bluuebunny/crossref_metadata_2025 huggingface dataset:
Individual differences in dissimilation: Do some people make more distinctions among targets' personalities than others?
Authors: Carlson Erika N. , Elsaadawy Norhan , Pringle Victoria , Rau Richard
Published: November 2023

Objective

People differ in how positively they tend to see others' traits, but people might also differ in how strongly they apply their perceptual styles. In two studies (Ns = 355, 303), the current research explores individual differences in how variable people's first impressions are across targets (i.e., within‐person variability), how and why these differences emerge, and who varies more in their judgments of others.

Method

Participants described themselves on personality measures and rated 30 (Study 1) or 90 (Study 2) targets on Big Five traits.

Results

Using the extended Social Relations Model (eSRM), results suggest that within‐person variability in impressions is consistent across trait ratings. People lower in extraversion, narcissism and self‐esteem tended to make distinctions across targets' Big Five traits that were more consistent with other perceivers (sensitivity). Furthermore, some people more than others tended to consistently make unique distinctions among targets (differentiation), and preliminary evidence suggests these people might be higher in social anxiety and lower in self‐esteem and emotional stability.

Conclusion

Overall then, a more complete account of person perception should consider individual differences in how variable people's impressions are of others.
One year later: Longer‐term maintenance effects of a digital intervention to change personality traits
Authors: Stieger Mirjam , Flückiger Christoph , Allemand Mathias
Published: November 2023

Objective

Recent research suggests that personality traits can be changed by psychological interventions. However, it is unclear whether these intended personality changes can be maintained or merely reflect ephemeral shifts.

Method

The present study reports 1‐year follow‐up effects of a 3‐month digital intervention for personality trait change. Personality traits were measured before the intervention (pretest: N = 1523), directly after the intervention (posttest: n = 554), and 3 months (follow‐up 1: n = 437) and 1 year (follow‐up 2: n = 157) after the end of the intervention.

Results

Attrition analyses suggest that participants who completed the 1‐year follow‐up were significantly more open to experience (d = 0.19), less neurotic (d = 0.20), more agreeable (d = 0.35) and more conscientious (d = 0.27) than participants who did not complete the 1‐year follow‐up. Also, until the 1‐year follow‐up, personality trait changes achieved remained stable (for those who wanted to increase in extraversion and conscientiousness) or even changed further in the desired direction (for those who wanted to decrease in neuroticism).

Conclusion

These results suggest that changes in personality traits due to a targeted intervention are not just ephemeral shifts and can even continue.
The genetic diversity in the ancient human population of Upper Xiajiadian culture
Authors: Zhu Kong‐Yang , Zhang Zhi‐Ping , Tao Le , Jiang Run‐Qi , Huang Wen‐Bo , Sun Yong‐Gang , He Hai‐Feng , Fu Hui‐Lin , Ma Hao , Yang Xiao‐Min , Guo Jian‐Xin , Jia Xin , Wang Chuan‐Chao
Published: November 2023

The West Liao River (WLR) and Yellow River (YR) basins are two major centers of millet farming in northern China. The result from flotation analyses and the spatial distribution of archeological sites indicate that two distinct survival strategies—agriculture and pastoralism were adopted in the southern and western regions of the WLR. Previous studies of ancient populations from the western area of the WLR suggested a correlation between a pastoral economy in the Bronze Age Upper Xiajiadian culture with a decreased genetic affinity with YR farmers. However, the population history of the southern WLR is unknown mainly due to the lack of ancient genetic data. Here we report the genomic data of an ancient individual from the Majiazishan site from the Late Bronze Age southern WLR region associated with Upper Xiajiadian culture. Unlike individuals from western WLR, this individual derived ancestry entirely from Late Neolithic YR farmers. We found a genetic substructure of the ancient human population of Upper Xiajiadian culture, which is consistent with the differences in the subsistence strategies of western and southern WLR. Climate deterioration led to different populations occupying the west and the south, respectively, in the WLR: the nomadic population from the Amur River (AR) in the west and the agricultural population from the YR in the south.
An analysis of time conceptualisations and good care in an acute hospital setting
Authors: Dewar Jan , Cook Catherine , Smythe Elizabeth , Spence Deborah
Published: November 2023

This study articulates the relationship between conceptualisations of time and the accounts of good care in an acute setting. Neoliberal healthcare services, with their focus on efficiencies, predominantly calculate quality care based on time‐on‐the‐clock workforce management planning systems. However, the ways staff conceptualise and then relate to diverse meanings of time have implications for good care and for staff morale. This phenomenological study was undertaken in acute medical–surgical wards, investigating the contextual, temporal nature of care embedded in human relations. The study interviews involved 17 participants: 11 staff, 3 previous patients and 3 family members. Data were analysed iteratively to surface the phenomenality of temporality and good care. The following constituents of the data set are explored that together illustrate the relationship between the conceptualisations of time and the accounts of good care in an acute setting: patient time as a relational journey; patient time, sovereign time and time ethics and time, teamwork and flow. The findings are clinically significant because they offer a contrasting narrative about the relationship between time and care quality. The experiences of giving and receiving good care are indivisible from how temporality is experienced and the social relations within which care is embedded. Healthcare staff experience temporality differently from patients and families, a point that healthcare participants in this study appeared to comprehend and accommodate. For all parties involved in providing care or being the recipient of care, however, the capacity to be present was valued as a humanising ethic of care. Our study reinforces the importance of not creating presumptive binaries about which temporal structures are more or less humanising—there is a place for a fast‐paced tempo, which can be experienced as being in the flow of human relations with one's team and on behalf of patients.
Low‐cost, 3D printed irradiation system for in vitro photodynamic therapy experiments
Authors: Acquah Chris , Pabis Zachary , Seth Sourav Kanti , Levi Liraz , Crespo‐Hernández Carlos E.
Published: November 2023

The development of a suitable irradiation setup is essential for in vitro experiments in photodynamic therapy (PDT). While various irradiation systems have been developed for PDT, only a few offer practical and high‐quality setups for precise and reproducible results in cell culture experiments. This report introduces a cost‐effective illumination setup designed for in vitro photodynamic treatments. The setup consists of a commercially available light‐emitting diode (LED) lamp, a cooling unit, and a specially designed 3D‐printed enclosure to accommodate a multiwell plate insert. The LED lamp is versatile, supporting various irradiation wavelengths and adjustable illumination fields, ensuring consistent and reliable performance. The study evaluates the setup through various parameters, including photon flux density, illumination uniformity, photon distribution across the multiwell plate, and temperature changes during irradiation. In addition, the effectiveness of the LED‐based illumination system is tested by treating mouse mammary breast carcinoma cells (4T1) with Rose Bengal and LED irradiation at around 525 nm. The resulting IC50 of 5.2 ± 0.9 μM and a minimum media temperature change of ca. 1.2°C indicate a highly promising LED‐based setup that offers a cost‐effective and technically feasible solution for achieving consistent, reproducible, and uniform irradiation, enhancing research capabilities and potential applications.
Polymerase iota plays a key role during translesion synthesis of UV‐induced lesions in the absence of polymerase eta
Authors: Martins Davi Jardim , Singh Jenny Kaur , Jahjah Tiya , Vessoni Alexandre Teixeira , Leandro Giovana da Silva , Silva Matheus Molina , Biard Denis Serge François , Quinet Annabel , Menck Carlos Frederico Martins
Published: November 2023

Xeroderma pigmentosum (XP) variant cells are deficient in the translesion synthesis (TLS) DNA polymerase Polη (eta). This protein contributes to DNA damage tolerance, bypassing unrepaired UV photoproducts and allowing S‐phase progression with minimal delay. In the absence of Polη, backup polymerases perform TLS of UV lesions. However, which polymerase plays this role in human cells remains an open question. Here, we investigated the potential role of Polι (iota) in bypassing ultraviolet (UV) induced photoproducts in the absence of Polη, using NER‐deficient (XP‐C) cells knocked down for Polι and/or Polη genes. Our results indicate that cells lacking either Polι or Polη have increased sensitivity to UVC radiation. The lack of both TLS polymerases led to increased cell death and defects in proliferation and migration. Loss of both polymerases induces a significant replication fork arrest and G1/S‐phase blockage, compared to the lack of Polη alone. In conclusion, we propose that Polι acts as a bona fide backup for Polη in the TLS of UV‐photoproducts.
Comparative analysis of BZR1/BES1 family transcription factors in Arabidopsis
Authors: Kim So‐Hee , Lee Se‐Hwa , Park Tae‐Ki , Tian Yanchen , Yu Kyoungjae , Lee Byeong‐ha , Bai Ming‐Yi , Cho Sung‐Jin , Kim Tae‐Wuk
Published: November 2023

Brassinazole Resistant 1 (BZR1) and bri1 EMS Suppressor 1 (BES1) are key transcription factors that mediate brassinosteroid (BR)‐responsive gene expression in Arabidopsis. The BZR1/BES1 family is composed of BZR1, BES1, and four BES1/BZR1 homologs (BEH1–BEH4). However, little is known about whether BEHs are regulated by BR signaling in the same way as BZR1 and BES1. We comparatively analyzed the functional characteristics of six BZR1/BES1 family members and their regulatory mechanisms in BR signaling using genetic and biochemical analyses. We also compared their subcellular localizations regulated by the phosphorylation status, interaction with GSK3‐like kinases, and heterodimeric combination. We found that all BZR1/BES1 family members restored the phenotypic defects of bri1‐5 by their overexpression. Unexpectedly, BEH2‐overexpressing plants showed the most distinct phenotype with enhanced BR responses. RNA‐Seq analysis indicated that overexpression of both BZR1 and BEH2 regulates BR‐responsive gene expression, but BEH2 has a much greater proportion of BR‐independent gene expression than BZR1. Unlike BZR1 and BES1, the BR‐regulated subcellular translocation of the four BEHs was not tightly correlated with their phosphorylation status. Notably, BEH1 and BEH2 are predominantly localized in the nucleus, which induces the nuclear accumulation of other BZR1/BES1 family proteins through heterodimerization. Altogether, our comparative analyses suggest that BEH1 and BEH2 play an important role in the functional interaction between BZR1/BES1 family transcription factors.
Peroxisome population control by phosphoinositide signaling at the endoplasmic reticulum‐plasma membrane interface
Authors: Knoblach Barbara , Rachubinski Richard A.
Published: November 2023

Phosphoinositides are lipid signaling molecules acting at the interface of membranes and the cytosol to regulate membrane trafficking, lipid transport and responses to extracellular stimuli. Peroxisomes are multicopy organelles that are highly responsive to changes in metabolic and environmental conditions. In yeast, peroxisomes are tethered to the cell cortex at defined focal structures containing the peroxisome inheritance protein, Inp1p. We investigated the potential impact of changes in cortical phosphoinositide levels on the peroxisome compartment of the yeast cell. Here we show that the phosphoinositide, phosphatidylinositol‐4‐phosphate (PI4P), found at the junction of the cortical endoplasmic reticulum and plasma membrane (cER‐PM) acts to regulate the cell's peroxisome population. In cells lacking a cER‐PM tether or the enzymatic activity of the lipid phosphatase Sac1p, cortical PI4P is elevated, peroxisome numbers and motility are increased, and peroxisomes are no longer firmly tethered to Inp1p‐containing foci. Reattachment of the cER to the PM through an artificial ER‐PM “staple” in cells lacking the cER‐PM tether does not restore peroxisome populations to the wild‐type condition, demonstrating that integrity of PI4P signaling at the cell cortex is required for peroxisome homeostasis.
Computation of Stagnation Point Convection Flow of Carbon Nanotube Nanofluids From a Stretching Sheet With Melting: Dual Solutions
Authors: Rubel M. Rifat Hasan , Ferdows M. , Tazin Tahia , Bég T. A. , Anwar Bég O. , Kadir Ali
Published: November 2023

A theoretical study in stagnation point flow is presented where melting heat transfer effects of carbon nanotube (CNT) from a stretching surface is appeared. Both carbon nanotubes like single-wall CNT (SWCNT) and multiwall CNT (MWCNT) are homogeneously dispersed in the base fluid. As the ordinary (or base) fluids, water and kerosene oil are employed. A set of nonlinear ordinary differential equations with appropriate boundary conditions is formed by transforming the governing equations via similarity transformations. The transformed nonlinear ordinary differential equations are then solved numerically using the bvp4c solver in matlab, an efficient numerical finite difference method. The impact of nanoparticle volume fraction, velocity, melting, stretching parameter, and CNT type on transport characteristics are explored and visualized graphically and in tabular forms. Verification of the matlab computations with available data in certain limiting cases is included showing excellent agreement. Existence of dual (upper and lower branch) solution is shown for a certain range of stretching sheet parameter. The obtained dual solutions are examined for velocity and temperature in detail. A stability analysis demonstrates that the first solution is a stable solution, and the second solution is an unstable solution. Local skin friction and local Nusselt number are also computed in order to determine critical values that can permit dual solutions. It is observed that when a dimensionless melting parameter is greater than 1, SWCNT nanofluids attain greater velocities than MWCNT nanofluids for water as well as kerosene oil base fluids. Moreover, the flow is accelerated for SWCNT compared with MWCNT for both water and kerosene oil. With increasing stretching parameter, the heat transfer rate (Nusselt number) increases, whereas skin friction coefficients decrease. Higher skin friction and Nusselt number are obtained for SWCNTs compared to MWCNTs due to their greater density and thermal conductivity. The study is relevant to phase change manufacturing fluid dynamics of nanomaterials.
High-Intensity Forward-Backward Plyometrics After the Warm-Up Entail Better Sprint and Change-of-Direction Performance Than Low-Intensity Side-to-Side Plyometrics
Authors: Ben Ayed Karim , Hammami Raouf , Gene-Morales Javier , Ajailia Amira , Werfelli Hanen , Rebai Haithem , Jiménez-Martínez Pablo , Flandez Jorge , Colado Juan C.
Published: November 2023

This study aimed to determine the acute effects of high-intensity forward-backward and low-intensity side-to-side plyometric jumps performed following the warm-up on sprint (5, 10, and 15 m) and change-of-direction (COD) (T-half test and repeated T-half tests) performance in youth volleyball players. After a familiarization week, 30 male volleyball players (age = 12.04 ± 1.03 years) performed three randomized conditions (no-plyometrics, high-intensity plyometrics, and low-intensity plyometrics) in three sessions. In a within-subject design, three sets of six repetitions of forward-backward 30-cm hurdle jumps (high-intensity) and side-to-side 20-cm hurdle jumps (low-intensity) were completed. Sprint and COD were tested after each of the conditions with a 2-min rest. A significant effect of the plyometric condition was observed on sprint (p < .001, range: .56–.70) and COD (p < .01, ), but not on repeated COD. More specifically, the high-intensity plyometric condition exhibited significantly better results compared with the low-intensity plyometric (Cohen’s d range: 0.73–1.21) and control conditions (Cohen’s d range: 0.91–2.21). Due to the importance of speed and COD in volleyball, these results suggest that young volleyball players may benefit from high-intensity forward-backward plyometric protocols following the warm-up to improve subsequent performance.
Narratives of childhood sexual abuse: healing through music in Ian McEwan’sOn Chesil Beach
Authors: Hejaz Neha , Singh Rajni
Published: November 2023

Narratives of survivors or by survivors offer useful and compelling insights into the experiences of abuse and its consequent effect on health. Reading such narratives can help a physician or clinician to understand the complexities of abuse. Furthermore, the critical study of narratives can open multiple therapeutic options for survivors of abuse to cater both their mental health and medical problems. In this article, we deal with the genre of childhood sexual abuse survivor’s narrative and its clinical application adding to the discourse of medical humanities and then critically examine one such narrative (On Chesil Beachby Ian McEwan) in particular and explore the therapeutics of music in abused victim’s clinical care.
Assessing the potential for healthier consumer food substitutions in Canada: population-level differences in dietary intakes of whole grains, refined grains, red meats, and legumes
Authors: Luongo Gabriella , Jago Emily , Mah Catherine L.
Published: November 2023

The potential for healthier consumer food substitutions is an important factor in the study of food environments, dietary choices, and population nutrition promotion. The burden of diet-related non-communicable diseases is unevenly distributed across Canada and variation in the food environment sub-nationally may be an important explanation. We used population-based 24 h dietary recall data from the 2015 Canadian Community Health Survey—Nutrition for Canadian adults ( n = 13 919) to examine dietary intakes of two food group pairings (whole grains/refined grains and legumes/red meats) where consumer substitutions have been recognized to be of importance in promoting healthy and sustainable population diet. We used an ANOVA followed by pairwise comparisons with Bonferroni correction to estimate differences in intakes between provinces for daily weight and proportion of total energy consumed. Based on the Global Burden of Disease Study, Canadians consumed below the average daily requirements of legumes and whole grains and well above the required range of red meat, suggesting room for broad improvements to population diet. Findings also demonstrate that there is potential for targeted shifts in dietary intakes among non-consumers of certain foods (e.g., legumes). This study may inform intervention development for the consumer nutrition environment including food accessibility and affordability to reduce non-communicable disease risk.
Detecting a periodic signal by a population of spiking neurons in the weakly nonlinear response regime
Authors: Schlungbaum Maria , Lindner Benjamin
Published: November 2023

Motivated by experimental observations, we investigate a variant of the cocktail party problem: the detection of a weak periodic stimulus in the presence of fluctuations and another periodic stimulus which is stronger than the periodic signal to be detected. Specifically, we study the response of a population of stochastic leaky integrate-and-fire (LIF) neurons to two periodic signals and focus in particular on the question, whether the presence of one of the stimuli can be detected from the population activity. As a detection criterion, we use a simple threshold-crossing of the population activity over a certain time window. We show by means of the receiver operating characteristics (ROC) that the detectability depends only weakly on the time window of observation but rather strongly on the stimulus amplitude. Counterintuitively, the detection of the weak periodic signal can be facilitated by the presence of a strong periodic input current depending on the frequencies of the two signals and on the dynamical regime in which the neurons operate. Beside numerical simulations of the model, we present an analytical approximation for the ROC curve that is based on the weakly nonlinear response theory for a stochastic LIF neuron.

Graphic abstract
A Novel Diabetes Prediction Model in Big Data Healthcare Systems Using DA-KNN Technique
Authors: Jayasri N. P. , Aruna R.
Published: November 2023

In the past decades, there is a wide increase in the number of people affected by diabetes, a chronic illness. Early prediction of diabetes is still a challenging problem as it requires clear and sound datasets for a precise prediction. In this era of ubiquitous information technology, big data helps to collect a large amount of information regarding healthcare systems. Due to explosion in the generation of digital data, selecting appropriate data for analysis still remains a complex task. Moreover, missing values and insignificantly labeled data restrict the prediction accuracy. In this context, with the aim of improving the quality of the dataset, missing values are effectively handled by three major phases such as (1) pre-processing, (2) feature extraction, and (3) classification. Pre-processing involves outlier rejection and filling missing values. Feature extraction is done by a principal component analysis (PCA) and finally, the precise prediction of diabetes is accomplished by implementing an effective distance adaptive-KNN (DA-KNN) classifier. The experiments were conducted using Pima Indian Diabetes (PID) dataset and the performance of the proposed model was compared with the state-of-the-art models. The analysis after implementation shows that the proposed model outperforms the conventional models such as NB, SVM, KNN, and RF in terms of accuracy and ROC.
Remediating the sky: the role of geoenvironmental engineers and applied geoscientists in geochemical carbon dioxide removal
Authors: Renforth P.
Published: November 2023

The largest environmental remediation project in human history has begun – that of removing hundreds of billions of tonnes of carbon dioxide (CO
2
) from the atmosphere over the coming century. This removal, together with deep and rapid emissions reduction, will be essential in preventing dangerous climate change. This briefing introduces the field of geochemical CO
2
removal (gCDR), which proposes to accelerate the natural reaction of atmospheric CO
2
with rocks or anthropogenic materials. It also explores the critical role that geoenvironmental engineers and geoscientists will have in researching and deploying these technologies. While currently at an early stage of development, it is possible that gCDR will operate at a global scale (billion tonnes of CO
2
per year) by mid/late-century, resulting in an industry that generates hundreds of billions to a trillion dollars in annual revenue, equivalent in scale to the present-day oil industry. The core technical competencies of this industry will be derived from geoscience disciplines requiring the contribution of thousands and possibly tens of thousands of workers globally. To realize these opportunities, our community needs to lead in the development of gCDR, help to pioneer its deployment, create standards for monitoring and verification, and incorporate gCDR into existing education programmes and professional development.

Thematic collection:
This article is part of the Climate change and resilience in Engineering Geology and Hydrogeology collection available at:
https://www.lyellcollection.org/topic/collections/Climate-change-and-resilience-in-engineering-geology-and-hydrogeology
From Virtual Reality to the Emerging Discipline of Perception Engineering
Authors: LaValle Steven M. , Center Evan G. , Ojala Timo , Pouke Matti , Prencipe Nicoletta , Sakcak Basak , Suomalainen Markku , Timperi Kalle G. , Weinstein Vadim
Published: November 2023

This article makes the case that a powerful new discipline, which we term perception engineering, is steadily emerging. It follows from a progression of ideas that involve creating illusions, from historical paintings and film to modern video games and virtual reality. Rather than creating physical artifacts such as bridges, airplanes, or computers, perception engineers create illusory perceptual experiences. The scope is defined over any agent that interacts with the physical world, including both biological organisms (humans and animals) and engineered systems (robots and autonomous systems). The key idea is that an agent, called a producer, alters the environment with the intent to alter the perceptual experience of another agent, called a receiver. Most importantly, the article introduces a precise mathematical formulation of this process, based on the von Neumann–Morgenstern notion of information, to help scope and define the discipline. This formulation is then applied to the cases of engineered and biological agents, with discussion of its implications for existing fields such as virtual reality, robotics, and even social media. Finally, open challenges and opportunities for involvement are identified.
Adaptive Designs in Implementation Science and Practice: Their Promise and the Need for Greater Understanding and Improved Communication
Authors: Kilbourne Amy , Chinman Matthew , Rogal Shari , Almirall Daniel
Published: November 2023

The promise of adaptation and adaptive designs in implementation science has been hindered by the lack of clarity and precision in defining what it means to adapt, especially regarding the distinction between adaptive study designs and adaptive implementation strategies. To ensure a common language for science and practice, authors reviewed the implementation science literature and found that the term adaptive was used to describe interventions, implementation strategies, and trial designs. To provide clarity and offer recommendations for reporting and strengthening study design, we propose a taxonomy that describes fixed versus adaptive implementation strategies and implementation trial designs. To improve impact, (a) futureimplementation studies should prespecify implementation strategy core functions that in turn can be taught to and replicated by health system/community partners, (b) funders should support exploratory studies that refine and specify implementation strategies, and (c) investigators should systematically address design requirements and ethical considerations (e.g., randomization, blinding/masking) with health system/community partners.
Lymphatic Drainage-Promoting Effects by Engraftment of Artificial Lymphatic Vascular Tissue Based on Human Adipose Tissue-Derived Mesenchymal Stromal Cells in Mice
Authors: Asano Yoshiya , Shimoda Hiroshi , Okano Daisuke , Matsusaki Michiya , Akashi Mitsuru
Published: November 2023

Regenerative medicine using lymphatic vascular engineering is a promising approach for treating lymphedema. However, its development lags behind that of artificial blood vascular tissue for ischemic diseases. In this study, we constructed artificial 3D lymphatic vascular tissue, termed ASCLT, by co-cultivation of ECM-nanofilm-coated human adipose tissue-derived mesenchymal stromal cells (hASCs) and human dermal lymphatic endothelial cells (HDLECs). The effect of hASCs in lymphatic vessel network formation was evaluated by comparison with the tissue based on fibroblasts, termed FbLT. Our results showed that the density of lymphatic vascular network in ASCLT was higher than that in FbLT, demonstrating a promoting effect of hASCs on lymphatic vascular formation. This result was also supported by higher levels of lymphangiogenesis-promoting factors, such as bFGF, HGF, and VEGF-A in ASCLT than in FbLT. To evaluate the therapeutic effects, FbLTs and ASCLTs were subcutaneously transplanted to mouse hindlimb lymphatic drainage interruption models by removal of popliteal and subiliac lymph nodes. Despite the restricted engraftment of lymphatic vessels, ASCLT promoted regeneration of irregular and diverse lymphatic drainage in the skin, as visualized by indocyanine green imaging. Moreover, transplantation of ASCLT to the popliteal lymph node resection area also resulted in lymphatic drainage regeneration. Histological analysis of the generated drainage visualized by FITC-dextran injection revealed that the drainage was localized in the subcutaneous area shallower than the dermal muscle. These findings demonstrate that ASCLT promotes lymphatic drainage in vivo and that hASCs can serve as an autologous source for treatment of secondary lymphedema by tissue engineering.
Figure S4 from PRMT5 Inhibitors Regulate DNA Damage Repair Pathways in Cancer Cells and Improve Response to PARP Inhibition and Chemotherapies
Authors: Carter Jack , Hulse Michael , Sivakumar Monisha , Burtell Jessica , Thodima Venkat , Wang Min , Agarwal Anjana , Vykuntam Komali , Spruance Jacob , Bhagwat Neha , Rager Joseph , Ruggeri Bruce , Scherle Peggy , Ito Koichi
Published: November 2023

PRMT5 inhibitors synergize with PARP inhibition and chemotherapy in breast and ovarian cancer cells in vitro and in vivo.
FIGURE 3 from PRMT5 Inhibitors Regulate DNA Damage Repair Pathways in Cancer Cells and Improve Response to PARP Inhibition and Chemotherapies
Authors: Carter Jack , Hulse Michael , Sivakumar Monisha , Burtell Jessica , Thodima Venkat , Wang Min , Agarwal Anjana , Vykuntam Komali , Spruance Jacob , Bhagwat Neha , Rager Joseph , Ruggeri Bruce , Scherle Peggy , Ito Koichi
Published: November 2023

C220 dysregulates chromatin- and splicing-mediated regulation of DDR pathways. A, ChIP-qPCR assays using primers against the proximal promoter of indicated DDR genes following capture of chromatin-bound PRMT5 in nontreated MCF7 cells. Data are shown as fold enrichment over IgG (n = 3). B, ChIP-qPCR assays using primers against the proximal promoter of DDR genes following capture of chromatin-bound H4R3me2 from MCF7 cells treated with 250 nmol/L C220 for 4 days. Data are shown as % input (n = 3) C, AS analysis of RNA-seq data from MCF7, HCC1569, and A2780 cells following treatment with 100 nmol/L C220 for 4 days. Total events represent the total number of AS with statistical significance (P < 0.05). RI = retained intron, SE = skipped exon, A3 = alternative 3′ splice-site, A5 = alternative 5′ splice site, MX = mutually exclusive exons, AF = alternative first exon, AL = alternative last exon. D, Violin plot of global intron retention and exon skipping events induced by C220 in A2780 cells annotated with select DDR genes with significant (P < 0.05) events. E and F, qPCR of total ATM or ATM retained intron in A2780 cells treated with 100 nmol/L C220 for 4 days.
Abstract 12507: Impella versus Intra-Aortic Balloon Pump in Acute Myocardial Infarction Complicated by Cardiogenic Shock: A Meta-Analysis
Authors: Jaiswal Vikash , Jaiswal Akash , Hanif Muhammad , Gupta Shiva , Evbayekha Endurance O , Agrawal Vibhor , Sai Santhosha Mrudula Alla
Published: November 2023

Background:
Acute myocardial infarction complicated by cardiogenic shock (AMICS) requires mechanical circulatory support, with IABP and Impella being commonly used options. The IABP's survival benefit is uncertain, and guideline recommendations differ. Studies comparing Impella and IABP have yielded mixed results and reported varying complication rates.

Aim:
This meta-analysis aims to comprehensively evaluate the effectiveness and safety of Impella versus IABP in AMICS.

Methods:
A systematic search was conducted in PubMed, EMBASE, Cochrane, and clincialtrials.gov from inception to April 2023 to identify studies comparing Impella and IABP in AMICS. A meta-analysis was performed to assess the short-term mortality as the primary efficacy endpoint, along with major bleeding, limb complications, acute kidney injury (AKI), stroke, and hemolysis as safety endpoints of interest.

Results:
A total of 10 studies (2 RCTs, 8 observational) with 6,634 patients were included in the final analysis. No significant difference was found in 30-day mortality (OR=1.03; 95% CI=0.74-1.42; p=0.87), in-hospital mortality (OR=1.14; 95% CI=0.45-2.85; p=0.79) and all-cause mortality (OR=1.00; 95% CI=0.55-1.81; p=0.99) between Impella and IABP. However, the analysis revealed a higher risk of major bleeding with Impella compared to IABP (OR=2.12; 95% CI=1.32-3.42; p=0.002) and an increased likelihood of limb complications (OR=3.86; 95% CI=1.57-9.48; p=0.003). There was no significant difference in the incidence of AKI (OR=0.91; 95% CI=0.56-1.48; p=0.70) and stroke (OR=0.72; 95% CI=0.42-1.24; p=0.24) between the two groups. Notably, the risk of hemolysis was significantly higher in the Impella group (OR=11.35; 95% CI=1.99-64.69; p=0.006).

Conclusion:
Impella and IABP showed similar short-term mortality, AKI, and stroke rates in AMICS patients. However, Impella was associated with a higher risk of major bleeding, limb complications, and hemolysis.
Abstract 12508: Association Between Statin Use and Chemotherapy Induced Cardiac Dysfunction Among Cancer Patients: A Meta-Analysis
Authors: Jaiswal Vikash , Ang Song Peng , Deb Novonil , Evbayekha Endurance O , Agrawal Vibhor , Jaiswal Akash
Published: November 2023

Background:
Chemotherapy-induced cardiac dysfunction (CICD) is a significant and concerning complication observed among cancer patients. Despite the demonstrated cardioprotective benefits of statins in various cardiovascular diseases, their effectiveness in mitigating CICD remains uncertain.

Objective:
This meta-analysis aims to comprehensively evaluate the potential cardioprotective role of statins in patients with CICD.

Methods:
A comprehensive systematic literature search was conducted using PubMed, Embase, and Scopus databases to identify relevant articles published from inception until 10th May 2023. The outcomes were assessed using pooled Odds Ratio (OR) for categorical data and Mean Difference (MD) for continuous data, with corresponding 95% confidence intervals (95% CI).

Results:
The meta-analysis comprised 8 studies involving a total of 5,232 patients, with 1,754 in the statin group and 3,478 in the control group. The study findings demonstrated a significant difference in left ventricular ejection fraction (LVEF) at the study's conclusion, with the control group exhibiting a substantially lower LVEF compared to the statin group (MD: 2.08, 95% CI: 0.86, 3.30; p < 0.001). Furthermore, the change in LVEF from baseline was also significant, with the control group demonstrating a greater decrease compared to the statin group (MD: 4.01, 95% CI: 0.84, 7.18; p= 0.01). Additionally, the statin group exhibited a notable reduction in the likelihood of heart failure compared to the control group (OR: 0.41, 95% CI: 0.27-0.62; p< 0.001). However, no statistically significant distinction in left ventricular end-diastolic volume was observed between the groups (MD: 1.55, 95% CI: -5.22, 8.33, p = 0.65).

Conclusion:
The results of this meta-analysis indicate that statin therapy may offer cardioprotective benefits for patients with CICD, improving left ventricular function and reducing the risk of heart failure.
Abstract 12511: Efficacy of Bivalirudin versus Heparin Use on Clinical Outcomes Post Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Controlled Trials
Authors: Jaiswal Vikash , Jaiswal Akash , Saleeb Marina , Jha Mayank , Arora Ananya , Gupta Shiva , Evbayekha Endurance O , Mohamed Taha Amira , Ang Song Peng , Grubb Kendra J
Published: November 2023

Background:
For patients undergoing percutaneous coronary intervention (PCI), Bivalirudin has been shown to reduce major bleeding, however, unfractionated heparin is currently considered the standard of care.
Objective:
We sought to perform an updated meta-analysis comparing the efficacy of bivalirudin versus heparin undergoing PCI with the inclusion of the most recently published trials.

Methods:
A systematic literature search was performed in PubMed, Embase, and Clinicaltrial.gov from inception to 10th May 2023 for studies comparing bivalirudin vs. heparin among PCI-undergoing patients. Pooled odds ratios (OR) were calculated using a random effect model, and a p-value of <0.05 was considered statistically significant.

Results:
A total of 14 randomized controlled trials with 35,533 patients (17765 in Bivalirudin treated group and 17768 patients in Heparin treated group). The pooled analysis shows that bivalirudin was associated with significant 21% reduction in net adverse clinical events (NACE) (OR, 0.79(95%CI: 0.71-0.88), P<0.01), cardiovascular mortality (CVM) by 24% (OR, 0.76(95%CI: 0.65-0.90), P<0.01), major bleeding by 36% (OR, 0.64(95%CI: 0.49-0.83), P<0.01), transfusion by 42% (OR, 0.58(95%CI: 0.44-0.77), P<0.01) compared to heparin. There was a trend of reduced all-cause mortality among bivalirudin groups (OR, 0.86(95%CI: 0.72-1.02) compared to the heparin group of patients, however, it didn't reach statistical significance. Incidence of stroke, major adverse cardiovascular events, myocardial infarction, and stent thrombosis was comparable between both groups of patients.

Conclusion:
Bivalirudin has shown to be superior to heparin among patients undergoing PCI with a reduction in bleeding, CVM, NACE, and a trend of reduced all-cause mortality.
Abstract 12512: Predictive Factors of Right Heart Catheterization to Diagnose Pulmonary Arterial Hypertension Using Least Absolute Shrinkage Selection Operator (LASSO) Regression
Authors: White R J , Klok Rogier , Harley Julia , Castellano Giorgio , Small Mark , Vizza Dario , Lautsch Dominik
Published: November 2023

Introduction:
Right Heart Catheterization (RHC) is the gold standard diagnostic test to confirm Pulmonary Arterial Hypertension (PAH). However, not all patients receive a RHC to confirm diagnosis.

Hypothesis:
This study analyzed a real-world PAH dataset to understand factors predictive of RHC being used to confirm diagnosis.

Methods:
Data were analyzed from the 2022 Adelphi PAH Disease Specific Programme™ containing physician-provided patient information for PAH patients in the US, France, Germany, Italy, Spain, UK and Japan. As our outcome (RHC at diagnosis) is binary, logistic regression was used behind LASSO for 113 covariates (predictors). LASSO regression inputs many covariates, only those associated with the outcome are presented. Each covariate is tested individually and against all others. In LASSO an odds ratio (OR) is generated. An OR > 1 or more indicates a predictor is associated with a higher likelihood of RHC at diagnosis, an OR < 1 indicates a lower likelihood. RHC at diagnosis was physician-confirmed from patient records.

Results:
A total of 529 PAH patients with complete data for all covariates were analyzed. Mean age was 55 and 51% were female. Overall, 75% received a RHC at diagnosis. Patient refusal (34%) and deemed unnecessary by managing physician due to other testing (29%) were the most frequently cited reasons for lack of RHC. Of the 113 initial predictors, 24 were considered important in predicting RHC (
Figure 1
). The leading predictors for RHC at diagnosis were patients classified as functional class (FC) III, those experiencing symptoms of dyspnea, palpitations and cyanosis, and those diagnosed at an accredited expert pulmonary hypertension (PH) center.

Conclusions:
Results indicate that RHC is more likely to be used for patients presenting with a higher FC, key PAH symptoms and diagnosed at PH expert centers. Further emphasis should be placed on RHC at diagnosis particularly within non-specialist settings to help achieve accurate diagnosis.
Abstract 12535: Spontaneous Coronary Artery Dissection in Women: A New Role for Autoimmunity?
Authors: Civieri Giovanni , Masiero Giulia , Vadori Marta , Iop Laura , pergola valeria , Cozzi Emanuele , Iliceto Sabino , Tona Francesco
Published: November 2023

Introduction:
Spontaneous coronary artery dissection (SCAD) is an uncommon cause of myocardial infarction (MI) in women, with a still unclear pathophysiology. Autoantibodies targeting angiotensin-II receptor type 1 (AT1R) and endothelin-1 receptor type A (ETAR) (AT1R-AAs and ETAR-AAs, respectively) lead to endothelial dysfunction and have already been associated with aortic dissection.

Hypothesis:
We hypothesized that titers of AT1R-AAs and ETAR-AAs are higher in patients with SCAD compared to controls.

Methods:
Our case-control study was conducted at Padua University Hospital between January 2022 and June 2022. Female patients diagnosed at coronary angiography with MI and SCAD were consecutively enrolled. Ten women with SCAD and 20 age-matched controls (10 women with ST-elevation MI (STEMI) and 10 healthy women) were included. Serum levels for AT1R-AAs and ETAR-AAs were determined for each participant. Absolute autoantibody titers and seropositivity prevalence were compared between SCAD patients, STEMI patients, and healthy women. Seropositivity was defined according to the threshold value suggested by the manufacturer (>10 U/mL).

Results:
Six out of 10 (60%) women with MI and SCAD were seropositive for AT1R-AAs and ETAR-AAs. In contrast, only one (10%) healthy woman and one (10%) STEMI patient were seropositive for AT1R-AAs (p=0.03 and p=0.03, respectively). One STEMI patient was seropositive for ETAR-AAs, while none of the healthy women was found to be seropositive (p=0.03 and p=0.01, respectively). The median autoantibody titer was significantly higher in SCAD patients than in healthy women (p=0.01 for AT1R-AAs; p=0.02 for ETAR-AAs) and STEMI patients (p<0.001 for AT1R-AAs; p=0.002 for ETAR-AAs).

Conclusions:
AT1R-AAs and ETAR-AAs seropositivity is significantly higher in SCAD women than in healthy women or female patients with STEMI. Our findings suggest a possible role for AT1R-AAs and ETAR-AAs in the pathophysiology of SCAD in women with MI.
Abstract 12538: Myocardial Bridge Induced Cardiomyopathy
Authors: Marwaha Bharat , Mahata Indrajeet , Kumar Navneet , Gupta Puneet , Singh Goldendeep , Riaz Iqra
Published: November 2023

Introduction:
A myocardial bridge(MB) is a condition in which the epicardial coronary artery traverses through the myocardium, has an intra-myocardial course of varying length, and then exits the myocardium and appears on the surface of the heart.

Clinical Presentation:
A 54-year-old male with no significant past medical history except tobacco abuse and anxiety presented to the hospital with retrosternal chest pain radiating to the back and shoulder and associated with nausea and diaphoresis. His SBP was 100/60, and his heart rate 46. His EKG showed ST elevation in inferior leads, and he was given a nitro tablet, which improved the chest pain to 5/10. He was emergently taken to the Cath lab and found to have proximal left circumflex artery occlusion and underwent PCI with a 2.25x23 Xience Drug-eluting stent. Troponin was elevated to 2.35. His cath also showed a significant mid-LAD myocardial bridge. His echocardiogram showed mid and apical anterior, anterior septal, apical wall, and inferior wall hypokinesis. His EF has been reduced to 30%. Coronary CTA showed mid-LAD has myocardial bridging, which is more than 2 cm long and 5 mm deep in the muscle. The patient has persistently low HR in 40-45, beta-blocker was not started. Due to significant cardiomyopathy induced by a myocardial bridge, unroofing of LAD was done off-pump. His EF improved to 55% after three months of surgery.

Discussion:
CABG or myotomy is the treatment of choice for patients with symptomatic myocardial bridging refractory to medical therapy, evidence of myocardial ischemia or infarction, or >75% systolic coronary compression on angiography. Incidental myocardial bridging finding without ischemia or symptoms does not require any treatment. Symptomatic patients with ischemia on stress tests can be offered beta or calcium channel blockers. Medical therapy is superior to revascularization with percutaneous intervention.
Abstract 13816: Clearing P16+ Cells Prevents Cardiac Dysfunction and Death in Mice With Acute Myocardial Infarction
Authors: Mehdizadeh Mozhdeh , Leblanc Francis , Naud Patrice , Altuntas Yasemin , Thorin Eric , Ferbeyre Gerardo , Tardif Jean-Claude , Sirois Martin G , Tanguay Jean-Francois , Lettre Guillaume , Nattel Stanley
Published: November 2023

Introduction:
Cellular senescence, a stress and age-related response, is often characterized by p16 expression in p16 positive (p16
+
) senescent cells. Senescent cells secrete profibrotic and proinflammatory factors as parts of a “senescence associated secretory phenotype”. The role of cellular senescence in myocardial infarction (MI) is unclear.

Aims:
To study the effect of p16
+
cell clearance on survival, cardiac remodeling and function after MI.

Methods:
We used INK ATTAC transgenic mice, in which p16
+
cells undergo targeted apoptosis upon exposure to a dimerizer, AP20187 (AP). MI mice were treated with AP or vehicle (V), twice a week for 1 month, beginning 3-4 hours post-MI. Cardiac function and structure were evaluated with echocardiography, hemodynamic parameters with a Millar catheter, infarct area with Masson’s Trichrome, gene expression with qPCR and single-nucleus RNA-sequencing (snRNAseq).

Results:
Survival post MI was dramatically increased in MI-AP vs MI-V mice (P<0.001, Fig A), primarily via prevention of cardiac rupture (CardRup). Left ventricular (LV) ejection fraction (EF%) and LV anterior wall thickness at end diastole (LVAWd) decreased in MI-V vs Sham and improved in MI-AP mice (Fig B), indicating preservation of cardiac function and structure with p16
+
cell clearance. Hemodynamic indices of LV function (max and min dP/dt) improved with AP (Fig C). Fibrosis-related gene expression (Col1a1, Col3a1 and Lox; Fig D) increased with MI and improved with AP, paralleling changes in infarct size (Fig E). snRNAseq showed that genes were principally upregulated in MI-V macrophages and neutrophils; significant responses were seen in TNF-α, inflammatory response pathways and gene programs associated with CardRup (Fig F).

Conclusion:
These results suggest that p16
+
cells play a significant role in the evolution of MI, apparently by modulating inflammatory signaling, pointing to an important pathophysiological role of cellular senescence.