bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetics of biologics in gastric cancer
Authors: Li Junyi , Turner David C. , Li Feifei , Chen Xi , Liao Michael Z. , Li Chunze
Published: January 2023

Gastric cancer (GC) remains one of the leading causes of cancer death worldwide despite improvements in therapeutic options. Several biologics have been investigated in patients with GC, including those approved in other solid tumors; however, the success rate of the pivotal trials that investigated these biologic molecules in GC remains low. Elevation in total clearance and a decrease in systemic pharmacokinetic (PK) exposure in GC compared with other indications have been observed in these biologics across different pathways. Achieving optimal exposure for patients with GC is an important factor in balancing risk and optimizing therapeutic benefit and thus maximizing chance of positive outcomes for pivotal trials. Therefore, in this review, we summarize the PK disposition of several molecules (e.g., anti‐HER2, anti‐VEGF, and anti‐PD1) evaluated in GC and showed a consistent trend of lower drug exposure as compared to other solid tumors. We hypothesize that two possible mechanisms: (1) hyper‐catabolism of endogenous and exogenous proteins due to cancer cachexia; and (2) gastric protein leakage due to local inflammation at the gastrointestinal tract may explain or partially explain the increase of clearance in patients with GC. Last, the potential implications of such findings on dose selection to optimize the benefit: risk profile for biologics in GC are also discussed.
A narrative review of outcome measures used in drug and alcohol inpatient withdrawal treatment research
Authors: Wang Jing , Deane Frank P. , Kelly Peter J. , Robinson Laura
Published: January 2023

Issues

Assessing drug and alcohol inpatient withdrawal treatment programs is important, as these represent a first step of treatment among people with alcohol and drug problems. However, there are many ways of measuring outcomes making it difficult for service providers to decide which domains and methods to use. This narrative review aims to clarify frequencies of the domains and methods used to assess withdrawal treatment outcomes.

Approach

We reviewed published studies that examined outcomes of inpatient drug and alcohol withdrawal treatment. The types of outcome measures used and the frequency of use were summarised.

Key Findings

The review showed that assessment of withdrawal treatment outcomes goes beyond traditional abstinence measures. Outcomes mainly focus on biological and psychological outcomes, with social outcomes rarely measured. Even within outcome domains (e.g., cravings), there were many assessment methods.

Implications

The review provides service providers with an outline of common outcome domains and measures. Given the importance of social functioning to recovery from alcohol and drug problems, greater emphasis on such measures is desirable. Future research could develop greater consensus on outcome measures for use in withdrawal management services to facilitate clarity around factors associated with treatment success.

Conclusion

Outcome assessment in withdrawal treatment goes beyond abstinence to include holistic measurement of biological, psychological and some social outcomes; but more work needs to be done to cohere the different assessment methods and broaden the scope to include social functioning.
Artificial intelligence adoption in a competitive market
Authors: Gans Joshua S.
Published: January 2023

Economists have often viewed the adoption of artificial intelligence (AI) as a standard process innovation where we expect that efficiency will drive adoption in competitive markets. This paper models AI based on recent advances in machine learning that allow firms to engage in better prediction. Focusing on prediction of demand, it is demonstrated that AI adoption is a complement to variable inputs whose levels are altered directly by predictions and whose use is economized by them (that is, labour). It is shown that in a competitive market, this increases the short‐run elasticity of supply and may or may not increase average equilibrium prices. Generically, there are externalities in adoption, with this reducing the profits of non‐adoptees when variable inputs are important, and increasing them otherwise. Thus AI does not operate as a standard process innovation, and its adoption may confer positive externalities on non‐adopting firms. In the long run, AI adoption is shown to lower prices generally and raise consumer surplus in competitive markets.
Tomato plant defense induced by methyl jasmonate impacts on foraging behavior and parasitism of Trichogramma pretiosum
Authors: Weber Nelson Cristiano , Sant'Ana Josué , Redaelli Luiza Rodrigues , Dawud Ezequiel Figueiredo
Published: January 2023

Indirect plant defense may be mediated by volatiles released after oviposition and/or herbivory or by exogenous application of plant hormones such as methyl jasmonate (MeJa), signaling host presence to parasitoids. There is still incipient information regarding phytohormone action on crop plant defense, especially among tomato plants (Solanum lycopersicum L., Solanaceae) and the parasitoid Trichogramma pretiosum Riley (Hymenoptera: Trichogrammatidae). We aimed to evaluate T. pretiosum chemotaxis and parasitism in response to eggs and tomato plants exposed to Tuta absoluta (Meyrick) (Lepidoptera: Gelichiidae) oviposition and herbivory, with and without MeJa. We conducted laboratory (olfactometry and parasitism) and semi‐field (parasitism) bioassays with T. pretiosum in response to treatments with MeJa (0.5 mM) applied to tomato plants, and the interaction with its host, on plants with T. absoluta oviposition and herbivory. Methyl jasmonate presence directly on eggs did not affect T. pretiosum chemotaxis and parasitism. However, it did intensify this natural enemy's foraging behavior and parasitism when applied to the plant. Therefore, the use of MeJa in the T. absoluta and T. pretiosum tomato system may be beneficial, increasing parasitoid recognition and parasitism. Strategies aimed at improving biological control combined with environmentally friendly techniques, such as the use of phytohormones, are of utmost importance towards more sustainable agriculture.
Synthesis and perspectives on the study of ant‐plant interaction networks: A global overview
Authors: Juárez‐Juárez Brenda , Dáttilo Wesley , Moreno Claudia E.
Published: January 2023

In recent decades, the interest in complexity of ant‐plant relationships has increased considerably. However, because the spatial and biological information generated on ant‐plant interaction networks is dispersed in the literature it is necessary to synthesise current information, detect knowledge gaps, and outline needs for research leading to the development of a broad and systematic view on the subject.

Here, we present a global synthesis of the scientific articles dealing with ant‐plant interaction networks, through a quantitative scientometric analysis to establish the state of the art in this topic and to propose future perspectives.

We gather 54 articles published between 2006 and 2020 in 32 different scientific journals, which were written by 132 different authors. The studies were conducted in 15 countries and 9 biomes (most of them (61%) were in tropical lowlands), but Brazil and Mexico represented 87% of the global scientific production. Although most studies are related to ant‐plant interactions involving extrafloral nectaries (72%) usually in diurnal samplings, we also found other types of ant‐plant relationships such as floral nectar, extrafloral nectar, sap, myrmecophyte, seed/fruit, foraging substrate, and nesting sites. Furthermore, most studies used a bipartite framework of ant‐plant interaction mediated by only one type of resource, and researchers often reported a nested pattern of species interactions.

Finally, we identify some regions, biotic interactions involving different types of resources, spatio‐temporal scales, and research questions that need further research for a better understanding of the complexity ant‐plant networks.
Niche theory for within‐host parasite dynamics: Analogies to food web modules via feedback loops
Authors: Ramesh Ashwini , Hall Spencer R.
Published: January 2023

Why do parasites exhibit a wide dynamical range within their hosts? For instance, why does infecting dose either lead to infection or immune clearance? Why do some parasites exhibit boom‐bust, oscillatory dynamics? What maintains parasite diversity, that is coinfection v single infection due to exclusion or priority effects? For insights on parasite dose, dynamics and diversity governing within‐host infection, we turn to niche models. An omnivory food web model (IGP) blueprints one parasite competing with immune cells for host energy (PIE). Similarly, a competition model (keystone predation, KP) mirrors a new coinfection model (2PIE). We then drew analogies between models using feedback loops. The following three points arise: first, like in IGP, parasites oscillate when longer loops through parasites, immune cells and resource regulate parasite growth. Shorter, self‐limitation loops (involving resources and enemies) stabilise those oscillations. Second, IGP can produce priority effects that resemble immune clearance. But, despite comparable loop structure, PIE cannot due to constraints imposed by production of immune cells. Third, despite somewhat different loop structure, KP and 2PIE share apparent and resource competition mechanisms that produce coexistence (coinfection) or priority effects of prey or parasites. Together, this mechanistic niche framework for within‐host dynamics offers new perspective to improve individual health.
Love is in the air and beyond the ocean: Taxonomic review ofNeotrogaspidiaLelej (Hymenoptera: Mutillidae: Trogaspidiini) in Northeast Asia highlights its unique distributional pattern
Authors: Okayasu Juriya
Published: January 2023

The genusNeotrogaspidiaLelej, 1996 is a small group of velvet ants with five species from the Australasian, Oriental and Palearctic Regions. The type species,N. pustulata(Smith, 1873) (♂♀), is the only Northeast Asian species known at present. In this paper,N. elpinice(Mickel, 1933),stat. resurr. et comb. nov.(♂♀) is resurrected from the junior synonym ofN. pustulata. Two new combinations are proposed forN. circumcincta(André, 1896),comb. nov.(♂♀) fromOrientidiaLelej, 1996 andN. recticarinata(Chen, 1957),comb. nov.(♂) fromTrogaspidiaAshmead, 1899. New synonymies are proposed forN. elpinicewithT.aestivalisHammer, 1949,syn. nov.andT.maritimaChen, 1957,syn. nov., andN. circumcinctawithT.yuliensisTsuneki, 1972,syn. nov.andKrombeinidia agricolaWilliams, 2019,syn. nov.An updated genus diagnosis and a key to all described species are provided. New records includeN. circumcinctafrom Laos and Vietnam,N. pustulatafrom North Korea, andN. recticarinatafrom Taiwan. The inflated endophallus of the male genitalia ofN. pustulatais illustrated. A potential host record, habitat records and mating observations ofNeotrogaspidiaare presented. The historical process of formation of the distributional patterns of this genus in Northeast Asia is discussed.
Epilepsy severity mediates association between mutation type and ADHD symptoms in tuberous sclerosis complex
Authors: Tye Charlotte , McEwen Fiona S. , Liang Holan , Woodhouse Emma , Underwood Lisa , Shephard Elizabeth , Barker Edward D. , Sheerin Fintan , Higgins Nicholas , Steenbruggen Juul ,   Tuberous Sclerosis 2000 Study Group, Bolton Patrick F.
Published: January 2023

The association between attention‐deficit/hyperactivity disorder (ADHD) and tuberous sclerosis complex (TSC) is widely reported, with support for the role of epilepsy, yet the mechanisms underlying the association across development are unclear. The Tuberous Sclerosis 2000 Study is a prospective longitudinal study of TSC. In Phase 1 of the study, baseline measures of epilepsy, cortical tuber load, and mutation were obtained with 125 children ages 0–16 years. In Phase 2, at an average of 8 years later, ADHD symptoms were measured for 81 of the participants. Structural equation modeling revealed an indirect pathway from genetic mutation, to cortical tuber load, to epileptic spasm severity in infancy, to ADHD symptoms in middle childhood and adolescence, in addition to a pathway linking current seizure severity to ADHD symptoms. Findings were retained when intelligence quotient (IQ) was entered as a correlated factor. The findings support a cascading developmental pathway to ADHD symptoms mediated by early‐onset and severe epilepsy in the first 2 years of life. This warrants detailed investigation of seizure characteristics and cognitive and behavioral sequelae associated with ADHD from early in life, to further the understanding of the association between ADHD and early‐onset epilepsy across syndromic and non‐syndromic populations.
CEO marital status and corporate cash holdings
Authors: Elnahas Ahmed , Hossain Md. Noman , Javadi Siamak
Published: January 2023

We examine the effect of CEO marital status on corporate cash holdings. Consistent with the classical agency framework, we find that firms with single CEOs hold more cash compared to otherwise similar firms with married CEOs and that the excess cash held by single CEOs is significantly discounted by shareholders. Our findings survive a battery of tests to ease endogeneity and selection bias, confirming that results are not simply reflecting innate heterogeneity in preferences. Overall, our findings indicate that a variable outside the common firm‐ and macro‐level determinants, CEO marital status, can significantly influence corporate policies.
Biochar co‐compost improves nitrogen retention and reduces carbon emissions in a winter wheat cropping system
Authors: Gao Si , Harrison Brendan P. , Thao Touyee , Gonzales Melinda L. , An Di , Ghezzehei Teamrat A. , Diaz Gerardo , Ryals Rebecca A.
Published: January 2023

Organic amendments, such as compost and biochar, mitigate the environmental burdens associated with wasting organic resources and close nutrient loops by capturing, transforming, and resupplying nutrients to soils. While compost or biochar application to soil can enhance an agroecosystem's capacity to store carbon and produce food, there have been few field studies investigating the agroecological impacts of amending soil with biochar co‐compost, produced through the composting of nitrogen‐rich organic material, such as manure, with carbon‐rich biochar. Here, we examine the impact of biochar co‐compost on soil properties and processes by conducting a field study in which we compare the environmental and agronomic impacts associated with the amendment of either dairy manure co‐composted with biochar, dairy manure compost, or biochar to soils in a winter wheat cropping system. Organic amendments were applied at equivalent C rates (8 Mg C ha−1). We found that all three treatments significantly increased soil water holding capacity and total plant biomass relative to the no‐amendment control. Soils amended with biochar or biochar co‐compost resulted in significantly less greenhouse gas emissions than the compost or control soils. Biochar co‐compost also resulted in a significant reduction in nutrient leaching relative to the application of biochar alone or compost alone. Our results suggest that biochar co‐composting could optimize organic resource recycling for climate change mitigation and agricultural productivity while minimizing nutrient losses from agroecosystems.
Normative influence and masstige purchase intention: Facilitators, inhibitors, and the moderating effect of celebrity endorsement
Authors: Gupta Swati , Raj Sahil , Singh Devinder Pal , Singh Amanpreet , Kastanakis Minas
Published: January 2023

Masstige marketing has gained considerable attention in the recent past as a theoretically significant and practically relevant concept. Masstige strategy encompasses all those activities directed to position the products for the masses, neither by offering drastic price reductions nor discounts. Rather its success depends on product innovation and promotion. Although it has been recognized as an important strategic construct, the nascent concept needs further investigation for better understanding. This research identifies significant gaps in the extant literature on fashion accessories masstige brands and intends to bridge them. The objective of the current study is to empirically investigate the factors that facilitate or inhibit masstige purchase intentions. Our study uncovers the role of normative influence in influencing the purchase intentions of a masstige fashion accessory brand, that is, Armani Exchange. Data were collected from 395 respondents, and structural equation modeling was applied to check the proposed hypotheses. The study's results revealed that conspicuous and social values play an important role as facilitators. In addition, the study highlighted that masstige brands need to overcome inhibitors like identity avoidance and deficit‐value avoidance to develop masstige purchase intention. Moderation analysis highlighted the significant influence of celebrity endorsement in strengthening the facilitators and overcoming inhibitors associated with masstige purchase intention. The study's results can help marketers to position their masstige brands by adopting the right strategies that can be formulated by taking into account the influence of stimulus, facilitators, inhibitors, and a moderating variable examined in the study.
Racial bias as a multi‐stage, multi‐actor problem: An analysis of pretrial detention
Authors: Grossman Joshua , Nyarko Julian , Goel Sharad
Published: January 2023

After arrest, criminal defendants are often detained before trial to mitigate potential risks to public safety. There is widespread concern, however, that detention decisions are biased against racial minorities. When assessing potential racial discrimination in pretrial detention, past studies have typically worked to quantify the extent to which the ultimate judicial decision is conditioned on the defendant's race. Although often useful, this approach suffers from three important limitations. First, it ignores the multi‐stage nature of the pretrial process, in which decisions and recommendations are made over multiple court appearances that influence the final judgment. Second, it does not consider the multiple actors involved, including prosecutors, defense attorneys, and judges, each of whom have different responsibilities and incentives. Finally, a narrow focus on disparate treatment fails to consider potential disparate impact arising from facially neutral policies and practices. Addressing these limitations, here we present a framework for quantifying disparate impact in multi‐stage, multi‐actor settings, illustrating our approach using 10 years of data on pretrial decisions from a federal district court. We find that Hispanic defendants are released at lower rates than white defendants of similar safety and nonappearance risk. We trace these disparities to decisions of assistant US attorneys at the initial hearings, decisions driven in part by a statutory mandate that lowers the procedural bar for moving for detention of defendants in certain types of cases. We also find that the Pretrial Services Agency recommends detention of Black defendants at higher rates than white defendants of similar risk, though we do not find evidence that these recommendations translate to disparities in actual release rates. Finally, we find that traditional disparate treatment analyses yield more modest evidence of discrimination in pretrial detention outcomes, highlighting the value of our more expansive analysis for identifying, and ultimately remediating, unjust disparities in the pretrial process. We conclude with a discussion of how risk‐based threshold release policies could help to mitigate observed disparities, and the estimated impact of various policies on violation rates in the partner jurisdiction.
Trophic ecology of juvenile bull sharks (Carcharhinus leucas) in the Coyote estuary, Costa Rica
Authors: De la Llata Quiroga Edna , Arauz Randall , Tripp Valdez Arturo , Porras Murillo Laura , Parallada Manuel Spinola , Sánchez‐Murillo Ricardo , Chávez Elpis J.
Published: January 2023

Bull shark (Carcharhinus leucas) is a near‐threatened elasmobranch species capable of moving between the fresh and salty waters of tropical and subtropical coastal areas, for which we still lack important ecological information. During their first years of life, bull sharks use estuarine systems as nursery areas, making them highly susceptible to environmental and anthropogenic pressures. We studied the trophic ecology of juveniles found in the Coyote estuary, a potential nursery area in Costa Rica, to understand the potential impact of further bull shark declines and gain knowledge that could aid in their conservation. We analysed the trophic ecology of juvenile bull sharks [81–103 cm total length (TL)] in the Coyote estuary, Costa Rica, using stable isotopes of δ15N and δ13C. Since one problem using this technique in juveniles is the confounding effect of the maternal signature, we sampled different tissues (muscle and plasma), verified the status of the shark's umbilical scar and identified the size at which the isotope signature is a result of the animal's current diet. The isotopic values of the muscle tissue reflected the maternal isotopic signature. In contrast, plasma values reflected the diet of juvenile bull sharks >95 cm TL and with a closed umbilical scar. Juvenile bull sharks fed primarily on teleost fishes of the order Anguilliformes and Siluriformes, and have a high trophic position (≥4.0) in the Coyote estuary. Our findings suggest that this estuary is an important feeding site for juvenile bull sharks of the Pacific of Costa Rica. Thus, the protection of essential habitats such as the Coyote estuary will benefit not only bull shark conservation, but also the conservation of an array of fish species that also use this habitat as a rookery, many of which are of commercial interest.
Older adults on the dating market: The role of family caregiving responsibilities
Authors: Harris Lauren E.
Published: January 2023

Objective

This study investigates how family care responsibilities impact older single adults' approach to and experience on the dating market.

Background

There is a growing population of single older adults, but very little understanding of their experiencing seeking romantic partners. Prior dating and marriage research has focused primarily on younger adults or single parents seeking remarriage. There is evidence of parenthood negatively impacting the search for a partner, but it is unclear how caregiving responsibilities impact this process for older adults.

Method

Here, 100 older adults, 50 men and 50 women ages 60–83, were recruited from online dating websites and interviewed about their experiences seeking romantic partners.

Results

Many men and women postponed dating until carework was complete. Additionally, men found women with care responsibilities less desirable, but women preferred men who were close to their families. Men were only less desirable when women believed the men would increase a woman's carework responsibilities.

Conclusion

This study reveals how family caregiving responsibilities have a noticeable and gendered impacted on older adults' experiences with repartnering. This study extends marriage market and marital search theories by highlighting the complicated and influential role of family, particularly family carework responsibilities, in older adults' opportunities and status on the dating and marriage market.
Institutional Transitions, Research and Development, and Exports from India
Authors: Kathuria Nishant , Majumdar Sumit K. , Peng Mike W.
Published: January 2023

Research and development (R&D) capabilities generally enable firms to export more. Left underexplored is this question: Does the positive relationship between R&D and exports hold during institutional transitions, which are fundamental and comprehensive changes introduced to the rules of the game? Among India's wide‐ranging market‐oriented institutional transitions, the implementation of the Foreign Exchange Management Act (FEMA) provides a natural experiment that helps us examine this question. Leveraging 22,049 firm‐year observations (with 5532 unique firms), our evidence suggests that although FEMA enabled innovative firms to generate more exports during the pre‐FEMA period, the positive relationship between R&D and exportsceasedduring the post‐FEMA period. We conclude that institutional transitions may not always yield positive effects.
Comparison of surface roughness of additively manufactured implant‐supported interim crowns fabricated with different print orientations
Authors: Ortega Nuria Martín , Revilla‐León Marta , Ortega Rocío , Gómez‐Polo Cristina , Barmak Abdul B. , Gómez‐Polo Miguel
Published: January 2023

Purpose

To assess the influence of print orientation on the surface roughness of implant‐supported interim crowns manufactured by using digital light processing (DLP) 3D printing procedures.

Materials and methods

An implant‐supported maxillary right premolar full‐contour crown was obtained. The interim restoration design was used to fabricate 30 specimens with 3 print orientations (0, 45, and 90 degrees) using an interim resin material (GC Temp PRINT) and a DLP printer (Asiga MAX UV) (n = 10). The specimens were manufactured, and each was cemented to an implant abutment with autopolymerizing composite resin cement (Multilink Hybrid Abutment). Surface roughness was assessed on the buccal surface of the premolar specimen by using an optical measurement system (InfiniteFocusG5 plus). The data were analyzed with a Shapiro–Wilk test, resulting in a normal distribution. One‐way ANOVA and the Tukey HSD tests were selected (α = 0.05).

Results

Statistically significant discrepancies were found in the surface roughness mean values among the groups tested (p < 0.001). The lowest mean ± standard deviation surface roughness was found with the 90‐degree group (1.2 ± 0.36 μm), followed by the 0‐degree orientation (2.23 ± 0.18 μm) and the 45‐degree group (3.18 ± 0.31 μm).

Conclusions

Print orientation parameter significantly impacted the surface roughness of the implant‐supported interim crowns manufactured by using the additive procedures tested.
Comparative pharmacokinetics of florfenicol in heifers after intramuscular and subcutaneous administration
Authors: Selimov Renat , Goncharova Elizaveta , Koriakovtsev Pavel , Gabidullina Diana , Karsakova Julia , Kozlov Sergey , Komarov Alexander , Engasheva Ekaterina , Engashev Sergey
Published: January 2023

Florfenicol was administered to five heifers intramuscularly at a dose rate of 20 mg/kg bwt and following wash‐out period, subcutaneously at a dose rate of 40 mg/kg bwt. Blood plasma samples were collected from heifers before injection of florfenicol and up to 120 h after intramuscular (IM) injection and up to 264 h after subcutaneous (SC) injection. Florfenicol concentrations in plasma were measured by high‐performance liquid chromatography with mass‐spectrometric detection. Pharmacokinetics of florfenicol was estimated using non‐compartment analysis. Mean maximum plasma concentration, area under the concentration–time curve and elimination half‐life for florfenicol were 3.2 μg/ml, 101.5 μg × h/ml and 24.5 h, respectively, after IM injection at 20 mg/kg bwt, and 2.7 μg/ml, 194.5 μg × h/ml and 103.8 h, respectively, after SC injection at 40 mg/kg bwt. The obtained results indicated that both administration routes provided comparable bioavailability, whereas SC route was attributed with lower peak levels and markedly slower absorption of florfenicol from injection site. Both administration routes provided plasma florfenicol levels which are expected to be effective against prevalent infectious agents of cattle.
Hetero‐ and cisnormativity—UK pharmacy education as a queer opponent
Authors: Mawdsley Andrew , Willis Sarah C.
Published: January 2023

Introduction

Queer pedagogy is a lens through which the hegemonic discourses of curricula and the heterosexual assumptions within them can be made visible. Using this lens, sexuality and gender norms incorporated in undergraduate medical and health curricula can be located and the lived experience of a curriculum examined. This paper seeks to determine the extent of hetero/cisnormativity within UK pharmacy education with the aim of problematising the normalisation of heterosexuality; following this, strategies to disrupt structured hetero/cisnormativity are considered.

Methods

Online cross‐sectional surveys were distributed to course leads (n = 29) and students enrolled on undergraduate pharmacy (MPharm) programmes. Surveys captured quantitative data on curriculum design and perceived barriers to implementation of inclusive curriculum design (the espoused LGBTQI+ curriculum), as well qualitative data on the lived experience of the hidden curriculum. Quantitative data were analysed using descriptive statistics, whereas qualitative data were analysed thematically.

Results

Responses were received from 19 course leads and students from 25 MPharm programmes, representing varying completion rates. Findings suggest the shared values and goals of pharmacy education act to normalise and legitimise hetero and cis identities within curriculum design that othering as a consequence of heterosexual normativity is experienced and that pharmacy education is an LGBTQI+ opponent and does not adopt an ally attitude. Moreover, both educator and student data suggest that the enacted and experienced curriculum fails to prepare learners to care for LGBTQI+ people.

Discussion

Despite findings suggesting the espoused or enacted curriculum absents LGBTQI+ people, and the hidden curriculum is experienced as homonegative, learners are questioning, resisting and disrupting the hetero‐ and cisnormative benevolent heterosexism within UK pharmacy curricula. This method of curricula interrogation can be adopted across health professions education as a means for ongoing problematising and disruption of normativity in clinical education.
A rust‐fungus Nudix hydrolase effector decaps mRNAin vitro and interferes with plant immune pathways
Authors: McCombe Carl L. , Catanzariti Ann‐Maree , Greenwood Julian R. , Desai Anna M. , Outram Megan A. , Yu Daniel S. , Ericsson Daniel J. , Brenner Steven E. , Dodds Peter N. , Kobe Bostjan , Jones David A. , Williams Simon J.
Published: January 2023

To infect plants, pathogenic fungi secrete small proteins called effectors. Here, we describe the catalytic activity and potential virulence function of the Nudix hydrolase effector AvrM14 from the flax rust fungus (Melampsora lini).

We completed extensive in vitro assays to characterise the enzymatic activity of the AvrM14 effector. Additionally, we used in planta transient expression of wild‐type and catalytically dead AvrM14 versions followed by biochemical assays, phenotypic analysis and RNA sequencing to unravel how the catalytic activity of AvrM14 impacts plant immunity.

AvrM14 is an extremely selective enzyme capable of removing the protective 5′ cap from mRNA transcripts in vitro. Homodimerisation of AvrM14 promoted biologically relevant mRNA cap cleavage in vitro and this activity was conserved in related effectors from other Melampsora spp. In planta expression of wild‐type AvrM14, but not the catalytically dead version, suppressed immune‐related reactive oxygen species production, altered the abundance of some circadian‐rhythm‐associated mRNA transcripts and reduced the hypersensitive cell‐death response triggered by the flax disease resistance protein M1.

To date, the decapping of host mRNA as a virulence strategy has not been described beyond viruses. Our results indicate that some fungal pathogens produce Nudix hydrolase effectors with in vitro mRNA‐decapping activity capable of interfering with plant immunity.
GhWRKY41 forms a positive feedback regulation loop and increases cotton defence response against Verticillium dahliae by regulating phenylpropanoid metabolism
Authors: Xiao Shenghua , Ming Yuqing , Hu Qin , Ye Zhengxiu , Si Huan , Liu Shiming , Zhang Xiaojun , Wang Weiran , Yu Yu , Kong Jie , Klosterman Steven J. , Lindsey Keith , Zhang Xianlong , Aierxi Alifu , Zhu Longfu
Published: January 2023

Despite the established significance of WRKY proteins and phenylpropanoid metabolism in plant immunity, how WRKY proteins modulate aspects of the phenylpropanoid pathway remains undetermined. To understand better the role of WRKY proteins in plant defence, we identified a cotton (Gossypium hirsutum) protein, GhWRKY41, that is, universally and rapidly induced in three disease‐resistant cotton cultivars following inoculation with the plant pathogenic fungus, Verticillium dahliae. We show that overexpression of GhWRKY41 in transgenic cotton and Arabidopsis enhances resistance to V. dahliae, while knock‐down increases cotton more susceptibility to the fungus. GhWRKY41 physically interacts with itself and directly activates its own transcription. A genome‐wide chromatin immunoprecipitation and high‐throughput sequencing (ChIP‐seq), in combination with RNA sequencing (RNA‐seq) analyses, revealed that 43.1% of GhWRKY41‐binding genes were up‐regulated in cotton upon inoculation with V. dahliae, including several phenylpropanoid metabolism master switches, receptor kinases, and disease resistance‐related proteins. We also show that GhWRKY41 homodimer directly activates the expression of GhC4H and Gh4CL, thereby modulating the accumulation of lignin and flavonoids. This finding expands our understanding of WRKY‐WRKY protein interactions and provides important insights into the regulation of the phenylpropanoid pathway in plant immune responses by a WRKY protein.
Jointly modeling behavioral and EEG measures of proactive control in task switching
Authors: Karayanidis Frini , Hawkins Guy E. , Wong Aaron S. W. , Aziz Fayeem , Hunter Montana , Steyvers Mark
Published: January 2023

In this study, we implement joint modeling of behavioral and single‐trial electroencephalography (EEG) data derived from a cued‐trials task‐switching paradigm to test the hypothesis that trial‐by‐trial adjustment of response criterion can be linked to changes in the event‐related potentials (ERPs) elicited during the cue‐target interval (CTI). Specifically, we assess whether ERP components associated with preparation to switch task and preparation of the relevant task are linked to a response criterion parameter derived from a simple diffusion decision model (DDM). Joint modeling frameworks characterize the brain‐behavior link by simultaneously modeling behavioral and neural data and implementing a linking function to bind these two submodels. We examined three joint models: The first characterized the core link between EEG and criterion, the second added a switch preparation input parameter and the third also added a task preparation input parameter. The criterion‐EEG link was strongest just before target onset. Inclusion of switch and task preparation parameters did not improve the performance of the criterion‐EEG link but was necessary to accurately model the ERP waveform morphology. While we successfully jointly modeled latent model parameters and EEG data from a task‐switching paradigm, these findings show that customized cognitive models are needed that are tailored to the multiple cognitive control processes underlying task‐switching performance. This is the first paper to implement joint modeling of behavioral measures and single‐trial electroencephalography (EEG) data derived from the cue‐target interval in a cued‐trials task‐switching paradigm. Model hyperparameters showed a strong link between response criterion and the pre‐target negativity amplitude. Additional parameters (switch preparation, task preparation) were necessary to model the cue‐locked ERP waveform morphology. This is consistent with multiple cognitive control processes underlying proactive control and points to the need for more nuanced models of task‐switching performance.
The Effect of Immediacy of Expected Goal Feedback on Persistence in a Physical Task
Authors: Gunn Christopher P. , Englert Chris , Ennigkeit Fabienne , Taylor Ian M.
Published: January 2023

Minimizing the temporal gap between behavior and reward enhances persistence, but the effect of other outcomes is unknown. Two concurrently run studies aimed to investigate whether persistence on a physical task would be influenced according to whether participants expected immediate versus delayed goal feedback. Furthermore, whether this effect occurs via intrinsic motivation (Studies 1 and 2) or delaying the desire–goal conflict (Study 2) was examined. Using a counterbalanced within-person design, 34 participants in each study (Study 1: 16 males, 18 females; Study 2: 15 males, 19 females) completed two wall-sit persistence tasks, one with immediate feedback expected (regarding the participant’s position on a leader board) and the other with feedback expected to be provided 1 week later. A two-way mixed analysis of variance found no significant differences in persistence between conditions in either study. Furthermore, no indirect effects were found via intrinsic motivation or delayed desire–goal conflict. Study findings did not support the hypothesis that the timing of expected feedback enhances persistence.
Loss of a gluconeogenic muscle enzyme contributed to adaptive metabolic traits in hummingbirds
Authors: Osipova Ekaterina , Barsacchi Rico , Brown Tom , Sadanandan Keren , Gaede Andrea H. , Monte Amanda , Jarrells Julia , Moebius Claudia , Pippel Martin , Altshuler Douglas L. , Winkler Sylke , Bickle Marc , Baldwin Maude W. , Hiller Michael
Published: January 2023

Hummingbirds possess distinct metabolic adaptations to fuel their energy-demanding hovering flight, but the underlying genomic changes are largely unknown. Here, we generated a chromosome-level genome assembly of the long-tailed hermit and screened for genes that have been specifically inactivated in the ancestral hummingbird lineage. We discovered that
FBP2
(fructose-bisphosphatase 2), which encodes a gluconeogenic muscle enzyme, was lost during a time period when hovering flight evolved. We show that
FBP2
knockdown in an avian muscle cell line up-regulates glycolysis and enhances mitochondrial respiration, coincident with an increased mitochondria number. Furthermore, genes involved in mitochondrial respiration and organization have up-regulated expression in hummingbird flight muscle. Together, these results suggest that
FBP2
loss was likely a key step in the evolution of metabolic muscle adaptations required for true hovering flight.
Combinatorial assembly and design of enzymes
Authors: Lipsh-Sokolik R. , Khersonsky O. , Schröder S. P. , de Boer C. , Hoch S.-Y. , Davies G. J. , Overkleeft H. S. , Fleishman S. J.
Published: January 2023

The design of structurally diverse enzymes is constrained by long-range interactions that are necessary for accurate folding. We introduce an atomistic and machine learning strategy for the combinatorial assembly and design of enzymes (CADENZ) to design fragments that combine with one another to generate diverse, low-energy structures with stable catalytic constellations. We applied CADENZ to endoxylanases and used activity-based protein profiling to recover thousands of structurally diverse enzymes. Functional designs exhibit high active-site preorganization and more stable and compact packing outside the active site. Implementing these lessons into CADENZ led to a 10-fold improved hit rate and more than 10,000 recovered enzymes. This design-test-learn loop can be applied, in principle, to any modular protein family, yielding huge diversity and general lessons on protein design principles.
Science in postwar Ukraine
Authors: Shulga Nataliya
Published: January 2023

Next month will mark 1 year since Russia escalated its war on Ukraine. The senseless casualties and destruction have been met with stunning resilience by Ukraine and international opposition to Russia. Although the war continues, there is hope that Ukraine will emerge as an open and free democracy, which would include rebuilding its scientific enterprise with new infrastructure and laws.
Future NASA scope would find life on alien worlds
Authors: Clery Daniel
Published: January 2023

Agency lays out initial plan for multibillion-dollar Habitable Worlds Observatory
Draft Genome Sequences of Two Enterobacter hormaechei subsp.
xiangfangensis
Strains Isolated from the Moroccan Sahara
Authors: Zouagui Houda , Manni Amina , Laamarti Meriem , Kartti Souad , Alouane Tarek , Lahlou Lamiaa , Benhrif Oussama , Temsamani Loubna , Eljamali Jamal-Eddine , Filali-Maltouf Abdelkarim , Ibrahimi Azeddine , Sbabou Laila
Published: January 2023

We report the draft genome sequences of
Enterobacter hormaechei
subsp.
xiangfangensis
strains MDMC82 and MDMC76, which were isolated from the sand dunes of the Merzouga desert in the Moroccan Sahara. These bacteria are able to tolerate the harsh environmental conditions of the Moroccan desert.
Complete Genome Sequences of
Massilia
sp. Strains B-10 and H-1, Isolated from the Water in the Shulgan-Tash Cave
Authors: Sazanova Anna , Belimov Andrey , Gogolev Yuri , Chirak Elizaveta , Afonin Alexey , Karlov Denis , Kuznetsova Irina , Guro Polina , Kuzmina Lyudmila , Safronova Vera
Published: January 2023

In this article, we report the complete genome sequences of
Massilia
sp. strains B-10 (RCAM05335) and H-1 (RCAM05339), which were isolated from the water of the Dal’nee Verkhnee Lake in the Shulgan-Tash cave in Russia (53°2′0″N, 57°3′0″E). The sequences were obtained using an Oxford Nanopore Technologies MinION system.
Interaction between Host and Microbes in the Semen of Patients with Idiopathic Nonobstructive Azoospermia
Authors: Chen Peigen , Li Yanqing , Zhu Xinning , Ma Menghui , Chen Haicheng , He Junxian , Liang Xiaoyan , Liu Guihua , Yang Xing
Published: January 2023

Idiopathic nonobstructive azoospermia is one of the great challenges in assisted reproductive therapy. Although microdissection testicular sperm extraction technology is currently available, many men with iNOA still face the problem of poor sperm retrieval and poor sperm quality.
Diabetes with poor-control HbA1c is cardiovascular disease ‘risk equivalent’ for mortality: UK Biobank and Hong Kong population-based cohort study
Authors: Wan Eric Yuk Fai , Yu Esther Yee Tak , Mak Ivy Lynn , Youn Hin Moi , Chan Kam Suen , Chan Esther W Y , Wong Ian C K , Lam Cindy Lo Kuen
Published: January 2023

Introduction

Type 2 diabetes mellitus (T2DM) has traditionally been considered a coronary heart disease ‘risk equivalent’ for future mortality, but significant heterogeneity exists across people with T2DM. This study aims to determine the risk of all-cause mortality of patients with cardiovascular disease (CVD) and T2DM in UK and Hong Kong, with stratifications for hemoglobin A1 (HbA1c) concentrations, compared with those without CVD and diabetes mellitus.

Research design and methods

This is a retrospective cohort study of 3 839 391 adults from Hong Kong and a prospective cohort study of 497 779 adults from the UK Biobank. Individuals were divided into seven disease groups: (1) no T2DM and CVD, (2) T2DM only with HbA1c <7%, (3) T2DM only with HbA1c 7%–7.9%, (4) T2DM only with HbA1c 8%–8.9%, (5) T2DM only with HbA1c ≥9%, (6) CVD only, and (7) T2DM and CVD. Differences in all-cause mortality between groups were examined using Cox regression.

Results

After around 10 years of median follow-up, 423 818 and 19 844 deaths were identified in the Hong Kong cohort and UK Biobank, respectively. Compared with individuals without T2DM and CVD, the adjusted HR for all-cause mortality in the other six disease groups for the Hong Kong cohort was 1.25 (95% CI 1.23 to 1.27) for T2DM only with HbA1c <7%, 1.21 (95% CI 1.19 to 1.23) for T2DM only with HbA1c 7%–7.9%, 1.36 (95% CI 1.33 to 1.39) for T2DM only with HbA1c 8%–8.9%, 1.82 (95% CI 1.78 to 1.85) for T2DM only with HbA1c ≥9%, 1.37 (95% CI 1.36 to 1.38) for CVD only, and 1.83 (95% CI 1.81 to 1.85) for T2DM and CVD, and for the UK Biobank the HR was 1.45 (95% CI 1.33 to 1.58), 1.50 (95% CI 1.32 to 1.70), 1.72 (95% CI 1.43 to 2.08), 2.51 (95% CI 2.05 to 3.08), 1.67 (95% CI 1.59 to 1.75) and 2.62 (95% CI 2.42 to 2.83), respectively. This indicates that patients with T2DM had an increased risk of mortality compared with those without T2DM and CVD, and in those with HbA1c ≥9% an even higher risk than people with CVD.

Conclusions

Patients with T2DM with poor HbA1c control (8%–8.9% and ≥9%) were associated with similar and higher risk of mortality compared with patients with CVD, respectively. Optimal HbA1c, controlled for risk reduction and prevention of mortality and complications in diabetes management, remains important.
Early initiation of antenatal care and its associated factors among pregnant women attending antenatal care at public health centres in Bahir Dar Zuria zone, Northwest Ethiopia, 2021: a cross-sectional study
Authors: Ambaye Eskahun , Regasa Zegeye Wordofa , Hailiye Gizaw
Published: January 2023

Objectives

This study aimed to assess the prevalence of, and factors associated with, early initiation of antenatal care (ANC) follow-up among pregnant women attending ANC services at Bahir Dar Zuria zone public health centres (HCs), Bahir Dar, Northwest Ethiopia.

Design

An institution-based, cross-sectional study was conducted from 15 December 2020 to 1 March 2021. A systematic random sampling technique was applied to select the study participants.

Setting

Five public HCs (Han HC, Shimbit HC, Dagmawi Minilik HC, Shumabo HC and Meshentie HC) in Bahir Dar Zuria zone.

Participants

Pregnant mothers who were attending their ANC service during the data collection period were enrolled in this study. A total of 592 mothers were interviewed for the study.

Outcome measure

Early initiation of ANC services (within 16 weeks of gestation).

Results

48.6% (95% CI 41.6% to 53.5%) of participants began their first ANC service before 16 weeks of gestation. Family size less than five (adjusted OR 2.0, 95% CI 1.25 to 3.25), urban residence (3.0, 1.48 to 6.17), secondary education (2.1, 1.3 to 3.6), college-level education and above (3.5, 1.8 to 6.8), primigravida (2.6, 1.65 to 4.14), planned pregnancy (3.5, 1.5 to 8.1) and knowledge about early initiation of ANC (1.7, 1.14 to 2.55) were significantly associated with early initiation of ANC.

Conclusion

A substantial number of participants had not received ANC services in a timely manner. Sociodemographic and obstetric characteristics of the respondents were associated with timely booking of ANC services. Dissemination of information about recommended time to initiate ANC services and efforts to improve women’s educational status to increase knowledge about early initiation of ANC are needed in the region.