bluuebunny/crossref_metadata_2025 huggingface dataset:
Chitosan induces delayed grapevine defense mechanisms and protects grapevine against Botrytis cinerea
Authors: De Bona Gicele Sbardelotto , Vincenzi Simone , De Marchi Fabiola , Angelini Elisa , Bertazzon Nadia
Published: February 2021

In the present study, a commercial chitosan soluble in acid solution and obtained from shrimp shell waste, with a molecular weight of 173 kDa and a degree of acetylation of 17%, named as chitosan (173/17), was investigated. Chitosan is a well-known biopolymer whose antimicrobial properties are highly influenced by the molecular weight, degree of acetylation as well as the preparation and derivatization methods used. Chitosan (173/17) was applied on grapevine leaves before Botrytis cinerea inoculation to verify its effectiveness as a preventive treatment against the fungal infection. The expression of a set of defense marker genes, as well as accumulation of stilbene phytoalexins, was investigated. Thanks to its fungistatic and filmogenic properties, chitosan (173/17) protected grapevine leaves against B. cinerea. Moreover, it induced grapevine defense response: three days after the treatment an induction of the jasmonic acid and ethylene-mediated response, a repression of the salicylic acid-mediated signaling, and a transient accumulation of trans-resveratrol were registered. Our data indicate that chitosan (173/17), when used in preventive application, is able to protect grapevine against B. cinerea infection. The effectiveness of chitosan (173/17) as a natural ecofriendly product for the control of B. cinerea on grapevine was demonstrated.
Palliative care competencies for geriatricians across Europe: a Delphi consensus study
Authors: Pautex Sophie , Roller-Wirnsberger Regina , Singler Katrin , Van den Noortgate Nele ,   the SIG palliative care, SIG education of the European Geriatric Medicine Society (EuGMS)
Published: February 2021

Purpose

Integration of palliative care competencies with geriatric medicine is important for quality of care for older people, especially in the last years of their life. Therefore, knowledge and skills about palliative care for older people should be mandatory for geriatricians. The European Geriatric Medicine Society (EuGMS) has launched a postgraduate curriculum for geriatric medicine recently.

Aim

Based on this work, the Special Interest Group (SIG) on Palliative care in collaboration with the SIG in Education and Training aimed to develop a set of specific palliative care competencies to be recommended for training at a postgraduate level.

Methods

Competencies were defined using a modified Delphi technique based upon a Likert like rating scale. A template to kick off the first round and including 46 items was developed based on pre-existing competencies developed in Switzerland and Belgium.

Results

Three Delphi rounds were necessary to achieve full consensus. Experts came from 12 EU countries. In the first round, the wording of 13 competencies and the content of 10 competencies were modified. We deleted or merged ten competencies, mainly because they were not specific enough. At the end of the 2nd round, one competence was deleted and for three questions the wordings were modified. These modifications had the agreement of the participants during the last round.

Conclusion

A list of 35 palliative care competencies for geriatricians is now available for implementation in European countries.
Palladium nanoparticle biosynthesis via Yerba Mate (Ilex paraguariensis) extract: an efficient eco-friendly catalyst for Suzuki–Miyaura reactions
Authors: Schmitt Cristiane R. , Duarte Fábio A. , Godoi Marcelo , Peixoto Carlos R. M. , Trombetta Fernanda , Rosa Gilber R.
Published: February 2021

This manuscript relates, for the first time, palladium nanoparticle production by bio-reduction using an Ilex paraguariensis aqueous extract. The solid obtained, PdISM, was used as a catalyst in Suzuki–Miyaura cross-coupling, composing a new eco-friendly, ligand-free, and low cost catalytic system. Excellent yields were obtained in the coupling of aryl iodides and bromides with phenylboronic acid. The same catalyst load was able to be recycled 3x.

Graphical Abstract
Optimisation of biodiesel production from dairy effluent scum using calcined egg shell as a transesterification catalyst
Authors: Kuipa O. , Marwizi T. S. , Kuipa P. K.
Published: February 2021

The production of biodiesel from dairy effluent scum using calcined egg shell as the transesterification catalyst has been explored. Eggshell powder was calcined at 900 °C for 3 h and used as catalyst. The influence of methanol-oil molar ratio, catalyst concentration and reaction temperature were studied using Response Surface Methodology employing a Central Composite Rotatable Design. An empirical model that relates the yield of biodiesel to the studied factors was obtained. The model has high statistical significance at 95% confidence interval with R2 and adjusted R2 values of 96.31% and 95.75% respectively. Results showed that among the three studied factors, the methanol-oil molar ratio had the greatest contribution to the yield of dairy effluent scum derived biodiesel followed by reaction temperature and finally, the catalyst concentration. Significant interaction effects were also present between methanol-oil ratio and catalyst, catalyst and reaction temperature and methanol-oil ratio and reaction temperature. Accordingly, the optimal variable settings were 14.355:1 methanol-oil molar ratio, 3.09% catalyst loading by weight of pre-treated dairy scum oil and 55.20°C reaction temperature; with a corresponding yield of 92.72%.
New collocation path-following approach for the optimal shape parameter using Kernel method
Authors: Saffah Zouhair , Timesli Abdelaziz , Lahmam Hassane , Azouani Abderrahim , Amdi Mohamed
Published: February 2021

The goal of this work is to develop a numerical method combining Radial Basic Functions (RBF) kernel and a high order algorithm based on Taylor series and homotopy continuation method. The local RBF approximation applied in strong form allows us to overcome the difficulties of numerical integration and to treat problems of large deformations. Furthermore, the high order algorithm enables to transform the nonlinear problem to a set of linear problems. Determining the optimal value of the shape parameter in RBF kernel is still an outstanding research topic. This optimal value depends on density and distribution of points and the considered problem for e.g. boundary value problems, integral equations, delay-differential equations etc. These have been extensively attempts in literature which end up choosing this optimal value by tests and error or some other ad-hoc means. Our contribution in this paper is to suggest a new strategy using radial basis functions kernel with an automatic reasonable choice of the shape parameter in the nonlinear case which depends on the accuracy and stability of the results. The computational experiments tested on some examples in structural analysis are performed and the comparison with respect to the state of art algorithms from the literature is given.
Robotics and Artificial Intelligence in Gastrointestinal Endoscopy: Updated Review of the Literature and State of the Art
Authors: Boškoski Ivo , Orlandini Beatrice , Papparella Luigi Giovanni , Matteo Maria Valeria , De Siena Martina , Pontecorvi Valerio , Costamagna Guido
Published: February 2021

Purpose of Review

Gastrointestinal endoscopy includes a wide range of procedures that has dramatically evolved over the past decades. Robotic endoscopy and artificial intelligence are expanding the horizons of traditional techniques and will play a key role in clinical practice in the near future. Understanding the main available devices and procedures is a key unmet need. This review aims to assess the current and future applications of the most recently developed endoscopy robots.

Recent Findings

Even though a few devices have gained approval for clinical application, the majority of robotic and artificial intelligence systems are yet to become an integral part of the current endoscopic instrumentarium. Some of the innovative endoscopic devices and artificial intelligence systems are dedicated to complex procedures such as endoscopic submucosal dissection, whereas others aim to improve diagnostic techniques such as colonoscopy.

A review on flexible endoscopic robotics and artificial intelligence systems is presented here, showing the m3ost recently approved and experimental devices and artificial intelligence systems for diagnosis and robotic endoscopy.
The reporting of sustainable development goals: is the integrated approach the missing link?
Authors: Trucco Sara , Demartini Maria Chiara , Beretta Valentina
Published: February 2021

This commentary argues that the integrated thinking could support the simultaneous consideration of different stakeholders' groups to ensure that the SDGs can be achieved as a whole. Prior research, indeed, has argued that social and environmental accounting should put forward actions against unsustainability. Recent literature and international bodies report action to mitigate the negative impacts of unsustainability globally, such as the introduction of the 17 Sustainable Development Goals (SDGs) to set an agenda for the implementation of sustainable development. The implementation of the SDGs has not thus far resulted in the expected outcomes, since there is a lack of focus on how to identify interdependencies among different goals. Integration in SDGs has emerged as an approach to promote actions in this regard, but only a limited number of studies have put forward how integrated reporting and thinking can support the implementation of actions and the monitoring of their progress. Therefore, a paradigm shift in the implementation of an integrated approach in monitoring sustainable development worldwide should be promoted. This could have economic, financial and business consequences; for instance, to support national development plans by creating national financing frameworks, to improve internal decision making and information for investors, to effectively engage the public in sustainability practices such as a Green New Deal and to enhance the perspective of both public and private sector. The adoption of integrated reporting (IR) can describe the value creation process of an organization, by considering the influence of the external environment, relationships, and various resources. By including the concept of sustainable development, the revised IR Framework can be translated at various levels of analysis, by helping firms, local authorities, countries, or other stakeholders in developing proper strategies to improve their process of sustainable development creation. Areas for fruitful future research can be addressed to identify those interdependencies among goals that could effectively enable the SDGs to be universal, indivisible, and interlinked. A further call for research could be focused on what interconnections in the SDGs could be developed across sectors, societal actors, and between and among low, medium, and high-income countries.
Prevalence and associated factors of sharps injuries and other blood/body fluid exposures among healthcare workers: A multicenter study
Authors: Yang Xi-Yao , Li Ruo-Jie , Wu Yi-Le , Hu Xiao-Qian , Wang Xue-Ping , Zhang Jing-Jing , Yang Li-Qi
Published: February 2021

A multicenter study of sharps injuries (SIs) and other blood or body fluid (OBBF) exposures was conducted among 33,156 healthcare workers (HCWs) from 175 hospitals in Anhui, China. In total, 12,178 HCWs (36.7%) had experienced at least 1 SI in the previous 12 months and 8,116 HCWs (24.5%) had experienced at least 1 OBBF exposure during the previous 12 months.
IS A SPECTRUM OF A NON-DISINTEGRATED FLAT STRONGLY MINIMAL MODEL COMPLETE THEORY IN A LANGUAGE WITH FINITE SIGNATURE
Authors: ANDREWS URI , MERMELSTEIN OMER
Published: February 2021

We build a new spectrum of recursive models (
$ \operatorname {\mathrm {SRM}}(T)$
) of a strongly minimal theory. This theory is non-disintegrated, flat, model complete, and in a language with a finite signature.
CONGRUENCE OF ULTRAFILTERS
Authors: ŠOBOT BORIS
Published: February 2021

We continue the research of the relation
$\hspace {1mm}\widetilde {\mid }\hspace {1mm}$
on the set
$\beta \mathbb {N}$
of ultrafilters on
$\mathbb {N}$
, defined as an extension of the divisibility relation. It is a quasiorder, so we see it as an order on the set of
$=_{\sim }$
-equivalence classes, where
$\mathcal {F}=_{\sim }\mathcal {G}$
means that
$\mathcal {F}$
and
$\mathcal {G}$
are mutually
$\hspace {1mm}\widetilde {\mid }$
-divisible. Here we introduce a new tool: a relation of congruence modulo an ultrafilter. We first recall the congruence of ultrafilters modulo an integer and show that
$=_{\sim }$
-equivalent ultrafilters do not necessarily have the same residue modulo
$m\in \mathbb {N}$
. Then we generalize this relation to congruence modulo an ultrafilter in a natural way. After that, using iterated nonstandard extensions, we introduce a stronger relation, which has nicer properties with respect to addition and multiplication of ultrafilters. Finally, we introduce a strengthening of
$\hspace {1mm}\widetilde {\mid }\hspace {1mm}$
and show that it also behaves well with respect to the congruence relation.
ARONSZAJN TREE PRESERVATION AND BOUNDED FORCING AXIOMS
Authors: FUCHS GUNTER
Published: February 2021

I investigate the relationships between three hierarchies of reflection principles for a forcing class

$\Gamma $
: the hierarchy of bounded forcing axioms, of

$\Sigma ^1_1$
-absoluteness, and of Aronszajn tree preservation principles. The latter principle at level

$\kappa $
says that whenever T is a tree of height

$\omega _1$
and width

$\kappa $
that does not have a branch of order type

$\omega _1$
, and whenever

${\mathord {\mathbb P}}$
is a forcing notion in

$\Gamma $
, then it is not the case that

${\mathord {\mathbb P}}$
forces that T has such a branch.

$\Sigma ^1_1$
-absoluteness serves as an intermediary between these principles and the bounded forcing axioms. A special case of the main result is that for forcing classes that don’t add reals, the three principles at level

$2^\omega $
are equivalent. Special attention is paid to certain subclasses of subcomplete forcing, since these are natural forcing classes that don’t add reals.
THE REVERSE MATHEMATICS OF THEOREMS OF JORDAN AND LEBESGUE
Authors: NIES ANDRÉ , TRIPLETT MARCUS A. , YOKOYAMA KEITA
Published: February 2021

The Jordan decomposition theorem states that every function
$f \colon \, [0,1] \to \mathbb {R}$
of bounded variation can be written as the difference of two non-decreasing functions. Combining this fact with a result of Lebesgue, every function of bounded variation is differentiable almost everywhere in the sense of Lebesgue measure. We analyze the strength of these theorems in the setting of reverse mathematics. Over
$\mathsf {RCA}_{0}$
, a stronger version of Jordan’s result where all functions are continuous is equivalent to
$\mathsf {ACA}_0$
, while the version stated is equivalent to
${\textsf {WKL}}_{0}$
. The result that every function on
$[0,1]$
of bounded variation is almost everywhere differentiable is equivalent to
${\textsf {WWKL}}_{0}$
. To state this equivalence in a meaningful way, we develop a theory of Martin–Löf randomness over
$\mathsf {RCA}_0$
.
SCOTT COMPLEXITY OF COUNTABLE STRUCTURES
Authors: ALVIR RACHAEL , GREENBERG NOAM , HARRISON-TRAINOR MATTHEW , TURETSKY DAN
Published: February 2021

We define the Scott complexity of a countable structure to be the least complexity of a Scott sentence for that structure. This is a finer notion of complexity than Scott rank: it distinguishes between whether the simplest Scott sentence is
$\Sigma _{\alpha }$
,
$\Pi _{\alpha }$
, or
$\mathrm {d-}\Sigma _{\alpha }$
. We give a complete classification of the possible Scott complexities, including an example of a structure whose simplest Scott sentence is
$\Sigma _{\lambda + 1}$
for
$\lambda $
a limit ordinal. This answers a question left open by A. Miller.

We also construct examples of computable structures of high Scott rank with Scott complexities
$\Sigma _{\omega _1^{CK}+1}$
and
$\mathrm {d-}\Sigma _{\omega _1^{CK}+1}$
. There are three other possible Scott complexities for a computable structure of high Scott rank:
$\Pi _{\omega _1^{CK}}$
,
$\Pi _{\omega _1^{CK}+1}$
,
$\Sigma _{\omega _1^{CK}+1}$
. Examples of these were already known. Our examples are computable structures of Scott rank
$\omega _1^{CK}+1$
which, after naming finitely many constants, have Scott rank
$\omega _1^{CK}$
. The existence of such structures was an open question.
CORES OVER RAMSEY STRUCTURES
Authors: MOTTET ANTOINE , PINSKER MICHAEL
Published: February 2021

We prove that if an
$\omega $
-categorical structure has an
$\omega $
-categorical homogeneous Ramsey expansion, then so does its model-complete core.
Little Ice Age to modern lake-level fluctuations from Ferguson's Gulf, Lake Turkana, Kenya, based on sedimentology and ostracod assemblages
Authors: Beck Catherine C. , Feibel Craig S. , Mortlock Richard A. , Quinn Rhonda L. , Wright James D.
Published: February 2021

Lacustrine sedimentary records and the proxies contained within them are valuable archives of past climate. However, the resolution of these records is frequently coarse or contains a high degree of uncertainty, making it difficult to resolve how climatic variability impacts the ecosystems on which humans depend. The goal of this study is to couple recent sediment cores sampled at centimeter-scale resolution with paleo- and historical information about lake levels to document how changes in the paleoenvironment impact the paleoecology of a rift basin lake. We present multiproxy data from three short cores collected from Ferguson's Gulf (FG), a shallow embayment connected to the western shore of Lake Turkana, Kenya. Five distinct biozones were interpreted on the basis of ostracods and geochemistry (δ18O, δ13C, and major elements), spanning the Little Ice Age (LIA) to the modern. Overall, ostracod total abundance and assemblage diversity decreased up-core, with the largest total abundance and genera diversity occurring during the LIA. This fits with regional datasets that indicate the Eastern Branch of the East African Rift System was wetter during the LIA than it is today. This also suggests that human impact in and around Lake Turkana has weakened the resiliency of the ecosystems in FG.
Universal and differential transcriptional regulatory pathways involved in the preparation of summer and winter diapauses in Pieris melete
Authors: Jiang Ting , Zhu Yulin , Peng Yingchuan , Zhang Wanna , Xiao Haijun
Published: February 2021

Much progress has been made in understanding the environmental and hormonal systems regulating winter diapause. However, transcriptional regulation of summer diapause is still largely unknown, making it difficult to understand an all-around regulation profile of seasonal adaptation. To bridge this gap, comparison RNA-seq to profile the transcriptome and to examine differential gene expression profiles between non-diapause, summer diapause, and winter diapause groups were performed. A total number of 113 million reads were generated and assembled into 79,117 unigenes, with 37,492 unigenes categorized into 58 functional gene ontology groups, 25 clusters of orthologous group categories, and 256 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. KEGG analysis mapped 2108 differentially expressed genes to 48 and 67 pathways for summer and winter diapauses, respectively. Enrichment statistics showed that 11 identical pathways similarly overlapped in the top 20 enriched functional groups both related to summer and winter diapauses. We also identified 35 key candidate genes for universal and differential functions related to summer and winter diapause preparation. Furthermore, we identified some genes involved in the signaling and metabolic pathways that may be the key drivers to integrate environmental signals into the summer and winter diapause preparation. The current study provided valuable insights into global molecular mechanisms underpinning diapause preparation.
Head and neck cancer surgery during the coronavirus pandemic: a single-institution experience
Authors: Jeannon J-P , Simo R , Oakley R , Townley W , Orfaniotis G , Fry A , Arora A , Taylor C , Ahmad I
Published: February 2021

Objective

The coronavirus disease 2019 pandemic resulted in the cessation of elective surgery. The continued provision of complex head and neck cancer surgery was extremely variable, with some UK centres not performing any cancer surgery. During the pandemic, Guy's and St Thomas’ NHS Foundation Trust received high numbers of coronavirus disease 2019 admissions. This paper presents our experience of elective complex major head and neck cancer surgery throughout the pandemic.

Methods

A head and neck cancer surgery hub was set up that provided a co-ordinated managed care pathway for cancer patients during the pandemic; the Guy's Cancer Centre provided a separate, self-enclosed coronavirus-free environment within the hospital campus.

Results

Sixty-nine head and neck cancer patients were operated on in two months, and 13 patients had a microvascular free tissue transfer. Nosocomial infection with coronavirus disease 2019 was detected in two cases (3 per cent), neither required critical care unit admission. Both patients made a complete recovery and were discharged home. There were no deaths.

Conclusion

Performing major head and neck surgery, including free flap surgery, is possible during the pandemic; however, significant changes to conventional practice are required to achieve desirable patient outcomes.
Electron trapping and acceleration in plasma wake field produced by an evolving hollow electron beam
Authors: Liu Xiangyang , Qu Junfan , Liu Peng , Fan Houchen , Cai Ling , Zhang Feng , Yu Qin , Li Xiaofeng , Zhang Linwen , Kong Qing
Published: February 2021

In this article, the electron trapping and acceleration in the wake field driven by an ultrarelativistic hollow electron beam is studied. When the hollow driver injects into plasma, there is a doughnut-shaped electron bubble formed because of the existence of a special ‘backflow’ beam in the centre of the electron bubble. At the same time, there is a transverse convergence of the hollow driver, which leads to the weakening of the backflow beam. This results in a local electron density transition at the rear of the bubble. During this process, there is an expansion of the longitudinal electron bubble size, and a bunch of background electrons is trapped by the wake field at the rear of the bubble. The tracks for the trapped electrons show that there are two sources: one is from the bubble sheath and the other is from the unique backflow beam. In the particle-in-cell simulation where the driving beam has initial energy of

$1.0$

GeV per particle, the trapped beam can be accelerated to energy of more than

$1.5$

GeV per particle and the corresponding transformer ratio is

$1.5$

. With the increase of driving beam energy up to

$40.0$

GeV, a transformer ratio of

$1.4$

still can be achieved. By adjusting the hollow beam density, it is possible to control the trapped beam charge value and beam quality, such as its energy spread and transverse emittance.
Islamic Traditionalism in a Globalizing World: Sunni Muslim identity in Kerala, South India
Authors: VISAKH M. S. , SANTHOSH R. , MOHAMMED ROSHAN C. K.
Published: February 2021

In our ethnography among traditionalist Sunni Muslims of Kerala, South India, we observe the emergence of new intellectual critiques of Islamic reformism and a revival of ‘traditional’ Islamic articulations. A new class of traditionalist Sunniulama, claiming to be ‘turbaned professionals’, plays an instrumental role in providing epistemic sanctioning to ‘traditional’ Islamic piety while simultaneously grounding it within the discourses and processes of neoliberal developmentalism. Such assertions of traditionalist Sunni Muslim identity challenge the conventional understanding of Islamic reformism as a hallmark of the progressive understanding of faith and traditionalism as its ‘anti-modern’ other. The article argues that this discursive shift of Sunni Islamic traditionalism in Kerala since the 1980s from defensive to more assertive forms has to be located in the context of wider socio-economic change within the community facilitated by structural as well as cultural forces of globalization. We point out that this process traverses the local, national, and global scales of identification, and results in intense negotiations between local identifications and ‘true Islamicate global imaginations’. These negotiations bring in new discourses around the question of ‘authentic’ Islamic practices and sensibilities among the traditionalist Sunni Muslims, forcing us to locate the question of their identity formation beyond the boundaries of communities and the nation states that ensconce them.
Peasants, Colonialism, and Sovereignty: The Garo rebellions in eastern India
Authors: MISRA SANGHAMITRA
Published: February 2021

This article studies two seismic decades in the history of the Garo community, marked out in colonial records as among the most violent and isolated people that British rule encountered in eastern and northeastern India. Through a densely knit historical narrative that hinges on an enquiry into the colonial reordering of the core elements of the regional political economy of eastern and northeastern India, it will train its focus on the figure of the rebellious Garo peasant and on the arresting display of Garo recalcitrance between 1807 and 1820. Reading a rich colonial archive closely and against the grain, the article will depart from extant historiography in its characterization of the colonial state in the early nineteenth century as well as of its relationship with ‘tribes’/‘peasants’ in eastern and northeastern India. A critique of the idea of primitive violence and the production of the ‘tribe’ under conditions of colonial modernity will occupy the latter half of the article. Here it will argue that the numerous and apparently disparate acts of headhunting, raids, plunder, and burning by the Garos on the lowlands of Bengal and Assam were in fact an assembling of the first of a series of sustained peasant rebellions in this part of colonial India—a powerful manifestation of a community's historical consciousness of the loss of its sovereign self under British rule.
Effects of Dynamic Model Errors in Task-Priority Operational Space Control
Authors: Di Lillo Paolo , Antonelli Gianluca , Natale Ciro
Published: February 2021

Control algorithms of many Degrees-of-Freedom (DOFs) systems based on Inverse Kinematics (IK) or Inverse Dynamics (ID) approaches are two well-known topics of research in robotics. The large number of DOFs allows the design of many concurrent tasks arranged in priorities, that can be solved either at kinematic or dynamic level. This paper investigates the effects of modeling errors in operational space control algorithms with respect to uncertainties affecting knowledge of the dynamic parameters. The effects on the null-space projections and the sources of steady-state errors are investigated. Numerical simulations with on-purpose injected errors are used to validate the thoughts.
Early onset obsessive–compulsive disorder: the biological and clinical phenotype
Authors: Grassi Giacomo , Cecchelli Chiara , Mazzocato Gloria , Vignozzi Luisa
Published: February 2021

Moving from a behavioral-based to a biological-based classification of mental disorders is a crucial step toward a precision-medicine approach in psychiatry. In the last decade, a big effort has been made in order to stratify genetic, immunological, neurobiological, cognitive, and clinical profiles of patients. Making the case of obsessive–compulsive disorder (OCD), a lot have been made in this direction. Indeed, while the Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnosis of OCD aimed to delineate a homogeneous group of patients, it is now clear that OCD is instead an heterogeneous disorders both in terms of neural networks, immunological, genetic, and clinical profiles. In this view, a convergent amount of literature, in the last years, indicated that OCD patients with an early age at onset seem to have a specific clinical and biological profile, suggesting it as a neurodevelopmental disorder. Also, these patients tend to have a worse outcome respect to adult-onset patients and there is growing evidence that early-interventions could potentially improve their prognosis. Therefore, the aim of the present paper is to review the current available genetic, immunological, neurobiological, cognitive, and clinical data in favor of a more biologically precise subtype of OCD: the early-onset subtype. We also briefly resume current available recommendations for the clinical management of this specific population.
Leptin administration during lactation leads to different nutritional, biometric, hemodynamic, and cardiac outcomes in prepubertal and adult female Wistar rats
Authors: de Souza Karyne Pollo , de Sousa Pedro Samuel , Rocha Nazareth Novaes , Marques Emiliana Barbosa , Scaramello Christianne Bretas Vieira
Published: February 2021

Literature reports that insults, such as hormonal disturbances, during critical periods of development may modulate organism physiology and metabolism favoring cardiovascular diseases (CVDs) later in life. Studies show that leptin administration during lactation leads to cardiovascular dysfunction in young and adult male Wistar rats. However, there are sex differences regarding CVD. Thus, the present work aimed to investigate neonatal leptin administration’s consequences on different outcomes in female rats at prepubertal and adult age. Newborn Wistar female rats were divided into two groups, Leptin and Control, receiving daily subcutaneous injections of this adipokine (8 μg/100 g) or saline for the first 10 of 21 d of lactation. Nutritional, biometric, hemodynamic, and echocardiographic parameters, as well as maximal effort ergometer performance, were determined at postnatal days (PND) 30 and 150. Leptin group presented lower food intake (p= 0.0003) and higher feed efficiency (p= 0.0058) between PND 21 and 30. Differences concerning echocardiographic parameters revealed higher left ventricle internal diameter (LVID) in systole (p= 0.0051), as well as lower left ventricle ejection fraction (LVEF) (p= 0.0111) and fractional shortening (FS) (p= 0.0405) for this group at PND 30. Older rats treated with leptin during lactation presented only higher LVID in systole (p= 0.0270). Systolic blood pressure and maximum effort ergometer test performance was similar between groups at both ages. These data suggest that nutritional, biometric, and cardiac outcomes due to neonatal leptin administration in female rats are age-dependent.
Selective recruitment of γδ T cells by a bispecific antibody for the treatment of acute myeloid leukemia
Authors: Ganesan Rajkumar , Chennupati Vijaykumar , Ramachandran Balaji , Hansen Michael Riis , Singh Sanjaya , Grewal Iqbal S.
Published: February 2021

Despite significant progress over the last few decades in the treatment of acute myeloid leukemia (AML), there still remains a major unmet medical need for this disease. Immunotherapy approaches for redirecting pan CD3+ T cells to target leukemia blasts have shown limited efficacy in clinical trials and often accompanied with severe toxicity in AML patients. We designed an alternative engager molecule (Anti-TRGV9/anti-CD123), a bispecific antibody that can simultaneously bind to the Vγ9 chain of the Vγ9Vδ2+ γδ T cell receptor and to AML target antigen, CD123, to selectively recruit Vγ9+ γδ T cells rather than pan T cells to target AML blasts. Our results suggest that prototypic bispecific antibodies (a) selectively activate Vγ9+ γδ T cells as judged by CD69 and CD25 surface expression, and intracellular Granzyme B expression, (b) selectively recruit Vγ9+ γδ T cells into cell–cell conjugate formation of γδ T cells with tumor cells indicating selective and effective engagement of effector and target tumor cells, and (c) mediate γδ T cell cytotoxicity (in vitro and in vivo) against tumor antigen-expressing cells. Collectively, these findings suggest that selectively redirecting Vγ9+ γδ T cells to target AML blasts has a potential for immunotherapy for AML patients and favors further exploration of this concept.
Polygenic burden has broader impact on health, cognition, and socioeconomic outcomes than most rare and high-risk copy number variants
Authors: Saarentaus Elmo Christian , Havulinna Aki Samuli , Mars Nina , Ahola-Olli Ari , Kiiskinen Tuomo Tapio Johannes , Partanen Juulia , Ruotsalainen Sanni , Kurki Mitja , Urpa Lea Martta , Chen Lei , Perola Markus , Salomaa Veikko , Veijola Juha , Männikkö Minna , Hall Ira M. , Pietiläinen Olli , Kaprio Jaakko , Ripatti Samuli , Daly Mark , Palotie Aarno
Published: February 2021

Copy number variants (CNVs) are associated with syndromic and severe neurological and psychiatric disorders (SNPDs), such as intellectual disability, epilepsy, schizophrenia, and bipolar disorder. Although considered high-impact, CNVs are also observed in the general population. This presents a diagnostic challenge in evaluating their clinical significance. To estimate the phenotypic differences between CNV carriers and non-carriers regarding general health and well-being, we compared the impact of SNPD-associated CNVs on health, cognition, and socioeconomic phenotypes to the impact of three genome-wide polygenic risk score (PRS) in two Finnish cohorts (FINRISK, n = 23,053 and NFBC1966, n = 4895). The focus was on CNV carriers and PRS extremes who do not have an SNPD diagnosis. We identified high-risk CNVs (DECIPHER CNVs, risk gene deletions, or large [>1 Mb] CNVs) in 744 study participants (2.66%), 36 (4.8%) of whom had a diagnosed SNPD. In the remaining 708 unaffected carriers, we observed lower educational attainment (EA; OR = 0.77 [95% CI 0.66–0.89]) and lower household income (OR = 0.77 [0.66–0.89]). Income-associated CNVs also lowered household income (OR = 0.50 [0.38–0.66]), and CNVs with medical consequences lowered subjective health (OR = 0.48 [0.32–0.72]). The impact of PRSs was broader. At the lowest extreme of PRS for EA, we observed lower EA (OR = 0.31 [0.26–0.37]), lower-income (OR = 0.66 [0.57–0.77]), lower subjective health (OR = 0.72 [0.61–0.83]), and increased mortality (Cox’s HR = 1.55 [1.21–1.98]). PRS for intelligence had a similar impact, whereas PRS for schizophrenia did not affect these traits. We conclude that the majority of working-age individuals carrying high-risk CNVs without SNPD diagnosis have a modest impact on morbidity and mortality, as well as the limited impact on income and educational attainment, compared to individuals at the extreme end of common genetic variation. Our findings highlight that the contribution of traditional high-risk variants such as CNVs should be analyzed in a broader genetic context, rather than evaluated in isolation.
Role of lysophosphatidic acid and its receptors in health and disease: novel therapeutic strategies
Authors: Geraldo Luiz Henrique Medeiros , Spohr Tânia Cristina Leite de Sampaio , Amaral Rackele Ferreira do , Fonseca Anna Carolina Carvalho da , Garcia Celina , Mendes Fabio de Almeida , Freitas Catarina , dosSantos Marcos Fabio , Lima Flavia Regina Souza
Published: February 2021

Lysophosphatidic acid (LPA) is an abundant bioactive phospholipid, with multiple functions both in development and in pathological conditions. Here, we review the literature about the differential signaling of LPA through its specific receptors, which makes this lipid a versatile signaling molecule. This differential signaling is important for understanding how this molecule can have such diverse effects during central nervous system development and angiogenesis; and also, how it can act as a powerful mediator of pathological conditions, such as neuropathic pain, neurodegenerative diseases, and cancer progression. Ultimately, we review the preclinical and clinical uses of Autotaxin, LPA, and its receptors as therapeutic targets, approaching the most recent data of promising molecules modulating both LPA production and signaling. This review aims to summarize the most update knowledge about the mechanisms of LPA production and signaling in order to understand its biological functions in the central nervous system both in health and disease.
Aberrantly high activation of a FoxM1–STMN1 axis contributes to progression and tumorigenesis in FoxM1-driven cancers
Authors: Liu Jun , Li Jipeng , Wang Ke , Liu Haiming , Sun Jianyong , Zhao Xinhui , Yu Yanping , Qiao Yihuan , Wu Ye , Zhang Xiaofang , Zhang Rui , Yang Angang
Published: February 2021

Fork-head box protein M1 (FoxM1) is a transcriptional factor which plays critical roles in cancer development and progression. However, the general regulatory mechanism of FoxM1 is still limited. STMN1 is a microtubule-binding protein which can inhibit the assembly of microtubule dimer or promote depolymerization of microtubules. It was reported as a major responsive factor of paclitaxel resistance for clinical chemotherapy of tumor patients. But the function of abnormally high level of STMN1 and its regulation mechanism in cancer cells remain unclear. In this study, we used public database and tissue microarrays to analyze the expression pattern of FoxM1 and STMN1 and found a strong positive correlation between FoxM1 and STMN1 in multiple types of cancer. Lentivirus-mediated FoxM1/STMN1-knockdown cell lines were established to study the function of FoxM1/STMN1 by performing cell viability assay, plate clone formation assay, soft agar assay in vitro and xenograft mouse model in vivo. Our results showed that FoxM1 promotes cell proliferation by upregulating STMN1. Further ChIP assay showed that FoxM1 upregulates STMN1 in a transcriptional level. Prognostic analysis showed that a high level of FoxM1 and STMN1 is related to poor prognosis in solid tumors. Moreover, a high co-expression of FoxM1 and STMN1 has a more significant correlation with poor prognosis. Our findings suggest that a general FoxM1-STMN1 axis contributes to cell proliferation and tumorigenesis in hepatocellular carcinoma, gastric cancer and colorectal cancer. The combination of FoxM1 and STMN1 can be a more precise biomarker for prognostic prediction.
Genome sequencing broadens the range of contributing variants with clinical implications in schizophrenia
Authors: Mojarad Bahareh A. , Yin Yue , Manshaei Roozbeh , Backstrom Ian , Costain Gregory , Heung Tracy , Merico Daniele , Marshall Christian R. , Bassett Anne S. , Yuen Ryan K. C.
Published: February 2021

The range of genetic variation with potential clinical implications in schizophrenia, beyond rare copy number variants (CNVs), remains uncertain. We therefore analyzed genome sequencing data for 259 unrelated adults with schizophrenia from a well-characterized community-based cohort previously examined with chromosomal microarray for CNVs (none with 22q11.2 deletions). We analyzed these genomes for rare high-impact variants considered causal for neurodevelopmental disorders, including single-nucleotide variants (SNVs) and small insertions/deletions (indels), for potential clinical relevance based on findings for neurodevelopmental disorders. Also, we investigated a novel variant type, tandem repeat expansions (TREs), in 45 loci known to be associated with monogenic neurological diseases. We found several of these variants in this schizophrenia population suggesting that these variants have a wider clinical spectrum than previously thought. In addition to known pathogenic CNVs, we identified 11 (4.3%) individuals with clinically relevant SNVs/indels in genes converging on schizophrenia-relevant pathways. Clinical yield was significantly enriched in females and in those with broadly defined learning/intellectual disabilities. Genome analyses also identified variants with potential clinical implications, including TREs (one inDMPK; two inATXN8OS) and ultra-rare loss-of-function SNVs inZMYM2(a novel candidate gene for schizophrenia). Of the 233 individuals with no pathogenic CNVs, we identified rare high-impact variants (i.e., clinically relevant or with potential clinical implications) for 14 individuals (6.0%); some had multiple rare high-impact variants. Mean schizophrenia polygenic risk score was similar between individuals with and without clinically relevant rare genetic variation; common variants were not sufficient for clinical application. These findings broaden the individual and global picture of clinically relevant genetic risk in schizophrenia, and suggest the potential translational value of genome sequencing as a single genetic technology for schizophrenia.
Targeted multi-epitope switching enables straightforward positive/negative selection of CAR T cells
Authors: Mosti Laura , Langner Lukas M. , Chmielewski Kay O. , Arbuthnot Patrick , Alzubi Jamal , Cathomen Toni
Published: February 2021

Chimeric antigen receptor (CAR) T cell technology has enabled successfully novel concepts to treat cancer patients, with substantial remission rates in lymphoid malignancies. This cell therapy is based on autologous T lymphocytes that are genetically modified to express a CAR that recognizes tumor-associated antigens and mediates the elimination of the respective tumor cells. Current limitations include laborious manufacturing procedures as well as severe immunological side effects upon administration of CAR T cells. To address these limitations, we integrated RQR8, a multi-epitope molecule harboring a CD34 epitope and two CD20 mimotopes, alongside a CD19-targeting CAR, into the CD52 locus. Using CRISPR-Cas9 and adeno-associated virus-based donor vectors, some 60% of genome-edited T cells were CAR+/CD20+/CD34+/CD52− without further selection. This could be increased to >95% purity after CD34 tag-based positive selection. These epitope-switched CAR T cells retained cell killing competence against CD19+ tumor cells, and were resistant to alemtuzumab (anti-CD52) but sensitive to rituximab (anti-CD20) in complement-dependent cytotoxicity assays. In conclusion, gene editing-based multiple epitope switching represents a promising development with the potential to improve both the manufacturing procedure as well as the clinical safety of CAR T cells.
Insights into triterpene synthesis and unsaturated fatty-acid accumulation provided by chromosomal-level genome analysis of Akebia trifoliata subsp. australis
Authors: Huang Hui , Liang Juan , Tan Qi , Ou Linfeng , Li Xiaolin , Zhong Caihong , Huang Huilin , Møller Ian Max , Wu Xianjin , Song Songquan
Published: February 2021

Akebia trifoliata subsp. australis is a well-known medicinal and potential woody oil plant in China. The limited genetic information available for A. trifoliata subsp. australis has hindered its exploitation. Here, a high-quality chromosome-level genome sequence of A. trifoliata subsp. australis is reported. The de novo genome assembly of 682.14 Mb was generated with a scaffold N50 of 43.11 Mb. The genome includes 25,598 protein-coding genes, and 71.18% (485.55 Mb) of the assembled sequences were identified as repetitive sequences. An ongoing massive burst of long terminal repeat (LTR) insertions, which occurred ~1.0 million years ago, has contributed a large proportion of LTRs in the genome of A. trifoliata subsp. australis. Phylogenetic analysis shows that A. trifoliata subsp. australis is closely related to Aquilegia coerulea and forms a clade with Papaver somniferum and Nelumbo nucifera, which supports the well-established hypothesis of a close relationship between basal eudicot species. The expansion of UDP-glucoronosyl and UDP-glucosyl transferase gene families and β-amyrin synthase-like genes and the exclusive contraction of terpene synthase gene families may be responsible for the abundant oleanane-type triterpenoids in A. trifoliata subsp. australis. Furthermore, the acyl-ACP desaturase gene family, including 12 stearoyl-acyl-carrier protein desaturase (SAD) genes, has expanded exclusively. A combined transcriptome and fatty-acid analysis of seeds at five developmental stages revealed that homologs of SADs, acyl-lipid desaturase omega fatty acid desaturases (FADs), and oleosins were highly expressed, consistent with the rapid increase in the content of fatty acids, especially unsaturated fatty acids. The genomic sequences of A. trifoliata subsp. australis will be a valuable resource for comparative genomic analyses and molecular breeding.
R2R3-MYB transcription factors, StmiR858 and sucrose mediate potato flavonol biosynthesis
Authors: Lin Sen , Singh Rajesh K. , Moehninsi  , Navarre Duroy A.
Published: February 2021

Flavonols and other phenylpropanoids protect plants from biotic and abiotic stress and are dietarily desirable because of their health-promoting properties. The ability to develop new potatoes (Solanum tuberosum) with optimal types and amounts of phenylpropanoids is limited by lack of knowledge about the regulatory mechanisms. Exogenous sucrose increased flavonols, whereas overexpression of the MYB StAN1 induced sucrolytic gene expression. Heterologous StAN1 protein bound promoter fragments from sucrolytic genes (SUSY1andINV1). Two additional MYBs and one microRNA were identified that regulated potato flavonols. Overexpression analysis showedMYB12AandCincreased amounts of flavonols and other phenylpropanoids. Endogenous flavonol amounts in light-exposed organs were much higher those in the dark. Expression levels ofStMYB12AandCwere high in flowers but low in tubers. Transient overexpression of miR858 altered potato flavonol metabolism. Endogenous StmiR858 expression was much lower in flowers than leaves and correlated with flavonol amounts in these organs. Collectively, these findings support the hypothesis that sucrose, MYBs, and miRNA control potato phenylpropanoid metabolism in a finely tuned manner that includes a feedback loop between sucrose and StAN1. These findings will aid in the development of potatoes with phenylpropanoid profiles optimized for crop performance and human health.
KSN heterozygosity is associated with continuous flowering of Rosa rugosa Purple branch
Authors: Bai Mengjuan , Liu Jinyi , Fan Chunguo , Chen Yeqing , Chen Hui , Lu Jun , Sun Jingjing , Ning Guogui , Wang Changquan
Published: February 2021

Rose (Rosaspp.) plants flower via two contrasting methods: once flowering (OF) and continuous flowering (CF). Purple branch is a rare continuously flowering variety ofRosa rugosathat is extensively cultivated in China. However, the genetic basis of its CF behavior is unknown. We demonstrated that Purple branch is heterozygous for theTFL1homologKSN. OneKSNallele with a 9 kb Copia insertion was found to be identical to that from continuously floweringRosa chinensisOld blush. The other allele was found to be a functional wild-type allele. The overall expression ofKSNwas closely linked to the floral transition, and it was significantly repressed in continuously flowering Purple branch compared with OF Plena. The promoter region of the normalKSNallele was hypermethylated, and histone methylation at H3H4, H3K9, and H3K27 of theKSNgene locus was modified in continuously flowering Purple branch. Silencing of the DNA methyltransferase genesMET1andCMT3and the histone methyltransferase geneSUVR5in Purple branch led to enhancedKSNexpression, but silencing of the histone demethylase geneJMJ12suppressedKSNexpression. Therefore, the CF habit of Purple branch may be due to reduced expression ofKSNcaused by the halved dose and may be associated with epigenetic modifications together with retrotransposon insertions along the chromosome. Our study revealed a novel mechanism underlying the CF behavior of rose plants.