bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing the post-WWII publication histories of oceanography and marine geoscience
Authors: Mitchell Neil C.
Published: May 2020

Oceanography and marine geosciences are closely related subjects, though they have had differing influences. The UK, which has experienced the financial benefits of North Sea oil and gas, while also having an extensive fishing industry and a science base linked to other English-speaking countries and European countries, potentially illustrates some changing influences and collaborative tendencies well. In this article, differences in article publication rates and collaborative tendencies, both globally and for the UK, are examined using the Web of Science™, Scopus™ and Georef™ for the period 1946–2018. The results show that publication rates of global oceanography articles rose exponentially faster than all global scientific publishing from the mid-1960s to 1980. Subsequently, the exponential rate of increase slowed though has remained faster than global science publishing. Global Marine Geoscience publication rates increased into the late 1980s, but have since declined. UK oceanography has roughly followed global trends, though its share of global oceanographic publishing declined from 28% in the 1950s to 8% in 2018. UK Marine Geoscience publishing has also generally followed global trends for that field. However, its share of global publications abruptly increased from 4.9% (average 1960–1980) to 13.2% by 1990, largely due to articles arising from UK participation in the Deep-Sea Drilling Project and Ocean Drilling Program. Oceanography and marine geoscience have also experienced strongly differing histories of collaborative articles over the last four decades. While oceanographic articles co-authored with researchers in other countries have been steadily increasing as a share of total UK Oceanography articles, those of marine geoscience peaked in 1990 and have since declined, though remained at high levels similar to those experienced by 2018 in Oceanography. Comparing global publication rates in both fields with measures of data and sample collection at sea suggests fundamental changes occurred in the way research was carried out. For example, Marine Geoscience publication rates were strongly correlated with geophysical track-line distances for the decade until ~1970, but were inversely correlated for the decade after then. This reflects, for example, the development of plate tectonics, which partly involved analysis of existing marine geophysical data, improved equipment capabilities and the increased role of scientific drilling.
Data generation for composite-based structural equation modeling methods
Authors: Schlittgen Rainer , Sarstedt Marko , Ringle Christian M.
Published: May 2020

Examining the efficacy of composite-based structural equation modeling (SEM) features prominently in research. However, studies analyzing the efficacy of corresponding estimators usually rely on factor model data. Thereby, they assess and analyze their performance on erroneous grounds (i.e., factor model data instead of composite model data). A potential reason for this malpractice lies in the lack of available composite model-based data generation procedures for prespecified model parameters in the structural model and the measurements models. Addressing this gap in research, we derive model formulations and present a composite model-based data generation approach. The findings will assist researchers in their composite-based SEM simulation studies.
Management of acute pulmonary embolism 2019: what is new in the updated European guidelines?
Authors: Konstantinides Stavros , Meyer Guy
Published: May 2020

Pulmonary embolism (PE) is the third most frequent acute cardiovascular syndrome. Annual PE incidence and PE-related mortality rates rise exponentially with age, and consequently, the disease burden imposed by PE on the society continues to rise as the population ages worldwide. Recently published landmark trials provided the basis for new or changed recommendations included in the 2019 update of the European Society of Cardiology Guidelines (developed in cooperation with the European Respiratory Society). Refinements in diagnostic algorithms were proposed and validated, increasing the specificity of pre-test clinical probability andd-dimer testing, and thus helping to avoid unnecessary pulmonary angiograms. Improved diagnostic strategies were also successfully tested in pregnant women with suspected PE. Non-vitamin K antagonist oral anticoagulants (NOACs) are now the preferred agents for treating the majority of patients with PE, both in the acute phase (with or without a brief lead-in period of parenteral heparin or fondaparinux) and over the long term. Primary reperfusion is reserved for haemodynamically unstable patients. Besides, the 2019 Guidelines endorse multidisciplinary teams for coordinating the acute-phase management of high-risk and (in selected cases) intermediate-risk PE. For normotensive patients, physicians are advised to include the assessment of the right ventricle on top of clinical severity scores in further risk stratification, especially if early discharge of the patient is envisaged. Further important updates include guidance (1) on extended anticoagulation after PE, taking into account the improved safety profile of NOACs; and (2) on the overall care and follow-up of patients who have suffered PE, with the aim to prevent, detect and treat late sequelae of venous thromboembolism.
A review on the state of knowledge, conceptual and theoretical contentions of major theories and principles governing groundwater flow modeling
Authors: Mussa Kassim Ramadhani , Mjemah Ibrahimu Chikira , Muzuka Alfred Nzibavuga Nyarubakula
Published: May 2020

Decision-makers require correct and adequate information on groundwater flow systems in a basin in order to formulate sustainable water resources development strategies. However, the practicality and realism of groundwater flow system models depend on the validity, reliability and availability of quality data and information, and how they are used in model development and calibration. This goes hand in hand with how the underlying theories, tenets and assumptions are understood, interpreted and applied. The more uncertain and contentious the information is, the wider are the knowledge and theoretical gaps, and thus the less useful the model results are for decision-making. The understanding of water table types in groundwater basins has become one of the additional factors for an in-depth understanding and modeling of nested groundwater flow systems. The classification of water table types using a water table ratio provides that if the ratio is more than 1, this depicts a topography-controlled area and a ratio of less than 1 depicts a recharge-controlled terrain. Log transformation of the water table ratio proved the same interpretation. This paper therefore reviews the evolution of groundwater flow systems theory, the prevailing knowledge and theoretical gaps by specifically pinpointing the theoretical and conceptual contentions and additional factors which can possibly limit the application of groundwater flow theories in regional groundwater modeling studies. The implications of how the conceptual and theoretical contentions affect groundwater modeling for decision-making in groundwater development and management are also pinpointed in this paper.
Live cell imaging and proteomic profiling of endogenous NEAT1 lncRNA by CRISPR/Cas9-mediated knock-in
Authors: Chen Bohong , Deng Shengcheng , Ge Tianyu , Ye Miaoman , Yu Jianping , Lin Song , Ma Wenbin , Songyang Zhou
Published: May 2020

In mammalian cells, long noncoding RNAs (lncRNAs) form complexes with proteins to execute various biological functions such as gene transcription, RNA processing and other signaling activities. However, methods to track endogenous lncRNA dynamics in live cells and screen for lncRNA interacting proteins are limited. Here, we report the development of CERTIS (CRISPR-mediated Endogenous lncRNA Tracking and Immunoprecipitation System) to visualize and isolate endogenous lncRNA, by precisely inserting a 24-repeat MS2 tag into the distal end of lncRNA locus through the CRISPR/Cas9 technology. In this study, we show that CERTIS effectively labeled the paraspeckle lncRNA NEAT1 without disturbing its physiological properties and could monitor the endogenous expression variation of NEAT1. In addition, CERTIS displayed superior performance on both short- and long-term tracking of NEAT1 dynamics in live cells. We found that NEAT1 and paraspeckles were sensitive to topoisomerase I specific inhibitors. Moreover, RNA Immunoprecipitation (RIP) of the MS2-tagged NEAT1 lncRNA successfully revealed several new protein components of paraspeckle. Our results support CERTIS as a tool suitable to track both spatial and temporal lncRNA regulation in live cells as well as study the lncRNA-protein interactomes.
Development and evaluation of a simulation-based transition to clerkship course
Authors: Austin Jared P. , Baskerville Mark , Bumsted Tracy , Haedinger Leslie , Nonas Stephanie , Pohoata Eugen , Rogers Meghan , Spickerman Megan , Thuillier Philippe , Mitchell Suzanne H.
Published: May 2020

Background Transition to clerkship courses bridge the curricular gap between preclinical and clinical medical education. However, despite the use of simulation-based teaching techniques in other aspects of medical training, these techniques have not been adequately described in transition courses. We describe the development, structure and evaluation of a simulation-based transition to clerkship course.

Approach Beginning in 2012, our institution embarked upon an extensive curricular transformation geared toward competency-based education. As part of this effort, a group of 12 educators designed, developed and implemented a simulation-based transition course. The course curriculum involved seven goals, centered around the 13 Association of American Medical Colleges Core Entrustable Professional Activities for entering residency. Instructional techniques included high-fidelity simulation, and small and large group didactics. Student competency was determined through a simulation-based inpatient-outpatient objective structured clinical examination, with real-time feedback and remediation. The effectiveness of the course was assessed through a mixed methods approach involving pre- and post-course surveys and a focus group.

Evaluation Of 166 students, 152 (91.6%) completed both pre- and post-course surveys, and nine students participated in the focus group. Students reported significant improvements in 21 out of 22 course objectives. Qualitative analysis revealed three key themes: learning environment, faculty engagement and collegiality. The main challenge to executing the course was procuring adequate faculty, material and facility resources.

Reflection This simulation-based, resource-heavy transition course achieved its educational objectives and provided a safe, supportive learning environment for practicing and refining clinical skills.
Review of Current Practices of Peripheral Nerve Blocks for Hip Fracture and Surgery
Authors: Dangle Jyoti , Kukreja Promil , Kalagara Hari
Published: May 2020

Purpose of Review

This article aims to describe the anatomical and technical aspects of various regional techniques used for fracture hip and hip surgery. We reviewed the commonly used nerve blocks, interfascial plane blocks and current evidence of their utility in hip fracture patients.

Recent Findings

Fascia iliaca compartment block (FICB) and femoral nerve block (FNB) are the most commonly used nerve blocks for providing pain relief for hip fracture patients. Supra-inguinal FICB has more consistent spread to all nerves and can enable better pain control. Both the FICB and FNB have shown analgesic efficacy with reduced pain scores, opioid sparing effect, and they enable better patient positioning for spinal in the operating room. These nerve blocks in the elderly patients can also have beneficial effects on delirium, reduced hospital length of stay, and decreased incidence of pneumonia. Some of the novel interfascial plane blocks like PEricapsular Nerve Group (PENG) blocks are now being explored to provide pain relief for fracture hip.

Hip fracture in the elderly has associated morbidity and mortality. Early surgical intervention has shown to reduce morbidity and mortality. Pain management in this elderly population poses a unique challenge and complementing with regional anesthesia for analgesia has shown numerous benefits.
Combining diagnostic memory clinic with rehabilitation follow-up after hip fracture
Authors: Jaatinen Roope , Luukkaala Tiina , Viitanen Matti , Nuotio Maria S.
Published: May 2020

Purpose

Cognitive impairment and dementia are common in older hip fracture patients. We describe new diagnoses of cognitive disorders (NDCDs) and associated factors in a two-year post-hip fracture follow-up including the use of the diagnostic facilities of a memory clinic.

Methods

Data were collected on admission and at outpatient assessment 4–6 months post-hip fracture. Diagnoses of cognitive disorders followed the evidence-based Finnish national care guideline including internationally accepted criteria. NDCDs up to 2 years post-hip fracture were extracted manually from the patient files. Logistic regression models were computed to examine the associations between the pre-fracture factors and the domains of the outpatient geriatric assessment and NDCDs.

Results

Of the 1165 hip fracture patients aged ≥ 65 years, 831 had no previous diagnosis of cognitive disorder. Of these, NDCD was documented in 23.3%. Alzheimer’s disease (AD) with or without vascular cognitive impairment (VCI) was the most common diagnosis. Cognitive disorder was usually at a moderate stage. Age, higher ASA score and poor nutritional status on admission were associated with new cognitive disorders. At the outpatient follow-up, poorer activities of daily living and mobility disability were associated with NDCD. Patients with a NDCD were more likely to suffer greater mobility impairment, poorer nutritional status and to have more supported living arrangements at follow-up than in the pre-fracture situation.

Conclusion

NDCDs are common after hip fracture and associated with impaired rehabilitation outcomes and poor nutritional status. A post-hip fracture assessment co-organized in the form of a memory clinic seems to be feasible to detect previously undiagnosed cognitive disorders. Earlier diagnosis of cognitive disorders is warranted.
Improving BMP Cost-Share Enrollment Rates: Insights from a Survey of Florida Farmers
Authors: Yehouenou Lauriane S. , Grogan Kelly A. , Bi Xiang , Borisova Tatiana
Published: May 2020

This paper investigates cost-share program attributes that would affect producers' willingness to enroll in a cost-share program to fund the adoption of best management practices to improve water quality and decrease water use. Through a survey administered to Florida agricultural producers, we conducted choice experiments to assess farmers’ preferences for cost-share programs using five attributes: contracting agency, length of contract, annual verification process, costs included, and percent of costs covered. Results suggest that producers prefer cost-share programs with shorter contract lengths, self-monitoring, and administration by agricultural (as opposed to environmental) agencies. Our findings suggest the importance of an existing trust between the local communities and the contracting agencies for higher enrollment rates in cost –share programs. Our results can inform policymakers on ways to increase enrollment rates that move towards long-term environmental goals.
The self-as-mother in the preschool years: an interpretive phenomenological analysis
Authors: Hansen Lauren
Published: May 2020

There has been little research into the well-being of mothers after 12 months post-partum, despite researchers finding that depressive symptoms are more prevalent at 4 years post-partum than at any other time preceding this. The literature suggests that a woman’s view of the mother role impacts on her well-being in the early years of parenting. This qualitative research study investigated the experiences of mothers of preschool-aged children in Melbourne, Australia, and how they incorporated the role of mother into their self. Eight semi-structured interviews were completed, and interpretive phenomenological analysis was used to explore the data. The data revealed four subthemes relating to the emergence of the maternal self: becoming a mother as a journey of self-discovery, the biological imperatives of becoming a mother, remothering and the continued challenges of the emerging mother role. Although the experiences of mothering are as diverse as women themselves, even in the mostly homogenous sample, as in this study, several themes were present that both support and diverge from the existing literature.
COVID-19: Stroke Admissions, Emergency Department Visits, and Prevention Clinic Referrals
Authors: Bres Bullrich Maria , Fridman Sebastian , Mandzia Jennifer L. , Mai Lauren M. , Khaw Alexander , Vargas Gonzalez Juan Camilo , Bagur Rodrigo , Sposato Luciano A.
Published: May 2020

We assessed the impact of the coronavirus disease 19 (COVID-19) pandemic on code stroke activations in the emergency department, stroke unit admissions, and referrals to the stroke prevention clinic at London’s regional stroke center, serving a population of 1.8 million in Ontario, Canada. We found a 20% drop in the number of code strokes in 2020 compared to 2019, immediately after the first cases of COVID-19 were officially confirmed. There were no changes in the number of stroke admissions and there was a 22% decrease in the number of clinic referrals, only after the provincial lockdown. Our findings suggest that the decrease in code strokes was mainly driven by patient-related factors such as fear to be exposed to the SARS-CoV-2, while the reduction in clinic referrals was largely explained by hospital policies and the Government lockdown.
How Does Forced-CEO-Turnover Experience Affect Directors?
Authors: Ellis Jesse , Guo Lixiong , Mobbs Shawn
Published: May 2020

We study changes in independent director behavior and labor-market outcomes after the experience of a forced Chief Executive Officer (CEO) turnover. We find that independent directors are more willing to fire CEOs of underperforming firms, hire outside CEOs after a firing, and encourage better board-meeting attendance by fellow directors. We also find that the shareholders of poorly performing firms react positively when experienced directors join the board. It does come with a small cost for directors, in terms of additional directorships, although the cost is not as great as that for directors who do not fire the CEO of a poorly performing firm.
Towards laser ion acceleration with holed targets
Authors: Hadjisolomou Prokopis , Bulanov S. V. , Korn G.
Published: May 2020

Although the interaction of a flat foil with currently available laser intensities is now considered a routine process, during the last decade, emphasis has been given to targets with complex geometries aiming at increasing the ion energy. This work presents a target geometry where two symmetric side holes and a central hole are drilled into the foil. A study of the various side-hole and central-hole length combinations is performed with two-dimensional particle-in-cell simulations for polyethylene targets and a laser intensity of

$5.2\times 10^{21}~\text{W}~\text{cm}^{-2}$

. The holed targets show a remarkable increase of the conversion efficiency, which corresponds to a different target configuration for electrons, protons and carbon ions. Furthermore, diffraction of the laser pulse leads to a directional high energy electron beam, with a temperature of

${\sim}40~\text{MeV}$

, or seven times higher than in the case of a flat foil. The higher conversion efficiency consequently leads to a significant enhancement of the maximum proton energy from holed targets.
The Political Effects of Policy Drift: Policy Stalemate and American Political Development
Authors: Galvin Daniel J. , Hacker Jacob S.
Published: May 2020

In recent years, scholars have made major progress in understanding the dynamics of “policy drift”—the transformation of a policy's outcomes due to the failure to update its rules or structures to reflect changing circumstances. Drift is a ubiquitous mode of policy change in America's gridlock-prone polity, and its causes are now well understood. Yet surprisingly little attention has been paid to the political consequences of drift—to the ways in which drift, like the adoption of new policies, may generate its own feedback effects. In this article, we seek to fill this gap. We first outline a set of theoretical expectations about how drift should affect downstream politics. We then examine these dynamics in the context of four policy domains: labor law, health care, welfare, and disability insurance. In each, drift is revealed to be both mobilizing and constraining: While it increases demands for policy innovation, group adaptation, and new group formation, it also delimits the range of possible paths forward. These reactions to drift, in turn, generate new problems, cleavages, and interest alignments that alter subsequent political trajectories. Whether formal policy revision or further stalemate results, these processes reveal key mechanisms through which American politics and policy develop.
Differential antimicrobial susceptibility profiles between symptomatic and asymptomatic non-typhoidal Salmonella infections in Vietnamese children
Authors: Parisi Andrea , Le Thi Phuong Tu , Mather Alison E. , Jombart Thibaut , Thanh Tuyen Ha , Phu Huong Lan Nguyen , Hoang Thu Trang Nguyen , Carrique-Mas Juan , Campbell James I. , Glass Kathryn , Kirk Martyn D. , Baker Stephen
Published: May 2020

Non-typhoidal Salmonella (NTS) serovars, sequences types and antimicrobial susceptibility profiles have specific associations with animal and human infections in Vietnam. Antimicrobial resistance may have an effect on the manifestation of human NTS infections, with isolates from asymptomatic individuals being more susceptible to antimicrobials than those associated with animals and human diarrhoea.
Healthy eating recommendations: good for reducing dietary contribution to the body’s advanced glycation/lipoxidation end products pool?
Authors: del Castillo María Dolores , Iriondo-DeHond Amaia , Iriondo-DeHond Maite , Gonzalez Ileana , Medrano Alejandra , Filip Rosana , Uribarri Jaime
Published: May 2020

The present review aims to give dietary recommendations to reduce the occurrence of the Maillard reaction in foods and in vivo to reduce the body’s advanced glycation/lipoxidation end products (AGE/ALE) pool. A healthy diet, food reformulation and good culinary practices may be feasible for achieving the goal. A varied diet rich in fresh vegetables and fruits, non-added sugar beverages containing inhibitors of the Maillard reaction, and foods prepared by steaming and poaching as culinary techniques is recommended. Intake of supplements and novel foods with low sugars, low fats, enriched in bioactive compounds from food and waste able to modulate carbohydrate metabolism and reduce body’s AGE/ALE pool is also recommended. In conclusion, the recommendations made for healthy eating by the Spanish Society of Community Nutrition (SENC) and Harvard University seem to be adequate to reduce dietary AGE/ALE, the body’s AGE/ALE pool and to achieve sustainable nutrition and health.
Response of the public and restaurant owners to the mandatory menu energy-labelling implementation in restaurants in Saudi Arabia
Authors: Alkhaldy Areej A , Taha Doha S , Alsahafi Shahad E , Naaman Rouba K , Alkhalaf Majid M
Published: May 2020

Objective:

Mandatory menu energy-labelling policy in restaurants has received increasing attention worldwide as a useful tool for promoting balanced energy intake and encouraging healthier food selection to reduce obesity prevalence. Therefore, we aimed to evaluate the knowledge, views and observations of the public and restaurant owners towards the mandatory menu energy-labelling policy (introduced in August 2018) in restaurants in Saudi Arabia.

Design:

In February 2019, we conducted a cross-sectional study using an electronic questionnaire.

Setting:

Saudi Arabia.

Participants:

Saudi individuals (n 1228) aged 18–80 years and forty-one restaurant owners.

Results:

Most participants identified the correct daily energetic requirements for moderately active men (51 %) and women (69 %), but not for inactive adults (36 %). Although 40 % reported adequate knowledge to select low-energetic meals and 55 % perceived the policy as useful, 51 % reported they would be less likely to eat at restaurants displaying energy. Most participants (76 %) mentioned they would choose lower-energetic meals, and 79 % would feel guilty after consuming high-energetic meals. Moreover, 62 % of participants reported that the new labelling policy affected their food selections, prompting them to order different food items, eat less, change restaurants or eat at restaurants less frequently. Among restaurant owners, half were aware of the reason for the implementation of this policy and supported this measure. However, they did not consider modifying recipes to reduce energy. Sales of low- and high-energetic meals increased and decreased in 44 % and 39 % of restaurants, respectively.

Conclusions:

This policy may be an effective public health tool for promoting balanced energy intake and encouraging healthier food selection in Saudi Arabia.
Does microgravity effect on oral and maxillofacial region?
Authors: Stevens Mark , Keyhan Seied Omid , Ghasemi Shohreh , Fallahi Hamid Reza , Akbarnia Shahriar , Dashti Mahmood , Akbar Boojar Fargol Mashhadi , Zadeh Maneli Ardeshir , Cheshmi Behzad
Published: May 2020

Since the beginning of the era of space travel, there have been mentions of related health effects. Various studies have described the effect of space travel and microgravity on health. Some of these studies involved short and extended follow-ups of the effect of microgravity on the head and neck of astronauts. Therefore, we aimed to analyse the oral and maxillofacial health effects associated with this sophisticated mission. It is essential to identify relevant problems and address microgravity complications. Humans have long dreamed of flying and in recent years, the dream has evolved to exploring space and creating new habitats on other planets such as Mars. This led to an increase in the need for dental treatment of the flight crew members, which led to the creation of aviation dentistry for the screening and treatment of the oral cavity of the flight crew. We are moving towards a more conservative approach than before, such as removing pulpless teeth in aircrew patients or extracting roots that had a fracture or incomplete extraction. With all the advancements in aerospace knowledge, the aviation dentistry has rarely or briefly been discussed in dental textbooks. Dentists must screen each flight crew member thoroughly and impose flight restrictions and ground them if necessary; the reasons will be discussed later within this paper. It is the duty of dentists and surgeons to notify their patients (aircrew members) about the postoperative flight consequences and restrictions.
Circulating microRNAs overexpressed in macrosomia: an experimental and bioinformatic approach
Authors: Ortiz-Dosal Alejandra , Arellanes-Licea Elvira del Carmen , Rodil-García Patricia , Salazar-Olivo Luis A.
Published: May 2020

Low birth weight (LBW) and macrosomia have been associated with later-in-life metabolic alterations. The aim of this study was to elucidate whether the expression levels of circulating microRNAs (c-miRNAs) associated with adult metabolic diseases are also dysregulated in newborns with LBW or macrosomia. The expression levels of five microRNAs (miRNAs) associated with metabolic diseases were quantified in dried blood spots of newborns with adequate birth weight, LBW and macrosomia by stem-loop real-time polymerase chain reaction. miR-29a-5p, miR-126-3p, miR-221-3p, and miR-486-5p were significantly overexpressed in newborns with macrosomia and showed no significant change in the LBW group compared to normal weight controls. miR-320a showed no statistical difference among groups. We predicted the putative target genes and pathways of the overexpressed miRNAs with bioinformatic tools. Bioinformatic analyses of overexpressed miRNAs predicted target genes involved in carbohydrate metabolism, participate in FoxO and PI3K/Akt signaling pathways, and are associated with diabetes, obesity, and cardiovascular diseases. The overexpression of circulating miR-29a-5p, miR-126-3p, miR-221-3p, and miR-486-5p may explain the increased risk of obesity and diabetes associated with macrosomia. The use of dried blood spots from newborn screening cards to quantify miRNAs expression levels could be an early and minimally invasive predictive tool for these metabolic alterations.
Risk of eating disorders in international adoptees: a cohort study using Swedish national population registers
Authors: Strand M. , Zhang R. , Thornton L. M. , Birgegård A. , D'Onofrio B. M. , Bulik C. M.
Published: May 2020

Aims

Compared to the general population, adoptees are more often referred to specialist psychiatric treatment, exhibit increased risk of suicide and display more symptoms of attention-deficit/hyperactivity-disorder. However, little is known about the impact of being an adoptee on the risk of developing an eating disorder. The aim of the present study was to assess whether international adoptees have a higher risk for eating disorders than native Swedes.

Methods

In the present retrospective cohort study, data from the Swedish total population registers on individuals born between 1979 and 2005 were used to assess whether international adoptees residing in Sweden (n = 25 287) have a higher risk for anorexia nervosa (AN) and other eating disorders (OED) than non-adoptees with Swedish-born parents from the general population (n = 2 046 835). The patterns of these results were compared to those for major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and anxiety disorders to determine whether any observed effects were unique to eating disorders or reflected a more general impact on mental health outcomes.

Results

A survival analysis adjusting for relevant demographic covariates revealed an elevated risk of all examined psychiatric disorders in international adoptees: hazard ratios (95% confidence intervals) are 1.21 (1.04–1.41) for AN, 1.60 (1.44–1.79) for OED, 1.90 (1.81–2.00) for MDD, 1.25 (1.09–1.44) for OCD, and 1.69 (1.60–1.78) for anxiety disorders.

Conclusions

Elevated risk of eating disorders as well as of MDD, OCD, and anxiety disorders was found in international adoptees. A parallel pattern between AN and OCD was observed, which both display less elevated rates than the other diagnoses. A considerable number of biological, environmental, and societal factors have been suggested to explain the observed differences in mental health between adoptees and non-adoptees, but they remain primarily theoretical.
Cohorts
Authors: Kaprio Jaakko , Boomsma Dorret I.
Published: May 2020

Cohort studies are essential for conducting large studies of multiple exposures and outcomes in humans. Recently, the ability to combine data from multiple cohorts in, for example, meta-analyses, and the willingness in the genetics community to collaborate to enable replication studies has led to many new insights into the genetic and environmental determinants of human health and behaviors. The contribution of Professor Nicholas Martin to the development of cohort studies, particularly of twin and twin-family studies, over a period of several decades is reviewed. He has contributed to the development and use of both Australian and international resources. The contributions of Australian twin studies to genomewide association projects are multiple, and across multiple domains, from biomarkers, lifestyle and behavior to disorders and disease.
Macrophysical and Microphysical Characteristics of Convective Rain Cells Observed During SOS‐CHUVA
Authors: Cecchini Micael Amore , Silva Dias Maria A. F. , Machado Luiz A. T. , Morales Rodriguez Carlos A. , Biscaro Thiago
Published: May 2020

In this study, we present a methodology to study the properties of convective precipitation in a holistic way. We apply a tracking algorithm to X‐band radar retrievals to store Lagrangian properties of convective rain cells. The height of maximum reflectivity (HZmax) is combined with the vertically integrated water (VIW) to provide a useful parameter space to constrain the microphysical study of the cells. This parameter determines most of the shape of the vertical structure of rain cells, where VIW acts as a modulating factor. Decreases in HZmax are likely associated to enhanced collection processes, which favor growth of reflectivity (Z), differential reflectivity (Zdr), differential attenuation (Kdp), and droplet mean volume diameter (D0). This growth is further favored under higher VIW conditions. By discriminating the microphysical analysis by HZmax and VIW, droplet growth can be analyzed in different types of rain cells and stages of life cycle. Overall, the results presented here can help understand the constraints of the vertical structure of rain cells and microphysical properties from the combination of HZmax and VIW. Contrary to the microphysical retrievals themselves, computations of HZmax and VIW do not depend on dual polarization.
Relative Crater Scaling Between the Major Moons of Saturn: Implications for Planetocentric Cratering and the Surface Age of Titan
Authors: Bell Samuel W.
Published: May 2020

The chronology of the moons of Saturn, especially Titan, has been limited by a lack of strong constraints on the cratering rate, low number statistics for small‐N counts of large‐diameter craters, and uncertainty about whether impactors are mostly heliocentric impactors orbiting the Sun or planetocentric impactors orbiting Saturn itself. Here, I propose to address these three problems. Instead of looking for an absolute cratering rate, I focus on the relative crater densities, calculating scaling relationships between the moons. I update crater analysis methodology by numerically modeling probability density functions of the uncertainty of crater density, enabling me to accurately assess the error of even single‐crater observations. Using these updated statistics, I show how the heliocentric cratering model leads to a dramatic increase in relative crater density for Mimas, Tethys, Dione, Rhea, and Iapetus with distance from Saturn. Under this model, the surface age of Titan is probably older than the cratered plains of Mimas—implying a very low erosion rate and minimal endogenic resurfacing on Titan. I explore possible explanations, concluding that the likeliest explanation is planetocentric cratering, although saturation effects cannot be ruled out. Under the planetocentric model, the relative crater densities of the cratered plains of Mimas, Tethys, Dione, Rhea, and Iapetus are all very close, with the relative crater density at Titan between 1 and 2 orders of magnitude lower. Under planetocentric cratering, the cratering rate on Titan allows for vigorous erosion and endogenic resurfacing.
Recent advances of sterile inflammation and inter-organ cross-talk in alcoholic liver disease
Authors: Shim Young-Ri , Jeong Won-Il
Published: May 2020

Alcoholic liver disease (ALD) is one of the fastest-growing concerns worldwide. In addition to bacterial endotoxins in the portal circulation, recent lines of evidence have suggested that sterile inflammation caused by a wide range of stimuli induces alcoholic liver injury, in which damage-associated molecular patterns (DAMPs) play critical roles in inducing de novo lipogenesis and inflammation through the activation of cellular pattern recognition receptors such as Toll-like receptors in non-parenchymal cells. Interestingly, alcohol-mediated metabolic, neurological, and immune stresses stimulate the generation of DAMPs that are released not only in the liver, but also in other organs, such as adipose tissue, intestine, and bone marrow. Thus, diverse DAMPs, including retinoic acids, proteins, lipids, microRNAs, mitochondrial DNA, and mitochondrial double-stranded RNA, contribute to a broad spectrum of ALD through the production of multiple pro-inflammatory cytokines, chemokines, and ligands in non-parenchymal cells, such as Kupffer cells, hepatic stellate cells, and various immune cells. Therefore, this review summarizes recent studies on the identification and understanding of DAMPs, their receptors, and cross-talk between the liver and other organs, and highlights successful therapeutic targets and potential strategies in drug development that can be used to combat ALD.
Destabilization of β-catenin and RAS by targeting the Wnt/β-catenin pathway as a potential treatment for triple-negative breast cancer
Authors: Ryu Won-Ji , Lee Jeong Dong , Park Jong-Chan , Cha Pu-Hyeon , Cho Yong-Hee , Kim Jee Ye , Sohn Joo Hyuk , Paik Soonmyung , Choi Kang-Yell
Published: May 2020

Triple-negative breast cancer (TNBC) is a severe and heterogeneous disease that lacks an approved targeted therapy and has a poor clinical outcome to chemotherapy. Although the RAS-ERK signaling axis is rarely mutated in TNBC, ~50% of TNBCs show an increased copy number and overexpression of epidermal growth factor receptor (EGFR). However, EGFR-targeted therapies have offered no improvement in patient survival, underscoring the need to explore downstream targets, including RAS. We found that both β-catenin and RAS, as well as epidermal growth factor receptor (EGFR), are overexpressed and correlated with one another in tumor tissues of TNBC patients. KYA1797K, an Axin-binding small molecule reducing β-catenin and RAS expression via degradation and suppressing EGFR expression via transcriptional repression, inhibited the proliferation and the metastatic capability of stable cell lines as well as patient-derived cells (PDCs) established from TNBC patient tissues. KYA1797K also suppressed the stemness of 3D-cultured PDCs and xenografted tumors established by using residual tumors from TNBC patients and those established by the TNBC cell line. Targeting both the Wnt/β-catenin and RAS-ERK pathways via small molecules simultaneously reducing the levels of β-catenin, RAS, and EGFR could be a potential therapeutic approach for TNBC.
Deep immune profiling of patients treated with lenalidomide and dexamethasone with or without daratumumab
Authors: Casneuf Tineke , Adams Homer C. , van de Donk Niels W.C.J. , Abraham Yann , Bald Jaime , Vanhoof Greet , Van der Borght Koen , Smets Tina , Foulk Brad , Nielsen Karl C. , Rusbuldt Joshua , Axel Amy , Lysaght Andrew , Ceulemans Hugo , Stevenaert Frederik , Usmani Saad Z. , Plesner Torben , Avet-Loiseau Herve , Nijhof Inger , Mutis Tuna , Schecter Jordan M. , Chiu Christopher , Bahlis Nizar J.
Published: May 2020

CD38-targeted antibody, daratumumab, is approved for the treatment of multiple myeloma (MM). Phase 1/2 studies GEN501/SIRIUS revealed a novel immunomodulatory mechanism of action (MOA) of daratumumab that enhanced the immune response, reducing natural killer (NK) cells without affecting efficacy or safety. We further evaluated daratumumab’s effects on immune cells in whole blood samples of relapsed/refractory MM patients from both treatment arms of the phase 3 POLLUX study (lenalidomide/dexamethasone [Rd] or daratumumab plus Rd [D-Rd]) at baseline (D-Rd, 40; Rd, 45) and after 2 months on treatment (D-Rd, 31; Rd, 33) using cytometry by time-of-flight. We confirmed previous reports of NK cell reduction with D-Rd. Persisting NK cells were phenotypically distinct, with increased expression of HLA-DR, CD69, CD127, and CD27. The proportion of T cells increased preferentially in deep responders to D-Rd, with a higher proportion of CD8+versus CD4+T cells. The expansion of CD8+T cells correlated with clonality, indicating generation of adaptive immune response with D-Rd. D-Rd resulted in a higher proportion of effector memory T cells versus Rd. D-Rd reduced immunosuppressive CD38+regulatory T cells. This study confirms daratumumab’s immunomodulatory MOA in combination with immunomodulatory drugs and provides further insight into immune cell changes and activation status following daratumumab-based therapy.
Decreased expression of FBXW7 by ERK1/2 activation in drug-resistant cancer cells confers transcriptional activation of MDR1 by suppression of ubiquitin degradation of HSF1
Authors: Mun Gil-Im , Choi Eun , Lee Yeongmin , Lee Yun-Sil
Published: May 2020

The acquisition of MDR1-mediated chemoresistance poses a major obstacle to the success of conventional chemotherapeutic agents. HSF1 is also involved in chemoresistance, and several studies have demonstrated the relationship between HSF1 and MDR1 but without any consistent results. Paclitaxel- and doxorubicin-resistant cancer cells showed higher expression of MDR1 and HSF1. Depletion of HSF1 decreased mdr1 expression at mRNA level, and HSF1 directly interacted with the promoter site of mdr1, suggesting its role as a transcriptional regulator of MDR1. Phosphorylation of Ser303/307, which was involved in protein stability of HSF1 by FBXW7-mediated degradation, was found to be important for transcriptional activation of mdr1. Drug-resistant cells showed decreased expression of FBXW7, which was mediated by the activation of ERK1/2, thus indicating that over-activation of ERK1/2 in drug-resistant cells decreased FBXW7 protein stability, which finally inhibited protein degradation of pHSF1 at Ser303/307. There was a positive correlation between immunofluorescence data of pHSF1 at Ser303/307 and MDR1 in carcinogen-induced rat mammary tumors and human lung cancers. These findings identified the post-translational mechanisms of HSF1 transcription in MDR1 regulation of drug resistance development.
HUWE1-dependent DNA-PKcs neddylation modulates its autophosphorylation in DNA damage response
Authors: Guo Zongpei , Wang Shaozheng , Xie Ying , Han Yang , Hu Sai , Guan Hua , Xie Dafei , Bai Chenjun , Liu Xiaodan , Gu Yongqing , Zhou Ping-Kun , Ma Teng
Published: May 2020

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is the core component of DNA-PK complex in the non-homologous end-joining (NHEJ) repair of DNA double-strand breaks, and its activity is strictly controlled by DNA-PKcs phosphorylation. The ubiquitin-like protein, NEDD8 is involved in regulation of DNA damage response, but it remains mysterious whether and how NEDD8-related neddylation affects DNA-PKcs and the NHEJ process. Here, we show that DNA-PKcs is poly-neddylated at its kinase domain. The neddylation E2-conjugating enzyme UBE2M and E3 ligase HUWE1 (HECT, UBA, and WWE domain containing E3 ubiquitin protein ligase 1) are responsible for the DNA-PKcs neddylation. Moreover, inhibition of HUWE1-dependent DNA-PKcs neddylation impairs DNA-PKcs autophosphorylation at Ser2056. Finally, depletion of HUWE1-dependent DNA-PKcs neddylation reduces the efficiency of NHEJ. These studies provide insights how neddylation modulates the activity of NHEJ core complex.
Computer simulations explain the anomalous temperature optimum in a cold-adapted enzyme
Authors: Sočan Jaka , Purg Miha , Åqvist Johan
Published: May 2020

Cold-adapted enzymes from psychrophilic species show the general characteristics of being more heat labile, and having a different balance between enthalpic and entropic contributions to free energy barrier of the catalyzed reaction compared to mesophilic orthologs. Among cold-adapted enzymes, there are also examples that show an enigmatic inactivation at higher temperatures before unfolding of the protein occurs. Here, we analyze these phenomena by extensive computer simulations of the catalytic reactions of psychrophilic and mesophilic α-amylases. The calculations yield temperature dependent reaction rates in good agreement with experiment, and also elicit the anomalous rate optimum for the cold-adapted enzyme, which occurs about 15 °C below the melting point. This result allows us to examine the structural basis of thermal inactivation, which turns out to be caused by breaking of a specific enzyme-substrate interaction. This type of behaviour is also likely to be relevant for other enzymes displaying such anomalous temperature optima.
Role of ferroelectric polarization during growth of highly strained ferroelectric materials
Authors: Liu Rui , Ulbrandt Jeffrey G. , Hsing Hsiang-Chun , Gura Anna , Bein Benjamin , Sun Alec , Pan Charles , Bertino Giulia , Lai Amanda , Cheng Kaize , Doyle Eli , Evans-Lutterodt Kenneth , Headrick Randall L. , Dawber Matthew
Published: May 2020

In ferroelectric thin films and superlattices, the polarization is intricately linked to crystal structure. Here we show that it can also play an important role in the growth process, influencing growth rates, relaxation mechanisms, electrical properties and domain structures. This is studied by focusing on the properties of BaTiO3 thin films grown on very thin layers of PbTiO3 using x-ray diffraction, piezoforce microscopy, electrical characterization and rapid in-situ x-ray diffraction reciprocal space maps during the growth using synchrotron radiation. Using a simple model we show that the changes in growth are driven by the energy cost for the top material to sustain the polarization imposed upon it by the underlying layer, and these effects may be expected to occur in other multilayer systems where polarization is present during growth. This motivates the concept of polarization engineering as a complementary approach to strain engineering.
Accumulation of ambient phosphate into the periplasm of marine bacteria is proton motive force dependent
Authors: Kamennaya Nina A. , Geraki Kalotina , Scanlan David J. , Zubkov Mikhail V.
Published: May 2020

Bacteria acquire phosphate (Pi) by maintaining a periplasmic concentration below environmental levels. We recently described an extracellular Pi buffer which appears to counteract the gradient required for Pi diffusion. Here, we demonstrate that various treatments to outer membrane (OM) constituents do not affect the buffered Pi because bacteria accumulate Pi in the periplasm, from which it can be removed hypo-osmotically. The periplasmic Pi can be gradually imported into the cytoplasm by ATP-powered transport, however, the proton motive force (PMF) is not required to keep Pi in the periplasm. In contrast, the accumulation of Pi into the periplasm across the OM is PMF-dependent and can be enhanced by light energy. Because the conventional mechanism of Pi-specific transport cannot explain Pi accumulation in the periplasm we propose that periplasmic Pi anions pair with chemiosmotic cations of the PMF and millions of accumulated Pi pairs could influence the periplasmic osmolarity of marine bacteria.
Magnetic cilia carpets with programmable metachronal waves
Authors: Gu Hongri , Boehler Quentin , Cui Haoyang , Secchi Eleonora , Savorana Giovanni , De Marco Carmela , Gervasoni Simone , Peyron Quentin , Huang Tian-Yun , Pane Salvador , Hirt Ann M. , Ahmed Daniel , Nelson Bradley J.
Published: May 2020

Metachronal waves commonly exist in natural cilia carpets. These emergent phenomena, which originate from phase differences between neighbouring self-beating cilia, are essential for biological transport processes including locomotion, liquid pumping, feeding, and cell delivery. However, studies of such complex active systems are limited, particularly from the experimental side. Here we report magnetically actuated, soft, artificial cilia carpets. By stretching and folding onto curved templates, programmable magnetization patterns can be encoded into artificial cilia carpets, which exhibit metachronal waves in dynamic magnetic fields. We have tested both the transport capabilities in a fluid environment and the locomotion capabilities on a solid surface. This robotic system provides a highly customizable experimental platform that not only assists in understanding fundamental rules of natural cilia carpets, but also paves a path to cilia-inspired soft robots for future biomedical applications.