bluuebunny/crossref_metadata_2025_split huggingface dataset:
A fungal ubiquitin ligase and arrestin binding partner contribute to pathogenesis and survival during cellular stress
Authors: du Plooy Lukas M. , Telzrow Calla L. , Nichols Connie B. , Probst Corinna , Castro-Lopez Natalia , Wormley Floyd L. , Alspaugh J. Andrew 
Published: September 2024

ABSTRACT

Cellular responses to external stress allow microorganisms to adapt to a vast array of environmental conditions, including infection sites. The molecular mechanisms behind these responses are studied to gain insight into microbial pathogenesis, which could lead to new antimicrobial therapies. Here, we explore a role for arrestin protein-mediated ubiquitination in stress response and pathogenesis in the pathogenic fungus
Cryptococcus neoformans
. In a previous study, we identified four arrestin-like proteins in
C. neoformans
and found that one of these is required for efficient membrane synthesis, likely by directing interaction between fatty acid synthases and the Rsp5 E3 ubiquitin ligase. Here, we further explore
Cn
Rsp5 function and determine that this single Ub ligase is absolutely required for pathogenesis and survival in the presence of cellular stress. Additionally, we show that a second arrestin-like protein, Ali2, similarly facilitates interaction between Rsp5 and some of its protein targets. Of the four postulated
C. neoformans
arrestin-like proteins, Ali2 appears to contribute the most to
C. neoformans
pathogenesis, likely by directing Rsp5 to pathogenesis-related ubiquitination targets. A proteomics-based differential ubiquitination screen revealed that several known cell surface proteins are ubiquitinated by Rsp5 and a subset also requires Ali2 for their ubiquitination. Rsp5-mediated ubiquitination alters the stability and the localization of these proteins. A loss of Rsp5-mediated ubiquitination results in cell wall defects that increase susceptibility to external stresses. These findings support a model in which arrestin-like proteins guide Rsp5 to ubiquitinate specific target proteins, some of which are required for survival during stress.

IMPORTANCE

Microbial proteins involved in human infectious diseases often need to be modified by specific chemical additions to be fully functional. Here, we explore the role of a particular protein modification, ubiquitination, in infections due to the human fungal pathogen
Cryptococcus neoformans
. We identified a complex of proteins responsible for adding ubiquitin groups to fungal proteins, and this complex is required for virulence. These proteins are fungal specific and might be targets for novel anti-infection therapy.
Actioning atrial fibrillation identified by ambulance services in England: a qualitative exploration
Authors: Wilkinson Chris , Moloney Susan , McClelland Graham , Todd Adam , Doran Tim , Price Christopher 
Published: September 2024

ObjectivesTo explore the acceptability and feasibility of detection of atrial fibrillation (AF) by emergency medical services (EMS) and identify potential barriers and facilitators to implementing a formal pathway to facilitate follow-up in primary care, which could reduce the risk of AF-related stroke.DesignQualitative study using focus groups and one-to-one interviews guided by a semistructured topic guide.SettingNorth East England.ParticipantsFocus groups with 18 members of the public and one-to-one online interviews with 11 healthcare and service providers (six paramedics and five experts representing cardiology, general practice (GP), public health, research, policy and commissioning).ResultsAll participant groups were supportive of a role of EMS in identifying AF as part of routine assessment and formalising the response to AF detection. However, this should not create delays for EMS since rate-controlled AF is non-urgent and alternative community mechanisms exist to manage it. Public participants were concerned about communication of the AF diagnosis and whether this should be ‘on scene’ or in a subsequent GP appointment. Paramedics reported frequent incidental identification of AF, but it is not always clear ‘on scene’ that this is a new diagnosis, and there is variation in practice regarding whether (and how) this is communicated to the GP. Paramedics also focused on ensuring the safety of non-conveyed patients and a perceived need for an ‘active’ reporting process, so that a finding of AF was actioned. Field experts felt that a formal pathway would be useful and favoured a simple intervention without adding to time pressures unnecessarily.ConclusionsThere is support for the development of a formal pathway to ensure follow-up for people with AF that is incidentally detected by EMS. This has the potential to improve anticoagulation rates and reduce the risk of stroke.
Empowering Portable Age-Related Macular Degeneration Screening: Evaluation of a Deep Learning Algorithm for a Smartphone Fundus Camera
Authors: Savoy Florian Mickael , Rao Divya Parthasarathy , Toh Jun Kai , Ong Bryan , Sivaraman Anand , Sharma Ashish , Das Taraprasad 
Published: September 2024

ObjectivesDespite global research on early detection of age-related macular degeneration (AMD), not enough is being done for large-scale screening. Automated analysis of retinal images captured via smartphone presents a potential solution; however, to our knowledge, such an artificial intelligence (AI) system has not been evaluated. The study aimed to assess the performance of an AI algorithm in detecting referable AMD on images captured on a portable fundus camera.Design, settingA retrospective image database from the Age-Related Eye Disease Study (AREDS) and target device was used.ParticipantsThe algorithm was trained on two distinct data sets with macula-centric images: initially on 108,251 images (55% referable AMD) from AREDS and then fine-tuned on 1108 images (33% referable AMD) captured on Asian eyes using the target device. The model was designed to indicate the presence of referable AMD (intermediate and advanced AMD). Following the first training step, the test set consisted of 909 images (49% referable AMD). For the fine-tuning step, the test set consisted of 238 (34% referable AMD) images. The reference standard for the AREDS data set was fundus image grading by the central reading centre, and for the target device, it was consensus image grading by specialists.Outcome measuresArea under receiver operating curve (AUC), sensitivity and specificity of algorithm.ResultsBefore fine-tuning, the deep learning (DL) algorithm exhibited a test set (from AREDS) sensitivity of 93.48% (95% CI: 90.8% to 95.6%), specificity of 82.33% (95% CI: 78.6% to 85.7%) and AUC of 0.965 (95% CI:0.95 to 0.98). After fine-tuning, the DL algorithm displayed a test set (from the target device) sensitivity of 91.25% (95% CI: 82.8% to 96.4%), specificity of 84.18% (95% CI: 77.5% to 89.5%) and AUC 0.947 (95% CI: 0.911 to 0.982).ConclusionThe DL algorithm shows promising results in detecting referable AMD from a portable smartphone-based imaging system. This approach can potentially bring effective and affordable AMD screening to underserved areas.
Protocol of digital decision support system (DDSS) embedded within a tele-primary healthcare platform in Pakistan: an assessment of usability, acceptability, effectiveness and perceived quality of care in a resource-constrained setting
Authors: Tahir Hasan Nawaz , Habib Shifa , Jabeen Rawshan , Dhanwani Anny , Jawed Samrah , Guerrero-Torres Lorena , Khurram Sara Saeed , Aga Iffat Zafar , Karim Mahek , Kazi Abdul Momin , Zaidi Shehla 
Published: September 2024

BackgroundA digital decision support system in healthcare is a digital health intervention that assists healthcare professionals in decision-making by providing treatment recommendations and enhancing diagnostic accuracy and quality of care. This will be the first study in Pakistan to assess the system’s usability, acceptability and effectiveness in improving healthcare outcomes while also evaluating the perceived quality of care. This comprehensive assessment will inform policy development in areas such as the scale-up of digital health interventions, data privacy and technology interoperability. Measures of effectiveness will include changes in clinical outcomes through a patient exit feedback survey. This study aims to evaluate the role of digital decision support systems in healthcare decision-making, which may be integrated into Pakistan’s tele-primary healthcare system.MethodsThe study will employ a multimethod approach. The data collection tools are adapted from the WHO’s digital health intervention monitoring and evaluation framework and include a technology assessment, healthcare provider surveys, patient exit interviews and focus group discussions with healthcare providers. Purposive sampling will be used for qualitative interviews with providers (doctors) and patients. Government stakeholders, private sectors, multilateral, academia and policymakers will be engaged through a consultative meeting. We will also conduct a literature review, as well as a comprehensive analysis of existing studies, documents and data relevant to digital decision support systems and digital health interventions implemented globally, and assess the performance, challenges and opportunities.Ethics and disseminationThe study has been approved by the Ethics Review Committee at The Aga Khan University (2023-8514-26533). The dissemination of study findings through scientific publications and seminars will enable programme managers and policymakers to design tools to improve the quality of care provided through telemedicine platforms. This will contribute to efficient decision-making, access and quality of care for primary healthcare in low-income and middle-income countries. This study will also inform policy regarding the scale-up of decision support systems in primary care settings, data privacy and technology interoperability.
Plasma proteomic signature of neonates in the context of placental histological chorioamnionitis
Authors: Liu Jing , Liu Die , Sun Qi , Su Yunchao , Tang Lijuan , Liang Haixiao , Ye Fang , Chen Yuanmei , Zhang Qi 
Published: September 2024

BackgroundPlacental histological chorioamnionitis (HCA) is recognised as a significant risk factor for various adverse neonatal outcomes. This study aims to explore if the inflammatory protein levels in neonates were associated with HCA.MethodsAll women with singleton births from February 2020 to November 2022 were selected and divided into three groups based on maternal placental pathology results: the HCA-stage 1 group (n=24), the HCA-stage 2 group (n=16) and the control group (n=17). Olink Target 96 Inflammation Panel was used to detect the levels of 92 inflammation-related proteins in the plasma of newborns from all three groups within 24 hours after birth. We compared the protein profiles through differential protein expression analysis.ResultsA total of six inflammation-related proteins exhibited significant differences between the HCA-stage 1 and the control group. Specifically, TRANCE and CST5 were significantly upregulated (p=0.006, p=0.025, respectively), whereas the expression of IFN-gamma, CXCL9, CXCL10 and CCL19 was significantly downregulated (p=0.040, p=0.046, p=0.007, p=0.006, respectively). HCA-stage 2 newborns had significantly elevated levels of CD5 and CD6 and decreased IFN-gamma, CXCL10 and CCL19 in comparison to controls. These differential proteins were significantly enriched in positive regulation of cytokine activity, leucocyte chemotaxis and positive regulation of T-cell activation pathway-related Gene Ontology terms. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that viral protein interaction with cytokine and cytokine receptor, interleukin-17/NF-kappa B/toll-like receptor/chemokine signalling pathway, and cytokine-cytokine receptor interaction exhibited significant differences. Spearman analysis demonstrated a significant positive connection between the levels of CD6 and CD5 proteins, not only in neonatal leucocytes but also in maternal leucocytes. Additionally, CD6 was found to be associated with neonatal birth weight.ConclusionsIn conclusion, placental histological changes associated with chorioamnionitis appear to influence the expression of inflammatory proteins in offspring. Notably, CD6 and CD5 proteins may potentially contribute to the pathogenesis of HCA-related neonatal diseases.
Abortion patients’ perspectives on enhancing a telemedicine model of post-abortion contraception: a qualitative study
Authors: Boydell Nicola , Buijsen Sophie , Reynolds-Wright John Joseph , Cameron Sharon T , Harden Jeni 
Published: September 2024

BackgroundAccess to post-abortion contraception (PAC) is critical for reducing unintended pregnancies and supporting reproductive decision-making. Patients often face challenges in identifying, accessing and initiating their preferred contraceptive methods post-abortion. This may be particularly so with telemedicine models of care with absence of in-person appointments, and reduced opportunities to provide some contraceptive methods. This qualitative service evaluation explored patients' perspectives on PAC consultations and decision-making to inform future PAC service models in the era of telemedicine.MethodsQualitative interviews with 15 patients who had telemedicine medical abortion at home up to 12 weeks’ gestation. Data were analysed using reflexive thematic analysis.ResultsContraceptive discussions during pre-abortion consultations were valued for supporting informed choices about future contraceptive use. Decision-making was influenced by previous contraception experiences, emotional state at the time of abortion and concerns about contraceptive ‘failure’. Some preferred non-hormonal methods due to past negative experiences with hormonal contraceptives. However, limited information about 'natural' contraceptive methods and concerns about discussing these with healthcare professionals were described. Barriers to accessing preferred methods, particularly long-acting reversible contraception (LARC), included reduced availability of appointments and caring responsibilities. Fast-tracked appointments for LARC fitting post-abortion were valued. The need for flexible PAC consultations and access after abortion, for example, remote consultations complemented by personalised interactions with sexual and reproductive health experts, was emphasised.ConclusionThe findings highlight the need for flexible and more accessible PAC service models in the era of telemedicine care to ensure timely access to preferred contraceptive methods.
Lee–Yang edge singularities in QCD via the Dyson–Schwinger equations
Authors: Wan Zi-Yan , Lu Yi , Gao Fei , Liu Yu-xin 
Published: September 2024

AbstractWe take the Dyson–Schwinger Equation approach of QCD for the quark propagator at complex chemical potential to study the QCD phase transition. The phase transition line of the $$(2+1)$$

(
2
+
1
)

-flavor QCD matter in the imaginary chemical potential region is computed via a simplified truncation scheme, whose curvature is found to be consistent with the one at real chemical potential. Moreover, the computation in the complex chemical potential plane allows us to determine the location of the Lee–Yang edge singularities. We show explicitly that the critical end point coincides with the Lee–Yang edge singularities on the real $$\mu _{B} $$

μ
B

axis. We also investigate the scaling behavior of the singularities and discuss the possibility of extrapolating the CEP from a certain range of chemical potential.
Study of commutator involving X-generalized skew derivations and annihilators in prime rings
Authors: Bera Nripendu , Dhara Basudeb , Kar Sukhendu 
Published: September 2024

Let [Formula: see text] be a prime ring of characteristic is not [Formula: see text], [Formula: see text] its right Martindale ring of quotient and [Formula: see text] be the extended centroid of [Formula: see text]. Suppose that [Formula: see text] is a noncentral multilinear polynomial over [Formula: see text] and [Formula: see text] with [Formula: see text]. When [Formula: see text] is a generalized skew derivation, then Yarbil et al. [Annihilators and centralizers of generalized skew derivations on multilinear polynomials, Beitr. Algebra Geom. 59(3) (2018) 573–595] studied the situation [Formula: see text] for all [Formula: see text] and then described the forms of the map [Formula: see text]. Recently, when [Formula: see text] is an [Formula: see text]-generalized skew derivation, then Prajapati and Gupta [On [Formula: see text]-generalized skew derivations having centralizing commutator in prime rings, Comm. Algebra 50(7) (2022) 2997–3006] studied [Formula: see text] for all [Formula: see text], and then described the forms of the map [Formula: see text]. In this paper, we study the above identity of Yarbil et al., that is, [Formula: see text] for all [Formula: see text], when [Formula: see text] is an [Formula: see text]-generalized skew derivation, and then we described all possible forms of the map.
TR-107, an Agonist of Caseinolytic Peptidase Proteolytic Subunit, Disrupts Mitochondrial Metabolism and Inhibits the Growth of Human Colorectal Cancer Cells
Authors: Giarrizzo Michael , LaComb Joseph F. , Patel Hetvi R. , Reddy Rohan G. , Haley John D. , Graves Lee M. , Iwanowicz Edwin J. , Bialkowska Agnieszka B. 
Published: September 2024

Abstract
Oxidative phosphorylation is an essential metabolic process for cancer proliferation and therapy resistance. The ClpXP complex maintains mitochondrial proteostasis by degrading misfolded proteins. Madera Therapeutics has developed a class of highly potent and selective small-molecule activators (TR compounds) of the ClpXP component caseinolytic peptidase proteolytic subunit (ClpP). This approach to cancer therapy eliminates substrate recognition and activates nonspecific protease function within mitochondria, which has shown encouraging preclinical efficacy in multiple malignancies. The class-leading compound TR-107 has demonstrated significantly improved potency in ClpP affinity and activation and enhanced pharmacokinetic properties over the multitargeting clinical agent ONC201. In this study, we investigate the in vitro efficacy of TR-107 against human colorectal cancer cells. TR-107 inhibited colorectal cancer cell proliferation in a dose- and time-dependent manner and induced cell cycle arrest at low nanomolar concentrations. Mechanistically, TR-107 downregulated the expression of proteins involved in the mitochondrial unfolded protein response and mitochondrial DNA transcription and translation. TR-107 attenuated oxygen consumption rate and glycolytic compensation, confirming inactivation of oxidative phosphorylation and a reduction in total cellular respiration. Multiomics analysis of treated cells indicated a downregulation of respiratory chain complex subunits and an upregulation of mitophagy and ferroptosis pathways. Further evaluation of ferroptosis revealed a depletion of antioxidant and iron toxicity defenses that could potentiate sensitivity to combinatory chemotherapeutics. Together, this study provides evidence and insight into the subcellular mechanisms employed by colorectal cancer cells in response to potent ClpP agonism. Our findings demonstrate a productive approach to disrupting mitochondrial metabolism, supporting the translational potential of TR-107.
Abstract A006 Targeting boundary cap cells leads to mouse Smarcb1-deficient peripheral nerve tumors recapitulating human peripheral rhabdoid tumors
Authors: HAN Zhi-Yan , Andrianteranagna Mamy , Fitte-Duval Stéphanie , Manriquez Valeria , Frah Magali , Bouarich Rachida , Turcynski Sandrina , Tauziède-Espariat Arnault , Beccaria Kevin , Masliah-Planchon Julien , Bourneix Christine , Guillemot Delphine , Reynaud Stéphanie , Pierron Gaelle , Veyssiere Maëva , Hoare Owen , Chauvin Céline , Thomson Grégory , Surdez Didier , Varlet Pascale , Dufour Christelle , Dangouloff-Ros Volodia , Waterfall Joshua J. , Piaggio Eliane , Delattre Olivier , Topilko Piotr , Bourdeaut Franck 
Published: September 2024

Abstract
Malignant rhabdoid tumors (MRT) are rare aggressive tumors of infancy characterized by the biallelic inactivation of SMARCB1. Their lineage of origin remains uncertain, but increasing evidence suggest a neural-crest origin. By analyzing the transcriptome of MRT occurring in peripheral and cranial nerves, we observe that their expression profiling was not distinct from any other tumor localization. We therefore investigated whether the development of Smarcb1-deficient tumors emerging from embryonic precursors of peripheral nerves in mice could recapitulate human MRT. we generated conditional Smarcb1 knockout in the Prss56-Cre mouse strain thereby targeting boundary cap cells which are neural crest derived Schwann cell precursor. All Smarcb1Flox/Flox;Prss56Cre+/+ showed ataxia within a median of two months, due to the development of massive intracranial tumor in the ponto-cerebellum angle. Smarcb1Flox/Flox;Prss56Cre+/- mainly developed paraplegia related to nerve root tumors, within a median delay of 7 months. Interestingly, transcriptome profiling confirmed the good correlation between mouse peripheral nerve tumors and human MRT; intracranial tumors in this new model correlated with MYC-ATRTs but with some specific features not observed in their human counterparts. All tumors harbored a significant immune infiltration, with some clonal T-cell expansion. Altogether, the Smarcb1Flox/Flox;Prss56-Cre mouse tumors offer a new model for human MRT and promising perspectives for immune-based innovative treatments.
Citation Format: Zhi-Yan HAN, Mamy Andrianteranagna, Stéphanie Fitte-Duval, Valeria Manriquez, Magali Frah, Rachida Bouarich, Sandrina Turcynski, Arnault Tauziède-Espariat, Kevin Beccaria, Julien Masliah-Planchon, Christine Bourneix, Delphine Guillemot, Stéphanie Reynaud, Gaelle Pierron, Maëva Veyssiere, Owen Hoare, Céline Chauvin, Grégory Thomson, Didier Surdez, Pascale Varlet, Christelle Dufour, Volodia Dangouloff-Ros, Joshua J. Waterfall, Eliane Piaggio, Olivier Delattre, Piotr Topilko, Franck Bourdeaut. Targeting boundary cap cells leads to mouse Smarcb1-deficient peripheral nerve tumors recapitulating human peripheral rhabdoid tumors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr A006.