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Management of livestock grazing in highly-productive mountain meadows is an important aspect for the economic viability and the environmental impact of a grassland-based farm. The main aim of this study was to build near infrared models to determine the chemical composition and in vitro organic matter digestibility of Romanian meadow forages. The treatments were organic and mineral fertilizer combinations, and forage samples were obtained from three fertilization experiments conducted in the Apuseni Mountains; these samples were analysed using classical and NIR methods. The samples were scanned in the NIR wavelength band. The CRA-W Gembloux ‘local’ calibration models were validated with Romanian meadow forages and then used in order to predict the forage quality of samples. A second objective of the study was to determine the effects of fertilization on forage quality. The results showed a decrease in crude protein content from the NPK treatment (150:75:75), which can be explained by a reduction of Fabaceae plants with this treatment from 17.25% of the populations in the control (semi-natural meadow not fertilized) to 6.25% in the fertilized plots. The decrease in protein content and in vitro organic matter digestibility was related to a reduced Fabaceae presence. Our recommendation is to use mineral fertilization with NPK doses less than 100:50:50 to improve meadow productivity; meanwhile organic fertilization can also be used to complement and maintain biodiversity and forage quality.

The time of arrival of people in Australia is an unresolved question. It is relevant to debates about when modern humans first dispersed out of Africa and when their descendants incorporated genetic material from Neanderthals, Denisovans and possibly other hominins. Humans have also been implicated in the extinction of Australias megafauna. Here we report the results of new excavations conducted at Madjedbebe, a rock shelter in northern Australia. Artefacts in primary depositional context are concentrated in three dense bands, with the stratigraphic integrity of the deposit demonstrated by artefact refits and by optical dating and other analyses of the sediments. Human occupation began around 65,000 years ago, with a distinctive stone tool assemblage including grinding stones, ground ochres, reflective additives and ground-edge hatchet heads. This evidence sets a new minimum age for the arrival of humans in Australia, the dispersal of modern humans out of Africa, and the subsequent interactions of modern humans with Neanderthals and Denisovans., Author(s): Chris Clarkson (corresponding author) [1]; Zenobia Jacobs (corresponding author) [2, 3]; Ben Marwick [3, 4]; Richard Fullagar [3]; Lynley Wallis [5]; Mike Smith [6]; Richard G. Roberts [2, 3]; [...]

Abstract Acute myeloid leukemia (AML) derives from hematopoietic stem and progenitor cells (HSPCs). To date, no AML‐exclusive, non‐HSPC‐expressed cell‐surface target molecules for AML selective immunotherapy have been identified. Therefore, to still apply surface‐directed immunotherapy in this disease setting, time‐limited combined immune‐targeting of AML cells and healthy HSPCs, followed by hematopoietic stem cell transplantation (HSCT), might be a viable therapeutic approach. To explore this, we generated a recombinant single‐chain variable fragment‐based bispecific T‐cell engaging and activating antibody directed against CD3 on T‐cells and CD117, the surface receptor for stem cell factor, expressed by both AML cells and healthy HSPCs. Bispecific CD117xCD3 targeting induced lysis of CD117‐positive healthy human HSPCs, AML cell lines and patient‐derived AML blasts in the presence of T‐cells at subnanomolar concentrations in vitro. Furthermore, in immunocompromised mice, engrafted with human CD117‐expressing leukemia cells and human T‐cells, the bispecific molecule efficiently prevented leukemia growth in vivo. Additionally, in immunodeficient mice transplanted with healthy human HSPCs, the molecule decreased the number of CD117‐positive cells in vivo. Therefore, bispecific CD117xCD3 targeting might be developed clinically in order to reduce CD117‐expressing leukemia cells and HSPCs prior to HSCT.

Illegal activities and abusive practices can occur in any organisation, public or private, small or large. They can take many forms, such as corruption or fraud, unfair business practices or negligence. If no action is taken, they may cause serious damage to the public interest. A law itself gives the appearance of a safety instrument for situations in which an official public or contract employee intends to refuse the execution of an order that he considers illegal. Although this provision is theoretically included in the legislation, any employee who does not fulfils an order outside of legality was subject to a series of unsustainable behaviors that resulted in removal or withdrawal from the system. At this moment, in the Romanian landscape, we lack a culture of integrity whistleblowers, and those who find the strength to report they are seen rather as an exception and idealised as heroes of the system. Perhaps we could rather say that there is a culture strongly marked by the traumas of the past in terms of reporting. Starting from the culture of the country which, at the moment, discourages integrity whistleblowers, we note that, just as in the European directive that we were obliged to transpose, this proposed law encourages and prioritises internal reporting. We can understand the reasons behind this encouragement, however, in the Romanian context, we believe that the prioritisation of internal reporting can and must be corroborated with subsequent instrumentation actions a anonymous reports. Seen as a measure that comes to consecrate the modernism of the Romanian legal system, but also as a measure of the legislative maturity it has reached after countless reforms, the initiation of investigations regarding integrity whistleblowers has become a reality. What will be the impact on Romanian society? How will they integrate into the judicial system? What will be the value as proof?

Introduction. This study aims to evaluate the impact of stoma formation on the quality of life of patients undergoing colonic surgery, considering both emergency and elective procedures. Several factors (demographic data, Charlson comorbidity score, type of surgical intervention, duration of hospitalization, postoperative outcomes and complications, etc.) were analyzed to understand their influence on patients' well-being. Materials and Methods. A retrospective analysis was performed on patients who underwent colorectal surgery that required stoma formation. A total of 270 patients were included in the study, with 69.25% undergoing emergency surgery and 30.74% undergoing elective procedures. Results. The Charlson comorbidity score was significantly higher in the emergency surgery group compared to the elective group, 8.51 vs 7.67, respectively (p < 0.05). Patients who underwent emergency surgery experienced more postoperative (including stoma-related) complications, leading to a lower quality of life score compared to those undergoing elective procedures. Conclusions. Especially in emergency cases, colostomy involves difficulties related to patient compliance and quality of life, a fact supported by higher scores regarding comorbidities and postoperative complications. Thus, presenting patients at early stages of disease, customized surgical techniques, and appropriate preoperative counseling can help improve both patient outcomes and overall well-being.

Diabetes mellitus is one of the most common comorbidities of patients undergoing surgery. Colorectal surgery is frequently associated with postoperative complications, and diabetic patients represent a population that presents a high risk of developing such complications. Understanding the interrelationships between neoplastic disease and diabetes, as well as the pathophysiological mechanisms underlying postoperative complications, are essential for effective therapeutic management. Genetic predispositions, alterations in the gut microbiota, inflammatory response, ischemic, thrombotic and infectious processes contribute significantly to the development of severe surgical complications, such as anastomotic fistulas. Postoperative ileus, characterized by gastrointestinal dysmotility, is common in diabetic patients due to neuropathic dysfunction and altered intestinal metabolism. In addition, diabetic patients are at increased risk of intestinal ischemia, requiring specific perioperative care. The strategies to avoid these complications assume an adequate surgical technique, a personalized anesthesia management, and last but not least, the best possible glycemic control. This article highlights the importance of a better understanding of the interaction between diabetes and postoperative complications, in order to obtain good results with an important impact on the patient's health and well-being.

Abstract Fermions are subject to the Pauli Exclusion Principle (PEP), which is grounded on the spin-statistics theorem and, hence, related to the very same structure of the underlying symmetries. The VIP-2 (VIolation of Pauli exclusion principle - 2) experiment has been performing extreme sensitivity tests of the PEP, up to its current and final configuration, exploiting several experimental setups designed to study different theoretical models of PEP violation, looking for a faint signal of physics Beyond the Standard Model.A current is introduced in the copper target to bring new electrons into the system and, hence, fulfill the requirements of the Messiah-Greenberg Super-Selection rule. The searched spin-statistics violating signal corresponds to X-rays emitted when the new electrons perform atomic transitions to the already filled fundamental level of copper. This work analyzes the set of the VIP-2 data corresponding to a test run of 68 days in a current modulated regime alternating no current with current data-taking in short periods (50 s each), instead the usual alternating months-long data-taking of each of these two phases. We propose an analysis method to improve the experiment’s sensitivity: a spectral analysis constraint with the Discrete Fourier Transformation of the data. Compared to the spectrum-only analysis, about a factor of 1.5 of improvement to the limit for the probability of PEP violation for electrons was obtained.

Abstract TP53-mutant acute myeloid leukemia (AML) and myelodysplastic neoplasms (MDS) are characterized by chemotherapy resistance and represent an unmet clinical need. Chimeric antigen receptor (CAR) T-cells might be a promising therapeutic option for TP53-mutant AML/MDS. However, the impact of TP53 deficiency in AML cells on the efficacy of CAR T-cells is unknown. We here show that CAR T-cells engaging TP53-deficient leukemia cells exhibit a prolonged interaction time, upregulate exhaustion markers, and are inefficient to control AML cell outgrowth in vitro and in vivo compared to TP53 wild-type cells. Transcriptional profiling revealed that the mevalonate pathway is upregulated in TP53-deficient AML cells under CAR T-cell attack, while CAR T-cells engaging TP53-deficient AML cells downregulate the Wnt pathway. In vitro rational targeting of either of these pathways rescues AML cell sensitivity to CAR T-cell-mediated killing. We thus demonstrate that TP53 deficiency confers resistance to CAR T-cell therapy and identify the mevalonate pathway as a therapeutic vulnerability of TP53-deficient AML cells engaged by CAR T-cells, and the Wnt pathway as a promising CAR T-cell therapy-enhancing approach for TP53-deficient AML/MDS.

The SIDDHARTA-2 collaboration has developed a novel X-ray detection system based on cadmium-zinc-telluride (CZT, CdZnTe), marking the first application of this technology at the DAΦNE electron-positron collider at INFN-LNF. This work aims to demonstrate the stability of the detectors’ performance in terms of linearity and resolution over short and long periods, thereby establishing their suitability for precise spectroscopic measurements within a collider environment. A reference calibration spectrum is presented in association with findings from assessments of linearity and resolution stability. Additionally, this study introduces a validated model of the response function of the detector. The relative deviations from the nominal values for the source transitions, obtained by fitting the entire spectrum with a background function and the previously introduced response function, are reported. Finally, a comparison of the calibration performance with and without beams circulating in the collider’s rings is presented. These promising results pave the way for applying CZT detectors in kaonic atom studies and, more generally, in particle and nuclear physics spectroscopy.

The circular economy with compost fertilization is included in the sustainable orchard paradigm, creating a holistic production ecosystem. Modern orchards are mostly intensive and super-intensive, requiring different rootstocks. This research presents the response to compost fertilization of two specific pear rootstocks (quince ‘CTS 212’ and ‘Farold® 40’) and own-rooted trees, analyzing six resistant cultivars in a circular production system. The dynamic of nitrogen and carbon concentration in leaves, soil respiration coefficient, the evolution of the fruit maturity stage in the field, and some biometric parameters such as trunk cross-section area, the annual vegetative growth, and fruiting shoots annual number were analyzed. The results highlighted that compost fertilization led to increased leaf nitrogen concentration over the first two years while carbon concentration remained relatively stable. Rootstock and compost fertilization influenced the fruit maturity dynamic, but a single pattern was not identified. Quince, as pear rootstock, expressed a higher sensitivity to compost application; the biometric parameters, such as trunk cross-section area, and almost all cultivars’ annual vegetative growth were higher than the controls’. Positive output can lead to future model upscaling in farms and households.

The energy efficiency in metal cutting is, sometimes, very low. Recent studies show that the energy consumed for detaching chips represents only about 15% of the total energy involved in material machining. The available solutions for energy optimization in cutting processes mentioned are the improvement of manufacturing equipment, the optimization of processes, and appropriate production scheduling. Already-performed research shows that to increase energy efficiency, the cutting force must be reduced, for example, by reducing the depth of the cut and by increasing the feed rate. However, this is applicable when the cutting force is quasi-constant during the process, which is not the case for gear teeth cutting when the cutting force significantly varies. The present paper proposes a new solution for energy efficiency increase in gear teeth cutting, namely, the smoothing of the cutting force variation during the machining process, by keeping the area of the detached chip section quasi-constant during the cutting process. This can be reached by replacing the constant rolling feed, currently used in gear teeth cutting, with a rolling feed that varies after an appropriate law. An algorithm dedicated to implementing this solution has been developed. It uses graphical modeling in CATIA to find the variation in the detached chip area. Original MatLab R2018a applications were developed (i) to identify the analytical form of the law that approximates this variation and (ii) to find the variation law of the feed during the rolling motion, if imposing a constant area of the detached chip. The algorithm was successfully applied in the cases of toothing with a rack tool (by slotting) and with a pinion cutter (by slotting and turning). A technical solution for method implementation in practice is also presented.

Background/Objectives: Chronic heart failure (CHF) is characterized by complex pathophysiology, leading to increased hospitalizations and mortality. Inflammatory biomarkers such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) provide valuable diagnostic insights. Methods: This study evaluates the prognostic relationship between NLR, PLR, and, in a specific subcohort, N-terminal pro B-type natriuretic peptide (NT-proBNP), alongside length of stay (LOS) and 90-day readmission rates in CHF patients, irrespective of heart failure phenotype. A retrospective analysis of 427 CHF admissions (males = 57.84%) was conducted. Results: The mean age of the entire population was 68.48 ± 11.53 years. The average LOS was 8.33 ± 5.26 days, with a readmission rate of 73 visits (17.09%) for 56 patients. The NLR (3.79 ± 3.32) showed a low but positive correlation with the LOS (r = 0.222, p < 0.001). Conversely, the PLR (144.84 ± 83.08) did not demonstrate a significant association with the LOS. The NLR presented a low negative correlation for days until the next admission (r = −0.023, p = 0.048). In a prespecified subanalysis of 323 admissions, the NT-proBNP exhibited a low positive Pearson correlation with the NLR (r = 0.241, p < 0.001) and PLR (r = 0.151, p = 0.006). Conclusions: The impact of the NLR across heart failure phenotypes may suggest the role of systemic inflammation in understanding and managing CHF.

The Pauli exclusion principle (PEP), a cornerstone of quantum mechanics and whole science, states that in a system, two fermions can not simultaneously occupy the same quantum state. Several experimental tests have been performed to place increasingly stringent bounds on the validity of PEP. Among these, the series of VIP experiments, performed at the Gran Sasso Underground National Laboratory of INFN, is searching for PEP-violating atomic X-ray transitions in copper. In this paper, the upgraded VIP-3 setup is described, designed to extend these investigations to higher-Z elements such as zirconium, silver, palladium, and tin. We detail the enhanced design of this setup, including the implementation of cutting-edge, 1 mm thick, silicon drift detectors, which significantly improve the measurement sensitivity at higher energies. Additionally, we present calculations of expected PEP-violating energy shifts in the characteristic lines of these elements, performed using the multi-configurational Dirac–Fock method from first principles. The VIP-3 realization will contribute to ongoing research into PEP violation for different elements, offering new insights and directions for future studies.

Recently, much research has focused on the search for new mixed donor–acceptor layers for applications in organic electronics. Organic heterostructures with layers based on the generation 1 poly(propylene thiophenoimine) (G1PPT) dendrimer, N,N′-diisopropylnaphthalene diimide (MNDI), and a combination of the two were prepared and their electrical properties were investigated. Single layers of G1PPT and MNDI and a mixed layer (G1PPT:MNDI) were obtained via spin coating on quartz glass, silicon, and glass/ITO substrates, using chloroform as a solvent. The absorption mechanism was investigated, the degree of disorder was estimated, and the emission properties of the layers were highlighted using spectroscopic methods (UV–Vis transmission and photoluminescence). The effects of the concentration and surface topographical particularities on the properties of the layers were analyzed via atomic force microscopy. All of the heterostructures realized with ITO and Au electrodes showed good conduction, with currents of the order of mA. Additionally, the heterostructure with a mixed layer exhibited asymmetry in the current–voltage curve between forward and reverse polarization in the lower range of the applied voltages, which was more significant at increased concentrations and could be correlated with rectifier diode behavior. Consequently, the mixed-layer generation 1 poly(propylene thiophenoimine) dendrimer with N,N′-diisopropylnaphthalene diimide can be considered promising for electronic applications.

The paper presents a computing procedure with the goal of suggesting applicable solutions to improve complex cases of major recurrent depression. The focus is on identifying the patients’ illness patterns and on finding solutions for alleviating problematic symptoms. The illness patterns synthesize the outcomes of the relationship between the patients’ life themes and symptoms. The testing of the effectiveness of illness improvement solutions was conducted by evaluating and comparing the Beck scores of patients after each psychotherapy session. In addition to latent semantic analysis used to identify semantic relationships between life themes and symptoms, the research also employed the correlation method to find life themes/symptoms that are experienced undistortedly and associations between life themes that amplify latent symptoms. The computing system was applied to eleven patients with severe forms of depression and their progress was monitored for six months. The results obtained following the application of the computing system demonstrated its ability to describe personalized illness patterns and to significantly improve, through its suggestions, the illness of all patients. These findings recommend the use of the computing system in severe cases of major recurrent depression.