bluuebunny/crossref_metadata_2025 huggingface dataset:
The therapeutic role of exercise training during menopause for reducing vascular disease
Authors: Shing Conan L. H. , Bond Bert , Moreau Kerrie L. , Coombes Jeff S. , Taylor Jenna L.
Published: November 2024

Menopause marks a major milestone in female reproductive ageing. It is characterized by the cessation of ovarian function and a concomitant decline in hormones such as oestradiol. Subsequently, females undergoing menopausal transition experience a progressive increase in cardiovascular and cerebrovascular disease risk. During menopause, reductions in nitric oxide (NO) bioavailability, endothelial dysfunction, increases in systemic inflammation, oxidative stress, and impaired vascular remodelling may contribute towards an accelerated decline in the function of cerebral and peripheral vascular systems. Historically, hormone therapy (HT) has been used as a means of managing vascular disease risk and reducing menopause‐associated vasomotor symptoms such as hot flushes, though some studies suggest regular exercise has the potential to be a promising alternative. Regular aerobic exercise during early postmenopause may slow vascular decline by improving NO and oestradiol bioavailability, promoting positive vascular remodelling and lowering systemic inflammation. However, exercise‐mediated improvements in markers of vascular function are not consistently observed in oestradiol‐deficient postmenopausal women. Emerging evidence suggests that due to the greater oestradiol bioavailability during early postmenopause, vascular adaptations to exercise may be enhanced during this stage, as opposed to late postmenopause. Subsequently it may be important to begin regular exercise in the years preceding and immediately following the final menstrual period to slow the progression of vascular disease risk during perimenopause and beyond. The present review will provide a summary of our current understanding of how vascular function is affected during menopause and the role of regular aerobic and resistance exercise training in managing vascular disease risk.
The Role and Benefits of Physical Therapy Following Sport-Related Concussions
Authors: Bishay Anthony E. , Godwin Siobhan L. , Jo Jacob , Williams Kristen L. , Terry Douglas P. , Zuckerman Scott L.
Published: November 2024

Context: Sport-related concussion management often requires referral to physical therapy (PT). Objectives: To (1) outline the role of PT in the management of sport-related concussion, (2) describe patients who underwent PT, and (3) discuss outcomes of athletes who underwent PT. Design: Retrospective cohort study. Setting: Single institution. Methods: Adolescent athletes aged 14–19 years old who sustained a sport-related concussion from November 2017 to April 2022 were evaluated. The cohort was dichotomized into 2 groups: PT versus no PT. The outcomes were days from initial PT visit to symptom resolution (SR) and return-to-play. Subgroup analyses compared recovery metrics between those initiating PT before and after 30 (1 mo) and 90 days (3 mo) of injury. A univariable and multivariable regression was used to determine predictors of recovery. Results: Of 1010 concussed athletes, 205 (20.3%) received referral for rehabilitation, and 58 (28.3%) patients received PT at the parent institution. Those who received PT had a higher number of prior concussions compared with those who did not (PT: 1.0 [1.2]; non-PT: 0.6 + 1.0; χ2 = 19.37, P = .007). A large proportion of PT recipients reported headache (n = 45, 81.0%); visual disturbances (n = 32, 65.5%); and vestibular (n = 37, 63.8%), cervical (n = 25, 43.1%), or oculomotor dysfunction (n = 25, 43.1%). Most patients received exertional therapy (n = 32, 55.1%), vestibular therapy (n = 31, 53.4%), and/or cervical therapy (n = 30, 51.7%). Those initiating PT before 1 and 3 months had significantly shorter median times to SR compared with those initiating after 1 and 3 months, respectively. Multivariable regression showed that a shorter time between injury and the initial PT visit was predictive of faster SR (β = 1.66, P = .048). Conclusions: Headache, dizziness, and visual disturbances were commonly reported symptoms by patients who received PT. Cervical, vestibular, and oculomotor deficits were common objective findings by physical therapists, and cervical, vestibular, and exertional therapy were common interventions. Delayed time to PT was independently associated with a longer time to SR.
Differential murine responses to
Schistosoma mansoni
eggs in the liver and small intestine lead to downmodulation of hepatic but not intestinal periovular granulomas
Authors: Montasser Ashgan , Dakrory Ahmad E. , Ibrahim Mohamed I. M. , El Zayyat Emad , Tallima Hatem , El Ridi Rashika
Published: November 2024

To control schistosomiasis mansoni, it is important to attempt preventing the worms’ egg-induced pathology in the liver and limiting pathogen transmission following egg exit from the intestines to the exterior. Therefore, the present study aimed to clarify the reasons behind the decades-long riddle of periovular granulomas downmodulation in the liver, but not the small intestine, with the progression of murine schistosomiasis mansoni. Outbred female CD-1 mice were percutaneously exposed to 15
Schistosoma mansoni
cercariae. The liver and small intestine were collected from mice harboring a minimum of a worm couple at 8, 12, 16, and 20 weeks post-infection, assessed for egg counts/g and histopathological changes, and used to prepare Triton X-100 extracts. Content of cytokines, saturated and unsaturated fatty acids, triglycerides, cholesterol, reactive oxygen species, and uric acid per mg tissue extract proteins were evaluated using capture enzyme-linked immunosorbent assays, gas chromatography-flame ionization detector, and standard commercially available reagents, respectively. Examination of hematoxylin-eosin-stained tissue sections confirmed the decrease in size and changes in cellular composition of periovular granulomas in the liver but not the small intestine, associated with wide differences in released cytokines types and amounts, and content of the bioactive lipids, arachidonic and docosahexaenoic acids, reactive oxygen species, and uric acid. The results together disclosed that the downmodulation of hepatic, but not the small intestine, circumoval granulomas with the progression of murine
S. mansoni
naturally results from site- and tissue- specific immunological and biochemical responses to the egg-derived antigens and molecules and suggested that the intestines appear to harbor immune-privileged sites.
Supplemental Material: Ordovician back-arc setting in the Tongbai orogen, central China: Geochronological and geochemical constraints from the Erlangping metabasites
Authors: Zhang Feifei , al. et
Published: November 2024

Zircon U-Pb dating, whole-rock major oxides, trace elemental and Sr-Nd-Pb isotopic analysed results for the metabasites from the Erlangping Group in the Tongbai orogen.
Supplemental Material: Early Triassic mid-ocean ridge basalt like diabase swarms in the southeastern segment of the Central Asian Orogenic Belt: A response to lithospheric extension triggered by Paleo-Asian oceanic slab break-off
Authors: Jing Yan , Ge Wen-chun , al. et
Published: November 2024

Supplemental Text S1 and Supplemental Tables S1-S5.
Aggregation Behavior of Carbamate-Functionalized Monocationic Morpholinium Surfactants in Aqueous Media
Authors: Gaynanova G. A. , Vasileva L. A. , Markelov A. K. , Kuznetsov D. M. , Lenina O. A. , Lyubina A. P. , Voloshina A. D. , Petrov K. A. , Zakharova L. Ya.
Published: November 2024

New morpholinium surfactants with a carbamate fragment between the amphiphile head group and its hydrophobic tail (CnMB-carb, where n = 8, 10, 12, 14, 16) were synthesized. The cmc values obtained by tensiometry for dodecyl, tetradecyl, and hexadecyl homologues are 3–4 times lower than those of 4-alkyl-4-methylmorpholinium bromides. The introduction of a carbamate fragment can be considered as tool for controlling cmc values. The calculation of the thermodynamic parameters of micellization, i.e., Gibbs free energy of micellization (∆Gmic), enthalpy of micellization (ΔHmic), entropy of micellization (ΔSmic), were carried out based on the temperature dependences of specific electrical conductivity as a function of surfactant concentration. It was determined that the aggregation of cationic surfactants is driven by the entropy and ΔG(CH2) is equal to 3.26 kJ/mol. The cmc values determined by fluorimetry were approximately two times lower than those obtained by tensiometry and conductometry, probably due to the ability to identify premicellar aggregates. Using the spectrophotometry, a twofold increase in the solubilization capacity of C16MB-carb (0.036 molOOT/molsurf) was established in comparison with a non-functionalized morpholinium surfactants with the same tail length (0.019 molOOT/molsurf). The “closed bottle test” showed that the degree of CnMB-carb biodegradation reaches 56.7–62.3%. It was found that the antimicrobial activity of the surfactants increases with the lengthening of the hydrocarbon tail with maximum activity for the tetradecyl homologue. In addition, dose-dependent activity of C14MB-carb and C16MB-carb on the cell wall, cell membrane, and membrane potential of Staphylococcus aureus was shown.
Comparison of baseline clinical characteristics and patterns of visual field defects between high-tension and normal-tension glaucoma
Authors: Chen Zidong , Yang Wenxin , Yang Yangfan , Jiang Yuzhen , Zhang Yuning , Zhang Xinyi , Luo Chongxuan , Wang Mingqin , Fan Yanmei , Liu Pingping , Nathwani Neil , Gazzard Gus , Yu Minbin
Published: November 2024

Aims

To compare the baseline clinical characteristics and patterns of visual field defects between high-tension glaucoma (HTG) and normal-tension glaucoma (NTG) in the Laser in Glaucoma and Ocular Hypertension (LiGHT) China subjects.

Methods

All patients (n=622) were recruited at Zhongshan Ophthalmic Center from 2015 to 2019. 1105 open-angle glaucoma eyes of 622 patients were classified as NTG (n=559) and HTG eyes (n=546) according to the baseline intraocular pressure (IOP) of 21 mm Hg. The mean deviation (MD), regional MD of the Glaucoma Hemifield Test regions and regional difference values were calculated. Daytime phasing IOP was recorded at 8:00, 10:00, 11:30, 14:30 and 17:00 hour. Multiple regression analyses were conducted for each regional difference.

Results

Patients with NTG were older, more likely to be female, hypertensive and suffer ischaemic heart disease than patients with HTG (p<0.05 for all comparisons). HTG showed higher mean daytime phasing IOP and higher daytime fluctuations than NTG (p<0.001 for all comparisons). HTG and NTG showed similar MD overall (p=0.665). NTG showed significantly greater hemifield asymmetry than HTG. The two arcuate regional differences in NTG were significantly associated with daytime IOP fluctuations (p<0.01 in both regions).

Conclusions

In the LiGHT China trial, NTG and HTG showed similar visual field defects severity at enrolment. However, NTG showed more severe hemifield asymmetry compared with HTG, and higher short-time IOP fluctuations might exacerbate this asymmetry in NTG.
Identifying colorectal cancer-specific vulnerabilities in the Wnt-driven long non-coding transcriptome
Authors: Schwarzmueller Laura J , Adam Ronja S , Moreno Leandro F , Nijman Lisanne E , Logiantara Adrian , Eleonora Steven , Bril Oscar , Vromans Sophie , de Groot Nina E , Giugliano Francesca Paola , Stepanova Ekaterina , Muncan Vanesa , Elbers Clara C , Lenos Kristiaan J , Zwijnenburg Danny A , van Eijndhoven Monique A J , Pegtel Dirk Michiel , van Neerven Sanne M , Loayza-Puch Fabricio , Dadali Tulin , Broom Wendy J , Maier Martin A , Koster Jan , Vermeulen Louis , Léveillé Nicolas
Published: November 2024

Background

Aberrant Wnt pathway activation is a key driver of colorectal cancer (CRC) and is essential to sustain tumour growth and progression. Although the downstream protein-coding target genes of the Wnt cascade are well known, the long non-coding transcriptome has not yet been fully resolved.

Objective

In this study, we aim to comprehensively reveal the Wnt-regulated long non-coding transcriptome and exploit essential molecules as novel therapeutic targets.

Design

We used global run-on sequencing to define β-catenin-regulated long non-coding RNAs (lncRNAs) in CRC. CRISPRi dropout screens were subsequently used to establish the functional relevance of a subset of these lncRNAs for long-term expansion of CRC.

Results

We uncovered thatLINC02418is essential for cancer cell clonogenic outgrowth. Mechanistically,LINC02418regulates MYC expression levels to promote CRC stem cell functionality and prevent terminal differentiation. Furthermore, we developed effective small interfering RNA (siRNA)-based therapeutics to targetLINC02418RNAin vivo.

Conclusion

We propose that cancer-specific Wnt-regulated lncRNAs provide novel therapeutic opportunities to interfere with the Wnt pathway, which has so far defied effective pharmacological inhibition.
How nesting support type interacts with vegetation greening and distance to nest trees of mixed-species to predict white stork nest density in a Mediterranean capital
Authors: Chahboun Chaymae , Hanane Saâd , Chehboun Benaceur , Qninba Abdeljebbar
Published: November 2024

White Stork (WS) ( Ciconia ciconia (Linnaeus, 1758)) ranks among the most common breeding birds in many Mediterranean cities, underscoring the importance of studying nest densities, particularly when populations are increasing. In this study, conducted in Rabat (Morocco), we aimed to investigate the effects of coloniality, landscape composition, and space to identify the best predictors of variation in the number of WS nests per nest support using generalized linear mixed models. The results revealed significant interactions between the type of support (trees vs. pylons) and normalized difference vegetation index (NDVI) as well as between the support type and the distance to the nearest support occupied by WS and Cattle Egret (CE) ( Bubulcus ibis (Linnaeus, 1758)) nests. A high number of nests are associated with an NDVI increase around pylons, while such an effect is insignificant around trees. In contrast, a high number of WS nests are noted close to supports occupied by both WS and CE nests, whereas in pylons, this number is recorded far away from them. The implementation of a scientific monitoring system is crucial for determining, at a defined time step, the direction and strength of relations between WS and CE populations in Rabat.
HHH whitepaper
Authors: Abouabid Hamza , Arhrib Abdesslam , Arnold Hannah , Azevedo Duarte , Brigljevic Vuko , Chen Maggie , Diaz Daniel , Duarte Javier , du Pree Tristan , El Falaki Jaouad , Ferencek Dinko , Ferreira Pedro. M. , Fuks Benjamin , Ganguly Sanmay , Karkout Osama , Kolosova Marina , Konigsberg Jacobo , Landsberg Greg , Liu Bingxuan , Moser Brian , Mühlleitner Margarete , Papaefstathiou Andreas , Pasechnik Roman , Robens Tania , Santos Rui , Sheldon Brian , Soyez Gregory , Stamenkovic Marko , Stylianou Panagiotis , Susa Tatjana , Tetlalmatzi-Xolocotzi Gilberto , Weiglein Georg , Zanderighi Giulia , Zhang Rui
Published: November 2024

We here report on the progress of the HHH Workshop, that took place in Dubrovnik in July 2023. After the discovery of a particle that complies with the properties of the Higgs boson of the Standard Model, all Standard Model (SM) parameters are in principle determined. However, in order to verify or falsify the model, the full form of the potential has to be determined. This includes the measurement of the triple and quartic scalar couplings.

We here report on ongoing progress of measurements for multi-scalar final states, with an emphasis on three SM-like scalar bosons at 125 $$\,\text {Ge}\hspace{-.08em}\text {V}$$

Ge

V

, but also mentioning other options. We discuss both experimental progress and challenges as well as theoretical studies and models that can enhance such rates with respect to the SM predictions.
Applicability of monitoring data of mercury soil–atmosphere transport in an old mining area for exposure risk assessment
Authors: Kondo Monami , Wang Jiajie , Komai Takeshi , Watanabe Noriaki
Published: November 2024

Mercury (Hg) is a widespread pollutant that poses significant risks to both ecosystems and human health. While previous studies have evaluated Hg concentrations in soils, few have measured Hg emissions in areas with high Hg concentrations or related these measurements to estimates of exposure via air inhalation based on Hg flux values. This study addresses this gap by proposing the use of gaseous elemental Hg (GEM) flux measurements for exposure risk assessments, with a particular focus on the importance of inhalation exposure, which has implications for future risk management strategies. Sensitivity analysis of the site-specific exposure and risk estimation model revealed that the fraction of land area in surface water had a significant impact on the estimated exposure through air inhalation. Additionally, the analysis showed that the GEM flux measured
in situ
in a high-Hg concentration area of Itomuka was not directly proportional to the Hg concentration, although the risk estimation model treated it as a function of concentration. Furthermore, we found that the flux values are influenced by both the fraction of land area in surface water and Hg concentration, indicating that this new flux-based indicator should be integrated into exposure risk assessments.
Chapter 2. Tectonics, Climate and Sedimentation in the Albertine Rift
Authors: Nicholas Christopher J.
Published: November 2024

The tectonically active early continental Albertine Rift basins are dynamic entities, constantly evolving through time. Periods of crustal extension cause rift valley floor subsidence to create accommodation space and accumulate sediment in basinal depositional centres (‘depocentres’). Periods when stress fields change across a rift can move the maximum rupture along main rift bounding faults to shift depocentre locations over time, often producing a series of syn-rift phases in basin development. In the Albertine Rift, the Lake Edward basin displays superb structural geomorphology that, in this study, could be mapped across the whole width of the rift valley. Often cited in the literature as a classic asymmetric half-graben, it is now clear that this basin is undergoing a change in rift phase, developing into an extremely asymmetric graben with a faulted eastern flexural arch. Tectonics does not operate alone, but forms a coupled dynamo with climate, that together drive and control the sedimentary fill of an early continental rift basin. The theoretical effects of this are modelled for Lake Edward to indicate basinal deposition when tectonics and climate are in, and out, of phase. Finally, the ‘sedimentary geodynamic elements’ that might be expected to characterise early continental rift basins are outlined.
Chapter 3. Release of Geothermal Energy: Hot Springs and Tufa-Travertines
Authors: Nicholas Christopher J.
Published: November 2024

Heat and groundwater flow through a rift basin are an integral part of its geodynamics, but predicting what is happening below the surface is often difficult due to a lack of direct information. Field observations on the occurrence, subaerial distribution, temperature and geochemistry of freshwater springs may help to form an idea of groundwater flow through the basin and what it is, or has been, flowing through. Hot springs in the Albertine Rift are common and their occurrence is directly linked to deep-seated main rift bounding faults, or major intra-basinal fault intersections. The majority of Lake Edward and Lake Albert active, or paleo-springs, are also associated with precipitation of localised tufa-travertine limestones. The cooler tufas may contain calcitised plant roots, leaf imprints and freshwater gastropods. Active scavenging of uranium can be demonstrated in the algae and cyanobacteria that inhabit active spring mouths and corresponding tufa-travertines are depleted in radioactive K, U and Th elements. The source for concentrated HCO3- in groundwater at depth, needed to precipitate limestones at the surface, remains problematic. However, REE+Y geochemistry of the tufa-travertines suggest end-member sources of either carbonatites or marine limestones, indicating the possibility of a pre-Neogene rift sequence beneath the Albertine Rift.
Chapter 4. Evidence of Working Petroleum Play Systems: Oil Seeps and Slicks
Authors: Nicholas Christopher J.
Published: November 2024

Maturation and accumulation of economic quantities of hydrocarbons are a common sedimentary component of continental rift basins around the world, both ancient and modern. Thus, groundwater is not the only fluid that may migrate along major rift faults away from basinal depocentres. De-risking petroleum exploration in rift basins requires demonstrating the presence of working petroleum play systems and the presence of leaking hydrocarbons to the surface is a primary way of demonstrating they are operating. Oil seeps have been known in Lake Albert since 1925 and the Kingfisher, Mputa-Waraga and Jobi-Rii petroleum play systems are due to go into full oil production. Lake Edward, however, has remained a virgin frontier exploration area. Tufa-travertine limestones along the eastern rift bounding fault of the Rwenzori Mountains have yielded organic residues which GCMS analyses indicate have a mature, oil-like distribution. Biomarkers suggest a marine shale source rock, the origin of which is at odds with both oils from Lake Albert and generation within the present EARS. A Lake Edward Slick Survey also sampled oil on the water surface that has the same biomarker signatures as the tufa-travertine-derived residues. Together they suggest maturation from a deeper pre-Neogene (?Mesozoic–Paleogene) rift sequence.
Chapter 6. Albertine Rift Marginal Lacustrine Environments
Authors: Nicholas Christopher J.
Published: November 2024

Marginal lacustrine depositional environments in the Albertine Rift are highly sensitive to short-term, climatically controlled lake level fluctuations. As such, they act as one of the prime recorders of paleo-shoreline transgression or regression in rift-fill stratigraphy. In both Lakes Edward and Albert, modern day seasonal winds blow parallel with the long-axis of the rift basin, developing wave dominated shorelines at the end of a lake, but sheltered rift flanks display coastal features associated with longshore drift. The different types of shoreline around Albertine Rift lakes today produce characteristic geomorphological features and associated lithofacies, with key sedimentary structures and fauna/flora that can include hippopotamus, elephant, crocodile and fish remains. These can be identified in Pleistocene – Holocene onshore sedimentary successions around the Lake Edward and Lake Albert rift basins, providing a record of glacial – interglacial climatic cyclicity in the Equatorial Tropics of East Africa. Northern hemisphere interglacials result in a wet phase and lake level rise in the Albertine Rift, with marginal lacustrine shorelines back-stepping landward. Whereas, high latitude glacials cause corresponding periods of aridification and rift lake level fall, with paleo-shorelines prograding out towards the centre of the basin.
Chebyshev Parameterization for Woven Fabric Modeling
Authors: Öhri Annika , Segall Aviv , Ren Jing , Sorkine-Hornung Olga
Published: November 2024

Distortion-minimizing surface parameterization is an essential step for computing 2D pieces necessary to fabricate a target 3D shape from flat material. Garment design and textile fabrication are a prominent application example. Common distortion measures quantify length, angle or area preservation in an isotropic manner, so that when applied to woven textile fabrication, they implicitly assume fabric behaves like paper, which is inextensible in all directions and does not permit shearing. However, woven fabric differs significantly from paper: it exhibits anisotropy along the yarn directions and allows for some degree of shearing. We propose a novel distortion energy based on Chebyshev nets that anisotropically penalizes shearing and stretching. Our energy formulation can be used as an optimization objective for surface parameterization and is simple to minimize via a local-global algorithm. We demonstrate its advantages in modeling nets or woven fabric behavior over the commonly used isotropic distortion energies.
Notice and Choice Cannot Stand Alone
Authors: Cranor Lorrie Faith
Published: November 2024

Privacy notice and choice has largely failed us so far because we are not giving it the legal and technical support it needs.
Urban Traffic Simulation with Shared Mobility Services: An Approach Using Spatiotemporal Network Kernel Density Estimation and MATSim
Authors: Khalil Jalal , Yan Da , Yuan Lyuheng , Jafarzadehfadaki Mostafa , Adhikari Saugat , Han Jiao , Sisiopiku Virginia , Jiang Zhe
Published: November 2024

The popularity of smartphones and 4G/5G network have enabled various novel transportation modes based on shared mobility, such as app-based ride-hailing services (e.g., Uber and Lyft) and shared micromobility services (e.g., Veo and Gotcha). However, little is known about to what degree their operations impact urban traffic, which is important for transportation planning and policy making. These companies seldom share their ride data due to business and user privacy reasons, and they are young and still exploring and growing their market to new locations. Recently, transportation engineering researchers began to collect data in large cities trying to understand the transportation impacts of shared mobility services, but (1) there does not exist a general analytics framework applicable to any city, and (2) the studies were based on historical data and cannot project the future easily to catch up with the rapid development of shared mobility services.

In this paper, we introduce a general framework for multi-modal urban traffic analytics. The goal is to build a digital twin of the transportation in a city, i.e., an accurate agent-based transportation simulation model, based on a medium-sized dataset of the interested transportation modes collected by the research group combined with other open data sources such as US Census Bureau. With this digital twin, transportation engineering researchers can flexibly analyze the impact of shared mobility services under different scenarios, such as “if the number of Uber drivers doubles” or “if the number of deployed e-scooters doubles”. The digital twin may also enable new opportunities, such as being an environment for learning policies with reinforcement learning. Our framework consists of three steps: (1) fitting the spatiotemporal distribution of the shared mobility rides on the underlying road network, (2) generating the travel day-plans of the entire urban population based on the learned spatiotemporal ride distribution and user-specified parameters, and (3) configuring an agent-based simulation software such as MATSim to execute the generated realistic day-plans, which provides detailed transportation data for analytics. At the core of our approach is a new spatiotemporal network kernel density estimation (KDE) method that fixes the flaw of prior methods where the contributions of different data samples are not equal. We also propose a crowdsourcing method to collect app-based ride data that is easy to carry out in any city. Using Birmingham, AL as an example, we demonstrate how our framework can be applied to help transportation engineering researchers analyze the impacts of Uber ride-hailing and Veo e-scooter services.
Plasma Glial Fibrillary Acid Protein and Phosphorated Tau 181 Association with Presynaptic Density-Dependent Tau Pathology at 18F-SynVesT-1 Brain PET Imaging
Authors: Wu Junhao , Li Binyin , Wang Jie , Huang Qi , Chen Xing , You Zhiwen , He Kun , Guo Qihao , Li Songye , Huang Yiyun Henry , Guo Tengfei , Dai Wenlin , Xiang Weiwei , Chen Weihuang , Yang Dake , Zhao Jun , Guan Yihui , Xie Fang
Published: November 2024

Plasma phosphorylated tau 181 (p-tau-181) and glial fibrillary acidic protein (GFAP) have potential predictive value for identifying synaptic density as measured using 18F-SynVesT-1 brain PET; the relationship of plasma p-tau-181 and GFAP with synapse loss might be influenced by tau aggregation rather than amyloid-β deposition or cortical thickness.
A Secure and Fair Client Selection Based on DDPG for Federated Learning
Authors: Wan Tao , Feng Shun , Liao Weichuan , Jiang Nan , Zhou Jie
Published: November 2024

Federated learning (FL) is a machine learning technique in which a large number of clients collaborate to train models without sharing private data. However, FL’s integrity is vulnerable to unreliable models; for instance, data poisoning attacks can compromise the system. In addition, system preferences and resource disparities preclude fair participation by reliable clients. To address this challenge, we propose a novel client selection strategy that introduces a security‐fairness value to measure client performance in FL. The value in question is a composite metric that combines a security score and a fairness score. The former is dynamically calculated from a beta distribution reflecting past performance, while the latter considers the client’s participation frequency in the aggregation process. The weighting strategy based on the deep deterministic policy gradient (DDPG) determines these scores. Experimental results confirm that our method fairly effectively selects reliable clients and maintains the security and fairness of the FL system.
Epidemiological Trends, Etiology, and Burden Study of Heart Failure in China, 1990–2019
Authors: Ying Tao , Wang Han , Nie Qiong , Yan Wei , Wu Jing
Published: November 2024

Background: Despite the enormous impact of heart failure (HF) in China, there is a relative lack of research on its epidemiologic trends and burden. Therefore, there is an urgent need for a comprehensive and in‐depth analysis of the epidemiologic patterns, underlying etiology, and overall burden of HF.

Objective: This study aimed to elucidate the epidemiology, etiology, and burden of HF in China and provided a comprehensive and up‐to‐date analysis, including temporal trends from 1900 to 2019.

Methods: The data for this study were derived from the Global Burden of Disease (GBD) study 2019. Descriptive analyses were conducted to examine the prevalence and years lived with disability (YLD) rates in China from 1990 to 2019, with variables including year, sex, and age. To illustrate the temporal trend spanning 1990 to 2019, estimated average annual percentage changes (AAPC) were calculated.

Results: In 2019, the number of prevalent HF cases in China was 18.51 million (95% uncertainty interval [UI]: 14.97 to 23.02 million), representing 32.9% of the global prevalence. Between 1990 and 2019, the number of cases and the prevalence rates of HF in China showed an increasing trend. The age‐standardized prevalence rates (ASPRs) demonstrated an overall declining trend (AAPC = −0.16, 95% confidence interval [CI]: −0.19 to −0.13, p < 0.01), as did the age‐standardized YLD rates (AAPC = −0.13, 95% CI: −0.16 to −0.1, p < 0.01). However, from 2017 to 2019, a gradual increase was observed (AAPC = 1.72, 95% CI: 1.47 to 1.96, p < 0.01). In the age‐based analysis, individuals aged 55 years and older accounted for 88.3% of the prevalent cases. Women exhibited higher case numbers and ASPR compared to men. In the cause‐based analysis, hypertensive heart disease emerged as the primary etiology of HF in China.

Conclusion: From 1990 to 2019, the ASPR and age‐standardized YLD rates for HF in China demonstrated an overall decreasing trend. Nevertheless, the trend increased from 2017 to 2019, with significant variations observed by gender and age. Therefore, continued attention to the disease burden of HF in China remains essential. Healthy lifestyles are important for minimizing the prevalence of HF. In addition, it is necessary to address and reduce the incidence of hypertension from all causes to mitigate the disease burden further.
Synthesis, Properties, and Environmental Impact of Hybrid Pigments
Authors: Randhawa Kawaljit Singh
Published: November 2024

This article investigates the evolving domain of hybrid pigments, which integrate both organic and inorganic constituents to yield novel color properties and enhanced performance. Beginning with an overview of their significance across industries, the study delves into various types of hybrid pigments, focusing on synthesis techniques and recent advancements. The study examines their utilization in paints, inks, plastics, and cosmetics, emphasizing their ability to meet industrial demands. Critical factors such as color stability, lightfastness, and environmental impact are evaluated, with a focus on sustainability metrics. The review encompasses diverse aspects including synthesis methods, color stability, applications across sectors, and environmental considerations of hybrid pigments.
A Phase II Basket Trial of Dual Anti–CTLA-4 and Anti–PD-1 Blockade in Rare Tumors SWOG S1609: Vulvar Cancers
Authors: Chae Young Kwang , Corthell Lucy , Patel Sandip Pravin , Edwards Robert , Scalici Jennifer M. , Kim Hye Sung , Chung Liam Il-Young , Othus Megan , McLeod Christine M. , Chen Helen X. , Sharon Elad , Streicher Howard , Ryan Christopher W. , Blanke Charles D. , Kurzrock Razelle
Published: November 2024

Purpose:

Dual PD-1/CTLA-4 inhibition shows promise in various malignancies. The SWOG S1609 Dual Anti–CTLA-4 and Anti–PD-1 Blockade in Rare Tumors (DART) trial presents initial results of ipilimumab/nivolumab in vulvar cancers.

Patients and Methods:

DART is a prospective/open-label/multicenter (1,016 US sites)/multicohort phase II clinical trial of ipilimumab (1 mg/kg intravenously every 6 weeks) plus nivolumab (240 mg intravenously every 2 weeks). The primary endpoint was objective response rate [ORR; confirmed complete response and partial response (PR)] per RECISTv1.1, whereas progression-free survival (PFS), overall survival, clinical benefit rate (CBR; ORR plus stable disease ≥6 months), and toxicity were secondary endpoints.

Results:

Sixteen evaluable patients (median age, 55.5 years; 0–6 prior therapies; no prior immunotherapy) were analyzed, all of whom had squamous cell carcinoma histology. The ORR was 18.8% (3/16), CBR was 25% (4/16), and CBR plus unconfirmed PR rate was 31% (5/16); the PFS was 34.1, 16.7. 15.5, 7.2, and 7.0 months for these five patients, respectively. The median PFS and overall survival were 2.2 and 7.6 months, respectively. The most common adverse events were diarrhea, fatigue, pruritus, anorexia, and nausea (25%, n = 4 each). Grade 3 to 4 adverse events occurred in 25% of patients (n = 4). There was one grade 1 to 2 adverse event (6.7%) that led to discontinuation and one (6.7%) grade 5 death adverse event.

Conclusions:

Ipilimumab plus nivolumab in vulvar cancers resulted in an objective response in 3 of 16 patients, all of whom had durable responses lasting over 1 year. Notably, two additional patients experienced durable stable disease and unconfirmed PR. Correlative studies to determine response and resistance markers are ongoing.
Quantitative and Morphology-Based Deep Convolutional Neural Network Approaches for Osteosarcoma Survival Prediction in the Neoadjuvant and Metastatic Settings
Authors: Coudray Nicolas , Occidental Michael A. , Mantilla Jose G. , Claudio Quiros Adalberto , Yuan Ke , Balko Jan , Tsirigos Aristotelis , Jour George
Published: November 2024

Purpose:

Necrosis quantification in the neoadjuvant setting using pathology slide review is the most important validated prognostic marker in conventional osteosarcoma. Herein, we explored three deep-learning strategies on histology samples to predict outcome for osteosarcoma in the neoadjuvant setting.

Experimental Design:

Our study relies on a training cohort from New York University (NYU; New York, NY) and an external cohort from Charles University (Prague, Czechia). We trained and validated the performance of a supervised approach that integrates neural network predictions of necrosis/tumor content and compared predicted overall survival (OS) using Kaplan–Meier curves. Furthermore, we explored morphology-based supervised and self-supervised approaches to determine whether intrinsic histomorphologic features could serve as a potential marker for OS in the neoadjuvant setting.

Results:

Excellent correlation between the trained network and pathologists was obtained for the quantification of necrosis content (R2 = 0.899; r = 0.949; P < 0.0001). OS prediction cutoffs were consistent between pathologists and the neural network (22% and 30% of necrosis, respectively). The morphology-based supervised approach predicted OS; P = 0.0028, HR = 2.43 (1.10–5.38). The self-supervised approach corroborated the findings with clusters enriched in necrosis, fibroblastic stroma, and osteoblastic morphology associating with better OS [log-2 hazard ratio (lg2 HR); −2.366; −1.164; −1.175; 95% confidence interval, (−2.996 to −0.514)]. Viable/partially viable tumor and fat necrosis were associated with worse OS [lg2 HR; 1.287; 0.822; 0.828; 95% confidence interval, (0.38–1.974)].

Conclusions:

Neural networks can be used to automatically estimate the necrosis to tumor ratio, a quantitative metric predictive of survival. Furthermore, we identified alternate histomorphologic biomarkers specific to the necrotic and tumor regions, which could serve as predictors.
Abstract A023: Arachidonic acid metabolism promoting cross resistance in melanoma cells
Authors: Stefanski Casey D. , Erkes Daniel A. , Purwin Timothy J. , Mersky Glenn L. , Kitterman Erica L. , Mustafa Manal , Haj Jelan , Melissaratos Diana , Aplin Andrew E.
Published: November 2024

Melanoma patients initially respond well to first line immunotherapy. However, cross resistance to immunotherapy and BRAF/MEK inhibitor is a clinical challenge for melanoma care. To investigate drug tolerant and resistant mechanisms promoting cross resistance, we analyzed RNA-sequencing and gene set enrichment targeted therapy resistant melanoma cells revealing an enriched arachidonic acid gene signature. Intracellular arachidonic acid levels were increased in drug resistant and drug tolerant melanoma models. Arachidonic acid is enzymatically converted by COX1 and COX2 to prostaglandins, which is subsequently secreted into the microenvironment. Drug tolerant and resistant cells had increased protein expression of COX1 and COX2 concurrently with increased secretion of prostaglandin E2. COX1/2 inhibition and COX2 knockdown in vitro had no effect on cell growth in drug tolerant or resistant cells compared to parental cells. However, secreted prostaglandins are known immunomodulators, thus we explored how COX1/2 inhibition in combination with BRAF inhibitor plus MEK inhibitor affected immune cell infiltration. COX1/2 inhibition increased CD4+ and CD8+ T cell infiltration as compared to BRAF inhibitor plus MEK inhibitor alone. Under constant BRAF inhibitor plus MEK inhibitor treatment, we found that COX1/2 inhibition upon reaching MRD status prevented tumor relapse in vivo and increased survival dependent on an immune system. Future studies will evaluate the importance of arachidonic acid metabolism in promoting cross resistance to immune checkpoint blockade and whether T cell depletion prevents the delayed tumor relapse. Overall, COX1/2 inhibition delayed tumor relapse and survival in an immune-dependent manner and demonstrated a potential cross resistant mechanism.

Citation Format: Casey D. Stefanski, Daniel A. Erkes, Timothy J. Purwin, Glenn L. Mersky, Erica L. Kitterman, Manal Mustafa, Jelan Haj, Diana Melissaratos, Andrew E. Aplin. Arachidonic acid metabolism promoting cross resistance in melanoma cells [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr A023.
Abstract B002: Dynamic response and evolving adaptation of pancreatic cancer cells to the prolonged acidic pH microenvironment
Authors: Wayne Chang Wun-Shaing
Published: November 2024

Solid tumor cells are often immersed in an acidic microenvironment. While many previous studies have investigated the short-term effects of extracellular acidity on tumor cells, little is known about how they adapt to the prolonged acidic microenvironmental stress and then advance to more aggressive stages. By challenging pancreatic tumor cells as an example with continuously and gradually acidified extracellular pH, a variety of cellular characteristics including phenotypic regulation, proliferation rates, autophagic control, metabolic plasticity and metastatic potentials were identified. More detailed evidence regarding the mitochondrial network dynamics and mechanistic control of pancreatic tumor cells in response to the extracellular acidosis will be presented at this conference to emphasize the critical effects of this stress factor as a selection force for tumor adaptation and progression. These findings not only highlight the importance of dynamic response and evolving adaptation of solid tumor cells to the chronic microenvironmental acidity, but also the potential of targeting the 'acid-mediated tumor malignancy' for anticancer therapy.

Citation Format: Wun-Shaing Wayne Chang. Dynamic response and evolving adaptation of pancreatic cancer cells to the prolonged acidic pH microenvironment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B002.
Abstract B010: Improving pancreatic cancer image classification with transfer learning: CD45 vs. PANCK
Authors: Thomas Miracle
Published: November 2024

Pancreatic ductal adenocarcinoma (PDAC) is known for its high aggressiveness and is the fourth most common cause of death of cancer-related death in the United States. It is highly malignant and often goes undiagnosed until advanced stages due to its late-onset symptoms, resulting in poor prognosis. Using quantitative analyses of histological features, such as the expression of prognostic biomarker, can provide valuable insight to guide treatment decisions, monitor disease progression and predict outcomes. Previous researchers have found that CD45 and PANCK play a huge role in characterizing the tumor microenvironment of PDAC. One study using single-cell RNA sequencing compared the microenvironments of healthy pancreata and pancreatic tumors, revealing differences in cellular composition. Tumor samples showed a higher proportion of immune cells, including CD45+ cells, compared to heathy samples and utilized PANCK to differentiate between epithelial and non-epithelial cells. This study aims to enhance the accuracy of classifying pancreatic cancer pathological images based on prognostic markers using transfer learning techniques. We curated and pre-processed a dataset of pancreatic cancer pathological images with different prognostic markers. Using the pre-trained convolutional neural network (CNN) model VGG16, we fine-tuned it with our dataset to better differentiate between two prognostic markers, CD45 and PANCK. The model's performance was evaluated using a similarity matrix to illustrate distinctions among the two prognostic markers. Our results demonstrate that the transfer learning approach significantly improves classification accuracy, achieving confusion matrix validation results of 90% between CD45 and PANCK prognostic markers. SSIM values were relatively low, highlighting the ability of our model to differentiate between the two prognostic markers. The low SSIM value also shows variability within the two prognostic markers, indicating heterogeneity in structural changes due to pancreatic cancer. These findings indicate that transfer learning can be a powerful tool for improving the classification of pathological images and that there is notable variability in the structural features associated with different prognostic markers in pancreatic cancer.

Citation Format: Miracle Thomas. Improving pancreatic cancer image classification with transfer learning: CD45 vs. PANCK [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B010.
Abstract B019: Regulatory macrophages contribute to tumor cell plasticity in colorectal cancer metastases
Authors: Cottam Matthew A. , Mirza Muhammad B. , Arner Emily N. , Siddiqui Marium , Lipscombe Clare , Hatem Zaid , Beckermann Katy E. , Idrees Kamran
Published: November 2024

Metastatic disease is the common cause of death in colorectal cancer. To better understand the cellular landscape of colorectal metastasis, we profiled primary tumors and liver, lung, and peritoneal metastases using single-cell RNA sequencing. Our analysis revealed a subset of tumor epithelial cells with a highly plastic transcription profile and, inversely, low expression of stemness markers. Tumor cells with plasticity markers were spatially enriched at the tumor- stroma interface with exposure to tissue microenvironmental factors. Cell-free malignant ascites, which recapitulates the tumor microenvironment, impaired expression of proliferation and stem- like markers in favor of plasticity markers and enhanced migration of tumor cells. Furthermore, Co-culture of colorectal tumor cells with CD11b+ macrophages isolated from malignant ascites from patients was sufficient to recapitulate tumor cell plasticity. Profiling of tumor-associated macrophages identified enrichment for a lipid-handling features and high spatial correlation with plastic tumor cells. Taken together, we demonstrate that tumor-associated macrophages contribute to disease progression through development of pro-malignant features.

Citation Format: Matthew A. Cottam, Muhammad B. Mirza, Emily N. Arner, Marium Siddiqui, Clare Lipscombe, Zaid Hatem, Katy E. Beckermann, Kamran Idrees. Regulatory macrophages contribute to tumor cell plasticity in colorectal cancer metastases [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B019.