bluuebunny/crossref_metadata_2025 huggingface dataset:
Assess Self-Efficacy of Individuals for Personal Protection in Ghana
Authors: Norman Ishmael D. , Kpeglo Emmanuel Dodzi
Published: November 2023

In this cross-sectional study, we assessed the self-efficacy of individuals for personal protective measures against the crime of robbery, kidnapping, defilement and rape to estimate the awareness-preparedness gap of the population as contribution to overall security and safety in Ghana. We relied on the Protection Motivation Theory (PMT). The intersection between social systems and technological interactions toward crime suppression and mitigation was analyzed using the Adaptive Structuration Theory (AST). The State as the “Referent Object” and the sole provider of security for itself and citizens was discussed from the lens of securitization theory in relation to the four crime types. Data were collected in 16 administrative districts in Ghana between 2021 and 2022. The sample size was [Formula: see text]. The test results showed that there was a statistically significant difference (Chi [Formula: see text], 67.604, 240.161, and 274.646; [Formula: see text], 0.000, 0.000, and 0.001, [Formula: see text], 2, 2, and 2) among the three categories of participants’ responses (not at all, somewhat worried, and highly worried) to the question “how worried are you about (kidnapping, armed robberies, defilement, and rape) in your daily life”. Although there was awareness of State and citizens about these four crimes, there was also the lack of credible intervention and mitigation strategies. This paper is unique in integrating these theories in assessing the self-efficacy of individuals’ ontological security.
Dr John Grant Malcolmson and a reconciliation of the Middle Devonian Lethen Bar and Lethen House fish-bearing nodule localities, with notes on the Middle Devonian nodule beds of the Moray Firth area
Authors: Davidson R. G. , Trewin N. H. , Armstrong J. , Waters S. R.
Published: November 2023

The area known as Lethen Bar and Clune, SE of Nairn, Scotland, is a classic Middle Devonian locality, which has yielded nodules or concretions, some of which contain fossil fishes with the highest quality of preservation. The locality was largely centred on farm limestone quarries situated around the perimeter of an isolated outlier of the main fishbed. It was first described in the 19th century, although the upsurge in collecting fossil fishes only occurred some 12 years after the quarries were first mentioned in the scientific literature. Our knowledge of the provenance of the locality is based on very limited accounts, which have never been scientifically tested; these accounts also contain apparent anomalies that have never been adequately addressed. Based on these anomalies, the author of a paper published in 1983 proposed that the locality had been untraceable since the late 19th century and that the outcrop was quarried out. In 2005, the present authors recorded the first scientifically detailed stratigraphical section of the fishbed, followed in 2021–23 by detailed field surveys and by a reappraisal of the literature. This work has resolved the 19th century anomalies and allowed us to confirm the locations of old quarries, to give affirmation to two previously unrecognized sites and to show that the outcrop is still present.

Thematic collection:
This article is part of the Geology of Scotland collection available at:
https://www.lyellcollection.org/topic/collections/geology-of-scotland
Rapid loading and deformation of soft sediments during emplacement of a lava delta in the Vøring Basin, Mid-Norwegian Margin
Authors: Maharjan Dwarika , Planke Sverre , Bellwald Benjamin , Millett John M. , Abdelmalak Mohamed Mansour , Manton Ben , Zastrozhnov Dmitrii , Jerram Dougal A. , Myklebust Reidun
Published: November 2023

Soft sediment deformation structures may form when denser sediments or fluids are deposited on or flow over unlithified and less dense sediments. This study presents a seismic geomorphological study of the basal contact between an extrusive volcanic sequence and underlying sediments, defining the ‘Base Basalt’ surface, on the Mid-Norwegian Margin. This contribution focuses in particular on the development of geomorphological features related to the rapid loading of a several 100 m-thick lava delta package of hyaloclastite onto poorly consolidated sediments of the pre-volcanic sedimentary basin fill. Seismic horizons, sequence boundaries, volcanic facies units and attribute maps are used to characterize the seismic geomorphological features imaged within a high-quality 3D seismic cube. The ‘Base Basalt’ horizon and attribute maps reveal incised channels and a network of polygonal to irregular depressions and ridges described here as an ‘egg-box network’. More than 150 depressions, with a typical diameter of 1 km and a depth of 100 m, have been mapped. The deformation features, which are restricted to the base of the Lava Delta seismic facies unit, are interpreted to be the result of rapid loading of the Lava Delta onto poorly consolidated unlithified pre-volcanic sediments. This study presents new evidence for the dynamic nature of the transition between sedimentary basins and large-scale volcanism found along volcanic margins and basins associated with rapid volcanic deposition.
Magmatically driven hydrocarbon generation and fluid flow in the Namibe Basin of Angola
Authors: Fiordalisi Edoardo , van Dongen Bart , Moore Julian , Rochelle-Bates Nathan , Machado Vladimir A. G. , Dixon Richard , Sharp Ian , Schröder Stefan
Published: November 2023

Magmatic activity can severely alter the thermal structure of a sedimentary basin, with variable effects on the petroleum system. The Namibe Basin of Angola (Cretaceous South Atlantic rift) contains well-exposed magmatic and petroleum system elements and allows integrated assessment of how magmatic activity can modify the petroleum system. The basin was affected by syn-rift and post-rift magmatic events, and bitumen is observed within both the Pre- and Post-Salt stratigraphical sections. In the Pre-Salt, fluorescent bitumen has a lacustrine signature and is associated with calcite and quartz cements. Onshore Pre-Salt units are thermally immature, and therefore the source rock that generated the Pre-Salt bitumen is likely located offshore. Hydrocarbons migrated or re-migrated via magmatically driven fluids, reaching the present-day onshore. Closer to magmatic units, non-fluorescent pyrobitumen was instead observed, evidencing hydrocarbon cracking processes following emplacement. In the Post-Salt, bitumen is
in situ
and shows marine-like signatures compatible with an immediate Post-Salt source rock depositional environment. In the immediate Post-Salt, units with very high total organic carbon values (TOC; up to 13.8%) and excellent source rock properties (hydrogen index >600 mgHC g
−1
TOC) have reached thermal maturation. Within the Namibe Basin these Post-Salt source units lie in proximity to major Turonian–Coniacian–Santonian volcanic centres and associated shallow intrusions, which are likely to have caused thermally forced maturation processes and generation of the Post-Salt hydrocarbons. This paper demonstrates the importance of an integrated field, petrographic and geochemical approach in unravelling the influence of magmatic activity on basin thermal structure and petroleum systems.
Eight Priorities for Instructional Videos in the Online Classroom
Authors: Robertson Sarah , Steele John , Mandernach Jean
Published: November 2023

To enhance student engagement and learning in the online classroom, instructional videos need to be thoughtfully created, curated, and integrated. Key considerations include making the videos learner-centered and relevant, ensuring easy access, keeping video length short, focusing on clarity over perfection, providing alternative means of accessing the information, fostering student interaction, and personalizing videos to enhance the sense of class participation and connection.
P2ANet: A Large-Scale Benchmark for Dense Action Detection from Table Tennis Match Broadcasting Videos
Authors: Bian Jiang , Li Xuhong , Wang Tao , Wang Qingzhong , Huang Jun , Liu Chen , Zhao Jun , Lu Feixiang , Dou Dejing , Xiong Haoyi
Published: November 2023

While deep learning has been widely used for video analytics, such as video classification and action detection, dense action detection with fast-moving subjects from sports videos is still challenging. In this work, we release yet another sports video benchmarkP2ANetforPingPong-Action detection, which consists of 2,721 video clips collected from the broadcasting videos of professional table tennis matches in World Table Tennis Championships and Olympiads. We work with a crew of table tennis professionals and referees on a specially designed annotation toolbox to obtain fine-grained action labels (in 14 classes) for every ping-pong action that appeared in the dataset, and formulate two sets of action detection problems—action localizationandaction recognition. We evaluate a number of commonly seen action recognition (e.g., TSM, TSN, Video SwinTransformer, and Slowfast) and action localization models (e.g., BSN, BSN++, BMN, TCANet), usingP2ANetfor both problems, under various settings. These models can only achieve 48% area under the AR-AN curve for localization and 82% top-one accuracy for recognition since the ping-pong actions are dense with fast-moving subjects but broadcasting videos are with only 25 FPS. The results confirm thatP2ANetis still a challenging task and can be used as a special benchmark for dense action detection from videos. We invite readers to examine our dataset by visiting the following link:https://github.com/Fred1991/P2ANET.
Multi-Compression Scale DNN Inference Acceleration based on Cloud-Edge-End Collaboration
Authors: Qi Huamei , Ren Fang , Wang Leilei , Jiang Ping , Wan Shaohua , Deng Xiaoheng
Published: November 2023

Edge intelligence has emerged as a promising paradigm to accelerate DNN inference by model partitioning, which is particularly useful for intelligent scenarios that demand high accuracy and low latency. However, the dynamic nature of the edge environment and the diversity of end devices pose a significant challenge for DNN model partitioning strategies. Meanwhile, limited resources of the edge server make it difficult to manage resource allocation efficiently among multiple devices. In addition, most of the existing studies disregard the different service requirements of the DNN inference tasks, such as its high accuracy-sensitive or high latency-sensitive. To address these challenges, we propose a Multi-Compression Scale DNN Inference Acceleration (MCIA) based on cloud-edge-end collaboration. We model this problem as a mixed-integer multi-dimensional optimization problem, jointly optimizing the DNN model version choice, the partitioning choice, and the allocation of computational and bandwidth resources to maximize the tradeoff between inference accuracy and latency depending on the property of the tasks. Initially, we train multiple versions of DNN inference models with different compression scales in the cloud, and deploy them to end devices and edge server. Next, a deep reinforcement learning-based algorithm is developed for joint decision making of adaptive collaborative inference and resource allocation based on the current multi-compression scale models and the task property. Experimental results show that MCIA can adapt to heterogeneous devices and dynamic networks, and has superior performance compared with other methods.
B Cell–Directed Therapy in Autoimmunity
Authors: Abeles Ilana , Palma Chris , Meednu Nida , Payne Aimee S. , Looney R. John , Anolik Jennifer H.
Published: November 2023

Autoimmune diseases with B cell–directed therapeutics approved by the US Food and Drug Administration are surprisingly diverse in clinical manifestations and pathophysiology. In this review, we focus on recent clinical and mechanistic insights into the efficacy of B cell depletion in these diverse autoimmune disorders, the rapidly expanding armamentarium of approved agents, and future approaches. The pathogenic roles for B cells include direct functions such as production of autoantibodies and proinflammatory cytokines and indirect functions via antigen presentation to T cells. The efficacy of B cell–depleting strategies varies across diseases and likely reflects the complexity of disease pathogenesis and relative contribution of B cell roles. Additionally, B cell–depleting therapies do not equally target all B cell subsets in all patients, and this likely explains some of the variability in responses. Recent reports of B cell depletion with novel chimeric antigen receptor (CAR) T cell approaches in an expanding number of autoimmune diseases highlight the potential role of B cell depletion in resetting immune tolerance. The relative importance of eliminating autoreactive B cells and plasma cells and approaches to doing so will also be discussed.
Metabolic Rewiring and Communication: An Integrative View of Kidney Proximal Tubule Function
Authors: Chrysopoulou Maria , Rinschen Markus M.
Published: November 2023

The kidney proximal tubule is a key organ for human metabolism. The kidney responds to stress with altered metabolite transformation and perturbed metabolic pathways, an ultimate cause for kidney disease. Here, we review the proximal tubule's metabolic function through an integrative view of transport, metabolism, and function, and embed it in the context of metabolome-wide data-driven research. Function (filtration, transport, secretion, and reabsorption), metabolite transformation, and metabolite signaling determine kidney metabolic rewiring in disease. Energy metabolism and substrates for key metabolic pathways are orchestrated by metabolite sensors. Given the importance of renal function for the inner milieu, we also review metabolic communication routes with other organs. Exciting research opportunities exist to understand metabolic perturbation of kidney and proximal tubule function, for example, in hypertension-associated kidney disease. We argue that, based on the integrative view outlined here, kidney diseases without genetic cause should be approached scientifically as metabolic diseases.
Statistical Brain Network Analysis
Authors: Simpson Sean L. , Shappell Heather M. , Bahrami Mohsen
Published: November 2023

The recent fusion of network science and neuroscience has catalyzed a paradigm shift in how we study the brain and led to the field of brain network analysis. Brain network analyses hold great potential in helping us understand normal and abnormal brain function by providing profound clinical insight into links between system-level properties and health and behavioral outcomes. Nonetheless, methods for statistically analyzing networks at the group and individual levels have lagged behind. We have attempted to address this need by developing three complementary statistical frameworks—a mixed modeling framework, a distance regression framework, and a hidden semi-Markov modeling framework. These tools serve as synergistic fusions of statistical approaches with network science methods, providing needed analytic foundations for whole-brain network data. Here we delineate these approaches, briefly survey related tools, and discuss potential future avenues of research. We hope this review catalyzes further statistical interest and methodological development in the field.
Relational Event Modeling
Authors: Bianchi Federica , Filippi-Mazzola Edoardo , Lomi Alessandro , Wit Ernst C.
Published: November 2023

Advances in information technology have increased the availability of time-stamped relational data, such as those produced by email exchanges or interaction through social media. Whereas the associated information flows could be aggregated into cross-sectional panels, the temporal ordering of the events frequently contains information that requires new models for the analysis of continuous-time interactions, subject to both endogenous and exogenous influences. The introduction of the relational event model (REM) has been a major development that has stimulated new questions and led to further methodological developments. In this review, we track the intellectual history of the REM, define its core properties, and discuss why and how it has been considered useful in empirical research. We describe how the demands of novel applications have stimulated methodological, computational, and inferential advancements.
The Relationship between Social Support, Empathy, Self-Efficacy, and Humanistic Practice Ability among Clinical Nurses in China: A Structural Equation Model
Authors: Liu Huan , Zhang Lin , Yan Jin , Huang Hui , Yi Qifeng , Peng Liming
Published: November 2023

Aim. This study aims to identify the factors that influence humanistic practice ability, validate the relationship among social support, empathy, self-efficacy, and humanistic practice, and provide reference basis for developing intervention measures. Background. Cultivating humanistic practice ability in clinical nurses is essential for improving the quality of nursing care. Methods. From February to March 2022, a cross-sectional survey was conducted in top three hospitals in central China. The study used a self-designed questionnaire to ascertain the general characteristics of the participants. The Nurses’ Humanistic Practice Ability Scale, Jefferson Empathy Scale, Perceived Social Support Scale, and General Self-Efficacy Scale were used. Data were analyzed using Spearman’s correlation and a structural equation model through statistical product and service solutions (SPSS) and analysis of moment structure (AMOS). Results. A total of 650 clinical nurses were included in this study. The average age was 32.35 ± 8.35 years. The Nurses’ Humanistic Practice ability Scales score was 107.49 ± 19.32. Nurses’ humanistic practice ability showed a positive correlation with social support (r = 0.455), self-efficacy (r = 0.369), and empathy (r = 0.375) (all

p

 < 0.001). Empathy totally mediated the relationship between social support and humanistic practice ability. In addition, self-efficacy and empathy served as sequential mediators in the association. Conclusion. Social support can influence the humanistic practice ability through self-efficacy. In addition, the higher the level of social support, the higher the level of self-efficacy, which further promotes the improvement of their empathy and eventually leads to stronger humanistic practice ability. Therefore, the corresponding measures to promote the humanistic practice ability of nurses can be formulated from the abovementioned three aspects. Implications for Nursing Management. We recommend that hospital administrators provide nurses with more comprehensive social support and develop intervention strategies to enhance nurses’ self-efficacy and empathy, which help to improve the nurse’s humanistic practice ability.
Tribological and Mechanical Properties of Gradient Coating on Al2O3-Based Coating Produced by Detonation Spraying Methods
Authors: Rakhadilov B. K. , Kakimzhanov D. N. , Buitkenov D. B. , Kozhanova R. S. , Zhurerova L. G. , Sagdoldina Zh. B.
Published: November 2023

This work is aimed at obtaining gradient coating of aluminum oxide (Al2O3) by detonation spraying. The influence of technological parameters of spraying on the formation of structure, phase composition. mechanical, and tribological characteristics of Al2O3 coatings have been investigated. It was determined that coatings obtained from the same raw powder materials under different technological conditions show different structural and phase characteristics. X-ray diffraction analysis showed that when the barrel is filled with gas mixture by 56%, the coating with the main phase α-Al2O3 is formed, and when the barrel is filled with gas mixture by 63%, the coating with the main phase γ-Al2O3, which is relatively more ductile than α-Al2O3, is formed. It is determined that the α-Al2O3 formed mainly on the surface provides good wear resistance. The bottom layer composed of γ-Al2O3 phase, which is relatively more ductile than α-Al2O3, provides good adhesion of the coating to the substrate. Tribological study showed that the coating obtained at 56% of filling shows good wear resistance compared to other samples. At 63% of filling the results of scratch test showed good adhesive strength. By varying the technological mode of detonation sputtering (56%, 53%, and 63%), Al2O3 coating with gradient structure was obtained, in which γ-Al2O3 smoothly transitions to α-Al2O3 from the substrate to the surface. The hardness of the coatings was found to increase smoothly from substrate to surface (12.4–14.2 GPa).
The Effect of a Patient Activation Tailored Intervention on Type 2 Diabetes Self-Management and Clinical Outcomes: A Study from Saudi Arabian Primary Care Settings
Authors: Almutairi Nasser , Gopaldasani Vinod , Hosseinzadeh Hassan
Published: November 2023

Background. Type 2 diabetes mellitus (T2DM) is a global public health challenge. T2DM self-management, including diet, physical activity, blood glucose self-monitoring, foot care, and adherence to medication, is considered a primary tool for managing diabetes. Patient activation, an individual’s knowledge, skill, and confidence in managing their health and healthcare, was recognized to be associated with better T2DM self-management and clinical outcomes. Patient activation intervention has been described as a potential approach for enhancing chronic disease self-management. This study is aimed at examining the effect of a patient activation-tailored intervention on T2DM self-management and clinical outcomes in primary care settings in Saudi Arabia. Method. A pre- and postintervention study was conducted among ≥18 years old T2DM patients attending primary healthcare centers in Saudi Arabia. Collected data included demographics, clinical data, the Patient Activation Measure (PAM), the Summary of Diabetes Self-Care Activities (SDSCA), the diabetes knowledge test (DKT2), the problem area in diabetes test (PAID-5), and the diabetes quality of life test (DQOL). The intervention was tailored based on the participants’ patient activation level. The intervention consisted of monthly face-to-face sessions for three months and a telephone follow-up per month for three months postintervention. Descriptive statistics, a paired sample

t

-test for scale variables, and Wilcoxon’s signed-rank test for categorical variables were used for data analysis. Results. A total of 82 patients, mostly female (61%) with a mean age of

51.3
±
9.9

years old, completed baseline and postintervention surveys. After six months of intervention, there was a significant change in patient activation score from 54.74 to 61.58 (

p
<
0.001

), hemoglobin A1c (HbA1c) from 8.38 to 7.55 (

p
<
0.001

), and body mass index (BMI) from 30.90 to 29.16 (

p
<
0.001

). Also, there was a significant change in SDSCA scores (diet from 3.12 to 3.67, exercise from 2.54 to 3.49, and blood glucose self-testing from 2.37 to 3.24) (

p
<
0.001

) and DKT from 6.29 to 7.22 (

p
=
0.01

). Conclusion. Our findings suggested that tailoring interventions based on patients’ activation levels is more likely to yield promising T2DM self-management and clinical outcomes.
Relationship between Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and the Risk of COVID-19: A Meta-Analysis
Authors: Luoyi Hu , Yan Pan , Qihong Fan
Published: November 2023

Introduction. Research shows the correlation between angiotensin-converting enzyme (ACE) deletion and insertion (D/I) polymorphism and COVID-19 risk; yet, conclusive evidence is still lacking. Thus, a meta-analysis of relevant articles was performed to more accurately estimate the relationship of ACE I/D polymorphism with the risk of COVID-19. Material and Methods. Relevant literature from the PubMed database was systematically reviewed, and odds ratios (ORs) and associated 95% confidence intervals (CIs) were measured. Additionally, the metapackage from Stata version 15.0 was used for statistical analysis. Results. The meta-analysis eventually contained 8 studies, including 1362 COVID-19 cases and 4312 controls. Based on the data, the ACE I/D polymorphism did not show an association with COVID-19 risk (D vs. I: [Formula: see text], 95% [Formula: see text]; DD vs. II: [Formula: see text], 95% [Formula: see text]; DI vs. II: [Formula: see text], 95% [Formula: see text]; dominant model: [Formula: see text], 95% [Formula: see text]; and recessive model: [Formula: see text], 95% [Formula: see text]). Further, subgroup analyses stratified based on case proved that the ACE D allele demonstrated an association with increasing risk of COVID-19 severity (D vs. I: [Formula: see text], 95% [Formula: see text]; DD vs. II: [Formula: see text], 95% [Formula: see text]; DI vs. II: [Formula: see text], 95% [Formula: see text]; dominant model: [Formula: see text], 95% [Formula: see text]; and recessive model: [Formula: see text], 95% [Formula: see text]). Conclusions. The ACE D allele was clearly related to an enhanced risk of COVID-19 severity. Hence, it is imperative to take into account the influence of genetic factors during the development of future vaccines.
Comparison of Cryotherapy and Topical Salicylic Acid in Common Warts: A Systematic Review and Meta‐Analysis
Authors: Chaudhary Dipika , Sun Yan , Gao Xinghua
Published: November 2023

Background. Common warts are most common complaint among children and adults caused by human papillomavirus (HPV). Cryotherapy and topical salicylic acid are common therapies. Objective. To compare the efficacy and safety of cryotherapy and topical salicylic acid in common warts. Methods. Randomized controlled trials (RCTs) comparing cryotherapy and topical salicylic acid treatment in patients with common warts were searched by using PubMed, Embase, Google Scholar, and Cochrane Database of Systematic Reviews up to Oct 20, 2021. The keywords were “common warts/verruca,” “cryotherapy,” and “salicylic acid.” The language was restrained to English. No age or gender limitation was conducted. The outcomes were complete remission of all warts at different observation times, recurrence rates, and side effects. Study‐specific effect sizes were pooled by using the fixed‐effects model and the Mantel–Haenszel method. I2 was used to assess heterogeneity of studies. Results. Seven articles involving 976 patients randomized into the cryotherapy group or salicylic acid group were included. Of whom, 487 patients received cryotherapy, while 489 received salicylic acid treatment. With the fixed‐effects model, the pool effect of complete clearance of warts at 12 weeks comparing cryotherapy and salicylic acid was not statistically significant (RR = 0.99 (0.84–1.17), I2 = 0%). Conclusion. Comparable efficacy of cryotherapy and topical salicylic acid was conducted in common wart treatment. More high‐quality pieces of evidence with more samples are needed to confirm the results for further recommendations.
Abducens Nerve Neuropraxia due to Acute Bacterial Rhinosinusitis: Case Report and Literature Review
Authors: Alghulikah Abdulrahman , Alseneidi Sarah , Alsaady Hedayah , Alhussien Ahmed , Al-Dousary Surayie , Alromaih Saud , AlHumaizi Abdulrahman
Published: November 2023

Background. Acute bacterial rhinosinusitis (ABRS) is a common infection of the paranasal sinuses that can lead to complications such as orbital and intracranial extension. The abducens nerve course is adjacent to the sphenoid sinus. Diplopia is rarely the initial presentation of sphenoid sinus pathology. In this article, we present the case of a middle-aged male who presented with diplopia and abducens nerve palsy secondary to ABRS, and we conducted a literature review in search of similar cases. Case Presentation. A 52-year-old male presented with diplopia secondary to ABRS. Imaging revealed the complete opacification of the bilateral sphenoid and frontal sinuses, with the extension of the inflammatory process to the optic nerve and cavernous sinus. The patient underwent a surgical intervention, which revealed a pyocele collection in the opticocarotid recess inside the sphenoid sinuses. After the surgery, the patient received antibiotics and reported a complete recovery. Conclusions. Acute bacterial rhinosinusitis can present with atypical symptoms and lead to serious complications, such as abducens nerve palsy. Early diagnosis, appropriate management, and timely referral to a multidisciplinary team are crucial to preventing residual nerve damage and ensuring favorable outcomes.
SSF‐Align: Point Cloud Registration Based on Statistical Shape Features with Manifold Metric
Authors: Ren Pu , Xu Chongbin , Sun Xiaomin , Li Yuan , Tao Haiying
Published: November 2023

As an important topic in 3D vision, the point cloud registration has been widely used in various applications, including location, reconstruction, and shape recognition. In this paper, we propose a new registration method for this topic, which utilizes statistical shape features (SSFs) and manifold metrics to estimate the transformation matrix. The SSFs are extracted to establish a compact representation for the original point cloud. Then, the representation is mapped into a manifold to reduce the influences of different scales and translations. Finally, the manifold metric is used to minimize the distance based on the compact representation and the pose can be estimated. The advantages of our method include robustness to nonuniform densities, insensitivity to missing parts, and better performance to handle large difference of poses. Experimental results show that our method achieves significant improvements compared to the state of the art methods.
Immunotherapy of MSI Cancer: Facts and Hopes
Authors: Wilbur H. Catherine , Le Dung T. , Agarwal Parul
Published: November 2023

Microsatellite instability (MSI) is a tumor molecular phenotype that evolves from loss of function in the mismatch repair (MMR) proteins through deleterious germline mutations, epigenetic inactivation, or somatic biallelic mutations. This phenotype is characterized by genomic hyper-mutability, increased neoantigen expression, and a favorable, immune-rich tumor microenvironment. These features confer a greater likelihood of response to treatment with the class of agents known as immune checkpoint inhibitors (ICI) and, potentially, other immune-based therapeutics. MSI as a predictive biomarker for response to treatment with ICIs ultimately led to the first tissue-agnostic approval of pembrolizumab for advanced, previously treated MSI or deficient MMR (dMMR) tumors. Nevertheless, response to ICIs in dMMR/MSI tumors is not universal. Identifying predictors of response and elucidating mechanisms of immune escape will be crucial to continued successful treatment of this subset. In this review, we aim to describe the pathogenesis and key immunologic features of dMMR/MSI tumors, provide a brief overview of the currently approved treatments, and discuss promising novel immune-based therapeutics currently under investigation.
Supplementary Data from First-in-Human, Phase 1 Dose-Escalation Study of Biparatopic Anti-HER2 Antibody–Drug Conjugate MEDI4276 in Patients with HER2-positive Advanced Breast or Gastric Cancer
Authors: Pegram Mark D. , Hamilton Erika P. , Tan Antoinette R. , Storniolo Anna Maria , Balic Kemal , Rosenbaum Anton I. , Liang Meina , He Peng , Marshall Shannon , Scheuber Anita , Das Mayukh , Patel Manish R.
Published: November 2023

Supplementary Data from First-in-Human, Phase 1 Dose-Escalation Study of Biparatopic Anti-HER2 Antibody–Drug Conjugate MEDI4276 in Patients with HER2-positive Advanced Breast or Gastric Cancer
Single-Cell RNA-Seq Analysis of Patient Myeloid-Derived Suppressor Cells and the Response to Inhibition of Bruton's Tyrosine Kinase
Authors: Savardekar Himanshu , Allen Carter , Jeon Hyeongseon , Li Jianying , Quiroga Dionisia , Schwarz Emily , Wu Richard C. , Zelinskas Sara , Lapurga Gabriella , Abreo Alexander , Stiff Andrew , Shaffer Jami , Blaser Bradley W. , Old Matthew , Wesolowski Robert , Xin Gang , Kendra Kari L. , Chung Dongjun , Carson William E.
Published: November 2023

Myeloid-derived suppressor cell (MDSC) levels are elevated in patients with cancer and contribute to reduced efficacy of immune checkpoint therapy. MDSC express Bruton's tyrosine kinase (BTK) and BTK inhibition with ibrutinib, an FDA-approved irreversible inhibitor of BTK, leads to reduced MDSC expansion/function in mice and significantly improves the antitumor activity of anti-PD-1 antibody treatments. Single-cell RNA sequencing (scRNA-seq) was used to characterize the effect of ibrutinib on gene expression of fluorescence-activated cell sorting-enriched MDSC from patients with different cancer types [breast, melanoma, head and neck squamous cell cancer (HNSCC)]. Melanoma patient MDSC were treated in vitro for 4 hours with 5 μmol/L ibrutinib or DMSO, processed for scRNA-seq using the Chromium 10× Genomics platform, and analyzed via the Seurat v4 standard integrative workflow. Baseline gene expression of MDSC from patients with breast, melanoma, and HNSCC cancer revealed similarities among the top expressed genes. In vitro ibrutinib treatment of MDSC from patients with melanoma resulted in significant changes in gene expression. GBP1, IL-1β, and CXCL8 were among the top downregulated genes whereas RGS2 and ABHD5 were among the top upregulated genes (P < 0.001). Double positive CD14+CD15+ MDSC and PMN-MDSC responded similarly to BTK inhibition and exhibited more pronounced gene changes compared with early MDSC and M-MDSC. Pathway analysis revealed significantly downregulated pathways including TREM1, nitric oxide signaling, and IL-6 signaling (P < 0.004).

Implications:

scRNA-seq revealed characteristic gene expression patterns for MDSC from different patients with cancer and BTK inhibition led to the downregulation of multiple genes and pathways important to MDSC function and migration.
Simvastatin Attenuates Cardiac Fibrosis under Pathophysiological Conditions of Heart Failure with Preserved Left Ventricular Ejection Fraction by Inhibiting TGF-β Signaling
Authors: Marunouchi Tetsuro , Matsumura Kasumi , Fuji Eriko , Iwamoto Akihiro , Tanonaka Kouichi
Published: November 2023

Introduction: There is still no effective treatment for heart failure with preserved left ventricular ejection fraction (HFpEF), and therapies to improve prognosis are urgently needed. Clinical studies in patients with HFpEF have shown that statins and HMG-CoA reductase inhibitors may reduce their mortality rate. However, the mechanisms underlying the effects of statins on HFpEF remain unknown. In the present study, we examined whether simvastatin administration inhibits the development of cardiac fibrosis in HFpEF model mice. We further examined the contribution of the Smad and mitogen-activated protein (MAP) kinase pathways to the transforming growth factor-β (TGF-β) signaling pathway in the development of HFpEF. Methods: HFpEF animals were prepared by feeding C57BL/6 N mice a high-fat diet and providing water containing N[w]-nitro-l-arginine methyl ester hydrochloride (l-NAME) for 15 weeks. Simvastatin (30 mg/kg/day) or vehicle was administered orally daily during the experimental period. Cardiac function was measured by echocardiography, and cardiac fibrosis was evaluated by Masson’s trichrome staining. Changes in the TGF-β signaling proteins in myocardial tissue were examined by Western blotting. Results: A high-fat diet and l-NAME solution load induced cardiac diastolic dysfunction with cardiac fibrosis. Simvastatin treatment markedly attenuated cardiac fibrosis and reduced cardiac diastolic dysfunction. In addition, simvastatin prevented the increase in phosphorylation levels of Smad (Smad2 and Smad3) and MAPK (c-Raf, Erk1/2) pathway proteins downstream of the TGF-β receptor in cardiac tissue. Conclusions: Our present study demonstrated that simvastatin attenuated diastolic dysfunction by reducing cardiac fibrosis in HFpEF hearts. Furthermore, our findings suggest that the mechanisms by which simvastatin attenuates HFpEF development involve, at least in part, inhibition of the TGF-β signaling pathway, which is activated in the HFpEF heart.
Growth and Treatment in Congenital Adrenal Hyperplasia: An Observational Study from Diagnosis to Final Height
Authors: Gidlöf Sebastian , Hogling Daniel Eriksson , Lönnberg Hanna , Ritzén Martin , Lajic Svetlana , Nordenström Anna
Published: November 2023

Introduction: Congenital adrenal hyperplasia (CAH) due to 21α-hydroxylase deficiency results in inadequate cortisol and aldosterone synthesis and concomitant overproduction of adrenal androgens. Despite adequate replacement, impaired growth and overweight remain a clinical challenge. The main objective was to investigate the differences in growth, final height (FH), and body mass index (BMI) between different CYP21A2 genotype groups and glucocorticoid treatment strategies during the different phases of growth. Methods: This is a population-based observational cohort study from diagnosis to FH. A total of 86 subjects were diagnosed with CAH in Sweden during 1989–1994. Eighty subjects were followed until FH. There were no interventions apart from the clinical standard of care treatment for CAH. The main outcome measure was the corrected FH standard deviation score (cFH SDS) and its correlation with genotype, accumulated total glucocorticoid dose, and treatment strategy. In addition, BMI and growth trajectories during infancy, childhood, and adolescence were studied. Results: FH was shorter in patients with the more severe CYP21A2 genotypes. Treatment doses of glucocorticoid were within the international treatment recommendations (10–15 mg/m2). Patients with the null and I2 splice genotypes lost approximately 1 SD in FH, whereas patients with the milder genotypes (I172N, P30L, and V281L) were within 0.5 to 0 SDS from target height. cFH SDS was negatively affected by the use of prednisolone but did not correlate with overall glucocorticoid treatment dose calculated as hydrocortisone equivalents. BMI at 18 years was higher in patients treated with prednisolone but did not correlate with genotype. Conclusions: Corrected FH was more affected in patients with severe CYP21A2 genotypes. The addition of a low dose of prednisolone to the hydrocortisone treatment, despite an equivalent total dose of glucocorticoids, was associated with shorter FH and higher BMI in growing subjects with CAH.
Impact of Bevacizumab Being Skipped due to Adverse Events of Special Interest for Bevacizumab in Patients with Unresectable Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab: An Exploratory Analysis of the Phase III IMbrave150 Study
Authors: Kudo Masatoshi , Tsuchiya Kaoru , Shao Yu-Yun , Finn Richard S. , Galle Peter R. , Ducreux Michel , Cheng Ann-Lii , Yamashita Tatsuya , Koga Hironori , Take Ryosuke , Yamada Kyoko , Asakawa Takashi , Nakagawa Yuki , Ikeda Masafumi
Published: November 2023

Introduction: The phase III IMbrave150 study established atezolizumab + bevacizumab as the global standard of care in patients with unresectable hepatocellular carcinoma (HCC). This exploratory analysis examined the impact of bevacizumab interruption due to bevacizumab adverse events of special interest (AESIs). Methods: Patients in IMbrave150 who were randomized to atezolizumab + bevacizumab and received treatment for ≥6 months (to reduce immortal time bias) were included in group A-1 if bevacizumab had ever been skipped due to bevacizumab AESIs or to group A-2 otherwise. Efficacy analyses included overall survival (OS) and progression-free survival (PFS) by whether bevacizumab was skipped (group A-1 vs. A-2). PFS was evaluated per independent review facility (IRF)-assessed Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 and HCC-modified RECIST (IRF-HCC mRECIST). Safety was also evaluated. Results: Of the 210 patients who received ≥6 months of atezolizumab + bevacizumab, 69 were assigned to group A-1 and 141 to A-2. At data cutoff (August 20, 2020), hazard ratio (HR) for OS was 1.04 (95% CI: 0.64, 1.69) for group A-1 versus A-2. HR for PFS was 1.07 (95% CI: 0.74, 1.55) per IRF-assessed RECIST 1.1 and 1.10 (95% CI: 0.76, 1.59; 15.5 vs. 9.7 months) per IRF-HCC mRECIST for group A-1 versus A-2. Safety profiles for atezolizumab and bevacizumab were largely similar between groups. More group A-1 patients had grade 3/4 adverse events. A separate analysis investigating the impact of immortal time bias in patients who received ≥3 months of atezolizumab + bevacizumab supported the appropriateness of the ≥6-month landmark analysis. Discussion/Conclusion: Efficacy was similar between patients who skipped bevacizumab due to bevacizumab AESIs and those who did not. Although this comparison was nonrandomized and exploratory, results suggest that skipping bevacizumab due to bevacizumab AESIs did not considerably impact the efficacy and safety of atezolizumab + bevacizumab.
Plasma Protein Profiling of Incident Cardiovascular Diseases: A Multisample Evaluation
Authors: Lind Lars , Titova Olga , Zeng Rui , Zanetti Daniela , Ingelsson Martin , Gustafsson Stefan , Sundström Johan , Ärnlöv Johan , Elmståhl Sölve , Assimes Themistocles , Michaëlsson Karl
Published: November 2023

Background:

Proteomic profiling could potentially disclose new pathophysiological pathways for cardiovascular diseases (CVD) and improve prediction at the individual level. We therefore aimed to study the plasma protein profile associated with the incidence of different CVDs.

Methods:

Plasma levels of 245 proteins suspected to be linked to CVD or metabolism were measured in 4 Swedish prospective population-based cohorts (SIMPLER [Swedish Infrastructure for Medical Population-Based Life-Course and Environmental Research], ULSAM (Uppsala Longitudinal Study of Adult Men), EpiHealth, and POEM [Prospective Investigation of Obesity, Energy Production, and Metabolism]) comprising 11 869 individuals, free of CVD diagnoses at baseline. Our primary CVD outcome was defined by a combined end point that included either incident myocardial infarction, stroke, or heart failure.

Results:

Using a discovery/validation approach, 42 proteins were associated with our primary composite end point occurring in 1163 subjects. In separate meta-analyses for each of the 3 CVD outcomes, 49 proteins were related to myocardial infarction, 34 to ischemic stroke, and 109 to heart failure. Thirteen proteins were related to all 3 outcomes. Of those, urokinase plasminogen activator surface receptor, adrenomedullin, and KIM-1 (kidney injury molecule 1) were also related to several markers of subclinical CVD in Prospective Investigation of Obesity, Energy production and Metabolism, reflecting myocardial or arterial pathologies. In prediction analysis, a lasso selection of 11 proteins in ULSAM improved the discrimination of CVD by 3.3% (
P
<0.0001) in SIMPLER when added to traditional risk factors.

Conclusions:

Protein profiling in multiple samples disclosed several new proteins to be associated with subsequent myocardial infarction, stroke, and heart failure, suggesting common pathophysiological pathways for these diseases. KIM-1, urokinase plasminogen activator surface receptor, and adrenomedullin were novel early markers of CVD. A selection of 11 proteins improved the discrimination of CVD.
Childhood Non-HDL Cholesterol and LDL Cholesterol and Adult Atherosclerotic Cardiovascular Events
Authors: Wu Feitong , Juonala Markus , Jacobs David R. , Daniels Stephen R. , Kähönen Mika , Woo Jessica G. , Sinaiko Alan R. , Viikari Jorma S.A. , Bazzano Lydia A. , Burns Trudy L. , Steinberger Julia , Urbina Elaine M. , Venn Alison J. , Raitakari Olli T. , Dwyer Terence , Magnussen Costan G.
Published: November 2023

BACKGROUND:

Although low-density lipoprotein cholesterol (LDL-C) remains the primary cholesterol target in clinical practice in children and adults, non–high-density lipoprotein cholesterol (non–HDL-C) has been suggested as a more accurate measure of atherosclerotic cardiovascular disease (ASCVD) risk. We examined the associations of childhood non–HDL-C and LDL-C levels with adult ASCVD events and determined whether non–HDL-C has better utility than LDL-C in predicting adult ASCVD events.

METHODS:

This prospective cohort study included 21 126 participants from the i3C Consortium (International Childhood Cardiovascular Cohorts). Proportional hazards regressions were used to estimate the risk for incident fatal and fatal/nonfatal ASCVD events associated with childhood non–HDL-C and LDL-C levels (age- and sex-specific
z
scores; concordant/discordant categories defined by guideline-recommended cutoffs), adjusted for sex, Black race, cohort, age at and calendar year of child measurement, body mass index, and systolic blood pressure. Predictive utility was determined by the C index.

RESULTS:

After an average follow-up of 35 years, 153 fatal ASCVD events occurred in 21 126 participants (mean age at childhood visits, 11.9 years), and 352 fatal/nonfatal ASCVD events occurred in a subset of 11 296 participants who could be evaluated for this outcome. Childhood non–HDL-C and LDL-C levels were each associated with higher risk of fatal and fatal/nonfatal ASCVD events (hazard ratio ranged from 1.27 [95% CI, 1.14–1.41] to 1.35 [95% CI, 1.13–1.60] per unit increase in the risk factor
z
score). Non–HDL-C had better discriminative utility than LDL-C (difference in C index, 0.0054 [95% CI, 0.0006–0.0102] and 0.0038 [95% CI, 0.0008–0.0068] for fatal and fatal/nonfatal events, respectively). The discordant group with elevated non–HDL-C and normal LDL-C had a higher risk of ASCVD events compared with the concordant group with normal non–HDL-C and LDL-C (fatal events: hazard ratio, 1.90 [95% CI, 0.98–3.70]; fatal/nonfatal events: hazard ratio, 1.94 [95% CI, 1.23–3.06]).

CONCLUSIONS:

Childhood non–HDL-C and LDL-C levels are associated with ASCVD events in midlife. Non–HDL-C is better than LDL-C in predicting adult ASCVD events, particularly among individuals who had normal LDL-C but elevated non–HDL-C. These findings suggest that both non–HDL-C and LDL-C are useful in identifying children at higher risk of ASCVD events, but non–HDL-C may provide added prognostic information when it is discordantly higher than the corresponding LDL-C and has the practical advantage of being determined without a fasting sample.
Efficacy and Safety of Direct Oral Anticoagulants for Stroke Prevention in Older Patients With Atrial Fibrillation: A Network Meta‐Analysis of Randomized Controlled Trials
Authors: Lin Donna Shu‐Han , Lo Hao‐Yun , Huang Kuan‐Chih , Lin Ting‐Tse , Lee Jen‐Kuang
Published: November 2023

Background

Although older patients with atrial fibrillation are at heightened risk of thromboembolic and bleeding events, their optimal treatment choice remains uncertain.

Methods and Results

This meta‐analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. We searched the PubMed, EMBASE, and Cochrane databases for randomized controlled trials that compared thromboembolic or bleeding outcomes between a direct oral anticoagulant (DOAC) and a vitamin K antagonist (VKA) and reported outcomes for patients aged ≥75 years with atrial fibrillation. The efficacy outcome was the composite of stroke and systemic embolism. Safety outcomes included major bleeding, any clinically relevant bleeding, and intracranial hemorrhage. Each DOAC and VKA was compared pairwise in a network meta‐analysis. High‐ and low‐dose regimens and factor IIa and Xa inhibitors were also compared. Seven randomized controlled trials were included in the analysis. Stroke and systemic embolism risks did not differ significantly among DOACs. There were no significant differences in major bleeding between each DOAC and VKA. Intracranial hemorrhage risk was significantly lower with dabigatran, apixaban, and edoxaban than with VKA and rivaroxaban, which had similar risks. High‐dose regimens led to lower risks of stroke or systemic embolism compared with VKA and low‐dose regimens, with both doses having similar bleeding risks.

Conclusions

In patients aged ≥75 years with atrial fibrillation, DOACs were associated with fewer thromboembolic events compared with VKA, whereas dabigatran, apixaban, and edoxaban were associated with lower risks of intracranial hemorrhage compared with VKA and rivaroxaban.

Registration

URL:
www.crd.york.ac.uk/prospero/
. Unique identifier: CRD42022329557.