bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of red blood cell utilization: Harnessing electronic health records data from the Information Standard for Blood and Transplant (ISBT) 128 system within the Biologics Effectiveness and Safety (BEST) initiative
Authors: Obidi Joyce , Sridhar Gayathri , Dores Graça M. , Whitaker Barbee , Villa Carlos H. , Storch Emily , Chada Kinnera , Schilling Lisa M. , Natarajan Karthik , Biondich Paul , Soares Andrey , Spotnitz Matthew , Falconer Thomas , Purkayastha Saptarshi , Draper Nicole L. , Wong Hui‐Lee , Stagg Matthew , Reich Christian , Anderson Steven , Shoaibi Azadeh 
Published: May 2024

AbstractBackgroundCurrent hemovigilance methods generally rely on survey data or administrative claims data utilizing billing and revenue codes, each of which has limitations. We used electronic health records (EHR) linked to blood bank data to comprehensively characterize red blood cell (RBC) utilization patterns and trends in three healthcare systems participating in the U.S. Food and Drug Administration Center for Biologics Evaluation and Research Biologics Effectiveness and Safety (BEST) initiative.MethodsWe used Information Standard for Blood and Transplant (ISBT) 128 codes linked to EHR from three healthcare systems data sources to identify and quantify RBC‐transfused individuals, RBC transfusion episodes, transfused RBC units, and processing methods per year during 2012–2018.ResultsThere were 577,822 RBC units transfused among 112,705 patients comprising 345,373 transfusion episodes between 2012 and 2018. Utilization in terms of RBC units and patients increased slightly in one and decreased slightly in the other two healthcare facilities. About 90% of RBC‐transfused patients had 1 (~46%) or 2–5 (~42%)transfusion episodes in 2018. Among the small proportion of patients with ≥12 transfusion episodes per year, approximately 60% of episodes included only one RBC unit. All facilities used leukocyte‐reduced RBCs during the study period whereas irradiated RBC utilization patterns differed across facilities.DiscussionISBT 128 codes and EHRs were used to observe patterns of RBC transfusion and modification methods at the unit level and patient level in three healthcare systems participating in the BEST initiative. This study shows that the ISBT 128 coding system in an EHR environment provides a feasible source for hemovigilance activities.
The Spx stress regulator confers high-level β-lactam resistance and decreases susceptibility to last-line antibiotics in methicillin-resistant
Staphylococcus aureus
Authors: Nielsen Tobias Krogh , Petersen Ida Birkjær , Xu Lijuan , Barbuti Maria Disen , Mebus Viktor , Justh Anni , Alqarzaee Abdulelah Ahmed , Jacques Nicolas , Oury Cécile , Thomas Vinai , Kjos Morten , Henriksen Camilla , Frees Dorte 
Published: May 2024

ABSTRACT

Infections caused by methicillin-resistant
Staphylococcus aureus
(MRSA) are a leading cause of mortality worldwide. MRSA has acquired resistance to next-generation β-lactam antibiotics through the horizontal acquisition of the
mecA
resistance gene. Development of high resistance is, however, often associated with additional mutations in a set of chromosomal core genes, known as potentiators, which, through poorly described mechanisms, enhance resistance. The
yjbH
gene was recently identified as a hot spot for adaptive mutations during severe infections. Here, we show that inactivation of
yjbH
increased β-lactam MICs up to 16-fold and transformed MRSA cells with low levels of resistance to being homogenously highly resistant to β-lactams. The
yjbH
gene encodes an adaptor protein that targets the transcriptional stress regulator Spx for degradation by the ClpXP protease. Using CRISPR interference (CRISPRi) to knock down
spx
transcription, we unambiguously linked hyper-resistance to the accumulation of Spx. Spx was previously proposed to be essential; however, our data suggest that Spx is dispensable for growth at 37°C but becomes essential in the presence of antibiotics with various targets. On the other hand, high Spx levels bypassed the role of PBP4 in β-lactam resistance and broadly decreased MRSA susceptibility to compounds targeting the cell wall or the cell membrane, including vancomycin, daptomycin, and nisin. Strikingly, Spx potentiated resistance independently of its redox-sensing switch. Collectively, our study identifies a general stress pathway that, in addition to promoting the development of high-level, broad-spectrum β-lactam resistance, also decreases MRSA susceptibility to critical antibiotics of last resort.
Factor analysis in residual soils of the Iberian Pyrite Belt (Spain): comparison between raw data, log-transformation data and compositional data
Authors: Martín-Méndez Iván , Llamas-Borrajo Juan , Llamas Lois Alberto , Locutura Juan 
Published: May 2024

The Iberian Pyrite Belt (IPB) is a metallogenic province in SW Spain and Portugal hosting the largest concentration of massive sulfide deposits worldwide. Exploration campaigns in both the Spanish and Portuguese sectors of the IPB have increased recently due to the rise in metal prices. Within this framework, distinguishing geochemical features associated with natural phenomena and isolating geogenic anomalies from anthropogenic ones can pose a challenge. This contribution uses the residual soil geochemical database of the IPB (Spain) to examine numerous variables, encompassing major, minor and trace elements. Some of these variables commonly exhibit high correlations owing to consistent geochemical behaviour. However, the influence of anthropogenic factors tends to elevate data variability, occasionally masking the natural relationships that govern their distributions.
We apply different treatments of data to develop factor analysis using log-transformed data, and centred log-ratio (clr) transformed data to compare and improve the geochemical interpretation of this important zone. Factor analysis has been developed with these results to compare with previously published research on factor analysis in raw data. Factor score interpolated maps were also generated using both lognormal and clr-transformed data to visualize better the distribution and the different geochemical associations in the IPB.
This study shows the importance of the different data treatments and the improvement of the clr-transformed multivariate analysis to reduce the dilution or overestimation of the results of some elements that cause erroneous interpretations of the data.
FSDedup: Feature-Aware and Selective Deduplication for Improving Performance of Encrypted Non-Volatile Main Memory
Authors: Du Chunfeng , Lin Zihang , Wu Suzhen , Chen Yifei , Wu Jiapeng , Wang Shengzhe , Wang Weichun , Wu Qingfeng , Mao Bo 
Published: May 2024

Enhancing the endurance, performance, and energy efficiency of encrypted Non-Volatile Main Memory (NVMM) can be achieved by minimizing written data through inline deduplication. However, existing approaches applying inline deduplication to encrypted NVMM suffer from substantial performance degradation due to high computing, memory footprint, and index-lookup overhead to generate, store, and query the cryptographic hash (fingerprint). In the preliminary ESD [
14
], we proposed the Error Correcting Code (ECC) assisted selective deduplication scheme, utilizing the ECC information as a fingerprint to identify similar data effectively and then leveraging the selective deduplication technique to eliminate a large amount of redundant data with high reference counts. In this article, we proposed FSDedup. Compared with ESD, FSDedup could leverage the prefetch cache to reduce the read overhead during similarity comparison and utilize the cache refresh mechanism to identify further and eliminate more redundant data. Extensive experimental evaluations demonstrate that FSDedup can enhance the performance of the NVMM system further than the ESD. Experimental results show that FSDedup can improve both write and read speed by up to 1.8×, enhance Instructions Per Cycle by up to 1.5×, and reduce energy consumption by up to 2.0×, compared to ESD.
Overcoming Delays in the Progress against Cancer: Identifying Tobacco Use among Cancer Patients Enrolled in Clinical Trials
Authors: Warren Graham W. , Presant Cary A. 
Published: May 2024

Abstract
Though smoking causes adverse cancer treatment outcomes and smoking cessation can improve survival, prior literature demonstrates deficits in collecting tobacco use information in clinical trials. Results by Streck and colleagues represent a thorough structured assessment of tobacco use and alternative tobacco product use in patients enrolled in cooperative group trials. Among patients with predominantly non–tobacco related cancers, observations demonstrate that approximately 27% of patients reported using one or more forms of tobacco use after diagnosis. Alternative tobacco use was reported by many patients, including patterns of dual use. Results demonstrate the feasibility of collecting comprehensive structured tobacco use information, and further support the need to address tobacco and cessation even among patients with non–tobacco related cancers.
See related article by Streck and colleagues, Cancer Epidemiol Biomarkers Prev 2023;32:1552–57
Activation of Hepatocyte Growth Factor/MET Signaling as a Mechanism of Acquired Resistance to a Novel YAP1/TEAD Small Molecule Inhibitor
Authors: Moure Casey J. , Vara Brandon , Cheng Mangeng M. , Sondey Christopher , Muise Eric , Park Eunsil , Vela Ramirez Julia Eulalia , Su Dan , D’Souza Shanti , Yan Qingyun , Yeung Charles S. , Zhang Minjia , Mansueto My Sam , Linn Doug , Buchanan Mark , Foti Robert , DiMauro Erin , Long Brian , Simov Vladimir , Barry Evan R. 
Published: May 2024

Abstract
Many tumor types harbor alterations in the Hippo pathway, including mesothelioma, where a high percentage of cases are considered YAP1/TEAD dependent. Identification of autopalmitoylation sites in the hydrophobic palmitate pocket of TEADs, which may be necessary for YAP1 protein interactions, has enabled modern drug discovery platforms to generate compounds that allosterically inhibit YAP1/TEAD complex formation and transcriptional activity. We report the discovery and characterization of a novel YAP1/TEAD inhibitor MRK-A from an aryl ether chemical series demonstrating potent and specific inhibition of YAP1/TEAD activity. In vivo, MRK-A showed a favorable tolerability profile in mice and demonstrated pharmacokinetics suitable for twice daily oral dosing in preclinical efficacy studies. Importantly, monotherapeutic targeting of YAP1/TEAD in preclinical models generated regressions in a mesothelioma CDX model; however, rapid resistance to therapy was observed. RNA-sequencing of resistant tumors revealed mRNA expression changes correlated with the resistance state and a marked increase of hepatocyte growth factor (HGF) expression. In vitro, exogenous HGF was able to fully rescue cytostasis induced by MRK-A in mesothelioma cell lines. In addition, co-administration of small molecule inhibitors of the MET receptor tyrosine kinase suppressed the resistance generating effect of HGF on MRK-A induced growth inhibition. In this work, we report the structure and characterization of MRK-A, demonstrating potent and specific inhibition of YAP1/TAZ-TEAD–mediated transcriptional responses, with potential implications for treating malignancies driven by altered Hippo signaling, including factors resulting in acquired drug resistance.
Exploiting Metabolic Defects in Glioma with Nanoparticle-Encapsulated NAMPT Inhibitors
Authors: Murray Matthew A. , Noronha Katelyn J. , Wang Yazhe , Friedman Anna P. , Paradkar Sateja , Suh Hee-Won , Sundaram Ranjini K. , Brenner Charles , Saltzman W.M. , Bindra Ranjit S. 
Published: May 2024

Abstract
The treatment of primary central nervous system tumors is challenging due to the blood–brain barrier and complex mutational profiles, which is associated with low survival rates. However, recent studies have identified common mutations in gliomas [isocitrate dehydrogenase (IDH)-wild-type and mutant, WHO grades II–IV; with grade IV tumors referred to as glioblastomas (GBM)]. These mutations drive epigenetic changes, leading to promoter methylation at the nicotinic acid phosphoribosyl transferase (NAPRT) gene locus, which encodes an enzyme involved in generating NAD+. Importantly, NAPRT silencing introduces a therapeutic vulnerability to inhibitors targeting another NAD+ biogenesis enzyme, nicotinamide phosphoribosyl transferase (NAMPT), rationalizing a treatment for these malignancies. Multiple systemically administered NAMPT inhibitors (NAMPTi) have been developed and tested in clinical trials, but dose-limiting toxicities—including bone marrow suppression and retinal toxicity—have limited their efficacy. Here, we report a novel approach for the treatment of NAPRT-silenced GBMs using nanoparticle (NP)-encapsulated NAMPTis administered by convection-enhanced delivery (CED). We demonstrate that GMX1778 (a NAMPTi) can be formulated in degradable polymer NPs with retention of potency for NAMPT inhibition and anticancer activity in vitro, plus sustained drug release in vitro and in vivo. Direct injection of these drugs via CED into the brain is associated with reduced retinal toxicity compared with systemic administration. Finally, we show that CED of NP-encapsulated GMX1778 to NAPRT-silenced intracranial GBM xenografts in mice exhibit significant tumor growth delay and extends survival. These data support an approach to treat gliomas harboring defects in NAD+ metabolism using CED of NP-encapsulated NAMPTis to greatly improve the therapeutic index and treatment efficacy for this class of drugs.
A Senescence-Mimicking (Senomimetic) VEGFR TKI Side Effect Primes Tumor Immune Responses via IFN/STING Signaling
Authors: Dolan Melissa , Shi Yuhao , Mastri Michalis , Long Mark D. , McKenery Amber , Hill James W. , Vaghi Cristina , Benzekry Sebastien , Barbi Joseph , Ebos John M.L. 
Published: May 2024

Abstract
Tyrosine kinase inhibitors (TKIs) that block the vascular endothelial growth factor receptors (VEGFRs) not only disrupt tumor angiogenesis but also have many unexpected side effects that impact tumor cells directly. This includes the induction of molecular markers associated with senescence, a form of cellular aging that typically involves growth arrest. We have shown that VEGFR TKIs can hijack these aging programs by transiently inducting senescence markers (SMs) in tumor cells to activate senescence-associated secretory programs that fuel drug resistance. Here we show that these same senescence-mimicking (“senomimetic”) VEGFR TKI effects drive an enhanced immunogenic signaling that, in turn, can alter tumor response to immunotherapy. By using a live cell sorting method to detect β-galactosidase, a commonly used SM, we found that subpopulations of SM-expressing (SM+) tumor cells have heightened IFN signaling and increased expression of IFN-stimulated genes (ISGs). These ISGs increase under the control of the STimulator of the INterferon Gene (STING) signaling pathway, which we found could be directly activated by several VEGFR TKIs. TKI-induced SM+ cells could stimulate or suppress CD8 T-cell activation depending on host–tumor cell contact while tumors grown from SM+ cells were more sensitive to PDL1 inhibition in vivo, suggesting that offsetting immune-suppressive functions of SM+ cells can improve TKI efficacy overall. Our findings may explain why some (but not all) VEGFR TKIs improve outcomes when combined with immunotherapy and suggest that exploiting senomimetic drug side effects may help identify TKIs that uniquely “prime” tumors for enhanced sensitivity to PDL1-targeted agents.
Pediatric Chordoma: A Tale of Two Genomes
Authors: O’Halloran Katrina , Hakimjavadi Hesamedin , Bootwalla Moiz , Ostrow Dejerianne , Kerawala Rhea , Cotter Jennifer A. , Yellapantula Venkata , Kaneva Kristiyana , Wadhwani Nitin R. , Treece Amy , Foreman Nicholas K. , Alexandrescu Sanda , Velazquez Vega Jose , Biegel Jaclyn A. , Gai Xiaowu 
Published: May 2024

Abstract
Little is known about the genomic alterations in chordoma, with the exception of loss of SMARCB1, a core member of the SWI/SNF complex, in poorly differentiated chordomas. A TBXT duplication and rs2305089 polymorphism, located at 6q27, are known genetic susceptibility loci. A comprehensive genomic analysis of the nuclear and mitochondrial genomes in pediatric chordoma has not yet been reported. In this study, we performed WES and mtDNA genome sequencing on 29 chordomas from 23 pediatric patients. Findings were compared with that from whole-genome sequencing datasets of 80 adult patients with skull base chordoma. In the pediatric chordoma cohort, 81% of the somatic mtDNA mutations were observed in NADH complex genes, which is significantly enriched compared with the rest of the mtDNA genes (P = 0.001). In adult chordomas, mtDNA mutations were also enriched in the NADH complex genes (P &lt; 0.0001). Furthermore, a progressive increase in heteroplasmy of nonsynonymous mtDNA mutations was noted in patients with multiple tumors (P = 0.0007). In the nuclear genome, rare likely germline in-frame indels in ARID1B, a member of the SWI/SNF complex located at 6q25.3, were observed in five pediatric patients (22%) and four patients in the adult cohort (5%). The frequency of rare ARID1B indels in the pediatric cohort is significantly higher than that in the adult cohort (P = 0.0236, Fisher’s exact test), but they were both significantly higher than that in the ethnicity-matched populations (P &lt; 5.9e−07 and P &lt; 0.0001174, respectively).
Implications: germline ARID1B indels and mtDNA aberrations seem important for chordoma genesis, especially in pediatric chordoma.
Figure S2 from EGFR-Driven Lung Adenocarcinomas Co-opt Alveolar Macrophage Metabolism and Function to Support EGFR Signaling and Growth
Authors: Kuhlmann-Hogan Alexandra , Cordes Thekla , Xu Ziyan , Kuna Ramya S. , Traina Kacie A. , Robles-Oteíza Camila , Ayeni Deborah , Kwong Elizabeth M. , Levy Stellar , Globig Anna-Maria , Nobari Matthew M. , Cheng George Z. , Leibel Sandra L. , Homer Robert J. , Shaw Reuben J. , Metallo Christian M. , Politi Katerina , Kaech Susan M. 
Published: May 2024

<p>Figure S2: Innate immune cells are regulated by GM-CSF and contributes to tumorigenesis.</p>
Do padrão do gosto em Hume: a crítica e a racionalidade
Authors: Cachel Andrea 
Published: May 2024

Hume shows, in the "Of the standard of taste" essay, how, despite the diversity inherent to taste, it is possible to establish an universal standard in thís matter, standing not on the object, but in human nature itself. He also poínts, however, that the finding of this standard is a result of experience, particularly, of that related to the practice of aesthetic criticism. He seems to establísh, therefore, the refinement as an essential item not only of the discovery of the standard of taste, but also as a component in the constitution of this standard. Our intention is, in this context, to investigate the role, in humean philosophy, of regulation in the processof establishing an universal principie for taste, as wellas pointing to, at last, some consequences of this subject to the analysis of the possibility of establishing a standard of rationality in a philosophy that separates experimental reason from demonstrative reason.
Counteracting Angiotensinogen Small-Interfering RNA-Mediated Antihypertensive Effects With REVERSIR
Authors: Ye Dien , Cruz-López Edwyn O. , Veghel Richard van , Garrelds Ingrid M. , Kasper Anne , Wassarman Kelly , Tu Ho-Chou , Zlatev Ivan , Danser A.H. Jan 
Published: May 2024

BACKGROUND:
Small-interfering RNA (siRNA) targeting hepatic AGT (angiotensinogen) mRNA depletes AGT, lowering blood pressure for up to 6 months. However, certain situations may require a rapid angiotensin increase. The REVERSIR (RVR) - reverse siRNA silencing technology a potential approach to counteract siRNA effects.

METHODS:
Spontaneously hypertensive rats received 10 mg/kg AGT siRNA, and 3 weeks later were given AGT-RVR (1, 10, or 20 mg/kg). One week after AGT-RVR dosing, a redose of AGT siRNA assessed its post-AGT-RVR effectiveness for 2 weeks. Additionally, the impact of AGT-RVR after an equihypotensive dose of valsartan (4 mg/kg per day) was examined.

RESULTS:
Baseline mean arterial pressure (MAP) was 144±1 mm Hg. AGT siRNA reduced MAP by ≈16 mm Hg and AGT by >95%, while renin increased 25-fold. All AGT-RVR doses restored MAP to baseline within 4 to 7 days. Notably, 10 and 20 mg/kg restored AGT and renin to baseline, while 1 mg/kg allowed ≈50% AGT restoration, with renin remaining above baseline. A second AGT siRNA treatment, following 1 mg/kg AGT-RVR, reduced MAP to the same degree as the initial dose, while following 10 mg/kg AGT-RVR, it resulted in ≈50% of the first dose’s MAP effect at 2 weeks. The valsartan-induced MAP reduction was unaffected by AGT-RVR.

CONCLUSIONS:
In spontaneously hypertensive rats, angiotensinogen-RVR dose-dependently reversed AGT siRNA-induced AGT reduction, normalizing MAP. MAP normalization persisted even with 50% recovered AGT levels, likely due to upregulated renin maintaining adequate angiotensin generation. Post-AGT-RVR dosing, a second AGT siRNA dose lowered MAP again.
Translational Research of the Acute Effects of Negative Emotions on Vascular Endothelial Health: Findings From a Randomized Controlled Study
Authors: Shimbo Daichi , Cohen Morgan T. , McGoldrick Matthew , Ensari Ipek , Diaz Keith M. , Fu Jie , Duran Andrea T. , Zhao Shuqing , Suls Jerry M. , Burg Matthew M. , Chaplin William F. 
Published: May 2024

Background
Provoked anger is associated with an increased risk of cardiovascular disease events. The underlying mechanism linking provoked anger as well as other core negative emotions including anxiety and sadness to cardiovascular disease remain unknown. The study objective was to examine the acute effects of provoked anger, and secondarily, anxiety and sadness on endothelial cell health.

Methods and Results

Apparently healthy adult participants (n=280) were randomized to an 8‐minute anger recall task, a depressed mood recall task, an anxiety recall task, or an emotionally neutral condition. Pre−/post‐assessments of endothelial health including endothelium‐dependent vasodilation (reactive hyperemia index), circulating endothelial cell‐derived microparticles (CD62E+, CD31+/CD42−, and CD31+/Annexin V+) and circulating bone marrow‐derived endothelial progenitor cells (CD34+/CD133+/kinase insert domain receptor+ endothelial progenitor cells and CD34+/kinase insert domain receptor+ endothelial progenitor cells) were measured. There was a group×time interaction for the anger versus neutral condition on the change in reactive hyperemia index score from baseline to 40 minutes (
P
=0.007) with a mean±SD change in reactive hyperemia index score of 0.20±0.67 and 0.50±0.60 in the anger and neutral conditions, respectively. For the change in reactive hyperemia index score, the anxiety versus neutral condition group by time interaction approached but did not reach statistical significance (
P
=0.054), and the sadness versus neutral condition group by time interaction was not statistically significant (
P
=0.160). There were no consistent statistically significant group×time interactions for the anger, anxiety, and sadness versus neutral condition on endothelial cell‐derived microparticles and endothelial progenitor cells from baseline to 40 minutes.

Conclusions
In this randomized controlled experimental study, a brief provocation of anger adversely affected endothelial cell health by impairing endothelium‐dependent vasodilation.