bluuebunny/crossref_metadata_2025_split 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

Abstract
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

Abstract
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

Abstract
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

Abstract

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

Abstract
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

Abstract

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* &lt;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 &lt; 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

AbstractAimsThere 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 resultsPatients (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 &lt; 0.001) patients.ConclusionThe 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 registrationThe 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

Abstract
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

Abstract

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

Abstract

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 &lt; 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

Abstract
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

Abstract

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.