bluuebunny/crossref_metadata_2025 huggingface dataset:
Microscopic analysis of the digestive and reproductive tracts of male Silpha obscura (Coleoptera: Silphidae)
Authors: Urbanová Michaela , Babosová Ramona , Langraf Vladimír , Petrovičová Kornélia , Özyurt Koçakoğlu Nurcan , Morovič Martin
Published: December 2024

Silpha obscura Linnaeus, 1758 (Coleoptera: Silphidae) is an omnivorous beetle species known for damaging agricultural crops, making it an important target for pest control strategies. Despite its impact, no studies have yet examined the anatomical and histological structures of the male digestive and reproductive tracts of S. obscura. Therefore, this study aimed to describe these structures in detail, which could provide insights into potential control methods. Twenty individuals were collected and histologically processed, with observations made using light microscopy. The digestive tract of S. obscura comprises 3 parts: a short foregut, a relatively long and wide midgut characterized by folds and numerous crypts of the blind intestine, and a narrow and elongated hindgut, which expands into the rectum. Malpighian tubules attach at the beginning of the hindgut, which continues with the ileum, colon, and rectum and ends at the anus. The male reproductive tract includes a pair of testes, a pair of efferent ducts (vas efferentia), a pair of deferent ducts (vas deferentia), a pair of seminal vesicles, 2 pairs of accessory glands, and the ductus ejaculatorius, which extends into the ejaculatorius bulbus. The reproductive tract terminates with the aedeagus. The testes consist of 2 lobes, each containing numerous follicles where spermatogenesis and spermiogenesis occur. This study provides detailed insights into the anatomy and histology of the digestive and male reproductive tracts of Silpha obscura. These findings may lead to new strategies for controlling this agricultural pest. Understanding these structures is crucial for further research.
Home Blood Pressure Monitoring
Authors: Liu Justin , Brettler Jeffrey , Ramirez Uriel A , Walsh Sophie , Sangapalaarachchi Dona , Narita Keisuke , Byfield Rushelle L , Reynolds Kristi , Shimbo Daichi
Published: December 2024

The diagnosis and management of hypertension have been based primarily on blood pressure (BP) measurement in the office setting. Higher out-of-office BP is associated with an increased risk of cardiovascular disease, independent of office BP. Home BP monitoring (HBPM) consists of the measurement of BP by a person outside of the office at home and is a validated approach for out-of-office BP measurement. HBPM provides valuable data for diagnosing and managing hypertension. Another validated approach, ambulatory BP monitoring (ABPM), has been considered to be the reference standard of out-of-office BP measurement. However, HBPM offers potential advantages over ABPM including being a better measure of basal BP, wide availability to patients and clinicians, evidence supporting its use for better office BP control, and demonstrated efficacy when using telemonitoring along with HBPM. This state-of-the-art review examines the current state of HBPM and includes discussion of recent hypertension guidelines on HBPM, advantages of using telemonitoring with HBPM, use of self-titration of antihypertensive medication with HBPM, validation of HBPM devices, best practices for conducting HBPM in the clinical setting, how HBPM can be used as an implementation strategy approach to improve BP control in the United States, health equity in HBPM use, and HBPM use among specific populations. Finally, research gaps and future directions of HBPM are reviewed.
Hypertension Canada Statement on the Use of Cuffless Blood Pressure Monitoring Devices in Clinical Practice
Authors: Landry Céderick , Dubrofsky Lisa , Pasricha Sachin V , Ringrose Jennifer , Ruzicka Marcel , Tran Karen C , Tsuyuki Ross T , Hiremath Swapnil , Goupil Rémi
Published: December 2024

BACKGROUND

Cuffless blood pressure (BP) devices are an emerging technology marketed as providing frequent, nonintrusive and reliable BP measurements. With the increasing interest in these devices, it is important for Hypertension Canada to provide a statement regarding the current place of cuffless BP measurements in hypertension management.

METHODS

An overview of the technology in cuffless BP devices, the potential with this technology and the challenges related to determining the accuracy of these devices.

RESULTS

Cuffless BP monitoring is an emerging field where various technologies are applied to measure BP without the use of a brachial cuff. None of the devices currently sold have been validated in static and dynamic conditions using a recognized validation standard. Important issues persist in regard to the accuracy and the place of these devices in clinical practice. Current data only support using validated cuff-based devices for the diagnosis and management of hypertension. Presently, readings from cuffless devices that are used for diagnosis or clinical management need to be confirmed using measurements obtained from a clinically validated BP device.

CONCLUSIONS

Cuffless BP devices are a developing technology designed to track BP in most daily life activities. However, many steps remain before they should be used in clinical practice.
Financial reimbursement of a pharmacist-led chronic care management program utilizing pharmacist extenders within a privately owned family medicine clinic
Authors: Mack Keri
Published: December 2024

Purpose

To evaluate the financial reimbursement of a pharmacist-led chronic care management (CCM) program utilizing student pharmacists and pharmacy residents as pharmacist extenders in a privately owned primary care practice.

Methods

A retrospective study assessing financial reimbursement of a pharmacist-led CCM program utilizing pharmacist extenders was conducted for the 12-month period from January 1 through December 31, 2022, at a privately owned family medicine practice. Return on investment (ROI) was the primary outcome. Secondary outcomes included the number of patients enrolled, number of billable patients, time spent delivering CCM (ie, “time-on-task”), and third-party claim reimbursement.

Results

During the 12-month study period, 203 patients were enrolled in the CCM program. Time-on-task was 463 hours. The number of billable patients for time-based CCM codes per month ranged from 19 to 121. Gross revenue from CCM was $55,104.64, and expenses totaled $9,482.64. Reimbursement for monthly CCM codes resulted in $44,042.31 (80%) of the gross revenue. Overall ROI was 481.1%, and ROI for monthly CCM codes alone was 364.5%. Out of the 1,046 CCM claims, 957 (92%) were paid.

Conclusion

Utilization of pharmacy residents and student pharmacists within the pharmacist-led CCM program resulted in a positive ROI, even in a small private practice. The ROI from monthly CCM codes alone was also positive, demonstrating sustainability of profits from the CCM program. Preceptors and schools of pharmacy should evaluate opportunities to utilize pharmacy learners to enhance sustainability of other pharmacist-led programs.
Use of 801 Acellular Dermal Matrices (ADMs) in Direct-to-Implant Breast Reconstruction: A Clinical Observation of Complication Profiles Over a 7-Year Period
Authors: Kaplan Haim Yoel , Rysin Roman
Published: December 2024

Background

The emergence of acellular dermal matrices (ADMs) revolutionized prepectoral breast reconstruction, allowing partial or complete implant coverage. ADM had been described to possess several important benefits; nevertheless, the literature described an increased postoperative complication rate.

Objectives

The aim of this study was to delineate H.Y.K.’s experience with ADM in direct-to-implant (DTI) breast reconstruction, and to describe complication rate and patient satisfaction.

Methods

This was a retrospective patient cohort that underwent primary or revisional breast reconstruction (DTI) utilizing DermaCell, from Jan 2017 to Jan 2024.

Results

A total of 230 consecutive patients, 410 breasts, and 801 DermaCell sheets were evaluated. All were DTI breast reconstructions. Complication rate was described per breast. A total of 92 cases of complication occurred (22.4%). Rippling was seen in 18 breasts (4.39%), skin ischemia in 21 breasts (5.12%), hematoma in 5 (1.21%), and seroma in 9 (2.19%). Seventeen breasts experienced capsular contraction. In the nonirradiated group, capsular contracture (CC), Baker grade 3 to 4, was seen in 4 breasts (1.11%), with 9 (18%) in the irradiated group. The postoperative follow-up period was 18 months (range: 6-84 months). BREAST-Q satisfaction with the breast increased by a mean of 10.45. Satisfaction with the implant was 6.61 out of 8.

Conclusions

This cohort study represents the most comprehensive and up-to-date experience with DermaCell for DTI breast reconstructive surgery. The favorable complication profile suggests that DermaCell ADM offers a safe and reliable option, making it an important tool in the armamentarium of reconstructive plastic surgeon. DermaCell is an important component in prepectoral breast reconstruction, contributing to better results, an improved complication profile, and patient satisfaction.

Level of Evidence: 4 (Therapeutic)
PDZK1 gene transfer ameliorates lipopolysaccharide-induced cholestasis in rats by rescuing hepatic ABC transporters
Authors: Wu Tao , Wu Ji , Liu Li , Song Hongping
Published: December 2024

Lipopolysaccharide (LPS) causes inflammatory cholestasis in sepsis. We investigated the role of PDZK1 in the repression of ABC transporters in LPS-induced cholestasis. Lentiviral gene transfer of PDZK1 to rats was conducted to explore its influence on cholestasis induced by LPS. And the effect of lentivirus-mediated shRNA targeting PDZK1 on ABC transporters in rat liver BRL-3A cells was evaluated. Lentiviral vector encoding rat PDZK1 was administered to rats by tail intravenous injection. Obviously elevated serum total bile acid level and liver biochemical markers in cholestatic rats were decreased by the Lv-PDZK1 delivery. Also, Lv-PDZK1 delivery stimulated the suppressed hepatic ABC transporters expression. In vitro, after the lentiviral vector LV3/PDZK1 shRNA transfection, no expression of PDZK1 and mild expression of ABC transporters were detected in BRL-3A cells by Western blotting. Our results indicate that the lentiviral-mediated hepatocyte PDZK1 expression ameliorates LPS-induced cholestasis in rats by rescuing hepatic ABC transporters expression.
UPicker: a semi-supervised particle picking transformer method for cryo-EM micrographs
Authors: Zhang Chi , Cheng Yiran , Feng Kaiwen , Zhang Fa , Han Renmin , Feng Jieqing
Published: December 2024

Automatic single particle picking is a critical step in the data processing pipeline of cryo-electron microscopy structure reconstruction. In recent years, several deep learning-based algorithms have been developed, demonstrating their potential to solve this challenge. However, current methods highly depend on manually labeled training data, which is labor-intensive and prone to biases especially for high-noise and low-contrast micrographs, resulting in suboptimal precision and recall. To address these problems, we propose UPicker, a semi-supervised transformer-based particle-picking method with a two-stage training process: unsupervised pretraining and supervised fine-tuning. During the unsupervised pretraining, an Adaptive Laplacian of Gaussian region proposal generator is proposed to obtain pseudo-labels from unlabeled data for initial feature learning. For the supervised fine-tuning, UPicker only needs a small amount of labeled data to achieve high accuracy in particle picking. To further enhance model performance, UPicker employs a contrastive denoising training strategy to reduce redundant detections and accelerate convergence, along with a hybrid data augmentation strategy to deal with limited labeled data. Comprehensive experiments on both simulated and experimental datasets demonstrate that UPicker outperforms state-of-the-art particle-picking methods in terms of accuracy and robustness while requiring fewer labeled data than other transformer-based models. Furthermore, ablation studies demonstrate the effectiveness and necessity of each component of UPicker. The source code and data are available at https://github.com/JachyLikeCoding/UPicker.
TraitTrainR: accelerating large-scale simulation under models of continuous trait evolution
Authors: Roa Lozano Jenniffer , Duncan Mataya , McKenna Duane D , Castoe Todd A , DeGiorgio Michael , Adams Richard
Published: December 2024

Motivation

The scale and scope of comparative trait data are expanding at unprecedented rates, and recent advances in evolutionary modeling and simulation sometimes struggle to match this pace. Well-organized and flexible applications for conducting large-scale simulations of evolution hold promise in this context for understanding models and more so our ability to confidently estimate them with real trait data sampled from nature.

Results

We introduce TraitTrainR, an R package designed to facilitate efficient, large-scale simulations under complex models of continuous trait evolution. TraitTrainR employs several output formats, supports popular trait data transformations, accommodates multi-trait evolution, and exhibits flexibility in defining input parameter space and model stacking. Moreover, TraitTrainR permits measurement error, allowing for investigation of its potential impacts on evolutionary inference. We envision a wealth of applications of TraitTrainR, and we demonstrate one such example by examining the problem of evolutionary model selection in three empirical phylogenetic case studies. Collectively, these demonstrations of applying TraitTrainR to explore problems in model selection underscores its utility and broader promise for addressing key questions, including those related to experimental design and statistical power, in comparative biology.

Availability and implementation

TraitTrainR is developed in R 4.4.0 and is freely available at https://github.com/radamsRHA/TraitTrainR/, which includes detailed documentation, quick-start guides, and a step-by-step tutorial.
m5c-iEnsem: 5-methylcytosine sites identification through ensemble models
Authors: Bilal Anas , Alarfaj Fawaz Khaled , Khan Rafaqat Alam , Suleman Muhammad Taseer , Long Haixia
Published: December 2024

Motivation

5-Methylcytosine (m5c), a modified cytosine base, arises from adding a methyl group at the 5th carbon position. This modification is a prevalent form of post-transcriptional modification (PTM) found in various types of RNA. Traditional laboratory techniques often fail to provide rapid and accurate identification of m5c sites. However, with the growing accessibility of sequence data, expanding computational models offers a more efficient and reliable approach to m5c site detection. This research focused on creating advanced in-silico methods using ensemble learning techniques. The encoded data was processed through ensemble models, including bagging and boosting techniques. These models were then rigorously evaluated through independent testing and 10-fold cross-validation.

Results

Among the models tested, the Bagging ensemble-based predictor, m5C-iEnsem, demonstrated superior performance to existing m5c prediction tools.

Availability and implementation

To further support the research community, m5c-iEnsem has been made available via a user-friendly web server at https://m5c-iensem.streamlit.app/.
Identification and annotation of centromeric hypomethylated regions with CDR-Finder
Authors: Mastrorosa Francesco Kumara , Oshima Keisuke K , Rozanski Allison N , Harvey William T , Eichler Evan E , Logsdon Glennis A
Published: December 2024

Motivation

Centromeres are chromosomal regions historically understudied with sequencing technologies due to their repetitive nature and short-read mapping limitations. However, recent improvements in long-read sequencing allow for the investigation of complex regions of the genome at the sequence and epigenetic levels.

Results

Here, we present Centromere Dip Region (CDR)-Finder: a tool to identify regions of hypomethylation within the centromeres of high-quality, contiguous genome assemblies. These regions are typically associated with a unique type of chromatin containing the histone H3 variant CENP-A, which marks the location of the kinetochore. CDR-Finder identifies the CDRs in large and short centromeres and generates a BED file indicating the location of the CDRs within the centromere. It also outputs a plot for visualization, validation, and downstream analysis.

Availability and implementation

CDR-Finder is available at https://github.com/EichlerLab/CDR-Finder.
SCARAP: scalable cross-species comparative genomics of prokaryotes
Authors: Wittouck Stijn , Eilers Tom , van Noort Vera , Lebeer Sarah
Published: December 2024

Motivation

Much of prokaryotic comparative genomics currently relies on two critical computational tasks: pangenome inference and core genome inference. Pangenome inference involves clustering genes from a set of genomes into gene families, enabling genome-wide association studies and evolutionary history analysis. The core genome represents gene families present in nearly all genomes and is required to infer a high-quality phylogeny. For species-level datasets, fast pangenome inference tools have been developed. However, tools applicable to more diverse datasets are currently slow and scale poorly.

Results

Here, we introduce SCARAP, a program containing three modules for comparative genomics analyses: a fast and scalable pangenome inference module, a direct core genome inference module, and a module for subsampling representative genomes. When benchmarked against existing tools, the SCARAP pan module proved up to an order of magnitude faster with comparable accuracy. The core module was validated by comparing its result against a core genome extracted from a full pangenome. The sample module demonstrated the rapid sampling of genomes with decreasing novelty. Applied to a dataset of over 31 000 Lactobacillales genomes, SCARAP showcased its ability to derive a representative pangenome. Finally, we applied the novel concept of gene fixation frequency to this pangenome, showing that Lactobacillales genes that are prevalent but rarely fixate in species often encode bacteriophage functions.

Availability and implementation

The SCARAP toolkit is publicly available at https://github.com/swittouck/scarap.
Urban–rural diversification in response to nighttime dim light stress in Drosophila suzukii
Authors: Sato Ayame , Takahashi Yuma
Published: December 2024

Human disturbance in cities leads to environmental changes, such as habitat fragmentation, raised ambient temperature, night lighting, and noise. Here, we examine the plastic response to artificial light at night (ALAN) of morphological and reproductive traits in isofemale strains derived from four rural and four urban populations of Drosophila suzukii. The individuals from urban and rural populations were reared under 12 h daylight, followed by either 12 h darkness (control) or dim light (treatment). Adult morphology changed with ALAN exposure regardless of fly origin, but the impact on morphological traits was more pronounced in rural populations. The level of male courtship activities was decreased by ALAN exposure, although the response varied between the rural and urban populations. Egg size and shape were slightly affected by ALAN for both rural and urban populations. The number of eggs laid increased more under ALAN stress in rural populations compared with urban populations. Our results suggest that exposure to ALAN induces a plastic response in these traits and that individuals in urban populations have evolved to mitigate the impacts of ALAN stress. These findings highlight the potential for urban populations to adapt to human-induced environmental stressors, with important implications for predicting species responses to urbanization.
Eyespot function in butterflyfishes (Chaetodontidae): comparing evidence for aposematism, automimicry, and predator mimicry
Authors: Karan Elizabeth A , Hodge Jennifer R , Alfaro Michael E
Published: December 2024

Many species of butterflyfish display false eyespots, but factors underlying eyespot diversity remain poorly understood. Eyespots are thought to function in predator avoidance, but there are multiple ways in which this might occur. An eyespot can function as deflection when distracting predators away from the true eye of the fish by mimicking it elsewhere on the body (automimicry). It can also function as intimidation, either by mimicking the appearance of predator eyes (predator mimicry) or by serving as a conspicuous warning to predators that the fish is spiny (warning coloration). Colour patterns that conceal the eye are common among butterflyfishes. Eye concealment is predicted under automimicry and can also occur in predator mimicry but is not predicted under warning coloration. Long median fin spines and deep bodies can make many species of butterflyfishes unpalatable, as predicted under intimidation. We adopt a comparative approach to examine relationships between eyespot presence, conspicuousness, and position on the body with eye coverage and physical defences, in order to evaluate evidence under the deflection vs. intimidation hypotheses within different trait complexes. Our results suggest that eyespots and eye coverage have evolved in conjunction with traits that facilitate predator evasion. We did not find evidence to support eyespots functioning as warning coloration for physical defences.
Green tea polyphenols alleviate di (2-ethylhexyl) phthalate-induced testicular injury in mice via lncRNA–miRNA–mRNA axis
Authors: Shi Heng , Zhao Xin-Hai , Peng Qin , Zhou Xian-Ling , Liu Si-Si , Sun Chuan-Chuan , Cao Qiu-Yu , Zhu Shi-Ping , Sun Sheng-Yun
Published: December 2024

Di(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer known for its toxic effects on the male reproductive system. Green tea polyphenols (GTPs), recognized for their antioxidant and anti-inflammatory properties, have demonstrated protective effects on various organs, but the mechanisms by which GTPs mitigate DEHP-induced testicular damage remain unclear. Healthy male C57BL/6J mice were divided into five groups: control, DEHP, DEHP + GTP treatment, GTP, and oil groups. Testicular histopathological changes were assessed using hematoxylin–eosin (H&E), periodic acid-Schiff (PAS), and Masson staining. Ultrastructural alterations were examined through transmission electron microscopy. High-throughput sequencing was performed to analyze the expression of mRNA, miRNA, and lncRNA and construct an lncRNA–miRNA–mRNA regulatory network for identifying key regulatory axes. Mice in the DEHP group exhibited significant testicular damage, including reduced sperm count, mitochondrial deformation, and endoplasmic reticulum dilation. GTP treatment notably improved testicular structural integrity, restored sperm count, and alleviated mitochondrial and endoplasmic reticulum damage. Additionally, DEHP significantly increased activated CD8+ T cells, which were reduced with GTP treatment. High-throughput sequencing revealed that GTP treatment exerted protective effects through the regulation of six key lncRNA–miRNA–mRNA axes. GTPs significantly protect against DEHP-induced testicular damage, and the lncRNA–miRNA–mRNA regulatory axes play a potential role in this process.
First Impressions Last? Lay-Judges’ Assessments of Credible Victimhood
Authors: Heber Anita , Fredriksson Tea
Published: December 2024

This article explores how Swedish lay-judges assess victims’ credibility in district court. Previous studies have explored how biases and emotional expressions impact credibility assessments. Adding to this, the present study analyses how lay-judges assess courtroom credibility from an intersectional perspective. Based on 24 in-depth interviews with lay-judges, the study explores three intertwined layers of credibility: appearances, narratives and emotions. The analysis concludes that these layers actualize balancing acts for both victims and the lay-judges assessing them. These layers of credibility can compound for victims, making them particularly credible in the eyes of the lay-judges, especially if and when they perform victimhood in line with expectations set by their intersectional characteristics.
Diagnostic performance of simultaneous multislice diffusion-weighted imaging in differentiating breast lesions: a systematic review and meta-analysis
Authors: Tan Yuqi , Ye Zheng , Lv Xinyang , Zhang Yiteng , Zhang Meng , Xia Chunchao , Li Zhenlin
Published: December 2024

Objectives

To investigate the diagnostic performance of simultaneous multislice diffusion-weighted imaging (SMS-DWI) in differentiating malignant and benign breast lesions, and compare it with conventional single shot and readout segmented echo planar imaging without the SMS technique.

Methods

The literature search was performed in PubMed, Embase, and Web of Science to identify comparative studies reporting the diagnostic performance of SMS-DWI and conventional DWI in patients with breast lesions. Histopathological analysis was used as a reference standard for malignant breast lesions. The methodological quality was evaluated using QUADAS-2 scale. The summary sensitivity, summary specificity, and area under the curve (AUC) of the summarized receiver operating characteristic curve were calculated and compared between SMS-DWI and conventional DWI using a bivariate random-effects model. Heterogeneity was explored with meta-regression and subgroup analyses.

Results

Six studies with 626 patients and 649 breast lesions (benign: 222, malignant: 427) were included. The summary sensitivity, summary specificity, and AUC for SMS-DWI were 0.89 (95% CI: 0.78-0.95), 0.94 (95% CI: 0.81-0.98), and 0.96 (95% CI: 0.94-0.98), respectively, and those for conventional DWI were 0.90 (0.95 CI: 0.84-0.94), 0.87 (95% CI: 0.80-0.92), and 0.94 (95% CI: 0.92-0.96), respectively. The diagnostic performance was not significantly different between SMS-DWI and conventional DWI (P = .337).

Conclusions

SMS-DWI has high diagnostic performance in differentiating breast lesions, which is not significantly different from the conventional DWI.

Advances in knowledge

There is no significant difference between SMS-DWI and conventional DWI in differentiating breast lesions, suggesting SMS-DWI may be a potential alternative to conventional DWI in breast imaging.
Measurement of Serum Free Vitamin D Concentrations: Importance, Challenges, and the Emerging Role of Mass Spectrometry
Authors: Alexandridou Anastasia , Stokes Caroline S , Volmer Dietrich A
Published: December 2024

Background

Serum total 25-hydroxyvitamin D [25(OH)D] concentration is the most widely used clinical biomarker for vitamin D status. Under certain physiological and pathological conditions, however, total 25(OH)D may not always be the best index for vitamin D status. Instead, the nonprotein-bound (free) fraction of total 25(OH)D has been suggested as a more appropriate marker in certain clinical situations.

Content

Free 25(OH)D levels can either be calculated or measured directly. Calculated free 25(OH)D depends on the concentrations of total serum 25(OH)D, vitamin D binding protein (VDBP), and albumin, as well as the affinity between analyte and binding proteins. Differences in VDBP concentrations are observed between populations as a result of health status, gene polymorphisms, and the assay used for determination. Direct measurement methods for free 25(OH)D are often complicated (dialysis, ultrafiltration) or susceptible to interferences, cross-reactivity, and type of antibody (immunoassays). Therefore, it is very important to develop tools that allow either accurate and precise measurement of VDBP or direct measurement of free 25(OH)D. For the latter, liquid chromatography combined with tandem mass spectrometry (LC–MS/MS) has recently shown promise for analysis of free vitamin D. In the current review, we present the importance and challenges regarding free 25(OH)D determination and the role of LC–MS-based methods in future studies.

More research is required to determine the role of free 25(OH)D in the assessment of vitamin D status in healthy subjects and in various clinical conditions. Recent advances in technology, including mass spectrometry, can provide the required assays for this purpose.
Can LLMs deeply detect complex malicious queries? A framework for jailbreaking via obfuscating intent
Authors: Shang Shang , Zhao Xinqiang , Yao Zhongjiang , Yao Yepeng , Su Liya , Fan Zijing , Zhang Xiaodan , Jiang Zhengwei
Published: December 2024

This paper delves into a possible security flaw in large language models (LLMs), particularly in their capacity to identify malicious intent within intricate or ambiguous inquiries. We have discovered that LLMs might overlook the malicious nature of highly veiled requests, even without alterations to the malevolent text in those queries, thus exposing a significant weakness in their content analysis systems. To be specific, we pinpoint and scrutinize two aspects of this vulnerability: (i) LLMs’ diminished capability to perceive maliciousness when parsing extremely obscured queries, and (ii) LLMs’ inability to discern malicious intent in queries that have been intentionally altered to increase their ambiguity by modifying the malevolent content itself. To illustrate and tackle this problem, we propose a theoretical framework and analytical strategy, and introduce a novel black-box jailbreak attack technique called IntentObfuscator. This technique exploits the identified vulnerability by concealing the genuine intentions behind user prompts, thereby compelling LLMs to inadvertently produce restricted content and circumvent their inherent content safety protocols. We elaborate on two specific applications within this framework: ”Obscure Intention” and ”Create Ambiguity,” which skillfully manipulate the complexity and ambiguity of queries to effectively dodge the detection of malicious intent. We empirically confirm the efficacy of the IntentObfuscator approach across various models, including ChatGPT-3.5, ChatGPT-4, Qwen, and Baichuan, achieving an average jailbreak success rate of 69.21%. Remarkably, our tests on ChatGPT-3.5, boasting 100 million weekly active users, yielded an impressive success rate of 83.65%. Additionally, we verify our approach across a range of sensitive content categories, including graphic violence, racism, sexism, political sensitivity, cybersecurity threats, and criminal techniques, further highlighting the considerable impact of our findings on refining ”Red Team” tactics against LLM content security frameworks.
CXCR4-targeted sensitive magnetic particle imaging for abdominal aortic aneurysm early detection and prognosis evaluation by recognizing total inflammatory cells
Authors: Cao Genmao , Zhang Ruijing , Jia Xiaohua , Jiang Bo , Li Yaling , Xuan Xuezhen , Tian Jie , Hui Hui , Xin Shijie , Dong Honglin
Published: December 2024

Aims

The maximum aortic diameter remains the diagnostic criteria and the indicator for prognosis prediction of abdominal aortic aneurysms (AAAs). An additional imaging modality is currently needed to help evaluate the prognosis of AAA as well as early detection of AAA formation. This study evaluated the most effective inflammatory markers for AAA using single-cell sequencing and, from these, developed probes to facilitate in vivo multimodal imaging of AAA inflammation.

Methods and results

Single-cell RNA sequencing (scRNAseq) of the human aortic aneurysms, GSE155468 and GSE166676 data sets, identified CXCR4 as the most representative marker. Anti-CXCR4-PE antibody was conjugated to superparamagnetic iron oxide nanoparticles to synthesize Fe3O4-anti-CXCR4-PE probes. The biocompatibility and specificity of the probes were validated in vivo and in vitro. Magnetic particle imaging (MPI) and fluorescence imaging (FLI) were performed to assess inflammation in early and advanced AAA mouse models. CXCR4-specific receptor inhibitor, AMD3100, was used for confirming CXCR4 as an excellent target for AAA imaging and therapy. scRNAseq indicated that chemokine-related pathways were upregulated in aortic aneurysms, and CXCR4 was the chemokine receptor that marks all AAA-related immune cells and inflammatory vascular cells. Fe3O4-anti-CXCR4-PE effectively recognized immune cells and inflammatory vascular cells, as strong MPI and FLI signals corresponded to increased CXCR4, CD45, and CD68 levels that represented AAA severity and rupture risk. Importantly, Fe3O4-anti-CXCR4-PE can help identify early AAA formation when ultrasound is undiagnosable. Finally, AMD3100 treatment in AAA mouse model inhibited AAA expansion and rupture and reduced aortic wall inflammation by inhibiting accumulation of immune cells and haematopoietic stem cells.

Conclusion

CXCR4 marks immune cells and inflammatory vascular cells in AAA and is associated with AAA prognosis in a mouse model of AAA. CXCR4-targeting multimodal MPI/FLI provides a novel approach for AAA prognosis prediction and early detection.
Tofacitinib versus Vedolizumab Among Bio-naïve Patients with Ulcerative Colitis: A Real-World Propensity-Weighted Comparison
Authors: Gros Beatriz , Constantine-Cooke Nathan , Kennedy Jake , Elford Alexander T , O’Hare Claire , Noble Colin , Jones Gareth-Rhys , Arnott Ian D , Lees Charlie W , Plevris Nikolas
Published: December 2024

BACKGROUND AND AIMS

Over the last decade, treatment options for moderate-to-severe ulcerative colitis (UC) have expanded. However, comparative studies between these agents are limited, especially among biologic-naïve patients. We aimed to compare the persistence, effectiveness and safety of tofacitinib and vedolizumab as the first advanced treatment for patients with UC.

METHODS

Patients who received either tofacitinib or vedolizumab as their first advanced therapy for UC in NHS Lothian were included. We used inverse probability of treatment weighting (IPTW). The probability of treatment assignment was calculated via logistic regression using age, sex, UC duration, Montreal extent, CRP, concomitant corticosteroids, and partial Mayo score at drug commencement.

RESULTS

We included n=158 patients, of whom n=81 (51.3%) received vedolizumab and n=77 (48.7%) tofacitinib. Median follow-up for vedolizumab patients was 3.1 years (IQR 1.6-4.8) and for tofacitinib patients 1.5 years (IQR 0.3-2.3). The cohort was 59.5% male with a median age of 41.1 years (IQR 31.5-51.8). At two years, vedolizumab persistence was superior to tofacitinib (p=0.005). At week 12 and week 52 clinical, biochemical and fecal biomarker steroid free remission were comparable between groups. Primary non-response and secondary loss of response were 9.9% and 17.3% for vedolizumab and 23.4% and 13% for tofacitinib respectively. Frequency of adverse events was comparable (11 [13.6%] vedolizumab vs 19 [24.7%] tofacitinib, p=0.629).

CONCLUSIONS

We found that the persistence and tolerability of vedolizumab was superior to tofacitinib in bio-naïve UC, although the rates of clinical and biomarker remission were comparable. These data may help inform positioning of advanced therapy.
The Partially-Matched-Sample Correction in Pseudo Panel Minimum Distance Estimation
Authors: Jia Fei
Published: December 2024

Certain repeated cross-sectional data sets, such as the Current Population Survey (CPS), use special sampling designs by which samples from different times periods are partially-matched. This paper proposes a correction to the optimal weighting matrix in minimum distance (MD) estimation of pseudo panel models to account for such partially-matched samples. This partially-matched-sample correction may be needed if the sample matching rate is nontrivial and, at the same time, there is a fixed effect, a serially correlated idiosyncratic error, or both in the underlying linear panel data model data generating process, all of which lead to a block diagonal structure of the optimal weighting matrix. Using the correction can result in considerable efficiency gains both in finite sample and asymptotically. Furthermore, it is shown that this correction is needed not only for the optimal MD estimator but for any MD estimator to make the inference right. As an illustration, the correction is applied to the classical question of estimating the monetary return to education using the yearly Merged Outgoing Rotation Group (MORG) files from CPS.
Foliage age affects pupal weight and development time, but not diapause induction in the biological control agent Hypena opulenta (Lepidoptera: Erebidae)
Authors: Seehausen M Lukas , Jones Ian M , Smith Sandy M , Bourchier Robert S
Published: December 2024

Facultative diapause is a life history trait that allows insects to undergo continuous development when conditions are favorable or to enter diapause when they are not. Insect voltinism can have an impact on the success of a weed-biological control agent because additional generations can increase agent population growth and reduce late-season recovery in the target weed. The most common factors that cue diapause are photoperiod and temperature; however, the role of nutrition is increasingly being recognized. We conducted a laboratory experiment to examine the effects of photoperiod and foliage age on diapause induction, pupal weight, and pupal development time in Hypena opulenta (Christoph) (Lepidoptera: Erebidae), a biological control agent for invasive swallow-worts in North America. A factorial experimental design was employed whereby H. opulenta was reared at long (16:8 h light:dark) and short (12:12 h) photoperiods on young and old swallow-wort foliage (Vincetoxicum rossicum Kleopow) Barbar. (Apocynaceae). Photoperiod was the only factor that affected diapause induction in H. opulenta. While foliage age did not affect diapause induction, it did affect pupal weight and pupal development time, with older foliage resulting in lower pupal weight and extended pupal phase. In field conditions, these impacts could affect pupal mortality through reduced winter preparedness and increased exposure to predators. These results support H. opulenta voltinism models based on photoperiods and indicate that the tendency of captive-reared H. opulenta to enter diapause after 2 or 3 generations, even in the absence of short photoperiods, is not a result of changing foliage age.
Plasma proteomics improves prediction of coronary plaque progression
Authors: Kraaijenhof Jordan M , Nurmohamed Nick S , Bom Michiel J , Gaillard E L , Ibrahim Shirin , Beverloo Cheyenne Y Y , Planken R Nils , Hovingh G Kees , Danad Ibrahim , Stroes Erik S G , Knaapen Paul
Published: December 2024

Aims

Coronary computed tomography angiography (CCTA) offers detailed imaging of plaque burden and composition, with plaque progression being a key determinant of future cardiovascular events. As repeated CCTA scans are burdensome and costly, there is a need for non-invasive identification of plaque progression. This study evaluated whether combining proteomics with traditional risk factors can detect patients at risk for accelerated plaque progression.

Methods and results

This long-term follow-up study included 97 participants who underwent two CCTA scans and plasma proteomics analysis using the Olink platform. Accelerated plaque progression was defined as rates above the median for percent atheroma volume (PAV), percent non-calcified plaque volume (NCPV), and percent calcified plaque volume (CPV). High-risk plaque (HRP) was identified by positive remodelling or low-density plaque at baseline and/or follow-up. Significant proteins associated with PAV, NCPV, CPV, and HRP development were incorporated into predictive models. The mean baseline age was 58.0 ± 7.4 years, with 63 (65%) male, and a median follow-up of 8.5 ± 0.6 years. The area under the curve (AUC) for accelerated PAV progression increased from 0.830 with traditional risk factors and baseline plaque volume to 0.909 with the protein panel (P = 0.023). For NCPV progression, AUC improved from 0.685 to 0.825 (P = 0.008), while no improvement was observed for CPV progression. For HRP development, AUC increased from 0.791 to 0.860 with the protein panel (P = 0.036).

Conclusion

Integrating proteomics with traditional risk factors enhances the prediction of accelerated plaque progression and high-risk plaque development, potentially improving risk stratification and treatment decisions without the need for repeated CCTAs.
Feasibility and accuracy of Dire

C

t

L

ung

U

ltrasound

E

valuation technique to monitor extravascular lung water in porcine lungs
Authors: Buttar Sana N , Møller-Sørensen Hasse , Perch Michael , Petersen Rene H , Møller Christian H
Published: December 2024

OBJECTIVES

Extravascular lung water precedes deterioration of pulmonary function. Current tools to assess extravascular lung water in a setting of donor lung procurement and ex vivo lung perfusion (EVLP) are either subjective or not feasible. Therefore, a direCt Lung Ultrasound Evaluation (CLUE) has been introduced. This study reassesses the feasibility and accuracy of CLUE by measuring its correlation with lung weight, wet-to-dry ratio (W/D ratio), dynamic compliance and pulmonary vascular resistance (PVR) in a porcine model.

METHODS

CLUE images, lung weight, dynamic compliance and PVR were recorded and lung samples for W/D ratio were taken before and after EVLP. CLUE score was calculated based on B-lines on images taken at each point of the lung using an established equation.

RESULTS

Eighteen porcine lungs were included. Total median of CLUE score, lung weight, W/D ratio and PVR increased significantly, while median of dynamic compliance decreased significantly after EVLP. Total median CLUE score increased significantly in all four surfaces after EVLP with equally high CLUE scores in posterior and diaphragm lines. CLUE score demonstrated a significant strong positive correlation with lung weight (r = 0.825) and W/D ratio (r = 0.837), while CLUE’s correlation with dynamic compliance and PVR was significantly moderate to strong (r = −0.669, r = 0.695, respectively).

CONCLUSIONS

CLUE technique is feasible to assess extravascular lung water in donor lungs after procurement and during EVLP. CLUE score correlated significantly with lung weight, W/D ratio, dynamic compliance and PVR. Transplant suitability of a donor lung may not solely depend on CLUE evaluation.
Spatial analysis of production technology, productivity and innovation
Authors: Alemayehu Fikru K , Kumbhakar Subal C
Published: December 2024

This study employs a state-of-the-art econometric methodology to investigate the relationship between firm productivity and innovation, considering the spatial heterogeneity of firms and locations. It examines significant variations in productivity and production technologies among firms and locations within Norwegian food and beverage (F&B) manufacturing. Analysing data from 336 firms over 12 years, our findings indicate that geographical location influences production processes, productivity and productivity persistence. This research contributes to existing knowledge by emphasising the influence of spatial heterogeneity on productivity and innovation in the F&B industry. It also recommends integrating geographical variations into regional development policies and firm-level strategies.
An empirical test of Baker’s law: dispersal favors increased rates of self-fertilization
Authors: McCauley Michelle A , Milligan William R , Lin Julie , Penley McKenna J , Quinn Lilja M , Morran Levi T
Published: December 2024

Baker’s law is the observation that recently dispersed populations are more likely to be self-fertilizing than populations at the range core. The explanatory hypothesis is that dispersal favors self-fertilization due to reproductive assurance. Caenorhabditis elegans nematodes reproduce via either self-fertilization or outcrossing and frequently disperse in small numbers to new bacterial food sources. While C. elegans males facilitate outcrossing, males and outcrossing are rare in natural C. elegans populations. Here, we use experimental evolution to test if frequent dispersal selects for the invasion of self-fertilization into predominantly outcrossing populations. C. elegans dispersal often occurs in the dauer alternative life stage. Therefore, we tested the effects of dispersal on rates of self-fertilization in populations exposed to dauer-inducing conditions and populations maintained under standard lab conditions. Overall, we found that populations required to disperse to new food sources rapidly evolved substantially elevated rates of self-fertilization compared to populations that were not required to disperse in both dauer and non-dauer populations. Our results demonstrate that frequent dispersal can readily favor the evolution of increased selfing rates in C. elegans populations, regardless of life stage. These data provide a potential mechanism to explain the dearth of outcrossing in natural populations of C. elegans.
The Core Circadian Clock Factor, Bmal1, Transduces Sex-specific Differences in Both Rhythmic and Nonrhythmic Gene Expression in the Mouse Heart
Authors: Zhang Xiping , Procopio Spencer B , Ding Haocheng , Semel Maya G , Schroder Elizabeth A , Viggars Mark R , Seward Tanya S , Du Ping , Wu Kevin , Johnson Sidney R , Prabhat Abhilash , Schneider David J , Stumpf Isabel G , Rozmus Ezekiel R , Huo Zhiguang , Delisle Brian P , Esser Karyn A
Published: December 2024

It has been well established that cardiovascular diseases exhibit significant differences between sexes in both preclinical models and humans. In addition, there is growing recognition that disrupted circadian rhythms can contribute to the onset and progression of cardiovascular diseases. However, little is known about sex differences between the cardiac circadian clock and circadian transcriptomes in mice. Here, we show that the core clock genes are expressed in common in both sexes, but the cardiac circadian transcriptome is very sex-specific. Hearts from female mice expressed significantly more rhythmically expressed genes (REGs) than male hearts, and the temporal distribution of REGs was distinctly different between sexes. To test the contribution of the circadian clock in sex-specific gene expression in the heart, we knocked out the core circadian clock factor Bmal1 in adult cardiomyocytes. The sex differences in the circadian transcriptomes were significantly diminished with cardiomyocyte-specific loss of Bmal1. Surprisingly, loss of cardiomyocyte Bmal1 also resulted in a roughly 8-fold reduction in the number of all differentially expressed genes between male and female hearts. We highlight sex-specific changes in several cardiac-specific transcription factors, including Gata4, Nkx2-5, and Tbx5. While there is still much to learn, we conclude that cardiomyocyte-specific Bmal1 is vital in conferring sex-specific gene expression in the adult mouse heart.