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Tuber magnatum is the most expensive truffle, but its large-scale cultivation is still a challenge compared to other valuable Tuber species. T. magnatum mycelium has never been grown profitably until now, which has led to difficulties to studying it in vitro. This study describes beneficial interactions between T. magnatum mycelium and never before described bradyrhizobia, which allows the in vitro growth of T. magnatum mycelium. Three T. magnatum strains were co-isolated on modified Woody Plant Medium (mWPM) with aerobic bacteria and characterised through microscopic observations. The difficulties of growing alone both partners, bacteria and T. magnatum mycelium, on mWPM demonstrated the reciprocal dependency. Three bacterial isolates for each T. magnatum strain were obtained and molecularly characterised by sequencing the 16S rRNA, glnII, recA and nifH genes. Phylogenetic analyses showed that all nine bacterial strains were distributed among five subclades included in a new monophyletic lineage belonging to the Bradyrhizobium genus within the Bradyrhizobium jicamae supergroup. The nifH genes were detected in all bacterial isolates, suggesting nitrogen-fixing capacities. This is the first report of consistent T. magnatum mycelium growth in vitro conditions. It has important implications for the development of new technologies in white truffle cultivation and for further studies on T. magnatum biology and genetics., (© 2024 The Authors. Environmental Microbiology Reports published by John Wiley & Sons Ltd.)

Postpartum haemorrhage (PPH) is an obstetric emergency causing nearly one-quarter of maternal deaths worldwide, 99% of these in low-resource settings (LRSs). Uterine balloon tamponade (UBT) devices are a non-surgical treatment to stop PPH. In LRSs, low-cost versions of UBT devices are based on the condom balloon tamponade (CBT) technique, but their effectiveness is limited. This paper discusses the experimental study to assess the usability and performance of a medical device, BAMBI, designed as an alternative to current CBT devices. The testing phase involved medical and non-medical personnel and was focused on testing BAMBI's usability and effectiveness compared to a standard CBT solution. We collected measures of the execution time and the procedure outcome. Different training procedures were also compared. Results show a significant preference for the BAMBI device. Besides, medical and non-medical subjects reached comparable outcomes. This aspect is highly relevant in LRSs where the availability of medical personnel could be limited., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sara Candidori, Francesco De Gaetano, Kasra Osouli, Serena Graziosi, Alberto Antonio Zanini and Maria Laura Costantino have patent “Uterine device for treating postpartum haemorrhage” (WO2021/220151) pending to Politecnico di Milano., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The 3.1 target of the Sustainable Development Goals of the United Nations aims to reduce the global maternal mortality ratio to less than 70 maternal deaths per 100,000 live births by 2030. The last updates on this target show a significant stagnation in the data, thus reducing the chance of meeting it. What makes this negative result even more serious is that these maternal deaths could be avoided through prevention and the wider use of pharmacological strategies and devices to stop postpartum haemorrhage (PPH). PPH is the leading obstetric cause of maternal mortality in low- and middle-income countries (LMICs). Despite low-cost devices based on the uterine balloon tamponade (UBT) technique are already available, they are not safe enough to guarantee the complete stop of the bleeding. When effective, they are too expensive, especially for LMICs. To address this issue, this study presents the design, mechanical characterisation and technology assessment performed to validate a novel low-cost UBT kit, particularly a novel component, i.e., the connector, which guarantees the kit's effectiveness and represents the main novelty. Results proved the device's effectiveness in stopping PPH in a simulated scenario. Moreover, economic and manufacturing evaluations demonstrated its potential to be adopted in LMICs., (© 2024. The Author(s).)

Currently, the identification of patient-specific therapies in cancer is mainly informed by personalized genomic analysis. In the setting of acute myeloid leukemia (AML), patient-drug treatment matching fails in a subset of patients harboring atypical internal tandem duplications (ITDs) in the tyrosine kinase domain of the FLT3 gene. To address this unmet medical need, here we develop a systems-based strategy that integrates multiparametric analysis of crucial signaling pathways, and patient-specific genomic and transcriptomic data with a prior knowledge signaling network using a Boolean-based formalism. By this approach, we derive personalized predictive models describing the signaling landscape of AML FLT3-ITD positive cell lines and patients. These models enable us to derive mechanistic insight into drug resistance mechanisms and suggest novel opportunities for combinatorial treatments. Interestingly, our analysis reveals that the JNK kinase pathway plays a crucial role in the tyrosine kinase inhibitor response of FLT3-ITD cells through cell cycle regulation. Finally, our work shows that patient-specific logic models have the potential to inform precision medicine approaches., Competing Interests: SL, VV, GM, VB, SG, GP, MI, FF, GM, JM, PC, GP, MH, DM, MB, TF, LP, FS No competing interests declared, (© 2023, Latini, Venafra et al.)

Learning from Nature and leveraging 3D printing, mechanical testing, and numerical modeling, this study aims to provide a deeper understanding of the structure-property relationship of crystal-lattice-inspired materials, starting from the study of single unit cells inspired by the cubic Bravais crystal lattices. In particular, here we study the simple cubic (SC), body-centered cubic (BCC), and face-centered cubic (FCC) lattices. Mechanical testing of 3D-printed structures is used to investigate the influence of different printing parameters. Numerical models, validated based on experimental testing carried out on single unit cells and embedding manufacturing-induced defects, are used to derive the scaling laws for each studied topology, thus providing guidelines for materials selection and design, and the basis for future homogenization and optimization studies. We observe no clear effect of the layer thickness on the mechanical properties of both bulk material and lattice structures. Instead, the printing direction effect, negligible in solid samples, becomes relevant in lattice structures, yielding different stiffnesses of struts and nodes. This phenomenon is accounted for in the proposed simulation framework. The numerical models of large arrays, used to define the scaling laws, suggest that the chosen topologies have a mainly stretching-dominated behavior─a hallmark of structurally efficient structures─where the modulus scales linearly with the relative density. By looking ahead, mimicking the characteristic microscale structure of crystalline materials will allow replicating the typical behavior of crystals at a larger scale, combining the hardening traits of metallurgy with the characteristic behavior of polymers and the advantage of lightweight architected structures, leading to novel materials with multiple functions.

The design of biomimetic porous scaffolds has been gaining attention in the biomedical sector lately. Shells, marine sponges, shark teeth, cancellous bone, sea urchin spine, and the armadillo armor structure are examples of biological systems that have already been studied to drive the design of innovative, porous, and multifunctional structures. Among these, triply periodic minimal surfaces (TPMSs) have attracted the attention of scientists for the fabrication of biomimetic porous scaffolds. The interest stems from their outstanding properties, which include mathematical controllable geometry features, highly interconnected porous architectures, high surface area to volume ratio, less stress concentration, tunable mechanical properties, and increased permeability. All these distinguishing features enable better cell adhesion, optimal integration to the surrounding tissue avoiding stress shieldings, a good permeability of fluid media and oxygen, and the possibility of vascularization. However, the sophisticated geometry of these TPMS-based structures has proven challenging to fabricate by conventional methods. The emergence of additive manufacturing (AM) and the enhanced manufacturing freedoms and flexibility it guarantees could solve some of the bottlenecks, thus leading to a surge of interest in designing and fabricating such structures in this field. Also, the feasibility of using AM technologies allows for obtaining size programmable TPMS printable in various materials, from polymers to metal alloys. Here, a comprehensive overview of 3D-printed TPMS porous structures is provided from a design for additive manufacturing (DfAM) and application perspective. First, design strategies, geometry design algorithms, and related topological optimization are introduced according to diverse requirements. Based on that, the performance control of TPMS and the pros and cons of the different AM processes for fabricating TPMS scaffolds are summarized. Lastly, practical applications of 3D-printed biomimetic TPMS porous structures for the biomedical field are presented to clarify the advantages and potential of such structures., Competing Interests: Declaration of Competing Interest The authors declare no competing interest., (Copyright © 2023. Published by Elsevier Inc.)

Research Question: In sperm samples with complete asthenozoospermia, pregnancies are achieved by intracytoplasmic sperm injection (ICSI), but this condition has a negative impact on fertilization and embryo development owing to the difficulty of identifying viable cells for oocyte injection. Is the selection of sperm cells with head birefringence properties under polarizing light a successful strategy to identify viable spermatozoa?, Design: This study included 192 ICSI cycles with complete asthenozoospermia (83 ejaculated and 109 testicular samples) performed under polarized light. Two types of sperm head birefringence were distinguished: partial (presumably reacted spermatozoa) and total (presumably intact acrosome). In some sperm cells, no birefringence was present. The main outcome of the study was the cumulative live birth rate (cLBR) per ICSI cycle., Results: Seventy-three deliveries resulted with 38.0% cLBR per ICSI cycle. The injection of birefringent spermatozoa led to significantly higher rates of fertilization, embryo development and implantation compared with the absence of birefringence (P < 0.001). Similarly, the resulting cLBR were 53.6% and 9.0%, respectively (P < 0.001). Spermatozoa with partial head birefringence yielded significantly higher fertilization and embryo utilization rates compared with total birefringence. The cLBR showed the same trend (62.7% and 46.7%, respectively, P = 0.048). Multiple logistic regression analysis showed the pattern of partial birefringence to be strongly associated with live birth rate., Conclusions: Immotile sperm cells with birefringence properties under polarized light have higher chances of inducing fertilization and embryo development compared with non-birefringent cells. In addition, a pattern of partial birefringence, associated with a reacted acrosome, is the strongest predictive factor for live birth delivery, both in ejaculated and testicular samples., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The insertion site of the internal tandem duplications (ITDs) in the FLT3 gene affects the sensitivity to tyrosine kinase inhibitors (TKIs) therapy in acute myeloid leukemia (AML). Patients with the ITD in the tyrosine kinase domain lack effective therapeutic options. Here, to identify genotype-driven strategies increasing the TKI therapy efficacy, we developed SignalingProfiler, a strategy supporting the integration of high-sensitive mass spectrometry-based (phospho)proteomics, RNA sequencing datasets with literature-derived signaling networks. The approach generated FLT3-ITD genotype-specific predictive models and revealed a conserved role of the WEE1-CDK1 axis in TKIs resistance. Remarkably, pharmacological inhibition of the WEE1 kinase synergizes and strengthens the pro-apoptotic effect of TKIs therapy in cell lines and patient-derived primary blasts. Finally, we propose a new molecular mechanism of TKIs resistance in AML and suggest the combination of WEE1 inhibitor and TKI as a therapeutic option to improve patients clinical outcome., (© 2022. The Author(s).)

Each year 65% of young athletes and 25% of physically active adults suffer from at least one musculoskeletal injury that prevents them from continuing with physical activity, negatively influencing their physical and mental well-being. The treatment of musculoskeletal injuries with the adhesive elastic kinesiology tape (KT) decreases the recovery time. Patients can thus recommence physical exercise earlier. Here, a novel KT based on auxetic structures is proposed to simplify the application procedure and allow personalization. This novel KT exploits the form-fitting property of auxetics as well as their ability to simultaneously expand in two perpendicular directions when stretched. The auxetic contribution is tuned by optimizing the structure design using analytical equations and experimental measurements. A reentrant honeycomb topology is selected to demonstrate the validity of the proposed approach. Prototypes of auxetic KT to treat general elbow pains and muscle tenseness in the forearm are developed., (© 2022. The Author(s).)