bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bespoke Instruments: A new tool for addressing unmeasured confounders
Authors: Richardson David B , Tchetgen Tchetgen Eric J 
Published: December 2021

Abstract
Suppose that an investigator is interested in quantifying an exposure-disease causal association in a setting where the exposure, disease, and some potential confounders of the association of interest have been measured. However, there remains concern about residual confounding of the association of interest by unmeasured confounders. We propose an approach to account for residual bias due to unmeasured confounders. The proposed approach uses a measured confounder to derive a “bespoke” instrumental variable that is tailored to the study population and is used to control for bias due to residual confounding. The approach may provide a useful tool for assessing and accounting for bias due to residual confounding. We provide a formal description of the conditions for identification of causal effects, illustrate the method using simulations, and provide an empirical example concerning mortality among Japanese atomic bomb survivors.
MYB42 inhibits hypocotyl cell elongation by coordinating brassinosteroid homeostasis and signalling in Arabidopsis thaliana
Authors: Zhuang Yamei , Lian Wenjun , Tang Xianfeng , Qi Guang , Wang Dian , Chai Guohua , Zhou Gongke 
Published: December 2021

Abstract

Background and Aims
The precise control of brassinosteroid (BR) homeostasis and signalling is a prerequisite for hypocotyl cell elongation in plants. Arabidopsis MYB42 and its paralogue MYB85 were previously identified to be positive regulators of secondary cell wall formation during mature stages. Here, we aim to reveal the role of MYB42 and MYB85 in hypocotyl elongation during the seedling stage and clarify how MYB42 coordinates BR homeostasis and signalling to regulate this process.

Methods
Histochemical analysis of proMYB42-GUS transgenic plants was used for determination of the MYB42 expression pattern. The MYB42, 85 overexpression, double mutant and some crossing lines were generated for phenotypic observation and transcriptome analysis. Transcription activation assays, quantitative PCR (qPCR), chromatin immunoprecipitation (ChIP)-qPCR and electrophoretic mobility shift assays (EMSAs) were conducted to determine the relationship of MYB42 and BRASSINAZOLE-RESISTANT 1 (BZR1), a master switch activating BR signalling.

Key Results
MYB42 and MYB85 redundantly and negatively regulate hypocotyl cell elongation. They function in hypocotyl elongation by mediating BR signalling. MYB42 transcription was suppressed by BR treatment or in bzr1-1D (a gain-of-function mutant of BZR1), and mutation of both MYB42 and MYB85 enhanced the dwarf phenotype of the BR receptor mutant bri1-5. BZR1 directly repressed MYB42 expression in response to BR. Consistently, hypocotyl length of bzr1-1D was increased by simultaneous mutation of MYB42 and MYB85, but was reduced by overexpression of MYB42. Expression of a number of BR-regulated BZR1 (non-)targets associated with hypocotyl elongation was suppressed by MYB42, 85. Furthermore, MYB42 enlarged its action in BR signalling through feedback repression of BR accumulation and activation of DOGT1/UGT73C5, a BR-inactivating enzyme.

Conclusions
MYB42 inhibits hypocotyl elongation by coordinating BR homeostasis and signalling during primary growth. The present study shows an MYB42, 85-mediated multilevel system that contributes to fine regulation of BR-induced hypocotyl elongation.
Poor acclimation to experimental field drought in subalpine forest tree seedlings
Authors: Goke Alex , Martin Patrick H 
Published: December 2021

AbstractThe ability of tree species to acclimate and tolerate projected increases in drought frequency and intensity has fundamental implications for future forest dynamics with climate change. Inquiries to date on the drought tolerance capacities of tree species, however, have focused almost exclusively on mature trees with scant in situ work on seedlings, despite the central role that regeneration dynamics play in forest responses to changing conditions. We subjected naturally established seedlings of co-dominant subalpine conifer species (Abies lasiocarpa and Picea engelmannii) in the southern Rocky Mountains to 2 years of in situ summer precipitation exclusion, simulating summer drought conditions similar to a failure of the North American monsoon. We compared the morphological and physiological responses of seedlings growing in drought vs. ambient conditions to assess the relative changes in drought tolerance traits as a function of seedling size. Drought treatments had a marked impact on soil moisture: volumetric water content averaged ≈5–8 % in drought treatments and ≈8–12 % in ambient controls. We detected no significant shifts in morphology (e.g. root biomass, leaf:stem area ratio) in response to drought for either species, but net photosynthesis in drought treatments was 78 % lower for spruce and 37 % lower for fir. Greater stomatal control associated with increasing stem diameter conferred greater water use efficiencies in larger seedlings in both species but was not significantly different between drought and ambient conditions, suggesting an overall lack of responsivity to water stress and a prioritization of carbon gain over investment in drought mitigation traits. These results indicate a canonization of traits that, while useful for early seedling establishment, may portend substantial vulnerability of subalpine seedling populations to prolonged or recurrent droughts, especially for spruce.
II—No Duty to Resist: Why Individual Resistance Is an Ineffective Response to Dominant Beauty Ideals
Authors: Widdows Heather 
Published: December 2021

AbstractIn this paper I argue that the way to reduce the power of overdemanding beauty ideals is not to advocate that individuals have a ‘duty to resist’, a duty to stop engaging in appearance enhancing practices and body work. I begin by arguing against the claim that women who ‘do’ beauty are suffering from false consciousness. I then give four further additional arguments against advocating a ‘duty to resist’ as an effective means to challenge dominant beauty norms. First, that as a tactic it is ineffective. Second, it is an individual approach which divides and silences. Third, it induces shame and blame, and undermines effective collective action. Fourth, it fails to recognize the privilege of the group norms which make resistance possible.
Prolonged neutrophilia is associated with worse outcomes after Esophagectomy
Authors: Bostock Ian C , Zhou Nicolas , Antonoff Mara B , Murphy Mariela Blum , Lin Steven , Maru Dipen , Mehran Reza , Rajaram Ravi , Rice David , Sepesi Boris , Swisher Stephen , Vaporciyan Ara , Walsh Garrett , Hofstetter Wayne 
Published: December 2021

Abstract
Neutrophilia is a potential biomarker for postoperative complications and oncologic outcomes. There is a paucity of data regarding neutrophilia in patients with esophageal adenocarcinoma. Our Institutional Database was queried for esophageal adenocarcinoma patients who underwent esophagectomy from 2006 to 2019. Complete blood counts (CBC), demographic characteristics, perioperative and oncologic outcomes were evaluated. Two groups were created based on the presence of prolonged neutrophilia (PN, &gt;7,000 absolute neutrophils 90 days after surgery). Univariate, multivariable, and survival analysis were performed (P-value &lt; 0.05). We identified 686 patients with complete CBC data: 565 in the no prolonged neutrophilia (NPN) and 121 in the PN groups (17.6%). The mean age was 54 versus 48 years in the NPN and PN groups (P = 0.01). There was no difference in height, weight, gender, race, tumor size, histology, pTNM, PS, ASA, salvage procedure, neoadjuvant treatment and comorbidities. On multivariable analysis, the PN group had increased transfusions (19.8% vs. 11.9%; P = 0.02), aspiration (13.2% vs. 2.5%; P = 0.002), pulmonary embolus (3.3% vs. 0.4%; P = 0.02), cardiac arrest (5% vs. 0.4%; P = 0.02) and hematologic complications (23.1% vs. 12.6%; P = 0.01). After controlling for any postoperative complication, PN had increased distant recurrence (24% vs. 12.7%; hazard ration [HR]: 2.3, 95% confidence interval [CI] 1.42–3.9; P = 0.001) and decreased OS (33.8% vs. 49.7%, HR: 1.83, 95% CI: 1.19–2.81; P = 0.006); median follow up 77 months (46–109). PN was predictive of distant recurrence and decreased overall survival. Further work investigating these neutrophil populations represents a potential area for biomarker research, immunomodulation, and may guide postoperative surveillance strategies.
Sustainable low-field cardiovascular magnetic resonance in changing healthcare systems
Authors: Qin Cathy , Murali Sanjana , Lee Elsa , Supramaniam Vaishnavi , Hausenloy Derek J , Obungoloch Johnes , Brecher Joanna , Lin Rongyu , Ding Hao , Akudjedu Theophilus N , Anazodo Udunna C , Jagannathan Naranamangalam R , Ntusi Ntobeko A B , Simonetti Orlando P , Campbell-Washburn Adrienne E , Niendorf Thoralf , Mammen Regina , Adeleke Sola 
Published: December 2021

AbstractCardiovascular disease continues to be a major burden facing healthcare systems worldwide. In the developed world, cardiovascular magnetic resonance (CMR) is a well-established non-invasive imaging modality in the diagnosis of cardiovascular disease. However, there is significant global inequality in availability and access to CMR due to its high cost, technical demands as well as existing disparities in healthcare and technical infrastructures across high-income and low-income countries. Recent renewed interest in low-field CMR has been spurred by the clinical need to provide sustainable imaging technology capable of yielding diagnosticquality images whilst also being tailored to the local populations and healthcare ecosystems. This review aims to evaluate the technical, practical and cost considerations of low field CMR whilst also exploring the key barriers to implementing sustainable MRI in both the developing and developed world.
Reliability of cephalometric superimposition for the assessment of craniofacial changes: a systematic review
Authors: Graf Carmen Camila , Dritsas Konstantinos , Ghamri Mohammed , Gkantidis Nikolaos 
Published: December 2021

Summary

Background
Superimposition of serial cephalometric radiographs enables the assessment of craniofacial changes over time, and therefore, several methods have been suggested in the literature.

Objective
The aim of the present study is to summarize and critically evaluate the available evidence on the reliability of methods used to superimpose serial cephalometric radiographs.

Search methods
Electronic searches were performed in MEDLINE, EMBASE, Google Scholar, and Cochrane Databases, without time limit (last update: 1 November 2020). Unpublished literature was searched on the Open Grey and Grey Literature Report databases.

Selection criteria
Studies that tested the accuracy, precision, or agreement between different cephalometric superimposition techniques, used to evaluate the craniofacial changes due treatment or growth.

Data collection and analysis
Reference lists of relevant articles were screened and authors were contacted, if needed. All study selection steps, data extraction, and risk of bias (QUADAS-2 tool) assessments were performed independently by two authors on predefined forms.

Results
There were 27 eligible studies. From these, 17 tested superimpositions methods on the anterior cranial base, 10 on the maxilla and 12 on the mandible. There were three studies that compared superimpositions on the cranial base with those on the maxilla and one that compared the cranial base with the mandibular superimposition. There was high heterogeneity among studies in terms of sample size, growth, radiographic machines, selection criteria, superimposition methods, references, and outcomes measured. Furthermore, almost all studies presented important methodological limitations, with only two studies having unclear risk of bias and the rest 25 presenting high risk.

Conclusions
Currently, there is no cephalometric superimposition method that has been proved to deliver accurate results. There is an urgent need for further research in this topic, since this is a primary assessment method to assess craniofacial changes over time for several relevant disciplines.

Registration
PROSPERO (CRD42020200349).
Distinct mechanoreceptor pezo-1 isoforms modulate food intake in the nematode Caenorhabditis elegans
Authors: Hughes Kiley , Shah Ashka , Bai Xiaofei , Adams Jessica , Bauer Rosemary , Jackson Janelle , Harris Emily , Ficca Alyson , Freebairn Ploy , Mohammed Shawn , Fernández Eliana M , Bainbridge Chance , Brocco Marcela , Stein Wolfgang , Vidal-Gadea Andrés G 
Published: December 2021

Abstract
Two PIEZO mechanosensitive cation channels, PIEZO1 and PIEZO2, have been identified in mammals, where they are involved in numerous sensory processes. While structurally similar, PIEZO channels are expressed in distinct tissues and exhibit unique properties. How different PIEZOs transduce force, how their transduction mechanism varies, and how their unique properties match the functional needs of the tissues they are expressed in remain all-important unanswered questions. The nematode Caenorhabditis elegans has a single PIEZO ortholog (pezo-1) predicted to have 12 isoforms. These isoforms share many transmembrane domains but differ in those that distinguish PIEZO1 and PIEZO2 in mammals. We used transcriptional and translational reporters to show that putative promoter sequences immediately upstream of the start codon of long pezo-1 isoforms predominantly drive green fluorescent protein (GFP) expression in mesodermally derived tissues (such as muscle and glands). In contrast, sequences upstream of shorter pezo-1 isoforms resulted in GFP expression primarily in neurons. Putative promoters upstream of different isoforms drove GFP expression in different cells of the same organs of the digestive system. The observed unique pattern of complementary expression suggests that different isoforms could possess distinct functions within these organs. We used mutant analysis to show that pharyngeal muscles and glands require long pezo-1 isoforms to respond appropriately to the presence of food. The number of pezo-1 isoforms in C. elegans, their putative differential pattern of expression, and roles in experimentally tractable processes make this an attractive system to investigate the molecular basis for functional differences between members of the PIEZO family of mechanoreceptors.
Genetic analysis of Caenorhabditis elegans pry-1/Axin suppressors identifies genes involved in reproductive structure development, stress responses, and aging
Authors: Mallick Avijit , Jhaveri Nikita , Jeon Jihae , Chang Yvonne , Shah Krupali , Hosein Hannah , Gupta Bhagwati P 
Published: December 2021

Abstract
The Axin family of scaffolding proteins regulates a wide array of developmental and post-developmental processes in eukaryotes. Studies in the nematode Caenorhabditis elegans have shown that the Axin homolog PRY-1 plays essential roles in multiple tissues. To understand the genetic network of pry-1, we focused on a set of genes that are differentially expressed in the pry-1-mutant transcriptome and are linked to reproductive structure development. Knocking down eight of the genes (spp-1, clsp-1, ard-1, rpn-7, cpz-1, his-7, cdk-1, and rnr-1) via RNA interference efficiently suppressed the multivulva phenotype of pry-1 mutants. In all cases, the ectopic induction of P3.p vulval precursor cell was also inhibited. The suppressor genes are members of known gene families in eukaryotes and perform essential functions. Our genetic interaction experiments revealed that in addition to their role in vulval development, these genes participate in one or more pry-1-mediated biological events. Whereas four of them (cpz-1, his-7, cdk-1, and rnr-1) function in both stress response and aging, two (spp-1 and ard-1) are specific to stress response. Altogether, these findings demonstrate the important role of pry-1 suppressors in regulating developmental and post-developmental processes in C. elegans. Given that the genes described in this study are conserved, future investigations of their interactions with Axin and their functional specificity promises to uncover the genetic network of Axin in metazoans.
Fast neutron mutagenesis in soybean enriches for small indels and creates frameshift mutations
Authors: Wyant Skylar R , Rodriguez M Fernanda , Carter Corey K , Parrott Wayne A , Jackson Scott A , Stupar Robert M , Morrell Peter L 
Published: December 2021

Abstract
The mutagenic effects of ionizing radiation have been used for decades to create novel variants in experimental populations. Fast neutron (FN) bombardment as a mutagen has been especially widespread in plants, with extensive reports describing the induction of large structural variants, i.e., deletions, insertions, inversions, and translocations. However, the full spectrum of FN-induced mutations is poorly understood. We contrast small insertions and deletions (indels) observed in 27 soybean lines subject to FN irradiation with the standing indels identified in 107 diverse soybean lines. We use the same populations to contrast the nature and context (bases flanking a nucleotide change) of single-nucleotide variants. The accumulation of new single-nucleotide changes in FN lines is marginally higher than expected based on spontaneous mutation. In FN-treated lines and in standing variation, C→T transitions and the corresponding reverse complement G→A transitions are the most abundant and occur most frequently in a CpG local context. These data indicate that most SNPs identified in FN lines are likely derived from spontaneous de novo processes in generations following mutagenesis rather than from the FN irradiation mutagen. However, small indels in FN lines differ from standing variants. Short insertions, from 1 to 6 bp, are less abundant than in standing variation. Short deletions are more abundant and prone to induce frameshift mutations that should disrupt the structure and function of encoded proteins. These findings indicate that FN irradiation generates numerous small indels, increasing the abundance of loss-of-function mutations that impact single genes.
A role for synaptonemal complex in meiotic mismatch repair
Authors: Voelkel-Meiman Karen , Oke Ashwini , Feil Arden , Shames Alexander , Fung Jennifer , MacQueen Amy J 
Published: December 2021

Abstract
A large subset of meiotic recombination intermediates form within the physical context of synaptonemal complex (SC), but the functional relationship between SC structure and homologous recombination remains obscure. Our prior analysis of strains deficient for SC central element proteins demonstrated that tripartite SC is dispensable for interhomolog recombination in Saccharomyces cerevisiae. Here, we report that while dispensable for recombination per se, SC proteins promote efficient mismatch repair at interhomolog recombination sites. Failure to repair mismatches within heteroduplex-containing meiotic recombination intermediates leads to genotypically sectored colonies (postmeiotic segregation events). We discovered increased postmeiotic segregation at THR1 in cells lacking Ecm11 or Gmc2, or in the SC-deficient but recombination-proficient zip1[Δ21-163] mutant. High-throughput sequencing of octad meiotic products furthermore revealed a genome-wide increase in recombination events with unrepaired mismatches in ecm11 mutants relative to wildtype. Meiotic cells missing Ecm11 display longer gene conversion tracts, but tract length alone does not account for the higher frequency of unrepaired mismatches. Interestingly, the per-nucleotide mismatch frequency is elevated in ecm11 when analyzing all gene conversion tracts, but is similar between wildtype and ecm11 if considering only those events with unrepaired mismatches. Thus, in both wildtype and ecm11 strains a subset of recombination events is susceptible to a similar degree of inefficient mismatch repair, but in ecm11 mutants a larger fraction of events fall into this inefficient repair category. Finally, we observe elevated postmeiotic segregation at THR1 in mutants with a dual deficiency in MutSγ crossover recombination and SC assembly, but not in the mlh3 mutant, which lacks MutSγ crossovers but has abundant SC. We propose that SC structure promotes efficient mismatch repair of joint molecule recombination intermediates, and that absence of SC is the molecular basis for elevated postmeiotic segregation in both MutSγ crossover-proficient (ecm11, gmc2) and MutSγ crossover-deficient (msh4, zip3) strains.
CLOCK Genetic Variations Are Associated With Age-Related Changes in Sleep Duration and Brain Volume
Authors: Kim Song E , Kim Soriul , Kim Hyeon-Jin , Kim Regina Eun-Young , Kim Sol-Ah , Shin Chol , Lee Hyang Woon 
Published: December 2021

AbstractBackgroundAlthough a connection between sleep disruption and brain aging has been documented, biological mechanisms need to be further clarified. Intriguingly, aging is associated with circadian rhythm and/or sleep dysfunction in a key gene regulating circadian rhythm, Circadian Locomotor Output Cycles Kaput (CLOCK), has been linked to both aging-related sleep disturbances and neurodegenerative diseases. This study aims to investigate how CLOCK genetic variation associates with sleep duration changes and/or volumetric brain alteration.MethodsThis population-based cross-sectional study used data from the Korean Genome Epidemiology Study and analyzed sleep characteristics and genetic and brain imaging data in 2 221 participants (mean 58.8 ± 6.8 years, 50.2% male). Eleven single-nucleotide polymorphisms (SNPs) in CLOCK were analyzed using PLINK software v1.09 to test for their association with sleep duration and brain volume. Haplotype analysis was performed by using pair-wise linkage disequilibrium of CLOCK polymorphisms, and multivariate analysis of covariance was for statistical analysis.ResultsDecreased sleep duration was associated with several SNPs in CLOCK intronic regions, with the highest significance for rs10002541 (p = 1.58 × 10−5). Five SNPs with the highest significance (rs10002541, rs6850524, rs4580704, rs3805151, rs3749474) revealed that CGTCT was the most prevalent. In the major CGTCT haplotype, decreased sleep duration over time was associated with lower cortical volumes predominantly in frontal and parietal regions. Less common haplotypes (GCCTC/CGTTC) had shorter sleep duration and more decreases in sleep duration over 8 years, which revealed smaller total and gray matter volumes, especially in frontal and temporal regions of the left hemisphere.ConclusionCLOCK genetic variations could be involved in age-related sleep and brain volume changes.