bluuebunny/crossref_metadata_2025 huggingface dataset:
Resistance to viral nervous necrosis in European sea bass (Dicentrarchus labrax L.): heritability and relationships with body weight, cortisol concentration, and antibody titer
Authors: Faggion Sara , Bertotto Daniela , Babbucci Massimiliano , Dalla Rovere Giulia , Franch Rafaella , Bovolenta Mauro , Laureau Stanislas , Pascoli Francesco , Toffan Anna , Bargelloni Luca , Carnier Paolo
Published: April 2021

Background

Susceptibility of European sea bass (Dicentrarchus labraxL.) to viral nervous necrosis (VNN) is well-known. Interest towards selective breeding as a tool to enhance genetic resistance in this species has increased sharply due to the major threat represented by VNN for farmed sea bass and limitations concerning specific therapeutical measures. A sea bass experimental population (N = 650) was challenged with nervous necrosis virus (NNV) to investigate genetic variation in VNN mortality. In addition, relationships of this trait with serum cortisol concentration after stress exposure, antibody titer against NNV antigens, and body weight at a fixed age were studied to identify potential indicator traits of VNN resistance.

Results

The estimate of heritability for VNN mortality was moderate and ranged from 0.15 (HPD95%, 95% highest posterior density interval: 0.02, 0.31) to 0.23 (HPD95%: 0.06, 0.47). Heritability estimates for cortisol concentration, antibody titer, and body weight were 0.19 (HPD95%: 0.07, 0.34), 0.36 (HPD95%: 0.16, 0.59) and 0.57 (HPD95%: 0.33, 0.84), respectively. Phenotypic relationships between traits were trivial and not statistically significant, except for the estimated correlation between antibody titer and body weight (0.24). Genetic correlations of mortality with body weight or antibody titer (− 0.39) exhibited a 0.89 probability of being negative. A negligible genetic correlation between mortality and cortisol concentration was detected. Antibody titer was estimated to be positively correlated with body weight (0.49).

Conclusions

Antibody titer against NNV offers the opportunity to use indirect selection to enhance resistance, while the use of cortisol concentration as an indicator trait in breeding programs for VNN resistance is questionable. The estimate of heritability for VNN mortality indicates the feasibility of selective breeding to enhance resistance to NNV and raises attention to the development of genomic prediction tools to simplify testing procedures for selection candidates.
Insomnia in adults with cystic fibrosis: strong association with anxiety/depression and impaired quality of life
Authors: Mulette Pauline , Ravoninjatovo Bruno , Guguen Camille , Barbe Coralie , Ancel Julien , Dury Sandra , Dumazet Antoine , Perdu Dominique , Perotin Jeanne-Marie , Guillard Thomas , Lebargy François , Deslee Gaëtan , Launois Claire
Published: April 2021

Background

While sleep disruption is a common complaint among children with cystic fibrosis (CF), only a few studies have investigated insomnia in adults. The aim of this study was to identify factors associated with insomnia in clinically stable adult CF patients.

Methods

Twenty-eight CF patients (18M/10F), with a median age of 27 (22–34) (median (interquartile range) years and a median of forced expiratory volume in one second of 72 (39–93) % predicted completed questionnaires on insomnia (Insomnia Severity Index, ISI), sleep quality (PSQI), daytime sleepiness (Epworth), restless legs syndrome (IRLS), pain (NRS), anxiety/depression (HAD) and quality of life (CFQ-R 14+). Respiratory assessment data, including symptoms, sputum analysis, arterial blood gases, 6-min walking test, pulmonary function tests and polysomnographic variables, were also analyzed.

Results

Forty-three percent of patients were insomniac (ISI > 7). Compared with non-insomniac patients (ISI ≤ 7), insomniac patients had more severely impaired quality of life and a higher HAD score: median anxiety score of 9 (8–11) vs 4 (3–6) (p < 0.0001), median depression score of 7 (5–10) vs 1 (1–4) (p < 0.001), with a positive correlation between ISI and HAD anxiety/depression scores (r = 0.702/r = 0.701, respectively, p < 0.0001). Insomnia was also associated with mMRC dyspnea scale ≥ 2, restless legs syndrome, pain and lower SpO2 during sleep.

Conclusions

The strong association between insomnia, impaired quality of life and increased HAD score should prompt physicians to be particularly attentive to the management of anxiety and depression in adult CF patients with insomnia.

Trial registration: On clinicaltrials.gov (NCT02924818, date of registration: October 5, 2016).
Reliability of distally based sural flap in elderly patients: comparison between elderly and young patients in a single center
Authors: Peng Ping , Dong Zhonggen , Wei Jianwei , Liu Lihong , Luo Zhaobiao , Cao Shu
Published: March 2021

Background

Reconstructions the soft-tissue defects of the distal lower extremities in the elderly patients (≥ 60 years old) are full of challenges because of many comorbidities. The purpose of this study was to report the clinical application of the distally based sural flap in the elderly patients, and to verify the reliability of this flap in the elderly patients.

Methods

Between March of 2005 and December of 2019, 53 patients aged over 60-year-old and 55 patients aged 18 to 30-year-old who underwent the procedure have been included in this study. The reconstruction outcomes, medical-related complications, flap viability-related complications and potential risk factors are compared between the group A (≥ 60 years old) and group B (ranging from 18 to 30 years old).

Results

The partial necrosis rate in group A (9.43%) is higher than group B (9.09%), but the difference is not significant (P > 0.05). The constitute ratio of the defects that were successfully covered using the sural flap alone or combining with simple salvage method (i.e., skin grafting) is 96.22% and 98.18% in group A and B, respectively (P > 0.05). The differences of the risk flaps factors that affected the survival of distally based sural flap were not significant between group A and B (P > 0.05).

Conclusions

The distally based sural flap can be effectively used to repair the soft-tissue defect of the lower extremity in the elderly patients. It is safe and reliable to harvest and transfer the flap in one stage, and the delay surgery is not necessary.
Let-7i-5p enhances cell proliferation, migration and invasion of ccRCC by targeting HABP4
Authors: Liu Yujie , Hu Xing , Hu Liang , Xu Changjing , Liang Xuemei
Published: March 2021

Background

Clear cell renal cell carcinoma (ccRCC) is one of the best-characterized and most pervasive renal cancers. The present study aimed to explore the effects and potential mechanisms of let-7i-5p in ccRCC cells.

Methods

Using bioinformatics analyses, we investigated the expression of let-7i-5p in The Cancer Genome Atlas (TCGA) database and predicted biological functions and possible target genes of let-7i-5p in ccRCC cells. Cell proliferation assay, wound healing assay and transwell invasion assay were conducted to characterize the effects of let-7i-5p in ccRCC cells. To verify the interactions between let-7i-5p and HABP4, dual-luciferase reporter assay, quantitative real-time polymerase chain reaction, and western blotting were conducted. Rescue experiments were used to investigate the relationship between let-7i-5p and HABP4.

Results

TCGA data analysis revealed that ccRCC tissues had significantly increased let-7i-5p expression, which was robustly associated with poor overall survival. Further verification showed that ccRCC cell proliferation, migration and invasion were inhibited by let-7i-5p inhibitor but enhanced by let-7i-5p mimics. Subsequently, HABP4 was predicted to be the target gene of let-7i-5p. TCGA data showed that ccRCC tissues had decreased expression of HABP4 and that HABP4 expression was negatively correlated with let-7i-5p. Further verification showed that downregulation of HABP4 expression promoted cell proliferation, migration and invasion. The dual-luciferase reporter gene assay suggested that the let-7i-5p/HABP4 axis was responsible for the development of ccRCC.

Conclusion

Our results provide evidence that let-7i-5p functions as a tumor promoter in ccRCC and facilitates cell proliferation, migration and invasion by targeting HABP4. These results clarify the pathogenesis of ccRCC and offer a potential target for its treatment.
Measuring the educational environment in a Sri Lankan medical school following curricular revision
Authors: Ellawala Amaya , Marasinghe Rohana B.
Published: March 2021

Background

In 2007, the Faculty of Medical Sciences, University of Sri Jayewardenepura revised its medical curriculum from discipline-based to one that was student-centered and integrated. This study aimed to evaluate the perceptions of students regarding the educational environment and compare them to those prior to curricular revision.

Methods

The Dundee Ready Education Environment Measure (DREEM) questionnaire was administered to all volunteering students enrolled in the medical degree programme at the time of the study (n = 595). Results were compared to DREEM scores obtained prior to curricular revision.

Results

The overall DREEM score and sub-scale scores were positive and showed improvement compared to previous scores. The score for Students’ Perceptions of Atmosphere showed progression from ‘there are many issues which need changing’ to the next highest category ‘a more positive attitude’. The mean scores in pre-clinical, para-clinical and clinical phases also showed an improvement. ‘The teachers are knowledgeable’ was the highest rated item overall and within each phase of learning. All sub-scales were rated highest by pre-clinical students and lowest by para-clinical students, in contrast to previous results where such patterns were not observed. Certain items, especially those related to teaching/learning, received exclusively low scores in particular student subsets.

Conclusions

Students’ perceptions towards the educational environment overall, have improved following curricular revision. However, certain negative areas warranting further evaluation were highlighted.
An engineered membrane-bound guanylyl cyclase with light-switchable activity
Authors: Tian Yuehui , Nagel Georg , Gao Shiqiang
Published: March 2021

Background

Microbial rhodopsins vary in their chemical properties, from light sensitive ion transport to different enzymatic activities. Recently, a novel family of two-component Cyclase (rhod)opsins (2c-Cyclop) from the green algaeChlamydomonas reinhardtiiandVolvox carteriwas characterized, revealing a light-inhibited guanylyl cyclase (GC) activity. More genes similar to 2c-Cyclop exist in algal genomes, but their molecular and physiological functions remained uncharacterized.

Results

Chlamyopsin-5 (Cop5) fromC. reinhardtiiis related toCr2c-Cyclop1 (Cop6) and can be expressed inXenopus laevisoocytes, but shows no GC activity. Here, we exchanged parts of Cop5 with the corresponding ones ofCr2c-Cyclop1. When exchanging the opsin part ofCr2c-Cyclop1 with that of Cop5, we obtained a bi-stable guanylyl cyclase (switch-Cyclop1) whose activity can be switched by short light flashes. The GC activity of switch-Cyclop1 is increased for hours by a short 380 nm illumination and switched off (20-fold decreased) by blue or green light. switch-Cyclop1 is very light-sensitive and can half-maximally be activated by ~ 150 photons/nm2of 380 nm (~ 73 J/m2) or inhibited by ~ 40 photons/nm2of 473 nm (~ 18 J/m2).

Conclusions

This engineered guanylyl cyclase is the first light-switchable enzyme for cGMP level regulation. Light-regulated cGMP production with high light-sensitivity is a promising technique for the non-invasive investigation of the effects of cGMP signaling in many different tissues.
MXene in the lens of biomedical engineering: synthesis, applications and future outlook
Authors: Zamhuri Adibah , Lim Gim Pao , Ma Nyuk Ling , Tee Kian Sek , Soon Chin Fhong
Published: April 2021

MXene is a recently emerged multifaceted two-dimensional (2D) material that is made up of surface-modified carbide, providing its flexibility and variable composition. They consist of layers of early transition metals (M), interleaved with n layers of carbon or nitrogen (denoted as X) and terminated with surface functional groups (denoted as Tx/Tz) with a general formula of Mn+1XnTx, where n = 1–3. In general, MXenes possess an exclusive combination of properties, which include, high electrical conductivity, good mechanical stability, and excellent optical properties. MXenes also exhibit good biological properties, with high surface area for drug loading/delivery, good hydrophilicity for biocompatibility, and other electronic-related properties for computed tomography (CT) scans and magnetic resonance imaging (MRI). Due to the attractive physicochemical and biocompatibility properties, the novel 2D materials have enticed an uprising research interest for application in biomedicine and biotechnology. Although some potential applications of MXenes in biomedicine have been explored recently, the types of MXene applied in the perspective of biomedical engineering and biomedicine are limited to a few, titanium carbide and tantalum carbide families of MXenes. This review paper aims to provide an overview of the structural organization of MXenes, different top-down and bottom-up approaches for synthesis of MXenes, whether they are fluorine-based or fluorine-free etching methods to produce biocompatible MXenes. MXenes can be further modified to enhance the biodegradability and reduce the cytotoxicity of the material for biosensing, cancer theranostics, drug delivery and bio-imaging applications. The antimicrobial activity of MXene and the mechanism of MXenes in damaging the cell membrane were also discussed. Some challenges for in vivo applications, pitfalls, and future outlooks for the deployment of MXene in biomedical devices were demystified. Overall, this review puts into perspective the current advancements and prospects of MXenes in realizing this 2D nanomaterial as a versatile biological tool.
Protocol for personal RF-EMF exposure measurement studies in 5th generation telecommunication networks
Authors: Velghe Maarten , Aerts Sam , Martens Luc , Joseph Wout , Thielens Arno
Published: April 2021

Background

The general population is exposed to Radio-Frequency Electromagnetic Fields (RF-EMFs) used by telecommunication networks. Previous studies developed methods to assess this exposure. These methods will be inadequate to accurately assess exposure in 5G technologies or other wireless technologies using adaptive antennas. This is due to the fact that 5G NR (new radio) base stations will focus actively on connected users, resulting in a high spatio-temporal variations in the RF-EMFs. This increases the measurement uncertainty in personal measurements of RF-EMF exposure. Furthermore, a user’s exposure from base stations will be dependent on the amount of data usage, adding a new component to the auto-induced exposure, which is often omitted in current studies.

Goals

The objective of this paper is to develop a general study protocol for future personal RF-EMF exposure research adapted to 5G technologies. This protocol will include the assessment of auto-induced exposure of both a user’s own devices and the networks’ base stations.

Method

This study draws from lessons learned from previous RF-EMF exposure research and current knowledge on 5G technologies, including studies simulating 5G NR base stations and measurements around 5G NR test sites.

Results

To account for auto-induced exposure, an activity-based approach is introduced. In survey studies, an RF-EMF sensor is fixed on the participants’ mobile device(s). Based on the measured power density, GPS data and movement and proximity sensors, different activities can be clustered and the exposure during each activity is evaluated. In microenvironmental measurements, a trained researcher performs measurements in predefined microenvironments with a mobile device equipped with the RF-EMF sensor. The mobile device is programmed to repeat a sequence of data transmission scenarios (different amounts of uplink and downlink data transmissions). Based on simulations, the amount of exposure induced in the body when the user device is at a certain location relative to the body, can be evaluated.

Conclusion

Our protocol addresses the main challenges to personal exposure measurement introduced by 5G NR. A systematic method to evaluate a user’s auto-induced exposure is introduced.
Integrated analysis of lncRNA, miRNA and mRNA profiles reveals potential lncRNA functions during early HIV infection
Authors: Ma Lianwei , Zhang Hui , Zhang Yue , Li Hailong , An Minghui , Zhao Bin , Ding Haibo , Xu Junjie , Shang Hong , Han Xiaoxu
Published: April 2021

Background

Long noncoding RNAs (lncRNAs) can regulate gene expression in acis-regulatory fashion or as “microRNA sponges”. However, the expression and functions of lncRNAs during early human immunodeficiency virus (HIV) infection (EHI) remain unclear.

Methods

3 HAART-naive EHI patients and 3 healthy controls (HCs) were recruited in this study to perform RNA sequencing and microRNA (miRNA) sequencing. The expression profiles of lncRNAs, mRNAs and miRNAs were obtained, and the potential roles of lncRNAs were analysed based on discovering lncRNAcis-regulatory target mRNAs and constructing lncRNA–miRNA–mRNA competing endogenous RNA (ceRNA) networks. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on 175 lncRNA-associated differentially expressed (DE) mRNAs to investigate the potential functions of DE lncRNAs in ceRNA networks.

Results

A total of 242 lncRNAs, 1240 mRNAs and 21 mature known miRNAs were determined as differentially expressed genes in HAART-naive EHI patients compared to HCs. Among DE lncRNAs, 44 lncRNAs were predicted to overlap with 41 target mRNAs, and 107 lncRNAs might regulate their nearby DE mRNAs. Two DE lncRNAs might regulate theircis-regulatory target mRNAsBTLAandZAP70,respectively, which were associated with immune activation. In addition, the ceRNA networks comprised 160 DE lncRNAs, 21 DE miRNAs and 175 DE mRNAs. Seventeen DE lncRNAs were predicted to regulateHIF1AandTCF7L2,which are involved in the process of HIV-1 replication. Twenty DE lncRNAs might share miRNA response elements (MREs) withFOS,FOSBandJUN,which are associated with both immune activation and HIV-1 replication.

Conclusions

This study revealed that lncRNAs might play a critical role in HIV-1 replication and immune activation during EHI. These novel findings are helpful for understanding of the pathogenesis of HIV infection and provide new insights into antiviral therapy.
Ruxolitinib treatment permits lower cumulative glucocorticoid dosing in children with secondary hemophagocytic lymphohistiocytosis
Authors: Chi Ying , Liu Rong , Zhou Zhi-xuan , Shi Xiao-dong , Ding Yu-chuan , Li Jian-guo
Published: April 2021

Background

This study aimed to analyze the effects of ruxolitinib on children with secondary hemophagocytic lymphohistiocytosis (HLH).

Methods

Eleven pediatric patients diagnosed with HLH and treated with ruxolitinib (ruxolitinib group: group R) between November 2017 and August 2018 were retrospectively analyzed. Eleven age-matched pediatric patients with HLH undergoing conventional treatment (control group: group C) during the same period were also analyzed.

Results

In group R, three patients who did not respond to methylprednisolone (MP) pulse and intravenous immunoglobulin (IVIG) therapies were treated with Ruxolitinib and their temperature decreased to normal levels. Four patients had normal temperature after conventional treatment (dexamethasone and etoposide, with or without cyclosporine A), but they had severe organ involvement, including obvious yellowing of the skin, increased liver enzyme levels and neuropsychiatric symptoms, and they were all ameliorated with ruxolitinib treatment. Four patients were relieved with ruxolitinib therapy alone. In group C, the body temperatures of eleven patients decreased to normal levels after conventional treatment. The body temperature of group R patients decreased to normal levels more rapidly than that of group C patients. The glucocorticoid dosage in group R was significantly lower than that in group C. Both groups were followed-up for 2–2.5 years. No obvious adverse drug reactions to ruxolitinib were observed during treatment and follow-up.

Conclusion

Ruxolitinib might be an effective drug in controlling body temperature and reducing inflammation indicators. It might be a potential replacement for glucocorticoid therapy for HLH treatment in children, thereby reducing or avoiding glucocorticoid-related adverse reactions.
Associations between lifestyle behaviour changes and the optimal well-being of middle-aged Japanese individuals
Authors: Takao Toshihiro , Sumi Naoki , Yamanaka Yoshiyuki , Fujimoto Sohachi , Kamada Tomoari
Published: April 2021

Background

Psychological well-being has been associated with reduced mortality rates in both healthy and diseased populations. However, there is considerably less evidence on the effect of lifestyle behaviours on positive health outcomes such as well-being. This study examines the association between lifestyle behaviours and optimal well-being.

Methods

From a total of 4324 Japanese individuals who participated in an annual health check-up in 2017, this study recruited 2295 participants (mean age: 49.3 ± 8.4 years; female: 54.3%) without a history of cerebrovascular, cardiovascular, or chronic renal disease and not on medication for hypertension, diabetes, or dyslipidaemia. The World Health Organization-Five Well-Being Index (WHO-5) scores were compared to self-reported scores on each of the following items: dietary habits, physical activity, smoking, alcohol consumption, and sleep quality. Logistic regression analysis was used to examine the association between optimal well-being (the top quartile of WHO-5 scores) and individual lifestyle behaviours. The association between change in dietary habits and physical activity from 2016 to 2017 and optimal well-being was also investigated.

Results

Good dietary habits and regular physical activity were associated with higher raw WHO-5 scores and were positively associated with optimal well-being after adjusting for age, sex, body mass index (BMI), and sleep quality. Raw WHO-5 scores were significantly higher in those who maintained good dietary and physical activity behaviours than in those who did not. Furthermore, maintaining regular physical activity for two years was positively associated with optimal well-being, after adjusting for age, sex, BMI, and sleep quality.

Conclusion

These results demonstrate that not only currently practising good dietary and physical activity behaviours but also maintaining such behaviours over time is associated with optimal well-being. Maintaining good lifestyle behaviours, particularly regarding physical activity, could potentially improve people’s well-being.
Evaluation of Mosquito Magnet and other collection tools for Anopheles mosquito vectors of simian malaria
Authors: Jeyaprakasam Nantha Kumar , Pramasivan Sandthya , Liew Jonathan Wee Kent , Van Low Lun , Wan-Sulaiman Wan-Yusoff , Ngui Romano , Jelip Jenarun , Vythilingam Indra
Published: April 2021

Background

Vector surveillance is essential in determining the geographical distribution of mosquito vectors and understanding the dynamics of malaria transmission. With the elimination of human malaria cases, knowlesi malaria cases in humans are increasing in Malaysia. This necessitates intensive vector studies using safer trapping methods which are both field efficient and able to attract the local vector populations. Thus, this study evaluated the potential of Mosquito Magnet as a collection tool for Anopheles mosquito vectors of simian malaria along with other known collection methods.

Methods

A randomized 4 × 4 Latin square designed experiment was conducted to compare the efficiency of the Mosquito Magnet against three other common trapping methods: human landing catch (HLC), CDC light trap and human baited trap (HBT). The experiment was conducted over six replicates where sampling within each replicate was carried out for 4 consecutive nights. An additional 4 nights of sampling was used to further evaluate the Mosquito Magnet against the “gold standard” HLC. The abundance of Anopheles sampled by different methods was compared and evaluated with focus on the Anopheles from the Leucosphyrus group, the vectors of knowlesi malaria.

Results

The Latin square designed experiment showed HLC caught the greatest number of Anopheles mosquitoes (n = 321) compared to the HBT (n = 87), Mosquito Magnet (n = 58) and CDC light trap (n = 13). The GLMM analysis showed that the HLC method caught significantly more Anopheles mosquitoes compared to Mosquito Magnet (P = 0.049). However, there was no significant difference in mean nightly catch of Anopheles mosquitoes between Mosquito Magnet and the other two trapping methods, HBT (P = 0.646) and CDC light traps (P = 0.197). The mean nightly catch for both An. introlatus (9.33 ± 4.341) and An. cracens (4.00 ± 2.273) caught using HLC was higher than that of Mosquito Magnet, though the differences were not statistically significant (P > 0.05). This is in contrast to the mean nightly catch of An. sinensis (15.75 ± 5.640) and An. maculatus (15.78 ± 3.479) where HLC showed significantly more mosquito catches compared to Mosquito Magnet (P < 0.05).

Conclusions

Mosquito Magnet has a promising ability to catch An. introlatus and An. cracens, the important vectors of knowlesi and other simian malarias in Peninsular Malaysia. The ability of Mosquito Magnet to catch some of the Anopheles mosquito species is comparable to HLC and makes it an ethical and safer alternative.

Graphical Abstract
H3K36 methylation reprograms gene expression to drive early gametocyte development in Plasmodium falciparum
Authors: Connacher Jessica , Josling Gabrielle A. , Orchard Lindsey M. , Reader Janette , Llinás Manuel , Birkholtz Lyn-Marié
Published: April 2021

Background

ThePlasmodiumsexual gametocyte stages are the only transmissible form of the malaria parasite and are thus responsible for the continued transmission of the disease. Gametocytes undergo extensive functional and morphological changes from commitment to maturity, directed by an equally extensive control program. However, the processes that drive the differentiation and development of the gametocyte post-commitment, remain largely unexplored. A previous study reported enrichment of H3K36 di- and tri-methylated (H3K36me2&3) histones in early-stage gametocytes. Using chromatin immunoprecipitation followed by high-throughput sequencing, we identify a stage-specific association between these repressive histone modifications and transcriptional reprogramming that define a stage II gametocyte transition point.

Results

Here, we show that H3K36me2 and H3K36me3 from stage II gametocytes are associated with repression of genes involved in asexual proliferation and sexual commitment, indicating that H3K36me2&3-mediated repression of such genes is essential to the transition from early gametocyte differentiation to intermediate development. Importantly, we show that the gene encoding the transcription factor AP2-G as commitment master regulator is enriched with H3K36me2&3 and actively repressed in stage II gametocytes, providing the first evidence ofap2-ggene repression in post-commitment gametocytes. Lastly, we associate the enhanced potency of the pan-selective Jumonji inhibitor JIB-04 in gametocytes with the inhibition of histone demethylation including H3K36me2&3 and a disruption of normal transcriptional programs.

Conclusions

Taken together, our results provide the first description of an association between global gene expression reprogramming and histone post-translational modifications duringP. falciparumearly sexual development. The stage II gametocyte-specific abundance of H3K36me2&3 manifests predominantly as an independent regulatory mechanism targeted towards genes that are repressed post-commitment. H3K36me2&3-associated repression of genes is therefore involved in key transcriptional shifts that accompany the transition from early gametocyte differentiation to intermediate development.
Novel operative technique of advancement urethral meatoplasty utilizing buccal mucosa for Vulvar Paget’s disease with urethral invasion: two case reports
Authors: Nakamura Masaki , Hakozaki Yuji , Iwata Shohei , Sato Yusuke , Makino Katsuhiro , Kawai Taketo , Yamada Yuta , Yamada Daisuke , Suzuki Motofumi , Omatsu Jun , Abe Masanobu , Hoshi Kazuto , Kume Haruki , Igawa Yasuhiko
Published: March 2021

Background

Vulvar Paget’s disease (VPD) is a rare malignant disorder originating in the external genitalia. It occasionally invades into urethral or vaginal mucosa of female, making surgical treatment more complicating. In case of urethral invasion of Paget’s cells, systematic mapping biopsy of urethral mucosa is the standard of care to determine the range of surgical resection. Resection of urethral mucosa and simple skin grafting often result in urethral stricture after surgery, which severely deteriorates patient’s quality of life.

Case presentation

We applied a new technique of advancement urethral meatoplasty using buccal mucosa, in two Japanese cases of VPD with urethral invasion. After broad resection of vulvar skin together with the urethral mucosa, buccal mucosa was implanted between advanced urethral mucosa and skin graft. In both cases, we could prevent urethral stricture one year and two years after surgery, respectively.

Conclusion

This technique prevented urethral stricture after surgery and could be a useful technique as part of urethroplasty for VPD.
Septic shock due to Escherichia coli meningoencephalitis treated with immunoglobulin-M-enriched immunoglobulin preparation as adjuvant therapy: a case report
Authors: Pota V. , Passavanti M. B. , Coppolino F. , Di Zazzo F. , De Nardis L. , Esposito R. , Fiore M. , Mangoni di Santostefano G. S. R. C. , Aurilio C. , Sansone P. , Pace M. C.
Published: March 2021

Background

Gram-negative bacteria are an uncommon etiology of spontaneous community-acquired adult meningitis and meningoencephalitis. Escherichia coli is a Gram-negative bacterium that is normally present in the intestinal microbial pool. Some Escherichia coli strains can cause diseases in humans and animals, with both intestinal and extraintestinal manifestations (extraintestinal pathogenic Escherichia coli) such as urinary tract infections, bacteremia with sepsis, and, more rarely, meningitis. Meningitis continues to be an important cause of mortality throughout the world, despite progress in antimicrobial chemotherapy and supportive therapy. The mortality rate fluctuates between 15% and 40%, and about 50% of the survivors report neurological sequelae. The majority of Escherichia coli meningitis cases develop as a result of hematogenous spread, with higher degrees of bacteremia also being related to worse prognosis. Cases presenting with impaired consciousness (that is, coma) are also reported to have poorer outcomes.

Case presentation

We describe the case of a 48-year-old caucasian woman with meningoencephalitis, with a marked alteration of consciousness on admission, and septic shock secondary to pyelonephritis caused by Escherichia coli, treated with targeted antimicrobial therapy and immunoglobulin-M-enriched immunoglobulin (Pentaglobin) preparation as adjuvant therapy.

Conclusion

Despite the dramatic presentation of the patient on admission, the conflicting data on the use of immunoglobulins in septic shock, and the lack of evidence regarding their use in adult Escherichia coli meningoencephalitis, we obtained a remarkable improvement of her clinical condition, accompanied by partial resolution of her neurological deficits.
The use of immunotherapy treatment in malignant pheochromocytomas/paragangliomas: a case report
Authors: Rodriguez Robin Raquel , Rizwan Saleha , Alhamad Khaled , Finley Gene Grant
Published: March 2021

Background

Pheochromocytomas are a subset of paragangliomas, which are a rare group of neural crest cell-derived tumors. Malignant cases of both pheochromocytomas and paragangliomas are even rarer, and currently there is no standard of care. This case report details the use of off-label immunotherapy and its efficacy in the management of the aforementioned tumor.

Case presentation

Herein is presented a case of a 60-year-old Caucasian female with a rare malignant pheochromocytoma. The tumor was determined to be unresectable because of involvement of surrounding organs. Radiation therapy was also not a viable option because of concerns over appreciable toxicity in relation to mass size. As there is no standard of care for malignant cases, the patient was started on chemotherapeutic agents but was soon shown to be intolerant to this treatment. As she was ineligible for several clinical trials, the patient was started on the off-label immunotherapeutic agents nivolumab and ipilimumab. Immunotherapy use resulted in decreased tumor size, improved quality of life, and reconsideration for radiation therapy.

Conclusions

The use of immunotherapy in pheochromocytoma in this patient clearly demonstrated substantial benefit, as she was able to be reconsidered for radiation therapy. Not only has the patient been tolerant of this treatment, but she has exhibited progression-free survival of over 20 months. As there is no current standard treatment for malignant pheochromocytomas, the success of its use in this patient lends support to the ongoing clinical trials regarding the use of immunotherapy in rare tumors, including pheochromocytomas.
Epstein–Barr virus-positive lymphoproliferative disorder manifesting as pulmonary disease in a patient with acute myeloid leukemia: a case report
Authors: Dutta Ritika , Miao Susanna Y. , Phan Paul , Fernandez-Pol Sebastian , Shiraz Parveen , Ho Dora , Mannis Gabriel N. , Zhang Tian Y.
Published: March 2021

Background

 Patients with lymphoproliferative disorders following hematopoietic stem cell transplant (HSCT) most commonly present with fever and lymphadenopathy within the first 5 months of transplant. Pulmonary post-transplant lymphoproliferative disorder (PTLD) is a particularly aggressive and rapidly progressive disease, with high morbidity and mortality. There are a very limited number of reported pulmonary PTLD cases following HSCT in patients with acute myeloid leukemia (AML). Early diagnosis and detection of pulmonary PTLD is critical given its high lethality. However, variable clinical presentations and nonspecific radiographic findings make pulmonary PTLD difficult to distinguish from other more common causes of pulmonary disease in AML patients.

Case presentation

Here, we describe a 68-year-old Caucasian man who presented for salvage induction therapy following relapse of his AML after a haploidentical allogeneic HSCT 10 months earlier. He developed recurrent fevers, dry cough, and hypoxemia, with chest computed tomography (CT) showing bibasilar consolidations and increased nodularity without increased lymphadenopathy. His symptoms initially improved with antibiotic and antifungal therapy, but his follow-up chest CT showed progression of disease despite symptomatic improvement. Epstein–Barr virus (EBV) was detected in his blood by polymerase chain reaction (PCR), and a lung biopsy revealed monomorphic PTLD with B cells positive for EBV. Unfortunately, the patient’s condition rapidly deteriorated, and he passed away prior to treatment initiation.

Conclusions

 To our knowledge, this is the first reported case of an AML patient developing pulmonary PTLD relatively late in his post-transplant course in the setting of relapsed disease and salvage therapy. Pulmonary PTLD, a rare but highly lethal disorder, can imitate the symptoms and radiographic findings of pneumonia, a common diagnosis in immunocompromised AML patients. This case illustrates the importance of considering pulmonary PTLD in the differential diagnosis for pulmonary disease in AML patients with a history of HSCT, especially in the setting of progressive radiographic findings despite broad antibacterial and antifungal therapy. Further, our case demonstrates the importance of biopsy and uninterrupted EBV DNA monitoring in the definitive diagnosis of PTLD, given nonspecific symptomatology and radiographic findings.
Ophthalmological symptoms in a patient with reversible cerebral vasoconstriction syndrome: a case report
Authors: Hayashi Rijo , Hayashi Shimmin , Machida Shigeki
Published: March 2021

Background

Reversible cerebral vasoconstriction syndrome is characterized by severe headache with reversible segmental constriction of the cerebral arteries. We present details on a patient with reversible cerebral vasoconstriction syndrome who initially visited an ophthalmologist because of visual symptoms.

Case presentation

A 34-year-old Japanese woman complained of sustained headache and insomnia starting 2 days after her first childbirth. In addition to the severe headache, a visual field defect was also observed 10 days later. Best corrected visual acuity at the initial visit was 20/20 and 20/25 for the right and left eye, respectively. Exudative retinal detachment was noted surrounding both optic heads. Visual field testing revealed left homonymous hemianopsia, while magnetic resonance imaging demonstrated the presence of edema and infarction of the bilateral basal nuclei and right occipital lobe. The homonymous hemianopsia and exudative retinal detachment recovered immediately after treatment with a free-radical scavenger and anticoagulant. There has been no recurrence of symptoms during the 4 years of follow-up.

Conclusions

We report a case of reversible cerebral vasoconstriction syndrome with ophthalmological symptoms that were reversible, including serous retinal detachment and homonymous hemianopsia.
Chance diagnosis of mixed gonadal dysgenesis in an adult case of malignant gonadal germ cell tumor: a case report
Authors: Kurose Yoshiko , Nagai Tomonori , Shigematsu Kousuke , Uotani Takahiro , Akahori Taichi , Takai Yasushi , Seki Hiroyuki
Published: March 2021

Background

Mixed gonadal dysgenesis (MGD) is a subtype of the disorders of sex development (DSD) associated with sex chromosome abnormalities characterized by abnormal external genitalia, short stature, and primary amenorrhea. This disease is generally diagnosed from the neonatal stage to early childhood, and by puberty at the latest. Cases that are phenotypically female or those with ambiguous genitalia experience a high risk of gonadal tumor formation. As tumor risk is known to increase with age, prophylactic bilateral gonadectomy is recommended following early diagnosis.

Case presentation

Here we report a case of an adult Japanese woman diagnosed with MGD during treatment for a giant pelvic tumor. The patient initially visited a gynecology clinic during puberty for primary amenorrhea, at which time an abnormality was found with the external genitalia. However, a diagnosis of MGD was not made at this time, resulting in the development of a malignant gonadal germ cell tumor in adulthood.

Conclusions

For early diagnosis of MGD and the prevention of gonadal tumor formation, it is essential that gynecologists fully understand MGD and other DSD.
Perampanel overdose in low body mass index patients with epilepsy: a case report and review of the literature
Authors: Phabphal Kanitpong , Koonalintip Prut
Published: March 2021

Background

Perampanel (PER) is a novel antiepileptic drug (AED) which employs a completely different mechanism of action compared to existing medications. Overall, PER is considered to be safe up to a dose of 12 mg per day. When used to treat refractory and super-refractory status epilepticus, PER seems to be extremely well tolerated; this is true even when used at doses of up to 32 mg. There are currently only three case reports on the effects of acute PER overdose in epilepsy patients.

Case presentation

We report a 16-year-old Thai woman with a low body weight, who took PER at a dose of 40 times that of the prescribed daily dose. She experienced only an alteration of consciousness, without any systemic medical effects, and made a full recovery within 3 days without gastric lavage or specific treatment.

Conclusion

Our report demonstrates that an acute PER overdose may not produce serious adverse systemic effects. Individuals with adverse central nervous system (CNS) effects, such as altered consciousness, can experience a rapid recovery.
A hybrid access method for broadcasting of safety messages in IEEE 802.11p VANETs
Authors: Lei Xiaoying , Chen Xiangjin , Rhee Seung Hyong
Published: April 2021

Vehicular Ad-hoc Networks (VANETs) can improve the road safety by transmitting safety-critical messages such as beacons and emergency messages. IEEE 802.11p VANETs have adopted the carrier sense multiple access with collision avoidance (CSMA/CA) mechanism for the multiple access control. The 802.11p media access control (MAC) protocol, however, can not guarantee the reliability of broadcasting data, since the reception of transmitted messages are not acknowledged. Moreover, the backoff scheme of the 802.11p MAC utilizes a fixed-size contention window for safety message broadcasting, which causes high collision probabilities especially in dense environments. In order to improve such drawbacks, we propose a hybrid access method as follows: Nodes are equipped to reserve time slots for the next round of broadcasting, while unoccupied time slots are preserved for those which have emergency needs. In addition, implicit feedbacks are enabled for detecting collisions incurred during random channel accesses in preserved time slots. We devise a mathematical model which optimally controls the parameters of our scheme while minimizes the cost caused by idle channels and collisions. Extensive simulations show that our mechanism can remarkably improve the performance of VANETs in broadcasting of the safety messages.
An efficient numerical approach for solving two-point fractional order nonlinear boundary value problems with Robin boundary conditions
Authors: Kim Hyunju , Lee Junseo , Jang Bongsoo
Published: April 2021

This article proposes new strategies for solving two-point Fractional order Nonlinear Boundary Value Problems (FNBVPs) with Robin Boundary Conditions (RBCs). In the new numerical schemes, a two-point FNBVP is transformed into a system of Fractional order Initial Value Problems (FIVPs) with unknown Initial Conditions (ICs). To approximate ICs in the system of FIVPs, we develop nonlinear shooting methods based on Newton’s method and Halley’s method using the RBC at the right end point. To deal with FIVPs in a system, we mainly employ High-order Predictor–Corrector Methods (HPCMs) with linear interpolation and quadratic interpolation (Nguyen and Jang in Fract. Calc. Appl. Anal. 20(2):447–476, 2017) into Volterra integral equations which are equivalent to FIVPs. The advantage of the proposed schemes with HPCMs is that even though they are designed for solving two-point FNBVPs, they can handle both linear and nonlinear two-point Fractional order Boundary Value Problems (FBVPs) with RBCs and have uniform convergence rates of HPCMs, $\mathcal{O}(h^{2})$
O
(

h
2

)
and $\mathcal{O}(h^{3})$
O
(

h
3

)
for shooting techniques with Newton’s method and Halley’s method, respectively. A variety of numerical examples are demonstrated to confirm the effectiveness and performance of the proposed schemes. Also we compare the accuracy and performance of our schemes with another method.
An inertial-type algorithm for approximation of solutions of Hammerstein integral inclusions in Hilbert spaces
Authors: Bello A. U. , Omojola M. T. , Yahaya J.
Published: March 2021

LetHbe a real Hilbert space. Let$F:H\rightarrow 2^{H}$F:H→2Hand$K:H\rightarrow 2^{H}$K:H→2Hbe two maximal monotone and bounded operators. Suppose the Hammerstein inclusion$0\in u+KFu$0∈u+KFuhas a solution. We construct an inertial-type algorithm and show its strong convergence to a solution of the inclusion. As far as we know, this is the first inertial-type algorithm for Hammerstein inclusions in Hilbert spaces. We also give numerical examples to compare the new algorithm with some existing ones in the literature.
animalcules: interactive microbiome analytics and visualization in R
Authors: Zhao Yue , Federico Anthony , Faits Tyler , Manimaran Solaiappan , Segrè Daniel , Monti Stefano , Johnson W. Evan
Published: March 2021

Background

Microbial communities that live in and on the human body play a vital role in health and disease. Recent advances in sequencing technologies have enabled the study of microbial communities at unprecedented resolution. However, these advances in data generation have presented novel challenges to researchers attempting to analyze and visualize these data.

Results

To address some of these challenges, we have developed animalcules, an easy-to-use interactive microbiome analysis toolkit for 16S rRNA sequencing data, shotgun DNA metagenomics data, and RNA-based metatranscriptomics profiling data. This toolkit combines novel and existing analytics, visualization methods, and machine learning models. For example, the toolkit features traditional microbiome analyses such as alpha/beta diversity and differential abundance analysis, combined with new methods for biomarker identification are. In addition, animalcules provides interactive and dynamic figures that enable users to understand their data and discover new insights. animalcules can be used as a standalone command-line R package or users can explore their data with the accompanying interactive R Shiny interface.

Conclusions

We present animalcules, an R package for interactive microbiome analysis through either an interactive interface facilitated by R Shiny or various command-line functions. It is the first microbiome analysis toolkit that supports the analysis of all 16S rRNA, DNA-based shotgun metagenomics, and RNA-sequencing based metatranscriptomics datasets. animalcules can be freely downloaded from GitHub at https://github.com/compbiomed/animalcules or installed through Bioconductor at https://www.bioconductor.org/packages/release/bioc/html/animalcules.html.
Relations between perceived teacher’s autonomy support, cognitive appraisals and boredom in physics learning among lower secondary school students
Authors: Ekatushabe Margaret , Kwarikunda Diana , Muwonge Charles M. , Ssenyonga Joseph , Schiefele Ulrich
Published: March 2021

Background

Boredom during learning activities has the potential of impeding attention, motivation, learning and eventually achievement. Yet, research focusing on its possible antecedents seems to have received less attention especially within the physics domain. Based on assumptions of the Control Value Theory of Achievement Emotions (CVTAE), this study aimed at examining gender differences and structural relationships between students’ reported perceived teacher autonomy support (PTAS), cognitive appraisals (self-efficacy and task value) and learning-related boredom in physics. A sample of 375 (56% females) randomly selected 9th grade students (mean age = 15.03 years; SD = 1.02) from five secondary schools in Masaka district of Uganda took part in the study.

Results

Data collected from students’ self-reports using standardised instruments revealed that higher levels of PTAS, self-efficacy, and task value were significantly associated with lower levels of boredom during physics learning. Females reported significantly greater task value for learning physics than the males. Self-efficacy (β = − .10, p < .05) and task value (β = − .09, p < .01) partially mediated the relationship between PTAS and boredom. PTAS showed significant direct negative contributions to boredom (β = − .34, p < .001).

Conclusion

These findings provide support for theory and practice about the importance of promoting autonomy among students by adjusting instructional behaviours among teachers of physics. Teacher autonomy supportive behaviours influence formation of students’ beliefs about ability, subjective value and learning-related boredom in physics. Implications and suggestions for further research are also discussed in this paper.