bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Biodistribution and Radiation Dosimetry of the P-Glycoprotein Radiotracer [11C]Metoclopramide
Authors: Bauer Martin , Barna Sandra , Blaickner Matthias , Prosenz Konstantin , Bamminger Karsten , Pichler Verena , Tournier Nicolas , Hacker Marcus , Zeitlinger Markus , Karanikas Georgios , Langer Oliver
Published: January 2021

Purpose

To assess in healthy volunteers the whole-body distribution and dosimetry of [11C]metoclopramide, a new positron emission tomography (PET) tracer to measure P-glycoprotein activity at the blood-brain barrier.

Procedures

Ten healthy volunteers (five women, five men) were intravenously injected with 387 ± 49 MBq of [11C]metoclopramide after low dose CT scans and were then imaged by whole-body PET scans from head to upper thigh over approximately 70 min. Ten source organs (brain, thyroid gland, right lung, myocardium, liver, gall bladder, left kidney, red bone marrow, muscle and the contents of the urinary bladder) were manually delineated on whole-body images. Absorbed doses were calculated with QDOSE (ABX-CRO) using the integrated IDAC-Dose 2.1 module.

Results

The majority of the administered dose of [11C]metoclopramide was taken up into the liver followed by urinary excretion and, to a smaller extent, biliary excretion of radioactivity. The mean effective dose of [11C]metoclopramide was 1.69 ± 0.26 μSv/MBq for female subjects and 1.55 ± 0.07 μSv/MBq for male subjects. The two organs receiving the highest radiation doses were the urinary bladder (10.81 ± 0.23 μGy/MBq and 8.78 ± 0.89 μGy/MBq) and the liver (6.80 ± 0.78 μGy/MBq and 4.91 ± 0.74 μGy/MBq) for female and male subjects, respectively.

Conclusions

[11C]Metoclopramide showed predominantly renal excretion, and is safe and well tolerated in healthy adults. The effective dose of [11C]metoclopramide was comparable to other 11C-labeled PET tracers.
Exploration for the real causative agents of licorice-induced pseudoaldosteronism
Authors: Makino Toshiaki
Published: January 2021

I investigated the causative agents of licorice-induced pseudoaldosteronism, which is a frequent side effect of Japanese traditional Kampo medicines. Glycyrrhizin (GL), the main ingredient of licorice, is absorbed after being metabolized to glycyrrhetinic acid (GA) by intestinal bacteria, and then metabolized in liver to 3-monoglucuronyl-glycyrrhetinic acid (3MGA). In normal condition, 3MGA is excreted into bile via a multidrug resistance-related protein (Mrp) 2, therefore, 3MGA does not appear in blood circulation. However, under the dysfunction of Mrp2, 3MGA appears in the blood circulation and is excreted into the urine by not glomerular filtration but tubular secretion via organic anion transporter (OAT) 1 and 3. At this time, 3MGA inhibits type 2 11β-hydroxysteroid dehydrogenase (11βHSD2) in tubular cells to cause pseudoaldosteronism. Since GA is not the substrates of these transporters, GA cannot inhibit 11βHSD2 in tubular cells. Therefore, it was considered that 3MGA was the causative agents of licorice-induced pseudoaldosteronism. After that, I isolated and identified three other GL metabolites, 22α-hydroxy-18β-glycyrrhetyl-3-O-sulfate-30-glucuronide (1), 22α-hydroxy-18β-glycyrrhetyl-3-O-sulfate (2), and 18β-glycyrrhetyl-3-O-sulfate (3) from the urine of Mrp2-deficient rats orally treated with GA, and found that their blood and urinary concentrations were much higher than 3MGA and that their pharmacokinetic behaviors were similar to 3MGA. 3MGA was not detected in the blood of patients with pseudoaldosteronism who developed rhabdomyolysis due to licorice, and compound 3 was detected at a high concentration. In addition, a multicenter retrospective study was conducted using the serum and urine of 97 patients who took Kampo medicines containing licorice. Of a total of 97 patients, 67 detected GA in the serum (median 122 nM, 5 nM–1.8 µM) and 68 detected compound 3 (median 239 nM, 2 nM–4.2 µM), and there were no cases of detection of GL, 3MGA, compounds 1, and 2. High blood concentrations of compound 3 were associated with low plasma renin activity, plasma aldosterone levels, and serum potassium levels. It is highly probable that compound 3 is the true causative agent of pseudoaldosteronism.
How Does Administrative Data Compare with Census Data for the Measurement of Internal Migration? The Case of Northern Ireland, 2001–2011
Authors: Foley Brian , Champion Tony , Shuttleworth Ian
Published: January 2021

The paper compares and contrasts internal migration measured by healthcard-based administrative data with census figures. This is useful because the collection of population data, its processing, and its dissemination by statistical agencies is becoming more reliant on administrative data. Statistical agencies already use healthcard data to make migration estimates and are increasingly confident about local population estimates from administrative sources. This analysis goes further than this work as it assesses how far healthcard data can produce reliable data products of the kind to which academics are accustomed. It does this by examining migration events versus transitions over a full intercensal period; population flows into and out of small areas; and the extent to which it produces microdata on migration equivalent to that in the census. It is shown that for most demographic groups and places healthcard data is an adequate substitute for census-based migration counts, the exceptions being for student households and younger people. However, census-like information is still needed to provide covariates for analysis and this will still be required whatever the future of the traditional census.
Recent Progress in Microfiber-Optic Sensors
Authors: Luo Wei , Chen Ye , Xu Fei
Published: January 2021

Recently, microfiber-optic sensors with high sensitivity, fast response times, and a compact size have become an area of interest that integrates fiber optics and nanotechnology. Distinct advantages of optical microfiber, such as large accessible evanescent fields and convenient configurability, provide attractive benefits for micro- and nano-scale optical sensing. Here, we review the basic principles of microfiber-optic sensors based on a broad range of microstructures, nanostructures, and functional materials. We also introduce the recent progress and state-of-the-art in this field and discuss the limitations and opportunities for future development.
Präferenzen von Menschen mit Pflegebedarf
Authors: Rommerskirch-Manietta Mike , Roes Martina , Stacke Tobias-Ingo , Manietta Christina , Bergmann Johannes-Michael , Purwins Daniel
Published: January 2021

Hintergrund

Die Beachtung von Präferenzen des alltäglichen Lebens wird in der pflegerischen Versorgung mit einer Vielzahl von positiven Versorgungsergebnissen assoziiert. Derzeit ist unbekannt, ob in bundesdeutschen Pflegeeinrichtungen Präferenzen von Menschen mit Pflegebedarf systematisch erhoben werden, und inwiefern diese in der Pflegedokumentation auffindbar sind.

Ziel

Das Ziel der Studie bestand darin zu untersuchen, welche und wie viele Präferenzen von Menschen mit Pflegebedarf in der Pflegedokumentation in verschiedenen pflegerischen Settings dokumentiert werden.

Methode

Eine explorative Analyse von Pflegedokumentationen (n = 24) wurde in 4 Settings der pflegerischen Versorgung durchgeführt. Die erhobenen Daten wurden inhaltsanalytisch induktiv sowie quantitativ ausgewertet.

Ergebnis

Es konnten 20 verschiedene Präferenzen identifiziert werden, die sich 5 Oberkategorien zuordnen ließen. Die Analyse zeigte in allen einbezogenen Settings, dass am häufigsten Präferenzen zu den Themen Pflege und Alltag in der Pflegedokumentation dokumentiert waren.

Schlussfolgerung

Die Verschriftlichung von Präferenzen in der Pflegedokumentation ist in allen Settings unsystematisch, zugleich wird die Beachtung von Präferenzen des alltäglichen Lebens als relevant für die Pflege erachtet. Hier bietet die Verwendung eines Instruments zur systematischen Erfassung von Präferenzen die Möglichkeiten, einerseits die Sensibilisierung für dieses Thema zu stärken und andererseits die Zufriedenheit der Menschen mit Pflegebedarf zu steigern.
Appendicitis: Clinical implications in negative appendectomy
Authors: Pooria Ali , Pourya Afsoun , Gheini Alireza
Published: January 2021

ABSTRACT

Objective:

Appendectomy is one of the most common surgical emergencies for appendicitis. Despite the improvement in diagnosis, increased incidence of negative appendectomy is widely reported. The aim of this study to investigate the incidence of negative appendectomy.

Method:

In this observational study, records 538 patients who underwent appendectomy were evaluated. Demographic data and pathological findings of the appendix were noted, and statistical analysis was conducted on the data obtained.

Result:

Among 200 female and 338 male patients, there were 28% and 18.3% negative appendectomies, respectively. Second half of the year was associated with greater frequency of negative appendectomy, 25.7%. According to the age groups, the highest incidence of the negative appendectomy was reported in patients aged 10–19 years and 50–59 years, respectively. Ovarian cyst had the greatest incidence among negative appendectomy cases.

Conclusions:

Our findings indicate that the incidence of negative appendectomy is more common in female gender and reproductive disorders can be the common cause of this. Furthermore, young people are exposed to the increased incidence of negative appendectomy. Diagnostic methods to distinguish gynecological and abdominal dysfunction with acute appendicitis can reduce the incidence of negative appendectomy.

Highlights
Humane Professions
Authors: Boddice Rob
Published: January 2021

In this compelling history of the co-ordinated, transnational defence of medical experimentation in the nineteenth and early twentieth centuries, Rob Boddice explores the experience of vivisection as humanitarian practice. He captures the rise of the professional and specialist medical scientist, whose métier was animal experimentation, and whose guiding principle was 'humanity' or the reduction of the aggregate of suffering in the world. He also highlights the rhetorical rehearsal of scientific practices as humane and humanitarian, and connects these often defensive professions to meaningful changes in the experience of doing science. Humane Professions examines the strategies employed by the medical establishment to try to cement an idea in the public consciousness: that the blood spilt in medical laboratories served a far-reaching human good.
A History of Palestinian Islamic Jihad
Authors: Skare Erik
Published: January 2021

Palestinian Islamic Jihad (PIJ) is one of the most important yet least understood Palestinian armed factions, both in terms of its history and ideology. Labelled a terrorist organization by the US and the EU, it has grown to become the second largest armed movement in the Gaza Strip and the third largest in the Occupied Palestinian Territories. Using a wealth of primary sources, this book traces the history of PIJ from its origins in the early 1980s to today. By looking at how the group was established, how it has developed in theory and practice, and how it understands religion and politics, Skare seeks to answer the key question of why the PIJ still exist despite the presence of its more powerful sister movement Hamas. In doing so, he fills an important empirical gap in the literature on Palestinian Islamism.
How the Biden Administration Can Reinvigorate Global Health Security, Institutions, and Governance
Authors: Gostin Lawrence O. , Friedman Eric A. , Wetter Sarah
Published: January 2021

Joseph R. Biden was elected President of the United States during a period of compound crises for global health and security: the worst pandemic in a century, as well as steep reverses in progress toward reducing poverty, hunger, and disease. The United States has been in full retreat from global health leadership, fraying relationships with allies, weakening global institutions, and engaging in nationalist populism that threatens global cooperation to address worldwide challenges. Yet these tragic circumstances are also fertile soil for deep structural reforms. President Biden can both bolster the immediate responses to COVID-19 and its vast ramifications, and spearhead lasting changes to create a healthier and safer world, from which the United States would richly benefit. His immediate task will be to bring U.S. economic and scientific strength to the COVID-19 response in partnership with the World Health Organization (WHO). The Biden administration should also assume financial and strategic leadership in bolstering world efforts to achieve the Sustainable Development Goals (SDGs), including its singular pledge to leave no one behind. Finally, President Biden should empower the WHO and lead on reforms to the global health architecture to advance the right to health.
Climate Change: Reversing the Past and Advancing the Future
Authors: Bodansky Daniel
Published: January 2021

After four years of not simply inaction but significant retrogression in U.S. climate change policy, the Biden administration has its work cut out. As a start, it needs to undo what Trump did. The Biden administration took a step in that direction on Day 1 by rejoining the Paris Agreement. But simply restoring the pre-Trump status quo ante is not enough. The United States also needs to push for more ambitious global action. In part, this will require strengthening parties’ nationally determined contributions (NDCs) under the Paris Agreement; but it will also require actions by what Sue Biniaz, the former State Department climate change lawyer, likes to call the Greater Metropolitan Paris Agreement—that is, the array of other international actors that help advance the Paris Agreement's goals, including global institutions such as the International Maritime Organization (IMO), the Montreal Protocol, and the World Bank, as well as regional organizations and non-state actors. Although the Biden administration can pursue some of these international initiatives directly through executive action, new regulatory initiatives will face an uncertain fate in the Supreme Court. So how much the Biden Administration is able to achieve will likely depend significantly on how much a nearly evenly-divided Congress is willing to support.
Complicated grief knowledge and practice: a qualitative study of general practitioners in Ireland
Authors: Muhammed Abiola , Dodd Anne , Guerin Suzanne , Delaney Susan , Dodd Philip
Published: January 2021

Objective:

Complicated grief is a debilitating condition that individuals may experience after losing a loved one. General practitioners (GPs) are well positioned to provide patients with support for grief-related issues. Traditionally, Irish GPs play an important role in providing patients with emotional support regarding bereavement. However, GPs have commonly reported not being aptly trained to respond to bereavement-related issues. This study explores GPs’ current knowledge of and practice regarding complicated grief.

Methods:

A qualitative study adopting a phenomenological approach to explore the experiences of GPs on this issue. Semi-structured interviews were carried out with a purposive sample of nine GPs (five men and four women) in Ireland. Potential participants were contacted via email and phone. Interviews were audio-recorded, transcribed and analysed using Braun & Clarke’s (2006) model of thematic analysis.

Results:

GPs had limited awareness of the concept of complicated grief and were unfamiliar with relevant research. They also reported that their training was either non-existent or outdated. GPs formed their own knowledge of grief-related issues based on their intuition and experiences. For these reasons, there was not one agreed method of how to respond to grief-related issues reported by patients, though participants recognised the need for intervention, onward referral and review.

Conclusions:

The research highlighted that GPs felt they required training in complicated grief so that they would be better able to identify and respond to complicated grief.
The δ13C, δ18O and Δ47records in biogenic, pedogenic and geogenic carbonate types from paleosol-loess sequence and their paleoenvironmental meaning
Authors: Zamanian Kazem , Lechler Alex R. , Schauer Andrew J. , Kuzyakov Yakov , Huntington Katharine W.
Published: January 2021

Paleoenvironmental reconstructions are commonly based on isotopic signatures of a variety of carbonate types, including rhizoliths and land-snail shells, present in paleosol-loess sequences. However, various carbonate types are formed through distinct biotic and abiotic processes over various periods, and therefore may record diverging environmental information in the same sedimentological layer. Here, we investigate the effects of carbonate type on δ13C, δ18O, and clumped isotope-derived paleotemperature [T(Δ47)] from the Quaternary Nussloch paleosol-loess sequence (Rhine Valley, SW Germany). δ13C, δ18O, and T(Δ47) values of co-occurring rhizoliths (-8.2‰ to -5.8‰, -6.1‰ to -5.9‰, 12–32°C, respectively), loess dolls (-7.0‰, -5.6‰, 23°C), land-snail shells (-8.1‰ to -3.2‰, -4.0‰ to -2.2‰, 12–38°C), earthworm biospheroliths (-11‰, -4.7‰, 8°C), and “bulk” carbonates (-1.9‰ to -0.5‰, -5.6‰ to -5.3‰, 78–120°C) from three sediment layers depend systematically on the carbonate type, admixture from geogenic carbonate, and the duration of formation periods. Based on these findings, we provide a comprehensive summary for the application of the three isotopic proxies of δ13C, δ18O, and Δ47in biogenic and pedogenic carbonates present in the same sediment layer to reconstruct paleoenvironments (e.g., local vegetation, evaporative conditions, and temperature). We conclude that bulk carbonates in Nussloch loess should be excluded from paleoenvironmental reconstructions. Instead, pedogenic and biogenic carbonates should be used to provide context for interpreting the isotopic signature for detailed site- and time-specific paleoenvironmental information.
The prevalence of tinnitus in China: a systematic review of the literature
Authors: Zhang D , Xu Q , Caimino C , Baguley D M
Published: January 2021

Objective

The aim of the present study was to identify reports of the prevalence of tinnitus in China and to present these findings in a review format.

Method

This study assessed and collated published prevalence estimates of tinnitus and tinnitus severity, creating a narrative synthesis of the data from publications identified from a combination of Chinese and English language databases.

Results

A total of 23 studies were included. Tinnitus prevalence ranged from 4.3 per cent to 51.33 per cent but varied with age and gender. The highest increase in prevalence from previous decade in age occurs during the fifth and sixth decades, and the highest prevalence was in the seventh decade at 32.47 per cent. There is also evidence that tinnitus prevalence is related to certain risk factors including comorbid disorders.

Conclusion

The prevalence of tinnitus in mainland China in this study is consistent with global data. With increasing awareness of the prevalence of tinnitus in China, the development of epidemiological standards is a priority.
Know your enemy – transcriptome of myxozoanTetracapsuloides bryosalmonaereveals potential drug targets against proliferative kidney disease in salmonids
Authors: Ahmad Freed , Debes Paul V. , Pukk Lilian , Kahar Siim , Hartikainen Hanna , Gross Riho , Vasemägi Anti
Published: January 2021

The myxozoanTetracapsuloides bryosalmonaeis a widely spread endoparasite that causes proliferative kidney disease (PKD) in salmonid fish. We developed anin silicopipeline to separate transcripts ofT. bryosalmonaefrom the kidney tissue of its natural vertebrate host, brown trout (Salmo trutta). After stringent filtering, we constructed a partial transcriptome assemblyT. bryosalmonae, comprising 3427 transcripts. Based on homology-restricted searches of the assembled parasite transcriptome and Atlantic salmon (Salmo salar) proteome, we identified four protein targets (Endoglycoceramidase, Legumain-like protease, Carbonic anhydrase 2, Pancreatic lipase-related protein 2) for the development of anti-parasitic drugs againstT. bryosalmonae. Earlier work of these proteins on parasitic protists and helminths suggests that the identified anti-parasitic drug targets represent promising chemotherapeutic candidates also againstT. bryosalmonae, and strengthen the view that the known inhibitors can be effective in evolutionarily distant organisms. In addition, we identified differentially expressedT. bryosalmonaegenes between moderately and severely infected fish, indicating an increased abundance ofT. bryosalmonaesporogonic stages in fish with low parasite load. In conclusion, this study paves the way for future genomic research inT. bryosalmonaeand represents an important step towards the development of effective drugs against PKD.
Collective foresight and intelligence for sustainability
Authors: Wood Sylvia L. R. , Luers Amy , Garard Jennifer , Gambhir Ajay , Chaudhari Kalpana , Ivanova Maria , Cronin Casey
Published: January 2021

Non-technical summary

Charting robust pathways towards more sustainable futures that ‘leave no one behind’ requires that diverse communities engage in collective foresight and intelligence exercises to better understand global systemic challenges, anticipate the emerging risks and opportunities that disruptions present, and share perspectives on how to respond and inform decision-making. We report on the recent use of an international rapid foresight survey to assess expected societal trends over the next 3 years following the COVID-19 crisis. The results illustrate the power of collective foresight approaches to provide timely, nuanced insights for decision-making across sectors and scales, particularly in times of uncertainty.

Technical summary

We present the findings of a rapid foresight survey launched in spring 2020 to draw on the collective intelligence of the global community on where the world is headed post-COVID-19. Respondents were asked to (i) assess five key societal trends in the coming 3 years, (ii) provide news headlines they both expect and hope to see, and (iii) assess the role of digital technologies during crises. Analysis of over 2000 responses from more than 90 countries revealed important regional differences in expected societal trends related to sustainability. More respondents in the Global South expected shifts towards less inequality while more respondents in the Global North expected shifts towards a smaller ecological footprint. Qualitative analysis of proposed news headlines revealed four broad themes of focus (environment, equity, health, and economy), and yielded insights into perspectives on critical drivers of change. Finally, the survey report found that the vast majority of respondents were not opposed to digital surveillance in crises. In presenting these results, we explore the value of collective foresight and intelligence exercises in providing pluralistic inputs to decision-making and in complementing more prevalent methods of forecasting.

Social media summary

Collective foresight exercises with diverse communities can help chart robust pathways to more sustainable futures.
Graduate Student Perspectives on Equitable Remote Learning
Authors: Bhatt EeShan , Blevins Morgan , Freeman Danielle , Taenzer Lina
Published: January 2021

Remote learning can be a catalyst for instructors and institutions to invest in teaching practices that reinforce growth mindsets and that help students share responsibility for learning outcomes.
Investigating rare pathogenic/likely pathogenic exonic variation in bipolar disorder
Authors: Jia Xiaoming , Goes Fernando S. , Locke Adam E. , Palmer Duncan , Wang Weiqing , Cohen-Woods Sarah , Genovese Giulio , Jackson Anne U. , Jiang Chen , Kvale Mark , Mullins Niamh , Nguyen Hoang , Pirooznia Mehdi , Rivera Margarita , Ruderfer Douglas M. , Shen Ling , Thai Khanh , Zawistowski Matthew , Zhuang Yongwen , Abecasis Gonçalo , Akil Huda , Bergen Sarah , Burmeister Margit , Chapman Sinéad , DelaBastide Melissa , Juréus Anders , Kang Hyun Min , Kwok Pui-Yan , Li Jun Z. , Levy Shawn E. , Monson Eric T. , Moran Jennifer , Sobell Janet , Watson Stanley , Willour Virginia , Zöllner Sebastian , Adolfsson Rolf , Blackwood Douglas , Boehnke Michael , Breen Gerome , Corvin Aiden , Craddock Nick , DiFlorio Arianna , Hultman Christina M. , Landen Mikael , Lewis Cathryn , McCarroll Steven A. , Richard McCombie W. , McGuffin Peter , McIntosh Andrew , McQuillin Andrew , Morris Derek , Myers Richard M. , O’Donovan Michael , Ophoff Roel , Boks Marco , Kahn Rene , Ouwehand Willem , Owen Michael , Pato Carlos , Pato Michele , Posthuma Danielle , Potash James B. , Reif Andreas , Sklar Pamela , Smoller Jordan , Sullivan Patrick F. , Vincent John , Walters James , Neale Benjamin , Purcell Shaun , Risch Neil , Schaefer Catherine , Stahl Eli A. , Zandi Peter P. , Scott Laura J.
Published: January 2021

Bipolar disorder (BD) is a serious mental illness with substantial common variant heritability. However, the role of rare coding variation in BD is not well established. We examined the protein-coding (exonic) sequences of 3,987 unrelated individuals with BD and 5,322 controls of predominantly European ancestry across four cohorts from the Bipolar Sequencing Consortium (BSC). We assessed the burden of rare, protein-altering, single nucleotide variants classified as pathogenic or likely pathogenic (P-LP) both exome-wide and within several groups of genes with phenotypic or biologic plausibility in BD. While we observed an increased burden of rare coding P-LP variants within 165 genes identified as BD GWAS regions in 3,987 BD cases (meta-analysis OR = 1.9, 95% CI = 1.3–2.8, one-sided p = 6.0 × 10−4), this enrichment did not replicate in an additional 9,929 BD cases and 14,018 controls (OR = 0.9, one-side p = 0.70). Although BD shares common variant heritability with schizophrenia, in the BSC sample we did not observe a significant enrichment of P-LP variants in SCZ GWAS genes, in two classes of neuronal synaptic genes (RBFOX2 and FMRP) associated with SCZ or in loss-of-function intolerant genes. In this study, the largest analysis of exonic variation in BD, individuals with BD do not carry a replicable enrichment of rare P-LP variants across the exome or in any of several groups of genes with biologic plausibility. Moreover, despite a strong shared susceptibility between BD and SCZ through common genetic variation, we do not observe an association between BD risk and rare P-LP coding variants in genes known to modulate risk for SCZ.
Molecular pathology associated with altered synaptic transcriptome in the dorsolateral prefrontal cortex of depressed subjects
Authors: Yoshino Yuta , Roy Bhaskar , Kumar Nilesh , Shahid Mukhtar M. , Dwivedi Yogesh
Published: January 2021

Disrupted synaptic plasticity is the hallmark of major depressive disorder (MDD), with accompanying changes at the molecular and cellular levels. Often, the maladaptive molecular changes at the synapse are the result of global transcriptional reprogramming dictated by activity-dependent synaptic modulation. Thus far, no study has directly studied the transcriptome-wide expression changes locally at the synapse in MDD brain. Here, we have examined altered synaptic transcriptomics and their functional relevance in MDD with a focus on the dorsolateral prefrontal cortex (dlPFC). RNA was isolated from total fraction and purified synaptosomes of dlPFC from well-matched 15 non-psychiatric controls and 15 MDD subjects. Transcriptomic changes in synaptic and total fractions were detected by next-generation RNA-sequencing (NGS) and analyzed independently. The ratio of synaptic/total fraction was estimated to evaluate a shift in gene expression ratio in MDD subjects. Bioinformatics and network analyses were used to determine the biological relevance of transcriptomic changes in both total and synaptic fractions based on gene–gene network, gene ontology (GO), and pathway prediction algorithms. A total of 14,005 genes were detected in total fraction. A total of 104 genes were differentially regulated (73 upregulated and 31 downregulated) in MDD group based on 1.3-fold change threshold and p < 0.05 criteria. In synaptosomes, out of 13,236 detectable genes, 234 were upregulated and 60 were downregulated (>1.3-fold, p < 0.05). Several of these altered genes were validated independently by a quantitative polymerase chain reaction (qPCR). GO revealed an association with immune system processes and cell death. Moreover, a cluster of genes belonged to the nervous system development, and psychological disorders were discovered using gene–gene network analysis. The ratio of synaptic/total fraction showed a shift in expression of 119 genes in MDD subjects, which were primarily associated with neuroinflammation, interleukin signaling, and cell death. Our results suggest not only large-scale gene expression changes in synaptosomes, but also a shift in the expression of genes from total to synaptic fractions of dlPFC of MDD subjects with their potential role in immunomodulation and cell death. Our findings provide new insights into the understanding of transcriptomic regulation at the synapse and their possible role in MDD pathogenesis.
Technology-enhanced learning: a role for video animation
Authors: Stadlinger Bernd , Jepsen Søren , Chapple Iain , Sanz Mariano , Terheyden Hendrik
Published: January 2021

The last 20 years has seen a shift in medical education from printed analogue formats of knowledge transfer to digital knowledge transfer via media platforms and virtual learning environments. Traditional university medical teaching was characterised by lectures and printed textbooks, which to a degree still have an important role to play in knowledge acquisition, but which in isolation do not engage the modern learner, who has become reliant on digital platforms and 'soundbite' learning. Recently, however, traditional methods of teaching and learning have been augmented by, and indeed sometimes replaced by, the alternative learning methods such as: problem-based learning; a greater integration of basic science and clinical considerations; smaller teaching groups; the 'flipped classroom' concept; and various technological tools which promote an interactive learning style. The aim of these new teaching methods is to overcome the well-documented limitations of traditional lectures and printed material in the transfer of knowledge from expert to student, by better engaging the minds of more visual learners and encouraging the use of diverse resources for lifelong learning. In this commentary paper, we share the concept of video animation as an additional educational tool, and one that can help to integrate molecular, cellular and clinical processes that underpin our understanding of biology and pathology in modern education. Importantly, while they can provide focused and attractive formats for 'soundbite' learning, their aim as a tool within the broader educational toolbox is to direct the interested reader towards more traditional formats of learning, which permit a deeper dive into a particular field or concept. In this manner, carefully constructed video animations can serve to provide a broad overview of a particular field or concept and to facilitate deeper learning when desired by the student.
Exposure to artificial light at night and risk of cancer: where do we go from here?
Authors: Jones Rena R.
Published: January 2021

Despite experimental and mechanistic data suggesting circadian disruption’s role in carcinogenesis, mixed findings from epidemiological investigations of artificial light at night and cancer risk in the general population are difficult to interpret due to exposure assessment limitations. It will be important for future studies to assess and validate individual-level exposures, ideally over the lifetime.
LINC01152 upregulates MAML2 expression to modulate the progression of glioblastoma multiforme via Notch signaling pathway
Authors: Wu Jianheng , Wang Nannan , Yang Ying , Jiang Guangyuan , Zhan Hui , Li Fuyong
Published: January 2021

Glioblastoma multiforme (GBM) brings serious physical and psychological pain to GBM patients, whose survival rate remains not optimistic. Long noncoding RNAs (lncRNAs) have been reported to participate in the progression of many cancers, including GBM. However, the mechanism and function of long intergenic non-protein coding RNA 1152 (LINC01152) in GBM are still unclear. In our study, we aimed to explore the function and mechanism of LINC01152 in GBM. Then qRT-PCR analysis was implemented to search the expression of RNAs in GBM tissues and cells. Functional assays such as EdU assay, colony formation assay, TUNEL assay and flow cytometry analysis were conducted to estimate GBM cell proliferation and apoptosis. RNA pull down assay, luciferase reporter assay, RIP and ChIP assays were implemented to search the binding between molecules. As a result, we discovered that LINC01152 was upregulated in GBM tissues and cells. LINC01152 and mastermind like transcriptional coactivator 2 (MAML2) could both play the oncogenic part in GBM. Moreover, LINC01152 positively regulated MAML2 in GBM by sponging miR-466 and recruiting SRSF1. In turn, RBPJ/MAML2 transcription complex was found to activate the transcription of LINC01152 in GBM cells. In conclusion, LINC01152 could upregulate the expression of MAML2 to promote tumorigenesis in GBM via Notch signaling pathway.
Tunnel field-effect transistors for sensitive terahertz detection
Authors: Gayduchenko I. , Xu S. G. , Alymov G. , Moskotin M. , Tretyakov I. , Taniguchi T. , Watanabe K. , Goltsman G. , Geim A. K. , Fedorov G. , Svintsov D. , Bandurin D. A.
Published: January 2021

The rectification of electromagnetic waves to direct currents is a crucial process for energy harvesting, beyond-5G wireless communications, ultra-fast science, and observational astronomy. As the radiation frequency is raised to the sub-terahertz (THz) domain, ac-to-dc conversion by conventional electronics becomes challenging and requires alternative rectification protocols. Here, we address this challenge by tunnel field-effect transistors made of bilayer graphene (BLG). Taking advantage of BLG’s electrically tunable band structure, we create a lateral tunnel junction and couple it to an antenna exposed to THz radiation. The incoming radiation is then down-converted by the tunnel junction nonlinearity, resulting in high responsivity (>4 kV/W) and low-noise (0.2 pW/$$\sqrt{{\rm{Hz}}}$$

Hz

) detection. We demonstrate how switching from intraband Ohmic to interband tunneling regime can raise detectors’ responsivity by few orders of magnitude, in agreement with the developed theory. Our work demonstrates a potential application of tunnel transistors for THz detection and reveals BLG as a promising platform therefor.
Stable inheritance of Sinorhizobium meliloti cell growth polarity requires an FtsN-like protein and an amidase
Authors: Krol Elizaveta , Stuckenschneider Lisa , Kästle Silva Joana M. , Graumann Peter L. , Becker Anke
Published: January 2021

In Rhizobiales bacteria, such asSinorhizobium meliloti, cell elongation takes place only at new cell poles, generated by cell division. Here, we show that the role of the FtsN-like protein RgsS inS. melilotiextends beyond cell division. RgsS contains a conserved SPOR domain known to bind amidase-processed peptidoglycan. This part of RgsS and peptidoglycan amidase AmiC are crucial for reliable selection of the new cell pole as cell elongation zone. Absence of these components increases mobility of RgsS molecules, as well as abnormal RgsS accumulation and positioning of the growth zone at the old cell pole in about one third of the cells. These cells with inverted growth polarity are able to complete the cell cycle but show partially impaired chromosome segregation. We propose that amidase-processed peptidoglycan provides a landmark for RgsS to generate cell polarity in unipolarly growing Rhizobiales.
High-resolution targeted 3C interrogation of cis-regulatory element organization at genome-wide scale
Authors: Downes Damien J. , Beagrie Robert A. , Gosden Matthew E. , Telenius Jelena , Carpenter Stephanie J. , Nussbaum Lea , De Ornellas Sara , Sergeant Martin , Eijsbouts Chris Q. , Schwessinger Ron , Kerry Jon , Roberts Nigel , Shivalingam Arun , El-Sagheer Afaf , Oudelaar A. Marieke , Brown Tom , Buckle Veronica J. , Davies James O. J. , Hughes Jim R.
Published: January 2021

Chromosome conformation capture (3C) provides an adaptable tool for studying diverse biological questions. Current 3C methods generally provide either low-resolution interaction profiles across the entire genome, or high-resolution interaction profiles at limited numbers of loci. Due to technical limitations, generation of reproducible high-resolution interaction profiles has not been achieved at genome-wide scale. Here, to overcome this barrier, we systematically test each step of 3C and report two improvements over current methods. We show that up to 30% of reporter events generated using the popular in situ 3C method arise from ligations between two individual nuclei, but this noise can be almost entirely eliminated by isolating intact nuclei after ligation. Using Nuclear-Titrated Capture-C, we generate reproducible high-resolution genome-wide 3C interaction profiles by targeting 8055 gene promoters in erythroid cells. By pairing high-resolution 3C interaction calls with nascent gene expression we interrogate the role of promoter hubs and super-enhancers in gene regulation.
Reverse dark current in organic photodetectors and the major role of traps as source of noise
Authors: Kublitski Jonas , Hofacker Andreas , Boroujeni Bahman K. , Benduhn Johannes , Nikolis Vasileios C. , Kaiser Christina , Spoltore Donato , Kleemann Hans , Fischer Axel , Ellinger Frank , Vandewal Koen , Leo Karl
Published: January 2021

Organic photodetectors have promising applications in low-cost imaging, health monitoring and near-infrared sensing. Recent research on organic photodetectors based on donor–acceptor systems has resulted in narrow-band, flexible and biocompatible devices, of which the best reach external photovoltaic quantum efficiencies approaching 100%. However, the high noise spectral density of these devices limits their specific detectivity to around 1013 Jones in the visible and several orders of magnitude lower in the near-infrared, severely reducing performance. Here, we show that the shot noise, proportional to the dark current, dominates the noise spectral density, demanding a comprehensive understanding of the dark current. We demonstrate that, in addition to the intrinsic saturation current generated via charge-transfer states, dark current contains a major contribution from trap-assisted generated charges and decreases systematically with decreasing concentration of traps. By modeling the dark current of several donor–acceptor systems, we reveal the interplay between traps and charge-transfer states as source of dark current and show that traps dominate the generation processes, thus being the main limiting factor of organic photodetectors detectivity.
Halo-fluorescein for photodynamic bacteria inactivation in extremely acidic conditions
Authors: Wang Ying , Li Jiazhuo , Zhou Zhiwei , Zhou Ronghui , Sun Qun , Wu Peng
Published: January 2021

Aciduric bacteria that can survive in extremely acidic conditions (pH < 4.0) are challenging to the current antimicrobial approaches, including antibiotics and photodynamic bacteria inactivation (PDI). Here, we communicate a photosensitizer design concept of halogenation of fluorescein for extremely acidic PDI. Upon halogenation, the well-known spirocyclization that controls the absorption of fluorescein shifts to the acidic pH range. Meanwhile, the heavy atom effect of halogens boosts the generation of singlet oxygen. Accordingly, several photosensitizers that could work at even pH < 2.0 were discovered for a broad band of aciduric bacteria families, with half maximal inhibitory concentrations (IC50) lower than 1.1 μM. Since one of the discovered photosensitizers is an FDA-approved food additive (2’,4’,5’,7’-tetraiodofluorescein, TIF), successful bacteria growth inhibition in acidic beverages was demonstrated, with greatly extended shelf life from 2 days to ~15 days. Besides, the in vivo PDI of Candidiasis with TIF under extremely acidic condition was also demonstrated.
Identifying the true number of specimens of the extinct blue antelope (Hippotragus leucophaeus)
Authors: Hempel Elisabeth , Bibi Faysal , Faith J. Tyler , Brink James S. , Kalthoff Daniela C. , Kamminga Pepijn , Paijmans Johanna L. A. , Westbury Michael V. , Hofreiter Michael , Zachos Frank E.
Published: January 2021

Native to southern Africa, the blue antelope (Hippotragus leucophaeus) is the only large African mammal species known to have become extinct in historical times. However, it was poorly documented prior to its extinction ~ 1800 AD, and many of the small number of museum specimens attributed to it are taxonomically contentious. This places limitations on our understanding of its morphology, ecology, and the mechanisms responsible for its demise. We retrieved genetic information from ten of the sixteen putative blue antelope museum specimens using both shotgun sequencing and mitochondrial genome target capture in an attempt to resolve the uncertainty surrounding the identification of these specimens. We found that only four of the ten investigated specimens, and not a single skull, represent the blue antelope. This indicates that the true number of historical museum specimens of the blue antelope is even smaller than previously thought, and therefore hardly any reference material is available for morphometric, comparative and genetic studies. Our study highlights how genetics can be used to identify rare species in natural history collections where other methods may fail or when records are scarce. Additionally, we present an improved mitochondrial reference genome for the blue antelope as well as one complete and two partial mitochondrial genomes. A first analysis of these mitochondrial genomes indicates low levels of maternal genetic diversity in the ‘museum population’, possibly confirming previous results that blue antelope population size was already low at the time of the European colonization of South Africa.
Modal coupling and crosstalk due to turbulence and divergence on free space THz links using multiple orbital angular momentum beams
Authors: Zhao Zhe , Zhang Runzhou , Song Hao , Pang Kai , Almaiman Ahmed , Zhou Huibin , Song Haoqian , Liu Cong , Hu Nanzhe , Su Xinzhou , Minoofar Amir , Sasaki Hirofumi , Lee Doohwan , Tur Moshe , Molisch Andreas F. , Willner Alan E.
Published: January 2021

Orbital-angular-momentum (OAM) multiplexing has been utilized to increase the channel capacity in both millimeter-wave and optical domains. Terahertz (THz) wireless communication is attracting increasing attention due to its broadband spectral resources. Thus, it might be valuable to explore the system performance of THz OAM links to further increase the channel capacity. In this paper, we study through simulations the fundamental system-degrading effects when using multiple OAM beams in THz communications links under atmospheric turbulence. We simulate and analyze the effects of divergence, turbulence, limited-size aperture, and misalignment on the signal power and crosstalk of THz OAM links. We find through simulations that the system-degrading effects are different in two scenarios with atmosphere turbulence: (a) when we consider the same strength of phasefront distortion, faster divergence (i.e., lower frequency; smaller beam waist) leads to higher power leakage from the transmitted mode to neighbouring modes; and (b) however, when we consider the same atmospheric turbulence, the divergence effect tends to affect the power leakage much less, and the power leakage increases as the frequency, beam waist, or OAM order increases. Simulation results show that: (i) the crosstalk to the neighbouring mode remains < − 15 dB for a 1-km link under calm weather, when we transmit OAM + 4 at 0.5 THz with a beam waist of 1 m; (ii) for the 3-OAM-multiplexed THz links, the signal-to-interference ratio (SIR) increases by ~ 5–7 dB if the mode spacing increases by 1, and SIR decreases with the multiplexed mode number; and (iii) limited aperture size and misalignment lead to power leakage to other modes under calm weather, while it tends to be unobtrusive under bad weather.
Phenotyping placental oxygenation in Lgals1 deficient mice using 19F MRI
Authors: Boehm-Sturm Philipp , Mueller Susanne , Freitag Nancy , Borowski Sophia , Foddis Marco , Koch Stefan P. , Temme Sebastian , Flögel Ulrich , Blois Sandra M.
Published: January 2021

Placental hypoperfusion and hypoxia are key drivers in complications during fetal development such as fetal growth restriction and preeclampsia. In order to study the mechanisms of disease in mouse models, the development of quantitative biomarkers of placental hypoxia is a prerequisite. The goal of this exploratory study was to establish a technique to noninvasively characterize placental partial pressure of oxygen (PO2) in vivo in the Lgals1 (lectin, galactoside-binding, soluble, 1) deficient mouse model of preeclampsia using fluorine magnetic resonance imaging. We hypothesized a decrease in placental oxygenation in knockout mice. Wildtype and knockout animals received fluorescently labeled perfluoro-5-crown-15-ether nanoemulsion i.v. on day E14-15 during pregnancy. Placental PO2 was assessed via calibrated 19F MRI saturation recovery T1 mapping. A gas challenge with varying levels of oxygen in breathing air (30%, 60% and 100% O2) was used to validate that changes in oxygenation can be detected in freely breathing, anesthetized animals. At the end of the experiment, fluorophore-coupled lectin was injected i.v. to label the vasculature for histology. Differences in PO2 between breathing conditions and genotype were statistically analyzed with linear mixed-effects modeling. As expected, a significant increase in PO2 with increasing oxygen in breathing air was found. PO2 in Lgals1 knockout animals was decreased but this effect was only present at 30% oxygen in breathing air, not at 60% and 100%. Histological examinations showed crossing of the perfluorocarbon nanoemulsion to the fetal blood pool but the dominating contribution of 19F MR signal is estimated at > 70% from maternal plasma based on volume fraction measurements of previous studies. These results show for the first time that 19F MRI can characterize oxygenation in mouse models of placental malfunction.