bluuebunny/crossref_metadata_2025 huggingface dataset:
Equity and Longitudinal Assessments: Perspectives from Physician Assistants/Associates (PAs) Participating in PANRE-LA
Authors: Kozikowski Andrzej , Goodman Joshua , Dallas Andrew , Jiang Yanlin
Published: February 2025

Introduction

Longitudinal assessments (LAs) may offer more flexibility and unique opportunities to enhance equity. Although prior findings on LAs demonstrate that they foster learning, limited research exists on potential differences in examinee perspectives by demographics and practice characteristics. Addressing this research gap is vital to ensuring that examinees from different backgrounds equally derive learning benefits from LAs.

Methods

We evaluated potential differences in perspectives and experiences of physician assistants/associates (PAs) participating in the PA National Recertifying Examination Longitudinal Assessment (PANRE-LA) program, considering a wide range of demographic and practice characteristics.

Results

Over 90% agreed that this type of assessment provides a learning experience, helps to identify gaps, provides an opportunity to improve, aligns with a lifelong learning perspective, and keeps core medical knowledge up-to-date. Approximately 84% believed it helps them to be a better practitioner, and 78.7% either anticipated or had applied learning from PANRE-LA to their clinical practice.

Discussion

Our findings suggest that PAs across diverse demographics and practice characteristics equally derive self-reported learning benefits from PANRE-LA. LAs, due to their formative components, may provide unique opportunities to promote equity in knowledge acquisition, foster continuous learning, and ultimately contribute to improved patient care.
Exact particle flow Daum-Huang filters for mobile robot localization in occupancy grid maps
Authors: Csuzdi Domonkos , Bécsi Tamás , Gáspár Péter , Törő Olivér
Published: February 2025

In this paper, we present a novel localization algorithm for mobile robots navigating in complex planar environments, a critical capability for various real-world applications such as autonomous driving, robotic assistance, and industrial automation. Although traditional methods such as particle filters and extended Kalman filters have been widely used, there is still room for assessing the capabilities of modern filtering techniques for this task. Building on a recent localization method that employs a chamfer distance-based observation model, derived from an implicit measurement equation, we explore its potential further by incorporating exact particle flow Daum–Huang filters to achieve superior accuracy. Recent advancements have spotlighted Daum–Huang filters as formidable contenders, outshining both the extended Kalman filters and traditional particle filters in various scenarios. We introduce two new Daum–Huang-based localization algorithms and assess their tracking performance through comprehensive simulations and real-world trials. Our algorithms are benchmarked against various methods, including the widely acclaimed Adaptive Monte–Carlo Localization algorithm. Overall, our algorithm demonstrates superior performance compared to the baseline models in simulations and exhibits competitive performance in the evaluated real-world application.
A Technique to Solve a Parabolic Equation by Point Symmetries that Incorporate Initial Data
Authors: Jamal Sameerah , Maphanga Rivoningo
Published: February 2025

In this paper, we show how transformation techniques coupled with a convolution integral can be used to solve a generalised option-pricing model, including the Black–Scholes model. Such equations are parabolic and the special convolutions are extremely involved as they arise from an initial value problem. New symmetries are derived to obtain solutions through an application of the invariant surface condition. The main outcome is that the point symmetries are effective in producing exact solutions that satisfy a given initial condition, such as those represented by a call-option.
Does Attending Work When Ill Vary Across Different Office Concepts? A Bayesian Analysis of Differences in Sickness Presenteeism using Nationally Representative Data
Authors: Borge Randi Hovden , Johannessen Håkon A. , Fostervold Knut Inge , Nielsen Morten Birkeland
Published: February 2025

Several studies have examined how sickness absence varies across different office concepts, but the potential role of sickness presenteeism (i.e., attending work when faced with health complaints) is poorly understood. We discuss how different office concepts may influence the decision between attending and not attending work when faced with health complaints, and the implications this may have for how observed differences in sickness absence are interpreted. We then use data from a nationwide probability sample from Norway (N = 3112) to explore (i) differences in presenteeism among employees in different office concepts with and without assigned workstations (i.e., private, conventional shared-room, conventional open-plan, non-territorial) and (ii) whether and how perceived health status moderates these differences. Based on a frequency measure of presenteeism, we infer about likely differences in presenteeism propensity by adjusting for perceived health status and self-certified sickness absence, in addition to important demographic and occupational covariates. Results from Bayesian cumulative probit models indicated similar levels of presenteeism among employees in private and conventional shared-room and open-plan offices and lower levels among employees in non-territorial offices. Differences in presenteeism between private and non-territorial offices increased as perceived health status deteriorated. Our study represents an important step towards a complete picture of attendance patterns across different office concepts. Our findings suggest that whether you have a personalized workstation may be relevant for attending or not attending work when faced with health complaints. Future studies should take this into account when interpreting differences in sickness absence observed across office concepts.
Systematic review and meta-analysis of acaricidal properties of plant derived products against Ixodid ticks population
Authors: Bisht Nisha , Fular Ashutosh , Ghosh Srikanta , Nanyiti Sarah
Published: February 2025

Application of plant extracts and plant-based formulations is one of the sustainable methods for the management of resistant ticks and thus managing the tick-borne diseases. In the present study, we comprehensively analyzed the research papers based on the acaricidal activity of plant extracts. A meta-analysis was conducted with an aim to highlight the potential candidates for further research for the development of ecofriendly and sustainable anti-tick herbal formulations. A total of 52 papers were analyzed up until December 2023, sourced from extensive searches of databases such as PubMed, Scopus, Science Direct and Google Scholar, focusing on the acaricidal activity of various plants against tick species. The plants belonging to Annonaceae and Burseraceae families were found significantly effective against ticks. Amongst the tick species, Rhipicephalus microplus was the highly studied tick species followed by Haemaphysalis bispinosa and Hyalomma dromedarii. The most responsive tick species to plant extracts were Hyalomma dromedarii and Ambylomma cajannense. With respect to the parts of the plants used, leaf (45%) was extensively utilized while the extracts prepared from the resin, stem and fruit peel of the plant showed highest acaricidal activity. The present study highlighted significant variability in the effectiveness of plant extracts depending on the plant species, plant parts used, type of extractant, and the tick species tested. These findings emphasize the need to develop a Standard Operating Protocol (SOP) for evaluating phytocompounds. Future research should prioritize isolating active compounds, elucidating their mechanisms of action, and optimizing formulations to ensure sustainable and effective tick management strategies.
Metabolic Responses of Eccentric Accentuated Flywheel Squats by a Multi-set Protocol with Increasing Loads
Authors: Neuendorf Tilo , Kaden Maurice , Wachler Ellen , Schumann Moritz , Nitzsche Nico
Published: February 2025

Inertia-based resistance exercise with flywheels leads to strong acute metabolic responses. However, the metabolic kinetics during a multi-set flywheel squat protocol with increasing loads remains unknown. The aim of the study was to assess the course of blood lactate concentrations (BLC), oxygen uptake (VO2), heart rate (HR) and power during a multi-set protocol of flywheel squat training. Seventeen recreationally trained healthy men (24.3 ± 3.8 years, BMI 24.1 ± 2.2, VO2max 49.4 ± 6.9 mL/min/kg) completed 5 sets and 15 repetitions flywheel squats. The BLC (ŋ
2 = 0.932), VO2 (ŋ
2 = 0.899) and HR (ŋ
2 = 0.879) increased significantly over the sets (P < 0.05). %HRmax and %VO2max increased significantly from pre to post-loading (P < 0.001), reaching a threshold of 80% HRmax after set 2 and 60% VO2max after set 4, respectively. The power parameters PMEAN (ŋ
2 = 0.191), PECC (ŋ
2 = 0.149) and PCON (ŋ
2 = 0.062) showed significant decreases after set 2 (P < 0.05). A multi-set flywheel squat protocol with increasing loads leads to high metabolic and cardiorespiratory demands, which appear to increase linearly with an increase in inertial load.
Short-term health effects of tear agents chlorobenzylidenemalononitrile and oleoresin capsicum during the civil riots of Santiago de Chile in 2019–2020
Authors: Jara Bravo Carlos , Cernuda Martínez José Antonio , Arcos González Pedro
Published: February 2025

Chlorobenzylidenemalononitrile (CS) and Oleoresin Capsicum (OC) were tear gasses used as anti-riot control agents during social unrest riots in Chile (October 2019–March 2020). This study posed as a research question what were the short-term health effects of CS and OC and their patterns of temporal occurrence in a sample of inhabitants and health care volunteer brigades of the Plaza Italia (city of Santiago, Chile) during the riots. A retrospective cross-sectional study was conducted in 112 exposed people (inhabitants and health care volunteers) affected by CS and OC. 62 harmful effects were studied classified in three time periods of occurrence: immediate effects (between exposure and one hour), secondary effects (from one hour after exposure and up to 24 h), and subsequent effects (days after exposure). The use of CS and OC in Santiago riots 2019–2020 produced harmful effects on both groups: inhabitants and brigade health care volunteers. The frequency of effects was, from most to least common: 62.5% eye pain or burning, 56.2% throat irritation, 54.4% respiratory distress, 52.6% skin pain or burning, 51.7% impaired vision, 37.5% skin erythema, 31.2% headache, 31.2% irregular breathing, 25.8% conjunctival injection, 29.4% nausea, 27.6% disorientation, 26.7 high blood pressure, 25.8% lip pain, 24.1% rhinitis, 24.1% skin sensitivity, 22.3% diarrhea, 20.5% contact dermatitis, 18.7% conjunctivitis, 16.9% skin vesicles, 16% tachycardia, 14.4 cough with phlegm and 9.8% corneal abrasion. 22 effects were more frequent (p < 0.05) in health care volunteers than among residents. High blood pressure was more frequent (p < 0.05) among residents. Immediate most frequent effects were pain or burning, impaired vision, respiratory difficulty, irregular breathing, skin pain and burning, skin erythema, nausea, tachycardia, and hypertension. Secondary effects were diarrhea, skin vesicles, and eye pain or burning. Subsequent most frequent effects among healthcare personnel were conjunctivitis, skin pain, burning, rhinitis, and diarrhea. Among residents, the most common effects were skin pain, burning, and impaired vision.
An exploratory prospective observational study of muscle cross-sectional area changes and energy balance in critically ill children: avoiding negative energy balance is necessary but not sufficient to maintain muscle mass in critically ill children
Authors: Mtaweh Haifa , Fuerte Keane , DeLorenzo Stephanie , Zoica Bogdana S. , Hulst Jessie M. , Floh Alejandro , MacDonald Cathy , Parshuram Christopher
Published: February 2025

Rationale

Muscle loss in critically ill children is likely multifactorial and linked to illness severity, immobility, and nutrition. Muscle ultrasound (US) is increasingly used to assess muscle changes, but studies using inaccurate energy expenditure equations have not consistently linked nutrition and muscle mass changes.

Objectives

To evaluate longitudinal change in muscle cross-sectional area (CSA) in critically ill children and explore its relationship with energy balance.

Methods

This nested prospective observational study enrolled intubated children (1month-18 years) eligible for indirect calorimetry measurements. Indirect calorimetry measurements were paired with two US measurements of the biceps brachii and rectus femoris. Percent change in muscle CSA and energy balance (%difference between energy expenditure and caloric delivery/energy expenditure) were calculated. Mann-Whitney tests compared energy balance between groups with and without muscle loss. Spearman correlation assessed the relationship between daily energy balance and muscle CSA.

Results

Energy expenditure and muscle CSA were measured in 23 patients (median age 6.2 years; 61% males). The rectus CSA decreased by a median (Q1, Q3) of 1.5% (-2.93, 0.83) per day, with greater losses in patients with negative energy balance (p = 0.03). Patients with energy balance ≤ -5% had a median change in rectus CSA of -18.7% (-22.9, -8.1). Daily change in rectus CSA and energy balance showed a moderate correlation (r = 0.59, p = 0.01). The rate of change in the biceps CSA was 0.28% (-4.67, 1.65) per day with no correlation with energy balance.

Conclusions

Muscle loss persists beyond the first week of critical illness and may be associated with energy deficits. Precision in nutrition and further study of muscle changes are needed to mitigate ICU-acquired morbidity.
J. Krishnamurti
Authors: Jones Constance A.
Published: February 2025

This Element explores the life, teaching, and legacy of philosopher and spiritual teacher Jiddu Krishnamurti. From an obscure childhood in south India, he was 'discovered' at age fourteen by the Theosophical Society as the vehicle for the prophesied World Teacher of this cosmic age. At age 34, he disaffiliated from the Society, became an independent teacher, and, for sixty years, traveled widely and addressed thousands of audiences on the need to develop awareness and attention for transformation of consciousness. His teaching defines the human condition as perilous, dominated almost completely by cultural and personal conditioning, fear, and negative emotions. Freedom from these perils, his teaching states, occurs through rigorous self-observation and inquiry in the search for truth. While extremely popular, Krishnamurti rejected the mantle of authority invariably attributed to spiritual masters and teachers. He created schools in his name to implement his pedagogy of non-authoritarianism and freedom from conditioning.
An Introduction to Solid Mechanics
Authors: Roy Chowdhury S. K. , Sahoo Prasanta
Published: February 2025

Solid Mechanics, as compared to Mechanics of Materials or Strength of Materials, is generally considered to be a higher-level course. It is usually taught in higher semesters to senior undergraduate students. However, there is no suitable textbook on this subject. The book is primarily aimed at this group of students and the text is an attempt to bridge the gap between complex formulations in the theory of elasticity and elementary strength of materials in a simplified manner. The book is intended to present the basics of Solid Mechanics in a simple and concise manner to the initial learners. A large number of solved problems on each topic have been included to illustrate the text materials. Because of the simpler approach adopted in solving difficult problems, the book will be useful for all student groups who wish to learn the basic solid mechanics without much difficulty.
Athens, 403 BC
Authors: Azoulay Vincent , Ismard Paulin , Osborne Robin
Published: February 2025

At the end of the fifth century BC, the Peloponnesian War resulted in Athens' shattering defeat by Sparta. Taking advantage of the debacle, a commission of thirty Athenians abolished the democratic institutions that for a century had governed the political life of the city and precipitated a year-long civil war. By autumn 403 BC, democracy was restored. Inspired by the model of the ancient chorus, this strikingly innovative book interprets a crucial moment in classical history through the prism of ten remarkable individuals and the shifting groups which formed around them. The former include more familiar names like the multifaceted Sokrates, the oligarch Kritias and the rhetorician Lysias, but also lesser-known figures like the scribe Nikomachos, the former slave Gerys and the priestess Lysimakhe. What leads a community to tear itself apart, even disintegrate, then rebuild itself? This question, explored through profound reflection on the past, echoes our tormented present.
German Syntax
Authors: Müller Gereon
Published: February 2025

Exploring the major syntactic phenomena of German, this book provides a state-of-the-art account of German syntax, as well as an outline of the key aspects of Chomsky's Minimalist Program. It is one of the first comprehensive studies of the entire syntactic component of a natural language within the Minimalist Program, covering core issues including clause structure, binding, case, agreement, control, and movement. It introduces a phase-based theory of syntax that establishes Remove, an operation that removes syntactic structure, as a mirror image of Merge, which builds syntactic structure. This unified approach resolves many cases of conflicting structure assignments in syntax, as they occur with passivization, restructuring, long-distance passivization, complex prefields, bridge verbs, applicatives, null objects, pseudo-noun incorporation, nominal concord, and ellipsis. It will pave the way for similar research into other languages and is essential reading for anyone interested in the syntax of German, syntactic theory, or the Minimalist Program.
Transdisciplinary Shakespeare Pedagogy
Authors: Heijes Coen
Published: February 2025

Building on a general trend in academia towards convergence in teaching and research, in which interdisciplinarity and relevance are cornerstones, Transdisciplinary Shakespeare Pedagogy offers a sense both of the opportunities and challenges in teaching Shakespeare beyond the confines of the English literature department by setting up structural partnerships across disciplinary units and provides possible ways forward on the road to wider cooperation, collaboration and integration between curriculums, teachers and students of different disciplines. With Shakespeare studies increasingly under fire, the author analyses, through four recent case studies of university courses for a variety of students, the potential for integration of Shakespeare studies, social sciences and societal challenges.
Luke's Unique Parables
Authors: Carmichael Calum
Published: February 2025

Calum Carmichael presents a new perspective on how parables unique to Luke's Gospel were composed. These parables took up moral issues that arose out of conflicts among figures such as Jacob and Esau, Joseph and his brothers, Judah and Tamar as portrayed in Genesis narratives. Providing literary and linguistic analyses, Carmichael demonstrates how Luke, like many of his contemporaries, absorbed the narrative legacy of the Hebrew Bible and used it to express ideas about Jesus. The Joseph story was of particular interest to Luke because Joseph's role during the Egyptian famine resulted in the rescue of his family, thereby giving the Israelite nation a future. Carmichael's radically different approach identifies the influence of ancestral wrongdoing on how Luke portrayed Jesus' moral teaching.
Elliptic Curves
Authors: McKean Henry , Moll Victor , Kasman Alex
Published: February 2025

The subject of elliptic curves is one of the jewels of nineteenth-century mathematics, originated by Abel, Gauss, Jacobi, and Legendre. This book, reissued with a new Foreword, presents an introductory account of the subject in the style of the original discoverers, with references to and comments about more modern developments. It combines three of the fundamental themes of mathematics: complex function theory, geometry, and arithmetic. After an informal preparatory chapter, the book follows an historical path, beginning with the work of Abel and Gauss on elliptic integrals and elliptic functions. This is followed by chapters on theta functions, modular groups and modular functions, the quintic, the imaginary quadratic field, and on elliptic curves. Requiring only a first acquaintance with complex function theory, this book is an ideal introduction to the subject for graduate students and researchers in mathematics and physics, with many exercises with hints scattered throughout the text.
Why Do We Want a Theory of Quantum Gravity?
Authors: Crowther Karen
Published: February 2025

The search for a new scientific theory is typically prompted by an encounter with something in the world that cannot be explained by current theories. This is not the case for the search for a theory of quantum gravity, which has been primarily motivated by theoretical and philosophical concerns. This Element introduces some of the motivations for seeking a theory of quantum gravity, with the aim of instigating a more critical perspective on how they are used in defining and constraining the theory sought. These motivations include unification, incompatibilities between general relativity and quantum field theory, consistency, singularity resolution, and results from black hole thermodynamics.
Kodaira–Spencer isomorphisms and degeneracy maps on Iwahori-level Hilbert modular varieties: the saving trace
Authors: Diamond Fred
Published: February 2025

We consider integral models of Hilbert modular varieties with Iwahori level structure at primes over p, first proving a Kodaira–Spencer isomorphism that gives a concise description of their dualizing sheaves. We then analyze fibres of the degeneracy maps to Hilbert modular varieties of level prime to p and deduce the vanishing of higher direct images of structure and dualizing sheaves, generalizing prior work with Kassaei and Sasaki (for p unramified in the totally real field F). We apply the vanishing results to prove flatness of the finite morphisms in the resulting Stein factorizations, and combine them with the Kodaira–Spencer isomorphism to simplify and generalize the construction of Hecke operators at primes over p on Hilbert modular forms (integrally and mod p).
Value and Implementation of Patient and Public Involvement and Engagement in Health Technology Assessment for Japan: implications from systematic searches
Authors: Kaneyasu Takako
Published: February 2025

Objectives

This study comprehensively reviewed reports on patient and public involvement and engagement (PPIE) in health technology assessment (HTA) overseas and identified the status and possible future measures, of PPIE in Japanese HTA.

Methods

The series of reviews targeted systematic reviews (SR#1), references in SR#1 (SR#2), and new articles after SR#1 (SR#3). The MEDLINE and Embase databases were searched through August 2024 using the terms “patient involvement/engagement,” “patient participation,” “community participation,” “public involvement/engagement,” and “health technology assessment.” The implementation details were extracted from information published on the websites of the HTA agencies.

Results

Three review articles in SR#1, 12 references in SR#2, and 10 articles in SR#3 were selected. The opportunities for countries, including Japan, to participate in discussions on the HTA process did not differ significantly; however, information on PPIE in Japan was scarce and did not indicate their purpose and value.

Conclusions

Collected articles indicated that the value of PPIE in HTA includes relevance, equity, fairness, legitimacy, and capacity building. The participation of patient and public representatives in Japanese discussions since 2005 appeared to be very limited to consider PPIE in HTA. In countries that implement PPIE in HTA, the value of PPIE is explicit: the process guidelines are specific and provide an appropriate environment for input that includes education, training, and feedback. Future reforms of the Japanese system will require discussions on PPIE purpose and value, implementation, and creating an environment in which a diverse range of patients and the public can easily express their views.
Percutaneous closure of anomalous left coronary artery from pulmonary artery rare procedure in desperate situation: case report
Authors: Kamran Mirza Mohd , Gopi Arun , Das Saurabhi , Lakhani Zeeshan , Sheikh Amira , Musthafa Janeel , Raghuram G. , Mohammad Musthafa P.P.
Published: February 2025

Background:

When anomalous left coronary artery from the pulmonary artery is diagnosed in infancy, it is associated with high mortality, but collaterals permit rare adult survival despite coronary steal. We report normalisation of perfusion abnormality after transcatheter proximal left coronary occlusion in a symptomatic adult with inducible ischaemia.

Methods:

A forty-eight-year-old female presented with exertional chest pain; EKG showed sinus rhythm with left axis deviation with intraventricular conduction defect. Echocardiogram diagnosed an anomalous left coronary artery arising from the pulmonary artery with normal ventricular function which was further confirmed by CT. The case was discussed with the surgical team, and it was decided to surgically ligate. The patient did not give consent for the surgical procedure; the patient was taken up for the procedure.

Results:

Device was released safely after confirming the position on echocardiogram after the procedure showed improvement in intraventricular conduction defect and QTc duration, and also no significant ischaemic changes were noted. Myocardial perfusion scintigraphy was done after 6 months of procedure which showed improvement in contractile function and perfusion of left ventricle.

Conclusions:

Device closure in long-standing anomalous left coronary artery from pulmonary artery case is safe, and long-term follow-up is needed.
AI in Education – Promise, Peril and a Path Forward
Authors: Leopold Matthew
Published: February 2025

LexisNexis’ Matthew Leopold explains how his team conducted a wide range of interviews with those involved in the legal education system – including librarians, academics, heads of law schools and university leaders – in order to gauge their feelings and thoughts on the impact artificial intelligence (AI) will have, and is having, on the sector. Matthew then goes through the findings, which shows a diverse set of views on AI.
Access to Legal Information Through Public Libraries in England and Wales
Authors: Reader Abi
Published: February 2025

England and Wales have no public law libraries, so how does the general public find legal information? This article, written by Abi Reader, Assistant Librarian at Certara Predictive Technologies, provides a starting point in understanding the availability of publicly available legal information. It explores the intersection of two austerity measures, cuts to legal aid and public library spending, through searching public library catalogues for primary sources of law. Public libraries provide computers and internet access to search free online legal information sites but overall provide limited access to print law reports. This article is based on research presented at the 54th Annual BIALL Conference.
Kintsugi in Knowledge Management: a Call to Arms from Three Conference Experiences to Empower Law Firm Knowledge Managers to Navigate AI Projects and Embrace Imperfection
Authors: Russell Hélène
Published: February 2025

The Japanese art of Kintsugi teaches that imperfections and failures are not flaws to hide but opportunities for growth and enrichment; it says that true strength and beauty come from embracing imperfection and learning from the fractures along the way. In this article Hélène Russell draws on insights from three conference experiences to show how KM professionals can make use of Kintsugi and act as the ‘golden joiners’ within their firms when it comes to AI projects, making use of their blend of resilience, organisational cultural awareness, communication skills, and adaptive knowledge-sharing practices.
“It seemed I was having a conversation with him”: Posthumous Dignity Therapy case series
Authors: Julião Miguel , Simões Carolina , Chochinov Harvey Max
Published: February 2025

Objectives

Dignity Therapy (DT) is a brief psychotherapeutic intervention designed to address the psychosocial and spiritual needs of terminally ill patients. Research demonstrates DT’s efficacy in reducing dignity-related distress and alleviating psychosocial symptoms like depression and anxiety in terminally ill patients. Its application has been extended to nonterminal patients with chronic conditions, mental health challenges, and children nearing the end of life, with promising results. DT also benefits families and caregivers, promoting emotional resilience and facilitating grieving. However, the potential for proxy applications, such as posthumous DT (p-DT) – conducted by relatives after a patient’s death or on behalf of individuals unable to participate – remains underexplored.

Methods

A case series report.

Results

This case series examines 3 relatives who engaged in p-DT, highlighting its feasibility and potential benefits.

Significance of results

Findings suggest p-DT may serve as a valuable tool for bereavement support, warranting further research to expand its scope and accessibility.
Science behind policy: implementing a modern circumference-based body fat equation with a physical fitness threshold is associated with lower musculoskeletal injury risk
Authors: McClung Holly L. , Bartlett P. Matthew , Spiering Barry A. , Foulis Stephen A. , Oliver Tyler E. , Walker Leila A. , Nguyen Vy T. , Proctor Susan P. , McClung James P. , Taylor Kathryn M.
Published: February 2025

Background

Body composition influences physical fitness (PF) and risk of musculoskeletal injury (MSKI). Assessing the relationship between body fat (BF), PF and MSKI risk in a large diverse military population may provide evidence basis informing health-care policies, practices, and programs for military and civilian populations.

Objective

Evaluate the validity of expedient methods to estimate BF (e.g., circumference-based equation (CBE) and bioelectrical impedance analysis (BIA)) and investigate relationships between BF and PF with MSKI risk in a large diverse population.

Methods

Participants were 1904 active-duty Soldiers (643 F) representing Army demographics sex, race/ethnicity (R/E), and age. PF, defined as the most recent Army Combat Fitness Test (ACFT) score and incidence of MSKI, were obtained from Army records. BF was determined by dual-energy x-ray absorptiometry (%BFDXA), bioelectrical impedance analysis (%BFBIA), and CBE using 3-site (Hodgdon, %BFHE) and 1-site (Taylor-McClung, %BFTM) equations. Results were stratified by race and sex, to evaluate differences in accuracy of estimated %BF (weighted root mean squared error from %BFDXA). Associations of BF and PF with MSKI risk were evaluated with logistic regression.

Results

CBE and BIA underestimated %BF compared to %BFDXA. %BFBIA differed from %BFDXA overall and by sex. %BFTM underestimation was uniform across both sex and R/E compared to %BFDXA. Mean differences from %BFDXA by sex (M;F) were lower when measured by %BFTM (4.38; 4.59) compared to %BFHE (5.88; 4.39). Individuals had a greater likelihood of MSKI if they failed BF standards (odds ratio 1.32). Scoring ≥ 540 total on ACFT exhibited a 31% (95% CI: 0.52, 0.92) lower MSKI risk during the following 12 months than those with a lower score.

Conclusions

A single-site BF equation (%BFTM) maintained similar accuracy across the Soldier population by sex, age, and R/E. Implementing a PF score threshold in lieu of passing Army BF standards was associated with lower MSKI risk.
Artificial intelligence-enabled microfluidic cytometer using gravity-driven slug flow for rapid CD4+ T cell quantification in whole blood
Authors: Dixit Desh Deepak , Graf Tyler P. , McHugh Kevin J. , Lillehoj Peter B.
Published: February 2025

The quantification of immune cell subpopulations in blood is important for the diagnosis, prognosis and management of various diseases and medical conditions. Flow cytometry is currently the gold standard technique for cell quantification; however, it is laborious, time-consuming and relies on bulky/expensive instrumentation, limiting its use to laboratories in high-resource settings. Microfluidic cytometers offering enhanced portability have been developed that are capable of rapid cell quantification; however, these platforms involve tedious sample preparation and processing protocols and/or require the use of specialized/expensive instrumentation for flow control and cell detection. Here, we report an artificial intelligence-enabled microfluidic cytometer for rapid CD4+ T cell quantification in whole blood requiring minimal sample preparation and instrumentation. CD4+ T cells in blood are labeled with anti-CD4 antibody-coated microbeads, which are driven through a microfluidic chip via gravity-driven slug flow, enabling pump-free operation. A video of the sample flowing in the chip is recorded using a microscope camera, which is analyzed using a convolutional neural network-based model that is trained to detect bead-labeled cells in the blood flow. The functionality of this platform was evaluated by analyzing fingerprick blood samples obtained from healthy donors, which revealed its ability to quantify CD4+ T cells with similar accuracy as flow cytometry (<10% deviation between both methods) while being at least 4× faster, less expensive, and simpler to operate. We envision that this platform can be readily modified to quantify other cell subpopulations in blood by using beads coated with different antibodies, making it a promising tool for performing cell count measurements outside of laboratories and in low-resource settings.
The epigenetic landscape of brain metastasis
Authors: Powell Aoibhín M. , Watson Louise , Luzietti Lara , Prekovic Stefan , Young Leonie S. , Varešlija Damir
Published: February 2025

Brain metastasis represents a significant challenge in oncology, driven by complex molecular and epigenetic mechanisms that distinguish it from primary tumors. While recent research has focused on identifying genomic mutation drivers with potential clinical utility, these strategies have not pinpointed specific genetic mutations responsible for site-specific metastasis to the brain. It is now clear that successful brain colonization by metastatic cancer cells requires intricate interactions with the brain tumor ecosystem and the acquisition of specialized molecular traits that facilitate their adaptation to this highly selective environment. This is best exemplified by widespread transcriptional adaptation during brain metastasis, resulting in aberrant gene programs that promote extravasation, seeding, and colonization of the brain. Increasing evidence suggests that epigenetic mechanisms play a significant role in shaping these pro-brain metastasis traits. This review explores dysregulated chromatin patterns driven by chromatin remodeling, histone modifications, DNA/RNA methylation, and other epigenetic regulators that underpin brain metastatic seeding, initiation, and outgrowth. We provide novel insights into how these epigenetic modifications arise within both the brain metastatic tumor and the surrounding brain metastatic tumor ecosystem. Finally, we discuss how the inherent plasticity and reversibility of the epigenomic landscape in brain metastases may offer new therapeutic opportunities.
PSMD14-mediated deubiquitination of CARM1 facilitates the proliferation and metastasis of hepatocellular carcinoma by inducing the transcriptional activation of FERMT1
Authors: Lu Jing , Wu Huita , Zhan Ping , Lu Yuyan , Fang Qinliang , Luo Changhong , Wang Fuqiang , Wen Jing , Xie Chengrong , Yin Zhenyu
Published: February 2025

Hepatocellular carcinoma (HCC) is a highly potent malignancy. The enzyme coactivator-associated arginine methyltransferase 1 (CARM1) is highly expressed in different types of cancer. However, the precise levels of expression, clinical significance, biological functions, and molecular mechanisms of CARM1 in HCC, particularly related to the downstream genes regulated by CARM1 through histone arginine methylation, remain unclear. In this study, we presented findings from the TCGA database and clinical samples, which collectively demonstrated the overexpression of CARM1 in HCC. Additionally, we found that the upregulation of CARM1 was mediated by PSMD14-induced deubiquitination. CARM1 promoted the proliferation and metastasis of HCC cells in vitro and in vivo. Mechanistic investigations further revealed that FERMT1 is a downstream gene of CARM1, and CARM1 activates the transcription of FERMT1 through the dimethylation of arginine 17 on histone 3 (H3R17me2). Additionally, administering SGC2085, a CARM1 inhibitor, effectively suppressed the malignant behaviors of HCC cells. To summarize, our findings provided strong evidence that CARM1 can serve as a key oncoprotein; thus, it holds promise as a therapeutic target for HCC.
MicroRNA-379-5p attenuates cancer stem cells and reduces cisplatin resistance in ovarian cancer by regulating RAD18/Polη axis
Authors: Shukla Devendra , Mishra Sanjay , Mandal Tanima , Charan Manish , Verma Ajeet Kumar , Khan Md Maqsood Ahamad , Chatterjee Nabanita , Dixit Amit Kumar , Ganesan Senthil Kumar , Ganju Ramesh K. , Srivastava Amit Kumar
Published: February 2025

Ovarian cancer (OC) is an aggressive malignancy of the female reproductive organs, associated with a low 5-year survival rate. Emerging evidence suggests the pivotal role of microRNAs (miRNAs) in regulating chemoresistance and metastasis in OC, primarily through cancer stem cells (CSCs), also known as cancer stem-like cells (CSLCs). Herein, we demonstrate that miR-379-5p is downregulated in several OC cell populations including both cell lines and patient tumor samples. Furthermore, overexpression of miR-379-5p effectively inhibits CSCs and counteracts cisplatin-induced expansion of CSCs. Further mechanistic investigations identify RAD18, a DNA repair protein involved in translesion DNA synthesis (TLS), as a direct target of miR-379-5p. Moreover, a negative correlation between miR-379-5p and RAD18 expression is observed in ovarian CSCs isolated from OC patients. The downregulation of RAD18 inhibits stem-like phenotypes and enhances the sensitivity of ovarian CSCs to cisplatin treatment. Importantly, miR-379-5p-mediated inhibition of RAD18 prevents the repair synthesis in CSCs by promoting the accumulation of DNA damage. In vivo studies further reveal that miR-379-5p enhances DNA damage, which, in turn, inhibits tumor cell proliferation in athymic nude mice. Remarkably, targeting of RAD18 by miR-379-5p prevents monoubiquitination of proliferating cell nuclear antigen (PCNA), resulting in reduced DNA Polymerase η (a TLS polymerase that helps to bypass DNA lesions) recruitment to lesion sites. In the absence of Polη, the persisting DNA lesions cause activation of cell cycle arrest and apoptosis pathway in CSCs. Therefore, our findings unveil a novel mechanism whereby miR-379-5p overexpression curtails CSCs by modulating the RAD18/Polη axis.
Predicting the need for diabetic macular oedema treatment from photographic screening in the Singapore Integrated Diabetic Retinopathy Programme (SiDRP)
Authors: Poh Stanley S. J. , Teo Kelvin Y. C. , Goh Rose Ann , Lee Qian Xin , Hamzah Haslina , Sim Serene S. C. , Tan Colin S. , Tan Ngiap Chuan , Wong Tien Yin , Tan Gavin S. W.
Published: February 2025

Objective

To identify diabetic maculopathy features from photographic screening that are predictive of treatment on referral to a tertiary care centre.

Methods

Retrospective review of participants who underwent screening by Singapore Integrated Diabetic Retinopathy Programme from 2015 to 2019. Participants underwent visual acuity (VA) test and non-stereoscopic retinal photographs. Maculopathy features include haemorrhages, microaneurysm and hard exudates (HE), stratified by inner and outer zone (1 and 1-2 disc diameter from fovea respectively) and VA of 6/12. Diabetic macular oedema (DMO) treatment was defined as intravitreal injection or macular photocoagulation up to 540 days from point of referral.

Results

16,712 patients screened had referable eye disease. Out of 3518 maculopathy suspects, 281 (8.0%) received DMO treatment within 540 days. Those treated for DMO had shorter duration of diabetes (6.90 vs. 9.13 years, p < 0.001), higher total cholesterol (4.65 ± 1.20 vs. 4.36 ± 1.13 mmol/L, p = 0.001) and LDL cholesterol (2.59 ± 1.05 vs. 2.37 ± 0.93 mmol/L, p < 0.05) than those without treatment. High-risk features, including inner zone haemorrhages with VA ≤ 6/12 (HR 12.0, 95% CI: 5.5–25.9) and inner zone hard exudates (HR 7.4, 95% CI: 3.4–15.8), significantly increased the likelihood of requiring DMO treatment compared to low-risk features. Higher body mass index is protective of DMO treatment in mild non-proliferative diabetic retinopathy (HR 0.84, 95% CI: 0.73–0.97).

Conclusion

Haemorrhages, microaneurysms and HE within inner zone are important photographic features predictive of DMO treatment. VA is an important stratification for screening especially in patients with only visible haemorrhages.
Direct observation of ultrafast symmetry reduction during internal conversion of 2-thiouracil using Coulomb explosion imaging
Authors: Jahnke Till , Mai Sebastian , Bhattacharyya Surjendu , Chen Keyu , Boll Rebecca , Castellani Maria Elena , Dold Simon , Frühling Ulrike , Green Alice E. , Ilchen Markus , Ingle Rebecca , Kastirke Gregor , Lam Huynh Van Sa , Lever Fabiano , Mayer Dennis , Mazza Tommaso , Mullins Terence , Ovcharenko Yevheniy , Senfftleben Björn , Trinter Florian , Atia-Tul-Noor  , Usenko Sergey , Venkatachalam Anbu Selvam , Rudenko Artem , Rolles Daniel , Meyer Michael , Ibrahim Heide , Gühr Markus
Published: February 2025

The photochemistry of heterocyclic molecules plays a decisive role for processes and applications like DNA photo-protection from UV damage and organic photocatalysis. The photochemical reactivity of heterocycles is determined by the redistribution of photoenergy into electronic and nuclear degrees of freedom, initially involving ultrafast internal conversion. Most heterocycles are planar in their ground state and internal conversion requires symmetry breaking. To lower the symmetry, the molecule must undergo an out-of-plane motion, which has not yet been observed directly. Here we show using the example of 2-thiouracil, how Coulomb explosion imaging can be utilized to extract comprehensive information on this molecular deformation, linking the extracted deplanarization of the molecular geometry to the previously studied temporal evolution of its electronic properties. Particularly, the protons of the exploded molecule are well-suited messengers carrying rich information on its geometry at distinct times after electronic excitation. We expect that our new analysis approach centered on these peripheral protons can be adapted as a general concept for future time-resolved studies of complex molecules in the gas phase.
Aspirin-responsive gene switch regulating therapeutic protein expression
Authors: Huang Jinbo , Teixeira Ana Palma , Gao Ting , Xue Shuai , Xie Mingqi , Fussenegger Martin
Published: February 2025

Current small-molecule-regulated synthetic gene switches face clinical limitations such as cytotoxicity, long-term side-effects and metabolic disturbances. Here, we describe an advanced synthetic platform inducible by risk-free input medication (ASPIRIN), which is activated by acetylsalicylic acid (ASA/aspirin), a multifunctional drug with pain-relieving, anti-inflammatory, and cardiovascular benefits. To construct ASPIRIN, we repurpose plant salicylic acid receptors NPR1 and NPR4. Through domain truncations and high-throughput mutant library screening, we enhance their ASA sensitivity. Optimized NPR1 fused with a membrane-tethering myristoylation signal (Myr-NPR1) forms a complex with NPR4, which is fused with a DNA binding domain (VanR) and a transactivation domain (VP16). ASA induces dissociation of the Myr-NPR1/NPR4-VanR-VP16 complex, allowing nuclear translocation of NPR4-VanR-VP16 to activate VanR-operator-controlled gene expression. In male diabetic mice implanted with microencapsulated ASPIRIN-engineered cells, ASA regulates insulin expression, restores normoglycemia, alleviates pain and reduces biomarkers of diabetic neuropathy and inflammation. We envision this system will pave the way for aspirin-based combination gene therapies.
Neoadjuvant triplet immune checkpoint blockade in newly diagnosed glioblastoma
Authors: Long Georgina V. , Shklovskaya Elena , Satgunaseelan Laveniya , Mao Yizhe , da Silva Inês Pires , Perry Kristen A. , Diefenbach Russell J. , Gide Tuba N. , Shivalingam Brindha , Buckland Michael E. , Gonzalez Maria , Caixeiro Nicole , Vergara Ismael A. , Bai Xinyu , Rawson Robert V. , Hsiao Edward , Palendira Umaimainthan , Phan Tri Giang , Menzies Alexander M. , Carlino Matteo S. , Quek Camelia , Grimmond Sean M. , Vissers Joseph H. A. , Yeo Dannel , Rasko John E. J. , Khasraw Mustafa , Neyns Bart , Reardon David A. , Ashley David M. , Wheeler Helen , Back Michael , Scolyer Richard A. , Drummond James , Wilmott James S. , Rizos Helen
Published: February 2025

Glioblastoma (GBM) is an aggressive primary adult brain tumor that rapidly recurs after standard-of-care treatments, including surgery, chemotherapy and radiotherapy. While immune checkpoint inhibitor therapies have transformed outcomes in many tumor types, particularly when used neoadjuvantly or as a first-line treatment, including in melanoma brain metastases, they have shown limited efficacy in patients with resected or recurrent GBM. The lack of efficacy has been attributed to the scarcity of tumor-infiltrating lymphocytes (TILs), an immunosuppressive tumor microenvironment and low tumor mutation burden typical of GBM tumors, plus exclusion of large molecules from the brain parenchyma. We hypothesized that upfront neoadjuvant combination immunotherapy, administered with disease in situ, could induce a stronger immune response than treatment given after resection or after recurrence. Here, we present a case of newly diagnosed IDH-wild-type, MGMT promoter unmethylated GBM, treated with a single dose of neoadjuvant triplet immunotherapy (anti-programmed cell death protein 1 plus anti-cytotoxic T-lymphocyte protein 4 plus anti-lymphocyte-activation gene 3) followed by maximal safe resection 12 days later. The anti-programmed cell death protein 1 drug was bound to TILs in the resected GBM and there was marked TIL infiltration and activation compared with the baseline biopsy. After 17 months, there is no definitive sign of recurrence. If used first line, before safe maximal resection, checkpoint inhibitors are capable of immune activation in GBM and may induce a response. A clinical trial of first-line neoadjuvant combination checkpoint inhibitor therapy in newly diagnosed GBM is planned (GIANT; trial registration no. NCT06816927).