bluuebunny/crossref_metadata_2025 huggingface dataset:
Enclaves as mushy magma strain archives: New perspectives on composite magmatic fabrics in plutons
Authors: Latimer Ben , McCarthy William , Mattsson Tobias , Reavy John
Published: September 2024

Mineral fabrics within igneous intrusions can archive both tectonic and magmatic processes. However, whether magmatic state fabrics reflect primary magmatic processes or regional tectonic strain is often ambiguous. To investigate when fabrics are formed, one can compare the mineral fabrics to primary magmatic features, such as the interface between solidified magmas in mingling zones. The monzodioritic Fanad pluton shows a NNE-SSW–aligned petrofabric parallel to the strike of a nearby shear zone, with dioritic enclaves aligned parallel and oblique to this petrofabric. We therefore aimed to test if the enclaves' internal fabrics are passive and align with enclave morphology or result from progressive overprint by regional tectonic strain. Crystallographic preferred orientation and anisotropy of magnetic susceptibility data from all enclaves and the host monzodiorite revealed a NNE-SSW petrofabric parallel to the regional tectonomagmatic fabric. However, anisotropy of anhysteretic remanent magnetization data within petrofabric-oblique enclaves revealed a primary fabric parallel to the enclave long axis. Therefore, we interpret enclave morphologies to reflect earlier magmatic state deformation, with fabrics being realigned to regional tectonic deformation. These two distinct petrofabrics were interpreted in the context of the magmatic processes and the evolving late Caledonian paleostress field, with earlier magma processes distinguished from subsequent tectonic overprinting occurring in the magmatic state. Our new data show that multiple fabrics are preserved within enclaves even though all fabric development occurred within a magmatic state. Our results also show that enclaves can effectively record successive strain events, providing new insight with which to decipher tectonomagmatic processes.
Suicidal behaviour is pathological: implications for psychiatric euthanasia
Authors: Sisti Dominic , Mann J John , Oquendo Maria A
Published: September 2024

Some have challenged the validity of labelling suicidal thoughts and behaviours (STB) as pathological. In this paper, we argue that STB is indeed pathological, thereby, situating suicide prevention within the realm of medicine, complicating calls for the legalisation of medical assistance in dying for individuals whose sole condition is psychiatric (psychiatric medical assistance in dying (MAID)). Evidence shows STB predicts the risk of suicide; moreover, several mental illnesses are associated with STB, and 70%–90% of suicide deaths are linked to psychiatric illness. Treating psychiatric illnesses can prevent suicide. We contend that this clinical evidence not only warrants the classification of STB as pathological but also necessitates its treatment and prevention. This perspective poses a challenge to legislation that would legalise psychiatric MAID.
Low predator and conspecific density lead to larger juveniles
Authors: Bath Devon R. , Gregory Robert S. , Snelgrove Paul V.R. , Geissinger Emilie A.
Published: September 2024

Predation is a key size-selective mechanism structuring juvenile fish populations, given typically greater susceptibility of small juveniles in a population to predation compared to larger individuals. We tested the hypothesis that greater predator abundance selectively removes the smallest age 0 Atlantic cod ( Gadus morhua) in nearshore habitat, truncating their size distribution in nursery habitats. We tested this hypothesis using fifteen years of historical data on nearshore fish abundance in Newman Sound, Newfoundland. Using skewness to estimate size–frequency distribution asymmetry, our analyses showed smaller age 0 cod were least prevalent under low predator and low conspecific densities. In contrast, high predator abundances corresponded to weak, size-selective removal of the smallest juveniles. Age 0 cod reached the largest sizes under lower predator and conspecific densities. Our analyses link size of individual juvenile fish in the wild with their survival, where predator abundance modulates the advantages gained by attaining larger size.
Evolutionary perspectives on thiamine supplementation of managed Pacific salmonid populations
Authors: Harder Avril M. , Reed Aimee N. , Rowland Freya E.
Published: September 2024

Thiamine deficiency complex (TDC) has been identified in an ever-expanding list of species and populations. In many documented occurrences of TDC in fishes, juvenile mortality can be high—up to 90% at the population level. Such sweeping demographic losses and concomitant decreases in genetic diversity due to TDC can be prevented by treating pre-spawn females or fertilized eggs with supplemental thiamine. However, some fisheries managers are hesitant to widely apply thiamine treatments due to the potential for unforeseen evolutionary consequences. With these concerns in mind, we first review the existing data regarding genetic adaptation to low-thiamine conditions and provide perspectives on evolution-informed treatment strategies with specific population examples. We also provide practical treatment information, consider the potential logistical constraints of thiamine supplementation, and explore the consequences of deciding against supplementation. Until new evidence bolsters or refutes the genetic adaptation hypothesis, we suggest that TDC mitigation strategies should be designed to support maximum population genetic diversity through thiamine supplementation.
Late times ΛCDM f(T) gravity model with parameterized q(z)
Authors: Shekh S. H. , Wankhade K. S. , Khan S. N. , Dixit A.
Published: September 2024

According to a number of astronomical studies, the universe is currently undergoing an accelerated expansion phase. We employed the recently proposed gravity, which holds that the current accelerated expansion phase of the universe is caused by a torsion scalar. The investigation is carried out using a parameterization of [Formula: see text] (where [Formula: see text] and [Formula: see text] are the model parameters) and the [Formula: see text] using [Formula: see text] is obtained. The model shows good agreement with recent observations, such as the LCDM model at late times. Finally, we examined how the cosmological parameters behaved in for constrained values.
Connecting the Dots: Bridging Innovation Management and Technology Transfer Through ISO 56002
Authors: Barboza Bertiene Maria Lack , Kovaleski Joaõ Luiz , Zola Fernanda Cavichioli , de Genaro Chiroli Daiane Maria
Published: September 2024

This paper highlights the significance of centralising innovation within organisations to gain a competitive edge in a rapidly changing world. It emphasises the pivotal role of ISO 56002, a standardised innovation management system, in fostering innovation capacity through diffusion, certification and development. By establishing innovation standards, organisations can consistently generate successful innovations, leveraging their resources and knowledge capital. However, technology transfer faces trust and inter-organisational cooperation barriers. ISO 56002 provides comprehensive guidelines to overcome these challenges and bridge standardisation and innovation perspectives. The proposed framework integrates technology transfer with the ISO 56002 system, consisting of five phases: engagement in innovation processes, certification of technology transferors, overcoming barriers, technology transfer agreements and analysing effectiveness. ISO 56002 facilitates collaboration, resource allocation, strategic planning and adopts a customer-centric approach. This framework fills a literature gap, offering organisations a competitive advantage in technology transfer. The study explores the relationship between ISO 56002 guidelines and technology transfer, emphasising collaboration, leadership, planning, support, operation, performance evaluation and improvement. ISO 56002 aligns with various aspects of technology transfer, emphasising sustainability, connectivity and competitiveness. Implementing ISO 56002 drives organisational growth and successful technology transfer.
The Neogene of the Vienna Basin: a synthesis
Authors: Harzhauser Mathias , Kranner Matthias , Siedl Wolfgang , Conradi Florian , Piller Werner E.
Published: September 2024

We present a revision of geological and palaeontological data of the Vienna Basin. The deposits comprise Miocene terrestrial, lacustrine and marine sediments, corresponding to the Ottnangian, Karpatian, Badenian, Sarmatian and Pannonian regional stages (=Burdigalian to Tortonian). New 3D seismics and the analyses of hundreds of core samples resulted in a wealth of information. Absolute ages were published for two tuffs and the lithostratigraphy was largely formalized. The evolution of the palaeoenvironments in the Vienna Basin strongly reflects the impact of global climatic events such as the Miocene Climatic Optimum, the Middle Miocene Climate Transition and the Tortonian Thermal Maximum. Global third-order sea-level cycles are reflected in the successions of marine depositional environments. Major drops of the relative sea-level caused strong erosion along the basin margins, with up to 300 m of palaeorelief. The strongest phase of erosion was linked to tectonics. Around the Early/Middle Miocene boundary, Lower Miocene strata became tilted during the Styrian Tectonic Phase. Subaerial canyons up to 600 m deep incised the basin at that time. A second phase of basin-wide erosion occurred during the Late Miocene when more than 200 m of upper Pannonian strata became removed from large parts of the Vienna Basin after 9 Ma.
The Styrian Basin: an overview with new insights from seismic data
Authors: Dax Florian , Sachsenhofer Reinhard F. , Schreilechner Marcellus G. , Tari Gabor
Published: September 2024

The Neogene Styrian Basin is the westernmost sub-basin of the Pannonian Basin System. The last comprehensive studies on the basin were published in the last millennium. This overview of the current understanding of basin evolution is based on the re-interpretation of partly unpublished reflection seismic data and a wealth of sedimentological and stratigraphic studies performed during the last 25 years. Reflection seismic data indicate the presence of a major east-to-southeast-dipping detachment horizon within the pre-Neogene basement reflecting high-strain upper crustal extension during the early Miocene syn-rift stage of basin evolution. Fault block rotations caused subsidence in several sub-basins, which developed often with marked asymmetric geometry. The maximum basin depth exceeds 4 km (Gnas Basin). Syn-rift deposits include thick alluvial fan and fan delta sediments overlain in the basin centre by deeper marine pelitic rocks. Subduction-related magmatic activity commenced during the syn-rift stage and continued into the middle to late Miocene post-rift stage. Syn- and post-rift sediments are separated by the middle Miocene ‘Styrian Unconformity’. Shallow marine sedimentation, controlled by third- and fourth-order sea-level variations, prevailed during the early post-rift stage. The final stage of basin evolution was characterized by differential surface uplift, erosion and Pliocene–Pleistocene basaltic magmatism.
MediKnit: Soft Medical Making for Personalized and Clinician-Designed Wearable Devices for Hand Edema
Authors: Kim Heather Jin Hee , Pourjafarian Narjes , Choudhury Arhan , Stilling Joan , Kao Cindy Hsin-Liu
Published: September 2024

Current rapid prototyping in medical domains relies on rigid 3D-printed materials, lacking flexibility, customization, and clinician-led input. This paper introduces MediKnit, a novel approach for the fabrication of soft medical devices, addressing critical limitations in existing design processes for medical devices. MediKnit provides a design tool empowering clinicians to personalize fabric-based devices for hand edema. This tool allows clinicians to adapt the design to individual patients' demands, thereby enhancing the overall effectiveness of therapy. The MediKnit device created by this tool consists of a machine-knit glove with active compression, which is programmable through a custom PCB. This device facilitates the mobilization of edema. To illustrate the practical implementation of our approach, this paper presents case studies involving six patients experiencing hand edema. The results demonstrate the adaptability and feasibility of our process for developing soft medical devices, highlighting its potential to broaden accessibility, facilitate personalized solutions, and empower clinicians as active medical makers.
Evaluating Autonomous Vehicle External Communication Using a Multi-Pedestrian VR Simulator
Authors: Tran Tram Thi Minh , Parker Callum , Yu Xinyan , Dey Debargha , Martens Marieke , Bazilinskyy Pavlo , Tomitsch Martin
Published: September 2024

With the rise of autonomous vehicles (AVs) in transportation, a pressing concern is their seamless integration into daily life. In multi-pedestrian settings, two challenges emerge: ensuring unambiguous communication to individual pedestrians via external Human-Machine Interfaces (eHMIs), and the influence of one pedestrian over another. We conducted an experiment (N=25) using a multi-pedestrian virtual reality simulator. Participants were paired and exposed to three distinct eHMI concepts: on the vehicle, within the surrounding infrastructure, and on the pedestrian themselves, against a baseline without any eHMI. Results indicate that all eHMI concepts improved clarity of communication over the baseline, but differences in their effectiveness were observed. While pedestrian and infrastructure communications often provided more direct clarity, vehicle-based cues at times introduced uncertainty elements. Furthermore, the study identified the role of co-located pedestrians: in the absence of clear AV communication, individuals frequently sought cues from their peers.
Evaluating the Privacy Valuation of Personal Data on Smartphones
Authors: Fan Lihua , Zhang Shuning , Kong Yan , Yi Xin , Wang Yang , Xu Xuhai "Orson" , Yu Chun , Li Hewu , Shi Yuanchun
Published: September 2024

Smartphones hold a great variety of personal data during usage, which at the same time poses privacy risks. In this paper, we used the selling price to reflect users' privacy valuation of their personal data on smartphones. In a 7-day auction, they sold their data as commodities and earn money. We first designed a total of 49 commodities with 8 attributes, covering 14 common types of personal data on smartphones. Then, through a large-scale reverse second price auction (N=181), we examined students' valuation of 15 representative commodities. The average bid-price was 62.8 CNY (8.68 USD) and a regression model with 14 independent variables found the most influential factors for bid-price to be privacy risk, ethnic and gender. When validating our results on non-students (N=34), we found that despite they gave significantly higher prices (M=109.8 CNY, 15.17 USD), "privacy risk" was still one of the most influential factors among the 17 independent variables in the regression model. We recommended that stakeholders should provide 8 attributes of data when selling or managing it.
HAIGEN: Towards Human-AI Collaboration for Facilitating Creativity and Style Generation in Fashion Design
Authors: Jiang Jianan , Wu Di , Deng Hanhui , Long Yidan , Tang Wenyi , Li Xiang , Liu Can , Jin Zhanpeng , Zhang Wenlei , Qi Tangquan
Published: September 2024

The process of fashion design usually involves sketching, refining, and coloring, with designers drawing inspiration from various images to fuel their creative endeavors. However, conventional image search methods often yield irrelevant results, impeding the design process. Moreover, creating and coloring sketches can be time-consuming and demanding, acting as a bottleneck in the design workflow. In this work, we introduce HAIGEN (Human-AI Collaboration for GENeration), an efficient fashion design system for Human-AI collaboration developed to aid designers. Specifically, HAIGEN consists of four modules. T2IM, located in the cloud, generates reference inspiration images directly from text prompts. With three other modules situated locally, the I2SM batch generates the image material library into a certain designer-style sketch material library. The SRM recommends similar sketches in the generated library to designers for further refinement, and the STM colors the refined sketch according to the styles of inspiration images. Through our system, any designer can perform local personalized fine-tuning and leverage the powerful generation capabilities of large models in the cloud, streamlining the entire design development process. Given that our approach integrates both cloud and local model deployment schemes, it effectively safeguards design privacy by avoiding the need to upload personalized data from local designers. We validated the effectiveness of each module through extensive qualitative and quantitative experiments. User surveys also confirmed that HAIGEN offers significant advantages in design efficiency, positioning it as a new generation of aid-tool for designers.
AirECG: Contactless Electrocardiogram for Cardiac Disease Monitoring via mmWave Sensing and Cross-domain Diffusion Model
Authors: Zhao Langcheng , Lyu Rui , Lei Hang , Lin Qi , Zhou Anfu , Ma Huadong , Wang Jingjia , Meng Xiangbin , Shao Chunli , Tang Yida , Chi Guoxuan , Yang Zheng
Published: September 2024

The electrocardiogram (ECG) has always served as a crucial biomedical examination for cardiac diseases monitoring and diagnosing. Typical ECG measurement requires attaching electrodes to the body, which is inconvenient for long-term monitoring. Recent wireless sensing maps wireless signals reflected from human chest into electrical activities of heart so as to reconstruct ECG contactlessly. While making great progress, we find existing works are effective only for healthy populations with normal ECG, but fall short when confronted with the most desired usage scenario: reconstructing ECG accurately for people with cardiac diseases such as atrial fibrillation, premature ventricular beat. To bridge the gap, we propose AirECG, which moves forward to reconstruct ECG for both healthy people and even cardiac patients with morbid ECG, i.e., irregular rhythm and anomalous ECG waveform, via contactless millimeter-wave sensing. To realize AirECG, we first custom-design a cross-domain diffusion model that can perform multiple iteration denoising inference, in contrast with the single-step generative models widely used in previous works. In this way, AirECG is able to identify and eliminate the distortion due to the unstable and irregular cardiac activities, so as to synthesize ECG even during abnormal beats. Furthermore, we enhance the determinacy of AirECG, i.e., to generate high-fidelity ECG, by designing a calibration guidance mechanism to combat the inherent randomness issue of the probabilistic diffusion model. Empirical evaluation demonstrates AirECG's ability of ECG synthesis with Pearson correlation coefficient (PCC) of 0.955 for normal beats. Especially for abnormal beats, the PCC still exhibits a strong correlation of 0.860, with 15.0%~21.1% improvement compared with state-of-the-art approaches.
PuppetMouse: Practical and Contactless Mouse Manipulation Attack via Intentional Electromagnetic Interference Injection
Authors: Song Wenfan , Liu Jianwei , Han Jinsong
Published: September 2024

Mouse is a ubiquitous input tool crucial for user-computer interaction in modern society. However, the inherent trust in the mouse may pose security risks. If the mouse is maliciously manipulated, the connected computer could be secretly controlled, endangering personal privacy and property. In this paper, we introduce PuppetMouse, the first intentional electromagnetic interference (IEMI) injection-based attack that can effectively manipulate mouse clicks and movements without physical contact. By adjusting the parameters of IEMI signals, PuppetMouse can precisely control the click side, as well as the movement direction and speed. We demonstrate PuppetMouse's effectiveness on 14 wired and wireless mice from popular brands. The short response delay (within 4 ms) affirms the real-time performance of PuppetMouse. Robustness analysis across different attack distances and material occlusions validate the stability and reliability of PuppetMouse. Two case studies on firewall disabling and malicious WiFi connection further prove the severe threats of PuppetMouse in the real world. We also propose an integrated set of hardware and software-based defensive mechanisms to mitigate the risks posed by PuppetMouse.
ChromaFlash: Snapshot Hyperspectral Imaging Using Rolling Shutter Cameras
Authors: Verma Dhruv , Ruffolo Ian , Lindell David B. , Kutulakos Kiriakos N. , Mariakakis Alex
Published: September 2024

Hyperspectral imaging captures scene information across narrow, contiguous bands of the electromagnetic spectrum. Despite its proven utility in industrial and biomedical applications, its ubiquity has been limited by bulky form factors, slow capture times, and prohibitive costs. In this work, we propose a generalized approach to snapshot hyperspectral imaging that only requires a standard rolling shutter camera and wavelength-adjustable lighting. The crux of this approach entails using the rolling shutter as a spatiotemporal mask, varying incoming light quicker than the camera's frame rate in order for the captured image to contain rows of pixels illuminated at different wavelengths. An image reconstruction pipeline then converts this coded image into a complete hyperspectral image using sparse optimization. We demonstrate the feasibility of this approach by deploying a low-cost system called ChromaFlash, which uses a smartphone's camera for image acquisition and a series of LEDs to change the scene's illumination. We evaluated ChromaFlash through simulations on two public hyperspectral datasets and assessed its spatial and spectral accuracy across various system parameters. We also tested the real-world performance of our prototype by capturing diverse scenes under varied ambient lighting conditions. In both experiments, ChromaFlash outperformed state-of-the-art techniques that use deep learning to convert RGB images into hyperspectral ones, achieving snapshot performance not demonstrated by prior attempts at accessible hyperspectral imaging.
Collecting Self-reported Physical Activity and Posture Data Using Audio-based Ecological Momentary Assessment
Authors: Le Ha , Lakshminarayanan Rithika , Li Jixin , Mishra Varun , Intille Stephen
Published: September 2024

μEMA is a data collection method that prompts research participants with quick, answer-at-a-glance, single-multiple-choice self-report behavioral questions, thus enabling high-temporal-density self-report of up to four times per hour when implemented on a smartwatch. However, due to the small watch screen, μEMA is better used to select among 2 to 5 multiple-choice answers versus allowing the collection of open-ended responses. We introduce an alternative and novel form of micro-interaction self-report using speech input - audio-μEMA- where a short beep or vibration cues participants to verbally report their behavioral states, allowing for open-ended, temporally dense self-reports. We conducted a one-hour usability study followed by a within-subject, 6-day to 21-day free-living feasibility study in which participants self-reported their physical activities and postures once every 2 to 5 minutes. We qualitatively explored the usability of the system and identified factors impacting the response rates of this data collection method. Despite being interrupted 12 to 20 times per hour, participants in the free-living study were highly engaged with the system, with an average response rate of 67.7% for audio-μEMA for up to 14 days. We discuss the factors that impacted feasibility; some implementation, methodological, and participant challenges we observed; and important considerations relevant to deploying audio-μEMA in real-time activity recognition systems.
GPTs and Hallucination
Authors: Waldo Jim , Boussard Soline
Published: September 2024

The findings in this experiment support the hypothesis that GPTs based on LLMs perform well on prompts that are more popular and have reached a general consensus yet struggle on controversial topics or topics with limited data. The variability in the applications's responses underscores that the models depend on the quantity and quality of their training data, paralleling the system of crowdsourcing that relies on diverse and credible contributions. Thus, while GPTs can serve as useful tools for many mundane tasks, their engagement with obscure and polarized topics should be interpreted with caution. LLMs' reliance on probabilistic models to produce statements about the world ties their accuracy closely to the breadth and quality of the data they're given.
Pivot: Panoramic-Image-Based VR User Authentication against Side-Channel Attacks
Authors: Xiao Gui , Ling Zhen , Fan Qunqun , Xu Xiangyu , Wu Wenjia , Ding Ding , Chen Chen , Fu Xinwen
Published: September 2024

With metaverse attracting increasing attention from both academic and industry, the application of virtual reality (VR) has extended beyond 3D immersive viewing/gaming to a broader range of areas, such as banking, shopping, tourism, education, and so on, which involves a growing amount of sensitive and private user data into VR systems. However, with current password-based user authentication schemes in mainstream VR devices, studies demonstrate that side-channel attacks can pose a severe threat to VR user privacy. To mitigate the threat, we propose a novel panoramic-image-based VR user authentication system, i.e.,
Pivot
, to defend against such attacks, yet maintain high usability. Specifically, in
Pivot
, we design an image-random-pivoting-based user interaction mechanism to assist users in quickly and securely selecting memorable points of interest in a panoramic image. Then an image region segmentation algorithm is designed to automatically scatter the points to regions to form the customized graphic password for the user, which could ensure a sufficiently large password space and also reduce the near-region point misclicks. Afterward, the region indexes are used to generate the hashed password for authentication. Both theoretical security analysis and extensive user studies demonstrate that
Pivot
is secure and user-friendly in practice.
FINEST
: Stabilizing Recommendations by Rank-Preserving Fine-Tuning
Authors: Oh Sejoon , Ustun Berk , Mcauley Julian , Kumar Srijan
Published: September 2024

Modern recommender systems may output considerably different recommendations due to small perturbations in the training data. Changes in the data from a single user will alter the recommendations as well as the recommendations of other users. In applications like healthcare, housing, and finance, this sensitivity can have adverse effects on user experience. We propose a method to stabilize a given recommender system against such perturbations. This is a challenging task due to (1) the lack of a “reference” rank list that can be used to anchor the outputs; and (2) the computational challenges in ensuring the stability of rank lists with respect to all possible perturbations of training data. Our method,
FINEST
, overcomes these challenges by obtaining reference rank lists from a given recommendation model and then
fine-tuning
the model under simulated perturbation scenarios with rank-preserving regularization on sampled items. Our experiments on real-world datasets demonstrate that
FINEST
can ensure that recommender models output stable recommendations under a wide range of different perturbations without compromising next-item prediction accuracy.
Floristic Composition, Diversity, and Regeneration of Woody Plant Species of Dabal Forest in Southeastern Ethiopia: Implication for Conservation
Authors: Sherafu Zinab , Egigu Meseret C. , J. M. Sasikumar
Published: September 2024

Floristic composition, population structure, and regeneration status of woody species of Dabal forest found in East Hararghe zone of Oromia Regional State, Ethiopia, were studied. Vegetation data were obtained from 52 main plots of 20 × 20 m for mature woody species and 5 subplots of 5 × 5 m for seedlings and saplings. Density and dbh of each live woody plant species found in each sample plot were recorded. Frequency, basal area, importance value, and Shannon–Wiener diversity indices were also computed. Totally 59 woody plant species distributed in 33 families were documented. Of these, 45.80, 44.10, and 5.08% were shrubs, trees, and lianas, respectively. Species diversity and evenness indices were 3.56 and 0.87, respectively. Stem count of all woody species was 3379 stems ha−1. Out of this, 44.6, 30.8, and 24.59% were seedlings (dbh <3.5 cm), saplings (dbh between 3.5 and 10 cm), and mature (dbh >10 cm) individuals, respectively. Total basal area of all individuals with dbh ≥3.5 cm was 29.88 m2 ha−1. Juniperus procera, Cupressus lusitanica, Eucalyptus globulus, Afrocarpus falcatus, Eucalyptus camaldulensis, Myrsine africana, Maytenus undata, Hagenia abyssinica, Ekebergia capensis, and Cordia africana were species with top ten IVI. Most of these species were top densest, dominant, and frequent. Analysis of population structure based on pooled densities of all species in each dbh class showed that density of seedling > sapling > mature individuals, signifying healthy population structure with good natural regeneration potential. On individual basis, however, 35.6 and 8.5% of species showed fair and poor regeneration statuses, respectively, that deserve attention for conservation.
Tumor-Infiltrating Lymphocytes in Necrotic Tumors after Melanoma Neoadjuvant Anti–PD-1 Therapy Correlate with Pathologic Response and Recurrence-Free Survival
Authors: Ma Kevin L. , Mitchell Tara C. , Dougher Meaghan , Sharon Cimarron E. , Tortorello Gabriella N. , Elder David E. , Morgan Eric E. , Gimotty Phyllis A. , Huang Alexander C. , Amaravadi Ravi K. , Schuchter Lynn M. , Flowers Ahron , Miura John T. , Karakousis Giorgos C. , Xu Xiaowei
Published: September 2024

Purpose:

Neoadjuvant anti–PD-1 therapy in melanoma may increase tumor-infiltrating lymphocytes (TIL), and more TIL are associated with better treatment response. A major pathologic response (MPR) in melanoma after neoadjuvant anti–PD-1 therapy usually comprises tumor necrosis and fibrosis. The role of TIL in necrotic tumor necrosis (nTIL) has not been explored.

Experimental Design:

We performed CD3 and CD8 IHC stains on 41 melanomas with geographic necrosis. Of the 41, 14 were immunotherapy-naïve, and 27 had been treated with one dose of neoadjuvant anti–PD-1 in two clinical trials. CD3+ and CD8+ nTIL were graded as absent/minimal or moderate/brisk. The percentage of necrotic areas in the tumor bed before and after treatment was quantified. The endpoints were MPR and 5-year recurrence-free survival (RFS).

Results:

In the immunotherapy-naïve cohort, 3/14 (21%) specimens had moderate/brisk CD3+, and 2/14 (14%) had moderate/brisk CD8+ nTIL. In the treated cohort, 16/27 (59%) specimens had moderate/brisk CD3+, and 15/27 (56%) had moderate/brisk CD8+ nTIL, higher than those of the naïve cohort (CD3, P = 0.046; CD8, P = 0.018). Tumor necrosis was significantly increased after anti–PD-1 therapy (P = 0.007). In the treated cohort, moderate/brisk CD3+ and CD8+ nTIL correlated with MPR (P = 0.042; P = 0.019, respectively). Treated patients with moderate/brisk CD3+ nTIL had higher 5-year RFS than those with absent/minimal nTIL (69% vs. 0%; P = 0.006). This persisted on multivariate analysis (HR, 0.16; 95% confidence interval, 0.03–0.84; P = 0.03), adjusted for pathologic response, which was borderline significant (HR, 0.26; 95% confidence interval, 0.07–1.01; P = 0.051).

Conclusions:

CD3+ and CD8+ nTIL are associated with pathologic response and 5-year RFS in patients with melanoma after neoadjuvant anti–PD-1 therapy.
FDA Approval Summary: Belzutifan for Patients with Advanced Renal Cell Carcinoma
Authors: Fallah Jaleh , Heiss Brian L. , Joeng Hee-Koung , Weinstock Chana , Gao Xin , Pierce William F. , Chukwurah Benjamin , Bhatnagar Vishal , Fiero Mallorie H. , Amiri-Kordestani Laleh , Pazdur Richard , Kluetz Paul G. , Suzman Daniel L.
Published: September 2024

On December 14, 2023, the U.S. FDA approved belzutifan (Welireg, Merck & Co., Inc.) for patients with advanced renal cell carcinoma (RCC) following treatment with a PD-1/PD-L1 inhibitor and a VEGF tyrosine kinase inhibitor. The FDA granted traditional approval based on LITESPARK-005 (NCT04195750), an open-label, randomized, head-to-head trial of 746 patients with advanced RCC that progressed following treatment with both a PD-1/PD-L1 inhibitor and a VEGF tyrosine kinase inhibitor. Patients were randomized (1:1) to receive belzutifan or everolimus. The primary endpoints were progression-free survival (PFS) assessed by blinded independent central review and overall survival. A statistically significant improvement in PFS was demonstrated for belzutifan compared with everolimus [HR = 0.75; 95% confidence interval (CI), 0.63–0.90; one-sided P value = 0.0008]. Kaplan–Meier curves reflected nonproportional hazards with similar median PFS estimates of 5.6 months (95% CI, 3.9–7.0) in the belzutifan arm and 5.6 months (95% CI, 4.8–5.8) in the everolimus arm. Although not reaching full maturity, the overall survival results seemed to show a favorable trend in the belzutifan arm compared with the everolimus arm (HR, 0.88; 95% CI, 0.73–1.07). The confirmed objective response rate by blinded independent central review was 22% and 3.6% in the belzutifan and everolimus arms, respectively. Observed toxicities differed between treatment arms, but drug discontinuations and interruptions due to treatment-emergent adverse events were lower in the belzutifan arm compared with the everolimus arm, and a descriptive analysis of patient-reported symptom and functional outcomes was suggestive of favorable tolerability for belzutifan compared with everolimus.
Antiangiogenic Tyrosine Kinase Inhibitors have Differential Efficacy in Clear Cell Renal Cell Carcinoma in Bone
Authors: Maksimovic Stefan , Boscolo Nina C. , La Posta Ludovica , Barrios Sergio , Moussa Mohammad Jad , Gentile Emanuela , Pesquera Pedro I. , Li Wenjiao , Chen Jianfeng , Gomez Javier A. , Basi Akshay , Burks Jared K. , Alvarez-Breckenridge Christopher , Gao Jianjun , Campbell Matthew T. , Dondossola Eleonora
Published: September 2024

Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney neoplasm; bone metastasis (BM) develops in 35% to 40% of metastatic patients and results in substantial morbidity and mortality, as well as medical costs. A key feature of ccRCC is the loss of function of the von Hippel–Lindau protein, which enhances angiogenesis via vascular endothelial growth factor release. Consequently, antiangiogenic tyrosine kinase inhibitors (TKI) emerged as a treatment for ccRCC. However, limited data about their efficacy in BM is available, and no systematic comparisons have been performed. We developed mouse models of bone and lung ccRCC tumors and compared their anticancer efficacy, impact on mouse survival, and mechanisms of action, including effects on tumor cells and both immune and nonimmune (blood vessels and osteoclasts) bone stromal components. This approach elucidates the efficacy of TKIs in ccRCC bone tumors to support rational interrogation and development of therapies.

Significance:

TKIs showed different efficacy in synchronous bone and lung metastases and did not eradicate tumors as single agents but induced extensive reprogramming of the BM microenvironment. This resulted in a significant decrease in neoangiogenic blood vessels, bone remodeling, and immune cell infiltration (including CD8 T cells) with altered spatial distribution.
Semaglutide Treatment in a Patient with Extreme Obesity and Massive Lymphedema: A Case Report
Authors: Nguyen Joanne Thanh-Tâm , Barbet-Massin Marie-Amélie , Pupier Emilie , Larroumet Alice , Bosc Laurène , Michelet Marie , Monsaingeon-Henry Maud , Gatta-Cherifi Blandine
Published: September 2024

Introduction: Extreme obesity (BMI ≥50 kg/m2) is a complex pathology to treat. One of the complications of extreme obesity is massive localized lymphedema (MLL), due to compromised lymphatic drainage. There is a lack of literature guiding the medical management of these conditions. Case Presentation: We present a 43-year-old male who was admitted to our specialized obesity center for weight management. His initial weight was 255 kg and BMI was 93.7 kg/m2. He suffered from massive multifocal lymphedema of his left leg. He was bedridden due to his condition and malnourished, as shown by multiple vitamin deficiencies. The patient received care from our multidisciplinary team including nurses, dieticians, physical therapists, and psychologists. Treatment with semaglutide was started in hospital and continued at home. The maximal dose used was 1 mg/week but decreased during follow-up to 0.25 mg/week to avoid malnutrition. Protein and nutritional supplements were added. At 28 weeks of therapy, the patient had lost 40 kg or 15.7% of his total body weight. His lymphedema decreased; he had lost at least 16 cm of his left thigh circumference. He was able to walk again and regain autonomy of his daily activities of living. Conclusion: Semaglutide can be effective in patients with extreme obesity, with the support of a multidisciplinary team in a specialized obesity center. It can also help decrease MLL. More data are needed to guide medical treatment of patients with extreme obesity and MLL.
Severe Thrombocytopenia from Trastuzumab and Pertuzumab Combination Therapy in a Patient with HER2-Positive Metastatic Rectal Cancer
Authors: Okemoto Dai , Yamaguchi Toshifumi , Yamaguchi Mariko , Kadono Toru , Yukami Hiroki , Fakhrejahani Elham , Nishikawa Hiroki
Published: September 2024

Introduction: In recent years, trastuzumab and pertuzumab have been used in treatment protocols for patients with HER2-positive colorectal cancer. Although severe thrombocytopenia is an uncommon side effect of anti-HER2 antibody therapy, we present the first patient with HER2-positive metastatic rectal cancer who developed significant thrombocytopenia after trastuzumab and pertuzumab administration. Case Presentation: The condition was identified as drug-induced immune thrombocytopenia associated with trastuzumab and pertuzumab. Despite the discontinuation of anti-HER2 treatment and administration of corticosteroids, and in addition to frequent platelet transfusions, a low platelet count persisted. Consequently, we determined that the patient presented with a condition similar to immune thrombocytopenic purpura (ITP) and selected a treatment approach consisting of eltrombopag, a thrombopoietin receptor agonist. Subsequently, the patient’s platelet count did not decrease further but rather improved. Conclusion: Although uncommon, anti-HER2 antibodies can cause severe thrombocytopenia. Furthermore, if thrombocytopenia persists after treatment discontinuation and the administration of corticosteroids, exploring treatment options aligned with managing ITP is essential.
Telomere Length Is Associated with Increased Risk of Cardiovascular Events in Patients with End-Stage Kidney Disease on Hemodialysis
Authors: Vostatek Rafaela , Hohensinner Philipp , Schmaldienst Sabine , Lorenz Matthias , Klauser-Braun Renate , Pabinger Ingrid , Säemann Marcus , Ay Cihan , Königsbrügge Oliver
Published: September 2024

Introduction: Patients with chronic kidney disease, especially those with end-stage kidney disease (ESKD) on hemodialysis (HD), are at increased risk for cardiovascular disease (CVD), including myocardial infarction and ischemic stroke. A shortening in telomere length, as a parameter for accelerated vascular aging, is an established biomarker for CVD in the general population. We aimed to elucidate the role of telomere length in ESKD patient on HD and its association with cardiovascular outcomes. Methods: Telomere length was measured in a prospective population-based cohort study of prevalent HD patients. DNA was isolated from whole blood, sampled at baseline, and analyzed for telomere length via a qPCR-based approach. The risk for the occurrence of the independently adjudicated three-point major adverse cardiovascular event outcome (myocardial infarction, ischemic stroke, and cardiovascular death) was statistically analyzed considering the competing risk of non-cardiovascular death. Results: In the cohort of 308 patients with ESKD (115 [37.3%] women, median [25th–75th percentile] age: 67.0 [56.8–76.0]), the median telomere length was 1.51 kb (25th–75th percentile 0.6–3.2 kb). The 3P-MACE outcome occurred with an incidence rate of 9.4 per 100 patient-years. Patients with longer telomere length more frequently had vascular nephropathy compared to patients with shorter telomere length. Interestingly, patients in the highest quartile of telomere length had a 1.8-fold increased risk for 3P-MACE (95% CI: 1.051–3.201, p = 0.033), after multivariable adjustment for age, history of stroke, myocardial infarction, venous thromboembolism, presence of heart valve replacement, atrial fibrillation, smoking, anticoagulation, or immunosuppressive use. Conclusion: Surprisingly, in this high-risk cohort of patients with ESKD on HD, longer telomere lengths were associated with increased risk of cardiovascular events.
Response to Biologic Therapy in Patients with Asthma and Reduced Pulmonary Diffusion Capacity
Authors: Biener Leonie , Morobeid Hussein , Pizarro Carmen , Nickenig Georg , Skowasch Dirk
Published: September 2024

Introduction: Asthma patients with a smoking history are usually excluded from asthma trials to exclude smoking-related comorbidities like chronic obstructive pulmonary disease (COPD). Therefore, little is known about the efficacy of biologic therapy in asthma patients with reduced diffusing capacity of the lungs for carbon monoxide (DLCO). Methods: This study aimed to assess the response to biologic therapy in asthma patients with reduced DLCO. A total of 77 consecutive patients undergoing biologic therapy in a routine clinical setting were included in the analysis and divided into three groups: DLCO ≥60%, DLCO <60% and <10 pack-years, and DLCO <60% and ≥10 pack-years = asthma and COPD comorbidity. Follow-up evaluations were conducted after a minimum of 6 months of therapy. Results: After 34.0 ± 10.2 weeks, comparable therapeutic responses were observed between the three groups. There were no differences between the groups in terms of reduction in the annual acute exacerbation rate (AE median −3 [25th percentile −5; 75th percentile −1] vs. −6.1 [−11.3;−2.2] vs. −3 [−6;−2], p = 0.067), oral corticosteroid (OCS) doses (−5 [−10;0] vs. −1 [−7.5;0] vs. −7.5 [−10;−4] mg, p = 0.136), improvement in Asthma Control Test (ACT) scores (4 [0;9.3] vs. 3 [−1;6] vs. 4 [3;10], p = 0.276) or forced expiratory volume in 1 s (FEV1) improvement (5.5 [−2;21.5] vs. 0.5 [−2.8;9.3] vs. 5 [0;16] % predicted, p = 0.328). Linear regression analysis revealed no significant correlation between DLCO levels and changes in OCS dosage or AE rate, nor between DLCO and improvements in ACT scores or FEV1. Notably, a smaller proportion of patients exhibited a reduced transfer coefficient (DLCO/VA) (n = 13, 16.9%). This parameter did not significantly impact therapy response either. Conclusion: Our findings suggest that biologic therapy can effectively manage asthma irrespective of DLCO measurements. Thus, reduced DLCO values should not preclude thorough asthma diagnosis and treatment. Further investigation into the utility of DLCO/VA assessment in this context is warranted.
Causal Associations between Tea Consumption and Rapid Eye Movement Sleep Behavior Disorder: A Mendelian Randomization Study
Authors: Li Jinyu , Zhang Zixuan , Li Fujia , Liu Yuning , Yin Peixiao , Wang Xi , Huang Shuming , Zu Jie , Zhang Shenyang , Dong Liguo , Xu Chuanying , Zhang Tao , Xu Ran , Sun Chao , Wang Zhi , Li Yumeng , Zhang Xueling , Cui Guiyun , Zhang Wei
Published: September 2024

Introduction: Previous studies have shown that tea consumption may have a protective effect against neurodegenerative diseases. However, the exact causal relationship between tea consumption and the precursor stages of certain neurodegenerative diseases, namely, REM sleep behavior disorder (RBD), remains unclear. To evaluate the causal association between tea consumption and RBD, we employed a Mendelian randomization study. Methods: We identified genetic instrumental variables that are significantly associated with tea consumption through genome-wide association studies (GWAS) in European populations. Bidirectional two-sample Mendelian randomization was utilized to determine the causal relationship between tea consumption and RBD, while sensitivity analyses were further employed to evaluate the robustness of the results. The multivariate Mendelian randomization method was used to assess the influence of relevant confounding factors on the results. Results: In the MR analysis using the inverse-variance weighting method, a significant causal relationship between tea consumption and RBD was observed (OR = 0.046, 95% CI: 0.004–0.563, p = 0.016). The consistency of findings across maximum likelihood, MR Pleiotropy RESidual Sum and Outlier, and multivariate MR after adjusting for potential confounding further supports this causal association. Sensitivity analyses revealed no evidence of heterogeneity or pleiotropy. Conclusions: The findings of our study demonstrate a robust causal association between tea consumption and RBD, indicating that tea consumption may serve as a protective factor against the development of RBD.
Resistant Hypertension and Mortality: An Observational Cohort Study
Authors: de la Sierra Alejandro , Ruilope Luis M. , Staplin Natalie , Gorostidi Manuel , Vinyoles Ernest , Segura Julián , Armario Pedro , Oliveras Anna , Williams Bryan
Published: September 2024

BACKGROUND:

Resistant hypertension is characterized by elevated blood pressure (BP) despite using 3 antihypertensive agents. Ambulatory BP monitoring (ABPM) detects the presence of white-coat resistant hypertension (24-hour BP <130/80 mm Hg). The aim of the study was to evaluate risks of death in resistant hypertension compared with controlled hypertension, as well as in ABPM-confirmed (24-hour BP ≥130 or 80 mm Hg), versus white-coat resistant hypertension.

METHODS:

We selected 8146 patients with controlled hypertension (office BP <140/90 mm Hg while being treated with ≤3 antihypertensive drugs) and 8577 with resistant hypertension (BP ≥140 or ≥90 mm Hg while being treated with ≥3 drugs). All-cause and cardiovascular mortalities (median follow-up, 9.7 years) were compared between groups, as well as between patients with white-coat (3289) and ABPM-confirmed (5288) resistant hypertension. Hazard ratios (HRs) from Cox models after adjustment for clinical confounders were used for comparisons.

RESULTS:

Compared with controlled hypertension, resistant hypertension was associated with an increased risk in all-cause (HR, 1.21 [95% CI, 1.12–1.30]) and cardiovascular mortalities (HR, 1.33 [95% CI, 1.17–1.51]) in confounder-adjusted models. Compared with white-coat, ABPM-confirmed resistant hypertension was associated with an increased risk of all-cause (HR, 1.45 [95% CI, 1.32–1.60]) and cardiovascular (HR, 1.68 [95% CI, 1.43–1.98]) mortalities. When ABPM-confirmed and white-coat resistant hypertension were separately compared with controlled hypertension, only the former was associated with an increased risk of death and cardiovascular death (HR, 1.36 [95% CI, 1.26–1.48] and 1.56 [95% CI, 1.36–1.79]), respectively.

CONCLUSIONS:

ABPM-confirmed resistant hypertension is associated with an increased risk of death and cardiovascular death with respect to both controlled hypertension and white-coat resistant hypertension.