bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic analysis of diverse organisms reveals the rareness of genetic assimilation in environmental adaptations
Authors: Chen Piaopiao , Zhang Jianzhi 
Published: February 2023

ABSTRACTGenetic assimilation is the evolutionary process by which an environmentally induced phenotype becomes genetically encoded and constitutive. Genetic assimilation has been proposed as the concluding step in the plasticity-first model of environmental adaptation and has been observed in multiple species, but its prevalence has not been systematically investigated. By analyzing transcriptomic data collected upon reciprocal transplant, we address this question in the experimental evolution, domestication, or natural evolution of a bacterial, a fungal, a plant, and four animal species. We find that genetic assimilation of environment-induced gene expression is the exception rather than the rule and that substantially more genes retain than lose their expression plasticity upon organismal adaptations to new environments. The probability of genetic assimilation varies among genes and decreases with the number of transcription factors controlling the gene and the expression level of the gene, supporting the hypothesis that genetic assimilation results primarily from passive losses of gene regulations that are not mutationally robust. Therefore, at the level of gene expression, our findings argue against the purported importance of genetic assimilation to environmental adaptation.
Acetylation-dependent coupling between G6PD activity and apoptotic signaling
Authors: Wu Fang , Muskat Natali H. , Dvilansky Inbar , Koren Omri , Shahar Anat , Gazit Roi , Elia Natalie , Arbely Eyal 
Published: February 2023

AbstractLysine acetylation has been discovered in thousands of non-histone human proteins, including most metabolic enzymes. Deciphering the functions of acetylation is key to understanding how metabolic cues mediate metabolic enzyme regulation and cellular signaling. Glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the pentose phosphate pathway, is acetylated on multiple lysine residues. Using site-specifically acetylated G6PD, we show that acetylation can activate (AcK89) and inhibit (AcK403) G6PD. Acetylation-dependent inactivation is explained by structural studies showing distortion of the dimeric structure and active site of G6PD. We provide evidence for acetylation-dependent K95/97 ubiquitylation of G6PD and Y503 phosphorylation, as well as interaction with p53 and induction of early apoptotic events. Notably, we found that the acetylation of a single lysine residue coordinates diverse acetylation-dependent processes. Our data provide an example of the complex roles of acetylation as a posttranslational modification that orchestrates the regulation of enzymatic activity, posttranslational modifications, and apoptotic signaling
Harnessing DNA replication stress to target RBM10 deficiency in lung adenocarcinoma
Authors: Machour Feras E. , Abu-Zhayia Enas , Kamar Joyce , Barisaac Alma Sophia , Simon Itamar , Ayoub Nabieh 
Published: February 2023

AbstractThe splicing factor RBM10 is frequently mutated in lung adenocarcinoma (LUAD) (9-25%). Most RBM10 cancer mutations are loss-of-function, correlating with increased tumorigenesis and limiting targeted therapy efficacy in EGFR-mutated lung cancer. Notably, therapeutic strategies leveraging RBM10 deficiency remain unexplored. Hence, we conducted RBM10 CRISPR-Cas9 synthetic lethality (SL) screen and identified ∼250 RBM10 SL genes, including WEE1 kinase. WEE1 inhibition sensitized RBM10-deficient LUAD cellsin-vitroandin-vivo. Mechanistically, we identified a splicing-independent role of RBM10 in promoting replication fork progression that underpins RBM10-WEE1 SL. Also, we revealed that RBM10 is associated with active replication forks, which is reliant on PRIM1, an enzyme synthesizing RNA primers for Okazaki fragments. Functionally, we demonstrated that RBM10 serves as an anchor for recruiting HDAC1 and facilitates H4K16 deacetylation to maintain replication fork stability. Collectively, our data revealed a hitherto unrecognized function of RBM10 in fine-tuning DNA replication, and provide therapeutic arsenal for targeting RBM10-deficient tumors.
The role of the topical nasal decongestant oxymetazoline as a novel therapeutic option for post‐acne erythema: A split‐face, double‐blind, randomized, placebo‐controlled trial
Authors: Washrawirul Chanudda , Puaratana‐arunkon Thanaporn , Chongpison Yuda , Noppakun Nopadon , Asawanonda Pravit , Kumtornrut Chanat 
Published: February 2023

AbstractPost‐acne erythema (PAE) is one of the most common sequelae of acne inflammation. Unfortunately, the treatment of PAE remains challenging due to limited effective topical treatments. The objectives of this study were to evaluate the efficacy and safety of topical oxymetazoline hydrochloride (OxH) 0.05% solution for PAE. This study was a split‐face, participants‐and investigators‐blinded, randomized, placebo‐controlled trial conducted between December 2021 and March 2022 in Bangkok, Thailand. Healthy adults aged from 18 to 45 years with mild to severe PAE, according to the Clinician's Erythema Assessment (CEA), on both sides of the face were eligible. After randomization, each participant applied the OxH to one side of their face and a placebo to the contralateral face twice daily for 12 weeks. The primary outcome was PAE lesion counts. The secondary outcomes were erythema index, clinical response rate at week 12 (“clear,” “almost clear,” or “at least two‐grade improvement” by CEA), and patient satisfaction scores. A total of 30 participants were enrolled. The OxH‐treated skin showed a significantly greater mean difference (MD) reduction in PAE lesion counts than the placebo after 8 weeks of treatment (4.30, 95% confidence interval [CI] 1.42–7.18). Similarly, the MD reduction of the erythema index was higher in the OxH‐treated skin from the second week (11.82, 95% CI 8.48–15.15). Additionally, the OxH‐treated side also achieved a higher clinical response rate after 8 weeks of treatment (40.00% vs. 6.67%; p = 0.002) and rated higher satisfaction than those using the placebo at the end of the study (mean [standard deviation] satisfaction score 8.30 [0.18] vs 7.40 [0.18], P < 0.001). There were no serious adverse events or flares of erythema during the study. In conclusion, our study demonstrated that the topical OxH 0.05% solution was effective, well‐tolerated, and safe for reducing PAE without a rebound effect. It could be a choice of PAE management. Trial Registration: Thai Clinical Trials Registry No. TCTR20211207004.
Boundedly Rational Decisions on Exploration Versus Exploitation in Alliance Portfolios: Problemistic and Slack Searches Under CEO Overconfidence
Authors: Zhang Fen , Yang Xiaotian , Yuan Changhong , Fan Weiguo 
Published: February 2023

AbstractHow do firms configure exploration versus exploitation in alliance portfolios under the premise of bounded rationality? From the behavioural perspective, problemistic and slack searches can be used as behavioural explanations for their configurations. Furthermore, the boundedly rational decision‐maker's limited cognitive capability in the form of CEO overconfidence also causes the subjective interpretation of information. This study investigates the links between below‐aspiration performance, slack, and firms’ boundedly rational decisions under the influence of CEO overconfidence in alliance portfolio configurations. A feasible generalized least‐squares regression is performed to test the model empirically using data from 224 publicly traded high‐tech firms in the United States. We find that below‐aspiration performance and slack both play roles in emphasizing exploration relative to exploitation in alliance portfolios. Further, CEO overconfidence intensifies the positive roles of below‐aspiration levels and slack in preference for exploration alliances. This study contributes to the bounded rationality literature by extending the implications of the behavioural theory of the firm to firms’ preference in alliance portfolio configurations in terms of the exploration‐to‐exploitation ratio. Furthermore, our findings deepen the understanding of the role of overconfidence in CEOs’ subjective interpretations, thus filling a critical research gap in extant behavioural research.
Instream sensor results suggest soil–plant processes produce three distinct seasonal patterns of nitrate concentrations in the Ohio River Basin
Authors: Gerlitz Morgan , Fox Jimmy , Ford William , Husic Admin , Mahoney Tyler , Armstead Mindy , Hendricks Susan , Crain Angela , Backus Jason , Pollock Erik , Ren Wei , Tao Bo , Riddle Brenden , White David 
Published: February 2023

AbstractThe Ohio River Basin (ORB) is responsible for 35% of total nitrate loading to the Gulf of Mexico yet controls on nitrate timing require investigation. We used a set of submersible ultraviolet nitrate analyzers located at 13 stations across the ORB to examine nitrate loading and seasonality. Observed nitrate concentrations ranged from 0.3 to 2.8 mg L−1 N in the Ohio River's mainstem. The Ohio River experiences a greater than fivefold increase in annual nitrate load from the upper basin to the river's junction with the Mississippi River (74–415 Gg year−1). The nitrate load increase corresponds with the greater drainage area, a 50% increase in average annual nitrate concentration, and a shift in land cover across the drainage area from 5% cropland in the upper basin to 19% cropland at the Ohio River's junction with the Mississippi River. Time‐series decomposition of nitrate concentration and nitrate load showed peaks centered in January and June for 85% of subbasin‐year combinations and nitrate lows in summer and fall. Seasonal patterns of the terrestrial system, including winter dormancy, spring planting, and summer and fall growing‐harvest seasons, are suggested to control nitrate timing in the Ohio River as opposed to controls by river discharge and internal cycling. The dormant season from December to March carries 51% of the ORB's nitrate load, and nitrate delivery is high across all subbasins analyzed, regardless of land cover. This season is characterized by soil nitrate leaching likely from mineralization of soil organic matter and release of legacy nitrogen. Nitrate experiences fast transit to the river owing to the ORB's mature karst geology in the south and tile drainage in the northwest. The planting season from April to June carries 26% of the ORB's nitrate and is a period of fertilizer delivery from upland corn and soybean agriculture to streams. The harvest season from July to November carries 22% of the ORB's nitrate and is a time of nitrate retention on the landscape. We discuss nutrient management in the ORB including fertilizer efficiency, cover crops, and nitrate retention using constructed measures.
Higher Education in the United States:Laissez‐Faire, Differentiation, and Research
Authors: Urquiola Miguel 
Published: February 2023

AbstractThe U.S. higher education system stands out in three dimensions. First, it has the highest number of leadingresearchuniversities. Second, it displays significantdifferentiation: multiple types of institutions offer services that differ in cost, prestige, etc. Third, it has alaissez‐faire/free‐market orientation: private and public entities are free to open schools and compete; essentially all schools enjoy substantial autonomy. This paper makes the case that these features are systematically related. The development of the American higher education market—which allowed market forces to operate and lacked centralized planning—contributed to the emergence of differentiation and a set of leading research universities.
Does private sector involvement improve the distribution efficiency of subsidized fertilizer? A natural experiment from Nepal
Authors: Thapa Ganesh , Gaihre Yam Kanta , Choudhary Dyutiman , Gautam Shriniwas 
Published: February 2023

AbstractDespite the government spending significant amounts on fertilizer subsidies, Nepal's average fertilizer application rate is lower than in other South Asian countries. The low application is attributed to poor access to fertilizer and an inefficient distribution system. The government of Nepal issued a “Fertilizer Distribution Directive (FDD) 2020” to improve the distribution system. We assessed the impacts of involving the private sector in selling fertilizer to farmers. We examined whether the market transaction cost proxied by farmers’ search cost (communication and travel cost), travel time to visit the stores, and the opportunity cost of time spent in purchasing fertilizer have been reduced by FDD 2020. A difference‐in‐difference approach refined with propensity score matching was used to estimate the fertilizer distribution efficiency using survey data from 619 households across six districts. Private sector involvement was found to reduce travel time to fertilizer retailers by about 10 min and transaction costs to purchase subsidized fertilizer by about 20 Nepalese Rupees (NPR) per season, compared to the conventional approach of sale by farmer cooperatives. Implementation of the directive has removed the bias of cooperatives selling fertilizer only to members, especially medium and large‐scale farmers. The directive and private sector involvement have led to a more equitable and efficient distribution of subsidized fertilizer. However, the government should routinely monitor and regulate the fertilizer mainly targeted to the private fertilizer retailers.
Derivation and validation of a risk prediction score for nonsteroidal anti‐inflammatory drug‐related serious gastrointestinal complications in the elderly
Authors: Lee Suhyun , Heo Kyu‐Nam , Lee Mee Yeon , Ah Young‐Mi , Shin Jaekyu , Lee Ju‐Yeun 
Published: February 2023

AimsFew studies have quantified the impact of risk factors on GI complications in elderly nonsteroidal anti‐inflammatory drug (NSAID) users. This study aimed to develop and validate a risk prediction score for severe GI complications to identify high‐risk elderly patients using NSAID.MethodsWe used the following two Korean claims datasets: customized data with an enrolment period 2016–2017 for model development, and the sample data in 2019 for external validation. We conducted a nested case–control study for model development and validation. NSAID users were identified as the elderly (≥65 years) who received NSAIDs for more than 30 days. Serious GI complications were defined as hospitalizations or emergency department visits, with a main diagnosis of GI bleeding or perforation. We applied the logistic least absolute shrinkage and selection operator (LASSO) regression model for variable selection and model fitting.ResultsWe identified 8176 cases and 81 760 controls with a 1:10 matched follow‐up period in the derivation cohort. In the external validation cohort, we identified 372 cases from 254 551 patients. The risk predictors were high‐dose NSAIDs, nonselective NSAID, complicated GI ulcer history, male sex, concomitant gastroprotective agents, relevant co‐medications, severe renal disease and cirrhosis. Area under the receiver operating characteristic curve was 0.79 (95% confidence interval, 0.77–0.81) in the external validation dataset.ConclusionsThe prediction model may be a useful tool for reducing the risk of serious GI complications by identifying high‐risk elderly patients.
DROID: Dose-Ranging Approach to Optimizing Dose in Oncology Drug Development
Authors: Guo Beibei , Yuan Ying 
Published: February 2023

Abstract
In the era of targeted therapy, there has been increasing concern about the development of oncology drugs based on the “more is better” paradigm, developed decades ago for chemotherapy. Recently, the US Food and Drug Administration (FDA) initiated Project Optimus to reform the dose optimization and dose selection paradigm in oncology drug development. To accommodate this paradigm shifting, we propose a dose-ranging approach to optimizing dose (DROID) for oncology trials with targeted drugs. DROID leverages the well-established dose-ranging study framework, which has been routinely used to develop non-oncology drugs for decades, and bridges it with established oncology dose-finding designs to optimize the dose of oncology drugs. DROID consists of two seamlessly connected stages. In the first stage, patients are sequentially enrolled and adaptively assigned to investigational doses to establish the therapeutic dose range (TDR), defined as the range of doses with acceptable toxicity and efficacy profiles, and the recommended phase 2 dose set (RP2S). In the second stage, patients are randomized to the doses in RP2S to assess the dose–response relationship and identify the optimal dose. The simulation study shows that DROID substantially outperforms the conventional approach, providing a new paradigm to efficiently optimize the dose of targeted oncology drugs. DROID aligns with the approach of a randomized, parallel dose-response trial design recommended by the FDA in the Guidance on Optimizing the Dosage of Human Prescription Drugs and Biological Products for the Treatment of Oncologic Diseases.
Homogeneity Tests of Covariance for High-Dimensional Functional Data with Applications to Event Segmentation
Authors: Zhong Ping-Shou 
Published: February 2023

Abstract
We consider inference problems for high-dimensional (HD) functional data with a dense number of T repeated measurements taken for a large number of p variables from a small number of n experimental units. The spatial and temporal dependence, high dimensionality, and dense number of repeated measurements pose theoretical and computational challenges. This paper has two aims; our first aim is to solve the theoretical and computational challenges in testing equivalence among covariance matrices from HD functional data. The second aim is to provide computationally efficient and tuning-free tools with guaranteed stochastic error control. The weak convergence of the stochastic process formed by the test statistics is established under the “large p, large T, and small n” setting. If the null is rejected, we further show that the locations of the change points can be estimated consistently. The estimator's rate of convergence is shown to depend on the data dimension, sample size, number of repeated measurements, and signal-to-noise ratio. We also show that our proposed computation algorithms can significantly reduce the computation time and are applicable to real-world data with a large number of HD-repeated measurements (e.g., functional magnetic resonance imaging (fMRI) data). Simulation results demonstrate both the finite sample performance and computational effectiveness of our proposed procedures. We observe that the empirical size of the test is well controlled at the nominal level, and the locations of multiple change points can be accurately identified. An application to fMRI data demonstrates that our proposed methods can identify event boundaries in the preface of the television series Sherlock. Code to implement the procedures is available in an R package named TechPhD.
Practitioners' perspectives on spatial reasoning in educational practice from birth to 7 years
Authors: Bates Kathryn E. , Williams Ashley Y. , Gilligan‐Lee Katie A. , Gripton Catherine , Lancaster Andrea , Williams Helen , Borthwick Alison , Gifford Sue , Farran Emily K. 
Published: February 2023

AbstractBackgroundThere is a growing evidence base for the importance of spatial reasoning for the development of mathematics. However, the extent to which this translates into practice is unknown.AimsWe aimed to understand practitioners' perspectives on their understanding of spatial reasoning, the extent to which they recognize and implement spatial activities in their practice, and the barriers and opportunities to support spatial reasoning in the practice setting.SampleStudy 1 (questionnaire) included 94 participants and Study 2 (focus groups) consisted of nine participants. Participants were educational practitioners working with children from birth to 7 years.MethodsThe study was mixed methods and included a questionnaire (Study 1) and a series of focus groups (Study 2).ResultsWe found that whilst practitioners engage in a variety of activities that support spatial reasoning, most practitioners reported little confidence in their understanding of what spatial reasoning is.ConclusionInformative and accessible resources are needed to broaden understanding of the definition of spatial reasoning and to outline opportunities to support spatial reasoning.
Transitional forestry in New Zealand: re‐evaluating the design and management of forest systems through the lens of forest purpose
Authors: Jones Alan G. , Cridge Andrew , Fraser Stuart , Holt Lania , Klinger Sebastian , McGregor Kirsty F. , Paul Thomas , Payn Tim , Scott Matthew B. , Yao Richard T. , Dickinson Yvette 
Published: February 2023

ABSTRACTForestry management worldwide has become increasingly effective at obtaining high timber yields from productive forests. In New Zealand, a focus on improving an increasingly successful and largelyPinus radiataplantation forestry model over the last 150 years has resulted in some of the most productive timber forests in the temperate zone. In contrast to this success, the full range of forested landscapes across New Zealand, including native forests, are impacted by an array of pressures from introduced pests, diseases, and a changing climate, presenting a collective risk of losses in biological, social and economic value. As the national government policies incentivise reforestation and afforestation, the social acceptability of some forms of newly planted forests is also being challenged. Here, we review relevant literature in the area of integrated forest landscape management to optimise forests as nature‐based solutions, presenting ‘transitional forestry’ as a model design and management paradigm appropriate to a range of forest types, where forest purpose is placed at the heart of decision making. We use New Zealand as a case study region, describing how this purpose‐led transitional forestry model can benefit a cross section of forest types, from industrialised forest plantations to dedicated conservation forests and a range of multiple‐purpose forests in between. Transitional forestry is an ongoing multi‐decade process of change from current ‘business‐as‐usual’ forest management to future systems of forest management, embedded across a continuum of forest types. This holistic framework incorporates elements to enhance efficiencies of timber production, improve overall forest landscape resilience, and reduce some potential negative environmental impacts of commercial plantation forestry, while allowing the ecosystem functioning of commercial and non‐commercial forests to be maximised, with increased public and biodiversity conservation value. Implementation of transitional forestry addresses tensions that arise between meeting climate mitigation targets and improving biodiversity criteria through afforestation, alongside increasing demand for forest biomass feedstocks to meet the demands of near‐term bioenergy and bioeconomy goals. As ambitious government international targets are set for reforestation and afforestation using both native and exotic species, there is an increasing opportunity to make such transitionsviaintegrated thinking that optimises forest values across a continuum of forest types, while embracing the diversity of ways in which such targets can be reached.