bluuebunny/crossref_metadata_2025 huggingface dataset:
A self calibrating, magnetic sensor approach accurately positions an aortic damage control stent in a porcine model
Authors: Kenawy Dahlia M , Zhang Yifan , Elsisy Moataz , Abdel-Rasoul Mahmoud , Chun Youngjae , Clark William C , Tillman Bryan W
Published: December 2023

Objectives

Non-compressible torso hemorrhage remains a high mortality injury, with difficulty mobilizing resources before exsanguination. Previous studies reported on a retrievable stent graft for damage control and morphometric algorithms for rapid placement, yet fluoroscopy is impractical for the austere environment. We hypothesized that magnetic sensors could be used to position stents relative to an external magnet placed on an anatomic landmark, whereas an electromagnet would allow self-calibration to account for environmental noise.

Methods

A magnetic sensor alone (MSA) and with integrated stent (MSIS) were examined in a porcine model under anesthesia. A target electromagnet was placed on the xiphoid process (position 0 cm). Sensors were placed in the aorta and measurements obtained at positions 0 cm, +4 cm, and +12 cm from the magnet and compared with fluoroscopy. Sensors were examined under conditions of tachycardia/hypertension, hypotension, vibration, and metal shrapnel to simulate environmental factors that might impact accuracy. General linear models compared mean differences between fluoroscopy and sensor readings.

Results

Both sensors were compatible with a 10 French catheter system and provided real-time assessment of the distance between the sensor and magnetic target in centimeters. Mean differences between fluoroscopy and both magnetic sensor readings demonstrated accuracy within ±0.5 cm for all but one condition at 0 cm and +4 cm, whereas accuracy decreased at +12 cm from the target. Using the control as a reference, there was no significant difference in mean differences between fluoroscopy and both MSA or MSIS readings at 0 cm and +4 cm for all conditions. The system retained effectiveness if the target was overshot.

Conclusion

Magnetic sensors achieved the highest accuracy as sensors approached the target. Oscillation of the electromagnet on and off effectively accounts for environmental noise.

This approach is promising for rapid and accurate placement of damage control retrievable stent grafts when fluoroscopy is impractical.

Level of evidence

Not applicable.
First search for resonant enhanced neutrinoless double electron capture in $$^{152}$$Gd and other rare decays in natural Gd isotopes
Authors: Laubenstein M. , Lehnert B. , Nagorny S. S. , Nisi S.
Published: December 2023

A first search for rare decays of gadolinium isotopes was performed with an ultra-low background high-purity germanium detector at Gran Sasso Underground Laboratory (Italy). A 198 g $$\hbox {Gd}_2$$

Gd
2

$$\hbox {O}_3$$

O
3

powder sample was measured for 63.8 d with a total Gd exposure of 12.6 kg $$\times $$
×
d. $$^{152}$$

152

Gd is the most promising isotope for resonant enhanced neutrinoless double electron capture which could significantly increase the decay rate over other neutrinoless double beta decay processes. The half-life for this decay was constrained to $$>4.2\times 10^{12}$$

>
4.2
×

10
12

 year (90% credibility). This limit is still orders of magnitude away from theoretical predictions but it is the first established limit on the transition paving the way for future experiments. In addition, other rare alpha and double beta decay modes were investigated in $$^{152}$$

152

Gd, $$^{154}$$

154

Gd, and $$^{160}$$

160

Gd with half-life limits in the range of $$10^{17-20}$$

10

17
-
20

year.
Transparency-Check: An Instrument for the Study and Design of Transparency in AI-based Personalization Systems
Authors: Schelenz Laura , Segal Avi , Adelio Oduma , Gal Kobi
Published: December 2023

As AI-based systems become commonplace in our daily lives, they need to provide understandable information to their users about how they collect, process, and output information that concerns them. The importance of such transparency practices has gained significance due to recent ethical guidelines and regulation, as well as research suggesting a positive relationship between the transparency of AI-based systems and users’ satisfaction. This article provides a new tool for the design and study of transparency in AI-based systems that use personalization. The tool, called Transparency-Check, is based on a checklist of questions about transparency in four areas of a system: input (data collection), processing (algorithmic models), output (personalized recommendations), and user control (user feedback mechanisms to adjust elements of the system). Transparency-Check can be used by researchers, designers, and end users of computer systems.

To demonstrate the usefulness of Transparency-Check from a researcher’s perspective, we collected the responses of 108 student participants who used the transparency checklist to rate five popular real-world systems (Amazon, Facebook, Netflix, Spotify, and YouTube). Based on users’ subjective evaluations, the systems showed low compliance with transparency standards, with some nuances about individual categories (specifically data collection, processing, and user control). We use these results to compile design recommendations for improving transparency in AI-based systems, such as integrating information about the system’s behavior during the user’s interactions with it.
Measuring the Accuracy of Automatic Speech Recognition Solutions
Authors: Kuhn Korbinian , Kersken Verena , Reuter Benedikt , Egger Niklas , Zimmermann Gottfried
Published: December 2023

For d/Deaf and hard of hearing (DHH) people, captioning is an essential accessibility tool. Significant developments in artificial intelligence mean that automatic speech recognition (ASR) is now a part of many popular applications. This makes creating captions easy and broadly available—but transcription needs high levels of accuracy to be accessible. Scientific publications and industry report very low error rates, claiming that artificial intelligence has reached human parity or even outperforms manual transcription. At the same time, the DHH community reports serious issues with the accuracy and reliability of ASR. There seems to be a mismatch between technical innovations and the real-life experience for people who depend on transcription. Independent and comprehensive data is needed to capture the state of ASR. We measured the performance of 11 common ASR services with recordings of Higher Education lectures. We evaluated the influence of technical conditions like streaming, the use of vocabularies, and differences between languages. Our results show that accuracy ranges widely between vendors and for the individual audio samples. We also measured a significant lower quality for streaming ASR, which is used for live events. Our study shows that despite the recent improvements of ASR, common services lack reliability in accuracy.
Life on the Edge: The Cambrian Marine Realm and Oxygenation
Authors: Pruss Sara B. , Gill Benjamin C.
Published: December 2023

The beginning of the Phanerozoic saw two biological events that set the stage for all life that was to come: (a) the Cambrian Explosion (the appearance of most marine invertebrate phyla) and (b) the Great Ordovician Biodiversification Event (GOBE), the subsequent substantial accumulation of marine biodiversity. Here, we examine the current state of understanding of marine environments and ecosystems from the late Ediacaran through the Early Ordovician, which spans this biologically important interval. Through a compilation and review of the existing geochemical, mineralogical, sedimentological, and fossil records, we argue that this interval was one of sustained low and variable marine oxygen levels that both led to animal extinction and fostered biodiversification events throughout the Cambrian and Early Ordovician. Therefore, marine ecosystems of this interval existed on the edge—with enough oxygen to sustain them but with the perennial risk of environmental stressors that could overwhelm them.▪We review the current research on geochemistry and paleontology of the Cambrian and Early Ordovician periods.▪Low and oscillating oxygen levels in the marine realm promoted diversification and evolutionary innovation but also drove several extinction events.▪Taphonomic modes and marine authigenic pathways that were abundant in the Cambrian were supported by oceans that were persistently less oxygenated than today's oceans.
Differential sensitivity to longitudinal and transverse stretch mediates transcriptional responses in mouse neonatal ventricular myocytes
Authors: Cao Shulin , Buchholz Kyle S. , Tan Philip , Stowe Jennifer C. , Wang Ariel , Fowler Annabelle , Knaus Katherine R. , Khalilimeybodi Ali , Zambon Alexander C. , Omens Jeffrey H. , Saucerman Jeffrey J. , McCulloch Andrew D.
Published: December 2023

Anisotropic stretch applied to micropatterned neonatal mouse ventricular myocytes induced markedly greater acute transcriptional responses when the major axis of stretch was parallel to the myofilament axis than when it was transverse. Analysis with a novel quantitative network model of mechanoregulated cardiomyocyte gene expression suggests that this difference is explained by higher cell sensitivity to longitudinal loading than transverse loading than by the activation of differential signaling pathways.
A DFT and TD-DFT Study of Two Hydralazine Derivatives for Organic Solar Cells and Nonlinear Optical Applications
Authors: Tamighang Remi Nkeih , Ajifack Dodo Lydie , Tasheh Stanley Numbonui , Nkungli Nyiang Kennet , Tsapi Charly Tedjeuguim , Numbonui Ghogomu Julius
Published: December 2023

In recent years, organic molecules have been the subject of in-depth research studies using in silico methods for their applications in solar cells and photonic devices. This study reports a theoretical investigation of the organic solar cell (OSC) and nonlinear optical (NLO) properties of (E)-1-(phthalazin-1-yl)-1-[(pyridin-2-yl)ethylidene]hydralazine (PPEH) and 1-[2-(1-(pyridine-3- yl)ethylidene)hydrazinyl]phthalazine (PEHP). The density functional theory (DFT) and its time-dependent extension (TD-DFT) were employed with the B2PLYP, M06-2X, BP86, CAM-B3LYP, and

ω

B97-XD functionals, alongside the def2-tzvp and def2-tzvpp basis sets. Geometrical and Frontier molecular orbital (FMO) analyses were performed. Reactivity descriptors, open circuit voltage (Voc), energy driving force (∆EL−L), light harvesting efficiencies (LHEs), NLO susceptibilities, and properties were also computed and discussed. The results show that PEPH and PPEH are good electron donor materials for organic solar cells as they possess high FMO energies, Vocs, ∆EL−Ls, and LHEs. Moreover, both molecules have static first and second hyperpolarizabilities as well as dynamic NLO responses that are on average 10 times greater than those of para-nitroaniline. PEPH and PPEH also exhibit properties such as second harmonic generation (SHG), electro-optic Pockels effect (EOPE), electric field-induced second harmonic generation (EFISHG), and optical Kerr effect (OKE). Indeed, these molecules are potential candidates for organic solar cells and NLO applications. Findings from this work may further accelerate the synthesis and development of green energy materials for optical solar cells and NLO applications in the future.
Development of Effervescent Tablets Containing Elderberry Vine Tea Compound and Evaluation of Their Antioxidant Activity
Authors: Sun Wanhao
Published: December 2023

Elderberry and vine tea, renowned for their wealth of bioactive constituents and potent antioxidant prowess, hold remarkable promise within a wide array of culinary contexts. This study presents a pioneering advancement in the realm of compound effervescent tablet formulation. Employing the response surface design optimization, this work develops a formulation comprising a total disintegrant (acid-to-base ratio 1.3 : 1) at 50%, elderberry extracts at 31.7%, ultra-micro vine tea powder at 8.3%, stevioside at 3.4%, PEG-6000 at 2.7%, mannitol at 2.9%, and PVP at 1%. Under these carefully optimized conditions, the resultant tablet exhibits remarkable attributes including an average disintegration time of

184.50
±
4.65
 
s

, foaming quantity of

30.64
±
2.10
 
mg
/
g

, and tablet hardness measuring

54.59
±
3.41
 
N

, with a weight uniformity well within the ±5%. Regarding the antioxidant efficacy, the total flavonoid content attains

76.79
±
3.76
 
mg
 

RE/g, and phenolic content reaches

94.84
±
4.95
 
mg
 
GAE
/
g

. Moreover, the

E

C

50

values for scavenging 1,1-diphenyl-2-picrohydrazine (DPPH), hydroxyl (OH), and 2, 2

′

-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS) radicals are determined at 0.4667 mg/mL, 0.9772 mg/mL, and 0.5014 mg/mL, respectively. This investigation underscores the performance of the effervescent tablet in satisfying stringent physicochemical standards, while also showcasing outstanding antioxidant potency, paving the way for the advancement of antioxidant-functional foods and sustainable exploitation of natural resources.
The Effect of Telenursing on Disease Outcomes in People with Type 2 Diabetes Mellitus: A Narrative Review
Authors: AkbariRad Mina , Dehghani Mohsen , Sadeghi Masoumeh , Torshizian Ashkan , Saeedi Nikoo , Sarabi Mehrdad , Sahebi Mahdieh , Shakeri Mohammad Taghi
Published: December 2023

Background and Aim. Diabetes is the most common chronic metabolic disease worldwide, requiring life-term follow-up. Telenursing is a suitable method to provide care to people with type 2 diabetes mellitus (T2DM). The present review assessed the effect of telenursing compared to routine care on the outcomes of people with T2DM. Method. A comprehensive search of online databases, including PubMed, Scopus, Cochrane Library, and Google Scholar, was performed using the following MeSH keywords: telenursing, telephone follow-up, diabetes mellitus, disease management, glycemic, self-care, treatment adherence, and quality of life, up to September 2023. Two reviewers independently screened pertinent studies based on the prespecified outcomes (treatment adherence, self-care, glycemic control, and quality of life) and extracted data from all eligible studies. Results. Of all retrieved records, 23 studies including 5 quasiexperimental (21%) and 18 randomized controlled trials (RCTs) (79%) from five continents met the inclusion criteria. Both male and female patients were considered in the included studies, with mean age of 56.2 years old and a follow-up range of 12 weeks to 18 months. Findings showed that telenursing or nurse telephone follow-up significantly increased mean self-care efficacy score, improved adherence to the treatment regimen, decreased glycosylated hemoglobin and plasma glucose levels (but not lipid profile and body mass index), and improved quality of life compared to the routine care in people with T2DM. Conclusion. Telenursing can effectively supplement healthcare professionals to manage PWT2D. Increasing patients’ knowledge about their drugs, insulin administration, and diabetes complications improves self-care behaviors and medical adherence. Consistently, improved self-care and regular use of treatment result in improved metabolic indicators and decreased rate of complications, which is associated with a better quality of life.
Can Soil Compaction Alter Morphophysiological Responses and Soybean Yield under Application of Selective Herbicides?
Authors: Pereira Bruno César Silva , Ferreira Camila Jorge Bernabé , Braz Guilherme Braga Pereira , Souza Matheus de Freitas , Tavares Rose Luiza Moraes , Rosa Márcio , do Carmo Eduardo Lima , Vian Gabriel Henrique , Silva Ana Paula Sousa , Machado Fellipe Goulart
Published: December 2023

Compacted soils may be negatively affecting the selectivity of herbicides applied in preemergence in the soybean crop. Therefore, the present work aimed to investigate possible negative effects on the morphophysiological characters of soybean plants, as well as on the agronomic and yield performances of this crop. For this purpose, two trials were carried out, one in a greenhouse and the other under field conditions. In a greenhouse, the study was carried out in a completely randomized design in a 2 × 8 factorial, with five replications, while in the field, the design used was randomized blocks, with the treatments arranged in split-plot (2 × 8), with six repetitions. The first factor/plot corresponded to the physical condition of the soil: compacted or not compacted, while the second factor/subplot was constituted by the application of preemergence herbicides: clomazone, diclosulam, flumioxazin, S-metolachlor, [imazethapyr + flumioxazin], [pyroxasulfone + flumioxazin], and [sulfentrazone + diuron], plus a control without herbicide. In the greenhouse study, there was a significant interaction between soil compaction and herbicides applied in preemergence for the relative index of chlorophyll b and root dry mass. Furthermore, the isolated herbicide factor did not promote significant changes in any of the morphophysiological variables evaluated. Compaction alone had a negative impact on the variables relative index of chlorophyll a and carbon assimilation rate, with reductions in the values of these variables when the soybean was submitted to growth in compacted soil. For the field experiment, there were no significant interactions between the factors for any of the analyzed variables, nor the effect of herbicides alone. The isolated soil compaction factor negatively impacted the plant stand and the thousand-grain mass of soybean, showing reductions in the values of this parameter when the soybean was grown in compacted soil.
Surface Functionalization of Activated Carbon Cloth for Wastewater Perchlorate Adsorption-Integrated Molecular Modeling and Experimental Energy Analysis
Authors: Kuan Wei-Fan , Ahmad Muhammad Sheraz , Hsieh Chia-Hsun , Bhuyar Prakash , Wang Tsing-Hai , Ou Shu-Ching , Chen Ching-Lung
Published: December 2023

Perchlorate (ClO4-) in drinking water is one of the most serious issues relating to drinking water contamination. This work reports both the experimental and computational investigation of wastewater perchlorate adsorption on surfactant-modified activated carbon cloth (ACC) in order to design an efficient water treatment system. Three different types of cationic surfactants including tetramethylammonium (TMA), benzyltrimethylammonium (BTMA), and dodecyltrimethylammonium (DDTMA) were employed in this study, and the ClO4- adsorption capacity of various adsorbents was determined in batch experiments for 24 hours. Among all, DDTMA-ACC exhibits the highest ClO4- adsorption capacity (4.5 times that of pristine ACC), the highest monolayer coverage capacity (

Γ

max

) value (0.59 mmol/g), an equilibrium adsorption constant (

K

L

) value (35.90 L/mmol), and the lowest

Δ

G

ads

value (-26.0 KJ/mol), revealing that ClO4- has a stronger affinity for ACC functionalized by DDTMA than ACC functionalized by other surfactants. Molecular dynamics (MD) simulations were also conducted to illustrate the interactions among ClO4-, surfactants, and a model graphite surface underwater environment. The relative number density profiles and cumulative number studies demonstrate that TMA/BTMA tends to form single-layered packing near the graphite surface, while DDTMA prefers to pack in a multilayered fashion. The dense packing behavior of DDTMA on the graphite surface can enhance the ClO4- adsorption, showing good agreement with experimental results.
Properties of Carbonated Steel Slag Admixture in the Cementitious System
Authors: Sun Lie , Wang Hui , Wang Yali
Published: December 2023

Global warming caused by carbon dioxide (CO2) emissions has emerged as an undeniable environmental concern. While advocating for energy conservation and emissions reduction, the challenge of addressing the substantial CO2 emissions cannot be underestimated. Currently, steel slag is utilized in carbon capture and storage technology due to its potential for carbonation. However, the carbonation of steel slag necessitates a stable and cost-effective carbon source. Industrial exhaust gases are considered a viable option, but they often have low CO2 concentrations, resulting in sluggish carbonation rates. Therefore, this study focuses on directly converting steel slag powder into concrete mineral admixtures to enhance the carbonation rate at low CO2 concentrations. Experimental results reveal that a carbonation time of 3–7 days, a liquid–solid ratio of 50%, and the selection of sodium silicate as the alkali activator yield the optimal carbonation conditions. Under these conditions, the CO2 uptake can reach 15.3%–16.0%, and the f-CaO content can be reduced to 0.2%–0.3%. Mixing 30% carbonated steel slag powder with P·Ⅰ 42.5 cement in mortar samples yields a compressive strength of 32.1 MPa at 7 days and 47.5 MPa at 28 days, along with a flexural strength of 6.2 MPa at 7 days and 8.0 MPa at 28 days. The addition of carbonated steel slag powder not only enhances the mechanical properties but also reduces the pore diameter in the hardened cementitious system. In 7 days, the pore size decreases from being concentrated around 349 nm to approximately 282 nm, and in 28 days, the pore size decreases from being concentrated around 62 nm to roughly 55 nm. This transformation is primarily attributed to the role played by calcite grains in the carbonated steel slag powder, which facilitates nucleation and filling effects.
Multiple PAHs’ Detection under CDOM Interference Based on Excitation-Emission Matrix and Interval Selection
Authors: Li Ruizhuo , Gao Limin , Wu Guojun , Dong Jing
Published: December 2023

Fluorescence technology is an effective tool for detecting polycyclic aromatic hydrocarbons (PAHs) in water. However, the accuracy of fluorescence detection is reduced by the spectral overlap of different PAHs and coexisting colored dissolved organic matter (CDOM). In this study, a single-excitation interval selection method based on an excitation-emission matrix is proposed to quantify four PAHs: fluorene, pyrene, phenanthrene, and benzo(a)pyrene under CDOM interference. The optimal excitation wavelength for each PAH was obtained by stability analysis, based on which the optimal emission interval was obtained by chaotic particle swarm optimization. The partial least squares (PLS) prediction models of four PAHs under interference were established. On comparing with other modeling methods, the results show that the models with interval selection have better prediction accuracy (mean relative error < 10%) under CDOM interference. The recovery rate and limit of detection of the method were also evaluated. This study provides a new and helpful strategy for fluorescence detection of interfering PAHs in water.
Surgical Management of Latissimus Dorsi and Teres Major Tears in a Water-Skiing Injury: A Case Report and Literature Review
Authors: Constantinou Demitri , Kastanos Konstantinos
Published: December 2023

Tears of the latissimus dorsi and/or teres major tendons are uncommon, with no definitive management. Surgical repair has been reported in high-level athletes, mostly in baseball players. Simultaneous tears of both latissimus dorsi and teres major tendons are rare, with little known of surgical intervention outcomes. We report on the first published case of surgical repair of both latissimus dorsi and teres major tendon tears from a water-skiing injury in a 45-year-old male with favorable outcomes.
Non-Take-Up of Benefits and Rights: The Universality-Selectivity Debate as Reflected in Online Information and User Patterns
Authors: Elek-BenMoshe Frida , Rafaeli Sheizaf
Published: December 2023

The present study adds valuable perspective to the ongoing theoretical and practical universality-selectivity debate in the context of (non-) take-up of benefits by delving into the online information angle. People with a digital divide may be affected by such differences since they are more likely to need selective benefits. Almost all researchers agree that knowledge is a crucial barrier to benefits take-up. However, most researchers place the information barrier at the client level and do not examine factors contributing to information incomprehensibility. Is the effectiveness of universality- or selectivity-based welfare policies reflected in the online information? Our study examined this question by a computerized text analysis of 2662 online information pages in “Kol Zchut,” a primary Israeli information website about benefits and rights, and its Google Analytics usage pattern data. The results indicated weak but significant differences between universal and selective information pages. Information complexity was higher in selective information pages. The findings were more complicated regarding usage patterns. In order to understand more deeply the information side of rights take-up, future research is needed.
Table S5 from Statin-induced Mitochondrial Priming Sensitizes Multiple Myeloma Cells to BCL2 and MCL-1 Inhibitors
Authors: Juarez Dennis , Buono Roberta , Matulis Shannon M. , Gupta Vikas A. , Duong Madeleine , Yudiono Jacob , Paul Madhuri , Mallya Sharmila , Diep Grace , Hsin Peter , Lu Alexander , Suh Sang Mi , Dong Vy M. , Roberts Andrew W. , Leverson Joel D. , Jalaluddin Muhammad , Liu Zhuangzhuang , Bueno Orlando F. , Boise Lawrence H. , Fruman David A.
Published: December 2023

Supplementary Table S5 presents multivariate analysis of pooled clinical trial data on R/R MM patients achieving complete response (CR) or better – variables include statin use, t11;14 status, prior lines of therapy, cytogenetic risk.
Figure S9 from Statin-induced Mitochondrial Priming Sensitizes Multiple Myeloma Cells to BCL2 and MCL-1 Inhibitors
Authors: Juarez Dennis , Buono Roberta , Matulis Shannon M. , Gupta Vikas A. , Duong Madeleine , Yudiono Jacob , Paul Madhuri , Mallya Sharmila , Diep Grace , Hsin Peter , Lu Alexander , Suh Sang Mi , Dong Vy M. , Roberts Andrew W. , Leverson Joel D. , Jalaluddin Muhammad , Liu Zhuangzhuang , Bueno Orlando F. , Boise Lawrence H. , Fruman David A.
Published: December 2023

Supplementary Figure 9 contains data on L363 cells with PUMA (BBC3) knockout or inducible knockdown.
Figure S5 from Statin-induced Mitochondrial Priming Sensitizes Multiple Myeloma Cells to BCL2 and MCL-1 Inhibitors
Authors: Juarez Dennis , Buono Roberta , Matulis Shannon M. , Gupta Vikas A. , Duong Madeleine , Yudiono Jacob , Paul Madhuri , Mallya Sharmila , Diep Grace , Hsin Peter , Lu Alexander , Suh Sang Mi , Dong Vy M. , Roberts Andrew W. , Leverson Joel D. , Jalaluddin Muhammad , Liu Zhuangzhuang , Bueno Orlando F. , Boise Lawrence H. , Fruman David A.
Published: December 2023

Supplementary Figure 5 contains viability data and PUMA expression data from PBMCs
FIGURE 7 from Statin-induced Mitochondrial Priming Sensitizes Multiple Myeloma Cells to BCL2 and MCL-1 Inhibitors
Authors: Juarez Dennis , Buono Roberta , Matulis Shannon M. , Gupta Vikas A. , Duong Madeleine , Yudiono Jacob , Paul Madhuri , Mallya Sharmila , Diep Grace , Hsin Peter , Lu Alexander , Suh Sang Mi , Dong Vy M. , Roberts Andrew W. , Leverson Joel D. , Jalaluddin Muhammad , Liu Zhuangzhuang , Bueno Orlando F. , Boise Lawrence H. , Fruman David A.
Published: December 2023

Statins induce two independent responses in multiple myeloma. As observed in AML, DLBCL, and now multiple myeloma, statins upregulate PUMA in a p53-independent manner. PUMA can contribute to BH3 mimetic killing by promiscuously binding prosurvival BCL2 family members. Activation of the integrated stress response is a multiple myeloma–specific statin response that influences apoptosis. Through a currently undefined mechanism, statins reduced general translation and activate the translation of ATF4. ATF4 is a master mediator of the ISR. One such output of ATF4 is upregulation of NOXA. NOXA can be partially reduced with ISRIB which results in the partial rescue from statin-mediated apoptotic sensitization to venetoclax. The MCL-1 selective activity of NOXA promotes sensitivity to venetoclax. However, this property also makes it a direct competitor with S63845. As such, ISRIB did not rescue from S63845 and statin-mediated killing.
FIGURE 5 from Statin-induced Mitochondrial Priming Sensitizes Multiple Myeloma Cells to BCL2 and MCL-1 Inhibitors
Authors: Juarez Dennis , Buono Roberta , Matulis Shannon M. , Gupta Vikas A. , Duong Madeleine , Yudiono Jacob , Paul Madhuri , Mallya Sharmila , Diep Grace , Hsin Peter , Lu Alexander , Suh Sang Mi , Dong Vy M. , Roberts Andrew W. , Leverson Joel D. , Jalaluddin Muhammad , Liu Zhuangzhuang , Bueno Orlando F. , Boise Lawrence H. , Fruman David A.
Published: December 2023

Activation of stress pathways is induced by pitavastatin and the ISR inhibitor, ISRIB, partially rescues from statin-mediated sensitization of BH3 mimetics. A, ATF4 and stress activated factors were assessed across our panel of cell lines by Western blot analysis, including five statin sensitive, and two statin insensitive MMCL (RPMI-8226 and U266). B, Puromycin incorporation was measured by flow cytometry as a marker for active translation, and was assessed after 15 minutes of puromycin exposure. MMCLs were treated with 20 or 40 hours of pitavastatin or pitavastatin/ISRIB. Fifteen minutes prior to puromycin exposure, control wells were treated with sodium arsenite (NaArs), NaArs/ISRIB, or cycloheximide. MFI of cycloheximide-treated cells served as background fluorescence and was subtracted from the MFI of all other samples. Data are presented relative to vehicle treated cells. Significance of ISRIB rescue was determined by one-way ANOVA and multiple comparisons were corrected by Holm-Sidak multiple comparisons test, *, P < 0.05; **, P < 0.01; ***, P < 0.001. C, AnnexinV-PI viability assays of L363 and OPM2. ISRIB rescues from the apoptosis induced by venetoclax and pitavastatin in L363 and OPM2, n = 3. D, Western blot analysis of ATF4 upregulation induced by pitavastatin after 16 or 40 hours for the purpose of assessing the effect of AMG-PERK44 (PERKi) in L363, OPM2, and NCI-H929. Upregulation of ATF4 is delayed in L363 relative to the t(4;14) MMCLs, OPM2 and NCI-H929, consistent with puromycin incorporation results. PERK inhibition blocks ATF4 upregulation in L363, but not OPM2 and NCI-H929.
Diagnostic Precision or Pitfalls: How to Apply the New Acute Myeloid Leukemia Classification Systems?
Authors: Carlson Karen-Sue , Cunningham Ashley , Stahl Maximilian , Winer Eric , Michaelis Laura C.
Published: December 2023

Background: The classification of acute myeloid leukemia (AML) has long been overseen by the World Health Organization (WHO) and published into a series of “Blue Books.” These ledgers serve as the reference manual for AML classification and, in turn, classification-based treatment decisions. In 2022, two separate groups, each of which included hematologic oncologists, hematopathologists, and geneticists – developed and published two parallel classification systems for AML. One is from the WHO (WHO 5th edition), and a second is from an International Advisory Consortium (International Consortium Classification [ICC]). Summary: Both modern classification systems originated from the revised 4th edition of the WHO Blue Books and thus share many similarities. There are never-the-less several important differences with the potential to substantially alter disease classification, access to clinical trials, and treatment decision-making. In this manuscript, we review the organization of the WHO and ICC classification systems for AML with emphasis on their similarities and differences, followed by areas in which their application to clinical scenarios may present difficulties. Key Messages: (1) The ICC and WHO 5th edition are concordant for the majority of AMLs. (2) Key differences between AML classification by the ICC and WHO 5th edition include (a) the overall framework of classification, (b) AML-defining blast threshold, definition of myelodysplasia-related AML, and (c) strategy for assigning therapy-related or germline-associated AML modifiers.
Orangutan (Pongo pygmaeus ssp. wurmbii) ranging pattern in Punggualas, Sebangau National Park, Central Kalimantan Indonesia
Authors: Panda Adventus , Meididit Ari , Simon Okta , Artama Wayan Tunas , Priyowidodo Dwi , Djohan Tjut Sugandawaty
Published: December 2023

Punggualas lies in the western part of Sebangau National Park (SNP). It is a logged-over forest, yet it is one of the major strongholds for the P. p. wurmbii population in the SNP. The range size, as well as the ranging pattern for Punggualas, has never been conducted. The study aimed to estimate orangutan ranging size and pattern as well as their distribution over the Punggualas forest. Ranging data within the area of interest (AOI) was collected from Feb 2015 – Dec 2019 (P1), and Mar 2020 – May 2022 (P2). Minimum convex polygon (MCP), range size of orangutan individual was calculated using adehabitatHR package in RStudio 4.1.1 for Windows. We visualized the distribution in ArcGIS 10.5 with Kernel Density (KD) tool.   The range size of Mother-Infant is the greatest (259,6 Ha) among all individuals being studied within the study periods. Moreover, the size estimation was found greater in Mother-Infant sex class compared to other orangutan studies areas, such as Peat Natural Laboratory, and CIMTROP-UPR which reported a flanged male HR Size reaching 250 Ha per annum. We have found that the ranging pattern significantly changes over the study period. However, during P1, the distribution area was located within the northern of AOI, while in the P2 have changed to the south-eastern part of the AOI.  We concluded that the ranging pattern indeed follows the fruit availability as well as fine-scale habitat quality.
Disordered Balance of T‐Cell Subsets in Arterial Tertiary Lymphoid Organs in Immunoglobulin G4–Related Vascular Disease
Authors: Kasashima Satomi , Kawashima Atsuhiro , Kurose Nozomu , Ozaki Satoru , Kasashima Fuminori , Matsumoto Yasushi , Takemura Hirofumi , Ikeda Hiroko , Harada Ken‐ichi
Published: December 2023

Background

Arterial/aortic tertiary lymphoid organs (ATLOs), characterized by germinal centers, control local arterial immune responses. T follicular helper cells (Tfh), resident in germinal centers, regulate immunoglobulin production and germinal center development. They consist of Tfh1, Tfh2, and Tfh17 subsets. T follicular regulatory (Tfr) cells possess suppressive functions as regulatory T cells and migrate into germinal centers. Immunoglobulin G4 (IgG4)–related diseases manifest in vascular lesions as frequently formed inflammatory aneurysms (IgG4‐related abdominal aortic aneurysm [IgG4‐AAAs]). IgG4‐AAAs contain several ATLOs.

Methods and Results

We performed whole‐slide immunohistochemical image analysis in surgical specimens of IgG4‐AAAs (n=21), non–IgG4‐related inflammatory AAAs (n=17), atherosclerotic AAAs (n=10), and Takayasu arteritis (n=5). IgG4‐AAA was characterized by numerous, large, irregular‐shaped ATLOs, and higher numbers of Tfr and Tfh2 cells than Tfh1 cells were present compared with others. The morphologic abnormalities (in number, area, and form) of ATLOs in IgG4‐AAAs and the increased number of Tfr cells are closely related to the activity of IgG4‐related diseases. All T‐cell subsets were more enriched within ATLOs than outside ATLOs. In particular, an increase in Tfr cells in IgG4‐AAAs was associated with ATLO formation. Increased Tfh17 cells were found in Takayasu arteritis, and atherosclerotic AAA and non–IgG4‐related inflammatory AAAs were characterized by increased Tfh1 cells.

Conclusions

In the classification of vascular lesions, considering the imbalance in T‐cell subsets, IgG4‐AAA should be positioned as adventitial vasculitis with predominant Tfr and Tfh2 cells, accompanied by the abnormal appearance of ATLOs.
Associations Between Life's Essential 8 and Abdominal Aortic Calcification Among Middle‐Aged and Elderly Populations
Authors: Cai Zongao , Liu Zaoqu , Zhang Yuyuan , Ma Hongxuan , Li Ruihui , Guo Shuang , Wu Shiyong , Guo Xueli
Published: December 2023

Background

Abdominal aortic calcification (AAC) is an independent risk factor for cardiovascular disease. We aim to examine the associations between Life's Essential 8 (LE8), the recently updated measurement of cardiovascular health (CVH), and AAC among participants aged ≥40 years.

Methods and Results

This population‐based cross‐sectional study used data from the National Health and Nutrition Examination Survey in 2013 to 2014. AAC (AAC score>0) and severe AAC (AAC score>6) were quantified by the Kauppila score system. Multiple linear, multivariable logistic, and restricted cubic spline models were used to assess the associations. A total of 2369 participants were included with a mean AAC score of 1.41 (0.13). Participants in the high‐cardiovascular‐health group had lower AAC scores, lower prevalence of AAC, and lower prevalence of severe AAC. After the adjustment of potential confounders (age, sex, race and ethnicity, education levels, marital status, poverty income ratio, estimated glomerular filtration rate, serum creatinine, serum uric acid, serum phosphorus, and serum total calcium), higher cardiovascular health was significantly associated with lower risk of AAC. Meanwhile, elevated nicotine exposure score, blood glucose score, and blood pressure score within the LE8 components were significantly associated with lower risk of AAC. Also, nonlinear dose–response relationships were observed. Subgroup analyses (age strata, sex, poverty income ratio, education levels, marital status) indicated the inverse associations of LE8 and AAC were generally similar in different populations.

Conclusions

LE8 was negatively and nonlinearly related to the risk of AAC among middle‐aged and older populations. Meanwhile, LE8 components should prioritize higher scores for nicotine exposure, blood glucose, and blood pressure evaluations.
Critical Analysis of Thrombocytopenia Associated With Glycoprotein IIb/IIIa Inhibitors and Potential Role of Zalunfiban, a Novel Small Molecule Glycoprotein Inhibitor, in Understanding the Mechanism(s)
Authors: Rikken Sem A. O. F. , van 't Hof Arnoud W. J. , ten Berg Jurriën M. , Kereiakes Dean J. , Coller Barry S.
Published: December 2023

Thrombocytopenia is a rare but serious complication of the intravenous glycoprotein IIb/IIIa (GPIIb/IIIa; integrin αIIbβ3) receptor inhibitors (GPIs), abciximab, eptifibatide, and tirofiban. The thrombocytopenia ranges from mild (50 000–100 000 platelets/μL), to severe (20 000 to <50 000/μL), to profound (<20 000/μL). Profound thrombocytopenia appears to occur in <1% of patients receiving their first course of therapy. Thrombocytopenia can be either acute (<24 hours) or delayed (up to ~14 days). Both hemorrhagic and thrombotic complications have been reported in association with thrombocytopenia. Diagnosis requires exclusion of pseudothrombocytopenia and heparin‐induced thrombocytopenia. Therapy based on the severity of thrombocytopenia and symptoms may include drug withdrawals and treatment with steroids, intravenous IgG, and platelet transfusions. Abciximab‐associated thrombocytopenia is most common and due to either preformed antibodies or antibodies induced in response to abciximab (delayed). Readministration of abciximab is associated with increased risk of thrombocytopenia. Evidence also supports an immune basis for thrombocytopenia associated with the 2 small molecule GPIs. The latter bind αIIbβ3 like the natural ligands and thus induce the receptor to undergo major conformational changes that potentially create neoepitopes. Thrombocytopenia associated with these drugs is also immune‐mediated, with antibodies recognizing the αIIbβ3 receptor only in the presence of the drug. It is unclear whether the antibody binding depends on the conformational change and whether the drug contributes directly to the epitope. Zalunfiban, a second‐generation subcutaneous small molecule GPI, does not induce the conformational changes; therefore, data from studies of zalunfiban will provide information on the contribution of the conformational changes to the development of GPI‐associated thrombocytopenia.
Cumulative Blood Pressure in Early Adulthood and Coronary Artery Calcium and Carotid Intima‐Media Thickness in Middle Age Among Adults With Maintained Blood Pressure of <130/80 mm Hg: A Post Hoc Analysis
Authors: Masrouri Soroush , Afaghi Siamak , Khalili Davood , Shapiro Michael D. , Hadaegh Farzad
Published: December 2023

Background

To examine the association of blood pressure (BP) levels with coronary artery calcium and carotid intima‐media thickness (CIMT) in people with maintained BP below the hypertension range based on current definitions.

Methods and Results

In this post hoc analysis of the CARDIA (Coronary Artery Risk Development in Young Adults) prospective observational cohort study conducted in 4 US cities, we examined 1233 study participants (mean [SD] age at year 20 examination was 45.3 [3.5] years; 65.4% women). Participants with BP assessments across 20 years and untreated BP of <130/80 mm Hg were included. Multivariable logistic or linear regression models, adjusted for age, sex, race, education, diabetes, body mass index, serum creatinine, smoking, alcohol intake, physical activity, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, and triglycerides, were used to examine the associations between cumulative BP measures with coronary artery calcium and CIMT. Higher long‐term cumulative systolic BP and pulse pressure across early adulthood were associated with higher CIMT (both
P
<0.001) but not coronary artery calcium in the multivariable‐adjusted model. The associations remained significant even after adjustment for a single BP measurement at year 0 or year 20. The odds ratio (OR) of a maximal CIMT >1.01 mm was ≈50% higher per 1‐SD increase in systolic BP (OR, 1.50 [95% CI, 1.19–1.88]) and pulse pressure (OR, 1.46 [95% CI, 1.19–1.79]). Similar findings for CIMT were observed among individuals with a coronary artery calcium score of 0 as well as those with maintained BP of <120/80 mm Hg throughout young adulthood.

Conclusions

Long‐term cumulative systolic BP and pulse pressure across early adulthood within the nonhypertensive range were associated with adverse midlife alterations in CIMT.
The Role of Translation in Enacting Multiscalar Climate Action: Insights from European Christian Faith-Based Actors
Authors: van Veelen Bregje , Hague Alice
Published: December 2023

The complex nature of climate change requires action at different scales and in different ways, but questions remain around how to produce climate action that is both multiscalar and joined up. Here we explore this question by adopting a relational approach to studying climate action by faith-based actors, who increasingly play an active role campaigning on climate action. Drawing on qualitative fieldwork with representatives of Christian churches in Sweden, Belgium, Scotland, and England, we identify two interrelated processes that explain how climate action “travels”: first, through horizontal circulation (between faith-based and non-faith-based spheres), and second, through vertical circulation (across individual, local, national, and international levels). However, such processes are not without friction. We demonstrate how processes of “translation” can ensure the integration of climate action into new contexts and result in producing new scalar relations but also exclusions. In doing so, we advance understandings of how multiscalar climate action is produced by nonstate actors.
Induced Innovation and International Environmental Agreements: Evidence from the Ozone Regime
Authors: Dugoua Eugenie
Published: December 2023

This paper revisits one of the rare success stories in global environmental cooperation: the Montreal Protocol and the phase-out of ozone-depleting substances. I show that the protocol increased science and innovation on alternatives to ozone-depleting substances and argue that agreements can indeed be useful in solving global public goods problems. This contrasts with game-theoretical predictions that agreements occur only when costs to the players are low and with the often-heard narrative that substitutes were readily available. I reconcile theory and empirics by discussing the role of induced innovation in models of environmental agreements.
Human Capital and the Managerial Revolution in the United States: Evidence from General Electric
Authors: Nicholas Tom
Published: December 2023

This paper estimates the returns to human capital accumulation during the first era of mega-firms in the United States by linking employees at General Electric—a canonical enterprise associated with the “visible hand” of managerial hierarchies—to the 1940 census. I find large returns to higher education through seniority in the hierarchy, span of control, earnings, and selection into management training, using the proximity of land-grant colleges and historical universities to birth states for identification. The findings highlight the human capital determinants of the managerial revolution at a prominent firm, driven by earlier public investments in the US education system.
How Flexible Is That Functional Form? Quantifying the Restrictiveness of Theories
Authors: Fudenberg Drew , Gao Wayne , Liang Annie
Published: December 2023

We propose a restrictiveness measure for economic models based on how well they fit pre-defined synthetic data. This measure, together with a measure for how well the model fits real data, outlines a Pareto frontier, where models that rule out more regularities, yet capture the regularities that are present in real data, are preferred. To illustrate our approach, we evaluate the restrictiveness of models in two laboratory settings—certainty equivalents and initial play—and one field setting—takeup of microfinance in Indian villages. The restrictiveness measure reveals insights about each, including that some economic models with only a few parameters are very flexible.
The Loss of the Greek Literary Society in Constantinople: The Dismantling of an Institution, Displacement of a Library, and Dissolution of an Intellectual Hub
Authors: Sümertaş Firuzan Melike
Published: December 2023

The conditions that paved the way for the population exchange, the unrest created by rising nationalism in Turkey and Greece, and the subsequent search for a homogeneous population on both sides of the Aegean had a direct impact on Istanbul’s intellectual environment, its artistic and literary production, and its architecture, in which Greeks had played a significant role. This article examines the main physical and intellectual properties of the Greek Literary Society in Constantinople, its headquarters in Pera, its library and archive, and their afterlives following their confiscation by Turkish officials. By focusing on the effects of the departure of renowned scholars from Istanbul, particularly those who had conducted archeological research, it discusses the extent of the knowledge and property accumulated within the Greek Literary Society’s circles and evaluates their loss, transportation, and transformation as “cultural (material and human) and social capital” and “brain drain.”