bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and efficacy of abiraterone acetate plus prednisolone in patients with castration-resistant prostate cancer: a prospective, observational, post-marketing surveillance study
Authors: Koroki Yosuke , Imanaka Keiichiro , Yasuda Yukiko , Harada Sayuri , Fujino Akiko
Published: May 2021

Background

Abiraterone acetate plus prednisolone is approved to treat patients with castration-resistant prostate cancer. This study evaluated the safety and efficacy of abiraterone acetate plus prednisolone in castration-resistant prostate cancer patients with or without previous chemotherapy in a real-world setting in Japan.

Methods

This study was an observational, prospective, post-marketing surveillance. Castration-resistant prostate cancer patients, who initiated abiraterone acetate after its approval in Japan, were enrolled. Data were collected during an observation period of 12 months and a follow-up period of another 12 months. Adverse events and adverse drug reactions were evaluated for safety. Prostate-specific antigen levels and overall survival were evaluated for efficacy.

Results

From 141 participating institutions, 497 patients were registered: 492 patients including 180 chemotherapy-naïve, 311 chemotherapy-experienced and one off-label-use patient received abiraterone and were evaluated for safety. Adverse events were observed in 225/492 patients (45.7%), adverse drug reactions in 131/492 patients (26.6%) and serious adverse drug reactions in 61/492 patients (12.4%). The most commonly observed adverse drug reaction was abnormal hepatic function (6.5%), followed by hypokalemia (3.0%) and decreased appetite (2.0%). At week 12, 110/432 patients (25.5%) achieved ≥50% decrease from baseline in prostate-specific antigen, and the proportion was higher in chemotherapy-naïve patients (56/161 patients; 34.8%) compared with chemotherapy-experienced patients (54/271 patients; 19.9%, P < 0.001). Survival rates at 24 months were 68.3% (295/432 patients), 73.9% (119/161 chemotherapy-naïve patients) and 64.9% (176/271 chemotherapy-experienced patients).

Conclusions

This large-scale, real-world, post-marketing surveillance study confirmed the safety and efficacy of abiraterone acetate plus prednisolone in Japanese castration-resistant prostate cancer patients with or without previous chemotherapy.
The RNA content of human sperm reflects prior events in spermatogenesis and potential post-fertilization effects
Authors: Corral-Vazquez C , Blanco J , Aiese Cigliano R , Sarrate Z , Rivera-Egea R , Vidal F , Garrido N , Daub C , Anton E
Published: May 2021

Transcriptome analyses using high-throughput methodologies allow a deeper understanding of biological functions in different cell types/tissues. The present study provides an RNA-seq profiling of human sperm mRNAs and lncRNAs (messenger and long non-coding RNAs) in a well-characterized population of fertile individuals. Sperm RNA was extracted from twelve ejaculate samples under strict quality controls. Poly(A)-transcripts were sequenced and aligned to the human genome. mRNAs and lncRNAs were classified according to their mean expression values (FPKM: Fragments Per Kilobase of transcript per Million mapped reads) and integrity. Gene Ontology analysis of the Expressed and Highly Expressed mRNAs showed an involvement in diverse reproduction processes, while the Ubiquitously Expressed and Highly Stable mRNAs were mainly involved in spermatogenesis. Transcription factor enrichment analyses revealed that the Highly Expressed and Ubiquitously Expressed sperm mRNAs were primarily regulated by zinc-fingers and spermatogenesis-related proteins. Regarding the Expressed lncRNAs, only one-third of their potential targets corresponded to Expressed mRNAs and were enriched in cell-cycle regulation processes. The remaining two-thirds were absent in sperm and were enriched in embryogenesis-related processes. A significant amount of post-testicular sperm mRNAs and lncRNAs was also detected. Even though our study is solely directed to the poly-A fraction of sperm transcripts, results indicate that both sperm mRNAs and lncRNAs constitute a footprint of previous spermatogenesis events and are configured to affect the first stages of embryo development.
Mergeomics 2.0: a web server for multi-omics data integration to elucidate disease networks and predict therapeutics
Authors: Ding Jessica , Blencowe Montgomery , Nghiem Thien , Ha Sung-min , Chen Yen-Wei , Li Gaoyan , Yang Xia
Published: May 2021

The Mergeomics web server is a flexible online tool for multi-omics data integration to derive biological pathways, networks, and key drivers important to disease pathogenesis and is based on the open source Mergeomics R package. The web server takes summary statistics of multi-omics disease association studies (GWAS, EWAS, TWAS, PWAS, etc.) as input and features four functions: Marker Dependency Filtering (MDF) to correct for known dependency between omics markers, Marker Set Enrichment Analysis (MSEA) to detect disease relevant biological processes, Meta-MSEA to examine the consistency of biological processes informed by various omics datasets, and Key Driver Analysis (KDA) to identify essential regulators of disease-associated pathways and networks. The web server has been extensively updated and streamlined in version 2.0 including an overhauled user interface, improved tutorials and results interpretation for each analytical step, inclusion of numerous disease GWAS, functional genomics datasets, and molecular networks to allow for comprehensive omics integrations, increased functionality to decrease user workload, and increased flexibility to cater to user-specific needs. Finally, we have incorporated our newly developed drug repositioning pipeline PharmOmics for prediction of potential drugs targeting disease processes that were identified by Mergeomics. Mergeomics is freely accessible at http://mergeomics.research.idre.ucla.edu and does not require login.
An exceptionally well-preserved herbaceous eudicot from the Early Cretaceous (late Aptian–early Albian) of Northwest China
Authors: Du Baoxia , Zhang Mingzhen , Sun Bainian , Li Aijing , Zhang Jing , Yan Defei , Xie Sanping , Wu Jingyu
Published: May 2021

A fossil eudicot, Gansufructus saligna gen. et sp. nov., is reported from the Early Cretaceous (late Aptian–early Albian) of the Gansu Province, Northwest China, based on numerous well-preserved axes with attached leaves and infructescences. The leaves are alternate, short petiolate and linear-lanceolate with low rank pinnate to reticulate venation. The infructescences are loose panicles bearing fruits in different stages of maturity, each containing four partly free carpels borne in a whorled arrangement. Each carpel has three to five seeds borne along its ventral margin. The nature of the leaves and axes indicates a terrestrial, herbaceous habit. In general organization, Gansufructus is closely similar to the fruit-bearing axes of Sinocarpus decussatus from the Early Cretaceous Jehol Biota, as well as other more or less contemporaneous angiosperms from the Far East, which together provide evidence of diverse eudicot angiosperms of low stature colonizing areas close to environments of deposition.
Use of Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry Analysis of Serum Peptidome to Classify and Predict Coronavirus Disease 2019 Severity
Authors: Gomila Rosa M , Martorell Gabriel , Fraile-Ribot Pablo A , Doménech-Sánchez Antonio , Albertí Miguel , Oliver Antonio , García-Gasalla Mercedes , Albertí Sebastián
Published: May 2021

Background

Classification and early detection of severe coronavirus disease 2019 (COVID-19) patients is required to establish an effective treatment. We tested the utility of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to classify and predict the severity of COVID-19.

Methods

We used MALDI-TOF MS to analyze the serum peptidome from 72 patients with COVID-19 (training cohort), clinically classified as mild (28), severe (23), and critical (21), and 20 healthy controls. The resulting matrix of peak intensities was used for Machine Learning (ML) approaches to classify and predict COVID-19 severity of 22 independent patients (validation cohort). Finally, we analyzed all sera by liquid chromatography mass spectrometry (LC-MS/MS) to identify the most relevant proteins associated with disease severity.

Results

We found a clear variability of the serum peptidome profile depending on COVID-19 severity. Forty-two peaks exhibited a log fold change ≥1 and 17 were significantly different and at least 4-fold more intense in the set of critical patients than in the mild ones. The ML approach classified clinical stable patients according to their severity with 100% accuracy and correctly predicted the evolution of the nonstable patients in all cases. The LC-MS/MS identified 5 proteins that were significantly upregulated in the critical patients. They included the serum amyloid protein A2, which probably yielded the most intense peak detected by MALDI-TOF MS.

Conclusions

We demonstrate the potential of the MALDI-TOF MS as a bench to bedside technology to aid clinicians in their decision making regarding patients with COVID-19.
Click chemistry-based pre-targeting cell delivery for cartilage regeneration
Authors: Co Cynthia M , Izuagbe Samira , Zhou Jun , Zhou Ning , Sun Xiankai , Borrelli Joseph , Tang Liping
Published: May 2021

A fraction of the OA patient population is affected by post-traumatic osteoarthritis (PTOA) following acute joint injuries. Stopping or reversing the progression of PTOA following joint injury could improve long-term functional outcomes, reduced disability, and medical costs. To more effectively treat articular cartilage injury, we have developed a novel cell-based therapy that involves the pre-targeting of apoptotic chondrocytes and the delivery of healthy, metabolically active chondrocytes using click chemistry. Specifically, a pre-targeting agent was prepared via conjugating apoptotic binding peptide (ApoPep-1) and trans-cyclooctene (TCO) onto polyethylene glycol (PEG) polymer carrier. The pre-targeting agent would be introduced to injured areas of articular cartilage, leading to the accumulation of TCO groups on the injured areas from actively binding to apoptotic chondrocytes. Subsequently, methyltetrazine (Tz)-bearing chondrocytes would be immobilized on the surface of TCO-coated injured cartilage via Tz-TCO click chemistry reaction. Using an ex vivo human cartilage explant PTOA model, the effectiveness of this new approach was evaluated. Our studies show that this novel approach (Tz-TCO click chemistry) significantly enhanced the immobilization of healthy and metabolically active chondrocytes to the areas of apoptotic chondrocytes. Histological analyses demonstrated that this treatment regimen would significantly reduce the area of cartilage degeneration and enhance ECM regeneration. The results support that Tz-TCO click chemistry-mediated cell delivery approach has great potential in clinical applications for targeting and treatment of cartilage injury.
Effects of management decisions on genetic evaluation of simulated calving records using random regression
Authors: MacNeil Michael D , Buchanan Justin W , Spangler Matthew L , Hay El Hamidi
Published: May 2021

The objective of this study was to evaluate the effects of various data structures on the genetic evaluation for the binary phenotype of reproductive success. The data were simulated based on an existing pedigree and an underlying fertility phenotype with a heritability of 0.10. A data set of complete observations was generated for all cows. This data set was then modified mimicking the culling of cows when they first failed to reproduce, cows having a missing observation at either their second or fifth opportunity to reproduce as if they had been selected as donors for embryo transfer, and censoring records following the sixth opportunity to reproduce as in a cull-for-age strategy. The data were analyzed using a third-order polynomial random regression model. The EBV of interest for each animal was the sum of the age-specific EBV over the first 10 observations (reproductive success at ages 2–11). Thus, the EBV might be interpreted as the genetic expectation of number of calves produced when a female is given 10 opportunities to calve. Culling open cows resulted in the EBV for 3-yr-old cows being reduced from 8.27 ± 0.03 when open cows were retained to 7.60 ± 0.02 when they were culled. The magnitude of this effect decreased as cows grew older when they first failed to reproduce and were subsequently culled. Cows that did not fail over the 11 yr of simulated data had an EBV of 9.43 ± 0.01 and 9.35 ± 0.01 based on analyses of the complete data and the data in which cows that failed to reproduce were culled, respectively. Cows that had a missing observation for their second record had a significantly reduced EBV, but the corresponding effect at the fifth record was negligible. The current study illustrates that culling and management decisions, and particularly those that affect the beginning of the trajectory of sustained reproductive success, can influence both the magnitude and accuracy of resulting EBV.
Effects of prescribed fire timing on vigor of the invasive forb sericea lespedeza (Lespedeza cuneata), total forage biomass accumulation, plant-community composition, and native fauna on tallgrass prairie in the Kansas Flint Hills
Authors: Alexander Jonathan A , Fick Walter H , Ogden Sarah B , Haukos David A , Lemmon Jack , Gatson Garth A , Olson K C
Published: May 2021

The predominant grazing-management practice of the Kansas Flint Hills involves annual prescribed burning in March or April with postfire grazing by yearling beef cattle at a high stocking density from April to August. There has been a dramatic increase in sericea lespedeza (Lespedeza cuneata [Dumont] G. Don) coincident with this temporally focused use of prescribed fire in the Flint Hills region. The species is an aggressive invader and a statewide noxious weed in Kansas. Control has generally been attempted using repeated herbicide applications. This approach has not limited proliferation of sericea lespedeza and resulted in collateral damage to nontarget flora and fauna. Alternative timing of prescribed fire has not been evaluated for its control. Our objectives for this 4-yr experiment were to (1) document the effects of prescribed burning during early April, early August, or early September on vigor of sericea lespedeza, standing forage biomass, and basal cover of native graminoids, forbs, and shrubs and (2) measure responses to fire regimes by grassland bird and butterfly communities. Whole-plant dry mass, basal cover, and seed production of sericea lespedeza were markedly less (P < 0.01) in areas treated with prescribed fire in August or September compared with April. Forage biomass did not differ (P ≥ 0.43) among treatments when measured during July; moreover, frequencies of bare soil, litter, and total basal plant cover were not different (P ≥ 0.29) among treatments. Combined basal covers of C4 grasses, C3 grasses, annual grasses, forbs, and shrubs also did not differ (P ≥ 0.11) between treatments. Densities of grasshopper sparrow (Ammodramus savannarum), dickcissel (Spiza americana), and eastern meadowlark (Sturnella magna) were not negatively affected (P > 0.10) by midsummer or late-summer fires relative to early-spring fires. There were no differences (P > 0.10) in densities of grassland-specialist butterfly species across fire regimes. Under the conditions of our experiment, prescribed burning during summer produced no detrimental effects on forage production, desirable nontarget plant species, grassland birds, or butterfly communities but had strong suppressive effects on sericea lespedeza. Additional research is warranted to investigate how to best incorporate late-summer prescribed fire into common grazing-management practices in the Kansas Flint Hills.
Effect of a Brief Supportive and Educational Intervention on the Psychological Well-Being of Mothers with Babies in Neonatal Wards of a Tertiary Hospital in Ibadan, Nigeria
Authors: Oyekunle Olufemi O , Bella-Awusah Tolulope , Ayede Adejumoke I , Omigbodun Olayinka O , Ani Cornelius C
Published: May 2021

OBJECTIVE

To assess the effect of a supportive educational intervention on the psychological wellbeing of mothers whose babies were admitted to Neonatal Care Unit (NCU) in Nigeria.

METHODS

Controlled trial involving 41 mothers whose babies were consecutively admitted into two NCUs (21 in the intervention group and 19 controls). The intervention group received two group-based sessions which included psychological coping strategies, and familiarity with NCU environment, equipment, personnel and procedures. The control group received usual care. Outcome measures were depressive symptoms (Edinburg Postnatal Depression Scale—EPDS), stress-related to NCU (Parental Stressor Scale: Neonatal Intensive Care Unit—PSS: NICU) and post-traumatic symptoms (Impact Event Scale-Revised—IES-R).

RESULTS

Difference-in-Differences (DiD) analysis showed a difference of −4.70 in PSS: NICU score in favour of the intervention group which was statistically significant [F(3, 75) = 9.47, p < 0.0001, R2 = 0.28]. The differences in EPDS (0.91) and IES-R (2.55) were not statistically significant [F(3, 75) = 10.10, p = 0.74] and [F(3, 75) = 10.13, p = 0.73], respectively. All the mothers in the treatment group expressed satisfaction with the intervention.

CONCLUSION

This brief group-based supportive educational intervention for mothers with babies in NCU was feasible, acceptable and helpful in reducing stress related to NCU. Larger controlled trials are recommended to establish the generalizability of these findings in this region.

LAY SUMMARY

Babies born too early and or with complications require admission to special hospital called Neonatal Care Unit (NCU) to help them to survive. However, parents whose babies are admitted to NCU can find the experience frightening. We examined how to reduce the fear and stress mothers in Nigeria experience when their babies are admitted to NCU.

We had two groups of mothers. The first group made up of 21 mothers was taught how to cope with the stress of having a baby in NCU. They were also shown how the various equipment in the NCU work, what the staff in NCU do and what types of things need to be done to help their babies. The second group of 19 mothers received usual care but did not have the extra teaching the first group received. After 2 weeks, we checked the level of depression and stress the mothers in both groups had compared with the level before the first group received the extra teaching.

We found that mothers in the first group who received the extra teaching were less stressed about having their babies in the NCU compared with the mothers that did not receive the teaching.
Protocol for Infant Massage in Home Settings: An e-Delphi Approach for Consensus Guidance Integrating Traditional Wisdom with Modern Medicine
Authors: Chaturvedi Sarika , Tillu Girish , Kale Anil , Pendse Aruna , Kulkarni Ashwini , Ambike Deepali , Krishnan Madhumita , Gaikwad Manoj , Mulay Monica , Prabhudesai Murlidhar , Nanal Nilangi , Tillu Neelima , Jog Pramod , Jamadar Samina , Kadam Sandeep , Singh Sarvesh Kumar , Komarajju Satyalakshmi , Agarkhedkar Sharad , Malwade Sudhir , Patwardhan Bhushan
Published: May 2021

Infant massage is a highly prevalent traditional practice in India and other parts of Asia. Clear guidance on safe and effective uses of infant massage is lacking especially in the contemporary times when the traditional knowledge is on the verge of extinction and preparations may differ from in the past. This paper presents a consensus guidance in the form of a standardized protocol for routine massage of infants in home settings. Furthermore, a feasible method to develop an integrative protocol involving traditional and modern medicine experts is described. A modified e-Delphi method was used to develop the protocol. A group of seventeen experts, including academicians and practitioners from disciplines as modern paediatrics, Ayurveda paediatrics, Physiotherapy and Naturopathy participated in three rounds of a Delphi study to evolve the consensus guidance. The present protocol for massage of infants born beyond 34 weeks of gestation and weighing above 1.8 kg is recommended for use by care givers. This provides guidance on the preparation for infant massage such as when to begin massaging the infant, checking fitness of the infant for massage, the appropriate time, environment, person and substance for infant massage and a detailed description of the procedure for infant massage. Paediatricians, obstetricians and other child care practitioners can use this protocol to guide care givers on how to peform infant massage.
The Natural Antisense Transcript DONE40 Derived from the lncRNA ENOD40 Locus Interacts with SET Domain Protein ASHR3 During Inception of Symbiosis in Arachis hypogaea
Authors: Ganguly Pritha , Roy Dipan , Das Troyee , Kundu Anindya , Cartieaux Fabienne , Ghosh Zhumur , DasGupta Maitrayee
Published: May 2021

The long noncoding RNA ENOD40 is required for cortical cell division during root nodule symbiosis (RNS) of legumes, though it is not essential for actinorhizal RNS. Our objective was to understand whether ENOD40 was required for aeschynomenoid nodule formation in Arachis hypogaea. AhENOD40 express from chromosome 5 (chr5) (AhENOD40-1) and chr15 (AhENOD40-2) during symbiosis, and RNA interference of these transcripts drastically affected nodulation, indicating the importance of ENOD40 in A. hypogaea. Furthermore, we demonstrated several distinct characteristics of ENOD40. (i) Natural antisense transcript (NAT) of ENOD40 was detected from the AhENOD40-1 locus (designated as NAT-AhDONE40). (ii) Both AhENOD40-1 and AhENOD40-2 had two exons, whereas NAT-AhDONE40 was monoexonic. Reverse-transcription quantitative PCR analysis indicated both sense and antisense transcripts to be present in both cytoplasm and nucleus, and their expression increased with the progress of symbiosis. (iii) RNA pull-down from whole cell extracts of infected roots at 4 days postinfection indicated NAT-AhDONE40 to interact with the SET (Su(var)3-9, enhancer of Zeste and Trithorax) domain containing absent small homeotic disc (ASH) family protein AhASHR3 and this interaction was further validated using RNA immunoprecipitation and electrophoretic mobility shift assay. (iv) Chromatin immunoprecipitation assays indicate deposition of ASHR3-specific histone marks H3K36me3 and H3K4me3 in both of the ENOD40 loci during the progress of symbiosis. ASHR3 is known for its role in optimizing cell proliferation and reprogramming. Because both ASHR3 and ENOD40 from legumes cluster away from those in actinorhizal plants and other nonlegumes in phylogenetic distance trees, we hypothesize that the interaction of DONE40 with ASHR3 could have evolved for adapting the nodule organogenesis program for legumes.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The Population of Sclerotinia sclerotiorum in Brazil Is Structured by Mycelial Compatibility Groups
Authors: Silva Rhaphael A. , Ferro Camila G. , Lehner Miller da S. , Paula Trazilbo J. , Mizubuti Eduardo S. G.
Published: May 2021

The genetic structure of the population of Sclerotinia sclerotiorum was analyzed using 238 individuals collected from different hosts. Individuals were characterized for microsatellite genotypes and mycelial compatibility groups (MCGs). A total of 22 MCGs and 64 multilocus lineages (MLLs) were identified. There was a close relationship between the MCGs and MLLs, but there was no association between MLLs and hosts or regions. At least 39 MCGs are present in Brazil, and 68.5% of the isolates were assigned to either MCG 1 or MCG 2. Eight new MCGs were found. Seven genetic groups were identified and associated with MCGs. Most genetic variation (70.0%) was because of differences among MCGs. High values of estimates of linkage disequilibrium among loci were more frequent in the total population (all MCGs). By contrast, there was evidence of random mating in subpopulations defined by MCGs 1 and 2. Additionally, there was evidence of outcrossing in the population of S. sclerotiorum in Brazil. The population was structured by MCGs; lineages originating from asexual reproduction or selfing prevail and are widely distributed in space, are persistent in time, and affect many hosts, but there is evidence of some degree of outcrossing, which may lead to a more genetically variable population in the future.
Investigating the Potential Mechanism of Pydiflumetofen Resistance in Sclerotinia sclerotiorum
Authors: Zhou F. , Cui Y. X. , Ma Y. H. , Wang J. Y. , Hu H. Y. , Li S. W. , Zhang F. L. , Li C.-W.
Published: May 2021

The necrotrophic pathogen Sclerotinia sclerotiorum is one of the most damaging and economically important plant pathogens. Pydiflumetofen, which was developed by Syngenta Crop Protection, has already been registered in China for the management of Sclerotinia stem rot, which was caused by S. sclerotiorum in oilseed rape. In an attempt to preempt and forestall the development of resistance to this useful fungicide, the current study was initiated to investigate the potential mechanism of resistance in laboratory mutants. Five pydiflumetofen-resistant S. sclerotiorum mutants were successfully generated by repeated exposure to the fungicide under laboratory conditions. Although the mutants had greatly reduced sensitivity to pydiflumetofen, they were also found to have significantly (P < 0.05) reduced fitness, exhibiting reduced mycelial growth and sclerotia formation on potato dextrose agar medium. However, three of the four mutants had significantly (P < 0.05) increased pathogenicity on detached soybean leaves compared with their respective parental isolates, indicating a moderate to high level of fungicide resistance risk according to the criteria of the Fungicide Resistance Action Committee. Sequence analysis of four succinate dehydrogenase (Sdh) target genes identified several nucleotide changes in the sequences of the pydiflumetofen-resistant mutants, most of which were synonymous and caused no changes to the predicted amino acid sequences. However, all of the pydiflumetofen-resistant mutants had two amino acid point mutations (A11V and V162A) in their predicted SsSdhB sequence. No similar changes were found in the SsSdhA, SsSdhC, and SsSdhD genes of any of the mutants tested. In addition, there was a positive cross-resistance between pydiflumetofen and boscalid, and no cross-resistance between pydiflumetofen and other commonly used fungicides, including tebuconazole, fludioxonil, cyprodinil, dimethachlone, prochloraz, pyraclostrobin, fluazinam, procymidone, and carbendazim. These results indicate that pydiflumetofen has great potential as an alternative fungicide for the control of S. sclerotiorum, especially where resistance to other fungicides has already emerged. Mixing or alternate application with fludioxonil, prochloraz, and fluazinam could be used to limit the risk of resistance to pydiflumetofen.
Fusarium Root Rot Complex in Soybean: Molecular Characterization, Trichothecene Formation, and Cross-Pathogenicity
Authors: Hafez Mohamed , Abdelmagid Ahmed , Aboukhaddour Reem , Adam Lorne R. , Daayf Fouad
Published: May 2021

Soybean is threatened by many pathogens that negatively affect this crop’s yield and quality, such as various Fusarium species that cause wilting and root rot diseases. Fusarium root rot (FRR) in soybean can be caused by F. graminearum and other Fusarium spp. that are associated with Fusarium head blight (FHB) in cereals. Therefore, it was important to inquire whether Fusarium pathogens from soybean can cause disease in wheat and vice versa. Here, we investigated the FRR complex in Manitoba (Canada) from symptomatic plants, using both culture- and molecular-based methods. We developed a molecular diagnostic toolkit to detect and differentiate between several Fusarium spp. involved in FHB and FRR, then we evaluated cross-pathogenicity of selected Fusarium isolates collected from soybean and wheat, and the results indicate that isolates recovered from one host can infect the other host. Trichothecene production by selected Fusarium spp. was also analyzed chemically via liquid chromatography mass spectrometry in both soybean (root) and wheat (spike) tissues. Trichothecenes were also analyzed in soybean seeds from plants with FRR to check the potentiality of trichothecene translocation from infected roots to the seeds. All of the tested Fusarium isolates were capable of producing trichothecenes in wheat spikes and soybean roots, but no trichothecenes were detected in soybean seeds. This study provided evidence, for the first time, that trichothecenes were produced by several Fusarium spp. (F. cerealis, F. culmorum, and F. sporotrichioides) during FRR development in soybean.
An Analysis of Postharvest Fungal Pathogens Reveals Temporal–Spatial and Host–Pathogen Associations with Fungicide Resistance-Related Mutations
Authors: Bradshaw Michael J. , Bartholomew Holly P. , Hendricks Dylan , Maust Autumn , Jurick Wayne M.
Published: May 2021

Fungicides are the primary tools to control a wide range of postharvest fungal pathogens. Fungicide resistance is a widespread problem that has reduced the efficacy of fungicides. Resistance to FRAC-1 (Fungicide Resistance Action Committee-1) chemistries is associated with mutations in amino acid position 198 in the β-tubulin gene. In our study, we conducted a meta-analysis of β-tubulin sequences to infer temporal, spatial, plant host, and pathogen genus patterns of fungicide resistance in postharvest fungal pathogens. In total, data were acquired from 2,647 specimens from 12 genera of fungal phytopathogens residing in 53 countries on >200 hosts collected between 1926 and 2020. The specimens containing a position 198 mutation were globally distributed in a variety of pathosystems. Analyses showed that there are associations among the mutation and the year an isolate was collected, the pathogen genus, the pathogen host, and the collection region. Interestingly, fungicide-resistant β-tubulin genotypes have been in a decline since their peak between 2005 and 2009. FRAC-1 fungicide usage data followed a similar pattern in that applications have been in a decline since their peak between 1997 and 2003. The data show that, with the reduction of selection pressure, FRAC-1 fungicide resistance in fungal populations will decline within 5 to 10 years. Based on this line of evidence, we contend that a β-tubulin position 198 mutation has uncharacterized fitness cost(s) on fungi in nature. The compiled dataset can inform end users on the regions and hosts that are most prone to contain resistant pathogens and assist decisions concerning fungicide resistance management strategies.
An Investigation on the Perceptions of Practicing Interdisciplinary Health Professionals on Rapid Cycle Deliberate Practice Simulation
Authors: Roszczynialski Kelly N. , Register Shilpa J. , Bergman Lisa , White Marjorie Lee
Published: May 2021

Introduction

Rapid cycle deliberate practice (RCDP) is a relatively new method for delivering simulation for a structured algorithm-based clinical content. We sought to understand how a group of practicing emergency medicine healthcare professionals would perceive RCDP as a learning method.

Methods

This was a qualitative study of participants' reactions to RCDP simulation during an orientation process to a new freestanding emergency department using grounded theory. Focus groups were held after simulation sessions to investigate the participants reactions to RCDP as well as the experience of multiple professions participating. Two investigators independently coded the focus group transcripts to detect themes and developed a list of codes, which were then confirmed by consensus. Data were organized into themes with contributing codes.

Results

Thirty-one individuals participated in the focus groups including physicians, nurse practitioners, nurses, respiratory therapists, and patient care technicians. Four themes were detected: the procedural components of RCDP, the behavioral response to RCDP, learning through RCDP, and RCDP as interprofessional experience. The participants view of emotions and interruptions and pauses had discrepant interpretation.

Conclusions

Participants received RCDP simulation positively. Initial negative reactions to the interruptions and pauses of RCDP dissipated as the simulation progressed. Ultimately, learners agreed that RCDP was extremely effective as compared with traditional simulation for medical resuscitation training because of the authenticity of the multidisciplinary aspect. This suggests that RCDP may be an effective tool for continuing education of practicing healthcare professionals.
Chemical Components of Smoke Produced From Versatile Training Tissue Models Using Electrocautery
Authors: Morimoto Gaku , Kawahira Hiroshi , Takayama Seiichiro , Lefor Alan Kawarai
Published: May 2021

Introduction

While exposure of surgeons and other staff to surgical smoke is an increasing health risk concern, there is a similar risk for users in surgical simulation and training. This study was undertaken to determine the chemical composition of smoke produced from a novel training model, Versatile Training Tissue (VTT), which is used for surgical simulation and training, and to compare this with smoke from a chemosynthetic model and porcine muscle and liver.

Methods

A variety of models (VTT, polyvinyl alcohol, porcine muscle and liver) were prepared and cauterized. Identification of chemical substances in smoke was performed using gas chromatography–mass spectrometry. Quantitative instrumental analysis was implemented with gas chromatography–mass spectrometry and high-performance liquid chromatography. A convenient analysis was performed with a general smoke tube kit.

Results

The main chemical components of smoke produced from VTT models include water and carbon dioxide. A small number of organic compounds were detected. Versatile Training Tissue models produced smoke with fewer compounds than smoke from a chemosynthetic model or porcine muscle.

Conclusions

The concentration of organic compounds from VTT models is considered to be below relevant health risk limits and lower than from polyvinyl alcohol and porcine muscle models. Although porcine liver smoke contains less of the main organic compounds of concern than a KM, it contains potentially hazardous nitrile compounds that are absent in KM smoke. Therefore, surgical simulation and training with VTT models should be considered relatively safe for trainees.
Understanding the psychological journey of patients with head and neck cancer in different periods: a qualitative study protocol
Authors: Li Yin , Ping Cheng , Yijian Li , Chunlian Yang , Ren Jiang , Jing Yang , Haixin Liang , Qinghua Jiang , Jianxia Lyu
Published: May 2021

Introduction

There are more than 900,000 new cases of head and neck tumors in the world every year, which is the sixth most common tumor in the world. During the treatment of head and neck cancer, patients often face various symptoms and psychological problems. In this qualitative study, patients with head and neck cancer were invited to share their psychological journey during diagnosis, treatment, and recovery to (1) understand their psychological status and feelings during different treatment stages, (2) their needs and concerns during different treatment stages, and (3) difficulties and problems in self-management.

Methods and analysis

We adopt qualitative study to understand these patient’ psychological journey with head and neck cancer, especially when they are at different times in the diagnosis, treatment and completion of head and neck tumors. Thematic analysis will be carried out following the six-phase iterative process suggested by Braun and Clarke: (1) familiarising oneself with data, (2) generating initial codes, (3) searching for themes, (4) reviewing themes,(5) defining and naming themes and (6) providing the report, which will be used to analyse the qualitative data.

Ethics and dissemination

This study has ethical approval from the Sichuan Cancer Hospital Ethics Committee. We will disseminate the findings through national and international conferences and international peer-reviewed journals.

Strengths and limitations

In this study, qualitative research was used to better understand the psychological process and feelings of patients with head and neck tumor at different stages of treatment.

The subjects were interviewed in the same tumor hospital. Patients in different grade hospitals in different regions may have different psychological processes and experiences.
Scabies outbreak management in refugee/migrant camps across Europe 2014-17: a retrospective qualitative interview study of healthcare staff experiences and perspectives
Authors: Richardson N. A. , Cassell J. A. , Head M. G. , Lanza S. , Schaefer C. , Walker S.L. , Middleton J.
Published: May 2021

Background

Scabies outbreaks were common in formal and informal refugee/migrant camps across Europe in 2014-17. This qualitative study aimed to provide insight into the experiences and perspectives of healthcare staff who treated scabies or managed outbreaks in these camps.

Methods

Recruitment was primarily through online networks of healthcare staff involved in medical care in refugee/migrant settings. Retrospective semi-structured telephone interviews were conducted, transcribed, and qualitative framework analysis carried out.

Results

Twelve participants who had worked in camps across seven European countries were interviewed. They reported that in the camps they had worked scabies diagnosis was primarily clinical, and without dermatoscopy, and treatment and outbreak management varied highly. Seven participants stated scabicide treatment was provided in camps whilst they were there, the remaining five reported only symptomatic management was offered. They described the camps as difficult places to work, with poor standards of living experienced by residents. Key perceived barriers to scabies control were (i) lack of Water, Sanitation and Hygiene facilities, specifically: absent/ limited showers (difficult to wash off irritant topical scabicides); inability to wash clothes and bedding (may have increased transmission/re-infestation), (ii) social factors: language; stigma; treatment non-compliance; mobility (interfering with contact tracing and follow-up treatments), (iii) healthcare factors: scabicide shortages and diversity; lack of examination privacy; staff inexperience, (iv) organisational factors: overcrowding; ineffective inter-organisational coordination; lack of support and maltreatment by state authorities (e.g. not providing basic facilities, and obstruction of self-care by camp residents and of aid efforts by NGOs).

Conclusions

We recommend development of accessible scabies guidelines for camps, use of consensus diagnostic criteria, and oral ivermectin mass treatments. In addition, as much of the work described was by small, volunteer staffed NGOs, we should reflect how we in the wider healthcare community can better support such initiatives, and those they serve.
The microbiological and physical properties of catheters for intermittent catheterization: A systematic review on the impact of reuse and cleaning methods
Authors: Grasdal Mark , Walter Matthias , Krassioukov Andrei V.
Published: May 2021

This systematic review provides an up to date and comprehensive summary of the clinical evidence of the effectiveness of various cleaning methods of intermittent catheterization that have been proposed to prepare catheters for reuse. This systematic review is registered at PROSPERO (registration number: CRD42020176065). A key word search of Medline (OVID), Excerpta Medica dataBASE (EMBASE, OVID), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL), in addition to manual searches of retrieved articles, was undertaken to identify all English, Russian and German language literature evaluating the effectiveness of various cleaning methods of intermittent catheterization. Studies selected for review included analytical experimental, prospective cohort, cross-sectional and case series study designs. Prospective cleaning methods analyzed included heat-based sterilization, chemical cleaning solutions, mechanical abrasion, photocatalytic sterilization, and combined methods. Studies that failed to assess the bacterial colonization or physical properties of catheters following cleaning were excluded. In total, 12 studies (i.e. 9 analytical experimental, 1 cohort study, 1 cross-sectional and 1 case series) were included. Two cleaning methods were identified as likely being most promising: five-minute submersion in 70% alcohol and the “Milton method”. Each eliminated bacterial colonization without affecting the physical properties of the catheters. All other cleaning methods were either non-bactericidal or caused gross visual or microscopic damage to the catheters, rendering their reuse unsafe. Additional higher-powered studies confirming the safety and efficacy of these cleaning methods must be obtained before we would feel comfortable challenging current clinical recommendations.
Oxymatrine Induces Autophagy and Apoptosis in Human Poorly Differentiated Gastric Adenocarcinoma Cells via Slit2/Robo1 Signals
Authors: He Mao-Tao , Zhang Ting , Hei Jing-ya , Ma Li-qiong
Published: May 2021

Oxymatrine (OMT), is a natural quinoxaline alkaloid from the traditional Chinese medicine herb and has been shown to exhibit anticancer properties on various types of cancer cells. Poorly differentiated gastric adenocarcinoma is a common malignancy of gastric cancer that is more aggressive and has a poor prognosis. In the present study, we investigate the effects of Slit2/Robo1 signals in poorly differentiated gastric adenocarcinoma and adjacent tissues, and the anticancer properties of OMT on human poorly differentiated gastric adenocarcinoma BGC-823 cells and evaluate their underlying mechanisms. The expression levels of Slit2 and Robo1 proteins were measured in 20 pairs of human poorly differentiated gastric adenocarcinoma tissues and adjacent normal tissues using western blot. The expression of apoptosis related proteins and autophagy-related proteins was detected by western blot. The cells viability was detected by CCK-8 assay. The migration of BGC-823 cells was detected by transwell experiments. The expression of related proteins was detected by western blot. The result shows that Slit2 and Robo1 are significantly increased in poorly differentiated gastric adenocarcinoma. The apoptosis and autophagy are inhibited in poorly differentiated gastric adenocarcinoma. OMT inhibits the growth and migration of BGC-823 cells in vitro. OMT inhibits the activation of Slit2/Robo1 signals and induces apoptosis and autophagy in BGC-823 cells. These findings suggest that the antitumor effects of OMT may be the result of inhibition of cell growth and migration, and inhibits the activation of Slit2/Robo1 signals pathway and induces apoptosis and autophagy. OMT may represent a novel anticancer therapy for the treatment of poorly differentiated gastric adenocarcinoma.
Cost-effectiveness of COVID-19 vaccination in low- and middle-income countries
Authors: Siedner Mark J. , Alba Christopher , Fitzmaurice Kieran P. , Gilbert Rebecca F. , Scott Justine A. , Shebl Fatma M. , Ciaranello Andrea , Reddy Krishna P. , Freedberg Kenneth A.
Published: May 2021

Despite the advent of safe and highly effective COVID-19 vaccines1–4, pervasive inequities in global distribution persist5. In response, multinational partners have proposed programs to allocate vaccines to low- and middle-income countries (LMICs)6. Yet, there remains a substantial funding gap for such programs7. Further, the optimal vaccine supply is unknown and the cost-effectiveness of investments into global vaccination programs has not been described. We used a validated COVID-19 simulation model8 to project the health benefits and costs of reaching 20%-70% vaccine coverage in 91 LMICs. We show that funding 20% vaccine coverage over one year among 91 LMICs would prevent 294 million infections and 2 million deaths, with 26 million years of life saved at a cost of US$6.4 billion, for an incremental cost effectiveness ratio (ICER) of US$250/year of life saved (YLS). Increasing vaccine coverage up to 50% would prevent millions more infections and save hundreds of thousands of additional lives, with ICERs below US$8,000/YLS. Results were robust to variations in vaccine efficacy and hesitancy, but were more sensitive to assumptions about epidemic pace and vaccination costs. These results support efforts to fund vaccination programs in LMICs and complement arguments about health equity9, economic benefits10, and pandemic control11.
The Impact of Past Pandemics on Economic and Gender Inequalities
Authors: Brzezinski Michal
Published: May 2021

This paper estimates how previous major pandemic events affected economic and gender inequalities in the short- to medium run. We consider the impact of six major pandemic episodes – H3N2 Flu (1968), SARS (2003), H1N1 Swine Flu (2009), MERS (2012), Ebola (2014), and Zika (2016) – on cross-country inequalities in a sample of up to 180 countries observed over 1950-2019. Results show that the past pandemics have moderately increased income inequality in the affected countries in the period of four to five years after the pandemic’s start. On the other hand, we do not find any robust negative impacts on wealth inequality. The results concerning gender inequality are less consistent, but we find some evidence of declining gender equality among the hardest hit countries, as well as of growing gender gaps in unemployment within the four years after the onset of the pandemic.