bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjustment of medical standards in disaster, crises and war: a scoping review of the literature
Authors: Wurmb Thomas Erik , Schade Janno , Schräder Stephanie-Julia , Meybohm Patrick , Weibel Stephanie , Kippnich Maximilian 
Published: September 2024

IntroductionCurrently, there is a lack of evidence on how societies and healthcare systems cope with disrupting situations like disasters, crisis and wars. The aim of the scoping review was to map evidence to the following questions: Is the fact of possible overwhelming of healthcare systems accepted or denied? Are medical standards adjusted? Are dedicated contingency concepts applied? Are there triage concepts for allocating scarce resources?MethodsWe conducted and reported the scoping review in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for scoping reviews. A review protocol was published a priori in the Open Science Framework. Medline via PubMed was used as data source. We considered reviews, systematic reviews, guidelines and case-control studies in English or German as eligible for this scoping review, regardless of publication year or publication status. We searched Medline via PubMed up to 8 March 2023, and updated on 20 July 2023. Title/Abstract screening, full-text screening and data extraction were performed in a dual-reviewer mode.ResultsA total of 2213 publications were identified and 71 publications were finally included. Of these, 87% generally accepted the possibility that the capacity of the healthcare system would be overwhelmed. A structured change of medical standards was reported in 89%. 51% deployed the crisis standard of care concept. International accepted guidelines for maintaining medical care do not exist. There is no common understanding of the medical care status with regard to the standards. There is a lack of political, legal and ethical agreement on the subject of triage.ConclusionFuture research must clarify which concepts and measures are suitable for building a robust healthcare system in order to maintain medical care according to accepted standards for as long as possible. Algorithms for the allocation of scarce resources must be defined in advance to enable medical staff to act with legal certainty in a crisis.
Christianson syndrome across the lifespan: genetic mutations and longitudinal study in children, adolescents, and adults
Authors: Kavanaugh Brian C , Elacio Jennifer , Best Carrie R , St Pierre Danielle G , Pescosolido Matthew F , Ouyang Qing , Biedermann John , Bradley Rebecca S , Liu Judy S , Jones Richard N , Morrow Eric M 
Published: September 2024

Objectives
Mutations in the X-linked endosomal Na+/H+ exchanger 6 (NHE6) cause Christianson syndrome (CS). Here, in the largest study to date, we examine genetic diversity and clinical progression in CS into adulthood.

Method

Data were collected as part of the International Christianson Syndrome and
NHE6
(
SLC9A6
) Gene Network Study. 44 individuals with 31 unique
NHE6
mutations, age 2–32 years, were followed prospectively, herein reporting baseline, 1 year follow-up and retrospective natural history.

Results
We present data on the CS phenotype with regard to physical growth and adaptive and motor regression across the lifespan including information on mortality. Longitudinal data on body weight and height were examined using a linear mixed model. The rate of growth across development was slow and resulted in prominently decreased age-normed height and weight by adulthood. Adaptive functioning was longitudinally examined; a majority of adult participants (18+ years) lost gross and fine motor skills over a 1 year follow-up. Previously defined core diagnostic criteria for CS (present in>85%)—namely non-verbal status, intellectual disability, epilepsy, postnatal microcephaly, ataxia, hyperkinesia—were universally present in age 6–16; however, an additional core feature of high pain tolerance was added (present in 91%). While neurologic examinations were consistent with cerebellar dysfunction, importantly, a majority of individuals (>50% older than 10) also had corticospinal tract abnormalities. Three participants died during the period of the study.

Conclusions
In this large and longitudinal study of CS, we begin to define the trajectory of symptoms and the adult phenotype thereby identifying critical targets for treatment.
Endovascular management of intracranial carotid blowout syndrome in patients with head and neck cancer
Authors: Yu Kai-Wei , Ling Kan , Wu Chia-Hung , Lin Te-Ming , Tai Wei-An , Yang Chung-Han , Kang Yu-Mei , Luo Chao-Bao , Chang Feng-Chi 
Published: September 2024

Background
Carotid blowout syndrome is a serious complication of head and neck cancer (HNC) that may involve the intracranial or extracranial internal carotid artery (ICA). Although parent artery occlusion (PAO) is the major endovascular treatment for intracranial carotid blowout syndrome (iCBS), the efficacy of using a balloon-expandable coronary stent-graft (BES) remains unclear.

Methods
This was a quasi-randomized trial, prospective study that included patients with iCBS treated by BES or PAO between 2018 and 2024. Patients were allocated to either group based on the last digit of their chart number; even numbers went to the BES group and odd numbers to the PAO group. The inclusion criteria of iCBS included the pathological process of CBS involving petrous and/or cavernous ICA detected by both imaging and clinical features. The primary outcome was defined as rebleeding events after intervention. The secondary outcome was defined as neurological complication after intervention.

Results
Fifty-nine patients with 61 iCBS lesions were enrolled. Thirty-three iCBS lesions were treated with BES and 28 underwent PAO. The results for the BES group versus the PAO group, respectively, were: rebleeding events, 5/33 (15.1%) vs 5/28 (17.8%) (p=0.78); neurological complication, 5/33 (15.1%) vs 5/28 (17.8%) (p=0.78); median hemostatic time (months), 10.0 vs 11.5 (p=0.22); and median survival time (months), 10.0 vs 11.5 (p=0.39).

Conclusions
No significant difference in rebleeding risk or neurological complication was observed between the BES and PAO groups. Our study confirmed the safety and effectiveness of applying BES for iCBS in HNC patients.
Acceptability of a rectal microbicide douche for HIV prevention: a mixed-methods analysis of a first-in-human formulation pilot study
Authors: Giguere Rebecca , Balán Iván C , Lentz Cody , Dolezal Curtis , Carballo-Diéguez Alex , Fuchs Edward J , Anton Peter , McGowan Ian , Ho Ken , Weld Ethel , Hendrix Craig W 
Published: September 2024

ObjectivesDREAM-01 was an open label, dose-escalation and variable osmolarity study to identify a tenofovir HIV-prevention douche/enema that could achieve protective colon tissue cell concentrations and high acceptability. To assess impact on sexual enjoyment, iso-osmolar and hypo-osmolar placebo douches were provided for at-home use before receptive anal sex (RAS).MethodsEighteen HIV-uninfected men who have RAS were administered three tenofovir douches at the research clinic: Product A, an iso-osmolar dose; Product B, an iso-osmolar escalation dose; and Product C, a hypo-osmolar escalation dose. Following Products A and C, participants were given a saline douche of matching osmolarity to use at home before RAS. Participants reported acceptability via a computer-assisted self-interview and in-depth interview in this mixed-methods study.ResultsAll three products were rated acceptable by 17 (95%) of the participants. A majority (94%) would be likely or very likely to use any of the three products before RAS. Of those who used the saline douches before RAS and then rated their sexual enjoyment, most reported that their sexual enjoyment was not affected. Interview data revealed that participants found the product easy to incorporate into their regular routine, but would prefer to use more liquid for cleansing.ConclusionsThese findings indicate that the hypo-osmolar Product C, which also provides the most rapid delivery of tenofovir for HIV prevention, is acceptable for future safety trials and that our sample reports high likelihood of using a rectal microbicide douche for HIV prevention. Our findings support continued pursuit of a tenofovir rectal microbicide douche.Trial registration numberNCT02750540.
Petrochemistry, mineralogy, and Nd isotopic analyses of Tithonian alkaline lamprophyric intrusions, north-central Newfoundland, Canada
Authors: Sandeman Hamish A.I. , Peace Alexander L. 
Published: September 2024

The Newfoundland Atlantic margin in Eastern Canada formed through protracted lithospheric extension, subsequent rifting, and ultimately, breakup. Mesozoic–Cenozoic magmatism on and offshore Newfoundland coincided with, and potentially resulted from, the concurrent rifting and breakup. In north-central Newfoundland, the alkali monzogabbroic Budgell Harbour and Dildo Pond stocks, an accompanying lamprophyre dyke swarm, and a peridotite sill collectively form the Notre Dame Bay Magmatic Province and are products of a punctuated alkaline magmatic pulse on the Newfoundland margin at ca. 148 Ma (Jurassic, Tithonian) with contemporaneous rifting and the formation of offshore petroliferous basins. The stocks comprise coarsely modally layered phlogopite–ilmenite–magnetite–kaersutite olivine gabbro or essexite. The radially disposed lamprophyre dykes are aphyric to ilmenite–magnetite–diopside ± olivine ± kaersutite ± phlogopite porphyritic camptonites containing common feldspathic- and/or carbonate-dominant ocelli. Silica-undersaturated (kirschsteinite), oxidized (esseneite, calderite), and incompatible-element-bearing minerals (barite, kainosite) form paragenetically late, small grains in the groundmass mantling other phases. Mineral chemistry, lithogeochemistry, and Nd isotopic data indicate the rocks are similar to ocean island basalt and alkaline lamprophyres and were generated via low degrees of partial melting of a Neoproterozoic, weakly garnetiferous lithospheric mantle source. The intrusions occur along the intersections of broadly northeast-trending, inherited, Appalachian-cycle lithospheric scale faults with a prominent east–west step in the northeast Newfoundland Mohorovičić discontinuity along the northeast Newfoundland coast. The convergence of inherited structures with the topographic variation of the lithosphere–asthenosphere boundary likely focussed decompression melting of the lithospheric mantle driven through distal, edge-driven upwelling associated with continued extension in the northwest Atlantic.
Criticality of the O(N) universality via global solutions to nonperturbative fixed-point equations
Authors: Tan Yang-yang , Huang Chuang , Chen Yong-rui , Fu Wei-jie 
Published: September 2024

AbstractFixed-point equations in the functional renormalization group approach are integrated from large to vanishing field, where an asymptotic potential in the limit of large field is implemented as initial conditions. This approach allows us to obtain a global fixed-point potential with high numerical accuracy, that incorporates the correct asymptotic behavior in the limit of large field. Our calculated global potential is in good agreement with the Taylor expansion in the region of small field, and it also coincides with the Laurent expansion in the regime of large field. Laurent expansion of the potential in the limit of large field for general case, that the spatial dimension d is a continuous variable in the range $$2\le d \le 4$$

2
≤
d
≤
4

, is obtained. Eigenfunctions and eigenvalues of perturbations near the Wilson–Fisher fixed point are computed with the method of eigenperturbations. Critical exponents for different values of d and N of the O(N) universality class are calculated.
Thallium enrichment mechanism and geological significance of the Xiangquan thallium deposit in Anhui Province, China
Authors: Guo Zhijuan , Xu Renting , Song Yuntao , Han Wei , Kong Mu , Fan Yang 
Published: September 2024

The discovery of the independent thallium (Tl) deposit in Xiangquan, Anhui Province, provides an example for the study of the enrichment and mineralization of the highly dispersed rare metal element Tl. In this paper, a range of methods are used to characterize the enrichment, depletion, migration and occurrence state of Tl in different types of rocks and ores: lithogeochemistry; electron microprobe and principal component analysis; and exploring the significance of geochemical anomalies on the geological indication of Tl deposit formation. The results show that Tl is mainly distributed in silicified rocks of the Ordovician Lunshan Formation, and its average content is 307.08

μ

g g
–1
. The contents of As, Sb, S, Fe
2
O
3
and Tl in wall rocks, altered rocks and ores are significantly correlated, indicating a close relationship with Tl accumulation. The geochemical characteristics confirm that pyrite in the study area originates from submarine hot-water deposition. The main carrier of Tl is pyrite of hydrothermal sedimentary origin, in which Tl occurs as isomorphs in fine grains of pyrite. Tl mineralization may be accompanied by silicification, and the metallogenic environment is in a relative oxidation state. The mineralization process results in the geochemical differentiation of elements. Under the influence of tectonic and low-temperature hydrothermal activities, ore-forming elements migrate to structurally favourable conditions for mineralization to occur. This study provides a basis for further understanding the mechanisms of co-enrichment and separation of Tl and guidance for Tl mineral exploration.
Creative Writing and Expository Writing. Flip Sides of the Same Coin?
Authors: Yaffe Philip 
Published: September 2024

Each "Communication Corner" essay is self-contained; however, they build on each other. For best results, before reading this essay exercise, go to the first essay "How an Ugly Duckling Became a Swan," and then read each succeeding essay.
Creative (fiction) writing and expository (non-fiction) writing have fundamentally different objectives. Creative writing seeks to amuse and entertain; expository writing seeks to inform and instruct. But while aiming at different targets, they share fundamentally important approaches and techniques. Ignoring these commonalities does serious harm to both genres.
A First-in-Human Study of Cinrebafusp Alfa, a HER2/4-1BB Bispecific Molecule, in Patients with HER2-Positive Advanced Solid Malignancies
Authors: Piha-Paul Sarina , Olwill Shane A. , Hamilton Erika , Tolcher Anthony , Pohlmann Paula , Liu Stephen V. , Wurzenberger Cornelia , Hasenkamp Laura-Carolin , Hansbauer Eva-Maria , Shroff Rachna , Hurvitz Sara , Krishnamurthy Anuradha , Patnaik Amita , Hahn Noah , Kumar Raman , Duerr Manuela , Zettl Markus , Aviano Kayti , Matis Louis , Bruns Ingmar , Ku Geoffrey 
Published: September 2024

Abstract

Purpose:
4-1BB (CD137) is a costimulatory immune receptor expressed on activated T cells, activated B cells, NK cells, and tumor-infiltrating lymphocytes, making it a promising target for cancer immunotherapy. Cinrebafusp alfa, a monoclonal antibody-like bispecific protein targeting HER2 and 4-1BB, aims to localize 4-1BB activation to HER2-positive tumors. This study evaluated the safety, tolerability, and preliminary efficacy of cinrebafusp alfa in patients with previously treated HER2-positive malignancies.

Patients and Methods:
This was a multicenter dose-escalation study involving patients with HER2-positive malignancies who received prior treatment. The study assessed the safety and efficacy of cinrebafusp alfa across various dose levels. Patients were assigned to different cohorts, and antitumor responses were evaluated. The study aimed to determine the MTD and to observe any clinical activity at different dose levels.

Results:
Of 40 evaluable patients in the “active dose” efficacy cohorts, five showed an antitumor response, resulting in an overall response rate of 12.5% and a disease-control rate of 52.5%. Clinical activity was observed at the 8 and 18 mg/kg dose levels, with confirmed objective response rates of 28.6% and 25.0%, respectively. Cinrebafusp alfa was safe and tolerable, with grade ≤2 infusion-related reactions being the most frequent treatment-related adverse event. MTD was not reached during the study.

Conclusions:
Cinrebafusp alfa demonstrates promising activity in patients with HER2-positive malignancies who have progressed on prior HER2-targeting regimens. Its acceptable safety profile suggests it could be a treatment option for patients not responding to existing HER2-directed therapies.
See related commentary by Eguren-Santamaría et al., p. 231
Abstract A005 TP53 variant clusters stratify the Li-Fraumeni spectrum and reveal an osteosarcoma-prone subgroup
Authors: Fischer Nicholas W. , Laverty Brianne , Alon Noa , Montellier Emilie , Hainaut Pierre , Maxwell Kara N. , Kratz Christian P. , Malkin David 
Published: September 2024

Abstract
Li-Fraumeni syndrome (LFS) has recently been redefined as a ‘spectrum’ cancer predisposition disorder to reflect its broad phenotypic heterogeneity. The wide functional gradient associated with different TP53 variants is thought to contribute to LFS heterogeneity, although it is still poorly understood and there is an unmet clinical need for risk stratification strategies. Leveraging p53 mutagenesis datasets, we performed an unsupervised cluster analysis that revealed five TP53 variant clusters with unique structural and functional consequences. Classifying variant carriers according to these clusters stratified cancer onset and survival using discovery and validation cohorts, and exposed important clinical characteristics to consider for patient management. In particular, we identified a subgroup of monomeric TP53 variant carriers prone to osteosarcoma, along with a cluster associated with less “LFS-like” phenotypes enriched in carriers with no history of cancer. Our classification of TP53 variants demonstrates the existence of a wide TP53-heritable cancer susceptibility spectrum and provides a new framework to delineate carriers toward personalized patient care.
Citation Format: Nicholas W. Fischer, Brianne Laverty, Noa Alon, Emilie Montellier, Pierre Hainaut, Kara N. Maxwell, Christian P. Kratz, David Malkin. TP53 variant clusters stratify the Li-Fraumeni spectrum and reveal an osteosarcoma-prone subgroup [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr A005.
Abstract A012 Unravelling the role of METTL1 in Myc driven pediatric cancers using CRISPR Cas13d
Authors: Liu Pei Y. , He Steven , Mayoh Chelsea , Salib Alice , De Weck Antoine , Ekert Paul G. 
Published: September 2024

Abstract
METTL1 is an RNA methyltransferase which catalyzes N7-methylguanosine (m7G) methylation on various RNAs, particularly on tRNAs. METTL1 has been reported to be amplified and/or overexpressed and high expression correlates with poor patient prognosis in different types of adult cancers. Our ZERO Childhood Cancer Program focuses on identifying and validating potential new drug targets and developing novel therapies for clinical use. ZERO has sequenced the whole genome and transcriptome in over 500 high-risk pediatric tumors and found that METTL1 gene copy number and gene expression are significantly higher in a subset of high-grade glioma, neuroblastoma, diffuse midline glioma and fusion positive rhabdomyosarcoma. Analysis of the publicly available SEQC microarray dataset showed that high METTL1 expression correlates with poor outcomes in MYCN amplified neuroblastoma patients. We validated the functional roles of METTL1 gene amplification and overexpression in a few pediatric cancer cell line models using the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) Cas13d knockdown system, in dual lentiviral constructs. We found that knocking down METTL1 significantly decreased METTL1 amplified neuroblastoma and rhabdomyosarcoma cell viability and colony formation but not in METTL1 non-amplified neuroblastoma and rhabdomyosarcoma cells. Gene Set Enrichment Analysis from RNA sequencing data revealed that knocking down METTL1 resulted in a decrease in Myc target gene expression, and an increased in apoptosis, interferon alpha response and p53 pathway hallmarks. Western blot analysis confirmed that knocking down METTL1 led to a decrease in the MCL-1 antiapoptotic protein expression and an increase in the proapoptotic protein expression such as cleaved PARP and caspase 3. Taken together, our data demonstrate that METTL1 is a potential therapeutic target in METTL1 amplified pediatric cancers.
Citation Format: Pei Y. Liu, Steven He, Chelsea Mayoh, Alice Salib, Antoine De Weck, Paul G. Ekert. Unravelling the role of METTL1 in Myc driven pediatric cancers using CRISPR Cas13d [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr A012.
Abstract A022 Characterizing the cell of origin of Ewing sarcoma
Authors: Vasileva Elena , Arata Claire , Crump Gage , Amatruda James 
Published: September 2024

Abstract
Ewing sarcoma (ES) is a malignant bone and soft tissue tumor that affects children, adolescents, and young adults. ES is characterized by the presence of a driver fusion oncogene, most frequently EWSR1-FLI1. The cell of origin of Ewing sarcoma and the mechanisms of EWSR1-FLI1-driven cell transformation are the subjects of long-standing debates, largely due to the absence of a representative mouse model. Previous reports have suggested that bone-marrow mesenchyme or/and neural crest cells may serve as potential cells of origin for Ewing sarcoma. These hypotheses have never been tested in vivo, as the EWSR1-FLI1 fusion causes severe developmental toxicity in most cell types. To address these questions, we developed a stable model enabling controlled expression of the human EWSR1-FLI1 oncofusion specifically in neural crest cells. Using this model, we demonstrated that expression of human EWSR1-FLI1 oncofusion in neural crest cells can lead to their transformation and the development of tumors in vivo. Here we applied innovative single-cell transcriptomic, genetic, and high-resolution imaging approaches to characterize cells giving rise to EWSR1-FLI1 driven tumors in zebrafish model of Ewing sarcoma. EWSR1-FLI1 hindered the normal differentiation of neural crest cells into glial and neuronal lineages. Instead, EWSR1-FLI1 strongly reprogrammed neural crest cells by upregulating the expression of mesodermal regulators, including the key mesodermal regulator tbxta (Brachyury or T) transcription factor. tbxta/TBXT expression was maintained in subset of zebrafish and human Ewing sarcomas. Our model provides a mechanism by which a neural crest cell population can be transformed to Ewing sarcoma, a malignancy with predominant mesenchymal features. Taken together, these findings shed light on the cellular and molecular mechanisms underlying Ewing sarcoma development and provide valuable insights into its pathogenesis.
Citation Format: Elena Vasileva, Claire Arata, Gage Crump, James Amatruda. Characterizing the cell of origin of Ewing sarcoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr A022.