bluuebunny/crossref_metadata_2025 huggingface dataset:
Oncogenetic landscape and clinical impact of IDH1 and IDH2 mutations in T-ALL
Authors: Simonin Mathieu , Schmidt Aline , Bontoux Christophe , Dourthe Marie-Émilie , Lengliné Etienne , Andrieu Guillaume P. , Lhermitte Ludovic , Graux Carlos , Grardel Nathalie , Cayuela Jean-Michel , Huguet Françoise , Arnoux Isabelle , Ducassou Stéphane , Macintyre Elizabeth , Gandemer Virginie , Dombret Hervé , Petit Arnaud , Ifrah Norbert , Baruchel André , Boissel Nicolas , Asnafi Vahid
Published: May 2021

IDH1 and IDH2 mutations (IDH1/2Mut) are recognized as recurrent genetic alterations in acute myeloid leukemia (AML) and associated with both clinical impact and therapeutic opportunity due to the recent development of specific IDH1/2Mut inhibitors. In T-cell acute lymphoblastic leukemia (T-ALL), their incidence and prognostic implications remain poorly reported. Our targeted next-generation sequencing approach allowed comprehensive assessment of genotype across the entire IDH1 and IDH2 locus in 1085 consecutive unselected and newly diagnosed patients with T-ALL and identified 4% of, virtually exclusive (47 of 49 patients), IDH1/2Mut. Mutational patterns of IDH1/2Mut in T-ALL present some specific features compared to AML. Whereas IDH2R140Q mutation was frequent in T-ALL (25 of 51 mutations), the IDH2R172 AML hotspot was absent. IDH2 mutations were associated with older age, an immature phenotype, more frequent RAS gain-of-function mutations and epigenetic regulator loss-of-function alterations (DNMT3A and TET2). IDH2 mutations, contrary to IDH1 mutations, appeared to be an independent prognostic factor in multivariate analysis with the NOTCH1/FBXW7/RAS/PTEN classifier. IDH2Mut were significantly associated with a high cumulative incidence of relapse and very dismal outcome, suggesting that IDH2-mutated T-ALL cases should be identified at diagnosis in order to benefit from therapeutic intensification and/or specific IDH2 inhibitors.
Allogeneic hematopoietic cell transplantation with cord blood versus mismatched unrelated donor with post-transplant cyclophosphamide in acute myeloid leukemia
Authors: Dholaria Bhagirathbhai , Labopin Myriam , Sanz Jaime , Ruggeri Annalisa , Cornelissen Jan , Labussière-Wallet Hélène , Blaise Didier , Forcade Edouard , Chevallier Patrice , Grassi Anna , Zubarovskaya Ludmila , Kuball Jürgen , Ceballos Patrice , Ciceri Fabio , Baron Frederic , Savani Bipin N. , Nagler Arnon , Mohty Mohamad
Published: May 2021

Background

Allogeneic hematopoietic cell transplantation (allo-HCT) using a mismatched unrelated donor (MMUD) and cord blood transplantation (CBT) are valid alternatives for patients without a fully human leukocyte antigen (HLA)-matched donor. Here, we compared the allo-HCT outcomes of CBT versus single-allele-mismatched MMUD allo-HCT with post-transplant cyclophosphamide (PTCy) in acute myeloid leukemia.

Methods

Patients who underwent a first CBT without PTCy (N = 902) or allo-HCT from a (HLA 9/10) MMUD with PTCy (N = 280) were included in the study. A multivariate regression analysis was performed for the whole population. A matched-pair analysis was carried out by propensity score-based 1:1 matching of patients (177 pairs) with known cytogenetic risk.

Results

The incidence of grade II–IV and grade III–IV acute graft-versus-host disease (GVHD) at 6 months was 36% versus 32% (p = 0.07) and 15% versus 11% (p = 0.16) for CBT and MMUD cohorts, respectively. CBT was associated with a higher incidence of graft failure (11% vs. 4%, p < 0.01) and higher 2-year non-relapse mortality (NRM) (30% vs. 16%, p < 0.01) compared to MMUD. In the multivariate analysis, CBT was associated with a higher risk of, NRM (HR = 2.09, 95% CI 1.46–2.99, p < 0.0001), and relapse (HR = 1.35, 95% CI 1–1.83, p = 0.05), which resulted in worse leukemia-free survival (LFS) (HR = 1.68, 95% CI 1.34–2.12, p < 0.0001), overall survival (OS) (HR = 1.7, 95% CI 1.33–2.17, p < 0.0001), and GVHD-free, relapse-free survival (GRFS) (HR = 1.49, 95% CI 1.21–1.83, p < 0.0001) compared to MMUD. The risk of grade II–IV acute GVHD (p = 0.052) and chronic GVHD (p = 0.69) did not differ significantly between the cohorts. These results were confirmed in a matched-pair analysis.

Conclusions

CBT was associated with lower LFS, OS, and GRFS due to higher NRM, compared to MMUD allo-HCT with PTCy. In the absence of a fully matched donor, 9/10 MMUD with PTCy may be preferred over CBT.
Functional and genetic determinants of mutation rate variability in regulatory elements of cancer genomes
Authors: Lee Christian A. , Abd-Rabbo Diala , Reimand Jüri
Published: May 2021

Background

Cancer genomes are shaped by mutational processes with complex spatial variation at multiple scales. Entire classes of regulatory elements are affected by local variations in mutation frequency. However, the underlying mechanisms with functional and genetic determinants remain poorly understood.

Results

We characterise the mutational landscape of 1.3 million gene-regulatory and chromatin architectural elements in 2419 whole cancer genomes with transcriptional and pathway activity, functional conservation and recurrent driver events. We develop RM2, a statistical model that quantifies mutational enrichment or depletion in classes of genomic elements through genetic, trinucleotide and megabase-scale effects. We report a map of localised mutational processes affecting CTCF binding sites, transcription start sites (TSS) and tissue-specific open-chromatin regions. Increased mutation frequency in TSSs associates with mRNA abundance in most cancer types, while open-chromatin regions are generally enriched in mutations. We identify ~ 10,000 CTCF binding sites with core DNA motifs and constitutive binding in 66 cell types that represent focal points of mutagenesis. We detect site-specific mutational signature enrichments, such as SBS40 in open-chromatin regions in prostate cancer and SBS17b in CTCF binding sites in gastrointestinal cancers. Candidate drivers of localised mutagenesis are also apparent: BRAF mutations associate with mutational enrichments at CTCF binding sites in melanoma, and ARID1A mutations with TSS-specific mutagenesis in pancreatic cancer.

Conclusions

Our method and catalogue of localised mutational processes provide novel perspectives to cancer genome evolution, mutagenesis, DNA repair and driver gene discovery. The functional and genetic correlates of mutational processes suggest mechanistic hypotheses for future studies.
The effect of omega-3 long chain polyunsaturated fatty acids on aggressive behaviour in adult male prisoners: a structured study protocol for a multi-centre, double-blind, randomised placebo-controlled trial and translation into policy and practice
Authors: Meyer Barbara J. , Byrne Mitchell K. , Cortie Colin H. , Parletta Natalie , Jones Alison , Eckermann Simon , Butler Tony , Greenberg David , Batterham Marijka , Fernandez Francesca , Schofield Peter W. , Winberg Pia C. , Bowles Kate , Dally Jean , Martin Anne-Maria , Grant Luke
Published: May 2021

Background

Interventions to better manage aggressive behaviour and reduce recidivism are a primary concern for corrective services. Nutritional interventions to correct prisoner behaviour have been largely overlooked in the literature. Emerging evidence suggests that dietary intake influences aggressive behaviours and that nutritional supplementation with omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) could attenuate both the severity and frequency of aggressive behaviour.

Methods

Adult male prisoners who have a history of aggressive behaviour (n = 600) will be recruited from at least 6 Correctional Centres and randomised to receive either n-3 LCPUFA or placebo supplementation for a 16-week duration. Treatment will be with either 1 g/day of n-3 LCPUFA (694 mg DHA and 397 mg EPA) or placebo capsules, which are a corn/soy oil blend and are identical in size and colour.

The primary outcome measure is the Inmate Behavioural Observation Scale (IBOS): an objective measure of aggressive behaviour. Secondary outcome measures include questionnaires (including aggression, attention deficit disorder, impulsivity, depression/anxiety/stress scales), engagement in programmes, recidivism and quality of life. Baseline and post-intervention assessments include the IBOS, questionnaires and blood to measure the levels of n-3 LCPUFA.

Discussion

To conclusively test the potential that increasing n-3 LCPUFA intakes can improve rates of prisoner aggression and associated mental health and violence-related social system management costs, we propose an adequately powered multi-centre, double-blind, randomised controlled trial, examining the effects of n-3 LCPUFA supplementation on aggressive behaviour in adult male prisoners. If successful, this study will inform prisoner policy with respect to nutrition and by inference contribute to a broader community approach to preventative mental health practices.

Trial registration

Australian New Zealand Clinical Trial Registry (ANZCTR)ACTRN12618001665224. Registered on 10 October 2018.
Assessing the suitability of mitochondrial and nuclear DNA genetic markers for molecular systematics and species identification of helminths
Authors: Chan Abigail Hui En , Chaisiri Kittipong , Saralamba Sompob , Morand Serge , Thaenkham Urusa
Published: May 2021

Background

Genetic markers are employed widely in molecular studies, and their utility depends on the degree of sequence variation, which dictates the type of application for which they are suited. Consequently, the suitability of a genetic marker for any specific application is complicated by its properties and usage across studies. To provide a yardstick for future users, in this study we assess the suitability of genetic markers for molecular systematics and species identification in helminths and provide an estimate of the cut-off genetic distances per taxonomic level.

Methods

We assessed four classes of genetic markers, namely nuclear ribosomal internal transcribed spacers, nuclear rRNA, mitochondrial rRNA and mitochondrial protein-coding genes, based on certain properties that are important for species identification and molecular systematics. For molecular identification, these properties are inter-species sequence variation; length of reference sequences; easy alignment of sequences; and easy to design universal primers. For molecular systematics, the properties are: average genetic distance from order/suborder to species level; the number of monophyletic clades at the order/suborder level; length of reference sequences; easy alignment of sequences; easy to design universal primers; and absence of nucleotide substitution saturation. Estimation of the cut-off genetic distances was performed using the ‘K-means’ clustering algorithm.

Results

The nuclear rRNA genes exhibited the lowest sequence variation, whereas the mitochondrial genes exhibited relatively higher variation across the three groups of helminths. Also, the nuclear and mitochondrial rRNA genes were the best possible genetic markers for helminth molecular systematics, whereas the mitochondrial protein-coding and rRNA genes were suitable for molecular identification. We also revealed that a general gauge of genetic distances might not be adequate, using evidence from the wide range of genetic distances among nematodes.

Conclusion

This study assessed the suitability of DNA genetic markers for application in molecular systematics and molecular identification of helminths. We provide a novel way of analyzing genetic distances to generate suitable cut-off values for each taxonomic level using the ‘K-means’ clustering algorithm. The estimated cut-off genetic distance values, together with the summary of the utility and limitations of each class of genetic markers, are useful information that can benefit researchers conducting molecular studies on helminths.

Graphical Abstract
Physiological characterization of chitin synthase A responsible for the biosynthesis of cuticle chitin in Culex pipiens pallens (Diptera: Culicidae)
Authors: Yang Xiaoshan , Xu Yang , Yin Qi , Zhang Hongbo , Yin Haitao , Sun Yan , Ma Lei , Zhou Dan , Shen Bo
Published: May 2021

Background

The pathogens transmitted by mosquitoes to humans and animals cause several emerging and resurgent infectious diseases. Increasing insecticide resistance requires rational action to control the target vector population. Chitin is indispensable for insect growth and development and absent from vertebrates and higher plants. Chitin synthase A (CHSA) is a crucial enzyme in chitin synthesis; therefore, identifying and characterizing how CHSA determines chitin content may contribute to the development of novel vector control strategies.

Results

The injection of small interfering RNA targeting CHSA (siCHSA) to knockdown CHSA transcripts in larval, pupal and adult stages of Culex pipiens pallens resulted in the appearance of different lethal phenotypes. When larval and pupal stages were injected with siCHSA, CHSA knockdown prevented larval molting, pupation and adult eclosion, and affected the production of chitin and chitin degradation, which resulted in an ecdysis defect phenotype of mosquitoes. When siCHSA was injected into mosquitoes in the adult stage, CHSA knockdown also affected the laminar organization of the mesoderm and the formation of pseudo-orthogonal patterns of the large fibers of the endoderm.

Conclusion

We provide a systematic and comprehensive description of the effects of CHSA on morphogenesis and metamorphosis. The results show that CHSA not only affects chitin synthesis during molting, but also might be involved in chitin degradation. Our results further show that CHSA is important for the structural integrity of the adult mosquito cuticle.

Graphical Abstract
Three putative DNA methyltransferases of Verticillium dahliae differentially contribute to DNA methylation that is dispensable for growth, development and virulence
Authors: Kramer H. Martin , Cook David E. , van den Berg Grardy C. M. , Seidl Michael F. , Thomma Bart P. H. J.
Published: May 2021

Background

DNA methylation is an important epigenetic control mechanism that in many fungi is restricted to genomic regions containing transposable elements (TEs). Two DNA methyltransferases, Dim2 and Dnmt5, are known to perform methylation at cytosines in fungi. While most ascomycete fungi encode both Dim2 and Dnmt5, only few functional studies have been performed in species containing both.

Methods

In this study, we report functional analysis of both Dim2 and Dnmt5 in the plant pathogenic fungus Verticillium dahliae.

Results

Our results show that Dim2, but not Dnmt5 or the putative sexual-cycle-related DNA methyltransferase Rid, is responsible for the majority of DNA methylation under the tested conditions. Single or double DNA methyltransferase mutants did not show altered development, virulence, or transcription of genes or TEs. In contrast, Hp1 and Dim5 mutants that are impacted in chromatin-associated processes upstream of DNA methylation are severely affected in development and virulence and display transcriptional reprogramming in specific hypervariable genomic regions (so-called adaptive genomic regions) that contain genes associated with host colonization. As these adaptive genomic regions are largely devoid of DNA methylation and of Hp1- and Dim5-associated heterochromatin, the differential transcription is likely caused by pleiotropic effects rather than by differential DNA methylation.

Conclusion

Overall, our study suggests that Dim2 is the main DNA methyltransferase in V. dahliae and, in conjunction with work on other fungi, is likely the main active DNMT in ascomycetes, irrespective of Dnmt5 presence. We speculate that Dnmt5 and Rid act under specific, presently enigmatic, conditions or, alternatively, act in DNA-associated processes other than DNA methylation.
Wellmap: a file format for microplate layouts
Authors: Kundert Kale
Published: May 2021

Objective

Microplates are ubiquitous in biological research because they make it easy to collect data for hundreds of different conditions in a single experiment. Despite this, there is no standard method to annotate the wealth of data contained in each plate.

Results

We introduce a new file format, called wellmap, for describing the layout of wells on microplates. The format is text-based and emphasizes being easy to read, write, and share. It is capable of describing any layout for any experiment. It is also accompanied by a tool for generating clear visualizations of layout files, and a simple API for parsing layout files in analysis scripts written in python or R. We have used wellmap in our own research to annotate data from a wide variety of experiments, including qPCR and flow cytometry. Given the large number of experiments that make use of microplates, it is our hope that other researchers will find this file format as useful as we have. For complete instructions on how to install and use wellmap, visit: https://wellmap.rtfd.io.
Acceptability, feasibility and implementation of a web-based U.S. Health Insurance Navigation Tool (HINT)
Authors: Zheng Caiwei , Caban-Martinez Alberto J.
Published: May 2021

Objective

In the U.S., health insurance is a crucial determinant of the affordability of healthcare services and access to care. Population-based studies indicate Americans do not have an adequate understanding of their insurance plans and face difficulties navigating their health insurance coverage. The purpose of this pilot study is to collect qualitative data using a key informant interview format to learn about the acceptability, feasibility and implementation of a newly devised online health insurance navigation tool (HINT).

Results

A total of 57 Florida residents completed the 18-item HINT web-based survey tool and provided feedback on their experience, of which 63.2% were women, 40.7% Black race, and had average sample age of 46.9 years. Participants reported the web tool to be of good length, easy readability, relevant, and overall helpful for insurance selection. All respondents reported that they would use the tool themselves should they find themselves in the process of selecting an insurance plan and 98.2% of respondents reported that they would suggest the web tool to a family or friend. The average time it took to complete the questionnaire was 4 min and 20 s.The HINT tool met study criteria on feasibility, implementation, and acceptability among study participants.
Classification of non-acute bronchial asthma according to allergy and eosinophil characteristics: a retrospective study
Authors: Jiang Yi , An Ruoli , Cheng Li , Yue Qianru , Zhang Hanwei , Zhang Yali , Kong Xiaomei , Ma Hongxia , Chen Fang , Guo Yufeng
Published: May 2021

Background

Investigating the endotypes of the different asthma phenotypes would help disease monitoring, prognosis determination, and improving asthma management standardization. This study aimed to classify asthma into four endotypes according to the allergic and eosinophilic characteristics and explore the phenotypes (clinical characteristics, pulmonary functions, and fractional expired nitric oxide (FeNO)) of each endotype.

Methods

This retrospective study included non-acute asthma patients treated at the First Hospital of Shanxi Medical University (05/2016–01/2018). The patients were classified into the eosinophilic allergic, eosinophilic non-allergic, non-eosinophilic allergic, and non-eosinophilic non-allergic asthma endotypes. Serum sIgE, lung function, FeNO, and induced sputum cytology were tested and compared among groups.

Results

Of the 171 included patients, 22 had eosinophilic allergic asthma, 17 had eosinophilic non-allergic asthma, 66 had non-eosinophilic allergic asthma, and 66 had non-eosinophilic non-allergic asthma. Lung function measurements (FEV1%, FEF25%, FEF50%, FEF75%, and FEF25–75%) showed that airway dysfunction was worse in eosinophilic non-allergic asthma than in the other three endotypes (all P < 0.001). In allergic asthma patients, eosinophilic asthma had worse airway dysfunction than non-eosinophilic asthma (all P < 0.05). Similar results were found in non-allergic asthma (all P < 0.01). The FeNO levels in eosinophilic allergic asthma were higher than in eosinophilic non-allergic and non-eosinophilic non-allergic asthma (both P = 0.001).

Conclusions

FeNO can objectively reflect eosinophilic airway inflammation in asthma. Endotypic classification of asthma patients regarding the allergic and eosinophilic characteristics is conducive to the effective management of patients with asthma.
Understanding PI-QUAL for prostate MRI quality: a practical primer for radiologists
Authors: Giganti Francesco , Kirkham Alex , Kasivisvanathan Veeru , Papoutsaki Marianthi-Vasiliki , Punwani Shonit , Emberton Mark , Moore Caroline M. , Allen Clare
Published: May 2021

Prostate magnetic resonance imaging (MRI) of high diagnostic quality is a key determinant for either detection or exclusion of prostate cancer. Adequate high spatial resolution on T2-weighted imaging, good diffusion-weighted imaging and dynamic contrast-enhanced sequences of high signal-to-noise ratio are the prerequisite for a high-quality MRI study of the prostate. The Prostate Imaging Quality (PI-QUAL) score was created to assess the diagnostic quality of a scan against a set of objective criteria as per Prostate Imaging-Reporting and Data System recommendations, together with criteria obtained from the image. The PI-QUAL score is a 1-to-5 scale where a score of 1 indicates that all MR sequences (T2-weighted imaging, diffusion-weighted imaging and dynamic contrast-enhanced sequences) are below the minimum standard of diagnostic quality, a score of 3 means that the scan is of sufficient diagnostic quality, and a score of 5 implies that all three sequences are of optimal diagnostic quality. The purpose of this educational review is to provide a practical guide to assess the quality of prostate MRI using PI-QUAL and to familiarise the radiologist and all those involved in prostate MRI with this scoring system. A variety of images are also presented to demonstrate the difference between suboptimal and good prostate MR scans.
Third time recurrent Boerhaave’s syndrome: a case report
Authors: Zeyara Adam , Jeremiasen Martin , Åkesson Oscar , Falkenback Dan , Hermansson Michael , Johansson Jan
Published: May 2021

Background

Effort rupture of the esophagus or Boerhaave’s syndrome is a rare entity, and prognosis is largely dependent on early diagnosis and treatment. Recurrent effort ruptures are very rare, only reported in a few case reports in English literature. We present a case with a third time effort rupture, and to the best of our knowledge there are no such previous publications. Furthermore, the presented case is also distinct because each episode was treated by different methods, reflecting the pathophysiology of recurrent disease as well as the last decade’s advancements in the management of esophageal perforations in our clinic and globally.

Case presentation

The patient is a 60-year-old White male, suffering from alcohol abuse, mild reflux esophagitis, and a history of effort esophageal ruptures on two previous occasions. He was now admitted to our ward once again because of a third bout of Boerhaave’s syndrome. The first time, 10 years ago, he was managed by thoracotomy and laparotomy with primary repair, and the second time, 5 years ago, by transhiatal mediastinal drainage through a laparotomy and endoscopic stent placement. Now he was successfully managed by endovascular vacuum-assisted closure therapy alone.

Conclusions

Recurrent cases of Boerhaave’s syndrome are very rare, and treatment must be tailored individually. The basic rationale is, however, no different from primary disease: (1) early diagnosis, (2) adequate drainage of extraesophageal contamination, and (3) restoration of esophageal integrity. Recurrent disease is usually contained and exceptionally suitable for primary endoscopic treatment. To cover the full panorama and difficult nature of complex esophageal disease, endoscopic modalities such as stent placement and endovascular vacuum-assisted closure, as well as the capacity for prompt extensive surgical interventions such as esophagectomy, should be readily accessible within every modern esophageal center.
Postpartum maternal collapse—a first-time presentation of severe mitral stenosis: a case report
Authors: Fessehaye Abraham , Tafere Yared Teshome , Abate Desalegn Degafu
Published: May 2021

Background

Among cardiac causes for postpartum maternal collapse, severe mitral stenosis is not listed as a potential cause in current literature. We report a rare case of severe mitral stenosis that presented with severe hypoxia and maternal decompensation in early postpartum period for the first time.

Case summary

A 30-year-old para 2, abortus 1, Ethiopian woman developed severe hypoxia and rapid deterioration on her sixth postoperative day after cesarean delivery for fetal bradycardia with a good fetal outcome. She was put on a mechanical ventilator when she developed respiratory failure. Initially, a diagnosis of pulmonary embolus was considered. After admission to the intensive care unit, severe mitral stenosis was diagnosed with the help of echocardiography. She was managed successfully for congestive heart failure and discharged from the intensive care unit with improvement.

Conclusion

The possibility of mitral stenosis, as a differential diagnosis, should be considered whenever a case of postpartum maternal collapse is encountered. We recommend a routine immediate echocardiography in any patient that experiences postpartum collapse, especially in the presence of a known trigger for heart failure such as long hours of labor, bleeding, anemia, hypotension, and infection.
Abdominal actinomycosis mimicking a transverse colon malignancy: a case report and review of the literature
Authors: Pamathy Gnanaselvam , Jayarajah Umesh , Gamlaksha Dayal Sathyajith , Constantine Roshana , Banagala Anura S. K.
Published: May 2021

Background

Actinomycosis is a rare inflammatory bacterial disease caused byActinomycesspecies which can infrequently affect the large intestine. Disseminated actinomycosis is reported as a rare complication associated with intrauterine devices. We report a case of intra-abdominal actinomycosis mimicking a transverse colon malignancy.

Case presentation

A previously healthy 40-year-old Sinhalese woman was evaluated for intermittent colicky left-sided abdominal pain for 2 months’ duration. Computed tomography of the abdomen showed a circumferential thickening of the wall and narrowing of the lumen of the descending colon with evidence of extraluminal extension to the adjacent parietal peritoneum and abdominal wall suggestive of a stage IV neoplasm. An exploratory laparotomy with extended left hemicolectomy was performed. Macroscopic evaluation revealed a mass lesion with multiple abscesses attached to the transverse and descending colon. Histology was suggestive of actinomycosis with no evidence of malignancy.

Conclusions

Abdominal actinomycosis should be considered in a young patient with chronic abdominal pain. It should be understood that the presentation may be vague and highly variable. Computed tomography-guided biopsy/fine needle aspiration or laparoscopy and biopsy may be useful in arriving at a diagnosis and can prevent unnecessary surgical intervention.
Primary Epstein–Barr virus infection shortly after primary Cytomegalovirus infection: a case report
Authors: Koyama Katsumasa , Anno Takatoshi , Urano Takashi , Shigemoto Ryo , Irie Shintaro , Kawasaki Fumiko , Kawanaka Miwa , Kawamoto Hirofumi , Kaneto Hideaki , Tomoda Koichi
Published: May 2021

Background

Infectious mononucleosis (IM) and mononucleosis-like illnesses are common viral infectious diseases which are often accompanied by a high fever, pharyngitis and lymphadenopathy in adults, although such infection in childhood is generally subclinical. Most cases of IM are caused by the Epstein–Barr virus (EBV) or Cytomegalovirus (CMV). However, it is difficult to diagnose IM only with subjective symptoms, and thus EBV and CMV are nearly indistinguishable in clinical practice.

Case presentation

A 20-year-old healthy Japanese woman had a 2-day history of high fever and consulted us. She had sex for the first time 6 months earlier. Her virus antibodies showed that she was infected with primary CMV. About 5 months later, she again experienced high fever and lymph node enlargement at the posterior cervical region. Her virus antibodies showed that she was infected with primary EBV at that time.

Conclusion

Herein, we report a healthy adult Japanese woman with primary EBV infection relatively soon after primary CMV infection. It is very interesting to compare the symptoms and/or clinical data after EBV and CMV infection in the same patient within a short period of time. Our patient was diagnosed based only on subjective symptoms, physical examination and laboratory data, without tests of such virus-related antibodies. Therefore, clinicians should bear in mind that primary EBV infection and/or primary CMV infection is possible when patients have symptoms such as high fever, pharyngitis and lymphadenopathy, even in healthy adults.
Ultrasound enhances the therapeutic potential of mesenchymal stem cells wrapped in greater omentum for aristolochic acid nephropathy
Authors: Yang Yuanjun , Geng Xiaodong , Chi Kun , Liu Chao , Liu Ran , Chen Xiangmei , Hong Quan , Cai Guangyan
Published: May 2021

Background

Mesenchymal stem cells (MSCs) have been reported to promote regeneration in both subjects with acute kidney injury (AKI) and chronic kidney disease (CKD), but their efficacy remains limited, probably because most of the cells accumulate in the lungs, liver, and spleen after an intravenous infusion. Therefore, ultrasound-guided administration of MSCs represents a possible approach to solve this problem. The greater omentum is used to promote cell survival due to its rich vasculature. We hypothesized that ultrasound-guided administration of MSCs combined with greater omentum might be more curative than currently available approaches.

Methods

In this study, we established an aristolochic acid nephropathy (AAN) model by intraperitoneally administering aristolochic acid I sodium salt (AA-I) at a dose of 5 mg/kg body weight on alternate days for 4 weeks. Subsequently, a laparotomy was performed, and the left kidney from which the capsule had been removed was wrapped with the greater omentum. A dose of 2 × 107 MSCs was injected into the space between the greater omentum and the left kidney. Equal amounts of MSCs were administered under ultrasound guidance every second week for a total of 4 treatments. Mice were sacrificed 4 weeks after surgery. Serum creatinine and blood urea levels were measured to assess renal function. qPCR, Western blot, and histological analyses were conducted to further investigate the therapeutic mechanism of MSCs.

Results

Ultrasound-guided injection of MSCs into the greater omentum that surrounds the kidney enriched cells in the kidney region for up to 5 days. Renal function tests indicated that MSCs improved renal function to a great extent, as reflected by decreased blood urea nitrogen and serum creatinine levels. In addition, histological analyses showed that MSCs noticeably attenuated kidney injury, as evidenced by the amelioration of tubular necrosis and peritubular interstitial fibrosis. Mitigation of renal interstitial fibrosis was further confirmed by immunohistochemistry, qPCR, and western blotting after MSC treatment. Moreover, immunofluorescence staining revealed that MSCs alleviated inflammatory responses by increasing the counts of CD206+ cells and decreasing the counts of CD68+ cells. MSC migration was initiated in response to AA-I-treated renal epithelial cells in an in vitro migration assay.

Conclusions

These findings suggested that administration of MSCs into the cavity formed by the injured kidney and the greater omentum under ultrasound guidance improved renal function, attenuated kidney injury, and mitigated renal interstitial fibrosis and inflammatory responses. Thus, this approach might be a safe and effective therapy for CKD.
The implications of herd entrustment practice for the sustainable use of cattle genetic resources in the (agro)-pastoral systems of West Africa: A case study from Benin
Authors: Vanvanhossou Sèyi Fridaïus Ulrich , Koura Ivan Bossima , Dossa Luc Hippolyte
Published: May 2021

West African (agro)-pastoralists have been increasingly using extra-household labour for the management of their cattle herds. This paper seeks to identify the factors influencing cattle owners’ decision to entrust their animals and to analyse the effects of the entrustment practice on the management and sustainable use of the animal genetic diversity within herds. Two hundred and eleven cattle farmers, including absentee-owners (n = 90) who entrusted their animals to professional herders, and owner-managers (n = 121) who look themselves after their cattle, were randomly selected and surveyed in Boukombe district in northwest Benin, the origin of the West African shorthorn Somba cattle breed. Households' socio-economic data and information on herds’ characteristics and management practices were collected using semi-structured questionnaires. The binary logistic regression technique was used to predict the adoption of entrustment by a given farmer in function of his herd’s and household's socio-economic characteristics. Effective population sizes and inbreeding rates for the communal non-entrusted and entrusted Somba populations were estimated and compared. The results revealed that the mode of acquisition of the initial stock, the total livestock units owned and the farmer’s ethnicity were the most important determinants of entrustment. The Somba indigenous cattle breed was threatened in entrusted herds by indiscriminate cross-breeding with Zebus. However, the non-entrusted population appeared to be more exposed to high inbreeding risks. While entrustment represents a good alternative for the efficient use of family labour, adequate strategies are needed to support this practice and encourage herd managers to adopt improved husbandry practices and sound breeding strategies.
McDonald versus Shirodkar cerclage technique in women requiring a prophylactic cerclage: a systematic review and meta-analysis protocol
Authors: Issah Ashad , Diacci Rosanna , Williams Kimberley P. , Aubin Anne-Marie , McAuliffe Liam , Phung Jason , Wang Carol , Maouris Panos , Pennell Craig E.
Published: May 2021

Background

Preterm birth (PTB) is the leading cause of death in children under five years. Spontaneous preterm birth (SPTB) is the major cause of preterm delivery. The key risk factors for SPTB are women who have a short cervix and women who have had previous preterm birth. Cervical cerclage has been used for several decades and has shown to decrease rates of preterm birth. The most commonly used cerclage techniques were described by Shirodkar and McDonald, with no current consensus on the preferred technique. The objective of this review is to determine and compare the effectiveness of both techniques.

Methods

Studies will be sourced from six electronic databases, as well as from experts in the field, reference lists, and grey literature. Eligible studies will include pregnant women, with a singleton or twin pregnancy, requiring a cervical cerclage, using either the Shirodkar or McDonald technique and run comparative analyses between the two techniques. Randomized control trials (RCT)s, non-randomized control trials, and cohort studies will be eligible. Two independent reviewers will conduct study screening at abstract and full-text level, data extraction and risk of bias assessment. Discrepancies will be resolved by a consensus third reviewer if required. Fixed-effects or random-effects models will be used where appropriate to synthesize results. Alternative synthesis methods will be investigated in instances where a meta-analysis is not appropriate, such as summarizing effect estimates, combiningPvalues, vote counting based on direction of effect, or synthesis in narrative form.

Discussion

This review will synthesize the evidence on both the Shirodkar and McDonald cerclage method, and will help clinicians and health services to determine and deliver best practice antenatal care that has the potential to make an impact on preterm birth.

Systematic review registration

PROSPERO on 25 of May, 2020 with registration numberCRD42020177386
Global bifurcation and constant sign solutions of discrete boundary value problem involving p-Laplacian
Authors: Ye Fumei
Published: May 2021

We study the unilateral global bifurcation result for the one-dimensional discrete p-Laplacian problem $$ \textstyle\begin{cases} -\Delta [\varphi _{p}(\Delta u(t-1))]=\lambda a(t)\varphi _{p}(u(t))+g(t,u(t), \lambda ),\quad t\in [1,T+1]_{Z}, \\ \Delta u(0)=u(T+2)=0, \end{cases} $$

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)
)
]
=
λ
a
(
t
)

φ
p

(
u
(
t
)
)
+
g
(
t
,
u
(
t
)
,
λ
)
,

t
∈

[
1
,
T
+
1
]

Z

,

Δ
u
(
0
)
=
u
(
T
+
2
)
=
0
,

where $\Delta u(t)=u(t+1)-u(t)$
Δ
u
(
t
)
=
u
(
t
+
1
)
−
u
(
t
)
is a forward difference operator, $\varphi _{p}(s)=|s|^{p-2}s$

φ
p

(
s
)
=

|
s
|

p
−
2

s
($1< p<+\infty $
1
<
p
<
+
∞
) is a one-dimensional p-Laplacian operator. λ is a positive real parameter, $a: [1,T+1]_{Z}\to [0,+\infty )$
a
:

[
1
,
T
+
1
]

Z

→
[
0
,
+
∞
)
and $a(t_{0})>0$
a
(

t
0

)
>
0
for some $t_{0}\in [1,T+1]_{Z}$

t
0

∈

[
1
,
T
+
1
]

Z

, $g :[1,T+1]_{Z}\times \mathbb{R}^{2}\to \mathbb{R}$
g
:

[
1
,
T
+
1
]

Z

×

R
2

→
R
satisfies the Carathéodory condition in the first two variables. We show that $(\lambda _{1},0)$
(

λ
1

,
0
)
is a bifurcation point of the above problem, and there are two distinct unbounded continua $\mathscr{C}^{+}$

C
+

and $\mathscr{C}^{-}$

C
−

, consisting of the bifurcation branch $\mathscr{C}$
C
from $(\lambda _{1},0)$
(

λ
1

,
0
)
, where $\lambda _{1}$

λ
1

is the principal eigenvalue of the eigenvalue problem corresponding to the above problem. Let $T>1$
T
>
1
be an integer, Z denote the integer set for $m, n\in Z$
m
,
n
∈
Z
with $m< n$
m
<
n
, $[m, n]_{Z}:=\{m, m+1,\ldots , n\}$

[
m
,
n
]

Z

:
=
{
m
,
m
+
1
,
…
,
n
}
.

As the applications of the above result, we prove more details about the existence of constant sign solutions for the following problem: $$ \textstyle\begin{cases} -\Delta [\varphi _{p}(\Delta u(t-1))]=\lambda a(t)f(u(t)),\quad t\in [1,T+1]_{Z}, \\ \Delta u(0)=u(T+2)=0, \end{cases} $$

{

−
Δ
[

φ
p

(
Δ
u
(
t
−
1
)
)
]
=
λ
a
(
t
)
f
(
u
(
t
)
)
,

t
∈

[
1
,
T
+
1
]

Z

,

Δ
u
(
0
)
=
u
(
T
+
2
)
=
0
,

where $f\in C(\mathbb{R},\mathbb{R})$
f
∈
C
(
R
,
R
)
with $sf(s)>0$
s
f
(
s
)
>
0
for $s\neq 0$
s
≠
0
.
Solving partial fractional differential equations by using the Laguerre wavelet-Adomian method
Authors: Aghazadeh Nasser , Mohammadi Amir , Ahmadnezhad Ghader , Rezapour Shahram
Published: May 2021

By using a nonlinear method, we try to solve partial fractional differential equations. In this way, we construct the Laguerre wavelets operational matrix of fractional integration. The method is proposed by utilizing Laguerre wavelets in conjunction with the Adomian decomposition method. We present the procedure of implementation and convergence analysis for the method. This method is tested on fractional Fisher’s equation and the singular fractional Emden–Fowler equation. We compare the results produced by the present method with some well-known results.
On a nonlinear dynamical system with both chaotic and nonchaotic behaviors: a new fractional analysis and control
Authors: Baleanu Dumitru , Sajjadi Samaneh Sadat , Jajarmi Amin , Defterli Özlem
Published: May 2021

In this paper, we aim to analyze the complicated dynamical motion of a quarter-car suspension system with a sinusoidal road excitation force. First, we consider a new mathematical model in the form of fractional-order differential equations. In the proposed model, we apply the Caputo–Fabrizio fractional operator with exponential kernel. Then to solve the related equations, we suggest a quadratic numerical method and prove its stability and convergence. A deep investigation in the framework of time-domain response and phase-portrait shows that both the chaotic and nonchaotic behaviors of the considered system can be identified by the fractional-order mathematical model. Finally, we present a state-feedback controller and a chaos optimal control to overcome the system chaotic oscillations. Simulation results demonstrate the effectiveness of the proposed modeling and control strategies.
New dynamic Hilbert-type inequalities in two independent variables involving Fenchel–Legendre transform
Authors: El-Deeb A. A. , Rashid Saima , Khan Zareen A. , Makharesh S. D.
Published: May 2021

In this paper, we establish some dynamic Hilbert-type inequalities in two independent variables on time scales by using the Fenchel–Legendre transform. We also apply our inequalities to discrete and continuous calculus to obtain some new inequalities as particular cases. Our results give more general forms of several previously established inequalities.
Does it pay to switch from free grazing to stall feeding? Impact of stall feeding practice on household welfare in Tigrai Ethiopia
Authors: Hadush Muuz
Published: May 2021

In this paper, efforts were made to the impact of full and seasonal stall feeding technology on households’ economic, ecological, and social welfare outcome indicators in rural Northern Ethiopia using data obtained from the survey of 518 rural farmers. In order to address our primary objective, an endogenous switching regression model was applied. The overall result indicated that SF adoption ensures significant gains in terms of the specified outcome indicators. Using endogenous switching regression models, we estimated different outcome indicators for both adopters from adoption (ATT), and non-adopters had they adopted (ATU). It is identified that there would be a decline of 21% in milk production and productivity if adopters would not have adopted this technology while non-adopters are estimated to increase their milk production and productivity by 100 and 48% if they would adopt this technology. The results further show that SF adoption had a significant increment in the lactation period. An increase of consumption expenditure by 17% from FSF and 44% in the case of SSF could be considered significant on livelihoods for smallholder farmers. On average, adoption of SF increased manure use in the range of 258–294 kg for adopters. The results showed that SF has decreased the propensity of hiring labor by about 29% and purchase of animal feed by 31%. We have found that participation in SF, on average, decreased total cattle stock by 1 TLU but increased the probability of keeping milking cow by 23%. The adoption of SF increased the likelihood of participating in an animal sale market by 29% for adopters and by 47% for non-adopters had they decided to adopt. The adoption of SF leads to a gain in a number of plants of 11 trees and 29 m of physical construction for the typical adopter and 36 trees and 133 m if the typical non-adopter were to adopt the SF technology on their plots. The adoption process also increased the propensity of growing trees by 19% and decreased household animal shock experience by a probability of 19% for adopters and about 15%.
The landscape of chromatin accessibility in skeletal muscle during embryonic development in pigs
Authors: Yue Jingwei , Hou Xinhua , Liu Xin , Wang Ligang , Gao Hongmei , Zhao Fuping , Shi Lijun , Shi Liangyu , Yan Hua , Deng Tianyu , Gong Jianfei , Wang Lixian , Zhang Longchao
Published: May 2021

Background

The development of skeletal muscle in pigs during the embryonic stage is precisely regulated by transcriptional mechanisms, which depend on chromatin accessibility. However, how chromatin accessibility plays a regulatory role during embryonic skeletal muscle development in pigs has not been reported. To gain insight into the landscape of chromatin accessibility and the associated genome-wide transcriptome during embryonic muscle development, we performed ATAC-seq and RNA-seq analyses of skeletal muscle from pig embryos at 45, 70 and 100 days post coitus (dpc).

Results

In total, 21,638, 35,447 and 60,181 unique regions (or peaks) were found across the embryos at 45 dpc (LW45), 70 dpc (LW70) and 100 dpc (LW100), respectively. More than 91% of the peaks were annotated within − 1 kb to 100 bp of transcription start sites (TSSs). First, widespread increases in specific accessible chromatin regions (ACRs) from embryos at 45 to 100 dpc suggested that the regulatory mechanisms became increasingly complicated during embryonic development. Second, the findings from integrated ATAC-seq and RNA-seq analyses showed that not only the numbers but also the intensities of ACRs could control the expression of associated genes. Moreover, the motif screening of stage-specific ACRs revealed some transcription factors that regulate muscle development-related genes, such as MyoG, Mef2c, and Mef2d. Several potential transcriptional repressors, including E2F6, OTX2 and CTCF, were identified among the genes that exhibited different regulation trends between the ATAC-seq and RNA-seq data.

Conclusions

This work indicates that chromatin accessibility plays an important regulatory role in the embryonic muscle development of pigs and regulates the temporal and spatial expression patterns of key genes in muscle development by influencing the binding of transcription factors. Our results contribute to a better understanding of the regulatory dynamics of genes involved in pig embryonic skeletal muscle development.
Anna Karenina and the subgingival microbiome associated with periodontitis
Authors: Altabtbaei Khaled , Maney Pooja , Ganesan Sukirth M. , Dabdoub Shareef M. , Nagaraja Haikady N. , Kumar Purnima S.
Published: May 2021

Background

Although localized aggressive periodontitis (LAP), generalized aggressive periodontitis (GAP), and chronic periodontitis (CP) are microbially driven diseases, our inability to separate disease-specific associations from those common to all three forms of periodontitis has hampered biomarker discovery. Therefore, we aimed to map the genomic content of, and the biological pathways encoded by, the microbiomes associated with these clinical phenotypes. We also estimated the extent to which these biomes are governed by the Anna Karenina principle (AKP), which states that eubiotic communities are similar between individuals while disease-associated communities are highly individualized.

Methods

We collected subgingival plaque from 25 periodontally healthy individuals and diseased sites of 59 subjects with stage 3 periodontitis and used shotgun metagenomics to characterize the aggregate of bacterial genes.

Results

Beta-dispersion metrics demonstrated that AKP was most evident in CP, followed by GAP and LAP. We discovered broad dysbiotic signatures spanning the three phenotypes, with over-representation of pathways that facilitate life in an oxygen-poor, protein- and heme-rich, pro-oxidant environment and enhance capacity for attachment and biofilm formation. Phenotype-specific indicators were more readily evident in LAP microbiome than GAP or CP. Genes that enable acetate-scavenging lifestyle, utilization of alternative nutritional sources, oxidative and nitrosative stress responses, and siderophore production were unique to LAP. An attenuation of virulence-related functionalities and stress response from LAP to GAP to CP was apparent. We also discovered that clinical phenotypes of disease resolved variance in the microbiome with greater clarity than the newly established grading system. Importantly, we observed that one third of the metagenome of LAP is unique to this phenotype while GAP shares significant functional and taxonomic features with both LAP and CP, suggesting either attenuation of an aggressive disease or an early-onset chronic disease.

Conclusion

Within the limitations of a small sample size and a cross-sectional study design, the distinctive features of the microbiomes associated with LAP and CP strongly persuade us that these are discrete disease entities, while calling into question whether GAP is a separate disease, or an artifact induced by cross-sectional study designs. Further studies on phenotype-specific microbial genes are warranted to explicate their role in disease etiology.