bluuebunny/crossref_metadata_2025_split huggingface dataset:
Full-length transcriptome analysis and identification of transcript structures in Eimeria necatrix from different developmental stages by single-molecule real-time sequencing
Authors: Gao Yang , Suding Zeyang , Wang Lele , Liu Dandan , Su Shijie , Xu Jinjun , Hu Junjie , Tao Jianping 
Published: September 2021

Abstract
Background
Eimeria necatrix is one of the most pathogenic parasites, causing high mortality in chickens. Although its genome sequence has been published, the sequences and complete structures of its mRNA transcripts remain unclear, limiting exploration of novel biomarkers, drug targets and genetic functions in E. necatrix.

Methods
Second-generation merozoites (MZ-2) of E. necatrix were collected using Percoll density gradients, and high-quality RNA was extracted from them. Single-molecule real-time (SMRT) sequencing and Illumina sequencing were combined to generate the transcripts of MZ-2. Combined with the SMRT sequencing data of sporozoites (SZ) collected in our previous study, the transcriptome and transcript structures of E. necatrix were studied.

Results
SMRT sequencing yielded 21,923 consensus isoforms in MZ-2. A total of 17,151 novel isoforms of known genes and 3918 isoforms of novel genes were successfully identified. We also identified 2752 (SZ) and 3255 (MZ-2) alternative splicing (AS) events, 1705 (SZ) and 1874 (MZ-2) genes with alternative polyadenylation (APA) sites, 4019 (SZ) and 2588 (MZ-2) fusion transcripts, 159 (SZ) and 84 (MZ-2) putative transcription factors (TFs) and 3581 (SZ) and 2039 (MZ-2) long non-coding RNAs (lncRNAs). To validate fusion transcripts, reverse transcription-PCR was performed on 16 candidates, with an accuracy reaching up to 87.5%. Sanger sequencing of the PCR products further confirmed the authenticity of chimeric transcripts. Comparative analysis of transcript structures revealed a total of 3710 consensus isoforms, 815 AS events, 1139 genes with APA sites, 20 putative TFs and 352 lncRNAs in both SZ and MZ-2.

Conclusions
We obtained many long-read isoforms in E. necatrix SZ and MZ-2, from which a series of lncRNAs, AS events, APA events and fusion transcripts were identified. Information on TFs will improve understanding of transcriptional regulation, and fusion event data will greatly improve draft versions of gene models in E. necatrix. This information offers insights into the mechanisms governing the development of E. necatrix and will aid in the development of novel strategies for coccidiosis control.

Graphical Abstract
Deep learning in cancer diagnosis, prognosis and treatment selection
Authors: Tran Khoa A. , Kondrashova Olga , Bradley Andrew , Williams Elizabeth D. , Pearson John V. , Waddell Nicola 
Published: September 2021

AbstractDeep learning is a subdiscipline of artificial intelligence that uses a machine learning technique called artificial neural networks to extract patterns and make predictions from large data sets. The increasing adoption of deep learning across healthcare domains together with the availability of highly characterised cancer datasets has accelerated research into the utility of deep learning in the analysis of the complex biology of cancer. While early results are promising, this is a rapidly evolving field with new knowledge emerging in both cancer biology and deep learning. In this review, we provide an overview of emerging deep learning techniques and how they are being applied to oncology. We focus on the deep learning applications for omics data types, including genomic, methylation and transcriptomic data, as well as histopathology-based genomic inference, and provide perspectives on how the different data types can be integrated to develop decision support tools. We provide specific examples of how deep learning may be applied in cancer diagnosis, prognosis and treatment management. We also assess the current limitations and challenges for the application of deep learning in precision oncology, including the lack of phenotypically rich data and the need for more explainable deep learning models. Finally, we conclude with a discussion of how current obstacles can be overcome to enable future clinical utilisation of deep learning.
Searching for synergy: combining systemic daptomycin treatment with localised phage therapy for the treatment of experimental pneumonia due to MRSA
Authors: Valente Luca G. , Federer Lea , Iten Manuela , Grandgirard Denis , Leib Stephen L. , Jakob Stephan M. , Haenggi Matthias , Cameron David R. , Que Yok-Ai , Prazak Josef 
Published: September 2021

Abstract
Objective
Bacteriophages (or phages) are viruses which infect and lyse bacteria. The therapeutic use of phages (phage therapy) has regained attention in the last decades as an alternative strategy to treat infections caused by antimicrobial-resistant bacteria. In clinical settings it is most likely that phages are administered adjunct to antibiotics. For successful phage therapy it is therefore crucial to investigate different phage-antibiotic combinations in vivo. This study aimed to elucidate the combinatorial effects of systemic daptomycin and nebulised bacteriophages for the treatment of experimental pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA).

Results
Using a rat model of ventilator-associated pneumonia caused by MRSA, the simultaneous application of intravenous daptomycin and nebulised phages was not superior to aerophage therapy alone at improving animal survival (55% vs. 50%), or reducing bacterial burdens in the lungs, or spleen. Thus, this combination does not seem to be of benefit for use in patients with MRSA pneumonia.
The Nereid on the rise: Platynereis as a model system
Authors: Özpolat B. Duygu , Randel Nadine , Williams Elizabeth A. , Bezares-Calderón Luis Alberto , Andreatta Gabriele , Balavoine Guillaume , Bertucci Paola Y. , Ferrier David E. K. , Gambi Maria Cristina , Gazave Eve , Handberg-Thorsager Mette , Hardege Jörg , Hird Cameron , Hsieh Yu-Wen , Hui Jerome , Mutemi Kevin Nzumbi , Schneider Stephan Q. , Simakov Oleg , Vergara Hernando M. , Vervoort Michel , Jékely Gáspár , Tessmar-Raible Kristin , Raible Florian , Arendt Detlev 
Published: September 2021

AbstractThe Nereid Platynereis dumerilii (Audouin and Milne Edwards (Annales des Sciences Naturelles 1:195–269, 1833) is a marine annelid that belongs to the Nereididae, a family of errant polychaete worms. The Nereid shows a pelago-benthic life cycle: as a general characteristic for the superphylum of Lophotrochozoa/Spiralia, it has spirally cleaving embryos developing into swimming trochophore larvae. The larvae then metamorphose into benthic worms living in self-spun tubes on macroalgae. Platynereis is used as a model for genetics, regeneration, reproduction biology, development, evolution, chronobiology, neurobiology, ecology, ecotoxicology, and most recently also for connectomics and single-cell genomics. Research on the Nereid started with studies on eye development and spiralian embryogenesis in the nineteenth and early twentieth centuries. Transitioning into the molecular era, Platynereis research focused on posterior growth and regeneration, neuroendocrinology, circadian and lunar cycles, fertilization, and oocyte maturation. Other work covered segmentation, photoreceptors and other sensory cells, nephridia, and population dynamics. Most recently, the unique advantages of the Nereid young worm for whole-body volume electron microscopy and single-cell sequencing became apparent, enabling the tracing of all neurons in its rope-ladder-like central nervous system, and the construction of multimodal cellular atlases. Here, we provide an overview of current topics and methodologies for P. dumerilii, with the aim of stimulating further interest into our unique model and expanding the active and vibrant Platynereis community.
Spectral CT of the abdomen: Where are we now?
Authors: Adam Sharon Z. , Rabinowich Aviad , Kessner Rivka , Blachar Arye 
Published: September 2021

AbstractSpectral CT adds a new dimension to radiological evaluation, beyond assessment of anatomical abnormalities. Spectral data allows for detection of specific materials, improves image quality while at the same time reducing radiation doses and contrast media doses, and decreases the need for follow up evaluation of indeterminate lesions. We review the different acquisition techniques of spectral images, mainly dual-source, rapid kV switching and dual-layer detector, and discuss the main spectral results available. We also discuss the use of spectral imaging in abdominal pathologies, emphasizing the strengths and pitfalls of the technique and its main applications in general and in specific organs.
Large-vessel vasculitis in graft-versus-host disease: a case report
Authors: Al-Heilfi Anmar , Nataraja Champa , Cooley Helen , Batt Tracey 
Published: September 2021

AbstractBackgroundGraft-versus-host disease is a common complication seen with allogenic stem cell transplant, which is used to treat a variety of hematological malignancies. Graft-versus-host disease is an allogenic syndrome and can present in a variety of ways, including symptoms mimicking various autoimmune diseases; however, it is quite rare to see graft-versus-host disease affecting the vascular system and causing vasculitis.Case presentationWe describe a case of a 59-year-old Caucasian man with follicular lymphoma and diffuse large B-cell transformation who developed graft-versus-host disease post allogenic hematopoietic stem cell transplantation and later progressed to neurological complication foot drop and large-vessel vasculitis.ConclusionThe life-threatening vascular complications associated with large-vessel vasculitis include arterial aneurysms and dissections, and ischemic or hemorrhagic stroke. Thus, this rare immunological association needs to be recognized and treated in a timely manner to prevent the long-term complications.
Management of toxic optic neuropathy via a combination of Wharton’s jelly-derived mesenchymal stem cells with electromagnetic stimulation
Authors: Özmert Emin , Arslan Umut 
Published: September 2021

AbstractPurposeTo investigate the effect of the combination of Wharton's jelly derived mesenchymal stem cells (WJ-MSC) and high frequency repetitive electromagnetic stimulation (rEMS) in the therapy of toxic optic neuropathies with severe symptoms after the available current therapy modalities which were unsucessful.Material and methodsThis prospective, open-label clinical phase-3 study was conducted at Ankara University Faculty of Medicine, Department of Ophthalmology between April 2019 and April 2021. Thirty-six eyes of 18 patients with toxic optic neuropathy (TON) were included in the study. Within 1–3 months after the emergency interventions, patients with various degrees of sequela visual disturbances were studied in this clinical trial. The cases were divided into three groups according to similar demographic characteristics. Group 1: Consists of 12 eyes of 12 patients treated with the WJ-MSC and rEMS combination in one eye. Group 2: Consists of 12 eyes of 12 patients treated with only rEMS in one eye. Group 3: Consists of 12 eyes of six patients treated with only WJ-MSC in both eyes. The course was evaluated by comparing the quantitive functional and structural assessment parameters measured before and at the fourth month of applications in each group.ResultsThe mean best corrected visual acuity (BCVA) delta change percentages of the groups can be ranked as: Group 1 (47%) > Group 3 (32%) > Group 2 (21%). The mean fundus perimetry deviation index (FPDI) delta change percentages of the groups can be ranked as: Group 1 (95%) > Group 2 (33%) > Group 3 (27%). The mean ganglion cell complex (GCC) thickness delta change (decrease in thickness) percentages can be ranked as: Group 1 (− 21%) > Group 3 (− 15%) > Group 2 (− 13%). The visual evoked potential (VEP) P100 latency delta change percentages of the groups can be ranked as: Group 1 (− 18%) > Group 3 (− 10%) > Group 2 (− 8%). The P100 amplitude delta change percentages of the groups can be ranked as: Group 1 (105%) > Group 3 (83%) > Group 2 (24%).ConclusionToxic optic neuropathies are emergent pathologies that can result in acute and permanent blindness. After poisoning with toxic substances, progressive apoptosis continues in optic nerve axons and ganglion cells. After the proper first systemic intervention in intensive care clinic, the WJ-MSC and rEMS combination seems very effective in the short-term period in cases with TON. To prevent permanent blindness, a combination of WJ-MSC and rEMS application as soon as possible may increase the chance of success in currently untreatable cases.Trial RegistrationClinicalTrials.gov ID: NCT04877067.
Relationship between epicardial fat volume measured by multi-detector computed tomography and coronary artery disease
Authors: Taha Doaa Ashour , El Shafey Rasha Ahmed Ali , Hamesa Manal Fathy , Abu-Dewan Khaled Abd El-Wahab , Nagy Hanan Ahmad 
Published: September 2021

Abstract
Background
The association between epicardial fat thickness and coronary artery disease (CAD) has been evaluated previously using echocardiography. Recently, multidetector computed tomography (MDCT), as a valuable tool in cardiovascular CT imaging, can improve characterization of CAD and give a more accurate volumetric quantitation of EF. The purpose of our study was to evaluate the relationship between the epicardial fat volume and CAD using multi-detector row CT.

Results
Out of the studied 120 patients, 22 patients were negative for CAD, while 98 patients had positive CAD. There was significant difference between both groups as regard epicardial fat volume (p < 0.001), and good relation was found between the amount of epicardial fat volume and coronary calcium score, number of affected vessel, plaque burden and degree of stenosis (p =  < 0.001).

Conclusion
EAT volume was larger in the presence of obstructive CAD and atheromatous plaques. These data suggest that EAT is associated with the development of coronary atherosclerosis and potentially the most dangerous types of plaques.
CT of cardiac and extracardiac vascular anomalies: embryological implications
Authors: Kamel Dalia Wageeh , Abdelhameed Abeer Maghawry , Mohammad Shaimaa Abdelsattar , Abbas Sherif Nabil 
Published: September 2021

Abstract
Background
Congenital heart disease (CHD) is the most common neonatal anomaly. Extracardiac findings are commonly associated with CHD. It is mandatory to evaluate extracardiac structures for potential associated abnormalities that might impact the surgical planning for these patients. The purpose of this study was to determine the extracardiac abnormalities that could associate cardiac anomalies and to give insights into their embryological aberrations.

Results
Thirty-two pediatric patients (22 males and 10 females) underwent CT angiography to assess CHD. Diagnosis of the CHD and associated extracardiac findings were recorded and tabulated by organ system and type of CHD. Retrospective ECG-gated low-peak kilovoltage (80Kvp) technique was used on 128MDCT GE machine. Patients were diagnosed according to their CHD into four groups: chamber anomalies 90%, septal anomalies 81.3%, conotruncal anomalies 59.4%, and valvular anomalies 59.4%. Extracardiac findings were found in 28 patients (87.5%) with a total of 76 findings. Vascular findings were the most prevalent as 50 vascular findings were observed in 28 patients. Aortic anomalies were the commonest vascular anomalies. Fourteen thoracic findings were observed in 12 patients; of them lung consolidation patches were the most common and 12 abdominal findings were found in seven patients, most of findings were related to situs abnormalities.

Conclusion
Extracardiac abnormalities especially vascular anomalies are commonly associating CHD. Along with genetic basis, aberrations in dynamics of blood flow could represent possible causes of this association.
Pregnancy Outcome in Women With APECED (APS-1): A Multicenter Study on 43 Females With 83 Pregnancies
Authors: Laakso Saila , Holopainen Elina , Betterle Corrado , Saari Viivi , Vogt Elinor , Schmitt Monica M , Winer Karen K , Kareva Maria , Sabbadin Chiara , Husebye Eystein S , Orlova Elizaveta , Lionakis Michail S , Mäkitie Outi 
Published: September 2021

Abstract

Context
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED; also known as autoimmune polyendocrine syndrome type 1) has a severe, unpredictable course. Autoimmunity and disease components may affect fertility and predispose to maternal and fetal complications, but pregnancy outcomes remain unknown.

Objective
To assess fetal and maternal outcomes and course of clinical APECED manifestations during pregnancy in women with APECED.

Design and Setting
A multicenter registry-based study including 5 national patient cohorts.

Patients
321 females with APECED.

Main Outcome Measure
Number of pregnancies, miscarriages, and deliveries.

Results
Forty-three patients had altogether 83 pregnancies at median age of 27 years (range, 17–39). Sixty (72%) pregnancies led to a delivery, including 2 stillbirths (2.4%) and 5 (6.0%) preterm livebirths. Miscarriages, induced abortions, and ectopic pregnancies were observed in 14 (17%), 8 (10%), and 1 (1.2%) pregnancies, respectively. Ovum donation resulted in 5 (6.0%) pregnancies. High maternal age, premature ovarian insufficiency, primary adrenal insufficiency, or hypoparathyroidism did not associate with miscarriages. Women with livebirth had, on average, 4 APECED manifestations (range 0-10); 78% had hypoparathyroidism, and 36% had primary adrenal insufficiency. APECED manifestations remained mostly stable during pregnancy, but in 1 case, development of primary adrenal insufficiency led to adrenal crisis and stillbirth. Birth weights were normal in &gt;80% and apart from 1 neonatal death of a preterm baby, no serious perinatal complications occurred.

Conclusions
Outcome of pregnancy in women with APECED was generally favorable. However, APECED warrants careful maternal multidisciplinary follow-up from preconceptual care until puerperium.
Teaching Labor Laws: Evidence from a Randomized Control Trial in South Africa
Authors: Bertrand Marianne , Crépon Bruno 
Published: September 2021

We assess whether imperfect knowledge of labor regulation hinders job creation at small and medium-sized firms. We partner with a labor law expert organization that provides information about labor regulation via newsletters and access to a specialized website. We randomly assign 1,800 firms to get access to this service for a 21-week period. Six months later, the average employment level at treatment firms was 12 percent higher than at control firms. The intervention decreased the perception that labor regulation is a constraint to hiring and increased optimal employment level. (JEL D22, D83, J63, L25, K31, O15)
Accessibility, inclusivity, and implementation of COVID-19 clinical management guidelines early in the pandemic: a global survey
Authors: Pilbeam Caitlin , Malden Deborah , Newell Katherine , Dagens Andrew , Kennon Kalynn , Michelen Melina , Gobat Nina , Sigfrid Louise 
Published: September 2021

Background: With a rapidly changing evidence base, high-quality clinical management guidelines (CMGs) are key tools for aiding clinical decision making and increasing access to best available evidence-based care. A rapid review of COVID-19 CMGs found most lacked methodological rigour, overlooked at-risk populations, and varied in treatment recommendations. Furthermore, social science literature highlights the complexity of implementing guidelines in local contexts where they were not developed and the resulting potential to compound health inequities. This study aimed to evaluate access to, inclusivity of, and implementation of COVID-19 CMGs in different settings. Methods: A cross-sectional survey of clinicians worldwide was conducted from 15th June to 20th July 2020, to explore access to and implementation of COVID-19 CMGs, and treatment and supportive care recommendations provided. Data on accessibility, inclusivity, and implementation of CMGs were analysed by geographic location. Results: 76 clinicians from 27 countries responded: 82% from high-income countries, 17% from lower middle-income countries (LMICs). Most respondents reported access to COVID-19 CMGs and confidence in their implementation. However, many respondents, particularly from LMICs, reported barriers to implementation, including limited access to treatment and equipment. Only 20% of respondents reported having access to CMGs covering care for children, 25% for pregnant women, and 50% for older adults (>65 years). Identified themes were for CMGs to include recommendations for at-risk populations and settings, include supportive care guidance, and be updated as evidence emerges, and for clinicians to have training and access to recommended treatments to support implementation. Conclusion: Our findings highlight important gaps in COVID-19 CMG development and implementation challenges during a pandemic, particularly affecting at-risk populations and lower resourced settings. This study identifies an urgent need for an improved CMG development framework that is inclusive and adaptable to emerging evidence and considers contextual implementation support, to improve access to evidence-based care globally.