bluuebunny/crossref_metadata_2025_split huggingface dataset:
SynergyX: a multi-modality mutual attention network for interpretable drug synergy prediction
Authors: Guo Yue , Hu Haitao , Chen Wenbo , Yin Hao , Wu Jian , Hsieh Chang-Yu , He Qiaojun , Cao Ji 
Published: February 2024

AbstractDiscovering effective anti-tumor drug combinations is crucial for advancing cancer therapy. Taking full account of intricate biological interactions is highly important in accurately predicting drug synergy. However, the extremely limited prior knowledge poses great challenges in developing current computational methods. To address this, we introduce SynergyX, a multi-modality mutual attention network to improve anti-tumor drug synergy prediction. It dynamically captures cross-modal interactions, allowing for the modeling of complex biological networks and drug interactions. A convolution-augmented attention structure is adopted to integrate multi-omic data in this framework effectively. Compared with other state-of-the-art models, SynergyX demonstrates superior predictive accuracy in both the General Test and Blind Test and cross-dataset validation. By exhaustively screening combinations of approved drugs, SynergyX reveals its ability to identify promising drug combination candidates for potential lung cancer treatment. Another notable advantage lies in its multidimensional interpretability. Taking Sorafenib and Vorinostat as an example, SynergyX serves as a powerful tool for uncovering drug-gene interactions and deciphering cell selectivity mechanisms. In summary, SynergyX provides an illuminating and interpretable framework, poised to catalyze the expedition of drug synergy discovery and deepen our comprehension of rational combination therapy.
On the core segmentation algorithms of copy number variation detection tools
Authors: Zhang Yibo , Liu Wenyu , Duan Junbo 
Published: February 2024

Abstract
Shotgun sequencing is a high-throughput method used to detect copy number variants (CNVs). Although there are numerous CNV detection tools based on shotgun sequencing, their quality varies significantly, leading to performance discrepancies. Therefore, we conducted a comprehensive analysis of next-generation sequencing-based CNV detection tools over the past decade. Our findings revealed that the majority of mainstream tools employ similar detection rationale: calculates the so-called read depth signal from aligned sequencing reads and then segments the signal by utilizing either circular binary segmentation (CBS) or hidden Markov model (HMM). Hence, we compared the performance of those two core segmentation algorithms in CNV detection, considering varying sequencing depths, segment lengths and complex types of CNVs. To ensure a fair comparison, we designed a parametrical model using mainstream statistical distributions, which allows for pre-excluding bias correction such as guanine-cytosine (GC) content during the preprocessing step. The results indicate the following key points: (1) Under ideal conditions, CBS demonstrates high precision, while HMM exhibits a high recall rate. (2) For practical conditions, HMM is advantageous at lower sequencing depths, while CBS is more competitive in detecting small variant segments compared to HMM. (3) In case involving complex CNVs resembling real sequencing, HMM demonstrates more robustness compared with CBS. (4) When facing large-scale sequencing data, HMM costs less time compared with the CBS, while their memory usage is approximately equal. This can provide an important guidance and reference for researchers to develop new tools for CNV detection.
Are brake response times altered post CT-guided cervical spine nerve root injections?
Authors: Hanley Marion , Eustace Sarah K , Ryan David T , McLoughlin Stephen , Hynes John P , Kavanagh Eoin C , Eustace Stephen J 
Published: February 2024

Abstract

Objectives
To assess if brake response times are altered pre and post CT-guided cervical spine nerve root injections.

Methods
Brake response times were assessed before and after CT-guided cervical spine nerve root injections in a cohort of patients. The average of 3 brake response times was recorded before and 30 min after injection. Statistical analysis was performed using GraphPad. A paired Student t-test was used to compare the times before and after the injections.

Results
Forty patients were included in this study. The mean age was 55 years. There were 17 male and 23 female patients. There was no significant difference in the mean pre and post CT-guided cervical spine nerve root injection brake response times; 0.94 s (range 0.4-1.2 s) and 0.93 s (range 0.5-1.25 s), respectively (P = .77).

Conclusions
Brake response time did not significantly differ pre and 30 min post CT-guided cervical spine nerve root injections.

Advances in knowledge
To the authors’ best knowledge, there are no current studies assessing brake response times post CT-guided cervical spine nerve root injections. While driving safety cannot be proven by a single metric, it is a useful study in demonstrating that this is not inhibited in a cohort of patients.
Pharmacokinetics and Optimal Dosing of Levofloxacin in Children for Drug-Resistant Tuberculosis: An Individual Patient Data Meta-Analysis
Authors: White Yasmine N , Solans Belen P , Denti Paolo , van der Laan Louvina E , Schaaf H Simon , Vonasek Bryan , Malik Amyn A , Draper Heather R , Hussain Hamidah , Hesseling Anneke C , Garcia-Prats Anthony J , Savic Radojka M 
Published: February 2024

Abstract

Background
Each year 25 000–32 000 children develop rifampicin- or multidrug-resistant tuberculosis (RR/MDR-TB), and many more require preventive treatment. Levofloxacin is a key component of RR/MDR-TB treatment and prevention, but the existing pharmacokinetic data in children have not yet been comprehensively summarized. We aimed to characterize levofloxacin pharmacokinetics through an individual patient data meta-analysis of available studies and to determine optimal dosing in children.

Methods
Levofloxacin concentration and demographic data were pooled from 5 studies and analyzed using nonlinear mixed effects modeling. Simulations were performed using current World Health Organization (WHO)–recommended and model-informed optimized doses. Optimal levofloxacin doses were identified to target median adult area under the time-concentration curve (AUC)24 of 101 mg·h/L given current standard adult doses.

Results
Data from 242 children (2.8 years [0.2–16.8] was used). Apparent clearance was 3.16 L/h for a 13-kg child. Age affected clearance, reaching 50% maturation at birth and 90% maturation at 8 months. Nondispersible tablets had 29% lower apparent oral bioavailability compared to dispersible tablets. Median exposures at current WHO-recommended doses were below the AUC target for children weighing &lt;24 kg and under &lt;10 years, resulting in approximately half of the exposure in adults. Model-informed doses of 16–33 mg/kg for dispersible tablets or 16–50 mg/kg for nondispersible tablets were required to meet the AUC target without significantly exceeding the median adult Cmax.

Conclusions
Revised weight-band dosing guidelines with doses of &gt;20 mg/kg are required to ensure adequate exposure. Further studies are needed to determine safety and tolerability of these higher doses.
A metagenomic alpha-diversity index for microbial functional biodiversity
Authors: Finn Damien R 
Published: February 2024

Abstract
Alpha-diversity indices are an essential tool for describing and comparing biodiversity. Microbial ecologists apply indices originally intended for, or adopted by, macroecology to address questions relating to taxonomy (conserved marker) and function (metagenome-based data). In this Perspective piece, I begin by discussing the nature and mathematical quirks important for interpreting routinely employed alpha-diversity indices. Secondly, I propose a metagenomic alpha-diversity index (MD) that measures the (dis)similarity of protein-encoding genes within a community. MD has defined limits, whereby a community comprised mostly of similar, poorly diverse protein-encoding genes pulls the index to the lower limit, while a community rich in divergent homologs and unique genes drives it toward the upper limit. With data acquired from an in silico and three in situ metagenome studies, I derive MD and typical alpha-diversity indices applied to taxonomic (ribosomal rRNA) and functional (all protein-encoding) genes, and discuss their relationships with each other. Not all alpha-diversity indices detect biological trends, and taxonomic does not necessarily follow functional biodiversity. Throughout, I explain that protein Richness and MD provide complementary and easily interpreted information, while probability-based indices do not. Finally, considerations regarding the unique nature of microbial metagenomic data and its relevance for describing functional biodiversity are discussed.
Benchmarking Algorithms for Gene Set Scoring of Single-cell ATAC-seq Data
Authors: Wang Xi , Lian Qiwei , Dong Haoyu , Xu Shuo , Su Yaru , Wu Xiaohui 
Published: February 2024

Abstract
Gene set scoring (GSS) has been routinely conducted for gene expression analysis of bulk or single-cell RNA sequencing (RNA-seq) data, which helps to decipher single-cell heterogeneity and cell type-specific variability by incorporating prior knowledge from functional gene sets. Single-cell assay for transposase accessible chromatin using sequencing (scATAC-seq) is a powerful technique for interrogating single-cell chromatin-based gene regulation, and genes or gene sets with dynamic regulatory potentials can be regarded as cell type-specific markers as if in single-cell RNA-seq (scRNA-seq). However, there are few GSS tools specifically designed for scATAC-seq, and the applicability and performance of RNA-seq GSS tools on scATAC-seq data remain to be investigated. Here, we systematically benchmarked ten GSS tools, including four bulk RNA-seq tools, five scRNA-seq tools, and one scATAC-seq method. First, using matched scATAC-seq and scRNA-seq datasets, we found that the performance of GSS tools on scATAC-seq data was comparable to that on scRNA-seq, suggesting their applicability to scATAC-seq. Then, the performance of different GSS tools was extensively evaluated using up to ten scATAC-seq datasets. Moreover, we evaluated the impact of gene activity conversion, dropout imputation, and gene set collections on the results of GSS. Results show that dropout imputation can significantly promote the performance of almost all GSS tools, while the impact of gene activity conversion methods or gene set collections on GSS performance is more dependent on GSS tools or datasets. Finally, we provided practical guidelines for choosing appropriate preprocessing methods and GSS tools in different application scenarios.
The Artistic Use Defence in Trademark Dilution Cases – Hermès’ Legal Setback in Its Attempt to Prevent Others from Using Its Iconic Birkin Handbag
Authors: Duhanic Ines 
Published: February 2024

Abstract
This opinion explores what constitutes a trademark parody in an artistic context and when it crosses the line of trademark infringement in dilution cases which occur beyond the traditional trademark protection from the likelihood of confusion. This is shown by analysing the latest two decisions regarding trademark parody handed down by the German Frankfurt am Main Regional Court in a case in which Hermès has suffered a setback in its attempt to prevent a fashion label from using its iconic Birkin handbag at the Berlin fashion show in 2023.
While parody is considered a protected form of speech or artistic expression, no clear-cut legal rule separates a legitimate parody from an infringing use, in particular in cases of so-called mixed expressions where the reference to the protected trademark is not closely tied to commercial use but still happens outside of a purely artistic context. Compared to the statutory copyright’s flexible fair use defence, there is simply too little case law available to draw on in trademark dilution law. The few rigid defences German courts have cobbled together in trademark cases illustrate that trademark could benefit from a clearer identification of use categories. The following analysis of these decisions aims at highlighting that urgent trademark reforms are necessary in the area of art-related fair use defences. Furthermore, the following analysis will illustrate how big corporations like Hermès can fail when attempting to use trademark rights to control the meaning not only of wealth and exclusivity but also of conspicuous consumption and the equally conspicuous display of wealth, status and power in male-dominated domains.
Using a Computational Cognitive Model to Understand Phishing Classification Decisions of Email Users
Authors: Shonman Matthew , Shi Xiaoyu , Kang Mingqing , Wang Zuo , Li Xiangyang , Dahbura Anton 
Published: February 2024

Abstract
Numerous studies of human user behaviours in cybersecurity tasks have used traditional research methods, such as self-reported surveys or empirical experiments, to identify relationships between various factors of interest and user security performance. This work takes a different approach, applying computational cognitive modelling to research the decision-making of cybersecurity users. The model described here relies on cognitive memory chunk activation to analytically simulate the decision-making process of a user classifying legitimate and phishing emails. Suspicious-seeming cues in each email are processed by examining similar, past classifications in long-term memory. We manipulate five parameters (Suspicion Threshold, Maximum Cues Processed, Weight of Similarity, Flawed Perception Level, Legitimate-to-Phishing Email Ratio in long-term memory) to examine their effects on accuracy, email processing time and decision confidence. Furthermore, we have conducted an empirical, unattended study of US participants performing the same task. Analyses on the empirical study data and simulation output, especially clustering analysis, show that these two research approaches complement each other for more insightful understanding of this phishing detection task. The analyses also demonstrate several limitations of this computational model that cannot easily capture certain user types and phishing detection strategies, calling for a more dynamic and sophisticated model construction.
Current Practice and Variation in Same-Day Services in Breast Imaging: A Multi-Institutional National Survey of the Society of Breast Imaging Membership
Authors: Dontchos Brian N , Dodelzon Katerina , Sonnenblick Emily , Reig Beatriu , Coffey Kristen , Kacharia Vidhi S , Grimm Lars J 
Published: February 2024

Abstract

Objective
The availability of same-day services in breast imaging is an important topic given potential advantages for timely diagnoses and patient experiences, but there are potential barriers that lead facilities to not offer these services. We sought to understand current practice patterns and radiologist perspectives on offering same-day services.

Methods
The Society of Breast Imaging (SBI) Patient Care & Delivery Committee developed a 19-question survey that was emailed to all 3449 active members of the SBI in May 2023. An exemption from the institutional review board was obtained at the lead author’s institution. The survey consisted of 19 questions that were designed to understand the scope, perceptions, barriers, and logistics of same-day services. Comparisons were made between responses for offering same-day services (screening interpretation, diagnostic examinations, biopsies) and respondent demographics.

Results
A total of 437 American and Canadian members participated, yielding a response rate of 12.7%. Respondents were most commonly in private practice (43.0%, 188/437), working in an outpatient medical center–based clinic (41.9%, 183/437), and without trainees (64.5%, 282/437). Respondents estimated 12.1% of screening examinations were interpreted while patients waited, which was significantly more common in free-standing breast imaging clinics (P = .028) and practices without trainees (P = .036). Respondents estimated 15.0% of diagnostic examinations were performed same day, which was more common in academic and private practices (P = .03) and practices without trainees (P = .01). Respondents estimated 11.5% of biopsies were performed the same day as the recommendation, which had no association with practice type/context, presence of trainees, number of mammography units, number of radiologists, or number of technologists. Long patient travel distance and limited patient mobility were the most cited reasons for offering patients same-day services.

Conclusion
Offering same-day breast imaging services varies among institutions and may be influenced by factors such as practice context and type and the presence of trainees.
Brochosome size variation and its influence on leafhopper (Hemiptera: Cicadellidae) wing wettability
Authors: Bello Elizabeth , Alleyne Marianne 
Published: February 2024

Abstract
Insect wing surfaces have nano- and microscale features that enable multi-functionality. Leafhoppers (Hemiptera: Cicadellidae) are unique in that they produce and excrete nanoscale particles, called brochocosomes, that are spread onto the integument by the insect. Brochosomes are extra-cuticular, removable, and make the integument both superhydrophobic and anti-reflective, 2 greatly desired properties in engineering and material science fields. Adaptations like this have captured the interest of researchers looking to draw inspiration from the natural world to create novel solutions and optimize current technologies. Here, we compare brochosome size and wettability across 8 species of leafhoppers using scanning electron microscopy and microgoniometry. We demonstrate that brochosome size is variable within species and that size and wettability are both significantly impacted by species. We report the extent of variability in each case and examine the relationship between brochosome size, body length, and hydrophobicity. In discussing potential applications for brochosomes, we comment on an emerging and rapid analysis technique for evaluating small biological particles. Additionally, we discuss a few recent brochosome-inspired designs and comment on important considerations. Our work provides valuable insight on a unique system that can guide the design of functionalized materials with enhanced hydrophobic and self-cleaning properties.
Unraveling biotypes of the northern house mosquito, Culex pipiens s.l. (Diptera: Culicidae): molecular differentiation and morphometric analysis
Authors: Alvial Ingrid E , Hernández-P Raquel , Suazo Manuel J , González Christian R , Véliz David , Benítez Hugo A 
Published: February 2024

Abstract
Geometric morphometrics was used to determine whether geographic isolation could explain differences in wing size and shape between and within continental (27°S to 41°S) and insular (Rapa Nui) populations of Culex pipiens s.s. Linnaeus and their biotypes (f. pipiens and f. molestus). Molecular protocols based on polymorphisms in the second intron of nuclear locus ace-2 (acetylcholinesterase-2) were used to differentiate Cx. pipiens s.s. from Cx. quinquefasciatus Say, and an assay based on polymorphisms in the flanking region of a microsatellite locus (CQ11) was used to identify biotypes. Culex pipiens f. molestus and hybrids shared larval habitats in all continental sites, while Cx. pipiens f. pipiens was found in 5 of the 10 sites. Only biotype molestus was found in Rapa Nui (Easter Island) Pipiens and molestus biotypes occur sympatrically in aboveground locations, and only molestus was found in the underground site (ME). Biotype molestus was dominant in rural locations and preferably anthropophilic. These results agree with the ecological descriptions previously reported for the biotypes of Cx. pipiens s.s. Procrustes ANOVA only showed differences in centroid size between biotypes in females and males and did not show significant differences in wing shape. However, we found significant differences among the geographic areas in the centroid size and wing shape of both females and males. Particularly, the population of Rapa Nui Island had shorter wings than the continental populations. The results highlight the effects of geographic and environmental processes on morphotypes in vector mosquitoes.
Effects of hormone receptor status on patient clinic and survival in HER2 positive breast cancer
Authors: Yılmaz Mukaddes , Erdiş Eda , Uçar Mahmut , Demir Necla , Alandağ Celal , Yücel Birsen 
Published: February 2024

Abstract

Background
In the current study, the effect of hormone receptor (HR) status on clinical and survival in early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer was investigated.

Methods
Two hundred ninety-one patients with HER2- positive were examined in two categories as HR-positive and HR-negative.

Results
Of these, 197 (68%) were HR-positive and 94 (32%) were HR-negative with a mean follow-up period of 68 ± 2.7 months. The groups were found to be similar in terms of age, menopausal status, comorbidity, pathologic type, stage, T stage, N stage, lymphovascular invasion, presence and percentage of intraductal component, multicentricity/focality and extracapsular invasion. Family history (P = 0.038), stage 2 tumor rate (P &lt; 0.001), and perineural invasion (P = 0.005) were significantly higher in the HR-positive group. In the HR-negative group, mean Ki-67 value (P = 0.014), stage 3 tumor rate (P &lt; 0.001), tumor necrosis (P = 0.004) and strong (3+) HER2 staining on immunohistochemical staining (P = 0.003) were higher. The incidence of relapse and metastasis, and the localization of metastasis were similar in both patient groups. The rate of locoregional relapse during the first 2 years was higher in the HR-negative patients than in the HR-positive patients (P = 0.023). Overall survival (OS) and disease-free survival (DFS) did not differ between the groups in univariate analysis. However, HR status was determined as an independent prognostic factor (HR: 2.11, 95% CI: 1.17–3.79; P = 0.012) for OS was not found to be significant for DFS in multivariate analysis.

Conclusion
Both clinicopathologic features and OS outcomes of HR-negative patients were worse than those of HR-positive patients.
Life history data of a Triatoma protracta nahuatlae, T. sinaloensis, and their laboratory hybrids (Hemiptera: Reduviidae)
Authors: Martínez-Ibarra José Alejandro , Grant-Guillén Yunuen , Nogueda-Torres Benjamín , Meraz-Medina Tzintli , Martínez-Grant Diana Monserrat 
Published: February 2024

Abstract
Chagas disease is one of the most significant vector-borne diseases in Mexico. The presence of “sylvatic” triatomine vectors of Trypanosoma cruzi (Chagas) inside human dwellings necessitates estimating their vectorial capacity. To estimate this capacity in Triatoma protracta nahuatlae (Ryckman), Triatoma sinaloensis (Ryckman), and their laboratory hybrids, 6 biological parameters were examined. Triatoma sinaloensis exhibited the shortest development time (155 days), with a median of 12 blood meals. Mortality rates varied from 35% to 45% in the 3 studied cohorts. All 3 cohorts were aggressive, initiating feeding within 0.5–1 min, and had similar feeding periods ranging from 10 to 18 min. A majority (75.3–97.9%) of the hybrids defecated when feeding, immediately after feeding, or in less than 1 min post-feeding. In contrast, only 7–42% of nymphs of T. sinaloensis defecated during the same period. Our results regarding the 6 parameters studied confirm the potential role of T. p. nahuatlae as an efficient vector of T. cruzi. Triatoma sinaloensis, on the other hand, exhibited limited vectorial capacity primarily due to its poor defecation behavior. Continued surveillance of these “sylvatic” triatomine populations is necessary to prevent an epidemiological problem.