bluuebunny/crossref_metadata_2025 huggingface dataset:
DysregulatedH19/Igf2expression disrupts cardiac-placental axis during development of Silver Russell Syndrome-like mouse models
Authors: Chang Suhee , Fulmer Diana , Hur Stella K. , Thorvaldsen Joanne L. , Li Li , Lan Yemin , Rhon-Calderon Eric A. , Leu N Adrian , Chen Xiaowen , Epstein Jonathan A. , Bartolomei Marisa S.
Published: March 2022

Dysregulation of the imprintedH19/IGF2locus can lead to Silver-Russell Syndrome (SRS) in humans. However, the mechanism of how abnormalH19/IGF2expression contributes to various SRS phenotypes remains unclear, largely due to incomplete understanding of the developmental functions of these two genes. We previously generated a mouse model with humanizedH19/IGF2ICR (hIC1) on the paternal allele that exhibitedH19/Igf2dysregulation together with SRS-like growth restriction and perinatal lethality. Here we dissect the role ofH19andIgf2in cardiac and placental development utilizing multiple mouse models with varying levels ofH19andIgf2. We report severe cardiac defects such as ventricular septal defects (VSDs) and thinned myocardium, placental anomalies including thrombosis and vascular malformations, together with growth restriction in mouse embryos that correlated with the extent ofH19/Igf2dysregulation. Transcriptomic analysis using cardiac endothelial cells of these mouse models shows thatH19/Igf2dysregulation disrupts pathways related to extracellular matrix (ECM) and proliferation of endothelial cells. Our work links the heart and placenta through regulation byH19andIgf2, demonstrating that accurate dosage of bothH19andIgf2is critical for normal embryonic development, especially related to the cardiac-placental axis.
Noise facilitates entrainment of a population of uncoupled limit cycle oscillators
Authors: Kumpost Vojtech , Hilbert Lennart , Mikut Ralf
Published: March 2022

Many biological oscillators share two properties: they are subject to stochastic fluctuations (noise) and they must reliably adjust their period to changing environmental conditions (entrainment). While noise seems to distort the ability of single oscillators to entrain, in populations of oscillators noise allows entrainment for a wider range of input amplitudes and periods. Here, we investigate, how this effect depends on the noise intensity and the number of oscillators in the population. We have found that, if a population consists of a sufficient number of oscillators, increasing noise intensity leads to faster entrainment after a phase change of the input signal (jet lag) and increases sensitivity to low-amplitude input signals.

SIGNIFICANCE

Live is characterized by rhythms, such as daily changes in activity or the heartbeat. These rhythms are reflected in molecular oscillations generated at the level of individual cells. These oscillations are inherently noisy, but still cells reliably synchronize to external signals and provide reliable timing for other biological processes. Here, we show how noise can be beneficial to cell populations in terms of synchronization to external signals. Specifically, noise can increase the sensitivity to weak external signals and speed up adjustment to jet-lag-like perturbations.
Growth instabilities shape morphology and genetic diversity of cellular aggregates
Authors: Golden Alexander , Dukovski Ilija , Segrè Daniel , Korolev Kirill S.
Published: March 2022

Cellular aggregates assume an incredible variety of shapes ranging from circular molds to irregular tumors. While we understand many of the mechanisms responsible for these spatial patterns, little is known about how the shape of an aggregate influences its ecology and evolution. Here, we investigate this relationship in the context of microbial colonies grown on hard agar plates. This a well-studied system that exhibits a transition from smooth circular disks to more irregular and rugged shapes as either the nutrient concentration or cellular motility is decreased. Starting from a mechanistic model of colony growth, we identify two dimensionless quantities that determine how morphology and genetic diversity of the population depend on the model parameters. Our simulations further reveal that population dynamics cannot be accurately described by the commonly-used surface growth models. Instead, one has to explicitly account for the emergent growth instabilities and demographic fluctuations. Overall, our work links together environmental conditions, colony morphology, and evolution. This link is essential for a rational design of concrete, biophysical perturbations to steer evolution in the desired direction.
Classification of Movement-Related Oscillations in sEEG Recordings with Machine Learning
Authors: Rockhill Alexander P. , Mantovani Alessandra , Stedelin Brittany , Raslan Ahmed M. , Swann Nicole C.
Published: March 2022

Previous electrophysiological research has characterized canonical oscillatory patterns associated with movement mostly from recordings of primary sensorimotor cortex. Less work has attempted to decode movement based on electrophysiological recordings from a broader array of brain areas such as those sampled by stereoelectroencephalography (sEEG). Here we decoded movement using a linear support vector machine (SVM). We were able to accurately classify sEEG spectrograms during a keypress movement in a task versus those during the inter-trial interval. Furthermore, the important time-frequency patterns for this classification recapitulated findings from previous studies that used non-invasive electroencephalography (EEG) and electrocorticography (ECoG) and identified brain regions that were not associated with movement in previous studies. Specifically, we found these previously described patterns: beta (13 - 30 Hz) desynchronization, beta synchronization (rebound), pre-movement alpha (8 - 15 Hz) modulation, a post-movement broadband gamma (60 - 90 Hz) increase and an event-related potential. These oscillatory patterns were newly observed in a wide range of brain areas accessible with sEEG that are not accessible with other electrophysiology recording methods. For example, the presence of beta desynchronization in the frontal lobe was more widespread than previously described, extending outside primary and secondary motor cortices. We provide evidence for a system of putative motor networks that exhibit unique oscillatory patterns by describing the anatomical extent of the movement-related oscillations that were observed most frequently across all sEEG contacts.

Significance Statement

Several major motor networks have been previously delineated in humans, however, much less is known about the population-level oscillations that coordinate this neural circuitry, especially in cortex. Therapies that modulate brain circuits to treat movement disorders, such as deep brain stimulation (DBS), or use brain signals to control movement, such as brain-computer interfaces (BCIs), rely on our basic scientific understanding of this movement neural circuitry. In order to bridge this gap, we used stereoelectroencephalography (sEEG) collected in human patients being monitored for epilepsy to assess oscillatory patterns during movement.
Transcriptional control of nucleus accumbens neuronal excitability by Retinoid X Receptor Alpha tunes sensitivity to drug rewards
Authors: Godino Arthur , Salery Marine , Durand-de Cuttoli Romain , Estill Molly S. , Holt Leanne M. , Futamura Rita , Browne Caleb J. , Mews Philipp , Hamilton Peter J. , Neve Rachael L. , Shen Li , Russo Scott J. , Nestler Eric J.
Published: March 2022

The complex nature of the transcriptional networks underlying addictive behaviors suggests intricate cooperation between diverse gene regulation mechanisms that go beyond canonical activity-dependent pathways. Here we implicate in this process a novel nuclear receptor transcription factor, Retinoid X Receptor Alpha (RXRα), which we identified bioinformatically as associated with addiction-like behaviors. In the nucleus accumbens (NAc) of male and female mice, we show that, while its own expression remains unaltered after cocaine exposure, RXRα controls plasticity- and addiction-relevant transcriptional programs in both dopamine receptor D1- and D2-expressing medium spiny neurons, which in turn modulate intrinsic excitability and synaptic activity of these NAc cell types. Behaviorally, bidirectional viral and pharmacological manipulation of RXRα regulates drug reward sensitivity in both non-operant and operant paradigms. Together, this study demonstrates a key role for NAc RXRα in promoting drug addiction, and paves the way for future studies of rexinoid signaling in psychiatric disease states.
Model-free Prediction Test with Application to Genomics Data
Authors: Cai Zhanrui , Lei Jing , Roeder Kathryn
Published: March 2022

Testing the significance of prediction in a regression model is one of the most important topics in statistics. This problem is especially difficult without any parametric assumptions on the data. This paper aims to test the null hypothesis that, given confounding variables Z, X does not significantly contribute to the prediction of Y under the model-free setting, where X and Z are possibly high dimensional. We propose a general framework that first fits nonparametric regression models on the Y|X and Y|(X, Z), then compares the prediction power of the two models. The proposed method allows us to leverage the strength of the most powerful regression algorithms developed from the modern machine learning community. The p-value for the test can be easily obtained by permutation. In simulations, we find that the proposed method is more powerful compared to existing methods. The proposed method allows us to draw biologically meaningful conclusions from two gene expression data analyses without strong distributional assumptions: (a) testing prediction power of sequencing RNA for the proteins in CITE-seq data, and (b) identification of spatially variable genes in spatially resolved transcriptomics data.
Assessment of the mediating effect of benchmarking workspace usage on portfolio optimization and client satisfaction: Indian information technology companies
Authors: Kaur Taran , Solomon Priya
Published: March 2022

Purpose

Many corporates in India are constantly adapting real estate benchmarks to reduce the workspace maintenance cost. However, anecdotally benchmarking the experience of clients while designing the workspace maintenance policies is not adequately taken into consideration in India. The focus of this study is on benchmarking workspace usage based on client usability.

Design/methodology/approach

The research is descriptive in nature. A structured questionnaire was sent to Information Technology (IT) companies in India to collect data through SurveyMonkey. Stratified sampling was used to collect a sample of 697 respondents which was also verified using G* software. The data collected was analysed using descriptive statistics and partial least square–structured equation modeling (PLS-SEM) to investigate the mediating effect of benchmarking the workspace usage on portfolio optimization and client satisfaction.

Findings

The structural model results obtained through the bootstrapping technique show that benchmarking workspace usage for real estate management positively impacts client satisfaction in the Indian IT workspace. The findings of this study support the full mediation effect (97%) and indicate that benchmarking practices are necessary for developing strategies for optimal portfolio asset utilization and are essential to survive in the current competitive business environment.

Research limitations/implications

The findings of this study were influenced by the feedback from the top 100 IT clients in India. The research findings vary according to the cost-benefit analysis of adopting benchmarking measures in small and medium-sized IT companies which still benchmark the workspace usage based on cost-saving measures. Also, very sparse research has been conducted in the workspace management domain of IT firms, so the results of this study can further be used as a reference to explore this area.

Practical implications

The study provides useful insights into how benchmarking in the workspace management domain of the CRE industry can be applied to address portfolio-related challenges, divergent client needs and improve workspace usability following energy-efficient policies. Practitioners can use this study as a guide to develop more effective workspace management policies.

Social implications

This study may guide other firms to benchmark their current workspace usage and evaluate the impact of their workspace management policies based on the theoretical framework of value-added balanced benchmarking criteria.

Originality/value

This research adds value to the limited literature available on the impact of technology-enabled portfolio optimization techniques through benchmarking which can reduce workspace usage and enhance the usability of the workspace.
An optimization-based methodology to design waveguides with metamaterial walls
Authors: Bellouch Ayoub , El Alami Amine , Messine Frederic , Raveu Nathalie
Published: March 2022

Purpose

The purpose of this sudy is to provide a complete optimization-based methodology to design waveguides with metamaterial walls. The present methodology is based on optimization. Indeed, the inverse problems of design are formulated as nonlinear black-box optimization problems with constraints. Two inequality black-box constraints are taken into account as penalized terms that are added to the objective function when the constraints are not satisfied. The numerical steps are done by using a finite element method solver (GetDP). Thus, different optimization software are tested to solve the nonlinear black-box optimization problems such as IPOPT, NLOPT and NOMAD from the Opti ToolBox in MatLab.

Design/methodology/approach

In this work, a methodology to design waveguides with metamaterial walls is proposed. The aim is to solve an inverse problem to find the best design where the electric field cartography is the closest to an imposed one.

Findings

The present methodology is applied to solve inverse problems of design and satisfactory results were provided by the three solvers IPOPT, NLOPT and NOMAD. Those numerical experiments show that NOMAD is the most efficient method to optimize the design of those cylindrical waveguide structures with metamaterial walls.

Research limitations/implications

The model is set to find solutions using a specific pattern of metamaterials. This is promising to take those geometries as variables of the optimization problems. Moreover, in this exploratory work, no constraint on the fabrication limits has been taken into account.

Originality/value

The originality is to formulate design problems of waveguide with metamaterial walls into optimization problems. These optimization problems are difficult to solve because the objective function and two inequality constraints are computed via a numerical simulation code based on finite element methods. Thus, an original approach based on penalization is implemented and three optimization software are used. Hence, the authors propose an optimization-based methodology and apply to solve two inverse problems of design.
Detecting the most appropriate delay analysis methods for mega airport projects
Authors: Cevikbas Murat , Işık Zeynep
Published: March 2022

Purpose

This study aims to detect the most appropriate delay analysis method in mega airport projects.

Design/methodology/approach

First, the criteria affecting the selection of delay analysis methods were detected through an in-depth literature review and an expert panel, which was conducted with 12 experts who have experience in delay analysis domain in mega airport projects. Later, fuzzy VIKOR (VIsekriterijumska optimizacija i KOmpromisno Resenje) approach was conducted by considering the detected selection criteria and the most common delay analysis methods.

Findings

Windows Analysis method was detected as the best option for mega airport projects. It was followed by Time Impact Analysis (TIA), collapsed as-built analysis, as-planned vs as-built method and impacted as-planned method, respectively.

Originality/value

Each project has its own characteristics and thus requires specific management techniques; therefore, selecting a delay analysis method without considering the project types and size may cause conflicts between the contracting parties. On the one hand, numerous fruitful studies concerning delay analysis methods have been conducted in the literature, but on the other hand, none of them has considered project characteristics in terms of project size and type while selecting the most appropriate delay analysis method. Moreover, the larger the size of a project is, the more vulnerable it is to encounter with delays. Mega airport construction projects are complex in their nature in that they are large size and involve multi-disciplinary processes; thus, they need special attention in the process of resolving delays. This study intended to fill this gap in the literature by focusing on selection of the most appropriate delay analysis method for mega airport projects, and it is clear that considering the project type and size in the selection of delay analysis methods will provide more reliable outcomes.
Exploring the mutually reinforcing relationship between theory of mind and reading in adult readers
Authors: Jackson Sophie
Published: March 2022

Background

Research with children shows that theory of mind predicts reading comprehension both concurrently and longitudinally, while research with adults shows increased print‐exposure relates to theory of mind understanding. However, until now whether reading and theory of mind have a mutually reinforcing relationship in which they promote one another in parallel has not been explored. Therefore, this study aims to explore further the relationship between theory of mind and reading by investigating reading comprehension, print‐exposure and theory of mind together.

Method

Theory of mind (Reading the Eyes in the Mind test), reading comprehension (subset of the York Adult Assessment Battery‐Revised) and print‐exposure (Authors Recognition Test) were measured in a sample of U.K. adults (N = 220).

Results

Findings showed that theory of mind was significantly related to both reading comprehension and reading print‐exposure. Further, mediation analysis showed that this relationship does not operate with theory of mind mediating the relationship between print‐exposure and reading comprehension as an indirect effect of print‐exposure on reading comprehension through theory of mind was not found after controlling for age, income and education.

Conclusions

The findings provide some initial evidence that, at least in adulthood, reading and theory of mind have a mutually reinforcing relationship in which they promote one another in parallel, but this relationship cannot be explained by theory of mind mediating the relationship between print‐exposure and reading comprehension.
Blind testing in firearms: Preliminary results from a blind quality control program
Authors: Neuman Maddisen , Hundl Callan , Grimaldi Aimee , Eudaley Donna , Stein Darrell , Stout Peter
Published: March 2022

Open proficiency tests meet accreditation requirements and measure examiner competence but may not represent actual casework. In December 2015, the Houston Forensic Science Center began a blind quality control program in firearms examination. Mock cases are created to mimic routine casework so that examiners are unaware they are being tested. Once the blind case is assigned to an examiner, the evidence undergoes microscopic examination and comparison to determine whether the fired evidence submitted was fired in the same firearm. Fifty‐one firearms blind cases resulting in 570 analysis and comparison determinations were reported between December 2015 and June 2021. No unsatisfactory results were obtained; however, 40.3% of comparisons in which the ground truth was either elimination or identification resulted in inconclusive conclusions. Due to the quality of some of the evidence submitted, inconclusive results were not unexpected. A ground truth of elimination and comparison result of inconclusive was observed at a rate of 74%, while a ground truth of identification and comparison result of inconclusive was observed at a rate of 31%. Bullets (61.8%) were the main contributors to inconclusive conclusions; variables such as the assigned examiners, training program, examiner experience, and the intended complexity of the case did not significantly contribute to the results. The program demonstrates that the quality management system and firearms section procedures can obtain accurate and reliable results and provides examiners added confidence in court. Additionally, the program can be tailored to target specific research questions and provide opportunities for collaboration with other laboratories and researchers.
Roast level and brew temperature significantly affect the color of brewed coffee
Authors: Yeager Sara E. , Batali Mackenzie E. , Lim Lik Xian , Liang Jiexin , Han Juliet , Thompson Ashley N. , Guinard Jean‐Xavier , Ristenpart William D.
Published: March 2022

Beverage color significantly affects perceived sensory quality and consumer preference. Although the color of coffee beans is well known to vary strongly with roast level, little work has examined how roast level and brewing conditions affect the color of the final beverage. Here, we report that the color of full immersion brewed coffee is significantly affected by both roast level and brewing temperature. Coffees from three different origins were each roasted to three different levels (light, medium, and dark) and then brewed at three different temperatures (4, 22, and 92°C). Each sample was brewed toward full extraction and then diluted to precisely 2% total dissolved solids so that differences in concentration would not confound color measurements. Absorbance spectra (UV‐vis) and color tristimulus values (L*a*b*) were then collected and analyzed. We find that roast level had the strongest impact on brew color, and that brew temperature had a significant impact on color for light and medium roasts, with less impact on dark roasts. Qualitatively, the cold brewed coffees tended to be redder, while the hot brewed coffees were blacker. The results suggest that there is an opportunity to manipulate and brand brewed coffee color through judicious choices of roast level and brewing temperature.

Practical Application

Color serves as an indicator of coffee quality and potentially could affect perceived sensory characteristics. Our results suggest that appropriate control of roast level and brew temperature could yield desired colors for novel coffee products.
ROBITT: A tool for assessing the risk‐of‐bias in studies of temporal trends in ecology
Authors: Boyd Robin J. , Powney Gary D. , Burns Fiona , Danet Alain , Duchenne François , Grainger Matthew J. , Jarvis Susan G. , Martin Gabrielle , Nilsen Erlend B. , Porcher Emmanuelle , Stewart Gavin B. , Wilson Oliver J. , Pescott Oliver L.
Published: March 2022

Aggregated species occurrence and abundance data from disparate sources are increasingly accessible to ecologists for the analysis of temporal trends in biodiversity. However, sampling biases relevant to any given research question are often poorly explored and infrequently reported; this can undermine statistical inference. In other disciplines, it is common for researchers to complete ‘risk‐of‐bias’ assessments to expose and document the potential for biases to undermine conclusions. The huge growth in available data, and recent controversies surrounding their use to infer temporal trends, indicate that similar assessments are urgently needed in ecology.

We introduce ROBITT, a structured tool for assessing the ‘Risk‐Of‐Bias In studies of Temporal Trends in ecology’. ROBITT has a similar format to its counterparts in other disciplines: it comprises signalling questions designed to elicit information on the potential for bias in key study domains. In answering these, users will define study inferential goal(s) and relevant statistical target populations. This information is used to assess potential sampling biases across domains relevant to the research question (e.g. geography, taxonomy, environment), and how these vary through time. If assessments indicate biases, then users must clearly describe them and/or explain what mitigating action will be taken.

Everything that users need to complete a ROBITT assessment is provided: the tool, a guidance document and a worked example. Following other disciplines, the tool and guidance document were developed through a consensus‐forming process across experts working in relevant areas of ecology and evidence synthesis.

We propose that researchers should be strongly encouraged to include a ROBITT assessment when publishing studies of biodiversity trends, especially when using aggregated data. This will help researchers to structure their thinking, clearly acknowledge potential sampling issues, highlight where expert consultation is required and provide an opportunity to describe data checks that might go unreported. ROBITT will also enable reviewers, editors and readers to establish how well research conclusions are supported given a dataset combined with some analytical approach. In turn, it should strengthen evidence‐based policy and practice, reduce differing interpretations of data and provide a clearer picture of the uncertainties associated with our understanding of reality.
The value of hybrid and non‐native ash for the conservation of ash specialists is limited following late stages of emerald ash borer invasion
Authors: Perry Kayla I. , Riley Christopher B. , Fan Fan , Radl James , Herms Daniel A. , Gardiner Mary M.
Published: March 2022

Widespread mortality of native North American ash caused by emerald ash borer (EAB; Agrilus planipennis Fairmaire) threatens native arthropod biodiversity, but hybrid ash populations with resistance to EAB may serve a role in supporting threatened communities of arthropods in managed landscapes impacted by EAB.

In this study, we investigated the hypothesis that a North American × Asian hybrid ash could serve as a refuge for North American arthropods in a common garden experiment by comparing beetle communities and herbivory on North American green and black ash, the Asian Manchurian ash, and the black × Manchurian hybrid ‘Northern Treasure’ ash.

We found that ash specialists were rare among trees in the common garden. Species richness and composition of herbivorous beetles, as well as levels of herbivory, were similar among ash taxa, and these patterns were driven by native generalists.

The lack of ash specialists collected suggests that regions that have experienced late stages of EAB‐induced ash mortality may have missed the opportunity to conserve populations of native specialist herbivores with EAB‐resistant ash genotypes. To maximize the potential for conserving native arthropod biodiversity of ash, it may be necessary to plant resistant ash prior to widespread EAB‐induced ash mortality, prioritizing efforts on the leading edge of expanding distribution of EAB.
Bupropion XL and SR have similar effectiveness and adverse event profiles when used to treat smoking among patients at a comprehensive cancer center
Authors: Robinson Jason D. , Karam‐Hage Maher , Kypriotakis George , Beneventi Diane , Blalock Janice A. , Cui Yong , Gonzalez Roberto , Tayar Jean , Chaftari Patrick , Cinciripini Paul M.
Published: March 2022

Background and Objectives

Bupropion extended‐release (XL; once‐daily dosing) has equal efficacy with the sustained‐release (SR) formulation (twice‐daily dosing) for treating depression, but no studies have compared the two formulations for the treatment of smoking. In a naturalistic open‐label study, we compared the effectiveness and the adverse event profiles of XL and SR in treating cancer patients for smoking.

Methods

Cancer patients (N = 648) were prescribed bupropion XL (n = 454) or SR (n = 194) alone or in combination with nicotine replacement therapy (NRT) for treating smoking from September 2006 to December 2017. We analyzed 7‐day point prevalence abstinence at end‐of‐treatment (EOT; 3 months postmedication initiation) and evaluated for noninferiority. We also analyzed the adverse event profile differences between the medications.

Results

There were no significant differences in abstinent rates at EOT between bupropion XL and SR when using intent‐to‐treat models, regardless of concomitant NRT. XL demonstrated noninferiority in treatment efficacy compared to SR when excluding those on combined treatment with NRT. Further, there were no significant differences in spontaneously reported adverse events between XL and SR.

Conclusions

Our data did not reveal a difference between bupropion XL and SR formulations in terms of effectiveness or adverse event profiles among cancer patients prescribed bupropion alone or in combination with NRTs to quit smoking.

Scientific Significance

In this first published direct comparison of their effectiveness and adverse event profiles, we found that bupropion XL is likely therapeutically equivalent to bupropion SR when treating smoking among cancer patients, and produces similar side effects.
Associations between muscle‐building exercise and alcohol use behaviors among adolescent boys: Results from the 2019 Youth Risk Behavior Survey
Authors: Ganson Kyle T. , Testa Alexander , Rodgers Rachel F. , Jackson Dylan B. , Nagata Jason M.
Published: March 2022

Background and Objectives

To explore the association between muscle‐building exercise (MBE) and alcohol use behaviors among adolescent boys.

Methods

Data from the 2019 Youth Risk Behavior Survey (N = 4120) were analyzed using multiple logistic regressions.

Results

A greater number of days of MBE in the past week was associated with higher odds of four alcohol use behaviors, including recent alcohol use and binge drinking.

Discussion and Conclusions

Findings extend prior research showing relationships between team sports participation and alcohol use behaviors.

Scientific Significance

This study is the first to examine associations between MBE and alcohol use behaviors among adolescent boys.
Extreme duration exercise affects old and younger men differently
Authors: Frandsen Jacob , Sahl Ronni Eg , Rømer Tue , Hansen Mikkel Thunestvedt , Nielsen Andreas Blaaholm , Lie‐Olesen Michelle Munk , Rasmusen Hanne Kruuse , Søgaard Ditte , Ingersen Arthur , Rosenkilde Mads , Westerterp Klaas , Holst Jens Juul , Andersen Jesper Løvind , Markowski Adam Roman , Blachnio‐Zabielska Agnieszka , Clemmensen Christoffer , Sacchetti Massimo , Cataldo Angelo , Traina Marcello , Larsen Steen , Dela Flemming , Helge Jørn Wulff
Published: March 2022

Aim & Methods

Extreme endurance exercise provides a valuable research model for understanding the adaptive metabolic response of older and younger individuals to intense physical activity. Here, we compare a wide range of metabolic and physiologic parameters in two cohorts of seven trained men, age 30 ± 5 years or age 65 ± 6 years, before and after the participants travelled ≈3000 km by bicycle over 15 days.

Results

Over the 15‐day exercise intervention, participants lost 2–3 kg fat mass with no significant change in body weight. V̇O2max did not change in younger cyclists, but decreased (p = 0.06) in the older cohort. The resting plasma FFA concentration decreased markedly in both groups, and plasma glucose increased in the younger group. In the older cohort, plasma LDL‐cholesterol and plasma triglyceride decreased. In skeletal muscle, fat transporters CD36 and FABPm remained unchanged. The glucose handling proteins GLUT4 and SNAP23 increased in both groups. Mitochondrial ROS production decreased in both groups, and ADP sensitivity increased in skeletal muscle in the older but not in the younger cohort.

Conclusion

In summary, these data suggest that older but not younger individuals experience a negative adaptive response affecting cardiovascular function in response to extreme endurance exercise, while a positive response to the same exercise intervention is observed in peripheral tissues in younger and older men. The results also suggest that the adaptive thresholds differ in younger and old men, and this difference primarily affects central cardiovascular functions in older men after extreme endurance exercise.
Endotracheal lactate reflects lower respiratory tract infections and inflammation in intubated patients
Authors: Kolpen Mette , Dalby Sørensen Christian , Faurholt‐Jepsen Daniel , Hertz Frederik Boëtius , Jensen Peter Østrup , Bestle Morten Heiberg
Published: March 2022

The aim of this study was to assess L‐lactate and D‐lactate in endotracheal aspirate from intubated patients hospitalized at the intensive care unit and explore their use as diagnostic biomarkers for inflammation and lower respiratory tract infections (LRTI). Tracheal aspirates from 91 intubated patients were obtained at time of intubation and sent for microbiological analyses, neutrophil count, and colorimetric lactate measurements. We compared the concentration of lactate from patients with microbiological verified LRTI or clinical/radiological suspicion of LRTI with a control group. In addition, associations between inflammation and the lactate isomers were examined by correlating L‐lactate and D‐lactate with sputum neutrophils and clinical assessments. The concentration of L‐lactate was increased in aspirates with verified or suspected LRTI (p < 0.001) relative to the control group at Day 0. Connections between L‐lactate and inflammation were indicated by the correlation between neutrophils and L‐lactate (p < 0.001). We found no increase in sputum D‐lactate from patients with verified or suspected LRTI relative to the control group and D‐lactate was not correlated with neutrophils. L‐lactate was found to be a potential indicator for inflammation and LRTI at the time of intubation. An association was found between neutrophil count and L‐lactate. Interestingly, the increase of L‐lactate in the control group after intubation may suggest that intubation challenges the host response by inflicting tissue damage or by introducing infectious microbes.
Multikink Quantile Regression for Longitudinal Data with Application to Progesterone Data Analysis
Authors: Wan Chuang , Zhong Wei , Zhang Wenyang , Zou Changliang
Published: March 2022

Motivated by investigating the relationship between progesterone and the days in a menstrual cycle in a longitudinal study, we propose a multikink quantile regression model for longitudinal data analysis. It relaxes the linearity condition and assumes different regression forms in different regions of the domain of the threshold covariate. In this paper, we first propose a multikink quantile regression for longitudinal data. Two estimation procedures are proposed to estimate the regression coefficients and the kink points locations: one is a computationally efficient profile estimator under the working independence framework while the other one considers the within-subject correlations by using the unbiased generalized estimation equation approach. The selection consistency of the number of kink points and the asymptotic normality of two proposed estimators are established. Second, we construct a rank score test based on partial subgradients for the existence of the kink effect in longitudinal studies. Both the null distribution and the local alternative distribution of the test statistic have been derived. Simulation studies show that the proposed methods have excellent finite sample performance. In the application to the longitudinal progesterone data, we identify two kink points in the progesterone curves over different quantiles and observe that the progesterone level remains stable before the day of ovulation, then increases quickly in 5 to 6 days after ovulation and then changes to stable again or drops slightly.
Does the stork bring home the owl? Dusky Eagle‐Owls Bubo coromandus breeding on Woolly‐necked Stork Ciconia episcopus nests
Authors: Sundar K. S. Gopi , Ahlawat Rakesh , Dalal Devender Singh , Kittur Swati
Published: March 2022

We documented nests built by Woolly‐necked Storks, a large waterbird, being preferentially reused by Dusky Eagle‐Owls, a large raptor, with nest sites located close to irrigation canals in Haryana, India. This novel commensal relationship observed in an agricultural landscape underscores the need to expand tropical ecology investigations to outside of protected forested reserves.
NCAPD2 promotes breast cancer progression through E2F1 transcriptional regulation of CDK1
Authors: He Jinsong , Gao Rui , Yang Jianbo , Li Feng , Fu Yang , Cui Junwei , Liu Xiaoling , Huang Kanghua , Guo Qiuyi , Zhou Zihan , Wei Wei
Published: March 2022

Breast cancer (BC) is a serious threat to women’s health worldwide. Non‐SMC condensin I complex subunit D2 (NCAPD2) is a regulatory subunit of the coagulin I complex, which is mainly involved in chromosome coagulation and separation. The clinical significance, biological behavior, and potential molecular mechanism of NCAPD2 in BC were investigated in this study. We found that NCAPD2 was frequently overexpressed in BC, and it had clinical significance in predicting the prognosis of BC patients. Moreover, loss‐of‐function assays demonstrated that NCAPD2 knockdown restrained the progression of BC by inhibiting proliferation and migration and enhancing apoptosis in vitro. It was further confirmed that the downregulation of NCAPD2 inhibited tumor growth in vivo. NCAPD2 promoted the progression of BC through the extracellular signal–regulated kinase 5 (ERK5) signaling pathway. Additionally, NCAPD2 could transcriptionally activate CDK1 by interacting with E2F transcription factor 1 (E2F1) in MDA‐MB‐231 cells. Overexpression of CDK1 alleviated the inhibitory effects of NCAPD2 knockdown in BC cells. In summary, the NCAPD2/E2F1/CDK1 axis may play a role in promoting the progression of BC, which may provide a blueprint for molecular therapy.
TBX20 inhibits colorectal cancer tumorigenesis by impairing NHEJ‐mediated DNA repair
Authors: Luo Jie , Chen Jie‐Wei , Zhou Jie , Han Kai , Li Si , Duan Jin‐Ling , Cao Chen‐Hui , Lin Jin‐Long , Xie Dan , Wang Feng‐Wei
Published: March 2022

DNA high methylation is one of driving force for colorectal carcinoma (CRC) pathogenesis. Transcription factors (TFs) can determine cell fate and play fundamental roles in multistep process of tumorigenesis. Dysregulation of DNA methylation of TFs should be vital for the progression of CRC. Here, we demonstrated that TBX20, a T‐box TF family protein, was downregulated with hypermethylation of promoter in early‐stage CRC tissues and correlated with a poor prognosis for CRC patients. Moreover, we identified PDZRN3 as the E3 ubiquitin ligase of TBX20 protein, which mediated the ubiquitination and degradation of TBX20. Furthermore, we revealed that TBX20 suppressed cell proliferation and tumor growth through impairing non‐homologous DNA end joining (NHEJ)‐mediated double‐stranded break repair by binding the middle domain of both Ku70 and Ku80 and therefore inhibiting their recruitment on chromatin in CRC cells. Altogether, our results reveal the tumor‐suppressive role of TBX20 by inhibiting NHEJ‐mediated DNA repair in CRC cells, and provide a potential biomarker for predicting the prognosis of patients with early‐stage CRC and a therapeutic target for combination therapy.
Novel cancer‐specific epidermal growth factor receptor antibody obtained from the serum of esophageal cancer patients with long‐term survival
Authors: Takagi‐Maeda Sayaka , Yajima Satoshi , Suzuki Takashi , Usami Katsuaki , Takahashi Nobuaki , Niwa Rinpei , Shimada Hideaki
Published: March 2022

Although esophageal cancer has a poor prognosis after recurrence, some patients have shown long‐term survival despite recurrence. We hypothesized that induction of either antitumor Abs or antitumor‐specific CTLs could play a role in long‐term survival (5 years or longer) in patients with recurrence and/or distant metastases. Therefore, we aimed to obtain Abs that specifically bind to cancer cells by using serum samples from patients with a good prognosis. A phage library was prepared using PBMC mRNA of the patients, and cell panning was carried out using an esophageal cancer cell line. Results showed the presence of an epidermal growth factor receptor (EGFR) Ab, KT112, that specifically bound to the cancer cell line. Notably, KT112 bound to only EGFR‐positive cancer cells but failed to bind to normal esophageal cells. Furthermore, KT112 was characterized by responses to EGFR expressed on cancer cells but not to the recombinant extracellular domain of EGFR. Immunohistochemical analysis showed that KT112 reacted with 17.4% of esophageal squamous cell carcinoma tissue but not with any other cancer or normal tissue, suggesting that the Ab recognizes cancer‐specific forms of EGFR and might have contributed to tumor suppression in patients with esophageal cancer. Furthermore, because of its high cancer specificity, KT112 could be a promising therapeutic option (e.g., in Ab‐drug conjugates) for esophageal cancer.
Physiological and pathological roles of the Hippo‐YAP/TAZ signaling pathway in liver formation, homeostasis, and tumorigenesis
Authors: Nishina Hiroshi
Published: March 2022

The liver plays central homeostatic roles in metabolism and detoxification, and has a remarkable capacity to fully recover from injuries caused by the various insults to which it is constantly exposed. To fulfill these functions, the liver must maintain a specific size and so must regulate its cell numbers. It must also remove senescent, transformed, and/or injured cells that impair liver function and can lead to diseases such as cirrhosis and liver cancer. Despite their importance, however, the mechanisms governing liver size control and homeostasis have resisted delineation. The discovery of the Hippo intracellular signaling pathway and its downstream effectors, the transcriptional coactivators Yes‐associated protein (YAP) and transcriptional coactivator with PDZ‐binding motif (TAZ), has provided partial elucidation of these mechanisms. The Hippo‐YAP/TAZ pathway is considered to be a cell’s sensor of its immediate microenvironment and the cells that surround it, in that this pathway responds to changes in elements such as the ECM, cell–cell tension, and cell adhesion. Once triggered, Hippo signaling negatively regulates the binding of YAP/TAZ to transcription factors such as TEAD and Smad, controlling their ability to drive gene expression needed for cellular responses such as proliferation, survival, and stemness. Numerous KO mouse strains lacking YAP/TAZ, as well as transgenic mice showing YAP/TAZ hyperactivation, have been generated, and the effects of these mutations on liver development, size, regeneration, homeostasis, and tumorigenesis have been reported. In this review, I summarize the components and regulation of Hippo‐YAP/TAZ signaling, and discuss this pathway in the context of liver physiology and pathology.
Approach to androgen excess in women: Clinical and biochemical insights
Authors: Cussen Leanne , McDonnell Tara , Bennett Gillian , Thompson Christopher J. , Sherlock Mark , O'Reilly Michael W.
Published: March 2022

Androgen excess in women typically presents clinically with hirsutism, acne or androgenic alopecia. In the vast majority of cases, the underlying aetiology is polycystic ovary syndrome (PCOS), a common chronic condition that affects up to 10% of all women. Identification of women with non‐PCOS pathology within large cohorts of patients presenting with androgen excess represents a diagnostic challenge for the endocrinologist, and rare pathology including nonclassic congenital adrenal hyperplasia, severe insulin resistance syndromes, Cushing's disease or androgen‐secreting tumours of the ovary or adrenal gland may be missed in the absence of a pragmatic screening approach. Detailed clinical history, physical examination and biochemical phenotyping are critical in risk‐stratifying women who are at the highest risk of non‐PCOS disorders. Red flag features such as rapid onset symptoms, overt virilization, postmenopausal onset or severe biochemical disturbances should prompt investigations for underlying neoplastic pathology, including dynamic testing and imaging where appropriate. This review will outline a proposed diagnostic approach to androgen excess in women, including an introduction to androgen metabolism and provision of a suggested algorithmic strategy to identify non‐PCOS pathology according to clinical and biochemical phenotype.
Highly diversified mitochondrial genomes provide new evidence for interordinal relationships in the Arachnida
Authors: Ban Xin‐Chao , Shao Zi‐Kai , Wu Li‐Jun , Sun Jing‐Tao , Xue Xiao‐Feng
Published: March 2022

Arachnida is an exceptionally diverse class in the Arthropoda, consisting of 20 orders and playing crucial roles in the terrestrial ecosystems. However, their interordinal relationships have been debated for over a century. Rearranged or highly rearranged mitochondrial genomes (mitogenomes) were consistently found in this class, but their various extent in different lineages and efficiency for resolving arachnid phylogenies are unclear. Here, we reconstructed phylogenetic trees using mitogenome sequences of 290 arachnid species to decipher interordinal relationships as well as diversification through time. Our results recovered monophyly of ten orders (i.e. Amblypygi, Araneae, Ixodida, Mesostigmata, Opiliones, Pseudoscorpiones, Ricinulei, Sarcoptiformes, Scorpiones and Solifugae), while rejecting monophyly of the Trombidiformes due to the unstable position of the Eriophyoidea. The monophyly of Acari (subclass) was rejected, possibly due to the long‐branch attraction of the Pseudoscorpiones. The monophyly of Arachnida was further rejected because the Xiphosura nested within arachnid orders with unstable positions. Mitogenomes that are highly rearranged in mites but less rearranged or conserved in the remaining lineages point to their exceptional diversification in mite orders; however, shared derived mitochondrial (mt) gene clusters were found within superfamilies rather than interorders, confusing phylogenetic signals in arachnid interordinal relationships. Molecular dating results show that arachnid orders have ancient origins, ranging from the Ordovician to the Carboniferous, yet have significantly diversified since the Cretaceous in orders Araneae, Mesostigmata, Sarcoptiformes, and Trombidiformes. By summarizing previously resolved key positions of some orders, we propose a plausible arachnid tree of life. Our results underline a more precise framework for interordinal phylogeny in the Arachnida and provide new insights into their ancient evolution.
Pneumatosis intestinalis after thoracic organ transplantation in children: A case series and review of the literature
Authors: Atwood Daniel , Nelson Amanda , Rosen Rachel , Esteso Paul , Visner Gary , Midyat Levent
Published: March 2022

Pneumatosis intestinalis (PI) is a rare complication after thoracic organ transplantation. There are several theories for explaining the pathophysiology of this disease. In this paper, we highlight three cases of PI in a single pediatric center, one after lung transplantation and two after heart transplantation. Although the presentations differed, all cases improved with non‐surgical therapies. There are not many articles in the pediatric literature about post‐transplantation PI, and there are still many questions regarding the incidence, etiology, and treatment for this disease.