bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectral Fidelity of Earth's Terrestrial and Aquatic Ecosystems
Authors: Thompson David R. , Brodrick Philip G. , Cawse‐Nicholson Kerry , Dana Chadwick K. , Green Robert O. , Poulter Benjamin , Serbin Shawn , Shiklomanov Alexey N. , Townsend Philip A. , Turpie Kevin R.
Published: July 2021

The Surface Biology and Geology (SBG) investigation will create global maps of spectral surface reflectance and emissivity at a cadence of 16 days or better, with coverage to address global questions about Earth's geology, cryosphere and ecosystems. The revolutionary potential poses a commensurate challenge: creating contiguous maps free from regional biases induced by atmosphere, observation geometry, or inversion error. This will require an accurate calibration with precise knowledge of each channel's spectral response. Here, we quantify the impact of spectral calibration on SBG's aquatic and terrestrial ecosystem objectives. We find that contemporary algorithms for ecosystem trait retrieval demand more accurate spectral calibration than historical missions. Errors due to drift or spatial nonuniformity in the wavelength calibration that have previously been considered acceptable can cause systematic errors larger than the instrument noise and of the same order as the variability SBG aims to measure. Moreover, their impact on atmospheric correction can induce climate‐dependent systematic errors that thwart comparisons between ecosystems. These results underscore the importance of spectral response accuracy in SBG mission design.
The newly identified MEK1 tyrosine phosphorylation target MACC1 is druggable by approved MEK1 inhibitors to restrict colorectal cancer metastasis
Authors: Kobelt Dennis , Perez-Hernandez Daniel , Fleuter Claudia , Dahlmann Mathias , Zincke Fabian , Smith Janice , Migotti Rebekka , Popp Oliver , Burock Susen , Walther Wolfgang , Dittmar Gunnar , Mertins Philipp , Stein Ulrike
Published: July 2021

Cancer metastasis causes >90% of cancer deaths and remains a major treatment challenge. Here we deciphered the impact of tyrosine phosphorylation of MACC1, a causative driver for cancer metastasis, for cancer cell signaling and novel interventions to restrict cancer metastasis. We identified MACC1 as new MEK1 substrate. MEK1 directly phosphorylates MACC1, leading to accelerated and increased ERK1 activation. Mutating in silico predicted hierarchical MACC1 tyrosine phosphorylation sites abrogates MACC1-induced migration, invasion, and MET expression, a transcriptional MACC1 target. Targeting MEK1 by RNAi or clinically applicable MEK1 inhibitors AZD6244 and GSK1120212 reduces MACC1 tyrosine phosphorylation and restricts MACC1-induced metastasis formation in mice. Although MEK1 levels, contrary to MACC1, are not of prognostic relevance for CRC patients, MEK1 expression was found indispensable for MACC1-induced metastasis. This study identifies MACC1 as new MEK1 substrate for tyrosine phosphorylation decisively impacting cell motility, tumor growth, and metastasis. Thus, MAP kinase signaling is not linear leading to ERK activation, but branches at the level of MEK1. This fundamental finding opens new therapeutic options for targeting the MEK1/MACC1 axis as novel vulnerability in patients at high risk for metastasis. This might be extended from CRC to further solid tumor entities.
Importance of test–retest reliability for promoting fMRI based screening and interventions in major depressive disorder
Authors: Compère Laurie , Siegle Greg J. , Young Kymberly
Published: July 2021

Proponents of personalized medicine have promoted neuroimaging in three areas of clinical application for major depression: clinical prediction, outcome evaluation, and treatment, via neurofeedback. Whereas psychometric considerations such as test–retest reliability are basic precursors to clinical adoption for most clinical instruments, we show, in this article, that basic psychometrics have not been regularly attended to in fMRI of depression. For instance, no fMRI neurofeedback study has included measures of test–retest reliability, despite the implicit assumption that brain signals are stable enough to train. We consider several factors that could be useful to aid clinical translation, including (1) attending to how the BOLD response is parameterized, (2) identifying and promoting regions or voxels with stronger psychometric properties, (3) accounting for within-individual changes (e.g., in symptomatology) across time, and (4) focusing on tasks and clinical populations that are relevant for the intended clinical application. We apply these principles to published prognostic and neurofeedback data sets. The broad implication of this work is that attention to psychometrics is important for clinical adoption of mechanistic assessment, is feasible, and may improve the underlying science.
Title: “Labels Matter: Is it stress or is it Trauma?”
Authors: Richter-Levin Gal , Sandi Carmen
Published: July 2021

In neuroscience, the term ‘Stress’ has a negative connotation because of its potential to trigger or exacerbate psychopathologies. Yet in the face of exposure to stress, the more common reaction to stress is resilience, indicating that resilience is the rule and stress-related pathology the exception. This is critical because neural mechanisms associated with stress-related psychopathology are expected to differ significantly from those associated with resilience.

Research labels and terminology affect research directions, conclusions drawn from the results, and the way we think about a topic, while choice of labels is often influenced by biases and hidden assumptions. It is therefore important to adopt a terminology that differentiates between stress conditions, leading to different outcomes.

Here, we propose to conceptually associate the term ‘stress’/‘stressful experience’ with ‘stress resilience’, while restricting the use of the term ‘trauma’ only in reference to exposures that lead to pathology. We acknowledge that there are as yet no ideal ways for addressing the murkiness of the border between stressful and traumatic experiences. Yet ignoring these differences hampers our ability to elucidate the mechanisms of trauma-related pathologies on the one hand, and of stress resilience on the other. Accordingly, we discuss how to translate such conceptual terminology into research practice.
Oxygen-doped hollow, porous NiCoP nanocages derived from Ni–Co prussian blue analogs for oxygen evolution
Authors: Li Di , Zhou Changjian , Xing Yingying , Shi Xiangli , Ma Wanxia , Li Longhua , Jiang Deli , Shi Weidong
Published: July 2021

An oxygen-doped, hollow, porous NiCoP nanocages electrocatalyst was synthesized via phosphorization and air-annealing treatment of Ni–Co Prussian blue analogs. This unique nanocage exhibited an overpotential of 310 mV at 10 mA cm−2 in the oxygen-evolution reaction.
Theoretical calculation of regioselectivity and solvation effects on B–H activation of O-carborane guided by directing group
Authors: Li Hui , Tang Wanyong , Ma Zifan
Published: July 2021

A DFT study was performed to uncover the regioselectivity, directing group, ligand, and solvation effect in B–H activation. The reaction mechanisms of the neutral and cationic pathways were unveiled.
Direct electrospinning preparation of Z-scheme mixed-crystal Bi2O3/g-C3N4 composite photocatalysts with enhanced visible-light photocatalytic activity
Authors: Zhang Liruhua , Shen Qianhong , Zheng SuHua , Yu LiXin , Huang Feilong , Zhang Changteng , Sheng Jiansong , Yang Hui
Published: July 2021

A novel Z-scheme mixed-crystal Bi2O3/g-C3N4 composite photocatalyst was successfully prepared by a simple electrospinning–calcination approach.
Design of a niobium tungsten oxide/C micro-structured electrode for fast charging lithium-ion batteries
Authors: Liu Weiwei , Xu Meng , Zhu Menghua
Published: July 2021

Secondary Nb18W16O93/C micro-grade particles are synthesized for use as a fast-charging anode with high stability and rate performance at 5C.
A review on the electrochemical reaction of Li-rich layered oxide materials
Authors: Yang Jingang , Niu Yubin , Wang Xi , Xu Maowen
Published: July 2021

Lithium-rich layered oxide materials xLi2MnO3·(1 − x)LiMO2 (M = Mn, Co, Ni, Fe, Cr, etc.) as promising cathode candidates for high energy Li-ion batteries have been summarized in this review.
High performance fiber-shaped supercapacitors based on core–shell fiber electrodes with adjustable surface wrinkles and robust interfaces
Authors: Shi Hang , Chen Song , Shi Wei , Peng Zefei , Li Junyun , Liu Zelin , Zhang Guangyong , Liu Lan
Published: July 2021

Constructing micro PPy wrinkles on the rGO/Alg fiber surface with strong interactions at the interface endows the fiber with excellent specific capacitance and cycling stability.
Room-temperature repeatedly processable baroplastic/boron nitride thermal management composite
Authors: Qiao Jia-Ning , Hu Yu-Fan , Ji Xu , Tang Jian-Hua , Lei Jun , Li Zhong-Ming
Published: July 2021

A baroplastic/boron nitride composite with low-temperature repeatable processing properties, excellent thermal conductivity performance, stability and suitable hardness that can replace conventional silicon pads is prepared.
Biological implications of genetic variations in autism spectrum disorders from genomics studies
Authors: Zhang Yue , Liu Xuanshi , Guo Ruolan , Xu Wenjian , Guo Qi , Hao Chanjuan , Ni Xin , Li Wei
Published: July 2021

Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental condition characterized by atypical social interaction and communication together with repetitive behaviors and restricted interests. The prevalence of ASD has been increased these years. Compelling evidence has shown that genetic factors contribute largely to the development of ASD. However, knowledge about its genetic etiology and pathogenesis is limited. Broad applications of genomics studies have revealed the importance of gene mutations at protein-coding regions as well as the interrupted non-coding regions in the development of ASD. In this review, we summarize the current evidence for the known molecular genetic basis and possible pathological mechanisms as well as the risk genes and loci of ASD. Functional studies for the underlying mechanisms are also implicated. The understanding of the genetics and genomics of ASD is important for the genetic diagnosis and intervention for this condition.
Effect of multi‐factors on heterocharges for oil‐impregnated paper in converter transformer using modified charge transport model
Authors: Yan Shen , Liu Jiefeng , Fan Xianhao , Zhang Yiyi , Shi Mingchen , Zhang Heng
Published: July 2021

The heterocharge accumulated in the oil‐paper insulation system of the converter transformer will enhance the local electric field and cause insulation deterioration. Numerical simulation is an effective method to analyze heterocharge. Currently, the numerical simulation of heterocharge is mainly based on the bipolar charge transport (BCT) model and the impurity ion transport (IIT) model. However, the effects of temperature, conductivity, and thickness of oil‐impregnated paper on charge transport have not been considered in these models. In view of this, a modified charge transport (MCT) model by introducing the Maxwell–Wagner model and heat conduction equation is proposed in this paper based on the BCT model and IIT model. Then, the influence of multi‐factors (temperature gradient, moisture content, and oil‐impregnated paper thickness) on heterocharge accumulation is investigated by using the MCT model. The simulation results obtained by the MCT model are more consistent with the experimental results than the BCT model, which proves the accuracy and superiority of the MCT model. Moreover, the increase in temperature gradient, moisture content, and oil‐impregnated paper thickness will enlarge the ion dissociation rate, conductivity, and trap density, and thus promote the generation of heterocharge. In that respect, the MCT model is expected to optimize the insulation design and provide a reference for space charge dynamic simulation.
Class structure‐aware adversarial loss for cross‐domain human action recognition
Authors: Chen Wanjun , Liu Long , Lin Guangfeng , Chen Yajun , Wang Jing
Published: July 2021

Cross‐domain action recognition is a challenging vision task due to the domain shift and the absence of labeled data in the target domain. With only labelled source domain and unlabelled target domain data during training, some existing methods rely on an adversarial framework to align the features from different domains to a common latent space. However, the existing adversarial‐based approaches have a major limitation of only attempting to perform the alignment from a holistic view, ignoring the underlying coherence of class structure across domains. A class structure‐aware adversarial loss (CSCAL) is presented to address this issue. The CSCAL incorporates the category information into the adversarial learning branch to capture the fine‐grained alignment of each class, effectively avoiding the false mixup of samples from different categories in the embedding space. Experiments on HMDB51, UCF101 and Olympic Sports datasets show significant improvement compared to the baseline. Code and trained model can be found at https://github.com/bregmangh/CSCAL.
Moving target inverse synthetic aperture radar image resolution enhancement based on two‐dimensional block sparse signal reconstruction
Authors: He Xingyu , Tong Ningning , Liu Tao
Published: July 2021

To achieve the high‐resolution inverse synthetic aperture radar (ISAR) imaging of moving targets, the range Doppler method and compressed sensing technique can be used. However, those methods are generally faced with the problem of migration through range cells and basis mismatch problems, and the imaging results can be improved. To solve these problems and improve the image quality, the problem of ISAR imaging is termed as a block‐sparse signal recovery problem by utilizing the block‐sparse structure of the ISAR images. A localized low‐rank promoting (LLP) method is introduced and extended to the complex case for the recovery of range compressed block‐sparse signals. The sparse recovery problem is solved by minimizing another function, which is the surrogate function that can be solved more effectively. Based on the LLP method, the coefficients of the range compressed echo signal are reconstructed and some 2 × 2 matrices can be obtained. And then the log‐determinant function is introduced to find the low rankness solutions for these matrices. Then the LLP method is also used in the cross‐range domain to reconstruct the ISAR image. Experimental results show that the proposed method can recover better focused and higher quality ISAR images compared with the traditional methods.
Rail transit OD‐matrix completion via manifold regularized tensor factorisation
Authors: Dong Hanxuan , Ding Fan , Tan Huachun , Wu Yuankai , Li Qin , Ran Bin
Published: July 2021

Urban rail transit has become an indispensable mode in major cities worldwide regarding the advantages of large capacity, high speed, punctuality, and environmental protection. Origin‐destination (OD) matrix data is crucial to the organisation of rail train operation and management. Nevertheless, rail transit OD matrices are inevitably suffered from data loss problems due to the data transmission and acquisition failures. Tensor completion is a state‐of‐the‐art method for missing data imputation. In this paper, a novel tensor completion method for OD‐ matrix completion is proposed. To this end, an OD‐matrix tensor is established to represent OD information, and the similarity matrix of OD‐matrix tensor for each dimension is extracted as a piece of auxiliary information expressing underlying multi‐mode relationships of OD data. Finally, a manifold regularised tensor factorisation is applied to impute the missing OD data, in which the Graph Laplacians inferred from similarity weight matrices are used as regularisation priors on factorisation factors. The proposed model is applied to a case study of the metro line in Xi'an, China. The experimental results indicate that the proposed method outperforms baselines. It can accurately impute missing data within the OD matrices and work well even when the missing ratio is up to 80%.
Healthcare Stereotype Threat and Health Outcomes Among LGB Individuals
Authors: Fingerhut Adam W , Martos Alexander J , Choi Soon Kyu , Abdou Cleopatra M
Published: July 2021

Background/Purpose

Health disparities between sexual minorities and heterosexuals are well documented and have been explained by differential access to healthcare as well as exposure to discrimination. The current research examines the role that healthcare stereotype threat, or the fear of being judged by healthcare providers based on negative group stereotypes, plays in the health of LGB individuals.

Methods

LGB individuals (N = 1507) in three age cohorts were recruited via random digit dialing to participate in a larger study on sexual minority health. Participants completed measures assessing healthcare stereotype threat, lifetime health diagnoses, life satisfaction, and number of bad physical health days and personal distress in the past 30 days.

Results

Healthcare stereotype threat was associated with higher psychological distress and number of reported bad physical health days. Additionally, the Younger and Middle cohorts reported more stereotype threat than the Older cohort, but reported significantly higher levels of life satisfaction in the face of this threat than those in the Older cohort.

Conclusions

Healthcare stereotype threat was related to poorer mental and physical health among LGB individuals; this was true when these outcomes were assessed over the past 30 days but not when they were assessed in general. Cohort differences in healthcare stereotype threat suggest potential important within group variation that needs further investigating. The research broadens the contexts to which stereotype threat is relevant and establishes a stressor related to LGB health.
A Colonial Legal Laboratory? Jurisprudential Innovation in British India
Authors: Likhovski Assaf
Published: July 2021

In this Article, I examine jurisprudence textbooks and related works written in British India in the late nineteenth and early twentieth centuries. Some of the jurisprudential works from India were not merely summaries of the leading English books, but were different from English works in three senses. First, the gap between English theories and Indian legal realities led some authors to question key English notions about the nature and development of law. Second, some of the works produced in India were more influenced by Continental and American legal theories than the equivalent English textbooks. Sometimes this was due to the fact that the authors of these works had some Continental training, and sometimes the non-English influence reflected a wider anticolonial nationalist move away from English culture. Finally, the influence of nationalism also led some Indian legal scholars to create a unique genre of jurisprudential works: Texts that used Western jurisprudential theories to describe the main features of Hindu (and, to a lesser extent, also Islamic) law.

These unique aspects of colonial jurisprudential works illustrate a broader phenomenon: the fact that legal scholars in imperial peripheries such as India were not always simply passive receivers of ideas produced at the center of empires, but in some cases created works containing interesting jurisprudential insights. The notion that India was a “legal laboratory” in which legal scholars experimented with new ideas has already been discussed in the literature, largely based on examples taken from the fields of legislation (the codification of English law in nineteenth-century India) or forensic science. This Article explores the extent to which India was also a site of jurisprudential innovation.
Early Black Worldmaking: Body, Compass, and Text
Authors: Madera Judith
Published: July 2021

“Early Black Worldmaking: Body, Compass, and Text” previews a Black cultural history of the abolition epoch. It focuses on eighteenth- and nineteenth-century author–activists. Judith Madera tracks an emancipatory network that linked pioneering abolitionist communities in the Caribbean and US by print channels and shared place-based histories. Madera states that Black geographies grew up in reading societies, church organizations, cottage industries, women’s leadership groups, social clubs, and political debate fora. Black women abolitionists, she claims, called for a civics that first needed to be built. They cast blueprints for better worlds because they could imagine that other worlds were possible.
Evolution of genome space occupation in ferns: linking genome diversity and species richness
Authors: Fujiwara Tao , Liu Hongmei , Meza-Torres Esteban I , Morero Rita E , Vega Alvaro J , Liang Zhenlong , Ebihara Atsushi , Leitch Ilia J , Schneider Harald
Published: July 2021

Background and Aims

The dynamics of genome evolution caused by whole genome duplications and other processes are hypothesized to shape the diversification of plants and thus contribute to the astonishing variation in species richness among the main lineages of land plants. Ferns, the second most species-rich lineage of land plants, are highly suitable to test this hypothesis because of several unique features that distinguish fern genomes from those of seed plants. In this study, we tested the hypothesis that genome diversity and disparity shape fern species diversity by recording several parameters related to genome size and chromosome number.

Methods

We conducted de novo measurement of DNA C-values across the fern phylogeny to reconstruct the phylogenetic history of the genome space occupation in ferns by integrating genomic parameters such as genome size, chromosome number and average DNA amount per chromosome into a time-scaled phylogenetic framework. Using phylogenetic generalized least square methods, we determined correlations between chromosome number and genome size, species diversity and evolutionary rates of their transformation.

Key Results

The measurements of DNA C-values for 233 species more than doubled the taxon coverage from ~2.2 % in previous studies to 5.3 % of extant diversity. The dataset not only documented substantial differences in the accumulation of genomic diversity and disparity among the major lineages of ferns but also supported the predicted correlation between species diversity and the dynamics of genome evolution.

Conclusions

Our results demonstrated substantial genome disparity among different groups of ferns and supported the prediction that alterations of reproductive modes alter trends of genome evolution. Finally, we recovered evidence for a close link between the dynamics of genome evolution and species diversity in ferns for the first time.
Stomatal development in the cycad family Zamiaceae
Authors: Coiro Mario , Barone Lumaga Maria Rosaria , Rudall Paula J
Published: July 2021

Background and Aims

The gymnosperm order Cycadales is pivotal to our understanding of seed-plant phylogeny because of its phylogenetic placement close to the root node of extant spermatophytes and its combination of both derived and plesiomorphic character states. Although widely considered a ‘living fossil’ group, extant cycads display a high degree of morphological and anatomical variation. We investigate stomatal development in Zamiaceae to evaluate variation within the order and homologies between cycads and other seed plants.

Methods

Leaflets of seven species across five genera representing all major clades of Zamiaceae were examined at various stages of development using light microscopy and confocal microscopy.

Key Results

All genera examined have lateral subsidiary cells of perigenous origin that differ from other pavement cells in mature leaflets and could have a role in stomatal physiology. Early epidermal patterning in a ‘quartet’ arrangement occurs in Ceratozamia, Zamia and Stangeria. Distal encircling cells, which are sclerified at maturity, are present in all genera except Bowenia, which shows relatively rapid elongation and differentiation of the pavement cells during leaflet development.

Conclusions

Stomatal structure and development in Zamiaceae highlights some traits that are plesiomorphic in seed plants, including the presence of perigenous encircling subsidiary cells, and reveals a clear difference between the developmental trajectories of cycads and Bennettitales. Our study also shows an unexpected degree of variation among subclades in the family, potentially linked to differences in leaflet development and suggesting convergent evolution in cycads.
Biochemical properties of CumA multicopper oxidase from plant pathogen, Pseudomonas syringae
Authors: Ishida Konan , Tsukamoto Yuya , Horitani Masaki , Ogawa Tomohisa , Tanaka Yoshikazu
Published: July 2021

Multicopper oxidases have a wide range of substrate specificity to be involved in various physiological reactions. Pseudomonas syringae, a plant pathogenic bacterium, has a multicopper oxidase, CumA. Multicopper oxidases have ability to degrade plant cell wall component, lignin. Once P. syringae enter apoplast and colonize, they start to disrupt plant immunity. Therefore, deeper understanding of multicopper oxidases from plant pathogens helps to invent measures to prevent invasion into plant cell, which brings agricultural benefits. Several biochemical studies have reported lower activity of CumA compared with other multicopper oxidase called CotA. However, the mechanisms underlying the difference in activity have not yet been revealed. In order to acquire insight into them, we conducted a biophysical characterization of PsCumA. Our results show that PsCumA has weak type I copper EPR signal, which is essential for oxidation activity. We propose that difference in the coordination of copper ions may decrease reaction frequency.
Functional kaurene-synthase-like diterpene synthases lacking a gamma domain are widely present in Oryza and related species
Authors: Itoh Akira , Nakazato Shinta , Wakabayashi Hiroki , Hamano Ayame , Shenton Matthew R , Miyamoto Koji , Mitsuhashi Wataru , Okada Kazunori , Toyomasu Tomonobu
Published: July 2021

Various diterpene synthases have been functionally identified in cultivated rice (Oryza sativa). These are the homologs of ent-copalyl diphosphate (ent-CDP) synthase and ent-kaurene synthase (KS) that are responsible for the biosynthesis of gibberellins, diterpenoid phytohormones. We isolated a cDNA encoding full-length OsKSL12, a previously uncharacterized KS like (KSL) enzyme that consists of a β-domain and an α-domain with an active center, but lacks an N-terminal γ-domain. Functional analysis using a bacterial expression system showed that recombinant OsKSL12 converted ent-CDP into ent-manool or ent-13-epi-manool. Comparative genomics revealed that functional OsKSL12 homologs exist in diverse wild species in the Oryzeae—Oryza nivara (Oryza rufipogon), Oryza coarctata, Oryza granulata, Leersia perrieri, and Leersia tisseranti. KSL12 homologs in O. granulata, L. perrieri, and L. tisseranti preferentially reacted with geranylgeranyl diphosphate rather than ent-CDP, resulting in geranyllinalool rather than ent-manool or ent-13-epi-manool as the main product, meaning that KSL12 functionally diversified during evolution in the Oryzeae.
Imperfect mimicry of host begging calls by a brood parasitic cuckoo: a cue for nestling rejection by hosts?
Authors: Noh Hee-Jin , Gloag Ros , Leitão Ana V , Langmore Naomi E
Published: July 2021

Coevolutionary interactions between avian brood parasites and their hosts often lead to the evolution of discrimination and rejection of parasite eggs or chicks by hosts based on visual cues, and the evolution of visual mimicry of host eggs or chicks by brood parasites. Hosts may also base rejection of brood parasite nestlings on vocal cues, which would in turn select for mimicry of host begging calls in brood parasite chicks. In cuckoos that exploit multiple hosts with different begging calls, call structure may be plastic, allowing nestlings to modify their calls to match those of their various hosts, or fixed, in which case we would predict either imperfect mimicry or divergence of the species into host-specific lineages. In our study of the little bronze-cuckoo (LBC) Chalcites minutillus and its primary host, the large-billed gerygone Gerygone magnirostris, we tested whether: (1) hosts use nestling vocalizations as a cue to discriminate cuckoo chicks; (2) cuckoo nestlings mimic the host begging calls throughout the nestling period; and (3) the cuckoo begging calls are plastic, thereby facilitating mimicry of the calls of different hosts. We found that the begging calls of LBCs are most similar to their gerygone hosts shortly after hatching (when rejection by hosts typically occurs) but become less similar as cuckoo chicks get older. Begging call structure may be used as a cue for rejection by hosts, and these results are consistent with gerygone defenses selecting for age-specific vocal mimicry in cuckoo chicks. We found no evidence that LBC begging calls were plastic.
Testing overidentifying restrictions with many instruments and heteroscedasticity using regularised jackknife IV
Authors: Carrasco Marine , Doukali Mohamed
Published: July 2021

This paper proposes a new overidentifying restrictions test in a linear model when the number of instruments (possibly weak) may be smaller or larger than the sample size n or even infinite in a heteroscedastic framework. The proposed J test combines two techniques: the jackknife method and the regularisation technique which consists in stabilising the projection matrix. We theoretically show that our new test achieves the asymptotically correct size in the presence of many instruments. The simulation results demonstrate that our modified J statistic test has better empirical properties in small samples than existing J tests. We also propose a regularised F-test to assess the strength of the instruments, which is robust to heteroscedasticity and many instruments.
Contemporary patterns of the management of truncus arteriosus (primary versus staged repair): outcomes from the Japanese National Cardiovascular Database
Authors: Ota Noritaka , Tachimori Hisateru , Hirata Yasutaka , Miyata Hiroaki , Suzuki Takaaki , Uchita Shunji , Takamoto Shinichi , Izutani Hironori
Published: July 2021

OBJECTIVES

Although primary repair in early infancy has for decades been the prevalent strategy for management of truncus arteriosus (TA), recent concerns about the levels of morbidity and mortality have led to consideration of a staged surgical approach. Our goal was to describe recent patterns of management, to characterize patients who underwent primary or staged repair and to evaluate risk factors associated with operative mortality in a contemporary multicentre cohort.

METHODS

In the Japanese Cardiovascular Surgery Database, we identified all cases of TA undergoing an initial surgical procedure from 2008 to 2018. Operative mortality was defined as death within 30 days of an operation or in-hospital death regardless of the length of hospital stay. The hospital volume was defined by the average volume of TA repairs per year.

RESULTS

The total number of patients undergoing initial surgery for TA was 286. Sixty-eight (24%, 68/286) underwent primary repair (primary repair group). The remaining 218 (76%, 218/286) underwent initial bilateral pulmonary artery banding as part of a planned staged approach (staged repair group). One hundred sixty-two patients out of 218 initially banded patients underwent the repair of TA during this study period. Concomitant diagnoses in the entire cohort included interrupted aortic arch repair in 36 patients and truncal valve regurgitation in 32. No centres handling an average of ≥2 truncus cases/year of the repair of TA were identified in this cohort. A total of 30% (85/286) of the cases were performed at centres that handled an average of ≥1 and <2 cases/year. The remaining 70% were at centres with <1 case/year. Overall, 37 patients (12.9%; 37/286) died. The operative mortality rates in the primary and staged repair groups were similar: that for the primary repair group was 16.2% (11/68) versus 11.9% for the staged repair group (26/218; P = 0.41). With multivariable logistic regression analysis, the factors most strongly associated with operative mortality were preoperative heart failure requiring catecholamine support (odds ratio, 4.18; 95% confidence interval 1.96–8.96) and the repeat bilateral pulmonary artery banding (odds ratio, 3.89; 95% confidence interval 1.08–14.07).

CONCLUSIONS

The staged repair of TA has emerged as the preferred option for surgical timing at most of the centres participating in the Japanese Cardiovascular Surgery Database. The management outcomes of the patients with TA were favourable, even for the patients at low-volume centres.
Biomechanical properties of the lips in a pre-orthodontic sample of adolescents and young adults
Authors: Hodgkinson Danielle , Prasad Sabarinath , Antoun Joseph S , Mei Li , Farella Mauro
Published: July 2021

Objectives

To assess biomechanical properties of the lip muscles and to investigate their relationship with sex, age, body mass index (BMI), and cephalometric variables.

Materials and methods

Demographic information and BMI were collected from 83 study participants seeking orthodontic treatment at the University of Otago. Tone, stiffness, and elasticity of the lip muscles were measured thrice at four different anatomical sites using a digital palpation device. To estimate method error, a duplicate set of measurements in a subsample of 20 participants was taken a week later. Sagittal and vertical cephalometric classifications were based on ANB and FMPA angles, respectively. Data were analysed using mixed models.

Results

Biomechanical properties of lip muscles were remarkably consistent both within and between different recording sessions. The lower lip had higher tone and stiffness than the upper lip. Both the upper and lower lip stiffness and tone were higher in females than in males, whereas upper lip elasticity was higher in males. Thinner upper lips had higher tone and were stiffer than thicker upper lips, whereas thinner lower lips were less elastic than thicker lower lips. Muscle tone and stiffness of both the upper and lower lips were lower in Class III than in Class I and Class II individuals. The upper lip of hyperdivergent individuals was less elastic than that of normodivergent and hypodivergent individuals, and stiffer than that of hypodivergent individuals.

Conclusions

The biomechanical properties of perioral soft tissues can be reliably measured and vary with anatomical site, sex, and cephalometric measurements.
Experimental mindset for environmental challenges: the puzzling case of public good contributions
Authors: Shogren Jason F , Hochard Jacob , Lee Katherine D , Varelas Henderson Leticia
Published: July 2021

The experimental mindset strips down and mimics social constructs in a setting we can use to understand how institutions create or destroy economic value. We explore how to use the mindset to consider climate change mitigation, in which more investment in climate mitigation by the collective, the less costly for each party. Using the lab to capture Conference of the Parties declining-cost environment with a jigsaw puzzle to mimic real-time costs, we find decreasing ‘cost’ of commitment increases contribution but not reaching the public good threshold. Highlighting the economies of scale might be an effective way to elicit greater commitment.
Interpretable artificial neural networks incorporating Bayesian alphabet models for genome-wide prediction and association studies
Authors: Zhao Tianjing , Fernando Rohan , Cheng Hao
Published: July 2021

In conventional linear models for whole-genome prediction and genome-wide association studies (GWAS), it is usually assumed that the relationship between genotypes and phenotypes is linear. Bayesian neural networks have been used to account for non-linearity such as complex genetic architectures. Here, we introduce a method named NN-Bayes, where “NN” stands for neural networks, and “Bayes” stands for Bayesian Alphabet models, including a collection of Bayesian regression models such as BayesA, BayesB, BayesC, and Bayesian LASSO. NN-Bayes incorporates Bayesian Alphabet models into non-linear neural networks via hidden layers between single-nucleotide polymorphisms (SNPs) and observed traits. Thus, NN-Bayes attempts to improve the performance of genome-wide prediction and GWAS by accommodating non-linear relationships between the hidden nodes and the observed trait, while maintaining genomic interpretability through the Bayesian regression models that connect the SNPs to the hidden nodes. For genomic interpretability, the posterior distribution of marker effects in NN-Bayes is inferred by Markov chain Monte Carlo approaches and used for inference of association through posterior inclusion probabilities and window posterior probability of association. In simulation studies with dominance and epistatic effects, performance of NN-Bayes was significantly better than conventional linear models for both GWAS and whole-genome prediction, and the differences on prediction accuracy were substantial in magnitude. In real-data analyses, for the soy dataset, NN-Bayes achieved significantly higher prediction accuracies than conventional linear models, and results from other four different species showed that NN-Bayes had similar prediction performance to linear models, which is potentially due to the small sample size. Our NN-Bayes is optimized for high-dimensional genomic data and implemented in an open-source package called “JWAS.” NN-Bayes can lead to greater use of Bayesian neural networks to account for non-linear relationships due to its interpretability and computational performance.
Selective functional inhibition of a tumor-derived p53 mutant by cytosolic chaperones identified using split-YFP in budding yeast
Authors: Denney Ashley S , Weems Andrew D , McMurray Michael A
Published: July 2021

Life requires the oligomerization of individual proteins into higher-order assemblies. In order to form functional oligomers, monomers must adopt appropriate 3D structures. Molecular chaperones transiently bind nascent or misfolded proteins to promote proper folding. Single missense mutations frequently cause disease by perturbing folding despite chaperone engagement. A misfolded mutant capable of oligomerizing with wild-type proteins can dominantly poison oligomer function. We previously found evidence that human-disease-linked mutations in Saccharomyces cerevisiae septin proteins slow folding and attract chaperones, resulting in a kinetic delay in oligomerization that prevents the mutant from interfering with wild-type function. Here, we build upon our septin studies to develop a new approach for identifying chaperone interactions in living cells, and use it to expand our understanding of chaperone involvement, kinetic folding delays, and oligomerization in the recessive behavior of tumor-derived mutants of the tumor suppressor p53. We find evidence of increased binding of several cytosolic chaperones to a recessive, misfolding-prone mutant, p53(V272M). Similar to our septin results, chaperone overexpression inhibits the function of p53(V272M) with minimal effect on the wild type. Unlike mutant septins, p53(V272M) is not kinetically delayed under conditions in which it is functional. Instead, it interacts with wild-type p53 but this interaction is temperature sensitive. At high temperatures or upon chaperone overexpression, p53(V272M) is excluded from the nucleus and cannot function or perturb wild-type function. Hsp90 inhibition liberates mutant p53 to enter the nucleus. These findings provide new insights into the effects of missense mutations.
Trajectories of Frailty in the 5 Years Prior to Death Among U.S. Veterans Born 1927–1934
Authors: Ward Rachel E , Orkaby Ariela R , Dumontier Clark , Charest Brian , Hawley Chelsea E , Yaksic Enzo , Quach Lien , Kim Dae H , Gagnon David R , Gaziano J Michael , Cho Kelly , Djousse Luc , Driver Jane A
Published: July 2021

Background

Electronic frailty indices (eFIs) are increasingly used to identify patients at risk for morbidity and mortality. Whether eFIs capture the spectrum of frailty change, including decline, stability, and improvement, is unknown.

Methods

In a nationwide retrospective birth cohort of U.S. Veterans, a validated eFI, including 31 health deficits, was calculated annually using medical record and insurance claims data (2002–2012). K-means clustering was used to assign patients into frailty trajectories measured 5 years prior to death.

Results

There were 214 250 veterans born between 1927 and 1934 (mean [SD] age at death = 79.4 [2.8] years, 99.2% male, 90.3% White) with an annual eFI in the 5 years before death. Nine frailty trajectories were identified. Those starting at nonfrail or prefrail had 2 stable trajectories (nonfrail to prefrail, n = 29 786 and stable prefrail, n = 28 499) and 2 rapidly increasing trajectories (prefrail to moderately frail, n = 28 244 and prefrail to severely frail, n = 22 596). Those who were mildly frail at baseline included 1 gradually increasing trajectory (mildly to moderately frail, n = 33 806) and 1 rapidly increasing trajectory (mildly to severely frail, n = 15 253). Trajectories that started at moderately or severely frail included 2 gradually increasing trajectories (moderately to severely frail, n = 27 662 and progressing severely frail, n = 14 478) and 1 recovering trajectory (moderately frail to mildly frail, n = 13 926).

Conclusions

Nine frailty trajectories, including 1 recovering trajectory, were identified in this cohort of older U.S. Veterans. Future work is needed to understand whether prevention and treatment strategies can improve frailty trajectories and contribute to compression of morbidity toward the end of life.
Functional assessment of two variants of unknown significance in TEK by endothelium-specific expression in zebrafish embryos
Authors: Bell Lorenz M , Holm Annegret , Matysiak Uta , Driever Wolfgang , Rößler Jochen , Schanze Denny , Wieland Ilse , Niemeyer Charlotte M , Zenker Martin , Kapp Friedrich G
Published: July 2021

Vascular malformations are most often caused by somatic mutations of the PI3K/mTOR and the RAS signaling pathways, which can be identified in the affected tissue. Venous malformations (VMs) commonly harbor PIK3CA and TEK mutations, whereas arteriovenous malformations (AVMs) are usually caused by BRAF, RAS or MAP2K1 mutations. Correct identification of the underlying mutation is of increasing importance, since targeted treatments are becoming more and more relevant, especially in patients with extensive vascular malformations. However, variants of unknown significance (VUSs) are often identified and their pathogenicity and response to targeted therapy cannot be precisely predicted. Here, we show that zebrafish embryos can be used to rapidly assess the pathogenicity of novel VUSs in TEK, encoding for the receptor TIE2, present on endothelial cells of VMs. Endothelium-specific overexpression of TEK mutations leads to robust induction of VMs, whereas MAP2K1 mutations cause AVMs in our zebrafish model. TEK mutations are often found as double mutations in cis; using our model, we show that double mutations have an additive effect in inducing VMs compared with the respective single variants. The clinically established mTOR-inhibitor sirolimus (rapamycin) efficiently abrogates the development of VMs in this zebrafish model. In summary, endothelium-specific overexpression of patient-derived TEK variants in the zebrafish model allows assessment of their pathogenic significance as well as testing of candidate drugs in a personalized and mutation-specific approach.
A Framework for Clinical Trials of Neurobiological Interventions That Target the Gut-Brain Axis in Inflammatory Bowel Disease
Authors: Tse Chung Sang , Singh Siddharth , Sandborn William J
Published: July 2021

A growing body of evidence from preclinical, translational, and clinical studies supports a bidirectional relationship within the gut-brain axis that contributes to neurobiological symptoms including anxiety, depression, fatigue, stress, and sleep disturbance. These symptoms have a significant impact on health-related quality of life and functional ability in individuals with inflammatory bowel disease. Clinical studies that generate high-quality evidence on pharmacological and nonpharmacological (eg, psychosocial, behavioral) interventions are needed to ultimately improve access to safe and effective therapies that have a meaningful impact on patients and to guide medical and regulatory decisions. This review outlines a framework for designing and conducting randomized controlled trials for interventions that target neurobiological symptoms in patients with inflammatory bowel disease based on the most recent guidance published within the past 5 years from policy makers, clinicians specialized in inflammatory bowel disease, patient-reported outcomes methodologists, health economists, patient advocates, industry representatives, ethicists, and clinical trial experts.
Efficacy of Vedolizumab in a Nationwide Cohort of Elderly Inflammatory Bowel Disease Patients
Authors: Khan Nabeel , Pernes Tyler , Weiss Alexandra , Trivedi Chinmay , Patel Manthankumar , Medvedeva Elina , Xie Dawei , Yang Yu-Xiao
Published: July 2021

Background

The elderly inflammatory bowel disease (IBD) population has historically been under-represented in clinical trials, and data on the efficacy of biologic medications in elderly IBD patients are generally lacking. Our study aims to evaluate the efficacy of vedolizumab (VDZ) among elderly IBD patients and compare it with younger IBD patients in a nationwide population-based cohort of IBD patients.

Methods

We conducted a retrospective cohort study of patients within the US national Veterans Affairs Healthcare System (VAHS). Patients were stratified into 2 groups based on age at the time of starting VDZ (60 years of age and older or younger than 60 years of age) with outcomes compared between the 2 groups. The primary outcome was steroid-free remission during the 6- to 12-month period after starting VDZ therapy among those patients who were on steroids when VDZ was started.

Results

There were 568 patients treated with VDZ, of whom 56.7% had Crohn’s disease and 43.3% had ulcerative colitis. Among them, 316 patients were on steroids when VDZ was started. The percentage of patients who were on VDZ and off steroids during the 6- to 12-month period after VDZ initiation was 46.8% and 40.1% for the younger and elderly groups, respectively (P = 0.2374). Rates of hospitalization for an IBD-related reason within 1 year of VDZ start among the whole cohort were nearly identical in the younger and elderly groups (11.2% vs 11.3%, P = 0.9737). Rates of surgery for an IBD-related reason within 1 year of VDZ start were also similar between the young and elderly (3.9% vs 3.9%, P = 0.9851).

Conclusions

In a nationwide real-world retrospective cohort study of elderly IBD patients, we found that the efficacy of VDZ was similar among younger and older IBD patients and comparable with the published data in clinical trials.
From Flatland to Jupiter: Searching for Rules of Interaction Across Biological Scales
Authors: Grillo Claudia A , Holford Mandë , Walter Nils G
Published: July 2021

Synopsis

In this future-spanning perspective, we examine how an agent-based model could be used to define general rules for interactions across biological systems and evolutionary time. To date, there have been a number of attempts to simulate the emergence of ecological communities using agent-based models of individuals that have evolving traits. Here we speculate whether it is possible to use this computational modeling to simulate self-organizing systems and, importantly, to decipher universal principles that govern biological interactions. This perspective is a thought exercise, meant to extrapolate from current knowledge to how we may make Jupiter-shot leaps to further advance the biosciences in the 21st century.