bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of RAG-like transposons in protostomes suggests their ancient bilaterian origin
Authors: Martin Eliza C. , Vicari Célia , Tsakou-Ngouafo Louis , Pontarotti Pierre , Petrescu Andrei J. , Schatz David G. 
Published: May 2020

Abstract
Background
V(D) J recombination is essential for adaptive immunity in jawed vertebrates and is initiated by the RAG1-RAG2 endonuclease. The RAG1 and RAG2 genes are thought to have evolved from a RAGL (RAG-like) transposon containing convergently-oriented RAG1-like (RAG1L) and RAG2-like (RAG2L) genes. Elements resembling this presumptive evolutionary precursor have thus far only been detected convincingly in deuterostomes, leading to the model that the RAGL transposon first appeared in an early deuterostome.

Results
We have identified numerous RAGL transposons in the genomes of protostomes, including oysters and mussels (phylum Mollusca) and a ribbon worm (phylum Nemertea), and in the genomes of several cnidarians. Phylogenetic analyses are consistent with vertical evolution of RAGL transposons within the Bilateria clade and with its presence in the bilaterian ancestor. Many of the RAGL transposons identified in protostomes are intact elements containing convergently oriented RAG1L and RAG2L genes flanked by terminal inverted repeats (TIRs) and target site duplications with striking similarities with the corresponding elements in deuterostomes. In addition, protostome genomes contain numerous intact RAG1L-RAG2L adjacent gene pairs that lack detectable flanking TIRs. Domains and critical active site and structural amino acids needed for endonuclease and transposase activity are present and conserved in many of the predicted RAG1L and RAG2L proteins encoded in protostome genomes.

Conclusions
Active RAGL transposons were present in multiple protostome lineages and many were likely transmitted vertically during protostome evolution. It appears that RAGL transposons were broadly active during bilaterian evolution, undergoing multiple duplication and loss/fossilization events, with the RAGL genes that persist in present day protostomes perhaps constituting both active RAGL transposons and domesticated RAGL genes. Our findings raise the possibility that the RAGL transposon arose earlier in evolution than previously thought, either in an early bilaterian or prior to the divergence of bilaterians and non-bilaterians, and alter our understanding of the evolutionary history of this important group of transposons.
The cholinergic system in subtypes of Alzheimer’s disease: an in vivo longitudinal MRI study
Authors:   for the Alzheimer’s Disease Neuroimaging Initiative, Machado Alejandra , Ferreira Daniel , Grothe Michel J. , Eyjolfsdottir Helga , Almqvist Per M. , Cavallin Lena , Lind Göran , Linderoth Bengt , Seiger Åke , Teipel Stefan , Wahlberg Lars U. , Wahlund Lars-Olof , Westman Eric , Eriksdotter Maria 
Published: May 2020

Abstract
Background
The heterogeneity within Alzheimer’s disease (AD) seriously challenges the development of disease-modifying treatments. We investigated volume of the basal forebrain, hippocampus, and precuneus in atrophy subtypes of AD and explored the relevance of subtype stratification in a small clinical trial on encapsulated cell biodelivery (ECB) of nerve growth factor (NGF) to the basal forebrain.

Methods
Structural MRI data was collected for 90 amyloid-positive patients and 69 amyloid-negative healthy controls at baseline, 6-, 12-, and 24-month follow-up. The effect of the NGF treatment was investigated in 10 biopsy-verified AD patients with structural MRI data at baseline and at 6- or 12-month follow-up. Patients were classified as typical, limbic-predominant, hippocampal-sparing, or minimal atrophy AD, using a validated visual assessment method. Volumetric analyses were performed using a region-of-interest approach.

Results
All AD subtypes showed reduced basal forebrain volume as compared with the healthy controls. The limbic-predominant subtype showed the fastest basal forebrain atrophy rate, whereas the minimal atrophy subtype did not show any significant volume decline over time. Atrophy rates of the hippocampus and precuneus also differed across subtypes. Our preliminary data from the small NGF cohort suggest that the NGF treatment seemed to slow the rate of atrophy in the precuneus and hippocampus in some hippocampal-sparing AD patients and in one typical AD patient.

Conclusions
The cholinergic system is differentially affected in distinct atrophy subtypes of AD. Larger studies in the future should confirm that this differential involvement of the cholinergic system may contribute to subtype-specific response to cholinergic treatment. Our preliminary findings suggest that future clinical trials should target specific subtypes of AD, or at least report treatment effects stratified by subtype.

Trial registration
ClinicalTrials.gov identifier: NCT01163825. Registered 14 July 2010.
Tsc1 haploinsufficiency in Nkx2.1 cells upregulates hippocampal interneuron mTORC1 activity, impairs pyramidal cell synaptic inhibition, and alters contextual fear discrimination and spatial working memory in mice
Authors: Haji Nabila , Riebe Ilse , Aguilar-Valles Argel , Artinian Julien , Laplante Isabel , Lacaille Jean-Claude 
Published: May 2020

Abstract
Background
Mutations in TSC1 or TSC2 genes cause tuberous sclerosis complex (TSC), a disorder associated with epilepsy, autism, and intellectual disability. TSC1 and TSC2 are repressors of the mechanistic target of rapamycin complex 1 (mTORC1), a key regulator of protein synthesis. Dysregulation of mTORC1 in TSC mouse models leads to impairments in excitation-inhibition balance, synaptic plasticity, and hippocampus-dependent learning and memory deficits. However, synaptic inhibition arises from multiple types of inhibitory interneurons and how changes in specific interneurons contribute to TSC remains largely unknown. In the present work, we determined the effect of conditional Tsc1 haploinsufficiency in a specific subgroup of inhibitory cells on hippocampal function in mice.

Methods
We investigated the consequences of conditional heterozygous knockout of Tsc1 in MGE-derived inhibitory cells by crossing Nkx2.1Cre/wt;Tsc1f/f mice. We examined the changes in mTORC1 activity and synaptic transmission in hippocampal cells, as well as hippocampus-related cognitive tasks.

Results
We detected selective increases in phosphorylation of ribosomal protein S6 in interneurons, indicating cell-specific-upregulated mTORC1 signaling. At the behavioral level, Nkx2.1Cre/wt;Tsc1f/wt mice exhibited intact contextual fear memory, but impaired contextual fear discrimination. They displayed intact spatial learning and reference memory but impairment in spatial working memory. Whole-cell recordings in hippocampal slices of Nkx2.1Cre/wt;Tsc1f/wt mice showed intact basic membrane properties, as well as miniature excitatory and inhibitory synaptic transmission, in pyramidal and Nkx2.1-expressing inhibitory cells. Using optogenetic activation of Nkx2.1 interneurons in slices of Nkx2.1Cre/wt;Tsc1f/wt mice, we found a decrease in synaptic inhibition of pyramidal cells. Chronic, but not acute treatment, with the mTORC1 inhibitor rapamycin reversed the impairment in synaptic inhibition.

Conclusions
Our results indicate that Tsc1 haploinsufficiency in MGE-derived inhibitory cells upregulates mTORC1 activity in these interneurons, reduces their synaptic inhibition of pyramidal cells, and alters contextual fear discrimination and spatial working memory. Thus, selective dysregulation of mTORC1 function in Nkx2.1-expressing inhibitory cells appears sufficient to impair synaptic inhibition and contributes to cognitive deficits in the Tsc1 mouse model of TSC.
Real-world experience with doxorubicin and olaratumab in soft tissue sarcomas in England and Northern Ireland
Authors: Gennatas Spyridon , Chamberlain Florence , Carter Thomas , Slater Susanna , Cojocaru Elena , Lambourn Beth , Stansfeld Anna , Todd Radha , Verrill Mark , Ali Nasim , Jones Robin L. , Simmonds Peter , Keay Nicola , McCarty Heather , Strauss Sandra , Karavasilis Vassilios , Dileo Palma , Benson Charlotte 
Published: May 2020

Abstract
Background
A randomised phase II trial demonstrated that the addition of olaratumab to doxorubicin significantly increased overall survival (OS) in patients with advanced soft tissue sarcomas (STS) compared to doxorubicin alone. The recently presented phase III study of doxorubicin and olaratumab in advanced soft tissue sarcoma was discordant with this finding.

Methods
We performed a retrospective analysis of adult patients with advanced-/metastatic STS treated with at least two cycles of doxorubicin and olaratumab at eight sarcoma units across England and Northern Ireland between May 2017 and March 2019.

Results
172 patients were evaluable and 40 patients (23.3%) had died at the time of analysis. Median ECOG performance status (PS) was 1. Median progression free survival (PFS) was 6.8 months (95% CI 5.9–7.7 months). Leiomyosarcoma was the most common histological subtype (75 patients, 43.6%), followed by liposarcomas (19, 11.0%). The mean number of cycles was 5 (doxorubicin range 2–6; olaratumab range 2–23). Two patients (1.2%) had a complete response and 34 (19.8%) had a partial response. 79 (45.9%) had stable and 58 (33.7%) progressive disease. 57 patients (33.1%) experienced grade ≥ 3 neutropenia and 7 patients (4.1%) grade ≥ 3 febrile neutropenia. Grade ≥ 3 anaemia was seen in 21 patients (12.2%). Grade ≥ 3 non-haematological toxicities were seen in 35 patients (20.3%). A clinically significant drop in left ventricular ejection fraction was seen in 6 patients (3.5%). 48 patients (27.9%) required a dose reduction. Overall survival (OS) is pending.

Conclusions
Our results are in keeping with the phase III study findings: response rate, PFS and OS were similar to those reported in the phase III ANNOUNCE trial.
New Hermite–Hadamard type inequalities for n-polynomial harmonically convex functions
Authors: Awan Muhammad Uzair , Akhtar Nousheen , Iftikhar Sabah , Noor Muhammad Aslam , Chu Yu-Ming 
Published: May 2020

AbstractIn the article, we introduce a class of n-polynomial harmonically convex functions, establish their several new Hermite–Hadamard type inequalities which are the generalizations and variants of the previously known results for harmonically convex functions.
Initial boundary value problem for generalized Zakharov equations with nonlinear function terms
Authors: Wang Xueqin , Shang Yadong , Lei Chunlin 
Published: May 2020

AbstractIn this paper, we consider the initial boundary value problem for generalized Zakharov equations. Firstly, we prove the existence and uniqueness of the global smooth solution to the problem by a priori integral estimates, the Galerkin method, and compactness theory. Furthermore, we discuss the approximation limit of the global solution when the coefficient of the strong nonlinear term tends to zero.
A novel time efficient structure-preserving splitting method for the solution of two-dimensional reaction-diffusion systems
Authors: Ahmed Nauman , Korkmaz Alper , Rafiq M. , Baleanu Dumitru , Alshomrani Ali Saleh , Rehman M. A. , Iqbal M. S. 
Published: May 2020

AbstractIn this article, the first part is concerned with the important questions related to the existence and uniqueness of solutions for nonlinear reaction-diffusion systems. Secondly, an efficient positivity-preserving operator splitting nonstandard finite difference scheme (NSFD) is designed for such a class of systems. The presented formulation is unconditionally stable as well as implicit in nature and even time efficient. The proposed NSFD operator splitting technique also preserves all the important properties possessed by continuous systems like positivity, convergence to the fixed points of the system, and boundedness. The proposed algorithm is implicit in nature but more efficient in time than the extensively used Euler method.
Is there prejudice from thin air? Replicating the effect of emotion on automatic intergroup attitudes
Authors: Dang Junhua , Ekim Zeynep E. , Ohlsson Sarah , Schiöth Helgi B. 
Published: May 2020

Abstract
Background
Previous studies showed that anger, rather than sadness, created automatic intergroup bias in a minimal group context.

Methods
The current research reports a single study (N = 99) aiming to replicate this finding and further to test whether the intergroup bias manifests as ingroup favoritism, outgroup derogation, or both.

Results
Our results failed to replicate the effect of anger on automatic bias. Intriguingly, participants across all emotion conditions exhibited high level of ingroup favoritism, but there was little evidence of outgroup derogation.

Conclusion
These results suggest that, when there is no competition or conflict between groups, individuals, even in a bad emotional state such as anger, generally show ingroup love rather than outgroup hate.
MRI visibility of the anterolateral ligament and the deep structures of the iliotibial tract
Authors: Liebensteiner Michael , Runer Armin , Kranewitter Christof , Nachtigal Philipp , Giesinger Johannes , Dammerer Dietmar , Henninger Benjamin 
Published: May 2020

Abstract
Purpose
The visualization of potentially injured anatomical structures is crucial. Lately the anterolateral ligament (ALL) and the deep structures of the iliotibial tract (ITT) have been of increased clinical interest because of their role as important lateral stabilizers of the knee. The aim of this study was to assess the visibility of the ALL and the deep structures of the ITT using MRI. Good intra- and inter-observer reproducibility was hypothesized.

Methods
Knee MRI data from patients without ligamentous lesions were retrospectively analyzed by two radiologists at two time points using axial and coronal sequences. The visibility of the different parts of the ALL (femoral, meniscal and tibial part) and of the deep ITT, namely the deep attachments of the ITT to the distal femur and capsulo-osseous layer of the ITT, were determined on a binary (yes/no) basis.

Results
Seventy-one cases (42 men, 29 women) were studied. Inter-observer agreement was high. Cohen’s kappa was 0.97 for the tibial part of the ALL and 0.76 for the femoral part. For the deep attachments of the ITT to the distal femur Cohen’s kappa was 0.94. For each of the investigated parameters absolute agreement between the observers was at least 88%. Regarding intra-observer agreement Cohen’s kappa was 0.62 for the femoral part of the ALL and 0.85 for the tibial part of the ALL. For the deep attachments of the ITT to the distal femur Cohen’s kappa was 0.94. For each investigated parameter absolute agreement between the two time points was at least 83%.

Conclusions
The presence of the anterolateral structures of the knee can be determined with substantial inter- and intra-observer agreement using MRI examination. This is applicable for both the ALL and the deep ITT.

Level of evidence
Diagnostic study – Level III.
In vitro regeneration and molecular characterization of Jatropha curcas plant
Authors: El-Sayed Mohamed , Aly Usama I. , Mohamed Mervat S. , Rady Mohamed R. 
Published: May 2020

Abstract
Background and objective
A simple, rapid, efficient, and reproducible protocol for callus induction and regeneration of plantlets from callus of Jatropha curcas plant was established.

Materials and methods
Randomly amplified polymorphic DNA (RAPD) and inter simple sequence repeat (ISSR) analyses were used to determine the genetic variation between the regenerated, micropropagated, and mother plants.

Results
The highest callus induction percentage from leaf explant was recorded with MS medium containing 2.5 mg/l BA (6-benzylaminopurine) + 1.0 mg/l NAA (1-naphthaleneacetic acid). Leaf-derived callus was grown on medium containing 2.0 mg/l BA + 0.2 mg/l IBA (indole-3-butyric acid) for adventitious shoot regeneration. In addition, using five random RAPD primers with the tested samples produced 117 amplified products out of which 25 were polymorphic bands resulting in 21.37% polymorphism, whereas the five ISSR primers used yielded 116 scorable bands out of which 22 were polymorphic bands producing a polymorphism pecentage of 18.96.

Conclusion
An optimized protocol for large-scale production of J. curcas plants using plant biotechnology tools was achieved. RAPD and ISSR techniques would introduce an alternative system for large-scale production and establishment of genetically stable plants.
Ductal carcinoma in situ (DCIS) in breast fibroadenoma
Authors: El-Essawy Manar , AL Haidary Amal , Khan Abdul Latif 
Published: May 2020

Abstract
Background
Fibroadenoma is the most common benign tumor; although malignant, changes are rare. Any changes or increase in size should be evaluated thoroughly to exclude any malignant formation.

Case presentation
A 25-year-old female presenting to our department complaining of enlargement of the previously stable mass underwent imaging assessment and biopsy which revealed ductal carcinoma in situ changes developed in a fibroadenoma.

Conclusion
Although malignant changes in a fibroadenoma are rare, biopsy of increasing size fibroadenoma is advised to avoid missing any malignant changes; the incidence is more in the complex fibroadenoma.
LIN28A binds to meiotic gene transcripts and modulates their translation in male germ cells
Authors: Wang Mei , Yu Luping , Wang Shu , Yang Fan , Wang Min , Li Lufan , Wu Xin 
Published: May 2020

ABSTRACT
The RNA-binding protein LIN28A is required for maintaining tissue homeostasis, including in the reproductive system, but the underlying mechanisms on how LIN28A regulates germline progenitors remain unclear. Here, we dissected LIN28A-binding targets using high-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP) in the mouse testes. LIN28A preferentially binds to mRNA coding sequence (CDS) or 3′UTR regions at sites enriched with GGAG(A) sequences. Further investigation of Lin28a-null mouse testes indicated that meiosis-associated mRNAs bound by LIN28A were differentially expressed. Next, ribosome profiling revealed that the mRNA levels of these targets were significantly reduced in the polysome fractions, and their protein expression levels decreased, in Lin28a-null mouse testes, even when meiotic arrest in the null mouse testes was not apparent. Collectively, these findings provide a set of LIN28A-regulated target mRNAs, and show that LIN28A binding might be a mechanism through which LIN28A acts to regulate undifferentiated spermatogonia fates and male fertility in mammals.
Rational and practical use of imaging in COVID-19 pneumonia
Authors: Sohail Saba 
Published: May 2020

The severe form of the COVID-19 pandemic caused by the SARS-CoV-2 virus, has largely manifested as a predominant respiratory illness causing severe pneumonia characterized by bilateral, subpleural ground glass haze, progressing to consolidation, and fibrosis on imaging. There is some discrepancy between the governmental guidelines, professional Societies and Radiology and Respiratory Medicine specialists with divided opinions between the use of the chest X-rays and CT scan, and whether the use be screening or diagnostic. So far, the most balanced recommendations have been proposed by the Fleischner Society, which are endorsed by the Radiological Society of Pakistan as well. This writeup describes the approach for a rational use of imaging to the best advantage in the current situation according to local resources, and restricting the spread of infection. The most practical compromise for Pakistan appears to be the use of portable digital radiography equipment, and point-of- care ultrasound; with CT scan reserved for clinical situations not explained by the above two modalities, or demanding disease stratification.
doi: https://doi.org/10.12669/pjms.36.COVID19-S4.2760
How to cite this:Sohail S. Rational and practical use of imaging in COVID-19 pneumonia. Pak J Med Sci. 2020;36(COVID19-S4):COVID19-S130-S133. doi: https://doi.org/10.12669/pjms.36.COVID19-S4.2760
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Does declared surgeon specialist interest influence the outcome of emergency laparotomy?
Authors: Hallam S , Bickley M , Phelan L , Dilworth M , Bowley DM 
Published: May 2020

Introduction In the UK, general surgeons must demonstrate competency in emergency general surgery before obtaining a certificate of completion of training. Subsequently, many consultants develop focused elective specialist interests which may not mirror the breadth of procedures encountered during emergency practice. Recent National Emergency Laparotomy Audit analysis found that declared surgeon special interest impacted emergency laparotomy outcomes, which has implications for emergency general surgery service configuration. We sought to establish whether local declared surgeon special interest impacts emergency laparotomy outcomes. Methods Adult patients having emergency laparotomy were identified from our prospective National Emergency Laparotomy Audit database from May 2016 to May 2019 and categorised as colorectal or oesophagogastric according to operative procedure. Outcomes included 30-day mortality, return to theatre and length of stay. Binomial logistic regression was used to identify any association between declared consultant specialist interest and outcomes. Results Of 600 laparotomies, 358 (58.6%) were classifiable as specialist procedures: 287 (80%) colorectal and 71 (20%) oesophagogastric. Discordance between declared specialty and operation undertaken occurred in 25% of procedures. For colorectal emergency laparotomy, there was an increased risk of 30-day mortality when performed by a non-colorectal consultant (unadjusted odds ratio 2.34; 95% confidence interval 1.10–5.00; p = 0.003); however, when adjusted for confounders within multivariate analysis declared surgeon specialty had no impact on mortality, return to theatre or length of stay. Conclusion Surgeon-declared specialty does not impact emergency laparotomy outcomes in this cohort of undifferentiated emergency laparotomies. This may reflect the on-call structure at Birmingham Heartlands Hospital, where a colorectal and oesophagogastric consultant are paired on call and provide cross-cover when needed.
The Social Life of Kimono: Japanese Fashion Past and Present, Sheila Cliffe (2017)
Authors: Boulton Emilia J. 
Published: May 2020

Review of: The Social Life of Kimono: Japanese Fashion Past and Present, Sheila Cliffe (2017)
London and New York: Bloomsbury Publishing, 249 pp.,
ISBN 978-1-47258-553-0, h/bk, £79.20