bluuebunny/crossref_metadata_2025 huggingface dataset:
Using the International Pandemic Instrument to Revitalize the Innovation Ecosystem for Antimicrobial R&D
Authors: Caceres Andrea Morales , Singh Kshitij Kumar , Minssen Timo , Van Katwyk Susan Rogers , Hoffman Steven J.
Published: March 2023

The inclusion of antimicrobial resistance (AMR) and increased research and development (R&D) capabilities in the most recent outline of the World Health Organization’s (WHO’s) international pandemic instrument signals an opportunity to reshape pharmaceutical R&D system in favour of antimicrobial product development. This article explains why the current innovation ecosystem has disadvantaged the creation of antimicrobial products for human use. It also highlights how the COVID-19 pandemic experience can inform and stimulate international cooperation to implement innovative R&D incentives to bring new, life-saving antimicrobial products to the market.
Embed Multisectoral Governance Mechanisms in the Pandemic Instrument for One Health Action
Authors: Palkovits Michèle , Van Katwyk Susan Rogers , Hoffman Steven J.
Published: March 2023

Despite recognition of the health threat posed at the human-animal-environment interface long ago, One Health has yet to be meaningfully integrated into global pandemic prevention, preparedness, and response. With the negotiation of the forthcoming pandemic instrument under the auspices of the World Health Organization (WHO) — which is inherently restricted by its own constitutional mandate of human health — One Health risks being sidelined once again. Genuine integration of a One Health approach into this treaty will require the institutionalization of formal One Health coordination mechanisms.
Turkey and African agency: the role of Islam and commercialism in Turkey's Africa policy
Authors: Süsler Buğra , Alden Chris
Published: March 2023

The concept of ‘agency’ and its role in capturing the dynamics between Africa and external actors feature increasingly in the African IR scholarship. Over the past decade, Turkey has become an increasingly prominent actor in Africa, strengthening political, cultural and economic ties with African states and providing humanitarian aid and development assistance. In this paper, we examine Turkey's relationship with Africa from the point of view of African agency and ask ‘How much and what kind of agency can we identify by examining the way in which Turkey approaches African states?’ The conventional understanding of the concept of African agency defines it in materialist terms and emphasises its transactional nature; it does not adequately explain incidents of enhanced outcomes for Africans in their relationship with Turkey. We argue that an under-examined aspect and a vital source of African agency lies within the discourses of Turkish policy which provide an enabling source of policy space for negotiation for Africans. We demonstrate that the notion of Muslim kinship in Turkish discourses not only distinguishes Turkey from most of the other external powers engaging with the continent but also enables African interlocutors to negotiate enhanced outcomes.
The rights way forward: reconciling the right to food with biodiversity conservation
Authors: Vasquez Winy , Sunderland Terry
Published: March 2023

The current paradigm of biodiversity conservation, with its continued focus on the notion of pristine nature, has resulted in the separation of humans and nature at the expense of both biological and cultural–linguistic diversity. The continued annexation of land for the cause of conservation has resulted in the curtailment of both rights and access to local and diverse food sources for many rural communities. Indigenous Peoples and local communities are fundamental to conserving biodiversity through sustainable use of nature despite repeated attempts to dispossess them from their lands, cultures and knowledge. It has been this traditional and land-based knowledge that has contributed to the conservation of biodiversity whilst also supporting healthy, diverse and nutritious diets. If we are to achieve a more just and sustainable future, we need to continue to centre conservation initiatives around rights, access and equity whilst respecting a plurality of perspectives, worldviews and knowledge systems. Here we review alternative approaches that help reconcile the right to food with biodiversity conservation, such as biocultural rights, rights-based approaches and integrated land management schemes, with the aim of identifying optimal ways forward for conservation that break away from the dichotomous view that pits people against nature and instead embrace the importance of this symbiotic relationship.
A practical risk calculator for suicidal behavior among transitioning U.S. Army soldiers: results from the Study to Assess Risk and Resilience in Servicemembers-Longitudinal Study (STARRS-LS)
Authors: Kearns Jaclyn C. , Edwards Emily R. , Finley Erin P. , Geraci Joseph C. , Gildea Sarah M. , Goodman Marianne , Hwang Irving , Kennedy Chris J. , King Andrew J. , Luedtke Alex , Marx Brian P. , Petukhova Maria V. , Sampson Nancy A. , Seim Richard W. , Stanley Ian H. , Stein Murray B. , Ursano Robert J. , Kessler Ronald C.
Published: March 2023

Background

Risk of suicide-related behaviors is elevated among military personnel transitioning to civilian life. An earlier report showed that high-risk U.S. Army soldiers could be identified shortly before this transition with a machine learning model that included predictors from administrative systems, self-report surveys, and geospatial data. Based on this result, a Veterans Affairs and Army initiative was launched to evaluate a suicide-prevention intervention for high-risk transitioning soldiers. To make targeting practical, though, a streamlined model and risk calculator were needed that used only a short series of self-report survey questions.

Methods

We revised the original model in a sample of n = 8335 observations from the Study to Assess Risk and Resilience in Servicemembers-Longitudinal Study (STARRS-LS) who participated in one of three Army STARRS 2011–2014 baseline surveys while in service and in one or more subsequent panel surveys (LS1: 2016–2018, LS2: 2018–2019) after leaving service. We trained ensemble machine learning models with constrained numbers of item-level survey predictors in a 70% training sample. The outcome was self-reported post-transition suicide attempts (SA). The models were validated in the 30% test sample.

Results

Twelve-month post-transition SA prevalence was 1.0% (s.e. = 0.1). The best constrained model, with only 17 predictors, had a test sample ROC-AUC of 0.85 (s.e. = 0.03). The 10–30% of respondents with the highest predicted risk included 44.9–92.5% of 12-month SAs.

Conclusions

An accurate SA risk calculator based on a short self-report survey can target transitioning soldiers shortly before leaving service for intervention to prevent post-transition SA.
6 Crete: Early Iron Age to Classical
Authors: Kotsonas Antonis
Published: March 2023

This review covers recent archaeological work on Early Iron Age to Classical Crete, focusing on research conducted and published in the 2010s. Proceeding from the west to the east part of the island, and encompassing material ranging from the 12th to the mid-fourth century BC, this study finds that, overall, the field is flourishing, despite the challenges created by the international financial crisis and the constraints posed by the global pandemic. In the last decade, the major archaeological projects which focus on Crete for the period under examination continued with their fieldwork and finds research, while new projects were also established. Additionally, as many as eight archaeological museums were opened, reopened, or are about to open. Nevertheless, final publication of large bodies of Cretan material from the period in question remain scarce, a condition which is more severe on the western half of the island. Notwithstanding its floruit, research on Early Iron Age to Classical Crete is often treated as relatively marginal, and – arguably – rather inconsequential to the grand narratives of Greek history, and art and archaeology. This paper traces the roots of this problem and shows that current work on the archaeology of Early Iron Age to Classical Crete has full potential for revolutionizing the largely Athenocentric paradigm which still pervades the study of ancient Greece.
9 A brief history of the BSA Museum Study Collection
Authors: Loy Michael
Published: March 2023

The BSA Museum houses a study collection of artefacts donated to the BSA and collected by its members up to the 1960s. The collection provides a valuable resource for teaching and research, enabling scholars to gain first-hand familiarity with objects from a range of material types (including ceramics, metals, stone, terracotta) dating from the Neolithic through to the Late Byzantine period. The collection comprises some 4,000 individual artefacts and over 46,000 sherds of pottery, objects that have been displayed in different parts of the BSA premises over the past 130 years. Of the whole collection, various small sections have been published in the Annual of the BSA. What has been lacking, however, is a narrative about the museum itself: where its objects came from, who studied them, how the collection as a whole has been catalogued and organized. This paper tells that story: from the collection’s humble beginnings, with the first donation of just a few sherds in 1892, through to recently completed digitization and public engagement projects.
3 Newsround
Authors: Martin Daphne D.
Published: March 2023

‘Newsround’ offers a platform for new discoveries that do not appear within the specialist contributions of this year’s Archaeological Reports, but which nevertheless warrant emphasis, either as a result of their particular characteristics or for the contribution they make to broader archaeological narratives. This section is not intended to be exhaustive, but rather an overview of archaeological research in Greece. It comprises largely preliminary reports (results of excavations that took place up to and including August 2022, where possible) that complement the digital content made available through Archaeology in Greece Online (https://chronique.efa.gr). Due to the diachronic nature of a number of the sites, and for ease of reference, the material is organized geographically in the first instance and then chronologically (earliest to latest) within each section as far as possible.
The intervention effect of ideological education means of college staff on improving mania of college students
Authors: Xiao Jian
Published: March 2023

Background

Mania is one of the common diseases in psychiatric department. With the accelerating pace of life, people are facing more and more pressure. Mental disorders and mentally ill patients are also increasing, especially in the student group. Patients with mania may have clinical symptoms such as self-talk and exaggerated actions, and depression. Seriou’s mania has a great impact on students’ life and mental state. In schools, teachers are more required to carry out correct ideological education and psychological counseling for students. Therefore, the research is conducted from the ideological education of college teachers and staff to improve students or treat students’ mania symptoms.

Subjects and Methods

108 manic patients were selected from 3 colleges and universities to participate in the designed manic intervention experiment. In the experiment, the subjects were divided into experimental group and control group. The control group was treated with routine relaxation training; The experimental group was treated with ideological education and regular relaxation training. The results were reflected by the Bech Rafaelsdn Mania Rating Scale (BRMS), Hamilton Anxiety Scale, and Depression Scale.

Results

Table 1 shows the results of manic scale scores in the intervention experiment. In Table 1, the BRMS score of the control group decreased from 25.46 before the experiment to 18.25, with a decrease of 7.21 points; The BRMS score of the experimental group decreased from 24.53 before the experiment to 12.15, a decrease of 12.38 points.Table 1.

RBMS score results of intervention experiment

Group CategoryBRMSBefore experimentThe first monthThe second monthThe third monthControl group25.46±1.0723.57±1.6720.47±1.6318.25±2.07Experimental group24.53±1.3820.14±2.1116.86±2.3312.15±1.48

Conclusions

Through the ideological education of college teachers and staff, the research conducted intervention treatment on students’ mania, and compared the decline trend of the scores of the two groups. The decline trend of the experimental group was more obvious. The method adopted by the experimental group was more effective in the treatment of students’ mania. It shows that the ideological education of teaching staff plays an important role in the mental health of students. Colleges and universities should give full play to the role of ideological education to ensure the mental health of students.

Acknowledgement

The research is supported by: Research Project on Undergraduate Teaching Reform of Liaoning Ordinary Undergraduate Higher Education, 2022 “Research on the Reform of the Open and Shared Management Mode of Multidisciplinary Laboratories in the National Experimental Teaching Demonstration Center of Fashion Design and Engineering” No. LNJXGG2022-371.
Non-Gaussian score-driven conditionally heteroskedastic models with a macroeconomic application
Authors: Blazsek Szabolcs , Escribano Álvaro , Licht Adrián
Published: March 2023

We contribute to the literature on empirical macroeconomic models with time-varying conditional moments, by introducing a heteroskedastic score-driven model with Student’st-distributed innovations, named the heteroskedastic score-driven$t$-QVAR (quasi-vector autoregressive) model. The$t$-QVAR model is a robust nonlinear extension of the VARMA (VAR moving average) model. As an illustration, we apply the heteroskedastic$t$-QVAR model to a dynamic stochastic general equilibrium model, for which we estimate Gaussian-ABCD and$t$-ABCD representations. We use data on economic output, inflation, interest rate, government spending, aggregate productivity, and consumption of the USA for the period of 1954 Q3 to 2022 Q1. Due to the robustness of the heteroskedastic$t$-QVAR model, even including the period of the coronavirus disease of 2019 (COVID-19) pandemic and the start of the Russian invasion of Ukraine, we find a superior statistical performance, lower policy-relevant dynamic effects, and a higher estimation precision of the impulse response function for US gross domestic product growth and US inflation rate, for the heteroskedastic score-driven$t$-ABCD representation rather than for the homoskedastic Gaussian-ABCD representation.
Language proficiency predictors of code-switching behavior in dual-language-learning children
Authors: Schächinger Tenés L. T. , Weiner-Bühler J. C. , Volpin L. , Grob A. , Skoruppa K. , Segerer R. K.
Published: March 2023

Code-switching, switching between different languages within the same conversation, is a prominent feature in bilingual communication. This study aimed to elucidate to what extent the linguistic abilities and age of dual-language-learning preschoolers influence the frequency and purposes of code-switching (compensatory, to bridge linguistic gaps; preferential, to express content as fluently as possible; pragmatic, to phrase something appropriately for the situation). Parental code-switching ratings of 101 German/French–Turkish/Italian dual-language learners aged 32–78 months were analyzed. Generalized linear mixed models revealed positive but no negative effects of societal- and heritage-language skills on children's code-switching frequencies independent of switching purposes and with no evidence of age effects. Hence, code-switching across the preschool age mainly reflects high linguistic competences. Models with linguistically and psychometrically parallelized language scores indicated a strong switching tendency toward the societal language when proficiency in both languages is high, and away from the societal language when language proficiencies are low.
Estimation of the extent of phenotypic diversity among cashew (Anacardium occidentaleL.) genotypes based on agro-morphological and physicochemical traits
Authors: Matos-Filho Carlos Humberto Aires , de Carvalho-Junior José Eduardo Vasconcelos , Costa Gérson do Nascimento , Costa Marcones Ferreira , Nunes José Airton Rodrigues , Lopes Ângela Celis de Almeida , Ferreira-Gomes Regina Lucia
Published: March 2023

Cashew (Anacardium occidentale L.) is cultivated in more than 30 countries because of its economic and nutritional importance. Despite having a significant agronomic role, little is known about the genetic and phenotypic diversity of cashew populations in Brazil. Thus, we aimed to characterize and estimate the diversity among cashew genotypes based on agro-morphological and physicochemical traits, with an objective of selection of varieties for breeding programmes. Forty-three cashew trees were evaluated based on 13 morphological traits and three physicochemical traits. A wide range of variations was recorded for the phenotypic characteristics, including total weight, fruit weight, pseudofruit length, kernel weight and total acidity, suggesting the existence of considerable variations for potential use in breeding programmes. Principal component analysis explained 79.74% of the total variation in the first two principal axes. The dendrogram based on the UPGMA method classified the 43 genotypes into six groups. Groups IV and VI were the most dissimilar, with emphasis on the genotypes 28 and 43, which were observed to be most divergent based on the Euclidean distance matrix (3.054). This makes it possible to select genotypes for hybridization with F1generation gains. Based on cluster analysis and comparison of means among the six groups, promising genotypes were identified with superior traits, such as fruit weight, pseudofruit length, kernel weight and total acidity. This suggests the importance of phenotypic characterization for cashew breeding programmes. In addition, the observed vast diversity is an important genetic basis for improving cashew yield in northeastern Brazil.
Corruption and Political Support: The Case of Peru’s Vacuna-gate Scandal
Authors: Castorena Oscar , Lupu Noam , Wolsky Adam D. , Zechmeister Elizabeth J.
Published: March 2023

Classic theories of public opinion suggest that negative shocks can undermine system support in weak democracies, but scant work has systematically assessed this thesis. We identify Peru’s explosive Vacuna-gate scandal as a most-likely case for finding a connection between corruption and political support. The scandal’s unexpected revelation in the middle of the 2021 AmericasBarometer Peru survey created conditions for a natural experiment. Applying an unexpected-event-during-survey design, we consider the consequences of the scandal for perceptions of corruption, system support, and support for democracy. We find robust evidence that the scandal increased even already high perceptions of corruption and lowered system support. Contrary to expectations derived from prior theories, we find no effect on explicit support for democracy. In the conclusion, we discuss the nuanced ways that scandal may shape democratic stability.
Zusammenhang zwischen unterschiedlichen Mobbingerfahrungen und der Ausprägung von Borderline-Persönlichkeitsstörungsmerkmalen bei Jugendlichen in der Kinder- und Jugendpsychiatrie
Authors: Seiffert Nora , Cavelti Marialuisa , Josi Johannes , Reichl Corinna , Koenig Julian , Mürner-Lavanchy Ines , Kaess Michael
Published: March 2023

Zusammenfassung: Theroretischer Hintergrund: Die vorliegende Studie untersucht den Zusammenhang zwischen Mobbing‍(–Arten) und der Ausprägung der Borderline-Persönlichkeitsstörung (BPS) bei Jugendlichen. Methode: 513 konsekutiv rekrutierte, jugendliche Patient_innen nahmen an einer umfassenden Diagnostik teil. Der Zusammenhang zwischen der Häufigkeit von Mobbingerfahrungen und der Anzahl der BPS-Kriterien wurde mit Hilfe von ordinalen logistischen Regressionen untersucht. Ergebnisse: Jugendliche Patient_innen, die in den vergangenen drei Monaten mehrmals pro Woche gemobbt wurden, wiesen eine stärkere BPS-Symptomatik auf als Jugendliche ohne Mobbingerfahrung (OR = 3.47, CI = 2.32 – 5.18, p < 0.001). Soziales Mobbing und Bedrohen erwiesen sich als wichtigste Prädiktoren für den Schweregrad der BPS-Symptomatik. Diskussion und Schlussfolgerung: Häufigere Mobbingerfahrungen, insbesondere sozialer und bedrohender Art, waren mit mehr Symptomen der BPS assoziiert. Programme zur Prävention von Mobbing an Schulen sollten gefördert sowie in der Behandlung von Patienten thematisiert werden.
High‐Frequency 3D LiDAR Measurements of a Debris Flow: A Novel Method to Investigate the Dynamics of Full‐Scale Events in the Field
Authors: Aaron Jordan , Spielmann Raffaele , McArdell Brian W. , Graf Christoph
Published: March 2023

Surging debris flows are among the most destructive natural hazards, and elucidating the interaction between coarse‐grained fronts and the trailing liquefied slurry is key to understanding these flows. Here, we describe the application of high‐resolution and high‐frequency 3D LiDAR data to explore the dynamics of a debris flow at Illgraben, Switzerland. The LiDAR measurements facilitate automated detection of features on the flow surface, and construction of the 3D flow depth and velocity fields through time. Measured surface velocities (2–3 m s−1) are faster than front velocities (0.8–2 m s−1), illustrating the mechanism whereby the flow front is maintained along the channel. Further, we interpret the relative velocity of different particles to infer that the vertical velocity profile varies between plug flow and one that features internal shear. Our measurements provide unique insights into debris‐flow motion, and provide the foundation for a more detailed understanding of these hazardous events.
Decompression and Fracturing Caused by Magmatically Induced Thermal Stresses
Authors: Kiss D. , Moulas E. , Kaus B. J. P. , Spang A.
Published: March 2023

Studies of host rock deformation around magmatic intrusions usually focus on the development of stresses directly related to the intrusion process. This is done either by considering an inflating region that represents the intruding body, or by considering multiphase deformation. Thermal processes, especially volume changes caused by thermal expansion are typically ignored. We show that thermal stresses around upper crustal magma bodies are likely to be significant and sufficient to create an extensive fracture network around the magma body by brittle yielding. At the same time, cooling induces decompression within the intrusion, which can promote the appearance of a volatile phase. Volatile phases and the development of a fracture network around the inclusion may thus be the processes that control magmatic‐hydrothermal alteration around intrusions. This suggests that thermal stresses likely play an important role in the development of magmatic systems. To quantify the magnitude of thermal stresses around cooling intrusions, we present a fully compressible 2D visco‐elasto‐plastic thermo‐mechanical numerical model. We utilize a finite difference staggered grid discretization and a graphics processing unit based pseudo‐transient solver. First, we present purely thermo‐elastic solutions, then we include the effects of viscous relaxation and plastic yielding. The dominant deformation mechanism in our models is determined in a self‐consistent manner, by taking into account stress, pressure, and temperature conditions. Using experimentally determined flow laws, the resulting thermal stresses can be comparable to or even exceed the confining pressure. This suggests that thermal stresses alone could result in the development of a fracture network around magmatic bodies.
The EUV Reflectance of Mercury's Surface Measured by BepiColombo/PHEBUS
Authors: Chaufray J.‐Y. , Quémerais E. , Koutroumpa D. , Robidel R. , Leblanc F. , Réberac A. , Yoshikawa I. , Yoshioka K. , Murakami G. , Korablev O. , Belyaev D. , Pelizzo M. G. , Corso A. J.
Published: March 2023

On 9 and 10 October 2021, Probing the Hermean Exosphere by Ultraviolet Spectroscopy aboard BepiColombo observed the disk‐integrated reflected light from the Sun by Mercury in the spectral range 90–160 nm at a phase angle of 70°. These observations are used to derive the EUV reflectance of the surface of Mercury in this wavelength range for the first time since the Mariner 10 observations in 1974–1975. Our observations are in agreement with a surface of Mercury darker by a factor ∼0.5–0.6 compared to the Moon in this wavelength range, with an average reflectance of 0.3% at a phase angle of 70°. This lower reflectance of Mercury could be due to the lower abundance of FeO. The derived reflectance near 160 nm is close to the derived reflectance at 220 nm by MESSENGER/MASCS at a similar phase angle. Possible spectral variations measured between 110 and 140 nm could be attributed to SiO2 glass, but the signal to noise ratio is low and other observations, possible at several periods during the rest of the cruise, are needed to confirm this last result.
Challenges in Hydrologic‐Land Surface Modeling of Permafrost Signatures—A Canadian Perspective
Authors: Abdelhamed Mohamed S. , Elshamy Mohamed E. , Razavi Saman , Wheater Howard S.
Published: March 2023

Permafrost thaw/degradation in the Northern Hemisphere due to global warming is projected to accelerate in coming decades. Assessment of this trend requires improved understanding of the evolution and dynamics of permafrost areas. Land surface models (LSMs) are well‐suited for this due to their physical basis and large‐scale applicability. However, LSM application is challenging because (a) LSMs demand extensive and accurate meteorological forcing data, which are not readily available for historic conditions and only available with significant biases for future climate, (b) LSMs possess a large number of model parameters, and (c) observations of thermal/hydraulic regimes to constrain those parameters are severely limited. This study addresses these challenges by applying the MESH‐CLASS modeling framework (Modélisation Environmenntale communautaire—Surface et Hydrology embedding the Canadian Land Surface Scheme) to three regions within the Mackenzie River Basin, Canada, under various meteorological forcing data sets, using the variogram analysis of response surfaces framework for sensitivity analysis and threshold‐based identifiability analysis. The study shows that the modeler may face complex trade‐offs when choosing a forcing data set; for current and future scenarios, forcing data require multi‐variate bias correction, and some data sets enable the representation of some aspects of permafrost dynamics, but are inadequate for others. The results identify the most influential model parameters and show that permafrost simulation is most sensitive to parameters controlling surface insulation and runoff generation. But the identifiability analysis reveals that many of the most influential parameters are unidentifiable. These conclusions can inform future efforts for data collection and model parameterization.
Deep Conditional Generative Adversarial Network Combined With Data‐Space Inversion for Estimation of High‐Dimensional Uncertain Geological Parameters
Authors: Fu Wenhao , Zhang Kai , Ma Xiaopeng , Liu Piyang , Zhang Liming , Yan Xia , Yang Yongfei , Sun Hai , Yao Jun
Published: March 2023

Inverse modeling can provide a reliable geological model for subsurface flow numerical simulation, which is a challenging issue that requires calibration of the uncertain parameters of the geological model to establish an acceptable match between simulation data and observation data. The general inverse modeling method needs to iteratively adjust the uncertain parameters, which is a difficult and time‐consuming high‐dimensional sampling problem. To address this problem, we propose a deep‐learning‐based inverse modeling method called pix2pixGAN‐DSI. In this method, the deep‐learning‐based image‐to‐image generative adversarial network (pix2pixGAN) is constructed to directly predict the posterior parameter fields from the posterior dynamic responses obtained by the data‐space inversion (DSI) method. This inverse modeling method does not need to iteratively adjust the uncertain parameters, which improves computational efficiency. The effectiveness of the proposed method is verified through a Gaussian model case and two non‐Gaussian channelized model cases. Through the analysis of posterior realizations, matching and forecast of production data, and uncertainty quantification, the results show that the proposed method can obtain reasonable estimates without iteration and parameterization.
Changes in neural responses during affective and non-affective tasks and improvement of posttraumatic stress disorder symptoms following trauma-focused psychotherapy
Authors: Korgaonkar Mayuresh S. , Felmingham Kim L. , Malhi Gin S. , Williamson Thomas H. , Williams Leanne M. , Bryant Richard A.
Published: March 2023

At least one-third posttraumatic stress disorder (PTSD) patients do not respond to trauma-focused psychotherapy (TF-psychotherapy), which is the treatment of choice for PTSD. To clarify the change mechanisms that may be associated with treatment response, this study examined changes in neural activations during affective and non-affective processing that occur with improvement of symptoms after TF-psychotherapy. This study assessed PTSD treatment-seeking patients (n = 27) prior to and after TF-psychotherapy using functional magnetic resonance imaging when they completed three tasks: (a) passive viewing of affective faces, (b) cognitive reappraisal of negative images, and (c) non-affective response inhibition. Patients then underwent 9 sessions of TF-psychotherapy, and were assessed on the Clinician-Administered PTSD Scale following treatment. Changes in neural responses in affect and cognitive processing regions-of-interest for each task were correlated with reduction of PTSD severity from pretreatment to posttreatment in the PTSD cohort. Data from 21 healthy controls was used for comparison. Improvement of symptoms in PTSD were associated with increased activation of left anterior insula, reductions in the left hippocampus and right posterior insula during viewing of supraliminally presented affective images, and reduced connectivity between the left hippocampus with the left amygdala and rostral anterior cingulate. Treatment response was also associated with reduced activation in the left dorsolateral prefrontal cortex during reappraisal of negative images. There were no associations between response and activation change during response inhibition. This pattern of findings indicates that improvement of PTSD symptoms following TF-psychotherapy is associated with changes in affective rather than non-affective processes. These findings accord with prevailing models that TF-psychotherapy promotes engagement and mastery of affective stimuli.

Clinical Trials Registration: Trial Registration: Prospectively registered at Australian and New Zealand Clinical Trials Registry, ACTRN12612000185864 and ACTRN12609000324213. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=83857
Imputation-powered whole-exome analysis identifies genes associated with kidney function and disease in the UK Biobank
Authors: Wuttke Matthias , König Eva , Katsara Maria-Alexandra , Kirsten Holger , Farahani Saeed Khomeijani , Teumer Alexander , Li Yong , Lang Martin , Göcmen Burulca , Pattaro Cristian , Günzel Dorothee , Köttgen Anna , Fuchsberger Christian
Published: March 2023

Genome-wide association studies have discovered hundreds of associations between common genotypes and kidney function but cannot comprehensively investigate rare coding variants. Here, we apply a genotype imputation approach to whole exome sequencing data from the UK Biobank to increase sample size from 166,891 to 408,511. We detect 158 rare variants and 105 genes significantly associated with one or more of five kidney function traits, including genes not previously linked to kidney disease in humans. The imputation-powered findings derive support from clinical record-based kidney disease information, such as for a previously unreported splice allele in PKD2, and from functional studies of a previously unreported frameshift allele in CLDN10. This cost-efficient approach boosts statistical power to detect and characterize both known and novel disease susceptibility variants and genes, can be generalized to larger future studies, and generates a comprehensive resource (https://ckdgen-ukbb.gm.eurac.edu/) to direct experimental and clinical studies of kidney disease.
Immune selection determines tumor antigenicity and influences response to checkpoint inhibitors
Authors: Zapata Luis , Caravagna Giulio , Williams Marc J. , Lakatos Eszter , AbdulJabbar Khalid , Werner Benjamin , Chowell Diego , James Chela , Gourmet Lucie , Milite Salvatore , Acar Ahmet , Riaz Nadeem , Chan Timothy A. , Graham Trevor A. , Sottoriva Andrea
Published: March 2023

In cancer, evolutionary forces select for clones that evade the immune system. Here we analyzed >10,000 primary tumors and 356 immune-checkpoint-treated metastases using immune dN/dS, the ratio of nonsynonymous to synonymous mutations in the immunopeptidome, to measure immune selection in cohorts and individuals. We classified tumors as immune edited when antigenic mutations were removed by negative selection and immune escaped when antigenicity was covered up by aberrant immune modulation. Only in immune-edited tumors was immune predation linked to CD8 T cell infiltration. Immune-escaped metastases experienced the best response to immunotherapy, whereas immune-edited patients did not benefit, suggesting a preexisting resistance mechanism. Similarly, in a longitudinal cohort, nivolumab treatment removes neoantigens exclusively in the immunopeptidome of nonimmune-edited patients, the group with the best overall survival response. Our work uses dN/dS to differentiate between immune-edited and immune-escaped tumors, measuring potential antigenicity and ultimately helping predict response to treatment.
Bioactivity of brassica seed meals and its compounds as ecofriendly larvicides against mosquitoes
Authors: Flor-Weiler Lina B. , Behle Robert W. , Berhow Mark A. , McCormick Susan P. , Vaughn Steven F. , Muturi Ephantus J. , Hay William T.
Published: March 2023

Strategic, sustainable, and ecofriendly alternatives to chemical pesticides are needed to effectively control mosquitoes and reduce the incidence of their vectored diseases. We evaluated several Brassicaceae (mustard family) seed meals as sources of plant derived isothiocyanates produced from the enzymatic hydrolysis of biologically inactive glucosinolates for the control of Aedesaegypti (L., 1762). Five defatted seed meals (Brassicajuncea (L) Czern., 1859, Lepidiumsativum L., 1753, Sinapisalba L., 1753, Thlaspiarvense L., 1753, and Thlaspiarvense—heat inactivated and three major chemical products of enzymatic degradation (allyl isothiocyanate, benzyl isothiocyanate and 4-hydroxybenzyl isothiocyanate) were assayed to determine toxicity (LC50) to Ae.aegypti larvae. All seed meals except the heat inactivated T.arvense were toxic to mosquito larvae. L.sativum seed meal was the most toxic treatment to larvae (LC50 = 0.04 g/120 mL dH2O) at the 24-h exposure. At the 72-h evaluation, the LC50 values for B.juncea,S.alba and T.arvense seed meals were 0.05, 0.08 and 0.1 g/120 mL dH2O, respectively. Synthetic benzyl isothiocyanate was more toxic to larvae 24-h post treatment (LC50 = 5.29 ppm) compared with allyl isothiocyanate (LC50 = 19.35 ppm) and 4-hydroxybenzyl isothiocyanate (LC50 = 55.41 ppm). These results were consistent with the higher performance of the benzyl isothiocyanate producing L.sativum seed meal. Isothiocyanates produced from seed meals were more effective than the pure chemical compounds, based on calculated LC50 rates. Using seed meal may provide an effective method of delivery for mosquito control. This is the first report evaluating the efficacy of five Brassicaceae seed meals and their major chemical constituent against mosquito larvae and demonstrates how natural compounds from Brassicaceae seed meals can serve as a promising ecofriendly larvicides to control mosquitoes.
Environmental effects on brain functional networks in a juvenile twin population
Authors: Tassi Emma , Maggioni Eleonora , Mauri Maddalena , Fagnani Corrado , Agarwal Nivedita , Bianchi Anna Maria , Stazi Maria A. , Nobile Maria , Brambilla Paolo
Published: March 2023

The brain’s intrinsic organization into large-scale functional networks, the resting state networks (RSN), shows complex inter-individual variability, consolidated during development. Nevertheless, the role of gene and environment on developmental brain functional connectivity (FC) remains largely unknown. Twin design represents an optimal platform to shed light on these effects acting on RSN characteristics. In this study, we applied statistical twin methods to resting-state functional magnetic resonance imaging (rs-fMRI) scans from 50 young twin pairs (aged 10–30 years) to preliminarily explore developmental determinants of brain FC. Multi-scale FC features were extracted and tested for applicability of classical ACE and ADE twin designs. Epistatic genetic effects were also assessed. In our sample, genetic and environmental effects on the brain functional connections largely varied between brain regions and FC features, showing good consistency at multiple spatial scales. Although we found selective contributions of common environment on temporo-occipital connections and of genetics on frontotemporal connections, the unique environment showed a predominant effect on FC link- and node-level features. Despite the lack of accurate genetic modeling, our preliminary results showed complex relationships between genes, environment, and functional brain connections during development. A predominant role of the unique environment on multi-scale RSN characteristics was suggested, which needs replications on independent samples. Future investigations should especially focus on nonadditive genetic effects, which remain largely unexplored.
In a secondary analysis from a randomised, double-blind placebo-controlled trial Dexmedetomidine blocks cholinergic dysregulation in delirium pathogenesis in patients with major surgery
Authors: Jacob Yanite , Schneider Bill , Spies Claudia , Heinrich Maria , von Haefen Clarissa , Kho Widuri , Pohrt Anne , Müller Anika
Published: March 2023

Dexmedetomidine is an alpha-2 adrenoreceptor agonist with anti-inflammatory and anti-delirogenic properties. Pathogenesis of postoperative delirium (POD) includes cholinergic dysfunction and deregulated inflammatory response to surgical trauma. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are discussed as biomarkers for both POD and severity in acute inflammation. To show whether there is a link between blood cholinesterase activities and dexmedetomidine, we performed a secondary analysis of a randomised, double-blind, placebo-controlled trial that recently showed a lower incidence of POD in the dexmedetomidine group. Abdominal or cardiac surgical patients aged ≥ 60 years were randomised to receive dexmedetomidine or placebo intra- and postoperatively in addition to standard general anaesthesia. We analysed the course of perioperative cholinesterase activities of 56 patients, measured preoperatively and twice postoperatively. Dexmedetomidine resulted in no change in AChE activity and caused a rapid recovery of BChE activity after an initial decrease, while placebo showed a significant decrease in both cholinesterase activities. There were no significant between-group differences at any point in time. From these data it can be assumed that dexmedetomidine could alleviate POD via altering the cholinergic anti-inflammatory pathway (CAIP). We advocate for further investigations to show the direct connection between dexmedetomidine and cholinesterase activity.
Fenretinide inhibits obesity and fatty liver disease but induces Smpd3 to increase serum ceramides and worsen atherosclerosis in LDLR−/− mice
Authors: Thompson Dawn , Mahmood Shehroz , Morrice Nicola , Kamli-Salino Sarah , Dekeryte Ruta , Hoffmann Philip A. , Doherty Mary K. , Whitfield Philip D. , Delibegović Mirela , Mody Nimesh
Published: March 2023

Fenretinide is a synthetic retinoid that can prevent obesity and improve insulin sensitivity in mice by directly altering retinol/retinoic acid homeostasis and inhibiting excess ceramide biosynthesis. We determined the effects of Fenretinide on LDLR−/− mice fed high-fat/high-cholesterol diet ± Fenretinide, a model of atherosclerosis and non-alcoholic fatty liver disease (NAFLD). Fenretinide prevented obesity, improved insulin sensitivity and completely inhibited hepatic triglyceride accumulation, ballooning and steatosis. Moreover, Fenretinide decreased the expression of hepatic genes driving NAFLD, inflammation and fibrosis e.g. Hsd17b13, Cd68 and Col1a1. The mechanisms of Fenretinide’s beneficial effects in association with decreased adiposity were mediated by inhibition of ceramide synthesis, via hepatic DES1 protein, leading to increased dihydroceramide precursors. However, Fenretinide treatment in LDLR−/− mice enhanced circulating triglycerides and worsened aortic plaque formation. Interestingly, Fenretinide led to a fourfold increase in hepatic sphingomyelinase Smpd3 expression, via a retinoic acid-mediated mechanism and a further increase in circulating ceramide levels, linking induction of ceramide generation via sphingomyelin hydrolysis to a novel mechanism of increased atherosclerosis. Thus, despite beneficial metabolic effects, Fenretinide treatment may under certain circumstances enhance the development of atherosclerosis. However, targeting both DES1 and Smpd3 may be a novel, more potent therapeutic approach for the treatment of metabolic syndrome.
A pilot study on lengthening potentials and biomechanical effects of double and triple hemisection on tendon with slide lengthening
Authors: Wang T. , Yu H. , Tian Guo-fu , Zhao Rui-xiang
Published: March 2023

The current study explored the slide-lengthening potentials of double and triple hemisections and the biomechanical effects of different inter-hemisection distances. Forty-eight porcine flexor digitorum profundus tendons were divided into double- and triple-hemisection groups (Groups A and B) and a control group (Group C). Group A was divided into Group A1 (distance between hemisections were the same as Group B) and Group A2 (distance between hemisections corresponded to the greatest distance between hemisections in Group B). Biomechanical evaluation, motion analysis, and finite element analysis (FEA) were performed. Failure load of intact tendon was significantly highest among groups. When the distance was 4 cm, the failure load of Group A increased significantly. When the distance between the hemisections was 0.5 or 1 cm, the failure load of Group B was significantly lower than Group A. Tendon elongation and failure load of Group B were significantly lower than those in Group A when the greatest distance between hemisections was the same. Consequently, Double hemisections had a similar lengthening ability to that of triple hemisections with the same distance, but better when the distances between extreme hemisections matched. However, the driving force for the initiation of lengthening may be greater.
The electronic medical record management systems may improve monitoring and control of disease activity in patients with ankylosing spondylitis
Authors: Huang Pei-Ju , Chen Yi-Hsing , Huang Wen-Nan , Chen Yi-Ming , Lai Kuo-Lung , Hsieh Tsu-Yi , Hung Wei-Ting , Lin Ching-Tsai , Tseng Chih-Wei , Tang Kuo-Tung , Chou Yin-Yi , Wu Yi-Da , Huang Chin-Yin , Hsieh Chia-Wei , Chen Yen-Ju , Liao Yu-Wan , Liu Yen-Tze , Chen Hsin-Hua
Published: March 2023

To investigate the impact of an electronic medical record management system (EMRMS) on disease activity and the frequency of outpatient visits among patients with ankylosing spondylitis (AS). We identified 652 patients with AS who were followed up for at least 1 year before and after the first Ankylosing Spondylitis Disease Activity Score (ASDAS) assessment and compared the number of outpatient visits and average visit time within 1 year before and after the initial ASDAS assessment. Finally, we analyzed 201 patients with AS who had complete data and received ≥ 3 continuous ASDAS assessments at an interval of 3 months, and we compared the results of the second and third ASDAS assessments with those of the first. The number of annual outpatient visits increased after ASDAS assessment (4.0 (4.0, 7.0) vs. 4.0 (4.0, 8.0), p < 0.001), particularly among those with a high initial disease activity. The average visit time was reduced within 1 year after ASDAS assessment (6.4 (8.5, 11.2) vs. 6.3 (8.3, 10.8) min, p = 0.073), especially among patients whose with an inactive disease activity was < 1.3 (ASDAS C-reactive protein (CRP) 6.7 (8.8, 11.1) vs. 6.1 (8.0, 10.3) min, p = 0.033; ASDAS erythrocyte sedimentation rate (ESR) 6.4 (8.7, 11.1) vs. 6.1 (8.1, 10.0) min, p = 0.027). Among patients who received at least three ASDAS assessments, the third ASDAS-CRP tended to be lower than the first (1.5 (0.9, 2.1) vs. 1.4 (0.8, 1.9), p = 0.058). The use of an EMRMS increased the frequency of ambulatory visits among AS patients with high and very high disease activity and reduced the visit time among those with an inactive disease. Continual ASDAS assessments may help control the disease activity of patients with AS.
ECG-guided non-invasive estimation of pulmonary congestion in patients with heart failure
Authors: Raghu Aniruddh , Schlesinger Daphne , Pomerantsev Eugene , Devireddy Srikanth , Shah Pinak , Garasic Joseph , Guttag John , Stultz Collin M.
Published: March 2023

Quantifying hemodynamic severity in patients with heart failure (HF) is an integral part of clinical care. A key indicator of hemodynamic severity is the mean Pulmonary Capillary Wedge Pressure (mPCWP), which is ideally measured invasively. Accurate non-invasive estimates of the mPCWP in patients with heart failure would help identify individuals at the greatest risk of a HF exacerbation. We developed a deep learning model, HFNet, that uses the 12-lead electrocardiogram (ECG) together with age and sex to identify when the mPCWP > 18 mmHg in patients who have a prior diagnosis of HF. The model was developed using retrospective data from the Massachusetts General Hospital and evaluated on both an internal test set and an independent external validation set, from another institution. We developed an uncertainty score that identifies when model performance is likely to be poor, thereby helping clinicians gauge when to trust a given model prediction. HFNet AUROC for the task of estimating mPCWP > 18 mmHg was 0.8 $$2\pm$$

2
±

0.01 and 0.$$81\pm$$

81
±

0.01 on the internal and external datasets, respectively. The AUROC on predictions with the highest uncertainty are 0.50 $$\pm$$
±
0.02 (internal) and 0.$$56\pm$$

56
±

0.04 (external), while the AUROC on predictions with the lowest uncertainty were 0.86 ± 0.01 (internal) and 0.82 ± 0.01 (external). Using estimates of the prevalence of mPCWP > 18 mmHg in patients with reduced ventricular function, and a decision threshold corresponding to an 80% sensitivity, the calculated positive predictive value (PPV) is 0.$$89\pm$$

89
±

0.01when the corresponding chest x-ray (CXR) is consistent with interstitial edema HF. When the CXR is not consistent with interstitial edema, the estimated PPV is 0.$$78\pm$$

78
±

0.02, again at an 80% sensitivity threshold. HFNet can accurately predict elevated mPCWP in patients with HF using the 12-lead ECG and age/sex. The method also identifies cohorts in which the model is more/less likely to produce accurate outputs.