bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Spillovers of Employment Guarantee Programs on Child Labor and Education
Authors: Li Tianshu , Sekhri Sheetal 
Published: November 2018

AbstractMany developing countries use employment guarantee programs to combat poverty. This study examines the consequences of such employment guarantee programs for the human capital accumulation of children. It exploits the phased roll-out of India’s flagship Mahatma Gandhi National Rural Employment Guarantee Scheme (MGNREGA) to study the effects on enrollment in schools and child labor. Introduction of MGNREGA results in lower relative school enrollment in treated districts. It also finds that the drop in enrollment is driven by primary school children. Children in higher grades are just as likely to attend school under MGNREGA, but their school performance deteriorates. Using nationally representative employment data, the study finds evidence indicating an increase in child labor highlighting the unintentional perverse effects of the employment guarantee schemes for human capital.
Teaching Critical Thinking: A Case for Instruction in Cognitive Biases to Reduce Diagnostic Errors and Improve Patient Safety
Authors: Royce Celeste S. , Hayes Margaret M. , Schwartzstein Richard M. 
Published: November 2018

Diagnostic errors contribute to as many as 70% of medical errors. Prevention of diagnostic errors is more complex than building safety checks into health care systems; it requires an understanding of critical thinking, of clinical reasoning, and of the cognitive processes through which diagnoses are made. When a diagnostic error is recognized, it is imperative to identify where and how the mistake in clinical reasoning occurred. Cognitive biases may contribute to errors in clinical reasoning. By understanding how physicians make clinical decisions, and examining how errors due to cognitive biases occur, cognitive bias awareness training and debiasing strategies may be developed to decrease diagnostic errors and patient harm. Studies of the impact of teaching critical thinking skills have mixed results but are limited by methodological problems.
This Perspective explores the role of clinical reasoning and cognitive bias in diagnostic error, as well as the effect of instruction in metacognitive skills on improvement of diagnostic accuracy for both learners and practitioners. Recent literature questioning whether teaching critical thinking skills increases diagnostic accuracy is critically examined, as are studies suggesting that metacognitive practices result in better patient care and outcomes. Instruction in metacognition, reflective practice, and cognitive bias awareness may help learners move toward adaptive expertise and help clinicians improve diagnostic accuracy. The authors argue that explicit instruction in metacognition in medical education, including awareness of cognitive biases, has the potential to reduce diagnostic errors and thus improve patient safety.
Abortion through telemedicine
Authors: Fok Wing Kay , Mark Alice 
Published: November 2018

Purpose of review
Medical abortion offers a well tolerated and effective method to terminate early pregnancy, but remains underutilized in the United States. Over the last decade, ‘telemedicine’ has been studied as an option for medical abortion to improve access when patients and providers are not together. A number of studies have explored various practice models and their feasibility as an alternative to in-person service provision.

Recent findings
A direct-to-clinic model of telemedicine medical abortion has similar efficacy with no increased risk of significant adverse events when compared with in-person abortion. A direct-to-consumer model is currently being studied in the United States. International models of direct-to-consumer medical abortion have shown promising results.

Summary
The introduction of telemedicine into abortion care has been met with early success. Currently, there are limitations to the reach of telemedicine because of specific restrictions on mifepristone in the United States as well as laws that specifically prohibit telemedicine for abortion. If these barriers are removed, telemedicine can potentially increase abortion access.
PD-1 Expression in HIV-Specific CD8+ T cells Before Antiretroviral Therapy Is Associated With HIV Persistence
Authors: Ghiglione Yanina , Trifone César , Salido Jimena , Rhodes Ajantha , Ruiz María Julia , Polo María Laura , Salomón Horacio , Laufer Natalia , Sued Omar , Lewin Sharon R. , Turk Gabriela 
Published: November 2018

Background:
The persistence of latently infected T cells remains the principal barrier to HIV cure. Understanding how the early immune responses shape persistence of HIV on antiretroviral therapy (ART) will be fundamental for potential eradication. Here, we aimed to determine the relationship between CD8+ T-cell function and phenotype before therapy and HIV persistence on ART.

Methods:
Blood samples from 29 individuals enrolled during primary HIV infection (at baseline and every 3 months up to 2 years post-ART initiation) were obtained. HIV-specific T-cell function and expression of the activation markers were evaluated before ART by flow cytometry. Cell-associated HIV DNA and unspliced (US)-RNA were quantified in purified CD4+ T cells by real-time polymerase chain reaction. Data were analyzed using nonparametric statistics.

Results:
Elevated immune activation, dominance of monofunctional CD8+ T cells, and skewed distribution of memory profile were observed before ART. After ART initiation, HIV DNA and US-RNA levels rapidly diminished, reaching a plateau by 30 weeks after ART. The proportion of baseline HIV-specific effector memory and terminal effector CD8+ T cells directly correlated with HIV DNA levels at 1 year after ART. A strong positive correlation was observed between the proportion of bulk and HIV-specific PD-1High CD8+ T cells measured before ART and HIV DNA at 1 year after ART.

Conclusions:
A higher proportion of terminally differentiated CD8+ T cells and increased PD1 expression were associated with HIV persistence on ART after treatment of primary infection. Thus, the quality of the early CD8+ T-cell immune response may serve as a predictor of HIV persistence on ART.
Human RNA cap1 methyltransferase CMTr1 cooperates with RNA helicase DHX15 to modify RNAs with highly structured 5′ termini
Authors: Toczydlowska-Socha Diana , Zielinska Magdalena M. , Kurkowska Malgorzata , Astha  , Almeida Catarina F. , Stefaniak Filip , Purta Elzbieta , Bujnicki Janusz M. 
Published: November 2018

The 5′-cap structure, characteristic for RNA polymerase II-transcribed RNAs, plays important roles in RNA metabolism. In humans, RNA cap formation includes post-transcriptional modification of the first transcribed nucleotide by RNA cap1 methyltransferase (CMTr1). Here, we report that CMTr1 activity is hindered towards RNA substrates with highly structured 5′ termini. We found that CMTr1 binds ATP-dependent RNA DHX15 helicase and that this interaction, mediated by the G-patch domain of CMTr1, has an advantageous effect on CMTr1 activity towards highly structured RNA substrates. The effect of DHX15 helicase activity is consistent with the strength of the secondary structure that has to be removed for CMTr1 to access the 5′-terminal residues in a single-stranded conformation. This is, to our knowledge, the first demonstration of the involvement of DHX15 in post-transcriptional RNA modification, and the first example of a molecular process in which DHX15 directly affects the activity of another enzyme. Our findings suggest a new mechanism underlying the regulatory role of DHX15 in the RNA capping process. RNAs with highly structured 5′ termini constitute a significant fraction of the human transcriptome. Hence, CMTr1–DHX15 cooperation is likely to be important for the metabolism of RNA polymerase II-transcribed RNAs.
This article is part of the theme issue ‘5′ and 3′ modifications controlling RNA degradation’.
RNA uridylation and decay in plants
Authors: de Almeida Caroline , Scheer Hélène , Gobert Anthony , Fileccia Veronica , Martinelli Federico , Zuber Hélène , Gagliardi Dominique 
Published: November 2018

RNA uridylation consists of the untemplated addition of uridines at the 3′ extremity of an RNA molecule. RNA uridylation is catalysed by terminal uridylyltransferases (TUTases), which form a subgroup of the terminal nucleotidyltransferase family, to which poly(A) polymerases also belong. The key role of RNA uridylation is to regulate RNA degradation in a variety of eukaryotes, including fission yeast, plants and animals. In plants, RNA uridylation has been mostly studied in two model species, the green algaeChlamydomonas reinhardtiiand the flowering plantArabidopsis thaliana. Plant TUTases target a variety of RNA substrates, differing in size and function. These RNA substrates include microRNAs (miRNAs), small interfering silencing RNAs (siRNAs), ribosomal RNAs (rRNAs), messenger RNAs (mRNAs) and mRNA fragments generated during post-transcriptional gene silencing. Viral RNAs can also get uridylated during plant infection. We describe here the evolutionary history of plant TUTases and we summarize the diverse molecular functions of uridylation during RNA degradation processes in plants. We also outline key points of future research.This article is part of the theme issue ‘5′ and 3′ modifications controlling RNA degradation’.
RNA polyadenylation and its consequences in prokaryotes
Authors: Hajnsdorf Eliane , Kaberdin Vladimir R. 
Published: November 2018

Post-transcriptional addition of poly(A) tails to the 3′ end of RNA is one of the fundamental events controlling the functionality and fate of RNA in all kingdoms of life. Although an enzyme with poly(A)-adding activity was discovered inEscherichia colimore than 50 years ago, its existence and role in prokaryotic RNA metabolism were neglected for many years. As a result, it was not until 1992 thatE. colipoly(A) polymerase I was purified to homogeneity and its gene was finally identified. Further work revealed that, similar to its role in surveillance of aberrant nuclear RNAs of eukaryotes, the addition of poly(A) tails often destabilizes prokaryotic RNAs and their decay intermediates, thus facilitating RNA turnover. Moreover, numerous studies carried out over the last three decades have shown that polyadenylation greatly contributes to the control of prokaryotic gene expression by affecting the steady-state level of diverse protein-coding and non-coding transcripts including antisense RNAs involved in plasmid copy number control, expression of toxin–antitoxin systems and bacteriophage development. Here, we review the main findings related to the discovery of polyadenylation in prokaryotes, isolation, and characterization and regulation of bacterial poly(A)-adding activities, and discuss the impact of polyadenylation on prokaryotic mRNA metabolism and gene expression.This article is part of the theme issue ‘5′ and 3′ modifications controlling RNA degradation’.
Role of oligouridylation in normal metabolism and regulated degradation of mammalian histone mRNAs
Authors: Meaux Stacie A. , Holmquist Christopher E. , Marzluff William F. 
Published: November 2018

Metazoan replication-dependent histone mRNAs are the only known cellular mRNAs that are not polyadenylated. Histone mRNAs are present in large amounts only in S-phase cells, and their levels are coordinately regulated with the rate of DNA replication. In mammals, the stemloop at the 3′ end of histone mRNA is bound to stemloop binding protein, a protein required for both synthesis and degradation of histone mRNA, and an exonuclease, 3′hExo (ERI1). Histone mRNAs are rapidly degraded when DNA synthesis is inhibited in S-phase cells and at the end of S-phase. Upf1 is also required for rapid degradation of histone mRNA as is the S-phase checkpoint. We report that Smg1 is required for histone mRNA degradation when DNA replication is inhibited, suggesting it is the PI-like kinase that activates Upf1 for histone mRNA degradation. We also show that some mutant Upf1 proteins are recruited to histone mRNAs when DNA replication is inhibited and act as dominant negative factors in histone mRNA degradation. We report that the pathway of rapid histone mRNA degradation when DNA replication is inhibited in S-phase cells that are activating the S-phase checkpoint is similar to the pathway of rapid degradation of histone mRNA at the end of S-phase.
This article is part of the theme issue ‘5′ and 3′ modifications controlling RNA degradation’.
The role of 3′ end uridylation in RNA metabolism and cellular physiology
Authors: Zigáčková Dagmar , Vaňáčová Štěpánka 
Published: November 2018

Most eukaryotic RNAs are posttranscriptionally modified. The majority of modifications promote RNA maturation, others may regulate function and stability. The 3′ terminal non-templated oligouridylation is a widespread modification affecting many cellular RNAs at some stage of their life cycle. It has diverse roles in RNA metabolism. The most prevalent is the regulation of stability and quality control. On the cellular and organismal level, it plays a critical role in a number of pathways, such as cell cycle regulation, cell death, development or viral infection. Defects in uridylation have been linked to several diseases. This review summarizes the current knowledge about the role of the 3′ terminal oligo(U)-tailing in biology of various RNAs in eukaryotes and describes key factors involved in these pathways.
This article is part of the theme issue ‘5′ and 3′ modifications controlling RNA degradation’.
A comprehensive analysis of single-cell transcriptome network underlying gastric premalignant lesions and early gastric cancer
Authors: Zhang Peng , Yang Mingran , Zhang Yiding , Xiao Shuai , Lai Xinxing , Tan Aidi , Li Shao 
Published: November 2018

SummaryIntestinal-type gastric cancer is preceded by premalignant lesions including chronic atrophic gastritis (CAG) and intestinal metaplasia (IM), which are characterized as changes in cell types. In this study, for the first time, we systematically constructed a single-cell atlas for a total of 31,164 high-quality cells from gastric mucosa biopsies of patients spanning a cascade of gastric premalignant lesions and early gastric cancer (EGC) using single-cell RNA sequencing (scRNA-seq). Based on the atlas, we construct a network underlying the changes of cellular and molecular characteristics of gastric epithelial cells across different lesions. We found the conversion of gland mucous cells (GMCs) toward a more intestinal-like stem cell phenotype during metaplasia, and identified OR51E1 as a novel marker for early-malignant enteroendocrine cells. We also found that HES6 might mark a goblet cell subset that precede morphologically identifiable goblet cells in IM mucosa, potentially aiding the identification of metaplasia at the early stage. Finally, we identified a panel of EGC-related specific signature, with clinical implications for the precise diagnosis of EGC. Our study offers unparalleled insights into the human gastric cellulome in premalignant and early-malignant lesions and provides an important data resource that will facilitate studies in gastritis-induced tumourigenesis and gastric cell biology.Significance StatementUnderstanding cellular characteristics in gastric premalignant and malignant lesions would help us better understand the gastric cancer (GC) pathogenesis. In this paper, for the first time, we systematically constructed a single-cell transcriptome network of human premalignant gastric mucosa and early GC (EGC) and derived novel findings from it. We identified OR51E1 as a novel marker for early-malignant enteroendocrine cells and a panel of genes as the EGC-specific signature, with clinical implications for the precise diagnosis of EGC. We also found HES6 might mark a goblet cell subset that precede morphologically identifiable goblet cells in IM mucosa, potentially aiding the identification of metaplasia at the early stage. Our study provided an unprecedented data resource that will facilitate studies underlying gastritis-induced tumorigenesis.
Multifaceted influence of pre-mitotic cytotoxicity of primed CD8 T cells on immunity and infection
Authors: Dandamudi Durga Bhavani , Blair David A , Arifa Raquel Duque do Nascimento , Lafaille Juan J , Dustin Michael L , Mayya Viveka 
Published: November 2018

AbstractGranzyme B mRNA is expressed in primed CD8 T cells within 12 hours, but the consequences of this for the immune response are unknown. We observed that substantial portion of the naïve CD8 T cell repertoire expressed granzyme B and became pre-mitotic cytotoxic cells (PMCs) immediately in response toListeria monocytogenesorLymphocytic choriomeningitis virusinfections. The surprising breadth arose from sufficiency of low potency peptide-MHC to induce granzyme B expression in the context of infection. PMCs killed antigen bearing dendritic cells (DCs) in a granzyme B-dependent but largely perforinindependent fashion between 1-2 days post infection. This terminated antigen presentation at 3 days and resulted in reduced clonal expansion. As additional consequences, we highlight that PMCs reduced the burden of DC-borne infectious agents, but also opened a window of vulnerability for secondary infection. Thus, PMCs serve antigen-specific, regulatory and host defence functions, that are innate-like in scale, at the onset of the adaptive immune response.
DUETT quantitatively identifies known and novel events in nascent RNA structural dynamics from chemical probing data
Authors: Xue Albert Y. , Yu Angela M , Lucks Julius B. , Bagheri Neda 
Published: November 2018

AbstractMotivationRNA molecules can undergo complex structural dynamics, especially during transcription, which influence their biological functions. Recently developed high-throughput chemical probing experiments study RNA cotranscriptional folding to generate nucleotide-resolution ‘reactivities’ for each length of a growing nascent RNA and reflect structural dynamics. However, the manual annotation and qualitative interpretation of reactivity across these large datasets can be nuanced, laborious, and difficult for new practitioners. We developed a quantitative and systematic approach to automatically detect RNA folding events from these datasets to reduce human bias/error, standardize event discovery, and generate hypotheses about RNA folding trajectories for further analysis and experimental validation.ResultsDetection ofUnknownEvents withTunableThresholds (DUETT) identifies RNA structural transitions in cotranscriptional RNA chemical probing datasets. DUETT employs a feedback control-inspired method and a linear regression approach and relies on interpretable and independently tunable parameter thresholds to match qualitative user expectations with quantitatively identified folding events. We validate the approach by identifying known RNA structural transitions within the cotranscriptional folding pathways of theEscherichia colisignal recognition particle (SRP) RNA and theBacillus cereus crcBfluoride riboswitch. We identify previously overlooked features of these datasets such as heightened reactivity patterns in the SRP RNA about 12 nucleotide lengths before base pair rearrangement. We then apply a sensitivity analysis to identify tradeoffs when choosing parameter thresholds. Finally, we show that DUETT is tunable across a wide range of contexts, enabling flexible application to study broad classes of RNA folding mechanisms.Availabilityhttps://github.com/BagheriLab/DUETTContactjblucks@northwestern.edu,n-bagheri@northwestern.edu
Long Non-Coding RNA LncKdm2b Regulates Cortical Neuronal Differentiation by Cis-Activating Kdm2b
Authors: Li Wei , Shen Wenchen , Zhang Bo , Tian Kuan , Li Yamu , Mu Lili , Luo Zhiyuan , Zhong Xiaoling , Wu Xudong , Liu Ying , Zhou Yan 
Published: November 2018

AbstractThe mechanisms underlying spatial and temporal control of cortical neurogenesis of the brain are largely elusive. Long non-coding RNAs (lncRNAs) have emerged as essential cell fate regulators. Here we found LncKdm2b (also known as Kancr), a lncRNA divergently transcribed from a bidirectional promoter of Kdm2b, is transiently expressed during early differentiation of cortical projection neurons. Interestingly, Kdm2b’s transcription is positively regulated in cis by LncKdm2b, which has intrinsic-activating function and facilitates a permissive chromatin environment at the Kdm2b’s promoter by associating with hnRNPAB. Lineage tracing experiments and phenotypic analyses indicated LncKdm2b and Kdm2b are crucial in proper differentiation and migration of cortical projection neurons. Moreover, KDM2B exerts its role relying on its leucine-rich repeats (LRR) but independent of its PRC1-related function. These observations unveiled a lncRNA-dependent machinery in regulating cortical neuronal differentiation.
Berberine chloride ameliorated PI3K/Akt-p/SIRT-1/PTEN signaling pathway in insulin resistance syndrome-induced rats
Authors: El-Zeftawy Marwa , Ghareeb Doaa , Saad Rasha , Mahmoud Salma , Elguindy Nihal , El-Sayed Mohammed 
Published: November 2018

AbstractInsulin resistance is one of dangerous factors as it leads to numerous metabolic disorders such as non-insulin dependent diabetes mellitus. It affects most tissues mainly adipose tissue, liver and muscle. Nowadays, berberine has several medical applications against diseases. The current study was carried out to identify the effect of berberine chloride (BER-chloride) on phosphatidyl inositol-3-kinase/ phosphorylated protein kinase B/ sirtuin type 1/ phosphatase and tension homologue (PI3K/Akt-p/SIRT-1/PTEN) pathway during insulin resistance phenomena. Insulin resistance model was performed in experimental rats by using high fat diet. Plasma glucose, serum insulin, lipid profiles, hepatic oxidative stress markers were estimated. Serum transaminases activities and kidney function tests were determined. Further, hepatic PI3K, AKt-p, SIRT-1; PTEN levels were assayed. The concentration of adiponectin in serum, hepatic tissue and white adipose tissue was determined. Moreover, fold change in hepatic insulin, insulin receptor and retinol binding protein-4 (RBP4) at molecular level was performed. Histopathological study of white adipose tissue was also determined. The results showed increase the rats’ body weights, blood glucose, homeostatic model assessment, glycated hemoglobin, insulin and lipid profiles levels in group of rats fed on high fat diet for eight weeks and this elevation was decreased after administration of BER-chloride for two weeks. Further, BER-chloride administration exhibited improvement of oxidative stress parameters, PI3K, AKt-p, SIRT-1 and PTEN. This was associated with down-regulation of RBP4. According to these data we conclude that, BER-chloride mediated several insulin signaling pathways that could be of therapeutic significance to insulin resistance.