −1.5, P < .0001) and −0.91 percentage points (95% CI −1.5, −0.30, P = .005), respectively, while adjusted body fat percentage remained stable, on average (P = .21). Hypoglycaemia indices remained unchanged following adjustment (n = 28, P > .05). Variability in all outcomes, including weight change, was considerable (57.9% were re‐randomized primarily due to loss of <2% body weight). No outcomes varied by diet.ConclusionsThree months of a diet, irrespective of macronutrient distribution or caloric restriction, resulted in weight loss while improving or maintaining HbA1c levels without increasing hypoglycaemia in adults with T1D.
Italian, European, and international neuroinformatics efforts: An overview
Authors: Redolfi Alberto , Archetti Damiano , De Francesco Silvia , Crema Claudio , Tagliavini Fabrizio , Lodi Raffaele , Ghidoni Roberta , Gandini Wheeler‐Kingshott Claudia A. M. , Alexander Daniel C. , D'Angelo Egidio 
Published: October 2022

AbstractNeuroinformatics is a research field that focusses on software tools capable of identifying, analysing, modelling, organising and sharing multiscale neuroscience data. Neuroinformatics has exploded in the last two decades with the emergence of the Big Data phenomenon, characterised by the so‐called 3Vs (volume, velocity and variety), which provided neuroscientists with an improved ability to acquire and process data faster and more cheaply thanks to technical improvements in clinical, genomic and radiological technologies. This situation has led to a ‘data deluge’, as neuroscientists can routinely collect more study data in a few days than they could in a year just a decade ago. To address this phenomenon, several neuroimaging‐focussed neuroinformatics platforms have emerged, funded by national or transnational agencies, with the following goals: (i) development of tools for archiving and organising analytical data (XNAT, REDCap and LabKey); (ii) development of data‐driven models evolving from reductionist approaches to multidimensional models (RIN, IVN, HBD, EuroPOND, E‐DADS and GAAIN BRAIN); and (iii) development of e‐infrastructures to provide sufficient computational power and storage resources (neuGRID, HBP‐EBRAINS, LONI and CONP). Although the scenario is still fragmented, there are technological and economical attempts at both national and international levels to introduce high standards for open and Findable, Accessible, Interoperable and Reusable (FAIR) neuroscience worldwide.
Ecological conditions predict the intensity of Hendra virus excretion over space and time from bat reservoir hosts
Authors: Becker Daniel J. , Eby Peggy , Madden Wyatt , Peel Alison J. , Plowright Raina K. 
Published: October 2022

AbstractThe ecological conditions experienced by wildlife reservoirs affect infection dynamics and thus the distribution of pathogen excreted into the environment. This spatial and temporal distribution of shed pathogen has been hypothesised to shape risks of zoonotic spillover. However, few systems have data on both long‐term ecological conditions and pathogen excretion to advance mechanistic understanding and test environmental drivers of spillover risk. We here analyse three years of Hendra virus data from nine Australian flying fox roosts with covariates derived from long‐term studies of bat ecology. We show that the magnitude of winter pulses of viral excretion, previously considered idiosyncratic, are most pronounced after recent food shortages and in bat populations displaced to novel habitats. We further show that cumulative pathogen excretion over time is shaped by bat ecology and positively predicts spillover frequency. Our work emphasises the role of reservoir host ecology in shaping pathogen excretion and provides a new approach to estimate spillover risk.
Drivers of population differentiation in phenotypic plasticity in a temperate conifer: A 27‐year study
Authors: de la Mata Raul , Zas Rafael , Bustingorri Gloria , Sampedro Luis , Rust Marc , Hernandez‐Serrano Ana , Sala Anna 
Published: October 2022

AbstractPhenotypic plasticity is a main mechanism for organisms to cope with changing environments and broaden their ecological range. Plasticity is genetically based and can evolve under natural selection, such that populations within a species show distinct phenotypic responses to the environment if evolved under different conditions. Understanding how intraspecific variation in phenotypic plasticity arises is critical to assess potential adaptation to ongoing climate change. Theory predicts that plasticity is favored in more favorable but variable environments. Yet, many theoretical predictions about benefits, costs, and selection on plasticity remain untested. To test these predictions, we took advantage of three genetic trials in the northern Rocky Mountains, USA, which assessed 23 closely located Pinus ponderosa populations over 27 years. Mean environmental conditions and their spatial patterns of variation at the seed source populations were characterized based on six basic climate parameters. Despite the small area of origin, there was significant genetic variation in phenotypic plasticity for tree growth among populations. We found a significant negative correlation between phenotypic plasticity and the patch size of environmental heterogeneity at the seed source populations, but not with total environmental spatial variance. These results show that populations exposed to high microhabitat heterogeneity have evolved higher phenotypic plasticity and that the trigger was the grain rather than the total magnitude of spatial heterogeneity. Contrary to theoretical predictions, we also found a positive relationship between population plasticity and summer drought at the seed source, indicating that drought can act as a trigger of plasticity. Finally, we found a negative correlation between the quantitative genetic variance within populations and their phenotypic plasticity, suggesting compensatory adaptive mechanisms for the lack of genetic diversity. These results improve our understanding of the microevolutionary drivers of phenotypic plasticity, a critical process for resilience of long‐lived species under climate change, and support decision‐making in tree genetic improvement programs and seed transfer strategies.
N6‐methyladenosine functions and its role in skin cancer
Authors: Ran Yanqin , Yan Zhuoxian , Jiang Bimei , Liang Pengfei 
Published: October 2022

AbstractN6‐methyladenosine (m6A) methylation is the most abundant mammalian mRNA modification. m6A regulates RNA processing, splicing, nucleation, translation and stability by transferring, removing and recognizing m6A methylation sites, which are critical for cancer initiation, progression, metabolism and metastasis. m6A is involved in pathophysiological tumour development by altering m6A modification and expression levels in tumour oncogenes and suppressor genes. Skin cancers are by far the most common malignancies in humans, with well over a million cases diagnosed each year. Skin cancers are grouped into two main categories: melanoma and non‐melanoma skin cancers (NMSC), based on cell origin and clinical behaviour. In this review, we summarize m6A methylation functions in different skin cancers, and discuss how m6A methylation is involved in disease development and progression. Moreover, we review potential prognostic biomarkers and molecular targets for early skin cancer diagnosis and treatment.
Positive interactions between corals and damselfish increase coral resistance to temperature stress
Authors: Shantz Andrew A. , Ladd Mark C. , Ezzat Leila , Schmitt Russell J. , Holbrook Sally J. , Schmeltzer Emily , Vega Thurber Rebecca , Burkepile Deron E. 
Published: October 2022

AbstractBy the century's end, many tropical seas will reach temperatures exceeding most coral species' thermal tolerance on an annual basis. The persistence of corals in these regions will, therefore, depend on their abilities to tolerate recurrent thermal stress. Although ecologists have long recognized that positive interspecific interactions can ameliorate environmental stress to expand the realized niche of plants and animals, coral bleaching studies have largely overlooked how interactions with community members outside of the coral holobiont shape the bleaching response. Here, we subjected a common coral, Pocillopora grandis, to 10 days of thermal stress in aquaria with and without the damselfish Dascyllus flavicaudus (yellowtail dascyllus), which commonly shelter within these corals, to examine how interactions with damselfish impacted coral thermal tolerance. Corals often benefit from nutrients excreted by animals they interact with and prior to thermal stress, corals grown with damselfish showed improved photophysiology (Fv/Fm) and developed larger endosymbiont populations. When exposed to thermal stress, corals with fish performed as well as control corals maintained at ambient temperatures without fish. In contrast, corals exposed to thermal stress without fish experienced photophysiological impairment, a more than 50% decline in endosymbiont density, and a 36% decrease in tissue protein content. At the end of the experiment, thermal stress caused average calcification rates to decrease by over 80% when damselfish were absent but increase nearly 25% when damselfish were present. Our study indicates that damselfish‐derived nutrients can increase coral thermal tolerance and are consistent with the Stress Gradient Hypothesis, which predicts that positive interactions become increasingly important for structuring communities as environmental stress increases. Because warming of just a few degrees can exceed corals' temperature tolerance to trigger bleaching and mortality, positive interactions could play a critical role in maintaining some coral species in warming regions until climate change is aggressively addressed.