bluuebunny/crossref_metadata_2025 huggingface dataset:
Defining Regions of Pre-Colonial Africa: A Controlled Vocabulary for Linking Open-Source Data in Digital History Projects
Authors: Lovejoy Henry B. , Lovejoy Paul E. , Hawthorne Walter , Alpers Edward A. , Candido Mariana , Hopper Matthew S. , Lydon Ghislaine , Kriger Colleen E. , Thornton John
Published: May 2021

Regionalizing pre-colonial Africa aids in the collection and interpretation of primary sources as data for further analysis. This article includes a map with six broad regions and 34 sub-regions, which form a controlled vocabulary within which researchers may geographically organize and classify disparate pieces of information related to Africa’s past. In computational terms, the proposed African regions serve as data containers in order to consolidate, link, and disseminate research among a growing trend in digital humanities projects related to the history of the African diasporas before c. 1900. Our naming of regions aims to avoid terminologies derived from European slave traders, colonialism, and modern-day countries.
‘Great angels’ in Antrim: Hugh Shearman, theosophist perceptions, and Ulster unionist public relations
Authors: Maume Patrick
Published: May 2021

This article argues that the career and writings of the Ulster unionist propagandist and man of letters Hugh Shearman (1915–99) were influenced by his commitment to theosophy, which he saw as a logical extension of Protestant belief in private judgement. His work as a publicist echoed theosophist preoccupation with illusion and the perceptions accessible to initiates. Many of his writings displayed theosophist in-jokes, esoteric references and mental reservations. His apologias reflected theosophist belief in the breaking down of personality compartmentalisation in order to merge with the world-soul. Shearman saw the Irish republic as the ‘Pakistan of the West’, represented by him as embodying self-destructive insularity shaped by Catholic authoritarianism. In response to the 1940s anti-partition campaign, Shearman developed an apologia for the Stormont government as an essentially progressive technocracy, which he saw as culminating in the regime of Terence O'Neill. This article uses previously unexplored writings to track Shearman's life and career into the 1990s, when he is shown to have combined a view of the Irish question formed in the 1940s with a semi-conspiratorial unionist narrative of British betrayal.
Carbonate fabric diversity and environmental heterogeneity in the late Mesoproterozoic Era
Authors: Kah Linda C. , Bartley Julie K.
Published: May 2021

Time-distinctive features within carbonate rocks, specifically the presence, abundance and distribution of stromatolites, molar-tooth fabric and specific morphologies of marine cement, have been identified as potential indicators of global-scale changes in the chemistry of marine environments. Recently, Cantineet al.(2019) introduced a database approach seeking to quantify spatial and temporal patterns in these carbonate features through the Precambrian. Despite the coarse temporal scale, results support earlier inferences of temporal change in carbonate sedimentation. Here, we use original field notes to dissect late Mesoproterozoic (˜1.3 to 1.0 Ga) carbonate strata at a high resolution, analyse time-distinctive carbonate fabrics within a database context and compare sedimentological patterns within this narrow time range to observations of the Proterozoic as a whole. Late Mesoproterozoic strata contain a variety of features (e.g. stromatolites, seafloor precipitates, herringbone carbonate, molar-tooth carbonate), often in close spatial and temporal proximity, that are commonly considered to be temporally restricted during the Precambrian. The spatial distribution of such features within Mesoproterozoic basins demonstrates the importance of recognizing even rare occurrences of time-distinctive facies and permits inference of environmental drivers that may have interacted to affect carbonate precipitation. Such spatial variability reflects a subtle division of Mesoproterozoic carbonate platform environments driven by globally high sea level, elevated carbonate saturation and a low-oxygen water column. The heterogeneous, mosaic nature of environments appears to be a hallmark of Mesoproterozoic carbonate sedimentation and emphasizes the importance of these basins in understanding longer-term trends in carbonate deposition.
Capsicum frutescens and Citrus limon: a new take on therapy against experimental trichinellosis
Authors: Salama Marwa Ahmed Mohamed , Mostafa Nahed E. , Abd El-Aal Naglaa Fathy , Mostafa Eman M. , Hammad Samar Kamel , Adel Rasha , Moawad Howayda Said Fouad
Published: May 2021

Trichinellosis is a zoonotic disease that endangers human health and can lead to death. Restricted absorption and poor results of conventional therapies demand new effective natural remedies to treat both enteral and parenteral trichinellosis. This study assessed the antiparasitic and anti-inflammatory effects of Citrus limon and Capsicum frutescens on murine trichinellosis and compared them with those of albendazole and prednisolone, which are conventionally used to treat trichinellosis. Overall, 50 Swiss albino male mice were divided into five groups, with ten mice in each group: negative control, positive control, albendazole combined with prednisolone, C. limon, and C. frutescens. Mice were sacrificed 7 and 35 days after infection, for intestinal and muscular phase analyses. Drug efficacies were parasitologically, biochemically, histopathologically and ultrastructurally assessed. Our results demonstrated the efficacy of C. frutescens and C. limon extracts as antiparasitic agents, showing a substantial decrease in adult and larval counts. Moreover, both extracts had the ability to decrease serum tumour necrosis factor-α levels during the intestinal and muscular phases. In addition to the improved histopathological changes in the small intestine and muscles, the destructive effects on adults and larvae were ultrastructurally evident on transmission electron microscopy. In conclusion, C. frutescens and C. limon extracts are promising remedies for the treatment of experimental trichinellosis, particularly, the C. frutescens extract.
Plants critical for Hawaiian land snail conservation: arboreal snail plant preferences in Puʻu Kukui Watershed, Maui
Authors: Meyer Wallace M. , Evans Lily M. , Kalahiki Connor J.K. , Slapcinsky John , Goulding Tricia C. , Robinson David G. , Kaniaupo-Crozier D. Pomaikaʻi , Kim Jaynee R. , Hayes Kenneth A. , Yeung Norine W.
Published: May 2021

The Hawaiian archipelago was formerly home to one of the most species-rich land snail faunas (> 752 species), with levels of endemism > 99%. Many native Hawaiian land snail species are now extinct, and the remaining fauna is vulnerable. Unfortunately, lack of information on critical habitat requirements for Hawaiian land snails limits the development of effective conservation strategies. The purpose of this study was to examine the plant host preferences of native arboreal land snails in Puʻu Kukui Watershed, West Maui, Hawaiʻi, and compare these patterns to those from similar studies on the islands of Oʻahu and Hawaiʻi. Concordant with studies on other islands, we found that four species from three diverse families of snails in Puʻu Kukui Watershed had preferences for a few species of understorey plants. These were not the most abundant canopy or mid canopy species, indicating that forests without key understorey plants may not support the few remaining lineages of native snails. Preference for Broussaisia arguta among various island endemic snails across all studies indicates that this species is important for restoration to improve snail habitat. As studies examining host plant preferences are often incongruent with studies examining snail feeding, we suggest that we are in the infancy of defining what constitutes critical habitat for most Hawaiian arboreal snails. However, our results indicate that preserving diverse native plant assemblages, particularly understorey plant species, which facilitate key interactions, is critical to the goal of conserving the remaining threatened snail fauna.
Genetics of obsessive-compulsive disorder
Authors: Mahjani Behrang , Bey Katharina , Boberg Julia , Burton Christie
Published: May 2021

Background

Obsessive-compulsive disorder (OCD) is a psychiatric disorder with multiple symptom dimensions (e.g. contamination, symmetry). OCD clusters in families and decades of twin studies clearly demonstrate an important role for genetics in the etiology of the disorder.

Methods

In this review, we summarize the genetic epidemiology and molecular genetic studies of OCD and obsessive-compulsive symptoms.

Results

OCD is a heritable, polygenic disorder with contributions from both common and rare variants, includingde novodeleterious variations. Multiple studies have provided reliable support for a large additive genetic contribution to liability to OCD, with discrete OCD symptom dimensions having both shared and unique genetic risks. Genome-wide association studies have not produced significant results yet, likely because of small sample sizes, but larger meta-analyses are forthcoming. Both twin and genome-wide studies show that OCD shares genetic risk with its comorbid conditions (e.g. Tourette syndrome and anorexia nervosa).

Conclusions

Despite significant efforts to uncover the genetic basis of OCD, the mechanistic understanding of how genetic and environmental risk factors interact and converge at the molecular level to result in OCD's heterogeneous phenotype is still mostly unknown. Future investigations should increase ancestral genetic diversity, explore age and/or sex differences in genetic risk for OCD and expand the study of pharmacogenetics, gene expression, gene × environment interactions and epigenetic mechanisms for OCD.
Association between risk of dementia and very late-onset schizophrenia-like psychosis: a Swedish population-based cohort study
Authors: Stafford J. , Dykxhoorn J. , Sommerlad A. , Dalman C. , Kirkbride J. B. , Howard R.
Published: May 2021

Background

Although the incidence of psychotic disorders among older people is substantial, little is known about the association with subsequent dementia. We aimed to examine the rate of dementia diagnosis in individuals with very late-onset schizophrenia-like psychosis (VLOSLP) compared to those without VLOSLP.

Methods

Using Swedish population register data, we established a cohort of 15 409 participants with VLOSLP matched by age and calendar period to 154 090 individuals without VLOSLP. Participants were born between 1920 and 1949 and followed from their date of first International Classification of Diseases [ICD], Revisions 8–10 (ICD-8/9/10) non-affective psychotic disorder diagnosis after age 60 years old (or the same date for matched participants) until the end of follow-up (30th December 2011), emigration, death, or first recorded ICD-8/9/10 dementia diagnosis.

Results

We found a substantially higher rate of dementia in individuals with VLOSLP [hazard ratio (HR): 4.22, 95% confidence interval (95% CI) 4.05–4.41]. Median time-to-dementia-diagnosis was 75% shorter in those with VLOSLP (time ratio: 0.25, 95% CI 0.24–0.26). This association was strongest in the first year following VLOSLP diagnosis, and attenuated over time, although dementia rates remained higher in participants with VLOSLP for up to 20 years of follow-up. This association remained after accounting for potential misdiagnosis (2-year washout HR: 2.22, 95% CI 2.10–2.36), ascertainment bias (HR: 2.89, 95% CI 2.75–3.04), and differing mortality patterns between groups (subdistribution HR: 2.89, 95% CI 2.77–3.03).

Conclusions

Our findings demonstrate that individuals with VLOSLP represent a high-risk group for subsequent dementia. This may be due to early prodromal changes for some individuals, highlighting the importance of ongoing symptom monitoring in people with VLOSLP.
The death-implicit association test and suicide attempts: a systematic review and meta-analysis of discriminative and prospective utility
Authors: Sohn Maya N. , McMorris Carly A. , Bray Signe , McGirr Alexander
Published: May 2021

Suicide risk assessment involves integrating patient disclosure of suicidal ideation and non-specific risk factors such as family history, past suicidal behaviour, and psychiatric symptoms. A death version of the implicit association test (D-IAT) has been developed to provide an objective measure of the degree to which the self is affiliated with life or death. However, this has inconsistently been associated with past and future suicidal behaviour. Here, we systematically review and quantitatively synthesize the literature examining the D-IAT and suicide attempts. We searched psychINFO, Medline, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception until 9 February 2021 to identify publications reporting D-IAT scores and suicide attempts (PROSPERO; CRD42020194394). Using random-effects models, we calculated standardized mean differences (SMD) and odds ratios (ORs) for retrospective suicide attempts. We then calculated ORs for future suicide attempts. ORs were dichotomized using a cutoff of zero representing equipoise between self-association with life and death. Eighteen studies met our inclusion criteria (n = 9551). The pooled SMD revealed higher D-IAT scores in individuals with a history of suicide attempt (SMD = 0.25, 95% CI 0.15 to 0.35); however, subgroup analyses demonstrated heterogeneity with acute care settings having lower effect sizes than community settings. Dichotomized D-IAT scores discriminated those with a history of suicide attempt from those without (OR 1.38 95% CI 1.01 to 1.89) and predicted suicide attempt over a six-month follow-up period (OR 2.99 95% CI 1.45 to 6.18; six studies, n = 781). The D-IAT may have a supplementary role in suicide risk assessment; however, determination of acute suicide risk and related clinical decisions should not be based solely on D-IAT performance.
Thresholds in Distributive Justice
Authors: Timmer Dick
Published: May 2021

Despite the prominence of thresholds in theories of distributive justice, there is no general account of what sort of role is played by the idea of a threshold within such theories. This has allowed an ongoing lack of clarity and misunderstanding around views that employ thresholds. In this article, I develop an account of the concept of thresholds in distributive justice. I argue that this concept contains three elements, which threshold views deploy when ranking possible distributions. These elements are (i) the level of the threshold, (ii) what constitutes the value of the threshold, and (iii) how benefits above and below the threshold must be allocated. I highlight three contributions that this particular account of thresholds makes: it clarifies the nature of the shift that occurs at the threshold; it resolves a common misunderstanding about headcount principles; and it shows how the arbitrariness objection can be met.
Nachweis von Nierensteinen
Authors: Tuma Jan
Published: May 2021

Zusammenfassung. Nephrolithiasis manifestiert sich als erstes oft in Form einer Nierenkolik. Diese wird meist durch Uretersteine, aber auch durch Blutkoagel, abgegangene Papillennekrosen, tumorbedingte Ureterstenosen oder eine urogenitale Tbc verursacht. Der Nachweis von Nierensteinen erfolgt heute in erster Linie sonografisch. Obwohl auch die CT-Untersuchung ohne Kontrastmittel eine hohe Sensitivität besitzt, wird diese wegen der Strahlenbelastung erst bei unklarem Befund empfohlen. Neben sorgfältiger Anamnese ist auch die ergänzende Diagnostik mit Urinuntersuchung (Hämaturie und Kristallurie, evtl. 24-h-Urinsammlung) sowie serologischen Bestimmungen (Kreatinin, Natrium, Kalium, Kalzium, Harnsäure, anorg. Phosphor) wichtig.
Digitale Plattform für den Dialog
Authors: Gurtner Caroline , Wisler Marcel , Sanchez Tomas , Hahn Sabine
Published: May 2021

Was ist zu diesem Thema bereits bekannt?

Digitale Angebote bieten flexible Möglichkeiten für Austausch und soziale Teilhabe.

Wie wird eine neue Perspektive eingebracht?

Benutzerzentriertes Design ermöglicht positive Erfahrungen und entscheidet über den Erfolg eines digitalen Angebots.

Was sind die Auswirkungen für die Praxis?

Interaktive Austauschformate können im Idealfall zu einer besseren Verständigung zwischen verschiedenen Nutzendengruppen beitragen.
E-Learning in der Psychiatrie
Authors: Golz Christoph , Richter Dirk , Lüthi Nick , Rapphold Benjamin D.
Published: May 2021

Was ist zu diesem Thema bereits bekannt?

Psychiatrien werden zunehmend digitalisiert. Die COVID-19-Pandemie hat diesen Prozess noch beschleunigt und gleichzeitig Weiterbildungsmöglichkeiten für das Gesundheitspersonal stark beschränkt.

Wie wird eine neue Perspektive eingebracht?

Ein E-Learning-Angebot bietet eine Lösung für die interne Weiterbildung und fördert Erlernen von nötigen digitalen Kompetenzen mit Hilfe von Augmented und Virtual Reality.

Was sind die Auswirkungen für die Praxis?

Entscheidungsträger müssen das Gesundheitspersonal in die Digitalisierung wertschätzend einbeziehen und eine Grundlage bieten, die für das Gesundheitspersonal positive Erfahrungen mit neuen Technologien ermöglicht.
Jobrotation im Krankenhaus
Authors: Knuhr Henning , Wesser Christin , Nienaber André
Published: May 2021

Was ist zu diesem Thema bekannt?

Jobrotation kann mit dem richtigen Konzept gute Erfolge erzielen, wird aber in der Praxis nur marginal umgesetzt.

Wie wird eine neue Perspektive eingebracht?

Jeder Mitarbeiter bringt durch den Stationstausch seine fachliche und soziale Expertise in den anderen Bereich ein und entwickelt sich weiter.

Was sind die Auswirkungen für die Praxis?

Bessere Ausfallkompensation, Akzeptanz und Wertschätzung untereinander sowie ein verbessertes Betriebsklima.
Herausforderung Akutpsychiatrie
Authors: Petersen Hans-Peter , Nienaber André
Published: May 2021

Was ist zu diesem Thema bekannt?

Es gibt wenig Beschreibungen über die Behandlungsmöglichkeiten von geistig behinderten Menschen in der Akutpsychiatrie.

Wie wird eine neue Perspektive eingebracht?

Im Mittelpunkt steht der Umgang mit den Herausforderungen, die einerseits die angemessene Begleitung geistig behinderter Menschen im akutpsychiatrischen Setting und andererseits das Erwirken einer Anschlussperspektive mit sich bringen.

Was sind die Auswirkungen für die Praxis?

Die Begleitung von geistig behinderten Menschen erfordert im Besonderen eine fürsorgliche Haltung und das zeitnahe Einbeziehen aller im Fallmanagement beteiligten Verantwortlichen.
Peter M. Shearer Receives 2020 Inge Lehmann Medal
Authors:   AGU
Published: May 2021

Peter M. Shearer was awarded the 2020 Inge Lehmann Medal at the virtual AGU Fall Meeting in December. The medal is for “contributions to the understanding of the structure, composition, and dynamics of the Earth’s mantle and core.”
Martian Meteorites Shed Light on Solar System’s Early Dynamics
Authors: Johnson-Groh Mara
Published: May 2021

Chemical compositions of rocks from Mars indicate that the earliest orbits of Jupiter and Saturn were more circular than they are today.
Sex differences in postnatal weight gain trajectories of extremely preterm newborns
Authors: Chou Fu-Sheng , Yeh Hung-Wen
Published: May 2021

Objective

Both postnatal growth and sex play a crucial role in long-term outcomes of extremely preterm newborns (EPNs), but the relationship between sex and postnatal growth is not clear. This study aims to assess sex differences in weight trajectories.

Study design

Weight data in the first 200 days of life from 4327 EPNs were used for generalized additive mixed modeling. We considered gestational age and sex as fixed-effects, and included random intercepts and random slopes for postnatal age. We assessed interactions between fixed-effects and postnatal age.

Results

Male EPNs had higher predicted weight trajectories than females. Weight z-score trajectories decreased in both sexes before term-equivalent age comparably, but females showed faster increases afterward. Although weight gain velocity was comparable between both sexes, weight gain velocity in male EPNs was lower compared to the corresponding reference values from the 2013 Fenton growth charts, which explained slower z-score rises.

Conclusion

Sex disparity exists in postnatal weight gain trajectories of EPNs after reaching the term-equivalent age.
Anomalous weak values via a single photon detection
Authors: Rebufello Enrico , Piacentini Fabrizio , Avella Alessio , Souza Muriel A. de , Gramegna Marco , Dziewior Jan , Cohen Eliahu , Vaidman Lev , Degiovanni Ivo Pietro , Genovese Marco
Published: May 2021

Is it possible that a measurement of a spin component of a spin-1/2 particle yields the value 100? In 1988 Aharonov, Albert and Vaidman argued that upon pre- and postselection of particular spin states, weakening the coupling of a standard measurement procedure ensures this paradoxical result1. This theoretical prediction, called weak value, was realised in numerous experiments2–9, but its meaning remains very controversial10–19, since its “anomalous” nature, i.e., the possibility to exceed the eigenvalue spectrum, as well as its “quantumness” are debated20–22. We address these questions by presenting the first experiment measuring anomalous weak values with just a single click, without the need for statistical averaging. The measurement uncertainty is significantly smaller than the gap between the measured weak value and the nearest eigenvalue. Beyond clarifying the meaning of weak values, demonstrating their non-statistical, single-particle nature, this result represents a breakthrough in understanding the foundations of quantum measurement, showing unprecedented measurement capability for further applications of weak values to quantum photonics.
Multifunctional metasurfaces enabled by simultaneous and independent control of phase and amplitude for orthogonal polarization states
Authors: Liu Mingze , Zhu Wenqi , Huo Pengcheng , Feng Lei , Song Maowen , Zhang Cheng , Chen Lu , Lezec Henri J. , Lu Yanqing , Agrawal Amit , Xu Ting
Published: May 2021

Monochromatic light can be characterized by its three fundamental properties: amplitude, phase, and polarization. In this work, we propose a versatile, transmission-mode all-dielectric metasurface platform that can independently manipulate the phase and amplitude for two orthogonal states of polarization in the visible frequency range. For proof-of-concept experimental demonstration, various single-layer metasurfaces composed of subwavelength-spaced titanium-dioxide nanopillars are designed, fabricated, and characterized to exhibit the ability of polarization-switchable multidimensional light-field manipulation, including polarization-switchable grayscale nanoprinting, nonuniform cylindrical lensing, and complex-amplitude holography. We envision the metasurface platform demonstrated here to open new possibilities toward creating compact multifunctional optical devices for applications in polarization optics, information encoding, optical data storage, and security.
Chronic oxytocin-driven alternative splicing of Crfr2α induces anxiety
Authors: Winter Julia , Meyer Magdalena , Berger Ilona , Royer Melanie , Bianchi Marta , Kuffner Kerstin , Peters Sebastian , Stang Simone , Langgartner Dominik , Hartmann Finn , Schmidtner Anna K. , Reber Stefan O. , Bosch Oliver J. , Bludau Anna , Slattery David A. , van den Burg Erwin H. , Jurek Benjamin , Neumann Inga D.
Published: May 2021

The neuropeptide oxytocin (OXT) has generated considerable interest as potential treatment for psychiatric disorders, including anxiety and autism spectrum disorders. However, the behavioral and molecular consequences associated with chronic OXT treatment and chronic receptor (OXTR) activation have scarcely been studied, despite the potential therapeutic long-term use of intranasal OXT. Here, we reveal that chronic OXT treatment over two weeks increased anxiety-like behavior in rats, with higher sensitivity in females, contrasting the well-known anxiolytic effect of acute OXT. The increase in anxiety was transient and waned 5 days after the infusion has ended. The behavioral effects of chronic OXT were paralleled by activation of an intracellular signaling pathway, which ultimately led to alternative splicing of hypothalamic corticotropin-releasing factor receptor 2α (Crfr2α), an important modulator of anxiety. In detail, chronic OXT shifted the splicing ratio from the anxiolytic membrane-bound (mCRFR2α) form of CRFR2α towards the soluble CRFR2α (sCRFR2α) form. Experimental induction of alternative splicing mimicked the anxiogenic effects of chronic OXT, while sCRFR2α-knock down reduced anxiety-related behavior of male rats. Furthermore, chronic OXT treatment triggered the release of sCRFR2α into the cerebrospinal fluid with sCRFR2α levels positively correlating with anxiety-like behavior. In summary, we revealed that the shifted splicing ratio towards expression of the anxiogenic sCRFR2α underlies the adverse effects of chronic OXT treatment on anxiety.
Altered estradiol-dependent cellular Ca2+ homeostasis and endoplasmic reticulum stress response in Premenstrual Dysphoric Disorder
Authors: Li Howard J. , Goff Allison , Rudzinskas Sarah A. , Jung Yonwoo , Dubey Neelima , Hoffman Jessica , Hipolito Dion , Mazzu Maria , Rubinow David R. , Schmidt Peter J. , Goldman David
Published: May 2021

Premenstrual Dysphoric Disorder (PMDD) is characterized by debilitating mood symptoms in the luteal phase of the menstrual cycle. Prior studies of affected women have implicated a differential response to ovarian steroids. However, the molecular basis of these patients’ differential response to hormone remains poorly understood. We performed transcriptomic analyses of lymphoblastoid cell lines (LCLs) derived from women with PMDD and asymptomatic controls cultured under untreated (steroid-free), estradiol-treated (E2), and progesterone-treated (P4) conditions. Weighted gene correlation network analysis (WGCNA) of transcriptomes identified four gene modules with significant diagnosis x hormone interactions, including one enriched for neuronal functions. Next, in a gene-level analysis comparing transcriptional response to hormone across diagnoses, a generalized linear model identified 1522 genes differentially responsive to E2 (E2-DRGs). Among the top 10 E2-DRGs was a physically interacting network (NUCB1, DST, GCC2, GOLGB1) involved in endoplasmic reticulum (ER)-Golgi function. qRT-PCR validation reproduced a diagnosis x E2 interaction (F(1,24)=7.01, p = 0.014) for NUCB1, a regulator of cellular Ca2+ and ER stress. Finally, we used a thapsigargin (Tg) challenge assay to test whether E2 induces differences in Ca2+ homeostasis and ER stress response in PMDD. PMDD LCLs had a 1.36-fold decrease in Tg-induced XBP1 splicing response compared to controls, and a 1.62-fold decreased response (p = 0.005), with a diagnosis x treatment interaction (F(3,33)=3.51, p = 0.026) in the E2-exposed condition. Altered hormone-dependent in cellular Ca2+ dynamics and ER stress may contribute to the pathophysiology of PMDD.
RAB39B-mediated trafficking of the GluA2-AMPAR subunit controls dendritic spine maturation and intellectual disability-related behaviour
Authors: Mignogna Maria Lidia , Musardo Stefano , Ranieri Giulia , Gelmini Susanna , Espinosa Pedro , Marra Paolo , Belloli Sara , Murtaj Valentina , Moresco Rosa Maria , Bellone Camilla , D’Adamo Patrizia
Published: May 2021

Mutations in the RAB39B gene cause X-linked intellectual disability (XLID), comorbid with autism spectrum disorders or early Parkinson’s disease. One of the functions of the neuronal small GTPase RAB39B is to drive GluA2/GluA3 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) maturation and trafficking, determining AMPAR subunit composition at glutamatergic postsynaptic neuronal terminals. Taking advantage of the Rab39b knockout murine model, we show that a lack of RAB39B affects neuronal dendritic spine refinement, prompting a more Ca2+-permeable and excitable synaptic network, which correlates with an immature spine arrangement and behavioural and cognitive alterations in adult mice. The persistence of immature circuits is triggered by increased hypermobility of the spine, which is restored by the Ca2+-permeable AMPAR antagonist NASPM. Together, these data confirm that RAB39B controls AMPAR trafficking, which in turn plays a pivotal role in neuronal dendritic spine remodelling and that targeting Ca2+-permeable AMPARs may highlight future pharmaceutical interventions for RAB39B-associated disease conditions.
Low-dose antithymocyte globulin plus low-dose posttransplant cyclophosphamide combined with cyclosporine and mycophenolate mofetil for prevention of graft-versus-host disease after HLA-matched unrelated donor peripheral blood stem cell transplantation
Authors: Sun Xi , Yang Jun , Cai Yu , Wan Liping , Huang Chongmei , Qiu Huiying , Tong Yin , Xu Xiaowei , Zhou Kun , Ding Xueying , Song Xianmin
Published: May 2021

The standard regimens for graft-versus-host disease (GvHD) prophylaxis in matched unrelated donor (MUD) transplantation were based on antithymocyte globulin (ATG) in combination with calcineurin inhibitors (CNIs). To improve the efficiency of GvHD prophylaxis in MUD peripheral blood stem cell transplantation (MUD-PBSCT), 51 patients with hematological malignancies received a novel regimen for GvHD prophylaxis, which is composed of low dose of ATG (5 mg/kg) plus low-dose posttransplant cyclophosphamide (PTCy, 50 mg/kg) (low-dose ATG/PTCy) combined with cyclosporine A (CsA) and mycophenolate mofetil (MMF). The cumulative incidences (CIs) of grades I–IV and II–IV acute GvHD (aGvHD) were 14.5% (95% CI, 9.4–19.6%) and 6.2% (95% CI, 2.8–9.6%) within 100 days after transplantation, respectively. The CI of mild-to-moderate chronic GvHD (cGvHD) within 1 year was 11.5% (95% CI, 6.6–16.4%). The 1-year probabilities of GvHD and relapse-free survival, relapse-free survival, and over survival were 70.6% (95% CI, 64.2–77.0%), 76.5% (95% CI, 70.6–82.4%), and 82.0% (95% CI, 76.5–87.5%), respectively. The CIs of CMV and EBV reactivation by day 180 were 10.4% (95% CI, 1.5–19.4%) and 8.3% (95% CI, 0.2–16.4%), respectively. The results suggested that low-dose ATG/PTCy combined with CsA/MMF as GvHD prophylaxis in MUD-PBSCT had promising activity.
New clinical and biological insights from the international TARGIT-A randomised trial of targeted intraoperative radiotherapy during lumpectomy for breast cancer
Authors: Vaidya Jayant S. , Bulsara Max , Baum Michael , Wenz Frederik , Massarut Samuele , Pigorsch Steffi , Alvarado Michael , Douek Michael , Saunders Christobel , Flyger Henrik , Eiermann Wolfgang , Brew-Graves Chris , Williams Norman R. , Potyka Ingrid , Roberts Nicholas , Bernstein Marcelle , Brown Douglas , Sperk Elena , Laws Siobhan , Sütterlin Marc , Corica Tammy , Lundgren Steinar , Holmes Dennis , Vinante Lorenzo , Bozza Fernando , Pazos Montserrat , Blanc-Onfroy Magali Le , Gruber Günther , Polkowski Wojciech , Dedes Konstantin J. , Niewald Marcus , Blohmer Jens , McReady David , Hoefer Richard , Kelemen Pond , Petralia Gloria , Falzon Mary , Joseph David , Tobias Jeffrey S.
Published: May 2021

Background

The TARGIT-A trial reported risk-adapted targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer to be as effective as whole-breast external beam radiotherapy (EBRT). Here, we present further detailed analyses.

Methods

In total, 2298 women (≥45 years, invasive ductal carcinoma ≤3.5 cm, cN0–N1) were randomised. We investigated the impact of tumour size, grade, ER, PgR, HER2 and lymph node status on local recurrence-free survival, and of local recurrence on distant relapse and mortality. We analysed the predictive factors for recommending supplemental EBRT after TARGIT-IORT as part of the risk-adapted approach, using regression modelling. Non-breast cancer mortality was compared between TARGIT-IORT plus EBRT vs. EBRT.

Results

Local recurrence-free survival was no different between TARGIT-IORT and EBRT, in every tumour subgroup. Unlike in the EBRT arm, local recurrence in the TARGIT-IORT arm was not a predictor of a higher risk of distant relapse or death. Our new predictive tool for recommending supplemental EBRT after TARGIT-IORT is at https://targit.org.uk/addrt. Non-breast cancer mortality was significantly lower in the TARGIT-IORT arm, even when patients received supplemental EBRT, HR 0.38 (95% CI 0.17–0.88) P = 0.0091.

Conclusion

TARGIT-IORT is as effective as EBRT in all subgroups. Local recurrence after TARGIT-IORT, unlike after EBRT, has a good prognosis. TARGIT-IORT might have a beneficial abscopal effect.

Trial registration

ISRCTN34086741 (21/7/2004), NCT00983684 (24/9/2009).
The clinical relevance of ultra-widefield angiography findings in patients with central retinal vein occlusion and macular oedema receiving anti-VEGF therapy
Authors: Nicholson Luke , Vazquez-Alfageme Clara , Sen Piyali , Patrao Namritha V. , Peto Tunde , Yang Yit , Sivaprasad Sobha , Hykin Philip G.
Published: May 2021

Aims

To report, using ultra-widefield angiography (UWFA) the area, distribution, and change in retinal capillary nonperfusion (RCNP) at baseline and 100 weeks in eyes with central retinal vein occlusion (CRVO) receiving anti-VEGF for macula oedema.

Methods

Prospective longitudinal multi-centre cohort study. Adults with CRVO treated with anti-VEGF therapy for macular oedema underwent UWFA at baseline and week-100. The area, distribution, and change in total, peripheral and posterior pole RCNP were determined.

Results

Of 153 eyes at baseline, mean area of RCNP was 34.3DA and 12 (7.8%) had ≥75DA RCNP. More than 10DA RCNP was present in the temporal periphery in 75.8% of eyes vs. 10.5% in the nasal periphery. At week-100, mean RCNP was 42.1DA with a median change from baseline of 3.3DA 95% CI [0.4, 7.3]; p < 0.01. Of 146 eyes with ≤10DA of posterior pole RCNP at baseline, 16/146 (11.0%) progressed to >10DA at week-100. These eyes had a median increase in total RCNP of 69.7DA [95% CI 27.2–85.4] vs 0DA [0.0–1.4]; p < 0.001 for those who did not, and two developed neovascular glaucoma. Larger baseline area of RCNP and history of glaucoma were risk factors for posterior pole RCNP developing.

Conclusions

With UWFA, significant baseline RCNP was identified in the majority of CRVO patients, notably in the temporal periphery, but large increases over 100 weeks were uncommon. Development of >10DA posterior pole RCNP is a marker for widespread RCNP and in such cases the risk of anterior segment neovascularisation is not abolished by concomitant anti-VEGF therapy.
First principles calculations of the structural, electronic, magnetic, and thermodynamic properties of the Nd2MgGe2 and Gd2MgGe2 intermetallic compounds
Authors: Menouer S. , Abid O. Miloud , Benzair A. , Yakoubi A. , Khachai H. , Schwingenschlögl U.
Published: May 2021

In recent years the intermetallic ternary RE2MgGe2(RE = rare earth) compounds attract interest in a variety of technological areas. We therefore investigate in the present work the structural, electronic, magnetic, and thermodynamic properties of Nd2MgGe2and Gd2MgGe2. Spin–orbit coupling is found to play an essential role in realizing the antiferromagnetic ground state observed in experiments. Both materials show metallicity and application of a Debye-Slater model demonstrates low thermal conductivity and little effects of the RE atom on the thermodynamic behavior.
Voxel and surface based whole brain analysis shows reading skill associated grey matter abnormalities in dyslexia
Authors: Kujala Teija , Sihvonen Aleksi J. , Thiede Anja , Palo-oja Peter , Virtala Paula , Numminen Jussi , Laasonen Marja
Published: May 2021

Developmental dyslexia (DD) is the most prevalent neurodevelopmental disorder with a substantial negative influence on the individual’s academic achievement and career. Research on its neuroanatomical origins has continued for half a century, yielding, however, inconsistent results, lowered total brain volume being the most consistent finding. We set out to evaluate the grey matter (GM) volume and cortical abnormalities in adult dyslexic individuals, employing a combination of whole-brain voxel- and surface-based morphometry following current recommendations on analysis approaches, coupled with rigorous neuropsychological testing. Whilst controlling for age, sex, total intracranial volume, and performance IQ, we found both decreased GM volume and cortical thickness in the left insula in participants with DD. Moreover, they had decreased GM volume in left superior temporal gyrus, putamen, globus pallidus, and parahippocampal gyrus. Higher GM volumes and cortical thickness in these areas correlated with better reading and phonological skills, deficits of which are pivotal to DD. Crucially, total brain volume did not influence our results, since it did not differ between the groups. Our findings demonstrating abnormalities in brain areas in individuals with DD, which previously were associated with phonological processing, are compatible with the leading hypotheses on the neurocognitive origins of DD.
Impact of diesel and biodiesel contamination on soil microbial community activity and structure
Authors: Mitter Eduardo K. , Germida James J. , de Freitas J. Renato
Published: May 2021

Soil contamination as a result of oil spills is a serious issue due to the global demand for diesel fuel. As an alternative to diesel, biodiesel has been introduced based on its high degradability rates and potential for reducing of greenhouse gases emissions. This study assessed the impacts diesel and biodiesel contamination on soil microbial community activity and structure. Our results suggest higher microbial activity in biodiesel contaminated soils and analysis of PLFA profiles confirmed shifts in microbial community structure in response to contamination. High-throughput 16S rRNA amplicon sequencing also revealed a lower bacterial richness and diversity in contaminated soils when compared to control samples, supporting evidence of the detrimental effects of hydrocarbons on soil microbiota. Control samples comprised mostly of Actinobacteria, whereas Proteobacteria were predominantly observed in diesel and biodiesel contaminated soils. At genus level, diesel and biodiesel amendments highly selected for Rhodococcus and Pseudomonas spp., respectively. Moreover, predicted functional profiles based on hydrocarbon-degrading enzymes revealed significant differences between contaminated soils mostly due to the chemical composition of diesel and biodiesel fuel. Here, we also identified that Burkholderiaceae, Novosphingobium, Anaeromyxobacter, Pseudomonas and Rhodococcus were the main bacterial taxa contributing to these enzymes. Together, this study supports the evidence of diesel/biodiesel adverse effects in soil microbial community structure and highlights microbial taxa that could be further investigated for their biodegradation potential.
Epileptogenic zone detection in MRI negative epilepsy using adaptive thresholding of arterial spin labeling data
Authors: Gajdoš Martin , Říha Pavel , Kojan Martin , Doležalová Irena , Mutsaerts Henk J. M. M. , Petr Jan , Rektor Ivan
Published: May 2021

Drug-resistant epilepsy is a diagnostic and therapeutic challenge, mainly in patients with negative MRI findings. State-of-the-art imaging methods complement standard epilepsy protocols with new information and help epileptologists to increase the reliability of their decisions. In this study, we investigate whether arterial spin labeling (ASL) perfusion MRI can help localize the epileptogenic zone (EZ). To that end, we developed an image processing method to detect the EZ as an area with hypoperfusion relative to the contralateral unaffected side, using subject-specific thresholding of the asymmetry index in ASL images. We demonstrated three thresholding criteria (termed minimal product criterion, minimal distance criterion, and elbow criterion) on 29 patients with MRI-negative epilepsy (age 32.98 ± 10.4 years). The minimal product criterion showed optimal results in terms of positive predictive value (mean 0.12 in postoperative group and 0.22 in preoperative group) and true positive rate (mean 0.71 in postoperative group and 1.82 in preoperative group). Additionally, we found high accuracy in determining the EZ side (mean 0.86 in postoperative group and 0.73 in preoperative group out of 1.00). ASL can be easily incorporated into the standard presurgical MR protocol, and it provides an additional benefit in EZ localization.
Grain size effect on the radiation damage tolerance of cubic zirconia against simultaneous low and high energy heavy ions: Nano triumphs bulk
Authors: Kalita Parswajit , Ghosh Santanu , Gutierrez Gaëlle , Rajput Parasmani , Grover Vinita , Sattonnay Gaël , Avasthi Devesh K.
Published: May 2021

Irradiation induced damage in materials is highly detrimental and is a critical issue in several vital science and technology fields, e.g., the nuclear and space industries. While the effect of dimensionality (nano/bulk) of materials on its radiation damage tolerance has been receiving tremendous interest, studies have only concentrated on low energy (nuclear energy loss (Sn) dominant) and high energy (electronic energy loss (Se) dominant) irradiations independently (wherein, interestingly, the effect is opposite). In-fact, research on radiation damage in general has almost entirely focused only on independent irradiations with low and/or high energy particles till date, and investigations under simultaneous impingement of energetic particles (which also correspond to the actual irradiation conditions during real-world applications) are very scarce. The present work elucidates, taking cubic zirconia as a model system, the effect of grain size (26 nm vs 80 nm) on the radiation tolerance against simultaneous irradiation with low energy (900 keV I) and high energy (27 meV Fe) particles/ions; and, in particular, introduces the enhancement in the radiation damage tolerance upon downsizing from bulk to nano dimension. This result is interpreted within the framework of the thermal-spike model after considering (1) the fact that there is essentially no spatial and time overlap between the damage events of the two ‘simultaneous’ irradiations, and (2) the influence of grain size on radiation damage against individual Sn and Se. The present work besides providing the first fundamental insights into how the grain size/grain boundary density inherently mediates the radiation response of a material to simultaneous Sn and Se deposition, also (1) paves the way for potential application of nano-crystalline materials in the nuclear industry (where simultaneous irradiations with low and high energy particles correspond to the actual irradiation conditions), and (2) lays the groundwork for understanding the material behaviour under other simultaneous (viz. Sn and Sn, Se and Se) irradiations.
Integrated RNA and miRNA sequencing analysis reveals a complex regulatory network of Magnolia sieboldii seed germination
Authors: Mei Mei , Wei Jun , Ai Wanfeng , Zhang Lijie , Lu Xiu-jun
Published: May 2021

Magnolia sieboldii K. Koch (M. sieboldii) is a deciduous Chinese tree species of the Magnoliaceae family with high ornamental, medicinal, and economic benefits. The germination of M. sieboldii seeds under natural conditions is extremely difficult, thereby hindering the cultivation and breeding of this important species. The molecular mechanisms underlying M. sieboldii seed germination remain unclear due to the lack of genomic and transcriptomic resources. Here, we integrated both mRNA and miRNA sequencing to identify the genes and pathways related to M. sieboldii germination. A comprehensive full-length transcriptome containing 158,083 high-quality unigenes was obtained by single-molecule real-time (SMRT) sequencing technology. We identified a total of 13,877 genes that were differentially expressed between non-germinated and germinated seeds. These genes were mainly involved in plant hormone signal transduction and diverse metabolic pathways such as those involving lipids, sugars, and amino acids. Our results also identified a complex regulatory network between miRNAs and their target genes. Taken together, we present the first transcriptome of M. sieboldii and provide key genes and pathways associated with seed germination for further characterization. Future studies of the molecular basis of seed germination will facilitate the genetic improvement M. sieboldii.
Cionin, a vertebrate cholecystokinin/gastrin homolog, induces ovulation in the ascidian Ciona intestinalis type A
Authors: Osugi Tomohiro , Miyasaka Natsuko , Shiraishi Akira , Matsubara Shin , Satake Honoo
Published: May 2021

Cionin is a homolog of vertebrate cholecystokinin/gastrin that has been identified in the ascidian Ciona intestinalis type A. The phylogenetic position of ascidians as the closest living relatives of vertebrates suggests that cionin can provide clues to the evolution of endocrine/neuroendocrine systems throughout chordates. Here, we show the biological role of cionin in the regulation of ovulation. In situ hybridization demonstrated that the mRNA of the cionin receptor, Cior2, was expressed specifically in the inner follicular cells of pre-ovulatory follicles in the Ciona ovary. Cionin was found to significantly stimulate ovulation after 24-h incubation. Transcriptome and subsequent Real-time PCR analyses confirmed that the expression levels of receptor tyrosine kinase (RTK) signaling genes and a matrix metalloproteinase (MMP) gene were significantly elevated in the cionin-treated follicles. Of particular interest is that an RTK inhibitor and MMP inhibitor markedly suppressed the stimulatory effect of cionin on ovulation. Furthermore, inhibition of RTK signaling reduced the MMP gene expression in the cionin-treated follicles. These results provide evidence that cionin induces ovulation by stimulating MMP gene expression via the RTK signaling pathway. This is the first report on the endogenous roles of cionin and the induction of ovulation by cholecystokinin/gastrin family peptides in an organism.