bluuebunny/crossref_metadata_2025 huggingface dataset:
A Quantile Dependence among Exchange Rate, Stock Prices and Oil Prices: An Empirical Evidence from India
Authors: Aldawsari Salem Hamad , Tan Wei Shuen , Elsherazy Tarek Abbas , Chang Bisharat Hussain , Alzoubi Haitham M. , Ognjanović Ivana
Published: November 2024

This study investigates the dynamic relationship between exchange rates, oil prices, and stock prices in the Indian market, considering bearish, bullish, and neutral market states. By utilizing the Quantile ARDL method, we explore long- and short-run relationships in differing market states. The variations in sensitivities of oil prices and exchange rates with stock prices across diverse quantiles reflect significant variations in the Indian equity markets. Importantly, our study provides actionable insights for policymakers and stakeholders within India, empowering them with specific strategies for managing currency, stock prices, and oil prices under diverse market states. These insights are not just theoretical but directly applicable to real-world economic and financial decision-making, enhancing the ability of policymakers and stakeholders to navigate the complex Indian market.
Remobilization of inverted normal faults drives active extension in the axial zone of the southern Apennine mountain belt (Italy)
Authors: Camanni G. , De Landro G. , Mazzoli S. , Michele M. , Muzellec T. , Ascione A. , Schaff D. P. , Tarantino S. , Zollo A.
Published: November 2024

The Irpinia region is one of the most seismically active areas of Italy owing to ongoing, late-orogenic extension in the axial zone of the Apennine mountain belt. However, the 3D architecture and the nature of the faults that drive this extension are still uncertain, posing challenges to seismic hazard assessment. Here, we address these uncertainties by integrating a new catalogue of high-resolution micro-seismicity (M
L
 < 3.5) complemented by earthquake focal mechanisms, with existing 3D seismic velocity models and geological data. We found that micro-seismicity is primarily taking place along a segmented, approximately 60 km long, deep-seated, Mesozoic normal fault that was inverted during the shortening stages of the Apennine orogeny and then extensionally reactivated during the Quaternary. These findings suggest that multiple events of reactivation of long-lived faults can weaken their strength, making them prone to co-seismic remobilization under newly imposed strain fields in active mountain belts.
Bringing Collaborative Positioning to Native 5G Systems for Enhanced 2D & 3D Location Services
Authors: Lin Yu-Tai , Matson N. Cameron , Sundaresan Karthikeyan
Published: November 2024

5G's large bandwidths and ubiquity make it a promising candidate for catalyzing future mobile services (emergency, V2X, XR, etc.) that benefit from accurate positioning over a wide area. However, we demonstrate that its heavy reliance on infrastructure base stations significantly limits its positioning ability in urban environments, where multi-story buildings and urban canyons are the norm, resulting in only a small fraction of devices being positioned, often only in 2D. To this end, we propose
CAMP,
a novel, collaboration-augmented paradigm for 2D and 3D positioning with cellular networks, where UEs leverage 5G NR's peer-peer Sidelink protocol to directly enable positioning measurements between each other in a scalable manner. Leveraging better connectivity (higher degree and SNR) between devices, CAMP overcomes the challenges inherent to infrastructure approaches. It brings algorithmic innovations in distributed, stochastic access and dynamic resource scheduling in a 5G-compliant manner to Sidelink measurements that are otherwise not scalable in conventional gNB-driven Sidelink operation.
CAMP
is implemented as a near real-time xApp service in the Open-RAN framework. Evaluations in a small cell 5G test-bed and a large-scale RAN on Colosseum, highlight its ability to position over 80% (72%) UEs with under 3m accuracy in 2D (3D) in real-world urban scenarios (compared to 30% with infrastructure approaches) and with 7-25x less overhead compared to baseline collaborative schemes.
Wixor: Dynamic TDD Policy Adaptation for 5G/xG Networks
Authors: Hassan Ahmad , Aggarwal Shivang , Ibrahim Mohamed , Sharma Puneet , Qian Feng
Published: November 2024

In the era of 5G and beyond, dynamic Time Division Duplex (TDD) has become essential for supporting applications that demand high bandwidth and low latency. Emerging uplink-intensive use cases such as real-time video analytics, autonomous vehicles and augmented reality further complicate the balance between uplink and downlink resources. Despite their potential, TDD policies employed by current 5G networks remain underexplored. Our investigation reveals that existing TDD policies are static and predominantly downlink-focused, failing to adapt to fluctuating network demands. We introduce Wixor, a robust dynamic TDD policy adaptation system tailored for 5G and next-generation (xG) networks. It proactively adjusts the allocation of TDD resources between uplink and downlink, addressing various practical challenges. Prototyped on a programmable testbed, Wixor demonstrates substantial performance improvements across diverse applications, achieving up to 96.5% enhancement in Quality of Experience (QoE) compared to existing baselines.
Helix: A RAN Slicing Based Scheduling Framework for Massive MIMO Networks
Authors: An Qing , Pandey Divyanshu , Doost-Mohammady Rahman , Sabharwal Ashutosh , Shakkottai Srinivas
Published: November 2024

An important aspect of 5G networks is the development of Radio Access Network (RAN) slicing, a concept wherein the virtualized infrastructure of wireless networks is subdivided into slices (or enterprises), tailored to fulfill specific use-cases. A key focus in this context is the efficient radio resource allocation to meet various enterprises' service-level agreements (SLAs). In this work, we introduce Helix: a channel-aware and SLA-aware RAN slicing framework for massive multiple input multiple output (MIMO) networks where resource allocation extends to incorporate the spatial dimension available through beamforming. Essentially, the same time-frequency resource block (RB) can be shared across multiple users through multiple antennas. Notably, certain enterprises, particularly those operating critical infrastructure, necessitate dedicated RB allocation, denoted as private networks, to ensure security. Conversely, some enterprises would allow resource sharing with others in the public network to maintain network performance while minimizing capital expenditure. Building upon this understanding, Helix comprises scheduling schemes under both scenarios: where different slices share the same set of RBs, and where they require exclusivity of allocated RBs. We validate the efficacy of our proposed schedulers through simulation by utilizing a channel data set collected from a real-world massive MIMO testbed. Our assessments demonstrate that resource sharing across slices using our approach can lead up to 60.9% reduction in RB usage compared to other approaches. Moreover, our proposed schedulers exhibit significantly enhanced operational efficiency, with significantly faster running time compared to exhaustive greedy approaches while meeting the stringent 5G sub-millisecond-level latency requirement.
VIGOR: Reviving Cloud Gaming Sessions
Authors: He Zhaoyuan , Yang Yifan , Li Shuozhe , Qiu Lili , Dai Diyuan , Yang Yuqing
Published: November 2024

Cloud gaming is a multi-billion dollar industry. A client in cloud gaming sends its movement to the game server on the Internet, which renders and transmits the resulting video back. In order to provide a good gaming experience, a latency below 80 ms is required. This means that video rendering, encoding, transmission, decoding, and displaying have to finish within that time frame, which is especially challenging to achieve due to server overload, network congestion, and losses. In this paper, we propose VIGOR, a new method to revive cloud gaming sessions by recovering lost or corrupted video frames. Unlike traditional video frame recovery, VIGOR uses game states to enhance recovery accuracy significantly and utilizes partially decoded frames to recover lost portions. We develop a holistic system that consists of (i) efficiently extracting game states, (ii) modifying H.264 video decoder to generate a mask to indicate which portions of video frames need recovery, and (iii) designing a novel neural network to recover either complete or partial video frames. VIGOR is extensively evaluated using iPhone 12 and laptop implementations, and we demonstrate the utility of game states in the game video recovery and the effectiveness of our overall design.
FlowChronicle: Synthetic Network Flow Generation through Pattern Set Mining
Authors: Cüppers Joscha , Schoen Adrien , Blanc Gregory , Gimenez Pierre-Francois
Published: November 2024

Network traffic datasets are regularly criticized, notably for the lack of realism and diversity in their attack or benign traffic. Generating synthetic network traffic using generative machine learning techniques is a recent area of research that could complement experimental test beds and help assess the efficiency of network security tools such as network intrusion detection systems. Most methods generating synthetic network flows disregard the temporal dependencies between them, leading to unrealistic traffic. To address this issue, we introduce
FlowChronicle
, a novel synthetic network flow generation tool from mined patterns and Bayesian networks. As a core component, we propose a novel pattern miner in combination with statistical models to preserve temporal dependencies. We empirically compare our method against state-of-the-art techniques on several criteria, namely realism, diversity, compliance, and novelty. This evaluation demonstrates the capability of
FlowChronicle
to achieve high-quality generation while significantly outperforming the other methods in preserving temporal dependencies between flows. Besides, in contrast to deep learning methods, the patterns identified by
FlowChronicle
are explainable, and experts can verify their soundness. Our work substantially advances synthetic network traffic generation, offering a method that enhances both the utility and trustworthiness of the generated network flows.
PACER: Accelerating Distributed GNN Training Using Communication-Efficient Partition Refinement and Caching
Authors: Mahmud Shohaib , Shen Haiying , Iyer Anand
Published: November 2024

Despite recent breakthroughs in distributed Graph Neural Network (GNN) training, large-scale graphs still generate significant network communication overhead, decreasing time and resource efficiency. Although recently proposed partitioning or caching methods try to reduce communication inefficiencies and overheads, they are not sufficiently effective due to their sampling pattern-agnostic nature. This paper proposes a Pipelined Partition Aware Caching and Communication Efficient Refinement System (Pacer), a communication-efficient distributed GNN training system. First, Pacer intelligently estimates each partition's access frequency to each vertex by jointly considering the sampling method and graph topology. Then, it uses the estimated access frequency to refine partitions and caching vertices in its two-level cache (CPU and GPU) to minimize data transfer latency. Furthermore, Pacer incorporates a pipeline-based minibatching method to mask the effect of the network communication. Experimental results on real-world graphs show that Pacer outperforms state-of-the-art distributed GNN training system in training time by 40% on average.
Design Systems Are Accessibility Delivery Vehicles
Authors: Wahid Shahtab
Published: November 2024

Design systems are infrastructure built for consumers—the designers and developers—working on applications. A successful one allows consumers in an organization to quickly scale design and development across applications, increase productivity, and establish consistency. Many consumers, however, are not prepared to build for accessibility. Couldn't an organization make building accessibility support for applications scalable, productive, and consistent? This article explores how a design system becomes an important vehicle to supporting accessibility.
Global Placement Exploiting Soft 2D Regularity
Authors: Fang Donghao , Zhang Boyang , Hu Hailiang , Li Wuxi , Yuan Bo , Hu Jiang
Published: November 2024

Cell placement is a step of paramount importance in chip physical design and requests relentless effort for continuous improvement. Recently, designs with two-dimensional (2D) processing element arrays have become popular primarily due to their deep neural network hardware applications. The 2D array regularity is similar to but different from the regularity of conventional datapath designs. To exploit the 2D array regularity, this work develops a new global placement technique, Placement of Arrays with SOft Regularity (PASOR), built upon RePlAce, the state-of-the-art placement framework. Experimental results from various designs show that the proposed approach can reduce global routing wirelength by 11% and 6% compared to RePlAce and a previous work on datapath driven placement, respectively.
Wi-Fi Sensing Techniques for Human Activity Recognition: Brief Survey, Potential Challenges, and Research Directions
Authors: Miao Fucheng , Huang Youxiang , Lu Zhiyi , Ohtsuki Tomoaki , Gui Guan , Sari Hikmet
Published: November 2024

Recent advancements in wireless communication technologies have made Wi-Fi signals indispensable in both personal and professional settings. The utilization of these signals for Human Activity Recognition (HAR) has emerged as a cutting-edge technology. By leveraging the fluctuations in Wi-Fi signals for HAR, this approach offers enhanced privacy compared to traditional visual surveillance methods. The essence of this technique lies in detecting subtle changes when Wi-Fi signals interact with the human body, which are then captured and interpreted by advanced algorithms. This article initially provides an overview of the key methodologies in HAR and the evolution of non-contact sensing, introducing sensor-based recognition, computer vision, and Wi-Fi signal based approaches, respectively. It then explores tools for Wi-Fi-based HAR signal collection and lists several high-quality datasets. Subsequently, the article reviews various sensing tasks enabled by Wi-Fi signal recognition, highlighting the application of deep learning networks in Wi-Fi signal detection. Experimental results are then presented that assess the capabilities of different networks. The findings indicate significant variability in the generalization capacities of neural networks and notable differences in test accuracy for various motion analyses.
Hypertension Management in Pregnancy
Authors: Ryan Kimberly , McGrath Lidija , Brookfield Kathleen
Published: November 2024

Chronic hypertension and preeclampsia spectrum disorders in pregnancy are important contributors to long-term maternal morbidity and mortality. Due to physiologic changes during pregnancy and the postpartum period, blood pressure expectations differ between primary care providers and obstetricians. The goal of this article is to describe the pathophysiology and definitions of hypertension in the obstetric context and review current evidence for management during pregnancy and the postpartum period. Longitudinal follow-up with a primary care provider after delivery is crucial for long-term cardiovascular risk reduction in hypertensive patients.
Understanding the effects of different transcranial magnetic stimulation control protocols: a behavioral and neural perspective
Authors: Peng Bo , Zhao Yan , Li Xiaopeng , Dong Ke , Li Tingni , Liu Dongxu , Dai Guangyan , Wu Xiuqin , Li Jingting , Chen Xi , Liu Peng , Liu Hanjun
Published: November 2024

This is the first study to provide neurobehavioral evidence comparing the effects of three transcranial magnetic stimulation (TMS) control protocols on vocal feedback control. The findings suggest that sham stimulation and real stimulation [continuous theta burst stimulation (c-TBS) over vertex and V1] produce similar neural and non-neural effects on vocal pitch regulation. Despite no differences in vocal responses, all protocols led to prolonged N1 latencies and reduced P2 amplitudes, emphasizing the importance of including a baseline condition to isolate genuine TMS effects.
Developing the Fear of Disasters Scale and Exploring Its Psychometric Properties
Authors: Güzel Aysun
Published: November 2024

Aims: The present methodological study attempted to develop the Fear of Disasters Scale (FDS) and reveal its psychometric properties.

Methods: While explanatory factor analysis (EFA) was carried out on the data of 265 voluntary participants, the data of 75 participants were used to explore the test–retest reliability of the scale. Confirmatory factor analysis (CFA) was carried out on the data of 150 participants. All analyses were performed on the Statistical Package for the Social Sciences (SPSS) 25.0 and linear structural relations (LISRELs) programs.

Results: Cronbach’s α value was calculated to be 0.93. The test–retest reliability analysis resulted in a significant, very strong, and positive correlation (p < 0.001; r = 0.92). The CFA yielded the following fit indices for the scale: p > 0.05, χ2/df = 1.51, root mean square error of approximation (RMSEA) = 0.05, standardized root mean square residual (SRMR) = 0.02, goodness of fit index (GFI) = 0.96, normed fit index (NFI) = 0.97.

Conclusions: The findings revealed that the one‐factor instrument with seven items is valid and reliable for measuring fear of disasters (FD) in the sample.
Late Diagnostic Clues in Rapidly Progressing Probable Heidenhain Variant of Creutzfeldt–Jakob Disease
Authors: Gaini Rahul , Denniss Julia , Lackey Elijah
Published: November 2024

Presenting symptoms of sporadic Creutzfeldt–Jakob disease (sCJD) are variable, and as imaging and EEG may be normal in the early to middle stages of the disease process, serial testing is vital when there is clinical suspicion for sCJD. We present a case of probable Heidenhain variant of sCJD (HvCJD) with notable rapid progression. A 72‐year‐old woman presented with neurological decline following new–onset visual changes. Over the course of 3 weeks, she developed ataxia followed by paranoia, memory impairment, and visual hallucinations. An extensive workup from 1 week prior at an outside hospital was unrevealing and included two magnetic resonance imaging (MRI) studies read as normal and an EEG without periodic sharp wave complexes. Repeat of imaging at our hospital showed cortical restricted diffusion in the right occipital lobe. In combination with new periodic sharp wave complexes visualized on prolonged EEG, concern was raised for sCJD. Palliative care was consulted early in the hospitalization, and the patient was transitioned to comfort care and discharged 3 days after admission. She declined quickly and passed away at home within a week, one day before her send out CSF sample resulted with a positive real‐time quaking‐induced conversion (RT‐QuiC) and markedly elevated T‐tau protein and 14‐3‐3 gamma. As there is no treatment for this fatal disease, palliative engagement and discussion of goals of care in cases of CJD is critical in providing compassionate care for the patient and their family. High clinical suspicion warrants discussion of comfort care measures even prior to confirmation with RT‐QuiC.
Multi‐Scale Geomechanical Modelling of Unconventional Shale Gas: The Implication on Assisting Geophysics–Geology–Engineering Integration
Authors: Xiao Yue , Liang Chong , Zhu Dawei , Zou Chunmei , Yan Jun , Bai Yu
Published: November 2024

In the development of unconventional shale play, simulation of the performance for wells needs to incorporate sufficient complexity in geology to take fully into account the variabilities in petrophysical and geomechanical properties. These parameters controlling the effective stimulated rock volume (eSRV) represent the heterogeneity and strong‐layering nature of unconventional reservoirs: high inter‐bedding anisotropy, flow behaviours and pre‐existing geological disconnections (bedding planes, faults, fissuring, natural fractures). This realistic simulation model includes direct information and interpreted understanding from data sources in a wide range of resolutions and scales and is finally coupled with hydraulic fracturing and reservoir depletion modelling in terms of mechanical. The multi‐scale geomechanical model incorporates processed seismic interpreted data (10 m scale), petrophysical core data (cm scale), routine scalar logs (m scale) and resistivity borehole image (0.25 cm scale). The vital role the multi‐scale geomechanical model plays during the entire workflow is to underpin the disconnection among actual well logs, conventional seismic interpretation and geological complexity by calculating and predicting field scale geomechanical parameters and in situ stresses distribution. Multiple research investigations and case studies on such integration include data acquisition and processing methods, modelling upscaling methodologies and data diagnostical techniques from multidisciplinary perspectives. Although these works show great progress in improved understanding of the spatial and temporal distribution of formation reservoir and geomechanical distribution, uncertainty remains as local stress variations and mechanical‐flow properties between layers are impossible to capture.
Isolation of Thermophilic Bacteria Geobacillus subterraneus From Mount Tangkuban Perahu and the Novelty as a Candidate for Streptococcus mutans Anti‐Biofilm
Authors: Rachmawati Emma , Asarina Shinta , Bagus Kennardi Gabriel , Tabina Tawangalun Akeyla , Arumimaniyah Candra , Indah Sari Kartika , Tjaturina Pramesti Hening , Safitri Ratu , Maskoen Ani Melani
Published: November 2024

Thermophilic bacteria living in extreme areas with high temperatures are capable of producing secondary metabolites, such as antimicrobial peptides (AMPs). AMPs are stable at high temperatures and show good antibacterial activity. Therefore, this study aimed to identify thermophilic bacteria from the crater of Mount Tangkuban Perahu around West Java and assess antibacterial effectiveness of AMPs against Streptococcus mutans, which contribute to oral biofilm formation. The isolate obtained was identified using 16S ribosomal ribonucleic acid (rRNA) gene sequencing, and the supernatant of the isolate was tested against S. mutans American Type Culture Collection (ATCC) 25175 using the disc assay method. To determine AMPs‐coding genes, its genome was uploaded to antibiotic and secondary metabolite analysis shell (antiSMASH) 5.0.0 platform and biofilm inhibition was tested using the microtiter plate technique (with a 96‐well bottom). Subsequently, the results were assessed using a microplate reader operating at 595 nm wavelength. The isolate was identified as Geobacillus subterraneus, with antibacterial activity against S. mutans, and produced an inhibition zone of 8.40 mm at an optimum pH of 8. The output of AMPs‐coding gene showed that AMPs of the isolate were a member of the lanthipeptide class I, or bacteriocin‐I group. AMPs of G. subterraneus suppressed the growth of S. mutans biofilm at a supernatant concentration of 5%, with the lowest optical density (OD) value of 0.061 and the highest percentage of biofilm growth inhibition at 28.24%. Based on the results, G. subterraneus derived from the crater of Mount Tangkuban Perahu showed potent antibacterial properties against S. mutans, making it a promising novel S. mutans anti‐biofilm candidate.
Table S3 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms In Vitro and in a First-In-Human Phase I Clinical Trial
Authors: Schwenzer Hagen , De Zan Erica , Elshani Mustafa , van Stiphout Ruud , Kudsy Mary , Morris Josephine , Ferrari Valentina , Um In Hwa , Chettle James , Kazmi Farasat , Campo Leticia , Easton Alistair , Nijman Sebastian , Serpi Michaela , Symeonides Stefan , Plummer Ruth , Harrison David J. , Bond Gareth , Blagden Sarah P.
Published: November 2024

Table S3 related to Figure 2: Genome wide haploid genetic screen identifies genes necessary for the activity of 3'-dA and NUC-7738.
Supplementary Materials from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms In Vitro and in a First-In-Human Phase I Clinical Trial
Authors: Schwenzer Hagen , De Zan Erica , Elshani Mustafa , van Stiphout Ruud , Kudsy Mary , Morris Josephine , Ferrari Valentina , Um In Hwa , Chettle James , Kazmi Farasat , Campo Leticia , Easton Alistair , Nijman Sebastian , Serpi Michaela , Symeonides Stefan , Plummer Ruth , Harrison David J. , Bond Gareth , Blagden Sarah P.
Published: November 2024

NMR spectra for synthesised compounds
Supplementary Data 3 from Functional Impact of Genomic Complexity on the Transcriptome of Multiple Myeloma
Authors: Ziccheddu Bachisio , Da Vià Matteo C. , Lionetti Marta , Maeda Akihiro , Morlupi Silvia , Dugo Matteo , Todoerti Katia , Oliva Stefania , D'Agostino Mattia , Corradini Paolo , Landgren Ola , Iorio Francesco , Pettine Loredana , Pompa Alessandra , Manzoni Martina , Baldini Luca , Neri Antonino , Maura Francesco , Bolli Niccolò
Published: November 2024

Differential gene expression analysis for tumor suppressor genes and chromosome 1q for different allelic status.
Supplementary Figure 5 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms In Vitro and in a First-In-Human Phase I Clinical Trial
Authors: Schwenzer Hagen , De Zan Erica , Elshani Mustafa , van Stiphout Ruud , Kudsy Mary , Morris Josephine , Ferrari Valentina , Um In Hwa , Chettle James , Kazmi Farasat , Campo Leticia , Easton Alistair , Nijman Sebastian , Serpi Michaela , Symeonides Stefan , Plummer Ruth , Harrison David J. , Bond Gareth , Blagden Sarah P.
Published: November 2024

Figure S5 related to figure 5: NUC-7738 down-regulates cell survival pathways and induces apoptosis. A) A) Renal 786-O and UM-RC-2 cells were treated with NUC-7738 for 24 hours and stained for NF-kB p65 and nuclear dsDNA (DAPI). P65 was seen in the nucleus of controls but disappeared after treatment with NUC-7738. B) Haematoxylin and Eosin (H&E) staining of ex vivo tissue treated with NUC-7738 for 24 hours. H&E examination showed increased numbers of shrunken pyknotic nuclei corresponding to caspase 3 positive cells.
Supplementary Figure 2 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms In Vitro and in a First-In-Human Phase I Clinical Trial
Authors: Schwenzer Hagen , De Zan Erica , Elshani Mustafa , van Stiphout Ruud , Kudsy Mary , Morris Josephine , Ferrari Valentina , Um In Hwa , Chettle James , Kazmi Farasat , Campo Leticia , Easton Alistair , Nijman Sebastian , Serpi Michaela , Symeonides Stefan , Plummer Ruth , Harrison David J. , Bond Gareth , Blagden Sarah P.
Published: November 2024

Figure S2 related to figure 3: Validation of top hits from genome wide haploid screen A) Genes of interest were deleted using an all-in-one gRNA-CRISPR/Cas9 construct and following Puromycin selection. Dose response curves of polyclonal HAP1 knockout cells (black) and wildtype control cells (red) from selected gene hits of the genome wide haploid screen. Cells were treated with NUC-7738 or 3'-dA for 48 hours. B) NUDT2 was deleted in HAP1 cells using all-in-one gRNA-CRISPR/CAS9, as shown by Western blot analysis of NUDT2 knockout cells using specific antibodies to NUDT2. Polyclonal wildtype control and knockout cells were treated with either NUC-7738 or 3'-dA. IC50 values were determined and the fold changes between knockout and wildtype cells were calculated. C) Single cell-derived clonal knockouts for NUDT2 (KO1 and KO2) and two wildtype isogenic cell lines. Western blot analysis of NUDT2 knockout cells using specific antibodies to NUDT2 is shown. IC50 values were determined following treatment with NUC-7738 or 3'-dA and the fold changes between knockout and wildtype cells were calculated. D) HINT1 knockout HAP1 cells were treated with 3'-dA or NUC-7738 and levels of cleaved PARP were analysed on a Western blot using specific antibodies.
Figure 6 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms In Vitro and in a First-In-Human Phase I Clinical Trial
Authors: Schwenzer Hagen , De Zan Erica , Elshani Mustafa , van Stiphout Ruud , Kudsy Mary , Morris Josephine , Ferrari Valentina , Um In Hwa , Chettle James , Kazmi Farasat , Campo Leticia , Easton Alistair , Nijman Sebastian , Serpi Michaela , Symeonides Stefan , Plummer Ruth , Harrison David J. , Bond Gareth , Blagden Sarah P.
Published: November 2024

Clinical validation of the activity of NUC-7738. A, Intracellular levels of 3′-dATP, 3′-dAMP, and NUC-7738 were measured in the PBMCs from 7 patients who received treatment with NUC-7738 at a dose of 400–900 mg/m2 in the ongoing NuTide:701 clinical study. High intracellular levels of 3′-dATP were detected 0.25 hours after the start of infusion and were maintained for at least 48 hours. h, hours. B, IHC staining for HINT1 and NF-κB p65 subunit of pre- and posttreated tissue samples obtained from a melanoma cancer specimen. C, MA Plot summarizing transcriptomic profiling of pre- and posttreated tissue samples. Red dots indicate genes passing a FDR < 10%.
Figure S4 from Fresh Tissue Multi-omics Profiling Reveals Immune Classification and Suggests Immunotherapy Candidates for Conventional Chondrosarcoma
Authors: Li Binghao , Li Guoqi , Yan Xiaobo , Zhu Dan , Lin Patrick P. , Wang Zenan , Qu Hao , He Xuexin , Fu Yanbiao , Zhu Xiuliang , Lin Peng , Zhang Jiangnan , Li Xiaoya , Dai Hui , Chen Huabiao , Poznansky Mark C. , Lin Nong , Ye Zhaoming
Published: November 2024

Figure S4
Data from Neoadjuvant FOLFIRINOX Therapy Is Associated with Increased Effector T Cells and Reduced Suppressor Cells in Patients with Pancreatic Cancer
Authors: Peng Hui , James C. Alston , Cullinan Darren R. , Hogg Graham D. , Mudd Jacqueline L. , Zuo Chong , Takchi Rony , Caldwell Katharine E. , Liu Jingxia , DeNardo David G. , Fields Ryan C. , Gillanders William E. , Goedegebuure S. Peter , Hawkins William G.
Published: November 2024

AbstractPurpose:
FOLFIRINOX has demonstrated promising results for patients with pancreatic ductal adenocarcinoma (PDAC). Chemotherapy-induced immunogenic cell death can prime antitumor immune responses. We therefore performed high-dimensional profiling of immune cell subsets in peripheral blood to evaluate the impact of FOLFIRINOX on the immune system.
Experimental Design:
Peripheral blood mononuclear cells (PBMC) were obtained from treatment-naïve (n = 20) and FOLFIRINOX-treated patients (n = 19) with primary PDAC tumors at the time of resection. PBMCs were characterized by 36 markers using mass cytometry by time of flight (CyTOF).
Results:
Compared with treatment-naïve patients, FOLFIRINOX-treated patients showed distinct immune profiles, including significantly decreased inflammatory monocytes and regulatory T cells (Treg), increased Th1 cells, and decreased Th2 cells. Notably, both monocytes and Treg expressed high levels of immune suppression-associated CD39, and the total CD39+ cell population was significantly lower in FOLFIRINOX-treated patients compared with untreated patients. Cellular alterations observed in responders to FOLFIRINOX included a significantly decreased frequency of Treg, an increased frequency of total CD8 T cells, and an increased frequency of CD27−Tbet+ effector/effector memory subsets of CD4 and CD8 T cells.
Conclusions:
Our study reveals that neoadjuvant chemotherapy with FOLFIRINOX enhances effector T cells and downregulates suppressor cells. These data indicate that FOLFIRINOX neoadjuvant therapy may improve immune therapy and clinical outcome in patients with PDAC.
Overcoming GABA-induced Treg suppression of immunity by ABAT to augment CD8+T cell anti-tumor immune response in liver cancer
Authors: Han Hui , Lu Yandi , Xu Suwen , Zhang Weirui , Lin Weisen , Zhan Jianwen , Chen Gengzhen , Gu Binbin
Published: November 2024

Background: ABAT, a key enzyme in GABA catabolism, modulates anti-tumor immune activity across various cancers. However, the molecular mechanisms by which the ABAT/GABA axis exerts immune regulation in the liver cancer microenvironment remain unclear.
Methods: ABAT expression in liver cancer tissues was scrutinized via the TCGA-LIHC database, and the 5-year survival rates of liver cancer patients were appraised through Kaplan-Meier survival analyses. The mRNA levels of ABAT in liver cancer cell lines were quantified by qRT-PCR. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), colony formation, and Transwell assays were employed to gauge the influence of ABAT overexpression on liver cancer cell growth, proliferation, migration, and invasion, respectively. Western blot evaluated EMT-related protein expression. ELISA quantified GABA, IL-10, TGF-β1, Granzyme B, and IFN-γ in the culture medium. Flow cytometry was used to measure the frequency of CD25+FOXP3+ cells and the expression of CD25, CD69, and PD-1 on CD8+T cells in co-culture. Carboxifluorescein diacetate succinimidyl ester (CFSE) dilution assays were performed to assess the proliferative activity of CD8+T cells.
Results: ABAT was found to be underexpressed in liver cancer tissues and cells, and such underexpression is indicative of a poorer prognosis for patients, while its overexpression was shown to curb the malignancy of liver cancer cells. Upon overexpression of ABAT, there is a decrease in GABA levels in the cell supernatant, coupled with an increase in IL-10 and TGF-β1 cell number, and an upsurge in the CD25+FOXP3+ cell ratios, all of which were restored by the addition of exogenous GABA. Furthermore, the depletion of ABAT led to a reduction in the proliferation and tumor-killing ability of CD8+T cells, effects that were reversed by the application of GABAA receptor inhibitors.
Conclusion: ABAT functions to inhibit Treg differentiation in liver cancer through downregulation of GABA, thus promoting the antitumor activity of CD8+T cells.
Gender Differences in Adverse Effects and Dosing Practices of Low-Dose Oral Minoxidil for Androgenetic Alopecia: A Retrospective Analysis of 310 Patients
Authors: Ong Michael M. , Do Huongly , Ho Benedict , Lipner Shari R.
Published: November 2024

Introduction: Off-label low-dose oral minoxidil (LDOM) is used for androgenetic alopecia (AGA) treatment, with limited safety data. We investigated LDOM adverse effects (AEs) in AGA patients. Methods: AGA patients taking LDOM were identified (January 1, 2010–December 3, 2022). AEs and management were recorded from follow-up and emergency room visits. Fisher’s exact test, logistic regression, and Benjamini-Hochberg procedure assessed significance and adjusted for multiple comparisons. Results: Three hundred ten AGA patients were analyzed with mean age 47.5 years and 53.2% females. The average LDOM dose was lower for females vs. males. AEs were observed in 14.9% of patients, with dizziness/lightheadedness, hypertrichosis, and extremity edema being most common. Higher doses were associated with increased likelihood of dizziness/lightheadedness. Females had higher overall incidence of AEs; however, gender differences did not persist after subgroup analysis. Among patients experiencing AEs, 11.1% adjusted their dosage and 28.9% discontinued treatment. Conclusion: A higher LDOM dose increased risk of dizziness/lightheadedness in both genders, with females more likely to experience any AE. Patients are often started at inappropriately high doses, causing AE-induced regimen changes. Therefore, we recommend a cautious approach when prescribing LDOM, starting with lower doses and gradually increasing as tolerated, and counseling female patients regarding their higher risk of AEs.
Hormone Regulation of Corticotropin-Releasing Factor Receptor 1 in the Female Mouse Brain
Authors: De Guzman Rose M. , Jacobskind Jason S. , Rosinger Zachary J. , Rybka Krystyna A. , Parra Katherine E. , Caballero Aya L. , Sharif Massoud S. , Justice Nicholas J. , Zuloaga Damian G.
Published: November 2024

Introduction: Corticotropin-releasing factor receptor 1 (CRFR1) is a key regulator of neuroendocrine and behavioral stress responses. Previous studies have demonstrated that CRFR1 in certain hypothalamic and preoptic brain areas is modified by chronic stress and during the postpartum period in female mice, although the potential hormonal contributors to these changes are unknown. Methods: This study focused on determining the contributions of hormones associated with stress and the maternal period (glucocorticoids, prolactin, estradiol/progesterone) on CRFR1 levels using a CRFR1-GFP reporter mouse line and immunohistochemistry. Results: Administration of dexamethasone, an agonist of the glucocorticoid receptor, elevated CRFR1 in the anteroventral periventricular nucleus (AVPV/PeN) and paraventricular hypothalamus (PVN) with no changes found in the medial preoptic area (MPOA) or arcuate nucleus. Treatment with prolactin for 5 days elevated CRFR1 levels in the MPOA with no changes in other regions. Finally, we utilized the hormone-simulated pseudopregnancy (HSP) paradigm to mimic changes in estradiol and progesterone across pregnancy and the early postpartum period. Female mice receiving HSP treatment, as well as mice receiving HSP treatment that then underwent 5 days of estrogen withdrawal (EW), showed alterations in CRFR1 relative to control groups that mirrored changes previously reported in postpartum mice. Specifically, CRFR1 levels increased in the AVPV/PeN and decreased in the MPOA and PVN, with no changes found in the arcuate nucleus. HSP- and EW-treated mice also showed decreases in tyrosine hydroxylase-expressing neurons in the AVPV/PeN. Discussion/Conclusion: Overall, these hormone-induced changes in stress-regulating CRFR1 neurons may impact behavioral and neuroendocrine stress responses.
Anatomical, functional, and prognostic results of vitrectomy in epiretinal membranes secondary to retinal vein occlusions
Authors: Chung Yoo-Ri , Mainguy Adam , Chatziralli Irini , Smaoui Anissa , Bodaghi Bahram , Paques Michel , Tadayoni Ramin , Cicinelli Maria Vittoria , Touhami Sarah
Published: November 2024

Introduction: We investigated the anatomical and functional results of vitrectomy associated with the peeling of secondary epiretinal membranes (ERM) in patients with retinal vein occlusion (RVO) and determined the prognostic factors of surgical outcomes.
Methods: This retrospective, multicenter, observational study included 50 patients with RVO who underwent vitrectomy with ERM removal between July 2012 and February 2021. Visual acuity (VA) and central macular thickness (CMT) were investigated up to three years. Univariate analysis identified the predictive factors associated with functional and anatomical outcomes.
Results: Fifty eyes from 50 patients (62% with central RVO) were included. The mean VA of 0.9 ± 0.7 logMAR preoperatively improved to 0.5 ± 0.5 logMAR after 24 months (p=0.01). Anatomically, the mean preoperative CMT was 501 ± 168 μm, decreasing to 348 ± 108 μm at month 24 (p=0.008). By 36 months, VA had improved or stabilized in 90% of the eyes, whereas CMT had reduced by at least 20% from baseline in 80% of the eyes. A lower number of intravitreal injections (IVI) was required after vitrectomy. Worse preoperative VA, absence of preoperative pan-retinal photocoagulation, and postoperative use of adjunctive IVI were associated with VA recovery. Higher baseline CMT and the use of preoperative dexamethasone injections were associated with an improvement in CMT.
Conclusion: Vitrectomy for ERM secondary to RVO was effective in improving VA and recovering CMT for up to 3 years and reduced the number of IVIs.
Analysis of Optic Disc Morphology and the Peripapillary Retinal and Choroidal Thickness by the Swept Source Optical Coherence Tomography in Patients with Moyamoya Disease
Authors: Yang Fei , Li Xiaochun , Wang Xijuan , Chen Xuanling , Niu Yaqian , Zhang Yan , Zhang Chengxia , Liu Guangfeng
Published: November 2024

Introduction: Moyamoya disease (MMD) is a chronic cerebrovascular occlusive disorder. Ocular involvement in patients with MMD has increasingly been recognized and reported in recent years. This study aimed to investigate the changes of optic disc morphology and the peripapillary retinal and choroidal thickness in patients with MMD. Methods: This cross-sectional study included 56 patients diagnosed with idiopathic MMD and 56 healthy controls matched by age and gender. All participants underwent swept-source optical coherence tomography to capture the optic disc morphology as well as the peripapillary retinal and choroidal thickness. Optic disc parameters, including cup area, rim area, cup volume, rim volume, cup-disc area ratio (CDR), linear CDR, and vertical CDR were measured and compared between the two groups. Additionally, the thickness of the whole peripapillary retina, retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and choroid were evaluated and analyzed across 12 clock-hour segments around the peripapillary region. Results: The rim area in MMD patients was significantly less than in controls, while the CDR in MMD patients was significantly larger than that in the control group. There was no statistically significant difference between the two groups regarding disc area, cup area, cup volume, rim volume, vertical and horizontal diameter of disc. The retinal thickness at the 7 o’clock position was significantly thinner in the MMD group compared to the control group and the temporal RNFL thickness, particularly at the 7 o’clock and 9 o’clock positions, was significantly reduced in the MMD group (p < 0.05). The GCL layer at the 7 o’clock position was thinner in the MMD group than in the control group (p < 0.05). The MMD group showed a notably reduced average choroidal thickness, particularly in the inferior-temporal region (p < 0.05). There was a correlation between peripapillary choroidal and GCL layer thickness in the MMD group, but no significant correlations were found with rim area, CDR, or RNFL. Conclusions: In patients with MMD, there is an increase in the CDR accompanied by a decrease in the rim area. Additionally, there is thinning of the temporal RNFL, GCL, and choroidal thickness, notably in the inferotemporal quadrant of the optic disc.
Comparison of efficacy and safety of different types of one-way valves in endoscopic lung volume reduction in patients with severe lung emphysema.
Authors: Sgarbossa Thomas , Borchers Philipp , Saccomanno Jacopo , Ahrens Katharina , Wüstefeld Hannah Friederike , Pappe Eva , Wuelfing Uta , Klein Ulrich , Witzenrath Martin , Stanzel Franz , Grah Christian , Hübner Ralf-Harto
Published: November 2024

Introduction
Endoscopic lung volume reduction with valves (ELVR) is an effective intervention in patients with severe lung emphysema. Two types of valves are established in clinical practice: Zephyr endobronchial valves (EBV) and Spiration Valve System (SVS). We aim to compare outcomes and the safety associated with these two types of one-way valves.

Methods
Data were collected from three German lung emphysema centers as part of a prospective observational study focusing on lung volume reduction. Two groups were formed based on valve types. In both groups, lung function (FEV1, RV, DLCO, pCO2), 6-minute walking distance (6-MWD), quality of life (SGRQ, mMRC, CAT), and complication rate were recorded at baseline and at follow-up three to six months later.

Results
A total of 54 patients were treated with SVS valves and 99 patients with EBV valves. There were no significant differences between both groups at baseline. Notably, both types of valves exhibited significant enhancements in lung function and quality of life. Interestingly, there were no significant differences in the mean change of all measured parameters for both groups, suggesting comparable improvements in EBV and SVS. Pneumothorax was the most common complication for both valve types. The incidence of adverse events did not differ significantly between groups.

Conclusion
Our study suggests that both types of valves are safe and effective in the treatment of severe lung emphysema. We recommend choosing the valve type based on individual bronchial anatomy. However, further randomized studies are needed to confirm our results.
CTCA Prior to Invasive Coronary Angiography in Patients With Previous Bypass Surgery: Patient-Related Outcomes, Imaging Resource Utilization, and Cardiac Events at 3 Years From the BYPASS-CTCA Trial
Authors: Kelham Matthew , Beirne Anne-Marie , Rathod Krishnaraj S. , Andiapen Mervyn , Wynne Lucinda , Learoyd Annastazia E. , Forooghi Nasim , Ramaseshan Rohini , Moon James C. , Davies Ceri , Bourantas Christos V. , Baumbach Andreas , Manisty Charlotte , Wragg Andrew , Ahluwalia Amrita , Pugliese Francesca , Mathur Anthony , Jones Daniel A.
Published: November 2024

BACKGROUND:

In patients with previous coronary artery bypass grafting, computed tomography cardiac angiography (CTCA) before invasive coronary angiography (ICA) was demonstrated in the BYPASS-CTCA trial (Randomized Controlled Trial to Assess Whether Computed Tomography Cardiac Angiography Can Improve Invasive Coronary Angiography in Bypass Surgery Patients) to reduce procedure time and incidence of contrast-associated acute kidney injury, with greater levels of patient satisfaction. Patient-related outcomes, utilization of further diagnostic imaging resources, and longer-term incidence of major adverse cardiac events were key secondary end points not yet reported.

METHODS:

Patients with prior coronary artery bypass grafting referred for ICA were randomized 1:1 to undergo CTCA before ICA or ICA alone and followed up for a median of 3 (2.2-3.4) years. Angina status was assessed using the Seattle Angina Questionnaire and overall quality of life using the EQ-5D-5L. The incidence of noninvasive imaging use and major adverse cardiac events were compared between the 2 groups.

RESULTS:

In all, 688 patients were randomized, 344 to CTCA+ICA and 344 to ICA only. The mean age of participants was 69.8 years, with 45% undergoing ICA for acute coronary syndromes and the remainder stable angina. At 3 months follow-up, patients in the CTCA+ICA group were more likely to be angina-free (51.7% versus 43.2%;
P
=0.03) with greater quality of life (EQ-5D-5L index, 81.6 versus 74.4;
P
=0.001), although these improvements did not persist. At 3 years follow-up, imaging resource use (35.8% versus 45.1%; odds ratio, 0.68 [95% CI, 0.50–0.92];
P
=0.013) and incidence of major adverse cardiac events were lower in the CTCA+ICA group (35.8% versus 43.5%; hazard ratio, 0.73 [95% CI, 0.58–0.93];
P
=0.010).

CONCLUSIONS:

In patients with prior coronary artery bypass grafting undergoing ICA, CTCA before ICA leads to reductions in the use of imaging resources and the rate of major cardiac events out to 3 years, but with similar patient-related outcome measures. Together with the initial findings of BYPASS-CTCA, these data are supportive of routinely undertaking a CTCA before ICA in patients with prior coronary artery bypass grafting.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03736018.