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Glioblastoma (GB) is one of the most aggressive and difficult-to-treat brain tumors, with a poor prognosis and limited treatment options. In recent years, sonodynamic therapy (SDT) and magnetic resonance focused ultrasound (MRgFUS) have emerged as promising approaches for the treatment of GB. SDT uses ultrasound waves in combination with a sonosensitizer to selectively damage cancer cells, while MRgFUS delivers high-intensity ultrasound waves to precisely target tumor tissue and disrupt the blood-brain barrier to enhance drug delivery. In this review, we explore the potential of SDT as a novel therapeutic strategy for GBM. We discuss the principles of SDT, its mechanisms of action, and the preclinical and clinical studies that have investigated its use in Gliomas. We also highlight the challenges, the limitations, and the future perspectives of SDT. Overall, SDT and MRgFUS hold promise as novel and potentially complementary treatment modalities for GB. Further research is needed to optimize their parameters and determine their safety and efficacy in humans, but their potential for selective and targeted tumor destruction makes them an exciting area of investigation in the field of brain cancer therapy.

Objective: to compare outcomes of cataract surgery combined with either anti-Vascular Endothelial Growth Factor (anti-VEGF) therapy or dexamethasone implant (DEX) in patients with diabetic macular oedema (DMO). Methods: Pubmed and Embase databases were searched for studies reporting outcomes of diabetic cataract surgery combined with either anti-VEGF or DEX, with a follow-up ≥3 months. The primary outcome was the mean change in central macular thickness (CMT). Mean change in best corrected visual acuity (BCVA) was considered as a secondary outcome. The mean difference between baseline and post-treatment values (MD) with 95%-Confidence Interval (95%CI) was calculated and meta-analyses were performed. Results: ninteen studies were included, 8 in the DEX group and 11 in the anti-VEGF group. A significant reduction of macular thickness was shown in the DEX group at 3 months (MD = −98.35 µm; 95% CI, −147.15/−49.54), while mean CMT change was non-significant in the anti-VEGF group (MD = −21.61 µm; 95% CI, −59.46/16.24; test of group differences, P < 0.001). At 3 months, no difference in visual gain was found between the two groups (P = 0.13). Conclusions: in DMO patients, cataract surgery combined with DEX seems to provide better anatomical outcomes compared with cataract surgery combined with anti-VEGF therapy. However, our evidence was limited by significant heterogeneity. Randomised trials comparing these two different combined approaches are warranted.

The HOLMES experiment aims to directly measure the ν mass studying the 163Ho electron capture decay spectrum developing arrays of TES-based microcalorimeters implanted with O(300 Bq/detector) Ho atoms. The embedding of the source inside detectors is a crucial step of the experiment. Because the 163Ho production process (neutron irradiation of a 162Er sample) is not perfectly free from impurities, Ho source must be separated from a lot of contaminants. A chemical processing removes every species other than Ho, but it is not sufficient to remove all isotope-related background sources: Indeed, 166mHo beta decay can produce fake signal in the region of interest. For this reason, a dedicated implantation system was set up. It is designed to achieve the separation power better than 5σ at 163/166 a.m.u. allowing an efficient Ho ions implantation inside microcalorimeter absorbers. Its main components are a 50 kV sputter-based ion source, a magnetic dipole and a target chamber. A specially designed co-evaporation system was designed to “grow” the gold microcalorimeter absorber during the implantation process, increasing the maximum achievable activity which can be implanted. The machine performances were evaluated by means of calibration runs using 63Cu/65Cu and Mo beams. A special care was given to the study of the more effective way to populate source plasma with Ho ions obtained from different Ho compounds by sputtering process. In this work, the machine development and commissioning are described.

In this article we discuss some applications of the construction of the Apéry set of a good semigroup in $\mathbb{N}^d$ given in the previous paper [Partition of the complement of good semigroup ideals and Apéry sets, Communications in Algebra, 49, No. 10, 4136-4158 (2021))]. In particular we study: the duality of a symmetric and almost symmetric good semigroup, the Apéry set of non-local good semigroups and the Apéry set of value semigroups of plane curves., 31 pages, 7 figures

Carnosol is a natural compound with antioxidant properties. Based on this evidence, in the present study we investigated whether this compound can protect retinal vascular endothelium from hyperglycemic insult responsible for diabetic retinopathy development. We performed

The need for axillary dissection (AD) is declining, but it is still essential for many patients with nodal involvement who risk developing breast-cancer-related lymphedema (BCRL) with lifelong consequences. Previous nonrandomized studies found axillary reverse mapping and selective axillary dissection (ARM-SAD) a safe and feasible way to preserve the arm's lymphatic drainage.The present two-arm prospective randomized clinical trial was held at a single comprehensive cancer center to ascertain whether ARM-SAD can reduce the risk of BCRL, compared with standard AD, in patients with node-positive breast cancer. Whatever the type of breast surgery or adjuvant treatments planned, 130 patients with nodal involvement met our inclusion criteria: 65 were randomized for AD and 65 for ARM-SAD. Twelve months after surgery, a physiatrist assessed patients for BCRL and calculated the excess volume of the operated arm. Lymphoscintigraphy was used to assess drainage impairment. Self-reports of any impairment were also recorded.The difference in the incidence of BCRL between the two groups was 21% (95% CI, 3-37; p = .03). A significantly lower rate of BCRL after ARM-SAD was confirmed by a multimodal analysis that included the physiatrist's findings, excess arm volume, and lymphoscintigraphic findings, but this was not matched by a significant difference in patients' self-reports.Our findings encourage a change of surgical approach when AD is still warranted. ARM-SAD may be an alternative to standard AD to reduce the treatment-related morbidity.

The development of novel chemical approaches for the fabrication of gold nanostructures with localized surface plasmon resonance (LSPR) falling in the near-infrared (NIR) region is one challenging topic in nanomaterials science. Due to their optical and photothermal properties triggered by light excitation in the therapeutic window (λmax = 650-1300 nm), gold-based nanostructures are appealing candidates in anticancer nanomedicine. Here, we report a novel method to prepare water-dispersible gold nanostructures with NIR-LSPR (λmax = 600-1000 nm) properties. The gold nanostructures were achieved in a single step by an unconventional method using NADH as a reducing agent and an amphiphilic choline-calix[4]arene derivative (CholCalix) forming micelles as a template. The CholCalix-Au nanostructures were characterized by UV-visible spectrophotometry, Raman spectroscopy, and atomic force microscopy. Agglomeration of the nanostructures due to multiple crosslinking interactions was observed and supported by modeling simulation. Effective anticancer photothermal-induced effect of the CholCalix-AuNPs was demonstrated on human breast cancer cells irradiated with biofriendly light at 808 nm.

This paper presents a systematic review of factors that correlate with attitudes toward bisexuals, and a meta-analysis to estimate the effect size of these relationships. A search strategy was designed to identify studies that had a measure of attitudes toward bisexuals and assessed the relationship between these attitudes and at least one attitude-relevant correlate. The strategy was then applied to PsycINFO, PsycEXTRA, Proquest Psychology Collection, EBSCO Psychology and Behavioral Sciences Collection and SociINDEX databases, and calls for unpublished data were circulated through relevant professional bodies. Effect size data were extracted from the articles, and meta-analyses were conducted on each of the applicable correlates. The meta-analyses revealed that age, contact (quality and quantity), income, political orientation, religion, sexual orientation, education, ethnicity, gender, and population density were related to negative attitudes toward bisexual individuals (Fisher’s Zs = 0.108, −0.418, −0.209, 0.221, 0.231, 0.346, & 0.831, and Hedges’ g’s = 0.365, 0.344, 0.278, & 0.193, respectively). In addition, a sub-group moderation analysis revealed these effect sizes for participant gender differed as a function of target gender (i.e., bisexual men vs. bisexual women).

Magnetic resonance imaging is considered the most accurate examination to study the spinal cord. Nevertheless, the use of diffusion tensor imaging (DTI) can demonstrate additional key details about spinal cord lesions. We examined the literature to investigate and discuss the role, limitations, and possible evolution as a prognostic tool of DTI in spinal cord injury (SCI). For this systematic literature review, a detailed search was performed using PubMed (2005-2021), Cochrane Database of Systematic Reviews (2016-2021), and Cochrane Central Register of Controlled Trials (2016-2021). To be included, studies had to report the use of DTI in SCIs, its clinical relevance, and its use as a prognostic tool. We identified 17 studies comprising 299 patients. The mean age of patients was 41.22 ± 10.62 years. There was a prevalence of males (70.9%) compared with females (29.1%). The main spinal cord tract involved and studied in SCIs was the cervical tract (57.5%), followed by conus terminalis (15.4%) and dorsal tract (13.7%). In all studies based on American Spine Injury Association impairment scale score for neurological assessment, a correlation was found between FA values and American Spine Injury Association impairment scale: patients with complete SCI had a statistically significative lower FA value at the injured site compared with patients with incomplete SCI. Published clinical studies showed promising results for the utility of DTI parameters as noninvasive biomarkers in SCI grade evaluation, remaining an evolving area of further investigation.

The ischemia/reperfusion mechanism is believed to be responsible for parenchymal damage caused by temporary hypoperfusion and worsened by the subsequent attempt of reperfusion. This represents a true challenge for physicians of several fields, including neurosurgeons. A limited number of papers have shed the light on a rare pathologic condition that affects patients experiencing an unexplained neurologic deficit after spine surgery, the so-called "white cord syndrome." This entity is believed to be caused by an "ischemia/reperfusion" injury on the spinal cord, documented by a postoperative intramedullary hyperintensity on T2-weighted magnetic resonance imaging sequences. To date, the cases of white cord syndrome reported in literature mostly refer to cervical spine surgery. However, the analysis of several reviews focusing on spine surgery outcome suggests postoperative neurologic deficits of new onset could be charged to a mechanism of ischemia/reperfusion, even if the physiopathology of this event is seldom explored or at least discussed. The same neuroradiologic finding can suggest mechanical damage due to inappropriate surgical manipulation. On this purpose, we performed a systematic review of the literature with the aim to identify and analyze all the factors potentially contributing to ischemic/reperfusion damage of the spinal cord that may potentially complicate any spinal surgery, without distinction between cervical or thoracic segments. Finally, we believe that postoperative neurologic deficit after spinal surgery constituting the "white cord syndrome" could be under-reported; both neurosurgeons and patients should be fully aware of this rare but potentially devasting complication burdening cervical and thoracic spine surgery.

The author makes brief Considerations on the Treatment of the Theme of the Relationship Between New Technologies and Private Law. In particular, she believes that the criticism of Lessig’s statement according to which “the values of real-space sovereigns will at first lose out” is correct, adding, however, that one must monitor the evolution of new technologies. We are, in fact, at the crossroads of a technological revolution which, as jurists, we are not able to fully understand. The author also questions the position taken in the volume on the US neoliberal approach v. European solidarity approach, inviting the authors to question the difference between the narrative that sees the European system as all about ensuring solidarity and the reality about the economic thinking that informs the different disciplines. Finally, she takes a position on the relationship between ordoliberalism and consumer protection.

The accurate monitoring of phenylalanine concentration plays a prominent role in the treatment of phenylketonuria (PKU). In this study, we present an enzymatic assay based on Phenylalanine Dehydrogenase/NAD+ and tris (bipyridine) Ruthenium (II/III) as a colorimetric mediator for the detection of Phenylalanine concentration. The amount of amino acid was quantitatively recognized by optical absorption measurements at 452 nm through the conversion of Ru (byp)33+ to Ru (byp)32+, which is induced by the neoformed NADH. A detection limit of 0.33 µM, a limit of quantification of 1.01 µM, and a sensitivity of 36.6 a.u nM−1 were obtained. The proposed method was successfully tested using biological specimens from patients affected by hyperphenylalaninemia. The proposed enzymatic assay showed a high selectivity, making it a promising alternative for the development of versatile assays for the detection of phenylalanine in diluted serums.

Mutations in the KEAP1-NRF2 pathway are common in NSCLC, albeit with a prevalence of KEAP1 mutations in lung adenocarcinoma and an equal representation of KEAP1 and NFE2L2 (the gene encoding for NRF2) alterations in lung squamous cell carcinoma. The KEAP1-NRF2 axis is a crucial modulator of cellular homeostasis, enabling cells to tolerate oxidative and metabolic stresses, and xenobiotics. The complex cytoprotective response orchestrated by NRF2-mediated gene transcription embraces detoxification mechanisms, ferroptosis protection, and metabolic reprogramming. Given that the KEAP1-NRF2 pathway controls core cellular functions, it is not surprising that a number of clinical studies connected KEAP1 mutations to increased resistance to chemotherapy, radiotherapy, and targeted agents. More recently, an immune-cold tumor microenvironment was described as a typical feature of KEAP1-mutant lung adenocarcinoma. Consistently, a reduced efficacy of immunotherapy was reported in the KEAP1-mutant background. Nevertheless, the connection between KEAP1 and immune resistance seems more complex and dependent on coexisting genomic alterations. Given the clinical implications of deregulated KEAP1-NRF2 pathway in lung cancer, the development of pathway-directed anticancer treatments should be considered a priority in the domain of thoracic oncology.

Nanotechnology has gained momentum in recent years in the field of drug delivery, including nanomedicine and nano-delivery systems. Several applications such as biological agents, chemotherapeutic agents and immunotherapeutic agents are used for the treatment of a number of diseases. This review compiles an updated summary on recent developments in this emerging field of nanomedicines and nanotechnology-based drug delivery systems. The study of nanostructured drug delivery systems helps to understand the efficient transport and controlled release of drugs to the diseased tissues of living organisms. This has stimulated the authors to highlight recent advances in smart nanocarriers composed of biopolymeric nanoparticles such as liposomes, dendrimers, and hydrogels. This review also highlights some critical issues in the design of nanocarrier systems for biomedical applications.

In this paper, we study the competition of healthcare institutions for medical supplies in emergencies caused by natural disasters. In particular, we develop a two-stage procurement planning model in a random environment. We consider a pre-event policy, in which each healthcare institution seeks to minimize the purchasing cost of medical items and the transportation time from the first stage, and a recourse decision process to optimize the expected overall costs and the penalty for the prior plan, in response to each disaster scenario. Thus, each institution deals with a two-stage stochastic programming model that takes into account the unmet demand at the first stage, and the consequent penalty. Then, the institutions simultaneously solve their own stochastic optimization problems and reach a stable state governed by the stochastic Nash equilibrium concept. Moreover, we formulate the problem as a variational inequality; both the discrete and the general probability distribution cases are described. We also present an alternative formulation using infinite-dimensional duality tools. Finally, we discuss some numerical illustrations applying the progressive hedging algorithm.

BackgroundMusculocontractural Ehlers−Danlos syndrome is caused by biallelic loss-of-function variants in CHST14 (mcEDS-CHST14) or DSE (mcEDS-DSE). Although 48 patients in 33 families with mcEDS-CHST14 have been reported, the spectrum of pathogenic variants, accurate prevalence of various manifestations and detailed natural history have not been systematically investigated.MethodsWe collected detailed and comprehensive clinical and molecular information regarding previously reported and newly identified patients with mcEDS-CHST14 through international collaborations.ResultsSixty-six patients in 48 families (33 males/females; 0–59 years), including 18 newly reported patients, were evaluated. Japanese was the predominant ethnicity (27 families), associated with three recurrent variants. No apparent genotype–phenotype correlation was noted. Specific craniofacial (large fontanelle with delayed closure, downslanting palpebral fissures and hypertelorism), skeletal (characteristic finger morphologies, joint hypermobility, multiple congenital contractures, progressive talipes deformities and recurrent joint dislocation), cutaneous (hyperextensibility, fine/acrogeria-like/wrinkling palmar creases and bruisability) and ocular (refractive errors) features were observed in most patients (>90%). Large subcutaneous haematomas, constipation, cryptorchidism, hypotonia and motor developmental delay were also common (>80%). Median ages at the initial episode of dislocation or large subcutaneous haematoma were both 6 years. Nine patients died; their median age was 12 years. Several features, including joint and skin characteristics (hypermobility/extensibility and fragility), were significantly more frequent in patients with mcEDS-CHST14 than in eight reported patients with mcEDS-DSE.ConclusionThis first international collaborative study of mcEDS-CHST14 demonstrated that the subtype represents a multisystem disorder with unique set of clinical phenotypes consisting of multiple malformations and progressive fragility-related manifestations; these require lifelong, multidisciplinary healthcare approaches.

Supplementary Data 5 from Specific Alterations of MicroRNA Transcriptome and Global Network Structure in Colorectal Carcinoma after Cetuximab Treatment

Supplementary Data 3 from Specific Alterations of MicroRNA Transcriptome and Global Network Structure in Colorectal Carcinoma after Cetuximab Treatment

Supplementary Data 6 from Specific Alterations of MicroRNA Transcriptome and Global Network Structure in Colorectal Carcinoma after Cetuximab Treatment

Supplementary Data 2 from Specific Alterations of MicroRNA Transcriptome and Global Network Structure in Colorectal Carcinoma after Cetuximab Treatment

Supplementary Data Legends from Specific Alterations of MicroRNA Transcriptome and Global Network Structure in Colorectal Carcinoma after Cetuximab Treatment

Supplementary Data 7 from Specific Alterations of MicroRNA Transcriptome and Global Network Structure in Colorectal Carcinoma after Cetuximab Treatment

Supplementary Data 4 from Specific Alterations of MicroRNA Transcriptome and Global Network Structure in Colorectal Carcinoma after Cetuximab Treatment

The relationship between therapeutic response and modifications of microRNA (miRNA) transcriptome in colorectal cancer (CRC) remains unknown. We investigated this issue by profiling the expression of 667 miRNAs in 2 human CRC cell lines, one sensitive and the other resistant to cetuximab (Caco-2 and HCT-116, respectively), through TaqMan real-time PCR. Caco-2 and HCT-116 expressed different sets of miRNAs after treatment. Specifically, 21 and 22 miRNAs were differentially expressed in Caco-2 or HCT-116, respectively (t test, P < 0.01). By testing the expression of differentially expressed miRNAs in CRC patients, we found that miR-146b-3p and miR-486-5p are more abundant in K-ras–mutated samples with respect to wild-type ones (Wilcoxon test, P < 0.05). Sixty-seven percent of differentially expressed miRNAs were involved in cancer, including CRC, whereas 19 miRNA targets had been previously reported to be involved in the cetuximab pathway and CRC. We identified 25 transcription factors putatively controlling these miRNAs, 11 of which have been already reported to be involved in CRC. On the basis of these data, we suggest that the downregulation of let-7b and let-7e (targeting K-ras) and the upregulation of miR-17* (a CRC marker) could be considered as candidate molecular markers of cetuximab resistance. Global network functional analysis (based on miRNA targets) showed a significant overrepresentation of cancer-related biological processes and networks centered on critical nodes involved in epidermal growth factor receptor internalization and ubiquitin-mediated degradation. The identification of miRNAs, whose expression is linked to the efficacy of therapy, should allow the ability to predict the response of patients to treatment and possibly lead to a better understanding of the molecular mechanisms of drug response. Mol Cancer Ther; 9(12); 3396–409. © 2010 AACR.

Supplementary Data 1 from Specific Alterations of MicroRNA Transcriptome and Global Network Structure in Colorectal Carcinoma after Cetuximab Treatment

Lipid nanoparticles (LNPs) are currently used to transport functional mRNAs, such as COVID-19 mRNA vaccines. The delivery of angiogenic molecules, such as therapeutic VEGF-A mRNA, to ischemic tissues for producing new blood vessels is an emerging strategy for the treatment of cardiovascular diseases. Here, the authors deliver VEGF-A mRNA via LNPs and study stoichiometric quantification of their uptake kinetics and how the transport of exogenous LNP-mRNAs between cells is functionally extended by cells’ own vehicles called extracellular vesicles (EVs). The results show that cellular uptake of LNPs and their mRNA molecules occurs quickly, and that the translation of exogenously delivered mRNA begins immediately. Following the VEGF-A mRNA delivery to cells via LNPs, a fraction of internalized VEGF-A mRNA is secreted via EVs. The overexpressed VEGF-A mRNA is detected in EVs secreted from three different cell types. Additionally, RNA-Seq analysis reveals that as cells’ response to LNP-VEGF-A mRNA treatment, several overexpressed proangiogenic transcripts are packaged into EVs. EVs are further deployed to deliver VEGF-A mRNA in vitro and in vivo. Upon equal amount of VEGF-A mRNA delivery via three EV types or LNPs in vitro, EVs from cardiac progenitor cells are the most efficient in promoting angiogenesis per amount of VEGF-A protein produced. Intravenous administration of luciferase mRNA shows that EVs could distribute translatable mRNA to different organs with the highest amounts of luciferase detected in the liver. Direct injections of VEGF-A mRNA (via EVs or LNPs) into mice heart result in locally produced VEGF-A protein without spillover to liver and circulation. In addition, EVs from cardiac progenitor cells cause minimal production of inflammatory cytokines in cardiac tissue compared with all other treatment types. Collectively, the data demonstrate that LNPs transform EVs as functional extensions to distribute therapeutic mRNA between cells, where EVs deliver this mRNA differently than LNPs. CC BY 4.0© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.E-mail: hadi.valadi@gu.seThe authors acknowledge the support from the National Genomics Infrastructure in Stockholm funded by Science for Life (SciLife) Laboratory, the Knut and Alice Wallenberg Foundation and the Swedish Research Council, and SNIC/Uppsala Multidisciplinary Center for Advanced Computational Science for assistance with massively parallel sequencing and access to the UPPMAX computational infrastructure. Moreover, the authors acknowledge Mr. Mario Soriano Navarro at the Responsable Servicio Microscopía Electrónica, Valencia Spain, for technical assistance. This work was supported by grants from the Swedish Foundation of Strategic Research (Stiftelsen för strategisk forskning: SSF) in the Industrial Research Centre, FoRmulaEx - Nucleotide Functional Drug Delivery (Grant ID: IRC15-0065), the Swedish research council (VR, Grant ID: 2020-01316), and the Swedish governmental agency for innovation systems (VINNOVA, Grant ID: 2017-02960). This research was also funded by the Systems Biology Research Centre at the University of Skövde under grants from the Knowledge Foundation (Grant ID: 20160330).

Introduction: To evaluate the pharmacological profile of ocular formulations based on cross-linked sodium hyaluronate (CL-SH), taurine (Tau), vitamin B6 (Vit B6) and vitamin B12 (Vit B12) using in vitro and in vivo paradigms.Methods: Rabbit corneal epithelial cells were used to assess wound healing and reactive oxygen species (ROS) formation by scratch assay and oxidative stress (0.3 mM H2O2; 30 min), respectively with or without ocular formulations exposure. In vivo studies were carried out on albino rabbits to evaluate corneal nerve regeneration and corneal wound healing with or without treatment with six different formulations. Animals were anesthetized, the corneal epithelium was removed, and formulations were topically administered (30 μL/eye; 3 times/day for 6 days). Slit-lamp observation was carried out at different time points. After 6 days the animals were killed, and corneas were collected to evaluate corneal re-innervation by immunohistochemistry of selective neuronal marker β-III tubulin.Results: Formulations containing the concentrations 0.16% or 0.32% of cross-linked sodium hyaluronate, taurine, vitamin B6 and vitamin B12 accelerated corneal wound healing. Cells exposed to H2O2 led to significant (p < 0.05) increase of reactive oxygen species concentration that was significantly (p < 0.05) counteract by formulations containing cross-linked sodium hyaluronate (0.32%) and taurine with or without vitamins. The extent of re-innervation, in terms of β-III tubulin staining, was 5-fold greater (p < 0.01) in the eye of rabbits treated with formulation containing 0.32% cross-linked sodium hyaluronate, taurine, vitamins (RenerviX®) compared with the control group (no treatment). Furthermore, re-innervation elicited by RenerviX® was significantly greater (p < 0.01) compared with the group treated with the formulation containing 0.32% cross-linked sodium hyaluronate and taurine without vitamins, and with the group treated with the formulation containing 0.5% linear sodium hyaluronate (SH), taurine, and vitamin B12, respectively.Discussion: In conclusion, among the formulations tested, the new ophthalmic gel RenerviX® was able to contrast oxidative stress, to accelerate corneal re-epithelization and to promote nerve regeneration.

The Hippo pathway plays a critical role for balancing proliferation and differentiation, thus regulating tissue homeostasis. The pathway acts through a kinase cascade whose final effectors are the Yes-associated protein (YAP) and its paralog transcriptional co‑activator with PDZ‑binding motif (TAZ). In response to a variety of upstream signals, YAP and TAZ activate a transcriptional program that modulates cellular proliferation, tissue repair after injury, stem cell fate decision, and cytoskeletal reorganization. Hippo pathway signaling is often dysregulated in gastric cancer and in Helicobacter pylori-induced infection, suggesting a putative role of its deregulation since the early stages of the disease. In this review, we summarize the architecture and regulation of the Hippo pathway and discuss how its dysregulation fuels the onset and progression of gastric cancer. In this setting, we also focus on the crosstalk between Hippo and other established oncogenic signaling pathways. Lastly, we provide insights into the therapeutic approaches targeting aberrant YAP/TAZ activation and discuss the related clinical perspectives and challenges.

The beta spectrum of the main transition of the beta-decay of 171Tm was measured using a double focalizing spectrometer. The instrument was lately improved in order to reduce its low energy threshold to 34 keV. We used the spectrometer to measure the beta spectrum end-point energy of the main transition of 171Tm decay using the Kurie plot formalism. We report a new value of 97.60(38) keV, which is in agreement with previous measurements. In addition, the spectrum shape was compared with the xi-approximation calculation where the shape factor is equal to 1 and good agreement was found between the theory and the measurement at the 1% level.

Additional file 1: Table S1. Descriptive statistics of antibiotic consumption. Table S2. Spearman correlation coefficients between indicators and antibiotic consumptions. Table S3. AMR proportions for combinations between pathogens and antibiotics. Table S4. Spearman correlation coefficients between indicators and proportion of AMR for each combination between pathogen and antibiotic. Table S5. Spearman correlation coefficients between aggregate indexes and antibiotic consumption. Table S6. Differences in indexes between clusters. Table S7. Differences in antibiotic use between clusters. Figure S1. Demographic index across European countries. Figure S2. Health index across European countries. Figure S3. Economic index across European countries. Figure S4. Governance index across European countries. Figure S5. Freedom and rights index across European countries.

Neutron capture cross-section measurements are fundamental in the study of astrophysical phenomena, such as the slow neutron capture (s-) process of nucleosynthesis operating in red-giant and massive stars. However, neutron capture measurements via the time-of-flight (TOF) technique on key $s$-process nuclei are often challenging. Difficulties arise from the limited mass ($\sim$mg) available and the high sample-related background in the case of the unstable $s$-process branching points. Measurements on neutron magic nuclei, that act as $s$-process bottlenecks, are affected by low (n,$γ$) cross sections and a dominant neutron scattering background. Overcoming these experimental challenges requires the combination of facilities with high instantaneous flux, such as n\_TOF-EAR2, with detection systems with an enhanced detection sensitivity and high counting rate capabilities. This contribution reviews some of the latest detector developments in detection systems for (n,$γ$) measurements at n\_TOF, such as i-TED, an innovative detection system which exploits the Compton imaging technique to reduce the dominant neutron scattering background and s-TED, a highly segmented total energy detector intended for high flux facilities. The discussion will be illustrated with results of the first measurement of key the $s$-process branching-point reaction $^{79}$Se(n,$γ$)., 7 pages, 4 figures (8 panels). Accepted for publication in EPJ-WOC (proceedings of the NPA-X conference). arXiv admin note: text overlap with arXiv:2301.11199