bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibiting disulphide bonding in truncated tau297-391 results in enhanced self-assembly of tau into seed-competent assemblies
Authors: Oakley Sebastian S. , Marshall Karen E. , Meisl Georg , Copsey Alice , Maina Mahmoud B. , Milton Robert , Vorley Thomas , Storey John M. D. , Harrington Charles R. , Wischik Claude , Xue Wei-Feng , Serpell Louise C.
Published: February 2025

Tau undergoes fibrillogenesis in a group of neurodegenerative diseases termed tauopathies. Each tauopathy is characterized by tau fibrils with disease-specific conformations, highlighting the complexity of tau self-assembly. This has led to debate surrounding the precise mechanisms that govern the self-assembly of tau in disease, especially the involvement of disulphide bonding (DSB) between cysteine residues. In this study, we use a truncated form of tau, dGAE, capable of forming filaments identical to those in disease. We reveal the impact of DSB in dGAE assembly and propagation by resolving the global mechanisms that dominate its assembly. We found evidence for surface-mediated secondary nucleation and fragmentation being active in dGAE assembly. The inhibition of DSB during dGAE assembly leads to an enhanced aggregation rate through a reduced lag phase, but with no effect on the global assembly mechanisms. We suggest this is due to the formation a dominant, seed-competent species in the absence of DSB that facilitates elongation and secondary nucleation resulting in enhanced assembly.In vitroseeding assays reveal the recruitment of endogenous tau in a cell model only when using dGAE species formed under conditions that inhibit DSB. Our results further support the use of thein vitrodGAE tau aggregation model for investigating the mechanism of tau assembly, the effect of varying conditions on tau assembly and how these conditions affect the resultant species. Further studies may utilise dGAE and its aggregates to investigate tau seeding, propagation and to highlight or test potential targets for therapies that reduce the spread of pathologic tau throughout the brain.
Enhanced virulence and stress tolerance are signatures of epidemiologically successfulShigella sonnei
Authors: Miles Sydney L , Santillo Dilys , Torraca Vincenzo , López Jiménez Ana Teresa , Jenkins Claire , Baker Stephen , Baker Kate S , Sancho-Shimizu Vanessa , Holt Kathryn E , Mostowy Serge
Published: February 2025

Shigellosis is a leading cause of diarrhoeal deaths worldwide, withShigella sonneiincreasingly implicated as a dominant agent.S. sonneiis divided into five monophyletic lineages all sharing a single O-antigen, yet most contemporary infections are caused by just a few clonal sub-lineages within globally dominant Lineage 3 that are quite distinct from the widely used Lineage 2 laboratory strain 53G. Factors underlying the success of these globally dominant lineages remain poorly understood in part due to a lack of complete genome sequences and available animal models. Here, we utilise a novel reference collection of representative Lineage 1, 2 and 3 isolates with complete genome sequences, and find that epidemiologically successfulS. sonneiharbour fewer genes encoding putative immunogenic components whilst key virulence-associated regions (such as the type three secretion system and O-antigen) remain highly conserved. Using a zebrafish infection model, we discover that Lineage 3 isolates are most virulent, driven by significantly increased dissemination and a greater neutrophil response. We show that Lineage 3 isolates have increased tolerance to complement-mediated killing and acidic conditions alongside upregulated expression of group four capsule synthesis genes. Consistent with these observations, infection of primary human neutrophils revealed that Lineage 3 isolates are more tolerant of phagosomal killing. Together, our findings link the epidemiological success ofS. sonneito heightened virulence and stress tolerance and highlight zebrafish as a valuable platform to illuminate factors underlying establishment ofShigellaepidemiological success.
microRNA-Mediated Effects of Caloric Restriction on Trophoblast Invasion and Angiogenic Signaling in a Mouse Model of Fetal Growth Restriction
Authors: Bardill James , Derderian Chris
Published: February 2025

Trophoblast invasion is essential for normal placentation, with failure resulting in a fetal growth restriction (FGR) phenotype. Utilizing a calorie-restricted mouse model, we report progressive epigenetic, molecular, and phenotypic placental changes throughout gestation. Following maternal caloric restriction initiated at E9, we observed a significant reduction in fetal and placental weights beginning at E12.5, with persistent growth restriction at E14.5, E16.5, and E17.5. Immunohistochemistry of the decidual invasion site at E17.5 demonstrated reduced 1) decidual depth, 2) trophoblast invasion distance, and 3) trophoblast quantity within the decidua. Preceding these phenotypic changes, RT-qPCR revealed downregulation of trophoblast invasion and angiogenesis genes, including MMP2, MMP9, EFNA1, Rac1, Rras, ASCL2, TRAP2C, Prl7b1, VEGFa, VEGFb, PDGF, and AKT3, beginning as early as E14.5. Notably, microRNA sequencing at E12.5, prior to these transcriptional changes, identified significant upregulation of miR-503-5p, a predicted inhibitor of several of these pathways. The summation of these observations suggests miR-503-5p may be an early driver of placental dysfunction in FGR, linking maternal malnutrition to impaired trophoblast invasion and angiogenesis. These findings provide insight into the molecular mechanisms underlying placental insufficiency and highlight miR-503-5p as a potential therapeutic target for improving pregnancy outcomes in FGR.
Bose-Einstein condensation in a rigidly rotating relativistic boson gas
Authors: Siri E. , Sadooghi N.
Published: February 2025

We study the Bose-Einstein condensation (BEC) of a free Bose gas under rigid rotation. The aim is to explore the impact of rotation on the thermodynamic quantities associated with BEC, including the Bose-Einstein (BE) transition temperature and condensate fraction. We begin by introducing the rotation in the Lagrangian density of free charged Klein-Gordon fields and determine the corresponding grand canonical partition function at finite temperature, chemical potential, and finite angular velocity. Assuming slow rotation, we derive analytical expressions for the pressure, energy, number, and angular momentum densities of a free Bose gas in nonrelativistic and ultrarelativistic limits in terms of the corresponding fugacities. We then focus on the phenomenon of BEC. We calculate the critical temperature of BEC transition and the condensate fraction in a slowly rotating Bose gas including only particles. Our findings indicate that the critical exponent associated with the BE transition in a rotating gas is lower compared to that in a nonrotating Bose gas. We also determine the fugacity in a rotating Bose gas in the aforementioned limits and examine how rotation affects its temperature dependence, both below and above the critical temperature. By analyzing the behavior of heat capacity at these temperatures, we demonstrate that in a nonrelativistic Bose gas, the rotation transforms the nature of the BE phase transition from a continuous to a discontinuous transition. In general, we find that a nonrelativistic Bose gas under rotation behaves similarly to a nonrotating Bose gas in ultrarelativistic limit.

Published by the American Physical Society
2025
Kontsevich-Segal criterion in the no-boundary state constrains anisotropy
Authors: Hertog Thomas , Janssen Oliver , Karlsson Joel
Published: February 2025

We show that the Kontsevich-Segal-Witten (KSW) criterion applied to the no-boundary state constrains anisotropic deformations of de Sitter space. We consider squashed S3 and S1×S2 boundaries and find that, in both models, the KSW criterion excludes a significant range of homogeneous but anisotropic configurations. For squashed S3 boundaries, the excluded range includes all surface geometries with negative scalar curvature, in line with dS/CFT reasoning. For S1×S2 boundaries, we find that KSW selects the low-temperature regime of configuration space where the S1 is sufficiently large compared to the S2. In both models, the KSW criterion renders the semiclassical wave function normalizable, up to one-loop effects.

Published by the American Physical Society
2025
Fluxification and scalarization of the conifold black holes
Authors: Buchel Alex
Published: February 2025

We study thermal states of the strongly coupled Klebanov-Witten N=1 superconformal gauge theory with R-symmetry chemical potential. The theory has two distinct dimension Δ=3 chiral primary operators that develop a condensate at the same critical value of the chemical potential. One instability is associated with the spontaneous (the appearance of the 3-form flux) of the holographic dual black hole, while the other one is associated with the spontaneous (the activation of the deformation mode of the conifold). Different phases dominate in grand canonical and microcanonical ensembles.

Published by the American Physical Society
2025
A data-driven problem-solving approach to performance improvement in healthcare systems: a case study in Tehran heart center hospital
Authors: Nakhostin Mohammad Masoud , Jolai Fariborz , Hadavandi Esmaeil , Chavosh Nejad Mohammad
Published: February 2025

Purpose

The primary goal of this research is to introduce a data-driven Problem-Solving Approach for Performance Improvement in Healthcare Systems (DPAPIH). This approach combines process mining and data mining techniques to enhance operational efficiency by identifying bottlenecks in Coronary Artery Bypass Grafting (CABG) procedures, particularly focusing on variability in Length of Stay (LOS) in the Intensive Care Unit (ICU). The study, implemented at Tehran Heart Center, aims to optimize patient flow, reduce ICU congestion and improve hospital efficiency by predicting and managing the occurrence of postoperative Atrial Fibrillation (AF), a significant cause of prolonged ICU stays.

Design/methodology/approach

The study introduces a data-driven problem-solving approach that integrates process mining and data mining techniques to improve performance in healthcare systems. Focusing on coronary artery bypass grafting (CABG) at Tehran Heart Center, the approach identifies bottlenecks, particularly variability in ICU length of stay (LOS) and predicts postoperative atrial fibrillation (AF). A mixed-methods approach is employed, combining quantitative process mining analyses with qualitative insights from expert consultations. The CHAID decision tree algorithm, alongside other models, is used to predict AF, enabling preemptive interventions, improving patient flow and optimizing resource allocation to reduce hospital congestion and costs.

Findings

The study reveals that postoperative Atrial Fibrillation (AF) significantly increases the length of stay (LOS) in the Intensive Care Unit (ICU), creating bottlenecks that delay subsequent surgeries and elevate hospital costs. A predictive model developed using CHAID decision tree algorithms achieved a prediction accuracy of 71.4%, allowing healthcare providers to anticipate AF occurrences. This capability enables proactive measures to reduce ICU congestion, improve patient flow and optimize resource allocation. The findings emphasize the importance of AF management in enhancing operational efficiency and improving patient outcomes in Coronary Artery Bypass Grafting (CABG) procedures.

Originality/value

This study presents an innovative integration of fuzzy process mining and data mining algorithms to address performance bottlenecks in healthcare systems, specifically within the coronary artery bypass surgery process. By identifying atrial fibrillation as a key factor in length of stay fluctuations and developing a robust predictive model, the research offers a novel, data-driven approach to performance improvement. The implementation at Tehran Heart Center validates the model’s practical applicability, demonstrating significant potential for enhancing patient outcomes, optimizing resource allocation and informing decision-making in healthcare management.
Going beyond tomato a fruit or vegetable debate: economic and policy challenges in tomato farming in India
Authors: Koyilathumpaday Sujit Sukumaran , M. Nandini
Published: February 2025

Learning outcomes

The case was an application of a market demand and supply mechanism and its impact on the product’s price and focus on the following objectives:▪ Analyze the vegetable market in India and the challenges faced by the farmers (tomatoes) using demand and supply concepts.▪ Examine the impact of price elasticity on the revenue of the farmers.▪ Assess the challenges faced by the government in controlling prices of vegetables and food inflation.▪ Evaluate diversification strategies in agriculture to mitigate risk.

Case overview/synopsis

The market for tomatoes was highly cyclical because of erratic rainfall, and farmers went through a difficult time, especially when the prices fell below the cost of production. They moved out for crops that had stable prices. They expected government support for price stability. Government and policymakers considered price fluctuations a short-term phenomenon that required limited interventions when prices were high. This case was about Dilip, a farmer who was into farming tomatoes on a large scale in Karnataka, India. He was facing a dilemma as to whether he had to continue or move to other crops because of the low price of tomatoes in May 2023 or to diversify into some small but related business. He was worried at the same time, curious to understand the volatility in the prices of tomatoes, government responses, risks and returns associated with the cultivation of this crop and Agri-supply chain. Based on his understanding, he should make decisions to continue or diversify into some other farming or related business.

Complexity academic level

This case was written for microeconomics and managerial economics of undergraduate and postgraduate students. This case demonstrates the application of the demand and supply mechanism for a perishable product such as tomatoes. Price fluctuations are common in these markets because of various uncontrollable factors such as rain, pests and natural calamities. The case could show the relationship between the firm’s elasticities and revenue. This case also highlights the policy constraints in controlling the prices in the short run. This case could also be used for understanding macroeconomic concepts such as food inflation and its impact on general price inflation. The students or target audience with a background in the functioning of the markets could very well relate to the concepts discussed.

Supplementary material

Teaching notes are available for educators only.

Subject Code

CSS: Entrepreneurship (3); Management Science (7).
To persist or not to persist: understanding student team responses to effectuation in the higher education classroom
Authors: Günzel-Jensen Franziska , Neergaard Helle , Robinson Sarah
Published: February 2025

Purpose

Entrepreneurship education is transforming from traditional teacher-led classrooms to student-centred learning environments, where effectuation principles are increasingly adopted as a pedagogical framework. Yet despite its promise for developing real-world entrepreneurial capabilities, the implementation of effectuation principles in classrooms reveals a striking pattern: while some student teams excel, others struggle or even revert to passive learning approaches. Such variation in team responses raises an important question about the underlying mechanisms influencing team responses. This article aims to fill that gap by understanding why some student teams excel and others struggle in the higher education (HE) effectuation classroom.

Design/methodology/approach

A multiple case study involving 29 student teams enrolled in an undergraduate entrepreneurship class that is based on effectuation principles at a HE institution was conducted.

Findings

The study identifies three distinct responses among student teams. The first group displays apathy, and the second group rejects the process after a few classroom sessions. Both groups encounter student-centred learning identity threats. In contrast, the third group, despite facing similar identity threats, manages to persist.

Originality/value

This study argues that teaching and learning effectuation is more complex than generally depicted in the literature. It uncovers necessary and sufficient conditions related to students overcoming student-centred learning identity threats. By doing so, the study contributes to the understanding of why the connection between teaching effectuation and learning effectual behaviour is more intricate than previously understood. Additionally, it offers important practical implications for entrepreneurship educators and programme designers at HE institutions.
A cyber-physical system based unmanned ground vehicles for safety inspection and rescue support in an underground mine
Authors: Behera Laxmidhar , Agarwal Siddhartha , Sandhan Tushar , Sharma Pratibha , Kumar Ashish , Ranjan Ayush , Watsa Sidhartha , Singh Atul , Kasina Jyothi Swaroop
Published: February 2025

Purpose

The unmanned ground vehicle (UGV) described in this manuscript is a robot designed by the authors to map the underground mine environments. The UGV works to develop a computational intelligence-based cyber-physical system (CPS)-based analytical framework for mining operations. The UGV demonstrated excellent semi-autonomous navigation capabilities in the absence of GNSS signals. The UGV has a suite that works in unison to provide relevant information. These sensors are integrated to form a robust sensor fusion-based architecture, creating a CPS with a wide range of capabilities such as data acquisition and navigation in challenging underground environments. UGVs can be used to enhance the efficacy of safety inspections, rescue during underground emergencies and assist miners in hazardous conditions.

Design/methodology/approach

In this research, an UGV was constructed whose operations are enabled by sensors including a D415i Red Blue Green (RGB) depth camera, a LiDAR, a FLIR C5 infrared camera and smart air quality sensors. This sensor fusion-based architecture forms a CPS. Data obtained remotely are processed by deep learning algorithms to achieve overall capabilities such as real-time image analysis for miner identification, object detection, posture analysis and identifying threats of roof falls and overhangs. Simultaneous localization and mapping (SLAM) algorithms create a 3D map, facilitate autonomous navigation and build a decision support system for delivering mine rescue support.

Findings

The aim of this study is to include this capacity in training situations when it has been validated and authorized by the Directorate General of Mines Safety (DGMS) Indian government regulatory agency for safety in mines and oil fields. The longwall demo mine, at IIT (ISM) is being used as the site of the first operations. Once approved by the respective enforcement agencies, this technology and the accompanying rescue and training process can be used in underground operations.

Originality/value

In fact, this paper is the first attempt at remotely operated UGVs based on CPSs, the CPS–UGV in Indian mine conditions, so as to revolutionize Indian mines based on the idea of Industry 4.0.
Validation and cross-cultural adaptation of health-related quality of life scale: a psychometric study for elderly care home residents
Authors: Abdalrahim Asem
Published: February 2025

Purpose

This study aims to validate and adapt the Health-Related Quality of Life (HRQoL) scale for use among elderly patients in Arabic-speaking care homes.

Design/methodology/approach

A total of 210 participants completed the Arabic-translated HRQoL scale to assess its reliability, validity and cultural adaptation. Internal consistency, test–retest reliability, exploratory factor analysis and content validity were examined.

Findings

Results demonstrated high internal consistency (Cronbach’s alpha = 0.85–0.90), robust test–retest reliability (intraclass correlation coefficient = 0.91) and strong construct validity

Originality/value

This study provides a culturally adapted and psychometrically validated HRQoL scale tailored for Arabic-speaking elderly care home residents. It addresses a significant gap in the availability of reliable tools to assess HRQoL in this population. By ensuring linguistic and cultural relevance, this study offers a robust instrument for evaluating quality of life, guiding interventions and improving care practices. The findings contribute to advancing evidence-based geriatric care in Arabic-speaking contexts, with implications for broader application in similar cultural settings. This work supports efforts to enhance the well-being and dignity of elderly individuals in care homes.
Spatiotemporal interactions between ocelots and agoutis in Neotropical protected forests
Authors: Vallejo‐Vargas Andrea F. , Semper‐Pascual Asunción , Sheil Douglas , Santos Fernanda , Lima Marcela Guimarães Moreira , Bischof Richard
Published: February 2025

Understanding how predators and their prey coexist in space and time is a core interest in ecology. Vast amounts of photographic detection data are now available from a growing number of camera‐trap studies worldwide. These data boost our ability to study an elusive yet important topic in ecology: species interactions in space and time.

Here, we investigated the spatiotemporal configuration of the activity of a typically nocturnal and crepuscular predator and a diurnal prey in protected areas. We explored whether agoutis (Dasyprocta leporina) respond to predation risks by adjusting the timing of activity to the occurrence and timing of activity of its potential predator, the ocelot (Leopardus pardalis) and whether the ocelot's occurrence responds to that of the prey.

Using a custom Bayesian occupancy model for two species, we analysed camera‐trap data collected over three protected tropical forests from Brazil and Suriname (2 to 9 years). Our model distinguishes between occupancy (i.e. spatial distribution) and detection (i.e. activity in space and time).

We detected a positive spatial association between predator and prey, suggesting that ocelots seek places where agoutis are present. Instead of segregating in space, agoutis appeared to respond to increased predation risk by reduced activity. The most pronounced reduction in agouti activity (i.e. probability of detection) was during twilight in sites where ocelots occurred.

Our results illustrate how jointly modelling interactions in both space and time informs our understanding of predator‐prey coexistence.
Asymmetric backlash against structural economic change: The electoral consequences of the coal phase‐out in Germany
Authors: STUTZMANN SOPHIA
Published: February 2025

Past research has often attributed electoral backlash to structural economic change to a lack of compensation and interest group representation for affected groups. Is that backlash then mitigated in contexts where both of these conditions are fulfilled? I argue that perceived economic deprivation fuelling political disengagement as well as disappointment with the issue‐owning party are important factors contributing to such a backlash. Using the case of Germany, I empirically analyse the electoral repercussions of a coal phase‐out in the presence of compensation for affected groups as well as active involvement of labour and business interests in political decision‐making. By employing a series of staggered difference‐in‐differences models, I investigate whether the closures of coal plants and mines between 2007 and 2022 affected voting behaviour at the municipal level. I find that these closures resulted in an asymmetric backlash in the form of lower vote shares for the issue owner, the Social Democratic Party and higher abstention rates in affected municipalities. With the significant politicisation around fossil fuel‐based energy generation, these findings have important implications for the remaining coal phase‐outs worldwide.
Comparing Outcomes of Per‐Oral Image‐Guided Gastrostomy With Radiologically Inserted Gastrostomy at a Quaternary Australian Hospital
Authors: Denton Matthew , Mitreski Goran , Owen Andrew , Ranatunga Dinesh , Lew Hin Boon , Brooks Duncan Mark , Asadi Hamed , Chin Kwang , Maingard Julian
Published: February 2025

Introduction

Per‐oral Image‐guided gastrostomy (PIG) is an alternative to conventional radiologically inserted gastrostomy (RIG). PIG is less frequently used in Australia, despite a favourable complication profile reported within the literature. This case control study compares success and complication rates of these procedures at a quaternary Australian Hospital.

Methods

Retrospective review of electronic medical records (EMR) was performed for patients undergoing radiological‐guided gastrostomy between January 2019 and January 2023. Clinical notes, operation reports, radiology reports and discharge summaries at the time and for subsequent readmissions within 3 months were reviewed. Outcomes measured included procedural indication, technical success rate, major and minor complications, readmission or death within 3 months.

Results

216 radiological guided gastrostomies were attempted (age 65.6 ± 12.6; range 20–93; 81 female and 135 male). Sixteen cases were abandoned prior to insertion. Gastrostomy was successful in 133/136 PIG (97.8%) and 63/64 RIG (98.4%). The most frequent indication for PIG was dysphagia secondary to Motor Neuron Disease (107/136) and for RIG was head and neck malignancy (41/64). There were significantly more major complications (15.6% vs. 6.6%, p = 0.043) and minor complications (14.0% vs. 2.9%, p = 0.003) with RIG compared to PIG. Tube malpositioning, leak/peritonitis, aspiration pneumonitis and tube dislodgement were significantly increased in RIG. There was no significant difference in readmission rate (5.1% for PIG vs. 9.4% for RIG) or mortality (2.2% vs. 7.8%).

Conclusion

Compared to conventional RIG, PIG showed a similar primary success rate and decreased incidence of both major and minor complications.
Safety and Efficacy of Selective Internal Radiation Therapy for Portal Vein Tumour Thrombus in Advanced Hepatocellular Carcinoma: A Single‐Centre Experience in Australia
Authors: Ormiston William , Samuelson Shaun , Van Wyk Matthys , Calzadilla‐Bertot Luis , Smith Briohny , Garas George , MacQuillan Gerry , Adams Leon A. , Jeffrey Gary P. , Wallace Michael , Tibballs Jonathan
Published: February 2025

Introduction

Portal vein tumour thrombus (PVTT) is a common complication of hepatocellular carcinoma (HCC) and has a poor prognosis. Selective internal radiation therapy (SIRT) with Yttrium‐90 (Y90) microspheres is a minimally invasive treatment option that has shown promise in treating PVTT. Studies have suggested a survival advantage of SIRT in this population, but data in the Australasian population are lacking. The aim of this study was to evaluate the safety and efficacy of SIRT in a series of patients at an Australian hospital with advanced HCC and PVTT.

Method

All patients underwent pre‐treatment imaging with MRI or CT, and immediate post‐treatment imaging with Y90 PET CT and MRIs at 3‐, 6‐, 9‐ and 12‐months. The primary endpoints were time to progression (TTP) and overall survival (OS) post‐SIRT. The secondary endpoint was safety.

Results

Of the 698 patients who underwent SIRT at our institution between 2007 and 2023, 64 patients had HCC and PVTT. 59/64 (92%) were male, with a median age of 61 years (range 37–86 years). The majority of patients had Child–Pugh a cirrhosis (87%), and the majority were ECOG 0 (91%). The majority had main PVTT at the time of SIRT. All patients underwent SIRT with Y90‐coated resin microspheres (SIR‐Spheres, Sirtex Medical, Australia). Personalised dosimetry planning was performed by the treating interventional radiologist. SIRT was well tolerated by most patients, with major complications reported in a minority of cases (19/64 patients had an episode of biochemical decompensation within 90 days following treatment). The median TTP was 4.8 months (range 1–48 months). The median OS was 11.5 months (range 1–80 months), with those with a favourable MAAPE score having a median OS of 21.2 months (12.6–29.7 months).

Conclusions

Our cohort suggests that SIRT is a safe and effective treatment option for a difficult‐to‐treat patient population. Our data suggest a longer OS for those with preserved liver function, good functional status and low AFP levels at 21.2 months. Poor pre‐treatment liver function and functional status are predictors of decompensation, and decompensation is a predictor of poor survival. These data provide an Australasian perspective and support the expanding role of SIRT in HCC treatment guidelines. Further prospective studies with larger sample sizes and longer follow‐up are warranted to confirm these findings.
Impact of nitroglycerin‐induced vasodilation on stroke volume and diuretic response in acute heart failure: A protocol for a mechanistic trial
Authors: Lau Frederik F. , El Caidi Nora Olsen , Hristovska Ana‐Marija , Noory Maryam , Lukoschewitz Jasmin Dam , Hove Jens Dahlgaard , Foss Nicolai Bang , Grand Johannes
Published: February 2025

Background

Acute heart failure is a clinical syndrome characterized by cardiac dysfunction and neurohumoral activation, encompassing complex underlying pathophysiology which may vary across phenotypes. Nitroglycerine is a nitrate donor with vasodilatory effects on both venous capacitance vessels and arterial resistance vessels in higher doses, typically used with the aim of reducing congestion, preload, and afterload. A limited number of studies have proposed that nitroglycerin could promote diuresis and natriuresis. However, the exact hemodynamic effects of nitroglycerin remain uncertain in the clinical setting of acute decompensated heart failure. We hypothesize that intravenous nitroglycerin induces a significant increase in stroke volume and urinary output while lowering cardiac filling pressures.

Methods

This will be a prospective single‐center interventional clinical study of 21 patients hospitalized with a diagnosis of AHF. Patients are examined before and after administration of intravenous nitroglycerin. To characterize hemodynamic phenotypes of AHF, continuous estimates of stroke volume will be obtained, and total blood volume estimated. Vital signs and estimates of peripheral perfusion will be recorded continuously. Measures of cardiac function, renal function, volume status, and autonomic function will be assessed sequentially.

Conclusion

This study will assess the acute effects of vasodilation on stroke volume and urinary output in hospitalized patients with AHF. Furthermore, characterizing the hemodynamic profile of the patient prior to vasodilation may help explore which patients will benefit from vasodilation.
Aging‐Associated Liver Sinusoidal Endothelial Cells Dysfunction Aggravates the Progression of Metabolic Dysfunction‐Associated Steatotic Liver Disease
Authors: Dai Qingqing , Ain Quratul , Seth Navodita , Zhao Hongchuan , Rooney Michael , Zipprich Alexander
Published: February 2025

Aging increases the susceptibility to metabolic dysfunction–associated steatotic liver disease (MASLD). Liver sinusoidal endothelial cells (LSECs) help in maintaining hepatic homeostasis, but the contribution of age‐associated LSECs dysfunction to MASLD is not clear. The aim of this study was to investigate the effect of aging‐associated LSECs dysfunction on MASLD. Free fatty acid–treated AML12 cells were co‐cultured with young and etoposide‐induced senescent TSEC cells to evaluate the senescence‐associated endothelial effects on the lipid accumulation in hepatocytes. In addition, young and aged rats were subjected to methionine‐choline‐deficient diet–induced metabolic dysfunction–associated steatohepatitis (MASH). Hepatic hemodynamics and endothelial dysfunction were evaluated by in situ liver perfusion. Liver tissue samples from young and aged healthy controls and MASH patients were also analyzed. Steatotic AML12 cells co‐cultured with young TSEC cells showed less lipid accumulation, and such effect was abolished by eNOS inhibitor or with senescent TSEC cells. However, co‐culture with resveratrol‐treated senescent TSEC cells could partially resume the NO‐mediated protective effects of endothelial cells. Furthermore, aged MASH rats showed more severe liver injury, steatosis, fibrosis, and endothelial and microcirculatory dysfunction. In addition, aged MASH patients showed more pronounced liver injury and fibrosis with lower hepatic eNOS, p‐eNOS, and SIRT1 protein levels than in young patients. Senescence compromises the protective effects of LSECs against hepatocyte steatosis. In addition, aging aggravates not only liver steatosis and fibrosis but also intensifies LSECs dysfunction in MASH rats. Accordingly aged MASH patients also showed endothelial dysfunction with more severe liver injury and fibrosis.
Which grading system better predicts 28‐day mortality in nontraumatic subarachnoid hemorrhage: Traditional clinical scores or combined grading systems?
Authors: Az Adem , Sogut Ozgur , Altinbilek Ertugrul , Oral Irem Yildirim , Calik Mustafa , Metiner Merve , Coskun Abuzer , Demirci Burak , Guven Ramazan , Altug Ertugrul , Durmus Burcu , Hokenek Nihat Mujdat , Tekedereli Eymen
Published: February 2025

Background

The objective was to investigate the predictive ability of traditional clinical, radiological scores, and combined grading systems for 28‐day mortality in patients with nontraumatic subarachnoid hemorrhage (SAH).

Methods

This multicenter cohort study enrolled 451 adults who presented to the emergency departments of six major tertiary care hospitals in Istanbul with nontraumatic aneurysmal SAH. Demographic data; clinical characteristics; and traditional clinical grading scores were recorded, including the Glasgow Coma Scale (GCS), Hunt and Hess scale (HHS), World Federation of Neurological Surgeons (WFNS) scale, modified Fisher scale (mFS), and two combined grading systems, the VASOGRADE and Ogilvy–Carter scales. These data were compared between survivors and nonsurvivors.

Results

A total of 451 patients were included, comprising 242 males (53.7%) and 209 females (46.3%), with a mean ± SD age of 54.8 ± 14.1 years. The overall mortality rate was 28.2% (n = 127). Nonsurvivors had significantly lower mean GCS scores and higher HHS, WFNS, mFS, and Ogilvy–Carter scores compared to survivors (all p < 0.001). A significantly higher proportion of nonsurvivors were categorized in the red group based on VASOGRADE (p < 0.001). Multivariable logistic regression analysis identified age, sex, HHS, mFS, WFNS, and VASOGRADE as independent predictors of mortality. The WFNS scale emerged as the most reliable predictor of mortality with an area under the curve of 0.878.

Conclusions

Although the GCS and Ogilvy–Carter scales effectively distinguished survivors from nonsurvivors, they were not independent predictors of mortality. The WFNS scale was identified as the most reliable predictor of mortality in aneurysmal SAH patients, followed by the mFS and HHS.
Don't Stand So Close: Social Crowding Negatively Impacts Reproduction in an Endangered, Territorial Hawaiian Bird
Authors: Flanagan A. M. , Masuda B. , Bailey H. , Swaisgood R. R.
Published: February 2025

Conservation breeding programs (CBPs) can play a vital role in preventing extinction. Housing considerations are particularly important in CBPs because suboptimal enclosures can negate efforts to promote animal well‐being, survival, reproduction, and the retention of natural behaviors. Moreover, the quality and quantity of enclosures also influence the social environment experienced by animals, an important determinant of reproduction. Extinct in the wild, the territorial ‘Alalā (Hawaiian crow, Corvus hawaiiensis) is the subject of intensive conservation breeding at two purpose‐built facilities in Hawai'i. To examine the role of space and social environment in this CBP, we evaluated reproductive outcomes for ‘Alalā pairs held in different‐sized enclosures (i.e., housed in one vs. two chambers within a stand‐alone aviary building), corresponding to important differences in social context, including the amount of space and enclosure architecture available for the pair, which we label “social crowding.” We tested the hypothesis that social crowding adversely impacts nest quality, clutches laid, egg fertilization, and hatching success. We found social crowding negatively impacted nest quality and decreased the probability of clutch production, suggesting that stress, derived from being housed in a social arrangement that does not align with the territorial nature of ‘Alalā, may compromise reproductive behavior and/or physiology. We did not find statistical evidence that crowding affected egg fertilization or hatching success, thus the impacts of crowding appear to manifest during the earlier reproductive stages. Broadly, our findings underscore the importance of aviary design and social context in avian CBPs and raise concerns about reduced breeding output due to housing territorial birds in smaller enclosures with denser social arrangements. Furthermore, our findings can guide decisions about strategic housing of pairs in aviaries and identify solutions that mitigate the consequences of social crowding on reproductive success.
Coding with a transdisciplinary team – A project exploring unhealthy urban development
Authors: Barnfield Andrew , Bates Geoff
Published: February 2025

We are a geographer and a public policy researcher who share an interest in public health. In this paper we will explore coding in thematic analysis in a transdisciplinary qualitative study. We begin by introducing a moment from our 16‐week coding phase to identify the challenges in working across disciplines on qualitative analysis. Transdisciplinary research is about meeting in space and time – between disciplines and ideas, currents of thought – and producing something greater than the sum of its parts. It creates challenges for producing good quality research while maintaining team cohesion. In discussing our coding practices and procedures, we highlight how paying attention to team dynamics and atmosphere creation is fundamental for working in large groups.
The relationship between trait‐ and state‐math anxiety and math engagement: The role of math learning context and task difficulty
Authors: Guo Siwen , Liao Shanhui
Published: February 2025

Background

Various findings regarding the relationship between math anxiety and engagement have been identified in the literature, with many focusing on general math anxiety and overall math engagement.

Objectives

Based on the control‐value theory, this study examined the relationships between trait‐ and state‐math anxiety and behavioural and cognitive engagement in math under daily practice and exam preparation conditions across math tasks of varying difficulty levels.

Methods

A survey study with 449 high school students and an experimental study with 33 freshmen were conducted. Students' trait‐ and state‐math anxiety, as well as behavioural and cognitive engagement in math, were measured under daily practice and exam preparation conditions across easy and difficult math tasks.

Results

A two‐level latent variable model was built in the survey study, and two‐way ANOVAs and regressions were used in the experimental study. Students exhibited greater state anxiety under exam preparation conditions in the survey study and showed differences in state‐math anxiety and engagement across learning contexts and math tasks in the experimental study. Students with higher trait‐math anxiety displayed less engagement in both studies, while those with higher state‐math anxiety when facing difficult tasks tended to engage more cognitively in the experiment.

Conclusions

These findings demonstrated discrepancies in the relationships between trait‐ and state‐math anxiety and math engagement, while accounting for learning context and task difficulty.
Characterisation of vent designs in flexible and navigable suction ureteric access sheaths
Authors: Menzies‐Wilson Richard , Williams Jessica , Rhodes Candace , Abbott Alycia , Ruiken Thijs , Turney Benjamin
Published: February 2025

Objectives

To evaluate the different vent designs in three commercially available flexible and navigable suction (FANS) access sheaths—ClearPetra® (Well lead, Guangzhou, China), Elephant II (YIGAOMedical, Hangzhou, China) and Tuohy‐Borst FANS access sheath (Seplou, Zhejiang, China)—and quantify the effects these differing designs have on the control of suction.

Methods

We conducted benchtop experiments to quantify the effect of pressure vent design on suction pressure control. Suction experiments were conducted both in an atmospheric beaker and in a phantom kidney model. With an indwelling 9.5‐F LithoVue™ (Boston Scientific, Marlborough, MA, USA) ureteroscope, constant suction was applied to the access sheath's suction port. The vents were incrementally closed and corresponding flow rates calculated as a proxy for suction pressure. A mathematical model was developed to predict the impact of pressure control vent design on suction pressure control, flow rates and intrarenal pressure.

Results

For both the ClearPetra and Elephant II suction access sheaths, opening the length of the vent has an exponential reduction in suction pressure. Negligible suction is exerted on the renal pelvis with ≥3 mm of vent open. The Seplou suction access sheath has a Tuohy‐Borst pressure vent, which allows finer control of suction pressures. The mathematical model showed strong agreement with experimental data.

Conclusion

Commercially available FANS access sheaths are similar in most aspects but have differing vent designs. With the vents open no suction is exerted on the renal collecting system. However, because the flexible access sheath intrarenal end is within the renal pelvis, outflow resistance is low and the pelvis will deflate, giving the impression of suction. We have developed a mathematical model that predicts flow at different suction pressures and with different degrees of the pressure vents open. This allows simulations across multidimensional parameter spaces and the resulting quantitative predictions can be exploited to assess the implications of FANS access sheath and ureteroscope design.
System level network data and models attack cancer drug resistance
Authors: Kerestély Márk , Keresztes Dávid , Szarka Levente , Kovács Borbála M. , Schulc Klára , Veres Dániel V. , Csermely Peter
Published: February 2025

Drug resistance is responsible for >90% of cancer related deaths. Cancer drug resistance is a system level network phenomenon covering the entire cell. Small‐scale interactomes and signalling network models of drug resistance guide directed drug development. Recently, proteome‐wide human interactome and signalling network data have become available, which have been extended by drug–target interactions, drug resistance‐inducing mutations, as well as by several cancer and drug resistance‐related multi‐omics datasets. System level signalling network models have become available examining therapy resistance, performing in silico clinical trials, and conducting large, in silico drug combination screens. Drug resistance network data and models have become interoperable and reliable. These advances paved the road for building proteome‐wide drug resistance models.
LncRNA‐MEG3 Mediated Diabetic Cerebral Ischemia–Reperfusion Injury‐Induced Apoptosis via Modulating Interaction Between Annexin A2 and Akt in Mitochondria
Authors: Zhou Wanqing , Tan Chongyi , Xiong Di , Chen Cheng , Zhao Yanfei , Xie Yongqiu , Sun Bei , Wang Zhihua , Xia Pingping , Ye Zhi
Published: February 2025

Background

In clinical domains, encompassing neurosurgery and macrovascular cardiac procedures, certain interventions result in cerebral ischemia‐ reperfusion injury (CIRI). Diabetes mellitus (DM) increases the risk of CIRI and worsens the severity of neurological impairment. It was documented that lncRNA‐MEG3 contributed to the pathogenesis of CIRI. However, the pivotal significance of lncRNA‐MEG3 in diabetic CIRI has never been studied.

Aims

This study's aims were two‐fold, to (1) figure out the influence of lncRNA‐MEG3 on neurological dysfunction subsequent to diabetic cerebral ischemic injury, (2) elucidate its potential role in mitochondria‐related apoptosis via modulating the Anxa2 signaling pathway.

Materials and Methods

We mainly collected plasma from clinical patients to measure the expression of lncRNA‐MEG3, and explored the molecular mechanism of lncRNA‐MEG3 in CIRI combined with DM by immunofluorescence, western blot, co‐ip and other molecular biology experiments in rat MACO+DM model and cellular OGD/R+HG model.

Results

LncRNA‐MEG3 expression in DM+AIS cases was remarkably higher than that in cases with AIS and healthy controls. Moreover, lncRNA‐MEG3 expression was strongly linked to the National Institutes of Health Stroke Scale (NIHSS) score. Additionally, the findings unveiled that lncRNA‐MEG3 depletion alleviated neurological impairments following CIRI in diabetic rats, and cellular death resulted from Oxygen‐glucose deprivation (OGD) plus hyperglycemic reperfusion in rat brain microvascular endothelial cells (RBMVECs) that was concomitant with the increased phosphorylation of Annexin A2 (Anxa2) at Tyr23. Meanwhile, over expression of Anxa2, identified as a lncRNA‐MEG3‐associated mitochondrial protein, remarkably suppressed mitochondria‐derived apoptosis. Importantly, lncRNA‐MEG3 knockdown enhanced the mitochondrial translocation of Anxa2 via promoting its phosphorylation at Tyr23 in OGD+HG‐treated RBMVECs. Furthermore, Anxa2 enhanced Akt phosphorylation at Ser473 and bound to Akt in mitochondria, which was involved in lncRNA‐MEG3 depletion‐induced neuroprotection. However, lncRNA‐MEG3 mobilized to mitochondria in a Plectin‐dependent manner and subsequently impeded the interaction between p‐Anxa2 and p‐Akt.

Discussion and Conclusion

The outcomes provided clinical evidence that lncRNA‐MEG3 appeared as an unfavorable prognostic factor for diabetic CIRI and revealed that lncRNA‐MEG3 knockdown could be protective against diabetic CIRI‐induced mitochondria‐related apoptosis through modulating Anxa2 binding to Akt in mitochondria.