bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of a Small-Molecule Inhibitor of KrasG12D in Immunocompetent Models of Pancreatic Cancer
Authors: Kemp Samantha B. , Cheng Noah , Markosyan Nune , Sor Rina , Kim Il-Kyu , Hallin Jill , Shoush Jason , Quinones Liz , Brown Natalie V. , Bassett Jared B. , Joshi Nikhil , Yuan Salina , Smith Molly , Vostrejs William P. , Perez-Vale Kia Z. , Kahn Benjamin , Mo Feiyan , Donahue Timothy R. , Radu Caius G. , Clendenin Cynthia , Christensen James G. , Vonderheide Robert H. , Stanger Ben Z. 
Published: December 2022

Abstract

Mutations in the KRAS oncogene are found in more than 90% of patients with pancreatic ductal adenocarcinoma (PDAC), with Gly-to-Asp mutations (KRASG12D) being the most common. Here, we tested the efficacy of a small-molecule KRASG12D inhibitor, MRTX1133, in implantable and autochthonous PDAC models with an intact immune system. In vitro studies validated the specificity and potency of MRTX1133. In vivo, MRTX1133 prompted deep tumor regressions in all models tested, including complete or near-complete remissions after 14 days. Concomitant with tumor cell apoptosis and proliferative arrest, drug treatment led to marked shifts in the tumor microenvironment (TME), including changes in fibroblasts, matrix, and macrophages. T cells were necessary for MRTX1133's full antitumor effect, and T-cell depletion accelerated tumor regrowth after therapy. These results validate the specificity, potency, and efficacy of MRTX1133 in immunocompetent KRASG12D-mutant PDAC models, providing a rationale for clinical testing and a platform for further investigation of combination therapies.

Significance:
Pharmacologic inhibition of KRASG12D in pancreatic cancer models with an intact immune system stimulates specific, potent, and durable tumor regressions. In the absence of overt toxicity, these results suggest that this and similar inhibitors should be tested as potential, high-impact novel therapies for patients with PDAC.
See related commentary by Redding and Grabocka, p. 260.
This article is highlighted in the In This Issue feature, p. 247
Association of Clinical Setting With Sociodemographics and Outcomes Following Endovascular Femoropopliteal Artery Revascularization in the United States
Authors: Raja Aishwarya , Wadhera Rishi K. , Choi Eunhee , Chen Siyan , Shen Changyu , Figueroa Jose F. , Yeh Robert W. , Secemsky Eric A. 
Published: December 2022

Background:
After the Centers for Medicare and Medicaid Services modified reimbursement rates for outpatient peripheral vascular intervention in 2008 with the intent of improving access to care, providers began to increasingly perform peripheral vascular interventions in privately owned office-based clinics. Little is known about the characteristics of patients treated in this setting and their long-term outcomes as compared with those treated in hospital-based centers.

Methods:
In this retrospective cohort study, Medicare beneficiaries ≥66 years undergoing outpatient femoropopliteal peripheral vascular interventions in office-based clinics and hospital-based centers from 2015 to 2017 were identified. Sociodemographics, comorbidities, and institutional characteristics were compared across sites. Multivariable Cox proportional hazards models were used to estimate the adjusted associations between practice site location and outcomes. The primary outcome was the composite of major amputation or death analyzed through the end of follow-up.

Results:
Among 134 869 patients, 29.9% were treated in office-based clinics and 70.1% in hospital-based centers. Patients treated in office-based clinics were more often Black (16.9% versus 11.9%), dually enrolled in Medicaid (26.3% versus 19.6%), and residents of lower-resourced regions (32.6% versus 25.6%). Over a median follow-up time of 800 days (interquartile range, 531–1119 days), patients treated in office-based clinics had reduced risks of major amputation or death compared with outpatients treated in hospital-based centers (hazard ratio, 0.92 [95% CI, 0.89–0.95]). They also had lower adjusted all-cause mortality (hazard ratio, 0.93 [95% CI, 0.90–0.96]), major lower extremity amputation (hazard ratio, 0.84 [95% CI, 0.79–0.89]), and all-cause hospitalization (hazard ratio, 0.86 [95% CI, 0.84–0.88]). These findings persisted after stratification by critical limb ischemia, race, dual enrollment, and regional socioeconomic status, as well as among operators treating patients in both clinical settings.

Conclusions:
In this large nationwide analysis of Medicare beneficiaries, office-based clinics treated a more socioeconomically disadvantaged population compared with hospital-based centers. Long-term outcomes were comparable between locations. As such, these clinics appear to be selecting lower-risk patients for outpatient peripheral vascular interventions, although there remains the possibility of unmeasured confounding.
Trends in Thrombolysis and Thrombectomy Use in Patients With Ischemic Stroke and Cancer
Authors: Otite Fadar Oliver , Somani Sana , Chaturvedi Seemant , Mehndiratta Prachi 
Published: December 2022

Background
To determine how intravenous thrombolysis (IV‐tPA) and mechanical thrombectomy (MT) use has changed in patients with acute ischemic stroke (AIS) with cancer (AIS‐C) compared with patients with AIS and noncancer (AIS‐NC) in the United States since publication of pivotal MT trials.

Methods
All primary AIS‐NC and AIS‐C admissions (weighted N=5 748 357) were identified from the 2007 to 2019 Nationwide Inpatient Sample. Joinpoint and multivariable‐adjusted models with interaction terms were used to compare the rate of change in IV‐tPA and MT use between AIS‐C and AIS‐NC.

Results

From 2007 to 2019, 4.4% of AIS admissions had active cancer. Overall IV‐tPA use in AIS‐C (6.4%) was lower than that of AIS‐NC (8.5%) (
P
<0.001) but use differed by cancer subtype (hematologic, 7.2%; metastatic, 4.2%). IV‐tPA use increased over time in all cancers, but analysis of status‐by‐time interaction revealed that the pace of increase was slower in metastatic compared with AIS‐NC admissions (rate ratio, 0.98;
P
=0.015) per year. In contrast, MT use in AIS‐C (2.2%) was greater than that of AIS‐NC (1.9%), but use was highest in metastatic (2.5%) and lowest in hematologic cancers (1.6%) (
P
values for all pairwise comparisons <0.001). MT use increased at a faster pace in metastatic AIS‐C (rate ratio, 1.06;
P
=0.001)/year compared with AIS‐NC. In‐hospital all‐cause mortality in AIS‐NC was 4.2% compared with 8.2% in AIS‐C (
P
<0.001). Mortality declined over time in all cancer groups, but the pace of decline was faster in solid and metastatic AIS‐C compared with AIS‐NC (
P
values <0.01).

Conclusions
Use of IV‐tPA and MT has increased in AIS‐C over the past decade. Contrary to prior studies, the current frequency and pace of increase in MT use is greater in metastatic AIS‐C compared with AIS‐NC. Future studies are needed to determine whether AIS‐C are more predisposed to large‐vessel occlusion.
Meta’s Oversight Board and Beyond – Corporations as Interpreters and Adjudicators of International Human Rights
Authors: Kulick Andreas 
Published: December 2022

Abstract
Social media platform corporations such as Meta (Facebook), Twitter, etc. find themselves in a position of having to interpret international human rights norms, in particular Article 19 of the International Covenant on Civil and Political Rights (ICCPR) (freedom of expression). Millions or even billions of content moderation decisions need to be taken on the platforms each day that affect users’ human rights interests. Since content moderation is integral to the technical and commercial set-up of these platforms, corporate decision-making vis-à-vis human rights and thus corporate interpretation of international human rights norms is inevitable. Yet, corporations are flawed interpreters. Whereas they act, like a court or tribunal, as triadic decision-makers, they, unlike a court or tribunal, do not share the neutrality, impartiality and independence of the latter. In particular, they are responsible to their shareholders and they pursue commercial interests when moderating content. This article grapples with the theoretical and doctrinal implications of flawed but inevitable corporate human rights interpretation. Taking the early practice of the Oversight Board, a body established by Meta, Inc. (Facebook), in order to tackle the “hard cases” of content moderation as a case study, the pitfalls and challenges of corporate human rights interpretation become apparent. In the end, I submit a few suggestions in order to remedy what seems to be here to stay with us at least for as long as an important part of public discourse is channelled through social media platforms.
The Fragility of the Philippines in the Context of Increasing China-U.S. Rivalry in the Western Pacific
Authors: Stach Łukasz 
Published: December 2022

Abstract
The situation in Southeast Asia is of concern not only to the countries in the region, but also to the world’s great powers. The growing economic and military power of the People’s Republic of China (PRC) and its rivalry with the United States (U.S.) are perceived as disruption of the regional status quo. Smaller Southeast Asian states try to secure their position in the changing international environment. These countries include the Philippines, which faces many internal and external security threats. The situation is worsened by the fact that the Philippines is considered by scholars to be a weak and fragile state. The article attempts to elucidate the issue of the Philippines’ fragile state and its influence on the country’s position in the age of growing China-U.S. competition. Moreover, the study tries to answer the question of why the Philippines earned the reputation of a fragile state. The article uses on content analysis of existing literature plus the data from readily accessible sources, and it mostly employs descriptive data analysis methodology.
Public Means for Private Ends? Local Electoral Incentives and Public Welfare Expenditures
Authors: Mendoza Maria Elize H. 
Published: December 2022

Abstract
The literature on distributive politics explores changes in public expenditures vis-à-vis the electoral incentives of politicians. In theory, term-limited politicians are not inclined to increase spending in the absence of re-election prospects. The Philippine case shows otherwise. Guided by theories and studies on Philippine local politics and the effects of term limits on electoral incentives, this article argues that even term-limited politicians can be driven to increase spending if they have a family member intended to succeed them in an upcoming election. Estimates from regression models that used panel data on public expenditures and elections in Philippine provinces and cities from 1992 to 2018 confirm this. Overall, this study provides insights on how electoral incentives and public spending behavior of term-limited politicians change once membership in a political family is factored in.
The Emotional (Un)making of the Family in Cross-European Parent–Child Relations
Authors: Shubin Sergei 
Published: December 2022

Abstract
This essay examines the emotions that make and unmake transnational families, drawing on interviews with migrant parents living in Scotland and separated from their children abroad. First, it explores the meaning of distance and its role in stimulating emotional connections and disconnections between family members. It emphasises the significance of separation for emotional well-being and the necessity of absences in stimulating different intensities of transnational emotional labour. Second, the essay broadens the conceptualisation of the ‘emotional’ to include emotional work and emotional worklessness. It highlights emotions of ‘longing’ and ‘hope’ that unwork the structures of intentionality and reveal passivity at the heart of familial relations. Emotional lives of transnational families are permeated by the imaginaries of co-presence and potential future. Exploring the simultaneous production and fragmentation of emotional connections, the essay suggests the reworking of the contestable family idea(l)s and attending to intimate practices beyond utility and familial normativities.
Music in Evolution and Evolution in Music
Authors: Jan Steven 
Published: December 2022

Music in Evolution and Evolution in Music by Steven Jan is a comprehensive account of the relationships between evolutionary theory and music. Examining the ‘evolutionary algorithm’ that drives biological and musical-cultural evolution, the book provides a distinctive commentary on how musicality and music can shed light on our understanding of Darwin’s famous theory, and vice-versa.
Comprised of seven chapters, with several musical examples, figures and definitions of terms, this original and accessible book is a valuable resource for anyone interested in the relationships between music and evolutionary thought. Jan guides the reader through key evolutionary ideas and the development of human musicality, before exploring cultural evolution, evolutionary ideas in musical scholarship, animal vocalisations, music generated through technology, and the nature of consciousness as an evolutionary phenomenon.
A unique examination of how evolutionary thought intersects with music, Music in Evolution and Evolution in Music is essential to our understanding of how and why music arose in our species and why it is such a significant presence in our lives.
Aberrant gray matter structure in neurosyphilis without conventional MRI abnormality: a pilot study with voxel and surface-based morphology
Authors: Lu Zi-Ning , Yao Sheng-Juan , Cao Yu , Cheng Yue , Li Xiao-Tian , Guo Hong-Shuai , Zhang Xiao-Dong 
Published: December 2022

Background The underlying mechanism of neurosyphilis was not fully understood. Purpose To assess gray matter (GM) microstructure in patients with early-stage neurosyphilis without overt conventional magnetic resonance imaging (MRI) abnormality using voxel-based morphometry (VBM) and surface-based morphometry (SBM) analyses. Material and Methods Three-dimensional high-resolution T1-weighted imaging data from 19 individuals with neurosyphilis and 19 healthy controls were analyzed. A battery of neuropsychological tests was performed before each MRI examination. The differences of GM volume and cerebral cortical morphological data between the two groups were compared. The correlations between MRI metrics and neuropsychology/laboratory tests in the patient group were investigated. Results Regional decreased GM volumes in patients with neurosyphilis were found in the left frontal cortices (Rolandic operculum, middle frontal, and precentral) and bilateral temporal/occipital cortices (bilateral middle temporal, left lingual, and right middle occipital) ( P < 0.05, FDR correction). SBM analysis showed significant cortical thickness reduction in the right medial orbitofrontal lobe, and reduced gyrification index in the left insula in patients with neurosyphilis ( P < 0.05, FDR correction). Additionally, in the patient group, the GM volume in the middle frontal gyrus, the cortical thickness of right medial orbitofrontal lobe, and the gyrification index in the left insula were negatively correlated to the number connection test-A scores. The gyrification index was also negatively correlated to cerebrospinal fluid white blood cell count. Conclusion Early-stage neurosyphilis without conventional MRI abnormality presented regional GM volume reduction and cortical morphological changes, which might be related to cognitive impairment and intra-cranial infection. VBM and SBM analyses might be useful for understanding the underlying neural trait of neurosyphilis.
Impact of Implementing Screening and Interventions to Target Prevention of Opioid Misuse and Accidental Overdose in the Inpatient Setting
Authors: Bjornson Siri , Grindeland Carlina J. , Werremeyer Amy B. 
Published: December 2022

Introduction: There are limited publications supporting the use of screening tools to implement upstream prevention of opioid-related problems. Opioid and Naloxone Education (ONE) is utilized in outpatient pharmacies to screen and identify patients at risk of opioid-related problems and make interventions. Objectives: To implement ONE in the inpatient setting to promote prevention of opioid-related problems and overdose risk mitigation. Methods: For this pilot, ONE screening tool was completed via chart review and patient interview for inpatients prescribed an opioid. Risk scores were calculated and recommendations were provided. Outcomes evaluated included morphine milligram equivalents (MME) prior to hospitalization, inpatient screening pre-, post-, and at discharge; naloxone orders at discharge; and comparison of overdose risk from different sources. Results: The control group (n = 44) had a mean MME decrease of 1.5, and following implementation of pharmacist interventions, the experimental group (n = 45) observed a mean MME decrease of 28.6 ( P = .0001). For the threshold of 50 MME, 8.6% of patients in the control group had a change from >50 MME to <50 MME at 24 hour follow up. This change occurred in 29% of patients in the experimental group ( P = .03). For non-opioid analgesics, 6.8% of patients in the control group had non-opioid analgesic orders added or increased compared to 26.6% in the experimental group ( P = .01). Conclusion: Screening for opioid misuse and accidental overdose risk appears impactful in the inpatient setting. Screening and appropriate risk-based intervention was associated with decreases in total daily MME and increased non-opioid analgesics.
Influence of sulfonated SBA - 15 on fuel cell performance of sulfonated polysulfone electrolyte membranes
Authors: V Prabhu N 
Published: December 2022

The prepared mesoporous SBA-15 (Santa Barbara Amorphous-15) was sulfonated and used as filler for the preparation of sulfonated polysulfone based composite electrolyte membranes. The SBA-15 and polysulfone were sulfonated using 3-mercaptopropyl trimethoxysilane and trimethylsilyl chlorosulfonate, respectively. The different weight percentages (1, 3, and 5 wt%) of sulfonated SBA-15 (SSBA-15) were used to prepare composite electrolyte membranes. Water uptake, ion exchange capacity, swelling ratio and proton conductivity of the composite membranes were studied for assessing the suitability of the electrolyte membranes for use in fuel cells. Characterization techniques such as FT-IR, XRD, SEM, TEM and Brunauer–Emmett– Teller were used to study the physico-chemical properties of the electrolyte membranes. TEM and BET analysis showed that SBA -15 retained its mesoporous structure even after sulfonation process. The prepared membranes were then tested in an in-house built single-cell fuel cell using hydrogen as fuel and oxygen as the oxidant. The fuel cell study showed that the presence of Sulfonated SBA-15 in the polymer matrix provided additional ion exchange sites and retained water for proton transfer which resulted in higher power density of 815 mW/cm2 with SPSU + 3% SSBA-15 membrane as compared with Nafion 117®.
Guidelines of Serious Game Design for Promoting Reframing
Authors: Gao Lanlan , Ward Rupert , Fabricatore Carlo 
Published: December 2022

Background. Reframing could be considered to represent individual and collective twofold values in social learning. When reframing is promoted, it benefits to generate learning processes involving collective inquiry occurring in inter and outer formal education. Digital games, popular as an application for the young generation, are considered a specific community in which social learning occurs by playing games. Serious games (SG) are a type of digital game involving educational purposes. Hence SG is selected as a suitable educational strategy to promote reframing. The previous research investigated features of a gameplay experience associated with reframing. This study develops further based on these game features to examine if/how they improved reframing capabilities. From an educational perspective, specific guidelines were proposed as the research findings to assist serious games in designing and applying game features to enhance the gameplay experience of reframing. Methods. An expert evaluation was used to assess the guidelines. The seven experts with experience in game design and teaching were chosen to review the designed guidelines. These experts were required to rate the guidelines using a 5-point Likert scale. All experts offered positive feedback on the finding. Results. Research data were analysed and validated via the Content Validity Index. The results showed that a total of 5 guidelines was remained and updated. Conclusion. These guidelines can be applied to assist students, game designers, related educators, and researchers who use games to promote reframing or require evidence to link game features with social learning.
Ocular Paraneoplastic Syndromes: A Critical Review of Diffuse Uveal Melanocytic Proliferation and Autoimmune Retinopathy
Authors: Weppelmann Thomas A. , Khalil Sabrina , Zafrullah Nabeel , Amir Sabah , Margo Curtis E. 
Published: December 2022

Background: Dozens of paraneoplastic syndromes affect the visual system ranging from conjunctival pemphigoid to encephalopathy of the occipital cortex. The most profiled ocular syndromes are bilateral diffuse uveal melanocytic proliferation (BDUMP) and the autoimmune retinopathies. Purpose: To review the critical features of these 2 entities then concentrate on advancements in treatment made within the last 10 years. Study Design: Literature review with structured data abstraction. Results: Major insights into pathogenesis have been wanting. Plasmapheresis appears to improve vision in a substantial proportion of patients with BDUMP. The number of clinical variables that influence visual outcome in paraneoplastic retinopathies combined with the variety of local and systemic treatment options makes interpretation of clinical effectiveness difficult. Conclusions: The rarity of these disorders makes randomized clinical trials unlikely. It may be time for a clinical professional organization to use a modified Delphi method to establish a consensus algorithm for the diagnosis and management of retinal paraneoplastic syndromes to augment clinical communications and clinical trials.