The use of synthetic fungicides to control fungal diseases has growing limitations due to eco-toxicological risks. Therefore, it is necessary to replace or integrate high risk chemicals with safer ...tools for human health and environment. Consequently, research on the selection, evaluation, characterization, and use of biocontrol agents (BCAs) has consistently increased in the last decades. BCA formulates, particularly in some countries, are still scarce in coping with the growing demand for their use in sustainable agricultural management. To foster development and utilization of new effective bioformulates, there is a need to optimize BCA activity, to share knowledge on their formulation processes and to simplify the registration procedures. Studies based on new molecular tools can significantly contribute to achieve such objectives. The present review provides the state of the art on biocontrol of fungal plant diseases with special emphasis on (i) features of the most studied BCAs; (ii) key strategies to optimize selection and use of BCAs (iii); mechanisms of action of the main BCAs; (iv) molecular tools and metagenomic studies in the selection and use of BCAs; (v) main issues and constraints in the registration and commercialization of BCAs, and (vi) perspectives in the biocontrol of fungal plant diseases.
Clinical outcome remains poor in patients with high-risk neuroblastoma, in which chemoresistant relapse is common following high-intensity conventional multimodal therapy. Novel treatment approaches ...are required. Although recent genomic profiling initiatives have not revealed a high frequency of mutations in any significant number of therapeutically targeted genes, two exceptions, amplification of the MYCN oncogene and somatically acquired tyrosine kinase domain point mutations in anaplastic lymphoma kinase (ALK), present exciting possibilities for targeted therapy. In contrast with the situation with ALK, in which a robust pipeline of pharmacologic agents is available from early clinical use in adult malignancy, therapeutic targeting of MYCN (and MYC oncoproteins in general) represents a significant medicinal chemistry challenge that has remained unsolved for two decades. We review the latest approaches envisioned for blockade of ALK activity in neuroblastoma, present a classification of potential approaches for therapeutic targeting of MYCN, and discuss how recent developments in targeting of MYC proteins seem to make therapeutic inhibition of MYCN a reality in the clinic.
Diving saves are the main duty of football goalkeepers. Few biomechanical investigations of dive techniques have been conducted, none in a sport-specific environment. The present study investigated ...the characteristics of goalkeepers’ dive in preferred (PS) and non-preferred (nPS) side through an innovative wearables-plus-principal-component analysis (PCA) approach. Nineteen competitive academy goalkeepers (16.5 ± 3.0 years) performed a series of high and low dives on their PS and nPS. Dives were performed in a regular football goal on the pitch. Full-body kinematics were collected through 17 wearable inertial sensors (MTw Awinda, Xsens). PCA was conducted to reduce data dimensionality (input matrix 310,878 datapoints). PCA scores were extracted for each kinematic variable and compared between PS and nPS if their explained variability was >5%. In high dive, participants exhibited greater hip internal rotation and less trunk lateral tilt (p < 0.047, ES > 0.39) in PS than nPS. In low dives, players exhibited greater ipsilateral hip abduction dominance and lower trunk rotation (p < 0.037, ES > 0.40) in PS than nPS. When diving on their nPS, goalkeepers adopted sub-optimal patterns with less trunk coordination and limited explosiveness. An ecological testing through wearables and PCA might help coaches to inspect relevant diving characteristics and improve training effectiveness.
Embryonal precursors of Wilms tumor Coorens, Tim H H; Treger, Taryn D; Al-Saadi, Reem ...
Science,
12/2019, Letnik:
366, Številka:
6470
Journal Article
Recenzirano
Odprti dostop
Adult cancers often arise from premalignant clonal expansions. Whether the same is true of childhood tumors has been unclear. To investigate whether Wilms tumor (nephroblastoma; a childhood kidney ...cancer) develops from a premalignant background, we examined the phylogenetic relationship between tumors and corresponding normal tissues. In 14 of 23 cases studied (61%), we found premalignant clonal expansions in morphologically normal kidney tissues that preceded tumor development. These clonal expansions were defined by somatic mutations shared between tumor and normal tissues but absent from blood cells. We also found hypermethylation of the
locus, a known driver of Wilms tumor development, in 58% of the expansions. Phylogenetic analyses of bilateral tumors indicated that clonal expansions can evolve before the divergence of left and right kidney primordia. These findings reveal embryonal precursors from which unilateral and multifocal cancers develop.
GD2 targeting CAR T cells for neuroblastoma Anderson, John; Barone, Giuseppe; Zehner, Alexandra
EJC paediatric oncology,
December 2024, 2024-12-00, 2024-12-01, Letnik:
4
Journal Article
Recenzirano
Odprti dostop
Treatment of neuroblastoma is a significant clinical unmet need in paediatric oncology epitomised by high-risk disease in which relapse is common and outcomes for children with relapse or primary ...refractory disease are typically poor, with 4-year progression-free survival for relapse/refractory disease of 6 %. Immunotherapy targeting disialoganglioside GD2 using monoclonal antibodies (mAb) has become a component of standard of care treatment in neuroblastoma following published studies that have demonstrated clinical activity and survival benefit associated with this treatment. Hence a number of research groups have developed and clinically evaluated chimeric antigen receptor gene modified T cells (CAR-T cells) targeting GD2 in patients with relapsed and refractory neuroblastoma. Preclinical and clinical results using a range of receptor technologies and immune effectors have demonstrated the basic safety and feasibility of this approach, progressing into clinical data exhibiting promise for sustained patient benefit.
•Neuroblastoma represents a significant clinical unmet need in paediatric oncology.•GD2 is a well-recognised and validated target antigen for neuroblastoma.•CAR-T cells targeting GD2 are a tractable novel therapeutic approach for refractory neuroblastoma.•GD2 CAR-T cells need engineering solutions for sustained clinical benefits.
The aim of the present case report was to provide a longitudinal functional assessment of a patient with transfemoral amputation from the preoperative status with socket-type prosthesis to one year ...after the osseointegration surgery. A 44 years-old male patient was scheduled for osseointegration surgery 17 years after transfemoral amputation. Gait analysis was performed through 15 wearable inertial sensors (MTw Awinda, Xsens) before surgery (patient wearing his standard socket-type prosthesis) and at 3-, 6-, and 12-month follow-ups after osseointegration. ANOVA in Statistical Parametric Mapping was used to assess the changes in amputee and sound limb hip and pelvis kinematics. The gait symmetry index progressively improved from the pre-op with socket-type (1.14) to the last follow-up (1.04). Step width after osseointegration surgery was half of the pre-op. Hip flexion-extension range significantly improved at follow-ups while frontal and transverse plane rotations decreased (
< 0.001). Pelvis anteversion, obliquity, and rotation also decreased over time (
< 0.001). Spatiotemporal and gait kinematics improved after osseointegration surgery. One year after surgery, symmetry indices were close to non-pathological gait and gait compensation was sensibly decreased. From a functional point of view, osseointegration surgery could be a valid solution in patients with transfemoral amputation facing issues with traditional socket-type prosthesis.
It is known that the energy transition can be achieved not only with the use of renewable energy sources but also with a new conception and management of the electricity system. Renewable energy ...communities are then introduced as organizations for maximizing the self-consumption of energy produced from renewable energy sources. To ensure that these energy communities can operate, there is a need for enabling technologies that allow for monitoring, data and algorithms processing as well as the enabling of the same algorithms. There exists a huge confusion in the actual technologies useful to implement the energy communities. This paper first describes and groups the main enabling technologies, analyzing the services that can be offered. The scope is to emphasize the importance of having accurate, efficient and effective technologies that allow the implementation of such communities, underlining how such technologies interact with each other. Using such technologies is important to observing the possible technical and energetic results; indeed, use cases concerning the use of these enabling technologies are proposed and analyzed, showing their operating and their good environmental and energy impact.
Aim of the study was to evaluate sagittal parameters modifications, with particular interest in thoracic kyphosis, in patients affected by adolescent idiopathic scoliosis (AIS) comparing hybrid and ...all-screws technique. From June 2010 to September 2018, 145 patients were enrolled. Evaluation included: Lenke classification, Risser scale, coronal Cobb angle, thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS). Patients were divided in two groups (1 all-screws and 2 hybrid); a further division, in both groups, was done considering preoperative TK values. Descriptive and inferential statistical analysis was conducted. 99 patients were in group 1, 46 in group 2 (mean follow-up 3.7 years). Patients with a normo-kyphotic profile developed a little variation in TK (Δ pre-post = 2.4° versus - 2.0° respectively). Hyper-kyphotic subgroups had a tendency of restoring a good sagittal alignment. Hypo-kyphotic subgroups, patients treated with all-screw implants developed a higher increase in TK mean Cobb angle (Δ pre-post = 10°) than the hybrid subgroup (Δ pre-post = 5.4°) (p = 0.01). All-screws group showed better results in restoring sagittal alignment in all subgroups compared to hybrid groups, especially in hypo-TK subgroup, with the important advantage to give better correction on coronal plane.
Purpose
Chin-on-chest deformity is a rare and severe condition mostly related with ankylosing spondylitis, traumas and/or cervical spine surgery. We present a case of 69 years old woman with a rare ...form of chin-on-chest secondary to dropped head syndrome (DHS), developed after radiotherapy for Hodgkin disease. In addition, we reviewed the few publications about this specific condition; management and surgical treatment of DHS are discussed.
Methods
We performed a pedicle subtraction osteotomy (PSO) and stabilization through a posterior approach. Intraoperative monitoring using motor and somatosensory evoked potentials and wake-up test were carried out.
Results
At 19th month follow-up, the patient reported a significant improvement of cervical pain, dysphagia and respiratory difficulty and a complete restoration of the neurological impairment. The achieved correction was successful and the patient was very satisfied by the restoration of forward gaze.
Conclusions
DHS is a very rare post-radiotherapy complication; there is lack of evidences in literature about its management. The only definitive treatment seems to be surgical intervention. PSO is a valid therapeutic option when fixed chin-on-chest deformity occurs; although it is a demanding technique and it presents high rate of complications, the actual neurological monitoring methods provide more intraoperative safety.
Osteoporosis is a major health problem in post-menopausal women (PMW). Exercise training is considered a cost-effective strategy to prevent osteoporosis in middle aged-older people. The purpose of ...this study is to summarize the effect of exercise on BMD among PMW. A comprehensive search of electronic databases was conducted through PubMed, Scopus, Web of Science, Cochrane, Science Direct, Eric, ProQuest, and Primo. BMD changes (standardized mean differences: SMD) of the lumbar spine (LS) femoral neck (FN) and/or total hip were considered as outcome measures. After subgroup categorization, statistical methods were used to combine data and compare subgroups. Seventy-five studies were included. The pooled number of participants was 5,300 (intervention group:
n
= 2,901, control group:
n
= 2,399). The pooled estimate of random effect analysis was SMD = 0.37, 95%-CI: 0.25–0.50, SMD = 0.33, 95%-CI: 0.23–0.43, and SMD = 0.40, 95%-CI: 0.28–0.51 for LS, FN, and total Hip-BMD, respectively. In the present meta-analysis, there was a significant (
p
< 0.001), but rather low effect (SMD = 0.33–0.40) of exercise on BMD at LS and proximal femur. A large variation among the single study findings was observed, with highly effective studies but also studies that trigger significant negative results. These findings can be largely attributed to differences among the exercise protocols of the studies. Findings suggest that the true effect of exercise on BMD is diluted by a considerable amount of studies with inadequate exercise protocols.
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