bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enactment of compassionate leadership by nursing and midwifery managers: results from an international online survey
Authors: Papadopoulos Irena , Wright Steve , Lazzarino Runa , Koulouglioti Christina , Aagard Magdeline , Akman Özlem , Alpers Lise-Merete , Apostolara Paraskevi , Araneda Julieta , Biglete-Pangilinan Sylvia , Eldar-Regev Orit , González-Gil Maria Teresa , Kouta Christiana , Krepinska Radka , Lesińska-Sawicka Małgorzata , Liskova Miroslava , Lopez-Diaz Lucero , Malliarou Maria , Martín-García Ángel , Muñoz-Salinas Mara , Nagórska Małgorzata , Ngunyulu Roinah Nkhensani , Nissim Sara , Nortvedt Line , Oconer-Rubiano Florinda , Oter-Quintana Cristina , Öztürk Candan , Papp Katalin , Piratoba-Hernandez Blanca , Rousou Elena , Tolentino-Diaz Maria Ymelda , Tothova Valerie , Zorba Akile 
Published: September 2021

AimTo explore the views of an international sample of nursing and midwifery managers concerning attributes that they associate with compassionate management.MethodA cross-sectional online survey. Using a snowballing sampling method, 1217 responses were collected from nursing and midwifery managers in 17 countries. A total of complete 933 responses to a question related to which actions and behaviours indicated that a manager was exercising compassionate leadership were analysed for this paper. First, content analysis of the responses was conducted, and second, a relative distribution of the identified themes for the overall sample and for each participating country was calculated.ResultsSix main themes were identified describing the attributes of a compassionate leader: (1) Virtuous support, (2) Communication, (3) Personal virtues of the manager, (4) Participatory communication, (5) Growth/flourishing/ nurturing and (6) Team cohesion. The first three themes mentioned above collectively accounted for 63% of the responses, and can therefore be considered to be the most important characteristics of compassionate management behaviour.ConclusionThe key indicators of compassionate management in nursing and midwifery which were identified emphasise approachability, active and sensitive listening, sympathetic responses to staff members’ difficulties (especially concerning child and other caring responsibilities), active support of and advocacy for the staff team and active problem solving and conflict resolution. While there were differences between the countries’ views on compassionate healthcare management, some themes were widely represented among different countries’ responses, which suggest key indicators of compassionate management that apply across cultures.
Postglacial sea-level lowstand on Cumberland Peninsula, Baffin Island, Nunavut
Authors: Cowan B. , Carter J. , Forbes D.L. , Bell T. 
Published: September 2021

This study investigates the postglacial sea-level history of eastern Cumberland Peninsula, a region of Baffin Island, Nunavut, where submerged terraces were documented in the 1970s. The elevation gradient of emerged postglacial marine-limit deltas and fiord-head moraines led Arthur Dyke to propose a conceptual model for continuous postglacial submergence of the eastern peninsula. Multibeam mapping over the past decade has revealed eight unequivocal submerged deltas at 19–45 m below present sea level (b.s.l.) and other relict shore-zone landforms (boulder barricade, spits, and sill platform) at 16–51 m b.s.l. Over a distance of 115 km from Qikiqtarjuaq to Cape Dyer, the submerged coastal features increase in depth toward the east, with a slope (0.36 m/km) less than that of the marine-limit shoreline previously documented (0.58–0.62 m/km). The submerged ice-proximal deltas, deglacial ice limits, and radiocarbon ages constrain the postglacial lowstand between 9.9 and 1.4 ka cal BP. The glacial-isostatic model ICE-7G_NA (VM7) computes a lowstand relative sea level at 8.0 ka, the depth of which increases eastward at 0.28 m/km. The difference between observed and model-derived lowstand depths ranges from 1 m in the west to 10 m in the east and the predicted tilt is significantly less than observed (p = 0.0008). The model results, emerging data on Holocene glacial readvances on eastern Baffin Island, and evidence for proglacial delta formation point to a Cockburn (9.5–8.2 ka) age for the lowstand, most likely later in this range. This study confirms the 1970s conceptual model of postglacial submergence in outer Cumberland Peninsula and provides field evidence for further refinement of glacial-isostatic adjustment models.
Elimination of Radiation-Induced Senescence in the Brain Tumor Microenvironment Attenuates Glioblastoma Recurrence
Authors: Fletcher-Sananikone Eliot , Kanji Suman , Tomimatsu Nozomi , Di Cristofaro Luis Fernando Macedo , Kollipara Rahul K. , Saha Debabrata , Floyd John R. , Sung Patrick , Hromas Robert , Burns Terry C. , Kittler Ralf , Habib Amyn A. , Mukherjee Bipasha , Burma Sandeep 
Published: September 2021

Abstract

Glioblastomas (GBM) are routinely treated with ionizing radiation (IR) but inevitably recur and develop therapy resistance. During treatment, the tissue surrounding tumors is also irradiated. IR potently induces senescence, and senescent stromal cells can promote the growth of neighboring tumor cells by secreting factors that create a senescence-associated secretory phenotype (SASP). Here, we carried out transcriptomic and tumorigenicity analyses in irradiated mouse brains to elucidate how radiotherapy-induced senescence of non-neoplastic brain cells promotes tumor growth. Following cranial irradiation, widespread senescence in the brain occurred, with the astrocytic population being particularly susceptible. Irradiated brains showed an altered transcriptomic profile characterized by upregulation of CDKN1A (p21), a key enforcer of senescence, and several SASP factors, including HGF, the ligand of the receptor tyrosine kinase (RTK) Met. Preirradiation of mouse brains increased Met-driven growth and invasiveness of orthotopically implanted glioma cells. Importantly, irradiated p21−/− mouse brains did not exhibit senescence and consequently failed to promote tumor growth. Senescent astrocytes secreted HGF to activate Met in glioma cells and to promote their migration and invasion in vitro, which could be blocked by HGF-neutralizing antibodies or the Met inhibitor crizotinib. Crizotinib also slowed the growth of glioma cells implanted in preirradiated brains. Treatment with the senolytic drug ABT-263 (navitoclax) selectively killed senescent astrocytes in vivo, significantly attenuating growth of glioma cells implanted in preirradiated brains. These results indicate that SASP factors in the irradiated tumor microenvironment drive GBM growth via RTK activation, underscoring the potential utility of adjuvant senolytic therapy for preventing GBM recurrence after radiotherapy.

Significance:
This study uncovers mechanisms by which radiotherapy can promote GBM recurrence by inducing senescence in non-neoplastic brain cells, suggesting that senolytic therapy can blunt recurrent GBM growth and aggressiveness.
Organoids Derived from Neoadjuvant FOLFIRINOX Patients Recapitulate Therapy Resistance in Pancreatic Ductal Adenocarcinoma
Authors: Farshadi Elham Aida , Chang Jiang , Sampadi Bharath , Doukas Michail , Van 't Land Freek , van der Sijde Fleur , Vietsch Eveline E. , Pothof Joris , Koerkamp Bas Groot , van Eijck Casper H.J. 
Published: September 2021

Abstract

Purpose:
We investigated whether organoids can be generated from resected tumors of patients who received eight cycles of neoadjuvant FOLFIRINOX chemotherapy before surgery, and evaluated the sensitivity/resistance of these surviving cancer cells to cancer therapy.

Experimental Design:
We generated a library of 10 pancreatic ductal adenocarcinoma (PDAC) organoid lines: five each from treatment-naïve and FOLFIRINOX-treated patients. We first assessed the histologic, genetic, and transcriptional characteristics of the organoids and their matched primary PDAC tissue. Next, the organoids' response to treatment with single agents—5-FU, irinotecan, and oxaliplatin—of the FOLFIRINOX regimen as well as combined regimen was evaluated. Finally, global mRNA-seq analyses were performed to identify FOLFIRINOX resistance pathways.

Results:
All 10 patient-derived PDAC organoids recapitulate histologic, genetic, and transcriptional characteristics of their primary tumor tissue. Neoadjuvant FOLFIRINOX-treated organoids display resistance to FOLFIRINOX (5/5), irinotecan (5/5), and oxaliplatin (4/5) when compared with treatment-naïve organoids (FOLFIRINOX: 1/5, irinotecan: 2/5, oxaliplatin: 0/5). 5-Fluorouracil treatment responses between naïve and treated organoids were similar. Comparative global transcriptome analysis of treatment-naïve and FOLFIRINOX samples—in both organoids and corresponding matched tumor tissues—uncovered modulated pathways mainly involved in genomic instability, energy metabolism, and innate immune system.

Conclusions:
Resistance development in neoadjuvant FOLFIRINOX organoids, recapitulating their primary tumor resistance, suggests continuation of FOLFIRINOX therapy as an adjuvant treatment may not be advantageous for these patients. Gene-expression profiles of PDAC organoids identify targetable pathways involved in chemoresistance development upon neoadjuvant FOLFIRINOX treatment, thus opening up combination therapy possibilities.
Randomized Phase II Study of PARP Inhibitor ABT-888 (Veliparib) with Modified FOLFIRI versus FOLFIRI as Second-line Treatment of Metastatic Pancreatic Cancer: SWOG S1513
Authors: Chiorean E. Gabriela , Guthrie Katherine A. , Philip Philip A. , Swisher Elizabeth M. , Jalikis Florencia , Pishvaian Michael J. , Berlin Jordan , Noel Marcus S. , Suga Jennifer M. , Garrido-Laguna Ignacio , Cardin Dana Backlund , Radke Marc R. , Duong Mai , Bellasea Shay , Lowy Andrew M. , Hochster Howard S. 
Published: September 2021

Abstract

Purpose:
PARP inhibitors synergize with topoisomerase inhibitors, and veliparib plus modified (m) FOLFIRI (no 5-FU bolus) had preliminary activity in metastatic pancreatic cancers. This study evaluated the safety and efficacy of second-line treatment with veliparib and mFOLFIRI versus FOLFIRI (control) for metastatic pancreatic cancer.

Patients and Methods:
This randomized phase II clinical trial led by the SWOG Cancer Research Network enrolled patients between September 1, 2016 and December 13, 2017. The median follow-up was 9 months (IQR 1–27). BRCA1/2 and homologous recombination DNA damage repair (HR-DDR) genetic defects were tested in blood and tumor biopsies. Patients received veliparib 200 mg twice daily, days 1–7 with mFOLFIRI days 3–5, or FOLFIRI in 14-day cycles.

Results:
After 123 of planned 143 patients were accrued, an interim futility analysis indicated that the veliparib arm was unlikely to be superior to control, and the study was halted. Median overall survival (OS) was 5.4 versus 6.5 months (HR, 1.23; P = 0.28), and median progression-free survival (PFS) was 2.1 versus 2.9 months (HR, 1.39; P = 0.09) with veliparib versus control. Grade 3/4 toxicities were more common with veliparib (69% vs. 58%, P = 0.23). For cancers with HR-DDR defects versus wild-type, median PFS and OS were 7.3 versus 2.5 months (P = 0.05) and 10.1 versus 5.9 months (P = 0.17), respectively, with FOLFIRI, and 2.0 versus 2.1 months (P = 0.62) and 7.4 versus 5.1 months (P = 0.10), respectively, with veliparib plus mFOLFIRI.

Conclusions:
Veliparib plus mFOLFIRI did not improve survival for metastatic pancreatic cancer. FOLFIRI should be further studied in pancreatic cancers with HR-DDR defects.
Losartan Blocks Osteosarcoma-Elicited Monocyte Recruitment, and Combined With the Kinase Inhibitor Toceranib, Exerts Significant Clinical Benefit in Canine Metastatic Osteosarcoma
Authors: Regan Daniel P. , Chow Lyndah , Das Sunetra , Haines Laurel , Palmer Eric , Kurihara Jade N. , Coy Jonathan W. , Mathias Alissa , Thamm Douglas H. , Gustafson Daniel L. , Dow Steven W. 
Published: September 2021

Abstract

Purpose:
There is increasing recognition that progress in immuno-oncology could be accelerated by evaluating immune-based therapies in dogs with spontaneous cancers. Osteosarcoma (OS) is one tumor for which limited clinical benefit has been observed with the use of immune checkpoint inhibitors. We previously reported the angiotensin receptor blocker losartan suppressed metastasis in preclinical mouse models through blockade of CCL2–CCR2 monocyte recruitment. Here we leverage dogs with spontaneous OS to determine losartan's safety and pharmacokinetics associated with monocyte pharmacodynamic endpoints, and assess its antitumor activity, in combination with the kinase inhibitor toceranib.

Patients and Methods:
CCL2 expression, monocyte infiltration, and monocyte recruitment by human and canine OS tumors and cell lines were assessed by gene expression, ELISA, and transwell migration assays. Safety and efficacy of losartan-toceranib therapy were evaluated in 28 dogs with lung metastatic OS. Losartan PK and monocyte PD responses were assessed in three dose cohorts of dogs by chemotaxis, plasma CCL2, and multiplex cytokine assays, and RNA-seq of losartan-treated human peripheral blood mononuclear cells.

Results:
Human and canine OS cells secrete CCL2 and elicit monocyte migration, which is inhibited by losartan. Losartan PK/PD studies in dogs revealed that a 10-fold-higher dose than typical antihypertensive dosing was required for blockade of monocyte migration. Treatment with high-dose losartan and toceranib was well-tolerated and induced a clinical benefit rate of 50% in dogs with lung metastases.

Conclusions:
Losartan inhibits the CCL2–CCR2 axis, and in combination with toceranib, exerts significant biological activity in dogs with metastatic osteosarcoma, supporting evaluation of this drug combination in patients with pediatric osteosarcoma.
See related commentary by Weiss et al., p. 571
Arrhythmias Other Than Atrial Fibrillation in Those With an Irregular Pulse Detected With a Smartwatch: Findings From the Apple Heart Study
Authors: Perino Alexander C. , Gummidipundi Santosh E. , Lee Justin , Hedlin Haley , Garcia Ariadna , Ferris Todd , Balasubramanian Vidhya , Gardner Rebecca M. , Cheung Lauren , Hung Grace , Granger Christopher B. , Kowey Peter , Rumsfeld John S. , Russo Andrea M. , True Hills Mellanie , Talati Nisha , Nag Divya , Tsay David , Desai Sumbul , Desai Manisha , Mahaffey Kenneth W. , Turakhia Mintu P. , Perez Marco V. ,   on behalf of the Apple Heart Study Investigators
Published: September 2021

Background:
The Apple watch irregular pulse detection algorithm was found to have a positive predictive value of 0.84 for identification of atrial fibrillation (AF). We sought to describe the prevalence of arrhythmias other than AF in those with an irregular pulse detected on a smartwatch.

Methods:
The Apple Heart Study investigated a smartwatch-based irregular pulse notification algorithm to identify AF. For this secondary analysis, we analyzed participants who received an ambulatory ECG patch after index irregular pulse notification. We excluded participants with AF identified on ECG patch and described the prevalence of other arrhythmias on the remaining participant ECG patches. We also reported the proportion of participants self-reporting subsequent AF diagnosis.

Results:
Among 419 297 participants enrolled in the Apple Heart Study, 450 participant ECG patches were analyzed, with no AF on 297 ECG patches (66%). Non-AF arrhythmias (excluding supraventricular tachycardias <30 beats and pauses <3 seconds) were detected in 119 participants (40.1%) with ECG patches without AF. The most common arrhythmias were frequent PACs (burden ≥1% to <5%, 15.8%; ≥5% to <15%, 8.8%), atrial tachycardia (≥30 beats, 5.4%), frequent PVCs (burden ≥1% to <5%, 6.1%; ≥5% to <15%, 2.7%), and nonsustained ventricular tachycardia (4–7 beats, 6.4%; ≥8 beats, 3.7%). Of 249 participants with no AF detected on ECG patch and patient-reported data available, 76 participants (30.5%) reported subsequent AF diagnosis.

Conclusions:
In participants with an irregular pulse notification on the Apple Watch and no AF observed on ECG patch, atrial and ventricular arrhythmias, mostly PACs and PVCs, were detected in 40% of participants. Defining optimal care for patients with detection of incidental arrhythmias other than AF is important as AF detection is further investigated, implemented, and refined.
Mendelian Randomization Focused Analysis of Vitamin D on the Secondary Prevention of Ischemic Stroke
Authors: Chan Yap-Hang , Schooling C. Mary , Zhao Jie , Au Yeung Shiu-Lun , Hai Jo Jo , Thomas G. Neil , Cheng Kar-Keung , Jiang Chao-Qiang , Wong Yuen-Kwun , Au Ka-Wing , Tang Clara S. , Cheung Chloe Y.Y. , Xu Aimin , Sham Pak-Chung , Lam Tai-Hing , Lam Karen Siu-Ling , Tse Hung-Fat 
Published: September 2021

Background and Purpose:
Experimental studies showed vitamin D (Vit-D) could promote vascular regeneration and repair. Prior randomized studies had focused mainly on primary prevention. Whether Vit-D protects against ischemic stroke and myocardial infarction recurrence among subjects with prior ischemic insults was unknown. Here, we dissected through Mendelian randomization any effect of Vit-D on the secondary prevention of recurrent ischemic stroke and myocardial infarction.

Methods:

Based on a genetic risk score for Vit-D constructed from a derivation cohort sample (n=5331, 45% Vit-D deficient, 89% genotyped) via high-throughput exome-chip screening of 12 prior genome-wide association study–identified genetic variants of Vit-D mechanistic pathways (
rs2060793
,
rs4588
, and
rs7041
; F statistic, 73;
P
<0.001), we performed a focused analysis on prospective recurrence of myocardial infarction (MI) and ischemic stroke in an independent subsample with established ischemic disease (n=441, all with prior first ischemic event; follow-up duration, 41.6±14.3 years) under a 2-sample, individual-data, prospective Mendelian randomization approach.

Results:

In the ischemic disease subsample, 11.1% (n=49/441) had developed recurrent ischemic stroke or MI and 13.3% (n=58/441) had developed recurrent or de novo ischemic stroke/MI. Kaplan-Meier analyses showed that genetic risk score predicted improved event-free survival from recurrent ischemic stroke or MI (log-rank, 13.0;
P
=0.001). Cox regression revealed that genetic risk score independently predicted reduced risk of recurrent ischemic stroke or MI combined (hazards ratio, 0.62 [95% CI, 0.48–0.81];
P
<0.001), after adjusted for potential confounders. Mendelian randomization supported that Vit-D is causally protective against the primary end points of recurrent ischemic stroke or MI (Wald estimate: odds ratio, 0.55 [95% CI, 0.35–0.81]) and any recurrent or de novo ischemic stroke/MI (odds ratio, 0.64 [95% CI, 0.42–0.91]) and recurrent MI alone (odds ratio, 0.52 [95% CI, 0.30–0.81]).

Conclusions:
Genetically predicted lowering in Vit-D level is causal for the recurrence of ischemic vascular events in persons with prior ischemic stroke or MI.
Rebelling against the Ruler: Egyptian Youth and Azhari Scholars’ Authority after the 2011 Uprising
Authors: Amin Nareman 
Published: September 2021

Abstract
Scholars have investigated statements by Azhari ʿulamāʾ (religious scholars) about the legality of protest in Egypt in 2011 and 2013 and their use of fiqh al-wāqiʿ, a jurisprudential method by which jurists consider social and political realities when issuing legal opinions. These studies focus on Islamic legal theory but do not examine the social implications of the legal. Based on textual analysis of televised statements by ʿulamāʾ and interviews with young Muslim Egyptians, I argue that, although some jurists discouraged the laity from joining the 2011 protests, religious youth were not deterred from protesting. Additionally, laypeople who are not well-versed in Islamic law grew suspicious of the shifting opinions of ʿulamāʾ on the legal status of protest, as happened in 2013. In the aftermath of the 2011 and 2013 movements, the moral capital of several Azhari scholars decreased as did the moral-legal purchase of the fatwās they issued.
‘No Ideas but in Things’: The Responsibility to Protect as Assemblage
Authors: MacLennan Jack Adam 
Published: September 2021

Abstract
This article establishes the need to engage with the Responsibility to Protect (R2P) as an assemblage in order to reckon with how material influences shape its politics. Through an analysis of the 2011 United States and North Atlantic Treaty Organization intervention in Libya, the paper illustrates how particular tools and techniques influence R2P. The example shows how the original impetus of the intervention was mediated and translated by the particular collection of elements brought together to realise the intervention in Libya. Rather than argue this illustrates how R2P is defined by specific techniques, the article situates and then builds upon the extant literature by labelling R2P as an assemblage. In this way the article highlights how material influences and the importance of mediation are missed in the extant literature. Further, it concludes by arguing for a more productive research agenda that foregrounds empirical engagements with specific practices in order to develop the current literature.
Othering within the Islamist Spectrum: Ennahda and the Political Salafists in Tunisia
Authors: Lorch Jasmin , Chakroun Hatem 
Published: September 2021

Abstract
While research on Islamist moderation has paid considerable attention to cross-ideological cooperation, it has barely explored whether and how the moderation of Islamist parties is related to interactions inside the Islamist spectrum. We attempt to bridge this gap by using othering as a theoretical-analytical lens with which to analyze the interplay between Ennahda’s moderation and the party’s relations to the political Salafists in Tunisia. We argue that the discursive act of othering the political Salafists has helped Ennahda construct itself both as a moderate, democratic actor representing the ‘true’ version of Tunisian Islam and as an effective and reliable political force. Moreover, while the concept of othering has barely been systematically applied to intra-Islamist relations, we show that it constitutes a fine-grained tool with which to study Islamist moderation in the context of intra-Islamist competition.
Radicalizing Life after Death: Dostoevskii’s ‘Bobok: Zapiski odnogo litsa’ (‘Bobok: Notes of a Certain Person’) and Petrushevskaia’s Nomer Odin, ili V sadakh drugikh vozmozhnostei (Number One, or in the Gardens of Other Opportunities)
Authors: Tigountsova Inna F. I. 
Published: September 2021

Abstract
The focus of this article is on Dostoevskii’s story “Bobok” [“Bobok,” 1873] and Petrushevskaia’s novel Nomer Odin, ili V sadakh drugikh vozmozhnostei [Number One, or In the Gardens of Other Opportunities, 2004]. These dialogical narratives explore the theme of life after death; they portray death as a transition to life that includes several stages, and focus on the process of dying, living in a different form, and dying again. I discuss how these radical views on death are expressed in “Bobok” and Nomer Odin (with some reference to Dostoevskii’s Zapiski iz podpol’ia [Notes from Underground, 1864] and Petrushevskaia’s Vremia: Noch’ [Time: Night, 1992]): from the “getting naked” (“zagolimsia,” “obnazhimsia”) preached and practised by the decaying corpses in Dostoevskii’s text, to transitions between different stages after death in Petrushevskaia’s novel, such as metempsychosis, as well as tropes used to denote these transitions.