bluuebunny/crossref_metadata_2025 huggingface dataset:
Learning spatial structures of proteins improves protein–protein interaction prediction
Authors: Song Bosheng , Luo Xiaoyan , Luo Xiaoli , Liu Yuansheng , Niu Zhangming , Zeng Xiangxiang
Published: December 2021

Spatial structures of proteins are closely related to protein functions. Integrating protein structures improves the performance of protein–protein interaction (PPI) prediction. However, the limited quantity of known protein structures restricts the application of structure-based prediction methods. Utilizing the predicted protein structure information is a promising method to improve the performance of sequence-based prediction methods. We propose a novel end-to-end framework, TAGPPI, to predict PPIs using protein sequence alone. TAGPPI extracts multi-dimensional features by employing 1D convolution operation on protein sequences and graph learning method on contact maps constructed from AlphaFold. A contact map contains abundant spatial structure information, which is difficult to obtain from 1D sequence data directly. We further demonstrate that the spatial information learned from contact maps improves the ability of TAGPPI in PPI prediction tasks. We compare the performance of TAGPPI with those of nine state-of-the-art sequence-based methods, and TAGPPI outperforms such methods in all metrics. To the best of our knowledge, this is the first method to use the predicted protein topology structure graph for sequence-based PPI prediction. More importantly, our proposed architecture could be extended to other prediction tasks related to proteins.
RadSigBench: a framework for benchmarking functional genomics signatures of cancer cell radiosensitivity
Authors: O’Connor John D , Overton Ian M , McMahon Stephen J
Published: December 2021

Multiple transcriptomic predictors of tumour cell radiosensitivity (RS) have been proposed, but they have not been benchmarked against one another or to control models. To address this, we present RadSigBench, a comprehensive benchmarking framework for RS signatures. The approach compares candidate models to those developed from randomly resampled control signatures and from cellular processes integral to the radiation response. Robust evaluation of signature accuracy, both overall and for individual tissues, is performed. The NCI60 and Cancer Cell Line Encyclopaedia datasets are integrated into our workflow. Prediction of two measures of RS is assessed: survival fraction after 2 Gy and mean inactivation dose. We apply the RadSigBench framework to seven prominent published signatures of radiation sensitivity and test for equivalence to control signatures. The mean out-of-sample R2 for the published models on test data was very poor at 0.01 (range: −0.05 to 0.09) for Cancer Cell Line Encyclopedia and 0.00 (range: −0.19 to 0.19) in the NCI60 data. The accuracy of both published and cellular process signatures investigated was equivalent to the resampled controls, suggesting that these signatures contain limited radiation-specific information. Enhanced modelling strategies are needed for effective prediction of intrinsic RS to inform clinical treatment regimes. We make recommendations for methodological improvements, for example the inclusion of perturbation data, multiomics, advanced machine learning and mechanistic modelling. Our validation framework provides for robust performance assessment of ongoing developments in intrinsic RS prediction.
Coping with COVID-19: Resilience Factors Amongst Community Social Workers
Authors: Itzhaki-Braun Yael
Published: December 2021

The COVID-19 pandemic has required health care professionals to cope with an unexpected emergency situation, and to provide solutions for a wide range of problems at the community level. As community social workers work on the macro level and deal with entire communities in emergency situations, the current study examined how well they functioned during the first wave of the pandemic in Israel. The study included in-depth interviews with twenty community social workers who work as managers of community social work departments in Israel. It utilised a qualitative-constructivist perspective. Three main themes were highlighted regarding the managers’ coping with the pandemic: (i) creative thinking, which was reflected in their development of solutions and fundraising, both in general and for special groups in particular; (ii) functional flexibility; and (iii) communal networking with community members and organisations. The unique qualities and personal resources of community social workers in public social services played an important role in their coping with the pandemic, and community practice is critical for dealing with emergency situations. Findings are discussed in light of the theoretical perspectives of resilience. Implications for community practice are outlined.
Interleukin-23 receptor expressing γδ T cells locally promote early atherosclerotic lesion formation and plaque necrosis in mice
Authors: Gil-Pulido Jesus , Amézaga Núria , Jorgacevic Ivana , Manthey Helga D , Rösch Melanie , Brand Theresa , Cidlinsky Peter , Schäfer Sarah , Beilhack Andreas , Saliba Antoine-Emmanuel , Lorenz Kristina , Boon Louis , Prinz Immo , Waisman Ari , Korn Thomas , Cochain Clément , Zernecke Alma
Published: December 2021

Aims

Atherosclerosis is a chronic inflammatory disease of the vessel wall controlled by local and systemic immune responses. The role of interleukin-23 receptor (IL-23R), expressed in adaptive immune cells (mainly T-helper 17 cells) and γδ T cells, in atherosclerosis is only incompletely understood. Here, we investigated the vascular cell types expressing IL-23R and addressed the function of IL-23R and γδ T cells in atherosclerosis.

Methods and results

IL-23R+ cells were frequently found in the aortic root in contrast to the aorta in low-density lipoprotein receptor deficient IL-23R reporter mice (Ldlr−/−Il23rgfp/+), and mostly identified as γδ T cells that express IL-17 and GM-CSF. scRNA-seq confirmed γδ T cells as the main cell type expressing Il23r and Il17a in the aorta. Ldlr−/−Il23rgfp/gfp mice deficient in IL-23R showed a loss of IL-23R+ cells in the vasculature, and had reduced atherosclerotic lesion formation in the aortic root compared to Ldlr−/− controls after 6 weeks of high-fat diet feeding. In contrast, Ldlr−/−Tcrδ−/− mice lacking all γδ T cells displayed unaltered early atherosclerotic lesion formation compared to Ldlr−/− mice. In both HFD-fed Ldlr−/−Il23rgfp/gfp and Ldlr−/−Tcrδ−/− mice a reduction in the plaque necrotic core area was noted as well as an expansion of splenic regulatory T cells. In vitro, exposure of bone marrow-derived macrophages to both IL-17A and GM-CSF induced cell necrosis, and necroptotic RIP3K and MLKL expression, as well as inflammatory mediators.

Conclusions

IL-23R+ γδ T cells are predominantly found in the aortic root rather than the aorta and promote early atherosclerotic lesion formation, plaque necrosis, and inflammation at this site. Targeting IL-23R may thus be explored as a therapeutic approach to mitigate atherosclerotic lesion development.
The Restatement of Foreign Sovereign Immunity: Tutto il Mondo è Paese
Authors: O’Keefe Roger
Published: December 2021

Chapter 5 of the Restatement of the Law (Fourth): The Foreign Relations Law of the United States provides a systematic, discerning and accessible account of the US law of foreign sovereign immunity as laid down in the Foreign Sovereign Immunities Act (FSIA), accompanied by consistent comparative reference to the international and foreign domestic law of state immunity. From the perspective of a non-US reader, however, where Chapter 5 adds greater value in its own right is in the attention it pays in the comments and reporters’ notes to a range of preliminary issues of domestic law on the determination of which the provisions of the FSIA turn but that the latter do not regulate. These issues, although superficially peculiar to the US law of foreign sovereign immunity, arise similarly in connection with the corresponding international and foreign domestic rules. In this way, what are ostensibly the most particular aspects of Chapter 5 may be those of most universal interest.
National networking in rare diseases and reduction of cardiac burden in thalassemia major
Authors: Pepe Alessia , Pistoia Laura , Gamberini Maria Rita , Cuccia Liana , Lisi Roberto , Cecinati Valerio , Maggio Aurelio , Sorrentino Francesco , Filosa Aldo , Rosso Rosamaria , Messina Giuseppe , Missere Massimiliano , Righi Riccardo , Renne Stefania , Vallone Antonino , Dalmiani Stefano , Positano Vincenzo , Midiri Massimo , Meloni Antonella
Published: December 2021

Aims

A tailored chelation therapy guided by magnetic resonance imaging (MRI) is a strategy to improve the prognosis in iron-loaded patients, in many cases still hampered by limited MRI availability. In order to address this issue, the Myocardial Iron Overload in Thalassemia (MIOT) network was established in Italy and we aimed to describe the impact of 10-year activity of this network on cardiac burden in thalassemia major (TM).

Methods and results

Within the MIOT network, 1746 TM patients (911 females; mean age 31.2 ± 9.1 years) were consecutively enrolled and prospectively followed by 70 thalassemia and 10 MRI centres. Patients were scanned using a multiparametric approach for assessing myocardial iron overload (MIO), biventricular function, and myocardial fibrosis. At the last MRI scan, a significant increase in global heart T2* values and a significantly higher frequency of patients with no MIO (all segmental T2* ≥20 ms) were detected, with a concordant improvement in biventricular function, particularly in patients with baseline global heart T2* <20 ms. Forty-seven percentage of patients changed the chelation regimen based on MRI. The frequency of heart failure (HF) significantly decreased after baseline MRI from 3.5 to 0.8% (P < 0.0001). Forty-six patients died during the study, and HF accounted for 34.8% of deaths.

Conclusion

Over 10 years, continuous monitoring of cardiac iron and a tailored chelation therapy allowed MIO reduction, with consequent improvement of cardiac function and reduction of cardiac complications and mortality from MIO-related HF. A national networking for rare diseases therefore proved effective in improving the care and reducing cardiac outcomes of TM patients.
Development and validation of a risk score for predicting pericardial effusion in patients undergoing leadless pacemaker implantation: experience with the Micra transcatheter pacemaker
Authors: Piccini Jonathan P , Cunnane Ryan , Steffel Jan , El-Chami Mikhael F , Reynolds Dwight , Roberts Paul R , Soejima Kyoko , Steinwender Clemens , Garweg Christophe , Chinitz Larry , Ellis Christopher R , Stromberg Kurt , Fagan Dedra H , Mont Lluis
Published: December 2021

Aims

There is limited information on what clinical factors are associated with the development of pericardial effusion after leadless pacemaker implantation. We sought to determine predictors of and to develop a risk score for pericardial effusion in patients undergoing Micra leadless pacemaker implantation attempt.

Methods and results

Patients (n = 2817) undergoing implant attempt from the Micra global trials were analysed. Characteristics were compared between patients with and without pericardial effusion (including cardiac perforation and tamponade). A risk score for pericardial effusion was developed from 18 pre-procedural clinical variables using lasso logistic regression. Internal validation and future prediction performance were estimated using bootstrap resampling. The scoring system was also externally validated using data from the Micra Acute Performance European and Middle East (MAP EMEA) registry. There were 32 patients with a pericardial effusion [1.1%, 95% confidence interval (CI): 0.8–1.6%]. Following lasso logistic regression, 11 of 18 variables remained in the model from which point values were assigned. The C-index was 0.79 (95% CI: 0.71–0.88). Patient risk score profile ranged from −4 (lowest risk) to 5 (highest risk) with 71.8% patients considered low risk (risk score ≤0), 16.6% considered medium risk (risk score = 1), and 11.7% considered high risk (risk score ≥2) for effusion. The median C-index following bootstrap validation was 0.73 (interquartile range: 0.70–0.75). The C-index based on 9 pericardial effusions from the 928 patients in the MAP EMEA registry was 0.68 (95% CI: 0.52–0.83). The pericardial effusion rate increased significantly with additional Micra deployments in medium-risk (P = 0.034) and high-risk (P < 0.001) patients.

Conclusion

The overall rate of pericardial effusion following Micra implantation attempt is 1.1% and has decreased over time. The risk of pericardial effusion after Micra implant attempt can be predicted using pre-procedural clinical characteristics with reasonable discrimination.

Clinical trial registration

The Micra Post-Approval Registry (ClinicalTrials.gov identifier: NCT02536118), Micra Continued Access Study (ClinicalTrials.gov identifier: NCT02488681), and Micra Transcatheter Pacing Study (ClinicalTrials.gov identifier: NCT02004873).
The effect of China’s compulsory education reforms on physiological health in adulthood: a natural experiment
Authors: Ye Xin , Zhu Dawei , Ding Ruoxi , He Ping
Published: December 2021

Lower education is related to higher biological risks for physiological health, but it remains unclear whether the risks can be reduced through policies aimed at increasing years of education. We utilized China’s compulsory education reforms as a unique natural experiment, which stipulates that primary and lower secondary education is mandatory and free for all school-age children. Using a regression discontinuity design (RDD), we assessed the effect of the reform eligibility on biomarkers. The reforms resulted in an increase in years of education for those from communities with the middle 1/3 per capita income (PCI) (β = 2.44, 95% CI = 0.23–4.64). Reform eligibility had no impact on allostatic risks for the total sample (β = 0.065, 95% CI = −0.70 to 0.83) and for those from communities with the lowest (β = 0.35, 95% CI = −0.77 to 1.47) or highest third of PCI (β = 0.68, 95% CI = −0.64 to 2.00), while it reduced the metabolic risk (β = −0.14, 95% CI = −0.26 to −0.015) and total allostatic load (β = −1.58, 95% CI = −3.00 to −0.16) among those from communities with the middle third PCI. The results were confirmed by sensitivity analyses of different placebo cut-off points and bandwidths. The reforms led to better physiological health to some extent, but the effect only manifested in people from communities with a moderate community PCI, and had little impact on affluent or disadvantaged groups. Our findings stressed that the institutional context and respondents’ socioeconomic environment must be taken into account when assessing the health impact of China’s compulsory education reforms.
Fetal alleles predisposing to metabolically favorable adiposity are associated with higher birth weight
Authors: Thompson William D , Beaumont Robin N , Kuang Alan , Warrington Nicole M , Ji Yingjie , Tyrrell Jessica , Wood Andrew R , Scholtens Denise M , Knight Bridget A , Evans David M , Lowe Jr William L , Santorelli Gillian , Azad Raq , Mason Dan , Hattersley Andrew T , Frayling Timothy M , Yaghootkar Hanieh , Borges Maria Carolina , Lawlor Deborah A , Freathy Rachel M
Published: December 2021

Background

Higher birthweight is associated with higher adult body mass index (BMI). Alleles that predispose to greater adult adiposity might act in fetal life to increase fetal growth and birthweight. Whether there are fetal effects of recently identified adult metabolically favorable adiposity alleles on birthweight is unknown.

Aim

We aimed to test the effect on birthweight of fetal genetic predisposition to higher metabolically favorable adult adiposity and compare that with the effect of fetal genetic predisposition to higher adult BMI.

Methods

We used published genome wide association study data (n = upto 406 063) to estimate fetal effects on birthweight (adjusting for maternal genotype) of alleles known to raise metabolically favorable adult adiposity or BMI. We combined summary data across single nucleotide polymorphisms (SNPs) with random effects meta-analyses. We performed weighted linear regression of SNP-birthweight effects against SNP-adult adiposity effects to test for a dose-dependent association.

Results

Fetal genetic predisposition to higher metabolically favorable adult adiposity and higher adult BMI were both associated with higher birthweight (3 g per effect allele (95% CI: 1–5) averaged over 14 SNPs; P = 0.002; 0.5 g per effect allele (95% CI: 0–1) averaged over 76 SNPs; P = 0.042, respectively). SNPs with greater effects on metabolically favorable adiposity tended to have greater effects on birthweight (R2 = 0.2912, P = 0.027). There was no dose-dependent association for BMI (R2 = −0.0019, P = 0.602).

Conclusions

Fetal genetic predisposition to both higher adult metabolically favorable adiposity and BMI is associated with birthweight. Fetal effects of metabolically favorable adiposity-raising alleles on birthweight are modestly proportional to their effects on future adiposity, but those of BMI-raising alleles are not.
Aortic arch type, a novel morphological indicator and the risk for acute type B aortic dissection
Authors: Sun Likun , Li Jiehua , Liu Zhenyu , Li Quanming , He Hao , Li Xin , Li Ming , Wang Tun , Wang Lunchang , Peng Yuan , Wang Hui , Shu Chang
Published: December 2021

OBJECTIVES

Aortic arch type is a readily recognizable and obtainable morphological feature of the aorta that does not require complex measurements. The goal of this study was to evaluate whether aortic arch type is a comparable and alternative morphological parameter for predicting acute type B aortic dissection (aTBAD) by comparing the prognostic value of the aortic arch type with that of other morphological parameters such as aortic length, angulation and tortuosity index.

METHODS

The patients with aTBAD (n = 216) were matched 1:1 with a control group (n = 263) by propensity score matching. The morphological data of the ascending aorta and the aortic arch, which included diameter, length, angulation and tortuosity index, were collected on a three-dimensional aortic model using 3mensio Vascular software. The aortic arch type was identified by the vertical distance from the origin of the brachiocephalic trunk to the top of the arch. The binary logistic regression models were analysed to determine the independent geometric variables related to the aTBAD. The nonparametric approach was performed to assess whether there were statistical differences between the area under the receiver operating characteristic curves (AUC) of the models.

RESULTS

After propensity score matching, 151 matched pairs of patients were selected. The diameters at the sinotubular junction and the mid-ascending aorta, the ascending aorta length and the ascending aorta angulation in the aTBAD group were significantly greater than those of the controls. Compared with the control group, the diameters at the proximal aortic arch, mid-aortic arch and distal aortic arch, the angulation and the tortuosity index of the aortic arch were significantly greater in the aTBAD group. The proportion of the type III arch in the patients with aTBAD is higher than that of the type I arch and the type II arch (χ2 = 70.187; P < 0.001). Binary logistic regression analysis showed that the diameter at the mid-aortic arch, the ascending aorta length, the aortic arch angulation and the tortuosity index were independently related to the aTBAD with an AUC value of 0.887. Another binary logistic regression analysis indicated that the diameter at the mid-aortic arch and the aortic arch type were independent correlative variables associated with the aTBAD with an AUC of 0.874. No significant difference was observed in the prognostic value of receiver operating characteristic curves between the 2 models (P = 0.716).

CONCLUSIONS

The type III arch, which has the characteristics of aortic elongation, incremental angulation and tortuosity index, is a comparable and alternative identifier for patients at high risk for aTBAD.
T-Cell Expression of Angiotensin-Converting Enzyme 2 and Binding of Severe Acute Respiratory Coronavirus 2
Authors: Welch Jennifer L , Xiang Jinhua , Chang Qing , Houtman Jon C D , Stapleton Jack T
Published: December 2021

The pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not completely understood. SARS-CoV-2 infection frequently causes significant immune function consequences including reduced T cell numbers and enhanced T cell exhaustion that contribute to disease severity. The extent to which T cell effects are directly mediated through infection or indirectly result from infection of respiratory-associated cells is unclear. We show that primary human T cells express sufficient levels of angiotensin converting enzyme 2 (ACE-2), the SARS-CoV-2 receptor, to mediate viral binding and entry into T cells. We further show that T cells exposed to SARS-CoV-2 particles demonstrate reduced proliferation and apoptosis compared to uninfected controls, indicating that direct interaction of SARS-CoV-2 with T cells may alter T cell growth, activation, and survival. Regulation of T cell activation and/or turnover by SARS-CoV-2 may contribute to impaired T cell function observed in patients with severe disease.
Emergence of VIM-producing Enterobacter cloacae complex in France between 2015 and 2018
Authors: Emeraud Cécile , Petit Caroline , Gauthier Lauraine , Bonnin Rémy A. , Naas Thierry , Dortet Laurent
Published: December 2021

Objectives

To genetically characterize VIM-producing Enterobacter cloacae complex (ECC) isolates recovered in France from 2015 to 2018.

Methods

WGS, species determination, MLST, clonal relationship and genetic characterization were performed on 149 VIM-producing ECC isolates.

Results

Among VIM-producing Enterobacterales, the prevalence of ECC increased drastically from 6% in 2012 to 52% in 2018. The most prevalent species were Enterobacter hormaechei subsp. hoffmannii (40.9%), E. hormaechei subsp. steigerwaltii (21.5%), E. hormaechei subsp. xiangfangensis (14.8%) and ECC clade S (17.4%). Major STs were ST-873 (17.5%), ST-66 (12.1%), ST-78 (9.4%), ST-419 (8.1%), ST-145 (4.7%), ST-50 (4.0%), ST-118 (4.0%) and ST-168 (4.0%). Finally, six different integrons were identified, with some being specific to a given blaVIM variant (In916 with blaVIM-1-aacA4′-aphA15-aadA1-catB2 and In416 with blaVIM-4-aacA7-dfrA1b-aadA1b-smr2 genes).

Conclusions

This study demonstrated the genetic diversity among VIM-producing ECC isolates, indicating that their spread is not linked to a single clone.
Influence of the adductor compartment resection on muscle strength and postoperative function in soft-tissue sarcoma of the thigh
Authors: Tanaka Atsushi , Okamoto Masanori , Kito Munehisa , Yoshimura Yasuo , Aoki Kaoru , Suzuki Shuichiro , Takazawa Akira , Komatsu Yukiko , Ishida Takaaki , Takahashi Jun
Published: December 2021

Objective

To predict the muscle strength and postoperative function for soft-tissue sarcoma arising from the adductor compartment of the thigh.

Methods

Between 2003 and 2019, 17 cases that underwent resection of the adductor muscle group (adductor longus, adductor magnus, adductor brevis, gracilis and pectineus) for soft-tissue sarcoma in the adductor compartment of the thigh were included. The muscle strength was measured with an isokinetic dynamometer for the knee joint and with a hand-held dynamometer for the hip joint (ratio of affected to unaffected side). The Musculoskeletal Tumor Society score, Toronto Extremity Salvage Score, European Quality of Life-5 Dimensions and maximum walking speed were used to assess postoperative function and examine correlations with muscle strength.

Results

In 13 cases that underwent an isolated resection of the adductor compartment, reduced adduction strength correlated with increased number of resected muscles in the adductor muscle group (P < 0.001). Postoperative function was maintained, showing no correlations with adduction strength. In four cases that underwent combined resections of other compartments, a decrease was observed in adduction strength as well as the muscle strength of other resected muscles, in addition to a decline in postoperative function. In the 4 or 5 adductor muscle resection group, the comparison between isolated and combined resection revealed comparable results for adduction strength but a significant decrease in postoperative function for the combined resection group.

Conclusions

Postoperative function can be preserved for isolated adductor compartment resection. Combined resections of multiple muscles in other compartments and most adductor muscles may result in decreased postoperative function.
Chemical genetics inSilene latifoliaelucidate regulatory pathways involved in gynoecium development
Authors: Bačovský Václav , Čegan Radim , Tihlaříková Eva , Neděla Vilém , Hudzieczek Vojtěch , Smrža Lubomír , Janíček Tomáš , Beneš Vladimír , Hobza Roman
Published: December 2021

Dioecious plants possess diverse sex determination systems and unique mechanisms of reproductive organ development; however, little is known about how sex-linked genes shape the expression of regulatory cascades that lead to developmental differences between sexes. In Silene latifolia, a dioecious plant with stable dimorphism in floral traits, early experiments suggested that female-regulator genes act on the factors that determine the boundaries of the flower whorls. To identify these regulators, we sequenced the transcriptome of male flowers with fully developed gynoecia, induced by rapid demethylation in the parental generation. Eight candidates were found to have a positive role in gynoecium promotion, floral organ size, and whorl boundary, and affect the expression of class B MADS-box flower genes. To complement our transcriptome analysis, we closely examined the floral organs in their native state using field emission environmental scanning electron microscopy, and examined the differences between females and androhermaphrodites in their placenta and ovule organization. Our results reveal the regulatory pathways potentially involved in sex-specific flower development in the classical model of dioecy, S. latifolia. These pathways include previously hypothesized and unknown female-regulator genes that act on the factors that determine the flower boundaries, and a negative regulator of anther development, SUPERMAN-like (SlSUP).
INTERMEDIUM-C mediates the shade-induced bud growth arrest in barley
Authors: Wang Hongwen , Seiler Christiane , Sreenivasulu Nese , von Wirén Nicolaus , Kuhlmann Markus
Published: December 2021

Tiller formation is a key agronomic determinant for grain yield in cereal crops. The modulation of this trait is controlled by transcriptional regulators and plant hormones, tightly regulated by external environmental conditions. While endogenous (genetic) and exogenous (environmental factors) triggers for tiller formation have mostly been investigated separately, it has remained elusive how they are integrated into the developmental program of this trait. The transcription factor gene INTERMEDIUM-C (INT-C), which is the barley ortholog of the maize domestication gene TEOSINTE BRANCHED1 (TB1), has a prominent role in regulating tiller bud outgrowth. Here we show that INT-C is expressed in tiller buds, required for bud growth arrest in response to shade. In contrast to wild-type plants, int-c mutant plants are impaired in their shade response and do not stop tiller production after shading. Gene expression levels of INT-C are up-regulated under light-limiting growth conditions, and down-regulated after decapitation. Transcriptome analysis of wild-type and int-c buds under control and shading conditions identified target genes of INT-C that belong to auxin and gibberellin biosynthesis and signaling pathways. Our study identifies INT-C as an integrator of the shade response into tiller formation, which is prerequisite for implementing shading responses in the breeding of cereal crops.
Quantifying the poor purity and completeness of morphological samples selected by galaxy colour
Authors: Smethurst Rebecca J , Masters Karen L , Simmons Brooke D , Garland Izzy L , Géron Tobias , Häußler Boris , Kruk Sandor , Lintott Chris J , O’Ryan David , Walmsley Mike
Published: December 2021

The galaxy population is strongly bimodal in both colour and morphology, and the two measures correlate strongly, with most blue galaxies being late-types (spirals) and most early-types, typically ellipticals, being red. This observation has led to the use of colour as a convenient selection criterion to make samples that are then labelled by morphology. Such use of colour as a proxy for morphology results in necessarily impure and incomplete samples. In this paper, we make use of the morphological labels produced by Galaxy Zoo to measure how incomplete and impure such samples are, considering optical (ugriz), near-ultraviolet (NUV), and near-infrared (NIR; JHK) bands. The best single colour optical selection is found using a threshold of g − r = 0.742, but this still results in a sample where only 56 per cent of red galaxies are smooth and 56 per cent of smooth galaxies are red. Use of the NUV gives some improvement over purely optical bands, particularly for late-types, but still results in low purity/completeness for early-types. No significant improvement is found by adding NIR bands. With any two bands, including NUV, a sample of early-types with greater than two-thirds purity cannot be constructed. Advances in quantitative galaxy morphologies have made colour–morphology proxy selections largely unnecessary going forward; where such assumptions are still required, we recommend studies carefully consider the implications of sample incompleteness/impurity.
The extreme solar and geomagnetic storms on 1940 March 20–25
Authors: Hayakawa Hisashi , Oliveira Denny M , Shea Margaret A , Smart Don F , Blake Seán P , Hattori Kentaro , Bhaskar Ankush T , Curto Juan J , Franco Daniel R , Ebihara Yusuke
Published: December 2021

In late 1940 March, at least five significant solar flares were reported. They likely launched interplanetary coronal mass ejections (ICMEs), and were associated with one of the largest storm sudden commencements (SSCs) since 1868, resulting in space weather hazards that would have significant societal impacts should it occur today. The initial solar activity is associated with a solar proton event. Afterwards, another flare was reported in the eastern solar quadrant (N12 E37-38) at 11:30–12:30 ut on March 23, with significant magnetic crochets (up to ≈ |80| nT at Eskdalemuir) during 11:07–11:40 ut. On their basis, we conservatively estimate the required energy flux of the source solar flare as X35 ± 1 in soft X-ray class. The resultant ICMEs caused enormous SSCs (up to >425 nT recorded at Tucson) and allowed us to estimate an extremely inward magnetopause position (estimated magnetopause stand-off position ≈3.4 RE). The time series of the resultant geomagnetic storm is reconstructed using a Dst estimate, which peaked at 20 ut on March 24 at ≈ −389 nT. Around the storm main phase, the equatorward boundary of the auroral oval extended ≤46.3° in invariant latitudes. This sequence also caused a solar proton event and Forbush decrease (≈3 per cent). These sequences indicate pile-up of multiple ICMEs, which even achieved a record value of inward magnetopause position. Our analyses of this historical pioneer event bring more insights into possible serious space weather hazards and provide a quantitative basis for future analyses and predictions.
Neutrophil:lymphocyte ratio correlates with the uremic toxin indoxyl sulfate and predicts the risk of death in patients on hemodialysis
Authors: Lano Guillaume , Sallée Marion , Pelletier Marion , Bataille Stanislas , Fraisse Megan , McKay Nathalie , Brunet Philippe , Dou Laetitia , Burtey Stéphane
Published: December 2021

Background

Chronic kidney disease (CKD) is a major public health issue associated with increased cardiovascular, infectious and all-cause mortality. The neutrophil:lymphocyte ratio (NLR) is a predictive marker of the risk of death and cardiovascular events. Uremic toxins, notably indoxyl sulfate (IS), are involved in immune deficiency and cardiovascular complications associated with CKD. The aim of this study was to assess whether the NLR was related to uremic toxins and could predict clinical outcome in hemodialysis (HD) patients.

Methods

We conducted a prospective cohort study of 183 patients on chronic HD. The main objective was to study the correlation between the NLR and uremic toxin serum levels. The secondary objective was to test if the NLR can predict the incidence of mortality, cardiovascular events and infectious events.

Results

Patients were separated into two groups according to the NLR median value (3.49). The NLR at inclusion was correlated with the NLR at the 6-month (r = 0.55, P < 0.0001) and 12-month (r = 0.62, P < 0.0001) follow-up. Among uremic toxins, IS levels were higher in the group with high NLR (104 µmol/L versus 81 µmol/L; P = 0.004). In multivariate analysis, the NLR remained correlated with IS (P = 0.03). The incidence of death, cardiovascular events and severe infectious events was higher in the group with high NLR [respectively, 38% versus 18% (P = 0.004), 45% versus 26% (P = 0.01) and 33% versus 21% (P = 0.02)] than in the low NLR group. Multivariate analysis showed an independent association of the NLR with mortality (P = 0.02) and cardiovascular events (P = 0.03) but not with severe infectious events.

Conclusions

In HD patients, the NLR predicted mortality and cardiovascular events but not severe infections and correlated positively with the level of the uremic toxin IS. The NLR could be an interesting marker for monitoring the risk of clinical events in CKD patients.
Parsing Intra- and Inter-Individual Covariation Between the Sensory Attributes and Appeal of E-Cigarettes: Associations and Gender Differences
Authors: Pang Raina D , Mason Tyler B , Kapsner Addison K , Leventhal Adam M
Published: December 2021

Introduction

Perceived sensory attributes of e-cigarettes may associate with their appeal. However, limited studies have accounted for individuals’ variability in sensory attributes or have addressed how associations of sensory attributes with appeal may differ by gender.

Methods

Individuals (n = 119, 32.8% female) who currently used combustible cigarettes and/or e-cigarettes attended one laboratory session in which they completed a standardized e-cigarette puffing procedure according to a 10 Flavor (green apple, strawberry, chocolate, vanilla, menthol, koolada, peppermint, spearmint, subtle tobacco, and full-flavored tobacco) × 2 Nicotine Formulation (free-base, salt) double-blind factorial design. The mean nicotine concentration was 23.4 (SD = 0.9) mg/mL in the nicotine salt formulations and 23.8 (SD = 1.7) mg/mL in the free-base formulations. Following each trial, participants completed ratings of sensory attributes (sweet, smooth, cool, bitter, harsh) and appeal (mean of liking, disliking [reverse-scored], and willingness-to-use-again ratings). Sensory attributes were partitioned into between-person and within-person variables. Gender was tested as a moderator of associations of sensory attributes with appeal.

Results

Sweet, smooth, and cool sensory attributes positively associated with appeal at the between- and within-person level (ps < .001). Bitter and harsh negatively associated with appeal at the between- and within-person level (ps < .001). The associations of between-person sweet, smooth, and cool ratings with appeal was larger in males compared to females. The associations of within-person smooth, bitter, and harsh with appeal was larger in females compared to males.

Conclusions

This study showed important gender differences in associations of sensory attributes and appeal.

Implications

While evidence suggests that sensory attributes may contribute to the appeal of e-cigarettes, there is little experimental evidence accounting for individual variability in sensory attributes and whether sensory attribute-appeal associations differ by gender. The current study provides evidence that average sweet, cool, and smooth ratings positively associated with appeal and that these associations were larger in males. Within-person bitter, harsh, and smooth ratings significantly associated with appeal in both genders, but these associations were larger in females compared to males. Data from the current report reinforces the need for researchers to study gender stratified effects in tobacco regulatory science.
Auxin Efflux Transporters OsPIN1c and OsPIN1d Function Redundantly in Regulating Rice (Oryza sativa L.) Panicle Development
Authors: Liu Jiajun , Shi Xi’an , Chang Zhongyuan , Ding Yanfeng , Ding Chengqiang
Published: December 2021

The essential role of auxin in plant growth and development is well known. Pathways related to auxin synthesis, transport and signaling have been extensively studied in recent years, and the PIN-FORMED (PIN) protein family has been identified as being pivotal for polar auxin transport and distribution. However, research focused on the functional characterization of PIN proteins in rice is still lacking. In this study, we investigated the expression and function of OsPIN1c and OsPIN1d in the japonica rice variety (Nipponbare) using gene knockout and high-throughput RNA sequencing analysis. The results showed that OsPIN1c and OsPIN1d were mainly expressed in young panicles and exhibited a redundant function. Furthermore, OsPIN1c or OsPIN1d loss-of-function mutants presented a mild phenotype compared with the wild type. However, in addition to significantly decreased plant height and tiller number, panicle development was severely disrupted in double-mutant lines of OsPIN1c and OsPIN1d. Severe defects included smaller inflorescence meristem and panicle sizes, fewer primary branches, elongated bract leaves, non-degraded hair and no spikelet growth. Interestingly, ospin1cd-3, a double-mutant line with functional retention of OsPIN1d, showed milder defects than those observed in other mutants. Additionally, several critical regulators of reproductive development, such as OsPID, LAX1, OsMADS1 and OsSPL14/IPA1, were differentially expressed in ospin1c-1 ospin1d-1, supporting the hypothesis that OsPIN1c and OsPIN1d are involved in regulating panicle development. Therefore, this study provides novel insights into the auxin pathways that regulate plant reproductive development in monocots.
Toward synthetic plant development
Authors: Brophy Jennifer A N
Published: December 2021

The ability to engineer plant form will enable the production of novel agricultural products designed to tolerate extreme stresses, boost yield, reduce waste, and improve manufacturing practices. While historically, plants were altered through breeding to change their size or shape, advances in our understanding of plant development and our ability to genetically engineer complex eukaryotes are leading to the direct engineering of plant structure. In this review, I highlight the central role of auxin in plant development and the synthetic biology approaches that could be used to turn auxin-response regulators into powerful tools for modifying plant form. I hypothesize that recoded, gain-of-function auxin response proteins combined with synthetic regulation could be used to override endogenous auxin signaling and control plant structure. I also argue that auxin-response regulators are key to engineering development in nonmodel plants and that single-cell -omics techniques will be essential for characterizing and modifying auxin response in these plants. Collectively, advances in synthetic biology, single-cell -omics, and our understanding of the molecular mechanisms underpinning development have set the stage for a new era in the engineering of plant structure.
Inhibition of structural joint damage progression with upadacitinib in rheumatoid arthritis: 1-year outcomes from the SELECT phase 3 program
Authors: Peterfy Charles G , Strand Vibeke , Friedman Alan , Hall Stephen , Mysler Eduardo , Durez Patrick , Baraliakos Xenofon , Enejosa Jeffrey V , Shaw Tim , Li Yihan , Chen Su , Song In-Ho
Published: December 2021

Objectives

To evaluate the inhibition of progression of structural joint damage through week 48 in patients with moderately to severely active RA receiving upadacitinib as monotherapy or in combination with MTX.

Methods

Radiographic progression was assessed in two phase 3 randomized controlled trials. MTX-naïve patients were randomized to upadacitinib 15 or 30 mg once daily or MTX monotherapy (SELECT-EARLY, n = 945), while MTX inadequate responders (IRs) were randomized to upadacitinib 15 mg once daily or adalimumab 40 mg every other week or placebo added to background MTX (SELECT-COMPARE, n = 1629). The mean changes from baseline in modified total Sharp score (mTSS), joint space narrowing and erosion scores were determined. Data were analysed both by linear extrapolation for missing data imputation and treatment switching and as observed.

Results

In patients naïve or with limited exposure to MTX (SELECT-EARLY), mean changes from baseline to week 48 in mTSS were 0.03 for upadacitinib 15 mg, 0.14 for upadacitinib 30 mg and 1.00 for MTX based on linear extrapolation (P < 0.001 for both upadacitinib doses vs MTX). Among patients with an inadequate response to MTX (SELECT-COMPARE), the mean change from baseline in mTSS was significantly reduced in the upadacitinib 15 mg plus MTX group vs placebo plus MTX (0.28 vs 1.73; P < 0.001). The mean change from baseline in the adalimumab plus MTX group was 0.39.

Conclusion

Upadacitinib monotherapy or in combination with background MTX was effective in inhibiting the progression of structural joint damage through week 48 in MTX-naïve and MTX-IR patients with RA.

Trial registration

ClinicalTrials.gov (https://clinicaltrials.gov), NCT02706873 and NCT02629159
Precision feeding gestating sows: effects on offspring growth performance and carcass and loin quality at slaughter
Authors: Hansen Lauren L , Stewart Victoria , Mandell Ira B , Huber Lee-Anne
Published: December 2021

A total of 601 pigs from 65 litters were used to determine the effects of closely meeting estimated daily Lys and energy requirements for sows during gestation for three consecutive parities on offspring postweaning growth performance and carcass and loin quality at slaughter. Sows were assigned a control (static diet composition; CON) or precision (individual daily blend of two diets to meet estimated Lys and energy requirements; PRE) feeding program between days 7 and 110 of gestation for three consecutive pregnancy cycles, starting with primiparous sows (parity 1: 12 CON and 12 PRE sows; parity 2: 8 CON and 13 PRE sows; parity 3: 8 CON and 12 PRE sows). At weaning (20 ± 2 d of age), up to 10 pigs per litter were randomly selected and placed in a pen (1 litter per pen). All pens received ad libitum access to commercial diets in six phases (four-phase nursery, grower, and finisher, respectively). Four pigs per pen were slaughtered at ~125 kg BW for evaluation of carcass characteristics and loin quality. The ADG and ADFI of offspring were not influenced by maternal feeding program in any parity during nursery phases I through III. During nursery phase IV, ADG and ADFI were greater for litters from PRE- vs. CON-fed sows (0.70 vs. 0.66 ± 0.03 and 1.15 vs. 1.08 ± 0.06 kg/d for ADG and ADFI, respectively; P < 0.05). The BW for litters from PRE- vs. CON-fed sows tended to be greater by day 66 of age (end of nursery period; 29.7 vs. 28.7 ± 1.1 kg; P = 0.076). Within the grower phase, litters from PRE-fed sows had a greater ADG in parity 2 but lower ADG in parity 3 vs. litters from CON-fed sows (0.99 vs. 0.94 and 0.93 vs. 1.01 ± 0.03 kg/d for parities 2 and 3, respectively; P < 0.05). No differences were observed for ADG or ADFI in the finisher phase or G:F in any phase for any parity. Loin eye area was smaller (52.2 vs. 55.0 ± 1.8 cm2; P < 0.05) for offspring from PRE- vs. CON-fed sows. In parity 2, carcass lean yield tended to be less for offspring from PRE- vs. CON-fed sows (58.6 vs. 59.6 ± 0.4%; P = 0.051). Minimal differences were observed for subjective and objective evaluations of loin quality. Closely meeting the estimated daily energy and Lys requirements for sows throughout gestation for three consecutive pregnancy cycles improved offspring growth performance (ADG and ADFI) in the final nursery stage, but generally did not affect growth performance in grower/finisher periods or carcass and loin quality at ~125 kg BW.
Assessing Direct and Residual Effects of Cover Crops on the Soybean Cyst Nematode, Heterodera glycines
Authors: Harbach Chelsea J. , Tylka Gregory L.
Published: December 2021

Greenhouse experiments were conducted to determine if cover crops directly decrease population densities of the soybean cyst nematode (SCN), Heterodera glycines, and/or have residual effects on reproduction of the nematode on soybean (Glycine max). Population densities of SCN were not significantly decreased by nine cover crop plants or three cover crop mixes compared with a non-planted soil control in a repeated 60-day-long greenhouse experiment. When susceptible soybeans were grown in the soils after cover crop growth, fewer SCN females formed after three annual ryegrass (Lolium multiflorum) cultivars (Bounty, King, and RootMax), the Daikon radish (Raphanus sativus var. longipinnatus) cultivar CCS779, Kodiak mustard (Brassica juncea), and a mix containing cereal rye, crimson clover (Trifolium incarnatum), plus Daikon radish (cultivars not stated) compared with following the non-planted control. In another repeated experiment, cover crops were grown for 56 days in SCN-infested soil in the greenhouse then exposed to Iowa winter conditions for 28 days to simulate winter termination of the plants. One treatment, a cover crop mix containing ‘Bounty’ annual ryegrass plus ‘Enricher’ Daikon radish, had a decrease in SCN population density greater than the non-planted control at the end of the experiment. Significantly fewer SCN females formed on soybeans grown after several cover crops, including the three annual ryegrass cultivars that had the suppressive residual effects in the first experiment. In summary, there were no cover crop treatments that consistently decreased SCN population densities across experiments, and only one cover crop treatment in one experiment significantly reduced SCN population densities more than a non-planted soil control. However, there was a somewhat consistent, adverse, residual effect of cover crops on reproduction of SCN on susceptible soybeans after growth of multiple cover crops.