bluuebunny/crossref_metadata_2025 huggingface dataset:
Critical reflections on sustainability reporting standard setting
Authors: Ali Irshad , Fukofuka Peni T. , Narayan Anil K.
Published: May 2023

Purpose

The aim of this paper is to provide critical reflections on the role of standard setters and the endeavours of various organisations to provide sustainability reporting standards.

Design/methodology/approach

The authors’ critical reflections are informed by the literature and websites of IASB, International Sustainability Standards Board (ISSB), global reporting initiative (GRI) and other relevant organisations. The authors use Bourdieu’s concept of field to support their analysis and critique.

Findings

The authors highlight how a disrupted standard-setting field will be a distraction from efforts to address real sustainability issues and concerns. Determining the “legitimate” sustainability reporting standards is likely to be an outcome of struggles between occupants in the sustainability standard-setting field. Accordingly, the shape of legitimate standards will be defined by those with power. The concern is the priority and the motive underpinning the endeavours of those with power. The authors propose that it is important for both the ISSB and GRI to serve the interest of a broad range of actors, including those who are not likely to have a say in sustainability reporting standard setting.

Practical implications

This paper contributes to sustainability reporting practice by putting forward a case for strengthening current sustainability reporting practices with appropriate changes to overcome some of the criticisms of the GRI.

Social implications

The authors highlight that there is a much broader group of stakeholders who require sustainability information and that it is important that the sustainability reporting standards serve the information needs of all stakeholders and not just those of the dominant actors. However, the ISSB with its economic focus will inevitably focus on the concern of investors and market participants.

Originality/value

The originality in this paper is the use of Bourdieu’s concept of field to theoretically highlight how a new standard setter may disrupt the sustainability standard-setting field and act as a distraction from efforts to address sustainability issues and concerns that the world faces.
Individual Ambidexterity, Relational Context and Academic Entrepreneurship Performance: Too Much of a Good Thing?
Authors: Chang Yi‐Ying , Chapman Gary , Hughes Paul , Chang Che‐Yuan
Published: May 2023

Scholars have called for a better understanding of the performance consequences of individual ambidexterity. In this work, we utilize the context of academic entrepreneurship to study how and why individual ambidexterity impacts academic entrepreneurship performance, and whether relational context moderates this link. Alongside the benefits, we argue that higher levels of individual ambidexterity generate switching, coordination and cognitive costs that can harm performance. Acknowledging the simultaneous presence of varying costs and benefits over the range of individual ambidexterity, we propose that individual ambidexterity has an inverted U‐shaped relationship with academic entrepreneurship performance, in which moderate levels produce superior performance. We further argue that relational context enhances the performance benefits of individual ambidexterity through providing access to novel knowledge and resources. In doing so, it shifts the turning point so that a higher level of individual ambidexterity produces peak academic entrepreneurship performance before the relationship turns. Utilizing data on Taiwanese scientists, we find strong evidence of an inverted U‐shaped relationship between individual ambidexterity and academic entrepreneurship performance, and for the moderating role of relational context.
Peptide hydrogels: Synthesis, properties, and applications in food science
Authors: Yu Shuang , Huang Yueying , Shen Biao , Zhang Wang , Xie Yan , Gao Qi , Zhao Dan , Wu Zufang , Liu Yanan
Published: May 2023

Due to the unique and excellent biological, physical, and chemical properties of peptide hydrogels, their application in the biomedical field is extremely wide. The applications of peptide hydrogels are closely related to their unique responsiveness and excellent properties. However, its defects in mechanical properties, stability, and toxicity limit its application in the food field. In this review, we focus on the fabrication methods of peptide hydrogels through the physical, chemical, and biological stimulations. In addition, the functional design of peptide hydrogels by the incorporation with materials is discussed. Meanwhile, the excellent properties of peptide hydrogels such as the stimulus responsiveness, biocompatibility, antimicrobial properties, rheology, and stability are reviewed. Finally, the application of peptide hydrogel in the food field is summarized and prospected.
HAX1‐related congenital neutropenia: Long‐term observation in paediatric and adult patients enrolled in the European branch of the Severe Chronic Neutropenia International Registry (SCNIR)
Authors: Pogozhykh Denys , Yilmaz Karapinar Deniz , Klimiankou Maksim , Gerschmann Natali , Ebetsberger‐Dachs Georg , Palmblad Jan , Carlsson Göran , Masmas Tania , Kinsey Sally , Bartels Marije , Mellor‐Heineke Sabine , Welte Karl , Skokowa Julia , Zeidler Cornelia
Published: May 2023

HAX1‐related congenital neutropenia (HAX1‐CN) is a rare autosomal recessive disorder caused by pathogenic variants in the HAX1 gene. HAX1‐CN patients suffer from bone marrow failure as assessed by a maturation arrest of the myelopoiesis revealing persistent severe neutropenia from birth. The disorder is strongly associated with severe bacterial infections and a high risk of developing myelodysplastic syndrome or acute myeloid leukaemia. This study aimed to describe the long‐term course of the disease, the treatment, outcome and quality of life in patients with homozygous HAX1 mutations reported to the European branch of the Severe Chronic Neutropenia International Registry. We have analysed a total of 72 patients with different types of homozygous (n = 68), compound heterozygous (n = 3), and digenic (n = 1) HAX1 mutations. The cohort includes 56 paediatric (<18 years) and 16 adult patients. All patients were initially treated with G‐CSF with a sufficient increase in absolute neutrophil counts. Twelve patients required haematopoietic stem cell transplantation for leukaemia (n = 8) and non‐leukaemic indications (n = 4). While previous genotype–phenotype reports documented a striking correlation between two main transcript variants and clinical neurological phenotypes, our current analysis reveals novel mutation subtypes and clinical overlaps between all genotypes including severe secondary manifestations, e.g., high incidence of secondary ovarian insufficiency.
Adolescent caregiving success as a predictor of social functioning from ages 13 to 33
Authors: Allen Joseph P. , Costello Meghan A. , Hellwig Amanda F. , Pettit Corey , Stern Jessica A. , Uchino Bert N.
Published: May 2023

Adolescent success providing satisfying support in response to a close friend's call in a caregiving task was examined as a potentially fundamental developmental competence likely to predict future social functioning, adult caregiving security, and physical health. Adolescents (86 males, 98 females; 58% White, 29% African American, 8% mixed race/ethnicity, 5% other) were followed from ages 13 to 33 (1998–2021) using multiple methods and reporters. Early caregiving success was found to predict greater self‐ and partner‐reported caregiving security, lower negativity in adult relationships, and higher adult vagal tone. Results are interpreted as advancing our understanding beyond simply recognizing that adolescent friendships have long‐term import, to now identifying specific capacities within friendships that are linked to longer‐term outcomes.
Efficacy of a cultural adaptation of theIdentity Projectintervention among adolescents attending multiethnic classrooms in Italy: A randomized controlled trial
Authors: Ceccon Chiara , Schachner Maja K. , Lionetti Francesca , Pastore Massimiliano , Umaña‐Taylor Adriana J. , Moscardino Ughetta
Published: May 2023

This registered report evaluated the efficacy of an Italian adaptation of theIdentity Project, a school‐based intervention promoting adolescents' cultural identity. Migration background and environmental sensitivity were explored as moderators. After adapting and piloting the intervention, a randomized controlled trial was conducted between October 2021 and January 2022 on 747 ethnically diverse adolescents (Mage = 15 years, 53% girls, 31% with migration background) attending 45 classrooms randomly assigned to the intervention or control condition. Bayesian analyses confirmed the efficacy of the Italian IP in enhancing exploration processes (Cohen'sd = .18), whereas no cascading effect on resolution emerged. Youth with higher (vs. lower) levels of environmental sensitivity benefited more in terms of exploration. Implications for developmental theory and practice are discussed.
Increased diagnostic yield from negative whole genome‐slice panels using automated reanalysis
Authors: Berger Seth I. , Pitsava Georgia , Cohen Andrea J. , Délot Emmanuèle C. , LoTempio Jonathan , Andrew Erin Hallie , Martin Gloria Mas , Marmolejos Sofia , Albert Jessica , Meltzer Beatrix , Fraser Jamie , Regier Debra S. , Kahn‐Kirby Amanda H. , Smith Erica , Knoblach Susan , Ko Arthur , Fusaro Vincent A. , Vilain Eric
Published: May 2023

We evaluated the diagnostic yield using genome‐slice panel reanalysis in the clinical setting using an automated phenotype/gene ranking system. We analyzed whole genome sequencing (WGS) data produced from clinically ordered panels built as bioinformatic slices for 16 clinically diverse, undiagnosed cases referred to the Pediatric Mendelian Genomics Research Center, an NHGRI‐funded GREGoR Consortium site. Genome‐wide reanalysis was performed using Moon™, a machine‐learning‐based tool for variant prioritization. In five out of 16 cases, we discovered a potentially clinically significant variant. In four of these cases, the variant was found in a gene not included in the original panel due to phenotypic expansion of a disorder or incomplete initial phenotyping of the patient. In the fifth case, the gene containing the variant was included in the original panel, but being a complex structural rearrangement with intronic breakpoints outside the clinically analyzed regions, it was not initially identified. Automated genome‐wide reanalysis of clinical WGS data generated during targeted panels testing yielded a 25% increase in diagnostic findings and a possibly clinically relevant finding in one additional case, underscoring the added value of analyses versus those routinely performed in the clinical setting.
scRNA‐seq and proteomics reveal the distinction of M2‐like macrophages between primary and recurrent malignant glioma and its critical role in the recurrence
Authors: You Guiting , Zheng Zhenyu , Huang Yulong , Liu Guifen , Luo Wei , Huang Jianhuang , Zhuo Longjin , Tang Binghua , Liu Shunyi , Lin Caihou
Published: May 2023

Aims

Tumor‐associated macrophages (TAMs) in the immune microenvironment play an important role in the increased drug resistance and recurrence of malignant glioma, but the mechanism remains incompletely inventoried. The focus of this study was to investigate the distinctions of M2‐like TAMs in the immune microenvironment between primary and recurrent malignant glioma and its influence in the recurrence.

Methods

We employed single‐cell RNA sequencing to construct a single‐cell atlas for a total of 23,010 individual cells from 6 patients with primary or recurrent malignant glioma and identified 5 cell types, including TAMs and malignant cells. Immunohistochemical techniques and proteomics analysis were performed to investigate the role of intercellular interaction between malignant cells and TAMs in the recurrence of malignant glioma.

Results

Six subgroups of TAMs were annotated and M2‐like TAMs were found to increase in recurrent malignant glioma significantly. A pseudotime trajectory and a dynamic gene expression profiling during the recurrence of malignant glioma were reconstructed. Up‐regulation of several cancer pathways and intercellular interaction‐related genes are associated with the recurrence of malignant glioma. Moreover, the M2‐like TAMs can activate the PI3K/Akt/HIF‐1α/CA9 pathway in the malignant glioma cells via SPP1‐CD44‐mediated intercellular interaction. Interestingly, high expression of CA9 can trigger the immunosuppressive response in the malignant glioma, thus promoting the degree of malignancy and drug resistance.

Conclusion

Our study uncovers the distinction of M2‐like TAMs between primary and recurrent glioma, which offers unparalleled insights into the immune microenvironment of primary and recurrent malignant glioma.
4,4′‐Thiobis(2‐tert‐butyl‐5‐methylphenol), an antioxidant in medical devices that may cause allergic contact dermatitis
Authors: Antelmi Annarita , Lejding Tina , Bruze Magnus , Mowitz Martin , Dahlin Jakob
Published: May 2023

Background

Antioxidants in medical devices, added to protect polymers or adhesives, may also cause contact dermatitis in some individuals.

Objectives

To present data on sensitization to 4,4′‐thiobis(2‐tert‐butyl‐5‐methylphenol), an antioxidant detected in some types of medical devices, for six patients that experienced eczematous reactions to different medical devices.

Methods

Patch testing with 4,4′‐thiobis(2‐tert‐butyl‐5‐methylphenol), 1% pet was performed. Gas chromatography‐mass spectrometry (GC‐MS) was used for identification of 4,4′‐thiobis(2‐tert‐butyl‐5‐methylphenol) in different medical device products.

Results

Six patients with contact allergy to 4,4′‐thiobis(2‐tert‐butyl‐5‐methylphenol) also had relevant contact allergic reactions to medical devices containing the antioxidant. The presence of the antioxidant in products was detected using GC‐MS analysis.

Conclusions

The antioxidant 4,4′‐thiobis(2‐tert‐butyl‐5‐methylphenol) may cause allergic contact dermatitis after exposure to different medical devices.
Excitatory/inhibitory balance in epilepsies and neurodevelopmental disorders: Depolarizing γ‐aminobutyric acid as a common mechanism
Authors: van van Hugte Eline J. H. , Schubert Dirk , Nadif Kasri Nael
Published: May 2023

Epilepsy is one of the most common neurological disorders. Although many factors contribute to epileptogenesis, seizure generation is mostly linked to hyperexcitability due to alterations in excitatory/inhibitory (E/I) balance. The common hypothesis is that reduced inhibition, increased excitation, or both contribute to the etiology of epilepsy. Increasing evidence shows that this view is oversimplistic, and that increased inhibition through depolarizing γ‐aminobutyric acid (GABA) similarly contributes to epileptogenisis. In early development, GABA signaling is depolarizing, inducing outward Cl− currents due to high intracellular Cl− concentrations. During maturation, the mechanisms of GABA action shift from depolarizing to hyperpolarizing, a critical event during brain development. Altered timing of this shift is associated with both neurodevelopmental disorders and epilepsy. Here, we consider the different ways that depolarizing GABA contributes to altered E/I balance and epileptogenesis, and discuss that alterations in depolarizing GABA could be a common denominator underlying seizure generation in neurodevelopmental disorders and epilepsies.
RETRACTED: The relationship between vitamin D deficiency and diabetic foot ulcer: A meta‐analysis
Authors: Li Xin , Kou Shaojie , Chen Guo , Zhao Bingjie , Xue Jingdong , Ding Rui , Zhao Xiaoyan , Ye Miaoqing , Yang Yueqing , Yue Rensong , Li Fenping
Published: May 2023

A meta‐analysis investigation to measure the relationship between vitamin D deficiency (VDD) and diabetic foot ulcer (DFU). A comprehensive literature inspection till February 2023 was applied and 1765 interrelated investigations were reviewed. The 15 chosen investigations enclosed 2648 individuals with diabetes mellitus in the chosen investigations' starting point, 1413 of them were with DFUs, and 1235 were without DFUs. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to compute the value of the relationship between VDD and DFU by the dichotomous and continuous approaches and a fixed or random model. Individuals with DFUs had significantly lower vitamin D levels (VDL) (MD, −7.14; 95% CI, −8.83 to −5.44, P < 0.001) compared to those without DFU individuals. Individuals with DFUs had a significantly higher number of VDD individuals (OR, 2.27; 95% CI, 1.63‐3.16, P < 0.001) compared to those without DFU individuals. Individuals with DFU had significantly lower VDL and a significantly higher number of VDD individuals compared to those without DFU individuals. However, caused of the small sample sizes of several chosen investigations for this meta‐analysis, care must be exercised when dealing with its values.
Does rapid discharge after breast cancer surgery have an impact on wound healing and complications? COVID‐19 pandemic experience
Authors: Pösteki Gökhan
Published: May 2023

The COVID‐19 pandemic has challenged the health systems worldwide. Because of high volume of COVID‐19 patients, all hospitals in our region were re‐configured as COVID‐19 centres and elective surgery procedures were cancelled. Our clinic was the only active centre in the region and grave increase in our patient volume urged our clinic to modify our discharge protocol. This retrospective study included all breast cancer patients underwent mastectomy and/or axillary dissection, in the Breast Surgery Clinic of Kocaeli State Hospital, a regional pandemic hospital, between December 2020 and January 2021. Patients were mostly discharged the day of surgery with drains because of congestion, while some of the patients had traditional stay, when beds were available. The patients were evaluated postoperatively (the first 30 days) in terms of wound complications, Clavien‐Dindo classification grade, satisfaction, presence of pain and nausea, and treatment costs during the follow‐up period of the study. Outcomes were compared between early discharged patients and patients who had traditional long stay. Compared with long‐stay patients, in the early discharged group, postoperative wound complications was significantly lower (P < .01) with significant cost savings. There were no significant changes in variables such as surgery type, ASA class, satisfaction, need for additional medication and Clavien‐Dindo between the groups. Adaptation to an early discharge protocol for breast cancer surgeries may be an efficient way of practicing surgery in a pandemic. Early discharge with drains may be beneficial for patients.
Molecular mechanisms ofEda‐mediated adaptation to freshwater in threespine stickleback
Authors: Rodríguez‐Ramírez Carlos E. , Hiltbrunner Melanie , Saladin Verena , Walker Stephanie , Urrutia Araxi , Peichel Catherine L.
Published: May 2023

A main goal of evolutionary biology is to understand the genetic basis of adaptive evolution. Although the genes that underlie some adaptive phenotypes are now known, the molecular pathways and regulatory mechanisms mediating the phenotypic effects of those genes often remain a black box. Unveiling this black box is necessary to fully understand the genetic basis of adaptive phenotypes, and to understand why particular genes might be used during phenotypic evolution. Here, we investigated which genes and regulatory mechanisms are mediating the phenotypic effects of theEdahaplotype, a locus responsible for the loss of lateral plates and changes in the sensory lateral line of freshwater threespine stickleback (Gasterosteus aculeatus) populations. Using a combination of RNAseq and a cross design that isolated theEdahaplotype on a fixed genomic background, we found that theEdahaplotype affects both gene expression and alternative splicing of genes related to bone development, neuronal development and immunity. These include genes in conserved pathways, like the BMP, netrin and bradykinin signalling pathways, known to play a role in these biological processes. Furthermore, we found that differentially expressed and differentially spliced genes had different levels of connectivity and expression, suggesting that these factors might influence which regulatory mechanisms are used during phenotypic evolution. Taken together, these results provide a better understanding of the mechanisms mediating the effects of an important adaptive locus in stickleback and suggest that alternative splicing could be an important regulatory mechanism mediating adaptive phenotypes.
Pollen limitation and context‐dependent alleviating mechanisms in a co‐flowering alpine grassland community
Authors: Wang Yuxian , Gao Erliang , Hou Meng , Ghazoul Jaboury , Zhao Zhigang
Published: May 2023

The consequences of community metrics (e.g. co‐flowering diversity and floral density) and plant traits (e.g. pollinator dependency and trait similarity) on pollen limitation (PL) may depend on pollinator‐mediated competitive or facilitative interactions among plants in co‐flowering communities, which could vary with community contexts (i.e. different altitude communities) and under human disturbances (e.g. livestock grazing). However, the mechanisms to alleviate PL under different contexts, considering pollinator‐mediated interactions among neighboring plants are unclear. We investigated PL under grazing versus ungrazing conditions in low versus high altitude alpine meadows on the Tibetan Plateau to uncover the underlying mechanisms mediating PL associated with livestock grazing. We found that PL is prevalent in alpine grasslands, irrespective of community contexts. Grazing exclusion decreased PL in the two sites but in different ways. At the high‐altitude site, PL was reduced by the exclusion of grazers through increased trait similarity (suggesting facilitation). While PL was reduced by decreased trait similarity (suggesting competition avoidance) under grazing exclusion at the low‐altitude site. Our results provide a mechanistic understanding of PL in co‐flowering alpine grassland communities under distinct human disturbances at different altitudes, emphasizing the role of pollinator‐mediated interactions among plants on plant reproductive success.
Warming and grazing independently and interactively impact plant defenses and palatability
Authors: Roth Jamila S. , Osborne Todd Z. , Reynolds Laura K.
Published: May 2023

The ecological impacts of multiple stressors are hard to predict but important to understand. When multiple stressors influence foundation species, the effects can cascade throughout the ecosystem. Gulf of Mexico seagrass ecosystems are currently experiencing a suite of novel stressors, including warmer water temperatures and increased herbivory due to tropicalization and conservation efforts. We investigated the impact of warming temperatures and grazing history on plant performance, morphology, and palatability by integrating a mesocosm study using the seagrass Thalassia testudinum with feeding trials using the sea urchin Lytechinus variegatus. Warming temperatures negatively impacted T. testudinum tolerance traits, reducing belowground biomass by 34%, productivity by 74%, shoot density by 10%, and number of leaves per plant by 24%, and negatively impacted resistance traits through 13% lower toughness of young leaves and a trend for reduced leaf carbon:nitrogen. Lytechinus variegatus individuals preferred to consume plants grown under heated conditions, which supports findings of enhanced palatability. Simulated turtle grazing impacted more plant traits than grazing by other herbivores, potentially diminishing plant resilience to future disturbances through reduced rhizome non‐structural carbohydrate concentrations and increasing palatability through reduced fiber content and 23% lower leaf carbon:phosphorus. Simulated turtle, simulated parrotfish, and urchin grazing reduced leaf carbon:nitrogen by 11%, also potentially increasing nutritive value. Interactions between warming temperatures and grazers on plant traits were additive for 16 out of 19 response variables. However, the stressors non‐additively impacted the number of leaves per plant, fiber content, and epiphyte load. We suggest that the impacts of grazers on leaf turnover rate and leaf age may vary based on water temperature, potentially driving these interactions. Overall, increased temperatures and grazing pressure will likely reduce seagrass resilience, structure, and biomass, potentially impacting feedback systems and producing negative consequences for seagrass cover, associated species, and ecosystem services.
Why sex matters in phenological research
Authors: Nakazawa Takefumi , Hsu Yu‐Hsun , Chen I‐Ching
Published: May 2023

Males and females often desynchronise their mating activity during the breeding season (intersexual phenological asynchrony). This suggests that the two sexes differentially use environmental cues to initiate seasonal reproduction, and climate change may cause phenological shifts in a sex‐specific manner, subsequently altering frequency distribution of mating attempts over time and influencing the emergence timing and recruitment success of juveniles. In this article, we tested these hypotheses through literature reviews and theoretical modelling. We found that the sex specificity of environmental cues and phenological shifts remain poorly understood in most sexually reproducing animal taxa because of sex‐specific publication bias and data limitations. Meanwhile, our theoretical model predicted that the ecological consequences of phenological shifts are sexually asymmetric, with earlier mating onset of males having generally greater negative effects on population growth than that of females. We therefore suggest that further research is necessary to collect and incorporate sex‐specific information on seasonal reproduction into the theory of phenological mismatch, for which previous work has mostly focused on interspecific trophic asynchrony. We also outline a future research agenda to better understand the consequences of sex‐specific phenological shifts on seasonal population dynamics and long‐term persistence of species.
Early spring snowmelt and summer droughts strongly impair the resilience of bacterial community and N cycling functions in a subalpine grassland ecosystem
Authors: Hafeez Farhan , Clément Jean‐Christophe , Bernard Lionel , Poly Franck , Pommier Thomas
Published: May 2023

Subalpine grasslands support biodiversity, agriculture, and tourism but their resilience to extreme climatic events is challenged accelerating their vulnerability to tipping points. Microbial communities, central in ecosystem functioning, are usually considered more resistant and highly resilient to extreme events albeit their functional redundancy and strong selection by local harsh climatic conditions. This study explored the soil microbial responses upon recurrent spring‐summer droughts associated with early snowmelt in subalpine grasslands mesocosms set‐up at the Lautaret Pass (French Alps). Potential soil microbial respiration, nitrification and denitrification activities were monitored over a period of two growing seasons along with quantification of related gene abundances. Impacts of simulated spring‐summer drought and early snowmelt were quantified to assess their resistance and recovery. Results revealed that droughts had a low and short‐term adverse impact on bacterial total respiration supporting their hypothesized high resilience, i.e. resistance and ability to recover. Nitrification and abundances of the corresponding functional guilds showed relatively strong resistance to summer droughts but declined in response to early snowmelt. This resistance of nitrification was paralleled by the recovery of denitrification and abundances of denitrifying communities from all climatic extremes, except from the summer droughts where nitrifiers were collapsed. Denitrification and respective functional groups faced high impact of applied stresses with strong reduction in abundance and activity. Although, consequently lower denitrifiers' competition for nitrate may be positive for plant biomass production, warnings exist when considering the potential nitrate leaching as well as risks of greenhouses gases emission such as N2O from these ecosystems.
Ecological boundaries and constraints on viable eco‐evolutionary pathways
Authors: Coblentz Kyle E. , DeLong John P.
Published: May 2023

Evolutionary dynamics are subject to constraints ranging from limitations on what is physically possible to limitations on the pathways that evolution can take. One set of evolutionary constraints, known as ‘demographic constraints', constrain what can occur evolutionarily due to the demographic or dynamical consequences of evolution leading to conditions that make populations susceptible to extinction. These demographic constraints can limit the strength of selection or the rates of environmental change populations can experience while remaining extant and the trait values a population can express. Here we further hypothesize that the population demographic and dynamic consequences of evolution also can constrain the eco‐evolutionary pathways that populations can traverse by defining ecological boundaries represented by areas of likely extinction. We illustrate this process using a model of predator evolution. Our results show that the populations that persist over time tend to be those whose eco‐evolutionary dynamics have avoided ecological boundaries representing areas of likely extinction due to stochastic deviations from a deterministic eco‐evolutionary expectation. We term this subset of persisting pathways viable eco‐evolutionary pathways. The potential existence of ecological boundaries constraining evolutionary pathways has important implications for predicting evolutionary dynamics, interpreting past evolution, and understanding the role of stochasticity and ecological constraints on eco‐evolutionary dynamics.
Accommodative disorders in non‐presbyopic subjects with type 1 diabetes without retinopathy: A comparative, cross‐sectional study
Authors: Silva‐Viguera María‐Carmen , Bautista‐Llamas María‐José
Published: May 2023

Purpose

The purpose of this study was to assess accommodative function in non‐presbyopic individuals diagnosed with type 1 diabetes (T1D) without any signs of retinopathy, to determine the existence of possible accommodative disorders related to this disease, and to determine the influence of T1D duration and glycosylated haemoglobin values on accommodative function.

Methods

This comparative, cross‐sectional study included 60 participants between 11 and 39 years old, 30 with T1D and 30 controls, with no previous eye surgery, ocular disease or medication that could affect the results of the visual examination. Amplitude of accommodation (AA), negative and positive relative accommodation (NRA and PRA), accommodative response (AR) and accommodative facility (AF) were assessed using the tests that showed the highest repeatability. Participants were classified based on normative values into ‘insufficiency, excess or normal results’, and a diagnosis of accommodative disorders (accommodative insufficiency, accommodative infacility and accommodative excess) was made.

Results

Participants with T1D had statistically significant lower AA and AF and higher NRA values than the controls. Furthermore, AA was significantly and inversely correlated with age and the duration of diabetes; however, AF and NRA were only correlated with disease duration. In the classification by accommodative variables, a higher percentage of ‘insufficiency values’ was observed in the T1D group (50%) than in the control group (6%; p < 0.001). In terms of accommodative disorders, accommodative infacility was the most prevalent (15%), followed by accommodative insufficiency (10%).

Conclusions

Our findings indicate that T1D affects most accommodative parameters, with accommodative insufficiency being associated with this disease.
The RUBY reporter enables efficient haploid identification in maize and tomato
Authors: Wang Dong , Zhong Yu , Feng Bin , Qi Xiaolong , Yan Tongzheng , Liu Jinchu , Guo Shuwei , Wang Yuwen , Liu Zongkai , Cheng Dehe , Zhang Yuling , Shi Yunlu , Zhang Shuaisong , Pan RuXue , Liu Chenxu , Chen Shaojiang
Published: May 2023

In vivo haploid induction has been extended from maize to monocotyledonous plants like rice, wheat, millet and dicotyledonous plants such as tomato, rapeseed, tobacco and cabbage. Accurate identification of haploids is a crucial step of doubled haploid technology, where a useful identification marker is very pivotal. R1‐nj is an extensively used visual marker for haploid identification in maize. RFP and eGFP have been shown to be feasible in identifying haploid. However, these methods are either limited to specific species, or require specific equipment. It still lacks an efficient visual marker that is practical across different crop species. In this study, we introduced the RUBY reporter, a betalain biosynthesis system, into maize and tomato haploid inducers as a new marker for haploid identification. Results showed that expression of RUBY could result in deep betalain pigmentation in maize embryos as early as 10 days after pollination, and enabled 100% accuracy of immature haploid embryo identification. Further investigation in tomato revealed that the new marker led to deep red pigmentation in radicles and haploids can be identified easily and accurately. The results demonstrated that the RUBY reporter is a background‐independent and efficient marker for haploid identification and would be promising in doubled haploid breeding across different crop species.
Experience of missed nursing care: A mixed method study
Authors: Mandal Lata , Seethalakshmi A.
Published: May 2023

Background

Missed nursing care is a global phenomenon affecting patient safety and quality of care. The working environment of nurses seems to play an important role in missed nursing care.

Aims

This study was conceptualized to explore the link of environmental constraints with missed nursing care in the Indian context.

Method

A convergent mixed‐method design was adopted, and data was collected using Kalisch's MISSCARE survey from 205 randomly selected nurses involved in direct patient care in the acute care settings of four tertiary care hospitals in India. In the qualitative phase, in‐depth interviews regarding nurses' experience of missed care were performed with 12 nurses chosen by maximum variant sampling from the quantitative sample.

Results

The integrated results revealed that nurses experience a sense of competing priority in the environment where curative and prescribed tasks like medication administration get more priority than activities like communication, discharge teaching, oral hygiene, and emotional support, which are frequently missed. The human resource and communication constraints together explained 40.6% of variance in missed nursing care. Human resource inadequacy in times of increased workload was the most frequently cited reason for missed care. Converging with this finding, nurses in the interviews expressed that maintaining a flexible number of staff and catering to the variable workload can effectively reduce missed nursing care. Frequent interruption of nursing activities by medical staff and lack of structure in some activities were cited as important reasons for missed care.

Linking Evidence to Action

Nursing leaders need to acknowledge missed care in nursing and develop policies to maintain flexible staffing based on situational workload. Methods of staffing like NHPPD (Nursing hour per patient day) which are more sensitive to nursing workload, and patient turnover, can be adopted instead of a fixed nurse–patient mandate. Mutual support from team members and multi‐professional cooperation can reduce frequent interruption of nursing tasks thereby reducing missed care.
Activation of TRPV4 channels promotes the loss of cellular ATP in organotypic slices of the mouse neocortex exposed to chemical ischemia
Authors: Pape Nils , Rose Christine R.
Published: May 2023

The vertebrate brain has an exceptionally high energy need. During ischemia, intracellular ATP concentrations decline rapidly, resulting in the breakdown of ion gradients and cellular damage. Here, we employed the nanosensor ATeam1.03YEMKto analyse the pathways driving the loss of ATP upon transient metabolic inhibition in neurons and astrocytes of the mouse neocortex. We demonstrate that brief chemical ischemia, induced by combined inhibition of glycolysis and oxidative phosphorylation, results in a transient decrease in intracellular ATP. Neurons experienced a larger relative decline and showed less ability to recover from prolonged (>5 min) metabolic inhibition than astrocytes. Blocking voltage‐gated Na+channels or NMDA receptors ameliorated the ATP decline in neurons and astrocytes, while blocking glutamate uptake aggravated the overall reduction in neuronal ATP, confirming the central role of excitatory neuronal activity in the cellular energy loss. Unexpectedly, pharmacological inhibition of transient receptor potential vanilloid 4 (TRPV4) channels significantly reduced the ischemia‐induced decline in ATP in both cell types. Imaging with Na+‐sensitive indicator dye ING‐2 furthermore showed that TRPV4 inhibition also reduced ischemia‐induced increases in intracellular Na+. Altogether, our results demonstrate that neurons exhibit a higher vulnerability to brief metabolic inhibition than astrocytes. Moreover, they reveal an unexpected strong contribution of TRPV4 channels to the loss of cellular ATP and suggest that the demonstrated TRPV4‐related ATP consumption is most likely a direct consequence of Na+influx. Activation of TRPV4 channels thus provides a hitherto unacknowledged contribution to the cellular energy loss during energy failure, generating a significant metabolic cost in ischemic conditions.

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Key points

In the ischemic brain, cellular ATP concentrations decline rapidly, which results in the collapse of ion gradients and promotes cellular damage and death.

We analysed the pathways driving the loss of ATP upon transient metabolic inhibition in neurons and astrocytes of the mouse neocortex.

Our results confirm the central role of excitatory neuronal activity in the cellular energy loss and demonstrate that neurons experience a larger decline in ATP and are more vulnerable to brief metabolic stress than astrocytes.

Our study also reveals a new, previously unknown involvement of osmotically activated transient receptor potential vanilloid 4 (TRPV4) channels to the reduction in cellular ATP in both cell types and indicates that this is a consequence of TRPV4‐mediated Na+influx.

We conclude that activation of TRPV4 channels provides a considerable contribution to the cellular energy loss, thereby generating a significant metabolic cost in ischemic conditions.
USP7 represses lineage differentiation genes in mouse embryonic stem cells by both catalytic and noncatalytic activities
Authors: Liu Chao , Sun Lingang , Tan Yijun , Wang Qi , Luo Tao , Li Chenlu , Yao Nan , Xie Yuting , Yi Xiao , Zhu Yi , Guo Tiannan , Ji Junfeng
Published: May 2023

USP7, a ubiquitin-specific peptidase (USP), plays an important role in many cellular processes through its catalytic deubiquitination of various substrates. However, its nuclear function that shapes the transcriptional network in mouse embryonic stem cells (mESCs) remains poorly understood. We report that USP7 maintains mESC identity through both catalytic activity–dependent and –independent repression of lineage differentiation genes.
Usp7
depletion attenuates SOX2 levels and derepresses lineage differentiation genes thereby compromising mESC pluripotency. Mechanistically, USP7 deubiquitinates and stabilizes SOX2 to repress mesoendodermal (ME) lineage genes. Moreover, USP7 assembles into RYBP-variant Polycomb repressive complex 1 and contributes to Polycomb chromatin–mediated repression of ME lineage genes in a catalytic activity–dependent manner. USP7 deficiency in its deubiquitination function is able to maintain RYBP binding to chromatin for repressing primitive endoderm–associated genes. Our study demonstrates that USP7 harbors both catalytic and noncatalytic activities to repress different lineage differentiation genes, thereby revealing a previously unrecognized role in controlling gene expression for maintaining mESC identity.
A histone deacetylase 3 and mitochondrial complex I axis regulates toxic formaldehyde production
Authors: Wit Niek , Gogola Ewa , West James A. , Vornbäumen Tristan , Seear Rachel V. , Bailey Peter S. J. , Burgos-Barragan Guillermo , Wang Meng , Krawczyk Patrycja , Huberts Daphne H. E. W. , Gergely Fanni , Matheson Nicholas J. , Kaser Arthur , Nathan James A. , Patel Ketan J.
Published: May 2023

Cells produce considerable genotoxic formaldehyde from an unknown source. We carry out a genome-wide CRISPR-Cas9 genetic screen in metabolically engineered HAP1 cells that are auxotrophic for formaldehyde to find this cellular source. We identify histone deacetylase 3 (HDAC3) as a regulator of cellular formaldehyde production. HDAC3 regulation requires deacetylase activity, and a secondary genetic screen identifies several components of mitochondrial complex I as mediators of this regulation. Metabolic profiling indicates that this unexpected mitochondrial requirement for formaldehyde detoxification is separate from energy generation. HDAC3 and complex I therefore control the abundance of a ubiquitous genotoxic metabolite.
High-precision monitoring of and feedback control over drug concentrations in the brains of freely moving rats
Authors: Gerson Julian , Erdal Murat Kaan , McDonough Matthew H. , Ploense Kyle L. , Dauphin-Ducharme Philippe , Honeywell Kevin M. , Leung Kaylyn K. , Arroyo-Curras Netzahualcoyotl , Gibson Jenny M. , Emmons Nicole A. , Meiring Wendy , Hespanha Joao P. , Plaxco Kevin W. , Kippin Tod E.
Published: May 2023

Knowledge of drug concentrations in the brains of behaving subjects remains constrained on a number of dimensions, including poor temporal resolution and lack of real-time data. Here, however, we demonstrate the ability of electrochemical aptamer-based sensors to support seconds-resolved, real-time measurements of drug concentrations in the brains of freely moving rats. Specifically, using such sensors, we achieve <4 μM limits of detection and 10-s resolution in the measurement of procaine in the brains of freely moving rats, permitting the determination of the pharmacokinetics and concentration-behavior relations of the drug with high precision for individual subjects. In parallel, we have used closed-loop feedback-controlled drug delivery to hold intracranial procaine levels constant (±10%) for >1.5 hours. These results demonstrate the utility of such sensors in (i) the determination of the site-specific, seconds-resolved neuropharmacokinetics, (ii) enabling the study of individual subject neuropharmacokinetics and concentration-response relations, and (iii) performing high-precision control over intracranial drug levels.
Whole-Genome Sequencing Reveals Differences among Kingella kingae Strains from Carriers and Patients with Invasive Infections
Authors: Murik Omer , Zeevi David A. , Mann Tzvia , Kashat Livnat , Assous Marc V. , Megged Orli , Yagupsky Pablo
Published: May 2023

The wide range of clinical severities exhibited by invasive
Kingella kingae
infections strongly suggests that isolates differ in their genomic contents, and strains associated with life-threatening endocarditis may harbor distinct genomic determinants that result in cardiac tropism and severe tissue damage. The results of the present study show that no single gene discriminated between asymptomatically carried isolates and invasive strains.
Building implementable packages for universal health coverage
Authors: Reynolds Teri , Wilkinson Thomas , Bertram Melanie Y , Jowett Matthew , Baltussen Rob , Mataria Awad , Feroz Ferozuddin , Jama Mohamed
Published: May 2023

Since no country or health system can provide every possible health service to everyone who might benefit, the prioritisation of a defined subset of services for universal availability is intrinsic to universal health coverage (UHC). Creating a package of priority services for UHC, however, does not in itself benefit a population—packages have impact only through implementation. There are inherent tensions between the way services are formulated to facilitate criteria-driven prioritisation and the formulations that facilitate implementation, and service delivery considerations are rarely well incorporated into package development. Countries face substantial challenges bridging from a list of services in a package to the elements needed to get services to people. The failure to incorporate delivery considerations already at the prioritisation and design stage can result in packages that undermine the goals that countries have for service delivery. Based on a range of country experiences, we discuss specific choices about package structure and content and summarise some ideas on how to build more implementable packages of services for UHC, arguing that well-designed packages can support countries to bridge effectively from intent to implementation.
Insights from a qualitative study of the procurement and manufacture of active pharmaceutical ingredients in India
Authors: Hamill Heather , Hampshire Kate , Vinaya Harshada , Mamidi Pavan
Published: May 2023

Medicine supply systems are a crucial part of health systems and access to effective essential medicines is a key pillar of Universal Health Coverage. However, efforts to expand access are compromised by the proliferation of substandard and falsified medicines. The vast majority of research to date on medicine supply chains has focused on the formulation and distribution of the finished product, overlooking the crucial steps of Active Pharmaceutical Ingredient production that precede this. In this paper, we draw on qualitative interviews with manufacturers and regulators in India to take a ‘deep dive’ into these understudied parts of medicine supply chains.
Digital mental health: challenges and next steps
Authors: Smith Katharine A , Blease Charlotte , Faurholt-Jepsen Maria , Firth Joseph , Van Daele Tom , Moreno Carmen , Carlbring Per , Ebner-Priemer Ulrich W , Koutsouleris Nikolaos , Riper Heleen , Mouchabac Stephane , Torous John , Cipriani Andrea
Published: May 2023

Digital innovations in mental health offer great potential, but present unique challenges. Using a consensus development panel approach, an expert, international, cross-disciplinary panel met to provide a framework to conceptualise digital mental health innovations, research into mechanisms and effectiveness and approaches for clinical implementation. Key questions and outputs from the group were agreed by consensus, and are presented and discussed in the text and supported by case examples in an accompanying appendix. A number of key themes emerged. (1) Digital approaches may work best across traditional diagnostic systems: we do not have effective ontologies of mental illness and transdiagnostic/symptom-based approaches may be more fruitful. (2) Approaches in clinical implementation of digital tools/interventions need to be creative and require organisational change: not only do clinicians and patients need training and education to be more confident and skilled in using digital technologies to support shared care decision-making, but traditional roles need to be extended, with clinicians working alongside digital navigators and non-clinicians who are delivering protocolised treatments. (3) Designing appropriate studies to measure the effectiveness of implementation is also key: including digital data raises unique ethical issues, and measurement of potential harms is only just beginning. (4) Accessibility and codesign are needed to ensure innovations are long lasting. (5) Standardised guidelines for reporting would ensure effective synthesis of the evidence to inform clinical implementation. COVID-19 and the transition to virtual consultations have shown us the potential for digital innovations to improve access and quality of care in mental health: now is the ideal time to act.