bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of Aesthetical and Functional Complications after Total Parotidectomy. First Long-Term Experiences with Dermal Matrix Surgimend ® in Patient Affected by Malignant Parotid Tumors
Authors: Bonavolonta Paola , Iaconetta Giorgio , Improda Giovanni , Germano Cristiana , Borriello Gerardo , Goglia Federica , Abbate Vincenzo , Piombino Pasquale , Califano Luigi , Dell’Aversana Orabona Giovanni
Published: July 2022

Background

This is an observational cohort study on patients affected by malignant parotid tumors treated with total parotidectomy. The aim of our work is to analyze and compare the effects and complications after parotidectomy, using or not SurgiMend ®.

Methods

40 patients were retrospectively enrolled between September 2014 and June 2020. Basing on the placement of SurgiMend ® for parotid lodge reconstruction, the samples were divided into two groups. Thus, the incidence rate of complications after the surgical procedure was analyzed between the two groups.

Results

Patients in whom SurgiMend ® was used reported a lower rate of complications. The ANOVA test (p = 0.05) revealed a significant difference of Vancouver Scar Scale (VSS) between the two groups, representation as vascularity and pigmentation improvement, changing scar color, scar height reduction, and increased pliability.

Conclusion

Although many techniques are available to fill the parotidectomy defect, improve facial contour and prevent Frey’s syndrome, the use of SurgiMend ® matrix is one of most effective and reliable method to address these complications, with the advantage of decreased operative time due to not require an additional surgical donor site.
Machine learning in scientific grant review: algorithmically predicting project efficiency in high energy physics
Authors: Sikimić Vlasta , Radovanović Sandro
Published: July 2022

As more objections have been raised against grant peer-review for being costly and time-consuming, the legitimate question arises whether machine learning algorithms could help assess the epistemic efficiency of the proposed projects. As a case study, we investigated whether project efficiency in high energy physics (HEP) can be algorithmically predicted based on the data from the proposal. To analyze the potential of algorithmic prediction in HEP, we conducted a study on data about the structure (project duration, team number, and team size) and outcomes (citations per paper) of HEP experiments with the goal of predicting their efficiency. In the first step, we assessed the project efficiency using Data Envelopment Analysis (DEA) of 67 experiments conducted in the HEP laboratory Fermilab. In the second step, we employed predictive algorithms to detect which team structures maximize the epistemic performance of an expert group. For this purpose, we used the efficiency scores obtained by DEA and applied predictive algorithms – lasso and ridge linear regression, neural network, and gradient boosted trees – on them. The results of the predictive analyses show moderately high accuracy (mean absolute error equal to 0.123), indicating that they can be beneficial as one of the steps in grant review. Still, their applicability in practice should be approached with caution. Some of the limitations of the algorithmic approach are the unreliability of citation patterns, unobservable variables that influence scientific success, and the potential predictability of the model.
Influence of order-disorder transition on the mechanical and thermophysical properties of A2B2O7 high-entropy ceramics
Authors: Zhu Jiatong , Wei Mingyue , Xu Jie , Yang Runwu , Meng Xuanyu , Zhang Ping , Yang Jinlong , Li Guangzhong , Gao Feng
Published: July 2022

The order-disorder transition (ODT) of A2B2O7 compounds obtained enormous attention owing to the potential application for thermal barrier coating (TBC) design. In this work, the influence of ODT on the mechanical and thermophysical properties of dual-phase A2B2O7 high-entropy ceramics was investigated by substituting Ce4+ and Hf4+ with different ionic radii on B-sites (Zr4+). The X-ray diffraction (XRD), Raman, and transmission electron microscopy (TEM) results show that $$r_{\rm{A}^{3+}}/r_{\rm{B}^{4+}}=1.47$$

r

A

3
+

/

r

B

4
+

=
1.47
is the critical value of ODT phase boundary with different doping B-site ion contents, and the energy dispersive spectroscopy (EDS) results further indicate the uniform distribution of elements. Interestingly, owing to the high intrinsic disorder derived from high-entropy effect, the A2B2O7 high-entropy ceramics exhibit unreduced modulus (E0 ≈ 230 GPa) and enhanced mechanical properties (HV ≈ 10 GPa, KIC ≈ 2.3 MPa·m0.5). A2B2O7 high-entropy ceramics exhibit excellent thermal stability with relatively high thermal expansion coefficients (TECs) (Hf0.25, 11.20×10−6 K−1, 1000 °C). Moreover, the matching calculation implied that the ODT further enhances the phonon scattering coefficient, leading to a relatively lower thermal conductivity of (La0.25Eu0.25Gd0.25Yb0.25)2(Zr0.85Ce0.15)2O7 (1.48–1.51 W/(m·K), 100–500 °C) compared with other components. This present work provides a novel composition design principle for high-entropy ceramics, as well as a material selection rule for high-temperature insulation applications.
Automated geometry measurement and deep rolling of butt welds
Authors: Heide Klaas Maximilian , Heikebrügge Steffen , Dänekas Christian , Breidenstein Bernd , Schaumann Peter
Published: July 2022

During the joining of two metal sheets by welding, a process-specific geometry of the weld is created. The local geometry of the created weld has a decisive influence on its fatigue strength. This is due to stress concentration at the geometric notches. In this paper, a process known from mechanical engineering called deep rolling is applied on butt welds. The influence on the local weld geometry and the local stress concentration after deep rolling is investigated. Additionally, a novel automated measurement system using optical laser line scanning is presented. The system is qualified for the evaluation of the local weld geometry regarding its flank angles and toe radii. The presented investigations show that the deep rolling process influences the stress concentrations determined by 2D-FE-simulations using real scan data. A correlation between the difference in toe radii or local notch stresses before and after deep rolling and the initial flank angle was found. This indicates that there are process and geometry specific conditions for the successful application of the deep rolling process.
A classification tree and decomposition based multi-objective evolutionary algorithm with adaptive operator selection
Authors: Geng Huantong , Xu Ke , Zhang Yanqi , Zhou Zhengli
Published: July 2022

Adaptive operator selection (AOS) is used to dynamically select the appropriate genic operator for offspring reproduction, which aims to improve the performance of evolutionary algorithms (EAs) by producing high-quality offspring during the evolutionary process. This paper proposes a novel classification tree based adaptive operator selection strategy for multi-objective evolutionary algorithm based on decomposition (MOEA/D-CTAOS). In our proposal, the classification tree is trained by the recorded data set which contains the information on the historical offspring. Before the reproduction at each generation, the classifier is used to predict each possible result obtained by different operators, and only one operator with the best result is selected to generate offspring next. Meanwhile, a novel differential evolution based on search inertia (SiDE) is designed to steer the evolutionary process in a more efficient way. The experimental results demonstrate that proposed MOEA/D-CTAOS outperforms other MOEA/D variants on UF and LZ benchmarks in terms of IGD and HV value. Further investigation also confirms the advantage of direction-guided search strategy in SiDE.
M&A and early investment decisions by digital platforms
Authors: Brutti Zelda , Rojas Luis E.
Published: July 2022

We propose an original theoretical framework that models early investment decisions of digital platform startups and use it to study how merger and acquisition policy affects consumer welfare by shaping such decisions. We formalize the investment options faced by digital platforms into a dual margin: investment in ‘customer engagement technology’, directed towards expanding the user base and in ‘intermediation technology’, directed towards lowering operational costs. Synergies through technological transfer and increased investment incentives in customer engagement explain consumer welfare improvements in the case of M&As occurring between platforms with disjoint user bases. On the other hand, lower competition erodes consumer welfare in the case of allowing M&As between platforms with overlapping user bases. We conclude that M&A policy guidance should depend on the relationship between the incumbent’s and startup’s target users and on the ability of the startup to catch up with the incumbent.
An equivalent approach for modelling butterfly-hysteresis passive variable friction damper
Authors: Wen Wenlu , Luo Ma , Chen Lin , Ma Zhenxiao , Pan Wen
Published: July 2022

This research work proposes an equivalent approach modelling the peculiar hysteretic behavior of passive variable friction damper, for engineers who call for a simplified way to simulate such damper in anti-earthquake engineering practice with acceptable accuracy. This approach models the special nonlinear behavior of the damper via paralleling 3 basic link elements that commonly built-in commercially available structural analysis software, instead of developing direct hysteretic model that demands for both post development functionality on software side and programming skill on engineer side. The mathematical derivation and analytical geometric equating work are comprehensively conducted. The numerical accuracy of analysis output yielded using equivalent model is digitally verified against the one yielded using generic FEM simulation of the same damper subject to several loading cases. Code-automated optimization workflow for yielding product-wise modelling parameters is developed that is convenient and straightforward for application by engineers without requirement of high expertise, which is demonstrated by generating optimized parameters to equivalently model tested specimen.

Article highlights

Passive variable friction damper can be modelled by assembling friction spring, elastic spring and wen model into parallel.

Code-automated optimization process can locate the most ideal modelling parameters combination in predefined numeral fields.

Hysteretic behaviors yielded from equivalent modelling approach match well corresponding ones from generic FEA simulation.
A preliminary study on wellbore flow interpretation of fiber optic vibration signals based on K-means clustering algorithm
Authors: Wu Xianzu , Gan Lixiong , Yuan Shixiong , Rui Deng
Published: July 2022

The wellbore flow analysis of optical fiber vibration signal depends on distributed optical fiber logging. Distributed optical fiber logging technology identifies the fluid in the well through distributed optical fiber acoustic sensor (DAS) and distributed optical fiber temperature sensor (DTS). Distributed optical fiber sensor has the advantages of small underground interference, high efficiency and low cost. In this paper, the wellhead data extracted by the distributed optical fiber acoustic sensor is used to calculate the upper bound of the fluid sound frequency band in the pipe by nonlinear least squares fitting. The K-means clustering algorithm is used to cluster the optical fiber vibration signals in the low frequency band. According to the clustering results, the ratio of the optical fiber signal eigenvalues of each production layers is obtained, and the trend of the ratio of the optical fiber signal eigenvalues of each production layers is judged to be close to the trend of the water absorption intensity. Compared with traditional acoustic logging, the wellbore flow analysis using distributed optical fiber acoustic sensor can quickly determine the production contribution of each layer and the change of fluid phase state in the production cycle. Combined with traditional production logging technology, distributed optical fiber logging shows its reliability and accuracy in data collection, logging interpretation and production application. Starting from the principle of distributed optical fiber acoustic sensing technology, this paper briefly expounds the properties of distributed optical fiber acoustic sensor and the principle of injection profile logging, systematically introduces the processing of distributed optical fiber acoustic data, and emphatically introduces the accuracy of K-means clustering algorithm for analyzing distributed optical fiber acoustic signal and qualitative judgment of production layer, which provides a new idea for judging the accuracy of production layers.
Type D Personality Independently Predicts Erectile Dysfunction in Taiwanese Young Men
Authors: Fan Yu-Hua , Liou Ying-Jay , Cheng Wei-Ming
Published: July 2022

Background

Studies have demonstrated that erectile dysfunction has a well-established bidirectional relationship with depression and have indicated an independent association of type D personality (TDP) with depression. Nevertheless, the relationship of erectile dysfunction with TDP has not been sufficiently examined.

Aim

To examine the associations among depression symptoms, TDP, and erectile dysfunction.

Methods

The cross-sectional study recruited 1740 sexually active Taiwanese men (age: 20–40 years) with erectile dysfunction. Participants completed an online questionnaire collecting general demographic information and containing the International Index of Erectile Function-5, Type D Scale-14, and Depression and Somatic Symptom Scale. Pearson’s chi squared or Student’s t’test was conducted for comparisons between participants with vs without TDP. We conducted multivariate and univariate logistic regression analysis to investigate the predictors of moderate/severe erectile dysfunction.

Outcomes

The prevalence of TDP and moderate/severe erectile dysfunction, the associations between TDP and the severities of depression symptoms and erectile dysfunction, and independent risk factors for moderate/severe erectile dysfunction.

Results

A total of 360 (15.9%) and 941 (54.08%) men had moderate/severe erectile dysfunction and TDP, respectively. Men with TDP reported significantly higher total and subscale scores in the International Index of Erectile Function-5 and the Depression and Somatic Symptom Scale; this group also exhibited higher prevalence of moderate or severe erectile dysfunction. According to the univariate analysis, all variables significantly predicted moderate or severe erectile dysfunction except for age and body mass index. A multivariate analysis revealed TDP status and depression symptoms to be independent predictors of moderate or severe erectile dysfunction. With regard to subscales of the Type D Scale-14, we discovered that social inhibition had a greater influence on moderate or severe erectile dysfunction than had negative affectivity. A mediation analysis indicated that the relationship between TDP and erectile dysfunction was mediated by depressive symptoms.

Clinical Implications

Research has suggested that compared with the general population, individuals with TDP are less willing to seek medical consultation, have lower medication adherence, and have heightened risk of depression; urologists should strive to identify patients with TDP.

Strengths & Limitations

This study is the first to investigate the association of TDP with erectile dysfunction in a large population of young men by using validated instruments. Conclusions on causality cannot be drawn due to the study’s cross-sectional nature.

Conclusion

This research revealed relationships among TDP, depression symptoms, and erectile dysfunction in Taiwanese young men.
Is Law Like Social Sciences? On ‘New Private Law Theory’ and the Call for Disciplinary Pluralism
Authors: Resta Giorgio
Published: July 2022

This article reflects upon the challenges arising from a “pluralistic” approach to private law theory. Having distinguished the different meanings of the notion of “pluralism”, it focuses on epistemic pluralism and stresses the importance of an interdisciplinary stance. At the same time, it criticizes the emphasis put mainly on the dialogue with social sciences, clearly mirrored by the traditional organization of the ERC panels. Finally, it advocates a deeper and more critical engagement with the economic approaches to law.
Civil Courts and Delocalized Justice: Reflections on the Shell Nigeria Cases in Light of Theories of Communication and Constitutionalization
Authors: Mak Chantal
Published: July 2022

In conversation with several chapters of Stefan Grundmann’s, Hans Micklitz’s, and Moritz Renner’s book on New Private Law Theory, this paper reflects on contributions that theories of communication and constitutionalization can make to our understanding of the changing role of private law in a globalizing world. More abstract ideals are checked against an assessment of recent judgments of Dutch courts in cases regarding oil company Shell’s responsibility for environmental pollution in Nigeria. Such theoretical readings of case law, it is held, in the spirit of New Private Law Theory, show new directions that private law theories may choose in order to understand and strengthen the private-legal framework for societal questions of our times.
Sex differences in longevity are relative, not independent
Authors: Wallentin Mikkel
Published: July 2022

I ask three questions related to the claims made within the staying alive theory (SAT): Is survival more fitness-enhancing for females than for males? Does the historical record on sex differences in mortality support the SAT? Is it possible to talk about “independent selective pressures on both male and female traits” when all we have are sex/gender comparisons?
Toward a more domain-specific conceptualization of female traits: A commentary on Benenson et al. (2022)
Authors: Crosby Courtney L. , Hahnel-Peeters Rebecka K. , Buss David M.
Published: July 2022

Benenson et al. (2022) amass impressive evidence of robust sex differences as support for expanding “staying alive” theory. We argue for a broader and more domain-specific conceptualization focusing on life history tradeoffs between survival and mating success. Using three examples – women's disgust, fear of rape, and cultivation of bodyguards – we illustrate these tradeoffs and suggest a broader theoretical framework.
Staying alive enhances both women's and men's fitness
Authors: Hagen Renée V. , Knorr Delaney A. , Li Sally , Mensing Ashley , Scelza Brooke A.
Published: July 2022

We argue that Benenson et al. need to consider not only sex differences in the effects of care on offspring survival but also in age-specific fertility when predicting how longevity affects fitness. We review evidence that staying alive has important effects on both women's and men's fitness, and encourage consideration of alternative explanations for observed sex differences in threat responses.
Bronchiolitis obliterans organising pneumonia secondary to tacrolimus toxicity in a pediatric cardiac transplant recipient
Authors: Karim Farida , Misra Amrit , Sehgal Swati
Published: July 2022

Background:

Bronchiolitis obliterans organising pneumonia is a rare complication associated with calcineurin inhibitors and mammalian target of rapamycin inhibitors. While bronchiolitis obliterans organising pneumonia in adult transplant patients has been reported, it has not been well described in pediatric transplant patients.

Case description:

We present a case of a 19-month-old male patient with dilated cardiomyopathy who underwent orthotropic heart transplantation at 14 months of life for heart failure refractory to medical therapy. Approximately 4 months post-transplant, he presented with diarrhea and vomiting with acute kidney injury secondary to dehydration. His tacrolimus level on admission and first week of hospitalisation was within target range of 10–12 ng/ml. He was diagnosed with esophagitis and prescribed proton pump inhibitors. Our patient subsequently developed significant respiratory distress with initial chest radiograph showing right lower lobe opacities. Repeat tacrolimus at the time of worsening respiratory status was 84.2 ng/dL and his tacrolimus was held. He required intubation due to significant hypoxia with progression of lung to disease and development of diffuse bilateral opacities consistent with acute respiratory distress syndrome. Despite initiation of steroids and aggressive ventilator management, he continued to be hypoxic on maximal respiratory support. After 28 days post admission, support was withdrawn. On autopsy, his lung biopsy findings were consistent with bronchiolitis obliterans organising pneumonia.

Conclusion:

Life-threatening bronchiolitis obliterans organising pneumonia can be seen in pediatric transplant patients on tacrolimus or when transitioning from tacrolimus to sirolimus, highlighting the need for close monitoring of heart transplant patients on immunosuppressive medications presenting with hypoxia.
Schematherapie
Authors: Jacob Gitta , Arntz Arnoud
Published: July 2022

Die Schematherapie ist eine wichtige Weiterentwicklung der kognitiven Verhaltenstherapie (KVT) für Patientinnen und Patienten mit Persönlichkeitsstörungen und anderen chronischen psychischen Problemen. In Studien hat sich insbesondere die Arbeit mit dem Schemamodus-Ansatz als hoch wirksam erwiesen. In der aktualisierten Auflage des Bandes, die insbesondere auch aktuelle Befunde zur Evidenz referiert, wird die Behandlung mit dem Modusmodell praxisnah dargestellt. Zahlreiche Fallbeispiele illustrieren das therapeutische Vorgehen.
Nach einer Einführung in die Kernkonzepte der Schematherapie wird auf die Diagnostik und Fallkonzeptualisierung eingegangen. Im Anschluss wird das therapeutische Vorgehen für jeden Modustyp erläutert. Wichtige Schwerpunkte bilden dabei die therapeutische Beziehung, die als begrenztes Nachbeeltern konzipiert ist, sowie emotionsfokussierende Techniken, wie z.B. Stuhldialoge und imaginative Techniken. In diesen beiden Punkten unterscheidet sich die Schematherapie besonders von der klassischen KVT. Typische Fallstricke und Probleme in einer Schematherapie sowie mögliche Variationen des Vorgehens werden ebenfalls beschrieben. Insgesamt bietet der Band eine kompakte Darstellung der Arbeit mit dem Schemamodus-Ansatz bei Persönlichkeitsstörungen.
Community Science Project Helps Track Geohazard Risks in Uganda
Authors: Dacey James
Published: July 2022

A community project in the Kigezi Highlands is helping to identify landslide and flooding hot spots and how the hazards are evolving.
Valley Networks and the Record of Glaciation on Ancient Mars
Authors: Grau Galofre A. , Whipple K. X. , Christensen P. R. , Conway S. J.
Published: July 2022

The lack of evidence for large‐scale glacial landscapes on Mars has led to the belief that ancient glaciations had to be frozen to the ground. Here we propose that the fingerprints of Martian wet‐based glaciation should be the remnants of the ice sheet drainage system instead of landforms generally associated with terrestrial ice sheets. We use the terrestrial glacial hydrology framework to interrogate how the Martian surface gravity affects glacial hydrology, ice sliding, and glacial erosion. Taking as reference the ancient southern circumpolar ice sheet that deposited the Dorsa Argentea formation, we compare the theoretical behavior of identical ice sheets on Mars and Earth and show that, whereas on Earth glacial drainage is predominantly inefficient, enhancing ice sliding and erosion, on Mars the lower gravity favors the formation of efficient subglacial drainage. The apparent lack of large‐scale glacial fingerprints on Mars, such as drumlins or lineations, is to be expected.
Circular RNA ROCK1, a novel circRNA, suppresses osteosarcoma proliferation and migration via altering the miR-532-5p/PTEN axis
Authors: Liu Yize , Qiu Guanzhen , Luo Yinzhou , Li Shanshan , Xu Yeqiu , Zhang Yuanzhuang , Hu Jiayuan , Li Peifeng , Pan Hai , Wang Yong
Published: July 2022

As the most prevalent bone tumor in children and adolescents, the pathogenesis and metastasis of osteosarcoma (OS) remain largely unclear. Here, we investigated the expression and function of a novel circular RNA (circRNA), circROCK1-E3/E4, which is back-spliced from exons 3 and 4 of Rho-associated coiled-coil containing protein kinase 1 (ROCK1) in OS. We found that circROCK1-E3/E4, regulated by the well-known RNA-binding protein quaking (QKI), was downregulated in OS and correlated with unfavorable clinical features of patients with OS. Functional proliferation and cell motility assays indicated that circROCK1-E3/E4 serves as a tumor suppressor in OS cells. Mechanistically, circROCK1-E3/E4 suppressed proliferation and migration by upregulating phosphatase and tensin homolog (PTEN) through microRNA-532-5p (miR-532-5p) sponging. In the constructed nude mouse model, circROCK1-E3/E4 inhibited tumor growth and lung metastasis in vivo. This study demonstrates the functions and molecular mechanisms of circROCK1-E3/E4 in the progression of OS. These findings may identify novel targets for the molecular therapy of OS.
Dietary regulation in health and disease
Authors: Wu Qi , Gao Zhi-Jie , Yu Xin , Wang Ping
Published: July 2022

Nutriments have been deemed to impact all physiopathologic processes. Recent evidences in molecular medicine and clinical trials have demonstrated that adequate nutrition treatments are the golden criterion for extending healthspan and delaying ageing in various species such as yeast, drosophila, rodent, primate and human. It emerges to develop the precision-nutrition therapeutics to slow age-related biological processes and treat diverse diseases. However, the nutritive advantages frequently diversify among individuals as well as organs and tissues, which brings challenges in this field. In this review, we summarize the different forms of dietary interventions extensively prescribed for healthspan improvement and disease treatment in pre-clinical or clinical. We discuss the nutrient-mediated mechanisms including metabolic regulators, nutritive metabolism pathways, epigenetic mechanisms and circadian clocks. Comparably, we describe diet-responsive effectors by which dietary interventions influence the endocrinic, immunological, microbial and neural states responsible for improving health and preventing multiple diseases in humans. Furthermore, we expatiate diverse patterns of dietotheroapies, including different fasting, calorie-restricted diet, ketogenic diet, high-fibre diet, plants-based diet, protein restriction diet or diet with specific reduction in amino acids or microelements, potentially affecting the health and morbid states. Altogether, we emphasize the profound nutritional therapy, and highlight the crosstalk among explored mechanisms and critical factors to develop individualized therapeutic approaches and predictors.
Polygenic resilience scores capture protective genetic effects for Alzheimer’s disease
Authors: Hou Jiahui , Hess Jonathan L. , Armstrong Nicola , Bis Joshua C. , Grenier-Boley Benjamin , Karlsson Ida K. , Leonenko Ganna , Numbers Katya , O’Brien Eleanor K. , Shadrin Alexey , Thalamuthu Anbupalam , Yang Qiong , Andreassen Ole A. , Brodaty Henry , Gatz Margaret , Kochan Nicole A. , Lambert Jean-Charles , Laws Simon M. , Masters Colin L. , Mather Karen A. , Pedersen Nancy L. , Posthuma Danielle , Sachdev Perminder S. , Williams Julie ,   the Alzheimer’s Disease Neuroimaging Initiative, Fan Chun Chieh , Faraone Stephen V. , Fennema-Notestine Christine , Lin Shu-Ju , Escott-Price Valentina , Holmans Peter , Seshadri Sudha , Tsuang Ming T. , Kremen William S. , Glatt Stephen J.
Published: July 2022

Polygenic risk scores (PRSs) can boost risk prediction in late-onset Alzheimer’s disease (LOAD) beyond apolipoprotein E (APOE) but have not been leveraged to identify genetic resilience factors. Here, we sought to identify resilience-conferring common genetic variants in (1) unaffected individuals having high PRSs for LOAD, and (2) unaffected APOE-ε4 carriers also having high PRSs for LOAD. We used genome-wide association study (GWAS) to contrast “resilient” unaffected individuals at the highest genetic risk for LOAD with LOAD cases at comparable risk. From GWAS results, we constructed polygenic resilience scores to aggregate the addictive contributions of risk-orthogonal common variants that promote resilience to LOAD. Replication of resilience scores was undertaken in eight independent studies. We successfully replicated two polygenic resilience scores that reduce genetic risk penetrance for LOAD. We also showed that polygenic resilience scores positively correlate with polygenic risk scores in unaffected individuals, perhaps aiding in staving off disease. Our findings align with the hypothesis that a combination of risk-independent common variants mediates resilience to LOAD by moderating genetic disease risk.
Professionalism in dentistry: deconstructing common terminology
Authors: Trathen Andrew , Scambler Sasha , Gallagher Jennifer E.
Published: July 2022

Background

There is a social expectation that dentists demonstrate professionalism. Although the General Dental Council puts it at the heart of their regulatory agenda, there is not yet consensus on the meaning and implications of the term.

Objective

To explore practising dentists’ understanding of the character traits commonly associated with professionalism and what these mean in practice.

Method

Constructivist grounded theory was employed throughout this study. Qualitative, in-depth interviews were conducted with dental professionals in England recruited through theoretical sampling to saturation point. Interviews used a topic guide informed by the literature, and analysis was conducted through constant comparison during data collection.

Results

The study found that traits commonly associated with professionalism in the literature were difficult for dentists to define clearly or operationalise in a clinical setting. There was disagreement over how some traits should be understood, and it was unclear to participants how, or indeed if, the listed traits were directly relevant to practice in their current form.

Conclusion

Rather than expecting unconditional adherence to an externally imposed definition, further exploration is required to understand how health professionals make sense of professionalism by reference to their lived experiences and worldviews.

In Brief

Institutional expectations of professionalism, defined through character traits and behaviours, do not appear to map neatly on to the experiences of dental professionals.

Straightforward, apparently uncontroversial terms elicited a wide range of responses, including disagreement. This brought in to question whether achieving consensus is possible.

Analysing how our respondents understood the terms by reference to the meanings they constructed from lived experience offers deeper insights.
UFL1 promotes antiviral immune response by maintaining STING stability independent of UFMylation
Authors: Tao Yijie , Yin Shulei , Liu Yang , Li Chunzhen , Chen Yining , Han Dan , Huang Jingyi , Xu Sheng , Zou Zui , Yu Yizhi
Published: July 2022

The precise regulation of STING homeostasis is essential for its antiviral function. Post-translational modification, especially ubiquitination, is important for the regulation of STING homeostasis. Previous studies have focused on how STING is degraded, but little is known about its maintenance. Here, we show that UFM1 specific ligase UFL1 promotes innate immune response by maintaining STING expression independent of UFMylation. Mechanistically, UFL1 inhibits TRIM29 to interact with STING, thereby reducing its ubiquitination at K338/K347/K370 and subsequent proteasomal degradation. DNA virus infection reduces the UFL1 expression, which may promote STING degradation and facilitate viral expansion. Our study identifies UFL1 as a crucial regulator for the maintenance of STING stability and antiviral function, and provides novel insights into the mechanistic explanation for the immunological escape of DNA virus.
Endothelial Caspase-8 prevents fatal necroptotic hemorrhage caused by commensal bacteria
Authors: Bader Stefanie M. , Preston Simon P. , Saliba Katie , Lipszyc Adam , Grant Zoe L. , Mackiewicz Liana , Baldi Andrew , Hempel Anne , Clark Michelle P. , Peiris Thanushi , Clow William , Bjelic Jan , Stutz Michael D. , Arandjelovic Philip , Teale Jack , Du Fashuo , Coultas Leigh , Murphy James M. , Allison Cody C. , Pellegrini Marc , Samson Andre L.
Published: July 2022

Caspase-8 transduces signals from death receptor ligands, such as tumor necrosis factor, to drive potent responses including inflammation, cell proliferation or cell death. This is a developmentally essential function because in utero deletion of endothelial Caspase-8 causes systemic circulatory collapse during embryogenesis. Whether endothelial Caspase-8 is also required for cardiovascular patency during adulthood was unknown. To address this question, we used an inducible Cre recombinase system to delete endothelial Casp8 in 6-week-old conditionally gene-targeted mice. Extensive whole body vascular gene targeting was confirmed, yet the dominant phenotype was fatal hemorrhagic lesions exclusively within the small intestine. The emergence of these intestinal lesions was not a maladaptive immune response to endothelial Caspase-8-deficiency, but instead relied upon aberrant Toll-like receptor sensing of microbial commensals and tumor necrosis factor receptor signaling. This lethal phenotype was prevented in compound mutant mice that lacked the necroptotic cell death effector, MLKL. Thus, distinct from its systemic role during embryogenesis, our data show that dysregulated microbial- and death receptor-signaling uniquely culminate in the adult mouse small intestine to unleash MLKL-dependent necroptotic hemorrhage after loss of endothelial Caspase-8. These data support a critical role for Caspase-8 in preserving gut vascular integrity in the face of microbial commensals.
Innovative multidimensional models in a high-throughput-format for different cell types of endocrine origin
Authors: Bornstein Stefan , Shapiro Igor , Malyukov Maria , Züllig Richard , Luca Edlira , Gelfgat Evgeny , Beuschlein Felix , Nölting Svenja , Berruti Alfredo , Sigala Sandra , Peitzsch Mirko , Steenblock Charlotte , Ludwig Barbara , Kugelmeier Patrick , Hantel Constanze
Published: July 2022

The adrenal gland provides an important function by integrating neuronal, immune, vascular, metabolic and endocrine signals under a common organ capsule. It is the central organ of the stress response system and has been implicated in numerous stress-related disorders. While for other diseases, regeneration of healthy organ tissue has been aimed at such approaches are lacking for endocrine diseases - with the exception of type-I-diabetes. Moreover, adrenal tumor formation is very common, however, appropriate high-throughput applications reflecting the high heterogeneity and furthermore relevant 3D-structures in vitro are still widely lacking. Recently, we have initiated the development of standardized multidimensional models of a variety of endocrine cell/tissue sources in a new multiwell-format. Firstly, we confirmed common applicability for pancreatic pseudo-islets. Next, we translated applicability for spheroid establishment to adrenocortical cell lines as well as patient material to establish spheroids from malignant, but also benign adrenal tumors. We aimed furthermore at the development of bovine derived healthy adrenal organoids and were able to establish steroidogenic active organoids containing both, cells of cortical and medullary origin. Overall, we hope to open new avenues for basic research, endocrine cancer and adrenal tissue-replacement-therapies as we demonstrate potential for innovative mechanistic insights and personalized medicine in endocrine (tumor)-biology.
UPF1/circRPPH1/ATF3 feedback loop promotes the malignant phenotype and stemness of GSCs
Authors: Xu Jinkun , Zhang Guoqing , Hu Jinpeng , Li Hao , Zhao Junshuang , Zong Shengliang , Guo Zhengting , Jiang Yang , Jing Zhitao
Published: July 2022

Glioblastoma multiforme (GBM) is the most lethal type of craniocerebral gliomas. Glioma stem cells (GSCs) are fundamental reasons for the malignancy and recurrence of GBM. Revealing the critical mechanism within GSCs’ self-renewal ability is essential. Our study found a novel circular RNA (circRPPH1) that was up-regulated in GSCs and correlated with poor survival. The effect of circRPPH1 on the malignant phenotype and self-renewal of GSCs was detected in vitro and in vivo. Mechanistically, UPF1 can bind to circRPPH1 and maintain its stability. Therefore, more existing circRPPH1 can interact with transcription factor ATF3 to further transcribe UPF1 and Nestin expression. It formed a feedback loop to keep a stable stream for stemness biomarker Nestin to strengthen tumorigenesis of GSCs continually. Besides, ATF3 can activate the TGF-β signaling to drive GSCs for tumorigenesis. Knocking down the expression of circRPPH1 significantly inhibited the proliferation and clonogenicity of GSCs both in vitro and in vivo. The overexpression of circRPPH1 enhanced the self-renewal of GSCs. Our findings suggest that UPF1/circRPPH1/ATF3 maintains the potential self-renewal of GSCs through interacting with RNA-binding protein and activating the TGF-β signal pathway. Breaking the feedback loop against self-renewing GSCs may represent a novel therapeutic target in GBM treatment.
Exosomal circPABPC1 promotes colorectal cancer liver metastases by regulating HMGA2 in the nucleus and BMP4/ADAM19 in the cytoplasm
Authors: Li Yang , Hu Jialei , Wang Meng , Yuan Yihang , Zhou Fangyuan , Zhao Haosen , Qiu Tianming , Liang Leilei
Published: July 2022

Liver metastasis is the leading cause of death in colorectal carcinoma (CRC). However, little is known about the mechanisms of transferring effector messages between the primary tumor and the site of metastasis. Exosomes provide a novel transfer message method, and exosomal circular RNAs (circRNAs) play critical regulatory roles in cancer biology. In this study, the results showed that the expression of circPABPC1 was aberrantly upregulated in CRC tissues and exosomes. Exosomal circPABPC1 was considered an oncogene by functional experimental analysis in vitro and in vivo. Mechanistically, circPABPC1 recruited KDM4C to the HMGA2 promoter, reduced its H3K9me3 modification and initiated the transcription process in the nucleus. Moreover, cytoplasmic circPABPC1 promoted CRC progression by protecting ADAM19 and BMP4 from miR-874-/miR-1292-mediated degradation. Our findings indicated that exosomal circPABPC1 is an essential regulator in CRC liver metastasis progression by promoting HMGA2 and BMP4/ADAM19 expression. CircPABPC1 is expected to be a novel biomarker and antimetastatic therapeutic target in CRC.
Landscape of somatic alterations in large-scale solid tumors from an Asian population
Authors: Wu Liqun , Yao Herui , Chen Hui , Wang Aodi , Guo Kun , Gou Wenli , Yu Yanfei , Li Xiang , Yao Ming , Yuan Shaohua , Pang Fei , Hu Jinwei , Chen Lijuan , Liu Wenjin , Yao Jicheng , Zhang Shuirong , Dong Xiaowei , Wang Weifeng , Hu Jing , Ling Qi , Ding Songming , Wei Yan , Li Qiang , Cao Weichun , Wang Shuang , Di Yang , Feng Feiling , Zhao Gang , Zhang Jian , Huang Ling , Xu Jia , Yan Wangjun , Tong Zhongsheng , Jiang Da , Ji Tao , Li Qiao , Xu Ling , He Huiying , Shang Liang , Liu Jin , Wang Kefeng , Wu Duoguang , Shen Jingnan , Liu Ye , Zhang Ting , Liang Chaojie , Wang Yusheng , Shang Yanhong , Guo Jianji , Liang Guanbiao , Xu Shifeng , Liu Junfeng , Wang Kai , Wang Minghui
Published: July 2022

Extending the benefits of tumor molecular profiling for all cancer patients requires a comprehensive analysis of tumor genomes across distinct patient populations worldwide. In this study, we perform deep next-generation DNA sequencing (NGS) from tumor tissues and matched blood specimens from over 10,000 patients in China by using a 450-gene comprehensive assay, developed and implemented under international clinical regulations. We perform a comprehensive comparison of somatically altered genes, the distribution of tumor mutational burden (TMB), gene fusion patterns, and the spectrum of various somatic alterations between Chinese and American patient populations. Here, we show 64% of cancers from Chinese patients in this study have clinically actionable genomic alterations, which may affect clinical decisions related to targeted therapy or immunotherapy. These findings describe the similarities and differences between tumors from Chinese and American patients, providing valuable information for personalized medicine.
Natural variation of DROT1 confers drought adaptation in upland rice
Authors: Sun Xingming , Xiong Haiyan , Jiang Conghui , Zhang Dongmei , Yang Zengling , Huang Yuanping , Zhu Wanbin , Ma Shuaishuai , Duan Junzhi , Wang Xin , Liu Wei , Guo Haifeng , Li Gangling , Qi Jiawei , Liang Chaobo , Zhang Zhanying , Li Jinjie , Zhang Hongliang , Han Lujia , Zhou Yihua , Peng Youliang , Li Zichao
Published: July 2022

Upland rice is a distinct ecotype that grows in aerobic environments and tolerates drought stress. However, the genetic basis of its drought resistance is unclear. Here, using an integrative approach combining a genome-wide association study with analyses of introgression lines and transcriptomic profiles, we identify a gene, DROUGHT1 (DROT1), encoding a COBRA-like protein that confers drought resistance in rice. DROT1 is specifically expressed in vascular bundles and is directly repressed by ERF3 and activated by ERF71, both drought-responsive transcription factors. DROT1 improves drought resistance by adjusting cell wall structure by increasing cellulose content and maintaining cellulose crystallinity. A C-to-T single-nucleotide variation in the promoter increases DROT1 expression and drought resistance in upland rice. The potential elite haplotype of DROT1 in upland rice could originate in wild rice (O. rufipogon) and may be beneficial for breeding upland rice varieties.
Discovering the drivers of clonal hematopoiesis
Authors: Pich Oriol , Reyes-Salazar Iker , Gonzalez-Perez Abel , Lopez-Bigas Nuria
Published: July 2022

Mutations in genes that confer a selective advantage to hematopoietic stem cells (HSCs) drive clonal hematopoiesis (CH). While some CH drivers have been identified, the compendium of all genes able to drive CH upon mutations in HSCs remains incomplete. Exploiting signals of positive selection in blood somatic mutations may be an effective way to identify CH driver genes, analogously to cancer. Using the tumor sample in blood/tumor pairs as reference, we identify blood somatic mutations across more than 12,000 donors from two large cancer genomics cohorts. The application of IntOGen, a driver discovery pipeline, to both cohorts, and more than 24,000 targeted sequenced samples yields a list of close to 70 genes with signals of positive selection in CH, available at http://www.intogen.org/ch. This approach recovers known CH genes, and discovers other candidates.
Postmitotic differentiation of human monocytes requires cohesin-structured chromatin
Authors: Minderjahn Julia , Fischer Alexander , Maier Konstantin , Mendes Karina , Nuetzel Margit , Raithel Johanna , Stanewsky Hanna , Ackermann Ute , Månsson Robert , Gebhard Claudia , Rehli Michael
Published: July 2022

Cohesin is a major structural component of mammalian genomes and is required to maintain loop structures. While acute depletion in short-term culture models suggests a limited importance of cohesin for steady-state transcriptional circuits, long-term studies are hampered by essential functions of cohesin during replication. Here, we study genome architecture in a postmitotic differentiation setting, the differentiation of human blood monocytes (MO). We profile and compare epigenetic, transcriptome and 3D conformation landscapes during MO differentiation (either into dendritic cells or macrophages) across the genome and detect numerous architectural changes, ranging from higher level compartments down to chromatin loops. Changes in loop structures correlate with cohesin-binding, as well as epigenetic and transcriptional changes during differentiation. Functional studies show that the siRNA-mediated depletion of cohesin (and to a lesser extent also CTCF) markedly disturbs loop structures and dysregulates genes and enhancers that are primarily regulated during normal MO differentiation. In addition, gene activation programs in cohesin-depleted MO-derived macrophages are disturbed. Our findings implicate an essential function of cohesin in controlling long-term, differentiation- and activation-associated gene expression programs.
Development of a nanoparticle-based immunotherapy targeting PD-L1 and PLK1 for lung cancer treatment
Authors: Reda Moataz , Ngamcherdtrakul Worapol , Nelson Molly A. , Siriwon Natnaree , Wang Ruijie , Zaidan Husam Y. , Bejan Daniel S. , Reda Sherif , Hoang Ngoc Ha , Crumrine Noah A. , Rehwaldt Justin P. C. , Bindal Akash , Mills Gordon B. , Gray Joe W. , Yantasee Wassana
Published: July 2022

Immune checkpoint inhibitors (ICIs) targeting PD-L1 and PD-1 have improved survival in a subset of patients with advanced non-small cell lung cancer (NSCLC). However, only a minority of NSCLC patients respond to ICIs, highlighting the need for superior immunotherapy. Herein, we report on a nanoparticle-based immunotherapy termed ARAC (Antigen Release Agent and Checkpoint Inhibitor) designed to enhance the efficacy of PD-L1 inhibitor. ARAC is a nanoparticle co-delivering PLK1 inhibitor (volasertib) and PD-L1 antibody. PLK1 is a key mitotic kinase that is overexpressed in various cancers including NSCLC and drives cancer growth. Inhibition of PLK1 selectively kills cancer cells and upregulates PD-L1 expression in surviving cancer cells thereby providing opportunity for ARAC targeted delivery in a feedforward manner. ARAC reduces effective doses of volasertib and PD-L1 antibody by 5-fold in a metastatic lung tumor model (LLC-JSP) and the effect is mainly mediated by CD8+ T cells. ARAC also shows efficacy in another lung tumor model (KLN-205), which does not respond to CTLA-4 and PD-1 inhibitor combination. This study highlights a rational combination strategy to augment existing therapies by utilizing our nanoparticle platform that can load multiple cargo types at once.
Supercurrent diode effect and magnetochiral anisotropy in few-layer NbSe2
Authors: Bauriedl Lorenz , Bäuml Christian , Fuchs Lorenz , Baumgartner Christian , Paulik Nicolas , Bauer Jonas M. , Lin Kai-Qiang , Lupton John M. , Taniguchi Takashi , Watanabe Kenji , Strunk Christoph , Paradiso Nicola
Published: July 2022

Nonreciprocal transport refers to charge transfer processes that are sensitive to the bias polarity. Until recently, nonreciprocal transport was studied only in dissipative systems, where the nonreciprocal quantity is the resistance. Recent experiments have, however, demonstrated nonreciprocal supercurrent leading to the observation of a supercurrent diode effect in Rashba superconductors. Here we report on a supercurrent diode effect in NbSe2 constrictions obtained by patterning NbSe2 flakes with both even and odd layer number. The observed rectification is a consequence of the valley-Zeeman spin-orbit interaction. We demonstrate a rectification efficiency as large as 60%, considerably larger than the efficiency of devices based on Rashba superconductors. In agreement with recent theory for superconducting transition metal dichalcogenides, we show that the effect is driven by the out-of-plane component of the magnetic field. Remarkably, we find that the effect becomes field-asymmetric in the presence of an additional in-plane field component transverse to the current direction. Supercurrent diodes offer a further degree of freedom in designing superconducting quantum electronics with the high degree of integrability offered by van der Waals materials.