bluuebunny/crossref_metadata_2025 huggingface dataset:
A marginal structural model for normal tissue complication probability
Authors: Tang Thai-Son , Liu Zhihui , Hosni Ali , Kim John , Saarela Olli
Published: July 2024

The goal of radiation therapy for cancer is to deliver prescribed radiation dose to the tumor while minimizing dose to the surrounding healthy tissues. To evaluate treatment plans, the dose distribution to healthy organs is commonly summarized as dose-volume histograms (DVHs). Normal tissue complication probability (NTCP) modeling has centered around making patient-level risk predictions with features extracted from the DVHs, but few have considered adapting a causal framework to evaluate the safety of alternative treatment plans. We propose causal estimands for NTCP based on deterministic and stochastic interventions, as well as propose estimators based on marginal structural models that impose bivariable monotonicity between dose, volume, and toxicity risk. The properties of these estimators are studied through simulations, and their use is illustrated in the context of radiotherapy treatment of anal canal cancer patients.
Psychological Protective and Risk Factors for Depression, Anxiety and Mental Well-Being in Social Workers
Authors: Maddock Alan
Published: July 2024

Social workers worldwide experience high rates of depression, anxiety and deficits in well-being. Depression, anxiety or poor mental well-being can have a significant effect on the individual social worker, and the quality of care they can provide. There have been limited attempts to examine and understand the underlying psychological protective and risk factors for depression, anxiety and poor well-being amongst social workers. Using the clinically modified Buddhist psychological model (CBPM) as a theoretical framework, this cross-sectional study examined a range of potential psychological protective and risk factors for depression, anxiety and mental well-being of 121 social workers in Northern Ireland, using structural equation modelling, and conditional process analyses. Mindfulness, acceptance, attention regulation/decentering skills, self-compassion, non-attachment and non-aversion could act as protective factors against depression, anxiety and poor mental well-being in social workers. Results also indicate that each of these variables could reduce the extent to which social workers worry and ruminate, further reducing the risk that social workers might experience depression, anxiety, or poor mental well-being. This study offers promising preliminary evidence that the CBPM is a useful explanatory framework which helps to explain variation in depression, anxiety and mental well-being amongst social workers.
Ethnic Disproportionality in the Child Welfare System: A Welsh Linked Administrative Data Study for 2011–2020
Authors: Jing Yongchao , Bailey Grace A , Cheung Sin Yi , Griffiths Lucy J , Scourfield Jonathan
Published: July 2024

Children’s chances of contact with the child welfare system at different stages vary significantly by their ethnicity. This study goes beyond recent UK studies on the scale of ethnic differences in children in care or on protection plans by improving data completeness through data linkage, considering the ethnic patterns in the wider population of children in need or receiving care and support, and reporting trends over time. We contribute to the literature on ethnic disproportionality in the child welfare system by reporting the patterns in Wales from 2011 to 2020. The trend of ethnic disproportionality was distinct from the changes in the absolute number of children in the child social welfare system by ethnicity. Over the ten-year period, Mixed-heritage children were the most overrepresented and Asian children the most underrepresented, with fluctuations in the level of overrepresentation between 1.1 and 1.5 and underrepresentation between 0.5 and 0.7. The level of representation for Black children fluctuated considerably between 0.8 and 1.2 over the years. The overall level of ethnic disproportionality in Wales increased from 2011 to 2016 and then decreased from 2017 to 2020. Ethnic disproportionality appeared more pronounced amongst girls and in age groups zero to four and sixteen to seventeen.
Molecular engineering of coumarins for enhanced 2-photon absorption property
Authors: Zhang Fan , Wang Yong-Hsin , Wu Cheng-Lin , Lin Tzu-Chau , Abe Manabu
Published: July 2024

A series of coumarin-based quadrupolar and octupolar derivatives containing electron-donating substituents (carbazole or diphenylamine groups) were synthesized. Their photophysical properties were explored in different organic solvents (toluene, dichloromethane, and dimethyl sulfoxide). Each donor group was connected via cyclic stilbene based on coumarin, resulting in compounds with large 2-photon absorption cross-sections.
The role of the mediodorsal thalamus in chemosensory preference and consummatory behavior in rats
Authors: Gartner Kelly E , Samuelsen Chad L
Published: July 2024

Experience plays a pivotal role in determining our food preferences. Consuming food generates odor–taste associations that shape our perceptual judgements of chemosensory stimuli, such as their intensity, familiarity, and pleasantness. The process of making consummatory choices relies on a network of brain regions to integrate and process chemosensory information. The mediodorsal thalamus is a higher-order thalamic nucleus involved in many experience-dependent chemosensory behaviors, including olfactory attention, odor discrimination, and the hedonic perception of flavors. Recent research has shown that neurons in the mediodorsal thalamus represent the sensory and affective properties of experienced odors, tastes, and odor–taste mixtures. However, its role in guiding consummatory choices remains unclear. To investigate the influence of the mediodorsal thalamus in the consummatory choice for experienced odors, tastes, and odor–taste mixtures, we pharmacologically inactivated the mediodorsal thalamus during 2-bottle brief-access tasks. We found that inactivation altered the preference for specific odor–taste mixtures, significantly reduced consumption of the preferred taste and increased within-trial sampling of both chemosensory stimulus options. Our results show that the mediodorsal thalamus plays a crucial role in consummatory decisions related to chemosensory preference and attention.
‘Mattering’ the circular economy: tackling the Achilles’ heel of sustainable places via adopting a critical-relational perspective
Authors: Ersoy Aksel , Lagendijk Arnoud
Published: July 2024

The transition towards a circular economy (CE) is seen as vital for developing sustainable places. CE is used as a new buzzword, as well as an inducement to innovate and change socio-economic practices, by a diverse set of actors to meet sustainability and other goals. Genuine transformation, we argue here, requires those practices to seriously alter discourses and metrics. We adopt a material critical-relational perspective, drawing on the assemblage notion of (counter)actualisation. Our contribution is both conceptual and empirical. Conceptually, we develop an assemblage-based framework featuring practices, discourses and metrics. Empirically, we apply this to national CE policy and local initiatives in the Netherlands. Our results point out both passions and challenges to come to a genuinely transformative discourse and use of metrics.
Rescue Therapies for Steroid-refractory Acute Severe Ulcerative Colitis: A Systematic Review and Network Meta-analysis
Authors: Huang Chih-Wen , Yen Hsu-Heng , Chen Yang-Yuan
Published: July 2024

Background and Aims

Approximately 40% of patients with steroid-refractory acute severe ulcerative colitis [SR ASUC] require colectomies. Advanced therapies may reduce the short-term colectomy rates in patients with SR ASUC. However, comparative clinical studies evaluating the effectiveness of these rescue therapies are lacking. Therefore, we conducted a network meta-analysis to study the effectiveness of rescue therapies for SR ASUC.

Methods

Six randomised, controlled trials and 15 cohort studies, including 2004 patients, were analysed. Rescue drugs included tofacitinib, infliximab with a 5 or 10 mg/kg induction dose at 0, 2, and 6 weeks [IFX and IFX10, respectively], IFX with an accelerated regimen of three 5-mg/kg induction doses timed according to clinical need [accelerated IFX], tacrolimus, ciclosporin [CyA], ustekinumab, and adalimumab. Treatments were compared with a placebo.

Results

Tofacitinib odds ratio [OR]: 0.09 (95% confidence interval [CI]: 0.02–0.52]), accelerated IFX (OR: 0.16 [95% CI: 0.03–0.94]), IFX (OR: 0.2 [95% CI: 0.07–0.58]), and tacrolimus (OR: 0.24 [95% CI: 0.06–0.96]) significantly reduced the short-term colectomy rates compared with placebo. IFX10 and CyA tended to prevent colectomies. However, ustekinumab and adalimumab did not significantly affect the colectomy rates.

Conclusion

This is the first network meta-analysis to investigate the efficacy of advanced therapies in reducing short-term colectomy rates in patients with SR ASUC. Tofacitinib, accelerated IFX, standard IFX, and tacrolimus significantly reduced the colectomy rates in SR ASUC patients compared with placebo. Thus, advanced therapies should be considered for rescue therapies in patients with SR ASUC.
Sexual life experiences after myocardial infarction: a systematic review and synthesis of qualitative studies
Authors: Arıkan Emine , Yavaş Gamze
Published: July 2024

Aims

This study aims to systematically interpret and synthesize the data obtained from qualitative research about the sexual lives of individuals who have experienced myocardial infarction (MI).

Methods and results

A thorough literature review was conducted between November and December 2023 across five electronic databases: PubMed, Web of Science, CINAHL, EBSCO, and Science Direct Embase. This article includes 12 studies published in English since 2000 that have examined the sexual experiences of individuals who have experienced MI. This research adhered to the Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) guidelines. We utilized the Critical Appraisal Skills Programme tool for qualitative research to evaluate the quality of all the papers included. To synthesize the data, the deductive and interpretation technique according to Sandelowski and Barroso's approach has been used. The sexual experiences of individuals who have experienced MI were summarized under four main themes: changes in sexual life, barriers to engaging in sexual intercourse, an unmet need: information, and sexuality as a part of routine care.

Conclusion

Patients’ expectations from counselling services regarding sexuality after MI are oriented towards these services providing more comprehensive information and incorporating multidisciplinary approaches. This demand clearly indicates the complex and multidimensional changes in sexual life after MI and underscores the necessity for healthcare professionals to play a more active role in this area.

Registration

PROSPERO: CRD42023483112.
A conceptual framework from the Philippines to analyse organizational capacities for health policy and systems research
Authors: Liwanag Harvy Joy , Famaloan Ferlie Rose Ann , Reyes Katherine Ann , Tamayo Reiner Lorenzo , Villamater Lynn Daryl , Cabañero-Gasgonia Renee Lynn , Frahsa Annika , Asuncion Pio Justin
Published: July 2024

Organizations that perform Health Policy and Systems Research (HPSR) need robust capacities, but it remains unclear what these organizations should look like in practice. We sought to define ‘HPSRIs’ (pronounced as ‘hip-srees’, i.e. ‘Health Policy and Systems Research Institutions’) as organizational models and developed a conceptual framework for assessing their capacities based on a set of attributes. We implemented a multi-method study in the Philippines that comprised: a qualitative analysis of perspectives from 33 stakeholders in the HPSR ecosystem on the functions, strengths and challenges of HPSRIs; a workshop with 17 multi-sectoral representatives who collectively developed a conceptual framework for assessing organizational capacities for HPSRIs based on organizational attributes; and a survey instrument development process that determined indicators for assessing these attributes. We defined HPSRIs to be formally constituted organizations (or institutions) with the minimum essential function of research. Beyond the research function, our framework outlined eight organizational attributes of well-performing HPSRIs that were grouped into four domains, namely: ‘research expertise’ (1) excellent research, (2) capacity-building driven; ‘leadership and management’ (3) efficient administration, (4) financially sustainable; ‘policy translation’ (5) policy orientation, (6) effective communication; and ‘networking’ (7) participatory approach, (8) convening influence. We developed a self-assessment instrument around these attributes that HPSRIs could use to inform their respective organizational development and collectively discuss their shared challenges. In addition to developing the framework, the workshop also analysed the positionality of HPSRIs and their interactions with other institutional actors in the HPSR ecosystem, and recommends the importance of enhancing these interactions and assigning responsibility to a national/regional authority that will foster the community of HPSRIs. When tailored to their context, HPSRIs that function at the nexus of research, management, policy and networks help achieve the main purpose of HPSR, which is to ‘achieve collective health goals and contribute to policy outcomes’.
Strathclyde minor groove binders (S-MGBs) with activity against Acanthamoeba castellanii
Authors: Mcgee Leah M C , Carpinteyro Sanchez Alemao G , Perieteanu Marina , Eskandari Kaveh , Bian Yan , Mackie Logan , Young Louise , Beveridge Rebecca , Suckling Colin J , Roberts Craig W , Scott Fraser J
Published: July 2024

Background

Acanthamoeba spp. is the causative agent of Acanthamoeba keratitis and granulomatous amoebic encephalitis. Strathclyde minor groove binders (S-MGBs) are a promising new class of anti-infective agent that have been shown to be effective against many infectious organisms.

Objectives

To synthesize and evaluate the anti-Acanthamoeba activity of a panel of S-MGBs, and therefore determine the potential of this class for further development.

Methods

A panel of 12 S-MGBs was synthesized and anti-Acanthamoeba activity was determined using an alamarBlue™-based trophocidal assay against Acanthamoeba castellanii. Cross-screening against Trypanosoma brucei brucei, Staphylococcus aureus and Escherichia coli was used to investigate selective potency. Cytotoxicity against HEK293 cells allowed for selective toxicity to be measured. DNA binding studies were carried out using native mass spectrometry and DNA thermal shift assays.

Results and discussion

S-MGB-241 has an IC50 of 6.6 µM against A. castellanii, comparable to the clinically used miltefosine (5.6 µM) and negligible activity against the other organisms. It was also found to have an IC50 > 100 µM against HEK293 cells, demonstrating low cytotoxicity. S-MGB-241 binds to DNA as a dimer, albeit weakly compared to other S-MGBs previously studied. This was confirmed by DNA thermal shift assay with a ΔTm = 1 ± 0.1°C.

Conclusions

Together, these data provide confidence that S-MGBs can be further optimized to generate new, potent treatments for Acanthameoba spp. infections. In particular, S-MGB-241, has been identified as a ‘hit’ compound that is selectively active against A. castellanii, providing a starting point from which to begin optimization of DNA binding and potency.
Systematic review and meta analysis of psychological interventions to prevent or treat pediatric chronic disease in rural communities
Authors: Lancaster Brittany D , Hefner Tristen , Leslie-Miller Calissa J , Sexton Kody , Bakula Dana M , Van Allen Jason , Cushing Christopher C , Lim Crystal S , Janicke David M , Jelalian Elissa , Dayani Katie , Davis Ann M
Published: July 2024

Objective

The purpose of this systematic review and meta-analysis was to examine the effectiveness of psychological interventions at improving physical or mental health outcomes for youth living in rural communities who have, or are at-risk for, any chronic medical condition in comparison to control interventions conducted in rural communities.

Methods

Following prospective registration (OSF.IO/7TDQJ), 7 databases were searched through July 1, 2023. Studies were included if they were a randomized control trial of a psychological intervention conducted with youth living in a rural area who had, or were at-risk for, a chronic medical condition. Risk of bias was assessed with the Cochrane risk of bias version 2 tool. A qualitative synthesis and meta-analysis were conducted.

Results

15 studies met inclusion criteria. Obesity studies (n = 13) primarily focused on body mass index metrics, with limited significant findings across studies. Asthma treatment interventions (n = 2) showed no impact on hospitalizations. 3 studies evaluated mental health outcomes with no significant group differences observed. We meta-analytically analyzed 9 studies that evaluated body mass index z-scores and identified an overall null effect (Hedge’s g = 0.01, 95% CI [−0.07, 0.09], p = .85).

Conclusions

Most included studies focused on pediatric obesity, and there was a limited range of health outcomes reported. Compared to controls, minimal significant improvements in health outcomes were identified for psychological interventions for youth living in rural communities. Future efforts may benefit from situating this work more systematically within a health disparities framework with a focus on understanding mechanisms of disparities and translating this work into interventions and policy changes.
A fractional Hawkes process model for earthquake aftershock sequences
Authors: Davis Louis , Baeumer Boris , Wang Ting
Published: July 2024

A new type of Hawkes process, known as the fractional Hawkes Process (FHP), has been recently introduced. This process uses a Mittag-Leffler density as the kernel function which is asymptotically a power law and so similar to the Omori–Utsu law, suggesting the FHP may be an appropriate earthquake model. However, it is currently an unmarked point process meaning it is independent of an earthquake’s magnitude. We extend the existing FHP, by incorporating Utsu’s aftershock productivity law and a time-scaling parameter from the fractional Zener Model to a marked version so that it may better model earthquake aftershock sequences. We call this model the ‘Seismic Fractional Hawkes Process’ (SFHP). We then estimate parameters via maximum likelihood and provide evidence for these estimates being consistent and asymptotically normal via a simulation study. The SFHP is then compared to the epidemic type aftershock sequence and FHP models on four aftershock sequences from Southern California and New Zealand. While it is inconclusive if the seismic fractional Hawkes process performs better in a retrospective predictive performance experiment, it does perform favourably against both models in terms of information criteria and residual diagnostics especially when the aftershock clustering is stronger.
The Gezer Inscription ʿṣd pšt ‘Bundling Flax’: Revising the Arabic Cognate Etymology
Authors: Neishtadt Mila
Published: July 2024

This article is dedicated to one of the main lexical cruxes of the Gezer tablet, the expression ʿṣd pšt in the third line of the inscription. I follow the longstanding understanding of the Gezer inscription, according to which pšt refers to flax. The primary innovation of the article lies in the re-evaluation of the cognate Arabic etymology. I argue that the cognate Arabic ʿḍd in both Classical and Modern Arabic does not signify ‘cutting’, as has been suggested in research thus far. Rather, it means ‘upper arm’. I then examine the Mishnaic Hebrew phrase פשתן חוצני ḥoṣne pištan ‘flax bundles’ (m. Pe’ah 6:5) which exhibits a semantic shift:  ḥōṣɛn ‘bosom’ > ‘amount carried under bosom’ > ‘bundle’. Based on the revised Arabic ʿḍd ‘upper arm’ meaning, I propose a semantic parallel: the Gezer inscription’s verbal noun ʿṣd (< Proto- Semitic ‘upper arm’) has possibly experienced a semantic shift similar to that of חוצני פשתן ḥoṣne pištan ‘flax bundles’ in m. Pe’ah 6:5: ‘upper arm’ > ‘armful of produce’ > ‘bundle’. Accordingly, I suggest ʿṣd pšt means ‘bundling flax’. This suggestion offers a straightforward solution which clarifies etymological data from various Semitic languages, fits within the context of the Gezer inscription and finally resolves the agricultural ‘cutting’ flax difficulty.
Genotype × environment × management analysis to define allometric rules between leaves and stems in wheat
Authors: Zhu Chen , Liu Shouyang , Parent Boris , Yin Xiaogang , de Solan Benoit , Jiang Dong , Ding Yanfeng , Baret Fred
Published: July 2024

Allometric rules provide insights into structure–function relationships across species and scales and are commonly used in ecology. The fields of agronomy, plant phenotyping, and modeling also need simplifications such as those provided by allometric rules to reconcile data at different temporal and spatial levels (organs/canopy). This study explores the variations in relationships for wheat in terms of the distribution of crop green area between leaves and stems, and the allocation of above-ground biomass between leaves and stems during the vegetative period, using a large dataset covering different years, countries, genotypes, and management practices. The results showed that the relationship between leaf and stem area was linear, genotype-specific, and sensitive to radiation. The relationship between leaf and stem biomass depended on genotype and nitrogen fertilization. The mass per area, associating area and biomass for both leaf and stem, varied strongly by developmental stage and was significantly affected by environment and genotype. These allometric rules were evaluated and shown to have satisfactory performance, and their potential use is discussed with regard to current phenotyping techniques and plant/crop models. Our results enable the definition of models and minimum datasets required for characterizing diversity panels and making predictions in various genotype × environment × management contexts.
Carbohydrate-active enzymes involved in rice cell wall metabolism
Authors: De Coninck Tibo , Desmet Tom , Van Damme Els J M
Published: July 2024

Plant cell walls are complex, multifunctional structures, built up of polysaccharides and proteins. The configuration and abundance of cell wall constituents determine cellular elongation and plant growth. The emphasis of this review is on rice, a staple crop with economic importance, serving as model for grasses/cereals. Recent advancements have contributed to a better understanding of the grass/cereal cell wall. This review brings together current knowledge of the organization and metabolism of the rice cell wall, and addresses gaps in the information regarding the cell wall and enzymes involved. Several cell wall fractions, including cellulose, mixed-linkage glucans, and glucuronoarabinoxylans, are well understood in rice and other grasses/grains. Conversely, there are still open questions and missing links in relation to xyloglucans, glucomannans, pectin, lignin, and arabinogalactan proteins. There is still a large and untapped potential to identify carbohydrate-active enzymes (CAZymes), to characterize their activity, and to elucidate their involvement in the metabolism of the mentioned cell wall fractions. This review highlights the involvement of carbohydrate-active enzymes in rice cell wall metabolism, providing an update of current understanding with the aim of demarcating research areas with potential for further investigations.
Instituting the global: The racial analytics of migration
Authors: van Reekum Rogier , Schinkel Willem
Published: July 2024

In this article, we regard concepts of inclusion and exclusion as epistemological obstacles for a political (rather than a critical) analysis of migration. Working with the rich conceptual innovations and scientific and philosophical genealogies developed by Denise Ferreira Da Silva in Toward a Global Idea of Race, we seek to show how concepts of inclusion and exclusion, as well as equations between migration and mobility fortify what Da Silva has called ‘globality’ and ‘raciality’. Either explicitly or implicitly according primacy to inclusion means that what Da Silva calls ‘the logic of exclusion’ ultimately folds into what she terms ‘the logic of obliteration’, which revolves around the necessary assimilation of the European other to the Euro-white subject. As we argue, today, the racial institution of the global operates to a large extent by way of the conceptual, classificatory and ocular practices that make up what is known as ‘migration’, which continues to be understood (falsely but constitutively) as cross-border mobility. We seek to show how ‘migration’, and its concomitant binary analytic of inclusion and exclusion, has become an apparatus separating what Da Silva calls the ‘transcendental I’, that is, the universal, self-determining, Euro-white subject, from those primarily characterized and known by what Da Silva calls ‘affectability’, that is, external determination. In the hierarchy of humans that ensues, migrants become recognizable as racially inferior, affectable not-quite-subjects.
Polymorphism-Aware Models in RevBayes: Species Trees, Disentangling Balancing Selection, and GC-Biased Gene Conversion
Authors: Braichenko Svitlana , Borges Rui , Kosiol Carolin
Published: July 2024

The role of balancing selection is a long-standing evolutionary puzzle. Balancing selection is a crucial evolutionary process that maintains genetic variation (polymorphism) over extended periods of time; however, detecting it poses a significant challenge. Building upon the Polymorphism-aware phylogenetic Models (PoMos) framework rooted in the Moran model, we introduce a PoMoBalance model. This novel approach is designed to disentangle the interplay of mutation, genetic drift, and directional selection (GC-biased gene conversion), along with the previously unexplored balancing selection pressures on ultra-long timescales comparable with species divergence times by analyzing multi-individual genomic and phylogenetic divergence data. Implemented in the open-source RevBayes Bayesian framework, PoMoBalance offers a versatile tool for inferring phylogenetic trees as well as quantifying various selective pressures. The novel aspect of our approach in studying balancing selection lies in polymorphism-aware phylogenetic models’ ability to account for ancestral polymorphisms and incorporate parameters that measure frequency-dependent selection, allowing us to determine the strength of the effect and exact frequencies under selection. We implemented validation tests and assessed the model on the data simulated with SLiM and a custom Moran model simulator. Real sequence analysis of Drosophila populations reveals insights into the evolutionary dynamics of regions subject to frequency-dependent balancing selection, particularly in the context of sex-limited color dimorphism in Drosophila erecta.
Structure analysis of the telomere resolvase from the Lyme disease spirochete Borrelia garinii reveals functional divergence of its C-terminal domain
Authors: Semper Cameron , Watanabe Nobuhiko , Karimullina Elina , Patel Deepak T , Di Leo Rosa , Castellanos Mildred , Patel Dhruvin H , Chaconas George , Savchenko Alexei
Published: July 2024

Borrelia spirochetes are the causative agents of Lyme disease and relapsing fever, two of the most common tick-borne illnesses. A characteristic feature of these spirochetes is their highly segmented genomes which consists of a linear chromosome and a mixture of up to approximately 24 linear and circular extrachromosomal plasmids. The complexity of this genomic arrangement requires multiple strategies for efficient replication and partitioning during cell division, including the generation of hairpin ends found on linear replicons mediated by the essential enzyme ResT, a telomere resolvase. Using an integrative structural biology approach employing advanced modelling, circular dichroism, X-ray crystallography and small-angle X-ray scattering, we have generated high resolution structural data on ResT from B. garinii. Our data provides the first high-resolution structures of ResT from Borrelia spirochetes and revealed active site positioning in the catalytic domain. We also demonstrate that the C-terminal domain of ResT is required for both transesterification steps of telomere resolution, and is a requirement for DNA binding, distinguishing ResT from other telomere resolvases from phage and bacteria. These results advance our understanding of the molecular function of this essential enzyme involved in genome maintenance in Borrelia pathogens.
DNA-terminus-dependent transcription by T7 RNA polymerase and its C-helix mutants
Authors: Yu Bingbing , Chen Yifan , Yan Yan , Lu Xueling , Zhu Bin
Published: July 2024

The remarkable success of messenger RNA (mRNA)-based vaccines has underscored their potential as a novel biotechnology platform for vaccine development and therapeutic protein delivery. However, the single-subunit RNA polymerase from bacteriophage T7 widely used for in vitro transcription is well known to generate double-stranded RNA (dsRNA) by-products that strongly stimulate the mammalian innate immune response. The dsRNA was reported to be originated from self-templated RNA extension or promoter-independent transcription. Here, we identified that the primary source of the full-length dsRNA during in vitro transcription is the DNA-terminus-initiated transcription by T7 RNA polymerase. Guanosines or cytosines at the end of DNA templates enhance the DNA-terminus-initiated transcription. Moreover, we found that aromatic residues located at position 47 in the C-helix lead to a significant reduction in the production of full-length dsRNA. As a result, the mRNA synthesized using the T7 RNA polymerase G47W mutant exhibits higher expression efficiency and lower immunogenicity compared to the mRNA produced using the wild-type T7 RNA polymerase.
Staphylococcal exoribonuclease YhaM destabilizes ribosomes by targeting the mRNA of a hibernation factor
Authors: Lipońska Anna , Lee Hyun , Yap Mee-Ngan F
Published: July 2024

The hibernation-promoting factor (Hpf) in Staphylococcus aureus binds to 70S ribosomes and induces the formation of the 100S complex (70S dimer), leading to translational avoidance and occlusion of ribosomes from RNase R-mediated degradation. Here, we show that the 3′-5′ exoribonuclease YhaM plays a previously unrecognized role in modulating ribosome stability. Unlike RNase R, which directly degrades the 16S rRNA of ribosomes in S. aureus cells lacking Hpf, YhaM destabilizes ribosomes by indirectly degrading the 3′-hpf mRNA that carries an intrinsic terminator. YhaM adopts an active hexameric assembly and robustly cleaves ssRNA in a manganese-dependent manner. In vivo, YhaM appears to be a low-processive enzyme, trimming the hpf mRNA by only 1 nucleotide. Deletion of yhaM delays cell growth. These findings substantiate the physiological significance of this cryptic enzyme and the protective role of Hpf in ribosome integrity, providing a mechanistic understanding of bacterial ribosome turnover.
Delayed migration of a Sapien 3 Ultra Resilia following transcatheter aortic valve implantation after selection of a smaller-sized valve
Authors: Mitsuoka Nagiko , Takaseya Tohru , Sasaki Ken-ichiro , Takagi Kazuyoshi , Itaya Naoki , Oshita Kensuke , Sasaki Masahiro , Yokomizo Michiko , Nohara Yume , Kuroki Hidefumi , Fukumoto Yoshihiro , Tayama Eiki
Published: July 2024

This report discusses a rare case of delayed migration of a Sapien 3 Ultra Resilia (S3UR) valve following transcatheter aortic valve implantation. An 81-year-old Japanese woman had a borderline aortic annular size of 20–23 mm according to the manufacturer’s size chart. We chose to implant a smaller S3UR of 20 mm with an 80/20 depth ratio to allow for a second intervention, ensuring good hemodynamics and minimizing paravalvular leak. The patient initially had a favorable outcome despite an accidental 50/50 depth ratio during implantation. On postoperative day 3, the S3UR migrated into the left ventricular outflow tract. Emergency surgical aortic valve replacement was performed to retrieve the migrated valve. Use of the S3UR has led to a growing preference for smaller valve sizes. However, the risk of migration should be recognized. When an accidental 50/50 depth ratio implantation is encountered, post-dilation or second valve implantation should be performed immediately.
Effector MoSDT1 enhances Magnaporthe oryzae virulence and plays a dual role in regulating rice defense
Authors: Chen Hongfeng , Su Shunyu , Yang Shumin , Zhao Tianqi , Tang Ping , Luo Qiong , Zhong Yuanyuan , Yang Jing
Published: July 2024

C2H2 zinc effectors are a class of pathogen proteins that play a dual role in plant–pathogen interactions, promoting pathogenicity and enhancing plant defense. In our previous research, we identified Magnaporthe oryzae Systemic Defense Trigger 1 (MoSDT1) as a C2H2 zinc effector that activates rice (Oryza sativa) defense when overexpressed in rice. However, its regulatory roles in pathogenicity and defense require further investigation. In this study, we generated an MoSDT1 overexpressing strain and 2 knockout strains of M. oryzae to assess the impact of MoSDT1 on pathogenicity, rice defense, and phenotypic characteristics. Our analyses revealed that MoSDT1 substantially influenced vegetative growth, conidia size, and conidiation, and was crucial for the virulence of M. oryzae while suppressing rice defense. MoSDT1 localized to the nucleus and cytoplasm of rice, either dependent or independent of M. oryzae delivery. Through RNA-seq, scRNA-seq, and ChIP-seq, we identified that MoSDT1 modulates rice defense by regulating the phosphorylation and ubiquitination of various rice signaling proteins, including transcription factors, transcription repressors, kinases, phosphatases, and the ubiquitin system. These findings provide valuable insights into the regulatory mechanisms of C2H2 zinc finger effector proteins and offer important foundational information for utilizing their target genes in disease resistance breeding and the design of targets for disease management.
Executory trusts: the scope for their creation (including within fundraising appeals)
Authors: Wilde David
Published: July 2024

This article seeks to explain what is meant by an ‘executory trust’. It argues that widely cited case law, suggesting an executory trust is only valid if it includes a highly detailed explanation of the intended final trust, is inconsistent with the weight of authority overall and may be wrong. And it argues that fundraising appeal collections may often give rise to executory trusts. Accordingly, it is suggested that executory trusts—a topic only mentioned at all in about half of trusts textbooks—may be more practically significant than is usually thought.
A diverse diet increases animal growth performance and carcass yield of grazing lambs
Authors: Beck Matthew R , Garrett Konagh , Marshall Cameron J , Gregorini Pablo
Published: July 2024

The current experiments were conducted across two lamb finishing seasons (2019 [experiment 1; Exp1] and 2020 [experiment 2; Exp2]). In both experiments lambs were provided a monotonous (MON) diet (annual ryegrass [Lolium multiflorum L.] during 2019 and perennial ryegrass [L. perenne L.] and white clover [Trifolium repens L.] during 2020) or a diverse (DIV) diet composed of spatially separated strips sown to chicory (Chicorium intybus L.), plantain (Plantago lanceolata L.), perennial ryegrass, lucerne (Medicago sativa L.), and dock (Rumex obtusifolius). During Exp1, the DIV lambs had a stocking rate (SR) of either 80, 95, 100, or 110 m2/lamb/wk, whereas the MON lambs had a 100 m2/lamb/wk SR. In Exp2, the SR aimed to allocate the MON lambs with twice the forage allowance (kg DM/lamb/d) as DIV lambs. In Exp1, all lambs provided DIV had a greater (P < 0.01) average daily gain (ADG; + 130%) than MON rams, independent of the SR. Accordingly, DIV had greater (P < 0.05) hot carcass weight (HCW; + 26%) and aged carcass weight (CW; + 27%) compared with MON, across all SR. The 80 m2/lamb/wk SR tended to have a greater (P = 0.10) dressing percentage and had similar (P = 0.29) drip loss percentage to the MON lambs, while the other DIV lamb SR all had greater (P < 0.05; +12%) dressing percentages and lower (P < 0.05) drip loss percentage than MON lambs. In Exp2, DIV lambs had greater (P < 0.01) ADG (+37%), HCW (+15%), and dressing percentage (+6%) compared with MON lambs. This improved animal performance occurred despite being offered 57% less (P = 0.01) dry matter (DM), 56% less (P < 0.01) digestible DM, and 57% less (P = 0.02) metabolizable energy per lamb per day. Ultimately, these experiments demonstrate that providing growing lambs a functionally diverse diet improves animal growth performance and carcass weight compared with a monotonous diet of annual ryegrass or a mixed sward containing perennial ryegrass with white clover.
VIIShakespeare
Authors: Rendall Edward B M , Smith Peter J , Fairbanks Chloe , Stelzer Emanuel , Bell Shirley , Hodgson Sarah , Baratta Luca
Published: July 2024

This chapter has four sections: 1. Editions and Textual Studies; 2. Shakespeare in the Theatre; 3. Shakespeare on Screen: this will be available as a double section in the next edition of YWES; 4. Criticism. Section 1 is by Edward B. M. Rendall; section 2 is by Peter J. Smith; section 3 is by Elinor Parsons; section 4(a) is by Chloe Fairbanks; section 4(b) is by Emanuel Stelzer; section 4(c) is by Shirley Bell; section 4(d) is by Sarah Hodgson; section 4(e) is by Luca Baratta.
Sex‐specific effect of antenatal Zika virus infection on murine fetal growth, placental nutrient transporters, and nutrient sensor signaling pathways
Authors: Pereira‐Carvalho Daniela , Chagas Valim Alessandra Cristina , Borba Vieira Andrade Cherley , Bloise Enrrico , Fontes Dias Ariane , Muller Oliveira Nascimento Veronica , Silva Alves Rakel Kelly , dos Santos Ronan Christian , Lopes Brum Felipe , Gomes Medeiros Inácio , Antunes Coelho Sharton Vinicius , Barros Arruda Luciana , Regina Todeschini Adriane , Barbosa Dias Wagner , Ortiga‐Carvalho Tania Maria
Published: July 2024

Maternal Zika virus (ZIKV) infection during pregnancy has been associated with severe intrauterine growth restriction (IUGR), placental damage, metabolism disturbances, and newborn neurological abnormalities. Here, we investigated the impact of maternal ZIKV infection on placental nutrient transporters and nutrient‐sensitive pathways. Immunocompetent (C57BL/6) mice were injected with Low (103 PFU‐ZIKVPE243) or High (5 × 107 PFU‐ZIKVPE243) ZIKV titers at gestational day (GD) 12.5, and tissue was collected at GD18.5 (term). Fetal–placental growth was impaired in male fetuses, which exhibited higher placental expression of the ZIKV infective marker, eukaryotic translation initiation factor 2 (eIF2α), but lower levels of phospho‐eIF2α. There were no differences in fetal–placental growth in female fetuses, which exhibited no significant alterations in placental ZIKV infective markers. Furthermore, ZIKV promoted increased expression of glucose transporter type 1 (Slc2a1/Glut1) and decreased levels of glucose‐6‐phosphate in female placentae, with no differences in amino acid transport potential. In contrast, ZIKV did not impact glucose transporters in male placentae but downregulated sodium‐coupled neutral amino acid 2 (Snat2) transporter expression. We also observed sex‐dependent differences in the hexosamine biosynthesis pathway (HBP) and O‐GlcNAcylation in ZIKV‐infected pregnancies, showing that ZIKV can disturb placental nutrient sensing. Our findings highlight molecular alterations in the placenta caused by maternal ZIKV infection, shedding light on nutrient transport, sensing, and availability. Our results also suggest that female and male placentae employ distinct coping mechanisms in response to ZIKV‐induced metabolic changes, providing insights into therapeutic approaches for congenital Zika syndrome.
Systematic pan‐cancer analysis insights into ICAM1 as an immunological and prognostic biomarker
Authors: Yang Chunjiao , Ni Bingqiang , Shen Ling , Li Zhenlong , Zhou Lu , Wu Huayun , Zhang Yuzhe , Liu Ling , Liu Jiao , Tian Liansheng , Yan Lirong , Jin Xin
Published: July 2024

Intercellular adhesion molecule 1 (ICAM1) is a cell surface adhesion glycoprotein in the immunoglobulin supergene family. It is associated with several epithelial tumorigenesis processes, as well as with inflammation. However, the function of ICAM1 in the prognosis of tumor immunity is still unclear. This study aimed to examine the immune function of ICAM1 in 33 tumor types and to investigate the prognostic value of tumors. Using datasets from the Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), Cancer Cell Lines Encyclopedia (CCLE), Human Protein Atlas (HPA), and cBioPortal, we investigated the role of ICAM1 in tumors. We explored the potential correlation between ICAM1 expression and tumor prognosis, gene mutations, microsatellite instability, and tumor immune cell levels in various cancers. We observed that ICAM1 is highly expressed in multiple malignant tumors. Furthermore, ICAM1 is negatively or positively associated with different malignant tumor prognoses. The expression levels of ICAM1 were correlated with the tumor mutation burden (TMB) in 11 tumors and with MSI in eight tumors. ICAM1 is a gene associated with immune infiltrating cells, such as M1 macrophages and CD8+ T cells in gastric and colon cancer. Meanwhile, the expression of ICAM1 is associated with several immune‐related functions and immune‐regulation‐related signaling pathways, such as the chemokine signaling pathway. Our study shows that ICAM1 can be used as a prognostic biomarker in many cancer types because of its function in tumorigenesis and malignant tumor immunity.
PA experiences in clinical trials
Authors: Eggleston Alice , Sarkodie Eleanor , Rokser Rachel
Published: July 2024

Objective:

Physician associate/assistant (PA) experience in clinical trials is poorly documented in medical literature. This survey aimed to describe the characteristics and experiences of PAs in clinical trial research.

Methods:

We performed descriptive analyses of data gathered in 2022 by the American Academy of Physician Associates and published in the organization's annual Salary Report, specifically of respondents who indicated experience in traditional and/or decentralized clinical trials.

Results:

About 73% of PAs eligible for the clinical trials survey indicated they were either involved in clinical trials or had been involved in the past and were interested in working in clinical trials in the future. PAs often serve in subinvestigator roles and perform various clinical trial tasks regardless of previous research experience.

Conclusions:

PAs working in clinical trials demonstrated broad responsibilities and skills in the research setting. They leveraged benefits to working in clinical trials despite institutional barriers. Clinical research may fit into numerous PAs' practices and let them contribute to medical advancements.
Challenges Experienced by Saudi Patients With Cancer and Their Family Caregivers in Using Digital Healthcare Technology Platforms in the COVID-19 Pandemic
Authors: Wazqar Dhuha Youssef
Published: July 2024

COVID-19 has provided a unique boost to the use of digital healthcare technology, putting many vulnerable people at risk of digital exclusion. To promote digital healthcare equity, it is important to identify the challenges that may inhibit cancer patients and family caregivers from benefiting from such technology. This study explored the challenges that cancer patients and family caregivers experience in using digital healthcare technology platforms during the COVID-19 pandemic. A qualitative descriptive study using face-to-face semistructured individual interviews was carried out. A purposive sample of 21 participants was recruited from a public cancer hospital in Saudi Arabia. Qualitative content analysis with an inductive approach was utilized. The factors that challenged the ability of participants to benefit from digital healthcare technology were similar. Four themes related to the challenges the two groups experienced emerged: access to platforms, use of platforms for cancer health–related purposes, attitudes toward these platforms, and individual user preferences. This study identified numerous areas for improvement regarding digital healthcare technology platform implementation, which could increase future benefits and equal use. This study's findings also provide useful information to investigators who intend to create digital nursing interventions for both groups amid COVID-19 and other worldwide health crises.
Women's perceptions and experiences with cannabis use in menopause: a qualitative study
Authors: Babyn Katherine , Quintanilha Maira , Ross Sue , Makowsky Mark , Kiang Tony , Yuksel Nese
Published: July 2024

Objectives

Since the legalization of recreational cannabis in 2018, the use of cannabis for medical reasons has increased in Canada. The aim of this study was to explore the experiences and perceptions of midlife women using cannabis for medical purposes coinciding with menopause symptom management.

Methods

Semistructured, one-on-one interviews were conducted using a qualitative description method. This was the second phase of a mixed methods study, where interviewees were purposefully selected from a sample of women (ages 35 and over, located in Alberta) surveyed during the first phase of the study. Interviews were by phone or virtual meeting, audio-recorded, and transcribed verbatim. Qualitative content analysis was applied to analyze the data collected.

Results

Twelve interviews were conducted between December 2020 and April 2021. Menopause was perceived as a complex experience for women. Cannabis was described as a therapeutic agent, providing symptom relief through the menopause transition. Women reported similarities in their menopause and cannabis use experiences in the lack of information available, limited role of healthcare providers, feelings of stigmatization, and emphasis on self-education. Women self-managed their cannabis use, learning from their own experiences or the anecdotal sharing of others', accessed cannabis from a variety of medical and nonmedical sources, and relied on experimentation, and a range of supports were described.

Conclusion

Midlife women pursued the use of cannabis medically to manage symptoms that overlap with menopause. Understanding how and why midlife women use cannabis medically can provide insight for future research and the development of educational resources to support women in menopause.