bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signatures of plant defense response specificity mediated by herbivore‐associated molecular patterns in legumes
Authors: Steinbrenner Adam D. , Saldivar Evan , Hodges Nile , Guayazán‐Palacios Natalia , Chaparro Antonio F. , Schmelz Eric A. 
Published: March 2022

SUMMARYChewing herbivores activate plant defense responses through a combination of mechanical wounding and elicitation by herbivore‐associated molecular patterns (HAMPs). HAMPs are wound response amplifiers; however, specific defense outputs may also exist that strictly require HAMP‐mediated defense signaling. To investigate HAMP‐mediated signaling and defense responses, we characterized cowpea (Vigna unguiculata) transcriptome changes following elicitation by inceptin, a peptide HAMP common in Lepidoptera larvae oral secretions. Following inceptin treatment, we observed large‐scale reprogramming of the transcriptome consistent with three different response categories: (i) amplification of mechanical wound responses, (ii) temporal extension through accelerated or prolonged responses, and (iii) examples of inceptin‐specific elicitation and suppression. At both early and late timepoints, namely 1 and 6 h, large sets of transcripts specifically accumulated following inceptin elicitation. Further early inceptin‐regulated transcripts were classified as reversing changes induced by wounding alone. Within key signaling‐ and defense‐related gene families, inceptin‐elicited responses included target subsets of wound‐induced transcripts. Transcripts displaying the largest inceptin‐elicited fold changes included transcripts encoding terpene synthases (TPSs) and peroxidases (POXs) that correspond with induced volatile production and increased POX activity in cowpea. Characterization of inceptin‐elicited cowpea defenses via heterologous expression in Nicotiana benthamiana demonstrated that specific cowpea TPSs and POXs were able to confer terpene emission and the reduced growth of beet armyworm (Spodoptera exigua) herbivores, respectively. Collectively, our present findings in cowpea support a model where HAMP elicitation both amplifies concurrent wound responses and specifically contributes to the activation of selective outputs associated with direct and indirect antiherbivore defenses.
In silico analysis of cis‐elements and identification of transcription factors putatively involved in the regulation of the OAS cluster genes SDI1 and SDI2
Authors: Rakpenthai Apidet , Apodiakou Anastasia , Whitcomb Sarah J. , Hoefgen Rainer 
Published: March 2022

SUMMARYArabidopsis thaliana sulfur deficiency‐induced 1 and sulfur deficiency‐induced 2 (SDI1 and SDI2) are involved in partitioning sulfur among metabolite pools during sulfur deficiency, and their transcript levels strongly increase in this condition. However, little is currently known about the cis‐ and trans‐factors that regulate SDI expression. We aimed at identifying DNA sequence elements (cis‐elements) and transcription factors (TFs) involved in regulating expression of the SDI genes. We performed in silico analysis of their promoter sequences cataloging known cis‐elements and identifying conserved sequence motifs. We screened by yeast‐one‐hybrid an arrayed library of Arabidopsis TFs for binding to the SDI1 and SDI2 promoters. In total, 14 candidate TFs were identified. Direct association between particular cis‐elements in the proximal SDI promoter regions and specific TFs was established via electrophoretic mobility shift assays: sulfur limitation 1 (SLIM1) was shown to bind SURE cis‐element(s), the basic domain/leucine zipper (bZIP) core cis‐element was shown to be important for HY5‐homolog (HYH) binding, and G‐box binding factor 1 (GBF1) was shown to bind the E box. Functional analysis of GBF1 and HYH using mutant and over‐expressing lines indicated that these TFs promote a higher transcript level of SDI1 in vivo. Additionally, we performed a meta‐analysis of expression changes of the 14 TF candidates in a variety of conditions that alter SDI expression. The presented results expand our understanding of sulfur pool regulation by SDI genes.
Developing a translational murine‐to‐canine pathway for anIL‐2/agonistanti‐CD40antibody cancer immunotherapy
Authors: Proksch Stephen Francis , Matthysen Clinton Petrus , Jardine John E. , Wyatt Ken Mark , Finlay Jessica Renee , Nelson Delia Jane 
Published: March 2022

AbstractHuman and canine sarcomas are difficult to treat soft tissue malignancies with an urgent need for new improved therapeutic options. Local recurrence rates for humans are between 10%–30%, and 30%–40% develop metastases. Outcomes for dogs with sarcoma vary with grade but can be similar. Pet dogs share the human environment and represent human cancer with genetic variation in hosts and tumours. We asked if our murine studies using genetically identical mice and cloned tumour cells were translatable to larger, genetically diverse domestic dogs with naturally occurring tumours, to (i) develop a canine cancer therapeutic, and (ii) to use as a translational pathway to humans. Our murine studies showed that intra‐tumoral delivery of interleukin‐2 (IL‐2) plus an agonist anti‐CD40 antibody (Ab) induces long‐term curative responses ranging from 30% to 100%, depending on tumour type. We developed an agonist anti‐canine‐CD40 Ab and conducted a phase I dose finding/toxicology 3 + 3 clinical trial in dogs (n = 27) with soft tissue sarcomas on account of suitability for intratumoral injection and straightforward monitoring. Dogs were treated with IL‐2 plus anti‐CD40 antibody for 2 weeks. Three dose levels induced tumour regression with minimal side effects, measured by monitoring, haematological and biochemical assays. Importantly, our mouse and canine studies provide encouraging fundamental proof‐of‐concept data upon which we can develop veterinary and human immunotherapeutic strategies.
High-Intensity Interval Exercise Performance in Judo Athletes: Physiological, Perceptual, and Pacing Responses
Authors: Kons Rafael L. , Detanico Daniele 
Published: March 2022

This study aimed to verify the behavior of physiological, perceptual, and performance responses during a high-intensity exercise in judo athletes and to identify if this protocol is able to discriminate athletes from different levels (national vs. state). Forty-five male judo athletes participated and were divided into two groups: state (age 24.2 ± 3.7 years) and national (22.1 ± 3.3 years). Judo athletes performed a judo-specific protocol contained high-intensity intermittent exercise consisted of 12 sets of 20 s in all-out intensity. During the protocol, the repetitions and heart rate were assessed over the sets, and at the end of the protocol, the rate of perceived exertion was measured. The results showed that the national group presented higher repetitions (29 ± 4 repetitions) during the high-intensity intermittent exercise compared with state (22 ± 2 repetitions). However, the national group showed a progressive decrease of repetitions up to the middle of the protocol, which coincided with higher values of heart rate compared with state (first and second sets). There was a decrease of repetitions from the first set (p < .001) and similar values of heart rate from the third set in the state. In conclusion, the performance (in repetitions) during the high-intensity intermittent exercise was able to discriminate athletes from different competitive levels. National athletes presented better performance, but worse pacing strategy compared with state.
Does the Earth have a pulse? Evidence relating to a potential underlying ~26–36-million-year rhythm in interrelated geologic, biologic, and astrophysical events
Authors: Rampino* Michael R. 
Published: March 2022

ABSTRACT
The existence of an ~26–36 m.y. rhythm in interrelated global tectonism, sea-level oscillations, climate, and resulting sedimentation patterns during Phanerozoic time (the last 541 m.y.) has long been suspected. A similar underlying ~26.4–27.5 m.y. cycle was reported independently in episodes of extinctions of marine and non-marine species. Subsequent spectral analyses of individual geologic events of the last 260 m.y., including changes in seafloor spreading and subduction, times of hotspot initiation and intraplate volcanism, eruptions of Large Igneous Provinces (LIPs), tectonic events, sea-level fluctuations, oceanic anoxia, atmospheric carbon dioxide levels, and global climate have revealed evidence for the 26–36 m.y. cycle and the temporal association of events with an apparent overall periodicity of ~27.5 m.y. modulated by an ~8–9 m.y. cycle.
The proposed episodes of geologic activity and environmental and biotic change may result from cyclical internal Earth processes that affect changes in mantle convection, plate motions, intraplate stresses, and/or periodic pulses of mantle-plume activity. Recently, the ~30 m.y. cycle has been linked to Earth’s long-term orbital changes within the Solar System, and it may also affect tectonism and climate. I also note considerable evidence for a similar ~30 m.y. cycle in the ages of terrestrial impact craters, which suggests possible astronomical connections. The shared geologic cycle time, formally ranging from ~26 to 36 m.y. (depending partly on varying data sets, geologic timescales, and statistical techniques utilized) is close to the estimated interval (~32 ± 3 m.y.) between our cyclical crossings of the crowded mid-plane region of the Milky Way Galaxy. Here I outline a proposed astrophysical pacing for the apparent pulses of both impact cratering and rhythmic geological episodes.
Deccan volcanism at K-Pg time
Authors: Mittal Tushar , Sprain Courtney J. , Renne* Paul R. , Richards Mark A. 
Published: March 2022

ABSTRACT
The last major mass extinctions in Earth history (e.g., end-Guadalupian, end-Permian, end-Triassic, and end-Cretaceous) are all correlated closely in time with the main-phase eruptions of major flood basalt provinces (Emeishan, Siberian, Central Atlantic Magmatic Province, and Deccan Traps, respectively). The causal relationship between flood volcanism and mass extinction is not clear, but likely involves the climate effects of outgassed volatile species such as CO2, SO2, Cl, F, etc., from some combination of magma and country rocks. In a surprising “coincidence,” the end-Cretaceous (K-Pg boundary) micro-faunal extinction also corresponds precisely in time to what may have been the largest meteor impact of the past billion years of Earth history, the Chicxulub crater at 66.05 Ma. The Deccan Traps eruptions were under way well before K-Pg/Chicxulub time and are most likely the result of the mantle plume “head” that initiated the presently active Reunion hotspot track—thus the Deccan Traps were clearly not generated, fundamentally, by the impact. However, recent high-precision 40Ar/39Ar geochronology indicates that conspicuous changes in basalt geochemistry, lava flow morphology, emplacement mode, and a possible 50% increase in eruption rate at the Lonavala/Wai subgroup transition in the Deccan Traps lava group corresponded, within radioisotopic age precision, to the K-Pg boundary and the Chicxulub impact. This has led to the testable hypothesis that the Mw ~11 seismic disturbance of the Chicxulub impact may have affected the Deccan eruptions. Here we review a broad landscape of evidence regarding Deccan volcanism and its relation to the K-Pg boundary and attempt to define what we see as the most important questions than can and should be answered by further research to better understand both the onshore and largely unknown offshore components of Deccan-related volcanism, and what their climate and environmental impacts at K-Pg time may have been.
Marginalized identities, mistreatment, discrimination, and burnout among US medical students: cross sectional survey and retrospective cohort study
Authors: Teshome Bethelehem G , Desai Mayur M , Gross Cary P , Hill Katherine A , Li Fangyong , Samuels Elizabeth A , Wong Ambrose H , Xu Yunshan , Boatright Dowin H 
Published: March 2022

AbstractObjectiveTo describe the association between mistreatment, burnout, and having multiple marginalized identities during undergraduate medical education.DesignCross sectional survey and retrospective cohort study.Setting140 US medical schools accredited by the Association of American Medical Colleges.Participants30 651 graduating medical students in 2016 and 2017.Main outcome measuresSelf-reported sex, race or ethnicity, and sexual orientation groups were considered, based on the unique combinations of historically marginalized identities held by students. Multivariable linear regression was used to determine the association between unique identity groups and burnout along two dimensions (exhaustion and disengagement) as measured by the Oldenburg Burnout Inventory for Medical Students while accounting for mistreatment and discrimination.ResultsStudents with three marginalized identities (female; non-white; lesbian, gay, or bisexual (LGB)) had the largest proportion reporting recurrent experiences of multiple types of mistreatment (88/299, P<0.001) and discrimination (92/299, P<0.001). Students with a higher number of marginalized identities also had higher average scores for exhaustion. Female, non-white, and LGB students had the largest difference in average exhaustion score compared with male, white, and heterosexual students (adjusted mean difference 1.96, 95% confidence interval 1.47 to 2.44). Mistreatment and discrimination mediated exhaustion scores for all identity groups but did not fully explain the association between unique identity group and burnout. Non-white and LGB students had higher average disengagement scores than their white and heterosexual counterparts (0.28, 0.19 to 0.37; and 0.73, 0.52 to 0.94; respectively). Female students, in contrast, had lower average disengagement scores irrespective of the other identities they held. After adjusting for mistreatment and discrimination among female students, the effect among female students became larger, indicating a negative confounding association.ConclusionIn this study population of US medical students, those with multiple marginalized identities reported more mistreatment and discrimination during medical school, which appeared to be associated with burnout.
Risk of hernia-related complications after transjugular intrahepatic portosystemic shunt creation in patients with pre-existing ventral abdominal hernias: 15-year experience at a quaternary medical center
Authors: McDaniel Charles , Bell Ruth , Farha Natalie , Vozzo Catherine , Bullen Jennifer , Rosen Michael , Romero-Marrero Carlos , Partovi Sasan , Kapoor Baljendra 
Published: March 2022

ObjectiveTransjugular intrahepatic portosystemic shunt (TIPS) placement is used to treat the sequelae of portal hypertension, including refractory variceal bleeding, ascites and hepatic hydrothorax. However, hernia-related complications such as incarceration and small bowel obstruction can occur after TIPS placement in patients with pre-existing hernias. The aim of this study was to determine the incidence of hernia complications in the first year after TIPS placement and to identify patient characteristics leading to an increased risk of these complications.DesignThis retrospective analysis included patients with pre-existing abdominal hernias who underwent primary TIPS placement with covered stents at our institution between 2004 and 2018. The 1-year hernia complication rate and the average time to complications were documented. Using a Wilcoxon rank-sum test, the characteristics of patients who developed hernia-related complications versus the characteristics of those without complications were compared.ResultsA total of 167 patients with pre-existing asymptomatic abdominal hernias were included in the analysis. The most common reason for TIPS placement was refractory ascites (80.6%). A total of 36 patients (21.6%) developed hernia-related complications after TIPS placement, including 20 patients with acute complications and 16 with non-acute complications. The mean time to presentation of hernia-related complications was 66 days. Patients who developed hernia-related complications were more likely than those without complications to have liver cirrhosis secondary to alcohol consumption (p=0.049), although this association was no longer significant after multivariate analysis.ConclusionWithin 1 year after TIPS placement, approximately 20% of patients with pre-existing hernias develop hernia-related complications, typically within the first 2 months after the procedure. Patients with pre-existing hernia undergoing TIPS placement should be educated regarding the signs and symptoms of hernia-related complications, including incarceration and small bowel obstruction.
Modelling study of the ability to diagnose acute rheumatic fever at different levels of the Ugandan healthcare system
Authors: Ndagire Emma , Ollberding Nicholas , Sarnacki Rachel , Meghna Murali , Pulle Jafesi , Atala Jenifer , Agaba Collins , Kansiime Rosemary , Bowen Asha , Longenecker Chris T , Oyella Linda , Rwebembera Joselyn , Okello Emmy , Parks Tom , Zang Huaiyu , Carapetis Jonathan , Sable Craig , Beaton Andrea Z 
Published: March 2022

ObjectiveTo determine the ability to accurately diagnose acute rheumatic fever (ARF) given the resources available at three levels of the Ugandan healthcare system.MethodsUsing data obtained from a large epidemiological database on ARF conducted in three districts of Uganda, we selected variables that might positively or negatively predict rheumatic fever based on diagnostic capacity at three levels/tiers of the Ugandan healthcare system. Variables were put into three statistical models that were built sequentially. Multiple logistic regression was used to estimate ORs and 95% CI of predictors of ARF. Performance of the models was determined using Akaike information criterion, adjusted R2, concordance C statistic, Brier score and adequacy index.ResultsA model with clinical predictor variables available at a lower-level health centre (tier 1) predicted ARF with an optimism corrected area under the curve (AUC) (c-statistic) of 0.69. Adding tests available at the district level (tier 2, ECG, complete blood count and malaria testing) increased the AUC to 0.76. A model that additionally included diagnostic tests available at the national referral hospital (tier 3, echocardiography, anti-streptolysin O titres, erythrocyte sedimentation rate/C-reactive protein) had the best performance with an AUC of 0.91.ConclusionsReducing the burden of rheumatic heart disease in low and middle-income countries requires overcoming challenges of ARF diagnosis. Ensuring that possible cases can be evaluated using electrocardiography and relatively simple blood tests will improve diagnostic accuracy somewhat, but access to echocardiography and tests to confirm recent streptococcal infection will have the greatest impact.
Efficacy, safety and cost-effectiveness of methotrexate, adalimumab or their combination in non-infectious non-anterior uveitis: a protocol for a multicentre, randomised, parallel three arms, active-controlled, phase III open label with blinded outcome assessment study
Authors: Rivas Ana Belen , Lopez-Picado Amanda , Calamia Valentina , Carreño Ester , Cocho Lidia , Cordero-Coma Miguel , Fonollosa Alex , Francisco Hernandez Felix M , Garcia-Aparicio Angel , Garcia-Gonzalez Javier , Mondejar Jose Juan , Lojo-Oliveira Leticia , Martínez-Costa Llucí , Munoz Santiago , Peiteado Diana , Pinto Jose Antonio , Rodriguez-Lozano Beatriz , Pato Esperanza , Diaz-Valle David , Molina Elena , Tebar Luis Alberto , Rodriguez-Rodriguez Luis 
Published: March 2022

IntroductionNon-infectious uveitis include a heterogeneous group of sight-threatening and incapacitating conditions. Their correct management sometimes requires the use of immunosuppressive drugs (ISDs), prescribed in monotherapy or in combination. Several observational studies showed that the use of ISDs in combination could be more effective than and as safe as their use in monotherapy. However, a direct comparison between these two treatment strategies has not been carried out yet.Methods and analysisThe Combination THerapy with mEthotrexate and adalImumAb for uveitis (CoTHEIA) study is a phase III, multicentre, prospective, randomised, single-blinded with masked outcome assessment, parallel three arms with 1:1:1 allocation, active-controlled, superiority study design, comparing the efficacy, safety and cost-effectiveness of methotrexate, adalimumab or their combination in non-infectious non-anterior uveitis. We aim to recruit 192 subjects. The duration of the treatment and follow-up will last up to 52 weeks, plus 70 days follow-up with no treatment. The complete and maintained resolution of the ocular inflammation will be assessed by masked evaluators (primary outcome). In addition to other secondary measurements of efficacy (quality of life, visual acuity and costs) and safety, we will identify subjects’ subgroups with different treatment responses by developing prediction models based on machine learning techniques using genetic and proteomic biomarkers.Ethics and disseminationThe protocol, annexes and informed consent forms were approved by the Reference Clinical Research Ethic Committee at the Hospital Clínico San Carlos (Madrid, Spain) and the Spanish Agency for Medicines and Health Products. We will elaborate a dissemination plan including production of materials adapted to several formats to communicate the clinical trial progress and findings to a broad group of stakeholders. The promoter will be the only access to the participant-level data, although it can be shared within the legal situation.Trial registration number2020-000130-18;NCT04798755.
Does difficulty in chewing induce subjective musculoskeletal symptoms? A case-control study
Authors: Tani Naomichi , Ohta Masanori , Higuchi Yoshiyuki , Yamamoto Ryoko , Akatsu Junichi 
Published: March 2022

ObjectivesRisk factors associated with the development of musculoskeletal disorders and symptoms remain an important issue worldwide. This study aimed to investigate the relationship between oral health problems such as difficulty chewing and the occurrence of stiff neck/shoulders (SN/S) and low back pain (LBP).DesignCase-control study.Setting and participantsThis study was conducted from 1 April 2018 to 31 March 2020. The subjects were 77 341 workers among 646 281 workers from several employers in Japan.Outcome measuresParticipants were asked to evaluate their subjective SN/S and LBP symptoms using a self-administered questionnaire.MethodsWe defined the chewing condition using a questionnaire, and workers who responded with ‘I can chew anything’ were classified as the good condition group (GCG), and those who responded with ‘Sometimes I have difficulty chewing due to problems with the teeth, gums, or bite’ or ‘I can hardly chew’ were classified as the poor condition group (PCG). Setting the year 2018 as the baseline, we performed a logistic regression model using propensity score and inverse probability weighting (IPW) methods and chewing condition groups as explanatory variables and SN/S and LBP as objective variables.ResultsThe IPW-adjusted logistic regression model showed that the OR of SN/S was approximately 1.25 (95% CI 1.17 to 1.33) times higher in the PCG than that in the GCG (p<0.001). Similarly, the OR of LBP was about 1.37 (95% CI 1.27 to 1.48) times higher in the PCG than that in the GCG in the IPW-adjusted logistic regression model (p<0.001).ConclusionsOur study suggests that the occurrence of SN/S and LBP symptoms in workers could be predicted depending on the presence of difficulty in chewing. Therefore, oral health and health guidance are gaining importance for the prevention of subjective musculoskeletal symptoms.