bluuebunny/crossref_metadata_2025 huggingface dataset:
Easy access: identification verification and shipping methods used by online vape shops
Authors: Bertrand Adrian , Diaz Megan C , Hair Elizabeth C , Schillo Barbara A
Published: January 2024

Objective

This project assesses how online vape shops (OVSs) verify buyer identification (ID) and the shipping methods used to send products within the USA.

Methodology

In January 2023, we conducted three online searches (eg, ‘best online vape shops’) from our office in Washington, District of Columbia, to identify popular OVSs. Two trained coders identified discrete features available within the site sections: ‘About Us’, ‘Shipping Policy’ and ‘Frequently Asked Questions’, or displayed within the site’s homepage. Coders recorded OVS listed locations, shipping discounts, shipping companies used and ID verification methods. Lastly, coders indicated if the site requested ID/age verification after adding an item to the shopping cart and initiating checkout procedures.

Results

We identified 64 unique OVSs; 92.2% (n=59) offered shipping and 82.8% (n=53) shipped to US buyers; 76.6% (n=49) allowed visitors to type a birthday or choose the ‘21 or older’ option to access the site. Of the 59 sites shipping to buyers, 76.3% (n=45) offered free shipping, 21.9% (n=14) required login to purchase products, while most sites (n=45, 76.3%) allowed visitors to reach the checkout page without ID verification. The US Postal Service is the most commonly used shipping carrier (n=23), in violation of the Preventing All Cigarette Trafficking Act.

Conclusions

Most OVSs rely on age self-certification, which underage youth can easily exploit to access these products. Findings warrant that the Food and Drug Administration, state and local policymakers explore additional actions regulating online tobacco sales to address the compliance issues our data elucidate. These include enhanced surveillance, compliance checks and stricter penalties.
Use of inhaled corticosteroids and the risk of hospitalisation for pneumonia in children with asthma: a nationwide cohort study
Authors: Sielinou Kamgang Karl-Hermann , Rhedin Samuel Arthur , Almqvist Catarina , Wintzell Viktor
Published: January 2024

Background

The potential association between the use of inhaled corticosteroids (ICS) and the risk of pneumonia among adults is disputed and paediatric-specific evidence is scarce.

Aim

To assess the potential association between ICS, use and the risk of hospitalisation for pneumonia among children (age 2–17 years) with asthma.

Methods

This was a cohort study based on nationwide data from routine clinical practice in Sweden (January 2007 to November 2021). From 425 965 children with confirmed asthma, episodes of new ICS use and no use were identified using records of dispensed drugs. We adjusted for potential confounders with propensity score overlap weighting and the risk of a hospitalisation with pneumonia as primary diagnosis was estimated. Multiple subgroup and sensitivity analyses were also performed.

Results

We identified 249 351 ICS (mean follow-up of 0.9 years) and 214 840 no-use (mean follow-up of 0.7 years) episodes. During follow-up, 369 and 181 events of hospitalisation for pneumonia were observed in the ICS and no-use episodes, respectively. The weighted incidence rates of hospitalisation for pneumonia was 14.5 per 10 000 patient-years for ICS use episodes and 14.6 for no-use episodes. The weighted HR for hospitalisation for pneumonia associated with ICS use was 1.06 (95% CI 0.88 to 1.28) and the absolute rate difference was −0.06 (95% CI −2.83 to 2.72) events per 10 000 patient-years, compared with no use.

Conclusions

In this nationwide cohort study, we found no evidence of an association between ICS use and the risk of hospitalisation for pneumonia among children with asthma, as compared with no use.
Bidirectional static loading tests on barrette piles. A case history from Ho Chi Minh City, Vietnam
Authors: Nguyen Tan , Fellenius Bengt H.
Published: January 2024

Bidirectional static loading tests were conducted on two strain-gage instrumented barrettes installed to 72 m depth in Ho Chi Minh City, Vietnam. The barrettes were to support a 16-storey building with 5 basements. The soil profile comprised layers of medium coarse to fine sand, medium clay, firm to stiff clayey soil, and dense sandy silt. The region is experiencing an ongoing land subsidence affecting the upper about 40 m of soil and, on average in the city, the ground surface is currently settling 16 mm/year. The test records were processed by means of effective stress analysis to provide the axial pile force distribution, load transfer functions, and equivalent head-down load–movement curve. The analysis was then used to obtain the equivalent pile-head load–movement response adjusted to the planned 22 m deep basement excavation. Load transfer functions were back-calculated from the test records and indicate that the construction will show somewhat large load-transfer movement. However, because the equilibrium plane will be below the subsiding layers, below 40 m depth, downdrag is not expected to affect the building. The load response of the barrettes is compared to the results of a bidirectional (BD) loading test on a 1.8 m diameter bored pile at an adjacent project.
ResQNets: a residual approach for mitigating barren plateaus in quantum neural networks
Authors: Kashif Muhammad , Al-Kuwari Saif
Published: January 2024

The barren plateau problem in quantum neural networks (QNNs) is a significant challenge that hinders the practical success of QNNs. In this paper, we introduce residual quantum neural networks (ResQNets) as a solution to address this problem. ResQNets are inspired by classical residual neural networks and involve splitting the conventional QNN architecture into multiple quantum nodes, each containing its own parameterized quantum circuit, and introducing residual connections between these nodes. Our study demonstrates the efficacy of ResQNets by comparing their performance with that of conventional QNNs and plain quantum neural networks through multiple training experiments and analyzing the cost function landscapes. Our results show that the incorporation of residual connections results in improved training performance. Therefore, we conclude that ResQNets offer a promising solution to overcome the barren plateau problem in QNNs and provide a potential direction for future research in the field of quantum machine learning.
The competition between α-decay and spontaneous fission for even–even isotopes of superheavy nuclei in the range 106≤Z≤124
Authors: Pahlavani M. R. , Ahmadvand F.
Published: January 2024

The [Formula: see text]-decay and spontaneous fission (SF) half-lives for even–even isotopes of superheavy nuclei in the range [Formula: see text] are predicted using nuclear double-folding and Coulomb potentials. The [Formula: see text]-decay half-lives are computed based on WKB approximation for tunneling probability through potential barrier. The half-lives of SF have also been calculated using a semi-empirical relation constructed by Santhosh et al. [Nucl. Phys. A 832, 220 (2009)]. Our calculated half-lives of cold SF and [Formula: see text]-decay are compared with the available experimental data. This comparison indicates that our obtained half-lives are in good agreement with the available experimental data. The competition between [Formula: see text]-decay and SF is also analyzed in detail and the decay modes are predicted for the unknown cases. Variation of [Formula: see text]-decay and SF half-lives with mass number of the parent isotopes for each nucleus revealed the major role played with shell effect.
Bounds of Two Toughnesses and Binding Numbers for Star Factors
Authors: Gao Yujia , Ji Zhen , Sun Xiaojie , Tong Qinghe
Published: January 2024

For a set [Formula: see text] of connected graphs, a spanning subgraph [Formula: see text] of a graph [Formula: see text] is an [Formula: see text]-factor if every component of [Formula: see text] is isomorphic to some member of [Formula: see text]. In this paper, we give a criterion for the existence of tight toughness, isolated toughness and binding number bounds in a graph of a strong [Formula: see text]-star factor, [Formula: see text]-factor and [Formula: see text]-star factor. Moreover, we show that the bounds of the sufficient conditions are sharp.
Sentiment Analysis Using Deep Learning Approaches on Multi-Domain Dataset in Telugu Language
Authors: Chattu Kannaiah , Sumathi D.
Published: January 2024

Recent advancements in Natural Language Processing (NLP) have made sentiment analysis an essential component of a variety of NLP jobs, including recommendation systems, question answering, and business intelligence products. While sentiment analysis research has, to put it mildly, been widely pursued in English, Telugu has barely ever attempted the task. The majority of research works concentrate on analysing the sentiments of Tweets, news, or reviews containing Hindi and English words. There is a growing interest among academics in studying how people express their thoughts and views in Indian languages like Bengali, Telugu, Malayalam, Tamil and so on. Due to a paucity of labelled datasets, microscopic investigation on Indian languages has been published to our knowledge. This work suggested a sentence-level sentiment analysis on multi-domain datasets that has been collected in Telugu. Deep learning models have been used in this work because it demonstrates the significant expertise in sentiment analysis and is widely regarded as the cutting-edge model in Telugu Sentiment Analysis. Our proposed work investigates a productive Bidirectional Long Short-Term Memory (BiLSTM) Network and Bidirectional GRU Network (BiGRU) for improving Telugu Sentiment Analysis by encapsulating contextual information from Telugu feature sequences using Forward-Backward encapsulation. Further, the model has been deployed by merging the domains so as to predict the accuracy and other performance metrics. The experimental test findings show that the deep learning models outperform when compared with the baseline traditional ML methods in four benchmark sentiment analysis datasets. There is evidence that the proposed sentiment analysis method has improved precision, recall, F1-score and accuracy in certain cases. The proposed model has achieved the F1-score of 86% for song datasets when compared with the other existing models.
Atrial Fibrillation Detection from Compressed ECG Measurements for Wireless Body Sensor Network
Authors: Chen Yongyong , Chen Junxin , Sun Shuang , Su Jingyong , Li Qiankun , Lyu Zhihan
Published: January 2024

Recent years have witnessed an increasing prevalence of wearable devices in the public, where atrial fibrillation (AF) detection is a popular application in these devices. Generally, AF detection is performed on cloud whereas this paper describes an on-device AF detection method. Technically, compressed sensing (CS) is first used for electrocardiograph (ECG) acquisition. Then QRS detection is proposed to be performed directly on the compressed CS measurements, rather than on the reconstructed signals on the powerful cloud server. Based on the extracted QRS information, AF is determined by quantitatively analyzing the (
RR
,
dRR
) plot. Databases with ECG samples collected from both medical-level (MIT-BIH afdb) and wearable ECG devices (Physionet Challenge 2017) are introduced for performance validation. The experiment results well demonstrate that our on-device AF detection algorithm can approach the performance of those implemented on the raw signals. Our proposal is suitable for AF screening directly on the wearable devices, without the support of the data center for signal reconstruction and intelligent analysis.
Text2EL
+
: Expert Guided Event Log Enrichment Using Unstructured Text
Authors: Kapugama Geeganage Dakshi Tharanga , Wynn Moe Thandar , ter Hofstede Arthur H. M.
Published: January 2024

Through the application of process mining, business processes can be improved on the basis of process execution data captured in event logs. Naturally, the quality of this data determines the quality of the improvement recommendations. Improving data quality is non-trivial, and there is great potential to exploit unstructured text, e.g., from notes, reviews, and comments, for this purpose and to
enrich
event logs. To this end, this article introduces Text2EL
+
 , a three-phase approach to enrich event logs using unstructured text. In its first phase, events and (case and event) attributes are derived from unstructured text linked to organisational processes. In its second phase, these events and attributes undergo a semantic and contextual validation before their incorporation in the event log. In its third and final phase, recognising the importance of human domain expertise, expert guidance is used to further improve data quality by removing redundant and irrelevant events. Expert input is used to train a Named Entity Recognition (NER) model with customised tags to detect event log elements. The approach applies natural language processing techniques, sentence embeddings, training pipelines and models, as well as contextual and expression validation. Various unstructured clinical notes associated with a healthcare case study were analysed, and completeness, concordance, and correctness of the derived event log elements were evaluated through experiments. The results show that the proposed method is feasible and applicable.
Analyzing user migration in blockchain online social networks through network structure and discussion topics of communities on multilayer networks
Authors: Ba Cheick Tidiane , Dileo Manuel , Galdeman Alessia , Zignani Matteo , Gaito Sabrina
Published: January 2024

User migration, i.e. the movement of large sets of users from one online social platform to another one, is one of the main phenomena occurring in modern online social networks and even involves the most recent alternative paradigms of online social networks, such as blockchain online social networks (BOSNs). In these platforms, user migration mainly occurs through hard forks of the supporting blockchain, i.e. a split of the original blockchain and the creation of an alternative blockchain, to which users may decide to migrate. However, our understanding of user migration and its mechanisms is still limited, particularly regarding the role of densely connected user groups (communities) during migration and fork events. Are there differences between users who stay and those who decide to leave, in terms of network structure and discussion topics? In this work, we show, through network-based analysis centered on the identification of communities on multilayer networks and text mining that a) the “position” of a group within the network of social and economic interactions is connected to the likelihood of a group to migrate, i.e. marginal groups are more likely to leave; b) group network structure is also important, as users in densely connected groups interacting through monetary transactions are more likely to stay; c) users who leave are characterized by different discussion topics; and d) user groups interacting through monetary transactions show interest in migration-related content if they are going to leave. These findings highlight the importance of social and economic relationships between users during a user migration caused by fork events In general, in the larger context of online social media, it motivates the need to investigate user migration through a network-inspired approach based on groups and specific subgraphs while leveraging user-generated content, at the same time.
Machine Translation Testing via Syntactic Tree Pruning
Authors: Zhang Quanjun , Zhai Juan , Fang Chunrong , Liu Jiawei , Sun Weisong , Hu Haichuan , Wang Qingyu
Published: January 2024

Machine translation systems have been widely adopted in our daily life, making life easier and more convenient. Unfortunately, erroneous translations may result in severe consequences, such as financial losses. This requires to improve the accuracy and the reliability of machine translation systems. However, it is challenging to test machine translation systems because of the complexity and intractability of the underlying neural models. To tackle these challenges, we propose a novel metamorphic testing approach by syntactic tree pruning (STP) to validate machine translation systems. Our key insight is that a pruned sentence should have similar crucial semantics compared with the original sentence. Specifically, STP (1) proposes a core semantics-preserving pruning strategy by basic sentence structures and dependency relations on the level of syntactic tree representation, (2) generates source sentence pairs based on the metamorphic relation, and (3) reports suspicious issues whose translations break the consistency property by a bag-of-words model. We further evaluate STP on two state-of-the-art machine translation systems (i.e., Google Translate and Bing Microsoft Translator) with 1,200 source sentences as inputs. The results show that STP accurately finds 5,073 unique erroneous translations in Google Translate and 5,100 unique erroneous translations in Bing Microsoft Translator (400% more than state-of-the-art techniques), with 64.5% and 65.4% precision, respectively. The reported erroneous translations vary in types and more than 90% of them are not found by state-of-the-art techniques. There are 9,393 erroneous translations unique to STP, which is 711.9% more than state-of-the-art techniques. Moreover, STP is quite effective in detecting translation errors for the original sentences with a recall reaching 74.0%, improving state-of-the-art techniques by 55.1% on average.
Characterizing Deep Learning Package Supply Chains in PyPI: Domains, Clusters, and Disengagement
Authors: Gao Kai , He Runzhi , Xie Bing , Zhou Minghui
Published: January 2024

Deep learning (DL) frameworks have become the cornerstone of the rapidly developing DL field. Through installation dependencies specified in the distribution metadata, numerous packages directly or transitively depend on DL frameworks, layer after layer, forming DL package supply chains (SCs), which are critical for DL frameworks to remain competitive. However, vital knowledge on how to nurture and sustain DL package SCs is still lacking. Achieving this knowledge may help DL frameworks formulate effective measures to strengthen their SCs to remain competitive and shed light on dependency issues and practices in the DL SC for researchers and practitioners. In this paper, we explore the domains, clusters, and disengagement of packages in two representative PyPI DL package SCs to bridge this knowledge gap. We analyze the metadata of nearly six million PyPI package distributions and construct version-sensitive SCs for two popular DL frameworks: TensorFlow and PyTorch. We find that popular packages (measured by the number of monthly downloads) in the two SCs cover 34 domains belonging to eight categories.
Applications
,
Infrastructure
, and
Sciences
categories account for over 85% of popular packages in either SC and TensorFlow and PyTorch SC have developed specializations on
Infrastructure
and
Applications
packages, respectively. We employ the Leiden community detection algorithm and detect 131 and 100 clusters in the two SCs. The clusters mainly exhibit four shapes: Arrow, Star, Tree, and Forest with increasing dependency complexity. Most clusters are Arrow or Star, while Tree and Forest clusters account for most packages (Tensorflow SC: 70.7%, PyTorch SC: 92.9%). We identify three groups of reasons why packages disengage from the SC (i.e., remove the DL framework and its dependents from their installation dependencies): dependency issues, functional improvements, and ease of installation. The most common reason in TensorFlow SC is dependency incompatibility and in PyTorch SC is to simplify functionalities and reduce installation size. Our study provides rich implications for DL framework vendors, researchers, and practitioners on the maintenance and dependency management practices of PyPI DL SCs.
17α-Estradiol alleviates high-fat diet-induced inflammatory and metabolic dysfunction in skeletal muscle of male and female mice
Authors: Bubak Matthew P. , Mann Shivani N. , Borowik Agnieszka K. , Pranay Atul , Batushansky Albert , Vieira de Sousa Neto Ivo , Mondal Samim A. , Doidge Stephen M. , Davidyan Arik , Szczygiel Marcelina M. , Peelor Frederick F. , Rigsby Sandra , Broomfield Matle E. , Lacy Charles I. , Rice Heather C. , Stout Michael B. , Miller Benjamin F.
Published: January 2024

Using a multiomics approach, we show that 17α-E2 alleviates HFD-induced metabolic detriments in skeletal muscle by altering bioactive lipid intermediates, inflammatory cytokines, and the abundance of proteins related to lipolysis and muscle contraction. The positive effects of 17α-E2 in skeletal muscle occur in both sexes but differ in their outcome.
Transcranial magnetic stimulation over supramarginal gyrus stimulates primary motor cortex directly and impairs manual dexterity: implications for TMS focality
Authors: Holmes Nicholas P. , Di Chiaro Nunzia Valentina , Crowe Emily M. , Marson Ben , Göbel Karen , Gaigalas Dominykas , Jay Talia , Lockett Abigail V. , Powell Eleanor S. , Zeni Silvia , Reader Arran T.
Published: January 2024

Transcranial magnetic stimulation (TMS) is often described as having an effective spatial resolution of ∼10 mm, because of the limited area of the scalp on which TMS produces motor-evoked potentials (MEPs) in resting muscles. We find that during natural hand movement TMS evokes MEPs from a much larger scalp area, in particular when stimulating over the supramarginal gyrus 55 mm away. Our results show that TMS can be effective at much larger distances than generally assumed.
Optimization of Process Parameters for the Production of Soy Protein by Ultrafiltration Using ANN
Authors: John Hima , Giri Saroj Kumar , Subeesh A. , Chandra Punit , Pandiselvam R.
Published: January 2024

The growing popularity of soy proteins among vegans and vegetarians, owing to their high protein content and widespread availability, has led to scientific studies on its various extraction methods mainly on ultrafiltration. This research employed artificial neural network (ANN) and Box-Behnken design (BBD) methodologies to predict the process parameters of ultrafiltration for the preparation of soy protein. Using BBD, the optimum process parameters of ultrafiltration were identified via the desirability function approach. The optimized permeate flux was 11.13 litres per hour (LPH) and 85.52% protein content in retentate. The identified ideal process parameters for ultrafiltration to achieve maximal protein retention encompassed a 10 kDa membrane module, a transmembrane pressure of 117 kPa (17 PSI), a volume concentration ratio of 3.5, diafiltration set at 1, and a flow rate of 65% of the pump capacity, exhibiting an absolute percent error value of 2.81. Employing these refined process parameters, the predicted value for protein retentate stood at 80.49%. The predictive accuracy of the model achieved an impressive 99.61% for protein retention. The ANN model effectively predicted the optimal ultrafiltration conditions, resulting in maximal protein retention and a protein content accuracy of 96.41% and 99.61%, respectively.
Confidence Levels Measurement of Mobile Phone Selection Using a Multiattribute Decision‐Making Approach with Unknown Attribute Weight Information Based on T‐Spherical Fuzzy Aggregation Operators
Authors: Khan Muhammad Rizwan , Ullah Kifayat , Khan Qaisar , Haleemzai Izatmand
Published: January 2024

Advancement in mobile phone (MP) technology has revolutionized the lifestyle. In recent years, we observed that MP technology had been involved in almost all aspects of life, such as communication purposes, e‐commerce, mobile baking, and social media connectivity. So, it becomes a hot research topic to select the best MP that fulfills the desired feathers requirement. In this paper, the expert’s familiarity with the examined objects is factored into the initial judgments under the T‐spherical fuzzy sets (T‐SFSs) environment. The T‐SFS is the extension of the picture fuzzy (PF) set (PFS), which gives wider scope for finding the most precise options than existing fuzzy frameworks. The multiattribute decision‐making (MADM) is a common and valuable method for aggregating information. For MADM, various aggregation operators (AOs) have been created over the years. The article introduces the newly proposed approach T‐spherical fuzzy (T‐SF) confidence level weighted averaging T − SFWAc and T‐SF confidence level weighted geometric T − SFWGc. Also, some desired properties of AOs are discussed, and the T‐SF entropy measure is introduced for selecting the weight criteria. A MADM framework is introduced, on the behalf of proposed operators. The proposed MADM framework is applied to solve the real‐life example of consumers’ preferences to show effectiveness and practicality. Lastly, the developed framework is set side by side with other prevailing approaches to demonstrate the superiority and significance of other existing AOs.
Aspects of Non-unique Solutions for Hiemenz Flow Filled with Ternary Hybrid Nanofluid over a Stretching/Shrinking Sheet
Authors: Jamrus Farah Nadzirah , Ishak Anuar , Waini Iskandar , Khan Umair , Siddiqui Md Irfanul Haque , Madhukesh J. K.
Published: January 2024

This study is carried out to scrutinize the Hiemenz flow for ternary hybrid nanofluid flow across a stretching/shrinking sheet. This study aims to inspect the impacts of variations in the stretching/shrinking parameter and the volume fraction of nanoparticles on key aspects of the ternary hybrid nanofluid flow, specifically the skin friction, Nusselt number (which relates to heat transfer), velocity profiles, and the temperature profiles. The flow equations transform into a system of ordinary differential equations (ODEs) using a similarity transformation. Subsequently, the system is numerically solved using the MATLAB software’s 4th-order accuracy boundary value problem solver, known as “bvp4c”. Numeric findings reveal that skin friction values exhibit variations based on the magnitude of the stretching/shrinking parameter. Moreover, in the specific context of the flow problem being studied, the heat conduction efficiency of the hybrid (ternary) nanofluid surpasses that of the hybrid nanofluid. The system yields two distinct solutions within a specific shrinking/stretching parameter interval. Through an examination of the temporal stability of the solutions, it was determined that only one remained stable over an extended period. Remember that these current findings hold solely for the combination of copper, alumina, and titania.
DNA Damage Response Pharmacogenomic (DDR_PGx) Score Predicts Response to Chemotherapy Consisting of Gemtuzumab Ozogamicin in Pediatric AML: A Report from the Children's Oncology Group
Authors: Shastri Vivek M. , Chauhan Lata , Gbadamosi Mohammed , Alonzo Todd A. , Wang Yi-Cheng , Aplenc Richard , Hirsch Betsy A. , Kolb Edward A. , Gamis Alan S. , Meshinchi Soheil , Lamba Jatinder K.
Published: January 2024

Purpose:

Comprehensive pharmacogenomics (PGx) evaluation of calicheamicin pathway to identify predictive PGx markers of response to gemtuzumab ozogamicin (GO) treatment in acute myeloid leukemia (AML).

Experimental Design:

SNPs in DNA damage response (DDR) pathway genes were tested for association with event-free survival (EFS), overall survival (OS), and risk of relapse after induction 1 (RR1) in patients treated with standard chemotherapy consisting of Ara-C, daunorubicin, and etoposide (ADE) with or without addition of GO on COG-AAML03P1 and COG-AAAML0531 trials (ADE+GO, n = 755; ADE n = 470). SNPs with significant association with any endpoint within ADE+GO arm but not in the ADE arm were tested using multi-SNP modeling to develop DDR_PGx7 score.

Results:

Patients with low DDR_PGx7 score (<0) had significantly worse EFS [HR = 1.51, 95% confidence interval (CI: 1.21–1.89), P < 0.001], worse OS [HR = 1.59, 95% CI (1.22–2.08), P < 0.001], and higher RR1 [HR = 1.87, 95% CI (1.41–2.47), P < 0.0001] compared with patients with high DDR_PGx7 score (≥0) when treated with GO (ADE+GO cohort). However, no difference between low and high DDR_PGx7 score groups was observed for EFS, OS, and RR1 (all P > 0.3) in patients treated on ADE arm.

Conclusions:

Our results suggest that DDR pathway–based pharmacogenomic score holds potential to predict outcome in patients treated with GO which consists of DNA damaging cytotoxin, calicheamicin. The potential clinical relevance for this score to personalize GO in AML requires further validation in independent and expanded cohorts.
Data from Adhesive Interactions Regulate Transcriptional Diversity in Malignant B Cells
Authors: Nadav-Dagan Liat , Shay Tal , Dezorella Nili , Naparstek Elizabeth , Domany Eytan , Katz Ben-Zion , Geiger Benjamin
Published: January 2024

Abstract
The genetic profiling of B-cell malignancies is rapidly expanding, providing important information on the tumorigenic potential, response to treatment, and clinical outcome of these diseases. However, the relative contributions of inherent gene expression versus microenvironmental effects are poorly understood. The regulation of gene expression programs by means of adhesive interactions was studied here in ARH-77 human malignant B-cell variants, derived from the same cell line by selective adhesion to a fibronectin matrix. The populations included cells that adhere to fibronectin and are highly tumorigenic (designated “type A” cells) and cells that fail to adhere to fibronectin and fail to develop tumors in vivo (“type F” cells). To identify genes directly affected by cell adhesion to fibronectin, type A cells deprived of an adhesive substrate (designated “AF cells”) were also examined. Bioinformatic analyses revealed a remarkable correlation between cell adhesion and both B-cell differentiation state and the expression of multiple myeloma (MM)–associated genes. The highly adherent type A cells expressed higher levels of NFκB-regulated genes, many of them associated with MM. Moreover, we found that the transcription of several MM-related proto-oncogenes is stimulated by adhesion to fibronectin. In contrast, type F cells, which display poor adhesive and tumorigenic properties, expressed genes associated with higher levels of B-cell differentiation. Our findings indicate that B-cell differentiation, as manifested by gene expression profiles, is attenuated by cell adhesion to fibronectin, leading to upregulation of specific genes known to be associated with the pathogenesis of MM. Mol Cancer Res; 8(4); 482–93. ©2010 AACR.
Data from Constitutive Activation of Caspase-3 and Poly ADP Ribose Polymerase Cleavage in Fanconi Anemia Cells
Authors: Lyakhovich Alex , Surrallés Jordi
Published: January 2024

Abstract
Fanconi anemia (FA) is a rare syndrome characterized by developmental abnormalities, progressive bone marrow failure, and cancer predisposition. Cells from FA patients exhibit hypersensitivity to DNA cross-linking agents and oxidative stress that may trigger apoptosis. Damage-induced activation of caspases and poly ADP ribose polymerase (PARP) enzymes have been described for some of the FA complementation groups. Here, we show the constitutive activation of caspase-3 and PARP cleavage in the FA cells without exposure to exogenous DNA-damaging factors. These effects can be reversed in the presence of reactive oxygen species scavenger N-acetylcystein. We also show the accumulation of oxidized proteins in FA cells, which is accompanied by the tumor necrosis factor (TNF)-α oversecretion and the upregulation of early stress response kinases pERK1/2 and p-P38. Suppression of TNF-α secretion by the extracellular signal-regulated kinase inhibitor PD98059 results in reduction of caspase-3 cleavage, suggesting a possible mechanism of caspases-3 activation in FA cells. Thus, the current study is the first evidence demonstrating the damage-independent activation of caspase-3 and PARP in FA cells, which seems to occur through mitogen-activated protein kinase activation and TNF-α oversecretion.Mol Cancer Res; 8(1); 46–56
Data from Hepatocyte Nuclear Factor-4–Independent Synthesis of Coagulation Factor VII in Breast Cancer Cells and Its Inhibition by Targeting Selective Histone Acetyltransferases
Authors: Koizume Shiro , Yokota Naho , Miyagi Etsuko , Hirahara Fumiki , Nakamura Yoshiyasu , Sakuma Yuji , Yoshida Akira , Kameda Yoichi , Tsuchiya Eiju , Ruf Wolfram , Miyagi Yohei
Published: January 2024

Abstract
Tissue factor/coagulation factor VII (fVII) complex formation on the surface of cancer cells plays important roles in cancer biology, such as cell migration and invasion, angiogenesis, and antiapoptotic effects. We recently found that various cancer cells ectopically synthesize fVII, resulting in activation of cell motility and invasion. Here, we characterized mechanisms of hepatic and ectopic fVII (FVII) gene expression to identify molecular targets enabling selective inhibition of the ectopic expression. Unlike hepatic expression, hepatocyte nuclear factor-4 binding to the promoter is not required for ectopic FVII expression, although Sp1 binding is essential. Furthermore, we found novel nuclear targets of basal hepatocytic and ectopic FVII expression. Notably, histone acetyltransferases p300 and cyclic AMP–responsive element binding protein–binding protein (CBP) are exclusively recruited to the promoter region of the FVII gene specifically in breast cancer cells. We further show that curcumin, a dietary compound, can selectively inhibit ectopic fVII expression by targeting p300/CBP activity. These results suggest a strategy to inhibit ectopic fVII-induced tumor progression without impairment of the physiologic hemostatic process. (Mol Cancer Res 2009;7(12):1928–36)
TABLE 3 from Analysis of Changes in Plasma Cytokine Levels in Response to IL12 Therapy in Three Clinical Trials
Authors: Schwarz Emily , Benner Brooke , Yu Lianbo , Tounkara Fode , Carson William E.
Published: January 2024

Statistical analysis of cytokine profile changes after IL12 treatment within patient response groups. Cytokine profiles consisting of 23 different cytokines were analyzed for significant changes between baseline and 72 hours post-IL12 therapy within three individual response groups; PD patients (n = 9), SD patients (n = 9), and CR/PR patients (n = 3). Results shown include only the changes deemed statistically significant (P ≤ 0.05)
FIGURE 5 from Analysis of Changes in Plasma Cytokine Levels in Response to IL12 Therapy in Three Clinical Trials
Authors: Schwarz Emily , Benner Brooke , Yu Lianbo , Tounkara Fode , Carson William E.
Published: January 2024

Baseline plasma levels of IL10 in PD, SD, and CR/PR patients. Plasma levels of IL10 (pg/mL) at baseline were measured in all patients and then analyzed according to post-therapy patient responses. Patient responses were classified into three groups; PD, SD, and CR/PR. Baseline levels were compared between the groups using t tests with post hoc Bonferroni corrections to detect any significant differences correlating with patient response. P values were deemed significant if *, P < 0.05.
FIGURE 4 from Analysis of Changes in Plasma Cytokine Levels in Response to IL12 Therapy in Three Clinical Trials
Authors: Schwarz Emily , Benner Brooke , Yu Lianbo , Tounkara Fode , Carson William E.
Published: January 2024

Extended timelines showing fluctuations in differentially expressed cytokine levels according to patient response. Cytokine levels of CCL3 (A), CCL4(B), and IL6 (pg/mL; C), collected 72 hours after IL12 administration, were measured at additional timepoints through cycle 3 for IL6 and cycle 12 for CCL3, and CCL4. Averages from each patient response group at the additional timepoints are plotted as individual points along the curves. Patient response groups are represented by PD patients, SD patients, and CR/PR patients.
FIGURE 1 from Analysis of Changes in Plasma Cytokine Levels in Response to IL12 Therapy in Three Clinical Trials
Authors: Schwarz Emily , Benner Brooke , Yu Lianbo , Tounkara Fode , Carson William E.
Published: January 2024

Plasma cytokine levels from all patients (n = 21) measured at baseline and 72-hour post-IL12 treatment. Patient plasma samples collected 72 hours after the first, second, or third dose of IL12 were measured for levels of 23 cytokines (pg/mL). Samples were run in triplicate using seven multiplex assays. The average of the triplicates was plotted for each patient, represented by a single dot. Results shown represent the nine cytokines found to have significantly upregulated mean levels following IL12 administration. P = 0.02 for IFNγ, P = 0.02 for GMCSF, P < 0.001 for TNFα, P < 0.001 for IL18, P < 0.001 for IL10, P = 0.01 for CCL2, P = 0.001 for CCL3, P = 0.002 for CCL4, P = 0.02 for CCL8, P = 0.03 for CCL22, and P < 0.001 for CXCL10. Two-sided paired t tests, *, P < 0.05; **, P < 0.01; ***, P < 0.001.
Data from Analysis of Changes in Plasma Cytokine Levels in Response to IL12 Therapy in Three Clinical Trials
Authors: Schwarz Emily , Benner Brooke , Yu Lianbo , Tounkara Fode , Carson William E.
Published: January 2024

Abstract
The ability of IL12 to stimulate natural killer (NK) cell and T-cell antitumor activity makes it an attractive candidate for the immune therapy of cancer. Our group has demonstrated that IL12 enhances the NK cell response to antibody-coated tumor cells and conducted three clinical trials utilizing IL12 with mAbs (OSU-9968, OSU-0167, and OSU-11010). To better characterize IL12-induced immunity, plasma cytokine levels were measured in 21 patients from these trials with favorable and unfavorable responses. t-statistics and linear modeling were used to test for differences within and between response groups by examining levels at baseline and post-IL12 administration. Patients exhibited significant increases in 11 cytokines post-IL12 administration when analyzed collectively. However, several cytokines were differentially induced by IL12 depending on response. GMCSF was significantly increased in complete/partially responding patients, while stable disease patients had significant increases in IL10 and decreases in VEGF-C. Patients who experienced progressive disease had significant increases in CCL3, CCL4, IL18, TNFα, CXCL10, CCL8, CCL2, IL6, and IFNγ. The increases in CCL3, CCL4, and IL6 in progressive disease patients were significantly higher than in clinically benefitting patients and most prominent within the first two cycles of IL12 therapy. This correlative pilot study has identified changes that occur in levels of circulating cytokines following IL12 administration to patients with cancer, but this report must be viewed as exploratory in nature. It is meant to spark further inquiry into the topic via the analysis of additional cohorts of patients with similar characteristics who have received IL12 in a uniform fashion.
Significance:
IL12 activates immune cells and is used to treat cancer. The profile of circulating cytokines was measured in an exploratory fashion in patients with cancer that received IL12 in combination with mAbs. This correlative pilot study could serve as the basis for additional studies of IL12 effects on the production of immune cytokines.
The Association of Glaucoma with Ischemic Stroke and Functional Outcome after Ischemic Stroke from the Perspective of Causality
Authors: He Qiang , Wang Wenjing , Xu Dingkang , Xiong Yang , Tao Chuanyuan , Ma Lu , You Chao
Published: January 2024

Introduction: Glaucoma may be related to ischemic stroke (IS) and poor outcomes after IS in observational studies, while the causal association remains unclear. Methods: We obtained single-nucleotide polymorphisms (SNPs) related to glaucoma from the genome-wide association study (GWAS) conducted by the FinnGen consortium. The GWAS included a total of 13,614 cases and 295,540 controls. The summary-level datasets regarding IS were collected from the MEGASTROKE consortium, including 34,217 cases and 406,111 controls. Furthermore, we acquired summary statistics datasets for functional outcomes following IS from the GWAS meta-analysis conducted by the GISCOME consortium, which involved 6,021 individuals. The genetic association estimates for functional outcomes at 90 days after IS were evaluated by the modified Rankin Score (mRS), including 3,741 cases with good functional outcomes (mRS = 0–2) and 2,280 subjects with poor functional outcomes post-stroke (mRS = 3–6). Inverse variance weighting (IVW) was used as the primary method, complemented by sensitivity analyses for pleiotropy and increasing robustness. Results: Genetically, glaucoma is associated with an increased risk of IS (odds ratio [OR] = 1.08, 95% confidence interval [CI] = 1.02–1.14, p = 0.0039), as well as poor prognosis after IS with adjustment for severity (OR = 1.64; 95% CI = 1.27–2.13, p = 0.0001) and functional outcome after IS (OR = 1.45, 95% CI = 1.12–1.87, p = 0.0038). Through sensitivity analyses, we confirmed the robustness of the results. In addition, we did not identify any causal association between IS, functional outcome after IS, and glaucoma in reverse analysis. Conclusion: Our study provides evidence suggesting potential genetic causal effects of glaucoma on an increased risk of IS, as well as a poor functional outcome following IS. Future studies are necessary to confirm these findings.
Time for “Code ICH”? Workflow Metrics of Hyperacute Treatments and Outcome in Patients with Intracerebral Haemorrhage
Authors: Bettschen Eva , Siepen Bernhard M. , Goeldlin Martina B. , Mueller Madlaine , Buecke Philipp , Prange Ulrike , Meinel Thomas R. , Drop Boudewijn R.H. , Bervini David , Dobrocky Tomas , Kaesmacher Johannes , Exadaktylos Aristomenis K. , Sauter Thomas C. , Volbers Bastian , Arnold Marcel , Jung Simon , Fischer Urs , Z’Graggen Werner , Seiffge David
Published: January 2024

Introduction: Knowledge about uptake and workflow metrics of hyperacute treatments in patients with non-traumatic intracerebral haemorrhage (ICH) in the emergency department is scarce. Methods: Single-centre retrospective study of consecutive patients with ICH between 01/2018–08/2020. We assessed uptake and workflow metrics of acute therapies overall and according to referral mode (stroke code, transfer from other hospital, or other). Results: We enrolled 332 patients (age 73 years, IQR: 63–81 and GCS 14 points, IQR: 11–15, onset-to-admission time 284 min, IQR: 111–708 min), of whom 101 patients (35%) had lobar haematoma. Mode of referral was stroke code in 129 patients (38%), transfer from other hospital in 143 patients (43%), and arrival by other means in 60 patients (18%). Overall, 143 of 216 (66%) patients with systolic blood pressure >150 mm Hg received IV-antihypertensive treatment, and 67 of 76 (88%) on therapeutic oral anticoagulation received prothrombin complex concentrate treatment (PCC). Forty-six patients (14%) received any neurosurgical intervention within 3 h of admission. Median treatment times from admission to first IV-antihypertensive treatment were 38 min (IQR: 18–72 min) and 59 min (IQR: 37–111 min) for PCC, with significant differences according to mode of referral (p < 0.001) but not early arrival (≤6 h of onset, p = 0.92). The median time in the emergency department was 139 min (IQR: 85–220 min), and among patients with elevated blood pressure, only 44% achieved a successful control (<140 mm Hg) during ED stay. In multivariate analysis, code ICH concordant treatment was associated with significantly lower odds for in-hospital mortality (aOR 0.30, 95% CI: 0.12–0.73, p = 0.008) and non-significant trends towards better functional outcome measured using the modified Rankin scale score at 3 months (aOR for ordinal shift 0.54, 95% CI: 0.26–1.12, p = 0.097). Conclusion: Uptake of hyperacute therapies for ICH treatment in the ED is heterogeneous. Treatment delays are short, but not all patients achieve treatment targets during ED stay. Code ICH-concordant treatment may improve clinical outcomes. Further improvements seem achievable by advocating for a “code ICH” to streamline acute treatments.
Cannabis-Induced Gastrointestinal Tract Symptoms in the Adult Population: A Systematic Review
Authors: Senderovich Helen , Meaney Christopher , Vashishtha Srishti
Published: January 2024

Objective: Cannabinoid usage is widespread in the self-management of various medical ailments. However, adverse effects have been reported with use, especially pertaining to the gastrointestinal system in adults and aged patients. These range from nausea, vomiting, bloating, or abdominal pain. This systematic review of previously reported cannabis-induced gastrointestinal symptoms in the adult population from the literature provides an analysis of relevant data to enhance knowledge and awareness of this topic. Methods: PubMed, Ovid MEDLINE, Cochrane Central, EMBASE, and Google Scholar databases were searched for relevant studies published from inception to March 2023. Results: The search yielded 598 results, of which 13 were deemed relevant and underwent further review. These included two systematic reviews, one retrospective cohort study, one retrospective chart review, two cross-sectional studies, one survey, and six case reports. The Cochrane Risk Tool for bias analysis was applied where relevant. The total number of people in the studies selected for analysis was 79, 779. Twelve out of the thirteen included studies reported some type of gastrointestinal tract symptoms experienced in medical and/or recreational cannabis users ranging from nausea, vomiting, diarrhoea, abdominal pain to adult intussusception. Conclusion: Potential limitations include small sample sizes, variation in research methodologies, varied studied designs, and limited availability of data on specific populations such as geriatric users. Further research is warranted to add to current evidence pertaining to this emerging topic of significance, fill the broad knowledge gaps and contribute to evidence-based guidelines for healthcare professionals, ensuring safe prescribing practices and provision of quality care.
Predictors for the Development of Thromboembolic Events in Cancer Patients Treated with Bevacizumab, Ramucirumab, and Aflibercept: A Single-Institution Retrospective Analysis
Authors: Kanbayashi Yuko , Ishikawa Takeshi , Otsuji Eigo , Takayama Koichi
Published: January 2024

Introduction: The risk of thromboembolic events developing limits the dose of antiangiogenic agents, thereby reducing their efficacy. This retrospective study therefore sought to identify predictors for the development of antiangiogenic agent-induced thromboembolic events and to elucidate whether differences in the likelihood of thromboembolic events exist between different antiangiogenic agents or cancer types, to guide future strategies for optimizing safety, efficacy, and quality of life in patients receiving chemotherapy. Methods: This study retrospectively investigated 468 cancer patients who received chemotherapy with bevacizumab, ramucirumab, or aflibercept at our outpatient chemotherapy center between December 2016 and April 2022. Variables related to the development of thromboembolic events were extracted from the medical records, and multivariate logistic regression analysis was performed to identify predictors for the development of thromboembolic events. The Wilcoxon/Kruskal-Wallis test was used to detect significant differences between groups. Results: Significant factors included serum albumin level (odds ratio [OR] = 0.363, 95% confidence interval [CI] = 0.193–0.685; p = 0.0017) and diabetes mellitus (OR = 5.356, 95% CI = 1.711–16.769; p = 0.0039). Renin-angiotensin system inhibitors (OR = 0.307) had low OR, although it was not significant. No difference in the development of thromboembolic events was evident between cancer types (p = 0.0781), but differences were identified between the three antiangiogenic agents (p = 0.0132). Ramucirumab was associated with a lower likelihood of thromboembolic events. Conclusion: Serum albumin level and diabetes mellitus were identified as significant predictors for the development of antiangiogenic agent-induced thromboembolic events. In addition, the likelihood of thromboembolic events did not differ between cancer types but differed between antiangiogenic agents.