bluuebunny/crossref_metadata_2025 huggingface dataset:
Disentangling river and swamp buffalo genetic diversity: initial insights from the 1000 Buffalo Genomes Project
Authors: Pineda Paulene S , Flores Ester B , Villamor Lilian P , Parac Connie Joyce M , Khatkar Mehar S , Thu Hien To , Smith Timothy P L , Rosen Benjamin D , Ajmone-Marsan Paolo , Colli Licia , Williams John L , Low Wai Yee ,   1000 Buffalo Genomes Consortium, Low Lloyd , Khatkar Mehar , Chen Tong , Nguyen Hanh Thi Hong , Tonhati Humberto , de Camargo Gregório Miguel Ferreira , Biffani Stefano , Han Jianlin , Zhang Yi , Liu Mei , Zhou Yang , Gómez Divier Antonio Agudelo , Kumarasamy P , Bhatti Jaswinder Singh , Mukesh Manishi , Priyono Dwi Sendi , Dakhlan Akhmad , Mokhber Mahdi , Williams John , Paolo Ajmone Marsan , Colli Licia , Carpio Mayra Gómez , Cimmino Roberta , Awan Ali Raza , Pineda Paulene S , Villamor Lilian P , Flores Ester B , Parac Connie Joyce , Parnpai Rangsun , Tuk Siri , Soysal M İhsan , Unal Emel Özkan , Isik Raziye , Jiang Zhihua , Lụ’c Ðỗ Ðụ’c , Thinh Nguyen Hoang
Published: September 2024

More people in the world depend on water buffalo for their livelihoods than on any other domesticated animals, but its genetics is still not extensively explored. The 1000 Buffalo Genomes Project (1000BGP) provides genetic resources for global buffalo population study and tools to breed more sustainable and productive buffaloes. Here we report the most contiguous swamp buffalo genome assembly (PCC_UOA_SB_1v2) with substantial resolution of telomeric and centromeric repeats, ∼4-fold more contiguous than the existing reference river buffalo assembly and exceeding a recently published male swamp buffalo genome. This assembly was used along with the current reference to align 140 water buffalo short-read sequences and produce a public genetic resource with an average of ∼41 million single nucleotide polymorphisms per swamp and river buffalo genome. Comparison of the swamp and river buffalo sequences showed ∼1.5% genetic differences, and estimated divergence time occurred 3.1 million years ago (95% CI, 2.6–4.9). The open science model employed in the 1000BGP provides a key genomic resource and tools for a species with global economic relevance.
Institutional change, sovereigntist contestation and the limits of populism: evidence from southern Europe
Authors: Giurlando Philip , Monteleone Carla
Published: September 2024

It is widely recognized that populists oppose the delegation of more decision-making to supranational actors and that this tendency can be constrained by other branches of government, geopolitical power pressures or factors such as whether populists are minor or major members of coalitions. The literature, however, has not elaborated on how the transformation of international organizations can affect populist politics. We aim to fill this gap with an examination of how the NextGenerationEU (NGEU), a redistributionist and solidaristic form of supranational governance, undermined populist opposition to the European Union in selected beneficiary countries. To demonstrate this, we explore populist discourses in France, Italy and Spain during four successive crises in the EU's history in which its structure and identity were at stake and which prompted debates on the future in/of the EU: the referendum on the Constitutional Treaty of 2005, the Greek referendum of 2015, the Brexit referendum of 2016 and the COVID–19 crisis, followed by the Recovery Fund/NGEU of 2020. Observing populist discourses during the acute phases of these four crises allows us to observe a consolidated trend of populist contestation until 2020, when the NGEU was announced, and supports the conclusion that populists, especially in Spain and Italy, went in a less sovereigntist direction as a result of the NGEU.
Goodbye, Wolf Warrior: charting China's transition to a more accommodating diplomacy
Authors: Yuan Shaoyu
Published: September 2024

China has abolished its previous wolf-warrior diplomacy and is increasingly adopting a softer diplomatic tone, primarily driven by internal economic challenges such as a slowing economy and the need for global economic stability to sustain its growth and development. In response to international pressures and the desire to avoid further isolation, China is adjusting its foreign policy to be more in line with global norms and expectations, which may improve its relations with western democracies. The shift in China's diplomacy reflects a broader strategy to recalibrate its global influence by presenting itself as a more responsible and cooperative international player, which is essential for maintaining its long-term geopolitical ambitions. Western democracies should: Avoid seeing China solely as an adversary. Instead, they should engage constructively, leveraging this diplomatic shift to build trust and foster cooperation on global challenges. Promote policies that encourage reciprocal openness and collaboration, ensuring that China's diplomatic softening goes beyond rhetoric and leads to tangible improvements in international relations. Continuously monitor China's evolving diplomatic strategies to adjust and optimize foreign policy approaches, balancing collaboration opportunities with cautionary measures against potential risks.
An Elliptic Generalization of A1 Spherical DAHA at K = 2
Authors: Arthamonov Semeon , Shakirov Shamil
Published: September 2024

We construct an algebra that is an elliptic generalization of $A_1$ spherical DAHA acting on its finite-dimensional module at $t=-q^{-K/2}$ with $K=2$. We prove that $PSL(2,\mathbb{Z})$ acts by automorphisms of the algebra we constructed, and provide an explicit representation of automorphisms and algebra operators alike by $3 \times 3$ matrices with matrix elements given by products of elliptic functions. A relation of this construction to the $K$-theory character of affine Laumon space is conjectured. We point out two potential applications, respectively to $SL(3,\mathbb{Z})$ symmetry of Felder–Varchenko functions and to new elliptic invariants of torus knots and Seifert manifolds.
A Longitudinal Analysis of Memory Immune Responses in Convalescent Crimean-Congo Hemorrhagic Fever Survivors in Uganda
Authors: Cohen Courtney A , Balinandi Stephen , Kuehne Ana I , Rock Michelle L , Bonagofski Luke G , Ricks Keersten M , Davis Ian , Abelson Dafna , Stonier Spencer W , Odongo Matthew , Bornholdt Zachary A , Zeitlin Larry , Moyer Crystal , Cose Stephen , Dye John M , Lutwama Julius J , Herbert Andrew S
Published: September 2024

Evaluating the adaptive immune responses to natural infection with Crimean-Congo hemorrhagic fever (CCHF) virus (CCHFV) in human survivors is critical to the development of medical countermeasures. However, the correlates of protection are unknown. As the most prevalent tick-borne human hemorrhagic fever virus with case fatality rates of 5%–30% and worldwide distribution, there is an urgent need to fill these knowledge gaps. Here, we describe adaptive immune responses in a cohort of Ugandan CCHF survivors via serial sampling over 6 years. We demonstrate persistent antibodies after infection and cross-neutralization against various clades of authentic CCHFV, as well as potent effector function. Moreover, we show for the first time persistent, polyfunctional antigen-specific memory T-cell responses to multiple CCHFV proteins up to 9 years after infection. Together, this data provides immunological benchmarks for evaluating CCHFV medical countermeasures and information that can be leveraged toward vaccine immunogen design and viral target identification for monoclonal antibody therapies.
A retrospective propensity-score-matched cohort study of the impact of procalcitonin testing on antibiotic use in hospitalized patients during the first wave of COVID-19
Authors: Sandoe Jonathan A T , Grozeva Detelina , Albur Mahableshwar , Bond Stuart E , Brookes-Howell Lucy , Dark Paul , Euden Joanne , Hamilton Ryan , Hellyer Thomas P , Henley Josie , Hopkins Susan , Howard Philip , Howdon Daniel , Knox-Macaulay Chikezie , Llewelyn Martin J , Maboshe Wakunyambo , McCullagh Iain J , Ogden Margaret , Parsons Helena K , Partridge David G , Powell Neil , Prestwich Graham , Shaw Dominick , Shinkins Bethany , Szakmany Tamas , Thomas-Jones Emma , Todd Stacy , West Robert M , Carrol Enitan D , Pallmann Philip
Published: September 2024

Background

Procalcitonin (PCT) is a blood marker used to help diagnose bacterial infections and guide antibiotic treatment. PCT testing was widely used/adopted during the COVID-19 pandemic in the UK.

Objectives

Primary: to measure the difference in length of early (during first 7 days) antibiotic prescribing between patients with COVID-19 who did/did not have baseline PCT testing during the first wave of the pandemic. Secondary: to measure differences in length of hospital/ICU stay, mortality, total days of antibiotic prescribing and resistant bacterial infections between these groups.

Methods

Multi-centre, retrospective, observational, cohort study using patient-level clinical data from acute hospital Trusts/Health Boards in England/Wales. Inclusion: patients ≥16 years, admitted to participating Trusts/Health Boards and with a confirmed positive COVID-19 test between 1 February 2020 and 30 June 2020.

Results

Data from 5960 patients were analysed: 1548 (26.0%) had a baseline PCT test and 4412 (74.0%) did not. Using propensity-score matching, baseline PCT testing was associated with an average reduction in early antibiotic prescribing of 0.43 days [95% confidence interval (CI): 0.22–0.64 days, P < 0.001) and of 0.72 days (95% CI: 0.06–1.38 days, P = 0.03] in total antibiotic prescribing. Baseline PCT testing was not associated with increased mortality or hospital/ICU length of stay or with the rate of antimicrobial-resistant secondary bacterial infections.

Conclusions

Baseline PCT testing appears to have been an effective antimicrobial stewardship tool early in the pandemic: it reduced antibiotic prescribing without evidence of harm. Our study highlights the need for embedded, rapid evaluations of infection diagnostics in the National Health Service so that even in challenging circumstances, introduction into clinical practice is supported by evidence for clinical utility.

Study registration number

ISRCTN66682918.
Determination of Aloin A, Aloin B, and Aloe-Emodin in Raw Materials and Finished Products Using HPLC Multilaboratory Validation Study, AOAC 2016.09, Final Action
Authors: Lee Isaac , Gao Quanyin , Liu Wei , Patel Darshan , Smith Malissa , You Hong , Patel Tushar , Aylozyan Karine , Babajanian Silva , Collins Teddy , Sullivan Darryl , Chang Peter , Swanson Gary
Published: September 2024

Background

A multilaboratory validation study was performed on AOAC Official Method 2016.09, for final action. Eight different laboratories throughout the world participated in the study and tested the same set of six different laboratory samples of raw materials (commercial) and formulated products (commercial), and all the laboratories successfully generated results within the acceptance criteria.

Objective

The intention of the study was to evaluate specificity, precision (variation), linearity/range, system suitability, LOD, and LOQ by multiple laboratories to satisfy the requirement for moving Official Method  2016.09 to final action status. Accuracy and ruggedness were already validated in earlier work through single-laboratory validation, and it was not necessary to include these validation parameters in the multilaboratory validation study.

Methods

Laboratory samples containing Aloe vera were sent out to participating laboratories. Each laboratory followed Official Method  2016.09 (First Action) to analyze the content of aloin A, aloin B, and aloe-emodin using HPLC. The results generated by each laboratory were collected and evaluated.

Results

The specificity results show that blank and matrix chromatograms do not contain major interfering peaks at the retention time of aloin A, aloin B, and aloe-emodin. The precision (variation) results of duplicated preparations are not more than 0.05 parts per million (ppm) different. The linearity/range results from six standards (10 parts per billion [ppb], 20 ppb, 40 ppb, 80 ppb, 160 ppb, and 500 ppb) have correlation coefficient (R) values of ≥0.999. The system suitability results meet the acceptance criteria to show the instrument validity. The LOD results show that the S/N ratios of the 10 ppb standards for all three components are about 3. The LOQ results show that the S/N ratios of 20 ppb standards for all three components are about 10.

Conclusion

The parameters (specificity, precision [variation], linearity/range, system suitability, LOD, and LOQ) have been validated and show that the test method is suitable for its intended use.

Highlights

The test method has been successfully validated by eight different laboratories around the world (United States, United Kingdom, Germany, and Canada). Each of the laboratories is managed independently by a site laboratory management team. This multilaboratory study has validated Official Method 2016.09 (First Action) and the method is fit for its intended purpose.
Impact of climate change on the geographical distribution of ticks of public health significance in Colombia: Amblyomma ovale (Ixodida: Ixodidae), the Amblyomma maculatum (Ixodida: Ixodidae) complex and the Amblyomma cajennense (Ixodida: Ixodidae) complex
Authors: Polo Gina , Gamarra Jorge , Robayo-Sánchez Laura Natalia , Cortés-Vecino Jesús A , Ramírez-Hernández Alejandro
Published: September 2024

Ticks of the Amblyomma maculatum (Ixodida Ixodidae) complex, the Amblyomma cajennense (Ixodida Ixodidae) complex and Amblyomma ovale (Ixodida Ixodidae) are known to transmit various Rickettsia species in Colombia, but their exact distribution is unknown. We built several models based on current climate and projected future climate changes using a maximum entropy approach. A total of 314 records of the A. cajennense complex (65.9%; n = 207), A. ovale (22.9%; n = 72), and the A. maculatum complex (11.1%; n = 35) were obtained. Amblyomma ovale has a current distribution in the Pacific, Caribbean and Andean regions and could be potentially found in the Amazon. Amblyomma maculatum has a current distribution in the Andean and could potentially be found in the Caribbean and Orinoco regions. Amblyomma mixtum can be found near the Caribbean Sea and in the Pacific region, and A. patinoi is likely to be found in the Andean region and the Caribbean. In 2070, it will be possible to find an expansion of A. ovale and A. maculatum and a decrease of A. mixtum and A. patinoi. The variables that best predict the distribution of these species are isothermality (small fluctuations in temperature) and annual precipitation. Amblyomma cajennense s.l and A. ovale, A. cajennese s.l and A. patinoi, as well as A. maculatum and A. patinoi, have an important environmental sympatry. Epidemiological and acarological surveillance is crucial to investigate rickettsiosis caused by R. parkeri in A. ovale regions, by R. rickettsii in A. patinoi and A. mixtum areas, and by R. parkeri s.s in A. maculatum regions.
DFF-ChIP: a method to detect and quantify complex interactions between RNA polymerase II, transcription factors, and chromatin
Authors: Spector Benjamin M , Santana Juan F , Pufall Miles A , Price David H
Published: September 2024

Recently, we introduced a chromatin immunoprecipitation (ChIP) technique utilizing the human DNA Fragmentation Factor (DFF) to digest the DNA prior to immunoprecipitation (DFF-ChIP) that provides the precise location of transcription complexes and their interactions with neighboring nucleosomes. Here we expand the technique to new targets and provide useful information concerning purification of DFF, digestion conditions, and the impact of crosslinking. DFF-ChIP analysis was performed individually for subunits of Mediator, DSIF, and NELF that that do not interact with DNA directly, but rather interact with RNA polymerase II (Pol II). We found that Mediator was associated almost exclusively with preinitiation complexes (PICs). DSIF and NELF were associated with engaged Pol II and, in addition, potential intermediates between PICs and early initiation complexes. DFF-ChIP was then used to analyze the occupancy of a tight binding transcription factor, CTCF, and a much weaker binding factor, glucocorticoid receptor (GR), with and without crosslinking. These results were compared to those from standard ChIP-Seq that employs sonication and to CUT&RUN which utilizes MNase to fragment the genomic DNA. Our findings indicate that DFF-ChIP reveals details of occupancy that are not available using other methods including information revealing pertinent protein:protein interactions.
Abolitionist Perspectives in Social Work
Authors: Toraif Noor , Frisella Alison
Published: September 2024

Abolitionist social work is a theoretical and practical orientation which seeks to end the carceral logics, practices, and discourses that pervade the field of social work. Aligned with the broader project of abolishing all carceral institutions, abolitionist social work recognizes that these institutions function as systems of social control, designed to maintain the interlocking oppressions of racial capitalism, settler colonialism, and heteropatriarchy. In place of carceral institutions, abolitionists call for non-punitive, community-based resources and strategies that meaningfully redress the harms caused by these interlocking systems of oppression. Abolitionist social work is particularly concerned with the field’s direct collaboration with and deference to the police and the criminal legal system, as well as social work’s role in family separation and surveillance as its primary means of ensuring child welfare. Abolitionist social workers therefore call to abolish institutions of policing, surveillance, and punishment, instead developing new ways to ensure that children, families, and communities have the resources they need, while also working to dismantle the systems of oppression which create these needs.
Children in Art History
Authors: Retford Kate
Published: September 2024

Images of children have been discussed by scholars in a wide range of disciplines, from anthropology and sociology, through social and cultural history, to art history, film and media studies. This article deals specifically with the discipline of art history, but it is important to note that the subject embraces a broad span of visual culture, encompassing paintings, drawings, sculpture, photographs, prints, and decorative arts. Charting the most concentrated areas of scholarly interest, with a focus on work in the English language, it lays out the strong bias to date on Western art. Much is still to be done to broaden discussions to the more fully Global. Furthermore, analysis of the theme of children in art somewhat peters out with late-19th-century material (for scholarship on more recent representations, see also the separate Oxford Bibliographies article Visual Representations of Childhood). A key preoccupation has been the degree to which children’s particular characteristics have, or have not, been engaged with in art works. This is rooted in the French historian Philippe Ariès’s use of visual material to argue that no concept of childhood existed before the twelfth century, and that a new sense of the significance of the child only arose in the Early Modern era. In Christian art the most frequently represented child is, of course, the infant Christ, although the childhoods of Mary and John the Baptist have also been important subjects. Other commonly represented children include Cupid (often shown as a naked boy), Hercules, and the cherubim and putti who feature in much medieval, Renaissance, and Baroque art. Child portraits were produced from the early Renaissance onwards, although these were generally commissioned by only the wealthiest members of society until the eighteenth century. A considerable body of scholarship centers on that latter period, traditionally seen as witnessing the arrival of the image of “the new child,” with a novel emphasis on distinctive and emotionally appealing childish characteristics. Children have also featured in works of genre. Prominent examples include images of childhood games and play in the 16th- and 17th-century Netherlands. Sometimes, such representations have been considered as engaging with the state and quality of childhood: at other times, they have been understood rather as vehicles through which to consider adult issues. Indeed, a key issue for this topic is the fact that children are almost always depicted by adults, for the benefit of adults.
Agency and Childhood
Authors: Eßer Florian , Kremer Lisa
Published: September 2024

Agency is unquestionably one of the key concepts of childhood studies. When these studies first arose in the 1980s and 1990s, the idea of regarding children as agents and valuing their contribution to social life was one of the main drivers of the new research field. The notion of children’s agency has proven extremely fruitful for empirical research and has given rise to a great number of publications on children’s active involvement in institutions of childhood and peer cultures since the 1990s. However, criticism has also been ongoing of the theoretical foundations on which the prevailing understanding of agency in childhood studies is based. In particular, objections have grown with regard to a certain tendency to regard agency as an individual, pre-social property of children and thus to neglect children’s dependence upon social structures and their embeddedness in social relations in favor of conceiving them as independent social actors. To overcome these theoretical shortcomings, scholars in the field of childhood studies have attempted to draw on discussions in social theory more generally. Among other approaches, relational approaches to the social seem to offer particular promise for addressing questions of agency in a way that goes beyond the common assumption of a dichotomy between structure and agency. In the course of these theoretical debates, concepts of agentic actorhood have been criticized for being Western-centered. Extending the analysis of agency beyond the so-called Western world has served to modify and further develop theoretical concepts. More recent studies also refer to the materiality of children’s agency by analyzing how material objects and bodies are involved in the production of agency. So when we can identify a “second wave” of childhood studies today, which take contemporary developments in social sciences into account, agency—as in the early days of childhood studies—again plays a crucial role as a key concept. Given the huge amount of theoretical and empirical literature that exists within the field of childhood studies and children’s geographies, this article can cite only selected contributions.
Battle of Agincourt
Authors: Curry Anne
Published: September 2024

On 25 October 1415, Henry V, king of England, achieved a great victory over a French army in a battle fought close to the village of Azincourt about forty miles south of Calais. Henry’s reasons for invading France in 1415 are relatively uncontentious, being linked not only to the causes of the Hundred Years’ War as a whole but also to the English kings hopes of exploiting divisions in France between the Burgundian and Armagnac factions in their struggles to control the government of the mad Charles VI. More debate has arisen on whether Henry was keen to face the French in battle or whether he was forced to do so by his enemy. There has also been controversy over the sizes of the respective armies and the deployment of the various kinds of troops, as well as over the precise location of the battle. Equally significant is the popular memorialization of the battle over the six centuries that have followed, fanned in particular by Shakespeare’s portrayal within his play Henry V, first performed in 1599.
China and International Humanitarian Law
Authors: Zhu Lijiang
Published: September 2024

International humanitarian law (IHL) is a branch of public international law aimed at limiting the means and methods of warfare of the parties to armed conflicts and protecting the victims of armed conflicts, whether international or non-international law, out of humanitarian reasons. The fundamental sprit of IHL, namely to advocate for humanitarianism in armed conflicts, has been deeply rooted in the Chinese history and constituted an important component of Chinese civilizations. The rich Chinese ancient thoughts and practices on humanitarianism necessitates an exploration, as they may have contemporary implications. Today, China is one of the five permanent member states of the Security Council of the United Nations, which assumes a primary responsibility of maintaining international peace and security. China is one of the ten states contributing troops and police to the United Nations Peacekeeping Operations and the largest among the five permanent member states of the Security Council of the United Nations. The Chinese People’s Liberation Army is the largest armed force in the world and is increasingly modernized. China does not commit to waiving use of force to settle the Taiwan problem, and has several territorial and maritime disputes with the neighboring countries in land and sea. All these factors render the importance of the topic of “China and international humanitarian law.” This article will present the main bibliographies on the research of this subject matter by Chinese and foreign experts in Chinese and English language. It will first present the research of a general overview of this subject matter, which generally introduces this subject matter and makes comments in Part 1, and then focus on the survey of modern Chinese practice of IHL on some specific years. Chinese history of IHL is a field attracting many researches, so the relevant bibliographies will be introduced later. Apart from the modern practice and history of IHL, the relevant bibliographies focus on sources of IHL, the determination and categorization of armed conflicts that are the preconditions for the applicability of IHL, and the special topic of relevance of IHL with UN peacekeeping operations. In IHL, the two pillars are the rules on means and methods of warfare (Hague Law) and rules on protection of victims affected by armed conflicts (Geneva Law); both have relevant bibliographies. Finally, the implementation of IHL also attracts much research; they will be introduced in the last part. It has to be noted that the criteria of selecting the relevant bibliographies is how well the relevant books or papers specifically address Chinese practice, views, perspectives, contributions, and so on, from either Chinese experts or foreign experts, and whether the topic is a general IHL topic or a topic specifically related to China.
Jusepe de Ribera
Authors: Friedman Hannah
Published: September 2024

Jusepe or José de Ribera (b. 1591–d. 1652), nicknamed “lo Spagnoletto,” was a prolific painter, draftsman, and printmaker whose art was a vital part of the visual and intellectual cultures of both Italy and Spain in the first half of the seventeenth century. A shoemaker’s son from the city of Játiva in the Kingdom of Valencia, Ribera moved to Italy in 1606, and settled in Naples in 1616 after a period of residence in Rome and travels in Northern Italy and Emilia, including short residence in Parma. The focus of his art is the human figure, though one finds brief forays into landscape painting and brilliant passages of still life within his oeuvre. Unlike many of his peers in the ranks of elite painters in his day, he seems never to have worked in fresco. His considerable stylistic range, the evolution of his art over the four decades of his career, and the difficulties that these pose for securely delineating his catalogue, have been central preoccupations of Ribera scholarship. Literate without being literary, Ribera has next to no written legacy, but his art evinces connections to the period’s intellectual culture in several areas, including antiquarianism, natural science, theology, philosophy, and literature. Ribera enjoyed elite patronage from an early date, particularly from the Viceroys of Naples. Many of his signatures advertise both his Spanish (and Valencian) roots and his Italian credentials, as for instance he was a member of the Roman Accademia di San Luca and a Knight of the Order of Christ. His biography suggests a social standing combining highs and lows, in which the central motif is his success in establishing himself as the dominant artistic voice in the highly competitive (and by no means peripheral) context of Naples, where he became the head of a substantial workshop and trained or influenced many of the next generation’s foremost painters. The city’s status as the capital of a wealthy Spanish viceroyalty, and Ribera’s extensive work for the Spanish nobility and royal court, provided him with a highly placed audience and a considerable impact in Spain during his own lifetime. In scholarship, Ribera has often been perceived, both despite and because of his success in Italy, as exemplifying a kind of essential Spanishness and viewed through the lens of stereotypes regarding religion and violence in early modern Iberia. Such views however, coexist with a varied corpus of nuanced, substantive understandings of the artist.
Chromosome doubling increases PECTIN METHYLESTERASE 2 expression, biomass, and osmotic stress tolerance in kiwifruit
Authors: Zhu Yanyan , Wang Xinlei , He Yan , Liu Yajing , Wang Runze , Liu Yongsheng , Wang Songhu
Published: September 2024

Chromosome doubling-induced polyploidization is a popular tool for crop breeding. Polyploidy crops commonly have multiple advantages, including increased biomass and stress tolerance. However, little is known about the genes responsible for these advantages. We found kiwifruit (Actinidia chinensis cv. Hongyang) PECTIN METHYLESTERASE 2 (AcPME2) is substantially upregulated in artificially created tetraploid plants that show increased biomass and enhanced tolerance to osmotic stress. Overexpression (OE) of AcPME2 led to increased biomass and enhanced stress tolerance in Arabidopsis (Arabidopsis thaliana), tomato (Solanum lycopersicum), and kiwifruit. Upon short-term osmotic stress treatment, AcPME2-OE plants showed higher levels of demethylesterified pectins and more Ca2+ accumulation in the cell wall than Col-0 plants, which led to increased cell wall stiffness. The stress-induced plasmolysis assays indicated that AcPME2 dynamically mediated the cell wall stiffness in response to osmotic stress, which is dependent on Ca2+ accumulation. Transcriptomic analysis discovered that dozens of stress-responsive genes were significantly upregulated in the AcPME2-OE plants under osmotic stress. Besides, AcPME2-mediated cell wall reinforcement prevented cell wall collapse and deformation under osmotic stress. Our results revealed a single gene contributes to two advantages of polyploidization (increased biomass and osmotic stress tolerance) and that AcPME2 dynamically regulates cell wall stiffness in response to osmotic stress.
The soybean NUCLEAR FACTOR-Y C4 and α-EXPANSIN 7 module influences phosphorus uptake by regulating root morphology
Authors: Liu Xiaoqian , Cai Yupeng , Yao Weiwei , Chen Li , Hou Wensheng
Published: September 2024

Soybean (Glycine max) is a globally important crop; however, its productivity is severely impacted by phosphorus (P) deficiency. Understanding the transcriptional regulation of low P (LP) response mechanisms is essential for enhancing soybean P use efficiency. In this study, we found that the Nuclear Factor-Y (NF-Y) transcription factor GmNF-YC4, in addition to its previously discovered role in regulating flowering time, possesses other functions in modulating root morphology and P uptake. Knockout of GmNF-YC4 notably boosted root proliferation and P uptake while also influencing the expression of genes related to LP stress. GmNF-YC4 acts as a specific DNA-binding transcriptional repressor, modulating the expression of the soybean α-EXPANSIN 7 (GmEXPA7) gene, which encodes a cell-wall-loosening factor, through direct binding to its promoter region. Further investigation revealed that GmEXPA7 expression is predominantly root-specific and induced by LP. Moreover, overexpression of GmEXPA7 in soybean hairy roots enhanced LP tolerance by stimulating root growth and P uptake. We further screened and obtained more potential target genes of GmNF-YC4 via DNA affinity purification sequencing, including those related to LP stress. These findings underscore the pivotal role of the GmNF-YC4-GmEXPA7 module as a key regulator in mitigating LP stress in soybeans.
Demographic and socio-economic inequalities in subjective wellbeing: analysis of repeated cross-sectional health surveys in England 2010–2019
Authors: Castelletti C , Ogunlayi F , Miret M , Lara E , Oyebode O.
Published: September 2024

Background

Good subjective wellbeing (SWB) is a key societal aspiration. The study of SWB determinants is of increasing interest. The present study aimed to examine national inequalities in SWB, and trends in these inequalities, for England across five demographic (sex and age) and socio-economic (educational level, household income and living alone) characteristics.

Method

The relative index of inequalities (RII) and slope index of inequalities (SII) were calculated from repeated cross-sectional data from the Health Survey for England from 2010 to 2019 (excluding 2017 and 2018 as our outcome variable was not collected in these years), in a total of 90 236 participants aged 16+. SWB was assessed using the Warwick-Edinburgh Mental Well-being Scale (WEMWBS), treated as a dichotomous variable with high and low levels of SWB > 40 and ≤ 40, respectively.

Results

There were significant inequalities in SWB by income (RII from 1.086 to 1.116), educational level (RII from 0.893 to 0.941) and between people living alone or not (RII from 0.908 to 0.937). The RII and SII trends were not statistically significant.

Conclusions

Higher socio-economic status could play a protective role for SWB, and people in the most deprived socio-economic positions may be at higher risk for low SWB. These associations have remained stable over time.
No Free Lunch? Welfare Analysis of Firms Selling Through Expert Intermediaries
Authors: Grennan Matthew , Myers Kyle R , Swanson Ashley , Chatterji Aaron
Published: September 2024

We study how firms target and influence expert intermediaries. In our context, pharmaceutical manufacturers provide payments to physicians during promotional interactions. We develop an identification strategy based on plausibly exogenous variation in payments driven by differential exposure to spillovers from AMC CoI policies. Using a case study of an important class of cardiovascular drugs, we estimate heterogeneous effects of payments on prescribing, with firms targeting highly responsive physicians. We also develop a model of supply and demand, which allows us to quantify how oligopoly prices reduce drug prescribing, and how payments move prescribing closer to the optimal level, but at great financial cost. In our estimated model, whether consumers are harmed by payments depends on whether there is substantial under-prescribing due to behavioural or other frictions. In a final exercise, we calibrate such frictions using clinical data and estimate that payments benefit consumers in this case study.
Climate change's implications for practice
Authors: Mueller Kenneth , Allstrom Heather , Smith Daniel J. , Downes Elizabeth , Modly Lori A.
Published: September 2024

Climate change is the greatest threat to global health. As climate change worsens, heat waves will be longer, more intense, and more frequent. Increased health risks from climate change and heat waves include heat-related illness (HRI). HRI increases ED visits, hospitalizations, and mortality. Healthcare providers should be aware of the impact of medications on risk for HRI. This article elucidates signs and symptoms, populations at risk, drugs and mechanisms that increase risk, and patient education to reduce risk.
Mitigating and preventing perioperative opioid-related harm
Authors: Harbell Monica W. , Cohen Jonathan , Balfanz Greg , Methangkool Emily
Published: September 2024

Purpose of review

Although necessary for treatment of acute pain, opioids are associated with significant harm in the perioperative period and further intervention is necessary perioperatively to mitigate opioid-related harm.

Recent findings

Opioid-naive patients are often first exposed to opioids when undergoing surgery, which can result in significant harm. Despite their benefits in reducing acute postsurgical pain, they are also associated with risks ranging from mild (e.g., pruritis, constipation, nausea) to potentially catastrophic (e.g. opioid-induced ventilatory impairment, respiratory depression, death). Overprescribing of opioids can lead to opioid diversion and drug driving. In this review, we will discuss opioid-related harm and what strategies can be used perioperatively to mitigate this harm. Interventions such as optimizing nonopioid analgesia, implementing Enhanced Recovery after Surgery programs, effective respiratory monitoring, patient education and opioid stewardship programs will be discussed.

We will review policy and guidelines regarding perioperative opioid management and identify challenges and future directions to mitigate opioid-related harm.
Assessing the Impact of Multidisciplinary Cancer Consultations on Cancer Quality Metrics
Authors: Sanchez Janeth I. , Doose Michelle , Zeruto Chris , Chollette Veronica , Gasca Natalie , Singla Anand , Weaver Sallie J.
Published: September 2024

Objective:

Multidisciplinary cancer consultations play a critical role in the delivery of quality cancer care by promoting treatment planning and collaborative decision-making. The objective of this study was to evaluate associations between multidisciplinary cancer consultations and receipt of guideline-recommended adjuvant treatments among breast, colorectal, or non-small cell lung cancer patients and assess these associations between and within racial and ethnic groups.

Methods:

This is a population-based retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER), Medicare-linked data (2006–2016) to identify Medicare beneficiaries diagnosed with nonmetastatic breast, colorectal, or non-small cell lung cancer. Multidisciplinary cancer consultation was based on encounters with 2 or more oncology providers within 2 months of diagnosis. Cancer quality metrics assessed included receipt of guideline-recommended adjuvant cancer treatment for each cancer type.

Results:

Patients with multidisciplinary cancer consultations were more likely to receive adjuvant cancer treatment compared with patients without multidisciplinary cancer consultations within racial and ethnic groups. However, non-Hispanic Black and Hispanic breast cancer patients with multidisciplinary cancer consultations were 24% and 41% less likely to receive hormone and radiation therapy, respectively, compared with NHWs with multidisciplinary cancer consultations.

Conclusions:

Patients with multidisciplinary cancer consultations were more likely to receive adjuvant cancer treatment, but racial and ethnic disparities in cancer care persist. Multidisciplinary cancer consultations are likely an important, but not fully sufficient, contributor to the receipt of adjuvant cancer treatment and may be a tool in the implementation of multipronged, team-based cancer care delivery models to reduce inequities in cancer-related outcomes.
Efficacy and Safety of Abemaciclib in Combination With Endocrine Therapy for HR+/HER2− Advanced or Metastatic Breast Cancer
Authors: Qureshi Zaheer , Jamil Abdur , Fatima Eeshal , Altaf Faryal , Siddique Rimsha
Published: September 2024

Objectives:

Breast cancer, particularly the hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2−) subtype, remains a major global health concern. Abemaciclib, a CDK4/6 inhibitor, has shown promising results in treating advanced cases. This study comprehensively assesses the efficacy and safety of abemaciclib in combination with endocrine therapy for HR+/HER2− advanced or metastatic breast cancer.

Methods:

Following PRISMA guidelines, a systematic review and meta-analysis was conducted. A thorough literature search was conducted on PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov til December 2023. Inclusion criteria encompassed randomized controlled trials and retrospective cohort studies reporting on abemaciclib in approved doses, either as monotherapy or in combination. Outcome assessments included progression-free survival (PFS), overall response rate (ORR), side effects/adverse effects (SE/AE), and overall survival (OS). Quality assessment utilized Cochrane’s revised risk of bias tool and Newcastle-Ottawa scale.

Results:

Pooled results of 22 studies involving 14,010 patients revealed that abemaciclib significantly improved PFS (hazard ratio=0.53; 95% CI: 0.48-0.59; P=0.00; I2=0%), ORR (risk ratio=2.31; 95% CI: 1.93-2.75; P=0.00; I2=0%), and OS (risk ratio=0.76 (95% CI: 0.65-0.87; P=0.001; I2=0%). However, abemaciclib increased the risk of adverse events in the fulvestrant and nonsteroidal aromatase inhibitor (NSAI) combinations, respectively.

Conclusions:

Abemaciclib, particularly in combination with fulvestrant, emerges as an effective therapeutic option for HR+/HER2− advanced or metastatic breast cancer, improving PFS and OS. The higher toxicity profile warrants cautious use, especially in treatment-naive patients.
Health-related quality of life (HRQL) assessments in a 52-week, double-blind, randomized, placebo-controlled phase III study of resmetirom (MGL-3196) in patients with metabolic dysfunction–associated steatohepatitis (MASH) and fibrosis
Authors: Younossi Zobair M. , Stepanova Maria , Racila Andrei , Henry Linda , Labriola Dominic , Taub Rebecca , Nader Fatema
Published: September 2024

Background and Aims:

Resmetirom, liver-directed thyroid-hormone receptor-β agonist, received approval for metabolic dysfunction–associated steatohepatitis (MASH) treatment. We assessed health-related quality of life (HRQL) in patients with MASH treated with resmetirom.

Approach and results:

Patients with MASH/NASH without cirrhosis and with confirmed/suspected fibrosis were enrolled in a 54-month double-blind randomized placebo-controlled phase III clinical trial with serial biopsy assessments at baseline and week 52 (MAESTRO-NASH, NCT03900429). HRQL was assessed using Chronic Liver Disease Questionnaire-NASH (CLDQ-NAFLD) and Liver Disease Quality of Life (LDQOL). Baseline HRQL score changes by treatment group (resmetirom 80 mg, resmetirom 100 mg, or placebo) and histological response (improvement of fibrosis without worsening of NAS or resolution of MASH/NASH without worsening of fibrosis) were compared after 52 weeks. Included were 966 intention-to-treat patients: 323 received resmetirom 100 mg, 322 resmetirom 80 mg, and 321 placebo. By weeks 24 and 52, patients receiving 80 or 100 mg resmetirom experienced HRQL improvement in CLDQ-NAFLD Worry domain (mean +0.21 to +0.24, p < 0.05). At week 52, subjects who met histologic endpoints after treatment with resmetirom (100 mg and 80 mg pooled) experienced HRQL improvement in CLDQ-NAFLD Worry +0.46 (41% met minimal clinically important difference [MCID]), LDQOL domains: Role Emotional +3.0 (28% met MCID), Health Distress +8.1 (38% MCID), Stigma +3.5 (39% MCID), and total LDQOL +2.2 (35% MCID) (all p < 0.05). Similar improvements were noted in histologic responders from 100 mg or 80 mg resmetirom groups when separated—no improvements in placebo or nonresponders. Baseline F3 histologic responders had similar/more pronounced HRQL improvements.

Conclusions:

Patients with MASH/NASH with fibrosis improvement or the resolution of MASH with resmetirom experienced clinically meaningful and statistically significant HRQL improvements.
Juvenile primary hypertension is associated with attenuated macro- and microvascular dilator function independently of body weight
Authors: Kos Martina , Nađ Tihana , Stupin Ana , Drenjančević Ines , Kolobarić Nikolina , Šušnjara Petar , Mihaljević Zrinka , Damašek Mia , Pušeljić Silvija , Jukić Ivana
Published: September 2024

Objective:

Hypertension has become a global medical and public health issue even in childhood. It is well accepted that hypertension is associated with impaired endothelium-dependent vascular reactivity in adult patients. However, there is a lack of data on hypertension-related endothelial dysfunction in hypertensive children. Thus, present study aimed to evaluate the association of primary hypertension in the pediatric population with macro- and microvascular function, and to assess the potential role of oxidative stress in that connection.

Methods:

Fifty-two children were enrolled in this study; 26 normotensive (NT) and 26 with primary hypertension (HT), both sexes, 9–17 years old. In addition to anthropometric, hemodynamic and biochemical measurements, peripheral microvascular responses to occlusion (postocclusive reactive hyperemia, PORH), local heating (local thermal hyperemia, LTH), iontophoretically applied acetylcholine (AChID) and sodium nitroprusside (SNPID) were evaluated by laser Doppler flowmetry (LDF). Furthermore, brachial artery flow-mediated dilation (FMD) was measured and biomarker of oxidative stress was determined.

Results:

PORH, AChID and LTH were impaired in hypertensive compared to normotensive children, while SNPID did not differ between groups. FMD was decreased in hypertensive compared to normotensive children. Serum concentration of 8-iso-PGF2α was significantly elevated in hypertensive compared to normotensive children.

Conclusion:

Even in childhood, primary hypertension is associated with attenuated endothelial function and reduced endothelium-dependent responses to various physiological stimuli. Juvenile hypertension is related to increased level of vascular oxidative stress. All changes are independent of BMI.
Defining childhood hypertension: is it too complicated? An evaluation of the potential impact of different approaches in an Australian paediatric population
Authors: Larkins Nicholas G. , Choong Catherine , Schlaich Markus , Quinlan Catherine , Mynard Jonathan P. , Kim Siah , Mori Trevor A. , Beilin Lawrence J.
Published: September 2024

Objectives:

Current American Academy of Pediatrics (AAP) and European Society of Hypertension (ESH) thresholds defining hypertension in children use blood pressure (BP) normalised to age, sex and height. However, scare data exists regarding the relative importance of these variables to accurately model the 95th quantile of BP. We hypothesised that height alone may fit the population data equally well compared to more complex definitions. We also compare the potential impact of various thresholds for defining hypertension in an Australian population.

Methods:

Longitudinal data from the Raine Study were used, with 2248 participants contributing 7479 valid BP values across the 3/5/10/14/17-year study visits. BP was measured after 5 min rest, ≥3 times at each visit, using a Dinamap device. Quantile regression was used to predict the 95th percentile of BP, with nonlinear modelling of covariates through restricted cubic spline terms.

Results:

At a single visit, 6–16% of young children exceeded the ESH threshold and 12–23% the AAP threshold. The transition to fixed thresholds (≥13 years AAP, ≥16 years ESH), increased the number of males (AAP only) and reduced the number of females considered hypertensive. A quantile regression model constructed with Raine Study data using height-only as the explanatory variable better predicted BP than the respective model using age-only (or a combination of the two).

Conclusions:

There may be large differences in the prevalence of hypertension according to AAP and ESH criteria, with a marked sex-discrepancy emerging from the point of fixed threshold application in adolescence. It may not be necessary to normalise BP by both age and height, the latter being a better predictor of childhood BP. Simpler methods may be preferable in clinical practice but require validation against clinical outcomes.