bluuebunny/crossref_metadata_2025 huggingface dataset:
An RNAi screen for genes that affect nuclear morphology in Caenorhabditis elegans reveals the involvement of unexpected processes
Authors: Maheshwari Richa , Rahman Mohammad M , Joseph-Strauss Daphna , Cohen-Fix Orna
Published: September 2021

Aberration in nuclear morphology is one of the hallmarks of cellular transformation. However, the processes that, when mis-regulated, result aberrant nuclear morphology are poorly understood. In this study, we carried out a systematic, high-throughput RNAi screen for genes that affect nuclear morphology in Caenorhabditis elegans embryos. The screen employed over 1700 RNAi constructs against genes required for embryonic viability. Nuclei of early embryos are typically spherical, and their NPCs are evenly distributed. The screen was performed on early embryos expressing a fluorescently tagged component of the nuclear pore complex (NPC), allowing visualization of nuclear shape as well as the distribution of NPCs around the nuclear envelope. Our screen uncovered 182 genes whose downregulation resulted in one or more abnormal nuclear phenotypes, including multiple nuclei, micronuclei, abnormal nuclear shape, anaphase bridges, and abnormal NPC distribution. Many of these genes fall into common functional groups, including some that were not previously known to affect nuclear morphology, such as genes involved in mitochondrial function, the vacuolar ATPase, and the CCT chaperonin complex. The results of this screen add to our growing knowledge of processes that affect nuclear morphology and that may be altered in cancer cells that exhibit abnormal nuclear shape.
Essential Cases: EU Law
Authors: O'Meara Noreen
Published: September 2021

Essential Cases: EU Law provides a bridge between course textbooks and key case judgments. Essential Cases provides you with succinct summaries of some of the landmark and most influential cases in EU law. Each summary begins with a review of the main case facts and decision. The summary is then concluded with expert commentary on the case from the author, Noreen O’Meara., including her assessment of the wider questions raised by the decision.
Essential Cases: Public Law
Authors: Webb Thomas E.
Published: September 2021

Essential Cases: Public Law provides a bridge between course textbooks and key case judgments. Essential Cases provides you with succinct summaries of some of the landmark and most influential cases in public law. Each summary begins with a review of the main case facts and decision. The summary is then concluded with expert commentary on the case from the author, Thomas Webb, including his assessment of the wider questions raised by the decision for you to consider.
1. Administration and the principles of the constitution
Authors: Endicott Timothy
Published: September 2021

Administrative law includes a complex variety of processes and doctrines that confer and control public power. This chapter outlines the underlying principles of administrative law. Topics discussed include the core principle of administrative law: opposition to arbitrary use of power. That principle is introduced through the story of habeas corpus from the middle ages to the twenty-first century. The constitutional principles of administrative law also include parliamentary sovereignty, the separation of powers, the rule of law, comity among constitutional authorities, accountability, and a newly emerging principle of open government. The chapter shows how the common law and legislation can achieve adherence to these principles of administrative law.
3. Human rights law
Authors: Endicott Timothy
Published: September 2021

The European Convention on Human Rights not only guaranteed certain rights, but also created an international Court. The Human Rights Act gives English judges dramatic but limited techniques for vindicating the Convention rights. This chapter explains what the judges in Strasbourg and in England have done with the techniques for control of administration that result from the Convention and the Human Rights Act. The chapter addresses the content and the structure of the Convention rights, the ways in which those rights are protected in English administrative law, particularly through the Human Rights Act 1998, and the tests of proportionality required by the Convention.
7. Discretion and deference
Authors: Endicott Timothy
Published: September 2021

This chapter discusses how judges can defer in appropriate ways to administrative authorities on some issues, while still opposing abuses of power. The chapter explains why the courts defer massively to administrative authorities on some issues involving foreign affairs and national security, public expenditure, planning, and legal and political processes. The mere fact that the law has allocated the power to an administrative body gives rise to a presumption that a court should not interfere unless there is a ground for review other than that the court would have reached a decision. The extent to which a court ought to defer is determined by the three reasons for allocating power to an administrative body: the body’s expertise, its political responsibility, and/or its decision-making processes.
13. Ombudsmen and inquiries
Authors: Endicott Timothy
Published: September 2021

This chapter examines ombudsmen and other facilities for investigation of the working of government, and the ways in which they can resolve disputes and improve administration. The ombudsmen’s role has four key features: (1) it is independent; (2) it investigates a complaint; (3) it looks for injustice caused by maladministration; and (4) it makes a report. The chapter explains the ombudsman process, the Parliamentary Ombudsman, local government ombudsmen, and the effects of ombudsmen’s reports. The chapter also explains the law on judicial review of ombudsman decisions and judicial review of the way in which public authorities respond to ombudsman reports, and argues that the judicial process has very little to offer in improving the operation of ombudsman schemes. The role of inquiries is also explained, with discussion of the Equality and Human Rights Commission, the Inquiries Act 2005, and public authorities’ duties to inquire under the common law and the European Convention on Human Rights.
Tort Law Concentrate
Authors: Brennan Carol
Published: September 2021

Each Concentrate revision guide is packed with essential information, key cases, revision tips, exam Q&As, and more. Concentrates show you what to expect in a law exam, what examiners are looking for, and how to achieve extra marks. Having begun with a consideration of the meaning of tort and the context of the ‘tort system’, Tort Law Concentrate covers the key elements of negligence: duty of care, breach of duty, and causation. Economic loss and psychiatric injury are specifically discussed. The book also explains the intentional torts: trespass to the person and to land as well as the tort in Wilkinson v Downton are covered, as is product liability. The family of nuisance torts, with their importance for environmental control are included, as is the key issue of remedies. This new edition includes coverage of recent case law, such as Barclays Bank plc v Various Claimants (2020) and Lachaux v Independent Print (2019). This edition has been fully updated in light of developments in the law, including the continuing impact of the Human Rights Act 1998 and the Consumer Rights Act 2015.
Introduction to the English Legal System
Authors: Partington Martin
Published: September 2021

Introduction to the English Legal System 2021–2022 has been fully updated to consider the latest developments in the English legal system. The underlying theme is change and the impact of the COVID-19 pandemic and the underlying approach is holistic. Changes to the criminal system (Chapter 5), the administrative system (Chapter 6), the family justice system (Chapter 7), and the civil and commercial (Chapter 8) justice systems are all considered. Developments in the ways in which the legal profession is regulated are also discussed (Chapter 9). Ways of funding access to justice and controlling the cost of litigating are considered (Chapter 10), as are the purposes and sources of law (Chapters 2 and 3). Chapter 11 offers a final reflection on a system in flux.
Complete Public Law
Authors: Webley Lisa , Samuels Harriet
Published: September 2021

Titles in the Complete series combine extracts from a wide range of primary materials with clear explanatory text to provide readers with a complete introductory resource. Complete Public Law combines clear explanatory text and practical learning features with extracts from a wide range of primary and secondary materials. The book has been structured with the needs of undergraduate courses in mind. Opening with consideration of basic constitutional principles (in which no previous knowledge is assumed), the chapters move on to cover all other essential areas, before closing with consideration of the principles and procedures of judicial review. This edition includes substantial updates to address the UK’s withdrawal from the European Union and the constitutional implications these new arrangements have, including in the context of devolution.
JC Smith's The Law of Contract
Authors: Davies Paul S.
Published: September 2021

Driven by exposition of the leading cases, JC Smith’s The Law of Contract offers the perfect balance between accessibility and authority. The strong focus on cases guides the reader through the intricacies of contract law with expert analysis ensuring key points are clear. The text begins with an introduction to contractual rights and duties. It looks at objectivity in contract law, the formation of bilateral and unilateral contracts, contract as agreement, offeror and offeree, estoppel, legal relations, and the role of third parties. It also considers the terms of the contract, interpretation of the contract, implication and rectification, and exclusion clauses and unfair terms. It goes on to look at issues such as duress, undue influence, good faith, capacity, illegality, contractual assumptions, breach of contract, remedies and damages, and remedies beyond compensatory damages.
Smith & Wood's Employment Law
Authors: Smith Ian , Baker Aaron , Warnock Owen
Published: September 2021

Smith & Wood’s Employment Law draws on the extensive teaching and practical experience of its authors to provide students with a clear explanation of essential legislation and case detail while also offering incisive academic commentary and critical detail to help with essay preparation and class work. Throughout the book, topics are carefully explained in their social and historical context, providing readers with an insight into the fast-paced development of employment law and offering perceptive analysis of its future direction. This fifteenth edition has been produced against the background of the 2019 election, the ensuing coronavirus crisis, and of course the largest elephant in the room: the continuing uncertainties of the details of our departure from the EU. Where appropriate it contains speculation as to possible effects. At the opposite end of the spectrum, this edition also contains the up-to-date case law on detailed employment law developments that continue in spite of such macro matters, for example in relation to the extent to which workers and unions have legal protection in cases involving what is generally referred to as the ‘gig economy’. In particular, the chapters on discrimination in employment, work–life balance and redundancy/reorganization and business transfers have been subject to substantial rewriting. Finally, the changes to the style and layout of the book adopted in the last two editions have been maintained and expanded upon by the addition of a ‘Context’ section at the beginning of each chapter, in order to aid accessibility for the reader, given the ever-increasing complexity of the law itself here.
Public Law Directions
Authors: Dennett Anne
Published: September 2021

Public Law Directions provides a balance of depth, detail, context, and critique. The aim is to empower readers to evaluate the law, understand its practical application, and confidently approach assessments. The text offers scene-setting introductions and highlighted case extracts, making the practical importance of the law clear. It shows readers when and how to critically evaluate the law by introducing the key areas of debate and encourages a questioning attitude towards the law. Topics covered include: the UK constitution; constitutional principles and values; power in the UK including an examination of the three arms of state; an analysis of the relationship between the individual and the state; and a close examination of human rights, including a look at the Human Rights Act 1998.
Human Rights Law Directions
Authors: Davis Howard
Published: September 2021

Without assuming prior legal knowledge, books in the Directions series introduce and guide readers through key points of law and legal debate. Self-test questions and exam questions help readers to engage fully with each subject and check their understanding as they progress. Human Rights Law Directions has been written expressly to guide you through your study of human rights law, and to explain clearly and concisely the key areas of this fascinating subject. Combining academic quality with innovative learning features and online support, this is an ideal text for those studying human rights law for the first time. This fifth edition has been fully updated with key developments in human rights law, including: discussion, in so far as information allows, of proposed reform of the legal protection of human rights in the United Kingdom, post-‘Brexit’; the ECtHR case law on unlawful rendition; deportation and human rights; the impact of human rights on warfare and the condition of British troops abroad; the impact of Article 8 on abortion and assisted suicide; concerns over surveillance and communications data; the impact of human rights law on controversies over religious dress (such as the burqa ban in France); and possible infringements of rights by the legal response to Coronavirus.
‘How come they don’t talk about it in school?’ Identifying adolescent barriers to PrEP use
Authors: Gailloud Leslie , Gonzalez-Argoti Tatiana , Philip Sophia , Josephs Lena S , Mantell Joanne E , Bauman Laurie J
Published: September 2021

Although 21% of new human immunodeficiency virus (HIV) diagnoses in the United States are in youth aged 13–24 years, adolescent awareness and uptake of the HIV prevention medication pre-exposure prophylaxis (PrEP) are low. This study explores the attitudes and challenges that adolescents face while taking PrEP. Thirty interviews were conducted with Black and Latine (we use the gender-inclusive term Latine rather than Latinx for more appropriate Spanish pronunciation) students aged 15–17 who received care at school-based health centers (SBHCs) in the Bronx, NY. Transcripts were coded inductively and deductively using thematic analysis. Most participants were unaware of PrEP, but nearly all were enthusiastic when informed about it; a majority denied that they would feel any stigma when taking PrEP. Despite this high receptivity, multiple barriers were identified, particularly confidentiality from parents, low perceived need of PrEP and concerns about daily adherence and side effects. Adolescents overall were enthusiastic about the availability of PrEP and felt it empowered them to have control over their health. SBHCs were considered trusted sources of confidential, accessible care, and we believe that they can be uniquely positioned to mitigate barriers to PrEP distribution in the future.
Effects of iron, vitamin A, and the interaction between the two nutrients on intestinal development and cell differentiation in piglets
Authors: Zhou Jing , Qin Yan , Xiong Xia , Wang Zhaobin , Wang Min , Wang Yancan , Wang Qiye Y , Yang Huansheng S , Yin Yulong
Published: September 2021

This study aimed to investigate the effects of iron, vitamin A (VA) and their interaction on intestinal development and differentiation of cells in suckling piglets. Therefore, 32 Duroc × Landrace × Yorkshire 0-d-old newborn boars with similar body weights were randomly divided into four groups, with eight replicates in each group and one pig in each replicate. All the piglets were breastfed. In addition, the piglets were given normal saline (CON group) or ferrous sulfate (OAFe group) or VA (VA group) or ferrous sulfate and VA (OAFe + VA group) on the 2nd, 7th, 12th, and 17th day, respectively. The piglets were then slaughtered on the 21st day, and intestinal samples were collected. The results showed that: 1) iron (P < 0.001) significantly increased the length, weight, relative weight, and the length to weight ratio of the small intestine. On the other hand, VA had a significant effect on the weight to length ratio (P = 0.015) and relative weight (P < 0.001) of the small intestine; 2) with regard to intestinal morphology, supplementation with iron (P <0.05) had obvious effects on the villus height (VH), crypt depth (CD), villus width (VW), and surface area. Additionally, both VA and interaction of VA and iron increased the VH (P < 0.05) and surface area (P = 0.001). The results also showed that iron (P < 0.01) increased the number of crypt goblet cells, Ki67-positive cells, and endocrine cells. Moreover, both VA and the interaction between VA and iron increased the number of endocrine cells in the villi (P = 0.05); 3) With regard to the mRNA expression levels of stem cell differentiation marker genes, iron (P < 0.05) decreased the expression of trophinin 2 (Trop2), leucine-rich repeat containing G protein-coupled receptor 5 positive (Lgr5+), male-specific lethal 1(Msl1), BMI 1 proto-oncogene, polycomb ring finger (Bmi1), and achaete-scute family bHLH transcription factor 2 (Ascl2). On the other hand, VA increased the expression of Ascl2 (P = 0.001) although the interaction of VA and iron (P < 0.05) had an effect on the expression of secreted phosphoprotein 1 (Spp1) and Bmi1. In addition, VA decreased the gene or mRNA expression of aconitase 1 (Aco1; P < 0.001), transferrin receptor (TFRC; P = 0.001), and solute carrier family 11 member 2 (DMT1; P = 0.003) in the Iron Reactive Element/Iron Regulatory Protein (IRE/IRP) signaling pathway although iron and the interaction of VA and iron had no effect on the genes’ expression. The results therefore showed that VA, iron, and their interaction can promote intestinal development and epithelial cell differentiation in piglets.
Factors Associated With Corticosteroid Treatment for Pediatric Acute Respiratory Tract Infections
Authors: Shapiro Daniel J , Palmer Nathan P , Bourgeois Florence T
Published: September 2021

Systemic corticosteroids are not recommended to treat children with acute respiratory tract infections (ARTIs). Using data from a national commercial health care company, we found that corticosteroid treatment occurred in 3.2% of ARTI encounters. The adjusted odds of corticosteroid treatment were highest for bronchitis/bronchiolitis, in emergency departments, and in the South.
A Case Report of Air Force Reserve Nurses Deployed to New York City for COVID-19 Support
Authors: Hernandez Stephen
Published: September 2021

Initial DoD support of Federal Emergency Management Agency (FEMA) operations for New York City (NYC) coronavirus disease 2019 (COVID-19) relief included the deployment of military medics to the Javits New York Medical Station and USNS Comfort. When Air Force (AF) Reservists arrived in NYC, 64th Air Expeditionary Group leaders worked with FEMA, Task Force New York/New Jersey, and NYC chains of command to send Airmen to NYC hospitals, including Lincoln Medical Center (LMC). Within 72 hours of arrival, 60 AF Reservists, including 30 registered nurses and 3 medical technicians, integrated into LMC to provide support during April and May 2020. This assistance began during the peak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Air Force nurses provided over 6,000 hours of care to over 800 patients in the emergency department and ad hoc intensive care and medical-surgical units. As infections declined, AF nurses shifted to providing care in established units. In these units, AF nurses provided patient care and worked directly with LMC nurses to provide directed teaching experiences to improve their comfort and competency with caring for acutely ill COVID-19 patients. The deployment of AF Reservists into civilian facilities was a success and bolstered the capability of three facilities struggling to care for SARS-CoV-2 patients. This effort was recognized by military and civilian healthcare leaders and resulted in over 600 military medical personnel being sent to support 11 NYC public hospitals.
Reducing Setup and Turnover Times in the OR With an Innovative Sterilization Container: Implications for the COVID-19 Era Military Medicine
Authors: Bradley David F , Romito Kenneth , Dockery James , Taylor Lance , ONeel Nicholas , Rodriguez Jose , Talbot Laura A
Published: September 2021

Introduction

The global 2019 coronavirus pandemic (COVID-19) is setting unprecedented demands on the nation and the military and surgical services. Surgical demands include a large backlog of surgical cases, strain on available resources, and the need for additional measures to prevent exposure. The purpose of this project was to evaluate the feasibility, duration, adverse events, and potential gains associated with using a Turbett Sterilization Pod (TSP) for total joint replacements.

Materials and Methods

A multidisciplinary team used the Plan–Do–Study–Act model to guide this project. A time–motion study was completed in the operating room (OR) to measure the average time required to set up surgical instrumentation for total joint replacement cases that required 12 or more instrument trays. We compared the amount of time it took to complete the setting up of instrumentation using the traditional method versus the TSP method. The traditional method consisted of unwrapping each surgical tray, checking for holes in the blue wrapper, and placing the tray on the back table. In the case of the TSP, the door of the pod was opened, and the instrument trays were transferred directly to the back table. We measured the time the staff took to perform the task using each of these methods.

Results

When compared to the traditional method, the use of the TSP resulted in improved turnover time, decreased room setup time, reduced environmental waste, and eliminated both the effect of damage to wrappers and the time previously spent wrapping surgical trays.

Conclusion

The TSP minimizes the time needed by the staff to set up an OR suite for a total joint replacement, therefore permitting them to focus more on direct patient care. This time improvement suggests that all surgical specialties, including those requiring greater than 12 traditional instrument sets, may experience reduced turnover time between cases. The use of the TSP is one means to help rectify the OR backlog brought on by COVID-19.
Neonatal Aeromedical Evacuation During COVID-19: An Interview With Captain Danielle James
Authors: James Danielle , Talbot Laura A
Published: September 2021

During the coronavirus-19 pandemic, limited information existed about the risks and consequences of severe acute respiratory syndrome coronavirus 2 infection associated with maternal transmission to neonates. With rapidly evolving evidence, Air Force Neonatal Intensive Care Unit nurses at U.S. Naval Hospital Okinawa, Japan, adapted their standard operating procedures to safeguard their at-risk neonatal patients. This interview describes an Air Force NICU nurse’s view of neonatal transport and nursing care during the coronavirus-19 pandemic.
Drosophila Evolution over Space and Time (DEST): A New Population Genomics Resource
Authors: Kapun Martin , Nunez Joaquin C B , Bogaerts-Márquez María , Murga-Moreno Jesús , Paris Margot , Outten Joseph , Coronado-Zamora Marta , Tern Courtney , Rota-Stabelli Omar , Guerreiro Maria P García , Casillas Sònia , Orengo Dorcas J , Puerma Eva , Kankare Maaria , Ometto Lino , Loeschcke Volker , Onder Banu S , Abbott Jessica K , Schaeffer Stephen W , Rajpurohit Subhash , Behrman Emily L , Schou Mads F , Merritt Thomas J S , Lazzaro Brian P , Glaser-Schmitt Amanda , Argyridou Eliza , Staubach Fabian , Wang Yun , Tauber Eran , Serga Svitlana V , Fabian Daniel K , Dyer Kelly A , Wheat Christopher W , Parsch John , Grath Sonja , Veselinovic Marija Savic , Stamenkovic-Radak Marina , Jelic Mihailo , Buendía-Ruíz Antonio J , Gómez-Julián Maria Josefa , Espinosa-Jimenez Maria Luisa , Gallardo-Jiménez Francisco D , Patenkovic Aleksandra , Eric Katarina , Tanaskovic Marija , Ullastres Anna , Guio Lain , Merenciano Miriam , Guirao-Rico Sara , Horváth Vivien , Obbard Darren J , Pasyukova Elena , Alatortsev Vladimir E , Vieira Cristina P , Vieira Jorge , Torres Jorge Roberto , Kozeretska Iryna , Maistrenko Oleksandr M , Montchamp-Moreau Catherine , Mukha Dmitry V , Machado Heather E , Lamb Keric , Paulo Tânia , Yusuf Leeban , Barbadilla Antonio , Petrov Dmitri , Schmidt Paul , Gonzalez Josefa , Flatt Thomas , Bergland Alan O
Published: September 2021

Drosophila melanogaster is a leading model in population genetics and genomics, and a growing number of whole-genome data sets from natural populations of this species have been published over the last years. A major challenge is the integration of disparate data sets, often generated using different sequencing technologies and bioinformatic pipelines, which hampers our ability to address questions about the evolution of this species. Here we address these issues by developing a bioinformatics pipeline that maps pooled sequencing (Pool-Seq) reads from D. melanogaster to a hologenome consisting of fly and symbiont genomes and estimates allele frequencies using either a heuristic (PoolSNP) or a probabilistic variant caller (SNAPE-pooled). We use this pipeline to generate the largest data repository of genomic data available for D. melanogaster to date, encompassing 271 previously published and unpublished population samples from over 100 locations in >20 countries on four continents. Several of these locations have been sampled at different seasons across multiple years. This data set, which we call Drosophila Evolution over Space and Time (DEST), is coupled with sampling and environmental metadata. A web-based genome browser and web portal provide easy access to the SNP data set. We further provide guidelines on how to use Pool-Seq data for model-based demographic inference. Our aim is to provide this scalable platform as a community resource which can be easily extended via future efforts for an even more extensive cosmopolitan data set. Our resource will enable population geneticists to analyze spatiotemporal genetic patterns and evolutionary dynamics of D. melanogaster populations in unprecedented detail.
A Daily-Updated Database and Tools for Comprehensive SARS-CoV-2 Mutation-Annotated Trees
Authors: McBroome Jakob , Thornlow Bryan , Hinrichs Angie S , Kramer Alexander , De Maio Nicola , Goldman Nick , Haussler David , Corbett-Detig Russell , Turakhia Yatish
Published: September 2021

The vast scale of SARS-CoV-2 sequencing data has made it increasingly challenging to comprehensively analyze all available data using existing tools and file formats. To address this, we present a database of SARS-CoV-2 phylogenetic trees inferred with unrestricted public sequences, which we update daily to incorporate new sequences. Our database uses the recently proposed mutation-annotated tree (MAT) format to efficiently encode the tree with branches labeled with parsimony-inferred mutations, as well as Nextstrain clade and Pango lineage labels at clade roots. As of June 9, 2021, our SARS-CoV-2 MAT consists of 834,521 sequences and provides a comprehensive view of the virus’ evolutionary history using public data. We also present matUtils—a command-line utility for rapidly querying, interpreting, and manipulating the MATs. Our daily-updated SARS-CoV-2 MAT database and matUtils software are available at http://hgdownload.soe.ucsc.edu/goldenPath/wuhCor1/UShER_SARS-CoV-2/ and https://github.com/yatisht/usher, respectively.
Mechanisms of irreversible aquaporin-10 inhibition by organogold compounds studied by combined biophysical methods and atomistic simulations
Authors: Pimpão Catarina , Wragg Darren , Bonsignore Riccardo , Aikman Brech , Pedersen Per Amstrup , Leoni Stefano , Soveral Graça , Casini Angela
Published: September 2021

The inhibition of glycerol permeation via human aquaporin-10 (hAQP10) by organometallic gold complexes has been studied by stopped-flow fluorescence spectroscopy, and its mechanism has been described using molecular modelling and atomistic simulations. The most effective hAQP10 inhibitors are cyclometalated Au(III) C^N compounds known to efficiently react with cysteine residues leading to the formation of irreversible C–S bonds. Functional assays also demonstrate the irreversibility of the binding to hAQP10 by the organometallic complexes. The obtained computational results by metadynamics show that the local arylation of Cys209 in hAQP10 by one of the gold inhibitors is mapped into a global change of the overall free energy of glycerol translocation across the channel. Our study further pinpoints the need to understand the mechanism of glycerol and small molecule permeation as a combination of local structural motifs and global pore conformational changes, which are taking place on the scale of the translocation process and whose study, therefore, require sophisticated molecular dynamics strategies.
Expression pattern and prognostic value of N6-methyladenosine RNA methylation key regulators in hepatocellular carcinoma
Authors: Deng Min , Fang Lin , Li Shao-Hua , Zhao Rong-Ce , Mei Jie , Zou Jing-Wen , Wei Wei , Guo Rong-Ping
Published: September 2021

Hepatocellular carcinoma (HCC) is still one of the most common malignancies worldwide. The accuracy of biomarkers for predicting the prognosis of HCC and the therapeutic effect is not satisfactory. N6-methyladenosine (m6A) methylation regulators play a crucial role in various tumours. Our research aims further to determine the predictive value of m6A methylation regulators and establish a prognostic model for HCC. In this study, the data of HCC from The Cancer Genome Atlas (TCGA) database was obtained, and the expression level of 15 genes and survival was examined. Then we identified two clusters of HCC with different clinical factors, constructed prognostic markers and analysed gene set enrichment, proteins’ interaction and gene co-expression. Three subgroups by consensus clustering according to the expression of the 13 genes were identified. The risk score generated by five genes divided HCC patients into high-risk and low-risk groups. In addition, we developed a prognostic marker that can identify high-risk HCC. Finally, a novel prognostic nomogram was developed to accurately predict HCC patients’ prognosis. The expression levels of 13 m6A RNA methylation regulators were significantly upregulated in HCC samples. The prognosis of cluster 1 and cluster 3 was worse. Patients in the high-risk group show a poor prognosis. Moreover, the risk score was an independent prognostic factor for HCC patients. In conclusion, we reveal the critical role of m6A RNA methylation modification in HCC and develop a predictive model based on the m6A RNA methylation regulators, which can accurately predict HCC patients’ prognosis and provide meaningful guidance for clinical treatment.
AC-motif: a DNA motif containing adenine and cytosine repeat plays a role in gene regulation
Authors: Hur Jeong Hwan , Kang Chan Young , Lee Sungjin , Parveen Nazia , Yu Jihyeon , Shamim Amen , Yoo Wanki , Ghosh Ambarnil , Bae Sangsu , Park Chin-Ju , Kim Kyeong Kyu
Published: September 2021

I-motif or C4 is a four-stranded DNA structure with a protonated cytosine:cytosine base pair (C+:C) found in cytosine-rich sequences. We have found that oligodeoxynucleotides containing adenine and cytosine repeats form a stable secondary structure at a physiological pH with magnesium ion, which is similar to i-motif structure, and have named this structure ‘adenine:cytosine-motif (AC-motif)’. AC-motif contains C+:C base pairs intercalated with putative A+:C base pairs between protonated adenine and cytosine. By investigation of the AC-motif present in the CDKL3 promoter (AC-motifCDKL3), one of AC-motifs found in the genome, we confirmed that AC-motifCDKL3 has a key role in regulating CDKL3 gene expression in response to magnesium. This is further supported by confirming that genome-edited mutant cell lines, lacking the AC-motif formation, lost this regulation effect. Our results verify that adenine-cytosine repeats commonly present in the genome can form a stable non-canonical secondary structure with a non-Watson–Crick base pair and have regulatory roles in cells, which expand non-canonical DNA repertoires.
Reinforcement of transcriptional silencing by a positive feedback between DNA methylation and non-coding transcription
Authors: Rothi M Hafiz , Tsuzuki Masayuki , Sethuraman Shriya , Wierzbicki Andrzej T
Published: September 2021

Non-coding transcription is an important determinant of heterochromatin formation. In Arabidopsis thaliana a specialized RNA polymerase V (Pol V) transcribes pervasively and produces long non-coding RNAs. These transcripts work with small interfering RNA to facilitate locus-specific establishment of RNA-directed DNA methylation (RdDM). Subsequent maintenance of RdDM is associated with elevated levels of Pol V transcription. However, the impact of DNA methylation on Pol V transcription remained unresolved. We found that DNA methylation strongly enhances Pol V transcription. The level of Pol V transcription is reduced in mutants defective in RdDM components working downstream of Pol V, indicating that RdDM is maintained by a mutual reinforcement of DNA methylation and Pol V transcription. Pol V transcription is affected only on loci that lose DNA methylation in all sequence contexts in a particular mutant, including mutants lacking maintenance DNA methyltransferases, which suggests that RdDM works in a complex crosstalk with other silencing pathways.
Consciousness in active inference: Deep self-models, other minds, and the challenge of psychedelic-induced ego-dissolution
Authors: Deane George
Published: September 2021

Predictive processing approaches to brain function are increasingly delivering promise for illuminating the computational underpinnings of a wide range of phenomenological states. It remains unclear, however, whether predictive processing is equipped to accommodate a theory of consciousness itself. Furthermore, objectors have argued that without specification of the core computational mechanisms of consciousness, predictive processing is unable to inform the attribution of consciousness to other non-human (biological and artificial) systems. In this paper, I argue that an account of consciousness in the predictive brain is within reach via recent accounts of phenomenal self-modelling in the active inference framework. The central claim here is that phenomenal consciousness is underpinned by ‘subjective valuation’—a deep inference about the precision or ‘predictability’ of the self-evidencing (‘fitness-promoting’) outcomes of action. Based on this account, I argue that this approach can critically inform the distribution of experience in other systems, paying particular attention to the complex sensory attenuation mechanisms associated with deep self-models. I then consider an objection to the account: several recent papers argue that theories of consciousness that invoke self-consciousness as constitutive or necessary for consciousness are undermined by states (or traits) of ‘selflessness’; in particular the ‘totally selfless’ states of ego-dissolution occasioned by psychedelic drugs. Drawing on existing work that accounts for psychedelic-induced ego-dissolution in the active inference framework, I argue that these states do not threaten to undermine an active inference theory of consciousness. Instead, these accounts corroborate the view that subjective valuation is the constitutive facet of experience, and they highlight the potential of psychedelic research to inform consciousness science, computational psychiatry and computational phenomenology.
A Novel Weave Tether Technique for Proximal Junctional Kyphosis Prevention in 71 Adult Spinal Deformity Patients: A Preliminary Case Series Assessing Early Complications and Efficacy
Authors: Rabinovich Emily P , Buell Thomas J , Sardi Juan P , Lazaro Bruno C R , Shaffrey Christopher I , Smith Justin S
Published: September 2021

BACKGROUND

Proximal junctional kyphosis (PJK) rates may be as high as 69.4% after adult spinal deformity (ASD) surgery. PJK is one of the greatest unsolved challenges in long-segment fusions for ASD and remains a common indication for costly and impactful revision surgery. Junctional tethers may help to reduce the occurrence of PJK by attenuating adjacent-segment stress.

OBJECTIVE

To report our experience and assess early safety associated with a novel “weave-tether technique” (WTT) for PJK prophylaxis in a large series of patients.

METHODS

This single-center retrospective study evaluated consecutive patients who underwent ASD surgery including WTT between 2017 and 2018. Patient demographics, operative details, standard radiographic measurements, and complications were analyzed.

RESULTS

A total of 71 patients (mean age 66 ± 12 yr, 65% women) were identified. WTT included application to the upper-most instrumented vertebrae (UIV) + 1 and UIV + 2 in 38(53.5%) and 33(46.5%) patients, respectively. No complications directly attributed to WTT usage were identified. For patients with radiographic follow-up (96%; mean duration 14 ± 12 mo), PJK occurred in 15% (mean 1.8 ± 1.0 mo postoperatively). Proximal junctional angle increased an average 4° (10° to 14°, P = .004). Rates of symptomatic PJK and revision for PJK were 8.8% and 2.9%, respectively.

CONCLUSION

Preliminary results support the safety of the WTT for PJK prophylaxis. Approximately 15% of patients developed radiographic PJK, no complications were directly attributed to WTT usage, and the revision rate for PJK was low. These early results warrant future research to assess longer-term efficacy of the WTT for PJK prophylaxis in ASD surgery.
Quantitative Anatomic Comparison of Microsurgical Transcranial, Endoscopic Endonasal, and Transorbital Approaches to the Spheno-Orbital Region
Authors: Agosti Edoardo , Turri-Zanoni Mario , Saraceno Giorgio , Belotti Francesco , Karligkiotis Apostolos , Rocca Gregorio , Buffoli Barbara , Raffetti Elena , Hirtler Lena , Rezzani Rita , Rodella Luigi Fabrizio , Ferrari Marco , Nicolai Piero , Bresson Damien , Herman Philippe , Dallan Iacopo , Castelnuovo Paolo , Locatelli Davide , Fontanella Marco Maria , Doglietto Francesco
Published: September 2021

BACKGROUND

The spheno-orbital region (SOR) is a complex anatomic area that can be accessed with different surgical approaches.

OBJECTIVE

To quantitatively compare, in a preclinical setting, microsurgical transcranial approaches (MTAs), endoscopic endonasal transpterygoid approach (EEA), and endoscopic transorbital approaches (ETOAs) to the SOR.

METHODS

These approaches were performed in 5 specimens: EEA, ETOAs (superior eyelid and inferolateral), anterolateral MTAs (supraorbital, minipterional, pterional, pterional-transzygomatic, and frontotemporal-orbitozygomatic), and lateral MTAs (subtemporal and subtemporal transzygomatic). All specimens underwent high-resolution computed tomography; an optic neuronavigation system with dedicated software was used to quantify working volume and exposed area for each approach. Mixed linear models with random intercepts were used for statistical analyses.

RESULTS

Anterolateral MTAs offer a direct route to the greater wings (GWs) and lesser wings (LWs); only they guarantee exposure of the anterior clinoid. Lateral MTAs provide access to a large area corresponding to the GW, up to the superior orbital fissure (SOF) anteriorly and the foramen rotundum medially. ETOAs also access the GW, close to the lateral portion of SOF, but with a different angle of view as compared to lateral MTAs. Access to deep and medial structures, such as the lamina papyracea and the medial SOF, is offered only by EEA, which exposes the LW and GW only to a limited extent.

CONCLUSION

This is the first study that offers a quantitative comparison of the most used approaches to SOR. A detailed knowledge of their advantages and limitations is paramount to choose the ideal one, or their combination, in the clinical setting.
Medicago SPX1 and SPX3 regulate phosphate homeostasis, mycorrhizal colonization, and arbuscule degradation
Authors: Wang Peng , Snijders Roxane , Kohlen Wouter , Liu Jieyu , Bisseling Ton , Limpens Erik
Published: September 2021

To acquire sufficient mineral nutrients such as phosphate (Pi) from the soil, most plants engage in symbiosis with arbuscular mycorrhizal (AM) fungi. Attracted by plant-secreted strigolactones (SLs), the fungi colonize the roots and form highly branched hyphal structures called arbuscules inside inner cortex cells. The host plant must control the different steps of this interaction to maintain its symbiotic nature. However, how plants sense the amount of Pi obtained from the fungus, and how this determines the arbuscule lifespan, are far from understood. Here, we show that Medicago truncatula SPX-domain containing proteins SPX1 and SPX3 regulate root Pi starvation responses, in part by interacting with PHOSPHATE RESPONSE REGULATOR2, as well as fungal colonization and arbuscule degradation. SPX1 and SPX3 are induced upon Pi starvation but become more restricted to arbuscule-containing cells upon the establishment of symbiosis. This induction in arbuscule-containing cells is associated with the presence of cis-regulatory AW-boxes and transcriptional regulation by the WRINKLED1-like transcription factor WRI5a. Under Pi-limiting conditions, SPX1 and SPX3 facilitate the expression of the SL biosynthesis gene DWARF27, which could help explain the increased fungal branching in response to root exudates. Later, in arbuscule-containing cells, SPX1 and SPX3 redundantly control arbuscule degradation. Thus, SPX proteins play important roles as phosphate sensors to maintain a beneficial AM symbiosis.
Woodland strawberry axillary bud fate is dictated by a crosstalk of environmental and endogenous factors
Authors: Andrés Javier , Caruana Julie , Liang Jiahui , Samad Samia , Monfort Amparo , Liu Zhongchi , Hytönen Timo , Koskela Elli A
Published: September 2021

Plant architecture is defined by fates and positions of meristematic tissues and has direct consequences on yield potential and environmental adaptation of the plant. In strawberries (Fragaria vesca L. and F. × ananassa Duch.), shoot apical meristems can remain vegetative or differentiate into a terminal inflorescence meristem. Strawberry axillary buds (AXBs) are located in leaf axils and can either remain dormant or follow one of the two possible developmental fates. AXBs can either develop into stolons needed for clonal reproduction or into branch crowns (BCs) that can bear their own terminal inflorescences under favorable conditions. Although AXB fate has direct consequences on yield potential and vegetative propagation of strawberries, the regulation of AXB fate has so far remained obscure. We subjected a number of woodland strawberry (F. vesca L.) natural accessions and transgenic genotypes to different environmental conditions and growth regulator treatments to demonstrate that strawberry AXB fate is regulated either by environmental or endogenous factors, depending on the AXB position on the plant. We confirm that the F. vesca GIBBERELLIN20-oxidase4 (FvGA20ox4) gene is indispensable for stolon development and under tight environmental regulation. Moreover, our data show that apical dominance inhibits the outgrowth of the youngest AXB as BCs, although the effect of apical dominance can be overrun by the activity of FvGA20ox4. Finally, we demonstrate that the FvGA20ox4 is photoperiodically regulated via FvSOC1 (F. vesca SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1) at 18°C, but at higher temperature of 22°C an unidentified FvSOC1-independent pathway promotes stolon development.
Early Identification of Deep-Tissue Pressure Injury Using Long-Wave Infrared Thermography: A Blinded Prospective Cohort Study
Authors: Simman Richard , Angel Carol
Published: September 2021

BACKGROUND

The current clinical standard for diagnosing deep-tissue pressure injury (DTPI) is visual inspection. This method is subjective and only presents to the observer the external “picture;” deeper tissues are disguised from the observer. In contrast, long-wave infrared thermography (LWIT) can capture an image of the area of concern and detect tissue temperature relative to the level of tissue perfusion.

OBJECTIVE

To determine the efficacy of a handheld LWIT device and software solution as an adjunct to the current clinical standard of visual skin assessment to detect nonvisual pathophysiologic changes of DTPI.

METHODS

Investigators performed a blinded, prospective cohort study scanning participants’ sacral area and bilateral heels with the LWIT device. Follow-up imaging took place throughout patient stays (on admission and 3, 7, 14, and 25 days thereafter). Clinicians were blinded to the LWIT images, and all participants received standard care for the prevention and treatment of wounds.

RESULTS

Among the 70 participants enrolled in this study, there were 131 anatomical areas with intact skin at the time of admission. Four areas with initially intact skin progressed to visually identifiable DTPI. On all four of these areas, the LWIT device identified a previsual temperature anomaly before there existed a visually identifiable DTPI.

CONCLUSIONS

The outcomes of this study suggest objective and quantitative documentation of temperature change using the LWIT device can serve as an indication of DTPI formation before visual identification is possible. Accordingly, it may allow for earlier detection of DTPI, decreasing the risk of associated complications to the patient and allowing for earlier, targeted intervention.
Abdominal Ultrasound Assists the Diagnosis and Management of Necrotizing Enterocolitis
Authors: Chan Belinda , Gordon Sasha , Yang Michelle , Weekes Jennifer , Dance Logan
Published: September 2021

Background:

Abdominal x-ray (KUB) routinely aids in detecting necrotizing enterocolitis (NEC), one of the most serious neonatal intestinal diseases. However, a KUB may miss up to 50% of the early signs of NEC. Recent advances in abdominal ultrasound (AUS) can expedite this diagnosis and improve clinical management.

Purposes:

To illustrate AUS findings that suggest NEC through 3 case examples. To review current literature regarding advantages and limitations of AUS compared with KUB.

Results:

The added visualization of intra-abdominal structures with AUS compared with KUB improves the diagnosis and management of NEC. Some AUS features are highly suggestive of impending bowel perforation, while others can confirm bowel perforation despite a negative radiograph.

Implications for Practice:

AUS expedites time to diagnosis of NEC and helps to stratify patients who may fail medical management and require surgical intervention.

Implications for research:

More quality improvement studies are needed to validate an AUS protocol for the management of NEC. Advances in technology, such as contrast-enhanced ultrasound, may improve NEC detection with AUS in the future.

Video Abstract available at
https://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx.