bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of cabozantinib and pembrolizumab in advanced gastric/gastroesophageal adenocarcinomas resistant or refractory to immune checkpoint inhibitors
Authors: Dayyani Farshid , Chao Joseph , Lee Fa-Chyi , Taylor Thomas H , Neumann Kristen , Cho May T 
Published: June 2024

Abstract

Background
Most patients with metastatic gastroesophageal adenocarcinoma (mGEA) progress on immune checkpoint inhibitors (ICIs). Novel approaches to overcome resistance to ICI in mGEA are needed. Cabozantinib is a multi-tyrosine kinase inhibitor thought to enhance the immunomodulatory effects of ICI. This study evaluated the combination of cabozantinib and pembrolizumab in ICI refractory or resistant mGEA.

Methods
Investigator-initiated, single-arm, single institution, and phase II study in patients with mGEA. Patients had progressed on ICI and/or had PD-L1 CPS score ≤10%. Cabozantinib dose was 40 mg p.o. daily on days 1-21 of a 21-day cycle, with pembrolizumab 200 mg i.v. on day 1. The primary endpoint was progression-free survival at 6 months (PFS-6).

Results
Twenty-seven patients were enrolled. Median age 58 years (24-87), female (n = 14), ECOG 0/1 = 13/14, GC/GEJ = 16/11, and non-Hispanic White/Hispanic/Asian = 12/8/7. The primary endpoint was met. After a median follow-up of 31.4 months (range 3.3-42.5), PFS-6 was 22.2% (95% CI 9.0-39.0). The median PFS and OS are 2.3 months (95% CI 1.7-4.1) and 5.5 months (3.1-14.0), respectively. The most common mutations were TP53 (78.3%) and CDH1/PIK3CA/CTNNB1 (17.4% each). The most common grade (G) treatment-related adverse events (TRAE) were diarrhea (25.9%), fatigue (18.5%), hypertension, and muscle cramps (14.8% each). G3-4 TRAE were seen in n = 3 patients (hypertension, thromboembolic event, esophageal perforation; each n = 1). No G5 was observed.

Conclusions
The addition of cabozantinib to pembrolizumab shows clinical benefit in ICI-resistant or refractory mGEA with a tolerable safety profile. (ClinicalTrials.gov Identifier: NCT04164979. IRB Approved: UCI 18-124, University of California Irvine IRB#20195426.)
Deleterious alterations in homologous recombination repair genes and efficacy of platinum-based chemotherapy in biliary tract cancers
Authors: Belli Carmen , Boscolo Bielo Luca , Repetto Matteo , Crimini Edoardo , Scalia Raimondo , Diana Anna , Orefice Jessica , Ascione Liliana , Pellizzari Gloria , Fusco Nicola , Barberis Massimo , Daniele Bruno , Guerini-Rocco Elena , Curigliano Giuseppe 
Published: June 2024

Abstract

Background
Platinum-based chemotherapy represents the standard first-line treatment for biliary tract cancers (BTC). Deficits in genes involved in the homologous recombination (HR) and DNA damage response (DDR) may confer higher sensitivity to platinum agents.

Methods
We retrospectively included patients affected by BTC from 2 Italian institutions. Inclusion criteria consist of the receipt of platinum-based chemotherapy in the metastatic setting and the availability of comprehensive genomic profiling using next-generation sequencing (NGS). Patients were included in the HRD-like group if demonstrated oncogenic or likely oncogenic alterations in HR-/DDR-genes. Clinical endpoints were compared between the HRD-like group and the non-HRD-like group.

Results
Seventy-four patients were included, of whom 25 (33%) in the HRD-like group and 49 (66%) in the non-HRD group. With a median follow-up of 26.04 months (interquartile-range [IQR] 9.41-29.27) in the HRD-like group and of 22.48 months (IQR 16.86-40.53) in the non-HRD group, no PFS difference emerged, with a mPFS of 5.18 months in the HRD-like group compared to 6.04 months in the non-HRD group (hazard ratio [HR], 1.017, 95% CI 0.58-1.78; P = .95). No differences were observed in DCR (64% [95 CI 45%-83%] vs 73% [95 CI 61%-86%]; P = .4), and CBR (45% [95% CI 28%-73%] vs 50% [95% CI, 37%-68%]; P = .9) between the HRD-like group and non-HRD groups, respectively. Median OS did not statistically differ between the HRD-like group and non-HRD group (26.7 vs 18.0 months, respectively; HR, 0.670, 0.33 to 1.37, P = .27).

Conclusion
HR-/DDR-genes, when assessed with regular tumor-only NGS panels, provide limited clinical validity to identify patients with BTC more likely to benefit from platinum-based chemotherapy.
Citizens’ trust in Bangladesh Police: A cross-sectional survey on urban population
Authors: Ahsan Abu Hossain Muhammad , Hasan Md Khalid , Rumi Maruf Hasan 
Published: June 2024

Abstract
The study assessed the level of trust in police among urban citizens in Bangladesh and examined the associated factors. An online cross-sectional survey was conducted through mobile phones to collect data from 1,680 respondents using a structured questionnaire. A 9-item scale was developed and validated to measure citizens’ trust in police using procedural- and outcome-based trust models. The urban citizens had a relatively low level of trust in the police. Factors like trust in neighbourhoods, satisfaction with governmental law and order operation, believing positive media reports on police, and personal safety awareness were significantly positively associated with trust in police. In contrast, increasing crime in the residential areas, believing negative media reports on police, and senior citizens were significantly associated with low levels of trust in police. Bangladesh police should adopt pro-people practices with effective implementation of law and order to increase their trust.
How can societally-targeted research funding shape researcher networks and practices?
Authors: Ramos-Vielba Irene , Bloch Carter , Thomas Duncan A , Povlsen Rikke E , Falkenberg Mette L , Stage Andreas K 
Published: June 2024

Abstract
Funding is considered to have a central role in defining the scope, content and direction of public research. However, we lack sufficient understanding of how funding can shape research networks and practices to enhance societal goals. In this paper, we apply a recent approach that explores the societal targeting of funding across four key dimensions: interdisciplinarity, transdisciplinarity, prioritized research problems, and user-oriented outputs. Through in-depth case studies of 12 funded research projects, we explore shaping in these dimensions by contrasting pre- and post-acquisition of a societally targeted project grant based on the accounts of principal investigators (PI). We examine cases across two research areas—renewable energy and food science—in three European countries—Denmark, Netherlands and Norway. Our analysis suggests that societally targeted funding can act as an enabler of inter- and transdisciplinary collaborations and the accumulation of experience to manage them. This funding also encourages research practices that prioritize societal research problems and foster users’ utilization of research outputs while still preserving researcher scientific autonomy. Shaping dynamics are then examined in connection with funding requirements across the four dimensions.
Indoor concentrations of radioactive aerosols from nuclear accidents
Authors: Orabi Momen 
Published: June 2024

Abstract
In previous studies, some of the important factors that affect the spread of radioactive aerosols into indoors were considered. The studies were based on a new CFD approach and provided good descriptions for the deposition of aerosol particles inside small spaces and the penetration of aerosols into buildings through wall cracks. In this article, an application of those studies is implemented, where all the graphical relations that are required to estimate the indoor concentrations of radioactive aerosols from nuclear accidents are provided. This includes the deposition velocities, deposition rate, and the penetration factor. Particular interest is in the Fukushima-Daiichi nuclear power plant accident that took place in Japan in 2011. The aerosols carrying the radioiodine iodine-131 and the radiocesium cesium-134 and cesium-137 are studied. Based on the model’s assumptions, and assuming steady-state air concentrations, the radioactive aerosols’ concentrations in indoor air are about 97% of the concentrations in outdoor air. The applications demonstrate the model to be convenient and practical.
Evaluation of the environmental and structural impacts on urban expansion using airborne geophysical data at Hurghada city, Northern Eastern Desert, Egypt
Authors: El-Qassas Reda Abdu Yousef 
Published: June 2024

Abstract
Airborne gamma-ray spectrometric and magnetic data were processed and interpreted aiming to evaluate the environmental and structural impacts on urban expansion, Hurghada City, Northern Eastern Desert, Egypt. The eastern (coastal area), northern, and southeastern parts of the study area possess the lowest level of absorbed dose rate (ADR) and annual effective dose equivalent (AEDE), which were estimated from the airborne gamma-ray spectral data of this area. Consequently, these parts are considered as suitable sites for urban expansion from the radioactivity point of view. The relatively high level of ADR and AEDE is associated with granitic rocks, some parts of Gabir formation and recent Wadi sediments, situated at southwestern, central, and eastern parts of the study area. The ADR and AEDE of these parts are considered harmful to individuals. Airborne magnetic data were also used to detect major structures that may affect various construction projects in the study area in the future. The NNW–SSE, NW–SE, N–S, and NE–SW trends represent the common structures in the study area. The obtained results of airborne gamma-ray spectrometric and magnetic data illustrated that the urban expansion should not be constructed to the west of the ring road. However, site investigations must be carried out on this part of the study area before starting any construction projects there. The present study proved the important role of airborne gamma-ray spectrometric and magnetic surveys as useful tools to delineate the environmental and structural impacts on urban expansion.
Mexico’s battle with monopolies: reputation-based autonomy and self-undermining effects in antitrust enforcement
Authors: Arslan Melike 
Published: June 2024

Abstract
Despite increased scholarly attention to competition law enforcement against corporate monopolies, our understanding of this topic in developing countries remains very limited. This article addresses this gap by focusing on Mexico, using enforcement statistics, expert interviews and documentary resources. I find that Mexico initially pursued surprisingly high levels of anti-monopoly enforcement, which was followed by an equally surprising decline. Departing from the previous research that emphasized the influence of expert ideas, business power and international models, this study highlights two factors shaping the enforcement of competition law on monopolies in developing country contexts: the strategies employed by newly established competition authorities to foster organizational autonomy through a positive public reputation, and the subsequent self-undermining effects of these strategies. In addition to advancing the existing literature on competition policies, these findings shed light on the factors behind local variations in globally diffused institutions and the limitations of reputation-based bureaucratic autonomy.
“Maybe We Should Start Paying the Hours Properly”: State Violence and Ambivalent Moments of Enforced Emancipation of Refugee Women
Authors: Øland Trine 
Published: June 2024

Abstract
Within integration programs and practices, refugee women are repeatedly offered rescue and emancipation. This article explores how emancipation intersects with material and social injustices of integration practices, and how refugee women in particular become subjects for emancipation. It examines the bordering practices of integration and emancipation, and identifies how integration practices symbolize refugee women as, here called, “oppressed,” “spoiled,” “willing,” “surprisingly productive,” or “familiar.” It investigates how these symbolizations circulate in emancipatory practices that are steeped in national imaginaries, as well as in welfare state work ethics. Emancipation is confined to submission to exploitative reproductive work and tied to consumerism. But it also has ambivalent moments around regularizing refugee women’s strategically needed care-work. The article suggests that differential emancipation reproduces complex and violent logics of gendered racial capitalism and coloniality of the Danish welfare state.
XThe Seventeenth Century, Part II
Authors: Stelzer Emily , Baker William , Airey Jennifer , Parry David 
Published: June 2024

Abstract
This chapter contains coverage of poetry, drama, and prose. In order to more conveniently note the contributions of various contributors, this chapter will offer, in lieu of a larger ‘General and Poetry’ section, numerous smaller sections on individual poets. Similarly, prose authors Hobbes, Locke, Aubrey, and Bunyan will each have their own section. This chapter has fourteen sections: 1. Marvell; 2. Herrick; 3. Cowley; 4. Crashaw; 5. Hester Pulter; 6. Rochester; 7. Traherne; 8. Vaughan; 9. Restoration Draman Excluding Dryden; 10. Dryden; 11. Hobbes; 12. Locke; 13. Aubrey; 14. Bunyan. There is no section on Pepys this year. Sections 1, 2, and 5 are by Emily Stelzer; sections 3, 4, 6, 7, 8, 11, 12, and 13 are by William Baker; sections 9 and 10 are by Jennifer Airey; section 14 is by David Parry. William Baker thanks Claudia Keelan, Joseph Sterrett, David Strong, and Helen and Allan Wilcox who made articles and journals, such as Scintilla, available and otherwise assisted.
Unraveling the role of lipid droplets and perilipin 2 in bovine luteal cells
Authors: Plewes Michele R. , Talbott Heather A. , Schott Micah B. , Wood Jennifer R. , Cupp Andrea S. , Davis John S. 
Published: June 2024

AbstractSteroidogenic tissues contain cytosolic lipid droplets that are important for steroidogenesis. Perilipin 2 (PLIN2), a structural coat protein located on the surface of lipid droplets in mammalian cells, plays a crucial role in regulating lipid droplet formation and contributing to various cellular processes such as lipid storage and energy homeostasis. Herein, we examine the role that PLIN2 plays in regulating progesterone synthesis in the bovine corpus luteum. Utilizing gene array databases and Western blotting, we have delineated the expression pattern of PLIN2 throughout the follicular to luteal transition. Our findings reveal the presence of PLIN2 in both ovarian follicular and steroidogenic luteal cells, demonstrating an increase in its levels as follicular cells transition into the luteal phase. Moreover, the depletion of PLIN2 via siRNA enhanced progesterone production in small luteal cells, whereas adenovirus‐mediated overexpression of both PLIN2 and Perilipin 3 (PLIN3) induced an increase in cytosolic lipid droplet accumulation and decreased hormone‐induced progesterone synthesis in these cells. Lastly, in vivo administration of the luteolytic hormone prostaglandin F2α resulted in an upregulation of PLIN2 mRNA and protein expression, accompanied by a decline in serum progesterone. Our findings highlight the pivotal role of PLIN2 in regulating progesterone synthesis in the bovine corpus luteum, as supported by its dynamic expression pattern during the follicular to luteal transition and its responsiveness to luteotropic and luteolytic hormones. We suggest PLIN2 as a potential therapeutic target for modulating luteal function.
Original Research: Nurses' Knowledge and Attitudes Regarding the Sustainable Development Goals: A Global Study
Authors: Hawkins Janice Evans , Chiu Patrick , Mumba Mercy Ngosa , Gray Sarah E. , Hawkins Robert Joseph 
Published: June 2024

ABSTRACT

Background:
Nurses have a critical role to play in achieving the United Nations' 17 Sustainable Development Goals (SDGs). While Goal 3 (good health and well-being) is of particular importance to nursing, every SDG contributes to the advancement of universal health and well-being. Yet many nurses are unfamiliar with the SDGs and how they relate to everyday nursing practices.

Purpose:
The purpose of this study was to examine RNs' knowledge of and attitudes toward the SDGs.

Methods:
This study used a descriptive correlational cross-sectional design. A convenience sample of RNs from multiple countries completed an anonymous online survey that included eight demographic items and 25 items exploring participants' knowledge of and attitudes toward the SDGs. Descriptive, parametric, and nonparametric statistics were used to analyze the data.

Results:
The majority of nurses in this study perceived themselves as lacking knowledge of the SDGs. Most wanted to know more, including how they could take action to help achieve the goals. Overall, participants agreed that the SDGs are relevant to nursing practice and that nurses are integral to their advancement. Participants who were younger than age 50, those living in the United States, and those who practiced primarily in a clinical or community setting were more likely than others to self-report lower SDG knowledge scores.

Conclusions:
The study findings contribute to our collective understanding of RNs' knowledge and attitudes regarding the SDGs. They can assist nurse educators and leaders worldwide in developing targeted strategies to better inform nurses and prepare them for actions that will advance these goals. Increasing nurses' knowledge of the SDGs, especially as these goals relate to daily clinical practice, may lead to greater nursing engagement and impact.
Skin Pigmentation Affects ViOptix T.Ox Performance in Variably Pigmented Preclinical Model of Flap Ischemia and Congestion
Authors: Westman Amanda M. , Ribaudo Joseph , Butler Michael , Shmuylovich Leonid , Pet Mitchell A. 
Published: June 2024

Background:
Free flap monitoring is more difficult in patients with dark skin because ischemia and congestion can be masked by pigmentation. For this reason, adjunct methods such as cutaneous near-infrared spectroscopy are of elevated importance in patients with highly pigmented skin. The purpose of this experiment is to determine if ViOpitx T.Ox performance is affected by cutaneous pigmentation.

Methods:
Swine with naturally occurring areas of nonpigmented and pigmented skin were used. Pigmentation of each animal was assessed using spectrophotometry and histopathology. During normoxemia, tissue oxygenation (StO2) measurements were taken of nonpigmented and pigmented skin using the T.Ox device. A bicolor pedicled rectus abdominis myocutaneous flap was raised, and T.Ox probe was adhered to adjacent areas of opposite coloration on the same flap. StO2 was measured continuously during reversible episodes of flap ischemia and congestion (n = 4 swine, n = 6 flaps).

Results:
There was not a significant difference between baseline StO2 values of nonpigmented (49% ± 7.9%) and pigmented skin (47% ± 6.2%). The absolute change in StO2 was significantly larger during both ischemia (6%) and congestion (16%) in nonpigmented skin compared with adjacent pigmented skin.

Conclusions:
T.Ox detects flap ischemia and congestion in both highly pigmented and nonpigmented skin. However, surgeons need to be aware that StO2 changes related to complete flap ischemia or congestion may be much more subtle than what is seen in nonpigmented skin. This study establishes a novel internally controlled porcine model that isolates the impact of skin pigmentation when assessing cutaneous devices measuring tissue oxygenation.
Assessing the Racial and Ethnic Diversity of Physician Assistant/Associate Program Graduates from 2010 to 2012 and 2019 to 2021
Authors: Ritsema Tamara S. , Herring Jordan R. , Straker Howard O. , Salsberg Edward 
Published: June 2024

Introduction
To assess the racial/ethnic diversity of graduates of US Physician Assistant/Associate (PA) programs compared with the diversity of the populations from which they draw students and to assess diversity changes over time among PA graduates.

Methods
We calculated proportion of Black or Hispanic PA graduates nationally and by school between 2010 to 2012 and 2019 to 2021 using the Integrated Postsecondary Education Data System (IPEDS) and compared it with the diversity of the 20 to 35-year-old population using the American Community Survey. We created benchmark populations for each school based on whether the school was public or private, with in-state/out-of-state proportions provided by the Physician Assistant Education Association. A diversity index (DI) was calculated for each program. A DI of 0.5 means that the representation of Black/Hispanic graduates is half their representation in the benchmark population.

Results
Although the numbers of Black/Hispanic graduates increased from 2010 to 2012 to 2019 to 2021, the percentage of Black graduates decreased. Nationally, the DI for Black graduates decreased from 0.28 to 0.23 and the Hispanic DI increased from 0.28 to 0.37 between 2010 to 2012 and 2019 to 2021. Among 213 PA programs included in the 2019 to 2021 dataset, 5 schools had a DI >1.0 for Black graduates and 7 schools had a DI >1.0 for Hispanic graduates.

Discussion
Using the IPEDS data, we found that Black and Hispanic graduates are underrepresented among PA program graduates. The PA education community needs to develop new strategies for diversifying the profession consistent with the new US Supreme Court decision banning race-conscious admissions.
Symmetry and Generalization in Local Learning of Predictive Representations
Authors: Keck Janis , Barry Caswell , Doeller Christian F. , Jost Jürgen 
Published: June 2024

AbstractIn spatial cognition, the Successor Representation (SR) from reinforcement learning provides a compelling candidate of how predictive representations are used to encode space. In particular, hippocampal place cells are hypothesized to encode the SR. Here, we investigate how varying the temporal symmetry in learning rules influences those representations. To this end, we use a simple local learning rule which can be made insensitive to the temporal order. We analytically find that a symmetric learning rule rule results in a successor representation under a symmetrized version of the experienced transition structure. We then apply this rule to a two-layer neural network model loosely resembling hippocampal subfields CA3 - with a symmetric learning rule and recurrent weights - and CA1 - with an asymmetric learning rule and no recurrent weights. Here, when exposed repeatedly to a linear track, neurons in our model in CA3 show less shift of the centre of mass than those in CA1, in line with existing empirical findings. Investigating the functional benefits of such symmetry, we find that using a symmetric learning rule yields representations which afford better generalization, when a model is probed to navigate to a new target without relearning the SR. This effect is reversed when the state space is not symmetric anymore. Thus, our results hint at a potential benefit of the inductive bias afforded by symmetric learning rules in areas employed in spatial navigation, where there naturally is a symmetry in the state space.