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Dual-Energy computed tomography (DECT) with its various advanced techniques, including Virtual Non-Contrast (VNC), effective atomic number (Z-eff) calculation, Z-maps, Iodine Density Index (IDI), and so on, holds great promise in the diagnosis and management of urogenital tumours. In this narrative review, we analyze the current status of knowledge of this technology to provide better lesion characterization, improve the staging accuracy, and give more precise treatment response assessments in relation to urological tumours. [ABSTRACT FROM AUTHOR]

Background: In atherothrombotic acute ischemic stroke (AIS), when the atheroma breaks down, the clot can incorporate foam cells (FCs). The identification of the correct etiology is paramount for secondary stroke prevention. This study aims to evaluate the presence of the FC in the arterial clot, and to determine whether patients with FCs and patients without FCs (NFCs) had different cerebrovascular risk factors, haemato-chemical parameters, and atherosclerotic disease incidence, in order to predict the etiological diagnosis. Methods: We collected 100 clots retrieved by mechanical thrombectomy from 495 consecutive AIS patients with large vessel occlusion. An expert pathologist evaluated the FC presence by histological examination stained with hematoxylin and eosin. Results: We observed FCs in 29/100 (29%) of retrieved clots and divided the patients into two groups, with/without FCs. The two groups had similar clinical and laboratory features, with a discrepancy between the FC presence in the clot and the clinical etiological diagnosis, even if not statistically significant. Conclusions: Our study showed the presence of FCs in approximately one-third of the retrieved clots, but the identification of the clot that presumably comes from the atheromatous plaque rupture tended to disagree with the clinical diagnosis. Future studies may reveal their potential to disclose clot origin or specific patient characteristics, guiding treatment options. [ABSTRACT FROM AUTHOR]

This study examined the impact of training load periodization on neuromuscular readiness in elite football players using the Locomotor Efficiency Index (LEI) as a measure of performance optimization. Throughout the 2021/22 and 2022/23 seasons, 106 elite male players (age: 19.5 ± 3.9 years) from an Italian professional football club were monitored using Global Positioning Systems (GPS) external load data. The LEI was derived from a machine learning model, specifically random forest regression, which compared predicted and actual PlayerLoad™ values to evaluate neuromuscular efficiency. Players were categorized by weekly LEI into three readiness states: bad, normal, and good. Analysis focused on the variation in weekly LEI relative to weekly load percentage variation (large decrease, moderate decrease, no variation, moderate increase, large increase), which included total distance, high-speed distance (above 25.2 km/h), and mechanical load, defined as the sum of accelerations and decelerations. Statistical analysis showed significant differences only with variations in total distance and mechanical load. Specifically, reducing weekly loads improved LEI in players in lower readiness states, while maintaining or slightly increasing loads promoted optimal readiness. This approach enables coaches to tailor training prescriptions more effectively, optimizing workload and recovery to sustain player performance throughout a demanding season. [ABSTRACT FROM AUTHOR]

The 16th European Network of Sport Education (ENSE) Forum was held in Rome, Italy at the University of Rome 'Foro Italico' on 21 and 22 September 2023. The Forum was organised under the theme Sport Education for Sustainable Development: The Euro-Med Perspective and featured presentations and input from over 40 researchers, officials and policymakers. In this report, we highlight the key themes addressed at the Forum and highlight some of the notable contributions at the event. [ABSTRACT FROM AUTHOR]

Deer antlers are the fastest growing tissue. Because they are based on proto-oncogenes, to avoid the risk of cancer, antlers evolved strong anticancer mechanisms, and thus their extract (DVA) is effective also against the few human tumours studied so far. We assessed whether DVA is a general anticancer compound by testing the direct effects in cells of different tumours: glioblastoma (GBM; lines U87MG and U251), colorectal (CRC; lines DLD-1, HT-29, SW480, and SW620), breast cancer (BRCA; lines MCF7, SKBR3, and PA00), and leukaemia (THP-1). DVA reduced the viability of tumours but not healthy cells (NHC; lines 293T and HaCaT). Mobility decreased at least for the longest test (72 h). Intraperitoneal/oral 200 mg DVA/kg administration in GBM xenograft mice for 28 d reduced tumour weight by 66.3% and 61.4% respectively, and it also reduced spleen weight (43.8%). In addition, tumours treated with DVA showed symptoms of liquefactive necrosis. Serum cytokines showed DVA up-regulated factors related to tumour fighting and down-regulated those related to inducing immune tolerance to the tumour. DVA shows general anticancer effects in the lines tested and, in GBM mice, also strong indirect effects apparently mediated by the immune system. DVA may contain a future anticancer medicine without secondary effects. [ABSTRACT FROM AUTHOR]

In this paper, we introduce an approach to the management of infectious disease diffusion through the formulation of a controlled compartmental SVIR (susceptible–vaccinated–infected–recovered) model. We consider a cost functional encompassing three distinct yet interconnected dimensions: the social cost, the disease cost, and the vaccination cost. The proposed model addresses the pressing need for optimized strategies in disease containment, incorporating both social control measures and vaccination campaigns. Through the utilization of advanced control theory, we identify optimal control strategies that mitigate disease proliferation while considering the inherent trade-offs among social interventions and vaccination efforts. Finally, we present the results from a simulation-based study employing a numerical implementation of the optimally controlled system through the forward–backward sweep algorithm. The baseline model considered incorporates parameters representative of typical values observed during the recent pandemic outbreak. [ABSTRACT FROM AUTHOR]

Defining successful aging continues to be a challenge, given the more recent transition from a bioscientific definition to a more comprehensive and holistic perspective. The holistic perspective may include more subjective aspects of aging. Research has shown that certain factors, such as lifestyle practices of spirituality, religious practice, meditation, communal support, and purposeful living, may be as influential as genetic factors in helping aging adults diminish age-related limitations. Spirituality and religiosity as lifestyle practice resources may assist older adults to mitigate the circumstances of chronic disease and positively impact aging, life quality, and well-being. Religious and/or spiritual communities, such as Women Religious and other clergy and monks, may provide insight into specific practices that promote social exchanges, life meaning, meditative practice, daily prayer, belief in the divine, communal living, and homogeneity of lifestyle that ultimately promote successful aging and resiliency into older age. Research has shown that lifestyle factors may mitigate diseases such as Alzheimer's and other forms of dementia in older age. The population of older adults has grown consistently on a global level since the turn of the century. This article review seeks to examine aging and emphasize, through research, which lifestyle practices and communities may impact the experience of aging in a more beneficial manner. [ABSTRACT FROM AUTHOR]

Hereditary breast and ovarian cancer (HBOC) syndrome is responsible for approximately 10% of breast cancers (BCs). The HBOC gene panel includes both high-risk genes, i.e., a four times higher risk of BC (BRCA1, BRCA2, PALB2, CDH1, PTEN, STK11 and TP53), and moderate-risk genes, i.e., a two to four times higher risk of BC (BARD1, CHEK2, RAD51C, RAD51D and ATM). Pathogenic germline variants (PGVs) in HBOC genes confer an absolute risk of BC that changes according to the gene considered. We illustrate and compare different BC risk estimation models, also describing their limitations. These models allow us to identify women eligible for genetic testing and possibly to offer surgical strategies for primary prevention, i.e., risk-reducing mastectomies and salpingo-oophorectomies. [ABSTRACT FROM AUTHOR]

Osteoporotic vertebral compression fractures (OVCFs) present a significant health concern, affecting a substantial portion of the older adult population worldwide. This narrative review explores the prevalence, diagnostic challenges and management strategies for OVCFs. Despite the increasing incidence and impact on morbidity and mortality, existing clinical guidelines lack consistency and clear diagnostic and therapeutic recommendations. The review addresses key questions faced by physicians dealing with older adult patients experiencing acute back pain, offering insights into triage, radiological assessments and classification systems. We propose a comprehensive algorithm for clearing OVCF, considering clinical presentation, radiological findings and morphological aspects. Emphasis is placed on the importance of medically treating osteoporosis alongside OVCF management. The review encompasses relevant literature from 1993 to 2023, provides a detailed discussion on triage issues and incorporates a clinically oriented classification system developed by the German Society for Orthopaedics and Trauma. The Material and Methods section outlines the extensive literature search carried out in PUBMED, encompassing clinical and experimental studies, systematic reviews and meta-analyses. The articles retained focused mainly on answering critical questions regarding radiological assessments, imaging modalities and the presence of a specific classification system for OVCFs. The review emphasises that the evaluation and management of OVCFs necessitates a multidisciplinary approach involving spine specialists and bone disease experts. It also addresses the role of conservative versus surgical treatments, with a focus on percutaneous vertebral augmentation. The conclusion summarises the algorithm derived for use in emergency departments and general practice, aiming to streamline OVCF management, reduce unnecessary examinations and ensure optimal patient care. The algorithm recommends primary diagnosis using computed tomography, with magnetic resonance imaging reserved for specific cases. The review advocates a holistic approach, integrating medical and surgical interventions to address the complex challenges posed by OVCFs in ageing populations. [ABSTRACT FROM AUTHOR]

Following the European recommendations on sustainable educational skills, a strong need has emerged to provide judo coaches with solid and updated knowledge, competences, and attitudes to train older judo practitioners (≥65 years old). This study illustrates the participatory research methodology used to develop and validate the content of the "Educating Judo Coaches for Older practitioners" (EdJCO) online educational programme. From seven countries, 22 judo and sport science experts of the EdJCO team engaged in a four-phase iterative process: (i) a systematic literature review; (ii) seven national focus groups involving 88 experts and an online survey involving 470 judo coaches; (iii) the online EDJCO programme development; and iv) the educational programme evaluation engaging 51 judo coaches as potential end-users. The EdJCO programme encompasses six modules on organization, aging, safety, physiology, psychology, and coaching methodology. Despite the overall positive evaluations, the experts were required to streamline the online programme to meet the coaches' demands, and to provide a comprehensive handbook to further deepen their knowledge. The cooperation among university scholars, experts from the International Judo Federation Academy, national-level sports clubs, and the judo coaches of older practitioners of different backgrounds and nationalities built a sustainable educational programme suitable for end-users to boost their teaching and training potential across their lifespan. [ABSTRACT FROM AUTHOR]

Pertuzumab and trastuzumab have been shown to improve the outcomes of patients with metastatic breast cancer, with a rate of left ventricular dysfunction of approximately 6%. We report the case of a postmenopausal woman who presented with Takotsubo syndrome during maintenance therapy with pertuzumab and trastuzumab, in association with fulvestrant (an anti-estrogen) and denosumab. After normalization of cardiac function, therapy with pertuzumab and trastuzumab was resumed in the absence of new cardiac toxicity. We report the first clinical case of Takotsubo syndrome during double anti-HER2 blockade in association with an antiestrogen. Furthermore, we show how anti-HER2 therapy can be safely resumed after the detection of Takotsubo syndrome. [ABSTRACT FROM AUTHOR]

Endovascular therapy (EVT) is the standard treatment for ischemic stroke caused by a large vessel occlusion (LVO). The effectiveness of EVT for distal medium vessel occlusions (MDVOs) is still uncertain, but newer, smaller devices show potential for EVT in MDVOs. The new Solitaire X 3 mm device offers a treatment option for MDVOs. Our study encompassed consecutive cases of primary and secondary MDVOs treated with the Solitaire X 3 mm stent-retriever as first-line EVT device between January and December 2022 at 12 European stroke centers. The primary endpoint was a first-pass near-complete or complete reperfusion, defined as a modified treatment in cerebral infarction (mTICI) score of 2c/3. Additionally, we examined reperfusion results, National Institutes of Health Stroke Scale (NIHSS) scores at 24 h and discharge, device malfunctions, complications and procedural technical parameters. Sixty-eight patients (38 women, mean age 72 ± 14 years) were included in our study. Median NIHSS at admission was 11 (IQR 6–16). In 53 (78%) cases, a primary combined approach was used as the frontline technique. Among all enrolled patients, first-pass mTICI 2c/3 was achieved in 22 (32%) and final mTICI 2c/3 in 46 (67.6%) patients after a median of 1.5 (IQR 1–2) passes. Final reperfusion mTICI 2b/3 was observed in 89.7% of our cases. We observed no device malfunctions. Median NIHSS at discharge was 2 (IQR 0–4), and no symptomatic intracranial hemorrhages were reported. Based on our analysis, the utilization of the Solitaire X 3 mm device appears to be both effective and safe for performing EVT in cases of MDVO stroke. [ABSTRACT FROM AUTHOR]

In water polo, the team's technical and tactical performance is determined by the sum of the players' activities. This study aimed to investigate the playing offensive performance of an Italian First League team performed during all matches (n = 19) of the 2021/22 championship using the Team Sport Assessment Procedure (TSAP). For all subjects (n = 15), gaining possession of the ball (received balls (RB) and conquered balls (CB)) and disposing of the ball (neutral balls (NB); lost balls (LB); offensive ball (OB) and successful Shots (SS)) parameters, as well as volume of play (VP), efficiency index (EI) and performance score (PS) indexes, were analyzed in relation to the playing positions, season phase, match location and final score difference. Multiple linear regression showed a significant association between the playing position and VP and PS. Perimetral players showed the highest VP (65%) and PS (66%) values, and center defenders showed the highest values of CB (30%), while center forwards gained the highest amount of exclusion when handling the ball (48%). Although they were not significant, the other contextual factors showed that season phase and match location could affect the TSAP indexes. For water polo coaches, the TSAP represents an effective tool to assess how players interpret the match. [ABSTRACT FROM AUTHOR]

Optimizing the anticoagulation therapy is of pivotal importance in patients with a malignant tumor, as venous thromboembolism (VTE) has become the second-leading cause of death in this population. Cancer can highly increase the risk of thrombosis and bleeding. Consequently, the management of cancer-associated VTE is complex. In recent years, translational research has intensified, and several studies have highlighted the role of inflammatory cytokines in cancer growth and progression. Simultaneously, the pleiotropic effects of anticoagulants currently recommended for VTE have emerged. In this review, we describe the anti-inflammatory and anticancer effects of both direct oral anticoagulants (DOACs) and low-molecular-weight heparins (LWMHs). [ABSTRACT FROM AUTHOR]

Judo coaches are urged to develop specific competencies and skills for addressing the special needs of older practitioners. Thus, the purpose of this study was to investigate the experts' opinions on judo training in late adulthood to develop sound educational programs for coaches of older judo practitioners. Overall, eighty-eight experts from an international consortium of judo and educational partners participated in national focus groups. During the focus groups, experts discussed five themes and generated statements pertinent to educate coaches to support older judo practitioners (e.g., benefits; necessary knowledge; risks; training groups definition; tools; and tests for monitoring training plans). The initial list of 262 statements was synthesized, validated, analyzed, and organized into a final list of 55 statements and six macro-areas: aging process (n = 10); safety and first aid (n = 6); physiology and fitness (n = 12); psychology and mental health (n = 11); organization and environment (n = 5); adapted judo teaching and training (n = 11). The present international eminence-based study, harmonizing diverse intercultural perspectives, highlighted the specific needs of older judo practitioners. The results of this study will contribute to the structure of a sound educational program for coaches of older judo practitioners to enhance the quality of older adults' sports experiences by linking safety, enjoyment, social interactions, and learning principles. [ABSTRACT FROM AUTHOR]

Migraine is a debilitating neurological condition affecting millions of people worldwide. Until a few years ago, preventive migraine treatments were based on molecules with pleiotropic targets, developed for other indications, and discovered by serendipity to be effective in migraine prevention, although often burdened by tolerability issues leading to low adherence. However, the progresses in unravelling the migraine pathophysiology allowed identifying novel putative targets as calcitonin gene-related peptide (CGRP). Nevertheless, despite the revolution brought by CGRP monoclonal antibodies and gepants, a significant percentage of patients still remains burdened by an unsatisfactory response, suggesting that other pathways may play a critical role, with an extent of involvement varying among different migraine patients. Specifically, neuropeptides of the CGRP family, such as adrenomedullin and amylin; molecules of the secretin family, such as pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP); receptors, such as transient receptor potential (TRP) channels; intracellular downstream determinants, such as potassium channels, but also the opioid system and the purinergic pathway, have been suggested to be involved in migraine pathophysiology. The present review provides an overview of these pathways, highlighting, based on preclinical and clinical evidence, as well as provocative studies, their potential role as future targets for migraine preventive treatment. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive degeneration of motor neurons (MNs). Astrocytes display a toxic phenotype in ALS, which results in MN damage. Glutamate (Glu)-mediated excitotoxicity and group I metabotropic glutamate receptors (mGluRs) play a pathological role in the disease progression. We previously demonstrated that in vivo genetic ablation or pharmacological modulation of mGluR5 reduced astrocyte activation and MN death, prolonged survival and ameliorated the clinical progression in the SOD1G93A mouse model of ALS. This study aimed to investigate in vitro the effects of mGluR5 downregulation on the reactive spinal cord astrocytes cultured from adult late symptomatic SOD1G93A mice. We observed that mGluR5 downregulation in SOD1G93A astrocytes diminished the cytosolic Ca2+ overload under resting conditions and after mGluR5 simulation and reduced the expression of the reactive glial markers GFAP, S100β and vimentin. In vitro exposure to an anti-mGluR5 antisense oligonucleotide or to the negative allosteric modulator CTEP also ameliorated the altered reactive astrocyte phenotype. Downregulating mGluR5 in SOD1G93A mice reduced the synthesis and release of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α and ameliorated the cellular bioenergetic profile by improving the diminished oxygen consumption and ATP synthesis and by lowering the excessive lactate dehydrogenase activity. Most relevantly, mGluR5 downregulation hampered the neurotoxicity of SOD1G93A astrocytes co-cultured with spinal cord MNs. We conclude that selective reduction in mGluR5 expression in SOD1G93A astrocytes positively modulates the astrocyte reactive phenotype and neurotoxicity towards MNs, further supporting mGluR5 as a promising therapeutic target in ALS. [ABSTRACT FROM AUTHOR]

Previous studies have shown that variation in PlayerLoad (PL) could be used to detect fatigue in soccer players. Machine learning techniques (ML) were used to develop a new locomotor efficiency index (LEI) based on the prediction of PL. Sixty-four elite soccer players were monitored during an entire season. GPS systems were employed to collect external load data, which in turn were used to predict PL during training/matches. Random Forest Regression (RF) produced the best performance (mean absolute percentage error = 0.10 ± 0.01) and was included in further analyses. The difference between the PL value predicted by the ML model and the real one was calculated, individualized for each player using a z-score transformation (LEI), and interpreted as a sign of fatigue (negative LEI) or neuromuscular readiness (positive LEI). A linear mixed model was used to analyze how LEI changed according to the period of the season, day of the week, and weekly load. Regarding seasonal variation, the lowest and highest LEI values were recorded at the beginning of the season and in the middle of the season, respectively. On a weekly basis, our results showed lower values on match day − 2, while high weekly training loads were associated with a reduction in LEI. [ABSTRACT FROM AUTHOR]

Chorioamnionitis (CA) at term of pregnancy can have an infectious and/or inflammatory origin and is associated with adverse outcomes. Triple I (intrauterine inflammation, infection, or both, TI) has been proposed to reduce the overdiagnosis of infection and neonatal overtreatment. The aim of this study is to identify clinical and histological variables that could predict adverse outcomes when TI is suspected and/or confirmed. This retrospective cohort study included 404 pregnancies (gestational age ≥ 37 weeks) that were divided into 5 all-inclusive and mutually exclusive groups. TI was defined according to the NICHD definition of 2015, and it could be confirmed (TI+) or not confirmed (TI−) via histological examination. Signs of infection/inflammation that did not conform to the definition of TI were classified as "clinical suspicion" and could be supported (CS+) or not supported (CS−) by histology. Cases of histological chorioamnionitis (HCA) without clinical manifestation represented a fifth group. Whole placental involvement (WPLI) was defined as a histological inflammation involving the maternal and fetal sides. There were 113 TI+, 30 TI−, 186 CS+, 35 CS−, and 40 isolated HCA cases. WPLI was diagnosed in 133 cases (39.2%). Composite neonatal outcome (CNO) occurred in 114 cases (28.2%) while composite maternal outcome (CMO) occurred in 192 cases (47.5%). Compared with CS+, TI+ was more predictive of CNO (p = 0.001), CMO (p < 0.001), and WPLI (p = 0.005). WPLI was related both to CNO (p < 0.001) and to CMO (p = 0.046). TI+ and WPLI showed similar sensitivity but different specificity in predicting CNO. At logistic regression, CNO was independently predicted by TI+ (OR 2.21; p = 0.001) and by WPLI (OR 2.23; p = 0.001). Compared with CS, TI is a better predictor of CNO and can be useful for the identification of newborns at risk. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is considered a relevant liver chronic disease. Variable percentages of NAFLD cases progress from steatosis to steatohepatitis (NASH), cirrhosis and, eventually, hepatocellular carcinoma (HCC). In this study, we aimed to deepen our understanding of expression levels and functional relationships between miR-182-5p and Cyld-Foxo1 in hepatic tissues from C57BL/6J mouse models of diet-induced NAFL/NASH/HCC progression. A miR-182-5p increase was detected early in livers as NAFLD damage progressed, and in tumors compared to peritumor normal tissues. An in vitro assay on HepG2 cells confirmed Cyld and Foxo1, both tumor-suppressor, as miR-182-5p target genes. According to miR-182-5p expression, decreased protein levels were observed in tumors compared to peritumor tissues. Analysis of miR-182-5p, Cyld and Foxo1 expression levels, based on datasets from human HCC samples, showed results consistent with those from our mouse models, and also highlighted the ability of miR-182-5p to distinguish between normal and tumor tissues (AUC 0.83). Overall, this study shows, for the first time, miR-182-5p overexpression and Cyld-Foxo1 downregulation in hepatic tissues and tumors from a diet-induced NAFLD/HCC mouse model. These data were confirmed by the analysis of datasets from human HCC samples, highlighting miR-182-5p diagnostic accuracy and demonstrating the need for further studies to assess its potential role as a biomarker or therapeutic target. [ABSTRACT FROM AUTHOR]

The thrombosis-related diseases are one of the leading causes of illness and death in the general population, and despite significant improvements in long-term survival due to remarkable advances in pharmacologic therapy, they continue to pose a tremendous burden on healthcare systems. The oxidative stress plays a role of pivotal importance in thrombosis pathophysiology. The anticoagulant and antiplatelet drugs commonly used in the management of thrombosis-related diseases show several pleiotropic effects, beyond the antithrombotic effects. The present review aims to describe the current evidence about the antioxidant effects of the oral antithrombotic therapies in patients with atherosclerotic disease and atrial fibrillation. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune-oncology has revolutionized the natural history of many cancers in the past decade, becoming a new therapeutic weapon. The identification of immune "checkpoints" (PD-1/CTLA-4) whose blockade stimulates anti-tumor immunity has changed outcomes for many ptients. However, immune checkpoint inhibitors (ICIs) produce novel response patterns across cancer types and can cause inflammatory side-effects known as immune-related adverse events (irAEs). Renal damage from ICIs is an infrequent event, and early diagnosis plays a key role in its treatment, so it is crucial to recognize and treat it early to avoid toxicities of all grades, as well as hospitalizations. Immunity plays a crucial role in fighting cancer, but tumours can evade the immune system and proliferate and metastasize. Enhancing immune responses is a new challenge in anticancer therapies. In this context, efficacy data are accumulating on immune checkpoint inhibitors and adjuvant therapies for various types of advanced-stage solid tumours. Unfortunately, immune-related adverse events are common. Although infrequent, renal toxicity may occur via several mechanisms and may require temporary or permanent drug suspension, renal biopsy, and/or immunosuppressive treatment. This short review aims to provide a practical approach to the multidisciplinary management of cancer patients with renal toxicity during treatment with immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Simple Summary: Molecular tumor boards (MTBs) aim to translate the results of genomic tests into clinical practice in order to set-up the most appropriate therapeutic strategy for the individual patient. Genomic tests represent a challenge for the Italian National Health System, which must set-up new paths for access to medicines and, at the same time, guarantee economic sustainability. Furthermore, the scientific and clinical skills of clinicians must be guaranteed to follow the complex and rapid evolution of cancer genetics and the availability of agnostic anticancer drugs. This review aims to analyze the role of MTBs in the management of patients with metastatic breast cancer (MBC). Molecular tumor boards (MTBs) are multidisciplinary groups that combine molecular and clinical data from cancer patients in order to formulate treatment recommendations for precision medicine. To date, there is insufficient data to support the use of singleplex or next-generation sequencing (NGS) technologies to select first-line therapy for patients with metastatic breast cancer (MBC), but considering the high number of level II alterations, according to the ESMO scale for clinical actionability of molecular targets (ESCAT), it is suggested to include patients in molecular screening programs in order to be able to offer targeted therapies for specific genomic alterations. This article aims at reviewing the most recent literature related to the most used methodologies/approaches for molecular diagnostics and variants' classification, summarizing the internationally published molecular screening studies in support of MTB activity and, in the end, discussing MTBs' current position and role in Italy, the number of which is increasing, also thanks to the thrust of institutions. [ABSTRACT FROM AUTHOR]

This systematic overview aimed to review studies investigating the benefits and risks of judo training in older people, and to explore practical methodological applications (Registration ID: CRD42021274825). Searches of EBSCOhost, ISI-WoS, and Scopus databases, with no time restriction up to December 2022, resulted in 23 records meeting the inclusion criteria. A quality assessment was performed through the following tools: ROBINS-I for 10 experimental studies, NIH for 7 observational studies, and AGREE-II for 6 methodological studies. A serious risk of bias emerged for 70% of the experimental studies, whereas 100% of the observational and 67% of the methodological studies presented a "fair" quality. When involving 1392 participants (63 ± 12 years; females: 47%), the studies investigated novice (n = 13), amateur/intermediate (n = 4), expert (n = 4), and unknown (n = 3) level judoka by means of device-based, self-reported, and visual evaluation measures. Mean training encompassed 2 ± 1 sessions. week−1 of 61 ± 17 min for 7 ± 6 months. In relation to judo training exposure and outcomes, three main themes emerged: (i) health (56% of studies; e.g., bones, anthropometry, quality of life); (ii) functional fitness (43%; e.g., balance, strength, walking speed); and iii) psychosocial aspects (43%; e.g., fear of falling, cognition, self-efficacy). Although the included studies presented relevant methodological weaknesses, the data support the positive effects of judo training with advancing age. Future research is needed to help coaches plan judo programs for older people. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of playing position and contextual factors (match outcome, final score difference, match location, travel duration, number of scored and conceded goals) on the internal match load, players’ perceived recovery and players’ well-being. The session-RPE (s-RPE), Perceived Recovery Scale (PRS) and Hooper Index (HI) of 17 male elite water polo players were monitored during all matches (regular season and play-out) of the 2021/22 Italian Serie A1 championship. Three separate, mixed linear models for repeated measures showed significant main effects: drawn compared to won matches led to higher s-RPE values (mean ± SE = 277 ± 17.6 vs. 237.3 ± 20.6), while longer travel duration (estimate = −0.148) and goals scored (estimate = −3.598) led to lower s-RPE values; balanced compared to unbalanced matches led to higher PRS values (mean ± SE = 6.8 ± 0.3 vs. 5.1 ± 0.4), while playing time (estimate = −0.041) and goals scored (estimate = −0.180) led to lower PRS values; higher scores of the HI were registered for regular season compared to the play-out (mean ± SE = 15.6 ± 0.9 vs. 13.5 ± 0.8). This study marks the importance of ecological and non-invasive monitoring tools to assess internal match load, recovery and the well-being of elite water polo players. [ABSTRACT FROM AUTHOR]

Featured Application: This work identifies a set of distinctive signs in handwriting movement performed by patients in the early stage of PD. The analysis here performed can be used for the design of a diagnostic protocol, comprising specific handwriting motor tasks. The analysis of specific features, depending on the task examined, could provide clinicians with a useful tool for supporting the early clinical diagnosis of the disease.Background: The analysis of handwriting movements to quantify motor and cognitive impairments in neurodegenerative diseases is increasingly attracting interest. Non-invasive and quick-to-administer tools using handwriting movement analysis can be used in early screening of Parkinson's disease (PD) and maybe in the diagnosis of other neurodegenerative disease. Theaim of this work is to identify the distinctive signs characterizing handwriting in the early stage of PD, in order to provide a diagnostic tool for the early detection of the disease. Compared to previous studies, here, we analyzed handwriting movements of patients on which the disease affects the contralateral side with respect to the one used for writing. Methods: We collected and analyzed a set of handwriting samples by PD patients and healthy subjects. Participants were asked to follow a novel protocol, containing handwriting patterns of various levels of complexity, using both familiar and unfamiliar movements. Results: We found that the signs characterizing the early stage of PD differ from those appearing in later stages. Our work provides evidence that early detection of PD, even when the disease affects mainly the contralateral side with respect to the one used for writing, could be achieved by analyzing specific features measured during the execution of specific handwriting tasks. Eventually, we found that patients' performance benefits from the execution of handwriting in specific conditions. Conclusions: The analysis provides the guidelines for the design of a diagnostic tool for the early detection of PD and some suggestions for reducing motor impairments in PD patients. [ABSTRACT FROM AUTHOR]

This study aimed at assessing the external [Player Load (PL), acceleration (ACC), changes of direction (COD), JUMP, and their relative values (PL/min; ACC/min; COD/min and JUMP/min)] and internal [percentage of the peak heart rate (%HRpeak) and the training load calculated with the session rating of perceived exertion (sRPE) method (sRPE-load)] loads of masters (senior citizen) basketball players during official games. Thirteen male basketball masters players (age: 66.6 ± 2.1 years; body mass: 89.9 ± 8.7 kg; stature: 183.7 ± 4.6 cm) were monitored during an official Lietuvos Krepsinio Veteranu Lyga (LKVL) 65-year game. Beside descriptive analysis, a chi-square goodness of fit test was adopted to assess the differences in the distribution within JUMP, ACC and COD classes of intensities (i.e., low, medium and high). The results revealed PL = 269.9 ± 83.3 AU and PL/min = 6.54 ± 1.29 AU/min. Moreover, significant differences (p < 0.001) in the distribution of the intensity classes were found for JUMP, ACC, and COD, with the lowest intensities as the most frequent. Finally, HRpeak = 81.7 ± 8.1% and sRPE-load = 148.9 ± 69.7 AU were found, with sRPE = ~3 AU. In conclusion, a low external load during an official basketball game was found compared to other basketball populations. Moreover, a high objective internal load did not correspond to a low perceived demand, which might increase the training adherence and motivation during long-term studies. [ABSTRACT FROM AUTHOR]

The growing attention to environmental issues is leading to an increasing integration of renewable energy sources into electrical grids. This integration process could contribute to power system decarbonization, supporting the diversification of primary energy sources and enhancing the security of energy supply, which is threatened by the uncertain costs of conventional energy sources. Despite these environmental and economical benefits, many technological and regulatory problems should be fixed in order to significantly increase the level of penetration of renewable power generators, which are connected to power transmission and distribution systems via power electronic interfaces. Indeed, these converter-interfaced generators (CIGs) perturb grid operation, especially those fueled by non-programmable energy sources (e.g., wind and solar generators), affecting the system stability and making power systems more vulnerable to dynamic perturbations. To face these issues, the conventional operating procedures based on pre-defined system conditions, which are currently adopted in power system operation tools, should be enhanced in order to allow the "online" solution of complex decision-making problems, providing power system operators with the necessary measures and alerts to promptly adjust the system. A comprehensive analysis of the most promising research directions and the main enabling technologies for addressing this complex issue is presented in this paper. [ABSTRACT FROM AUTHOR]

BCAAs supplementation has been widely used for post-exercise recovery. However, no evidence is currently available to answer the question of whether BCAAs supplementation can attenuate muscle damage and ameliorate recovery after a bout of change of direction (COD) sprinting, which is an exercise motion frequently used during team sport actions. This study aimed to assess the effect of BCAAs supplementation on muscle damage markers, subjective muscle soreness, neuromuscular performance, and the vascular health of collegiate basketball players during a 72 h recovery period after a standardized COD protocol. Participants orally received either BCAAs (0.17 g/kg BCAAs + 0.17 g/kg glucose) or placebo (0.34 g/kg glucose) supplementation before and immediately after a COD exercise protocol in a randomized, crossover, double-blind, and placebo-controlled manner. Creatine kinase increased immediately after exercise and peaked at 24 h, muscle soreness remained elevated until 72 h, whilst arterial stiffness decreased after exercise for both supplemented conditions. A negligibly lower level of interleukin-6 was found in the BCAAs supplemented condition. In conclusion, the results of this study do not support the benefits of BCAAs supplementation on mitigating muscle damage and soreness, neuromuscular performance, and arterial stiffness after COD for basketball players. [ABSTRACT FROM AUTHOR]

Simple Summary: Spinal meningiomas (SMs) are slow growing lesions, often occurring in middle- and old-aged patients. Few data about age-related prognostic factors are available in the literature to date. We analyzed a series of elderly patients undergoing surgery for a SM in the last twenty years in four different European tertiary referral centers. This work aimed to assess the surgical outcome and to identify possible outcome predictors. In this international multicentric retrospective study involving 72 patients older than ≥75 years, we highlight that functional preoperative score (according to modified McCormick scale) and age at surgery correlate with functional outcome. (1) Background: With the increasing life expectancy in the Western world, an increasing number of old patients presents with spinal meningioma. Considering the benign nature of these tumors, the functional outcome remains of great importance, since more people reach old age in general conditions of well-being and satisfactory autonomy. (2) Methods: We conducted an international multicenter retrospective study to investigate demographic, clinical and radiological data in a population of elderly patients (≥75 years of age) undergoing surgery for SM from January 2000 to December 2020 in four European referral centers. The aim was to identify prognostic and predictive factors for a good postoperative functional outcome. (3) Results: 72 patients were included in the study. Complete tumor resection (Simpson I or II) was achieved in 67 (95.7%) cases. Intraoperative complications were reported in 7 (9.9%) patients while postoperative complications were found in 12 (16.7%). An excellent general postoperative status (McCormick I and II) was achieved in 65.3%. Overall, surgical resection had a good impact on patients' functional outcome (86.1% either showing an improvement or maintaining a good preoperative status). Uni- and multivariate analyses found that both age and preoperative modified McCormick independently correlated with relative outcome (coeff = −0.058, p = 0.0251; coeff = 0.597, p < 0.0001) and with postoperative status (coeff = 0.058, p = 0.02507; coeff = 0.402, p = 0.00027), respectively. (4) Conclusions: Age and preoperative modified McCormick were found to be independent prognostic factors. Nevertheless, advanced age (≥75), per se, did not seem to contraindicate surgery, even in those with severe preoperative neurological deficits. The functional results sustain the need for surgical resection of SM in the elderly. [ABSTRACT FROM AUTHOR]

Simple Summary: This retrospective observational study aims at highlighting the response to pertuzumab, trastuzumab and docetaxel treatment (THP), without using anthracycline, in patients with HER2-positive early breast cancer. We add evidence to the suitability of THP in real life to reach higher pathological complete response rates, with a good safety profile for patients. An exploratory analysis of the mutational status of PIK3CA was performed as well, and 21% mutated samples were identified, with overall higher pCR rates in PIK3CA mutant patients and, particularly, in those who were THP-treated. Our original results open the door to further studies focused on more in-depth analysis of the molecular and clinical features related to the response to anthracycline-free neoadjuvant treatment in HER2-positive early breast cancer patients. HER2 is considered one of the most traditional prognostic and predictive biomarkers in breast cancer. Literature data confirmed that the addition of pertuzumab to a standard neoadjuvant chemotherapy backbone (either with or without anthracyclines), in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC), leads to a higher pathological complete response (pCR) rate, which is known to correlate with a better prognosis. In this retrospective analysis, 47 consecutive patients with HER2-positive EBC received sequential anthracyclines and taxanes plus trastuzumab (ATH) or pertuzumab, trastuzumab and docetaxel (THP). Despite the limited sample size, this monocentric experience highlights the efficacy (in terms of pCR) and safety of THP in the neoadjuvant setting of HER2-positive EBC as an anthracycline-free approach. Given the role of PIK3CA as a prognostic and therapeutic target in breast cancer, tumors were also analyzed to assess the PIK3CA mutational status. Thirty-eight out of forty-seven patients were evaluated, and PIK3CA variants were identified in 21% of tumor samples: overall, one mutation was detected in exon 4 (2.6%), two in exon 9 (5.3%) and four in exon 20 (10.5%). Of note, one sample showed concurrent mutations in exons 9 (codon 545) and 20 (codon 1047). Among patients reaching pCR (n = 13), 38.5% were PIK3CA mutants; on the other hand, among those lacking pCR (n = 25), just 12% showed PIK3CA variants. Regarding THP-treated mutant patients (n = 5), 80% reached pCR (three hormone-receptor-negative, one hormone-receptor-positive). Interestingly, the only patient not achieving pCR had a tumor with two co-occurring PIK3CA mutations. In conclusion, this study provides new evidence about the efficacy and good safety profile of THP, compared to the ATH regimen, as an anthracycline-free neoadjuvant treatment of HER2-positive EBC. Further studies on larger/multicentric cohorts are planned for more in-depth analysis to confirm our molecular and clinical results. [ABSTRACT FROM AUTHOR]

Purpose. Nerve growth factor efficacy was demonstrated for corneal lesions treatment, and recombinant human NGF (rhNGF) was approved for neurotrophic keratitis therapy. However, NGF-induced molecular responses in cornea are still largely unknown. We analyzed microRNAs expression in human epithelial corneal cells after time-dependent rhNGF treatment. Methods. Nearly 700 microRNAs were analyzed by qRT-PCR. MicroRNAs showing significant expression differences were examined by DIANA-miRpath v.3.0 to identify target genes and pathways. Immunoblots were performed to preliminarily assess the strength of the in silico results. Results. Twenty-one microRNAs (miR-26a-1-3p, miR-30d-3p, miR-27b-5p, miR-146a-5p, miR-362-5p, mir-550a-5p, mir-34a-3p, mir-1227-3p, mir-27a-5p, mir-222-5p, mir-151a-5p, miR-449a, let7c-5p, miR-337-5p, mir-29b-3p, miR-200b-3p, miR-141-3p, miR-671-3p, miR-324-5p, mir-411-3p, and mir-425-3p) were significantly regulated in response to rhNGF. In silico analysis evidenced interesting target genes and pathways, including that of neurotrophin, when analyzed in depth. Almost 80 unique target genes (e.g., PI3K, AKT, MAPK, KRAS, BRAF, RhoA, Cdc42, Rac1, Bax, Bcl2, FasL) were identified as being among those most involved in neurotrophin signaling and in controlling cell proliferation, growth, and apoptosis. AKT and RhoA immunoblots demonstrated congruence with microRNA expression, providing preliminary validation of in silico data. Conclusions. MicroRNA levels in response to rhNGF were for the first time analyzed in corneal cells. Novel insights about microRNAs, target genes, pathways modulation, and possible biological responses were provided. Importantly, given the putative role of microRNAs as biomarkers or therapeutic targets, our results make available data which might be potentially exploitable for clinical applications. [ABSTRACT FROM AUTHOR]

Mental fatigue can impair physical, technical, and tactical performance in sports. Since most previous research used general cognitive tasks to elicit mental fatigue, the aim of this study was to investigate whether a more sport-specific task could induce the effects of mental fatigue and impair the subsequent physical and technical performance in a soccer small-sided game. Ten soccer players performed two small-sided games on two different days in a crossover design. Before each small-sided game, they performed a video-based tactical task (30 min) and a control task (documentary watching, 30 min) in a randomized and counterbalanced order. Mental effort was measured through a visual analog scale after the tactical and control tasks. Subjective ratings of perceived exertion were assessed through the RPE questionnaire after the end of the SSG. Physical performance was assessed during the SSG through GPS technology. Results showed no differences (p > 0.05) in physical performance between the two conditions. None of the technical variables were negatively affected by the video-based tactical condition, with the number of total passes (p = 0.003; ES = 0.72 medium) and successful passes (p = 0.003; ES = 0.82 large) results even improved by the video-based tactical task. The mental effort required by the video-tactical task was significantly higher than the control task (p = 0.002; ES = 2.09 huge). However, overall RPE did not differ between conditions. The video-based tactical task did not elicit mental fatigue and did not impair subsequent physical and technical performance. The higher ecological validity of the task and the higher motivation of the participants might have contributed to the results. [ABSTRACT FROM AUTHOR]

This study aimed to assess the basketball ball-drills workload analyzing: (1) the effect of varying the number of players involved on physiological and technical demands; (2) the temporal changes in players' responses across bouts; and (3) the relationship of players' workload with their maturation status and training age. Twelve young male basketball players (mean ± SD; age 13.9 ± 0.7 years; height 1.76 ± 0.06 m; body mass 65.7 ± 12.5 kg; HRmax 202 ± 8 beat·min-1) completed three bouts of 4 min interspersed by 2 min of passive recovery of two vs. two and four vs. four ball-drills. The mean percentage of HRmax (%HRmax) and ratings of perceived exertion (RPE) were collected. Technical actions (TAs) (dribbles, passes, shots, interceptions, steals, rebounds, and turnovers) were calculated through notational analysis. Players' genitalia development (GD) and pubic hair (PH) growth were assessed using Tanner scale. Results showed a higher %HRmax (p = 0.018), RPE (p = 0.042), dribbles (p = 0.007), shots (p = 0.003), and rebounds (p = 0.006) in two vs. two compared to four vs. four condition. Furthermore, a statistical difference was found for %HRmax (p = 0.005) and number of passes (p = 0.020) between bouts. In addition, no correlation between GD, PH, and training age with %HRmax, RPE, and TAs was found. These findings suggest that variations of the number of players involved affect ball-drills workload and that ball-drills training intensity varies across bouts. Finally, ball-drills elicit an adequate training stimulus, regardless of players' maturation status and training age. [ABSTRACT FROM AUTHOR]

Land subsidence resulting from groundwater extractions is a global phenomenon adversely affecting many regions worldwide. Understanding the governing processes and mitigating associated hazards require knowing the spatial distribution of the implicated factors (piezometric levels, lithology, ground deformation), usually only known at discrete locations. Here, we propose a methodology based on the Kriging with External Drift (KED) approach to interpolate sparse point measurements of variables influencing land subsidence using high density InSAR measurements. In our study, located in the Alto Guadalentín basin, SE Spain, these variables are GPS vertical velocities and the thickness of compressible soils. First, we estimate InSAR and GPS rates of subsidence covering the periods 2003-2010 and 2004-2013, respectively. Then, we apply the KED method to the discrete variables. The resulting continuous GPS velocity map shows maximum subsidence rates of 13 cm/year in the center of the basin, in agreement with previous studies. The compressible deposits thickness map is significantly improved. We also test the coherence of Sentinel-1 data in the study region and evaluate the applicability of this methodology with the new satellite, which will improve the monitoring of aquifer-related subsidence and the mapping of variables governing this phenomenon. [ABSTRACT FROM AUTHOR]

The evolution of Eco Industrial Parks (EIPs) in Italy is a development opportunity for many territories and companies. Starting from the initial experiences in the 1980s, the Eco Industrial Parks model has spread throughout many of the central and northern regions of the country. The key element of Italian Eco Industrial Parks is the management body, an entity provided by national legislation to manage and coordinate companies and to develop more environmentally sustainable production practices. The survey results describe the role and activities of the management bodies concerning the actions implemented, the interaction with the main stakeholders and the resources and investments. The following research introduces an important environmental management experience implemented in Italy. [ABSTRACT FROM AUTHOR]

This study aimed to analyze different predictive analytic techniques to forecast the risk of muscle strain injuries (MSI) in youth soccer based on training load data. Twenty-two young soccer players (age: 13.5 ± 0.3 years) were recruited, and an injury surveillance system was applied to record all MSI during the season. Anthropometric data, predicted age at peak height velocity, and skeletal age were collected. The session-RPE method was daily employed to quantify internal training/match load, and monotony, strain, and cumulative load over the weeks were calculated. A countermovement jump (CMJ) test was submitted before and after each training/match to quantify players' neuromuscular fatigue. All these data were used to predict the risk of MSI through different data mining models: Logistic Regression (LR), Random Forest (RF), Support Vector Machine (SVM). Among them, SVM showed the best predictive ability (area under the curve = 0.84 ± 0.05). Then, Decision tree (DT) algorithm was employed to understand the interactions identified by the SVM model. The rules extracted by DT revealed how the risk of injury could change according to players' maturity status, neuromuscular fatigue, anthropometric factors, higher workloads, and low recovery status. This approach allowed to identify MSI and the underlying risk factors. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is a chronic metabolic disorder affecting almost half a billion people worldwide. Impaired function of pancreatic β-cells is both a hallmark of T2D and an underlying factor in the pathophysiology of the disease. Understanding the cellular mechanisms regulating appropriate insulin secretion has been of long-standing interest in the scientific and clinical communities. To identify novel genes regulating insulin secretion we developed a robust arrayed siRNA screen measuring basal, glucose-stimulated, and augmented insulin secretion by EndoC-βH1 cells, a human β-cell line, in a 384-well plate format. We screened 521 candidate genes selected by text mining for relevance to T2D biology and identified 23 positive and 68 negative regulators of insulin secretion. Among these, we validated ghrelin receptor (GHSR), and two genes implicated in endoplasmic reticulum stress, ATF4 and HSPA5. Thus, we have demonstrated the feasibility of using EndoC-βH1 cells for large-scale siRNA screening to identify candidate genes regulating β-cell insulin secretion as potential novel drug targets. Furthermore, this screening format can be adapted to other disease-relevant functional endpoints to enable large-scale screening for targets regulating cellular mechanisms contributing to the progressive loss of functional β-cell mass occurring in T2D. [ABSTRACT FROM AUTHOR]

Vaccines have represented the breakthrough in the fight against COVID-19. Based on reported headache attacks after vaccination in randomized controlled trials, we focused on the effects of COVID-19 vaccine administration on the migraine population, using an online questionnaire published on Italian Facebook groups oriented to headache patients. We collected data about the demographics and clinical parameters of migraine severity, COVID-19 infection, vaccination, and characteristics of headaches following vaccination. Out of 841 migraine patients filling in the questionnaire, 66.47% and 60.15% patients experienced a headache attack (from 1 hour to 7 days) after the first and the second vaccine dose, respectively. The main finding concerns headaches perceived by 57.60% of patients: attacks following vaccination were referred to as more severe (50.62% of patients), long-lasting (52.80% of patients) and hardwearing (49.69% of patients) compared to the usually experienced migraine attacks. This could be related to the production of inflammatory mediators such as type Iβ interferon. Considering the high prevalence of migraine in the general population, awareness of the possibility of headaches worsening following COVID-19 vaccination in these patients may allow both patients and clinicians to face this clinical entity with conscious serenity, and to reduce the waste of resources towards inappropriate health-care. [ABSTRACT FROM AUTHOR]

The detection of circulating microRNA (miRNA)-based biomarkers represents an innovative, non-invasive method for the early detection of cancer. However, the low concentration of miRNAs released in body fluids and the difficult identification of the tumor site have limited their clinical use as effective cancer biomarkers. To evaluate if ultrasound treatment could amplify the release of extracellular cancer biomarkers, we treated a panel of prostate cancer (PCa) cell lines with an ultrasound-based prototype and profiled the release of miRNAs in the extracellular space, with the aim of identifying novel miRNA-based biomarkers that could be used for PCa diagnosis and the monitoring of tumor evolution. We provide evidence that US-mediated sonoporation amplifies the release of miRNAs from both androgen-dependent (AD) and -independent (AI) PCa cells. We identified four PCa-related miRNAs, whose levels in LNCaP and DU145 supernatants were significantly increased following ultrasound treatment: mir-629-5p, mir-374-5p, mir-194-5p, and let-7d-5p. We further analyzed a publicly available dataset of PCa, showing that the serum expression of these novel miRNAs was upregulated in PCa patients compared to controls, thus confirming their clinical relevance. Our findings highlight the potential of using ultrasound to identify novel cell-free miRNAs released from cancer cells, with the aim of developing new biomarkers with diagnostic and predictive value. [ABSTRACT FROM AUTHOR]

We devise a theoretical model to shed light on the dynamics leading to toxic relationships. We investigate what intervention policy people could advocate to protect themselves and to reduce suffocating addiction in order to escape from physical or psychological abuses either inside family or at work. Assuming that the toxic partner's behavior is exogenous and that the main source of addiction is income or wealth we find that an asymptotically stable equilibrium with positive love is always possible. The existence of a third unconditionally reciprocating part as a benchmark, i.e., presence of another partner, support from family, friends, private organizations in helping victims, plays an important role in reducing the toxic partner's appeal. Analyzing our model, we outline the conditions for the best policy to heal from a toxic relationship. [ABSTRACT FROM AUTHOR]

The advent of Next Generation Sequencing technologies brought with it the discovery of several microRNA (miRNA) variants of heterogeneous lengths and/or sequences. Initially ascribed to sequencing errors/artifacts, these isoforms, named isomiRs, are now considered non-canonical variants that originate from physiological processes affecting the canonical miRNA biogenesis. To date, accurate IsomiRs abundance, biological activity, and functions are not completely understood; however, the study of isomiR biology is an area of great interest due to their high frequency in the human miRNome, their putative functions in cooperating with the canonical miRNAs, and potential for exhibiting novel functional roles. The discovery of isomiRs highlighted the complexity of the small RNA transcriptional landscape in several diseases, including cancer. In this field, the study of isomiRs could provide further insights into the miRNA biology and its implication in oncogenesis, possibly providing putative new cancer diagnostic, prognostic, and predictive biomarkers as well. In this review, a comprehensive overview of the state of research on isomiRs in different cancer types, including the most common tumors such as breast cancer, colorectal cancer, melanoma, and prostate cancer, as well as in the less frequent tumors, as for example brain tumors and hematological malignancies, will be summarized and discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients affected by spinal meningioma globally exhibit an excellent postoperative functional outcome despite tumor size and severity of spinal cord compression. This work aims to analyze the impact of tumor size and other radiological findings on clinical functional preoperative status and postoperative outcome. In this multicentric retrospective study involving 90 adult patients, we found that spinal cord and tumor occupancy as well as cord compression and tumor volume are correlated with low preoperative functional status. Higher tumor occupancy and tumor-canal volume ratio corresponded to lower postoperative neurological recovery. Cord re-expansion did not show any correlation with postoperative outcome, while preoperative signs of cord myelopathy were predictors of worse postoperative outcome. These findings suggest that these radiological features should be taken into consideration during preoperative counselling. Background: Radiological parameters predicting the postoperative neurological outcome after resection of a spinal meningioma (SM) are poorly studied, with controversial results. Methods: Observational multicenter cohort (2011–2018) of adult patients undergoing surgery for resection of SM. Tumor-canal volume ratio (TCR), the areas related to the cord and tumor occupancy at maximum compression, the presence of dural tail, calcifications, signs of myelopathy, and postoperative cord expansion were compared with the modified McCormick scale (mMCS) preoperative and at follow-up. Results: In the cohort (n = 90 patients), cord and tumor occupancy as well as cord compression and tumor volume showed a correlation with preoperative mMCS (p < 0.05, R −0.23; p < 0.001, R 0.35; p < 0.005, R −0.29; p < 0.001, R 0.42). Cord occupancy had a strong correlation with cord compression (p < 0.001, R 0.72). Tumor occupancy and TCR were correlated with relative outcome at follow-up (p < 0.005 R 0.3; p < 0.005 R 0.29). No correlation was found between cord re-expansion and clinical outcome at follow-up. Finally, a correlation was shown between preoperative signs of cord myelopathy and mMCS (p < 0.05 R 0.21) at follow-up. Conclusions: Larger tumors showed lower preoperative functional status and a worse clinical outcome. Moreover, preoperative T2 cord signal changes are correlated with a poorer outcome. [ABSTRACT FROM AUTHOR]

Despite recent advances, the causes of and effective therapies for pediatric chronic cholestatic diseases remain elusive, and many patients progress to liver failure and need liver transplantation. Malnutrition is a common complication in these patients and is a well-recognized, tremendous challenge for the clinician. We undertook a narrative review of both recent and relevant older literature, published during the last 20 years, for studies linking nutrition to pediatric chronic cholestasis. The collected data confirm that malnutrition and failure to thrive are associated with increased risks of morbidity and mortality, and they also affect the outcomes of liver transplantation, including long-term survival. Malnutrition in children with chronic liver disease is multifactorial and with multiple potential nutritional deficiencies. To improve life expectancy and the quality of life, patients require careful assessments and appropriate management of their nutritional statuses by multidisciplinary teams, which can identify and/or prevent specific deficiencies and initiate appropriate interventions. Solutions available for the clinical management of these children in general, as well as those directed to specific etiologies, are summarized. We particularly focus on fat-soluble vitamin deficiency and malnutrition due to fat malabsorption. Supplemental feeding, including medium-chain triglycerides, essential fatty acids, branched-chain amino acids, and the extra calories needed to overcome the consequences of anorexia and high energy requirements, is reviewed. Future studies should address the need for further improving commercially available and nutritionally complete infant milk formulae for the dietary management of this fragile category of patients. The aid of a specialist dietitian, educational training regarding nutritional guidelines for stakeholders, and improving family nutritional health literacy appear essential. [ABSTRACT FROM AUTHOR]

Stand-alone (SA) zero-profile implants are an alternative to cervical plating (CP) in anterior cervical discectomy and fusion (ACDF). In this study, we investigate differences in surgical outcomes between SA and CP in ACDF. We conducted a retrospective analysis of 166 patients with myelopathy and/or radiculopathy who had ACDF with SA or CP from Jan 2013–Dec 2016. We measured surgical outcomes including Bazaz dysphagia score at 3 months, Nurick grade at last follow-up, and length of hospital stay. 166 patients (92F/74M) were reviewed. 92 presented with radiculopathy (55%), 37 with myelopathy (22%), and 37 with myeloradiculopathy (22%). The average operative time with CP was longer than SA (194 ± 69 vs. 126 ± 46 min) (p < 0.001), as was the average length of hospital stay (2.1 ± 2 vs. 1.5 ± 1 days) (p = 0.006). At 3 months, 82 patients (49.4%) had a follow-up for dysphagia, with 3 patients reporting mild dysphagia and none reporting moderate or severe dysphagia. Nurick grade at last follow-up for the myelopathy and myeloradiculopathy cohorts improved in 63 patients (85%). Prolonged length of stay was associated with reduced odds of having an optimal outcome by 0.50 (CI = 0.35–0.85, p = 0.003). Overall, we demonstrate that there is no significant difference in neurological outcome or rates of dysphagia between SA and CP, and that both lead to overall improvement of symptoms based on Nurick grading. However, we also show that the SA group has shorter length of hospital stay and operative time compared to CP. [ABSTRACT FROM AUTHOR]

(1) Background: The elevation of glucose metabolism is linked to high-grade gliomas such as glioblastoma multiforme (GBM). The high glycolytic phenotype is associated with cellular proliferation and resistance to treatment with chemotherapeutic agents in GBM. MicroRNA-542-3p (miR-542-3p) has been implicated in several tumors including gliomas. However, the role of miR-542-3p in glucose metabolism in human gliomas remains unclear; (2) Methods: We measured the levels of cellular proliferation in human glioma cells. We measured the glycolytic activity in miR-542-3p knockdown and over-expressed human glioma cells. We measured the levels of miR-542-3p and HK2 in glioma tissues from patients with low- and high-grade gliomas using imaging analysis; (3) Results: We show that knockdown of miR-542-3p significantly suppressed cellular proliferation in human glioma cells. Knockdown of miR-542-3p suppressed HK2-induced glycolytic activity in human glioma cells. Consistently, over-expression of miR-542-3p increased HK2-induced glycolytic activity in human glioma cells. The levels of miR-542-3p and HK2 were significantly elevated in glioma tissues of patients with high-grade gliomas relative to that in low-grade gliomas. The elevation of HK2 levels in patients with high-grade gliomas were positively correlated with the high levels of miR-542-3p in GBM and low-grade gliomas (LGG) based on the datasets from the Cancer Genome Atlas (TCGA) database. Moreover, the high levels of miR-542-3p were associated with poor survival rate in the TCGA database; (4) Conclusions: miR-542-3p contributes to the HK2-mediated high glycolytic phenotype in human glioma cells. [ABSTRACT FROM AUTHOR]