bluuebunny/crossref_metadata_2025 huggingface dataset:
Bekämpfung der Spielwettbewerbsmanipulation
Authors: Memmert Daniel , Brinkschulte Michel , Breuer Christoph
Published: July 2021

Spielmanipulation stellt heutzutage eine der größten Bedrohungen für die Integrität des Sports dar, da sie zu einem Vertrauensverlust in die Fairness des Wettbewerbs führt. Als Reaktion auf Vorfälle in der Vergangenheit kommen im deutschen Sport deshalb zunehmend Bemühungen auf, Präventionsmaßnahmen zu entwickeln und durchzuführen. Der wissenschaftliche Stand zu den Präventionsmethoden von Spielmanipulation in Deutschland ist allerdings noch rudimentär. Das Ziel der vorliegenden Studie ist daher, eine Bestandsaufnahme der im deutschen Fußballsport vorhandenen Präventionsmaßnahmen und durchführenden Institutionen zu machen. Zudem sollten ebendiese Maßnahmen und Institutionen mit Hilfe eines Online-Fragebogens von den daran teilnehmenden Personen (Spieler, Trainer*innen/Funktionär*innen sowie Schiedsrichter*innen der Bundesliga, 2. Bundesliga und A‑Jugend-Bundesliga) bewertet werden. Die Ergebnisse der Bestandsaufnahme zeigen, dass sich der deutsche Fußballsport bereits sehr fortschrittlich mit der Prävention von Spielmanipulation auseinandersetzt und eine Vielzahl von präventiven Angeboten vorhanden ist. Die Ergebnisse der Befragung zeigen, dass die durchgeführten Maßnahmen zwar in fast allen Aspekten als gut bis sehr gut bewertet wurden, die allgemeine Kenntnis über die vorhandenen Maßnahmen muss allerdings als gering eingestuft werden (23,0% der Teilnehmer kannten keine der vorhandenen Maßnahmen und durchführenden Institutionen). Dies deutet auf ein fehlendes Bewusstsein und Reibungsverluste in der Informationsvermittlung bezüglich des Themas Spielmanipulation hin.
Diaphanous related formin 3 knockdown suppresses cell proliferation and metastasis of osteosarcoma cells
Authors: Zhang Zehua , Dai Fei , Luo Fei , Wu Wenjie , Zhang Shuai , Zhou Rui , Xu Jianzhong , Zhou Qiang , Song Lei
Published: July 2021

Osteosarcoma is a malignant osteoblastic tumor that can gravely endanger the lives and health of children and adolescents. Therefore, there is an urgent need to explore new biomarkers for osteosarcoma and determine new targeted therapies to improve the efficacy of osteosarcoma treatment. Diaphanous related formin 3 (DIAPH3) promotes tumorigenesis in hepatocellular carcinoma and lung adenocarcinoma, suggesting that DIAPH3 may be a target for tumor therapy. To date, there have been no reports on the function of DIAPH3 in osteosarcoma. DIAPH3 protein expression in osteosarcoma tissues and healthy bone tissues adjacent to cancer cells was examined by immunohistochemical staining. DIAPH3 mRNA expression correlates with overall survival and reduced disease-free survival. DIAPH3 protein is upregulated in osteosarcoma tissues, and its expression is significantly associated with tumor size, tumor stage, node metastasis, and distant metastasis. Functional in vitro experiments revealed that DIAPH3 knockdown suppressed cell proliferation and suppressed cell migration and invasion of osteosarcoma cell lines MG-63 and HOS. Functional experiments demonstrated that DIAPH3 knockdown inhibited subcutaneous tumor growth and lung metastasis in vivo. In conclusion, DIAPH3 expression can predict the clinical outcome of osteosarcoma. In addition, DIAPH3 is involved in the proliferation and metastasis of osteosarcoma, and as such, DIAPH3 may be a potential therapeutic target for osteosarcoma.
Wearable cardioverter-defibrillators after myocardial infarction: a review of its clinical utility and unmet needs in current clinical practice
Authors: Hioki Hirofumi , Kozuma Ken , Kobayashi Yoshio , Ando Kenji , Morino Yoshihiro , Kishihara Jun , Ako Junya , Ikari Yuji
Published: July 2021

Sudden cardiac death is one of the leading causes of death in the older population. Compared with the general population, patients who experienced a myocardial infarction are four to six times more likely to experience sudden cardiac death. Though primary percutaneous coronary intervention considerably reduces mortality in patients who experienced a myocardial infarction, a non-negligible number of sudden cardiac deaths still occurs. Despite the high incidence rate of sudden cardiac deaths during the first month after myocardial infarction, prophylactic use of implantable cardioverter-defibrillators has so far failed to convey a survival benefit. Therefore, current clinical guidelines recommend that cardioverter-defibrillator implantation is contraindicated until 90 days after myocardial infarction. Wearable cardioverter-defibrillators were first approved for clinical use in 2002 and are currently considered as a bridge to therapy in patients with myocardial infarction with a reduced left ventricular ejection fraction in whom cardioverter-defibrillator implantation is temporarily not indicated. However, there is insufficient recognition among interventional cardiologists of the use of wearable cardioverter-defibrillators for preventing sudden cardiac death after myocardial infarction. Hence, we reviewed the evidence of the efficacy of wearable cardioverter-defibrillators used in patients following myocardial infarction to achieve better management of sudden cardiac death.
Modelling cryptographic distinguishers using machine learning
Authors: Brunetta Carlo , Picazo-Sanchez Pablo
Published: July 2021

Cryptanalysis is the development and study of attacks against cryptographic primitives and protocols. Many cryptographic properties rely on the difficulty of generating an adversary who, given an object sampled from one of two classes, correctly distinguishes the class used to generate that object. In the case of cipher suite distinguishing problem, the classes are two different cryptographic primitives. In this paper, we propose a methodology based on machine learning to automatically generate classifiers that can be used by an adversary to solve any distinguishing problem. We discuss the assumptions, a basic approach for improving the advantage of the adversary as well as a phenomenon that we call the “blind spot paradox”. We apply our methodology to generate distinguishers for the NIST (DRBG) cipher suite problem. Finally, we provide empirical evidence that the distinguishers might statistically have some advantage to distinguish between the DRBG used.
On exceptional zeros of Garrett–Hida p-adic L-functions
Authors: Bertolini Massimo , Seveso Marco Adamo , Venerucci Rodolfo
Published: July 2021

This article proves a case of the p-adic Birch and Swinnerton-Dyer conjecture for Garrett p-adic L-functions of [6], in the exceptional zero setting of extended analytic rank 2.
Technology-Based Assessments and Treatments of Anxiety in Autistic Individuals: Systematic Review and Narrative Synthesis
Authors: Adams Lucy , Valmaggia Lucia , Simonoff Emily
Published: July 2021

This systematic review (Prospero Registration Number: CRD42019142910) aimed to narratively synthesise technology-aided assessments and treatments of anxiety in individuals with autism spectrum disorder (ASD) for the first time. Sixteen studies were identified: 5 assessment studies and 11 treatment studies. Assessment studies targeted state anxiety using ecological momentary assessment, wearables, or computerised tasks. Treatment studies targeted specific fears/phobias using electronic screen media or transdiagnostic anxiety using telemedicine. Broadly, results indicated technology-aided assessments and treatments may be feasible and effective at targeting anxiety in ASD, except treatments involving social scripts or peer modelling. Assessment results further indicated that state anxiety in ASD has a distinct psychophysiological signature and is evoked by idiosyncratic triggers. However, larger scale studies with representative samples are needed.
Approaches for multicriteria decision-making based on the hesitant fuzzy best–worst method
Authors: Li Jian , Niu Li-li , Chen Qiongxia , Wang Zhong-xing
Published: July 2021

Hesitant fuzzy preference relations (HFPRs) have been widely applied in multicriteria decision-making (MCDM) for their ability to efficiently express hesitant information. To address the situation where HFPRs are necessary, this paper develops several decision-making models integrating HFPRs with the best worst method (BWM). First, consistency measures from the perspectives of additive/multiplicative consistent hesitant fuzzy best worst preference relations (HFBWPRs) are introduced. Second, several decision-making models are developed in view of the proposed additive/multiplicatively consistent HFBWPRs. The main characteristic of the constructed models is that they consider all the values included in the HFBWPRs and consider the same and different compromise limit constraints. Third, an absolute programming model is developed to obtain the decision-makers’ objective weights utilizing the information of optimal priority weight vectors and provides the calculation of decision-makers’ comprehensive weights. Finally, a framework of the MCDM procedure based on hesitant fuzzy BWM is introduced, and an illustrative example in conjunction with comparative analysis is provided to demonstrate the feasibility and efficiency of the proposed models.
Research on college gymnastics teaching model based on multimedia image and image texture feature analysis
Authors: Wu Ying , Liu Jikun
Published: July 2021

With the rapid development of gymnastics technology, novel movements are also emerging. Due to the emergence of various complicated new movements, higher requirements are put forward for college gymnastics teaching. Therefore, it is necessary to combine the multimedia simulation technology to construct the human body rigid model and combine the image texture features to display the simulation image in texture form. In the study, GeBOD morphological database modeling was used to provide the data needed for the modeling of the whole-body human body of the joint and used for dynamics simulation. Simultaneously, in order to analyze and summarize the technical essentials of the innovative action, this experiment compared and analyzed the hem stage of the cross-headstand movement of the subject and the hem stage of the 180° movement. Research shows that the method proposed in this paper has certain practical effects.
Testing Character Evolution Models in Phylogenetic Paleobiology
Authors: Wright April , Wagner Peter J. , Wright David F.
Published: July 2021

Macroevolutionary inference has historically been treated as a two-step process, involving the inference of a tree, and then inference of a macroevolutionary model using that tree. Newer models blend the two steps. These methods make more complete use of fossils than the previous generation of Bayesian phylogenetic models. They also involve many more parameters than prior models, including parameters about which empiricists may have little intuition. In this Element, we set forth a framework for fitting complex, hierarchical models. The authors ultimately fit and use a joint tree and diversification model to estimate a dated phylogeny of the Cincta (Echinodermata), a morphologically distinct group of Cambrian echinoderms that lack the fivefold radial symmetry characteristic of extant members of the phylum. Although the phylogeny of cinctans remains poorly supported in places, this Element shows how models of character change and diversification contribute to understanding patterns of phylogenetic relatedness and testing macroevolutionary hypotheses.
Planetary Health
Authors: Haines Andy , Frumkin Howard
Published: July 2021

We live in unprecedented times - the Anthropocene - defined by far-reaching human impacts on the natural systems that underpin civilisation. Planetary Health explores the many environmental changes that threaten to undermine progress in human health, and explains how these changes affect health outcomes, from pandemics to infectious diseases to mental health, from chronic diseases to injuries. It shows how people can adapt to those changes that are now unavoidable, through actions that both improve health and safeguard the environment. But humanity must do more than just adapt: we need transformative changes across many sectors - energy, housing, transport, food, and health care. The book discusses specific policies, technologies, and interventions to achieve the change required, and explains how these can be implemented. It presents the evidence, builds hope in our common future, and aims to motivate action by everyone, from the general public to policymakers to health practitioners.
International Law
Authors: Shaw Malcolm N.
Published: July 2021

International Law is the definitive and authoritative text on the subject. It has long been established as a leading authority in the field, offering an unbeatable combination of clarity of expression and academic rigour, ensuring understanding and analysis in an engaging and authoritative style. Explaining the leading rules, practice and caselaw, this treatise retains and develops the detailed referencing which encourages and assists the reader in further study. This new edition has been fully updated to reflect recent developments. In particular, it has expanded the treatment of space law and of international economic law, and introduced new sections on cyber operations and cyber warfare, as well as reflecting the Covid-19 crisis. Both clarifying fundamental principles and facilitating additional research, International Law is invaluable for students and for those occupied in private practice, governmental service and international organisations.
(Co)end Calculus
Authors: Loregian Fosco
Published: July 2021

The language of ends and (co)ends provides a natural and general way of expressing many phenomena in category theory, in the abstract and in applications. Yet although category-theoretic methods are now widely used by mathematicians, since (co)ends lie just beyond a first course in category theory, they are typically only used by category theorists, for whom they are something of a secret weapon. This book is the first systematic treatment of the theory of (co)ends. Aimed at a wide audience, it presents the (co)end calculus as a powerful tool to clarify and simplify definitions and results in category theory and export them for use in diverse areas of mathematics and computer science. It is organised as an easy-to-cite reference manual, and will be of interest to category theorists and users of category theory alike.
From microscopic price dynamics to multidimensional rough volatility models
Authors: Rosenbaum Mathieu , Tomas Mehdi
Published: July 2021

Rough volatility is a well-established statistical stylized fact of financial assets. This property has led to the design and analysis of various new rough stochastic volatility models. However, most of these developments have been carried out in the mono-asset case. In this work, we show that some specific multivariate rough volatility models arise naturally from microstructural properties of the joint dynamics of asset prices. To do so, we use Hawkes processes to build microscopic models that accurately reproduce high-frequency cross-asset interactions and investigate their long-term scaling limits. We emphasize the relevance of our approach by providing insights on the role of microscopic features such as momentum and mean-reversion in the multidimensional price formation process. In particular, we recover classical properties of high-dimensional stock correlation matrices.
On gradual-impulse control of continuous-time Markov decision processes with exponential utility
Authors: Guo Xin , Kurushima Aiko , Piunovskiy Alexey , Zhang Yi
Published: July 2021

We consider a gradual-impulse control problem of continuous-time Markov decision processes, where the system performance is measured by the expectation of the exponential utility of the total cost. We show, under natural conditions on the system primitives, the existence of a deterministic stationary optimal policy out of a more general class of policies that allow multiple simultaneous impulses, randomized selection of impulses with random effects, and accumulation of jumps. After characterizing the value function using the optimality equation, we reduce the gradual-impulse control problem to an equivalent simple discrete-time Markov decision process, whose action space is the union of the sets of gradual and impulsive actions.
When Managers Become Robin Hoods: A Mixed Method Investigation
Authors: Cropanzano Russell , Skarlicki Daniel P. , Nadisic Thierry , Fortin Marion , Van Wagoner Phoenix , Keplinger Ksenia
Published: July 2021

When subordinates have suffered an unfairness, managers sometimes try to compensate them by allocating something extra that belongs to the organization. These reactions, which we label asmanagerial Robin Hood behaviors, are undertaken without the consent of senior leadership. In four studies, we present and test a theory of managerial Robin Hoodism. In study 1, we found that managers themselves reported engaging in Robin Hoodism for various reasons, including a moral concern with restoring justice. Study 2 results suggested that managerial Robin Hoodism is more likely to occur when the justice violations involve distributive and interpersonal justice rather than procedural justice violations. In studies 3 and 4, when moral identity (trait or primed) was low, both distributive and interpersonal justice violations showed similar relationships to managerial Robin Hoodism. However, when moral identity was high, interpersonal justice violations showed a strong relationship to managerial Robin Hoodism regardless of the level of distributive justice.
Insurer's liability under concurrent causation: English law and Chinese law compared
Authors: Zhao Liang
Published: July 2021

This paper examines the different regimes of insurer liability under concurrent causation in English law and Chinese law. The analysis shows that neither English law nor Chinese law is satisfactory in terms of the insurer's liability in such cases. It is argued that only one proximate cause should be identified among multiple causes except in the circumstance where an excluded risk and an insured risk concurrently and independently cause a loss of the subject matter insured. Under this exception, the liability in apportionment approach might be an appropriate solution to the question of the insurer's liability under concurrent causation. This approach, however, is not suggested for concurrent causation where an uninsured risk is one of the proximate causes.
Marker-assisted stacking of null Kunitz trypsin inhibitor and off-flavour generating lipoxygenase-2 in soybean
Authors: Kumar V. , Rani A. , Anshu A. K. , Tayalkar T.
Published: July 2021

Soybean varieties genetically free from Kunitz trypsin inhibitor (KTI) and lipoxygenase-2 (Lox2) are desirable to increase human consumption, as the former is an antinutritional factor that affects protein digestibility while the latter is a principal contributor to off-flavour. In the present investigation, soybean genotypes free from both these undesirable components were developed by introgression of null allele of Lox2 from NRC109 (lox2lox2) into two KTI-free soybean genotypes derived from genotypes JS97-52 and NRC7. Foreground selection of plants in F1, F2, BC1F1, BC1F2, BC2F1 and BC2F2 generations developed from two cross combinations i.e. NRC7-derived KTI-free genotype (N7KTIF)×NRC109 (parental combination 1) and JS97-52 derived KTI free genotype (JKTIF)×NRC109 (parental combination 2) was performed using null allele specific markers and tightly linked simple sequence repeat (SSR) markers for both KTI and Lox2 genes for the identification of homozygous recessive (titilox2lox2) plants. Background selection was performed using 239 and 241 polymorphic SSR markers across the genome. This resulted in the development of 9 and 13 soybean lines stacked for null alleles of both KTI and Lox2 (titilox2lox2) exhibiting recurrent parent genome content more than 97 and 96%, respectively. Days-to-flowering, days-to-maturity, 100-seed weight and yield per plant of the stacked lines developed from both the parental combinations were at par with the respective recurrent parents.
Mindfulness-based therapy for insomnia for older adults with sleep difficulties: a randomized clinical trial
Authors: Perini Francesca , Wong Kian Foong , Lin Jia , Hassirim Zuriel , Ong Ju Lynn , Lo June , Ong Jason C. , Doshi Kinjal , Lim Julian
Published: July 2021

Objective

Poor sleep is a modifiable risk factor for multiple disorders. Frontline treatments (e.g. cognitive-behavioral therapy for insomnia) have limitations, prompting a search for alternative approaches. Here, we compare manualized Mindfulness-Based Therapy for Insomnia (MBTI) with a Sleep Hygiene, Education, and Exercise Program (SHEEP) in improving subjective and objective sleep outcomes in older adults.

Methods

We conducted a single-site, parallel-arm trial, with blinded assessments collected at baseline, post-intervention and 6-months follow-up. We randomized 127 participants aged 50–80, with a Pittsburgh Sleep Quality Index (PSQI) score ⩾5, to either MBTI (n = 65) or SHEEP (n = 62), both 2 hr weekly group sessions lasting 8 weeks. Primary outcomes included PSQI and Insomnia Severity Index, and actigraphy- and polysomnography-measured sleep onset latency (SOL) and wake after sleep onset (WASO).

Results

Intention-to-treat analysis showed reductions in insomnia severity in both groups [MBTI: Cohen's effect size d = −1.27, 95% confidence interval (CI) −1.61 to −0.89; SHEEP: d = −0.69, 95% CI −0.96 to −0.43], with significantly greater improvement in MBTI. Sleep quality improved equivalently in both groups (MBTI: d = −1.19; SHEEP: d = −1.02). No significant interaction effects were observed in objective sleep measures. However, only MBTI had reduced WASOactigraphy (MBTI: d = −0.30; SHEEP: d = 0.02), SOLactigraphy (MBTI: d = −0.25; SHEEP: d = −0.09), and WASOPSG (MBTI: d = −0.26; SHEEP (d = −0.18). There was no change in SOLPSG. No participants withdrew because of adverse effects.

Conclusions

MBTI is effective at improving subjective and objective sleep quality in older adults, and could be a valid alternative for persons who have failed or do not have access to standard frontline therapies.
Survey investigating the knowledge and awareness of payers and patient advocacy groups about the health technology assessment process in Lebanon
Authors: Al-Harakeh Lama , Abbas Hanine , Hassan Hamad , Hallal Zainoun , Hamadeh Ghassan , Kurdi Mazen , Abou Selwan Carla , Karam Rita
Published: July 2021

The survey aims to assess the knowledge and awareness of Reimbursement Bodies (RBs) and Patient Advocacy Groups (PAGs) in Lebanon and the possible involvement of patients in the health technology assessment (HTA) process in the absence of a well-established HTA structure and to identify the actions to be taken at this level. Structured questionnaires were administered to eleven key participants from both RBs and PAGs. The survey utilized two different questionnaires, each composed of two open-ended questions and ten close-ended questions. RBs recognized the need for clinical and technical guidelines to optimize the HTA process, whereas PAGs stated that they are familiar with the current assessment and reimbursement process. A lack of interaction between the payers and the PAGs was reported mainly due to the absence of laws that involve patients in the assessment process. All the payers and three out of five of PAGs encouraged the involvement of PAGs in the assessment process. They reported that patients require support, education, and training to be efficiently involved. A short-term plan for involving patients in the assessment process can be implemented in light of RBs' and PAGs' openness for such involvement. In the long run, the collaboration between both parties needs to be more formalized and structured. Education and training programs are to be suggested for other PAGs. The institutionalization of an HTA body that unifies all the fragmented RBs, including a patient's representation to optimize the reimbursement process and to engage patients, is recommended.
Religion without doctrine or clergy: the case of Ancient Greece
Authors: Tridimas George
Published: July 2021

The paper examines doctrinal and political reasons to explain why the Ancient Greek religion did not feature a distinct class of professional priests as suppliers of religious goods. Doctrinal reasons relate to worshiping a multitude of powerful anthropomorphic gods with flawed characters; absence of a founder of religion and of a scripture; lack of religious doctrine and of a code of moral behaviour and piety manifested as mass participation in rituals. These factors denied religious suppliers the opportunity to form a monopoly acting as an autonomous intermediary between humans and gods. Political reasons relate to the supremacy of the demos which watchfully guarded its decision-making powers and prevented other actors like a priestly interest group to challenge its authority.
Sound Velocities in FeSi at Lower Mantle Conditions and the Origin of Ultralow‐Velocity Zones
Authors: Mergner V. , Kupenko I. , Spiekermann G. , Petitgirard S. , Libon L. , Chariton S. , Krug M. , Steinbrügge R. , Sergueev I. , Sanchez‐Valle C.
Published: July 2021

The origin of ultralow‐velocity zones (ULVZs) remains an open question despite recent advances in mineral physics and seismology. Here, we examine the hypothesis that FeSi formed from core‐mantle chemical reactions is a plausible source of ULVZs at the core‐mantle boundary (CMB). The sound velocities of B2‐structured FeSi were measured up to 115(2) GPa and 1600(200) K by nuclear inelastic scattering (NIS) in laser‐heated diamond anvil cells (LH‐DACs). Within uncertainties, the sound velocities of B2‐FeSi display negligible anharmonicity, hence validating the extrapolation of velocity‐density relations (Birch's law) to P‐T conditions of the CMB. The sound velocities of B2‐FeSi are significantly lower compared to other candidate phases in a lowermost mantle assemblage, and the Preliminary Reference Earth Model at CMB conditions. Less than 8.4 vol% of FeSi in the aggregate is thus sufficient to explain both the velocity decrements and the high density anomaly observed in a wide range of ULVZs.
Sea Level‐Driven Marsh Migration Results in Rapid Net Loss of Carbon
Authors: Smith Alexander J. , Kirwan Matthew L.
Published: July 2021

Sea level rise alters coastal carbon cycling by driving the rapid migration of coastal ecosystems, salinization of freshwater systems, and replacement of terrestrial forests with tidal wetlands. Wetland soils accumulate carbon (C) at faster rates than terrestrial soils, implying that sea level rise may lead to enhanced carbon accumulation. Here, we show that carbon stored in tree biomass greatly exceeds carbon stored in adjacent marsh soils so that marsh migration reduces total carbon stocks by ∼50% in less than 100 years. Continued marsh soil carbon accumulation may eventually offset forest carbon loss, but we estimate that the time for replacement is similar to estimates of marsh survival (i.e., centuries), which suggests that forest C may never be replaced. These findings reveal a critical C source not included in coastal C budgets driven by migrating ecosystems and rapidly shifting allocations between carbon stored in soils and biomass.
Changes in Source‐Specific Black Carbon Aerosol and the Induced Radiative Effects Due to the COVID‐19 Lockdown
Authors: Liu Huikun , Wang Qiyuan , Ye Jianhuai , Su Xiaoli , Zhang Ting , Zhang Yong , Tian Jie , Dong Yunsheng , Chen Yang , Zhu Chongshu , Han Yongming , Cao Junji
Published: July 2021

The impacts of anthropogenic emissions on the reduction of source‐specific equivalent black carbon (eBC) aerosols and their direct radiative effects (DREs) were investigated during the lockdown of the coronavirus outbreak in a megacity of China in 2020. Five eBC sources were identified using a hybrid environmental receptor model. Results showed that biomass burning, traffic‐related emissions, and coal combustion were the dominant contributors to eBC. The generalized additive model indicated that the reduction of traffic‐related eBC during the lockdown was entirely attributed to the decrease of emissions. Decreased biomass‐burning activities and favorable meteorological factors are both important drivers for the biomass‐burning eBC reduction during the lockdown. A radiative transfer model showed that the DRE efficiency of eBC from biomass burning was the strongest, followed by coal combustion and traffic‐related emissions. This study highlights that aggressive reduction in the consumption of residential solid fuels would be effective in achieving climate change mitigation.
Drivers of Subseasonal Forecast Errors of the East African Short Rains
Authors: Kolstad E. W. , MacLeod D. , Demissie T. D.
Published: July 2021

The ‘short rains’ in East Africa from October to December have significant year‐to‐year variability. Their abundance or deficiency is often associated with floods or droughts for which early warning is crucial, though even in normal seasons skillful forecasts facilitate planning and preparedness. Here we study the relationship between initial‐state sea surface temperatures and subseasonal rainfall forecast errors in the European Center for Medium‐Range Weather Forecasts model in the region. We demonstrate that the initial mode of the Indian Ocean Dipole (IOD) is a partial control on the rainfall error in weeks 3–4. This relationship is also clear on the seasonal scale, exemplified by too‐wet forecasts during the 2015 season when the IOD was positive, and too‐dry forecasts in 2010 when it was negative. Our results provide an entry point for model improvement, and we show that a priori forecast corrections based on the initial IOD index are feasible.
The Integration of Clinical Decision Support Systems Into Pediatric Subspecialty Care
Authors: Urban Tamaki Hosoda , Counts Nathaniel , Lois Becky Hashim , Risser Heather Jill
Published: July 2021

Objective: This review aims to provide a brief introduction of clinical decision support systems (CDSSs) and discuss the role of psychology for the integration of CDSSs for child mental health into pediatric subspecialty care. Methods: A review of literature regarding CDSSs used for physical and mental health services was conducted to lay the foundation for our recommendations. Results: Children with chronic physical illness are twice as likely to suffer from mental illness as compared to healthy controls. These mental health problems are often discovered in pediatric subspecialty care. Yet their mental health needs are often unaddressed when the sections of pediatric subspecialty care and mental health are not well coordinated. CDSSs could help subspecialty providers with evidence-based decision-making regarding mental health screening and referrals. That is, CDSSs could enhance the access to most effective mental health treatment for children. However, the implementation of CDSSs in pediatric subspecialty care is very limited. Conclusions: Psychologists could assist subspecialty providers with advocating CDSSs to administrative and information technology staff, as well as build, customize, evaluate, and update CDSSs.

Implications for Impact Statement

This review discusses a need for integrating clinical decision support systems (CDSSs) into pediatric subspecialty care to improve care coordination between pediatric subspecialty care and mental health sections. A role of pediatric psychology is proposed.
A novel missense variant in the EML1 gene associated with bilateral ribbon-like subcortical heterotopia leads to ciliary defects
Authors: Markus Fenja , Kannengießer Annika , Näder Patricia , Atigbire Paul , Scholten Alexander , Vössing Christine , Bültmann Eva , Korenke G. Christoph , Owczarek-Lipska Marta , Neidhardt John
Published: July 2021

Heterotopia is a brain malformation caused by a failed migration of cortical neurons during development. Clinical symptoms of heterotopia vary in severity of intellectual disability and may be associated with epileptic disorders. Abnormal neuronal migration is known to be associated with mutations in the doublecortin gene (DCX), the platelet-activating factor acetylhydrolase gene (PAFAH1B1), or tubulin alpha-1A gene (TUBA1A). Recently, a new gene encoding echinoderm microtubule-associated protein-like 1 (EML1) was reported to cause a particular form of subcortical heterotopia, the ribbon-like subcortical heterotopia (RSH).EML1mutations are inherited in an autosomal recessive manner. Only six unrelated EML1-associated heterotopia-affected families were reported so far. The EML1 protein is a member of the microtubule-associated proteins family, playing an important role in microtubule assembly and stabilization as well as in mitotic spindle formation in interphase. Herein, we present a novel homozygous missense variant inEML1(NM_004434.2: c.692G>A, NP_004425.2: p.Gly231Asp) identified in a male RSH-affected patient. Our clinical and molecular findings confirm the genotype-phenotype associations ofEML1mutations and RSH. Analyses of patient-derived fibroblasts showed the significantly reduced length of primary cilia. In addition, our results presented, that the mutated EML1 protein did not change binding capacities with tubulin. The data described herein will expand the mutation spectrum of theEML1gene and provide further insight into molecular and cellular bases of the pathogenic mechanisms underlying RSH.
White matter in prolonged glucocorticoid response to psychological stress in schizophrenia
Authors: Goldwaser Eric L. , Chiappelli Joshua , Kvarta Mark D. , Du Xiaoming , Millman Zachary B. , Adhikari Bhim M. , O’Neill Hugh , Sewell Jessica , Lightner Samantha , Vodapalli Shreya , Ma Yizhou , Bruce Heather , Chen Shuo , Tan Yunlong , Kochunov Peter , Elliot Hong L.
Published: July 2021

Stress is implicated in psychosis etiology and exacerbation, but pathogenesis toward brain network alterations in schizophrenia remain unclear. White matter connects limbic and prefrontal regions responsible for stress response regulation, and white matter tissues are also vulnerable to glucocorticoid aberrancies. Using a novel psychological stressor task, we studied cortisol stress responses over time and white matter microstructural deficits in schizophrenia spectrum disorder (SSD). Cortisol was measured at baseline, 0-, 20-, and 40-min after distress induction by a psychological stressor task in 121 SSD patients and 117 healthy controls (HC). White matter microstructural integrity was measured by 64-direction diffusion tensor imaging. Fractional anisotropy (FA) in white matter tracts were related to cortisol responses and then compared to general patterns of white matter tract deficits in SSD identified by mega-analysis. Differences between 40-min post-stress and baseline, but not acute reactivity post-stress, was significantly elevated in SSD vs HC, time × diagnosis interaction F2.3,499.9 = 4.1, p = 0.013. All SSD white matter tracts were negatively associated with prolonged cortisol reactivity but all tracts were positively associated with prolonged cortisol reactivity in HC. Individual tracts most strongly associated with prolonged cortisol reactivity were also most impacted in schizophrenia in general as established by the largest schizophrenia white matter study (r = −0.56, p = 0.006). Challenged with psychological stress, SSD and HC mount similar cortisol responses, and impairments arise in the resolution timeframe. Prolonged cortisol elevations are associated with the white matter deficits in SSD, in a pattern previously associated with schizophrenia in general.
Inequalities in the decline and recovery of pathological cancer diagnoses during the first six months of the COVID-19 pandemic: a population-based study
Authors: Hamilton Ashleigh C. , Donnelly David W. , Loughrey Maurice B. , Turkington Richard C. , Fox Colin , Fitzpatrick Deirdre , O’Neill Ciaran E. , Gavin Anna T. , Coleman Helen G.
Published: July 2021

Background

The restructuring of healthcare systems to cope with the demands of the COVID-19 pandemic has led to a reduction in clinical services such as cancer screening and diagnostics.

Methods

Data from the four Northern Ireland pathology laboratories were used to assess trends in pathological cancer diagnoses from 1st March to 12th September 2020 overall and by cancer site, sex and age. These trends were compared to the same timeframe from 2017 to 2019.

Results

Between 1st March and 12th September 2020, there was a 23% reduction in cancer diagnoses compared to the same time period in the preceding 3 years. Although some recovery occurred in August and September 2020, this revealed inequalities across certain patient groups. Pathological diagnoses of lung, prostate and gynaecological malignancies remained well below pre-pandemic levels. Males and younger/middle-aged adults, particularly the 50–59-year-old patient group, also lagged behind other population demographic groups in terms of returning to expected numbers of pathological cancer diagnoses.

Conclusions

There is a critical need to protect cancer diagnostic services in the ongoing pandemic to facilitate timely investigation of potential cancer cases. Targeted public health campaigns may be needed to reduce emerging inequalities in cancer diagnoses as the COVID-19 pandemic continues.
ALPK2 acts as tumor promotor in development of bladder cancer through targeting DEPDC1A
Authors: Wang Yuchen , Wu Jie , Luo Wenjie , Zhang Hailiang , Shi Guohai , Shen Yijun , Zhu Yao , Ma Chunguang , Dai Bo , Ye Dingwei , Zhu Yiping
Published: July 2021

Bladder cancer is one of the most common malignant tumors in the urinary system. The development and improvement of treatment efficiency require the deepening of the understanding of its molecular mechanism. This study investigated the role of ALPK2, which is rarely studied in malignant tumors, in the development of bladder cancer. Our results showed the upregulation of ALPK2 in bladder cancer, and data mining of TCGA database showed the association between ALPK2 and pathological parameters of patients with bladder cancer. In vitro and in vivo experiments demonstrated that knockdown of ALPK2 could inhibit bladder cancer development through regulating cell proliferation, cell apoptosis, and cell migration. Additionally, DEPDC1A is identified as a potential downstream of ALPK2 with direct interaction, whose overexpression/downregulation can inhibit/promote the malignant behavioral of bladder cancer cells. Moreover, the overexpression of DEPDC1A can rescue the inhibitory effects of ALPK2 knockdown on bladder cancer. In conclusion, ALPK2 exerts a cancer-promoting role in the development of bladder cancer by regulating DEPDC1A, which may become a promising target to improve the treatment strategy of bladder cancer.
Interactions between ShPP2-1, an F-box family gene, and ACR11A regulate cold tolerance of tomato
Authors: Song Jianwen , Shang Lele , Chen Shiwei , Lu Yongen , Zhang Yuyang , Ouyang Bo , Ye Zhibiao , Zhang Junhong
Published: July 2021

There is a critical need to identify germplasm resources and genes that promote cold tolerance of tomato because global tomato production is threatened by cold stress. We found that the expression of an F-box gene family member named ShPP2-1 from Solanum habrochaites is cold inducible and studied its contribution to cold tolerance. Overexpression of ShPP2-1 in cultivated tomato (AC) reduced cold tolerance by intensifying damage to cell membranes. To explore the underlying molecular mechanism, we conducted a yeast two-hybrid library screen and found that a protein containing ACT domain repeats named ACR11A interacts with PP2-1. Overexpression of SlACR11A in AC enhanced the cold tolerance of seedlings and germinating seeds. Cold tolerance decreased in tomato plants that overexpressed both of these genes. Additionally, we performed seed germination experiments in the cold with 177 tomato accessions and identified two alleles of SlACR11A that differ in one single-nucleotide polymorphism. We found that one of these alleles, SlACR11AG, is significantly enriched in cold-tolerant tomato plants. Taken together, our findings indicate that the combination of low expression levels of PP2-1 and high expression levels of ACR11A can promote cold tolerance. These genes may therefore serve as direct targets for both genetic engineering and improvement projects that aim to enhance the cold tolerance of tomato.
Shared and tailored common bean transcriptomic responses to combined fusarium wilt and water deficit
Authors: Leitão Susana T. , Santos Carmen , Araújo Susana de Sousa , Rubiales Diego , Vaz Patto Maria Carlota
Published: July 2021

Common bean (Phaseolus vulgaris L.), one of the most consumed food legumes worldwide, is threatened by two main constraints that are found frequently together in nature, water deficit (WD) and fusarium wilt (Fop). To understand the shared and unique responses of common bean to Fop and WD, we analyzed the transcriptomic changes and phenotypic responses in two accessions, one resistant and one susceptible to both stresses, exposed to single and combined stresses. Physiological responses (photosynthetic performance and pigments quantification) and disease progression were also assessed. The combined FopWD imposition negatively affected the photosynthetic performance and increased the susceptible accession disease symptoms. The susceptible accession revealed a higher level of transcriptional changes than the resistant one, and WD single stress triggered the highest transcriptional changes. While 89 differentially expressed genes were identified exclusively in combined stresses for the susceptible accession, 35 were identified in the resistant one. These genes belong mainly to “stress”, “signaling”, “cell wall”, “hormone metabolism”, and “secondary metabolism” functional categories. Among the up-regulated genes with higher expression in the resistant accession, the cysteine-rich secretory, antigen 5 and Pr-1 (CAP) superfamily protein, a ribulose bisphosphate carboxylase family protein, and a chitinase A seem promising targets for multiple stress breeding.
The apple C2H2-type zinc finger transcription factor MdZAT10 positively regulates JA-induced leaf senescence by interacting with MdBT2
Authors: Yang Kuo , An Jian-Ping , Li Chong-Yang , Shen Xue-Na , Liu Ya-Jing , Wang Da-Ru , Ji Xing-Long , Hao Yu-Jin , You Chun-Xiang
Published: July 2021

Jasmonic acid (JA) plays an important role in regulating leaf senescence. However, the molecular mechanisms of leaf senescence in apple (Malus domestica) remain elusive. In this study, we found that MdZAT10, a C2H2-type zinc finger transcription factor (TF) in apple, markedly accelerates leaf senescence and increases the expression of senescence-related genes. To explore how MdZAT10 promotes leaf senescence, we carried out liquid chromatography/mass spectrometry screening. We found that MdABI5 physically interacts with MdZAT10. MdABI5, an important positive regulator of leaf senescence, significantly accelerated leaf senescence in apple. MdZAT10 was found to enhance the transcriptional activity of MdABI5 for MdNYC1 and MdNYE1, thus accelerating leaf senescence. In addition, we found that MdZAT10 expression was induced by methyl jasmonate (MeJA), which accelerated JA-induced leaf senescence. We also found that the JA-responsive protein MdBT2 directly interacts with MdZAT10 and reduces its protein stability through ubiquitination and degradation, thereby delaying MdZAT10-mediated leaf senescence. Taken together, our results provide new insight into the mechanisms by which MdZAT10 positively regulates JA-induced leaf senescence in apple.
Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer
Authors: Luu Maik , Riester Zeno , Baldrich Adrian , Reichardt Nicole , Yuille Samantha , Busetti Alessandro , Klein Matthias , Wempe Anne , Leister Hanna , Raifer Hartmann , Picard Felix , Muhammad Khalid , Ohl Kim , Romero Rossana , Fischer Florence , Bauer Christian A. , Huber Magdalena , Gress Thomas M. , Lauth Matthias , Danhof Sophia , Bopp Tobias , Nerreter Thomas , Mulder Imke E. , Steinhoff Ulrich , Hudecek Michael , Visekruna Alexander
Published: July 2021

Emerging data demonstrate that the activity of immune cells can be modulated by microbial molecules. Here, we show that the short-chain fatty acids (SCFAs) pentanoate and butyrate enhance the anti-tumor activity of cytotoxic T lymphocytes (CTLs) and chimeric antigen receptor (CAR) T cells through metabolic and epigenetic reprograming. We show that in vitro treatment of CTLs and CAR T cells with pentanoate and butyrate increases the function of mTOR as a central cellular metabolic sensor, and inhibits class I histone deacetylase activity. This reprogramming results in elevated production of effector molecules such as CD25, IFN-γ and TNF-α, and significantly enhances the anti-tumor activity of antigen-specific CTLs and ROR1-targeting CAR T cells in syngeneic murine melanoma and pancreatic cancer models. Our data shed light onto microbial molecules that may be used for enhancing cellular anti-tumor immunity. Collectively, we identify pentanoate and butyrate as two SCFAs with therapeutic utility in the context of cellular cancer immunotherapy.
One-way dependent clusters and stability of cluster synchronization in directed networks
Authors: Lodi Matteo , Sorrentino Francesco , Storace Marco
Published: July 2021

Cluster synchronization in networks of coupled oscillators is the subject of broad interest from the scientific community, with applications ranging from neural to social and animal networks and technological systems. Most of these networks are directed, with flows of information or energy that propagate unidirectionally from given nodes to other nodes. Nevertheless, most of the work on cluster synchronization has focused on undirected networks. Here we characterize cluster synchronization in general directed networks. Our first observation is that, in directed networks, a cluster A of nodes might be one-way dependent on another cluster B: in this case, A may remain synchronized provided that B is stable, but the opposite does not hold. The main contribution of this paper is a method to transform the cluster stability problem in an irreducible form. In this way, we decompose the original problem into subproblems of the lowest dimension, which allows us to immediately detect inter-dependencies among clusters. We apply our analysis to two examples of interest, a human network of violin players executing a musical piece for which directed interactions may be either activated or deactivated by the musicians, and a multilayer neural network with directed layer-to-layer connections.