bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural evolution of the North Himalaya domes as revealed by crustal-scale seismic-reflection surveying
Authors: Shi Zhuoxuan , Gao Rui , Lu Zhanwu , Li Wenhui , Li Hongqiang , Liang Hongda , Qi Rui , Deng Xiaofan , Dong Xinyu 
Published: December 2023

Abstract
As the typical products of collisional orogeny, gneiss domes are important geological units with which to decipher the crustal deformation and evolutionary history of continental collision. However, their formation mechanisms remain poorly understood. This issue is well illustrated by the debate surrounding the origin of the North Himalaya gneiss dome zone, which has been attributed to middle-crustal channel flow, thrust-duplex development, extensional detachment faulting, or diapiric flow related to partial crustal melting. These models predict different internal structures within individual domes that can be tested by high-resolution seismic imaging. Here, we present newly acquired seismic-reflection data collected along an ~120-km-long north-south traverse across the central segment of the North Himalaya gneiss dome zone. Analysis and interpretation of the seismic data constrained by surface geology observations imply that (1) the subducting Indian lower crust is decoupled from the deformed middle and upper crust in the North Himalaya, (2) a crustal-scale stack of antiformal duplexes with a structural thickness of ~35 km defines the cores of the gneiss domes imaged by the seismic survey, and (3) highly reflective, sheetlike bodies imaged in our seismic profile are best interpreted as leucocratic intrusions developed synchronously during gneiss dome development. As a whole, our work suggests that the North Himalaya gneiss dome zone was created by coeval crustal shortening and partial melting of orogenic crust.
Supplemental Material: A global database of Mars-relevant hydrovolcanic environments on Earth with potential biosignature preservation
Authors: Ryan Catheryn H. , al. et 
Published: December 2023

<div> Includes an expanded database with age, composition, setting, location, and structure name(s) for 45 volcanic fields; GIS data compatible with Esri ArcGIS Pro and Google Earth data of all 716 volcanic structures in database; map attribute table with location data for all 716 structures; and compiled major element geochemistry and FeO<sup>total</sup> versus SiO<sub>2</sub> and total-alkali silica charts for all volcanic fields where data is available. </div>
Assessing the influence of abdominal compression on time to return of circulation during resuscitation of asphyxiated newborn lambs: a randomised preclinical study
Authors: Polglase Graeme R , Hwang Colin , Blank Douglas A , Badurdeen Shiraz , Crossley Kelly J , Kluckow Martin , Gill Andrew W , Camm Emily , Galinsky Robert , Brian Yoveena , Hooper Stuart B , Roberts Calum T 
Published: December 2023

ObjectiveDuring neonatal resuscitation, the return of spontaneous circulation (ROSC) can be achieved using epinephrine which optimises coronary perfusion by increasing diastolic pressure. Abdominal compression (AC) applied during resuscitation could potentially increase diastolic pressure and therefore help achieve ROSC. We assessed the use of AC during resuscitation of asystolic newborn lambs, with and without epinephrine.MethodsNear-term fetal lambs were instrumented for physiological monitoring and after delivery, asphyxiated until asystole. Resuscitation was commenced with ventilation followed by chest compressions. Lambs were randomly allocated to: intravenous epinephrine (20 µg/kg, n=9), intravenous epinephrine+continuous AC (n=8), intravenous saline placebo (5 mL/kg, n=6) and intravenous saline+AC (n=9). After three allocated treatment doses, rescue intravenous epinephrine was administered if ROSC had not occurred. Time to achieve ROSC was the primary outcome. Lambs achieving ROSC were ventilated and monitored for 60 min before euthanasia. Brain histology was assessed for micro-haemorrhage.ResultsUse of AC did not influence mean time to achieve ROSC (epinephrine lambs 177 s vs epinephrine+AC lambs 179 s, saline lambs 602 s vs saline+AC lambs 585 s) or rate of ROSC (nine of nine lambs, eight of eight lambs, one of six lambs and two of eight lambs, respectively). Application of AC was associated with higher diastolic blood pressure (mean value >10 mm Hg), mean and systolic blood pressure and carotid blood flow during resuscitation. Cortex and deep grey matter micro-haemorrhage was more frequent in AC lambs.ConclusionUse of AC during resuscitation increased diastolic blood pressure, but did not impact time to ROSC.
Diagnostic and prognostic role of synovial tissue analysis in juvenile idiopathic arthritis: a monocentric study
Authors: Costi Stefania , Armiraglio Elisabetta , Pregnolato Francesca , Chighizola Cecilia Beatrice , Marino Achille , Randelli Pietro Simone , Parafioriti Antonina , Caporali Roberto 
Published: December 2023

ObjectivesThis study investigates the diagnostic role of synovial tissue analysis in children presenting with arthritis and assesses its prognostic significance to predict clinical outcome in juvenile idiopathic arthritis (JIA).MethodsSynovial samples of paediatric patients undergoing synovial biopsy between 1995 and 2020 were analysed histologically and immunohistochemically. Relationships between histological/immunohistochemical parameters and clinical variables were assessed.ResultsSynovial biopsy was performed for diagnosis in 65 cases allowing to correctly classify 79% of patients.At histological analysis on 42 JIA samples, any difference in the number of synovial lining layers, subsynovial elementary lesions, fibrin deposit, Krenn Synovitis Score, inflammatory infiltrate score and pattern emerged between JIA subsets or on treatment exposure. Synovial tissue analysis predicted outcome: higher number of synovial layers predicted worse disease course (>4 flares during follow-up; 4.5 vs 3.0, p=0.035), even after adjusting for age at diagnosis and observation time (OR 2.2, p=0.007); subjects who had switched>2 biological disease-modifying antirheumatic drugs had higher prevalence of subsynovial elementary lesions (55.6% vs 10.3%, p=0.005) and fibrin deposits in synovial lining (60.0% vs 22.6%, p=0.049), even after adjustment for observation time and age at diagnosis (OR 8.1, p=0.047). At immunohistochemistry on 31 JIA samples, higher CD3 expression was described in polyarticular compared with oligoarticular subset (p=0.040). Patients with severe disease course had higher CD20+ rate (OR 7, p=0.023), regardless of JIA subset and treatment exposure.ConclusionsSynovial tissue analysis might support the clinicians in the diagnostic approach of paediatric patients presenting with arthritis and guide the clinical management in JIA.
Review of "Violent Exceptions: Children's Human Rights and Humanitarian Rhetorics by Wendy S. Hesford," Hesford, W. S. (2021). Violent Exceptions: Children's Human Rights and Humanitarian Rhetorics. The Ohio State University Press.
Authors: Lantz Susan Jennings 
Published: December 2023

Will someone please think of the children?
W.C. Fields has been notoriously associated with the warning "never to work with children and animals." And he was right! Both varieties of co-performers are guaranteed to steal the show from any adult in the general vicinity. It is generally accepted that commercials with a cute puppy and a Sarah Mclachlan soundtrack, or a baby amid famine and natural disaster is much more likely tug at heartstrings and garner cash donations than a city planner with a spreadsheet and a clip board. Consequently, the "adorable baby" cliché can be found everywhere from sitcoms to advertisements for products as diverse as healthcare, luxury brand cars, and banking securities services.
Osimertinib Covalently Binds to CD34 and Eliminates Myeloid Leukemia Stem/Progenitor Cells
Authors: Xia Li , Liu Jie-Yang , Yang Meng-Ying , Zhang Xue-Hong , Jiang Yue , Yin Qian-Qian , Luo Chen-Hui , Liu Hong-Chen , Kang Zhi-Jie , Zhang Cheng-Tao , Gao Bei-Bei , Zhou Ai-Wu , Cai Hai-Yan , Waller Edmund K. , Yan Jin-Song , Lu Ying 
Published: December 2023

Abstract

Osimertinib is a third-generation covalent EGFR inhibitor that is used in treating non–small cell lung cancer. First-generation EGFR inhibitors were found to elicit pro-differentiation effect on acute myeloid leukemia (AML) cells in preclinical studies, but clinical trials yielded mostly negative results. Here, we report that osimertinib selectively induced apoptosis of CD34+ leukemia stem/progenitor cells but not CD34− cells in EGFR-negative AML and chronic myeloid leukemia (CML). Covalent binding of osimertinib to CD34 at cysteines 199 and 177 and suppression of Src family kinases (SFK) and downstream STAT3 activation contributed to osimertinib-induced cell death. SFK and STAT3 inhibition induced synthetic lethality with osimertinib in primary CD34+ cells. CD34 expression was elevated in AML cells compared with their normal counterparts. Genomic, transcriptomic, and proteomic profiling identified mutation and gene expression signatures of patients with AML with high CD34 expression, and univariate and multivariate analyses indicated the adverse prognostic significance of high expression of CD34. Osimertinib treatment induced responses in AML patient-derived xenograft models that correlated with CD34 expression while sparing normal CD34+ cells. Clinical responses were observed in two patients with CD34high AML who were treated with osimertinib on a compassionate-use basis. These findings reveal the therapeutic potential of osimertinib for treating CD34high AML and CML and describe an EGFR-independent mechanism of osimertinib-induced cell death in myeloid leukemia.

Significance:
Osimertinib binds CD34 and selectively kills CD34+ leukemia cells to induce remission in preclinical models and patients with AML with a high percentage of CD34+ blasts, providing therapeutic options for myeloid leukemia patients.
Harnessing p53 to Improve Immunotherapy for Lung Cancer Treatment
Authors: Niu Xiaoteng , Martinez Luis 
Published: December 2023

Abstract
Immunotherapy, especially immune checkpoint blockade (ICB), has become a critical therapy for lung cancer treatment in recent years. Tumor mutational burden (TMB) is one of the decisive biomarkers for predicting ICB effect. Writing in Cancer Cell, Zhu and colleagues use autochthonous and syngeneic mouse models to show that p53 mutation and tumor heterogeneity may be responsible for resistance in patients with lung cancer. Pole-induced high TMB shows enhanced immunogenicity in KrasG12D mice, however, loss of p53 in KrasG12D PoleP286/+ mice can lead to an immune suppressive profile of lung tumors, which diminishes immune response to ICB. Moreover, high TMB causes high shared mutations, which helps promote immune protection and immune memory. Heterogeneity can drive immune escape to tumor cells causing resistance to ICB. Decreased cGAS/STING signaling may explain possible resistance to ICB. On the basis of the new model found by Zhu and colleagues for lung cancer, combined ICB with STING agonists or p53 inducers may be new therapeutic options to improve the efficacy of ICB for patients with lung cancer with high TMB.
Exploring the Role of Hyperinsulinemia in Obesity-Associated Tumor Development
Authors: Vélez-Bonet Ericka , Gumpper-Fedus Kristyn , Cruz-Monserrate Zobeida 
Published: December 2023

Abstract
Although there has been a long-standing connection between hyperinsulinemia and cancer development, there is a lack of understanding of the role of the insulin receptor on cells that can become cancerous. In a recent issue of Cell Metabolism, Zhang and colleagues, using a diet-induced obesity mouse model, identified a direct function of insulin receptors on pancreatic acinar cells expressing a KRASG12D mutation in promoting obesity-associated pancreatic cancer. Furthermore, insulin receptor signaling from hyperinsulinemia promoted the secretion of digestive enzymes that contributed to acinar to ductal metaplasia. These findings highlight an important connection between obesity, diabetes, and pancreatic tumor development and suggest potential strategies for obesity-associated cancer prevention targeting the insulin receptor signaling pathways.
Single-Nucleus Analysis Reveals Tumor Heterogeneity of Aldosterone-Producing Adenoma
Authors: Murakami Masanori , Hara Kazunari , Ikeda Kenji , Horino Masato , Okazaki Rei , Niitsu Yoshihiro , Takeuchi Akira , Aoki Jun , Shiba Kumiko , Tsujimoto Kazutaka , Komiya Chikara , Nakamura Yuki , Kurata Morito , Akashi Takumi , Fujii Yasuhisa , Yamada Tetsuya 
Published: December 2023

BACKGROUND:
Recent advances in omics techniques have allowed detailed genetic characterization of aldosterone-producing adenoma (APA). The pathogenesis of APA is characterized by tumorigenesis-associated aldosterone synthesis. The pathophysiological intricacies of APAs have not yet been elucidated at the level of individual cells. Therefore, a single-cell level analysis is speculated to be valuable in studying the differentiation process of APA.

METHODS:

We conducted single-nucleus RNA sequencing of APAs with
KCNJ5
mutation and nonfunctional adenomas obtained from 3 and 2 patients, respectively.

RESULTS:
The single-nucleus RNA sequencing revealed the intratumoral heterogeneity of APA and identified cell populations consisting of a shared cluster of nonfunctional adenoma and APA. In addition, we extracted 2 cell fates in APA and obtained a cell population specialized in aldosterone synthesis. Genes related to ribosomes and neurodegenerative diseases were upregulated in 1 of these fates, whereas those related to the regulation of glycolysis were upregulated in the other fate. Furthermore, the total RNA reads in the nucleus were higher in hormonally activated clusters, indicating a marked activation of transcription per cell.

CONCLUSIONS:

The single-nucleus RNA sequencing revealed intratumoral heterogeneity of APA with
KCNJ5
mutation. The observation of 2 cell fates in
KCNJ5
-mutated APAs provides the postulation that a heterogeneous process of cellular differentiation was implicated in the pathophysiological mechanisms underlying APA tumors.
We don’t need no (Confucian) education! A Northern Song Reading of the Liezi
Authors: Sage Richard J. 
Published: December 2023

Abstract
One of the common traits ancient speculative Daoist texts share is their aversion to a society based on Confucian morals. The Liezi’s anecdote about Huazi has often been cited as prime example for this attitude and its inherent yearning for a return to the Dao. Remarkably, one of the most radical interpretations of this passage was authored by a high-ranking member of the Northern Song imperial court. Combining references to other classics with Buddhist concepts and terminology to expound a mysticism rooted in the Daoist tradition, Fan Zhixu’s 范致虛 (?–1129) commentary is not only a masterpiece of exegetical literature, but also provides valuable insights into the unique intellectual atmosphere at and around Emperor Huizong’s court. This case study serves as introduction to Fan’s forgotten work and simultaneously to a widely neglected set of sources regarding the religio-political developments during Huizong’s controversial reign.
The Zen of Mahāvairocana, Or: Does Bodhidharma’s Nose Preach the Dharma?
Authors: Licha Stephan Kigensan 
Published: December 2023

Abstract
This paper addresses the relationship between Zen and tantric or esoteric Buddhism in premodern Japan from the point of view of the Buddhas and Buddha bodies considered to be preaching these two traditions. After surveying theories on the dharmakāya teaching already present in Chinese Buddhism, it considers the development of this doctrinal notion in the Japanese tantric traditions. The paper demonstrates that this tantric discourse on the Buddha as preacher provided thinkers such as Enni 圓爾 (1202–1280) and Chikotsu Daie 癡兀大慧 (1229–1312) with a framework to integrate Zen into a tantric world. Eventually, and under the influence of embryological motifs circulating widely in medieval Buddhism, Zen practitioners came to establish their own theories on the human as Buddha body. The paper concludes that medieval Zen and medieval tantric Buddhism should be considered sister movements.
Cell cross talk within the lymphoma tumor microenvironment: follicular lymphoma as a paradigm
Authors: Laurent Camille , Dietrich Sascha , Tarte Karin 
Published: December 2023

AbstractFollicular lymphoma (FL) is an indolent yet incurable germinal center B-cell lymphoma retaining a characteristic follicular architecture. FL tumor B cells are highly dependent on direct and indirect interactions with a specific and complex tumor microenvironment (TME). Recently, great progress has been made in describing the heterogeneity and dynamics of the FL TME and in depicting how tumor clonal and functional heterogeneity rely on the integration of TME-related signals. Specifically, the FL TME is enriched for exhausted cytotoxic T cells, immunosuppressive regulatory T cells of various origins, and follicular helper T cells overexpressing B-cell and TME reprogramming factors. FL stromal cells have also emerged as crucial determinants of tumor growth and remodeling, with a key role in the deregulation of chemokines and extracellular matrix composition. Finally, tumor-associated macrophages play a dual function, contributing to FL cell phagocytosis and FL cell survival through long-lasting B-cell receptor activation. The resulting tumor-permissive niches show additional layers of site-to-site and kinetic heterogeneity, which raise questions about the niche of FL-committed precursor cells supporting early lymphomagenesis, clonal evolution, relapse, and transformation. In turn, FL B-cell genetic and nongenetic determinants drive the reprogramming of FL immune and stromal TME. Therefore, offering a functional picture of the dynamic cross talk between FL cells and TME holds the promise of identifying the mechanisms of therapy resistance, stratifying patients, and developing new therapeutic approaches capable of eradicating FL disease in its different ecosystems.
Polypharmacy and pattern of medication use among patients with gastroesophageal reflux disease: results from Pars Cohort study
Authors: Ghamar-Shooshtari Arash , Rahimian Zahra , Poustchi Hossein , Mohammadi Zahra , Mesgarpour Bita , Akbari Mohammadreza , Kamalipour Alireza , Abdipour-Mehrian Seyed Reza , Hashemi Elham-Sadat , Zare Pooria , Lankarani Kamran Bagheri , Malekzadeh Reza , Malekzadeh Fatemeh , Vardanjani Hossein Molavi 
Published: December 2023

AbstractBackgroundGastroesophageal Reflux Disease (GERD) is a common chronic condition. Its chronic nature may affect the pattern of medication use. This study aimed to investigate the prevalence, associated factors, and patterns of polypharmacy and medication use among GERD patients in southwestern Iran.MethodsWe used data from the Pars Cohort Study. We classified drugs using the Anatomical Therapeutic Chemical classification system. The Lexicomp® database was used to assess potential drug-drug interactions. Multivariable Poisson regression was applied. Adjusted prevalence ratio (PR) and its 95% confidence interval (CI) were estimated.ResultsA total of 9262 participants were included. Among 2,325 patients with GERD, age-standardized prevalence of polypharmacy was 9.5% (95% CI: 7.5%, 11.6%) in males, and 19.3% (95% CI: 17.2%, 21.4%) in females. The PR of experiencing Polypharmacy by GERD patients compared to non-GERD patients was 1.82 (95% CI: 1.61, 2.05%). Multimorbidity (PR: 3.33; CI: 2.66, 4.15), gender (PR: 1.68; CI: 1.30, 2.18), and metabolic syndrome (PR: 1.77; CI: 1.45, 2.15) were associated with polypharmacy among GERD patients. Drugs for acid-related disorders were the most common used drugs among men, women and elders. We found that 13.9%, 4.2%, and 1.1% of GERD patients had type C, D and X drug interactions, respectively.ConclusionGERD is correlated with a higher prevalence of polypharmacy. Among GERD patients, females, those with multi-morbidities, and those with metabolic syndrome may be affected more by polypharmacy. Considering the fairly high rate of interactions identified, a review of the medication list is essential when approaching GERD patients, and physicians must check for medications that may worsen GERD.
Impact of a wearable-based physical activity and sleep intervention in multimorbidity patients: protocol for a randomized controlled trial
Authors: Neves Bernardo , Haghighi Eduardo D. , Pereira Hugo V. , Costa Filipe , Carlos João S. , Ferreira Daniel , Moreno Plinio , Ferreira Pedro M. , Machado Jaime , Goncalves Breno , Moreira José Maria , Leite Francisca , da Silva Nuno André 
Published: December 2023

Abstract
Background
The benefits of physical activity (PA) and adequate sleep are well documented, and their importance strengthens with the increasing prevalence of chronic diseases and multimorbidity (MM). Interventions to promote physical activity and sleep that use commercial activity trackers may be useful non-pharmacological approaches to managing individual health; however, limited evidence exists on their use to improve physical activity in older adult patients with MM.

Methods
This study aims to measure the effects of behavioral change techniques (BCTs) delivered by a wearable device on physical activity and quality of sleep (QS) in older adult patients with MM. We designed an open-label randomized controlled trial with participants recruited through primary care and a specialist outpatient clinic. Participants must be more than 65 years old, have MM, and have access to smartphones. All eligible participants will receive PA promotion content and will be randomly assigned to wear a smartwatch. The primary outcome will be the participants’ PA measurement at baseline and at six months using the International Physical Activity Questionnaire - Short Form (IPAQ-SF). Secondary outcomes will include changes in the participants’ frailty status, biometric measurements, quality of life, and biopsychosocial assessments. A sample size of 40 participants per arm was calculated to detect group differences, with 50 participants planned to recruit and randomize into each arm.

Discussion
This study aims to contribute to a better understanding of PA patterns and the impact of wearable-based PA interventions in patients with MM. In addition, we aim to contribute to more knowledge about the relationship between PA patterns, Patient Reported Outcomes Measures (PROMs), and healthcare resource utilization in patients with MM. To achieve this, the study will leverage a locally developed PROMs registry and assess data from participants’ medical records, in order to understand the added impact of wearable data and medical information data on predicting PROMs and unplanned hospital admissions.

Trial registration
NCT05777291