bluuebunny/crossref_metadata_2025_split huggingface dataset:
Further prediction on the possible double-peak structure of the X17 particle
Authors: Chen Hua-Xing 
Published: May 2024

The [Formula: see text] particle, discovered by [A. J. Krasznahorkay et al., Phys. Rev. Lett. 116, 042501 (2016), doi:10.1103/PhysRevLett.116.042501] at ATOMKI, was recently confirmed in the [Formula: see text] invariant mass spectra by [K. U. Abraamyan, C. Austin, M. I. Baznat, K. K. Gudima, M. A. Kozhin, S. G. Reznikov and A. S. Sorin, arXiv:2311.18632] at JINR. We notice with surprise and interest that the [Formula: see text] seems to have a double-peak structure. This is in a possible coincidence with our QCD sum rule study of [H.-X. Chen, arXiv:2006.01018], where we interpreted the [Formula: see text] as a tetraquark state composed of four bare quarks ([Formula: see text]), and claimed that “A unique feature of this tetraquark assignment is that we predict two almost degenerate states with significantly different widths”. These two different tetraquark states are described by two different chiral tetraquark currents [Formula: see text] and [Formula: see text]. To verify whether the tetraquark assignment is correct or not, we replace the up and down quarks by the strange quarks, and apply the QCD sum rule method to study the other four chiral tetraquark currents [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text]. We calculate their correlation functions, and find that non-perturbative QCD effects do not contribute much to them. Our results suggest that there may exist four almost degenerate tetraquark states with masses about [Formula: see text] MeV. Each of these states is composed of four bare quarks, either [Formula: see text] or [Formula: see text].
Kureika–Tunguska Composite Tectono-Sedimentary Element, northern East Siberia
Authors: Frolov Sergey V. , Akhmanov Grigorii G. , Korobova Nataliya I. , Bakay Elena A. , Fadeeva Nataliya P. , Shevchuk Nadejda S. 
Published: May 2024

The Kureika–Tunguska Composite Tectono-Sedimentary Element (KT CTSE) is located in East Siberia. Geologically, it is confined to the homonymic basin in the northwestern part of the Siberian Craton. The basement of the basin is composed of Archean–Early Proterozoic metamorphic rocks. The sedimentary cover is composed of Mesoproterozoic, Neoproterosoic and Early Paleozoic predominantly carbonate rocks capped with a succession of Pennsylvanian–Permian coal-bearing sediments overlain by thick section of Early Triassic tuffs and lavas. The entire sedimentary cover, especially its upper part, is saturated with mafic intrusive bodies. The maximum depth to the top basement can exceed 10 km.
The KT CTSE is characterized by a very low degree of exploration. The rather scarce prospecting work carried out on oil and gas in the CTSE has not yet yielded positive results. However, indirect data such as, for example, numerous bitumen fields and evidence of the source rocks are promising for potential discoveries including large hydrocarbon accumulations.
Estrogen Induces LCAT to Maintain Cholesterol Homeostasis and Suppress Hepatocellular Carcinoma Development
Authors: He Wenzhi , Wang Min , Zhang Xuechun , Wang Yilan , Zhao Dongli , Li Wenhua , Lei Fang , Peng Min , Zhang Zhonglin , Yuan Yufeng , Huang Zan 
Published: May 2024

Abstract
Hepatocellular carcinoma (HCC) is an aggressive disease that occurs predominantly in men. Estrogen elicits protective effects against HCC development. Elucidation of the estrogen-regulated biological processes that suppress HCC could lead to improved prevention and treatment strategies. Here, we performed transcriptomic analyses on mouse and human liver cancer and identified lecithin cholesterol acyltransferase (LCAT) as the most highly estrogen-upregulated gene and a biomarker of favorable prognosis. LCAT upregulation inhibited HCC in vitro and in vivo and mediated estrogen-induced suppression of HCC in an ESR1-dependent manner. LCAT facilitated high-density lipoprotein cholesterol production and uptake via the LDLR and SCARB1 pathways. Consistently, high HDL-C levels corresponded to a favorable prognosis in HCC patients. The enhanced HDL-C absorption induced by LCAT impaired SREBP2 maturation, which ultimately suppressed cholesterol biosynthesis and dampened HCC cell proliferation. HDL-C alone inhibited HCC growth comparably to the cholesterol-lowering drug lovastatin, and SREBF2 overexpression abolished the inhibitory activity of LCAT. Clinical observations and cross-analyses of multiple databases confirmed the correlation of elevated LCAT and HDL-C levels to reduced cholesterol synthesis and improved HCC patient prognosis. Furthermore, LCAT deficiency mimicked whereas LCAT overexpression abrogated the tumor growth–promoting effects of ovariectomy in HCC-bearing female mice. Most importantly, HDL-C and LCAT delayed the development of subcutaneous tumors in nude mice, and HDL-C synergized with lenvatinib to eradicate orthotopic liver tumors. Collectively, this study reveals that estrogen upregulates LCAT to maintain cholesterol homeostasis and to dampen hepatocarcinogenesis. LCAT and HDL-C represent potential prognostic and therapeutic biomarkers for targeting cholesterol homeostasis as a strategy for treating HCC.
Significance: Estrogen mediates the sex differences in hepatocellular carcinoma development by reducing cholesterol biosynthesis through activation of an LCAT/HDL-C axis, providing strategies for improving liver cancer prevention, prognosis, and treatment.
CDKN2A/B Homozygous Deletion Sensitizes IDH-Mutant Glioma to CDK4/6 Inhibition
Authors: Nasser Ali M. , Melamed Lisa , Wetzel Ethan A. , Chang Jenny Chia-Chen , Nagashima Hiroaki , Kitagawa Yosuke , Muzyka Logan , Wakimoto Hiroaki , Cahill Daniel P. , Miller Julie J. 
Published: May 2024

Abstract

Purpose:
Treatment paradigms for isocitrate dehydrogenase (IDH)–mutant gliomas are rapidly evolving. Although typically indolent and responsive to initial treatment, these tumors invariably recur at a higher grade and require salvage treatment. Homozygous deletion of the tumor suppressor gene CDKN2A/B frequently emerges at recurrence in these tumors, driving poor patient outcomes. We investigated the effect of CDK-Rb pathway blockade on IDH-mutant glioma growth in vitro and in vivo using CDK4/6 inhibitors (CDKi).

Experimental Design:
Cell viability, proliferation assays, and flow cytometry were used to examine the pharmacologic effect of two distinct CDKi, palbociclib and abemaciclib, in multiple patient-derived IDH-mutant glioma lines. Isogenic models were used to directly investigate the influence of CDKN2A/B status on CDKi sensitivity. Orthotopic xenograft tumor models were used to examine the efficacy and tolerability of CDKi in vivo.

Results:
CDKi treatment leads to decreased cell viability and proliferative capacity in patient-derived IDH-mutant glioma lines, coupled with enrichment of cells in the G1 phase. CDKN2A inactivation sensitizes IDH-mutant glioma to CDKi in both endogenous and isogenic models with engineered CDKN2A deletion. CDK4/6 inhibitor administration improves survival in orthotopically implanted IDH-mutant glioma models.

Conclusions:
IDH-mutant gliomas with deletion of CDKN2A/B are sensitized to CDK4/6 inhibitors. These results support the investigation of the use of these agents in a clinical setting.
MEK Inhibition Enhances the Antitumor Effect of Radiotherapy in NF1-Deficient Glioblastoma
Authors: Ioannou Maria , Lalwani Kriti , Ayanlaja Abiola A. , Chinnasamy Viveka , Pratilas Christine A. , Schreck Karisa C. 
Published: May 2024

Abstract
Individuals with neurofibromatosis type 1, an autosomal dominant neurogenetic and tumor predisposition syndrome, are susceptible to developing low-grade glioma and less commonly high-grade glioma. These gliomas exhibit loss of the neurofibromin gene [neurofibromin type 1 (NF1)], and 10% to 15% of sporadic high-grade gliomas have somatic NF1 alterations. Loss of NF1 leads to hyperactive RAS signaling, creating opportunity given the established efficacy of MEK inhibitors in plexiform neurofibromas and some individuals with low-grade glioma. We observed that NF1-deficient glioblastoma neurospheres were sensitive to the combination of an MEK inhibitor (mirdametinib) with irradiation, as evidenced by synergistic inhibition of cell growth, colony formation, and increased cell death. In contrast, NF1-intact neurospheres were not sensitive to the combination, despite complete ERK pathway inhibition. No neurosphere lines exhibited enhanced sensitivity to temozolomide combined with mirdametinib. Mirdametinib decreased transcription of homologous recombination genes and RAD51 foci, associated with DNA damage repair, in sensitive models. Heterotopic xenograft models displayed synergistic growth inhibition to mirdametinib combined with irradiation in NF1-deficient glioma xenografts but not in those with intact NF1. In sensitive models, benefits were observed at least 3 weeks beyond the completion of treatment, including sustained phosphor-ERK inhibition on immunoblot and decreased Ki-67 expression. These observations demonstrate synergistic activity between mirdametinib and irradiation in NF1-deficient glioma models and may have clinical implications for patients with gliomas that harbor germline or somatic NF1 alterations.
Evaluation of Copanlisib in Combination with Eribulin in Triple-negative Breast Cancer Patient-derived Xenograft Models
Authors: Guo Zhanfang , Luo Jingqin , Mashl R. Jay , Hoog Jeremy , Maiti Piyush , Fettig Nikki , Davies Sherri R. , Aft Rebecca , Held Jason M. , Govindan Ramaswamy , Ding Li , Li Shunqiang , von Morze Cornelius , Wulf Gerburg M. , Shoghi Kooresh I. , Ma Cynthia X. 
Published: May 2024

Abstract

The PI3K pathway regulates essential cellular functions and promotes chemotherapy resistance. Activation of PI3K pathway signaling is commonly observed in triple-negative breast cancer (TNBC). However previous studies that combined PI3K pathway inhibitors with taxane regimens have yielded inconsistent results. We therefore set out to examine whether the combination of copanlisib, a clinical grade pan-PI3K inhibitor, and eribulin, an antimitotic chemotherapy approved for taxane-resistant metastatic breast cancer, improves the antitumor effect in TNBC. A panel of eight TNBC patient-derived xenograft (PDX) models was tested for tumor growth response to copanlisib and eribulin, alone or in combination. Treatment-induced signaling changes were examined by reverse phase protein array, immunohistochemistry (IHC) and 18F-fluorodeoxyglucose PET (18F-FDG PET). Compared with each drug alone, the combination of eribulin and copanlisib led to enhanced tumor growth inhibition, which was observed in both eribulin-sensitive and -resistant TNBC PDX models, regardless of PI3K pathway alterations or PTEN status. Copanlisib reduced PI3K signaling and enhanced eribulin-induced mitotic arrest. The combination enhanced induction of apoptosis compared with each drug alone. Interestingly, eribulin upregulated PI3K pathway signaling in PDX tumors, as demonstrated by increased tracer uptake by 18F-FDG PET scan and AKT phosphorylation by IHC. These changes were inhibited by the addition of copanlisib. These data support further clinical development for the combination of copanlisib and eribulin and led to a phase I/II trial of copanlisib and eribulin in patients with metastatic TNBC.

Significance:
In this research, we demonstrated that the pan-PI3K inhibitor copanlisib enhanced the cytotoxicity of eribulin in a panel of TNBC PDX models. The improved tumor growth inhibition was irrespective of PI3K pathway alteration and was corroborated by the enhanced mitotic arrest and apoptotic induction observed in PDX tumors after combination therapy compared with each drug alone. These data provide the preclinical rationale for the clinical testing in TNBC.
Conduit Flow Compensates for Impaired Left Atrial Passive and Booster Functions in Advanced Diastolic Dysfunction
Authors: Aronson Doron , Sliman Hend , Abadi Sobhi , Maiorov Ida , Perlow Daniel , Mutlak Diab , Lessick Jonathan 
Published: May 2024

BACKGROUND:
Quantification of left atrial (LA) conduit function and its contribution to left ventricular (LV) filling is challenging because it requires simultaneous measurements of both LA and LV volumes. The functional relationship between LA conduit function and the severity of diastolic dysfunction remains controversial. We studied the role of LA conduit function in maintaining LV filling in advanced diastolic dysfunction.

METHODS:
We performed volumetric and flow analyses of LA function across the spectrum of LV diastolic dysfunction, derived from a set of consecutive patients undergoing multiphasic cardiac computed tomography scanning (n=489). From LA and LV time-volume curves, we calculated 3 volumetric components: (1) early passive emptying volume; (2) late active (booster) volume; and (3) conduit volume. Results were prospectively validated on a group of patients with severe aortic stenosis (n=110).

RESULTS:

The early passive filling progressively decreased with worsening diastolic function (
P
<0.001). The atrial booster contribution to stroke volume modestly increases with impaired relaxation (
P
=0.021) and declines with more advanced diastolic function (
P
<0.001), thus failing to compensate for the reduction in early filling. The conduit volume increased progressively (
P
<0.001), accounting for 75% of stroke volume (interquartile range, 63–81%) with a restrictive filling pattern, compensating for the reduction in both early and booster functions. Similar results were obtained in patients with severe aortic stenosis. The pulmonary artery systolic pressure increased in a near-linear fashion when the conduit contribution to stroke volume increased above 60%. Maximal conduit flow rate strongly correlated with mitral E-wave velocity (r=0.71;
P
<0.0001), indicating that the increase in mitral E wave in diastolic dysfunction represents the increased conduit flow.

CONCLUSIONS:
An increase in conduit volume contribution to stroke volume represents a compensatory mechanism to maintain LV filling in advanced diastolic dysfunction. The increase in conduit volume despite increasing LV diastolic pressures is accomplished by an increase in pulmonary venous pressure.
Mao's Cambodian Legacy: An “Ideological Victory” and a Strategic Failure
Authors: Chenyi Wang 
Published: May 2024

Abstract
Drawing on untapped Chinese primary sources, including archival documents, the biographies and memoirs of Chinese Communist Party (CCP) officials involved in managing policy toward the Khmer Rouge in Cambodia, and, in particular, the memoirs of members of Huayun (an ethnic Chinese revolutionary movement) in Cambodia, this article shows that under Mao Zedong the CCP's policies toward the Khmer Rouge were subordinated to Mao's political needs and indistinguishable from his domestic policies. The Khmer Rouge's victory in Cambodia was significant to Mao in light of the bankrupt Cultural Revolution at home and isolation by the other Communist parties abroad. In 1973 and 1974, Chinese leaders rejected U.S. proposals to restore Prince Sihanouk to power in Cambodia and later refrained from any criticism of the mass slaughter perpetrated by the Khmer Rouge, including the systematic killing of ethnic Chinese in Cambodia. As a result, the post-Mao leaders were unable to disengage from Cambodia or to restrain the Khmer Rouge. Mao's “ideological victory” eventually translated into a strategic debacle for the PRC.
The Unpublished Medicina contracta of Arnold Geulincx
Authors: Strazzoni Andrea 
Published: May 2024

Abstract
In this paper I provide a commentary on and edition of the unpublished and apparently incomplete Medicina contracta of the Flemish philosopher Arnold Geulincx (1624–1669). This short treatise, dating to c. 1668–1669, was not included in the edition of Geulincx’s works edited by J.P.N. Land, on the ground of its apparent unoriginality. However, it reveals the attempt, by Geulincx, to develop a medicine based on a new account of disease (intended in Cartesian-Platonic terms of the impossibility of the mind using the body through animal spirits), and integrating avant-garde solutions typical of iatrochemistry (in particular those of Franciscus Sylvius) and iatromechanics. The text, which I also consider in the light of Geulincx’s disputations in physiology, is moreover revelatory of his ongoing efforts in understanding the nature of respiration and its related diseases and conditions, such as apoplexy, and of his progressive, albeit not uncritical acceptance of Cartesianism.
Determinants of Road Traffic Crash Fatalities: A Case of Road Accidents in India, 2004–2018
Authors: Kunroo Mohd Hussain , Alam Md. Absar 
Published: May 2024

The purpose of this study is to determine the factors that influence deaths in road accidents in India. The study uses panel econometric methodologies such as the fixed effects model, random effects model, and Hausman–Taylor instrumental variable technique to achieve this goal. Unobserved heterogeneity between states/union territories (UTs) and time is accounted for by time-fixed and state-fixed effects. Based on the panel data set from Indian states/UTs for the period 2004–2018, the study confirms previous results that motorisation, population, urbanisation and income level are all potential contributors to road accidents and fatalities. It also shows that spending on health care and law enforcement appears to help the Indian states minimise mortality in road traffic accidents. On the one hand, spending on health care facilities can provide health-related assistance to persons who have been involved in traffic accidents; on the other hand, spending on police increases the enforcement of rules, resulting in a reduction in traffic accidents. Thus, to lessen the economic and financial cost of road accidents in the country, the government should focus on boosting both per capita health expenditure and per capita police expenditure. JEL Codes: C23, C26, H51, I18, L92, O18, R41, R42
Cerebrospinal venous obstruction and breast cancer: A pilot study
Authors: Thibault Paul K 
Published: May 2024

Breast cancer has important co-morbidities including vascular disease but there has been little research undertaken on a possible link between venous disease and breast cancer. This pilot study aims to explore a possible relationship. Methods The venous drainage of the breasts is described and the cerebrospinal venous systems (CSVS) of six patients with treated breast cancer were assessed using duplex ultrasound to measure venous blood volume flows in the neck veins. Results All six patients with breast cancer showed evidence of cerebrospinal venous obstruction (CSVO). Further, all six demonstrated collateral flow in the erect position in the internal jugular vein on the same side as the diagnosed breast cancer. Conclusion There is an indication for a well-designed case-control study using the duplex ultrasound neck vein examination, comparing patients treated for breast cancer with healthy women.
Multi-walled carbon nanotubes/woven glass/epoxy hybrid nanocomposites: Effect of fabrication methods and types of epoxy matrices
Authors: Nik Amrul Faaizol Nik Amira Natasha , Mustapha Mariatti , Rejab Nik Akmar , Vahabi Henri 
Published: May 2024

The hybridization of nanofillers into glass fibre reinforcement is a promising strategy to improve the properties of the composite materials. The study aims to investigate the properties of hybrid nanocomposites consisting of multi-walled carbon nanotube (MWCNT)/woven glass/epoxy composites. The effect of different fabrication methods and different types of epoxy matrices was also investigated. For method 1, MWCNT was mixed with epoxy and impregnated into 3-ply woven glass fabrics using the hand lay-up method, followed by a vacuum bagging process. Meanwhile, for method 2, the woven glass fabrics were spray coated with MWCNT aqueous suspension and 3-ply woven glass fabrics were stacked together and impregnated with epoxy using the hand lay-up method followed by vacuum bagging. Results showed that composite laminates prepared by method 2 with 0.5 wt% MWCNT exhibit higher impact and flexural strength with 32.9% and 29% increments compared to method 1, respectively. Based on the flammability test, it was observed that hybrid laminate composites fabricated by both methods could self-extinguish. It was found that hybrid laminated composites using bisphenol A as an epoxy matrix show higher impact strength and flexural strength with 20.7% and 12% increments compared to epoxy bio-resins, respectively.
3D nonlinear finite element investigation of laminated bamboo plate strengthened prestressed concrete slab
Authors: Wang Zhao , Wan Baolin , Xu Qingfeng 
Published: May 2024

Due to environment and recycling concerns, interest in applying natural fiber reinforced polymer (NFRP) as an alternative for glass/carbon FRP to strengthen concrete structures has been increasing. This study developed a 3D nonlinear finite element (FE) model for laminated bamboo (LB) plate strengthened prestressed concrete slab. By involving temperature load on defined temperature sensitive material, the proposed model provided good simulation of prestressing process. The accuracy of the developed model was confirmed through comparisons with experimental data, representing peak load discrepancies of only 6.5% and 8.2% for un-strengthened and strengthened slabs, respectively. The parametric study examined the impact of LB plate dimensions and tensile strength, alongside the use of FRP wraps, on concrete slab performance. The results show that the 15 mm thick LB plate can enhance the slab’s peak load by 83.2%. Variations in LB plate tensile strength by up to 10% do not significantly affect the performance of the strengthened prestressed concrete. The increases of the peak load for strengthened cases with LB plate width of 150 mm, 300 mm and 460 mm were 29.4%, 41.9% and 50.2%, respectively. It also shows that FRP end wraps can increase the performance of thick LB plate strengthened prestressed concrete slab.