bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changing Trends in Mechanical Circulatory Support Utilization and Outcomes in Patients Undergoing Percutaneous Coronary Interventions for Acute Coronary Syndrome Complicated with Cardiogenic Shock: Insights from a Nationwide Registry in Japan
Authors: Nishimoto Yuji , Inohara Taku , Kohsaka Shun , Sakakura Kenichi , Kawai Tsutomu , Kikuchi Atsushi , Watanabe Tetsuya , Yamada Takahisa , Fukunami Masatake , Yamaji Kyohei , Ishii Hideki , Amano Tetsuya , Kozuma Ken ,   J-PCI Registry Investigators
Published: May 2023

AbstractBackgroundTemporal trends in the management of acute coronary syndrome (ACS) complicated with cardiogenic shock (CS) after the revision of the guideline recommendations for intra-aortic balloon pump (IABP) use and the approval of the Impella require further investigation as their impact remains uncertain.MethodsUsing the Japanese Percutaneous Coronary Intervention (J-PCI) registry database from 2019 to 2021 (734,379 patients from 1,190 hospitals), we extracted 24,516 patients undergoing PCI for ACS complicated with CS. Of those, 12,171 patients (49.6%) used mechanical circulatory support (MCS) during the procedure. The patients were stratified into three groups: (i) IABP alone, (ii) Impella, and (iii) venoarterial extracorporeal membrane oxygenation (VA-ECMO); the VA-ECMO group was further stratified into (iiia) VA-ECMO alone, (iiib) VA-ECMO in combination with the IABP, and (iiic) VA-ECMO in combination with the Impella (ECPella). The quarterly prevalence and outcomes were reported.ResultsDuring the study period, there were notable changes in the prevalence of different MCS modalities and their associated outcomes. The use of an IABP alone and VA-ECMO decreased significantly from 63.5% and 34.4% in the first quarter of 2019 to 58.3% and 33.0% in the fourth quarter of 2021, respectively (P for trend = 0.01 and 0.02, respectively). Among the subset of patients who required VA-ECMO (n= 4,245), the use of VA-ECMO in combination with the IABP decreased significantly from 78.7% to 67.3%, whereas the use of ECPella increased significantly from 4.2% to 17.0% (P for trend <0.001 for both). There was no significant change in the use of VA-ECMO alone. In-hospital mortality decreased significantly over time in both the overall population of patients requiring MCS and those requiring VA-ECMO (P for trend = 0.004 and <0.001, respectively).ConclusionsIn conclusion, our study revealed significant changes in the use of different MCS modalities and associated outcomes in ACS complicated with CS, highlighting the evolving patterns of MCS utilization during the study period.
The Dark Side of Mentalizing: Learning Signals in the Default Network During Social Exchanges Support Cooperation and Exploitation
Authors: Allen Timothy A. , Hallquist Michael N. , Dombrovski Alexandre Y. 
Published: May 2023

AbstractThe evolution of human social cognitive capacities such as mentalizing was associated with the expansion of frontoparietal cortical networks, particularly the default network. Mentalizing supports prosocial behaviors, but recent evidence indicates it may also serve a darker side of human social behavior. Using a computational reinforcement learning model of decision-making on a social exchange task, we examined how individuals optimized their approach to social interactions based on a counterpart’s behavior and prior reputation. We found that learning signals encoded in the default network scaled with reciprocal cooperation and were stronger in individuals who were more exploitative and manipulative, but weaker in those who were more callous and less empathic. These learning signals, which help to update predictions about others’ behavior, accounted for associations between exploitativeness, callousness, and social reciprocity. Separately, we found that callousness, but not exploitativeness, was associated with a behavioral insensitivity to prior reputation effects. While the entire default network was involved in reciprocal cooperation, sensitivity to reputation was selectively related to the activity of the medial temporal subsystem. Overall, our findings suggest that the emergence of social cognitive capacities associated with the expansion of the default network likely enabled humans to not only cooperate effectively with others, but to exploit and manipulate others as well.SignificanceTo navigate complex social lives, humans must learn from their interactions with others and adjust their own behavior accordingly. Here, we show that humans learn to predict the behavior of social counterparts by integrating reputational information with both observed and counterfactual feedback acquired during social experience. We find that superior learning during social interactions is related to empathy and compassion and associated with activity of the brain’s default network. Paradoxically however, learning signals in the default network are also associated with manipulativeness and exploitativeness, suggesting that the ability to anticipate others’ behavior can serve both the light and dark sides of human social behavior.
Multiplexed fluorescence and scatter detection with single cell resolution using on-chip fiber optics for droplet microfluidic applications
Authors: Gupta Preksha , Mohan Ambili , Mishra Apurv , Nair Atindra , Chowdhury Neeladri , Balekai Dhanush , Rai Kavyashree , Mehta Pooja , Prabhakar Anil , Saiyed Taslimarif 
Published: May 2023

ABSTRACTDroplet microfluidics has emerged as a critical component of several high-throughput single cell analysis techniques in biomedical research and diagnostics. However, while there has been significant progress in the individual assays being developed, multi-parametric optical sensing of droplets and their encapsulated contents remains challenging. The current common approach of microscopy based high-speed imaging of droplets is technically complex and requires expensive instrumentation limiting their large-scale adoption. Here we have adapted the principles of the widely established technique of flow cytometry to a novel optofluidic setup – the OptiDrop platform, with on-chip detection of scatter and multiple fluorescence signals from microfluidic droplets and their contents using optical fibers. The highly customizable on-chip optical fiber-based signal detection system enables simplified, miniaturized, low-cost, multi-parametric sensing of optical signals with high sensitivity and single cell resolution within each droplet. Our work on differential expression analysis of the Major Histocompatibility Complex (MHC) protein in response to IFNγ stimulation further demonstrates the OptiDrop platforms capabilities in sensitively detecting cell surface biomarkers using fluorescently labeled antibodies. The OptiDrop platform thus combines the versatility of flow cytometry with the power of droplet microfluidics to provide wide-ranging optical sensing solutions for research and diagnostics.
Generation of a humanTropomyosin 1knockout iPSC line
Authors: Wilken Madison B , Maguire Jean Ann , Dungan Lea V , Gagne Alyssa , Osorio-Quintero Catherine , Waxman Elisa A , Chou Stella T , Gadue Paul , French Deborah L , Thom Christopher S 
Published: May 2023

AbstractThe CHOPWT17_TPM1KOc28 iPSC line was generated to interrogate the functions ofTropomyosin 1(TPM1) in primary human cell development. This line was reprogrammed from a previously published wild type control iPSC line.
Endothelial cells signaling and patterning under hypoxia: a mechanistic integrative computational model including the Notch-Dll4 pathway
Authors: Oliveira Rebeca Hannah M , Annex Brian H. , Popel Aleksander S. 
Published: May 2023

ABSTRACTSeveral signaling pathways are activated during hypoxia to promote angiogenesis, leading to endothelial cell patterning, interaction, and downstream signaling. Understanding the mechanistic signaling differences between normoxia and hypoxia can guide therapies to modulate angiogenesis. We present a novel mechanistic model of interacting endothelial cells, including the main pathways involved in angiogenesis. We calibrate and fit the model parameters based on well-established modeling techniques. Our results indicate that the main pathways involved in the patterning of tip and stalk endothelial cells under hypoxia differ, and the time under hypoxia affects how a reaction affects patterning. Interestingly, the interaction of receptors with Neuropilin1 is also relevant for cell patterning. Our simulations under different oxygen concentrations indicate time- and oxygen-availability-dependent responses for the two cells. Following simulations with various stimuli, our model suggests that factors such as period under hypoxia and oxygen availability must be considered for pattern control. This project provides insights into the signaling and patterning of endothelial cells under hypoxia, contributing to studies in the field.
Engineered cytokine/antibody fusion proteins improve delivery of IL-2 to pro-inflammatory cells and promote antitumor activity
Authors: Leonard Elissa K. , Tomala Jakub , Gould Joseph R. , Leff Michael I. , Lin Jian-Xin , Li Peng , Porter Mitchell J. , Johansen Eric R. , Thompson Ladaisha , Cao Shanelle D. , Henclova Tereza , Huliciak Maros , Vaněk Ondřej , Kovar Marek , Leonard Warren J. , Spangler Jamie B. 
Published: May 2023

AbstractProgress in cytokine engineering is driving therapeutic translation by overcoming the inherent limitations of these proteins as drugs. The interleukin-2 (IL-2) cytokine harbors great promise as an immune stimulant for cancer treatment. However, the cytokine’s concurrent activation of both pro-inflammatory immune effector cells and anti-inflammatory regulatory T cells, its toxicity at high doses, and its short serum half-life have limited clinical application. One promising approach to improve the selectivity, safety, and longevity of IL-2 is complexation with anti-IL-2 antibodies that bias the cytokine towards the activation of immune effector cells (i.e., effector T cells and natural killer cells). Although this strategy shows therapeutic potential in preclinical cancer models, clinical translation of a cytokine/antibody complex is complicated by challenges in formulating a multi-protein drug and concerns about complex stability. Here, we introduce a versatile approach to designing intramolecularly assembled single-agent fusion proteins (immunocytokines, ICs) comprising IL-2 and a biasing anti-IL-2 antibody that directs the cytokine’s activities towards immune effector cells. We establish the optimal IC construction and further engineer the cytokine/antibody affinity to improve immune biasing function. We demonstrate that our IC preferentially activates and expands immune effector cells, leading to superior antitumor activity compared to natural IL-2 without inducing toxicities associated with IL-2 administration. Collectively, this work presents a roadmap for the design and translation of immunomodulatory cytokine/antibody fusion proteins.One Sentence SummaryWe developed an IL-2/antibody fusion protein that expands immune effector cells and shows superior tumor suppression and toxicity profile versus IL-2.
Delivery of human adipose-derived stromal cells withinin situforming chitosan/PEG-PTMC hydrogels induces adverse outcomes in a femoral artery ligation model in athymicnu/numice
Authors: Serack Fiona E. , Ronald John A. , Amsden Brian G. , Hess David A. , Flynn Lauren E. 
Published: May 2023

AbstractThe delivery of human adipose-derived stromal cells (hASCs) to ischemic tissues represents a promising strategy to promote vascular regeneration for patients with critical limb ischemia (CLI). Building on previous work, this study focused on thein vivocharacterization of a hydrogel cell delivery platform for hASCs composed of peptide-functionalized methacrylated glycol chitosan (MGC-RGD) and a terminally acrylated triblock copolymer of poly(ethylene glycol) and poly(trimethylene carbonate) (PEG(PTMC-A)2) in athymicnu/numice with femoral artery ligation-induced critical limb ischemia (FAL-CLI). This immunodeficient mouse strain was selected to enable human cell transplantation in a model with conserved monocyte/macrophage function, recognizing that macrophages are key regulators of the biomaterial implant response, as well as vascular repair and regeneration. The hASCs were engineered to co-express tdTomato and firefly luciferase to enable longitudinal cell tracking using bioluminescence imaging (BLI). Interestingly, the hASCs were better retained following delivery in saline compared to hydrogel delivery. However, laser Doppler perfusion imaging (LDPI) analysis indicated that the restoration of hindlimb perfusion was similar between the two cell treatment groups. Critically, delivery of the hASCs within the hydrogels was associated with adverse outcomes only observed within this treatment group, including severe swelling, discoloration, and necrosis, which necessitated early euthanasia of some mice. CD45 staining supported that the combination of the cells and the hydrogels induced an inflammatory host response. These findings contrast with previous positive results when the platform was tested for hASC delivery in more severely immunocompromised NOD/SCID mice with FAL-CLI, as well as allogeneic rat ASC delivery in a healthy immunocompetent rat model. Overall, this study emphasizes the potential importance of testing cell delivery platforms in pre-clinical disease models that have retained host immune cell function, especially for immunomodulatory cell populations such as ASCs.
Direct quantification of chemogenetic H2O2production in live human cells
Authors: den Toom Wytze T. F. , van Soest Daan M. K. , Polderman Paulien E. , van Triest Miranda H. , Bruurs Lucas J. M. , De Henau Sasha , Burgering Boudewijn M. T. , Dansen Tobias B. 
Published: May 2023

AbstractReactive Oxygen Species (ROS) in the form of H2O2can act both as physiological signaling molecules as well as damaging agents, depending on its concentration and localization. The downstream biological effects of H2O2were often studied making use of exogenously added H2O2, generally as a bolus and at supraphysiological levels. But this does not mimic the continuous, low levels of intracellular H2O2production by for instance mitochondrial respiration. The enzyme D-Amino Acid Oxidase (DAAO) catalyzes H2O2formation using D-amino acids, which are absent from culture media, as a substrate. Ectopic expression of DAAO has recently been used in several studies to produce inducible and titratable intracellular H2O2. However, a method to directly quantify the amount of H2O2produced by DAAO has been lacking, making it difficult to assess whether observed phenotypes are the result of physiological or artificially high levels of H2O2. Here we describe a simple assay to directly quantify DAAO activity by measuring the oxygen consumed during H2O2production. The oxygen consumption rate of DAAO can directly be compared to the basal mitochondrial respiration in the same assay, allowing to estimate whether the ensuing level of H2O2production is within the range of physiological mitochondrial ROS production. We show that the assay can also be used to select clones that express differently localized DAAO with the same absolute level of H2O2production to be able to discriminate the effects of H2O2production at different subcellular locations from differences in total oxidative burden. This method therefore greatly improves the interpretation and applicability of DAAO-based models, thereby moving the redox biology field forward.
Inhibition of dopamine neurons prevents incentive value encoding of a reward cue: With revelations from deep phenotyping
Authors: Iglesias Amanda G. , Chiu Alvin S. , Wong Jason , Campus Paolo , Li Fei , Liu Zitong (Nemo) , Patel Shiv A. , Deisseroth Karl , Akil Huda , Burgess Christian R. , Flagel Shelly B. 
Published: May 2023

AbstractThe survival of an organism is dependent on their ability to respond to cues in the environment. Such cues can attain control over behavior as a function of the value ascribed to them. Some individuals have an inherent tendency to attribute reward-paired cues with incentive motivational value, or incentive salience. For these individuals, termed sign-trackers, a discrete cue that precedes reward delivery becomes attractive and desirable in its own right. Prior work suggests that the behavior of sign-trackers is dopamine-dependent, and cue-elicited dopamine in the nucleus accumbens is believed to encode the incentive value of reward cues. Here we exploited the temporal resolution of optogenetics to determine whether selective inhibition of ventral tegmental area (VTA) dopamine neurons during cue presentation attenuates the propensity to sign-track. Using male tyrosine hydroxylase (TH)-Cre Long Evans rats it was found that, under baseline conditions, ∼84% of TH-Cre rats tend to sign-track. Laser-induced inhibition of VTA dopamine neurons during cue presentation prevented the development of sign-tracking behavior, without affecting goal-tracking behavior. When laser inhibition was terminated, these same rats developed a sign-tracking response. Video analysis using DeepLabCut revealed that, relative to rats that received laser inhibition, rats in the control group spent more time near the location of the reward cue even when it was not present and were more likely to orient towards and approach the cue during its presentation. These findings demonstrate that cue-elicited dopamine release is critical for the attribution of incentive salience to reward cues.Significance StatementActivity of dopamine neurons in the ventral tegmental area (VTA) during cue presentation is necessary for the development of a sign-tracking, but not a goal-tracking, conditioned response in a Pavlovian task. We capitalized on the temporal precision of optogenetics to pair cue presentation with inhibition of VTA dopamine neurons. A detailed behavioral analysis with DeepLabCut revealed that cue-directed behaviors do not emerge without VTA dopamine. Importantly, however, when optogenetic inhibition is lifted, cue-directed behaviors increase, and a sign-tracking response develops. These findings confirm the necessity of VTA dopamine during cue presentation to encode the incentive value of reward cues.
Factors associated with non-use of ART among men living with HIV in South Africa: findings from a population-based household survey
Authors: Naqvi Nuha , Swart Xan , Chikovore Jeremiah , Ayalew Kassahun , Moyo Sizulu , Morof Diane , Makapela David , Bedford Jason 
Published: May 2023

AbstractIntroductionAlthough South Africa adopted the World Health Organization’s Test and Treat strategy for HIV epidemic control in 2016, antiretroviral therapy (ART) treatment initiation and retention remain below target. In 2017, an estimated 56.3% of men living with HIV were on ART. We aimed to investigate factors associated with non-use of ART among men in South Africa.MethodsUtilizing data from the fifth South African National HIV Prevalence, Incidence, Behavior and Communication (SABSSM V) cross-sectional survey conducted in 2017, a subset of data from HIV-positive men was stratified based on presence/absence of antiretroviral drugs (ARVs) detected in dried blood spot samples. Data were weighted to be representative of the national population and analyzed using multivariable logistic regression to assess predictors of non-use of ART; p<0.05 was considered significant.ResultsA total of 6,920 men aged ≥15 years old were enrolled in the study, of whom 953 (13.8%) tested HIV-positive. Among those HIV-positive, 810 (85%) had a known ARV test result: 470 (58%) had ARVs detected, and 340 (42%) did not have ARVs detected. Non-use of ART in men was associated with high-risk alcohol use (adjusted odds ratio (AOR)=3.68, 95% confidence interval (CI): 1.03-13.23), being a widower compared to being unmarried (AOR=6.99, 95%CI: 1.46-33.42), and having drug-resistant HIV (AOR=28.12, 95%CI: 13.89-56.94). Per year increase in age (AOR=0.67, 95%CI: 0.47-0.96), residence in rural tribal localities compared to urban localities (AOR=0.38, 95%CI: 0.18-0.78), or having a co-morbidity such as tuberculosis or diabetes (AOR=0.06, 95%CI: 0.03-0.14) were positively associated with ART use.ConclusionsNon-use of ART was strongly associated with HIV drug resistance. Young men who are living with HIV, those with high-risk alcohol use, and widowers, should be a priority for HIV programming and linkage to care. Identifying interventions that are effective at linking these men to ART will help reduce the burden of HIV in South Africa.
Transcriptome-Wide Association Analysis Identifies Novel Candidate Susceptibility Genes for Prostate-Specific Antigen Levels in Men Without Prostate Cancer
Authors: Chen Dorothy M. , Dong Ruocheng , Kachuri Linda , Hoffmann Thomas , Jiang Yu , Berndt Sonja I. , Shelley John P. , Schaffer Kerry R. , Machiela Mitchell J. , Freedman Neal D. , Huang Wen-Yi , Li Shengchao A. , Lilja Hans , Van Den Eeden Stephen K. , Chanock Stephen , Haiman Christopher A. , Conti David V. , Klein Robert J. , Mosley Jonathan D. , Witte John S. , Graff Rebecca E. 
Published: May 2023

AbstractDeciphering the genetic basis of prostate-specific antigen (PSA) levels may improve their utility to screen for prostate cancer (PCa). We thus conducted a transcriptome-wide association study (TWAS) of PSA levels using genome-wide summary statistics from 95,768 PCa-free men, the MetaXcan framework, and gene prediction models trained in Genotype-Tissue Expression (GTEx) project data. Tissue-specific analyses identified 41 statistically significant (p < 0.05/12,192 = 4.10e-6) associations in whole blood and 39 statistically significant (p < 0.05/13,844 = 3.61e-6) associations in prostate tissue, with 18 genes associated in both tissues. Cross-tissue analyses that combined associations across 45 tissues identified 155 genes that were statistically significantly (p < 0.05/22,249 = 2.25e-6) associated with PSA levels. Based on conditional analyses that assessed whether TWAS associations were attributable to a lead GWAS variant, we found 20 novel genes (11 single-tissue, 9 cross-tissue) that were associated with PSA levels in the TWAS. Of these novel genes, five showed evidence of colocalization (colocalization probability > 0.5):EXOSC9, CCNA2, HIST1H2BN, RP11-182L21.6, andRP11-327J17.2. Six of the 20 novel genes are not known to impact PCa risk. These findings yield new hypotheses for genetic factors underlying PSA levels that should be further explored toward improving our understanding of PSA biology.