bluuebunny/crossref_metadata_2025 huggingface dataset:
Enoxacin Up‐Regulates MicroRNA Biogenesis and Down‐Regulates Cytotoxic CD8 T‐Cell Function in Autoimmune Cholangitis
Authors: Itoh Arata , Adams David , Huang Wenting , Wu Yuehong , Kachapati Kritika , Bednar Kyle J. , Leung Patrick S. C. , Zhang Weici , Flavell Richard A. , Gershwin M. Eric , Ridgway William M.
Published: January 2021

Background and Aims

Primary biliary cholangitis (PBC) is a prototypical organ‐specific autoimmune disease that is mediated by autoreactive T‐cell attack and destruction of cholangiocytes. Despite the clear role of autoimmunity in PBC, immune‐directed therapies have failed to halt PBC, including biologic therapies effective in other autoimmune diseases. MicroRNA (miRNA) dysregulation is implicated in the pathogenesis (PBC). In the dominant‐negative TGF‐β receptor type II (dnTGFβRII) mouse model of PBC, autoreactive CD8 T cells play a major pathogenic role and demonstrate a striking pattern of miRNA down‐regulation. Enoxacin is a small molecule fluoroquinolone that enhances miRNA biogenesis, partly by stabilizing the interaction of transactivation response RNA‐binding protein with Argonaute (Ago) 2.

Approach and Results

We hypothesized that correcting aberrant T‐cell miRNA expression with enoxacin in dnTGFβRII mice could modulate autoreactive T‐cell function and prevent PBC. Here, we show that liver‐infiltrating dnTGFβRII CD8 T cells have significantly decreased levels of the miRNA biogenesis molecules prolyl 4‐hydroxylase subunit alpha 1 (P4HA1) and Ago2 along with significantly increased levels of granzyme B and perforin. Enoxacin treatment significantly up‐regulated miRNAs in dnTGFβRII CD8 T cells and effectively treated autoimmune cholangitis in dnTGFβRII mice. Enoxacin treatment directly altered T cells both ex vivo and in vitro, resulting in altered memory subset numbers, decreased proliferation, and decreased interferon‐γ production. Enoxacin significantly decreased CD8 T‐cell expression of the transcription factor, Runx3, and significantly decreased perforin expression at both the mRNA and protein levels.

Conclusions

Enoxacin increases miRNA expression in dnTGFβRII CD8 T cells, reduces CD8 T‐cell pathogenicity, and effectively halted progression of autoimmune biliary disease. Targeting the miRNA pathway is a therapeutic approach to autoimmunity that corrects pathological miRNA abnormalities in autoreactive T cells.
Mother's exposure to domestic and community violence and its association with child's behavioral outcomes
Authors: Chen Wan‐Yi , Lee Yookyong
Published: January 2021

This study investigated the potential cumulative effect of maternal exposure to violence both at home and in community on children. This study used the data (N = 2506) from the Fragile Families and Child Wellbeing study. We found that maternal nonphysical victimization, either by witnessing violence in the community or by experiencing psychological domestic violence, had a direct negative effect on children's depression and anxiety. Maternal nonphysical victimization also indirectly elevated child's aggression through mother's use of psychological and physical aggression toward the child. Witnessing community violence by mothers, directly and indirectly, worsened the child's withdrawal behaviors through the mother's psychological aggression toward the child. Mother's direct victimization by community violence and physical domestic violence was not related to child's behavioral outcomes after controlling for other risk factors. This study points to important considerations for devising intervention and prevention for mothers and children. Implications for research and practice are discussed.
Applying “think‐pair‐share” for virtual curriculum retreat
Authors: Ramesh Aruna , Case Allison , Stockstill Leah , Dragan Irina
Published: January 2021

With coronavirus disease 2019 (COVID‐19) leading to ubiquitous changes across the education system, Tufts University School of Dental Medicine took advantage of their new, fast‐changing environment to foster engagement among faculty members regarding curricular modifications and their impact on assessment outcomes. A virtual curricular retreat was planned, where adaptations could be discussed through the lens of Miller's Pyramid. The retreat provided an opportunity for faculty to participate in a guided dialogue via a “think‐pair‐share” activity that resulted in documenting the outcomes of recent curriculum changes while allowing for reflection for future improvement.
Follow‐up of SARS‐CoV‐2 positive subgroup from the Asymptomatic novel CORonavirus iNFection study
Authors: Meyers Kristin J. , Dillman Brian , Williams Charles , Jiang Jianfei , Clifford Nancy , Miller Jennifer L. , Jones Meghan E. , Goetz Iris A. , Botros Fady T. , Knorr Jack , Manner David H. , Woodward Brad
Published: January 2021

A nested longitudinal study within theAsymptomatic novel CORonavirus iNFfection study followed participants with positive nasopharyngeal swab to query for development of symptoms and assess duration of positive reverse transcription‐polymerase chain reaction (RT‐PCR) test results. Of the 91 participants initially testing positive, 86 participated in follow‐up approximately 14 days after study enrollment; of those 86 participants, 19 (22.1%) developed at least one symptom at any time after the initial positive severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) test result. The median number of days to symptom development after their initial positive test result was 6 (range 1–29 days). No participants reported a SARS‐CoV‐2‐related hospitalization. The most frequently reported symptoms were fatigue or muscle aches (10.5%), headache (9.3%), fever (5.8%), and shortness of breath (5.8%). Of the 78 participants who submitted a nasopharyngeal swab for repeat RT‐PCR testing, 17 (21.8%) remained positive at Day 14, 4 of which continued to test positive at Day 28. These findings reinforce the probable role of silent SARS‐CoV‐2 infections in community transmission, and that reliance on symptom development will miss a large proportion of infections. Broad testing programs not limited to individuals presenting with symptoms are critical for identifying persons with SARS‐CoV‐2 infection and ultimately slowing transmission.
Cochlear Implantation in Meniere's Disease: A Systematic Review and Meta‐Analysis
Authors: Villavisanis Dillan F. , Mavrommatis Maria A. , Berson Elisa R. , Bellaire Christopher P. , Rutland John W. , Fan Caleb J. , Wanna George B. , Cosetti Maura K.
Published: January 2021

Objectives/Hypothesis

Meniere's disease (MD) is a debilitating condition characterized by hearing loss, vertigo, and tinnitus. The objective of this study was to systematically investigate outcomes in MD after cochlear implantation (CoI), with and without labyrinthectomy.

Study Design

Systematic review and meta‐analysis.

Methods

A systematic review of articles in Medline and Embase was performed to identify all studies of patients with MD who underwent CoI. This analysis evaluates outcomes of speech recognition, pure tone audiometry, vertigo, tinnitus, and quality of life.

Results

Of 321 studies identified, 37 were included, involving 216 patients. Mean age at implantation was 61.4 years (range 27–85 years) with average length of follow‐up at 1.7 years (range 0–9 years). Forty‐four (20.4%) patients underwent labyrinthectomy. Meta‐analysis demonstrated significant improvements in audiometric outcomes following CoI. There was a statistically significant improvement in Hearing in Noise Test performance, with a mean difference improvement of 44.7 (95% confidence interval [CI] [8.8, 80.6]) at 6 months and 60.1 (95% CI [35.3, 85.0]) at 12 months. The Freiburger Monosyllabic Test (FMT) and Consonant‐Nucleus‐Consonant (CNC) also improved significantly, with mean difference improvements of 46.2 (95% CI [30.0, 62.4]) for FMT and 19.3 (95% CI [8.1, 30.4]) for CNC. There was a statistically significant decrease in tinnitus, as measured by a mean difference reduction of 48.1 (95% CI [1.0, 95.2]) in the Tinnitus Handicap Index.

Conclusions

CoI with and without simultaneous labyrinthectomy is a viable treatment option for patients with MD, yielding high rates of tinnitus suppression and vertigo control. Post‐CoI MD patients demonstrate similar postoperative speech perception outcomes to non‐MD implant recipients. Laryngoscope, 131:1845–1854, 2021
Role of plunge depth on the joint formation and mechanical behavior of Al6063‐AZ91 dissimilar lap joint produced by friction stir welding
Authors: Supriyanka R. , Kondaiah V.V. , Raju L.R. , Dumpala R. , Ratna Sunil B.
Published: January 2021

Dissimilar lap joint of Al6063 aluminium and AZ91 magnesium alloys was successfully produced by friction stir welding. Three different plunge depths (3.2 mm, 3.25 mm, and 3.3 mm) were adopted during welding. Similar Al6063–Al6063 lap joints were also produced along with the dissimilar Al6063–AZ91 joints for the purpose of comparing the joint formation. With the increased plunge depth, the width of the similar Al6063 ‐ Al6063 lap joint was increased. On the contrary, joint width was decreased for the dissimilar joint with increased plunge depths. The dissimilar joint was formed with a strong metallurgical bonding between the Al6063 and AZ91 alloys, which is attributed to the mechanical mixing of these alloys in the nugget zone. Additionally, the formation of intermetallics was also observed from the x‐ray diffraction analysis. The variations within the measured hardness values were higher at the joint interface due to the mixing of aluminium and magnesium alloys in the nugget zone. From the tensile shear tests, increased strength and decreased elongation were measured with the increased plunge depth. The results demonstrate the importance of the plunge depth on the lap joint formation between dissimilar Al6063–AZ91 alloys during friction stir welding.
Machining characteristics, wear and corrosion behavior of AZ91 magnesium alloy ‐ fly ash composites produced by friction stir processing
Authors: Patle H. , Sunil B.R. , Dumpala R.
Published: January 2021

In the present work, fine grained AZ91 magnesium alloy – fly ash composite has been successfully fabricated by friction stir processing. Microhardness measurements show marginally higher hardness with uniform distribution compared with the base material. No significant difference in the mean cutting force was observed during drilling of the base metal and the composite. However, lower cutting forces were recorded in the sub‐surface region of the composites. Interestingly, decreased corrosion resistance was noticed for the composite compared with the base material. Lower mass loss has been observed for the composite during reciprocating wear experiments. The results strongly suggest that the surface composite of AZ91 magnesium alloy – fly ash exhibits better mechanical and wear properties. However, decreased corrosion resistance is a significant observation that warns the applicability of these composites in corroding environment.
Magnetic resonance parameter mapping using model‐guided self‐supervised deep learning
Authors: Liu Fang , Kijowski Richard , El Fakhri Georges , Feng Li
Published: January 2021

Purpose

To develop a model‐guided self‐supervised deep learning MRI reconstruction framework called reference‐free latent map extraction (RELAX) for rapid quantitative MR parameter mapping.

Methods

Two physical models are incorporated for network training in RELAX, including the inherent MR imaging model and a quantitative model that is used to fit parameters in quantitative MRI. By enforcing these physical model constraints, RELAX eliminates the need for full sampled reference data sets that are required in standard supervised learning. Meanwhile, RELAX also enables direct reconstruction of corresponding MR parameter maps from undersampled k‐space. Generic sparsity constraints used in conventional iterative reconstruction, such as the total variation constraint, can be additionally included in the RELAX framework to improve reconstruction quality. The performance of RELAX was tested for accelerated T1 and T2 mapping in both simulated and actually acquired MRI data sets and was compared with supervised learning and conventional constrained reconstruction for suppressing noise and/or undersampling‐induced artifacts.

Results

In the simulated data sets, RELAX generated good T1/T2 maps in the presence of noise and/or undersampling artifacts, comparable to artifact/noise‐free ground truth. The inclusion of a spatial total variation constraint helps improve image quality. For the in vivo T1/T2 mapping data sets, RELAX achieved superior reconstruction quality compared with conventional iterative reconstruction, and similar reconstruction performance to supervised deep learning reconstruction.

Conclusion

This work has demonstrated the initial feasibility of rapid quantitative MR parameter mapping based on self‐supervised deep learning. The RELAX framework may also be further extended to other quantitative MRI applications by incorporating corresponding quantitative imaging models.
Theoretical Analysis of the Heterocyclic [4+2] Cycloaddition Between Pyridinium Ion and Enol Ether
Authors: Nakahara Masataka , Hanaya Kengo , Sugai Takeshi , Higashibayashi Shuhei
Published: January 2021

Dearomative heterocyclic [4+2] cycloaddition between the N‐(2,4‐dinitrophenyl)pyridinium ion of nicotinamide and an enol ether was analyzed by Density Functional Theory (DFT) calculations. The calculation revealed that the reaction undergoes stepwise bond formation rather than occurring in a concerted manner. The experimental products were found to be both kinetically and thermodynamically favored. The calculated transition states and intermediate suggested that the high diastereoselectivity is derived from the electrostatic interaction between the 2‐nitro group of the pyridinium ion and the hydrogen of the enol ether.
Looking Forward to the Year's Regulatory Agenda
Authors: Moody Chris
Published: January 2021

Last year, while the country adjusted to a changing world faced with new challenges from COVID‐19, and despite an active deregulatory agenda, the US Environmental Protection Agency (USEPA) continued to develop regulations for the water sector.
Regulation of the microsomal proteome by salicylic acid and deficiency of phosphatidylinositol‐4‐kinases β1 and β2 in Arabidopsis thaliana
Authors: Junková Petra , Neubergerová Michaela , Kalachova Tetiana , Valentová Olga , Janda Martin
Published: January 2021

Phosphatidylinositol‐4‐kinases β1 and β2 (PI4Kβ1/PI4Kβ2), which are responsible for phosphorylation of phosphatidylinositol to phosphatidylinositol‐4‐phosphate, have important roles in plant vesicular trafficking. Moreover, PI4Kβ1/PI4Kβ2 negatively regulates biosynthesis of phytohormone salicylic acid (SA), a key player in plant immune responses. The study focused on the effect of PI4Kβ1/PI4Kβ2 deficiency and SA level on the proteome of microsomal fraction. For that purpose we used four Arabidopsis thaliana genotypes: wild type; double mutant with impaired function of PI4Kβ1/PI4Kβ2 (pi4kβ1/pi4kβ2) exhibiting high SA level; sid2 mutant with impaired SA biosynthesis depending on the isochorismate synthase 1 and triple mutant sid2/pi4kβ1/pi4kβ2. We identified 1797 proteins whose levels were changed between genotypes. We showed that increased SA concentration affected the levels of 473 proteins. This includes typical SA pathway markers but also points to connections between SA pathway and clathrin‐independent endocytosis (flotillins) and exocytosis/protein secretion (syntaxins, tetraspanin) to be investigated in future. In contrast to SA, the absence of PI4Kβ1/PI4Kβ2 itself affected only 27 proteins. Among them we identified CERK1, a receptor for chitin. Although PI4Kβ1/PI4Kβ2 deficiency itself did not have a substantial impact on the proteome of the microsomal fraction, our data clearly show that it enhances proteome changes when SA pathway is modulated in parallel.
Predicting models of depression or complicated grief among bereaved family members of patients with cancer
Authors: Aoyama Maho , Miyashita Mitsunori , Masukawa Kento , Morita Tatsuya , Kizawa Yoshiyuki , Tsuneto Satoru , Shima Yasuo , Akechi Tatsuo
Published: January 2021

Objective

To derive and validate a risk scoring system for predicting major depressive disorder (MDD) and complicated grief (CG) among bereaved family members of patients with cancer that is feasible for clinical use.

Methods

We conducted a secondary analysis of two cross‐sectional nationwide bereavement surveys in Japan. From a total of 17,312 bereaved family members of patients with cancer, 8618 and 8619 were randomly assigned to a derivation and a validation group. The Patient Health Questionnaire 9 (PHQ‐9) and the Brief Grief Questionnaire (BGQ) were used to assess MDD (PHQ‐9 score ≥ 10) and CG (BGQ score ≥ 8), respectively. We compared five models with potential predictive variables that could be easily obtained in daily practice and were included in the bereavement survey (i.e., sociodemographic data).

Results

The model which included variables such as the families' physical/mental health status and preparedness toward bereavement, in addition to their sociodemographic data, was considered modest for predicting the risk of both MDD and CG. The areas around the curve for MDD and CG were 0.74 (95% CI: 0.73–0.76) and 0.74 (95% CI: 0.72–0.75) and 0.78 (95% CI: 0.76–0.79) and 0.77 (95% CI: 0.76–0.79) in the derivation and validation groups, respectively.

Conclusions

We developed a clinical risk score for predicting MDD and CG among bereaved family members of patients with cancer. However, further research is needed for external validation and assessment regarding its implementation in actual practice.
Early predictions of response and survival from a tumor dynamics model in patients with recurrent, metastatic head and neck squamous cell carcinoma treated with immunotherapy
Authors: González‐García Ignacio , Pierre Vadryn , Dubois Vincent F. S. , Morsli Nassim , Spencer Stuart , Baverel Paul G. , Moore Helen
Published: January 2021

We developed and evaluated a method for making early predictions of best overall response (BOR) and overall survival at 6 months (OS6) in patients with cancer treated with immunotherapy. This method combines machine learning with modeling of longitudinal tumor size data. We applied our method to data from durvalumab‐exposed patients with recurrent/metastatic head and neck cancer. A fivefold cross‐validation was used for model selection. Independent trial data, with various degrees of data truncation, were used for model validation. Mean classification error rates (90% confidence intervals [CIs]) from cross‐validation were 5.99% (90% CI 2.98%–7.50%) for BOR and 19.8% (90% CI 15.8%–39.3%) for OS6. During model validation, the area under the receiver operating characteristic curves was preserved for BOR (0.97, 0.97, and 0.94) and OS6 (0.85, 0.84, and 0.82) at 24, 18, and 12 weeks, respectively. These results suggest our method predicts trial outcomes accurately from early data and could be used to aid drug development.
Effects of phytochemicals on macrophage cholesterol efflux capacity: Impact on atherosclerosis
Authors: Soltani Saba , Boozari Motahareh , Cicero Arrigo F. G. , Jamialahmadi Tannaz , Sahebkar Amirhossein
Published: January 2021

High‐density lipoprotein cholesterol (HDL) is the major promoter of reverse cholesterol transport and efflux of excess cellular cholesterol. The functions of HDL, such as cholesterol efflux, are associated with cardiovascular disease rather than HDL levels. We have reviewed the evidence base on the major classes of phytochemicals, including polyphenols, alkaloids, carotenoids, phytosterols, and fatty acids, and their effects on macrophage cholesterol efflux and its major pathways. Phytochemicals show the potential to improve the efficiency of each of these pathways. The findings are mainly in preclinical studies, and more clinical research is warranted in this area to develop novel clinical applications.
On the probabilistic degree of OR over the reals
Authors: Bhandari Siddharth , Harsha Prahladh , Molli Tulasimohan , Srinivasan Srikanth
Published: January 2021

We study the probabilistic degree over of the OR function on n variables. For , the ‐error probabilistic degree of any Boolean function f : {0, 1}n → {0, 1} over is the smallest nonnegative integer d such that the following holds: there exists a distribution P of polynomials of degree at most d such that for all , we have . It is known from the works of Tarui (Theoret. Comput. Sci. 1993) and Beigel, Reingold, and Spielman (Proc. 6th CCC 1991), that the ‐error probabilistic degree of the OR function is at most . Our first observation is that this can be improved to which is better for small values of . In all known constructions of probabilistic polynomials for the OR function (including the above improvement), the polynomials P in the support of the distribution P have the following special structure: where each Li(x1, … , xn) is a linear form in the variables x1, … , xn, that is, the polynomial is a product of affine forms. We show that the ‐error probabilistic degree of OR when restricted to polynomials of the above form is , thus matching the above upper bound (up to poly‐logarithmic factors).
A new remarkably preserved fossil assassin bug (Insecta, Heteroptera, Reduviidae) from the Eocene Green River Formation of Colorado
Authors: Swanson Daniel R. , Heads Sam W. , Taylor Steven J. , Wang Yinan
Published: January 2021

We describe a new Eocene fossil assassin bug, Aphelicophontes danjuddi gen. et sp. nov. (Reduviidae: Harpactorinae), from the Green River Formation of Colorado. The specimens informing this description are extraordinarily preserved, particularly in the external and internal structures of the adult male genitalia. We discuss implications of the new species for the systematics and evolutionary history of the group, as well as the strength of phylogenetic signal in harpactorine genitalia.
IGFBPs mediate IGF-1's functions in retinal lamination and photoreceptor development during pluripotent stem cell differentiation to retinal organoids
Authors: Zerti Darin , Molina Marina Moya , Dorgau Birthe , Mearns Sarah , Bauer Roman , Al-Aama Jumana , Lako Majlinda
Published: January 2021

Development of the retina is regulated by growth factors, such as insulin-like growth factors 1 and 2 (IGF-1/2), which coordinate proliferation, differentiation, and maturation of the neuroepithelial precursors cells. In the circulation, IGF-1/2 are transported by the insulin growth factor binding proteins (IGFBPs) family members. IGFBPs can impact positively and negatively on IGF-1, by making it available or sequestering IGF-1 to or from its receptor. In this study, we investigated the expression of IGFBPs and their role in the generation of human retinal organoids from human pluripotent stem cells, showing a dynamic expression pattern suggestive of different IGFBPs being used in a stage-specific manner to mediate IGF-1 functions. Our data show that IGF-1 addition to culture media facilitated the generation of retinal organoids displaying the typical laminated structure and photoreceptor maturation. The organoids cultured in the absence of IGF-1, lacked the typical laminated structure at the early stages of differentiation and contained significantly less photoreceptors and more retinal ganglion cells at the later stages of differentiation, confirming the positive effects of IGF-1 on retinal lamination and photoreceptor development. The organoids cultured with the IGFBP inhibitor (NBI-31772) and IGF-1 showed lack of retinal lamination at the early stages of differentiation, an increased propensity to generate horizontal cells at mid-stages of differentiation and reduced photoreceptor development at the later stages of differentiation. Together these data suggest that IGFBPs enable IGF-1's role in retinal lamination and photoreceptor development in a stage-specific manner.
How User-Centered Design Supports Situation Awareness for Complex Interfaces
Authors: Oury Jacob D. , Ritter Frank E.
Published: January 2021

This chapter moves the discussion of how to design an operation center down a level towards implementation. We present user-centered design (UCD) as a distinct design philosophy to replace user experience (UX) when designing systems like the Water Detection System (WDS). Just like any other component (e.g., electrical system, communications networks), the operator has safe operating conditions, expected error rates, and predictable performance, albeit with a more variable range for the associated metrics. However, analyzing the operator’s capabilities, like any other component in a large system, helps developers create reliable, effective systems that mitigate risks of system failure due to human error in integrated human–machine systems (e.g., air traffic control). With UCD as a design philosophy, we argue that situation awareness (SA) is an effective framework for developing successful UCD systems. SA is an established framework that describes operator performance via their ability to create and maintain a mental model of the information necessary to achieve their task. SA describes performance as a function of the operator’s ability to perceive useful information, comprehend its significance, and predict future system states. Alongside detailed explanations of UCD and SA, this chapter presents further guidance and examples demonstrating how to implement these concepts in real systems.
Cognition and Operator Performance
Authors: Oury Jacob D. , Ritter Frank E.
Published: January 2021

Developing systems that foster situation awareness in operators requires that stakeholders can make informed decisions about the design. These decisions must account for the operator’s underlying cognitive processes based on perception, comprehension, and projection of the system state. This chapter reviews the core cognitive processes responsible for monitoring and responding to changes in system state. Operators must perceive information before they can act in response, and the interface design affects operator accuracy and speed via known mechanisms (i.e., effects of color on visual search time). Perception of key information also relies on how the operator thinks during tasks, and certain design choices can support better attention control and detection of signals. After perceiving the information, operators also must comprehend and interpret the information. Design guidance and factors related to supporting comprehension are presented alongside explanations of how cognitive load and working memory affect the operator’s ability to develop and maintain a useful mental model of the system. This review of cognitive mechanisms gives designers a strong foundation to make informed decisions ranging from choosing an alarm color to assessing how much information should be on screen at once.
Conclusion and Final Comments
Authors: Oury Jacob D. , Ritter Frank E.
Published: January 2021

The foundational design philosophy of user-centered design (UCD) offers an ideal approach for systems engineers, programmers, designers, and any other stakeholder involved with the design of high-stakes systems with human operators. Furthermore, UCD, as presented here, is tailor-made to meet the unique needs of critical human–machine systems in systems like air traffic control towers, 911 call centers, or NASA’s Mission Control Center. Whenever the operator is a mission-critical component of the system, stakeholders must be able to make informed decisions during the design process, and this book provides the tools necessary to make those decisions.
Key Issues and Progress in Understanding Climate Risk in Africa
Authors: Vincent Katharine , Conway Declan
Published: January 2021

Adaptations and strategies to build resilience are needed to manage current impacts and will be increasingly vital as the world continues to warm. But making adaptation decisions can be complex, requiring careful consideration of multiple factors and perspectives, and balancing different priorities over different timescales. Society is embarking on a learning process that will continue for decades. This chapter and the book it introduces aim to contribute to this process. The book draws extensively from the Future Climate for Africa (FCFA) research programme that aimed to support adaptation and resilience in sub-Saharan Africa. In this chapter, we first briefly review the planning landscape for adaptation and building resilience and then consider how applications are changing the nature of climate information and the context of its use. This is followed by a review of the current status of climate information, particularly future projections for Africa and the enduring challenge that uncertainty represents to their active use. We then ask how we can improve the use of climate information for resilience building and adaptation and present an overview of the coming chapters. The demand for information and guidance on adaptation is continuing to grow, and is highlighting the need for new types and formats of data, and more innovative interactions with users to increase usability and application. Climate plays a dynamic role within complex, rapidly evolving social-ecological systems; this requires the climate science, resilience and adaptation communities to engage widely with other sectors and actors to make the agenda relevant and tractable for policy and practice.
Scale and isolation sensitivity of diphoton distributions at the LHC
Authors: Gehrmann Thomas , Glover Nigel , Huss Alexander , Whitehead James
Published: January 2021

Abstract

Precision measurements of diphoton distributions at the LHC display some tension with theory predictions, obtained at next-to-next-to-leading order (NNLO) in QCD. We revisit the theoretical uncertainties arising from the approximation of the experimental photon isolation by smooth-cone isolation, and from the choice of functional form for the renormalisation and factorisation scales. We find that the resulting variations are substantial overall, and enhanced in certain regions. We discuss the infrared sensitivity at the cone boundaries in cone-based isolation in related distributions. Finally, we compare predictions made with alternative choices of dynamical scale and isolation prescriptions to experimental data from ATLAS at 8 TeV, observing improved agreement. This contrasts with previous results, highlighting that scale choice and isolation prescription are potential sources of theoretical uncertainty that were previously underestimated.
HIF1α is a direct regulator of steroidogenesis in the adrenal gland
Authors: Watts Deepika , Stein Johanna , Meneses Ana , Bechmann Nicole , Neuwirth Ales , Kaden Denise , Krüger Anja , Sinha Anupam , Alexaki Vasileia Ismini , Luis Gustavo Perez-Rivas  , Kircher Stefan , Martinez Antoine , Theodoropoulou Marily , Eisenhofer Graeme , Peitzsch Mirko , El-Armouche Ali , Chavakis Triantafyllos , Wielockx Ben
Published: January 2021

Endogenous steroid hormones, especially glucocorticoids and mineralocorticoids, derive from the adrenal cortex, and drastic or sustained changes in their circulatory levels affect multiple organ systems. Although hypoxia signaling in steroidogenesis has been suggested, knowledge on the true impact of the HIFs (Hypoxia-Inducible Factors) in the adrenocortical cells of vertebrates is scant. By creating a unique set of transgenic mouse lines, we reveal a prominent role for HIF1α in the synthesis of virtually all steroids in vivo. Specifically, mice deficient in HIF1α in adrenocortical cells displayed enhanced levels of enzymes responsible for steroidogenesis and a cognate increase in circulatory steroid levels. These changes resulted in cytokine alterations and changes in the profile of circulatory mature hematopoietic cells. Conversely, HIF1α overexpression resulted in the opposite phenotype of insufficient steroid production due to impaired transcription of necessary enzymes. Based on these results, we propose HIF1α to be a vital regulator of steroidogenesis as its modulation in adrenocortical cells dramatically impacts hormone synthesis with systemic consequences. In addition, these mice can have potential clinical significances as they may serve as essential tools to understand the pathophysiology of hormone modulations in a number of diseases associated with metabolic syndrome, auto-immunity or even cancer.
Geochemical signatures of mineralizing events in the Juomasuo Au–Co deposit, Kuusamo belt, northeastern Finland
Authors: Vasilopoulos Mikael , Molnár Ferenc , O’Brien Hugh , Lahaye Yann , Lefèbvre Marie , Richard Antonin , André-Mayer Anne-Sylvie , Ranta Jukka-Pekka , Talikka Matti
Published: January 2021

The Juomasuo Au–Co deposit, currently classified as an orogenic gold deposit with atypical metal association, is located in the Paleoproterozoic Kuusamo belt in northeastern Finland. The volcano-sedimentary sequence that hosts the deposit was intensely altered, deformed, and metamorphosed to greenschist facies during the 1.93–1.76 Ga Svecofennian orogeny. In this study, we investigate the temporal relationship between Co and Au deposition and the relationship of metal enrichment with protolith composition and alteration mineralogy by utilizing lithogeochemical data and petrographic observations. We also investigate the nature of fluids involved in deposit formation based on sulfide trace element and sulfur isotope LA-ICP-MS data together with tourmaline mineral chemistry and boron isotopes. Classification of original protoliths was made on the basis of geochemically immobile elements; recognized lithologies are metasedimentary rocks, mafic, intermediate-composition, and felsic metavolcanic rocks, and an ultramafic sill. The composition of the host rocks does not control the type or intensity of mineralization. Sulfur isotope values (δ34S − 2.6 to + 7.1‰) and trace element data obtained for pyrite, chalcopyrite, and pyrrhotite indicate that the two geochemically distinct Au–Co and Co ore types formed from fluids of different compositions and origins. A reduced, metamorphic fluid was responsible for deposition of the pyrrhotite-dominant, Co-rich ore, whereas a relatively oxidized fluid deposited the pyrite-dominant Au–Co ore. The main alteration and mineralization stages at Juomasuo are as follows: (1) widespread albitization that predates both types of mineralization; (2) stage 1, Co-rich mineralization associated with chlorite (± biotite ± amphibole) alteration; (3) stage 2, Au–Co mineralization related to sericitization. Crystal-chemical compositions for tourmaline suggest the involvement of evaporite-related fluids in formation of the deposit; boron isotope data also allow for this conclusion. Results of our research indicate that the metal association in the Juomasuo Au–Co deposit was formed by spatially coincident and multiple hydrothermal processes.
TriGAN: image-to-image translation for multi-source domain adaptation
Authors: Roy Subhankar , Siarohin Aliaksandr , Sangineto Enver , Sebe Nicu , Ricci Elisa
Published: January 2021

Most domain adaptation methods consider the problem of transferring knowledge to the target domain from a single-source dataset. However, in practical applications, we typically have access to multiple sources. In this paper we propose the first approach for multi-source domain adaptation (MSDA) based on generative adversarial networks. Our method is inspired by the observation that the appearance of a given image depends on three factors: thedomain, thestyle(characterized in terms of low-level features variations) and thecontent. For this reason, we propose to project the source image features onto a space where only the dependence from the content is kept, and then re-project this invariant representation onto the pixel space using the target domain and style. In this way, new labeled images can be generated which are used to train a final target classifier. We test our approach using common MSDA benchmarks, showing that it outperforms state-of-the-art methods.
Subjective cognitive complaints and permanent work disability: a prospective cohort study
Authors: Pihlajamäki Minna , Arola Heikki , Ahveninen Heini , Ollikainen Jyrki , Korhonen Mikko , Nummi Tapio , Uitti Jukka , Taimela Simo
Published: January 2021

Purpose

Work disability (WD) is a medico-legal concept that refers to disability benefits (DB) granted due to diseases. We assessed whether subjective cognitive complaints (SCC)—presenting as self-rated difficulties of concentration, memory, clear thinking, and decision making—predict permanent WD in knowledge-intensive occupations.

Methods

In this prospective cohort study with up to 7-year follow-up, we combined the SCC questionnaire results with reliable registry data on the DBs of 7161 professional/managerial employees (46% females). We excluded employees who were on long-term sickness absence (SA) or had received a DB at baseline. The exposure variable was the presence of SCC. Age and SA before the questionnaire as a proxy measure of general health were treated as confounders and the analyses were conducted by gender. The outcome variable was a granted DB. The cumulative incidence function illustrates the difference between SCC categories, and the Fine-Gray model estimates the predictors of WD during the 8-year follow-up.

Results

The annual incidence of DB was 0.15% in the entire cohort: 0.18% among the females, and 0.12% among the males (p = 0.795). The most common primary reasons for permanent WD were mental (36%) and musculoskeletal (20%) disorders. SCC predicted DB in both genders when controlling for age and prior SA. Hazard ratios were 2.9 with a 95% confidence interval 1.4–6.0 for the females and 3.7 (1.8–7.9) for the males.

Conclusion

Subjective cognitive complaints predict permanent WD in knowledge-intensive occupations. This finding has implications for supporting work ability and preventing work disability among employees with cognitively demanding tasks.
Metacognition in adult ADHD: subjective and objective perspectives on self-awareness of cognitive functioning
Authors: Butzbach Marah , Fuermaier Anselm B. M. , Aschenbrenner Steffen , Weisbrod Matthias , Tucha Lara , Tucha Oliver
Published: January 2021

Although attention deficit hyperactivity disorder (ADHD) in adulthood is associated with marked cognitive impairment, research on metacognition in adult ADHD is scarce. Deficits in metacognition may have a negative impact on treatment adherence, functional outcomes, and everyday life. This study explores metacognition, specifically self-awareness of cognitive performance, in adults with ADHD by combining objective and subjective assessments. Forty-seven patients with ADHD and 47 control individuals completed a neuropsychological assessment battery including tests for attention, executive functions and memory (objective assessment), as well as questionnaires for cognitive functioning and symptom severity (subjective assessment; self- and informant-report). Participants evaluated their test performance of the objective assessment after test completion by selecting a percentile rank which was subtracted from their normed test result, yielding a discrepancy score. Compared to controls, adults with ADHD showed impairments in attention (medium effects) and memory (small and medium effects), but not in executive functions. The discrepancy scores between self-evaluation and cognitive performance revealed deficits in self-awareness of attentional functions (small effects), but not in executive functions and memory in patients with ADHD compared to controls. Discrepancy scores between self- and informant-reports of cognitive functioning revealed no significant differences. Adults with ADHD show impairments in metacognition in attentional functions, but may have intact metacognitive abilities in other domains. Patients with ADHD tend to overestimate their abilities, especially in attentional functions. Subjective and objective measures of metacognition may not correspond, highlighting the need for clinicians to not solely rely on patients’ self-report in their assessment.
Simulation of turbulent effective wakes for propellers in off-design conditions by a correction factor approach
Authors: Sánchez-Caja Antonio , Martio Jussi , Viitanen Ville M. , Siikonen Timo
Published: January 2021

This paper presents a procedure for the estimation of propeller effective wakes in oblique flows. It shows how a recently developed method for controlling coupling errors can be applied to analyze propellers operating in off-design conditions. The approach allows the use of fast potential flow methods for the representation of the propeller in the context of viscous flow solvers and works accurately for a wide range of advance numbers and incidence angles with a minimum computational cost. The new method makes it possible to disclose flow phenomena on the effective wake that were hidden in conventional approaches of effective wake simulation. Different application cases are analyzed, such as a propeller-shaft configuration in inclined flow, a pod propulsor in an oblique inflow, and a ship hull advancing at a yaw angle. A dipole-like distortion on the effective wake is unmasked for a uniform flow incident to a propeller mounted on an inclined shaft. The flow component perpendicular to the axis is found to be responsible for the distortion. The effect of the direction of propeller rotation on the effective wake is illustrated for a single-shaft ship moving at a yaw angle. In particular, keel vortices are either attracted to or repelled from the propeller disk depending on the sign of the yaw angle or alternatively on that of the propeller rotation.
Gender differences in patient journey to diagnosis and disease outcomes: results from the European Map of Axial Spondyloarthritis (EMAS)
Authors: Garrido-Cumbrera Marco , Poddubnyy Denis , Gossec Laure , Mahapatra Raj , Bundy Christine , Makri Souzi , Sanz-Gómez Sergio , Christen Laura , Delgado-Domínguez Carlos J. , Navarro-Compán Victoria ,   on behalf of the EMAS Working Group
Published: January 2021

Introduction/objectives

To evaluate the journey to diagnosis, disease characteristics and burden of disease in male and female patients with axial spondyloarthritis (axSpA) across Europe.

Method

Data from 2846 unselected patients participating in the European Map of Axial Spondyloarthritis (EMAS) study through an online survey (2017–2018) across 13 countries were analysed. Sociodemographic characteristics, lifestyle, diagnosis, disease characteristics and patient-reported outcomes (PROs) [disease activity –BASDAI (0–10), spinal stiffness (3–12), functional limitations (0–54) and psychological distress (GHQ-12)] were compared between males and females using chi-square (for categorical variables) and student t (for continuous variables) tests.

Results

In total, 1100 (38.7%) males and 1746 (61.3%) females participated in the EMAS. Compared with males, females reported considerable longer diagnostic delay (6.1 ± 7.4 vs 8.2 ± 8.9 years; p < 0.001), higher number of visits to physiotherapists (34.5% vs 49.5%; p < 0.001) and to osteopaths (13.3% vs 24.4%; p < 0.001) before being diagnosed and lower frequency of HLA-B27 carriership (80.2% vs 66.7%; p < 0.001). In addition, females reported higher degree of disease activity in all BASDAI aspects and greater psychological distress through GHQ-12 (4.4 ± 4.2 vs 5.3 ± 4.1; p < 0.001), as well as a greater use of alternative therapies.

Conclusion

The patient journey to diagnosis of axSpA is much longer and arduous in females, which may be related to physician bias and lower frequency of HLA-B27 carriership. Regarding PROs, females experience higher disease activity and poorer psychological health compared with males. These results reflect specific unmet needs in females with axSpA needing particular attention.

Key Points• Healthcare professionals’ perception of axSpA as a predominantly male disease may introduce some bias during the diagnosis and management of the disease. However, evidence about male-female differences in axSpA is scarce.• EMAS results highlight how female axSpA patients report longer diagnostic delay and higher burden of the disease in a large sample of 2846 participants of 13 European countries.• Results reflect unmet needs of European female patients. Healthcare professionals should pay close attention in order to accurately diagnose and efficiently manage axSpA cases while further research should be developed on the cause of reported gender differences.
Anti-phospholipids antibodies and immune complexes in COVID-19 patients: a putative role in disease course for anti-annexin-V antibodies
Authors: Cristiano Antonio , Fortunati Valentina , Cherubini Fabio , Bernardini Sergio , Nuccetelli Marzia
Published: January 2021

Introduction

Besides distinctive respiratory and digestive hallmarks, COVID-19 has been recently associated with a high prevalence of pro-inflammatory and hypercoagulable states known as “COVID-19 Associated Coagulopathy” (CAC), corresponding to a worsening in patients’ conditions, whose causes are still to be elucidated. A link between anti-phospholipid antibodies (aPLs) and viral infections has long been suggested. APLs are assessed for anti-phospholipid syndrome (APS) diagnosis, characterized by thrombocytopenia, thrombosis, and coagulopathy. Furthermore, circulating immune complexes (CICs), arisen upon inflammatory responses and related immune dysregulation, can lead to endothelial cell damage and thrombotic complications.

Method

We performed an extended panel including IgG/IgM anti-cardiolipin, IgG/IgM anti-β2-glycoprotein-1, coupled with IgG/IgM anti-prothrombin, IgG/IgM anti-annexin-V on two COVID-19 patient groups (early and late infection time), and a negative control group. IgG CIC analysis followed to evaluate inflammatory status, through a possible complement system activation.

Results

Our results showed low positive case percentage in IgG/IgM anti-cardiolipin and IgG/IgM anti-β2-glycoprotein-1 assays (4.54%, 6.25%, and 4.55%; in early infection group, late infection group, and control group, respectively); few positive cases in IgG/IgM anti-prothrombin and IgG/IgM anti-annexin-V immunoassays; and no IgG CIC positivity in any patient.

Conclusions

In conclusion, our data show a low aPL prevalence, likely excluding an involvement in the pathogenesis of CAC. Interestingly, IgG/IgM anti-prothrombin and anti-annexin-V positive cases, detected in late infection group, suggest that aPLs could temporarily increase or could trigger a “COVID-19-induced-APS-like-syndrome” in predisposed patients.

Key Points•To our knowledge, anti-prothrombin (aPT) antibodies, anti-annexin-V antibodies and CICs in COVID-19 patients have not been reported in the scientific literature.•Lack of uniformity and the low percentage of aCL/aβ2GP1 positivity preclude a putative role in CAC pathogenesis.•IgG/IgM anti-prothrombin and IgG/IgM anti-annexin-V data show that distribution of positive case number increases in late infection patients, significantly in anti-annexin-V results, suggesting a possible role for these anti-phospholipid antibodies in disease course.•aPLs can arise transiently in some patients with critical illness and SARS-CoV-2 infection (disappearing in a few weeks), as well as in other genetically predisposed patients; they could trigger a “COVID-19-induced-APS-like-syndrome”.
Reform des Europäischen Stabilitätsmechanismus — eine Einordnung
Authors: Matthes Jürgen
Published: January 2021

Ende November 2020 wurde eine Reform des Europäischen Stabilitätsmechanismus beschlossen, die nicht unterschätzt werden sollte. Im Mittelpunkt steht die Einführung einer staatlichen Letztabsicherung für den europäischen Bankenrettungsfonds ab 2022. Doch auch weitere Änderungen sind relevant und werden in diesem Beitrag eingeordnet.