Search

Abstract The DUNE far detector has been designed to detect photons and electrons generated by the charged products of the interaction of neutrinos with a massive liquid argon (LAr) target. The photon detection system (PDS) of the first DUNE far detector (FD1) is composed of 6000 photon detection units, named X-ARAPUCA. The detection of the prompt light pulse generated by the particle energy release in LAr will complement and boost the DUNE LAr Time Projection Chamber. It will improve the non-beam events tagging and enable at low energies the trigger and the calorimetry of the supernova neutrinos. The X-ARAPUCA is an assembly of several components. Its photon detection efficiency (PDE) depends on the design of the assembly, on the grade of the individual components and on their coupling. The X-ARAPUCA PDE is one of the leading parameters for the PDS sensitivity, that in turn determines the sensitivity of the DUNE for the detection of core-collapse supernova within the galaxy and for nucleon decay searches. In this work we present the final assessment of the absolute PDE of the FD1 X-ARAPUCA baseline design, measured in two laboratories with independent methods and setups. Preliminary results were reported in Palomares (JINST 18(02):C02064, https://doi.org/10.1088/1748-0221/18/02/C02064 , 2023). One hundred sixty units of these X-ARAPUCA devices have been deployed in the NP04 facility at the CERN Neutrino Platform, the 1:20 scale FD1 prototype, and will be operated during the year 2024. The assessed value of the PDE is a key parameter both in the NP04 and in the DUNE analysis and reconstruction studies.

Introduction: The aim of our study was to treat two similar groups of patients suffering from BPH: one group with a complex based on phycocyanin, PEA and selenium; the other group with dutasteride. So the effectiveness of these treatments was checked, especially regarding the improvement of LUTS and the reduction of PSA and prostate volume. Materials and methods: We included 104 patients in the study. All patients aged between 50 and 70 years, PSA values between 4 and 10 ng/ml, prostate volume calculated by transrectal ultrasound between 50 and 70 cc, flowmetry with maximum flow value greater than or equal to 10 ml/s, no suspicious nodules on DRE, no suspicious lesions on MRI (PI-RADS 1-2), negative previous prostatic biopsies or never bioptied, moreover absence of diabetes mellitus or chronic renal failure (blood creatinine >2 mg/dl). We considered: -Group A of 54 men who used the complex; -Group B of 50 patients treated with dutasteride. Then we controlled all patients 6 months after starting therapy, considering the following parameters: PSA, prostate volume, flowmetry. Results: Our results showed that both dutasteride and complex decreased PSA levels (both had a p

The Module-0 Demonstrator is a single-phase 600 kg liquid argon time projection chamber operated as a prototype for the DUNE liquid argon near detector. Based on the ArgonCube design concept, Module-0 features a novel 80k-channel pixelated charge readout and advanced high-coverage photon detection system. In this paper, we present an analysis of an eight-day data set consisting of 25 million cosmic ray events collected in the spring of 2021. We use this sample to demonstrate the imaging performance of the charge and light readout systems as well as the signal correlations between the two. We also report argon purity and detector uniformity measurements and provide comparisons to detector simulations.

Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for studying the structure and dynamics of various non-covalent interactions. However, often spectral parameters that are applicable for estimation of parameters of one type of non-covalent interaction will be inapplicable for another. Therefore, researchers are compelled to use spectral parameters that are specifically tailored to the type of non-covalent interaction being studied. This complexity makes it difficult to compare different types of non-covalent interactions with each other and, consequently, to establish a strict unified classification for them. This pioneering study proposes to use phosphine selenides as universal probes for investigating hydrogen and halogen bonding in solution. The study was carried out using the example of triethylphosphine selenide Et3PSe complexes with hydrogen bonds of Se⋯HO type and R3PSe (where R: Me, Et, n-Bu, t-Bu and Ph) with halogen bonds of Se⋯X type (where X: I and Br) in solution. The presence of non-covalent interactions was confirmed experimentally by means of 1H, 31P and 77Se NMR, as well as by quantum chemical calculation methods (optimization: PW6B95-D3/def2-QZVP; NMR: B97-2/pcsSeg-2). [ABSTRACT FROM AUTHOR]

The DUNE far detector has been designed to detect photons and electrons generated by the charged products of the interaction of neutrinos with a massive liquid argon (LAr) target. The photon detection system (PDS) of the first DUNE far detector (FD1) is composed of 6000 photon detection units, named X-ARAPUCA. The detection of the prompt light pulse generated by the particle energy release in LAr will complement and boost the DUNE LAr Time Projection Chamber. It will improve the non-beam events tagging and enable at low energies the trigger and the calorimetry of the supernova neutrinos. The X-ARAPUCA is an assembly of several components. Its photon detection efficiency (PDE) depends on the design of the assembly, on the grade of the individual components and on their coupling. The X-ARAPUCA PDE is one of the leading parameters for the PDS sensitivity, that in turn determines the sensitivity of the DUNE for the detection of core-collapse supernova within the galaxy and for nucleon decay searches. In this work we present the final assessment of the absolute PDE of the FD1 X-ARAPUCA baseline design, measured in two laboratories with independent methods and setups. Preliminary results were reported in Palomares (JINST 18(02):C02064, https://doi.org/10.1088/1748-0221/18/02/C02064, 2023). One hundred sixty units of these X-ARAPUCA devices have been deployed in the NP04 facility at the CERN Neutrino Platform, the 1:20 scale FD1 prototype, and will be operated during the year 2024. The assessed value of the PDE is a key parameter both in the NP04 and in the DUNE analysis and reconstruction studies. [ABSTRACT FROM AUTHOR]

The Module-0 Demonstrator is a single-phase 600 kg liquid argon time projection chamber operated as a prototype for the DUNE liquid argon near detector. Based on the ArgonCube design concept, Module-0 features a novel 80k-channel pixelated charge readout and advanced high-coverage photon detection system. In this paper, we present an analysis of an eight-day data set consisting of 25 million cosmic ray events collected in the spring of 2021. We use this sample to demonstrate the imaging performance of the charge and light readout systems as well as the signal correlations between the two. We also report argon purity and detector uniformity measurements and provide comparisons to detector simulations. [ABSTRACT FROM AUTHOR]

Introduction: The aim of our study was to treat 2 similar groups of patients suffering from benign prostatic hyperplasia (BPH): one group with a complex of phytochemicals based on phycocyanin, Palmitoylethanolamide (PEA) and selenium; the other group with dutasteride. The effectiveness of these treatments was checked, especially regarding the improvement of lower urinary tract symptoms (LUTS) and the reduction of prostatic specific antigen (PSA) and prostate volume. Materials and methods: We included 104 patients in the study. All patients were aged between 50 and 70 years, with PSA values between 4 and 10 ng/ml, prostate volume, as calculated by transrectal ultrasound between 50 and 70 cc, maximum flow value greater than or equal to 10 ml/s at flowmetry, no suspicious nodules on difital rectal examination (DRE), no suspicious lesions on magnetic resonance imaging MRI (PI-RADS 1-2), negative previous prostatic biopsies or never biopsied, moreover absence of diabetes mellitus or chronic renal failure (blood creatinine > 2 mg/dl). We considered: Group A of 54 men who used the complex of phytochemicals; Group B of 50 patients treated with dutasteride. We followed all the patients for 6 months after starting therapy, considering the following parameters: PSA, prostate volume, and flowmetry. Results: Our results showed that both dutasteride and the phytochemicals complex decreased PSA levels (p < 0.0001 for both), with a more significant effect of dutasteride (mean decrease of -2.743 ng/ml vs -0.971 ng/ml). Uroflowmetry also improved in both groups ( p < 0.0001) with a mean increase in maximum flow of urine of + 3.03 ml/min for the dutasteride group and + 13.02 ml/min for phytochemicals complex group. Lastly, dutasteride proved to be highly effective on reducing the prostate volume on transrectal ultrasound (TRUS) (-22.14 ml, p < 0.0001) compared to the complex of phytochemicals, which showed a mean decrease of -10.04 ml (p < 0.0001). Moreover, the reduction in prostate volume obtained through the use of dutasteride proved to be more consistent than the one obtained by using the complex of phytochemicals even at statistical analysis (p < 0.0001). Conclusions: Both the complex of phytochemicals and dutasteride showed reduction of PSA values after 6 months of treatment. The complex based on phycocyanin, PEA and selenium showed a statistically significant improvement in urinary flow, while dutasteride acted more on the volume of the prostate. However, the natural complex is a product with good efficacy on the phlogistic component and does not have the side effects of dutasteride (eg gynecomastia, reduced libido). Therefore, we believe it can be used by a large part of the population with BPH, in order to reduce LUTS and PSA and improve urinary flow, without side effects. [ABSTRACT FROM AUTHOR]

The liver, a pivotal organ in human metabolism, serves as a primary site for heme biosynthesis, alongside bone marrow. Maintaining precise control over heme production is paramount in healthy livers to meet high metabolic demands while averting potential toxicity from intermediate metabolites, notably protoporphyrin IX. Intriguingly, our recent research uncovers a disrupted heme biosynthesis process termed 'porphyrin overdrive' in cancers that fosters the accumulation of heme intermediates, potentially bolstering tumor survival. Here, we investigate heme and porphyrin metabolism in both healthy and oncogenic human livers, utilizing primary human liver transcriptomics and single-cell RNA sequencing (scRNAseq). Our investigations unveil robust gene expression patterns in heme biosynthesis in healthy livers, supporting electron transport chain (ETC) and cytochrome P450 function without intermediate accumulation. Conversely, liver cancers exhibit rewired heme biosynthesis and a massive downregulation of cytochrome P450 gene expression. Notably, despite diminished drug metabolism, gene expression analysis shows that heme supply to the ETC remains largely unaltered or even elevated with patient cancer progression, suggesting a metabolic priority shift. Liver cancers selectively accumulate intermediates, which are absent in normal tissues, implicating their role in disease advancement as inferred by expression analysis. Furthermore, our findings in genomics establish a link between the aberrant gene expression of porphyrin metabolism and inferior overall survival in aggressive cancers, indicating potential targets for clinical therapy development. We provide in vitro proof-of-concept data on targeting porphyrin overdrive with a drug synergy strategy. [ABSTRACT FROM AUTHOR]

The electrostatic attraction between charges of opposite signs and the repulsion between charges of the same sign are ubiquitous and influential phenomena in recognition and self-assembly processes. However, it has been recently revealed that specific attractive forces between ions with the same sign are relatively common. These forces can be strong enough to overcome the Coulomb repulsion between ions with the same sign, leading to the formation of stable anion⋯anion and cation⋯cation adducts. Hydroden bonds (HBs) are probably the best-known interaction that can effectively direct these counterintuitive assembly processes. In this review we discuss how σ-hole and π-hole bonds can break the paradigm of electrostatic repulsion between like-charges and effectively drive the self-assembly of anions into discrete as well as one-, two-, or three-dimensional adducts. σ-Hole and π-hole bonds are the attractive forces between regions of excess electron density in molecular entities (e.g., lone pairs or π bond orbitals) and regions of depleted electron density that are localized at the outer surface of bonded atoms opposite to the σ covalent bonds formed by atoms (σ-holes) and above and below the planar portions of molecular entities (π-holes). σ- and π-holes can be present on many different elements of the p and d block of the periodic table and the self-assembly processes driven by their presence can thus involve a wide diversity of mono- and di-anions. The formed homomeric and heteromeric adducts are typically stable in the solid phase and in polar solvents but metastable or unstable in the gas phase. The pivotal role of σ- and π-hole bonds in controlling anion⋯anion self-assembly is described in key biopharmacological systems and in molecular materials endowed with useful functional properties. [ABSTRACT FROM AUTHOR]

Background: There is no appropriate tool to predict recombinant human growth hormone (rhGH) response before therapy initiation in short-stature children in late puberty. The current study aimed to explore the associations between magnetic resonance imaging (MRI) stages of the knee growth plates and rhGH response in short-stature children in late puberty. Methods: In this prospective cohort study, short-stature children in late puberty were treated with rhGH and followed up for 6 months. We proposed a novel knee MRI staging system according to the growth plate states of distal femurs or proximal tibias and divided the participants into three groups: unclosed growth plate group, marginally closed growth plate group, and nearly closed growth plate group. The primary outcomes were height gain and growth velocity (GV), which were assessed three months later. Results: Fifty participants were enrolled, including 23 boys and 27 girls. GV and height gain after 6 months of rhGH therapy decreased successively in the three groups with an increased degree of growth plate fusion, especially when grouped by proximal tibias (GV1-3 mon from 9.38 to 6.08 to 4.56 cm/year, GV4-6 mon from 6.75 to 4.92 to 3.25 cm/year, and height gain from 4.03 to 2.75 to 1.95 cm, all P < 0.001). Moreover, the MRI stages of growth plates independently served as a significant variable for GV and height gain after therapy, especially when grouped by proximal tibias (all P < 0.01). Conclusion: The MRI staging method is expected to be an effective tool for predicting rhGH response before therapy initiation in short-stature children in late puberty. [ABSTRACT FROM AUTHOR]

Ovarian transposition (OT) has been proposed as a protective measure against radiation-induced damage to ovarian function and fertility. Despite its historical use, limited research has focused on evaluating endocrine and exocrine ovarian function after OT performed in adolescents and young adults (AYAs) before or during puberty. The purpose of our study was to investigate the fertility, pubertal development, and ovarian function of women with a previous history of OT during childhood, adolescence or young adulthood. In an observational bicentric retrospective study, we included 32 young female cancer patients who underwent OT before the age of 26 between 1990 and 2015 at Lyon Léon Bérard Cancer Center or Nancy University Hospital. The mean age at the time of OT was 15.6 years with a cancer diagnosis at 15 ± 4.8 years. Among the 10 women attempting pregnancy post-treatment, 60% achieved successful pregnancies. After a mean follow-up of 9.6 ± 7 years, 74% (17 out of 23) of women recovered spontaneous menstrual cycles (seven out of eight evaluable women with OT before or during puberty). Notably, 35% of women who did not attempt pregnancy demonstrated adequate ovarian reserve. Ovarian reserve and function recovery were influenced by the specific chemotherapy received. Importantly, our findings suggest that OT's effectiveness on ovarian activity resumption does not significantly differ when performed before or during puberty compared to pubertal stages. This study contributes valuable insights into the long-term reproductive outcomes of young women undergoing OT, emphasizing its potential efficacy in preserving ovarian function and fertility across different developmental stages. [ABSTRACT FROM AUTHOR]

Supramolecular polymers are able to change their structure, morphology and function in response to external stimuli. However, controlling the independence of stimuli-responses in these systems is challenging. Herein, we exploit halogen bonding (XB) as a reversible network element to regulate the photoresponsive and adaptive behavior of supramolecular polymers. To this end, we have designed a two-component system comprising an amphiphilic XB acceptor with the ability to self-assemble in aqueous media (OPE-Py) and a molecule with a dual photoresponsive and XB donor function [(E)-Azo-I]. OPE-Py self-assembles in aqueous media into supramolecular polymers, which transform into nanoparticle assemblies upon co-assembly with (E)-Azo-I. Interestingly, a third type of assembly (2D sheets) is obtained if OPE-Py is treated with (E)-Azo-I and exposed to photoirradiation. At ambient conditions, both nanoparticles and 2D sheets remain invariant over time. However, heating dissociates the XB interactions present in both assemblies, resulting in their transformation to the original fiber-like morphology of OPE-Py. Thus, breaking the communication between self-assembly and the stimuli-responses upon heating restores the original state of the system, drawing parallels to feedback loops in programming language. This work broadens the still limited scope of XB in solution assemblies and paves the way for multifunctional adaptive supramolecular systems., (© 2024 Wiley-VCH GmbH.)

The -N + (CH 3 ) 3 residue is present in acetylcholine (ACh) and in many of its analogues which are used as selective ACh agonist or antagonists for human therapy. The X-ray structures of four ACh derivatives show the presence of short and linear contacts between the C atoms of -N + (CH 3 ) 3 groups and lone pair possessing atoms. These contacts can be rationalized as tetrel bonds (TtBs) thanks to their geometric features. Interrogation of the Protein Data Bank suggests that similar -N + -C⋅⋅⋅nucleophile contacts affect the details of the binding of ACh and its derivatives to proteins. Quantum theory of atoms in molecules, noncovalent interaction plot, and natural bond orbital analyses consistently confirm that the -N + -C⋅⋅⋅nucleophile contacts observed in small molecule crystals and in substrate/protein complexes are attractive in nature and can be rationalized as TtBs. TtBs involving methyl groups of the -N + (CH 3 ) 3 moiety can be proposed as a new item in the palette of interactions allowing the compounds containing this pharmacophoric unit to bind to their target protein and/or to express their biological/pharmacological properties., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

The solid-state synthesis and fast crystallization under kinetic control of poly-[n]-catenanes self-assembled of mechanically interlocked metal organic cages (MOCs) is virtually unexplored. This is in part, due to the lack of suitable crystals for single crystal X-ray diffraction (SC-XRD) analysis which limits their progress as advanced functional materials. Here we report the unprecedented inclusion of paracetamol in the cavities of amorphous materials constituted of M 12 L 8 , interlocked MOCs synthesized by mechanochemistry under kinetic control. Full structure determination of a low-crystallinity and low-resolution powders of the M 12 L 8 poly-[n]-catenane including paracetamol has been carried out combining XRD data and Density Functional Theory (DFT) calculations using a multi-step approach. Each M 12 L 8 cage contains six paracetamol guests which is confirmed by thermal analysis and NMR spectroscopy. The paracetamol loading has been also carried out by the instant synthesis method using a saturated paracetamol solution in which TPB and ZnI 2 self-assemble immediately (i. e., 1-5 seconds) encapsulating ~7 paracetamol molecules in the M 12 L 8 nanocages under kinetic control also giving a good selectivity. Benzaldehyde has been included in the M 12 L 8 cages using amorphous M 12 L 8 polycatenanes showing that the icosahedral cages can serve as potential nanoreactors for instance to study Henry reactions in the solid-state., (© 2024 Wiley-VCH GmbH.)

Despite significant advancements in understanding the causes and progression of tumors, cancer remains one of the leading causes of death worldwide. In light of advances in cancer therapy, there has been a growing interest in drug repurposing, which involves exploring new uses for medications that are already approved for clinical use. One such medication is edaravone, which is currently used to manage patients with cerebral infarction and amyotrophic lateral sclerosis. Due to its antioxidant and anti-inflammatory properties, edaravone has also been investigated for its potential activities in treating cancer, notably as an anti-proliferative and cytoprotective drug against side effects induced by traditional cancer therapies. This comprehensive review aims to provide updates on the various applications of edaravone in cancer therapy. It explores its potential as a standalone antitumor drug, either used alone or in combination with other medications, as well as its role as an adjuvant to mitigate the side effects of conventional anticancer treatments. [ABSTRACT FROM AUTHOR]

Cervical cancer is frequently diagnosed in women during their reproductive years, and fertility preservation is an essential part of their cancer treatment. In highly selected patients with early stage, low-risk cervical cancer and a tumor size ≤ 2 cm, several treatment strategies can be offered for patients wishing to preserve fertility, including radical/simple trachelectomy or conization with pelvic lymph node assessment. Trachelectomy can be performed through a vaginal, abdominal, or minimally invasive approach and has been shown to have an equivalent oncologic outcome compared to radical hysterectomy. All surgical approaches for radical trachelectomy seem to have excellent survival with comparable oncologic outcomes. Nevertheless, patients undergoing vaginal trachelectomy have better obstetric outcomes compared to the other routes. In patients with larger tumors (2–4 cm), neoadjuvant chemotherapy followed by fertility-sparing surgery is an alternative option. Several chemotherapy regimens have been used for this indication, with a pathologic complete response rate of 17–73%. For locally advanced diseases that require radical hysterectomy or primary chemoradiation, fertility preservation can be performed using oocyte, embryo, or ovarian tissue cryopreservation, as well as ovarian transposition. For these patients, future pregnancy is possible through surrogacy. In addition to fertility preservation, ovarian transposition, where the ovaries are repositioned outside of the radiation field, is performed to maintain ovarian hormonal function and prevent premature ovarian failure. In summary, fertility-preservation treatment strategies for patients with early stage cervical cancer are continuously evolving, and less radical surgeries are becoming more acceptable. Additional and ongoing evidence is helping determine the impact of conservative procedures on oncologic and obstetric outcomes in these patients. [ABSTRACT FROM AUTHOR]