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The cytokine context present in the reproductive tract of cows is closely involved in normal uterine functions, including the estrous cycle and the establishment and maintenance of pregnancy. However, the roles of some cytokines in the uterus, and their relation with reproductive performance remain to be elucidated. Thus, this study aimed to examine the protein expression of several cytokines such as TNFα, IL-6, IL-8, IFNγ, IL-4, and TGF-β3 in endometrial biopsies previous to conception, to evaluate the possible association with delayed conception in dairy cows. Protein expression levels were evaluated by immunohistochemistry. Results showed that the protein expression levels of TNFα, IL-6, IL-4 and TGF-β3 were not associated with the parturition-conception interval, whereas the high protein expression levels of IFNγ were associated with the parturition-conception interval. Finally, the low protein expression of IL-8 showed a statistical tendency to be associated with delayed conception. This is the first report about the protein expression of IFN-γ in the endometrium of dairy cows and also, this cytokine could enhance the favorable conditions to achieve an early pregnancy. [ABSTRACT FROM AUTHOR]

Despite increasing knowledge about small extracellular vesicle (sEV) composition and functions in cell–cell communication, the mechanism behind their biogenesis remains unclear. Here, we reveal for the first time that sEV biogenesis and release into the microenvironment are tightly connected with another important organelle, Lipid Droplets (LDs). The correlation was observed in several human cancer cell lines as well as patient‐derived colorectal cancer stem cells (CR‐CSCs). Our results demonstrated that external stimuli such as radiation, pH, hypoxia or lipid‐interfering drugs, known to affect the number of LDs/cell, similarly influenced sEV secretion. Importantly, through multiple omics data, at both mRNA and protein levels, we revealed RAB5C as a potential important molecular player behind this organelle connection. Altogether, the potential to fine‐tune sEV biogenesis by targeting LDs could significantly impact the amount, cargos and properties of these sEVs, opening new clinical perspectives. [ABSTRACT FROM AUTHOR]

The evaluation of epigenetic features such as DNA methylation is becoming increasingly important in many biochemical processes like gene expression and transcription as well as in several diseases like schizophrenia or diabetes. Here, we report that self-assembled nanomechanical resonators entirely composed of DNA molecules can be used to explore gross changes in DNA methylation levels (0–25–50%), while careful control of tensile stress is needed to reduce the variability of resonance frequency for rigorous quantification. The effect of the tensile stress retained by the suspended DNA nanoresonators on the application of the technique is extensively explored using a combination of laser Doppler vibrometry and atomic force spectroscopy. DNA nanoresonators are real-time, label-free sensors and could avoid chemical functionalization and sample amplification. Therefore, they may represent in the future a key complementary routine tool for global DNA methylation analysis needed to evaluate the consequences of environmental stresses on the human genome. [ABSTRACT FROM AUTHOR]

(1) Background: Femicide is an increasing phenomenon consisting of the murder of a woman for gender-related reasons. Despite the enactment of new laws aimed at controlling the phenomenon by toughening the penalties and introducing aggravating circumstances, there is an increasing trend that testifies to the persistence of a flaw in the actual measures. (2) Case Presentation. We report the case of the murder of a 32-year-old woman—perpetrated by an ex-husband who refused to accept the end of the marriage—the analysis of which allowed us to frame the case as femicide. (3) Discussion. Despite global awareness of this phenomenon, the identification of risk factors to predict and prevent femicide is of utmost importance. This can be achieved by a multidisciplinary approach involving police officers, legal professionals, hospitals, governmental and nongovernmental organizations, and medico-legal departments aimed at promoting standardized methodologies. (4) Conclusions. We evaluate the contribution of forensic investigations to the identification of key elements that can help frame the murder of a woman as a femicide. Considering the devastating consequences for children who witness this kind of violence within the domestic setting, the planning of more impactful preventive actions is, thus, mandatory to minimize effects on public health. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells, due to their multipotent ability, are considered one of the best candidates to be used in regenerative medicine. To date, the most used source is represented by the bone marrow, despite the limited number of cells and the painful/invasive procedure for collection. Therefore, the scientific community has investigated many alternative sources for the collection of mesenchymal stem cells, with the adipose tissue representing the best option, given the abundance of mesenchymal stem cells and the easy access. Although adipose mesenchymal stem cells have recently been investigated for their multipotency, the molecular mechanisms underlying their adipogenic potential are still unclear. In this scenario, this communication is aimed at defining the role of miRNAs in adipogenic potential of adipose-derived mesenchymal stem cells via real-time PCR. Even if preliminary, our data show that cell culture conditions affect the expression of specific miRNA involved in the adipogenic potential of mesenchymal stem cells. The in vitro/in vivo validation of these results could pave the way for novel therapeutic strategies in the field of regenerative medicine. In conclusion, our research highlights how specific cell culture conditions can modulate the adipogenic potential of adipose mesenchymal stem cells through the regulation of specific miRNAs. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) tumors are composed of heterogeneous and plastic cell populations, including a pool of cancer stem cells that express LGR5. Whether these distinct cell populations display different mechanical properties, and how these properties might contribute to metastasis is poorly understood. Using CRC patient derived organoids (PDOs), we find that compared to LGR5- cells, LGR5+ cancer stem cells are stiffer, adhere better to the extracellular matrix (ECM), move slower both as single cells and clusters, display higher nuclear YAP, show a higher survival rate in response to mechanical confinement, and form larger transendothelial gaps. These differences are largely explained by the downregulation of the membrane to cortex attachment proteins Ezrin/Radixin/Moesin (ERMs) in the LGR5+ cells. By analyzing single cell RNA-sequencing (scRNA-seq) expression patterns from a patient cohort, we show that this downregulation is a robust signature of colorectal tumors. Our results show that LGR5- cells display a mechanically dynamic phenotype suitable for dissemination from the primary tumor whereas LGR5+ cells display a mechanically stable and resilient phenotype suitable for extravasation and metastatic growth. The mechanical properties of heterogeneous cell populations in colorectal tumors and the relevance to cancer metastasis remain not fully understood. Here, the authors suggest that the variations in malignant phenotypes between LGR5-positive cancer stem cells and LGR5-negative cells could be due to their distinct mechanical phenotypes observed in vitro, determined by the membrane to cortex attachment proteins Ezrin/Radixin/Moesin. [ABSTRACT FROM AUTHOR]

Self‐healing ionic conductive hydrogels have shown significant potential in applications like wearable electronics, soft robotics, and prosthetics because of their high strain sensitivity and mechanical and electrical recovery after damage. Despite the enormous interest in these materials, conventional fabrication techniques hamper their use in advanced devices since only limited geometries can be obtained, preventing proper conformability to the complexity of human or robotic bodies. Here, a photocurable hydrogel with excellent sensitivity to mechanical deformations based on a semi‐interpenetrating polymeric network is reported, which holds remarkable mechanical properties (ultimate tensile strain of 550%) and spontaneous self‐healing capabilities, with complete recovery of its strain sensitivity after damages. Furthermore, the developed material can be processed by digital light processing 3D printing technology to fabricate complex‐shaped strain sensors, increasing mechanical stress sensitivity with respect to simple sensor geometries, reaching an exceptional pressure detection limit below 1 Pa. Additionally, the hydrogel is used as an electrolyte in the fabrication of a laser‐induced graphene‐based supercapacitor, then incorporated into a 3D‐printed sensor to create a self‐powered, fully integrated device. These findings demonstrate that by using 3D printing, it is possible to produce multifunctional, self‐powered sensors, appropriately shaped depending on the various applications, without the use of bulky batteries. [ABSTRACT FROM AUTHOR]

The experimental observation of quantum phase transitions predicted by the quantum Rabi model in quantum critical systems is usually challenging due to the lack of signature experimental observables associated with them. Here, we describe a method to identify the dynamical critical phenomenon in the quantum Rabi model consisting of a three-level atom and a cavity at the quantum phase transition. Such a critical phenomenon manifests itself as a sudden change of steady-state output photons in the system driven by two classical fields, when both the atom and the cavity are initially unexcited. The process occurs as the high-frequency pump field is converted into the low-frequency Stokes field and multiple cavity photons in the normal phase, while this conversion cannot occur in the superradiant phase. The sudden change of steady-state output photons is an experimentally accessible measure to probe quantum phase transitions, as it does not require preparing the equilibrium state. Quantum Rabi model as an outstanding model can support superradiant phase transitions, and gets increasing interest in the quantum physics. This work presents an effective method to demonstrate the dynamical critical phenomenon in quantum Rabi model without preparing the Confirmed equilibrium state, i.e., a sudden change of the photon number distribution. [ABSTRACT FROM AUTHOR]

In this work, the oxidation of sponge‐like nanostructured Zn films exploiting their interaction with water in liquid and vapor phases is investigated. By simply exposing the sputtered porous metal layers to a water vapor atmosphere or incubating them in water at different temperatures, the full conversion to ZnO is obtained. Depending on the kind of treatment, the oxidized ZnO layers exhibit different morphologies and physico‐chemical properties. When in combination with low heating of the surface, a better crystallinity and the growth of hexagonal nanocrystals (nanoprisms and nanoflowers) from the nanobranched Zn structure is observed, preserving the sponge‐like morphology of the starting material. Good photocatalytic activities for the degradation of an organic dye are measured under simulated sunlight irradiation. The piezoelectric and semiconducting response of the oxidized ZnO layers is also examined, revealing appealing performance in both cases and envisaging their use as nanogenerators and photoanode material in dye‐sensitized solar cells. The multifunctional properties of the oxidized ZnO film are discussed in terms of the selected water oxidation approach that tune the corresponding morphology and crystallinity. The low‐temperature oxidation approaches here proposed allow the fabrication of flexible semiconductive ZnO films highly desirable in different fields of nanoelectronics. [ABSTRACT FROM AUTHOR]

Modifying material properties within a specific spatial region is a pivotal stage in the fabrication of microelectronic devices. Laser annealing emerges as a compelling technology, offering precise control over the crystalline structure of semiconductor materials and facilitating the activation of doping ions in localized regions. This obviates the necessity for annealing the entire wafer or device. The objective of this review is to comprehensively investigate laser annealing processes specifically targeting the crystallization of amorphous silicon (Si) and silicon carbide (SiC) samples. Silicon finds extensive use in diverse applications, including microelectronics and solar cells, while SiC serves as a crucial material for developing components designed to operate in challenging environments or high-power integrated devices. The review commences with an exploration of the underlying theory and fundamentals of laser annealing techniques. It then delves into an analysis of the most pertinent studies focused on the crystallization of these two semiconductor materials. [ABSTRACT FROM AUTHOR]

Background: Diffuse large B-cell lymphoma (DLBCL) is a hematological malignancy representing one-third of non-Hodgkin’s lymphoma cases. Notwithstanding immunotherapy in combination with chemotherapy (RCHOP) is an effective therapeutic approach for DLBCL, a subset of patients encounters treatment resistance, leading to low survival rates. Thus, there is an urgent need to identify predictive biomarkers for DLBCL including the elderly population, which represents the fastest-growing segment of the population in Western countries. Methods: Gene expression profiles of n=414 DLBCL biopsies were retrieved from the public dataset GSE10846. Differentially expressed genes (DEGs) (fold change >1.4, p-value <0.05, n=387) have been clustered in responder and non-responder patient cohorts. An enrichment analysis has been performed on the top 30 up-regulated genes of responder and non-responder patients to identify the signatures involved in gene ontology (MSigDB). The more significantly upregulated DEGs have been validated in our independent collection of formalin-fixed paraffin-embedded (FFPE) biopsy samples of elderly DLBCL patients, treated with R-CHOP as first-line therapy. Results: From the analysis of two independent cohorts of DLBCL patients emerged a gene signature able to predict the response to R-CHOP therapy. In detail, expression levels of EBF1, MYO6, CALR are associated with a significant worse overall survival. Conclusions: These results pave the way for a novel characterization of DLBCL biomarkers, aiding the stratification of responder versus non-responder patients. [ABSTRACT FROM AUTHOR]

Regulation 2017/625 allows and encourages the use of rating schemes as a means to increase transparency in the agri-food chain. Since its implementation, a need for greater fairness, consistency, transparency, and objectivity in official controls has been reported by member states. The present study compares the results of inspection activities concerning food hygiene principles in ethnic and traditional butcheries. The sample consists of 50 food business activities randomly selected from traditional and ethnic butcheries subject to official control in Turin from January to June 2019. Our objectives were to evaluate the degree of awareness and training of food business operators (FBOs) and to compare the written records drawn up by the competent authorities (CAs) during official inspections to evaluate their completeness and uniformity. The presence of old equipment is a common finding in both traditional and ethnic butchers. This could lead to ineffective cleaning operations and inappropriate functioning, which in turn could lead to a dangerous loss of control over products' temperatures. Ethnic butchers showed a higher number of non-compliances for documentary examination, the presence/correctness of self-control plans, and management aspects such as by-product disposal and personnel hygiene. Training is the key point for both CAs and FBOs; inspectors must maintain their professionalism but also adhere to harmonized and intellectually supported criteria, and FBOs must prevent improper behavior. Eventually, we propose strategies to increase the efficacy and homogeneity of records, together with suggestions on how to implement training both for consultants and operators. [ABSTRACT FROM AUTHOR]

Multiwalled carbon nanotubes and Vulcan carbon were functionalized with a 30 %v/v hydrogen peroxide solution and employed as supports for Pt and PtSn catalysts prepared by the polyol method. PtSn catalysts with a Pt loading of 20 wt.% and a Pt : Sn atomic ratio equal to 3 : 1 were evaluated in the ethanol electrooxidation reaction. The effects of the oxidizing treatment on the surface area and the surface chemical nature were analyzed through N2 adsorption, isoelectric point, and temperature‐programmed desorption measurements. Results showed that the H2O2 treatment affects the surface area of the carbons to a great extent. Characterization results indicated that the performance of the electrocatalysts strongly depends both on the presence of Sn and on the support functionalization. PtSn/CNT−H2O2 electrocatalyst displays a high electrochemical surface area and enhanced catalytic activity for ethanol oxidation in comparison to other catalysts in the present study. [ABSTRACT FROM AUTHOR]

Determining the cause of death is one of the main goals of forensic pathology. However, conditions can occur in which common approaches—external inspection, autopsy, histology, etc.—might not be conclusive. With the advancement of molecular biology, several investigative techniques have been developed over the years, and the application as approaches complementary to routine procedures has proved useful in these cases. In this context, microRNA (miRNA) profiling has attracted increasing interest due to these molecules' ability to regulate physiological and pathological processes. The evidence of differential miRNA expression in both animal models and human samples of traumatic brain injury (TBI) has laid the basis for comprehension of the underlying pathophysiological mechanisms, thus allowing us to identify some of them as possible TBI diagnostic biomarkers. The present narrative review aims to explore the primary miRNAs involved in the mechanisms underlying TBI, which could be considered for future evaluation as possible markers in a post mortem setting. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) can be divided into four consensus molecular subtypes (CMS), each with distinct biological features. CMS4 is associated with epithelial-mesenchymal transition and stromal infiltration (Guinney et al., Nat Med 21:1350–6, 2015; Linnekamp et al., Cell Death Differ 25:616–33, 2018), whereas clinically it is characterized by lower responses to adjuvant therapy, higher incidence of metastatic spreading and hence dismal prognosis (Buikhuisen et al., Oncogenesis 9:66, 2020). Methods: To understand the biology of the mesenchymal subtype and unveil specific vulnerabilities, a large CRISPR-Cas9 drop-out screen was performed on 14 subtyped CRC cell lines to uncover essential kinases in all CMSs. Dependency of CMS4 cells on p21-activated kinase 2 (PAK2) was validated in independent 2D and 3D in vitro cultures and in vivo models assessing primary and metastatic outgrowth in liver and peritoneum. TIRF microscopy was used to uncover actin cytoskeleton dynamics and focal adhesion localization upon PAK2 loss. Subsequent functional assays were performed to determine altered growth and invasion patterns. Results: PAK2 was identified as a key kinase uniquely required for growth of the mesenchymal subtype CMS4, both in vitro and in vivo. PAK2 plays an important role in cellular attachment and cytoskeletal rearrangements (Coniglio et al., Mol Cell Biol 28:4162–72, 2008; Grebenova et al., Sci Rep 9:17171, 2019). In agreement, deletion or inhibition of PAK2 impaired actin cytoskeleton dynamics in CMS4 cells and, as a consequence, significantly reduced invasive capacity, while it was dispensable for CMS2 cells. Clinical relevance of these findings was supported by the observation that deletion of PAK2 from CMS4 cells prevented metastatic spreading in vivo. Moreover, growth in a model for peritoneal metastasis was hampered when CMS4 tumor cells were deficient for PAK2. Conclusion: Our data reveal a unique dependency of mesenchymal CRC and provide a rationale for PAK2 inhibition to target this aggressive subgroup of colorectal cancer. [ABSTRACT FROM AUTHOR]

Despite being widely recognized as of paramount importance in molecular biology, real-time monitoring of structural transitions in DNA complexes is currently limited to complex techniques and chemically modified oligonucleotides. Here, we show that nanomechanical resonators made of different DNA complexes, such as pristine dsDNA, ssDNA, and DNA intercalated with dye molecules or chemotherapeutic agents, are characterized by unique fingerprint curves when their flexural resonance frequency is tracked as a function of temperature. Such frequency shifts can be successfully used to monitor structural variations in DNA complexes, such as B-to-A form and helix-to-coil transitions, thus opening implications in both environmental studiesfor example, trucking the effects of heavy metal exposure on human or vegetable DNA moleculesand in vitro experiments for the evaluation of the effects of drugs on patient DNA. [ABSTRACT FROM AUTHOR]

Background: Complex perianal fistulas are a major challenge for modern surgery since 10–35% of patients have functional problems after treatment. Sphincter-saving techniques have a wide range of efficacy (10–80%). We hypothesised that autologous adipose-derived stromal vascular fraction in combination with platelet rich plasma is a new therapeutic strategy with enhanced cure and function preservation rates. Methods: Adult patients with complex cryptoglandular perianal fistulas were treated with injection of autologous adipose-derived stromal vascular fraction in combination with platelet rich plasma around and inside the fistulous tract between May 2018 and April 2019 at the General and Emergency Surgery Operative Unit of the University Hospital "P. Giaccone" of Palermo. Fistulas were confirmed by magnetic resonance imaging. Patients completed the Short Form-36 score on quality of life and the Wexner and Vaizey scores on faecal incontinence, and they were functionally studied using a three-dimensional anorectal manometry. The clinical and functional follow-up was performed at 1 year and 2 years after surgery. Results: Nine patients (4 males, 5 females; median age 42 years [19–63 years]) with high trans-sphincteric or horseshoe fistulas were treated. The average number of previous surgeries per patient was 4.8. At 1 year follow-up, 77.7% of patients were cured, while at 2 years there was 1case of relapse. The variation in Short Form-36 score in cured patients was not significant (p = 0.0936). No statistically significant differences were found in continence scores. Conclusions: The proposed treatment is a treatment option that preserves sphincter integrity and function, potentially avoiding postoperative incontinence and the need of repeated treatments. [ABSTRACT FROM AUTHOR]

The recovery of severely altered cadavers (i.e., extensively decomposed, mummified, charred or dismembered) can be a challenge for forensic pathologists due to the difficulties in identification, PMI estimation and manner and cause of death determination. In such cases, integrating routine approaches (autopsy, histology, toxicology) to more specific forensic branches can be fundamental to improving the investigative process. In this paper a systematic review using PubMed, Scopus and Web of Science databases has been performed. The aim was to evaluate the forensic approaches implemented in the management of severely altered bodies due to decomposition, mummification, skeletonization, charring or dismemberment (to which we refer to as "complex"), and the role of each approach in the solution of a case. Then, the literature revision results were used to propose a schematic flowchart summarizing the post mortem activities that can be performed in forensic practice, adaptable in relation to each case. [ABSTRACT FROM AUTHOR]

In a scenario where eco-sustainability and a reduction in chemotherapeutic drug waste are certainly a prerogative to safeguard the biosphere, the use of natural products (NPs) represents an alternative therapeutic approach to counteract cancer diseases. The presence of a heterogeneous cancer stem cell (CSC) population within a tumor bulk is related to disease recurrence and therapy resistance. For this reason, CSC targeting presents a promising strategy for hampering cancer recurrence. Increasing evidence shows that NPs can inhibit crucial signaling pathways involved in the maintenance of CSC stemness and sensitize CSCs to standard chemotherapeutic treatments. Moreover, their limited toxicity and low costs for large-scale production could accelerate the use of NPs in clinical settings. In this review, we will summarize the most relevant studies regarding the effects of NPs derived from major natural sources, e.g., food, botanical, and marine species, on CSCs, elucidating their use in pre-clinical and clinical studies. [ABSTRACT FROM AUTHOR]

This work describes a new methodology used in large scale retail trades in official food safety auditing processes developed during COVID19 emergency. The aim is to evaluate Food Business Operators’ (FBOs) Food Safety Management System and its dynamic implementation and to understand the FBO’s level of cultural maturity about food safety according to EU Regulation 2021/382. The innovation mainly consists of: a) a pre-audit phase when auditors analyse food business operator’s (FBO) selfchecked plan and further documents to identify “markers” and useful evidences (that would be collected in on-site inspections) to evaluate the application of plan by FBO’s workers; b) an audit phase consisted of both a check of the company procedures and documents performed by the auditors via web conference and of contextually onsite inspections in a sample of company’s supermarkets performed by inspectors teams. The audit methodology here described may be useful, even though it is expensive in terms of time and energy used, for both Competent Authority (CA) and FBOs, regardless of the period of the COVID emergency. The so-structured official control allows the auditors to collect both documentary and on-site evidence at the same time, reaching a broader vision of auditees (not limited to single supermarkets) and a compliant with reality FBOs risk classification. The new approach may give advantages to both audit actors, CA as well as FBO, who may collect “markers” and evidence of the self-checked plan useful to improve FBO’s food safety system on the basis of the critical aspects detected during auditing process. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) plays a key role in promoting and sustaining cancer growth. Adipose tissue (AT), due to its anatomical distribution, is a prevalent component of TME, and contributes to cancer development and progression. Cancer-associated adipocytes (CAAs), reprogrammed by cancer stem cells (CSCs), drive cancer progression by releasing metabolites and inflammatory adipokines. In this review, we highlight the mechanisms underlying the bidirectional crosstalk among CAAs, CSCs, and stromal cells. Moreover, we focus on the recent advances in the therapeutic targeting of adipocyte-released factors as an innovative strategy to counteract cancer progression. [ABSTRACT FROM AUTHOR]

The need of a minimally invasive approach, especially in cases of cultural or religious oppositions to the internal examination of the body, has led over the years to the introduction of postmortem CT (PMCT) methodologies within forensic investigations for the comprehension of the cause of death in selected cases (e.g., traumatic deaths, acute hemorrhages, etc.), as well as for personal identification. The impossibility to yield clear information concerning the coronary arteries due to the lack of an active circulation to adequately distribute contrast agents has been subsequently overcome by the introduction of coronary-targeted PMCT Angiography (PMCTA), which has revealed useful in the detection of stenoses related to calcifications and/or atherosclerotic plaques, as well as in the suspicion of thrombosis. In parallel, due to the best ability to study the soft tissues, cardiac postmortem MR (PMMR) methodologies have been further implemented, which proved suitable for the detection and aging of infarcted areas, and for cardiomyopathies. Hence, the purpose of the present work to shed light on the state of the art concerning the value of both coronary-targeted PMCTA and PMMR in the diagnosis of coronary artery disease and/or myocardial infarction as causes of death, further evaluating their suitability as alternatives or complementary approaches to standard autopsy and histologic investigations. [ABSTRACT FROM AUTHOR]

Background. In recent years, due to the increase of complaints for medical malpractice, the Sicilian Regional Health System has adopted proceedings for the direct management of claims by each healthcare facility with the aim of reducing costs of insurance premiums and their relative taxes. Thus this management has led to increased awareness and management of clinical risk through the introduction of mandatory sentinel event monitoring Case report. A 55-year-old man with acute ischemic heart disease, due to three-vasal coronary diasease, underwent angioplasty perfomed on the second diagonal branch of the anterior descending artery. Simultaneously following the discovery of a major middle tract stenosis, he underwent further angioplasty surgery during which guidewire entrapment occurred, precisely in the proximal section of the vessel, resulting in the rupture and persistence of some fragments despite attempts to extract them. Subsequent antiplatelet therapy was prescribed and no further procedures were indicated for the removal of the guide wire, meanwhile a persistent reactive anxious-depressive state was established. Conclusion. The medico-legal analysis of the case excluded liabilty since it was a fortuitous, unpredictable and inevitable event. However, the patient had not been adequately informed about the possibility of the complication presented, which resulted in prolonged hospitalization and compensation for the psychological disorder suffered as a result of the adverse event. The attempted economic agreement was unsuccessful. A civil lawsuit was subsequently filed by the patient and the Judge's report confirmed the corporate CMC assessment and ruled out that the side effects related to the guideline fragment. [ABSTRACT FROM AUTHOR]

The objective of this study was to describe a case of a granulosa cell tumour (GCT) of incipient formation and to characterize it by its immunohistochemical pattern and hormonal profile. The case presented corresponds to a 7‐year‐old Holstein cow without reproductive disorders. No alterations were observed at rectal palpation, neither in the ultrasonography nor in the hormonal profile. A GCT concomitant with normal follicular development was diagnosed. Through a panel of immunohistochemical markers, a highly differentiated pattern could be determined in the GCT, which preserves the expression of steroid receptors (ESR1, ESR2 and PR) typical of granulosa cells, but does not express the enzymes for the synthesis of androgens (CYP17A1) and oestrogens (CYP19A1). In addition, the expression of co‐regulators of steroid hormone receptors and neuroendocrine markers was described for the first time in a GCT in cattle. These results increase the information about GCTs in cattle before the ovarian function is compromised. [ABSTRACT FROM AUTHOR]

Laser graphenization of polymeric surfaces has emerged as one of the most promising technologies to fabricate flexible electrodes. Unfortunately, despite the large number of materials suitable for laser‐induced graphene (LIG) fabrication, there is a lack of stretchable polymers, hindering the full exploitation of LIG for flexible electronics. Herein, the laser graphenization of polydimethylsiloxane (PDMS), the most exploited elastomeric substrate for flexible electronic device fabrication, is proposed for the first time. The low carbon content and the absence of aromatic structures strongly limit the graphenization process resulting in limited conduction properties. Nevertheless, by adding triethylene glycol (TEG) as carbon source into the PDMS matrix, it is possible to improve the graphenization and to reduce the sheet resistance of the written LIG by two orders of magnitude down to 130 ohm sq−1. The PDMS‐TEG material becomes a suitable candidate for flexible microsupercapacitor fabrication with specific capacitance values as high as 287 µF cm−2 and energy and power density approaching LIG‐based supercapacitors fabricated onto traditional polyimide substrates. [ABSTRACT FROM AUTHOR]

The extreme miniaturization in NEMS resonators offers the possibility to reach an unprecedented resolution in high-performance mass sensing. These very low limits of detection are related to the combination of two factors: a small resonator mass and a high quality factor. The main drawback of NEMS is represented by the highly complex, multi-steps, and expensive fabrication processes. Several alternatives fabrication processes have been exploited, but they are still limited to MEMS range and very low-quality factor. Here we report the fabrication of rigid NEMS resonators with high-quality factors by a 3D printing approach. After a thermal step, we reach complex geometry printed devices composed of ceramic structures with high Young's modulus and low damping showing performances in line with silicon-based NEMS resonators ones. We demonstrate the possibility of rapid fabrication of NEMS devices that present an effective alternative to semiconducting resonators as highly sensitive mass and force sensors. NEMS devices, nano-electro-mechanical systems, by virtue of their minute size, offer ultra-high sensitivity, though at the expense of manufacturing complexity. Here, Stassi et al succeed in manufacturing high quality factor NEMS devices using high resolution 3D printing. [ABSTRACT FROM AUTHOR]

The present paper deals with the selective laser writing of textile yarns in order to induce a conductive path useful for smart textiles application. The incident power of the laser induces a conversion of an aramid fiber surface into graphene-based conductive material with tunable electrical properties depending on the laser writing parameters. The physical-chemical properties of the resulting smart yarns have been intensively characterized by electron microscopy, Raman spectroscopy, electrical and mechanical investigations. The results confirm the few-layer graphene fingerprint of the written paths onto the textile yarn with suitable properties for their application into electronic textiles. Indeed, a yarn-shape strain sensor with excellent performance has been developed and characterized to demonstrate the potential application of the proposed technology to the wearable electronic field. [ABSTRACT FROM AUTHOR]

One of the major bottlenecks of the traditional current transformer energy harvester (CTEH) is the instable output induced by the wide‐range variations of the current in transmission lines. In this work, a novel CTEH capable of generating a stable output is demonstrated by using a core fabricated with saturable magnetic material. The stable output of the CTEH is enabled by the constant voltage‐time product in its saturable characteristic. The proposed CTEH is implemented with a resistive load representing the load of electronic devices. When the current in the primary side of the CTEH's increases from 1 to 1000 A, the maximum power on the load can reach about 0.5 W, demonstrating the feasibility of using the CTEH with the saturable magnetic core as a quasi‐stable power supply. [ABSTRACT FROM AUTHOR]

Phononic materials are artificial composites with unprecedented abilities to control acoustic waves in solids. Their performance is mainly governed by their architecture, determining frequency ranges in which wave propagation is inhibited. However, the dynamics of phononic materials also depends on the mechanical and material properties of their constituents. In the case of viscoelastic constituents, such as most polymers, it is challenging to correctly predict the actual dynamic behavior of real phononic structures. Existing studies on this topic either lack experimental evidence or are limited to specific materials and architectures in restricted frequency ranges. A general framework is developed and employed to characterize the dynamics of polymer phononic materials with different architectures made of both thermoset and thermoplastic polymers, presenting qualitatively different viscoelastic behaviors. Through a comparison of experimental results with numerical predictions, the reliability of commonly used elastic and viscoelastic material models is evaluated in broad frequency ranges. Correlations between viscous effects and the two main band‐gap formation mechanisms in phononic materials are revealed, and experimentally verified guidelines on how to correctly predict their dissipative response are proposed in a computationally efficient way. Overall, this work provides comprehensive guidelines for the extension of phononics modeling to applications involving dissipative viscoelastic materials. [ABSTRACT FROM AUTHOR]

Despite the recent advances in cancer patient management and in the development of targeted therapies, systemic chemotherapy is currently used as a first-line treatment for many cancer types. After an initial partial response, patients become refractory to standard therapy fostering rapid tumor progression. Compelling evidence highlights that the resistance to chemotherapeutic regimens is a peculiarity of a subpopulation of cancer cells within tumor mass, known as cancer stem cells (CSCs). This cellular compartment is endowed with tumor-initiating and metastasis formation capabilities. CSC chemoresistance is sustained by a plethora of grow factors and cytokines released by neighboring tumor microenvironment (TME), which is mainly composed by adipocytes, cancer-associated fibroblasts (CAFs), immune and endothelial cells. TME strengthens CSC refractoriness to standard and targeted therapies by enhancing survival signaling pathways, DNA repair machinery, expression of drug efflux transporters and anti-apoptotic proteins. In the last years many efforts have been made to understand CSC-TME crosstalk and develop therapeutic strategy halting this interplay. Here, we report the combinatorial approaches, which perturb the interaction network between CSCs and the different component of TME. [ABSTRACT FROM AUTHOR]

Since their discovery in ancient China, fireworks rapidly spread throughout the world, where they have always been used to celebrate either popular or private events. Their use is nonetheless related to several risks, especially within production factories, since several injuries or even death can occur following an accidental ignition. In cases of major disasters related to fireworks explosions, stating the accidental or intentional nature of the event might prove challenging, thus raising the need of a multidisciplinary approach. In this regard, we here discuss the case of an accidental explosion that occurred in a fireworks production factory, accountable for five deaths and two hospitalisations. [ABSTRACT FROM AUTHOR]

A medico-legal consult is frequently required in a clinical context in order to assess the eventual compatibility of specific wounds with a self- or hetero-infliction. Accordingly, the case of a 52-year-old man with a single, penetrating stab wound of the neck, reported as self-inflicted, is here presented. The forensic aspects, taken into account in order to determine the self- or hetero-infliction nature of the wound, are further discussed and compared to cases described in the literature. [ABSTRACT FROM AUTHOR]

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The concept of autoerotic asphyxiation refers to the use of devices or substances intended to enhance one's arousal by inducing cerebral hypoxia, which can involuntarily lead to death. Although in most cases death occurs accidentally, it is nonetheless true that the same devices might be used by the practitioners in order to attempt suicide. The case of a 34-year-old practitioner of autoerotic asphyxiation found dead in his apartment with bondage-like ligatures and masking is reported here. The case raised some issues concerning the accidental or suicidal nature of the act. The aspects taken into account in the management of the case are discussed, along with a compared approach to the data provided by literature. [ABSTRACT FROM AUTHOR]

Resistive switching (RS) devices based on self-assembled nanowires (NWs) and nanorods (NRs) represent a fascinating alternative to conventional devices with thin film structure. The high surface-to-volume ratio may indeed provide the possibility of modulating their functionalities through surface effects. However, devices based on NWs usually suffer from low resistive switching performances in terms of operating voltages, endurance and retention capabilities. In this work, we report on the resistive switching behaviour of ZnO NW arrays, grown by hydrothermal synthesis, that exhibit stable, bipolar resistive switching characterized by SET/RESET voltages lower than 3 V, endurance higher than 1100 cycles and resistance state retention of more than 105 s. The physical mechanism underlying these RS performances can be ascribed to nanoionic processes involving the formation/rupture of conductive paths assisted by oxygen-related species in the ZnO active layer. The reported results represent, to the best of our knowledge, the best resistive switching performances observed in ZnO NW arrays in terms of endurance and retention. [ABSTRACT FROM AUTHOR]

So far, superconducting quantum computers have certain constraints on qubit connectivity, such as nearest-neighbor couplings. To overcome this limitation, we propose a scalable architecture to simultaneously connect several pairs of distant qubits via a dispersively coupled quantum bus. The building block of the bus is composed of orthogonal coplanar waveguide resonators connected through ancillary flux qubits working in the ultrastrong coupling regime. This regime activates virtual processes that boost the effective qubit–qubit interaction, which results in quantum gates on the nanosecond timescale. The interaction is switchable and preserves the coherence of the qubits. [ABSTRACT FROM AUTHOR]

Cattle undergo numerous environmental and management stressors that reduce fertility and affect ovulation. The extracellular matrix of the follicle wall can be altered by matrix metalloproteinases (MMPs), the activities of which are regulated by interleukins and tissue-specific inhibitors of metalloproteinases (TIMPs), especially during ovulation. The aims of the present study were to: (1) evaluate changes in the hormone milieu, the localisation and activity of MMP2 and MMP9 and the localisation of MMP14, TIMP1 and TIMP2 in response to adrenocorticotrophic hormone (ACTH) during the preovulatory period in cows; and (2) determine the direct effects of ACTH on the mRNA expression of MMP2 and MMP9 in the cultured follicle wall of bovine ovaries obtained from an abattoir. 100 IU ACTH was administered during pro-oestrus every 12 h until ovariectomy, which was performed before ovulation. Cortisol concentrations in the plasma and follicular fluid (FF) of preovulatory follicles were higher in ACTH-treated than control cows. Progesterone presented subluteal concentrations in plasma of ACTH-treated cows (P < 0.05). MMP2 immunostaining and activity in ovaries were higher in ACTH-treated than control cows (P < 0.05), whereas MMP9 immunostaining was similar between the two groups. However, unlike in control cows, MMP9 activity was absent in the FF of ACTH-treated cows. These results suggest that the administration of ACTH during the preovulatory period in cows could cause changes that culminate in modifications in the content and activation of MMPs and TIMPs in the ovary, which could interfere with the ovulation process. Cattle undergo numerous stress situations during their lives that can affect fertility and production. Ovulation is a sensitive event that involves numerous molecules, including enzymes like metalloproteases and their regulators. This study evaluated the activity and expression of these molecules and the effects of adrenocorticotrophic hormone on the bovine ovary in pro-oestrus. We found changes that could alter the ovulation process in response to stress. [ABSTRACT FROM AUTHOR]

In this work, PtSn bimetallic catalysts supported on three different carbons were prepared by two methods: a) conventional impregnation followed by a reduction treatment under H2-flow (CI) and b) deposition-reduction in liquid phase (RLP). All the catalysts were tested in the selective hydrogenation of citral to the unsaturated alcohols (UA). A strong influence of the preparation method and the support was found over the selectivity to UA. For CI prepared catalysts, low Sn loadings give a metallic phase with highly ordered PtSn alloys, while for RLP catalysts, high Sn loadings give highly ordered phases with Sn ionic species intercalated in the Pt metallic phase. Both ordered phases are highly effective to promote the hydrogenation of carbonyl group. For the RLP method, high Sn/Pt molar ratios in solution leads to the formation of PtSn complexes with a good interaction between metals. [ABSTRACT FROM AUTHOR]

Prenatal testosterone (T) excess, partly via androgenic programming, enhances follicular recruitment/persistence in sheep as in women with polycystic ovarian syndrome (PCOS). Decreased anti-Mullerian hormone (AMH) in early growing and increased AMH in antral follicles may underlie enhanced recruitment and persistence, respectively. Changes in AMH may be mediated by steroidogenic factor 1 (SF1), an enhancer of AMH, and dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 (DAX1), that antagonizes SF1. Another mediator could be forkhead box 03 (FOXO3) which regulates follicular recruitment/atresia. To test if androgen-programmed changes in SF1, DAX1, and FOXO3 proteins contribute to follicular defects in prenatal T-treated sheep, ovaries from control, prenatal T-, and dihydrotestosterone (DHT)-treated (days 30–90 of gestation) animals at fetal day (FD) 90, FD140, and 1 and 2 years-of-age were studied. Prenatal T increased DAX1 in granulosa cells of primordial through large preantral and theca cells of large preantral follicles at FD140 and increased SF1 in the granulosa cells of preantral and antral and theca cells of large preantral follicle at 2 years-of-age. Prenatal T increased FOXO3 only in theca cells of preantral (FD140) and antral (2 years-of-age) follicles. Prenatal DHT increased DAX1 in granulosa cells from small preantral follicles at FD140 while increasing SF1 in granulosa cells from antral follicles at 1 year-of-age. These age-dependent changes in DAX1/SF1 partly via androgen-programming are consistent with changes in AMH and may contribute to the enhanced follicular recruitment/persistence, and multifollicular phenotype of prenatal T-treated females and may be of translational relevance to PCOS. [ABSTRACT FROM AUTHOR]

Summary: Ovulation is considered an inflammatory, cytokine-mediated event. Cytokines, which are recognized as growth factors with immunoregulatory properties, are involved in many cellular processes at the ovarian level. In this sense, cytokines affect fertility and are involved in the development of different ovarian disorders such as bovine cystic ovarian disease (COD). Because it has been previously demonstrated that ovarian cells represent both sources and targets of cytokines, the aim of this study was to examine the expression of several cytokines, including IL-1β, IL-1RA, IL-1RI, IL-1RII, IL-4 and IL-8, in ovarian follicular structures from cows with spontaneous COD. The protein expression of these cytokines was evaluated by immunohistochemistry. Additionally, IL-1β, IL-4 and IL-8 concentrations in follicular fluid (FF) and serum were determined by enzyme-linked immunosorbent assay (ELISA). In granulosa and theca cells, IL-1RI, IL-1RII, IL-1RA and IL-4 expression levels were higher in cystic follicles than in the control dominant follicles. The serum and FF concentrations of IL-1β and IL-4 showed no differences between groups, whereas IL-8 concentration was detected only in FF of cysts from cows with COD. The FF and serum concentrations of IL-1β and IL-8 showed no significant differences, whereas IL-4 concentration was higher in FF than in serum in both the control and COD groups. These results evidenced an altered expression of cytokines in ovaries of cows with COD that could contribute to the pathogenesis of this disease. [ABSTRACT FROM AUTHOR]

MRI guided Focused Ultrasound (MRgFUS) has shown to be effective therapeutic modality for non-invasive clinical interventions in ablating of uterine fibroids, in bone metastasis palliative treatments, and in breast, liver, and prostate cancer ablation. MRgFUS combines high intensity focused ultrasound (HIFU) with MRI images for treatment planning and real time thermometry monitoring, thus enabling non-invasive ablation of tumor tissue. Although in the literature there are several studies on the Ultrasound (US) effects on cell in culture, there is no systematic evidence of the biological effect of Magnetic Resonance guided Focused Ultrasound Surgery (MRgFUS) treatment on osteosarcoma cells, especially in lower dose regions, where tissues receive sub-lethal acoustic power. The effect of MRgFUS treatment at different levels of acoustic intensity (15.5-49 W/cm2) was investigated on Mg-63 and Saos-2 cell lines to evaluate the impact of the dissipation of acoustic energy delivered outside the focal area, in terms of cell viability and osteogenic differentiation at 24 h, 7 days, and 14 days after treatment. Results suggested that the attenuation of FUS acoustic intensities from the focal area (higher intensities) to the "far field" (lower intensities) zones might determine different osteosarcoma cell responses, which range from decrease of cell proliferation rates (from 49 W/cm2 to 38.9 W/cm2) to the selection of a subpopulation of heterogeneous and immature living cells (from 31.1 W/cm2 to 15.5 W/cm2), which can clearly preserve bone tumor cells. [ABSTRACT FROM AUTHOR]

In the last decades, the role of the microenvironment in tumor progression and therapeutic outcome has gained increasing attention. Cancer-associated fibroblasts (CAFs) have emerged as key players among stromal cells, owing to their abundance in most solid tumors and their diverse tumor-restraining/promoting roles. The interplay between tumor cells and neighboring CAFs takes place by both paracrine signals (cytokines, exosomes and metabolites) or by the multifaceted functions of the surrounding extracellular matrix. Here, we dissect the most recent identified mechanisms underlying CAF-mediated control of tumor progression and therapy resistance, which include induction of the epithelial-to-mesenchymal transition (EMT), activation of survival pathways or stemnessrelated programs and metabolic reprogramming in tumor cells. Importantly, the recently unveiled heterogeneity in CAFs claims tailored therapeutic efforts aimed at eradicating the specific subset facilitating tumor progression, therapy resistance and relapse. However, despite the large amount of pre-clinical data, much effort is still needed to translate CAF-directed anti-cancer strategies from the bench to the clinic. [ABSTRACT FROM AUTHOR]

Introduction. Water intoxication is a well-recognized cause of symptomatic hyponatremia, whose often fatal consequences are described in a wide variety of conditions such as psychiatric disorders, metabolic dysfunctions, child abuse, drug abuse and several medical procedures. The case. We here report a rare case of a 67-year-old woman with severe acute hyponatremia due to an excessive voluntary water intake - 14 litres in two days - following a chiropractic prescription. The patient developed sudden severe symptoms, including water retention, sensory alteration, altered mental status and tonic-clonic seizures. She was thus admitted to the Intensive Care Unit with a diagnosis of coma due to electrolyte alterations following water intoxication. Conclusion. The evaluation, in the present case, of the medicolegal implications related to malpractice involving a practitioner of Complementary and Alternative Medicine, led to the admission of a professional liability of the chiropractor. [ABSTRACT FROM AUTHOR]

The authors evaluate the importance of prevention measures and health care from their own experience and briefly analyse the factors that may have contributed to the rapid spread of Covid-19 in Italy, and hope this will feed into appropriate and new and improved health policies. [ABSTRACT FROM AUTHOR]