bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ataxia-Telangiectasia Mutated Loss-of-Function Displays Variant and Tissue-Specific Differences across Tumor Types
Authors: Pilié Patrick G. , Giuliani Virginia , Wang Wei-Lien , McGrail Daniel J. , Bristow Christopher A. , Ngoi Natalie Y.L. , Kyewalabye Keith , Wani Khalida M. , Le Hung , Campbell Erick , Sanchez Nora S. , Yang Dong , Gheeya Jinesh S. , Goswamy Rohit Vivek , Holla Vijaykumar , Shaw Kenna Rael , Meric-Bernstam Funda , Liu Chiu-Yi , Ma XiaoYan , Feng Ningping , Machado Annette A. , Bardenhagen Jennifer P. , Vellano Christopher P. , Marszalek Joseph R. , Rajendra Eeson , Piscitello Desiree , Johnson Timothy I. , Likhatcheva Maria , Elinati Elias , Majithiya Jayesh , Neves Joana , Grinkevich Vera , Ranzani Marco , Luzarraga Marina Roy , Boursier Marie , Armstrong Lucy , Geo Lerin , Lillo Giorgia , Tse Wai Yiu , Lazar Alexander J. , Kopetz Scott E. , Geck Do Mary K. , Lively Sarah , Johnson Michael G. , Robinson Helen M.R. , Smith Graeme C.M. , Carroll Christopher L. , Di Francesco M. Emilia , Jones Philip , Heffernan Timothy P. , Yap Timothy A. 
Published: February 2024

Abstract

Purpose:
Mutations in the ATM gene are common in multiple cancers, but clinical studies of therapies targeting ATM-aberrant cancers have yielded mixed results. Refinement of ATM loss of function (LOF) as a predictive biomarker of response is urgently needed.

Experimental Design:
We present the first disclosure and preclinical development of a novel, selective ATR inhibitor, ART0380, and test its antitumor activity in multiple preclinical cancer models. To refine ATM LOF as a predictive biomarker, we performed a comprehensive pan-cancer analysis of ATM variants in patient tumors and then assessed the ATM variant-to-protein relationship. Finally, we assessed a novel ATM LOF biomarker approach in retrospective clinical data sets of patients treated with platinum-based chemotherapy or ATR inhibition.

Results:
ART0380 had potent, selective antitumor activity in a range of preclinical cancer models with differing degrees of ATM LOF. Pan-cancer analysis identified 10,609 ATM variants in 8,587 patient tumors. Cancer lineage–specific differences were seen in the prevalence of deleterious (Tier 1) versus unknown/benign (Tier 2) variants, selective pressure for loss of heterozygosity, and concordance between a deleterious variant and ATM loss of protein (LOP). A novel ATM LOF biomarker approach that accounts for variant classification, relationship to ATM LOP, and tissue-specific penetrance significantly enriched for patients who benefited from platinum-based chemotherapy or ATR inhibition.

Conclusions:
These data help to better define ATM LOF across tumor types in order to optimize patient selection and improve molecularly targeted therapeutic approaches for patients with ATM LOF cancers.
89Zr-ImmunoPET for the Specific Detection of EMP2-Positive Tumors
Authors: Chan Ann M. , Olafsen Tove , Tsui Jessica , Salazar Felix B. , Aguirre Brian , Zettlitz Kirstin A. , Condro Michael , Wu Anna M. , Braun Jonathan , Gordon Lynn K. , Ashki Negin , Whitelegge Julian , Xu Shili , Ikotun Oluwatayo , Lee Jason Thanh , Wadehra Madhuri 
Published: February 2024

Abstract
Epithelial membrane protein-2 (EMP2) is upregulated in a number of tumors and therefore remains a promising target for mAb-based therapy. In the current study, image-guided therapy for an anti-EMP2 mAb was evaluated by PET in both syngeneic and immunodeficient cancer models expressing different levels of EMP2 to enable a better understanding of its tumor uptake and off target accumulation and clearance. The therapeutic efficacy of the anti-EMP2 mAb was initially evaluated in high- and low-expressing tumors, and the mAb reduced tumor load for the high EMP2-expressing 4T1 and HEC-1-A tumors. To create an imaging agent, the anti-EMP2 mAb was conjugated to p-SCN-Bn-deferoxamine (DFO) and radiolabeled with 89Zr. Tumor targeting and tissue biodistribution were evaluated in syngeneic tumor models (4T1, CT26, and Panc02) and human tumor xenograft models (Ramos, HEC-1-A, and U87MG/EMP2). PET imaging revealed radioactive accumulation in EMP2-positive tumors within 24 hours after injection, and the signal was retained for 5 days. High specific uptake was observed in tumors with high EMP2 expression (4T1, CT26, HEC-1-A, and U87MG/EMP2), with less accumulation in tumors with low EMP2 expression (Panc02 and Ramos). Biodistribution at 5 days after injection revealed that the tumor uptake ranged from 2 to approximately 16%ID/cc. The results show that anti-EMP2 mAbs exhibit EMP2-dependent tumor uptake with low off-target accumulation in preclinical cancer models. The development of improved anti-EMP2 Ab fragments may be useful to track EMP2-positive tumors for subsequent therapeutic interventions.
Glioblastoma-Infiltrating CD8+ T Cells Are Predominantly a Clonally Expanded GZMK+ Effector Population
Authors: Wang Anthony Z. , Mashimo Bryce L. , Schaettler Maximilian O. , Sherpa Ngima D. , Leavitt Lydia A. , Livingstone Alexandra J. , Khan Saad M. , Li Mao , Anzaldua-Campos Markus I. , Bradley Joseph D. , Leuthardt Eric C. , Kim Albert H. , Dowling Joshua L. , Chicoine Michael R. , Jones Pamela S. , Choi Bryan D. , Cahill Daniel P. , Carter Bob S. , Petti Allegra A. , Johanns Tanner M. , Dunn Gavin P. 
Published: February 2024

Abstract

Recent clinical trials have highlighted the limited efficacy of T cell–based immunotherapy in patients with glioblastoma (GBM). To better understand the characteristics of tumor-infiltrating lymphocytes (TIL) in GBM, we performed cellular indexing of transcriptomes and epitopes by sequencing and single-cell RNA sequencing with paired V(D)J sequencing, respectively, on TILs from two cohorts of patients totaling 15 patients with high-grade glioma, including GBM or astrocytoma, IDH-mutant, grade 4 (G4A). Analysis of the CD8+ TIL landscape reveals an enrichment of clonally expanded GZMK+ effector T cells in the tumor compared with matched blood, which was validated at the protein level. Furthermore, integration with other cancer types highlights the lack of a canonically exhausted CD8+ T-cell population in GBM TIL. These data suggest that GZMK+ effector T cells represent an important T-cell subset within the GBM microenvironment and may harbor potential therapeutic implications.

Significance:
To understand the limited efficacy of immune-checkpoint blockade in GBM, we applied a multiomics approach to understand the TIL landscape. By highlighting the enrichment of GZMK+ effector T cells and the lack of exhausted T cells, we provide a new potential mechanism of resistance to immunotherapy in GBM.
This article is featured in Selected Articles from This Issue, p. 897
Potential Effects of Mild Atrial Secondary Mitral Regurgitation in Patients With Isolated Atrial Fibrillation
Authors: Akashi Jun , Iwataki Mai , Nabeshima Yosuke , Onoue Takeshi , Hayashi Atsushi , Tanaga Tetsuo , Nishino Shun , Kimura Toshiyuki , Yano Mitsuhiro , Watanabe Nozomi , Tsuda Yuki , Araki Masaru , Shibata Yoshisato , Nishimura Yosuke , Otsuji Yutaka , Kataoka Masaharu 
Published: February 2024

BACKGROUND:
Patients with only moderate atrial secondary mitral regurgitation (asMR) frequently develop heart failure (HF). Mechanisms of HF with moderate asMR and the impact of mild asMR remain unclarified. Although mild/moderate primary mitral regurgitation is compensated by left ventricular (LV) dilatation, the LV is not dilated in asMR. We hypothesized that patients with mild asMR without LV dilatation may have impaired hemodynamics and higher risks of subsequent symptomatic HF deterioration.

METHODS:
Stroke volume, cardiac output, and systolic pulmonary artery pressure were measured by echocardiography in 142 patients with isolated atrial fibrillation and 30 healthy controls. The prognosis of patients with isolated atrial fibrillation was followed up.

RESULTS:

In the 142 patients with isolated atrial fibrillation, asMR was no/trivial in 55, mild in 83, moderate in 4, while none had severe asMR. Compared with controls and patients with no/trivial asMR, LV end-diastolic volume index was not increased and hemodynamic parameters were abnormal in patients with mild asMR (LV end-diastolic volume index, 65±6 versus 58±8 versus 60±8 mL/m²; stroke volume index, 42±4 versus 35±4 versus 29±6 mL/m²;
P
<0.001 versus other 2 groups; cardiac output index, 2.8±0.4 versus 2.8±0.5 versus 2.3±0.6 L/min per m²;
P
<0.001; systolic pulmonary artery pressure, 21±3 versus 26±5 versus 37±9 mm Hg;
P
<0.001). Although the event-free rate of HF symptomatic deterioration or hospitalization in patients with no/trivial asMR during a median 13.9 months follow-up was 86.9% and 100%, the rate in mild asMR was 59.4% and 85.0% (
P
<0.001 or
P
=0.032), respectively.

CONCLUSIONS:
In the presence of isolated AF and no compensatory LV dilatation, impaired hemodynamics and higher risks of symptomatic HF deterioration were associated with mild asMR, requiring further studies of causalities.
Islamic Apocalyptic Jurisprudence
Authors: Khadem Ali Rod 
Published: February 2024

Abstract
This article introduces Islamic apocalyptic jurisprudence (theories of final law that will govern humanity in the End Times) to academic study. Section 1 considers why the topic has remained unexamined and suggests a basic taxonomy. Section 2 exposes the apocalyptic jurisprudence of two case studies, representing the “reversionist” and “progressivist” poles of Sunni discourses: the Islamic State of Iraq and Syria (“isis”), and Dāwūd and his “Awaited Mahdī” movement in Egypt. Section 3 considers two further case studies, representing the “revanchist” and “idealist” orientations in Shi‘i discourses: the Islamic Republic of Iran, and al-Ṣadr, a theorist of the Iraqi Ṣadrist movement. Throughout, the following aspects of the final legal system are considered: sources of law; conflicts between Islamic, Jewish, Christian, and international laws; the jurist’s role; changes to classical Islamic legal theory, including qiyas and ijtihad; the legitimacy of legal schools; and new positive laws, policies, and rules of evidence.
Urban-Rural Differences in Life Satisfaction
Authors: Grosse Ingrid 
Published: February 2024

Abstract
International research has shown that residents in urban versus rural areas differ concerning their satisfaction in life. Researchers agree upon the relevance of economic aspects for explaining urban-rural satisfaction levels: life satisfaction is dependent on income levels and rural habitants usually have lower income levels and lower levels of life satisfaction internationally. However, there is a lot of variation unexplained: in several studies, researchers found that in some countries rural residents are unexpectedly more satisfied with their lives than their economic and objective life situation would suggest (e.g. in China, Thailand, and in Western European, post-communist, Anglo-Saxon, and Latin American countries). Some researchers argue that cultural and social aspects, in addition to economic aspects, are better to explain urban-rural differences in life satisfaction. The author will extend this research by focusing on cultural factors in relation to Cultural World Regions. In addition, she will use newer data from the World Values Survey and the World Bank. The guiding questions are 1) how relevant are economic-materialistic aspects for life satisfaction? And 2) in how far are there differences between cultural world regions, such as East and Central Asia, Western and post-communist Europe, Latin America, Anglo-Saxon countries, and Arabic and Sub-Saharan Africa?
Characteristics of Generating Cells in Wintertime Orographic Clouds
Authors: Tessendorf Sarah A. , Ikeda Kyoko , Rasmussen Roy M. , French Jeffrey , Rauber Robert M. , Korolev Alexei , Xue Lulin , Blestrud Derek R. , Dawson Nicholas , Meadows Melinda , Kunkel Melvin L. , Parkinson Shaun 
Published: February 2024

Abstract
During the Seeded and Natural Orographic Wintertime clouds: the Idaho Experiment (SNOWIE) field campaign, cloud-top generating cells were frequently observed in the very high-resolution W-band airborne cloud radar data. This study examines multiple flight segments from three SNOWIE cases that exhibited cloud-top generating cells structures, focusing on the in situ measurements inside and outside these cells to characterize the microphysics of these cells. The observed generating cells in these three cases occurred in cloud tops of −15° to −30°C, with and without overlying cloud layers, but always with shallow layers of atmospheric instability observed at cloud top. The results also indicate that liquid water content, vertical velocity, and drizzle and ice crystal concentrations are greater inside the generating cells compared to the adjacent portions of the cloud. The generating cells were predominantly <500 m in horizontal width and frequently exhibited drizzle drops coexisting with ice. The particle imagery indicates that ice particle habits included plates, columns, and rimed and irregular crystals, likely formed via primary ice nucleation mechanisms. Understanding the sources of natural ice formation is important to understanding precipitation formation in winter orographic clouds, and is especially relevant for clouds that may be targeted for glaciogenic cloud seeding as well as to improve model representation of these clouds.

Significance Statement
This study presents the characteristics of cloud-top generating cells in winter orographic clouds, and documents that fine-scale generating cells are ubiquitous in clouds over complex terrain in addition to having been observed in other types of clouds. The generating cells exhibited enhanced concentrations of larger drizzle and ice particles, which suggests the environments of these fine-scale features promote ice formation and growth. The source of ice formation in winter clouds is critical to understanding and modeling the precipitation formation process. Given the ubiquity of cloud-top generating cells in many types of clouds around the world, this study further motivates the need to investigate methods for representing subgrid-scale environments to improve ice formation in numerical models.
Coupled Stratospheric Ozone and Atlantic Meridional Overturning Circulation Feedbacks on the Northern Hemisphere Midlatitude Jet Response to 4xCO2
Authors: Orbe Clara , Rind David , Waugh Darryn W. , Jonas Jeffrey , Zhang Xiyue , Chiodo Gabriel , Nazarenko Larissa , Schmidt Gavin A. 
Published: February 2024

Abstract
Stratospheric ozone, and its response to anthropogenic forcings, provides an important pathway for the coupling between atmospheric composition and climate. In addition to stratospheric ozone’s radiative impacts, recent studies have shown that changes in the ozone layer due to 4xCO2 have a considerable impact on the Northern Hemisphere (NH) tropospheric circulation, inducing an equatorward shift of the North Atlantic jet during boreal winter. Using simulations produced with the NASA Goddard Institute for Space Studies (GISS) high-top climate model (E2.2), we show that this equatorward shift of the Atlantic jet can induce a more rapid weakening of the Atlantic meridional overturning circulation (AMOC). The weaker AMOC, in turn, results in an eastward acceleration and poleward shift of the Atlantic and Pacific jets, respectively, on longer time scales. As such, coupled feedbacks from both stratospheric ozone and the AMOC result in a two-time-scale response of the NH midlatitude jet to abrupt 4xCO2 forcing: a “fast” response (5–20 years) during which it shifts equatorward and a “total” response (∼100–150 years) during which the jet accelerates and shifts poleward. The latter is driven by a weakening of the AMOC that develops in response to weaker surface zonal winds that result in reduced heat fluxes out of the subpolar gyre and reduced North Atlantic Deep Water formation. Our results suggest that stratospheric ozone changes in the lower stratosphere can have a surprisingly powerful effect on the AMOC, independent of other aspects of climate change.
Pathophysiology of cluster headache: From the trigeminovascular system to the cerebral networks
Authors: Coppola Gianluca , Abagnale Chiara , Sebastianelli Gabriele , Goadsby Peter J. 
Published: February 2024

Background Despite advances in neuroimaging and electrophysiology, cluster headache’s pathogenesis remains unclear. This review will examine clinical neurophysiology studies, including electrophysiological and functional neuroimaging, to determine if they might help us construct a neurophysiological model of cluster headache. Results Clinical, biochemical, and electrophysiological research have implicated the trigeminal-parasympathetic system in cluster headache pain generation, although the order in which these two systems are activated, which may be somewhat independent, is unknown. Electrophysiology and neuroimaging have found one or more central factors that may cause seasonal and circadian attacks. The well-known posterior hypothalamus, with its primary circadian pacemaker suprachiasmatic nucleus, the brainstem monoaminergic systems, the midbrain, with an emphasis on the dopaminergic system, especially when cluster headache is chronic, and the descending pain control systems appear to be involved. Functional connection investigations have verified electrophysiological evidence of functional changes in distant brain regions connecting to wide cerebral networks other than pain. Conclusion We propose that under the impact of external time, an inherited misalignment between the primary circadian pacemaker suprachiasmatic nucleus and other secondary extra- suprachiasmatic nucleus clocks may promote disturbance of the body’s internal physiological clock, lowering the threshold for bout recurrence.
Parameters influencing electrospun nanofiber diameter of polylactide incorporated with cellulose nanofibrils and nanocrystals
Authors: Sari Burcu , Kaynak Cevdet 
Published: February 2024

The main purpose of this study was to investigate effects of various electrospinning parameters on the morphology and diameter of cellulose nanofibril (CNF) filled polylactide (PLA) nanofibers. For this purpose, first of all effects of three important electrospinning parameters; polymer solution concentration, solution feeding rate and collector distance to feeding tip were studied. Then, effects of using higher amount of CNF, effects of using cellulose nanocrystal (CNC) particles, and effects of adding potassium chloride salt were also investigated. It was observed that when optimum electrospinning parameters were determined, then it was possible to obtain almost “bead-free” morphology and “finest” average diameter of 232 nm for PLA/CNF electrospun fibers. Increasing values of feeding rate and collector distance parameters resulted in bead formation and thicker diameters. On the other hand, increasing CNF amount, using CNC particles and adding KCl salt, all resulted in further decreases in the diameter down to 152 nm; mainly due to increased charge density of the polymer solution. Moreover, in vitro degradation analysis of all types of electrospun nanofiber mats in a simulated body fluid revealed that increasing the immersion period increased their degradation rate in terms of “% weight loss”. It was also observed that, mats with fine diameter fibers had higher degradation rate.
Impact of preeclampsia on infant and maternal health among women with rheumatic diseases
Authors: Milne Megan E , Clowse Megan EB , Zhao Congwen , Goldstein Benjamin A , Eudy Amanda M 
Published: February 2024

Objectives We sought to identify the impact of preeclampsia on infant and maternal health among women with rheumatic diseases. Methods A retrospective single-center cohort study was conducted to describe pregnancy and infant outcomes among women with systemic lupus erythematosus (SLE) with and without preeclampsia as compared to women with other rheumatic diseases with and without preeclampsia. Results We identified 263 singleton deliveries born to 226 individual mothers (mean age 31 years, 35% non-Hispanic Black). Overall, 14% of women had preeclampsia; preeclampsia was more common among women with SLE than other rheumatic diseases (27% vs 8%). Women with preeclampsia had a longer hospital stay post-delivery. Infants born to mothers with preeclampsia were delivered an average of 3.3 weeks earlier than those without preeclampsia, were 4 times more likely to be born preterm, and twice as likely to be admitted to the neonatal intensive care unit. The large majority of women with SLE in this cohort were prescribed hydroxychloroquine and aspirin, with no clear association of these medications with preeclampsia. Conclusions We found preeclampsia was an important driver of adverse infant and maternal outcomes. While preeclampsia was particularly common among women with SLE in this cohort, the impact of preeclampsia on the infants of all women with rheumatic diseases was similarly severe. In order to improve infant outcomes for women with rheumatic diseases, attention must be paid to preventing, identifying, and managing preeclampsia.
Nurses’ ethical responsibilities: Whistleblowing and advocacy in patient safety
Authors: Ibrahim Ateya Megahed 
Published: February 2024

Background In the dynamic landscape of healthcare, nurses play a crucial role as ethical stewards, responsible for whistleblowing, nurse advocacy, and patient safety. Their duties involve ensuring patient well-being through ethical practices and advocacy initiatives. Aim This study investigates the ethical responsibilities of nurses regarding whistleblowing and advocacy in reporting concerns about patient safety. Research Design A cross-sectional study utilized cluster and simple random sampling to gather a representative sample of actively practicing registered nurses. Data collection involved a demographic form, Nurse Whistleblowing Intentions Scale, Nursing Advocacy Scale, and Clinical Decision-Making Scale. Participants and Research Context The study utilizing a robust sample size determination formula for reliable findings included 96 diverse nurses, predominantly females. Engaged actively in direct patient care across various outpatients clinics. The recruitment process specifically sought individuals with expertise in safety protocols and reporting, contributing to a nuanced understanding of the study’s focus. Ethical Considerations Ethical approval was obtained from the ethics committee of the university and the hospitals involved. Written consent was obtained from the participants. A thorough ethical review was conducted to guarantee participant protection and adherence to ethical principles. Results Surveyed nurses demonstrated positive whistleblowing (Overall Mean Score: 3.58), high advocacy (Overall Mean Score: 12.2), and nuanced ethical decision-making for patient safety (Overall Mean Score: 15.78). Demographic factors, such as nationality and ethical training, significantly impacted whistleblowing intentions, while age, gender, and ethical training correlated with nursing advocacy behavior. Associations with experience and qualification emerged in ethical decision-making. Conclusion The gained insights foster targeted interventions, improving ethical practices, advocacy, and informed decision-making in nursing. This study explores the intricate link between demographics and ethical considerations among surveyed nurses, acting as a catalyst for ongoing initiatives to strengthen the ethical foundation in healthcare sector.