bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantification of the relationship between desmopressin concentration and Von Willebrand factor in Von Willebrand disease type 1: A pharmacodynamic study
Authors: Heijdra Jessica M. , Cloesmeijer Michael E. , de Jager Nico C.B. , Leebeek Frank W.G. , Kruip Marieke H.J.A. , Cnossen Marjon H. , Mathôt Ron A.A. ,   for the OPTI‐CLOT/ To WiN study group and SYMPHONY consortium
Published: May 2022

AbstractIntroductionDesmopressin can be used to prevent bleeding in von Willebrand disease (VWD), but the relationship between desmopressin and von Willebrand factor activity (VWF:Act) has yet to be quantified.AimTo quantify the relationship between desmopressin dose, its plasma concentration and the VWF:Act response in type 1 VWD patients.MethodsForty‐seven VWD patients (median age 25 years, IQR: 19–37; median body weight 71 kg, IQR: 59–86) received an IV desmopressin dose of .3 mcg/kg. In total, 177 blood samples were available for analysis. We developed an integrated population pharmacokinetic‐pharmacodynamic (PK‐PD) model using nonlinear mixed effect modelling. Subsequently, we performed Monte Carlo simulations to investigate the efficacy of the current dosing regimen.ResultsA one‐compartment PK model best described the time profile of the desmopressin concentrations. In the PD turnover model, the relationship between desmopressin plasma concentration and release of VWF:Act from the vascular endothelium was best described with an Emax model. Typically, VWF:Act increased 452% with an EC50 of .174 ng/ml. Simulations demonstrated that after .3 mcg/kg desmopressin intravenously, >90% patients with a VWF:Act baseline of ≥.20 IU/mL attain a VWF:Act >.5 IU/ml up to ≥4 h after administration. A capped dose of 30 mcg was sufficient in patients weighing over 100 kg.ConclusionThe relationship between desmopressin and VWF:Act was quantified in a PK‐PD model. The simulations provide evidence that recently published international guidelines advising an intravenous desmopressin dose of .3 mcg/kg with a capped dose of 30 mcg > 100 kg gives a sufficient desmopressin response.
Safety of intramuscular COVID‐19 vaccination in patients with haemophilia
Authors: Tiede Andreas , Leise Hendrik , Horneff Silvia , Oldenburg Johannes , Halimeh Susan , Heller Christine , Königs Christoph , Holstein Katharina , Pfrepper Christian 
Published: May 2022

AbstractBackgroundGuidelines recommend that patients with haemophilia should preferably receive vaccination subcutaneously. COVID‐19 and other vaccines, however, are only licenced for intramuscular application.AimsTo assess the safety of intramuscular COVID‐19 vaccination in patients living with haemophilia.MethodsPart A of this prospective observational study enrolled consecutive patients with haemophilia A (HA) and B (HB) of all ages and severities and assessed injection site bleeding and other complications within 30 days of vaccination. Part B enrolled patients providing informed consent for detailed data collection including medication and prophylaxis around the time of vaccination. Logistic regression was performed to assess potential risk factors for bleeding.ResultsFour hundred and sixty‐one patients were enrolled into part A. The primary endpoint injection site bleeding occurred in seven patients (1.5%, 95% confidence interval .7–3.1%). Comprehensive analysis of 214 patients (404 vaccinations, part B) revealed that 97% of patients with severe haemophilia had prophylaxis before vaccination, either as part of their routine prophylaxis or using additional doses. 56% and 30% of patients with moderate and mild haemophilia, respectively, received prophylaxis before vaccination. Among the seven bleeds recorded, three occurred when intramuscular vaccination was done without prophylaxis (odds ratio 12).ConclusionsThis is the first prospective study reporting on the safety of intramuscular vaccination in haemophilia. The rate of injection site bleeding was low in mild haemophilia, and in moderate and severe haemophilia if patients received factor prophylaxis.
A community jury study exploring the public acceptability of using risk stratification to determine eligibility for cancer screening
Authors: Dennison Rebecca A. , Boscott Rachel A. , Thomas Rae , Griffin Simon J. , Harrison Hannah , John Stephen D. , Moorthie Sowmiya A. , Morris Stephen , Rossi Sabrina H. , Stewart Grant D. , Thomas Chloe V. , Usher‐Smith Juliet A. 
Published: May 2022

AbstractIntroductionUsing risk stratification to determine eligibility for cancer screening is likely to improve the efficiency of screening programmes by targeting resources towards those most likely to benefit. We aimed to explore the implications of this approach from a societal perspective by understanding public views on the most acceptable stratification strategies.MethodsWe conducted three online community juries with 9 or 10 participants in each. Participants were purposefully sampled by age (40–79 years), sex, ethnicity, social grade and English region. On the first day, participants were informed of the potential benefits and harms of cancer screening and the implications of different ways of introducing stratification using scenarios based on phenotypic and genetic risk scores. On the second day, participants deliberated to reach a verdict on the research question, ‘Which approach(es) to inviting people to screening are acceptable, and under what circumstances?’ Deliberations and feedback were recorded and analysed using thematic analysis.ResultsAcross the juries, the principle of risk stratification was generally considered to be an acceptable approach for determining eligibility for screening. Disregarding increasing capacity, the participants considered it to enable efficient resource allocation to high‐risk individuals and could see how it might help to save lives. However, there were concerns regarding fair implementation, particularly how the risk assessment would be performed at scale and how people at low risk would be managed. Some favoured using the most accurate risk prediction model whereas others thought that certain risk factors should be prioritized (particularly factors considered as non‐modifiable and relatively stable, such as genetics and family history). Transparently justifying the programme and public education about cancer risk emerged as important contributors to acceptability.ConclusionUsing risk stratification to determine eligibility for cancer screening was acceptable to informed members of the public, particularly if it included risk factors they considered fair and when communicated transparently.Patient or Public ContributionTwo patient and public involvement representatives were involved throughout this study. They were not involved in synthesizing the results but contributed to producing study materials, co‐facilitated the community juries and commented on the interpretation of the findings and final report.
Qualitative and quantitative aspects of child‐directed parental talk and the relation to 2‐year‐old's developing vocabulary
Authors: Sundqvist Annette , Koch Felix‐Sebastian , Söderberg Mimmi , Barr Rachel , Heimann Mikael 
Published: May 2022

AbstractAlthough prior research has independently linked vocabulary development with toddlers' media usage, parental mental state talk (MST), and parent–child conversational turn‐taking (CTT), these variables have not been investigated within the same study. In this study, we focus on associations between these variables and 2‐year‐old's (N = 87) vocabulary. Child vocabulary and digital media use were measured through online questionnaires. We took a multimethod approach to measure parents' child‐directed talk. First, we used a home sound environment recording (Language ENvironment Analysis technology) to estimate parents' talk (CTT). Second, parents narrated a picture book, the Frog story, to assess the parent's MST. There was a negative association between how much children watched video content and their vocabulary. However, parents reported that they frequently co‐viewed and engaged with the child and media. The negative association first displayed between the amount of video content viewed and the child's developing vocabulary was fully mediated by the parents' qualitative and quantitative talk as measured by MST and CCT, respectively. We propose that the parent relative level of MST and CTT also occurs when parents engage with the child during media use.
Potassium content is the main driver for salinity tolerance in sweet potato before tuber formation
Authors: Mondal Shimul , Rahaman Ebna Habib Md Shofiur , Asch Folkard 
Published: May 2022

AbstractSweet potato (Ipomoea batatas L.) is mostly grown in Asia, which accounts for 86% of global production. However, its production is under threat by salinity. Little is known about genotypic responses to salinity in sweet potato. Phenotypic responses or physiological processes linked to salt tolerance that could be developed into a reliable screening tool to assist breeding have not yet been developed for sweet potato. In a hydroponic cultivation system, 12 contrasting sweet potato genotypes were subjected to 0, 50, 100 and 150 mM root zone salinity (RZS). Genotypic thresholds for dry matter accumulation and the genotypic slopes for additional dry matter reduction when the RZS increased beyond the genotypic threshold were determined. Sodium, chlorine and potassium (K) were determined from above‐ground biomass and correlated with the genotypic thresholds found. Genotypic threshold levels were linearly negatively correlated with the difference in tissue K content at 75 mM RZS and the tissue K content at control levels. Based on the genotypic ability to retain high tissue potassium levels under increasing RZS, we propose a screening tool based on these experimental data that can distinguish between salt‐tolerant and salt‐sensitive genotypes and indicate the potential yield level of the sweet potato genotypes.
Anguilla sp. diseases diagnoses and treatments: The ideal methods at the crossroads of conservation and aquaculture purposes
Authors: Parchemin Christelle , Tapissier‐Bontemps Nathalie , Sasal Pierre , Faliex Elisabeth 
Published: May 2022

AbstractAnguilla anguilla, A. japonica and A. rostrata are the most fished and consumed eel species. However, these species are Critically Endangered, Endangered and Endangered, respectively. A combination of factors is thought to be responsible for their decline including fisheries, climate change, habitat destruction, barriers to migration, pollution and pathogens. Among them, viruses, bacteria and parasites are causing weakening of wild eels and serious economic losses for fishermen and eel farmers. Early detection of pathogens is essential to provide appropriate responses both for conservation reasons and to limit economic losses. Classic diagnosis approaches are time consuming and invasive and usual treatments, for example, antipathogenic substances are becoming obsolete because of pathogen resistance and environmental impact problems. The need for early and non‐invasive diagnostic methods as well as effective and environmentally friendly treatments has increased. Vaccine development and diet supplementation have known a growing interest since their use could allow prevention of diseases. In this review, we summarize the main pathogens—viruses, bacteria and parasites—of the three northern temperate eel species, the methods used to detect these pathogens and the different treatments used. We discussed and highlighted the need for non‐invasive, rapid and efficient detection methods, as well as effective and environmentally friendly treatments for both conservation and aquaculture purposes.
Nurses’ substance use disorder in disciplinary procedures: A retrospective document analysis
Authors: Luurila Katrimaija , Kangasniemi Mari , Hult Marja , Häggman‐Laitila Arja 
Published: May 2022

AbstractAim and objectivesTo describe nurses with substance use disorder (SUD) in authority disciplinary actions.BackgroundNurses with SUD risk patient safety. Research evidence on the identification of nurses’ SUD and related management procedures is currently sparse.DesignRetrospective document analysis of decisions related to SUD in nurses’ disciplinary actions.MethodDecisions on nurses (N = 171) made by the Finnish National Supervisory Authority for Welfare and Health in Finland during 2007–2016 were used as data. An electronic extraction sheet was developed for data collection including variables (N = 34), of which 18 were analysed in this study with descriptive statistical methods and chi‐squared statistics. The study reported in accordance with the STROBE checklist for cross‐sectional studies.ResultsThe mean age of the nurses was 43 years (SD 8.7). The most mentioned reasons for notifications leading to disciplinary actions were substance abuse with working while intoxicated and drug theft. The most mentioned intoxicants used were medicines and alcohol. On average, the first disciplinary decision was given at 6.4 months (SD 3.9) and the final decision was given at 17.9 months (SD 13.1). The most common decision was restriction of the right to practice.ConclusionThe results supported findings from previous decades and different continents, showing similar trends are prevalent globally and continue today. In future studies, countries’ registers of nurses with SUD could be used to clarify the profile of nurses and develop appropriate procedures. Qualitative studies could be conducted to investigate to shed light on concealment of the phenomenon.Relevance to clinical practiceThere is a need for early identification, intervention and referral to treatment as well as effective protocols for reducing nurses’ risks of disciplinary actions related to SUD. It is important to be aware of the signs and symptoms of SUD and training for this is needed.
Implementing a resistance training programme for patients on short daily haemodialysis: A feasibility study
Authors: Ribeiro Heitor S. , Cunha Vinícius A. , Dourado Gustavo Í. , Duarte Marvery P. , Almeida Lucas S. , Baião Victor M. , Inda‐Filho Antônio J. , Viana João L. , Nóbrega Otávio T. , Ferreira Aparecido P. 
Published: May 2022

AbstractBackgroundKidney failure patients receiving haemodialysis experience protein‐energy wasting, muscle mass loss and physical function impairment. Intradialytic exercise interventions seem to modify these features, but they are often not implemented as a clinical routine.ObjectiveTo investigate the feasibility of implementing a supervised intradialytic resistance training programme as a clinical routine for patients receiving short daily haemodialysis.DesignA prospective longitudinal study.ParticipantsEighteen patients in a supervised intradialytic resistance training programme for 8 months.MeasurementsIt consisted of a warm‐up, lower‐ and upper‐limb resistance exercises and a cool‐down. Patients performed the resistance training during the first half of haemodialysis, twice a week, supervised by exercise physiologists and physiotherapists. The feasibility was assessed by the total and partial adherences, the reasons for refusing or for not exercising and the intradialytic complications.ResultsFrom a total of 953 potential exercise sessions, 759 were performed, with a 79.6% adherence rate. In the first 9 weeks, the adherence rate was 86.6% and the lowest rate was in the 19–27 weeks (73.5%). The main intradialytic complication during exercise sessions was hypotension (n = 31; 4.1%). The highest number of complications was reported during the first 9 weeks (n = 27; 9.1%). The main reasons for refusing or for not performing the intradialytic exercise sessions were clinical complications previous to exercise time (n = 63; 32.5%) and self‐reported indisposition (n = 62; 32.0%).ConclusionsThe intradialytic resistance training programme, supervised by exercise physiologists and physiotherapists, had very low complications, achieved a high long‐term adherence rate and showed to be feasible as a clinical routine for patients receiving short daily haemodialysis.
Medicare accountable care organization characteristics associated with participation in 2‐sided risk
Authors: Zhu Xi , Huang Huang , MacKinney A. Clinton , Ullrich Fred , Mueller Keith 
Published: May 2022

AbstractPurposeTo examine the associations of accountable care organization (ACO) characteristics with the likelihood of participation in 2‐sided risk tracks in the Medicare Shared Savings Program (SSP).MethodsCMS ACO Public Use Files and Provider‐Level Research Identifiable Files were used to trace Medicare ACOs’ participation in the SSP between 2012 and 2020 and measure ACO characteristics, including size, rurality of the service area, affiliation with supporting organizations, program experience, and performance. Logistic regression and survival analysis were used to test the associations between ACO characteristics and the probability of ACOs initially participating in or subsequently switching to 2‐sided risk tracks.FindingsAmong the 624 Medicare SSP ACOs that started between 2012 and 2017, 26 participated in 2‐sided risk tracks in their initial contracts and 95 switched to 2‐sided risk tracks subsequently. ACO characteristics were not significantly associated with the probability of participating in 2‐sided risk tracks in initial contracts. ACO size, affiliation with supporting organizations, and performance were positively associated with the likelihood of switching to 2‐sided risk. Rural ACOs were less likely to switch to 2‐sided risk than their urban counterparts.ConclusionsSmall and rural ACOs are less prepared to transition into 2‐sided risk swiftly.
Genomics analysis of Lactobacillus paracasei SLP16
Authors: Zhao X. , Hu R. , Liu Y. , He Y. , Li S. , Yang J. , Zhou J. , Zhang J. 
Published: May 2022

Abstract
Lactobacillus paracasei SLP 16 was obtained from liquor cellar mud, and it was analysed by genome sequencing on Illumina Hiseqq platform. Then the biological information of L. paracasei SLP16 was analysed by ExPasy (website), and the toxin safety of the strain SLP 16 was analysed by PSI/PHI in the virulence factor database VFDB. Through the second-generation DNA sequencing platform technology, the whole genome information of L. paracasei SLP16 was obtained, which showed that the genome size of the strain SLP 16 was 2·65 mol l−1, and the GC content of the strain SLP 16 was 46·9%. And a total of 3131 genes were detected, including 3067 genes encoding protein and 63 genes encoding RNA. Whole genome analysis showed that L. paracasei SLP16 had five coding genes of F0F1-ATPase, four coding genes of Na+/H+ antiporter and three coding genes of A-ATPase, which were closely related to the acid tolerance of lactic acid bacteria (LAB). Whole genome analysis of L. paracasei SLP16 showed that SLP 16 had only one CFA synthetic coding gene, and no important BSH coding gene; however, it had F0F1-ATPase, Na+/H+ antiporter and several two-component regulatory systems, and which were related to bile salt tolerance of LAB. Safety evaluation in L. paracasei SLP16 showed that it did not have the virulence factor coding gene related to toxin. Common antibiotic sensitivity tests showed that L. paracasei SLP16 was resistant to compounds such as sulfamethoxazole, ciprofloxacin, gentamicin and lincomycin. In summary, L. paracasei SLP16 had coding genes closely related to acid tolerance and bile salt tolerance, and no coding gene of virulence factors related to toxins, and few kinds of resistant antibiotics. Therefore, whole genome analysis showed that L. paracasei SLP16 was a safe probiotic strain that can be safely applied.
Discovery of a novel type IIb RelBE toxin‐antitoxin system in Mycobacterium tuberculosis defined by co‐regulation with an antisense RNA
Authors: Dawson Clinton C. , Cummings Jason E. , Starkey Julie M. , Slayden Richard A. 
Published: May 2022

AbstractToxin‐antitoxin loci regulate adaptive responses to stresses associated with the host environment and drug exposure. Phylogenomic studies have shown that Mycobacterium tuberculosis encodes a naturally expanded type II toxin‐antitoxin system, including ParDE/RelBE superfamily members. Type II toxins are presumably regulated exclusively through protein–protein interactions with type II antitoxins. However, experimental observations in M. tuberculosis indicated that additional control mechanisms regulate RelBE2 type II loci under host‐associated stress conditions. Herein, we describe for the first time a novel antisense RNA, termed asRelE2, that co‐regulates RelE2 production via targeted processing by the Mtb RNase III, Rnc. We find that convergent expression of this coding‐antisense hybrid TA locus, relBE2‐asrelE2, is controlled in a cAMP‐dependent manner by the essential cAMP receptor protein transcription factor, Crp, in response to the host‐associated stresses of low pH and nutrient limitation. Ex vivo survival studies with relE2 and asrelE2 knockout strains showed that RelE2 contributes to Mtb survival in activated macrophages and low pH to nutrient limitation. To our knowledge, this is the first report of a novel tripartite type IIb TA loci and antisense post‐transcriptional regulation of a type II TA loci.
Two Magnaporthe appressoria‐specific (MAS) proteins, MoMas3 and MoMas5, are required for suppressing host innate immunity and promoting biotrophic growth in rice cells
Authors: Gong Ziwen , Ning Na , Li Zhiqiang , Xie Xin , Wilson Richard A. , Liu Wende 
Published: May 2022

AbstractIn the devastating rice blast fungus Magnaporthe oryzae, six Magnaporthe appressoria‐specific (MAS) proteins are encoded by MoGAS1, MoGAS2 and MoMAS3–MoMAS6. MoGAS1 and MoGAS2 were previously characterized as M. oryzae virulence factors; however, the roles of the other four genes are unknown. Here, we found that, although the loss of any MAS gene did not affect appressorial formation or vegetative growth, ∆Momas3 and ∆Momas5 mutant strains (but not the others) were reduced in virulence on susceptible CO‐39 rice seedlings. Focusing on ∆Momas3 and ∆Momas5 mutant strains, we found that they could penetrate host leaf surfaces and fill the first infected rice cell but did not spread readily to neighbouring cells, suggesting they were impaired for biotrophic growth. Live‐cell imaging of fluorescently labelled MoMas3 and MoMas5 proteins showed that during biotrophy, MoMas3 localized to the apoplastic compartment formed between fungal invasive hyphae and the plant‐derived extra‐invasive hyphal membrane while MoMas5 localized to the appressoria and the penetration peg. The loss of either MoMAS3 or MoMAS5 resulted in the accumulation of reactive oxygen species (ROS) in infected rice cells, resulting in the triggering of plant defences that inhibited mutant growth in planta. ∆Momas3 and ∆Momas5 biotrophic growth could be remediated by inhibiting host NADPH oxidases and suppressing ROS accumulation. Thus, MoMas3 and MoMas5 are novel virulence factors involved in suppressing host plant innate immunity to promote biotrophic growth.