bluuebunny/crossref_metadata_2025_split huggingface dataset:
No unleashed expression without language
Authors: Carston Robyn 
Published: February 2023

AbstractWhile the metarepresentational structure of ostensive communication may explain the unleashing of human expression, it neither explains the open-endedness of the thoughts expressed/communicated, nor how the multiply embedded nature of the metarepresentational structure invoked arose. These both require the recursivity of human language, a capacity which must be distinguished from external (public) languages and their use in communication.
Poset Ramsey numbers: large Boolean lattice versus a fixed poset
Authors: Axenovich Maria , Winter Christian 
Published: February 2023

Abstract
Given partially ordered sets (posets)

$(P, \leq _P\!)$

and

$(P^{\prime}, \leq _{P^{\prime}}\!)$

, we say that

$P^{\prime}$

contains a copy of

$P$

if for some injective function

$f\,:\, P\rightarrow P^{\prime}$

and for any

$X, Y\in P$

,

$X\leq _P Y$

if and only if

$f(X)\leq _{P^{\prime}} f(Y)$

. For any posets

$P$

and

$Q$

, the poset Ramsey number

$R(P,Q)$

is the least positive integer

$N$

such that no matter how the elements of an

$N$

-dimensional Boolean lattice are coloured in blue and red, there is either a copy of

$P$

with all blue elements or a copy of

$Q$

with all red elements. We focus on a poset Ramsey number

$R(P, Q_n)$

for a fixed poset

$P$

and an

$n$

-dimensional Boolean lattice

$Q_n$

, as

$n$

grows large. We show a sharp jump in behaviour of this number as a function of

$n$

depending on whether or not

$P$

contains a copy of either a poset

$V$

, that is a poset on elements

$A, B, C$

such that

$B\gt C$

,

$A\gt C$

, and

$A$

and

$B$

incomparable, or a poset

$\Lambda$

, its symmetric counterpart. Specifically, we prove that if

$P$

contains a copy of

$V$

or

$\Lambda$

then

$R(P, Q_n) \geq n +\frac{1}{15} \frac{n}{\log n}$

. Otherwise

$R(P, Q_n) \leq n + c(P)$

for a constant

$c(P)$

. This gives the first non-marginal improvement of a lower bound on poset Ramsey numbers and as a consequence gives

$R(Q_2, Q_n) = n + \Theta \left(\frac{n}{\log n}\right)$

.
Working in a UK national proton radiotherapy facility: the therapeutic radiographer perspective
Authors: Bailey R. 
Published: February 2023

Abstract
The first national UK proton beam therapy centre opened at The Christie NHS Foundation Trust in 2018, which alongside University College London Hospitals NHS Foundation Trust (UCLH) proton beam therapy centre, is expected to treat approximately seven-hundred and fifty patients per year at service ramp up.
The aim of this editorial is to share with a wider audience the role of a Band 6 proton senior treatment radiographer working in a national NHS service and future developments of the service. Prior to the service being clinical, a range of processes were followed, including the creation of quality documents, departmental training and end-to-end testing, with the first patient receiving treatment in December 2018.
Proton senior radiographers are responsible for the delivery of safe and accurate radiotherapy and ensuring a smooth patient pathway, through a multi-collaborative team approach. Although there are key differences between proton and photon radiotherapy, the fundamental aspects, including radiation principles, governance and patient advice are the same. The training package for proton senior radiographers includes an individual local induction as part of the proton education and competency framework, which incorporates practical learning, including clinical supervision and workshops, plus audio-visual presentations and workbooks to complete.
Future developments of proton beam therapy include proton arc therapy and flash therapy, alongside educational developments, such as training the future workforce and advanced practice consultant radiographer roles. Shared learning through multi-collaboration of international proton beam therapy centres is crucial to improve care for future service users.
Strategies for and Barriers to Collaboratively Developing Anti‐Racist Policies and Resources as Described by Geoscientists of Color Participating in the Unlearning Racism in Geoscience (URGE) Program
Authors: Burton Carlene , Duran Gabriel , Wright Vashan , Chmiel Rebecca 
Published: February 2023

AbstractThe Unlearning Racism in Geosciences (URGE) program guides groups of geoscientists as they draft, implement, and assess anti‐racist policies and resources for their workplace. Some participating Geoscientists of Color (GoC) shared concerns about microaggression, tokenism, and power struggles within their groups. These reports led us to collect and analyze data that describe the experiences of GoC in URGE. The data are from five discussion groups and two surveys. Our analyses revealed that participating GoC want to continue working with White colleagues on anti‐racist work. GoC want White colleagues not to shy away from doing anti‐racist work. Instead, GoC want White colleagues (a) to create and adhere to robust behavioral codes of conduct, (b) to focus discussions on anti‐racism, (c) to act on anti‐racism initiatives, (d) not to prompt GoC to educate them or reveal trauma, and (e) to refrain from microaggressions and tokenism. These desired outcomes were achieved in some groups with varying degrees of success. Correcting a history of mistrust relating to racism and anti‐racism action is key to implementing and assessing effective anti‐racist policies and resources. This requires leadership support, following through on anti‐racism action, and deepening relationships between GoC and White colleagues. Future anti‐racist programs should spend a substantial amount of time on and demonstrate the importance of training participants how to discuss racism effectively and how to create and adhere to robust behavioral codes of conduct. Future programs should also explore developing a robust program‐wide code of conduct that includes a policy for reporting offenses.
Statistical Properties of Lower Hybrid Waves in the Magnetopause Reconnection Exhaust Region
Authors: Ren Yong , Dai Lei , Wang Chi , Lavraud Benoit 
Published: February 2023

AbstractLower hybrid waves (LHWs) are frequently observed associated with magnetic reconnection. A general picture of the statistical properties of LHWs in magnetopause reconnection, however, has not yet been established. Here we report such a statistical study of LHWs using magnetospheric multiscale mission data in the magnetopause reconnection exhaust region. LHWs are identified in reconnection outflow regions over a broad range of magnetic local time. Most of the LHWs are near strong density gradients located on the low‐density magnetospheric side of the reconnection layer. The wave amplitude is typically several mV/m but can occasionally reach a few tens of mV/m. Compared with intervals that do not exhibit LHWs, intervals with LHWs show a ∼50% increase in parallel electron temperature, providing statistical evidence that LHWs contribute to parallel electron heating in reconnection exhausts and the dayside low‐latitude boundary layer.
Generating in vitro models of NTRK-fusion mesenchymal neoplasia as tools for investigating kinase oncogenic activation and response to targeted therapy
Authors: Vanoli Fabio , Herviou Laurie , Tsuda Yusuke , Sung Patricia , Xie Ziyu , Fishinevich Eve , Min Soe S. , Mallen William , de Wardin Henry de Traux , Zhang Yanming , Jasin Maria , Antonescu Cristina R. 
Published: February 2023

AbstractThe discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions as pan-tumor oncogenic drivers has led to new personalized therapies in oncology. Recent studies investigating NTRK fusions among mesenchymal neoplasms have identified several emerging soft tissue tumor entities displaying various phenotypes and clinical behaviors. Among them, tumors resembling lipofibromatosis or malignant peripheral nerve sheath tumors often harbor intra-chromosomal NTRK1 rearrangements, while most infantile fibrosarcomas are characterized by canonical ETV6::NTRK3 fusions. However, appropriate cellular models to investigate mechanisms of how kinase oncogenic activation through gene fusions drives such a wide spectrum of morphology and malignancy are lacking. Progress in genome editing has facilitated the efficient generation of chromosomal translocations in isogenic cell lines. In this study we employ various strategies to model NTRK fusions, including LMNA::NTRK1 (interstitial deletion) and ETV6::NTRK3 (reciprocal translocation) in human embryonic stem (hES) cells and mesenchymal progenitors (hES-MP). Here, we undertake various methods to model non-reciprocal, intrachromosomal deletions/translocations by induction of DNA double strand breaks (DSBs) exploiting either the repair mechanisms of homology directed repair (HDR) or non-homologous end joining (NHEJ). Expression of LMNA::NTRK1 or ETV6::NTRK3 fusions in either hES cells or hES-MP did not affect cell proliferation. However, the level of mRNA expression of the fusion transcripts was significantly upregulated in hES-MP, and phosphorylation of the LMNA::NTRK1 fusion oncoprotein was noted only in hES-MP but not in hES cells. Similarly, an NTRK1-driven transcriptional profile related to neuronal and neuroectodermal lineage was upregulated mainly in hES-MP, supporting the importance of appropriate cellular context in modeling cancer relevant aberrations. As proof of concept of the validity of our in vitro models, phosphorylation was depleted by two TRK inhibitors, Entrectinib and Larotrectinib, currently used as targeted therapy for tumors with NTRK fusions.
Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions
Authors: Chen Zhou , Han Fangfang , Du Yan , Shi Huaqing , Zhou Wence 
Published: February 2023

AbstractHaving a hypoxic microenvironment is a common and salient feature of most solid tumors. Hypoxia has a profound effect on the biological behavior and malignant phenotype of cancer cells, mediates the effects of cancer chemotherapy, radiotherapy, and immunotherapy through complex mechanisms, and is closely associated with poor prognosis in various cancer patients. Accumulating studies have demonstrated that through normalization of the tumor vasculature, nanoparticle carriers and biocarriers can effectively increase the oxygen concentration in the tumor microenvironment, improve drug delivery and the efficacy of radiotherapy. They also increase infiltration of innate and adaptive anti-tumor immune cells to enhance the efficacy of immunotherapy. Furthermore, drugs targeting key genes associated with hypoxia, including hypoxia tracers, hypoxia-activated prodrugs, and drugs targeting hypoxia-inducible factors and downstream targets, can be used for visualization and quantitative analysis of tumor hypoxia and antitumor activity. However, the relationship between hypoxia and cancer is an area of research that requires further exploration. Here, we investigated the potential factors in the development of hypoxia in cancer, changes in signaling pathways that occur in cancer cells to adapt to hypoxic environments, the mechanisms of hypoxia-induced cancer immune tolerance, chemotherapeutic tolerance, and enhanced radiation tolerance, as well as the insights and applications of hypoxia in cancer therapy.
Artificial intelligence-enabled screening strategy for drug repurposing in monoclonal gammopathy of undetermined significance
Authors: Ryu Alexander J. , Kumar Shaji , Dispenzieri Angela , Kyle Robert A. , Rajkumar S. Vincent , Kingsley Thomas C. 
Published: February 2023

AbstractMonoclonal gammopathy of undetermined significance (MGUS) is a benign hematological condition with the potential to progress to malignant conditions including multiple myeloma and Waldenstrom macroglobulinemia. Medications that modify progression risk have yet to be identified. To investigate, we leveraged machine-learning and electronic health record (EHR) data to screen for drug repurposing candidates. We extracted clinical and laboratory data from a manually curated MGUS database, containing 16,752 MGUS patients diagnosed from January 1, 2000 through December 31, 2021, prospectively maintained at Mayo Clinic. We merged this with comorbidity and medication data from the EHR. Medications were mapped to 21 drug classes of interest. The XGBoost module was then used to train a primary Cox survival model; sensitivity analyses were also performed limiting the study group to those with non-IgM MGUS and those with M-spikes >0.3 g/dl. The impact of explanatory features was quantified as hazard ratios after generating distributions using bootstrapping. Medication data were available for 12,253 patients; those without medications data were excluded. Our model achieved a good fit of the data with inverse probability of censoring weights concordance index of 0.883. The presence of multivitamins, immunosuppression, non-coronary NSAIDS, proton pump inhibitors, vitamin D supplementation, opioids, statins and beta-blockers were associated with significantly lower hazard ratio for MGUS progression in our primary model; multivitamins and non-coronary NSAIDs remained significant across both sensitivity analyses. This work could inform subsequent prospective studies, or similar studies in other disease states.
‘Potentially curative therapies’ for hepatocellular carcinoma: how many patients can actually be cured?
Authors: Cucchetti Alessandro , Elshaarawy Omar , Han Guohong , Chong Charing C. N. , Serra Carla , O’Rourke Joanne Marie , Crew Richard , Felicani Cristina , Ercolani Giorgio , Shah Tahir , Vogel Arndt , Lai Paul B. S. , Johnson Philip J. 
Published: February 2023

Abstract
Background
Treatment of hepatocellular carcinoma (HCC) is predicated on early diagnosis such that ‘curative therapies’ can be successfully applied. The term ‘curative’ is, however, poorly quantitated. We aimed to complement our previous work by developing a statistical model to predict cure after ablation and to use this analysis to compare the true curative potential of the various ‘curative’ therapies.

Methods
We accessed data from 1571 HCC patients treated in 5 centres receiving radiofrequency (RFA) or microwave (MWA) ablation and used flexible parametric modelling to determine the curative fraction. The results of this analysis were then combined with our previous estimations to provide a simple calculator applicable to all patients undergoing potentially curative therapies.

Results
The cure fraction was 18.3% rising to about 40% in patients with good liver function and very small tumours.

Conclusion
Cure for HCC treated with ablation occurs in the order of 20% to 30%, similar to that achievable by resection but much inferior to transplantation where the analogous figure is >70%. We provide a ‘calculator’ that permits clinicians to estimate the chance of cure for any individual patient, based on readily available clinical features.
Single cell epigenomic and transcriptomic analysis uncovers potential transcription factors regulating mitotic/meiotic switch
Authors: Zhang Fa-Li , Feng Yan-Qin , Wang Jing-Ya , Zhu Ke-Xin , Wang Lu , Yan Jia-Mao , Li Xiu-Xiu , Wang Jun-Jie , Ge Wei , De Felici Massimo , Shen Wei 
Published: February 2023

AbstractIn order to reveal the complex mechanism governing the mitotic/meiotic switch in female germ cells at epigenomic and genomic levels, we examined the chromatin accessibility (scATAC-seq) and the transcriptional dynamics (scRNA-seq) in germ cells of mouse embryonic ovary between E11.5 to 13.5 at single-cell resolution. Adopting a strict transcription factors (TFs) screening framework that makes it easier to understand the single-cell chromatin signature and a TF interaction algorithm that integrates the transcript levels, chromatin accessibility, and motif scores, we identified 14 TFs potentially regulating the mitotic/meiotic switch, including TCFL5, E2F1, E2F2, E2F6, E2F8, BATF3, SP1, FOS, FOXN3, VEZF1, GBX2, CEBPG, JUND, and TFDP1. Focusing on TCFL5, we constructed Tcfl5+/− mice which showed significantly reduced fertility and found that decreasing TCFL5 expression in cultured E12.5 ovaries by RNAi impaired meiotic progression from leptotene to zygotene. Bioinformatics analysis of published results of the embryonic germ cell transcriptome and the finding that in these cells central meiotic genes (Stra8, Tcfl5, Sycp3, and E2f2) possess open chromatin status already at the mitotic stage together with other features of TCFL5 (potential capability to interact with core TFs and activate meiotic genes, its progressive activation after preleptotene, binding sites in the promoter region of E2f2 and Sycp3), indicated extensive amplification of transcriptional programs associated to mitotic/meiotic switch with an important contribution of TCFL5. We conclude that the identified TFs, are involved in various stages of the mitotic/meiotic switch in female germ cells, TCFL5 primarily in meiotic progression. Further investigation on these factors might give a significant contribution to unravel the molecular mechanisms of this fundamental process of oogenesis and provide clues about pathologies in women such as primary ovarian insufficiency (POI) due at least in part to meiotic defects.
Association between levels of exposure to heavy metals and renal function indicators of residents in environmentally vulnerable areas
Authors: Kwon Jung-Yeon , Lee Seungho , Surenbaatar Ulziikhishig , Lim Hyoun-Ju , Kim Byoung-Gwon , Eom Sang-Yong , Cho Yong Min , Kim Woo Jin , Yu Byeng-Chul , Lee Kwan , Hong Young-Seoub 
Published: February 2023

AbstractAbandoned metal mines and refineries are considered environmentally vulnerable areas owing to high levels of exposure to heavy metals. This study examined the association between heavy metal exposure and renal function indicators. We studied a total of 298 participants, of which 74 and 68 resided in low- and high-exposure abandoned metal mine areas, respectively, with 121 in the refinery area and 35 in the control area. Blood and urine samples were collected from the participants to analyze the levels of blood lead, cadmium, and creatinine and urinary cadmium, NAG, and β2-MG. The estimated glomerular filtration rate, which is calculated using the Chronic Kidney Disease Epidemiology Collaboration equation, was used for assessments. The study participants comprised more females than males, and their mean age was 70.3 years. The blood lead and cadmium as well as urinary cadmium levels were 2.12 μg/dL, 1.89 μg/L, and 2.11 μg/L, respectively, in the heavy metal-exposure areas, and 1.18 μg/dL, 0.89 μg/L, and 1.11 μg/L, respectively, in the control area. The odds ratio (OR) for exceeding the reference value showed that blood cadmium in the refinery area was 38 times higher than that in the control area. Urinary cadmium was seven times higher in the low-exposure abandoned metal mine area than in the control area. NAG showed a positive correlation with urinary cadmium in all areas. In the refinery area, correlations were observed between β2-MG and urinary cadmium levels and the eGFR and blood cadmium level; in the high-exposure abandoned metal mine area, correlations were observed between NAG, β2-MG, and the eGFR and blood cadmium. In this study, the association between Cd exposure and some renal function indicators was observed. This study’s findings and the obtained biological samples can serve as a basis for future molecular biological research.
Identifying ways of producing pigs more sustainably: tradeoffs and co-benefits in land and antimicrobial use
Authors: Bartlett Harriet , Balmford Andrew , Wood James L. N. , Holmes Mark A. 
Published: February 2023

AbstractPork accounts for the largest proportion of meat consumed globally and demand is growing rapidly. Two important externalities of pig farming are land use and antimicrobial resistance (AMR) driven by antimicrobial use (AMU). Land use and AMU are commonly perceived to be negatively related across different production systems, so those with smaller land footprints pose greater risk to human health. However, the relationship between land use and AMU has never been systematically evaluated. We addressed this by measuring both outcomes for 74 highly diverse pig production systems. We found weak evidence of an AMU/land use tradeoff. We also found several systems characterized by low externality costs in both domains. These potentially promising systems were spread across different label and husbandry types and indeed no type was a reliable indicator of low-cost systems in both externalities. Our findings highlight the importance of using empirical evidence in decision-making, rather than relying on assumptions.
Corrosion damage and life prediction of concrete structure in the coking ammonium sulfate workshop of iron and steel industry
Authors: Lv Yao , Niu Ditao , Liu Xiguang , Lin Mingqiang , Li Yue-chen 
Published: February 2023

AbstractIron and steel plants emit a large amount of CO2 and SO2 in the production process, and the high concentrations of acid gases lead to serious corrosion damage of concrete structures. In this paper, the environmental characteristics and corrosion damage degree of concrete in a 7-year-old coking ammonium sulfate workshop were investigated, and the neutralization life prediction of the concrete structure was carried out. Besides, the corrosion products were analyzed through concrete neutralization simulation test. The average temperature and relative humidity in the workshop were 34.7 °C and 43.4%, and they were 1.40 times higher and 1.70 times less than those of the general atmospheric environment, respectively. Both the concentrations of CO2 and SO2 were significantly different in various sections of the workshop, and they were much higher than those of the general atmospheric environment. The appearance corrosion and compressive strength loss of concrete were more serious in the sections with high SO2 concentration, such as vulcanization bed section and crystallization tank section. The neutralization depth of concrete in the crystallization tank section was the largest, with an average value of 19.86 mm. The corrosion products gypsum and CaCO3 were obviously visible in the surface layer of concrete, while only CaCO3 could be observed at 5 mm. The prediction model of concrete neutralization depth was established, and the remaining neutralization service life in the warehouse, synthesis section (indoor), synthesis section (outdoor), vulcanization bed section, and crystallization tank section were 69.21 a, 52.01 a, 88.56 a, 29.62 a, and 7.84 a, respectively.