bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular and humoral immune responses associated with protection in sheep vaccinated against Teladorsagia circumcincta
Authors: Machín Cynthia , Corripio-Miyar Yolanda , Hernández Julia N. , Pérez-Hernández Tara , Hayward Adam D. , Wright Harry W. , Price Daniel R. G. , Matthews Jacqueline B. , McNeilly Tom N. , Nisbet Alasdair J. , González Jorge F.
Published: June 2021

Due to increased anthelmintic resistance, complementary methods to drugs are necessary to control gastrointestinal nematodes (GIN). Vaccines are an environmentally-friendly and promising option. In a previous study, a Teladorsagia circumcincta recombinant sub-unit vaccine was administered to two sheep breeds with different levels of resistance against GIN. In the susceptible Canaria Sheep (CS) breed, vaccinates harboured smaller worms with fewer eggs in utero than the control group. Here, we extend this work, by investigating the cellular and humoral immune responses of these two sheep breeds following vaccination and experimental infection with T. circumcincta. In the vaccinated CS group, negative associations between antigen-specific IgA, IgG2 and Globule Leukocytes (GLs) with several parasitological parameters were established as well as a higher CD4+/CD8+ ratio than in control CS animals, suggesting a key role in the protection induced by the vaccine. In the more resistant Canaria Hair Breed (CHB) sheep the vaccine did not significantly impact on the parasitological parameters studied and none of these humoral associations were observed in vaccinated CHB lambs, although CHB had higher proportions of CD4+ and CD8+ T cells within the abomasal lymph nodes, suggesting higher mucosal T cell activation. Each of the component proteins in the vaccine induced an increase in immunoglobulin levels in vaccinated groups of each breed. However, levels of immunoglobulins to only three of the antigens (Tci-MEP-1, Tci-SAA-1, Tci-ASP-1) were negatively correlated with parasitological parameters in the CS breed and they may be, at least partially, responsible for the protective effect of the vaccine in this breed. These data could be useful for improving the current vaccine prototype.
Ulam–Hyers–Mittag-Leffler stability for tripled system of weighted fractional operator with TIME delay
Authors: Almalahi Mohammed A. , Panchal Satish K. , Jarad Fahd , Abdeljawad Thabet
Published: June 2021

This study is aimed to investigate the sufficient conditions of the existence of unique solutions and the Ulam–Hyers–Mittag-Leffler (UHML) stability for a tripled system of weighted generalized Caputo fractional derivatives investigated by Jarad et al. (Fractals 28:2040011 2020) in the frame of Chebyshev and Bielecki norms with time delay. The acquired results are obtained by using Banach fixed point theorems and the Picard operator (PO) method. Finally, a pertinent example of the results obtained is demonstrated.
Aggressive infantile myofibromatosis with intestinal involvement
Authors: Römer Tristan , Wagner Norbert , Braunschweig Till , Meyer Robert , Elbracht Miriam , Kontny Udo , Moser Olga
Published: June 2021

Background

Infantile myofibromatosis (IM) is the most common cause of multiple fibrous tumors in infancy. Multicentric disease can be associated with life-threatening visceral lesions. Germline gain-of-function mutations in PDGFRB have been identified as the most common molecular defect in familial IM.

Case presentation

We here describe an infant with PDGFRB-driven IM with multiple tumors at different sites, including intestinal polyposis with hematochezia, necessitating temporary chemotherapy.

Conclusions

PDGFRB-driven IM is clinically challenging due to its fluctuating course and multiple organ involvement in the first years of life. Early molecular genetic analysis is necessary to consider tyrosine kinase inhibitor treatment in case of aggressive visceral lesions.
SMAD1 as a biomarker and potential therapeutic target in drug-resistant multiple myeloma
Authors: Wu Jian , Zhang Min , Faruq Omar , Zacksenhaus Eldad , Chen Wenming , Liu Aijun , Chang Hong
Published: June 2021

Background

SMAD1, a central mediator in TGF-β signaling, is involved in a broad range of biological activities including cell growth, apoptosis, development and immune response, and is implicated in diverse type of malignancies. Whether SMAD1 plays an important role in multiple myeloma (MM) pathogenesis and can serve as a therapeutic target are largely unknown.

Methods

Myeloma cell lines and primary MM samples were used. Cell culture, cytotoxicity and apoptosis assay, siRNA transfection, Western blot, RT-PCR, Soft-agar colony formation, and migration assay, Chromatin immunoprecipitation (Chip), animal xenograft model studies and statistical analysis were applied in this study.

Results

We demonstrate that SMAD1 is highly expressed in myeloma cells of MM patients with advanced stages or relapsed disease, and is associated with significantly shorter progression-free and overall survivals. Mechanistically, we show that SMAD1 is required for TGFβ-mediated proliferation in MM via an ID1/p21/p27 pathway. TGF-β also enhanced TNFα-Induced protein 8 (TNFAIP8) expression and inhibited apoptosis through SMAD1-mediated induction of NF-κB1. Accordingly, depletion of SMAD1 led to downregulation of NF-κB1 and TNFAIP8, resulting in caspase-8-induced apoptosis. In turn, inhibition of NF-κB1 suppressed SMAD1 and ID1 expression uncovering an autoregulatory loop. Dorsomorphin (DM), a SMAD1 inhibitor, exerted a dose-dependent cytotoxic effect on drug-resistant MM cells with minimal cytotoxicity to normal hematopoietic cells, and further synergized with the proteasomal-inhibitor bortezomib to effectively kill drug-resistant MM cells in vitro and in a myeloma xenograft model.

Conclusions

This study identifies SMAD1 regulation of NF-κB1/TNFAIP8 and ID1-p21/p27 as critical axes of MM drug resistance and provides a potentially new therapeutic strategy to treat drug resistance MM through targeted inhibition of SMAD1.
Real-time automatic uncertainty estimation of coseismic single rectangular fault model using GNSS data
Authors: Ohno Keitaro , Ohta Yusaku , Kawamoto Satoshi , Abe Satoshi , Hino Ryota , Koshimura Shunichi , Musa Akihiro , Kobayashi Hiroaki
Published: June 2021

Rapid estimation of the coseismic fault model for medium-to-large-sized earthquakes is key for disaster response. To estimate the coseismic fault model for large earthquakes, the Geospatial Information Authority of Japan and Tohoku University have jointly developed a real-time GEONET analysis system for rapid deformation monitoring (REGARD). REGARD can estimate the single rectangular fault model and slip distribution along the assumed plate interface. The single rectangular fault model is useful as a first-order approximation of a medium-to-large earthquake. However, in its estimation, it is difficult to obtain accurate results for model parameters due to the strong effect of initial values. To solve this problem, this study proposes a new method to estimate the coseismic fault model and model uncertainties in real time based on the Bayesian inversion approach using the Markov Chain Monte Carlo (MCMC) method. The MCMC approach is computationally expensive and hyperparameters should be defined in advance via trial and error. The sampling efficiency was improved using a parallel tempering method, and an automatic definition method for hyperparameters was developed for real-time use. The calculation time was within 30 s for 1 × 106samples using a typical single LINUX server, which can implement real-time analysis, similar to REGARD. The reliability of the developed method was evaluated using data from recent earthquakes (2016 Kumamoto and 2019 Yamagata-Oki earthquakes). Simulations of the earthquakes in the Sea of Japan were also conducted exhaustively. The results showed an advantage over the maximum likelihood approach with a priori information, which has initial value dependence in nonlinear problems. In terms of application to data with a small signal-to-noise ratio, the results suggest the possibility of using several conjugate fault models. There is a tradeoff between the fault area and slip amount, especially for offshore earthquakes, which means that quantification of the uncertainty enables us to evaluate the reliability of the fault model estimation results in real time.
Experimental validation of absolute SPECT/CT quantification for response monitoring in patients with coronary artery disease
Authors: van de Burgt Alina , Dibbets-Schneider Petra , Slump Cornelis H. , Scholte Arthur J. H. A. , Atsma Douwe E. , de Geus-Oei Lioe-Fee , van Velden Floris H. P.
Published: June 2021

Background

Quantitative SPECT enables absolute quantification of uptake in perfusion defects. The aim of this experimental study is to assess quantitative accuracy and precision of a novel iterative reconstruction technique (Evolution; GE Healthcare) for the potential application of response monitoring using 99mTc-tetrofosmin SPECT/CT in patients with coronary artery disease (CAD).

Methods

Acquisitions of an anthropomorphic torso phantom with cardiac insert containing defects (with varying sizes), filled with 99mTc-pertechnetate, were performed on a SPECT/CT (Discovery 670 Pro, GE Healthcare). Subsequently, volumes of interest of the defects were manually drawn on CT to assess the recovery coefficient (RC). Bull’s eye plots were composed to evaluate the uptake per segment. Finally, 99mTc-tetrofosmin SPECT/CT scans of 10 CAD patients were used to illustrate clinical application.

Results

The phantom study indicated that Evolution showed convergence after 7 iterations and 10 subsets. The average repeatability deviation of all configurations was 2.91% and 3.15% (%SD mean) for filtered (Butterworth) and unfiltered data, respectively. The accuracy after post-filtering was lower compared to the unfiltered data with a mean (SD) RC of 0.63 (0.05) and 0.70 (0.07), respectively (p < 0.05). More artificial defects were found on Bull’s eye plots created with the unfiltered data compared to filtered data. Eight out of ten patients showed significant changes in uptake before and after treatment (p < 0.05).

Conclusion

Quantification of 99mTc-tetrofosmin SPECT/CT seems feasible for CAD patients when 7 iterations (10 subsets), Butterworth post-filtering (cut off frequency 0.52 in cycles/cm, order of 5) and manual CT-delineation are applied. However, future prospective patient studies are required for clinical application.
Development of a complex arts-based intervention for patients with end-stage kidney disease whilst receiving haemodialysis
Authors: Carswell Claire Elizabeth , Reid Joanne , Walsh Ian , Johnston William , Lee Jenny B. , McAneney Helen , Mullan Robert , Nelson Hugh , Matthews Michael , Weatherup Elizabeth , Spencer Andrea , Michelo Jean , Quail Anne , Kielty Grainne , Mackenzie Alistair , Elliott Jenny , Noble Helen
Published: June 2021

Background

Patients with end-stage kidney disease who receive haemodialysis experience a protracted treatment regimen that can result in an increased risk of depression and anxiety. Arts-based interventions could address this unique issue; however, no arts-based interventions have been developed for delivery within a haemodialysis unit and evaluation within a randomised controlled trials (RCTs).

Aim

To develop a complex arts-based intervention for patients with end-stage kidney disease whilst receiving haemodialysis.

Methods

The development process utilised the Arts in Health framework (Fancourt, 2017). The framework was addressed through the establishment of an interdisciplinary advisory group, collaboration and consultation with stakeholders, a scoping and realist review, shadowing of artists-in-residence, personal arts practice and logic modelling.

Results

The intervention involved six 1-h long, one-to-one facilitated sessions focused on creative writing and visual art. Patients could choose between art form and self-select a subject matter. The sessions had a primary focus on skill development and were delivered using principles derived from the psychological theory of flow.

Conclusion

The Arts in Health framework provided an appropriate and pragmatic approach to intervention development. Complex arts-based interventions can be developed for the purpose of evaluation within a trial framework. This intervention was designed to strike a balance between standardised components, and a person-centred approach necessary to address existential boredom.
Hyaluronate/black phosphorus complexes as a copper chelating agent for Wilson disease treatment
Authors: Kim Seong-Jong , Han Hye Hyeon , Hahn Sei Kwang
Published: June 2021

Background

Wilson disease (WD) is a genetic disorder of copper storage, resulting in pathological accumulation of copper in the body. Because symptoms are generally related to the liver, chelating agents capable of capturing excess copper ions after targeted delivery to the liver are highly required for the treatment of WD.

Methods

We developed hyaluronate-diaminohexane/black phosphorus (HA-DAH/BP) complexes for capturing copper ions accumulated in the liver for the treatment of WD.

Results

HA-DAH/BP complexes showed high hepatocyte-specific targeting efficiency, selective copper capturing capacity, excellent biocompatibility, and biodegradability. HA enhanced the stability of BP nanosheets and increased copper binding capacity. In vitro cellular uptake and competitive binding tests verified targeted delivery of HA-DAH/BP complexes to liver cells via HA receptor mediated endocytosis. The cell viability test confirmed the high biocompatibility of HA-DAH/BP complexes.

Conclusion

HA-DAH/BP complexes would be an efficient copper chelating agent to remove accumulated copper in the liver for the WD treatment.
Maltese as a foreign language educators’ acquisition of intercultural capabilities
Authors: Żammit Jacqueline
Published: June 2021

This study sought to understand how teachers of Maltese as a foreign language (MFL) develop intercultural capabilities by exploring the importance of intercultural competence (IC) to MFL teachers, the characteristics of interculturally competent MFL educators, and the ways in which educators develop IC. The study adopted the interpretivist paradigm and a case study research design to collect qualitative data. Seventeen MFL teachers of adult learners were purposefully selected because they all taught MFL to non-native adults. These educators were interviewed, by answering the researcher’s ten unstructured questions. A smartphone was used to record the interviewees. Findings regarding the perceptions of the teachers who were interviewed are as follows. Firstly, the participants stated that IC is important for MFL teachers because it helps them to embrace diversity, to help adult learners to learn the target language (i.e. Maltese) better, and to be sensitive and accommodative to learners from different backgrounds. Secondly, according to the participants, an interculturally capable person is one who knows their own culture and others’ cultural aspects, respects and accepts other cultures. It was also found that teachers develop intercultural capabilities through learning at a school and by visiting other countries and being immersed in the cultures of those countries. The implications of the findings as supported by existing literature, are that IC is important for foreign language teachers and as a result, intercultural training, learning through interactions with others and visits to other countries are necessary to develop intercultural capabilities.
Etheno adducts: from tRNA modifications to DNA adducts and back to miscoding ribonucleotides
Authors: Guengerich F. Peter , Ghodke Pratibha P.
Published: June 2021

Etheno (and ethano) derivatives of nucleic acid bases have an extra 5-membered ring attached. These were first noted as wyosine bases in tRNAs. Some were fluorescent, and the development of etheno derivatives of adenosine, cytosine, and guanosine led to the synthesis of fluorescent analogs of ATP, NAD+, and other cofactors for use in biochemical studies. Early studies with the carcinogen vinyl chloride revealed that these modified bases were being formed in DNA and RNA and might be responsible for mutations and cancer. The etheno bases are also derived from other carcinogenic vinyl monomers. Further work showed that endogenous etheno DNA adducts were present in animals and humans and are derived from lipid peroxidation. The chemical mechanisms of etheno adduct formation involve reactions with bis-electrophiles generated by cytochrome P450 enzymes or lipid peroxidation, which have been established in isotopic labeling studies. The mechanisms by which etheno DNA adducts miscode have been studied with several DNA polymerases, aided by the X-ray crystal structures of these polymerases in mispairing situations and in extension beyond mispairs. Repair of etheno DNA adduct damage is done primarily by glycosylases and also by the direct action of dioxygenases. Some human DNA polymerases (η, κ) can insert bases opposite etheno adducts in DNA and RNA, and the reverse transcriptase activity may be of relevance with the RNA etheno adducts. Further questions involve the extent that the etheno adducts contribute to human cancer.
An Axin2 mutation and perinatal risk factors contribute to sagittal craniosynostosis: evidence from a Chinese female monochorionic diamniotic twin family
Authors: Xu Jin , Yan Qing , Song Chengcheng , Liang Jingjia , Zhao Liang , Zhang Xin , Weng Zhenkun , Xu Cheng , Liu Qian , Xu Shuqin , Pang Lu , Zhang Liye , Sun Yuan , Wang Gang , Gu Aihua
Published: June 2021

Background

Craniosynostosis, defined as premature fusion of one or more cranial sutures, affects approximately 1 in every 2000–2500 live births. Sagittal craniosynostosis (CS), the most prevalent form of isolated craniosynostosis, is caused by interplay between genetic and perinatal environmental insults. However, the underlying details remain largely unknown.

Methods

The proband (a female monochorionic twin diagnosed with CS), her healthy co-twin sister and parents were enrolled. Obstetric history was extracted from medical records. Genetic screening was performed by whole exome sequencing (WES) and confirmed by Sanger sequencing. Functional annotation, conservation and structural analysis were predicted in public database. Phenotype data of Axin2 knockout mice was downloaded from The International Mouse Phenotyping Consortium (IMPC, http://www.mousephenotype.org).

Results

Obstetric medical records showed that, except for the shared perinatal risk factors by the twins, the proband suffered additional persistent breech presentation and intrauterine growth restriction. We identified a heterozygous mutation of Axin2 (c.1181G > A, p.R394H, rs200899695) in monochorionic twins and their father, but not in the mother. This mutation is not reported in Asian population and results in replacement of Arg at residue 394 by His (p.R394H). Arg 394 is located at the GSK3β binding domain of Axin2 protein, which is highly conserved across species. The mutation was predicted to be potentially deleterious by in silico analysis. Incomplete penetrance of Axin2 haploinsufficiency was found in female mice.

Conclusions

Axin2 (c.1181G > A, p.R394H, rs200899695) mutation confers susceptibility and perinatal risk factors trigger the occurrence of sagittal craniosynostosis. Our findings provide a new evidence for the gene-environment interplay in understanding pathogenesis of craniosynostosis in Chinese population.
Six-minute walk distance predicts hospitalization in elderly peritoneal dialysis patients: a single-center prospective cohort study
Authors: Yabe Hiroki , Imoto Yuto , Onoyama Ayaka , Ito Sayaka , Kono Kenichi , Moriyama Yoshifumi , Okada Keiko , Kasuga Hirotake , Ito Yasuhiko
Published: June 2021

Background

The risk of adverse events associated with peritoneal dialysis (PD) in elderly patients has not been thoroughly investigated. The purpose of this study was to assess the association between physical function and hospitalization in elderly PD patients.

Methods

This is a single-center prospective observational cohort study. Thirty-three aged patients (74.8 ± 5.9 years) participated in a 6-min walk distance, short physical performance battery (SPPB), lower extremity muscle strength, and 10-m walk speed. All subjects were followed until hospitalization to the end of the follow-up period.

Results

The 6-min walk distance was 332 ± 112.5 m; SPPB was 11 (8.3–12) points; the lower extremity muscle strength was 36.6 ± 9.6%; 10-m walk speed was 1.1± 0.2 m/s. During the follow-up, 19 patients (57.5%) were hospitalized. In the Kaplan-Meier survival analysis and log-rank test, a lower 6-min walk distance and PD vintage were significantly associated with hospitalization (p<0.05). After adjustment for PD vintage in Cox proportional analysis, the 6-min walk distance remained associated with hospitalization (95% confidence interval, 0.98–0.99).

Conclusion

Lower exercise tolerance assessed by the 6-min walk distance was significantly associated with hospitalization in elderly PD patients. Our findings indicate that measurement and intervention of exercise intolerance are essential to predict the clinical outcomes of elderly PD patients.

Trial registration

This study was prospectively registered at inception in the UMIN Clinical Trials Registry under identification number UMIN000038405.
Metamaterials subwavelength terahertz resonant cavities
Authors: Al-Rubaiee M. , Al-Janabi A. H. , Fleming S. C. , Argyros A.
Published: June 2021

One of the unique properties of metamaterials is the ability to manipulate electromagnetic waves at subwavelength scales, made possible by their structure on these scales. Here, rather than consider effective bulk properties, we consider the properties of microscopic features based on considering resonant unit cells. We used wire array metamaterials to form localized resonant cavities by changing the resonance frequency of one or more unit cells, surrounded by unchanged unit cells that do not support resonance for the propagating mode (i.e. forming a band gap). We validate our approach experimentally with electromagnetic waves in the terahertz range, demonstrating and characterizing subwavelength resonant cavities in this range. These resonant cavities can pave the way for ultra-compact subwavelength waveguides and other optical components.
Integrated management of Meloidogyne incognita on tomato using combinations of abamectin, Purpureocillium lilacinum, rhizobacteria, and botanicals compared with nematicide
Authors: El-Ashry R. M. , Ali Mohamed A. S. , Elsobki Ahmed E. A. , Aioub Ahmed A. A.
Published: June 2021

Background

Acceptable alternative eco-friendly tools in the present study were tested to control the root-knot nematode, Meloidogyne incognita, on greenhouse-cultivated vegetables. The nematicidal effect of rhizobacteria (Pseudomonas and Serratia), egg parasitic fungus (Purpureocillium lilacinum), abamectin (Streptomyces avermitilis), and 3 botanicals (colocynth, Citrullus colocynthis; moringa, Moringa oleifera; marigold, Tagetes erecta L.) singly or in combination was tested against M. incognita, in comparison with emamectin benzoate.

Results

In vitro treatments revealed that egg hatching and juvenile mortality were influenced by the type of bioagents, plant species of botanicals, and exposure time. All the tested bioagents and botanicals displayed nematicidal potential via their ovicidal and larvicidal action on egg hatching and J2 mortality of M. incognita. Three and 5 days post-treatment, abamectin and emamectin benzoate were more effective than P. lilacinum, Serratia and Pseudomonas, and C. colocynthis in inhibiting egg hatching: 96.31 and 94.88%; 95.79 and 94.05%; 94.11 and 94.46%; 85.54 and 87.28%; 88.87 and 84.30%, respectively. On the other hand, after 10 days, P. lilacinum gave the highest inhibition percentage (99.00%), followed by abamectin (89.25%). However, the difference was insignificant compared with the inhibition percentage of rhizobacteria, Serratia and Pseudomonas (88.69%; p ≤ 0.05). Moreover, juvenile mortality was 100.0, 96.80, and 91.60% after 10 days of treatment, respectively. However, botanicals showed a lower effect on egg hatching and juvenile mortality. Under greenhouse conditions, potential antagonism towards M. incognita by application the mixture of biocontrol agents and botanicals was more effective in controlling M. incognita than single treatments.

Conclusions

The combination of abamectin and/or emamectin benzoate with P. lilacinum and rhizobacteria was the most effective against M. incognita, followed by rhizobacteria and P. lilacinum, not only in decreasing galls and reproduction of M. incognita but also in increasing plant growth of tomato parameters than the control. The application of various bioagents including abamectin might be a potential antagonism strategy against phytonematodes in protected agricultural areas.
Fire, land cover, and temperature drivers of bat activity in winter
Authors: Jorge Marcelo H. , Sweeten Sara E. , True Michael C. , Freeze Samuel R. , Cherry Michael J. , Garrison Elina P. , Taylor Hila , Gorman Katherine M. , Ford W. Mark
Published: June 2021

Background

Understanding the effects of disturbance events, land cover, and weather on wildlife activity is fundamental to wildlife management. Currently, in North America, bats are of high conservation concern due to white-nose syndrome and wind-energy development impact, but the role of fire as a potential additional stressor has received less focus. Although limited, the vast majority of research on bats and fire in the southeastern United States has been conducted during the growing season, thereby creating data gaps for bats in the region relative to overwintering conditions, particularly for non-hibernating species. The longleaf pine (Pinus palustris Mill.) ecosystem is an archetypal fire-mediated ecosystem that has been the focus of landscape-level restoration in the Southeast. Although historically fires predominately occurred during the growing season in these systems, dormant-season fire is more widely utilized for easier application and control as a means of habitat management in the region. To assess the impacts of fire and environmental factors on bat activity on Camp Blanding Joint Training Center (CB) in northern Florida, USA, we deployed 34 acoustic detectors across CB and recorded data from 26 February to 3 April 2019, and from 10 December 2019 to 14 January 2020.

Results

We identified eight bat species native to the region as present at CB. Bat activity was related to the proximity of mesic habitats as well as the presence of pine or deciduous forest types, depending on species morphology (i.e., body size, wing-loading, and echolocation call frequency). Activity for all bat species was influenced positively by either time since fire or mean fire return interval.

Conclusion

Overall, our results suggested that fire use provides a diverse landscape pattern at CB that maintains mesic, deciduous habitat within the larger pine forest matrix, thereby supporting the diverse bat community at CB during the dormant season and early spring.
Vertically transmitted microbiome protects eggs from fungal infection and egg failure
Authors: Bunker M. E. , Elliott G. , Heyer-Gray H. , Martin M. O. , Arnold A. E. , Weiss S. L.
Published: June 2021

Background

Beneficial microbes can be vertically transmitted from mother to offspring in many organisms. In oviparous animals, bacterial transfer to eggs may improve egg success by inhibiting fungal attachment and infection from pathogenic microbes in the nest environment. Vertical transfer of these egg-protective bacteria may be facilitated through behavioral mechanisms such as egg-tending, but many species do not provide parental care. Thus, an important mechanism of vertical transfer may be the passage of the egg through the maternal cloaca during oviposition itself. In this study, we examined how oviposition affects eggshell microbial communities, fungal attachment, hatch success, and offspring phenotype in the striped plateau lizard,Sceloporus virgatus, a species with no post-oviposition parental care.

Results

Relative to dissected eggs that did not pass through the cloaca, oviposited eggs had more bacteria and fewer fungal hyphae when examined with a scanning electron microscope. Using high throughput Illumina sequencing, we also found a difference in the bacterial communities of eggshells that did and did not pass through the cloaca, and the diversity of eggshell communities tended to correlate with maternal cloacal diversity only for oviposited eggs, and not for dissected eggs, indicating that vertical transmission of microbes is occurring. Further, we found that oviposited eggs had greater hatch success and led to larger offspring than those that were dissected.

Conclusions

Overall, our results indicate that femaleS. virgatuslizards transfer beneficial microbes from their cloaca onto their eggs during oviposition, and that these microbes reduce fungal colonization and infection of eggs during incubation and increase female fitness. Cloacal transfer of egg-protective bacteria may be common among oviparous species, and may be especially advantageous to species that lack parental care.
Indigestible cowpea proteins reduced plasma cholesterol after long-term oral administration to Sprague-Dawley rats
Authors: Alashi Adeola M. , Wu Hongyi , Aluko Rotimi E.
Published: June 2021

Cowpea protein isolate (CPI) was subjected to various dry and wet heat pretreatments followed by sequential digestion with pepsin and pancreatin; the undigested residues were isolated as the indigestible cowpea proteins (ICPs). All the ICPs exhibited in vitro bile acid-binding capacity but ICP from the slow cooling-induced gelation had the highest yield (68%) and was used for rat feeding experiments to determine effect on plasma total cholesterol (TC). Groups consisting of 3 male and 3 female Sprague-Dawley rats each were fed hypercholesterolemic diets that contained casein only or casein that was partially substituted with ICP of CPI for 6 weeks. Results showed diet that contained 5% (w/w) ICP was more effective in preventing TC increase (1.8 mmol/L) when compared to increases of 9.34 and 4.15 mmol/L for CPI and casein only diets, respectively.

Graphical abstract
Is population an asset or a liability to Nigeria’s economic growth? Evidence from FM-OLS and ARDL approach to cointegration
Authors: Alimi Olorunfemi Yasiru , Fagbohun Akinola Christopher , Abubakar Mohammed
Published: June 2021

The controversial debate on whether high population translates to weak or better economic growth has been a topical discussion in the area of development economics. This study therefore uses the data of the Nigerian economy to investigate the links among population growth, growth in output and income per capita growth for the periods of 1981–2018. The study employs both ARDL bound testing approach to cointegration and fully modified least square methods to evaluate the parameter estimates. We found that there exists a long-run relationship between population growth and economic growth in Nigeria. Further, the study found that the statistical and significant effect of population growth is more on long-run income growth than long-run income per capita growth. Meanwhile, in the short-run, an adverse effect is reported from population growth to economic growth, implying that the former has a detrimental effect on the latter. The reason for the adverse effects of population growth in the short-run results from the high number of dependents, whereas, in the long-run, there is a chance of demographic dividend that makes the young people becomes productive in their adulthood. Our findings, therefore, support the league of many studies that population growth is an asset to the long-run economic growth of Nigeria. In contrast, it has a poor impact on economic performance in the short-run. Thus, there is a need for proper and adequate utilization of the country’s rising population in appropriate areas of the economy where their efforts would be fully utilized towards improving the overall growth of Nigeria.
Complicated acute appendicitis in a child with left atrial isomerism: a case report
Authors: Tabbara Faysal , Ataya Karim Wehby , Annous Youssef , Alamiddine Kawsar , Zaghal Ahmad
Published: June 2021

Background

Heterotaxy syndrome is a rare clinical entity that is characterized by abnormal visceral organ arrangement in the chest and abdomen. Left atrial isomerism is a subcategory of heterotaxy syndrome characterized by the presence of multiple spleens with or without cardiac anomalies. Patients may remain asymptomatic their whole lives until they are diagnosed incidentally. Given that patients with left atrial isomerism might demonstrate atypical presentations of acute intrabdominal pathologies, it is important to keep a high index of suspicion when encountering such cases.

Case presentation

In this report, we present a case of a 9-year-old boy with a known history of left atrial isomersim who presented with left lower quadrant pain and positive McBurney, psoas, and obturator signs on the left side. A computed tomography scan of the abdomen confirmed the diagnosis of perforated acute appendicitis on the left, which prompted an emergent laparoscopic appendectomy.

Conclusion

Our case highlights the importance of keeping a high index of suspicion for a heterotaxy syndrome that is complicated by acute appendicitis in pediatric patients presenting with vague abdominal pain. Planning the location of trocar placement in patients with situs anomalies is of paramount importance to avoid technical difficulties in laparoscopic procedures.
Nivolumab (NIVO) plus ipilimumab (IPI) or NIVO plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced esophageal squamous cell carcinoma (ESCC): First results of the CheckMate 648 study.
Authors: Chau Ian , Doki Yuichiro , Ajani Jaffer A. , Xu Jianming , Wyrwicz Lucjan , Motoyama Satoru , Ogata Takashi , Kawakami Hisato , Hsu Chih-Hung , Adenis Antoine , El Hajbi Farid , Di Bartolomeo Maria , Braghiroli Maria Ignez Freitas Melro , Holtved Eva , Xynos Ioannis , Liu Xuan , Lei Ming , Kondo Kaoru , Kato Ken , Kitagawa Yuko
Published: June 2021

LBA4001

Background: NIVO demonstrated superior overall survival (OS) vs chemo in previously treated patients (pts) with ESCC (ATTRACTION-3). We report OS and progression-free survival (PFS) from CheckMate 648, the first global phase III study to evaluate both an immuno-oncology (I-O)/chemo combination and an I-O/I-O combination in advanced ESCC. Methods: Adults with previously untreated, unresectable advanced, recurrent or metastatic ESCC were enrolled regardless of tumor cell PD-L1 expression. Pts were randomized to NIVO (240 mg Q2W) + chemo (fluorouracil + cisplatin Q4W), NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), or chemo alone. Primary endpoints for both comparisons were OS and PFS per blinded independent central review (BICR) in pts with tumor cell PD-L1 ≥ 1%. Hierarchically tested secondary endpoints included OS and PFS in all randomized pts. Results: 970 pts were randomized to NIVO + chemo, NIVO + IPI, and chemo arms (49% with tumor cell PD-L1 ≥ 1%). With 13 months (mo) minimum follow-up, NIVO + chemo and NIVO + IPI led to statistically significant improvement in OS vs chemo in pts with tumor cell PD-L1 ≥ 1% and all randomized pts (Table). Statistically significant PFS benefit was also observed for NIVO + chemo vs chemo (HR 0.65 [98.5% CI 0.46–0.92]; P = 0.0023) in pts with tumor cell PD-L1 ≥ 1%. PFS in NIVO + IPI vs chemo in pts with tumor cell PD-L1 ≥ 1% did not meet the prespecified boundary for significance. The objective response rate (per BICR) was 53% (NIVO + chemo), 35% (NIVO + IPI), and 20% (chemo) in pts with tumor cell PD-L1 ≥ 1% and in all randomized pts was 47%, 28%, and 27%, respectively; longer median (95% CI) duration of response was observed vs chemo for pts with tumor cell PD-L1 ≥ 1%: 8.4 (6.9–12.4), 11.8 (7.1–27.4), and 5.7 (4.4–8.7) mo and for all randomized pts: 8.2 (6.9–9.7), 11.1 (8.3–14.0), and 7.1 (5.7–8.2) mo, respectively. No new safety signals were identified (Table). Conclusions: NIVO plus chemo and NIVO plus IPI both demonstrated superior OS vs chemo, along with durable objective responses and acceptable safety, in pts with advanced ESCC, and each represents a potential new 1L treatment option. Clinical trial information: NCT03143153. [Table: see text]
Monitoring of Circulating Tumor DNA Improves Early Relapse Detection After Axicabtagene Ciloleucel Infusion in Large B-Cell Lymphoma: Results of a Prospective Multi-Institutional Trial
Authors: Frank Matthew J. , Hossain Nasheed M. , Bukhari Ali , Dean Erin , Spiegel Jay Y. , Claire Gursharan K. , Kirsch Ilan , Jacob Allison P. , Mullins Chelsea D. , Lee Lik Wee , Kong Katherine A. , Craig Juliana , Mackall Crystal L. , Rapoport Aaron P. , Jain Michael D. , Dahiya Saurabh , Locke Frederick L. , Miklos David B.
Published: June 2021

PURPOSE

Although the majority of patients with relapsed or refractory large B-cell lymphoma respond to axicabtagene ciloleucel (axi-cel), only a minority of patients have durable remissions. This prospective multicenter study explored the prognostic value of circulating tumor DNA (ctDNA) before and after standard-of-care axi-cel for predicting patient outcomes.

METHODS

Lymphoma-specific variable, diversity, and joining gene segments (VDJ) clonotype ctDNA sequences were frequently monitored via next-generation sequencing from the time of starting lymphodepleting chemotherapy until progression or 1 year after axi-cel infusion. We assessed the prognostic value of ctDNA to predict outcomes and axi-cel–related toxicity.

RESULTS

A tumor clonotype was successfully detected in 69 of 72 (96%) enrolled patients. Higher pretreatment ctDNA concentrations were associated with progression after axi-cel infusion and developing cytokine release syndrome and/or immune effector cell–associated neurotoxicity syndrome. Twenty-three of 33 (70%) durably responding patients versus 4 of 31 (13%) progressing patients demonstrated nondetectable ctDNA 1 week after axi-cel infusion ( P < .0001). At day 28, patients with detectable ctDNA compared with those with undetectable ctDNA had a median progression-free survival and OS of 3 months versus not reached ( P < .0001) and 19 months versus not reached ( P = .0080), respectively. In patients with a radiographic partial response or stable disease on day 28, 1 of 10 patients with concurrently undetectable ctDNA relapsed; by contrast, 15 of 17 patients with concurrently detectable ctDNA relapsed ( P = .0001). ctDNA was detected at or before radiographic relapse in 29 of 30 (94%) patients. All durably responding patients had undetectable ctDNA at or before 3 months after axi-cel infusion.

CONCLUSION

Noninvasive ctDNA assessments can risk stratify and predict outcomes of patients undergoing axi-cel for the treatment of large B-cell lymphoma. These results provide a rationale for designing ctDNA-based risk-adaptive chimeric antigen receptor T-cell clinical trials.
Concomitant Pheochromocytoma and Primary Aldosteronism: A Case Series and Literature Review
Authors: Mao Jimmy J , Baker Jessica E , Rainey William E , Young William F , Bancos Irina
Published: June 2021

Context

The detection and management of concomitant pheochromocytoma (PHEO) and primary aldosteronism (PA) is not well understood.

Objective

To investigate varying presentations and outcomes of cases with coexisting PHEO and PA to provide an approach to its diagnosis and management.

Methods

We conducted a retrospective case series of adult patients with concomitant PHEO and PA at Mayo Clinic from 2000-2020 and an additional review of cases before 2000 and from the medical literature. Clinical, biochemical, radiologic, and histologic parameters were measured.

Results

Fifteen patients (53% men, median age 53 years) were diagnosed with concomitant PHEO and PA. The majority presented with hypertension (13, 87%) and hypokalemia (13, 87%), and 6 (40%) presented with symptoms suggestive of catecholamine excess. All patients who underwent preoperative workup for catecholamine excess (14, 93%) were found to have biochemical levels above the upper limits of normal. Adrenal vein sampling (AVS) was performed in 9 patients (60%), where 5 (56%) were diagnosed with bilateral PA, and 4 (44%) with unilateral PA. Patients underwent either unilateral (12, 80%) or bilateral (3, 20%) adrenalectomy. Biochemical improvement or resolution of catecholamine excess was confirmed in all cases with documented measurements. Recurrence of PHEO was not observed. Six patients (40%) displayed persistent PA postoperatively.

Conclusion

Concomitant PHEO and PA is a rare but likely underreported condition. Hypertension with or without hypokalemia should prompt evaluation for PA, while any indeterminate adrenal mass should be assessed for PHEO. Coexisting disease warrants consideration of AVS to determine the laterality of PA to ensure appropriate management.
SDHB-Associated Paraganglioma Syndrome in Africa—A Need for Greater Genetic Testing
Authors: Siddiqui Nida , Seedat Faheem , Bulbulia Saajidah , Mtshali Nompumelelo Z , Botha Adam , Krause Amanda , Daya Reyna , Bayat Zaheer
Published: June 2021

A germline mutation is identified in almost 40% of pheochromocytoma/paraganglioma (PPGL) syndromes. Genetic testing and counseling are essential for the management of index cases as well as presymptomatic identification and preemptive management of affected family members. Mutations in the genes encoding the mitochondrial enzyme succinate dehydrogenase (SDH) are well described in patients with hereditary PPGL. Among patients of African ancestry, the prevalence, phenotype, germline mutation spectrum, and penetrance of SDH mutations is poorly characterized. We describe a multifocal paraganglioma in a young African male with an underlying missense succinate dehydrogenase subunit B (SDHB) mutation and a history of 3 first-degree relatives who died at young ages from suspected cardiovascular causes. The same SDHB mutation, Class V variant c.724C>A p.(Arg242Ser), was detected in one of his asymptomatic siblings. As there are limited data describing hereditary PPGL syndromes in Africa, this report of an SDHB-associated PPGL is a notable contribution to the literature in this growing field. Due to the noteworthy clinical implications of PPGL mutations, this work highlights the existing need for broader genetic screening among African patients with PPGL despite the limited healthcare resources available in this region.
Does PSA level affect the choice of prostate puncture methods among MRI-ultrasound fusion targeted biopsy, transrectal ultrasound systematic biopsy or the combination of both?
Authors: Liu Yunyun , Dong Lin , Xiang Lihua , Zhou Boyang , Wang Hanxiang , Zhang Ying , Xu Guang , Wu Jian , Wang Shuai , Zhang Yifeng , Xu Huixiong
Published: June 2021

Objectives:

To explore whether prostate-specific antigen (PSA) affects the choice of prostate puncture methods by comparing MRI-ultrasound fusion targeted biopsy (MRI-TBx) with transrectal ultrasound systematic biopsy (TRUS-SBx) in the detection of prostate cancer (PCa), clinically significant prostate cancer (csPCa) and non-clinically significant prostate cancer (nsPCa) in different PSA groups (<10.0,10.0–20.0 and>20.0 ng ml−1).

Methods:

A total of 190 patients with 215 lesions who underwent both MRI-TBx and TRUS-SBx were included in this retrospective study. PSA was measured pre-operatively and stratified to three levels. The detection rates of PCa, csPCa and nsPCa through different methods (MRI-TBx, TRUS-SBx, or MRI-TBx +TRUS SBx) were compared with stratification by PSA.

Results:

Among the 190 patients, the histopathological results revealed PCa in 126 cases, including 119 csPCa. In PSA <10.0 ng ml−1 group, although the detection rates of PCa and csPCa by MRI-TBx were higher than those of TRUS-SBx, no significant differences were observed (p = 0.741; p = 0.400). In PSA 10.0–20.0 ng ml−1 group, difference between the detection rate of csPCa with TRUS-SBx and the combined method was statistically significant (p = 0.044). As for PSA >20.0 ng ml−1, MRI-TBx had a higher csPCa rate than TRUS-SBx with no statistical significance noted (p = 0.600).

Conclusion:

MRI-TBx combined with TRUS-SBx could be suitable as a standard detection approach for csPCa in patients with PSA 10.0–20.0 ng ml−1. As for PSA >20.0 and <10.0 ng ml−1, both MRI-TBx and TRUS-SBx might provide effective solutions for tumor detection.

Advances in knowledge:

This study gives an account of choosing appropriate prostate puncture methods through PSA level.
Η κοινωνική διάσταση της ανώτατης εκπαίδευσης
Authors: Ευαγγελάκου Παναγιώτα
Published: June 2021

Η παρούσα διδακτορική διατριβή διερευνά την ικανοποίηση των φοιτητικών αναγκών από τις υπηρεσίες φοιτητικής στήριξης που έχουν συσταθεί εντός των πανεπιστημίων για την κάλυψη αυτών των αναγκών, στο πλαίσιο της κοινωνικής διάστασης της αποστολής τους. Πιο συγκεκριμένα, υπό το πρίσμα της κοινωνικής διάστασης, τα πανεπιστήμια έχουν αναπτύξει μια σειρά από υπηρεσίες στήριξης (σίτιση, στέγαση, αθλητικές εγκαταστάσεις, υπηρεσίες ψυχολογικής στήριξης, επαγγελματικού προσανατολισμού, σταδιοδρομίας, υγείας κλπ), με σκοπό να ικανοποιήσουν τις πολλαπλές και διαφοροποιημένες ανάγκες των φοιτητών τους, όπως έχουν προκύψει εξαιτίας της διεύρυνσης της πρόσβασης και της αύξησης του φοιτητικού πληθυσμού στα ανώτατα εκπαιδευτικά ιδρύματα. Το γεγονός αυτό θεωρείται ότι έχει ως αποτέλεσμα την έγκαιρη ολοκλήρωση των σπουδών τους και την ελάχιστη δυνατή φοιτητική διαρροή, λαμβάνοντας υπόψη ότι ένα σοβαρό πρόβλημα που αντιμετωπίζει η ανώτατη εκπαίδευση είναι η παράταση και η εγκατάλειψη των σπουδών των φοιτητών. Ωστόσο, το ερώτημα που θέτει η συγκεκριμένη μελέτη είναι αν οι ανάγκες των φοιτητών ικανοποιούνται μέσω των πανεπιστημιακών υπηρεσιών στήριξης και, τελικά, αν επιτυγχάνεται η κοινωνική διάσταση του πανεπιστημίου. Την απάντηση σε αυτό το ερώτημα επιχείρησε να δώσει η ποσοτική και η ποιοτική έρευνα που πραγματοποιήθηκε σε φοιτητές άνω του δευτέρου έτους του Πανεπιστημίου Πατρών. Τα αποτελέσματα της έρευνας έδειξαν ότι, παρά το γεγονός ότι το Πανεπιστήμιο Πατρών παρέχει στους φοιτητές ένα σύνολο υπηρεσιών στήριξης, η επίτευξη της κοινωνικής διάστασης φαίνεται να μην επιτυγχάνεται πλήρως. Η διαπίστωση αυτή έγκειται, αφενός, στη μη χρήση των υπηρεσιών στήριξης από τη συντριπτική πλειονότητα των φοιτητών (με εξαίρεση τη σίτιση και το Γυμναστήριο), αφετέρου, στην αδυναμία των υπηρεσιών που χρησιμοποιούνται να ικανοποιήσουν πλήρως τις φοιτητικές ανάγκες. Συνεπώς, η συνεισφορά της συγκεκριμένης διδακτορικής διατριβής είναι η ανάδειξη της αναγκαιότητας ενίσχυσης της κοινωνικής διάστασης του πανεπιστήμιου, η οποία φαίνεται να συνίσταται τόσο στη χρήση των υπηρεσιών στήριξης από τους φοιτητές όσο και στην ικανοποίηση των φοιτητικών αναγκών από αυτές. Με τη σειρά της, η χρήση των υπηρεσιών στήριξης φαίνεται να εξαρτάται από τη διαρκή ενημέρωση προς τους φοιτητές για την ύπαρξή τους καθώς και από την ανάπτυξη εμπιστοσύνης εκ μέρους των φοιτητών προκειμένου να τις χρησιμοποιήσουν. Από την άλλη, η ικανοποίηση των φοιτητικών αναγκών φαίνεται να συνδέεται με τις συνθήκες λειτουργίας της υπηρεσίας (χώρος, ωράριο) και με τον τρόπο οργάνωσής της (οργάνωση και διαχείριση του ανθρώπινου δυναμικού και των εργασιών της). Τέλος, ανατροφοδότηση για την ικανοποίηση των φοιτητών από τις υπηρεσίες στήριξης φαίνεται να προσφέρει η αξιολόγησή τους, η οποία είναι σημαντικό να μην παραλείπεται από κάθε πανεπιστήμιο που επιδιώκει τη βελτίωση των παρεχόμενων υπηρεσιών του και την αύξηση της ποιότητάς τους.