bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inference of the distribution of fitness effects of mutations is affected by single nucleotide polymorphism filtering methods, sample size and population structure
Authors: Andersson Bea Angelica , Zhao Wei , Haller Benjamin C. , Brännström Åke , Wang Xiao‐Ru 
Published: June 2023

AbstractThe distribution of fitness effects (DFE) of new mutations has been of interest to evolutionary biologists since the concept of mutations arose. Modern population genomic data enable us to quantify the DFE empirically, but few studies have examined how data processing, sample size and cryptic population structure might affect the accuracy of DFE inference. We used simulated and empirical data (from Arabidopsis lyrata) to show the effects of missing data filtering, sample size, number of single nucleotide polymorphisms (SNPs) and population structure on the accuracy and variance of DFE estimates. Our analyses focus on three filtering methods—downsampling, imputation and subsampling—with sample sizes of 4–100 individuals. We show that (1) the choice of missing‐data treatment directly affects the estimated DFE, with downsampling performing better than imputation and subsampling; (2) the estimated DFE is less reliable in small samples (<8 individuals), and becomes unpredictable with too few SNPs (<5000, the sum of 0‐ and 4‐fold SNPs); and (3) population structure may skew the inferred DFE towards more strongly deleterious mutations. We suggest that future studies should consider downsampling for small data sets, and use samples larger than 4 (ideally larger than 8) individuals, with more than 5000 SNPs in order to improve the robustness of DFE inference and enable comparative analyses.
An exploratory study of the impact of tax freedom on geographic living‐cost differentials
Authors: Cebula Richard J. , Duquette Christopher M. , Jolley G. Jason 
Published: June 2023

AbstractIn the United States, there exist enormous geographic differentials in the cost of living. A sound, basic understanding of factors that influence such geographic living‐cost differentials is important to help formulate useful policies to address various contemporary economic and social problems such as public‐school funding across counties. In this exploratory study of the effects of tax freedom on geographic living‐cost differentials, the following hypothesis is investigated using panel data for the period 2009 through 2020. The higher the average overall freedom from taxation in a state in the forms of personal income taxation, property taxation, and sales taxation, the lower the overall cost of living in the state. In this exploratory study, strong empirical support is obtained for this heretofore effectively overlooked hypothesis.
Pars plana vitrectomy versus intravitreal antibiotics for endophthalmitis management following intravitreal anti‐VEGF agents: A meta‐analysis
Authors: Issa Mariam , Balas Michael , Popovic Marko M. , Lytvyn Yuliya , Kertes Peter J. , Muni Rajeev H. 
Published: June 2023

AbstractIn this meta‐analysis, we aim to compare the efficacy and safety of pars plana vitrectomy (PPV) versus tap‐and‐inject (TAI) of intravitreal antibiotics for the management of endophthalmitis secondary to intravitreal injections of anti‐vascular endothelial growth factor (VEGF) agents. A systematic literature search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Central (January 2005–October 2022). The primary analysis compared initial PPV versus TAI and the secondary analysis examined the efficacy and safety of TAI alone compared to TAI followed by PPV. The quality of non‐randomized observational studies was assessed using the Newcastle‐Ottawa Scale. The quality of the evidence was assessed for each outcome. A random effects meta‐analysis was performed. Weighted mean differences (WMDs) with 95% confidence intervals were reported. Of the 7474 screened studies, nine studies reporting on 153 eyes were included. The change in mean best corrected visual acuity (BCVA) between endophthalmitis presentation and last follow‐up did not significantly differ between the initial TAI versus PPV groups (WMD = 0.05 units; 95% CI −0.12 to 0.22; p = 0.59; heterogeneity p = 0.41). The difference in pre‐ to post‐treatment mean BCVA did not significantly differ between eyes that received TAI alone or TAI followed by PPV (WMD = 0.04 units; 95% CI −0.42 to 0.51; p = 0.85; heterogeneity p = 0.74). While the meta‐analysis revealed no significant difference in the change in BCVA between PPV and TAI to treat endophthalmitis secondary to anti‐VEGF agents, the quality of evidence was low with potential for confounding and selection bias. Further well‐designed studies in this setting are needed.
Do farmers' professional cooperatives improve agricultural technical efficiency? Evidence using a national‐level dataset of China
Authors: Li Menglu , Zhang Shemei , Khan Nawab 
Published: June 2023

AbstractThis study examines the impact of farmers' professional cooperatives (FPCs) on agricultural technical efficiency (TE), using panel data from 30 provinces of China from 2015 to 2020 and the stochastic frontier function (SFF) method. The number of members of each cooperative, the proportion of demonstration cooperatives, and the proportion of standard cooperatives are introduced as proxy variables for the development level of FPCs. The results show that although the development of FPCs is imperfect, its development has a significant positive impact on improving China's agricultural TE. Through the continuous increase in the number of cooperative members and the vigorous promotion of standardized production, agricultural TE has been significantly improved. However, the construction of model cooperatives has not played a positive role but inhibited the growth of agricultural TE. It is suggested to expand the cooperative membership and promote standardized production. The government and policymakers should focus on improving the standardization level of cooperatives and the development quality of FPCs from the aspects of innovating cooperation models, standardizing internal governance, and giving full play to the synergistic effect of agricultural science and technology.
ICU triage decisions and biases about time and identity
Authors: Räsänen Joona 
Published: June 2023

AbstractWe often show a greater inclination to assist and avoid harming people identified as those at high risk of great harm than to assist and avoid harming people who will suffer similar harm but are not identified (as yet). Call this the identified person bias. Some ethicists think such bias is justified; others disagree and claim that the bias is discriminatory against statistical people. While the issue is present in public policy and politics, perhaps the most notable examples can be found in medical ethics such as in ICU triage decisions made during the COVID‐19 pandemic. The Rule of Rescue, as the application of the identified person bias is sometimes called, states that spending large amounts of resources rescuing identifiable individuals who are in imminent danger is justified. In this paper, I show that our distorted attitudes toward time play a role in identified person bias. I claim that ICU triage decisions are better explained by a preference to treat people sooner rather than later, which is at least partially due to near bias (positive events are to be preferred to be near rather than distant), than by a preference to treat identified lives over statistical lives. Thus, another bias, near bias, is involved in the reasoning behind the identified person bias and the Rule of Rescue.
Accelerated drug approval: Meeting the ethical yardstick
Authors: Andreoletti Mattia , Blasimme Alessandro 
Published: June 2023

AbstractDrugs addressing unmet medical needs can change the lives of millions. Developing and validating new drugs can, however, take many years. To streamline the assessment of new drugs, regulatory agencies have long established shortened review pathways. Among these programs, Accelerated Approval (AA) has recently come under scrutiny due to the U.S. Food and Drug Administration's decision to authorize Aducanumab, the first Alzheimer's disease drug. This decision attracted fierce criticism due to the allegedly insufficient evidence about the safety and efficacy of the drug. While considerable scholarly attention has been devoted to this case, the ethical aspects of the AA regulatory pathway have so far remained relatively unexplored. In this paper, we set out to fill this gap. We illustrate six conditions that should be met for AA to be ethically acceptable: moral solicitude, evidence, risk mitigation, impartiality, sustainability, and transparency. We discuss such conditions and suggest practical steps to implement them in regulatory and oversight processes. Taken together, our six conditions represent a benchmark for assessing the ethical validity of AA processes and decisions.
An automatic workflow for risk analysis on spatial output properties using kriging‐based surrogate models—Application to stratigraphic forward modelling
Authors: Gervais Véronique , Granjeon Didier , Bouquet Sarah 
Published: June 2023

AbstractStratigraphic numerical forward process‐based models represent the formation and evolution of sedimentary basins through time. Their main deliverable is a 3D digital grid which can help to better understand the sedimentary basin infill. These models depend on several input parameters that need to be characterized for the studied basin. However, available data such as well logs and seismic data may not provide enough information to identify a unique possible value for these parameters. It is then crucial to take the uncertainty induced by this non‐uniqueness into account in the decision‐making process. As a single numerical stratigraphic forward simulation can be very time consuming, solutions are needed to limit the computational cost required to estimate such uncertainties. In particular, machine learning techniques can be used to build meta‐models that mimic the simulator and provide fast estimations of its outputs for any values of the input parameters. The key step for the efficiency of such an approach stands in the choice of the set of simulations (or training set) used to build the meta‐models: it should be informative enough to obtain accurate predictions for the output properties of interest, but also of reasonable size to limit simulation time. Then, meta‐models can be used to investigate a large number of models and make uncertainty quantification easier. Here, we focus on the prediction of spatial outputs of interest approximated from the joint use of several kriging‐based meta‐models combined to reduced basis decomposition. Sequential approaches have been proposed in the literature to identify training sets iteratively for a kriging‐based meta‐model, building upon the specific structure of such surrogates. We propose here to extend these approaches to the context of spatial output predictors. The results obtained on two synthetic test cases, representing a carbonate platform and a clastic environment, highlight the potential of the proposed approach for risk analysis to iteratively build training sets with a satisfactory efficiency in terms of simulation time and prediction accuracy.
Intratumor heterogeneity in colorectal cancer: Distribution of tumor suppressor gene variants with regard to patient lymph node status
Authors: Wątor Gracjan , Seweryn Michał , Kapusta Przemysław , Świrta Jarosław , Wałęga Piotr , Barczyński Marcin , Wołkow Paweł P. 
Published: June 2023

AbstractIntratumor heterogeneity (ITH) results from accumulation of somatic mutations in the fractions of successive cancer cell generations. We aimed to use deep sequencing to investigate ITH in colorectal tumors with particular emphasis on variants in oncogenes (ONC) and tumor suppressor genes (TSG). Samples were collected from 16 patients with colorectal cancer and negative or positive lymph node status (n = 8 each). We deep‐sequenced a panel of 56 cancer‐related genes in the central and peripheral locations of T3 size primary tumors and healthy mucosa. The central region of T3 tumors has a different frequency profile and composition of genetic variants. This mutation profile is capable of independently discriminating patients with different lymph node status (p = 0.028) in the central region. We noted an increasing number of mutations outside of the central region of the tumor and a higher number of mutations in tumors from node‐positive patients. Unexpectedly, in the healthy mucosa, we identified somatic mutations with variant allele frequencies, characteristic not only of heterozygotes and homozygotes but also of other discrete peaks (e.g., around 10%, 20%), suggestive of clonal expansion of certain mutant alleles. We found differences in the distribution of variant allele frequencies in TSGs when comparing node‐negative and node‐positive tumors (p = 0.029), as well as central and peripheral regions (p = 0.00399). TSGs may play an important role in the escape of the tumor toward metastatic colonization.
Tacrolimus pharmacokinetics are influenced by CYP3A5, age, and concomitant fluconazole in pediatric kidney transplant patients
Authors: Alghamdi Alaa , Seay Sarah , Hooper David K. , Varnell Charles D. , Darland Leanna , Mizuno Tomoyuki , Lazear Danielle , Ramsey Laura B. 
Published: June 2023

AbstractTacrolimus, the most common immunosuppressant for organ transplant, has a narrow therapeutic range and is metabolized by CYP3A4/5. Trough concentration monitoring and dosing adjustments are used to reach a therapeutic range. CYP3A5 intermediate and normal metabolizers (*1 allele carriers; IM/NM) demonstrate faster tacrolimus metabolism than poor metabolizers (PM). We analyzed the electronic health records of 93 patients aged <21 years for the first 8 weeks after a kidney transplant between January 2010 and December 2021. The target tacrolimus trough was 10–15 ng/mL in the first 4 weeks and 7–10 ng/mL in the next 4 weeks. Banked DNA was collected and genotyped for CYP3A5*3, *6, *7, and *8 alleles. We found that CYP3A5 IM/NM (n = 21) took longer than PM (n = 72) to reach the therapeutic range (7 vs. 4 days, p = 0.048). IM/NM had more dose adjustments (8 vs. 6, p = 0.025) and needed >150% of the required daily dose compared with PM. The concentration/dose ratio was influenced by age and concomitant fluconazole (p = 0.0003, p = 0.034, respectively) and the average daily dose decreases with age in CYP3A5 PM (p = 0.001). Tremors were more common in patients who ever had a trough concentration >15 ng/mL compared with those who never had a trough concentration >15 ng/mL (OR 3.31, 95% CI 1.03–8.98, p = 0.038). Using standard dosing, CYP3A5 IM/NM took longer to reach the goal range and require more dose adjustments and higher doses than PM. Preemptive genotyping could decrease the number of dose changes necessary to reach a therapeutic dose. We have implemented pre‐transplant CYP3A5 testing at our institution.
Associations between infant amygdala functional connectivity and social engagement following a stressor: A preliminary investigation
Authors: Hu Yannan , Chen Haitao , Li Xiaomei , Larsen Ryan J. , Sutton Bradley P. , Gao Wei , McElwain Nancy L. 
Published: June 2023

AbstractFunctional architecture of the infant brain, especially functional connectivity (FC) within the amygdala network and between the amygdala and other networks (i.e., default‐mode [DMN] and salience [SAL] networks), provides a neural basis for infant socioemotional functioning. Yet, little is known about the extent to which early within‐ and between‐network amygdala FC are related to infant stress recovery across the first year of life. In this study, we examined associations between amygdala FC (i.e., within‐network amygdala connectivity, and between‐network amygdala connectivity with the DMN and SAL) at 3 months and infant recovery from a mild social stressor at 3, 6 and 9 months. At 3 months, thirty‐five infants (13 girls) underwent resting‐state functional magnetic resonance imaging during natural sleep. Infants and their mothers completed the still‐face paradigm at 3, 6, and 9 months, and infant stress recovery was assessed at each time point as the proportion of infant social engagement during the reunion episode. Bivariate correlations indicated that greater positive within‐network amygdala FC and greater positive amygdala‐SAL FC, but not amygdala‐DMN FC, at 3 months predicted lower levels of stress recovery at 3 and 6 months, but were nonsignificant at 9 months. These findings provide preliminary evidence that early functional synchronization within the amygdala network, as well as segregation between the amygdala and the SAL, may contribute to infant stress recovery in the context of infant–mother interaction.
Individualized orthotic alignment and footwear for balance and mobility in children with bilateral spastic cerebral palsy: A randomized trial
Authors: Bjornson Kristie F. , Fatone Stefania , Orendurff Michael , Zhou Chuan , Hurvitz Philip M. , Shippen Garth 
Published: June 2023

AbstractAimTo examine whether designed‐to‐be‐rigid ankle–foot orthoses and footwear combinations with individualized alignment and footwear designs (AFO‐FC/IAFD) would be more effective than designed‐to‐be‐rigid AFO with non‐individualized alignment and footwear designs (AFO‐FC/NAFD) in children with cerebral palsy (CP).MethodNineteen children with bilateral spastic CP were randomized to AFO‐FC/NAFD (n = 10) or AFO‐FC/IAFD (n = 9) groups. Fifteen were male, average age 6 years 11 months (range 4 years 2 months–9 years 11 months), classified in Gross Motor Function Classification System levels II (n = 15) and III (n = 4). The Pediatric Balance Scale (PBS), Gait Outcomes Assessment List (GOAL), Patient‐Reported Outcomes Measurement Information System (PROMIS), and Orthotic and Prosthetic Users' Survey (OPUS) measures of satisfaction were collected at baseline and after 3 months' wear.ResultsCompared with the AFO‐FC/NAFD group, those with AFO‐FC/IAFD demonstrated greater change in PBS total scores (mean 12.8 [standard deviation 10.5] vs 3.5 [5.8]; p = 0.03) and GOAL total scores (3.5 [5.8] vs −0.44 [5.5]; p = 0.03). There were no significant changes in OPUS or PROMIS scores.InterpretationAfter 3 months, individualized orthosis alignment and footwear designs had a greater positive effect on balance and parent‐reported mobility than a non‐individualized approach. No effect was documented for the PROMIS and OPUS. Results may inform orthotic management for ambulatory children with bilateral spastic CP.What this paper adds

Balance and parent‐reported mobility increased more over time for the ankle–foot orthoses and footwear combinations with individualized alignment and footwear designs (AFO‐FC/IAFD) group.
Changes in balance over time suggest a therapeutic effect of the AFO‐FC/IAFD approach.
Diamondback moth egg susceptibility to rainfall: effects of leaf surface properties on the direct and indirect impact of simulated rain
Authors: Rahman Md Mahbubur , Zalucki Myron P. , Furlong Michael J. 
Published: June 2023

AbstractDiamondback moth (DBM), Plutella xylostella L. (Lepidoptera: Plutellidae), eggs are vulnerable to rainfall, but the impact is dependent on host plant properties and the nature of oviposition sites. The effects of host plants, common cabbage (Brassica oleracea L. var. capitata) and Chinese cabbage (Brassica rapa L. var. pekinensis) (Brassicaceae), and oviposition sites on the fate of eggs subjected to simulated raindrops were investigated in laboratory experiments. In oviposition studies, DBM deposited more eggs on leaf veins than on leaf laminas on both host plants. In common cabbage plants, eggs laid on lower leaves (leaf 2) were less susceptible to dislodgment by rainfall than eggs laid on upper leaves (leaf 6). Eggs laid on the veins on the abaxial surfaces of leaves 2 and 6 of common cabbage plants were less susceptible to dislodgment by raindrops than eggs laid at other sites on this host plant. In Chinese cabbage plants, eggs laid on the veins were less susceptible to dislodgment by raindrops than eggs laid on leaf laminas. When DBM laid eggs in clusters, eggs were less susceptible to dislodgment by raindrops. The presence of waxes on leaf surfaces and concave veins affected egg placement and the retention of eggs at oviposition sites when subjected to raindrops. Eggs were more resistant to raindrops on the concave veined and less waxy leaves of Chinese cabbage plants than on waxy surfaces of smooth common cabbage leaves. When epicuticular wax crystals were removed from common cabbage leaves before oviposition, eggs were more resistant to dislodgment by raindrops. Leaf orientation or angle (horizontal plane vs. an angle of 45°) did not affect the susceptibility of eggs to raindrops. However, eggs were affected indirectly, and vibrations caused by the impact of raindrops resulted in egg removal from both adaxial and abaxial surfaces. Overall, eggs were less likely to be dislodged by raindrops when laid on concave veins and less waxy leaf surfaces. In oviposition tests, DBM laid fewer eggs on plant parts from which they were most easily removed by raindrops, and when they did lay eggs at these sites, they often deposited them in clusters which were more resistant than single eggs to removal by raindrops. The study reiterates the species‐specific nature of DBM‐host plant interactions and shows that female DBM can modify their behaviour to improve the probability of egg survival when substrates available for oviposition are sub‐optimal.
Simulated climate warming causes asymmetric responses in insect life‐history timing potentially disrupting a classic ecological speciation system
Authors: Lackey Alycia C. R. , Deneen Pheobe M. , Ragland Gregory J. , Feder Jeffrey L. , Hahn Daniel A. , Powell Thomas H. Q. 
Published: June 2023

AbstractClimate change may alter phenology within populations with cascading consequences for community interactions and on‐going evolutionary processes. Here, we measured the response to climate warming in two sympatric, recently diverged (~170 years) populations of Rhagoletis pomonella flies specialized on different host fruits (hawthorn and apple) and their parasitoid wasp communities. We tested whether warmer temperatures affect dormancy regulation and its consequences for synchrony across trophic levels and temporal isolation between divergent populations. Under warmer temperatures, both fly populations developed earlier. However, warming significantly increased the proportion of maladaptive pre‐winter development in apple, but not hawthorn, flies. Parasitoid phenology was less affected, potentially generating ecological asynchrony. Observed shifts in fly phenology under warming may decrease temporal isolation, potentially limiting on‐going divergence. Our findings of complex sensitivity of life‐history timing to changing temperatures predict that coming decades may see multifaceted ecological and evolutionary changes in temporal specialist communities.