bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bridging the Gap from Bench to Bedside: A Call for In Vivo Preclinical Models to Advance Endometrial Cancer and Cervical Cancer Immuno-oncology Research
Authors: Chambers Laura , Haight Paulina , Chalif Julia , Mehra Yogita , Spakowicz Daniel , Backes Floor J. , Cosgrove Casey M. , O’Malley David M. , Vargas Roberto , Corr Bradley R. , Bae-Jump Victoria L. , Arend Rebecca C. 
Published: April 2024

Abstract
Advanced-stage endometrial and cervical cancers are associated with poor outcomes despite contemporary advances in surgical techniques and therapeutics. Recent clinical trial results have led to a shift in the treatment paradigm for both malignancies, in which immunotherapy is now incorporated as the standard of care up front for most patients with advanced endometrial and cervical cancers as the standard of care. Impressive response rates have been observed, but unfortunately, a subset of patients do not benefit from immunotherapy, and survival remains poor. Continued preclinical research and clinical trial development are crucial for our understanding of resistance mechanisms to immunotherapy and maximization of therapeutic efficacy. In this setting, syngeneic models are preferred over xenograft models as they allow for the evaluation of the tumor–immune interaction in an immunocompetent host, most closely mimicking the tumor–immune interaction in patients with cancer. Unfortunately, significant disparities exist about syngeneic models in gynecologic malignancy, in which queries from multiple large bioscience companies confirm no commercial availability of endometrial or cervical cancer syngeneic cell lines. Published data exist about the recent development of several endometrial and cervical cancer syngeneic cell lines, warranting further investigation. Closing the disparity gap for preclinical models in endometrial and cervical cancers will support physician scientists, basic and translational researchers, and clinical trialists who are dedicated to improving outcomes for our patients with advanced disease and poor prognosis.
Clinical and Biomarker Analysis of a Phase I/II Study of PDR001 Plus Imatinib for Advanced Treatment-Refractory Gastrointestinal Stromal Tumors
Authors: Kim Hyung-Don , Ryu Min-Hee , Park Young Soo , Yoo Changhoon , Kim Sung-Joo , Kang Yoon-Koo 
Published: April 2024

Abstract

Purpose:
In this phase Ib/II study, we aimed to evaluate the safety and efficacy of PDR001, an anti-PD1 antibody, in combination with imatinib in patients with treatment-refractory gastrointestinal stromal tumor (GIST).

Patients and Methods:
Patients with advanced GIST whose disease had progressed on imatinib, sunitinib, and regorafenib were enrolled. In phase Ib, the standard 3 + 3 dose escalation scheme was applied. Intravenous administration of PDR001 at 400 mg for every 4 weeks plus imatinib (300 and 400 mg daily for dose levels I and II, respectively) was given. The primary outcome for phase II was the disease control rate at 12 weeks. Exploratory biomarker analysis was performed based on PDL1 IHC, next-generation sequencing, and multiplexed IHC.

Results:
No dose-limiting toxicity was observed in the phase Ib part (n = 10), and dose level II was selected as the recommended phase II dose. In the phase II part (n = 29), there was no objective response, and the disease control rate at 12 weeks was 37.9%, not meeting the primary efficacy endpoint. For patients in phase Ib–dose level II and phase II (n = 36), the median progression-free survival (PFS) and overall survival were 2.3 and 9.5 months, respectively. The most common grade 3 to 4 adverse event was anemia. Exploratory biomarker analysis indicated that a higher CD8+ T-cell density was associated with a favorable PFS but to a limited degree. Tumor mutational burden and PDL1 were not associated with better PFS.

Conclusions:
In patients with treatment-refractory GIST, PDR001 in combination with imatinib was generally tolerable, but it was not effective.
Germline Testing Identifies Pathogenic/Likely Pathogenic Variants in Patients with Pancreatic Neuroendocrine Tumors
Authors: Mohindroo Chirayu , Baydogan Seyda , Agarwal Parul , Wright Robin D. , Prakash Laura R. , Mork Maureen E. , Klein Alison P. , Laheru Daniel A. , Maxwell Jessica E. , Katz Matthew H.G. , Dasari Arvind , Kim Michael P. , He Jin , McAllister Florencia , De Jesus-Acosta Ana 
Published: April 2024

Abstract
Ten percent of pancreatic neuroendocrine tumors (pNET) are related to inherited syndromes (MEN1, MEN4, VHL, NF1, and TSC). Growing evidence suggests that clinically sporadic pNETs can also harbor germline pathogenic variants. In this study, we report the prevalence of pathologic/likely pathologic (P/LP) germline variants in a high-risk cohort and an unselected cohort. We collected clinical data of patients with pNETs seen at MD Anderson Cancer Center and Johns Hopkins Hospital. The high-risk cohort included (n = 132) patients seen at MD Anderson Cancer Center who underwent germline testing for high-risk criteria (early onset, personal or family history of cancer, and syndromic features) between 2013 and 2019. The unselected cohort included (n = 106) patients seen at Johns Hopkins Hospital who underwent germline testing following their diagnosis of pNETs between 2020 and 2022. In the high-risk cohort (n = 132), 33% (n = 44) had P/LP variants. The majority of the patients had P/LP variants in MEN1 56% (n = 25), followed by DNA repair pathways 18% (n = 8), and 7% (n = 3) in MSH2 (Lynch syndrome). Patients with P/LP were younger (45 vs. 50 years; P = 0.002). In the unselected cohort (n = 106), 21% (n = 22) had P/LP. The majority were noted in DNA repair pathways 40% (n = 9) and MEN1 36% (n = 8). Multifocal tumors correlated with the presence of P/LP (P = 0.0035). MEN1 germline P/LP variants correlated with younger age (40 vs. 56 years; P = 0.0012), presence of multifocal tumors (P &lt; 0.0001), and World Health Organization grade 1 histology (P = 0.0078). P/LP variants are prevalent in patients with clinically sporadic pNET irrespective of high-risk features. The findings support upfront universal germline testing in all patients with pNET.
Prevention Relevance: Here, we present germline data from the largest reported cohort of patients with pNET (n = 238), comprising both a high-risk cohort and an unselected cohort. In both cohorts, we identify a high number of P/LPs, including those in the DNA repair pathway. Our findings support universal germline testing in patients with pNET.
Differential Impact In Vivo of Pf4-ΔCre–Mediated and Gp1ba-ΔCre–Mediated Depletion of Cyclooxygenase-1 in Platelets in Mice
Authors: Tang Soon Yew , Lordan Ronan , Meng Hu , Auerbach Benjamin J. , Hennessy Elizabeth J. , Sengupta Arjun , Das Ujjalkumar S. , Joshi Robin , Marcos-Contreras Oscar A. , McConnell Ryan , Grant Gregory R. , Ricciotti Emanuela , Muzykantov Vladimir R. , Grosser Tilo , Weiljie Aalim M. , FitzGerald Garret A. 
Published: April 2024

BACKGROUND:

Low-dose aspirin is widely used for the secondary prevention of cardiovascular disease. The beneficial effects of low-dose aspirin are attributable to its inhibition of platelet Cox (cyclooxygenase)-1–derived thromboxane A
2
. Until recently, the use of the Pf4 (platelet factor 4) Cre has been the only genetic approach to generating megakaryocyte/platelet ablation of Cox-1 in mice. However, Pf4-ΔCre displays ectopic expression outside the megakaryocyte/platelet lineage, especially during inflammation. The use of the Gp1ba (glycoprotein 1bα) Cre promises a more specific, targeted approach.

METHODS:

To evaluate the role of Cox-1 in platelets, we crossed Pf4-ΔCre or Gp1ba-ΔCre mice with Cox-1
flox/flox
mice to generate platelet Cox-1
−/−
mice on normolipidemic and hyperlipidemic (Ldlr
−/−
; low-density lipoprotein receptor) backgrounds.

RESULTS:

Ex vivo platelet aggregation induced by arachidonic acid or adenosine diphosphate in platelet-rich plasma was inhibited to a similar extent in Pf4-ΔCre Cox-1
−/−
/Ldlr
−/−
and Gp1ba-ΔCre Cox-1
−/−
/Ldlr
−/−
mice. In a mouse model of tail injury, Pf4-ΔCre–mediated and Gp1ba-ΔCre–mediated deletions of Cox-1 were similarly efficient in suppressing platelet prostanoid biosynthesis. Experimental thrombogenesis and attendant blood loss were similar in both models. However, the impact on atherogenesis was divergent, being accelerated in the Pf4-ΔCre mice while restrained in the Gp1ba-ΔCres. In the former, accelerated atherogenesis was associated with greater suppression of PGI
2
biosynthesis, a reduction in the lipopolysaccharide-evoked capacity to produce PGE
2
(prostaglandin E) and PGD
2
(prostanglandin D), activation of the inflammasome, elevated plasma levels of IL-1β (interleukin), reduced plasma levels of HDL-C (high-density lipoprotein receptor-cholesterol), and a reduction in the capacity for reverse cholesterol transport. By contrast, in the latter, plasma HDL-C and α-tocopherol were elevated, and MIP-1α (macrophage inflammatory protein-1α) and MCP-1 (monocyte chemoattractant protein 1) were reduced.

CONCLUSIONS:
Both approaches to Cox-1 deletion similarly restrain thrombogenesis, but a differential impact on Cox-1–dependent prostanoid formation by the vasculature may contribute to an inflammatory phenotype and accelerated atherogenesis in Pf4-ΔCre mice.
Wnt Signaling Inhibition Prevents Postnatal Inflammation and Disease Progression in Mouse Congenital Myxomatous Valve Disease
Authors: Xu Na , Alfieri Christina M. , Yu Yang , Guo Minzhe , Yutzey Katherine E. 
Published: April 2024

BACKGROUND:
Myxomatous valve disease (MVD) is the most common cause of mitral regurgitation, leading to impaired cardiac function and heart failure. MVD in a mouse model of Marfan syndrome includes valve leaflet thickening and progressive valve degeneration. However, the underlying mechanisms by which the disease progresses remain undefined.

METHODS:

Mice with
Fibrillin 1
gene variant
Fbn1

C1039G/+

recapitulate histopathologic features of Marfan syndrome, and Wnt (Wingless-related integration site) signaling activity was detected in
TCF/Lef-lacZ
(T-cell factor/lymphoid enhancer factor-β-galactosidase) reporter mice. Single-cell RNA sequencing was performed from mitral valves of wild-type and
Fbn1

C1039G/+

mice at 1 month of age. Inhibition of Wnt signaling was achieved by conditional induction of the secreted Wnt inhibitor Dkk1 (Dickkopf-1) expression in periostin-expressing valve interstitial cells of
Periostin
-Cre;
tetO-Dkk1; R26rtTA; TCF/Lef-lacZ; Fbn1

C1039G/+

mice. Dietary doxycycline was administered for 1 month beginning with MVD initiation (1-month-old) or MVD progression (2-month-old). Histological evaluation and immunofluorescence for ECM (extracellular matrix) and immune cells were performed.

RESULTS:

Wnt signaling is activated early in mitral valve disease progression, before immune cell infiltration in
Fbn1

C1039G/+

mice. Single-cell transcriptomics revealed similar mitral valve cell heterogeneity between wild-type and
Fbn1

C1039G/+

mice at 1 month of age. Wnt pathway genes were predominantly expressed in valve interstitial cells and valve endothelial cells of
Fbn1

C1039G/+

mice. Inhibition of Wnt signaling in
Fbn1

C1039G/+

mice at 1 month of age prevented the initiation of MVD as indicated by improved ECM remodeling and reduced valve leaflet thickness with decreased infiltrating macrophages. However, later, Wnt inhibition starting at 2 months did not prevent the progression of MVD.

CONCLUSIONS:
Wnt signaling is involved in the initiation of mitral valve abnormalities and inflammation but is not responsible for later-stage valve disease progression once it has been initiated. Thus, Wnt signaling contributes to MVD progression in a time-dependent manner and provides a promising therapeutic target for the early treatment of congenital MVD in Marfan syndrome.
Universities and Cities: The Impact of Higher Education on Urban Innovation, Entrepreneurship, and Economic Growth
Authors: Peng Chong , Xu Hongwei 
Published: April 2024

Abstract
While universities play a pivotal role in fostering the growth and progress of their surrounding cities, the extent of this influence remains underexplored and warrants deeper empirical investigation. Through a comprehensive literature review, we identify three main mechanisms that describe the developmental impact: urban innovation, urban entrepreneurship, and economic growth. Using panel data from 239 Chinese cities spanning 2004 to 2016, we show that the positive externalities from universities are region-specific. The development of universities not only stimulates urban innovation and entrepreneurship but also promotes economic growth in urban areas, shaping the overall influence of cities. Additionally, the positive externalities generated by high-quality and large-scale universities on local development are significant.
Tax Farming, the Provincial Council and the Nature of the Late Ottoman State
Authors: Aykan Yavuz 
Published: April 2024

Abstract
This article focuses on the Council (Divan) of Amid in Diyarbekir Province as a petition-receiving institution throughout the eighteenth century. By drawing on the court records of the city of Harput, one of the sub-districts of Diyarbekir, and the tax farming registers of the larger province, the article discusses the role of the provincial governor in legal procedures. It argues that the Provincial Council had an important function in the operative field of law as it made it possible for the petitioning subjects in Harput to obtain judgments reviewed in the court of Harput in the form of ‘trial de novo’. While situating the emergence of the Council in the political-economic context of the time, the article also argues that the Provincial Council was an early modern institution which, in part, paved the way to the constitution of the nineteenth century provincial administration of the Tanzimat state.
A Situationist Portrait of Power: Cybernetics, May ’68, and The Situationist International
Authors: Routhier Dominique 
Published: April 2024

Abstract
This article presents the critique of cybernetics as central to the history of one of the twentieth century’s most infamous avant-garde movements: the Situationist International (SI). Bringing together and analysing a series of seemingly marginal events in the build-up to May ’68, this article shows how the SI’s portrait of cybernetics as an emerging form of social power and control foreshadows later developments in French radical thought. This little-noted trajectory in the situationist movement also highlights the ways in which aesthetics, theory, and politics are inextricably tied together in the events of May ’68.
A Constructive Trinitarian Theology of the First Article for the Religiously Pluralistic and Secular World
Authors: Kärkkäinen Veli-Matti 
Published: April 2024

Abstract
Even laypersons, such as systematic theologians, who are not trained in law enforcement are familiar enough with crime investigation to know that the detective works circles around a few simple questions such as: Who committed the crime? What happened? How was the crime executed? Why did the criminal do what he or she did? In the first part of my essay, as a way of introducing the nature, “method,” and distinctive features as well as the motifs behind the five-volume constructive theology, I will follow that simple template. The second major part will zoom in on the given task of this essay, namely, the theology of the first article of the creed, the doctrine of God. As the distinctive Christian conception of God is trinitarian by its very nature, that discussion in its form and content is thoroughly triune. Consequently, my main argument comes in two successive steps. First, the first-article theology—similarly to the second- and third-article theologies, respectively—is trinitarian. Second, its distinctive feature in comparison to the second- and third-article theologies is that the works of the triune God are considered and investigated from the perspective of what the Father, alongside Son and Spirit, is doing in the world.
Witnessing to Jesus the Spirit Baptizer
Authors: Simatupang Florian M.P. 
Published: April 2024

Abstract
This response proceeds in two parts. It begins by conversing with the broad-strokes sketch Frank Macchia offers in his article in this issue and his christological thoughts from his other, more extensive work. This is followed by an articulation of the author’s pentecostal Christology to offer a teleological assist to fill in some of the gaps in Macchia’s approach. The telos of Christology is to witness and testify to the forming of the character of Christ in all things (Col 1:17). This complementing response to Macchia utilizes one of the significant Jewish particularities of Jesus the Spirit baptizer, outlined in the definition of anointing that he spoke at his inaugural sermon in Nazareth. Jesus’s Jewish identity creates a framework to christologize in a way that is informed by the author’s context as an Indonesian pentecostal theologian.
Neglected Tropical Diseases and Long-Term Captive Animals: Ethical Considerations with Venom Lab Snakes
Authors: Halm Derek 
Published: April 2024

Abstract
Venomous snakebite is a neglected tropical disease and disease of poverty, affecting hundreds of thousands of people annually. The only effective medical intervention for snakebite is antivenom, produced primarily using captive venomous snakes as a source of venom. This paper analyzes snakes’ welfare at venom labs within this global health context. I recommend significant changes to improve the welfare of captive snakes, particularly in light of recent ethological research and attention on snakes. These recommendations are broadly consequentialist, aiming to improve the lives of the snakes and ensure that people have increased access to affordable antivenom.
Natural Religion, Isaac Watts, and Early Eighteenth-Century Evangelical Devotion
Authors: Stokes W. Britt 
Published: April 2024

Abstract
The early eighteenth-century English Enlightenment is a transformative period in the history of the Christian church. Among other paradigm shifts, the rise of natural religion and physico-theology became a common means by which theologians and churchmen of the era begin interacting with Enlightenment thought. Among these pastor-theologians, stands the well-known hymnwriter Isaac Watts. This article seeks to examine how Watts uses natural religion to frame a doctrine of heaven for purposes of Christian devotion. This will in turn further situate Watts among the figures within the early eighteenth century to begin integrating natural religion into devotional prose. Additionally, it will further our understanding of Watts as an important transitional figure between the English Puritans and eighteenth-century Evangelicals.
‘You Never Stop Working’
Authors: Perigo Jeremy 
Published: April 2024

Abstract
Theological analysis of the most popular worship song lyrics reflects that American Christians may be singing the American work ethic to the God who rested. Employing Brueggeman’s Sabbath as Resistance and Heschel’s The Sabbath alongside current discussions in evangelical liturgical studies, this article seeks to answer the following: 1) do the current most utilized congregational songs in America reveal a God who rests, and 2) what lyrical or musical possibilities exist to embody a theology of Sabbath rest. This analysis highlights liturgical and theological dissonance, while exploring musical and lyrical models that display a God who rests in an overworked culture.
Ability of States to Implement  Planned Budget in India: An  Assessment Using PEFA Framework
Authors: Jena Pratap Ranjan 
Published: April 2024

A credible budget complies with budget contracts voted in Parliament and improves the efficiency of government expenditure. Deviations, as a result of weak capacity to forecast revenue or execute the planned activities, pose risks to both existing and future programme management. This budgetary tenet assumes significance as the states have to respond to disruption in revenues, rising expenditure burdens and changes in priorities in the wake of COVID-19 pandemic and face challenges to restore fiscal consolidation process. The article assesses the budget credibility of states in India from 2012–13 to 2018–19 following the international standard given by the Public Expenditure and Financial Accountability (PEFA) framework. It also focuses on strengthening institutional framework to utilise fiscal instruments optimally for better service delivery and development. JEL Codes: H61, H68, E62
Exploring Experiences of Drink and Needle Spiking Incidents Among Global Drug Survey Respondents from 22 Countries
Authors: Davies Emma L. , Piatkowski Timothy , Frankovitch Alex , Puljević Cheneal , Barratt Monica J. , Ferris Jason A. , Winstock Adam R. 
Published: April 2024

This study explored experiences of spiking following the re-opening of nightlife settings post COVID-19 lockdown. Global Drug Survey 2022, respondents were asked about experience, context, and consequences of drink/needle spiking. In a sample of 7697 respondents 2% reported experiencing spiking the last 12 months, and 20% over a year ago. Most occurred in clubs/bars (54.8%), but a quarter occurred in a private home. 84.9% of respondents suspected a drug was added to their drink; 4.2% thought they had been injected with a drug. Almost a fifth experienced sexual assault during the incident. Only 7.2% who experienced drink spiking reported it to police. Higher AUDIT scores, being a woman, recent illicit substance use and recent clubbing experience were also associated with recent spiking. Low rates of reporting means it is difficult to understand prevalence and causes. However, media reports of an epidemic of spiking appear to have been disproportionately emphasised.
Romantic partner communication, familism values, and Latine young adults’ relationship maintenance
Authors: Boron Dawson E. , Killoren Sarah E. , Monk J. Kale , Rivero Avelina , Kanter Jeremy B. , Proulx Christine M. 
Published: April 2024

Negative communication between partners can impede the enactment of prosocial, relationship maintenance behaviors. These processes are especially critical to consider for Latine young adults who hold cultural values, like familism, which emphasize the great importance of personal relationships. Using a sample of 475 Latine young adults ( M = 24.8 years, SD = 3.22), we examined the moderating role of familism on the association between negative communication (e.g., partners’ propensity to withdraw or criticize during interactions) and relationship maintenance (e.g., affectionate and supportive efforts to sustain the relationship). We found that negative communication was inversely associated with individuals’ own relationship maintenance enactment. However, familism buffered the association between negative communication and relationship maintenance; under conditions of high familism, the association between negative communication and relationship maintenance remained negative, but with a weaker effect than under conditions of low familism. Findings reinforce the negative effects of maladaptive communication in relationships more broadly and highlight the protective role of relationally oriented cultural values.