bluuebunny/crossref_metadata_2025 huggingface dataset:
Philosophical Hermeneutics
Authors: Najman Hindy
Published: December 2024

The Hodayot’s forward-moving trajectory constitutes a sustained focus on the relationship between God and the human, which makes the Hodayot one of the first works in Hebrew that we can speak of as biblical theology. The Hodayot as a collection participates in what we could identify as both the biblical and extra-biblical as it looks back towards earlier biblical precedents but also paves the way for new pathways for the performative and liturgical expression of human essence, and liturgical imagination. The Hodayot thus vitalize and revitalize biblical traditions through liturgical idioms which are heavily scripturalized. In reading the Hodayot as an organic whole, we observe that they collapse time in such a way that past and present and future are simultaneous with respect to creation, end-time or death, and the exigencies of the present. This collection can be read as an integrated meditation on the possibility of an emerging self and the ever-aspiring nature of the human towards the creator. The repetition of the various phrases and stages of the self creates a momentum towards improvement and transformation. Reading with this approach reflects on new composition as performance, as creative and innovative composition, and as the growth of biblical tradition itself, an expansion which redefines the period of Second Temple Judaism as a central flashpoint for biblical growth and vitality.
The Chemistry of Milk Components
Authors: Kelly Alan , Fox Patrick , Cogan Tim
Published: December 2024

The main components of milk, in order of concentration from the highest to lowest, are water, lactose, fat, protein, and mineral salts. The production of dairy products depends very much on the properties of each of these, individually or collectively, and so this chapter discusses the properties of each in turn, including a basic introduction to their chemistry as related to the processing of milk. It describes, for example, the two types of protein in milk, casein and whey proteins, each with very different properties that relate to the production of products as diverse as cheese, yoghurt, and high-value protein supplements.
The Microbiology of Milk
Authors: Kelly Alan , Fox Patrick , Cogan Tim
Published: December 2024

This chapter reviews the science of microorganisms, particularly bacteria. It begins by explaining what they are and describing their structure and how they are counted and identified. The chapter then goes on to review the structure of nucleic acids, the genetic material of microorganisms as well as the metabolism of microorganisms and various factors affecting their growth. The chapter focuses in particular on the important pathogens that can occur in dairy products, as well as important sources of contamination of raw milk. Microorganisms, called psychrotrophs, which grow at low temperatures, are addressed in particular, given their importance in dairy production.
Starters for Fermented Dairy Products
Authors: Kelly Alan , Fox Patrick , Cogan Tim
Published: December 2024

This chapter introduces techniques for the production of lactic acid from lactose, which is an important step in the manufacture of fermented dairy products and is carried out by specific species of lactic acid bacteria, called starters. The chapter shows how development and use of these starters is critical for the production of fermented dairy products like cheese and yoghurt. It also considers the historical development of starters, their composition, the role of genetic material and elements called plasmids, how the bacteria metabolize lactose, how they respond to temperature, and the role of viruses that attack starters (bacteriophage).
Butter
Authors: Kelly Alan , Fox Patrick , Cogan Tim
Published: December 2024

One of the oldest dairy products in many countries is butter—e.g., its production in Ireland has been traced back to several centuries bc—because it is a simple and effective way of preserving the key energy-rich component of milk—fat—for storage and consumption in times of scarcity. This chapter describes the principles of making butter (separation of cream, by gravity or mechanically, churning, separation of butter grains from buttermilk, and salting if applied, before molding and storage), the factors affecting spreadability, one of its most important properties for consumers, and the production of lactic butter, a variety common in continental European countries. The chapter also considers the emergence of alternative products to butter, such as spreads in which some of the milk fat is replaced by softer and perhaps healthier plant fats and oils, as well as the key principles of formulating and producing such products.
Concentrated and Dried Dairy Products
Authors: Kelly Alan , Fox Patrick , Cogan Tim
Published: December 2024

One of the most effective ways to extend the shelf-life of milk is to remove some or all of the water; dried forms of milk such as skimmed milk and whole milk powders are major commodities traded internationally. This chapter explains how these are produced, with the help of simple diagrams. It describes the steps in the process, typically evaporation to concentrate the milk solids followed by drying, originally in a process called roller-drying, but today, in most cases, through a highly efficient process called spray-drying. It explains the importance of ensuring that any powder can later easily be returned to a fluid state by mixing with water, as well as the factors affecting this. Finally, it explores the products that are made by concentrating milk without drying (evaporated or condensed milk and sweetened condensed milk), including their production and properties.
Ice Cream
Authors: Kelly Alan , Fox Patrick , Cogan Tim
Published: December 2024

This chapter considers ice cream, one of the most popular dairy products in many countries, which has a long history stretching back to Marco Polo. It outlines the production of high-quality ice cream, which depends on a combination of factors, including the careful selection of ingredients (cream, sugar, emulsifiers, stabilizers, and flavors) and appropriate processing, including heating, homogenization, and freezing. It then describes the influence of each of these factors on the properties of ice cream, especially the role of sugar in controlling the freezing properties of water to ensure that the final product does not become too hard. Finally, the chapter reviews the role of stabilizers in maintaining the quality of ice cream during prolonged frozen storage.
Challenges in the Modern Dairy Sector
Authors: Kelly Alan , Fox Patrick , Cogan Tim
Published: December 2024

Despite the very long history of dairy products, and their high level of consumption across the world today, the future of dairy is perhaps under more threat now than at any other point in history, with emerging concerns about health, ethical and environmental impacts of dairy production, and the rise of veganism and the associated desire for dairy alternatives. Some of these concerns are explored in this chapter, alongside some trends in the way in which dairy products are produced, as influenced by factors such as consumer desires for less processed foods, to try and end the book with a sense of the future of the dairy sector.
Impact of frailty, malnutrition and socioeconomic status on perioperative outcomes
Authors: Stretton Brandon , Booth Andrew E C , Kovoor Joshua , Gupta Aashray , Edwards Suzanne , Hugh Tom , Maddison John , Talley Nicholas J , Plummer Mark , Meyer Emily , Horowitz Michael , Barreto Savio , Padbury Robert , Bacchi Stephen , Maddern Guy , Boyd Mark
Published: December 2024

Background

Frailty, malnutrition and low socioeconomic status may mutually perpetuate each other in a self-reinforcing and interdependent manner. The intertwined nature of these factors may be overlooked when investigating impacts on perioperative outcomes. This study aimed to investigate the impact of frailty, malnutrition and socioeconomic status on perioperative outcomes.

Methods

A multicentre cohort study involving six Australian tertiary hospitals was undertaken. All consecutive surgical patients who underwent an operation were included. Frailty was defined by the Hospital Frailty Risk Score, malnutrition by the Malnutrition Universal Screening Tool (MUST) and low socioeconomic status by the Index of Relative Socioeconomic Disadvantage. Linear mixed-effects and binary logistic generalised estimated equation models were performed for the outcomes: inpatient mortality, length of stay, 30-day readmission and re-operation.

Results

A total of 21 976 patients were included. After controlling for confounders, malnutrition and socioeconomic status, patients at high risk of frailty have a mean hospital length of stay 3.46 times longer (mean ratio = 3.46; 95% confidence interval (CI): 3.20, 3.73; P value < .001), odds of 30-day readmission 2.4 times higher (odds ratio = 2.40; 95% CI: 2.19, 2.63; P value < .001) and odds of in-hospital mortality 12.89 times greater than patients with low risk of frailty (odds ratio = 12.89; 95% CI: 4.51, 36.69; P value < .001). Elevated MUST scores were also significantly associated with worse outcomes, but to a lesser extent. Socioeconomic status had no association with outcomes.

Conclusion

Perioperative risk evaluation should consider both frailty and malnutrition as separate, significant risk factors. Despite strong causal links with frailty and malnutrition, socioeconomic disadvantage is not associated with worse postoperative outcomes. Additional studies regarding the prospective identification of these patients with implementation of strategies to mitigate frailty and malnutrition and assessment of perioperative risk are required.
Body size and occupational physical activity during the life course and gastrointestinal cancers
Authors: Sassano Michele , Nalini Mahdi , Seyyedsalehi Monireh Sadat , Roshandel Gholamreza , Poustchi Hossein , Khoshnia Masoud , Kamangar Farin , Dawsey Sanford M , Abnet Christian , Malekzadeh Reza , Boffetta Paolo , Etemadi Arash
Published: December 2024

Evidence on the associations of body size and occupational physical activity (PA) during the life course with gastrointestinal cancers is inconclusive.

We analyzed data from the Golestan Cohort Study, a population-based prospective cohort study from Iran, with 50,045 individuals aged 40-75 years enrolled during 2004-2008 and followed through April 2023. Body size during adolescence, early adulthood, and at cohort baseline was assessed using validated pictograms.

Large adolescent body size was associated with total gastrointestinal cancers (hazard ratio, HR: 1.09; 95% confidence interval, CI: 1.02-1.16) and liver cancer (HR: 1.49; 95% CI: 1.11-2.01). Large early-adulthood body size was associated with liver cancer (HR: 1.85; 95% CI: 1.35-2.52).

Compared with normal weight during all stages, overweight or obesity during adolescence only or early adulthood only were associated with stomach cancer, esophageal squamous cell carcinoma, and liver cancer.

Lower levels of adolescent occupational PA were associated with colon cancer (HR: 1.39; 95% CI: 1.10-1.75), while lower levels at cohort baseline were positively associated with colon cancer and inversely associated with rectal cancer.

Our findings suggest that timing of obesity during the life course might differently affect risk of gastrointestinal cancers, while occupational PA was found to be associated with colon cancer only
Family criminal legal system exposure and early adolescents’ pubertal development: The mediating role of family strain
Authors: Del Toro Juan , Roettger Michael , Jackson Dylan B , Wilson Sylia
Published: December 2024

Pubertal trends, wherein adolescents today are experiencing puberty earlier than prior generations, have coincided with the expansion of the criminal legal system, which is disproportionately impacting communities of color. However, whether pubertal development and criminal legal system exposure among adolescents are inter-related is unknown. We tested whether family members’ criminal legal system exposure predicted adolescents’ pubertal development, whether family strain explained the relation between criminal legal system exposure and pubertal development, and whether race/ethnicity moderated our results. We used three yearly waves of longitudinal data among a national sample of 9,518 adolescents. Results illustrated that 40% of Black, 20% of Latinx, 16% of Other, and 10% of White adolescents experienced one or more family criminal legal system exposures. In structural equation models within a case-crossover design controlling for measured confounders and unmeasured confounders that do not change over time, including neighborhood-level socioeconomic status and crime, family criminal legal system exposure predicted adolescents’ advanced pubertal development, and family strain explained this relation between family criminal legal system exposure and pubertal development. The United States’ approach to law and order has public health implications that may be perpetuating health inequities, as accelerated pubertal development can have downstream consequences across the life course.
Philosophy moves and meta-moves
Authors: Kelley David
Published: December 2024

Philosophers sometimes refer to ‘moves’ made in the context of a philosophical debate. Once familiar with these recognizable tropes, we then possess them as tools – a suite of possible moves to make in novel contexts. In this paper, I outline three such philosophy moves, then demonstrate how moves can be combined. Examples of moves and some combinations feature throughout the paper.
Root growth control by negative regulation of MYB50 under ABA signaling in Arabidopsis
Authors: Mase Kosuke , Kamiya Yukino , Sakaoka Satomi , Morikami Atsushi , Tsukagoshi Hironaka
Published: December 2024

Plant growth is finely tuned by environmental changes, with abscisic acid (ABA) playing a key role in balancing stress tolerance and growth regulation. The target genes of MYB50, which regulate root growth, include genes that respond to ABA; however, the precise role of MYB50 in ABA signaling remains unclear. Therefore, this study aimed to elucidate the function of MYB50 under ABA signaling. Our experiments demonstrated that ABA treatment reduced MYB50 expression and promoted the degradation of MYB50 protein. This degradation alleviates the inhibitory effects of MYB50 on root growth. Furthermore, ABA differentially regulates MYB50 compared with ABI5, another key transcription factor involved in root growth under ABA signaling, suggesting that ABA uses distinct regulatory pathways for root growth. Our study suggests that ABA controls root growth by modulating MYB50 at both the transcriptional and post-translational levels, thus ensuring balanced root development in response to ABA.
Screening of novel lactic acid bacteria with high induction of immunoglobulin A production, dendritic cell activation, and interleukin-12 production
Authors: Tsuruno Keigo , Mawatari Takashi , Tanaka-Azuma Yukimasa , Yamatsu Atsushi , Tanabe Soichi
Published: December 2024

In this study, we screened 308 lactic acid bacteria strains for high immunoglobulin A (IgA) production, dendritic cell activation, and interleukin-12 (IL-12) production using human-derived cells. Among them, Lactobacillus helveticus GCL1815 demonstrated superior performance in all aspects, indicating its remarkable potential for immunomodulatory functions in both innate and adaptive immunity.
Effects of experimental nest treatment with herbs on ectoparasites and body condition of nestlings
Authors: Glądalski Michał , Norte Ana Cláudia , Bartos Maciej , Demeško Iwona , Kaliński Adam , Markowski Marcin , Skwarska Joanna , Wawrzyniak Jarosław , Zieliński Piotr , Bańbura Jerzy
Published: December 2024

Nest fumigation behavior involves the incorporation of fresh green plant fragments that contain ectoparasite-repellent volatile compounds into birds’ nests. This behavior is relatively rare among bird species, and there is ongoing debate about whether it benefits parental breeding success. In this study, we experimentally tested whether the inclusion of aromatic-herbal plant fragments in the nests of great tits Parus major affects the physiological condition of nestlings, as indicated by blood levels of hematocrit, hemoglobin, glucose, and body condition indices, such as weight and wing length. We divided the nests into 2 groups, adding aromatic herbs to the test group’s nests and non-aromatic plants to the control group. After the nestlings fledged, all nest materials were collected to extract, identify, and count arthropod ectoparasites. Nestlings in nests supplemented with aromatic plant fragments had elevated levels of hematocrit and hemoglobin, indicating improved physiological condition compared to the control group. Ectoparasites were present in both groups, although ticks (Ixodidae) occurred less frequently in nests with aromatic plants. The experimental treatment did not affect fledging success. Further experimental studies are needed to explore the effects of incorporating aromatic plant fragments into tit nests within the frameworks of both the nest protection hypothesis and the drug hypothesis.
BICEP: Bayesian inference for rare genomic variant causality evaluation in pedigrees
Authors: Ormond Cathal , Ryan Niamh M , Cap Mathieu , Byerley William , Corvin Aiden , Heron Elizabeth A
Published: December 2024

Next-generation sequencing is widely applied to the investigation of pedigree data for gene discovery. However, identifying plausible disease-causing variants within a robust statistical framework is challenging. Here, we introduce BICEP: a Bayesian inference tool for rare variant causality evaluation in pedigree-based cohorts. BICEP calculates the posterior odds that a genomic variant is causal for a phenotype based on the variant cosegregation as well as a priori evidence such as deleteriousness and functional consequence. BICEP can correctly identify causal variants for phenotypes with both Mendelian and complex genetic architectures, outperforming existing methodologies. Additionally, BICEP can correctly down-weight common variants that are unlikely to be involved in phenotypic liability in the context of a pedigree, even if they have reasonable cosegregation patterns. The output metrics from BICEP allow for the quantitative comparison of variant causality within and across pedigrees, which is not possible with existing approaches.
Inferring single-cell resolution spatial gene expression via fusing spot-based spatial transcriptomics, location, and histology using GCN
Authors: Xue Shuailin , Zhu Fangfang , Chen Jinyu , Min Wenwen
Published: December 2024

Spatial transcriptomics (ST technology allows for the detection of cellular transcriptome information while preserving the spatial location of cells. This capability enables researchers to better understand the cellular heterogeneity, spatial organization, and functional interactions in complex biological systems. However, current technological methods are limited by low resolution, which reduces the accuracy of gene expression levels. Here, we propose scstGCN, a multimodal information fusion method based on Vision Transformer and Graph Convolutional Network that integrates histological images, spot-based ST data and spatial location information to infer super-resolution gene expression profiles at single-cell level. We evaluated the accuracy of the super-resolution gene expression profiles generated on diverse tissue ST datasets with disease and healthy by scstGCN along with their performance in identifying spatial patterns, conducting functional enrichment analysis, and tissue annotation. The results show that scstGCN can predict super-resolution gene expression accurately and aid researchers in discovering biologically meaningful differentially expressed genes and pathways. Additionally, scstGCN can segment and annotate tissues at a finer granularity, with results demonstrating strong consistency with coarse manual annotations. Our source code and all used datasets are available at https://github.com/wenwenmin/scstGCN and https://zenodo.org/records/12800375.
Multi-kernel feature extraction with dynamic fusion and downsampled residual feature embedding for predicting rice RNA N6-methyladenine sites
Authors: Liu Mengya , Sun Zhan-Li , Zeng Zhigang , Lam Kin-Man
Published: December 2024

RNA N$^{6}$-methyladenosine (m$^{6}$A) is a critical epigenetic modification closely related to rice growth, development, and stress response. m$^{6}$A accurate identification, directly related to precision rice breeding and improvement, is fundamental to revealing phenotype regulatory and molecular mechanisms. Faced on rice m$^{6}$A variable-length sequence, to input into the model, the maximum length padding and label encoding usually adapt to obtain the max-length padded sequence for prediction. Although this can retain complete sequence information, resulting in sparse information and invalid padding, reducing feature extraction accuracy. Simultaneously, existing rice-specific m$^{6}$A prediction methods are still at an early stage. To address these issues, we develop a new end-to-end deep learning framework, MFDm$^{6}$ARice, for predicting rice m$^{6}$A sites. In particular, to alleviate sparseness, we construct a multi-kernel feature fusion module to mine essential information in max-length padded sequences by multi-kernel feature extraction function and effectively transfer information through global–local dynamic fusion function. Concurrently, considering the complexity and computational efficiency of high-dimensional features caused by invalid padding, we design a downsampling residual feature embedding module to optimize feature space compression and achieve accurate feature expression and efficient computational performance. Experiments show that MFDm$^{6}$ARice outperforms comparison methods in cross-validation, same- and cross-species independent test sets, demonstrating good robustness and generalization. The application on maize m$^{6}$A indicates the MFDm$^{6}$ARice’s scalability. Further investigations have shown that combining different kernel features, focusing on global channel-local spatial, and employing reasonable downsampling and residual connections can improve feature representation and extraction, ensure effective information transfer, and significantly enhance model performance.
Polyphonia: detecting inter-sample contamination in viral genomic sequencing data
Authors: Krasilnikova Lydia A , Tomkins-Tinch Christopher H , Gayton Alton C , Schaffner Stephen F , Dobbins Sabrina T , Gladden-Young Adrianne , Siddle Katherine J , Park Daniel J , Sabeti Pardis C
Published: December 2024

In viral genomic research and surveillance, inter-sample contamination can affect variant detection, analysis of within-host evolution, outbreak reconstruction, and detection of superinfections and recombination events. While sample barcoding methods exist to track inter-sample contamination, they are not always used and can only detect contamination in the experimental pipeline from the point they are added. The underlying genomic information in a sample, however, carries information about inter-sample contamination occurring at any stage. Here, we present Polyphonia, a tool for detecting inter-sample contamination directly from deep sequencing data without the need for additional controls, using intrahost variant frequencies. We apply Polyphonia to 1102 SARS-CoV-2 samples sequenced at the Broad Institute and already tracked using molecular barcoding for comparison.

Availability and implementation

Polyphonia is available as a standalone Docker image and is also included as part of viral-ngs, available in Dockstore. Full documentation, source code, and instructions for use are available at https://github.com/broadinstitute/polyphonia.
HBFormer: a single-stream framework based on hybrid attention mechanism for identification of human-virus protein–protein interactions
Authors: Zhang Liyuan , Wang Sicong , Wang Yadong , Zhao Tianyi
Published: December 2024

Motivation

Exploring human-virus protein–protein interactions (PPIs) is crucial for unraveling the underlying pathogenic mechanisms of viruses. Limitations in the coverage and scalability of high-throughput approaches have impeded the identification of certain key interactions. Current popular computational methods adopt a two-stream pipeline to identify PPIs, which can only achieve relation modeling of protein pairs at the classification phase. However, the fitting capacity of the classifier is insufficient to comprehensively mine the complex interaction patterns between protein pairs.

Results

In this study, we propose a pioneering single-stream framework HBFormer that combines hybrid attention mechanism and multimodal feature fusion strategy for identifying human-virus PPIs. The Transformer architecture based on hybrid attention can bridge the bidirectional information flows between human protein and viral protein, thus unifying joint feature learning and relation modeling of protein pairs. The experimental results demonstrate that HBFormer not only achieves superior performance on multiple human-virus PPI datasets but also outperforms 5 other state-of-the-art human-virus PPI identification methods. Moreover, ablation studies and scalability experiments further validate the effectiveness of our single-stream framework.

Availability and implementation

Codes and datasets are available at https://github.com/RmQ5v/HBFormer.
DPAM-AI: a domain parser for AlphaFold models powered by artificial intelligence
Authors: Durham Jesse , Zhang Jing , Schaeffer Richard D , Cong Qian
Published: December 2024

Motivation

Due to the breakthrough in protein structure prediction by AlphaFold, the scientific community has access to 200 million predicted protein structures with near-atomic accuracy from the AlphaFold protein structure DataBase (AFDB), covering nearly the entire protein universe. Segmenting these models into domains and classifying them into an evolutionary hierarchy hold tremendous potential for unraveling essential insights into protein function.

Results

We introduce DPAM-AI, a Domain Parser for AlphaFold Models based on Artificial Intelligence. DPAM-AI utilizes a convolutional neural network trained with previously classified domains in the Evolutionary Classification Of protein Domains (ECOD) database. DPAM-AI integrates inter-residue distances, predicted aligned errors, and sequence and structural alignments to previously classified domains detected via sequence (HHsuite) and structural (Dali) similarity searches. DPAM-AI has demonstrated its power through rigorous tests, excelling in several benchmark sets compared to its predecessor, DPAM, and other recently published domain parsers, Merizo and Chainsaw. We applied DPAM-AI to representative AFDB models for proteins classified in Pfam. We obtained representative 3D structures for 18 487 (89%) of the 20 795 Pfam families. The remaining families either (i) belong to viral proteins that were excluded from AFDB or (ii) do not adopt globular 3D structures. Our structure-aware domain delineation uncovered a considerable fraction (15%) of Pfam domains containing multiple structural and evolutionary units and refined the boundaries for over half.

Availability and implementation

Pfam and corresponding DPAM-AI domains are at http://prodata.swmed.edu/DPAM-pfam/. Our code is deposited at https://github.com/Jsauce5p/DPAM/tree/dpam_ai, and updates will be released through https://github.com/CongLabCode/DPAM.
AURKA inhibits the decidualization of the eutopic endometrium in endometriosis through nuclear factor-κB p65
Authors: Sun Fangyuan , Yu Ting , Zhang Ying , Zhong Xiaoyan , Wang Dan , Li Yuanyuan , Wang Mengxue , Zhang Shucai , Yang Tingting
Published: December 2024

Endometriosis is an estrogen dependent disease, which is related to infertility. Decidualization is a prerequisite for successful implantation of human embryos, and endometriosis affects the occurrence of decidualization. However, the mechanism that affects decidualization in endometriosis is not fully understood. Here, we find that Aurora kinase A (AURKA) is upregulated in the eutopic endometrium of endometriosis. AURKA inhibits the decidualization of stromal cells in the eutopic endometrium of endometriosis. Furthermore, in animal experiments, AURKA promotes endometriosis and inhibits decidualization in mice with endometriosis, leading to decreased expression of decidualization markers, such as prolactin, insulin-like growth factor-binding protein-1, and desmin. Afterwards, we find that nuclear factor-κB (NF-κB) p65 is a new substrate of AURKA. AURKA interacts with p65 to promote its phosphorylation and nuclear translocation. Meanwhile, AURKA enhances the protein stability of p65 by prolonging its half-life. In summary, AURKA inhibits the decidualization of the eutopic endometrium in patients with endometriosis by regulating p65, which may provide new ideas for improving decidualization defect in patients with endometriosis.
Leveraging collective impact to characterize and identify solutions to cultural challenges within scientific societies
Authors: Lightner Taylor , Soso Simone , Etson Candice M , Greenler Robin McC , Mugo Mercy , Segarra Verónica A
Published: December 2024

A consortium of scientific societies recently identified challenges to inclusivity within the biology communities they represent. Specifically, societies encounter difficulties collecting member demographic data effectively, integrating scientists at transitional career stages, and diversifying their leadership. In response, the Leveraging, Enhancing, and Developing Biology (LED-BIO) research coordination network (NSF 2134725) organized two meetings at the Marine Biological Laboratory in Woods Hole, MA to gather stakeholders and employ top-down and bottom-up organizational approaches to address these challenges. These meetings included Town Hall and Think Tank events to facilitate open dialogue and gather feedback on policies and programs from national organizations in attendance. These discussions provided valuable insights into the barriers societies face and the available resources and interventions societies use to promote inclusivity. This article uses the LED-BIO research coordination network as a case study to discuss the Town Hall-Think Tank-Consensus Building (TTC) methodology for advancing inclusive excellence in scientific communities.
Emerging role of regulatory T cells in the immunopathogenesis of vitiligo and implications for treatment
Authors: Liu Yang , Liu Ziqi , Li Dan , He Xuanxuan , Xiang Leihong , Li Bin , Zhang Chengfeng
Published: December 2024

Vitiligo is an autoimmune skin disease that targets pigment-producing melanocytes and results in depigmentation. This disfiguring condition frequently affects visible areas of the body and therefore causes a heavy psychological burden and a decreased quality of life. Although it remains intractable, the ever-growing understanding of its immunopathogenesis has dramatically shaped the treatment paradigm for vitiligo. With the impact of autoreactive cytotoxic T cells explained extensively, accumulating evidence suggests the unique role of regulatory T cells (Tregs) in the immune microenvironment of vitiligo. We systematically reviewed Treg deficiency, instability, reduced vitality and dysfunction in people with vitiligo, combined with novel findings regarding Treg function modulation in autoimmune backgrounds, including metabolic alteration, post-translational modifications and interaction with other immune cells. We further summarized classic and advanced Treg-targeted therapeutics in vitiligo practice and research. Herein, we share up-to-date knowledge of Tregs in vitiligo, providing insights into novel Treg-based therapeutic strategies.
Appendiceal diverticulitis: a rare pathology disguised as acute appendicitis
Authors: Chen John L , Kalidindi Venugopala , Mayor-Jerez Jorge , Sadler Timothy J , Bell Daniel J
Published: December 2024

Appendiceal diverticulitis, although rare, is an important differential diagnosis in cases of right iliac fossa pain. Previously, it has often been considered as a variant of acute appendicitis, due to its seemingly similar clinical presentation. However, recent research indicates that appendiceal diverticulitis is a distinct clinical entity, with demographic characteristics and clinical features that are different to acute appendicitis. It is also associated with higher risk of severe morbidity and mortality, necessitating timely diagnosis and management. In this report, we present a case of a 58-year-old male patient with diverticulitis of the vermiform appendix and review the relevant literature. We describe the classification of appendiceal diverticulosis and diverticulitis, their clinical presentation, and their potential complications. We outline the radiological findings of appendiceal diverticulitis and acute appendicitis and discuss the important role of diagnostic imaging in distinguishing between these two conditions.
Who asked for this? The curious case of Readiness for Professional Practice in England
Authors: Hanley Joe
Published: December 2024

This article critically analyses plans for a new Readiness for Professional Practice framework in England. The new framework is being introduced by the regulator, Social Work England, with the stated aim to promote consistency across social work qualifying programmes. The framework and the regulatory context of social work qualifying in England are first introduced, as well as the contemporary challenges facing social work educators and students. The article then examines the evidence that underpins RPP, interrogating the limited research and flawed consultation process used to justify its introduction. Following this, some contextual factors are considered in relation to the new framework, including the already crowded landscape of frameworks for social workers in England and chronically poor working conditions. These discussions also raise the question of why this new framework is being introduced when an already existing framework, the Professional Capabilities Framework, is so widely employed and supported within the profession. The article then looks at how Readiness for Professional Practice fits within other national reforms in the sector, drawing on learning from similar experiences in initial teacher education to suggest that the new framework may be more about governmental control than student support.
Percutaneous repair of the Achilles tendon with one knot offers equivalent results as the same procedure with two knots. A comparative prospective study
Authors: Maffulli Nicola , Christidis George , Gougoulias Nikolaos , Christidis Panagiotis , Poku Daryl , Hassan Rifat , Migliorini Filippo , Oliva Francesco
Published: December 2024

Purpose

The present prospective comparative study included patients with acute Achilles tendon rupture (ATR) who underwent percutaneous repair with one knot compared to percutaneous repair with two knots.

Methods

All patients underwent the procedure under local anesthesia. A total of 29 patients underwent percutaneous repair with two knots (Group A), and 33 patients underwent percutaneous repair with one knot (Group B). All patients were treated by a single surgeon between 2019 and 2021 and were followed prospectively for 24 months.

Results

Patients’ characteristics at baseline were similar between the two groups, except for age [38.0(15.0) vs 32.0(15.0) years, P = 0.028]. The procedure took longer for the two knots technique [19.0(4.0) vs 13.0(3.0) min, P < 0.001]. The Achilles tendon total rupture score was not different between the two techniques (90.7 ± 3.26 vs 90.5 ± 2.18, P = 0.737), as was the elongation of the gastrosoleus-Achilles tendon complex measured by the Achilles tendon resting angle [−1.0(2.0) vs − 1.0(2.0), P < 0.380]. The calf circumference of the injured and non-injured leg did not differ between the groups. Plantarflexion strength of the operated leg was significantly weaker than the non-operated leg in both groups. The European Foot and Ankle Society and patient reported outcome measures score by Piedade et al. scores were not statistically significant different between the two groups. No patient experienced a re-rupture, a venous thrombo-embolism episode, or injury to the sural nerve.

Conclusion

The modified technique offered similar objective and subjective outcome measures, in addition to reduced operative time.
The role of dystrophin isoforms and interactors in the brain
Authors: Tetorou Konstantina , Aghaeipour Artadokht , Singh Simran , Morgan Jennifer E , Muntoni Francesco
Published: December 2024

Dystrophin is a protein crucial for maintaining the structural integrity of skeletal muscle. So far, attention has been focused on the role of dystrophin in muscle, in view of the devastating progression of weakness and early death that characterizes Duchenne muscular dystrophy. However, in the last few years, the role of shorter dystrophin isoforms, including development and adult expression-specific mechanisms, has been a greater focus.

Within the cerebral landscape, various cell types, such as glia, oligodendrocytes and Purkinje, cerebellar granule and vascular-associated cells express a spectrum of dystrophin isoforms, including Dp427, Dp140, Dp71 and Dp40. The interaction of these isoforms with a multitude of proteins suggests their involvement in neurotransmission, influencing several circuit functions.

This review presents the intricate interactions among dystrophin isoforms and diverse protein complexes across different cell types and brain regions, as well as the associated clinical complications. We focus on studies investigating protein interactions with dystrophin in the past 30 years at a biochemical level. In essence, the brain's dystrophin landscape is a thrilling exploration of diversity, challenging preconceptions and opening new avenues for understanding CNS physiology. It also holds potential therapeutic implications for neurological complications involving brain dystrophin deficiency. By revealing the molecular complexities related to dystrophin, this review paves the way for future investigations and therapeutic interventions for this CNS aspect of Duchenne muscular dystrophy.
Nanomedicine embraces the treatment and prevention of acute kidney injury to chronic kidney disease transition: evidence, challenges, and opportunities
Authors: Li Jia , Duan Jiayu , Hua Chaoyang , Pan Shaokang , Li Guangpu , Feng Qi , Liu Dongwei , Liu Zhangsuo
Published: December 2024

Acute kidney injury (AKI), a common kidney disease in which renal function decreases rapidly due to various etiologic factors, is an important risk factor for chronic kidney disease (CKD). The pathogenesis of AKI leading to CKD is complex, and effective treatments are still lacking, which seriously affects the prognosis and quality of life of patients with kidney disease. Nanomedicine, a discipline at the intersection of medicine and nanotechnology, has emerged as a promising avenue for treating kidney diseases ranging from AKI to CKD. Increasing evidence has validated the therapeutic potential of nanomedicine in AKI; however, little attention has been paid to its effect on AKI for patients with CKD. In this review, we systematically emphasize the major pathophysiology of the AKI-to-CKD transition and summarize the treatment effects of nanomedicine on this transition. Furthermore, we discuss the key role of nanomedicine in the regulation of targeted drug delivery, inflammation, oxidative stress, ferroptosis, and apoptosis during the transition from AKI to CKD. Additionally, this review demonstrates that the integration of nanomedicine into nephrology offers unprecedented precision and efficacy in the management of conditions ranging from AKI to CKD, including the design and preparation of multifunctional nanocarriers to overcome biological barriers and deliver therapeutics specifically to renal cells. In summary, nanomedicine holds significant potential for revolutionizing the management of AKI-to-CKD transition, thereby providing a promising opportunity for the future treatment of kidney diseases.
Testicular sex cord–stromal tumors in mice with constitutive activation of PI3K and loss of Pten
Authors: Dinevska Marija , McAloney Lachlan , Widodo Samuel S , Filiz Gulay , Anderson Jeremy , Dworkin Sebastian , Windley Simon P , Wilhelm Dagmar , Mantamadiotis Theo
Published: December 2024

Testicular tumors are the most common malignancy of young men, and tumors affecting the testis are caused by somatic mutations in germ or germ-like cells. The PI3K pathway is constitutively activated in about one-third of testicular cancers. To investigate the role of the PI3K pathway in transforming stem-like cells in the testis, we investigated tumors derived from mice with post-natal, constitutive activation of PI3K signaling and homozygous deletion of tumor suppressor Pten, targeted to Nestin-expressing cells. Mice developed aggressive tumors, exhibiting heterogeneous histopathology and hemorrhaging. The tumors resemble the rare testis tumor type, testicular sex cord–stromal Leydig cell tumors. Single-cell resolution spatial tissue analysis demonstrated that T-cells are the dominant tumor-infiltrating immune cell type, with very few infiltrating macrophages observed in the tumor tissue, with CD8+ T-cells predominating. Further analysis showed that immune cells preferentially localize to, or accumulate within stromal regions.
The role of interleukin 17 in cancer: a systematic review
Authors: Begagic Emir , Vranic Semir , Sominanda Ajith
Published: December 2024

Interleukin 17 (IL17) is a cytokine involved in immune regulation and has been increasingly recognized for its role in cancer progression. This systematic review aims to integrate data on IL17’s role in various tumors to better understand its implications for cancer prognosis and treatment. The review included 105 studies (27.6% experimental and 72.4% clinical). Clinical studies involved 9266 patients: 31.2% males, 60.0% females, and 8.8% with undefined gender. IL17A and IL17 were the most studied subtypes (36.2% and 33.3%, respectively). Breast cancer (26.7%), colorectal carcinoma (13.3%), and hematologic malignancies (10.5%) were the most researched neoplasms. IL17A promoted tumor growth in breast cancer and correlated with poor outcomes in colorectal, breast, and lung cancers. IL17 also played a significant role in immune modulation in gliomas and other tumors. IL17A significantly influences tumor growth and prognosis across various cancers, with notable roles in immune modulation and poor outcomes in multiple cancer types.
Chronology of Practice: Chinese Practice in Private International Law in 2023
Authors: He Qisheng
Published: December 2024

The survey of the Chinese practices in private international law in 2023 highlights the following aspects: First, four new laws and two administrative regulations, three judicial interpretations by the Supreme People’s Court (“SPC”) have been formulated, and six groups of 44 typical cases have been selected by the SPC. Notably, China acceded to the Hague Apostille Convention this year. Additionally, Chinese courts concluded 24,000 foreign-related civil and commercial cases, 16,000 maritime cases, and 16,000 commercial arbitration judicial review cases. Second, Part IV of the Civil Procedure Law was amended to include new provisions addressing jurisdiction, service of process abroad, taking of evidence and periods, as well as recognition and enforcement of foreign judgments and arbitral awards. These new rules and relevant cases are presented throughout the Survey. Third, the application of international treaties and practices has emerged as a significant topic, with new rules in the Foreign Relations Law and the SPC Interpretation of International Treaties and International Practices. Additionally, the SPC selected 14 representative cases in this regard. Fourth, concerning the ascertainment of foreign laws, the SPC issued two judicial interpretations and selected three relevant cases. Fifth, regarding the judicial review of arbitration cases, the SPC has selected several Typical Cases of Judicial Review of Arbitration, which serve as significant guiding examples.
The Sino-Indian Boundary Dispute: Exploring Its Historical Roots and Addressing Colonial Cartography Using Innovative Methodology beyond the Western International Law Framework
Authors: Lone Fozia Nazir
Published: December 2024

The ongoing Sino–Indian Border Dispute (SIBD) has yet to be effectively addressed by international law. Westphalian notions of sovereignty have hindered negotiations between the two nations, resulting in a stagnant conflict. This article explores the SIBD’s historical roots and suggests innovative pathways towards resolution that consider the socio-political, geographical, and historical context of Sino–Indian relations. To resolve the SIBD, extreme nationalist views in China and India must be restrained. This article proposes establishing a commission within the Shanghai Cooperation Organisation that adopts a tailor-made methodology, informed by Third World and New Haven Approaches to International Law and supplemented by a negotiation framework guided by the Five Principles of Coexistence—a cornerstone of peaceful Sino–Indian diplomatic relations. Through the commission’s efforts, an era could begin that moves away from the British Indian colonial cartographic legacy and Westphalian International Law on territories that created the current status quo. This innovative approach would improve economic conditions, protect human rights, and increase security for those living in precarious border regions. Although these methodologies have limitations, they offer a more comprehensive and sustainable map-making approach that is better suited to the region’s unique needs.
Sharing regional capacity in deceased donor kidney transplantation: experience from a regional collaborative in a metropolitan area
Authors: Wanigasekera Tamara , Kim Isaac , Maple Hannah , Massey Ashish , Kiliaris Maria , Das Sharmistha , Ahmed Rafez , Malik Ahmed , Game David , Ghazanfar Abbas , Mamode Nizam , Mohamed Ismail , Motallebzadeh Reza , Olsburgh Jonathon , Popoola Joyce , Rajakariar Ravindra , Silas Lisa , Willicombe Michelle , Dor Frank J M F , Jones Gareth
Published: December 2024

Background

Access to deceased donor kidney transplantation may be restricted in the event of resource limitation induced by extreme peaks in activity or local major incidents, which exceed centre capacity. An organ-sharing protocol was developed by the five London transplant units in 2019 to establish a system for safe transfer of organs and recipients between five regional kidney transplant units. We describe the activity and outcomes over the initial 20-month period.

Methods

National data on kidney transplants performed via the collaborative scheme were obtained from National Health Service Blood and Transplant. Outcomes data was collected locally and analysed.

Results

Sixteen recipients were transplanted between November 2020 and July 2022. The reasons for referral were theatre capacity and an information technology systems failure. Donor kidneys were from 10 brainstem death donors (62.5%) and six circulatory death donors (37.5%). Half of the donors fulfilled standard criteria. Twelve patients (75%) were first transplant recipients. Three (18.75%) were highly sensitized (calculated reaction frequency ≥85%). Three (18.75%) patients required arterial reconstruction. Seven patients (43.75%) had delayed graft function. Median creatinine at 12 months post-transplantation was 134 µmol/L. The median length of stay was 7.5 days. Three recipients (18.75%) died within the first year, two from SARS-CoV-2 infection.

Conclusions

This unique organ sharing collaborative scheme involving five hospitals in London enabled 16 transplants to proceed which otherwise would not have occurred. Although initially established for low-risk donors and recipients, the scheme has evolved to enable transplantation for a wide variety of recipients of varying complexity.