bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNMT3A Harboring Leukemia-Associated Mutations Directs Sensitivity to DNA Damage at Replication Forks
Authors: Venugopal Kartika , Feng Yang , Nowialis Pawel , Xu Huanzhou , Shabashvili Daniil E. , Berntsen Cassandra M. , Kaur Prabhjot , Krajcik Kathryn I. , Taragjini Christina , Zaroogian Zachary , Casellas Román Heidi L. , Posada Luisa M. , Gunaratne Chamara , Li Jianping , Dupéré-Richer Daphné , Bennett Richard L. , Pondugula Santhi , Riva Alberto , Cogle Christopher R. , Opavsky Rene , Law Brian K. , Bhaduri-McIntosh Sumita , Kubicek Stefan , Staber Philipp B. , Licht Jonathan D. , Bird Jonathan E. , Guryanova Olga A. 
Published: October 2021

Abstract

Purpose:
In acute myeloid leukemia (AML), recurrent DNA methyltransferase 3A (DNMT3A) mutations are associated with chemoresistance and poor prognosis, especially in advanced-age patients. Gene-expression studies in DNMT3A-mutated cells identified signatures implicated in deregulated DNA damage response and replication fork integrity, suggesting sensitivity to replication stress. Here, we tested whether pharmacologically induced replication fork stalling, such as with cytarabine, creates a therapeutic vulnerability in cells with DNMT3A(R882) mutations.

Experimental Design:
Leukemia cell lines, genetic mouse models, and isogenic cells with and without DNMT3A(mut) were used to evaluate sensitivity to nucleoside analogues such as cytarabine in vitro and in vivo, followed by analysis of DNA damage and signaling, replication restart, and cell-cycle progression on treatment and after drug removal. Transcriptome profiling identified pathways deregulated by DNMT3A(mut) expression.

Results:
We found increased sensitivity to pharmacologically induced replication stress in cells expressing DNMT3A(R882)-mutant, with persistent intra–S-phase checkpoint activation, impaired PARP1 recruitment, and elevated DNA damage, which was incompletely resolved after drug removal and carried through mitosis. Pulse-chase double-labeling experiments with EdU and BrdU after cytarabine washout demonstrated a higher rate of fork collapse in DNMT3A(mut)-expressing cells. RNA-seq studies supported deregulated cell-cycle progression and p53 activation, along with splicing, ribosome biogenesis, and metabolism.

Conclusions:
Together, our studies show that DNMT3A mutations underlie a defect in recovery from replication fork arrest with subsequent accumulation of unresolved DNA damage, which may have therapeutic tractability. These results demonstrate that, in addition to its role in epigenetic control, DNMT3A contributes to preserving genome integrity during replication stress.
See related commentary by Viny, p. 573
Stapafurdius, a new genus of Bulimulidae (Mollusca, Eupulmonata) from Bahia, Brazil, with two new species
Authors: Simone Luiz Ricardo L. 
Published: October 2021

The new genus Stapafurdius gen. nov. is introduced collected from Bahia, Brazil, including two new species: S. glaber sp. nov., the type species, occurs in Ibicoara; and S. costiferus sp. nov., from Andaraí regions. The new genus includes species of about 10 mm, elongated shell, reticulated protoconch, elongated peristome, and wide umbilicus. Both species differ mainly by the sculpture, as S. glaber sp. nov. is smooth, while S. costiferus sp. nov. has strong axial sculpture. urn:lsid:zoobank.org:pub:C851695E-6BF1-4418-8D8A-8BC7D10CC2FE.
Elevated Aortic Pulse Wave Velocity Relates to Longitudinal Gray and White Matter Changes
Authors: Bown Corey W. , Khan Omair A. , Moore Elizabeth E. , Liu Dandan , Pechman Kimberly R. , Cambronero Francis E. , Terry James G. , Nair Sangeeta , Davis L. Taylor , Gifford Katherine A. , Landman Bennett A. , Hohman Timothy J. , Carr John Jeffrey , Jefferson Angela L. 
Published: October 2021

Objective:
To determine whether baseline aortic stiffness, measured by aortic pulse wave velocity (PWV), relates to longitudinal cerebral gray or white matter changes among older adults. Baseline cardiac magnetic resonance imaging will be used to assess aortic PWV while brain magnetic resonance imaging will be used to assess gray matter and white matter hyperintensity (WMH) volumes at baseline, 18 months, 3 years, 5 years, and 7 years.

Approach and Results:

Aortic PWV (m/s) was quantified from cardiac magnetic resonance. Multimodal 3T brain magnetic resonance imaging included
T

1

-weighted imaging for quantifying gray matter volumes and
T

2

-weighted fluid-attenuated inversion recovery imaging for quantifying WMHs. Mixed-effects regression models related baseline aortic PWV to longitudinal gray matter volumes (total, frontal, parietal, temporal, occipital, hippocampal, and inferior lateral ventricle) and WMH volumes (total, frontal, parietal, temporal, and occipital) adjusting for age, sex, race/ethnicity, education, cognitive diagnosis, Framingham stroke risk profile,
APOE
(apolipoprotein E)-ε4 carrier status, and intracranial volume. Two hundred seventy-eight participants (73±7 years, 58% male, 87% self-identified as non-Hispanic White, 159 with normal cognition, and 119 with mild cognitive impairment) from the Vanderbilt Memory & Aging Project (n=335) were followed on average for 4.9±1.6 years with PWV measurements occurring from September 2012 to November 2014 and longitudinal brain magnetic resonance imaging measurements occurring from September 2012 to June 2021. Higher baseline aortic PWV was related to greater decrease in hippocampal (β=−3.6 [mm
3
/y]/[m/s]; [95% CI, −7.2 to −0.02]
P
=0.049) and occipital lobe (β=−34.2 [mm
3
/y]/[m/s]; [95% CI, −67.8 to −0.55]
P
=0.046) gray matter volume over time. Higher baseline aortic PWV was related to greater increase in WMH volume over time in the temporal lobe (β=17.0 [mm
3
/y]/[m/s]; [95% CI, 7.2–26.9]
P
<0.001). All associations may be driven by outliers.

Conclusions:
In older adults, higher baseline aortic PWV related to greater decrease in gray matter volume and greater increase in WMHs over time. Because of unmet cerebral metabolic demands and microvascular remodeling, arterial stiffening may preferentially affect certain highly active brain regions like the temporal lobes. These same regions are affected early in the course of Alzheimer disease.
Perinatal Administration of C-Phycocyanin Protects Against Atherosclerosis in apoE-Deficient Mice by Modulating Cholesterol and Trimethylamine-N-Oxide Metabolisms
Authors: Coué Marine , Croyal Mikael , Habib Marina , Castellano Blandine , Aguesse Audrey , Grit Isabelle , Gourdel Mathilde , Billard Hélène , Lépine Olivier , Michel Catherine , Ouguerram Khadija 
Published: October 2021

Objective:
Gestational hypercholesterolemia concomitantly with a highly oxidative environment is associated with higher atherosclerosis in human and animal offspring. This work aimed to determine whether perinatal administration of a C-phycocyanin concentrate, a powerful antioxidant, can protect against atherosclerosis development in genetically hypercholesterolemic mice in adult life.

Approach and Results:

C-Phycocyanin was administered during gestation solely or gestation and lactation to apolipoprotein E-deficient mice. Male and female offspring were studied until 25 weeks old. Progenies born to supplemented mothers displayed significantly less atherosclerotic root lesions than control group in all groups excepted in male supplemented during gestation and lactation. Female born to supplemented mothers had a greater gallbladder total bile acid pool, lower secondary hydrophobic bile acid levels such as lithocholic acid, associated with less plasma trimethylamine
N
-oxide at 16 weeks old compared with control mice. Regarding male born to C-Phycocyanin administrated mothers, they expressed a higher high-density lipoprotein cholesterol level, more soluble bile acids such as β-muricholic acids, and a decreased plasma trimethylamine at 16 weeks old. Liver reduced-to-oxidized glutathione ratio were increased and liver gene expression of superoxide dismutase and glutathione peroxidase were significantly decreased in male born to gestational supplemented mothers. No difference in the composition of cecal microbiota was found between groups, regardless of sex.

Conclusions:
Our findings suggest a protective effect of perinatal antioxidant administration on atherosclerosis development in apolipoprotein E-deficient mice involving sex-specific mechanisms.
Impact of High-Power Short-Duration Radiofrequency Ablation on Esophageal Temperature Dynamic
Authors: Yavin Hagai D. , Bubar Zachary P. , Higuchi Koji , Sroubek Jakub , Kanj Mohamed , Cantillon Daniel , Saliba Walid I. , Tarakji Khaldoun G. , Hussein Ayman A. , Wazni Oussama , Anter Elad 
Published: October 2021

Background:
High-power short-duration (HP-SD) radiofrequency ablation (RFA) has been proposed as a method for producing rapid and effective lesions for pulmonary vein isolation. The underlying hypothesis assumes an increased resistive heating phase and decreased conductive heating phase, potentially reducing the risk for esophageal thermal injury. The objective of this study was to compare the esophageal temperature dynamic profile between HP-SD and moderate-power moderate-duration (MP-MD) RFA ablation strategies.

Methods:
In patients undergoing pulmonary vein isolation, RFA juxtaposed to the esophagus was delivered in an alternate sequence of HP-SD (50 W, 8–10 s) and MP-MD (25 W, 15–20 s) between adjacent applications (distance, ≤4 mm). Esophageal temperature was recorded using a multisensor probe (CIRCA S-CATH). Temperature data included magnitude of temperature rise, maximal temperature, time to maximal temperature, and time return to baseline. In swine, a similar experimental design compared the effect of HP-SD and MP-MD on patterns of esophageal injury.

Results:

In 20 patients (68.9±5.8 years old; 60% persistent atrial fibrillation), 55 paired HP-SD and MP-MD applications were analyzed. The esophageal temperature dynamic profile was similar between HP-SD and MP-MD ablation strategies. Specifically, the magnitude of temperature rise (2.1 °C [1.4–3] versus 2.0 °C [1.5–3];
P
=0.22), maximal temperature (38.4 °C [37.8–39.3] versus 38.5 °C [37.9–39.4];
P
=0.17), time to maximal temperature (24.9±7.5 versus 26.3±6.8 s;
P
=0.1), and time of temperature to return to baseline (110±23.2 versus 111±25.1 s;
P
=0.86) were similar between HP-SD and MP-MD ablation strategies. In 6 swine, esophageal injury was qualitatively similar between HP-SD and MP-MD strategies.

Conclusions:
Esophageal temperature dynamics are similar between HP-SD and MP-MD RFA strategies and result in comparable esophageal tissue injury. Therefore, when using a HP-SD RFA strategy, the shorter application duration should not prompt shorter intervals between applications.
Differences Between Patients With Intermittent Claudication and Critical Limb Ischemia Undergoing Endovascular Intervention: Insights From the Excellence in Peripheral Artery Disease Registry
Authors: Patel Kunal , Liu Yulun , Etaee Farshid , Patel Chirag , Monteleone Peter , Patel Mitul , Amer Alaiti Mohamad , Metzger Christopher , Banerjee Avantika , Minniefield Nicole , Tejani Ishita , Brilakis Emmanouil S. , Shishehbor Mehdi H. , Banerjee Subhash 
Published: October 2021

Background:
There are limited data on differences in angiographic distribution of peripheral artery disease and endovascular revascularization strategies in patients presenting with intermittent claudication (IC) and critical limb ischemia (CLI). We aimed to compare anatomic features, treatment strategies, and clinical outcomes between patients with IC and CLI undergoing endovascular revascularization.

Methods:
We examined 3326 patients enrolled in the Excellence in Peripheral Artery Disease registry from 2006 to 2019 who were referred for endovascular intervention for IC (n=1983) or CLI (n=1343). The primary outcome was 1-year major adverse limb events, which included death, repeat target limb revascularization, or target limb amputation.

Results:

Patients with CLI were older and more likely to have diabetes and chronic kidney disease and less likely to receive optimal medical therapy compared with IC. Patients with IC had higher femoropopliteal artery interventions (IC 87% versus CLI 65%;
P
<0.001), while below the knee interventions were more frequent in CLI (CLI 47% versus IC 12%;
P
<0.001). Patients with CLI were more likely to have multilevel peripheral artery disease (CLI 32% versus IC 15%,
P
<0.001). Patients with IC were predominantly revascularized with stents (IC 48% versus CLI 37%;
P
<0.001) while balloon angioplasty was more frequent in CLI (CLI 37% versus IC 25%;
P
<0.001). All-cause mortality was higher in patients with CLI (CLI 4% versus IC 2%;
P
=0.014). Major adverse limb event rates for patients with IC and CLI were 16% and 26%, respectively (
P
<0.001) and remained higher in CLI after multivariable adjustment of baseline risk factors.

Conclusions:
Patients with IC and CLI have significant anatomic, lesion, and treatment differences with significantly higher mortality and adverse limb outcomes in CLI.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01904851.

Graphic Abstract:

A
graphic abstract
is available for this article.
Which Road to Recovery?: Factors Influencing Postacute Stroke Discharge Destinations: A Delphi Study
Authors: Stein Joel , Rodstein Barry M. , Levine Steven R. , Cheung Ken , Sicklick Alyse , Silver Brian , Hedeman Robin , Egan Abigail , Borg-Jensen Pamela , Magdon-Ismail Zainab ,   on behalf of the Northeast Cerebrovascular Consortium Stroke Rehabilitation and Recovery Delphi Study Group
Published: October 2021

Background and Purpose:
The criteria for determining the level of postacute care for patients with stroke are variable and inconsistent. The purpose of this study was to identify key factors influencing the selection of postacute level of care for these patients.

Methods:
We used a collaborative 4-round Delphi process to achieve a refined list of factors influencing postacute level of care selection. Our Delphi panel of experts consisted of 32 panelists including physicians, physical therapists, occupational therapists, speech-language pathologists, nurses, stroke survivors, administrators, policy experts, and individuals associated with third-party insurance companies.

Results:
In round 1, 207 factors were proposed, with subsequent discussion resulting in consolidation into 15 factors for consideration. In round 2, 15 factors were ranked with consensus on 10 factors; in round 3,10 factors were ranked with consensus on 9 factors. In round 4, the final round, 9 factors were rated with Likert scores ranging from 5 (most important) to 1(not important). The percentage of panelists who provided a rating of 4 or above were as follows: likelihood to benefit from an active rehabilitation program (97%), need for clinicians with specialized rehabilitation skills (94%), need for active and ongoing medical management and monitoring (84%), ability to tolerate an active rehabilitation program (74%), need for caregiver training to return to the community (48%), family/caregiver support (39%), likelihood to return to community/home (39%), ability to return to physical home environment (32%), and premorbid dementia (16%).

Conclusions:
This study provides an expert, consensus-based set of key factors to be considered when determining where stroke patients are discharged for postacute care. These factors may be useful in developing a decision support tool for use in clinical settings.
וילך שם (Ezra 10:6): “Wandering About” as a Sign of Mourning
Authors: Shemesh Yael 
Published: October 2021

Abstract
In a fascinating article, Michael L. Barré noted the topos of “wandering about” as a symptom of depression and mourning in world literature in general, and in the literature of the ancient Near East and the Bible in particular. Building on his insights, this paper argues that the phrase “he went there” (וילך שם) from Ezra 10:6 builds another instance of the topos of “wandering about.” Thus, there is no need to emed MT to “he spent the night there” (וילן שם), as has often been suggested.
A Cathedral with Disconnected Chapels? Reassessing the Cognitive Capacities of Neanderthals in Light of Recent Archaeological Discoveries
Authors: Liu Cheng 
Published: October 2021

Abstract
The reconstruction of hominins’ cognitive evolution has always been a crucial but challenging task. Researchers from various disciplines have tried to approach this issue, among which British archaeologist Steven Mithen’s cathedral model is regarded as one of the earliest and most creative attempts. In this model, he proposed that the Neanderthal’s mind is like a cathedral with disconnected chapels. Specifically, Neanderthals possessed advanced social, natural history, technical, and even linguistic intelligence modules, but the first three modules are isolated from each other, meaning they cannot effectively use the knowledge from one domain to address the issue of another domain. This article challenges his reconstruction of Neanderthals’ cognitive capacities by presenting multiple forms of archaeological evidence bearing on various kinds of cross-domain thinking that has arisen over the past two decades.
Between Sanudo and Fedanzola: Ashtori Ha-Parḥi as Mediator
Authors: Schwartz Amichay 
Published: October 2021

Abstract
This essay will examine the close similarity between the treatises of a Franciscan monk named Giovanni di Fedanzola and a Jewish sage named Ashtori Ha-Parḥi in the fourteenth-century Holy Land. The absence of guides for Christian pilgrims after the final departure of the Crusaders in 1291 was filled inter alia by Jews, and some new traditions regarding toponyms and geographical identifications were adopted by Christians as a result. Fedanzola mostly relied on his predecessors Burchardus de Monte Sion and Marino Sanudo. However, I will demonstrate that there are some instances where Fedanzola accepts Jewish traditions regarding locations mentioned in the Old Testament, with Ashtori Ha-Parḥi as his source. I will also show that positing a relationship between the two can clarify some obscure passages in Ashtori’s treatise, Kaftor va-feraḥ.
Divine Incomprehensibility and Human Faith in John Chrysostom
Authors: Edwards Robert G.T. 
Published: October 2021

Abstract
Although often considered a moralist, John Chrysostom frequently discusses the incomprehensibility of God. This paper both contextualizes his teaching on divine incomprehensibility within a pro-Nicene tradition and demonstrates what is particular to his own theology. It puts forward two major arguments. First, Chrysostom expands upon a pro-Nicene discourse of divine incomprehensibility – as also seen in Basil of Caesarea and Gregory of Nazianzus – to include not only the incomprehensibility of God’s essence but also the incomprehensibility of God’s economies. Second, Chrysostom’s apparently simplistic biblicism and doctrine of faith are in fact theological corollaries of this doctrine of divine incomprehensibility. In these ways, Chrysostom’s moral teaching is seen to have a robust theological basis.
Why Did Jesus Surrender to the Cross?
Authors: Mowbray John 
Published: October 2021

Abstract
Evidence from secular sources shows that the Romans did not attempt to crucify all in the empire who rose against them; rather, they crucified leaders as a warning to others, but often let followers go. Jesus believed or hoped that if he surrendered to the cross, though the Romans would crucify him as leader, they would let his followers go. He surrendered himself accordingly, to save his followers from suffering a similar fate. As a historical fact, this was successful, and his followers were preserved to become the beginnings of the church.
Gender and Transnational Dynamics in Immigrant Entrepreneurship
Authors: You (游天龙) Tianlong , Zhou (周敏) Min 
Published: October 2021

Abstract
Immigrant enterprises, especially those in the service sector of the urban economy, are largely gendered and seemingly localized. However, the intersection of gender and transnationalism is often overlooked in the research literature. To fill this gap, we draw on the literature of mixed embeddedness and transnationalism to advance an analytical framework of simultaneous embeddedness to explain the gendered pattern of immigrant entrepreneurship. We do so by taking an in-depth look at a female-dominant industry – Chinese-owned nail salons in New York City. Using data collected from face-to-face interviews and on-site observations in New York City, as well as archival records and media reports about labor-market dynamics in both the United States and China, we find that the development of Chinese-owned nail salons is shaped by contextual factors in both home and host countries beyond socioeconomic characteristics of individual entrepreneurs. Home-country factors in China include labor-force demographics, access to economic opportunities, and the gap between education and career aspiration among young women. These home-country factors are intertwined with changes in US immigration policy, local labor-market reception, and gender discrimination, which function to exacerbate the problem of labor shortage for Chinese-owned nail salons in New York City. We discuss the significance of simultaneous embeddedness and gender in understanding contemporary immigrant entrepreneurship.
Past Facts and the Nature of History
Authors: Currie Adrian , Swaim Daniel 
Published: October 2021

Abstract
We defend a realist account of history: past facts are discoveries not creations. We show how ‘moderate’ realists, who admit the critical role of perspective, while insisting on history’s metaphysical independence from historians, can accommodate Paul Roth’s arguments in favor of irrealism. Moreover, our position is consistent with a dynamic past: as history unfurls past events gain new properties. Realism is necessary, we argue, to capture substantive disputes within history. It also grounds history’s reflexivity: the point of the continual re-examination of history (and history’s history!) turns in part on there being mind-independent past facts to be had.
The Extended-Expert-As-Teacher (EEAT) Model
Authors: Blado Joseph E. 
Published: October 2021

Abstract
Recently, social epistemologists have sought to establish what the governing epistemic relationship should be between novices and experts. In this article, the author argues for, and expands upon, Helen De Cruz’s expert-as-teacher model. For although this model is vulnerable to significant challenges, the author proposes that a specifically extended version can sufficiently overcome these challenges (call this the “extended-expert-as-teacher” model, or the “EEAT” model). First, the author shows the respective weaknesses of three influential models in the literature. Then, he argues the expert-as-teacher model can overcome its weaknesses by adding what he calls the “Authority Clause”, “Advisor Clause”, and “Ex Post Facto Clause” of the EEAT model. After developing a robust account of these clauses, the author entertains three major objections. First, he responds to the charge that the EEAT model is little better than the expert-as-authority model. Second, he responds to a double-counting objection. Lastly, he responds to a pragmatic objection from complexity.