bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fibroblasts in the Aged Pancreas Drive Pancreatic Cancer Progression
Authors: Zabransky Daniel J. , Chhabra Yash , Fane Mitchell E. , Kartalia Emma , Leatherman James M. , Hüser Laura , Zimmerman Jacquelyn W. , Delitto Daniel , Han Song , Armstrong Todd D. , Charmsaz Soren , Guinn Samantha , Pramod Sneha , Thompson Elizabeth D. , Hughes Steven J. , O'Connell Jennifer , Egan Josephine M. , Jaffee Elizabeth M. , Weeraratna Ashani T. 
Published: February 2024

Abstract

Pancreatic cancer is more prevalent in older individuals and often carries a poorer prognosis for them. The relationship between the microenvironment and pancreatic cancer is multifactorial, and age-related changes in nonmalignant cells in the tumor microenvironment may play a key role in promoting cancer aggressiveness. Because fibroblasts have profound impacts on pancreatic cancer progression, we investigated whether age-related changes in pancreatic fibroblasts influence cancer growth and metastasis. Proteomics analysis revealed that aged fibroblasts secrete different factors than young fibroblasts, including increased growth/differentiation factor 15 (GDF-15). Treating young mice with GDF-15 enhanced tumor growth, whereas aged GDF-15 knockout mice showed reduced tumor growth. GDF-15 activated AKT, rendering tumors sensitive to AKT inhibition in an aged but not young microenvironment. These data provide evidence for how aging alters pancreatic fibroblasts and promotes tumor progression, providing potential therapeutic targets and avenues for studying pancreatic cancer while accounting for the effects of aging.

Significance:
Aged pancreatic fibroblasts secrete GDF-15 and activate AKT signaling to promote pancreatic cancer growth, highlighting the critical role of aging-mediated changes in the pancreatic cancer microenvironment in driving tumor progression.
See related commentary by Isaacson et al., p. 1185
Identification and Characterization of a Small Molecule Bcl-2 Functional Converter
Authors: Kopparapu Prasad R. , Pearce Martin C. , Löhr Christiane V. , Duong Cathy , Jang Hyo Sang , Tyavanagimatt Shanthakumar , O'Donnell Edmond F. , Nakshatri Harikrishna , Kolluri Siva K. 
Published: February 2024

Abstract

Cancer cells exploit the expression of anti-apoptotic protein Bcl-2 to evade apoptosis and develop resistance to therapeutics. High levels of Bcl-2 leads to sequestration of pro-apoptotic proteins causing the apoptotic machinery to halt. In this study, we report discovery of a small molecule, BFC1108 (5-chloro-N-(2-ethoxyphenyl)-2-[(4-methoxybenzyol)amino]benzamide), which targets Bcl-2 and converts it into a pro-apoptotic protein. The apoptotic effect of BFC1108 is not inhibited, but rather potentiated, by Bcl-2 overexpression. BFC1108 induces a conformational change in Bcl-2, resulting in the exposure of its BH3 domain both in vitro and in vivo. BFC1108 suppresses the growth of triple-negative breast cancer xenografts with high Bcl-2 expression and inhibits breast cancer lung metastasis. This study demonstrates a novel approach to targeting Bcl-2 using BFC1108, a small molecule Bcl-2 functional converter that effectively induces apoptosis in Bcl-2–expressing cancers.

Significance:
We report the identification of a small molecule that exposes the Bcl-2 killer conformation and induces death in Bcl-2–expressing cancer cells. Selective targeting of Bcl-2 and elimination of cancer cells expressing Bcl-2 opens up new therapeutic avenues.
Plasma S1P Orchestrates the Reverse Transendothelial Migration of Aortic Intimal Myeloid Cells in Mice
Authors: Polenz Chanele K. , Scipione Corey A. , Hyduk Sharon J. , Althagafi Marwan G. , Ibrahim Hisham M. , Cybulsky Myron I. 
Published: February 2024

BACKGROUND:
Myeloid cells (MCs) reside in the aortic intima at regions predisposed to atherosclerosis. Systemic inflammation triggers reverse transendothelial migration (RTM) of intimal MCs into the arterial blood, which orchestrates a protective immune response that clears intracellular pathogens from the arterial intima. Molecular pathways that regulate RTM remain poorly understood. S1P (sphingosine-1-phosphate) is a lipid mediator that regulates immune cell trafficking by signaling via 5 G-protein–coupled receptors (S1PRs [S1P receptors]). We investigated the role of S1P in the RTM of aortic intimal MCs.

METHODS:

Intravenous injection of lipopolysaccharide was used to model a systemic inflammatory stimulus that triggers RTM. CD11c
+
intimal MCs in the lesser curvature of the ascending aortic arch were enumerated by en face confocal microscopy. Local gene expression was evaluated by transcriptomic analysis of microdissected intimal cells.

RESULTS:

In wild-type C57BL/6 mice, lipopolysaccharide induced intimal cell expression of
S1pr1
,
S1pr3
, and
Sphk1
(a kinase responsible for S1P production). Pharmacological modulation of multiple S1PRs blocked lipopolysaccharide-induced RTM and modulation of S1PR1 and S1PR3 reduced RTM in an additive manner. Cre-mediated deletion of
S1pr1
in MCs blocked lipopolysaccharide-induced RTM, confirming a role for myeloid-specific S1PR1 signaling. Global or hematopoietic deficiency of
Sphk1
reduced plasma S1P levels, the abundance of CD11c
+
MCs in the aortic intima, and blunted lipopolysaccharide-induced RTM. In contrast, plasma S1P levels, the abundance of intimal MCs, and lipopolysaccharide-induced RTM were rescued in

Sphk1
−/−

mice transplanted with
Sphk1

+/+

or mixed
Sphk1

+/+

and

Sphk1
−/−

bone marrow. Stimulation with lipopolysaccharide increased endothelial permeability and intimal MC exposure to circulating factors such as S1P.

CONCLUSIONS:
Functional and expression studies support a novel role for S1P signaling in the regulation of lipopolysaccharide-induced RTM and the homeostatic maintenance of aortic intimal MCs. Our data provide insight into how circulating plasma mediators help orchestrate intimal MC dynamics.
Neighborhood Disadvantage and Risk of Heart Failure: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Malla Gargya , Long D. Leann , Cherrington Andrea , Goyal Parag , Guo Boyi , Safford Monika M. , Khodneva Yulia , Cummings Doyle M. , McAlexander Tara P. , DeSilva Shanika , Judd Suzanne E. , Hidalgo Bertha , Levitan Emily B. , Carson April P. 
Published: February 2024

BACKGROUND:
Heart failure (HF) affects >6 million US adults, with recent increases in HF hospitalizations. We aimed to investigate the association between neighborhood disadvantage and incident HF events and potential differences by diabetes status.

METHODS:

We included 23 645 participants from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke), a prospective cohort of Black and White adults aged ≥45 years living in the continental United States (baseline 2005–2007). Neighborhood disadvantage was assessed using a
Z
score of 6 census tract variables (2000 US Census) and categorized as quartiles. Incident HF hospitalizations or HF-related deaths through 2017 were adjudicated. Multivariable-adjusted Cox regression was used to examine the association between neighborhood disadvantage and incident HF. Heterogeneity by diabetes was assessed using an interaction term.

RESULTS:

The mean age was 64.4 years, 39.5% were Black adults, 54.9% females, and 18.8% had diabetes. During a median follow-up of 10.7 years, there were 1125 incident HF events with an incidence rate of 3.3 (quartile 1), 4.7 (quartile 2), 5.2 (quartile 3), and 6.0 (quartile 4) per 1000 person-years. Compared to adults living in the most advantaged neighborhoods (quartile 1), those living in neighborhoods in quartiles 2, 3, and 4 (most disadvantaged) had 1.30 (95% CI, 1.06–1.60), 1.36 (95% CI, 1.11–1.66), and 1.45 (95% CI, 1.18–1.79) times greater hazard of incident HF even after accounting for known confounders. This association did not significantly differ by diabetes status (interaction
P
=0.59). For adults with diabetes, the adjusted incident HF hazards comparing those in quartile 4 versus quartile 1 was 1.34 (95% CI, 0.92–1.96), and it was 1.50 (95% CI, 1.16–1.94) for adults without diabetes.

CONCLUSIONS:
In this large contemporaneous prospective cohort, neighborhood disadvantage was associated with an increased risk of incident HF events. This increase in HF risk did not differ by diabetes status. Addressing social, economic, and structural factors at the neighborhood level may impact HF prevention.
Cost of Cardiovascular Disease Event and Cardiovascular Disease Treatment–Related Complication Hospitalizations in the United States
Authors: Tajeu Gabriel S. , Ruiz-Negrón Natalia , Moran Andrew E. , Zhang Zugui , Kolm Paul , Weintraub William S. , Bress Adam P. , Bellows Brandon K. 
Published: February 2024

BACKGROUND:
Cardiovascular disease (CVD) is among the costliest conditions in the United States, and cost-effectiveness analyses can be used to assess economic impact and prioritize CVD treatments. We aimed to develop standardized, nationally representative CVD events and selected possible CVD treatment–related complication hospitalization costs for use in cost-effectiveness analyses.

METHODS:

Nationally representative costs were derived using publicly available inpatient hospital discharge data from the 2012-2018 National Inpatient Sample. Events were identified using the principal
International Classification of Diseases
,
Ninth Revision
and
International Classification of Diseases
,
Tenth Revision
codes. Facility charges were converted to costs using charge-to-cost ratios, and total costs were estimated by applying a published professional fee ratio. All costs are reported in 2021 US dollars. Mean costs were estimated for events overall and stratified by age, sex, and survival status at discharge. Annual costs to the US health care system were estimated by multiplying the mean annual number of events by the mean total cost per discharge.

RESULTS:
The annual mean number of hospital discharges among CVD events was the highest for heart failure (1 087 000 per year) and cerebrovascular disease (800 600 per year). The mean cost per hospital discharge was the highest for peripheral vascular disease ($33 700 [95% CI, $33 300–$34 000]) and ventricular tachycardia/ventricular fibrillation ($32 500 [95% CI, $32 100–$32 900]). Hospitalizations contributing the most to annual US health care costs were heart failure ($19 500 [95% CI, $19 300–$19 800] million) and acute myocardial infarction ($18 300, [95% CI, $18 200–$18 500] million). Acute kidney injury was the most frequent possible treatment complication (515 000 per year), and bradycardia had the highest mean hospitalization costs ($17 400 [95% CI, $17 200–$17 500]).

CONCLUSIONS:
The hospitalization cost estimates and statistical code reported in the current study have the potential to increase transparency and comparability of cost-effectiveness analyses for CVD in the United States.
Safety and Effectiveness of the High-Sensitivity Cardiac Troponin HEART Pathway in Patients With Possible Acute Coronary Syndrome
Authors: Mahler Simon A. , Ashburn Nicklaus P. , Paradee Brennan E. , Stopyra Jason P. , O’Neill James C. , Snavely Anna C. 
Published: February 2024

BACKGROUND:
The HEART Pathway (History, Electrocardiogram, Age, Risk factors, Troponin) can be used with high-sensitivity cardiac troponin to risk stratify emergency department patients with possible acute coronary syndrome. However, data on whether a high-sensitivity HEART Pathway (hs-HP) are safe and effective is lacking.

METHODS:

An interrupted time series study was conducted at 5 North Carolina sites in 26 126 adult emergency department patients being investigated for possible acute coronary syndrome and without ST-segment–elevation myocardial infarction. Patients were accrued into 16-month preimplementation and postimplementation cohorts with a 6-month wash-in phase. Preimplementation (January 2019 to April 2020), the traditional HEART Pathway was used with 0- and 3-hour contemporary troponin measures (Siemens). In the postimplementation period (November 2020 to February 2022), a modified hs-HP was used with 0- and 2-hour high-sensitivity cardiac troponin (Beckman Coulter) measures. The primary safety and effectiveness outcomes were 30-day all-cause death or myocardial infarction and 30-day hospitalizations. These outcomes and early discharge rate (emergency department discharge without stress testing or coronary angiography) were determined from health records and death index data. Outcomes were compared preimplementation versus postimplementation using χ
2
tests and multivariable logistic regression to adjust for potential confounders.

RESULTS:

Preimplementation and postimplementation cohorts included 12 317 and 13 809 patients, respectively, of them 52.7% (13 767/26 126) were female with a median age of 54 years (interquartile range, 42–66). Rates of 30-day death or MI were 6.8% (945/13 809) postimplementation and 7.7% (948/12 317) preimplementation (adjusted odds ratio, 1.00 [95% CI, 0.90–1.11]). hs-HP implementation was associated with 19.9% (95% CI, 18.7%–21.1%) higher early discharges (post versus pre: 63.6% versus 43.7%; adjusted odds ratio, 2.22 [95% CI, 2.10–2.35]). The hs-HP was also associated with 16.1% (95% CI, 14.9%–17.3%) lower 30-day hospitalizations (postimplementation versus preimplementation, 31.4% versus 47.5%; adjusted odds ratio, 0.51 [95% CI, 0.48–0.54]). Among early discharge patients, death or myocardial infarction occurred in 0.5% (41/8780) postimplementation versus 0.4% (22/5383) preimplementation (
P
=0.61).

CONCLUSIONS:
hs-HP implementation is associated with increased early discharges without increasing adverse events. These findings support the use of a modified hs-HP to improve chest pain care.
Alpha Oscillations and Temporal Binding Windows in Perception—A Critical Review and Best Practice Guidelines
Authors: Schoffelen Jan-Mathijs , Pesci Ugo Giulio , Noppeney Uta 
Published: February 2024

Abstract
An intriguing question in cognitive neuroscience is whether alpha oscillations shape how the brain transforms the continuous sensory inputs into distinct percepts. According to the alpha temporal resolution hypothesis, sensory signals arriving within a single alpha cycle are integrated, whereas those in separate cycles are segregated. Consequently, shorter alpha cycles should be associated with smaller temporal binding windows and higher temporal resolution. However, the evidence supporting this hypothesis is contentious, and the neural mechanisms remain unclear. In this review, we first elucidate the alpha temporal resolution hypothesis and the neural circuitries that generate alpha oscillations. We then critically evaluate study designs, experimental paradigms, psychophysics, and neurophysiological analyses that have been employed to investigate the role of alpha frequency in temporal binding. Through the lens of this methodological framework, we then review evidence from between-subject, within-subject, and causal perturbation studies. Our review highlights the inherent interpretational ambiguities posed by previous study designs and experimental paradigms and the extensive variability in analysis choices across studies. We also suggest best practice recommendations that may help to guide future research. To establish a mechanistic role of alpha frequency in temporal parsing, future research is needed that demonstrates its causal effects on the temporal binding window with consistent, experimenter-independent methods.
Completeness degree of publication metadata in eight free-access scholarly databases
Authors: Delgado-Quirós Lorena , Ortega José Luis 
Published: February 2024

Abstract
The main objective of this study is to compare the amount of metadata and the completeness degree of research publications in new academic databases. Using a quantitative approach, we selected a random Crossref sample of more than 115,000 records, which was then searched in seven databases (Dimensions, Google Scholar, Microsoft Academic, OpenAlex, Scilit, Semantic Scholar, and The Lens). Seven characteristics were analyzed (abstract, access, bibliographic info, document type, publication date, language, and identifiers), to observe fields that describe this information, the completeness rate of these fields, and the agreement among databases. The results show that academic search engines (Google Scholar, Microsoft Academic, and Semantic Scholar) gather less information and have a low degree of completeness. Conversely, third-party databases (Dimensions, OpenAlex, Scilit, and The Lens) have more metadata quality and a higher completeness rate. We conclude that academic search engines lack the ability to retrieve reliable descriptive data by crawling the web, and the main problem of third-party databases is the loss of information derived from integrating different sources.
New Directions for Thinking about the Bible and Nonhuman Animals: A Review of Works by Peter Atkins, Dong Hyeon Jeong, and Saul Olyan
Authors: Millar Suzanna 
Published: February 2024

Abstract
Three new monographs have appeared in 2023 that explore the Bible and nonhuman animals: Peter Joshua Atkins, The Animalising Affliction of Nebuchadnezzar in Daniel 4: Reading Across the Human-Animal Boundary (London: T&T Clark, 2023; pp. xiv + 260); Dong Hyeon Jeong, Embracing the Nonhuman in the Gospel of Mark (Atlanta: SBL Press, 2023; pp. xii+177); Saul M. Olyan, Animal Rights and the Hebrew Bible (New York: OUP, 2023; pp. xii+144). This review brings these books into conversation, suggesting six questions that they grapple with and which might stimulate further research.
Making of the Hindu Nation, Masculinity and the Citizen – Critical Reading of Children’s Magazines in South Asia and the Place of Muslims
Authors: Noorunnida M. 
Published: February 2024

Abstract
This study critically analyses popular and children’s science magazines published in Kerala, a southern state of India. It examines how these magazines construct an ideal Hindu nation and citizen through different narratives. Here, I argue that the imagery of popular children’s magazines in Kerala is rooted in the Hindu ideal – wherein dominant masculine characters and a glorified Hindu cultural past are foregrounded. In these magazines, the idealisation of Hindu masculinity takes place through presenting Muslims as less progressive / incapable of acquiring “modern standards”. In this context, the Hindu emerges as a reformer who helps the Muslim to “acquire modernity”. Also, children’s science magazines view science as a means for liberation from religion and irrational beliefs through critiquing “irrational” stories in popular Malayalam children’s magazines. But a close examination of science magazines reveals that it is embedded in the very religious ideologies from which it is seeking liberation.
The Problem of Evil in the Early Modern Ottoman Period: ʿAbd al-Ghanī al-Nābulusī’s Synthetic Metaphysics of Faith and Disbelief
Authors: Kawanishi Hiroaki 
Published: February 2024

Abstract
The early modern Muslim world witnessed unparalleled development in theological discussion, of which the problem of evil is a part. This paper aims to uncover a new discourse on the problem of evil in the Ottoman period, by examining the eleventh/ seventeenth-century polymath ʿAbd al-Ghanī al-Nābulusī’s (d. 1143/1731) synthetic theology of evil. More specifically, the study will analyze the way al-Nābulusī discusses the issue of faith (īmān) and disbelief (kufr) in his Ashʿarī kalām and Akbarian Sufism. Looking first at al-Nābulusī’s kalām metaphysics of īmān and kufr and then his mystical metaphysics, the paper corroborates how between the two sciences, there is a coherent logic in al-Nābulusī’s concordia theology.
Engage, educate, escape: The New Jersey Department of Health Project Firstline Escape Room
Authors: McLaughlin Kelly , Davis Jasmine , Gonzales Miriam , Koh Celina , Taylor Laura , Crowell Tara L 
Published: February 2024

Objective: Participating in an escape room is not just an entertainment but can also be a form of education. Because of this, the New Jersey Department of Health (NJDOH), Project Firstline (PFL) created an escape room interactive training tool and skills-building exercise to encourage the identification and use of key infection control principles by current and future healthcare workers. Design and Setting: PFL is a US initiative that aims to provide infection prevention and control (IPC) knowledge to frontline healthcare workers. This article details health educators’ descriptions and experiences of an escape room developed as part of this initiative; guidance on how to incorporate this modality of learning into present and future teaching; and assessment data and feedback from participants to begin to understand the impact and effectiveness of this approach to learning. Methods: A total of 8 sessions, conducted in 3 locations, with 64 participants, yielded survey assessment data from 41 participants. Results: Quantitative results indicated that participants were highly satisfied with the escape room experience and reported an increased level of knowledge after participation. In addition, participants reported extremely high levels of intention to implement the training they received, and all would recommend the escape room experience to a friend or a colleague. Qualitative data supports the overall findings and provides specific examples of how participants said they would implement the knowledge they learned, along with additional positive feedback. Conclusion: Current and continuing efforts to promote PFL’s escape room are described, along with improvements and future actions.
Bone Marrow Stimulation for Arthroscopic Rotator Cuff Repair: A Meta-analysis of Randomized Controlled Trials
Authors: Hurley Eoghan T. , Crook Bryan S. , Danilkowicz Richard M. , Jazrawi Laith M. , Mirzayan Raffy , Dickens Jonathan F. , Anakwenze Oke , Klifto Christopher S. 
Published: February 2024

Background: Bone marrow stimulation (BMS) has been proposed to augment healing at the time of arthroscopic rotator cuff repair (ARCR) by creating several bone marrow vents in the footprint of the rotator cuff, allowing mesenchymal stem cells, platelets, and growth factors to cover the area as a “crimson duvet.” Purpose: To perform a meta-analysis of randomized controlled trials (RCTs) to compare the outcomes after BMS and a control for those undergoing ARCR. Study Design: Meta-analysis; Level of evidence, 1. Methods: A literature search of 3 databases was performed based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. RCTs comparing BMS and a control for ARCR were included. Clinical outcomes were compared, and a P value <.05 was considered to be statistically significant. Results: A total of 7 RCTs with 576 patients were included. Overall, 18.8% of patients treated with BMS and 21.0% of patients treated with a control had a retear ( I2 = 43%; P = .61). With BMS, the mean Constant score was 88.2, and with the control, the mean Constant score was 86.7 ( P = .12). Additionally, there was no significant difference in the American Shoulder and Elbow Surgeons score (94.3 vs 93.2, respectively; P = .31) or visual analog scale score (0.9 vs 0.9, respectively; P = .89). Conclusion: The level 1 evidence in the literature did not support BMS as a modality to improve retear rates or clinical outcomes after ARCR.