bluuebunny/crossref_metadata_2025 huggingface dataset:
Emergence of Acquired Dolutegravir Resistance in Treatment-experienced People With HIV in Lesotho
Authors: Tschumi Nadine , Lukau Blaise , Tlali Katleho , Motaboli Lipontso , Kao Mpho , Kopo Mathebe , Haenggi Kathrin , Mokebe Moleboheng , Naegele Klaudia , Ayakaka Irene , Leuzinger Karoline , Brown Jennifer A , Labhardt Niklaus D
Published: April 2024

Background

Since 2019, the World Health Organization has recommended dolutegravir-based antiretroviral therapy (ART) as the preferred regimen for human immunodeficiency virus management. Large-scale programmatic transitioning to dolutegravir-based ART was subsequently implemented across Africa, often in the absence of recent viral load testing and without access to genotypic resistance testing (GRT) in case of viremia.

Methods

This study assessed emerging dolutegravir resistance in the routine care of the Viral Load Cohort North-East Lesotho. We included pediatric and adult participants who changed from nonnucleoside reverse transcriptase inhibitor– to dolutegravir-based ART and had at least 1 viral load assessment before and after the change. We sequenced available samples of participants fulfilling the additional virological criteria of having 2 viremic episodes while taking dolutegravir, with at least 1 viral load ≥500 copies/mL taken ≥18 months after changing to dolutegravir.

Results

Among 15 349 participants, 157 (1.0%) met the virological criteria, and GRT was successful for 85 (0.6%). Among these 85, 8 (9.4%) had dolutegravir resistance, with 2 (2.4%) and 6 (7.1%) predicted to have intermediate- and high-level dolutegravir resistance, respectively. One participant had 2, 2 had 1, and 5 had 0 active drugs in their regimen. A GRT from before the change to dolutegravir was available for 5 of these 8 participants: 4 had 0 and 1 had 1 active drug in their nonnucleoside transcriptase inhibitor–based regimen.

Conclusions

Nine percent of people with persistent or recurring human immunodeficiency virus viremia ≥18 months after changing to dolutegravir-based ART had dolutegravir resistance. Detection and management of emerging dolutegravir resistance must be addressed across Africa.
A female patient with Dent disease due to skewed X-chromosome inactivation
Authors: D'Ambrosio Viola , Wan Elizabeth R , Siew Keith , Hayes Wesley , Walsh Stephen B
Published: April 2024

X-linked proximal tubulopathies are rare diseases that predominantly affect men. Women are generally carriers and clinical or biochemical manifestations are usually absent or mild. We present the case of a young woman who presented with a full phenotype of Dent disease type 1 due to a de novo mutation in the CLCN5 gene and a skewed X-chromosome inactivation. Although cases of overt Dent disease type 2 and Lowe syndrome in women have been described in the literature, to our knowledge this is the first case of overt Dent disease type 1.
Remarkably High Repeat Content in the Genomes of Sparrows: The Importance of Genome Assembly Completeness for Transposable Element Discovery
Authors: Benham Phred M , Cicero Carla , Escalona Merly , Beraut Eric , Fairbairn Colin , Marimuthu Mohan P A , Nguyen Oanh , Sahasrabudhe Ruta , King Benjamin L , Thomas W Kelley , Kovach Adrienne I , Nachman Michael W , Bowie Rauri C K
Published: April 2024

Transposable elements (TE) play critical roles in shaping genome evolution. Highly repetitive TE sequences are also a major source of assembly gaps making it difficult to fully understand the impact of these elements on host genomes. The increased capacity of long-read sequencing technologies to span highly repetitive regions promises to provide new insights into patterns of TE activity across diverse taxa. Here we report the generation of highly contiguous reference genomes using PacBio long-read and Omni-C technologies for three species of Passerellidae sparrow. We compared these assemblies to three chromosome-level sparrow assemblies and nine other sparrow assemblies generated using a variety of short- and long-read technologies. All long-read based assemblies were longer (range: 1.12 to 1.41 Gb) than short-read assemblies (0.91 to 1.08 Gb) and assembly length was strongly correlated with the amount of repeat content. Repeat content for Bell's sparrow (31.2% of genome) was the highest level ever reported within the order Passeriformes, which comprises over half of avian diversity. The highest levels of repeat content (79.2% to 93.7%) were found on the W chromosome relative to other regions of the genome. Finally, we show that proliferation of different TE classes varied even among species with similar levels of repeat content. These patterns support a dynamic model of TE expansion and contraction even in a clade where TEs were once thought to be fairly depauperate and static. Our work highlights how the resolution of difficult-to-assemble regions of the genome with new sequencing technologies promises to transform our understanding of avian genome evolution.
Fat soluble vitamins
Authors: Kiely Mairead E.
Published: April 2024

This chapter focuses on the dietary and other sources and biomarkers of the nutritional status of each of the fat soluble vitamins. It starts with vitamin A which includes retinoids and carotenoids before acknowledging vitamin A deficiency as a serious public health nutrition problem worldwide. The major role of vitamin D, which is synthesized in the skin on exposure to ultraviolet irradiation in sunshine, is related to the maintenance of calcium homeostasis, and regulation of cell proliferation and differentiation in many tissues. The chapter also considers the importance of vitamin E and vitamin K before detailing the impact of their respective deficiencies. It evaluates the scientific basis for dietary requirements for each aforementioned vitamin.
Infancy, childhood, and adolescence
Authors: Christian Parul , Evans Charlotte
Published: April 2024

This chapter examines the changing characteristics of growth and maturation from birth through adolescence and shows how these alter nutrient requirements. Growth, development, and functional maturation mark the postnatal period of infancy, childhood, and adolescence. Thus, nutrition considerations are specific and strongly linked to chronologic age, although the condition at birth is critical in setting the trajectory. The chapter explains that each stage of growth is strongly influenced by endocrine factors and a myriad of environmental and psychosocial factors as well as activity, body composition, and dietary intakes. It cites the public health concerns surrounding specific nutrient deficiencies, malnutrition and obesity in many countries.
Vegan/vegetarian diets
Authors: Sanders Thomas A. B.
Published: April 2024

This chapter provides an overview of vegan and vegetarianism. It defines vegetarianism as the voluntary abstinence from eating meat and fish, while vegans consume no food of animal origin to avoid the exploitation of animals. People with eating disorders often report following a vegetarian or vegan diet, but there is a lack of evidence to show that vegetarian/vegan diets increase the risk of developing an eating disorder. The chapter considers the relevance of plant-based diets under the context of climate change while mentioning how nutrients in those diets might be lacking. It clarifies how the health of vegans and vegetarians differ from the health of omnivores.
Obesity
Authors: Magkos Faidon , Astrup Arne
Published: April 2024

This chapter focuses on key concepts surrounding obesity, which refers to the excessive accumulation of fat in the body. The extent of fat accumulation often impairs normal physiological functions and increases the risk of medical complications. Excess body fat is associated with the development of metabolic diseases such as type 2 diabetes, dyslipidaemia, non-alcoholic fatty liver disease, and certain types of cancer and cardiovascular disorders. The chapter acknowledges the physiological consequences of obesity and associated health risks while considering its worldwide prevalence and causal factors. It then discusses the different approaches for obesity prevention and treatment, including diet, exercise, drugs, and surgery.
Sustainable and inclusive global food systems
Authors: Cohen Marc J.
Published: April 2024

This chapter focuses on sustainable and inclusive global food systems. It provides an overview of the paradoxical nature of contemporary food insecurity and the growing integration of global markets providing promise for better food supplies and needs. Technological and institutional innovation will continue to allow food production to keep pace with environmental costs, population growth, and rising food demand. The chapter then considers access to food and the impact of globalization on food security. It then looks into policy actions needed to achieve food security in developing countries while ensuring sustainable natural resource management based on which food production depends.
Protein
Authors: Deane Colleen S. , Wilkinson Daniel J. , Atherton Philip J.
Published: April 2024

This chapter is concerned with proteins, the fundamental structures of life. They exist as functional elements within every cell and undergo extensive metabolic interaction. This widespread metabolic interaction is intimately linked to the metabolism of energy and other nutrients. At the most basic level, proteins are made from a combination of 20 different amino acids, which determines the structure and function. Dietary protein and exercise are the two key stimuli that promote positive protein turnover, which can be accurately and reliably measured using stable isotope methods. The potency of the anabolic response to dietary protein is dependent upon the protein quality, which can be measured via the Digestible Indispensable Amino Acid Score, Protein Digestibility Corrected Amino Acid Score, and/or using stable isotope tracers. In situations of protein deficiency, significant body mass can be lost, drastically impairing health and quality of life, requiring dietary protein therapy to help overcome/manage these conditions.
Water, Electrolytes, and Acid–base Balance
Authors: James Lewis J. , Evans Gethin H.
Published: April 2024

This chapter looks at water, electrolytes, and the acid–base balance. From a biological perspective, water is the most abundant compound in the human body and is the nutrient both consumed and lost in the largest amount each day. Despite its abundance in the body, water stores are regulated within a narrow physiological range, and even small deviations from normal body water stores exerts strong physiological, subjective, and behavioural responses that lead to the correction of the imbalance. The chapter then looks at the significance and functions of sodium and potassium, before discussing acid–base balance. Small changes in plasma pH, also called acid–base disturbances, can have significant consequences, as many enzymes and processes require a certain optimum pH in which they can operate.
Overweight and Obesity
Authors: Lean Mike
Published: April 2024

This chapter addresses issues related to being overweight and obese. In the past, obesity was considered simply as a state in which fat stores are visibly excessive, impairing health and quality of life. It was viewed largely as the result of excessive food consumption (gluttony) and lack of exercise (sloth), reflecting poor decision-making and lack of self-control. Body fat, at a degree that is excessive for an individual's age, sex, and race, impairs every aspect of health—physical, mental, social, and genomic. As such, obesity has become an exciting field of biomedical research, with more complete understanding of its biological basis. Both biological and environmental conditions are necessary to perturb the complex regulation of energy balance: in order to avoid weight gain and/or to lose weight, an individual must negotiate a powerful obesogenic environment. The chapter then looks at the measurement, clinical consequences, and management of obesity.
Protein-Energy Malnutrition
Authors: Truswell A. Stewart
Published: April 2024

This chapter focuses on malnutrition. People, young or old, who eat less food than they usually eat and need, lose body weight. The deficit of energy (or calories) in the diet is made up by drawing on the body's energy reserves: first fat, later muscle. Undernutrition can be mild or severe, beneficial (in someone who was obese) or dangerous. The loss of weight is a manifestation of energy depletion. Essential nutrients, protein, and micronutrients are likely to be depleted at the same time, but some micronutrients have large stores in the body, and requirements of some others are lower when energy intake is reduced. In children, who have higher protein requirements than adults, important depletion of protein is likely to accompany serious undernutrition. The chapter then looks at protein-energy malnutrition and famine.
Pre-pregnancy, Pregnancy, and Lactation
Authors: Anderson Annie S.
Published: April 2024

This chapter studies how the life-long nutritional status of a mother, from her own conception and throughout her life to the birth of her baby, impacts on the health and well-being of that baby. Indeed, the particular importance of the mother's nutrition in the months before conception is now recognized. Here the emphasis is on the achievement of appropriate body weight and optimal nutritional status (and stores) for the months ahead. Moreover, pre-pregnancy nutrition takes account of the needs of the very early stages of pregnancy (embryogenesis) when the woman may not know she is pregnant. Maternal nutrition also has a profound effect on all aspects of reproduction, including fertility. The chapter then considers lactation; during pregnancy, the mother's body prepares for lactation by storing some nutrients and energy.
Examining Women’s HIV Protective Behaviors in Nepal
Authors: Raut Shambika , Kagotho Njeri
Published: April 2024

Women’s autonomy in decision making has important sexual and reproductive health implications. This study uses a nationwide analysis in Nepal to examine women’s autonomy, attitude toward intimate partner violence (IPV) behaviors, and HIV-related knowledge in the execution of HIV protective behaviors such as having one sexual partner or getting an HIV test to prevent HIV transmission. Secondary data analysis was conducted using the nationally represented Nepal Demographic and Health Survey (2016–2021) dataset. The sample included 9,904 women ages 15 to 49 who self-identified as ever married. Factor analysis for women’s autonomy, attitude toward IPV behaviors, and HIV-related knowledge were conducted based on social dominance theory. Structural equation modeling was conducted, and the results indicated that higher autonomy decreased the risk of HIV infection through having one sexual partner. Factors related to multiple sex partners included unemployment, religious affiliation, and age. Similarly, higher autonomy, HIV-related knowledge, having a formal job, and urban residence increased women’s likelihood of taking an HIV test. Women’s higher education, greater wealth, religious affiliation, and youth also correlate with HIV testing. Future HIV prevention interventions should include strategies that support women’s social and economic empowerment and enhance women’s ability to make informed choices about their health and risks.
Problems with Paralogs: The Promise and Challenges of Gene Duplicates in Evo-Devo Research
Authors: Deem Kevin D , Brisson Jennifer A
Published: April 2024

Synopsis

Gene duplicates, or paralogs, serve as a major source of new genetic material and comprise seeds for evolutionary innovation. While originally thought to be quickly lost or nonfunctionalized following duplication, now a vast number of paralogs are known to be retained in a functional state. Daughter paralogs can provide robustness through redundancy, specialize via sub-functionalization, or neo-functionalize to play new roles. Indeed, the duplication and divergence of developmental genes have played a monumental role in the evolution of animal forms (e.g., Hox genes). Still, despite their prevalence and evolutionary importance, the precise detection of gene duplicates in newly sequenced genomes remains technically challenging and often overlooked. This presents an especially pertinent problem for evolutionary developmental biology, where hypothesis testing requires accurate detection of changes in gene expression and function, often in nontraditional model species. Frequently, these analyses rely on molecular reagents designed within coding sequences that may be highly similar in recently duplicated paralogs, leading to cross-reactivity and spurious results. Thus, care is needed to avoid erroneously assigning diverged functions of paralogs to a single gene, and potentially misinterpreting evolutionary history. This perspective aims to overview the prevalence and importance of paralogs and to shed light on the difficulty of their detection and analysis while offering potential solutions.
The spatiotemporal distribution prediction method for distributed photovoltaic installed capacity based on power supply measurement data
Authors: Yang Zhichun , Yang Fan , Liu Yu , Min Huaidong , Zeng Hao , Zhou Zhiqiang , Xiao Ming
Published: April 2024

With the anticipated expansion of distributed power grid integration in the foreseeable future, the consideration of distributed power’s impact on power balance becomes paramount in distribution network planning. In this research, we presented a novel approach for predicting the spatial and temporal distribution of distribution network planning areas, with a specific focus on estimating the installed capacity of distributed photovoltaic (PV) systems. Our method leveraged the saturated capacity of distributed PV, requiring minimal data inputs. By establishing a quantitative model that elucidated the relationship between installed distributed PV capacity and land area, we generated PV installed capacity evolution curves for various types of land. Subsequently, we derived the development coefficient of distributed PV installed capacity. By combining this coefficient with the current status of installed distributed PV capacity in the target area’s land parcels, we forecasted the spatial and temporal distribution of future distributed PV capacity within the region. The proposed prediction model held significant implications for the planning of new distribution networks. Additionally, this study predicted the installed distributed PV capacity for distinct land use types, including residential, commercial, and industrial land, using a regional power supply unit as a representative example. We employed the installed PV capacity unit to forecast the electricity loss rate and energy saving rate within the planning area. By validating the model and method through exemplary test results, we demonstrated the model’s feasibility and accuracy. Furthermore, our model effectively predicted the impact of distributed PV integration on overall load forecasting, thereby offering the power grid more precise load forecasting capabilities.
Discovering the Contributions of Academic Wives to the Development of Labour Law: Liesel Kahn-Freund
Authors: Zahn Rebecca , Kullmann Miriam
Published: April 2024

This article’s starting point is a strand of historical and sociological studies literature on ‘academic wives’ which reveals the social and, above all, unpaid labour that facilitated an academic career up until the mid-twentieth century. The article then draws on primary and secondary sources in order to trace the life of Otto Kahn-Freund’s wife, Elisabeth (Liesel) Kahn-Freund. We suggest that Liesel was an indispensable facilitator of her husband’s career. She provided valuable scholarly and intellectual support; by taking on responsibility for domestic tasks and care responsibilities, she gave her husband uninterrupted time and space to build his network, travel internationally, and, perhaps most importantly, concentrate on and pursue his research. In doing so, she, and many like her, played a significant albeit largely unrecognised role in the creation of labour law as we now know it. A better understanding of the labour performed by an “academic wife” provides a more nuanced picture of where labour law has come from and the factors that went into its creation. It also encourages labour law scholars to re-evaluate what kind of labour is recognised as part of labour law and is the focus of future labour law scholarship.
Estimating the Potential Public Health Value of BCG Revaccination
Authors: Clark Rebecca A , Sumner Tom , Weerasuriya Chathika K , Bakker Roel , Scriba Thomas J , White Richard G
Published: April 2024

An upcoming trial may provide further evidence that adolescent/adult-targeted BCG revaccination prevents sustained Mycobacterium tuberculosis infection, but its public health value depends on its impact on overall tuberculosis morbidity and mortality, which will remain unknown. Using previously calibrated models for India and South Africa, we simulated BCG revaccination assuming 45% prevention-of-infection efficacy, and we evaluated scenarios varying additional prevention-of-disease efficacy between +50% (reducing risk) and −50% (increasing risk). Given the assumed prevention-of-infection efficacy and range in prevention-of-disease efficacy, BCG revaccination may have a positive health impact and be cost-effective. This may be useful when considering future evaluations and implementation of adolescent/adult BCG revaccination.
Injunctions and damages for patent infringement under the UPCA in light of the principle of proportionality—Part II: damages
Authors: Hofmann Franz , Raue Benjamin
Published: April 2024

This article examines the availability of injunctions and the award of damages for patent infringement under the Agreement on a Unified Patent Court (UPCA), in light of the principle of proportionality. Part I, published in the previous issue, focused on injunctive relief and analysed the application of the principle of proportionality to injunctions, outlining key factors and scenarios. Part II discusses the principles and methods applicable to the calculation of damages, assessing their suitability in light of the principle of proportionality, as defined in European Union law and in the case law of select contracting states.
The changing dynamics of work from home and its association with sleep disturbance through work–family conflict during the COVID-19 pandemic
Authors: Jung Jaehyuk , Lim Jiyoung , Cho Yong Hyuk , Park Jae Bum , Jeong Inchul
Published: April 2024

Objectives:

Work from home (WFH) can increase sleep disturbances. However, only few studies have examined the connection between WFH and sleep disturbance while considering work–family conflict (WFC) and the changes brought about by the COVID-19 pandemic. This study aimed to examine the association between WFH and sleep disturbance, considering WFC, and assess how this association changed during the COVID-19 pandemic.

Methods:

We used data from the fifth and sixth Korean Working Conditions Survey. WFH workers and a control group were selected using propensity score matching. Conditional logistic regression analysis was used to estimate the odds ratios (ORs) with 95% CIs for sleep disturbance in the WFH and control groups.

Results:

The workers working from home showed significantly higher ORs for sleep disturbance before (4.26; 95% CI, 3.59-5.05) and during (1.52; 95% CI, 1.26-1.83) the COVID-19 pandemic. When stratified by WFC, the association was significant only in the workers with WFC before COVID-19. However, the association was not significant during COVID-19 among the workers with WFC.

Conclusions:

WFH was significantly associated with sleep disturbance among workers before COVID-19, but this association was not observed during the COVID-19 pandemic. Considering the significant role that WFC plays in this association, companies should provide a family-friendly WFH environment when adopting WFH practices.
Impact of increasing number of mental health conditions on healthcare costs and resource utilization among individuals with type 2 diabetes: a cross-sectional study
Authors: Bounthavong Mark , Medina Aysell , Wallace Brooke M , Sepassi Aryana , Morello Candis M
Published: April 2024

Objectives

To evaluate the association between the number of mental health conditions among individuals with type 2 diabetes (T2D) and healthcare expenditures in the USA.

Methods

A cross-sectional study was conducted to evaluate the relationship between multiple mental health conditions (0, 1, and 2 or more mental health conditions) among individuals with T2D on healthcare expenditures using data from the 2019 US Medical Expenditure Panel Survey.

Key findings

A total of 24,091,931 weighted individuals with T2D were included for analysis; 76.8% had no co-occurring mental health conditions, 15.5% had one mental health condition, and 7.7% had two or more mental health conditions. Individuals with one and two or more mental health conditions had significantly greater total healthcare costs (+$7135 and +$7168), office-based costs (+$1196 and +$1483), prescription costs (+$2091 and +$3757), office-based visits (+3.55 and +6.46), and prescriptions fills (+13.97 and +26.77) than individuals with no mental health conditions.

Conclusions

Individuals with T2D and an increasing number of co-occurring mental health conditions were associated with increased healthcare costs and resource utilization. Underlying mechanisms for this relationship remain unclear, and further investigations are needed to accurately assess the impact this may have on health outcomes.
In vitro analysis on the adhesion potential of Lactiplantibacillus plantarum from infant faeces and its gastrointestinal localization, growth promotion, and immunomodulation in Wistar rats: a preliminary study
Authors: Narayanan Rakhie , T R Keerthi
Published: April 2024

Lactic acid bacteria, found in heterogenous niches, are known for their health-endorsing properties and are in demand as prospective probiotics. Hence, the scientific community around the globe is in continuous search for novel and new potential strains with extensive applicability and minimum risk. In this context, the present study evaluated the efficiency of Lactiplantibacillus plantarum (P2F2) of human origin, a highly autoaggregating and coaggregating (with pathogens) strain, for its colonization, growth promotion, and immunomodulation. Results indicated moderate hydrophobicity on adhesion to xylene and n-hexadecane and weak electron-donating properties with chloroform. The biofilm of P2F2 formed on polystyrene was strong and highly correlated to exopolysaccharide production. The autoaggregation was moderately correlated with hydrophobicity and biofilm production. It was noted that the P2F2 strain modulated the gut microbiota and increased intestinal villi length in Wistar rats. The lipid and glucose profiles remained intact. P2F2 treatment increased the activity of reactive oxygen species-generating cells in the peritoneal cavity, besides augmenting the mitogen-induced splenocyte proliferation and maintained the immunoglobulins at the normal level. Results from this study conclusively suggest that the strain P2F2 adheres to the intestine and modulates the gut ecosystem besides enhancing cell-mediated immunity without altering the serological parameters tested.
Confounded by Time and Love: An Interview with Jericho Brown
Authors: Brown Cameron , Floreani Tracy
Published: April 2024

This interview with poet Jericho Brown, winner of the 2020 Pulitzer Prize for Poetry for his book The Tradition (2019), includes anecdotes from his childhood, reflections on life and writing after receiving a major literary prize, meditations on his role as a teacher, a description of inventing a new poetic form, his journey to declare identity within his art, the upheavals of 2020, and shifting attitudes around social justice, censorship, and public education.
Resolving the intricate binding of neomycin B to multiple binding motifs of a neomycin-sensing riboswitch aptamer by native top-down mass spectrometry and NMR spectroscopy
Authors: Heel Sarah Viola , Juen Fabian , Bartosik Karolina , Micura Ronald , Kreutz Christoph , Breuker Kathrin
Published: April 2024

Understanding small molecule binding to RNA can be complicated by an intricate interplay between binding stoichiometry, multiple binding motifs, different occupancies of different binding motifs, and changes in the structure of the RNA under study. Here, we use native top-down mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy to experimentally resolve these factors and gain a better understanding of the interactions between neomycin B and the 40 nt aptamer domain of a neomycin-sensing riboswitch engineered in yeast. Data from collisionally activated dissociation of the 1:1, 1:2 and 1:3 RNA-neomycin B complexes identified a third binding motif C of the riboswitch in addition to the two motifs A and B found in our previous study, and provided occupancies of the different binding motifs for each complex stoichiometry. Binding of a fourth neomycin B molecule was unspecific according to both MS and NMR data. Intriguingly, all major changes in the aptamer structure can be induced by the binding of the first neomycin B molecule regardless of whether it binds to motif A or B as evidenced by stoichiometry-resolved MS data together with titration data from 1H NMR spectroscopy in the imino proton region. Specific binding of the second and third neomycin B molecules further stabilizes the riboswitch aptamer, thereby allowing for a gradual response to increasing concentrations of neomycin B, which likely leads to a fine-tuning of the cellular regulatory mechanism.
Convicting Peaceful Protesters: Proportionality’s Proper Place at Criminal Trial
Authors: Martin Richard
Published: April 2024

Suppose that a defendant’s conviction would amount to an interference with their right to peaceful protest, protected by articles 10 and 11 of the European Convention on Human Rights. Is a court then obliged to make a conviction turn on a fact-sensitive proportionality assessment justifying the interference? Drawing on the jurisprudence of the domestic and Strasbourg courts, this article argues that the case law has crystallised into two paradigms that provide distinct answers: the ‘justificatory paradigm’ in European human rights law and the ‘offence-centric’ paradigm in domestic law. The article exposes how and why this divergence has developed, what is at stake at the level of constitutional values and how this conflict might be resolved. It is argued that compliance with Strasbourg now depends on the integration of the justificatory paradigm into domestic law. The article imagines how this might be done in a manner sensitive to domestic constitutional values, using the mechanics on offer in the Human Rights Act 1998.
Discovery and Characterization of Two Highly Divergent Variants of a Novel Potyvirus Species Infecting Madagascar Periwinkle (Catharanthus roseus)
Authors: Alabi Olufemi J. , Stevens Kristian , Oladokun John O. , Villegas Cecilia , Hwang Min Sook , Al Rwahnih Maher , Tian Tongyan , Hernandez Isaias , Ouro-Djobo Ashrafou , Sétamou Mamoudou , Jifon John L.
Published: April 2024

During the summer of 2022, a cluster of Madagascar periwinkle plants with white and mauve flowers were observed with foliar mild yellow mosaic symptoms on a private property in Harlingen, Cameron County, Texas. The symptoms were reproduced on mechanically inoculated periwinkle and Nicotiana benthamiana plants. Virions of 776 to 849 nm in length and 11.7 to 14.8 nm in width were observed in transmission electron microscopy of leaf dip preparations made from symptomatic periwinkle leaves. High-throughput sequencing (HTS) analysis of total RNA extracts from symptomatic leaves revealed the occurrence of two highly divergent variants of a novel Potyvirus species as the only virus-like sequences present in the sample. The complete genomes of both variants were independently amplified via reverse transcriptase PCR, cloned, and Sanger sequenced. The 5′ and 3′ of the genomes were acquired using random amplification of cDNA ends methodology. The assembled virus genomes were 9,936 and 9,944 nucleotides (nt) long, and they shared 99.9 to 100% identities with the respective HTS-derived genomes. Each genome encoded hypothetical polyprotein of 3,171 amino acids (aa) (362.6 kilodaltons [kDa]) and 3,173 aa (362.7 kDa), respectively, and they shared 77.3/84.4% nt/aa polyprotein identities, indicating that they represent highly divergent variants of the same Potyvirus species. Both genomes also shared below-species-threshold polyprotein identity levels with the most closely phylogenetically related known potyviruses, thus indicating that they belong to a novel species. The name periwinkle mild yellow mosaic virus (PwMYMV) is given to the potyvirus with complete genomes of 9,936 nt for variant 1 (PwMYMV-1) and 9,944 nt for variant 2 (PwMYMV-2). We propose that PwMYMV be assigned into the genus Potyvirus (family Potyviridae).
Suppression of AGRN enhances CD8+ T cell recruitment and inhibits breast cancer progression
Authors: Tao Jing , Shen Li , Zhuang Minyu , Zhai Changyuan , Zeng Hanling , Mao Yuan , Liu Xiaoan
Published: April 2024

Breast cancer (BC) stands as a prominent contributor to global cancer‐related mortality, with an increasing incidence annually. This study aims to investigate AGRN gene expression in BC, as well as explore its influence on the tumor immune microenvironment. AGRN displayed a pronounced upregulation in BC tissues relative to paracancerous tissues. Single‐cell RNA analysis highlighted AGRN‐specific elevation within cancer cell clusters and also showed expression expressed in stromal as well as immune cell clusters. AGRN upregulation was positively correlated with clinicopathological stage and negatively correlated with BC prognosis. As revealed by the in vitro experiment, AGRN knockdown effectively hinders BC cells in terms of proliferation, invasion as well as migration. AGRN protein, which may interact with EXT1, LRP4, RAPSN, etc., was primarily distributed in the cell cytoplasm. Notably, immune factors might interact with AGRN in BC, evidenced by its discernible associations with immunofactors like IL10, CD274, and PVRL2. Mass spectrometry and immunohistochemistry revealed that the reduction of AGRN led to an increase in CD8+ T cells with triple‐negative breast cancer (TNBC). Mechanistically, the connection between TRIM7 and PD‐L1 is improved by AGRN, acting as a scaffold, thereby facilitating the accelerated degradation of PD‐L1 by TRIM7. Downregulation of AGRN inhibits BC progression and increases CD8+ T cell recruitment. Targeting AGRN may contribute to BC treatment. The biomarker AGRN, serving as a therapeutic target for BC, emerges as a prospective avenue for enhancing both diagnosis and prognosis in BC cases.
PRMT4 interacts with NCOA4 to inhibit ferritinophagy in cisplatin‐induced acute kidney injury
Authors: Zhou Lizhi , Deng Zebin , Wang Yilong , Zhang Hao , Yan Shu , Kanwar Yashpal S. , Wang Yinhuai , Dai Yingbo , Deng Fei
Published: April 2024

Cisplatin‐induced acute kidney injury (AKI) is commonly seen in the clinical practice, and ferroptosis, a type of non‐apoptotic cell death, plays a pivotal role in it. Previous studies suggested that protein arginine methyltransferase 4 (PRMT4) was incorporated in various bioprocesses, but its role in renal injuries has not been investigated. Our present study showed that PRMT4 was highly expressed in renal proximal tubular cells, and it was downregulated in cisplatin‐induced AKI. Besides, genetic disruption of PRMT4 exacerbated, while its overexpression attenuated, cisplatin‐induced redox injuries in renal proximal epithelia. Mechanistically, our work showed that PRMT4 interacted with NCOA4 to inhibit ferritinophagy, a type of selective autophagy favoring lipid peroxidation to accelerate ferroptosis. Taken together, our study demonstrated that PRMT4 interacted with NCOA4 to attenuate ferroptosis in cisplatin‐induced AKI, suggesting that PRMT4 might present as a new therapeutic target for cisplatin‐related nephropathy.
Effects of repeated weight cycling on non‐alcoholic steatohepatitis in diet‐induced obese mice
Authors: Inia José A. , de Jong Jelle C. B. C. , Keijzer Nanda , Menke Aswin L. , Princen Hans M. G. , Jukema J. Wouter , van den Hoek Anita M.
Published: April 2024

Lifestyle interventions remain the treatment of choice for patients with obesity and metabolic complications, yet are difficult to maintain and often lead to cycles of weight loss and regain (weight cycling). Literature on weight cycling remains controversial and we therefore investigated the association between weight cycling and metabolic complications using preexistent obese mice. Ldlr−/−.Leiden mice received a high‐fat diet (HFD) for 20 weeks to induce obesity. Subsequently, weight‐cycled mice were switched between the healthy chow diet and HFD for four 2‐week periods and compared to mice that received HFD for the total study period. Repeated weight cycling tended to decrease body weight and significantly reduced fat mass, whereas adipose tissue inflammation was similar relative to HFD controls. Weight cycling did not significantly affect blood glucose or plasma insulin levels yet significantly reduced plasma free fatty acid and alanine transaminase/aspartate transaminase levels. Hepatic macrovesicular steatosis was similar and microvesicular steatosis tended to be increased upon weight cycling. Weight cycling resulted in a robust decrease in hepatic inflammation compared to HFD controls while hepatic fibrosis and atherosclerosis development were not affected. These results argue against the postulate that repeated weight cycling leads to unfavorable metabolic effects, when compared to a continuous unhealthy lifestyle, and in fact revealed beneficial effects on hepatic inflammation, an important hallmark of non‐alcoholic steatohepatitis.
The Gathering Storm: The 2023 Rovenstine Lecture*
Authors: Sessler Daniel I.
Published: April 2024

Anesthesiologists are currently in demand and highly compensated. What appears to be a great success from our perspective is considered problematic from every other healthcare perspective. Consequently, there are powerful healthcare forces seeking to improve anesthesia access and reduce service cost. They will try to impose solutions that may radically change operative anesthesia. The Rovenstine lecture, delivered on World Anesthesia Day 2023, identified substantial challenges our specialty faces and discusses solutions that might be forced on us. It also presented opportunities in perioperative care.
Perceptions of Racial-Ethnic Inequities in COVID-19 Healthcare and Willingness to Receive the COVID-19 Vaccine
Authors: Sherchan Juliana S. , Fernandez Jessica R. , Njoku Anuli , Brown Tyson H. , Forde Allana T.
Published: April 2024

Background:

Perceptions of the US healthcare system can impact individuals’ healthcare utilization, including vaccination intentions. This study examined the association between perceived racial–ethnic inequities in COVID-19 healthcare and willingness to receive the COVID-19 vaccine.

Methods:

This study used data from REACH-US, a nationally representative online survey of a large, diverse sample of U.S. adults (N=5145 January 26, 2021-March 3, 2021). Confirmatory factor and regression analyses examined a latent factor of perceived racial–ethnic inequities in COVID-19 healthcare, whether the factor was associated with willingness to receive the COVID-19 vaccine, and whether associations varied across racial–ethnic groups reported as probit estimates (B) and 95% confidence intervals (CIs).

Results:

Perceived racial–ethnic inequities in COVID-19 healthcare were highest among Black/African American adults (mean latent factor score: 0.65 ± 0.43) and lowest among White adults (mean latent factor score: 0.04 ± 0.67). Black/African American (B = −0.08; 95% CI = −0.19, 0.03) and Native Hawaiian/Pacific Islander (B = −0.08; 95% CI = −0.23, 0.07) adults who perceived greater racial–ethnic inequities in COVID-19 healthcare were less willing than participants who perceived lower inequities. In contrast, American Indian/Alaska Native (B = 0.15; 95% CI = −0.01, 0.30), Asian (B = 0.20; 95% CI = 0.08, 0.31), Hispanic/Latino (English language preference) (B = 0.22; 95% CI = 0.01, 0.43), Multiracial (B = 0.23; 95% CI = 0.09, 0.36), and White (B = 0.31; 95% CI = 0.19, 0.43) adults who perceived greater racial–ethnic inequities in COVID-19 healthcare were more willing to receive the COVID-19 vaccine than participants perceiving higher inequities.

Conclusions:

Greater perceived racial–ethnic inequities in COVID-19 healthcare were associated with less willingness to receive the COVID-19 vaccine among Black/African American and Native Hawaiian/Pacific Islander adults.
Society and Nuclear Energy: What Is the Role for Radiological Protection?
Authors: Allison Wade
Published: April 2024

The harm that society expects from ionizing radiation does not match experience. Evidently there is some basic error in this assumption. A reconsideration based on scientific principles shows how simple misunderstandings have exaggerated dangers. The consequences for society are far-reaching. The immediate impact of ionizing radiation on living tissue is destructive. However, this oxidative damage is similar to that produced during normal metabolic activity where the subsequent biological reaction is not only protective but also stimulates enhanced protection. This adaptation means that the response to oxidative damage depends on past experience. Similarly, social reaction to a radiological accident depends on the regulations and attitudes generated by the perception of previous instances. These shape whether nuclear technology and ionizing radiation are viewed as beneficial or as matters to avoid. Evidence of the spurious damage to society caused by such persistent fear in the second half of the 20th century suggests that these laws and attitudes should be rebased on evidence. The three stages of radiological impact—the initial physical damage, the subsequent biological response, and the personal and social reaction—call on quite different logic and understanding. When these are confused, they lead to regulations and public policy decisions that are often inept, dangerous, and expensive. One example is when the mathematical rigor of physics, appropriate to the immediate impact, is misapplied to the adaptive behavior of biology. Another, the tortured historical reputation of nuclear technology, is misinterpreted as justifying a radiological protection policy of extreme caution.

Specialized education and closed groups of experts tend to lock in interdisciplinary misperceptions. In the case of nuclear technology, the resulting lack of independent political confidence endangers the adoption of nuclear power as the replacement for fossil fuels. In the long term, nuclear energy is the only viable source of large-scale primary energy, but this requires a re-working of public understanding.
En Face Depth Resolved OCTA Monitoring of Macular Outer Retinal Deposits in a Case of Multifocal Choroiditis Mimicking Syphilitic Uveitis
Authors: Akotoye Christian , Hoyek Sandra , Garg Itika , Singh Nakul , Miller John B. , Sobrin Lucia , Patel Nimesh A
Published: April 2024

Purpose:

Multifocal choroiditis (MFC) is a rare inflammatory condition characterized by retinal and choroidal lesions that may present similarly to ocular pathology of various etiologies. Here we present a case of MFC mimicking syphilitic uveitis with unique en face optical coherence tomography angiography (OCTA) imaging characteristics

Methods:

Case report.

Results:

A 61-year-old woman presented with blurry vision, floaters and multiple whitish subretinal deposits on en face swept-source OCTA in the left eye. Fluorescent treponemal antibody test absorption was positive which led to the initial diagnosis of syphilitic uveitis and subsequent treatment with intravenous penicillin. During follow-up, OCTA of the left eye revealed the development of new choroidal neovascular membrane and new punched-out lesions in the posterior pole. The patient was eventually diagnosed with MFC and treated with aflibercept injections.

Conclusions:

Immune-mediated uveitis can simulate infectious and neoplastic uveitis. En face OCTA is unique imaging modality that allowed for the complete characterization and monitoring of the sub-macular deposits. This expands the clinical spectrum of multifocal choroiditis.
A CASE OF ALSTRÖM SYNDROME WITH A NOVEL VARIANT IN ALMS1 GENE PRESENTING WITH CONE ROD DYSTROPHY AS FIRST FINDING
Authors: Yen Busra , Ciftci Mukaddes Damla , Afrashi Filiz , Onay Huseyin , Goksen Damla
Published: April 2024

Purpose:

Alström Syndrome (AS) is a rare autosomal recessive monogenic ciliopathy which is caused by a mutation of the Alström syndrome 1 (ALMS1) gene. It is a multisystemic disorder characterized by insulin resistance, childhood obesity, cardiomyopathy, progressive hepatic and renal failure, sensorineural hearing loss and retinal degeneration. Herein, we aimed to report a novel variant in ALMS1 gene causing AS in a patient presenting with visual impairment.

Methods:

Case report.

Results:

A 10-year-old male patient presented with photophobia and visual impairment in both eyes. Anterior and posterior segment examinations were unremarkable bilaterally. Optical coherence tomography (OCT) showed attenuated ellipsoid zone. Electroretinography revealed diminished cone and rod responses consistent with cone rod dystrophy (CRD). Genetic testing demonstrated a novel homozygous variant in ALMS1 (NM_015120.4) gene. The patient also was found to have early-stage dilated cardiomyopathy through systemic evaluation after the diagnosis of AS.

Conclusion:

Cone-rod dystrophy in pediatric population is relatively rare condition that can be associated with syndromic ciliopathies. The authors presented a case of AS with a novel variant in ALMS1 gene based on ophthalmic findings. Ophthalmologists play an important role in the diagnosis of this syndrome and early detection of systemic manifestations.
Hemodynamical Evaluation of a New Surgically Implanted Pulsatile Right Ventricular Assist Device Driven by a Conventional Intra-Aortic Balloon Pump Console
Authors: Knigge Sara , Dogan Günes , Deniz Ezin , Ismail Youseph , Optenhöfel Jörg , Schana Liam , Merzah Ali S. , Hanke Jasmin S. , Ismail Issam , Malchin Oren , Bastos Marcelo , Popov Aron F. , Weymann Alexander , Ruhparwar Arjang , Schmack Bastian , Schmitto Jan D.
Published: April 2024

Severe right heart failure, often overlooked and challenging to manage, has prompted a growing interest in innovative approaches to provide functional support. This study uses experimentation in large porcine models to introduce a novel prototype of a pulsatile mechanical circulatory support device and document its effects when deployed as a right ventricular assist device (RVAD). The pulsatile ventricular assist platform (pVAP), featuring a membrane pump driven by an intra-aortic balloon pump console, actively generates pulsatile flow to propel right ventricular blood into the pulmonary artery. This novel prototype demonstrates promising potential in addressing the challenges of right heart failure management. After preliminary in vitro assessments, the pVAP was tested on seven porcine models in a healthy state and after the induction of right ventricular failure. During the procedure, a set of standard (ie, standard-of-care) hemodynamic measurements was obtained. Additionally, invasive pressure-volume loop analysis was employed to examine left ventricular hemodynamics. Results indicated that activation of the pVAP during right ventricular failure significantly improved systemic hemodynamics and enhanced left ventricular function. This study sheds light on the potential of the pVAP in managing right heart failure.