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Background: Regular and consistent disease assessment could provide a clearer picture of burden in generalised myasthenia gravis (gMG) and improve patient care; however, the use of assessment tools in practice lacks standardisation. This modified Delphi approach was taken to review current evidence on assessment tool use in gMG and develop expert‐derived consensus recommendations for good practice. Methods: A European expert panel of 15 experienced gMG neurologists contributed to development of this consensus, four of whom formed a lead Sub‐committee. The PICO (Population, Intervention, Control, Outcomes) framework was used to define six clinical questions on gMG assessment tools, a systematic literature review was conducted, and evidence‐based statements were developed. According to a modified Delphi voting process, consensus was reached when ≥70% of the experts rated agreement with a statement as ≥8 on a scale of 1–10. Results: Eighteen expert‐ and evidence‐based consensus statements based on six themes were developed. Key recommendations include: consistent use of the Myasthenia Gravis Activities of Daily Living score (MG‐ADL) across clinical settings, followed by a simple question (e.g., Patient Acceptable Symptom State [PASS]) or scale to determine patient satisfaction in clinical practice; use of a Quantitative Myasthenia Gravis [QMG] or quality of life [QoL] assessment when the MG‐ADL indicates disease worsening; and consideration of symptom state to determine the timing and frequency of recommended assessments. Expert panel consensus was reached on all 18 statements after two voting rounds. Conclusions: This process provided evidence‐ and expert consensus‐based recommendations for the use of objective and subjective assessment tools across gMG research and care to improve management and outcomes for patients. [ABSTRACT FROM AUTHOR]

Objective: The dentato‐thalamo‐cortical tract (DTT) is the main cerebellar efferent pathway. Degeneration of the DTT is a core feature of Friedreich ataxia (FRDA). However, it remains unclear whether DTT disruption is spatially specific, with some segments being more impacted than others. This study aimed to investigate microstructural integrity along the DTT in FRDA using a profilometry diffusion MRI (dMRI) approach. Methods: MRI data from 45 individuals with FRDA (mean age: 33.2 ± 13.2, Male/Female: 26/19) and 37 healthy controls (mean age: 36.5 ± 12.7, Male/Female:18/19) were included in this cross‐sectional multicenter study. A profilometry analysis was performed on dMRI data by first using tractography to define the DTT as the white matter pathway connecting the dentate nucleus to the contralateral motor cortex. The tract was then divided into 100 segments, and dMRI metrics of microstructural integrity (fractional anisotropy, mean diffusivity and radial diffusivity) at each segment were compared between groups. The process was replicated on the arcuate fasciculus for comparison. Results: Across all diffusion metrics, the region of the DTT connecting the dentate nucleus and thalamus was more impacted in FRDA than downstream cerebral sections from the thalamus to the cortex. The arcuate fasciculus was minimally impacted. Interpretation: Our study further expands the current knowledge about brain involvement in FRDA, showing that microstructural abnormalities within the DTT are weighted to early segments of the tract (i.e., the superior cerebellar peduncle). These findings are consistent with the hypothesis of DTT undergoing anterograde degeneration arising from the dentate nuclei and progressing to the primary motor cortex. [ABSTRACT FROM AUTHOR]

Background: The dentate nuclei of the cerebellum are key sites of neuropathology in Friedreich ataxia (FRDA). Reduced dentate nucleus volume and increased mean magnetic susceptibility, a proxy of iron concentration, have been reported by magnetic resonance imaging studies in people with FRDA. Here, we investigate whether these changes are regionally heterogeneous. Methods: Quantitative susceptibility mapping data were acquired from 49 people with FRDA and 46 healthy controls. The dentate nuclei were manually segmented and analyzed using three dimensional vertex‐based shape modeling and voxel‐based assessments to identify regional changes in morphometry and susceptibility, respectively. Results: Individuals with FRDA, relative to healthy controls, showed significant bilateral surface contraction most strongly at the rostral and caudal boundaries of the dentate nuclei. The magnitude of this surface contraction correlated with disease duration, and to a lesser extent, ataxia severity. Significantly greater susceptibility was also evident in the FRDA cohort relative to controls, but was instead localized to bilateral dorsomedial areas, and also correlated with disease duration and ataxia severity. Conclusions: Changes in the structure of the dentate nuclei in FRDA are not spatially uniform. Atrophy is greatest in areas with high gray matter density, whereas increases in susceptibility—reflecting iron concentration, demyelination, and/or gliosis—predominate in the medial white matter. These findings converge with established histological reports and indicate that regional measures of dentate nucleus substructure are more sensitive measures of disease expression than full‐structure averages. Biomarker development and therapeutic strategies that directly target the dentate nuclei, such as gene therapies, may be optimized by targeting these areas of maximal pathology. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

HER2 activating mutations have emerged as oncogenic drivers and therapeutic targets in a variety of human tumors. In breast cancer, these deregulations occur at low frequency, and are mostly detected in HER2‐nonamplified, metastatic disease. Preclinical evidence has clarified the role of hotspot mutations in HER2 constitutive activation, defining them as an alternative mechanism to HER2 gene amplification. Furthermore, recent clinical studies have indicated the emergence of newly acquired HER2 deregulations in significant proportions of breast cancer patients who experience disease progression following both endocrine and HER2‐targeted therapies. As the involvement of HER2 mutation in therapy resistance may profoundly impact patient outcomes on successive therapies, several clinical trials are currently investigating the efficacy of various HER2‐targeted drugs in HER2‐mutant breast cancer. In this review, we firstly summarize the structural organization of the HER2 oncogene and its historical impact on breast cancer prognosis and therapeutic advancement. Then, we provide an overview of the frequencies and functional relevance of clinically recurrent HER2 mutations in breast cancer with a special focus on their role in therapeutic resistance. Finally, we provide a collection of the clinical trials that are currently exploring novel therapeutic approaches for this patient subset and discuss the related perspectives and challenges. [ABSTRACT FROM AUTHOR]

Background and purpose: Generalized myasthenia gravis (gMG) continues to present significant challenges for clinical management due to an unpredictable disease course, frequent disease fluctuations, and varying response to therapy. The recent availability of new pharmacologic therapies presents a valuable opportunity to reevaluate how this disease is classified, assessed, and managed and identify new ways to improve the clinical care of patients with gMG. Methods: Narrative review was made of publications identified via searches of PubMed and selected congresses (January 2000–September 2022). Results: New consensus definitions are required to ensure consistency, to better characterize patients, and to identify patients who will benefit from specific drugs and earlier use of these agents. There is a need for more frequent, standardized patient assessment to identify the cause of motor function deficits, provide a clearer picture of the disease burden and its impact on daily living and quality of life (QoL), and better support treatment decision‐making. Novel approaches that target different components of the immune system will play a role in more precise treatment of patients with gMG, alongside the development of new algorithms to guide individualized patient management. Conclusions: gMG has a physical, mental, and social impact, resulting in a considerable burden of disease and substantially decreased QoL, despite standard treatments. The availability of novel, targeted treatments that influence key pathological mediators of gMG, together with new biomarkers, offers the potential to optimize patient management and ultimately enables a greater number of patients to achieve minimal manifestation status and a reduced burden of disease. [ABSTRACT FROM AUTHOR]

Objectives: To report oncological outcomes of active surveillance (AS) at a single non‐academic institution adopting the standardised Prostate Cancer Research International Active Surveillance (PRIAS) protocol. Patients and Methods: Competing risk analyses estimated the incidence of overall mortality, metastases, conversion to treatment, and grade reclassification. The incidence of reclassification and adverse pathological findings at radical prostatectomy were compared between patients fulfilling all PRIAS inclusion criteria vs those not fulfilling at least one. Results: We analysed 341 men with Grade Group 1 prostate cancer (PCa) followed on AS between 2010 and 2022. There were no PCa deaths, two patients developed distant metastases and were alive at the end of the study period. The 10‐year cumulative incidence of metastases was 1.9% (95% confidence interval [CI] 0.33–6.4%). A total of 111 men were reclassified, and 127 underwent definitive treatment. Men not fulfilling at least one PRIAS inclusion criteria (n = 43) had a higher incidence of reclassification (subdistribution hazards ratio 1.73, 95% CI 1.07–2.81; P = 0.03), but similar rates of adverse pathological findings at radical prostatectomy. Conclusion: Metastases in men on AS at a non‐academic institution are as rare as those reported in established international cohorts. Men followed without stringent inclusion criteria should be counselled about the higher incidence of reclassification and reassured they can expect rates of adverse pathological findings comparable to those fulfilling all criteria. Therefore, AS should be proposed to all men with low‐grade PCa regardless of whether they are followed at academic institutions or smaller community hospitals. [ABSTRACT FROM AUTHOR]

Background and purpose: Therapy for myasthenia gravis (MG) is undergoing a profound change, with new treatments being tested. These include complement inhibitors and neonatal Fc receptor (FcRn) blockers. The aim of this study was to perform a meta‐analysis and network meta‐analysis of randomized and placebo‐controlled trials of innovative therapies in MG with available efficacy data. Methods: We assessed statistical heterogeneity across trials based on the Cochrane Q test and I2 values, and mean differences were pooled using the random‐effects model. Treatment efficacy was assessed after 26 weeks of eculizumab and ravulizumab, 28 days of efgartigimod, 43 days of rozanolixizumab, 12 weeks of zilucoplan, and 16, 24 or 52 weeks of rituximab treatment. Results: We observed an overall mean Myasthenia Gravis‐Activities of Daily Living scale (MG‐ADL) score change of −2.17 points (95% confidence interval [CI] −2.67, −1.67; p < 0.001) as compared to placebo. No significant difference emerged between complement inhibitors and anti‐FcRn treatment (p = 0.16). The change in Quantitative Myasthenia Gravis scale (QMG) score was −3.46 (95% CI −4.53, −2.39; p < 0.001), with a higher reduction with FcRns (−4.78 vs. −2.60; p < 0.001). Rituximab did not significantly improve the MG‐ADL (−0.92 [95% CI −2.24, 0.39]; p = 0.17) or QMG scores (−1.9 [95% CI −3.97, 0.18]; p = 0.07). In the network meta‐analysis, efgartigimod had the highest probability of being the best treatment, followed by rozanolixizumab. Conclusion: Anti‐complement and FcRn treatments both proved to be effective in MG patients, whereas rituximab did not show a significant benefit for patients. Within the limitations of this meta‐analysis, including efficacy time points, FcRn treatments showed a greater effect on QMG score in the short term. Real‐life studies with long‐term measurements are needed to confirm our results. [ABSTRACT FROM AUTHOR]

Objective: To compare the effectiveness and safety of galcanezumab, fremanezumab, and erenumab for the treatment of chronic and episodic migraine, through real‐world data. Background: Monoclonal antibodies (mAbs) targeting the calcitonin gene–related peptide (CGRP) pathway have been tested extensively in several clinical trials for both episodic and chronic migraine, showing high effectiveness, safety, and tolerability; however, there are no prospective real‐world studies intending to compare their efficacy and safety. Methods: This is a prospective observational cohort study comparing the effectiveness and safety profiles of galcanezumab, fremanezumab, and erenumab for the treatment of chronic and episodic migraine. We enrolled 140 patients at the Headache Centre of University Federico II of Naples, with a history of multiple failed treatments with validated migraine preventatives. Framenezumab, erenumab, or galcanezumab were administered for 12 months. The mean monthly days with headache, Migraine Disability Assessment (MIDAS) score, and adverse events were evaluated during the run‐in period and every 3 months by reviewing standardized paper patient headache diaries. Results: We found a mean reduction of migraine monthly days from baseline of −12.0 (−9.8, −14.1) in the galcanezumab group, −12.3 (−10.2, −14.3) in the fremanezumab group, and −10.8 (−8.5, −13.1) in the erenumab group (for all, p < 0.001). We found a mean reduction of MIDAS score of −32.6 (−26.6, −38.5) in the galcanezumab group, −33.4 (−28.0, −38.9) in the fremanezumab group, and −29.2 (−23.0, −35.4) in the erenumab group (for all, p < 0.001). We found no significant differences between mAbs in the reduction of mean monthly days with headache and MIDAS score. We found a more rapid effect of galcanezumab and erenumab compared to fremanezumab in medication overuse headache patients after 3 months of treatment (−10.8 and −11.1 vs. −4.0 days; p = 0.029). Conclusion: Our results confirm the therapeutic benefits of anti‐CGRP mAbs. There is no evidence that suggests that one antibody may be superior to the others in terms of effectiveness, both in chronic and episodic patients. [ABSTRACT FROM AUTHOR]

Keywords: digital droplet PCR; Midichloria-like organism; rainbow trout; recirculating aquaculture system; red mark syndrome EN digital droplet PCR Midichloria-like organism rainbow trout recirculating aquaculture system red mark syndrome 1889 1892 4 11/11/22 20221201 NES 221201 Red mark syndrome is a non-lethal skin disease, reported to affect farmed rainbow trout over 50 g worldwide (Metselaar et al., 2022). The manuscript by Oh et al. (2019) describes several cases of the disease in rainbow trout in South Korea, in which macroscopic lesions resembling RMS can be seen in juvenile rainbow trout weighed less than 30 g. [Extracted from the article]

The development of platforms and techniques for emerging Big Data and Machine Learning applications requires the availability of real‐life datasets. A possible solution is to synthesize datasets that reflect patterns of real ones using a two‐step approach: first, a real dataset X is analyzed to derive relevant patterns Z and, then, to use such patterns for reconstructing a new dataset X′ that preserves the main characteristics of X. This survey explores two possible approaches: (1) Constraint‐based generation and (2) probabilistic generative modeling. The former is devised using inverse mining (IFM) techniques, and consists of generating a dataset satisfying given support constraints on the itemsets of an input set, that are typically the frequent ones. By contrast, for the latter approach, recent developments in probabilistic generative modeling (PGM) are explored that model the generation as a sampling process from a parametric distribution, typically encoded as neural network. The two approaches are compared by providing an overview of their instantiations for the case of discrete data and discussing their pros and cons. This article is categorized under:Fundamental Concepts of Data and Knowledge > Big Data MiningTechnologies > Machine LearningAlgorithmic Development > Structure Discovery [ABSTRACT FROM AUTHOR]

Background and purpose: Real‐world data on alemtuzumab are limited and do not provide evidence of its effectiveness after various disease‐modifying therapies (DMTs). Our aim was to provide real‐world data on the impact of clinical variables and previous DMTs on clinical response to alemtuzumab. Methods: Sixteen Italian multiple sclerosis centers retrospectively included patients who started alemtuzumab from January 2015 to December 2018, and recorded demographics, previous therapies, washout duration, relapses, Expanded Disability Status Scale (EDSS) score, and magnetic resonance imaging data. Negative binomial regression models were used to assess the effect of factors on annualized relapse (ARR) after alemtuzumab initiation. Results: We studied 322 patients (mean age 36.8 years, median EDSS score 3, median follow‐up 1.94 years). Previous treatments were: fingolimod (106), natalizumab (80), first‐line oral agents (56), first‐line injectables (interferon/glatiramer acetate; 30), and other drugs (15). Thirty‐five patients were treatment‐naïve. The pre‐alemtuzumab ARR was 0.99 and decreased to 0.13 during alemtuzumab treatment (p < 0.001). The number of previous‐year relapses was associated with alemtuzumab ARR (adjusted risk ratio [RR] 1.38, p = 0.009). Progression‐free survival was 94.5% after 1 year, and 89.2% after 2 years of alemtuzumab treatment. EDSS score improvement occurred in 13.5% after 1 year, and 20.6% after 2 years. Re‐baselining patients after 6 months of alemtuzumab treatment, led to no evidence of disease activity status in 71.6% after 1 year and 58.9% after 2 years. Conclusions: Alemtuzumab decreases ARR independent of previous therapy, including patients with disease activity during natalizumab treatment. Overall, 90% of patients showed no disease progression, and 20% an improvement after 2 years of alemtuzumab. [ABSTRACT FROM AUTHOR]

Background: A recent meta‐analysis (Human Reproduction Update 23, 2017 and 265) reported positive sperm retrieval rates (SRR) in 50% of patients with Klinefelter syndrome (KS) undergoing testicular sperm extraction (TESE). However, these results do not reflect the rates of SR that we observe in clinical practice. We assessed the rate and potential predictors of SR in Klinefelter patients in the real‐life setting. Materials and Methods: We reviewed clinical data of 103 KS men who underwent TESE between 08/2008 and 03/2019 at five tertiary referral Andrology centers. Patients underwent testis ultrasound, hormonal evaluation, and genetic testing. All patients were azoospermic based on the 2010 WHO reference criteria. Conventional TESE (cTESE) or microsurgical TESE (mTESE) was performed based on the surgeon's preference. We used descriptive statistics and logistic regression models to describe the whole cohort. Results: Median (IQR) patient's age was 32 (24‐37) years. Baseline serum FSH and total testosterone levels were 29.5 (19.9‐40.9) mUI/mL and 3.8 (2.5‐11.0) ng/mL, respectively. Conventional TESE and mTESE were performed in 38 (36.5%) and 65 (63.5%) men, respectively. The sperm retrieval rate was 21.4% (22/103 men). Fifteen patients used spermatozoa for ICSI and five ended in live birth children. Patients with positive SR were similar to those with a negative TESE in terms of clinical, hormonal, and procedural parameters (all P >.05). Logistic regression analyses confirmed the lack of association between clinical, hormonal, and procedural parameters with SR outcome. Discussion: Given the conflicting results in the literature regarding SRR in KS, patients should be carefully counseled regarding TESE outcomes based on data from published literature and local results. Conclusions: In the real‐life setting, we observed a lower SRR (21.4%) than that reported in meta‐analyses in our cohort of KS patients. No associations between clinical, hormonal, and procedural variables with TESE success were found. [ABSTRACT FROM AUTHOR]

Background and purpose: Heterozygous mutations in the STUB1 gene have recently been associated with an autosomal dominant form of spinocerebellar ataxia (SCA) associated with cerebellar cognitive‐affective syndrome (CCAS), named SCA48. Methods: Molecular screening was performed in a cohort of 235 unrelated patients with adult‐onset, autosomal dominant (17) or sporadic (218) cerebellar ataxia, negative for pathological trinucleotide expansions in the common SCAs, FRDA and FXTAS loci, by using targeted multigene panels or whole‐exome sequencing. Bioinformatics analyses, detailed neurological phenotyping and family segregation studies corroborated the pathogenicity of the novel STUB1 mutations. Clinico‐diagnostic findings were reviewed to define the phenotypic spectrum. Results: Eight heterozygous STUB1 mutations were identified, six of which were novel in 11 patients from eight index families, giving an estimated overall frequency of 3.4% (8/235) for SCA48 in our study cohort, rising to 23.5% (4/17) when considering only familial cases. All our SCA48 patients had cerebellar ataxia and dysarthria associated with cerebellar atrophy on brain magnetic resonance imaging; of note, many cases were also associated with parkinsonism, chorea and dystonia. CCAS also occurred frequently, whereas definite signs of pyramidal tract dysfunction and peripheral nervous system involvement were absent. One SCA48 patient presented with hypogonadism, associated with other autoimmune endocrine dysfunctions. Conclusions: Our results support SCA48 as a significant cause of adult‐onset SCA. Besides CCAS, our SCA48 patients often showed movement disorders and other clinical manifestations previously described in SCAR16, linked to biallelic variants in the same gene, thus suggesting a continuous clinical spectrum and significant overlap amongst recessive and dominantly inherited mutations in STUB1. [ABSTRACT FROM AUTHOR]

Background: Spasticity is a frequent multifactorial manifestation of multiple sclerosis (MS), affecting mostly the chronic courses of the disease. Its impact on patient functioning and quality of life is profound. Treatment of spasticity includes oral and intrathecal anti‐spastic drugs, muscle injections with relaxant agents, physical therapy, electrical and magnetic stimulation and peripheral nerve stimulation, alone or in various combinations. Methods: This Italian consensus on the treatment of spasticity in MS was produced by a large group of Italian MS experts in collaboration with neurophysiologists, experts in the production of guidelines and patients' representatives operating under the umbrella of the Italian Neurological Society, the Associazione Italiana Sclerosi Multipla and the European Charcot Foundation. This guideline was developed in accordance with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A total of 11 questions were formulated following the PICO framework (patients, intervention, comparator, outcome). Controlled studies only were included in the analysis. Results: Despite some consistent limitations due to the poor methodological quality of most studies, there was a consensus on a strong recommendation for the use of intrathecal baclofen, oromucosal spray of nabiximols and intramuscular injection of botulinum toxin. The level of recommendation was weak for oral baclofen, tizanidine, gabapentin, benzodiazepines and transcranial magnetic stimulation. Conclusions: There is a clear need for new larger multicentre well‐designed clinical trials with a duration that allows the persistence of the effects and the long‐term safety of the interventions to be evaluated. [ABSTRACT FROM AUTHOR]

BKPyV replication is a risk factor for the development of polyomavirus‐associated nephropathy in kidney transplant recipients. Here, the case of a 42 years old Caucasian patient is described who developed a kidney allograft failure because of uncontrolled BKPyV replication 7 months after transplant despite a strong reduction of the immunosuppressive therapy. The genetic analysis of the noncoding control region did not show rearrangement but two point mutations at nucleotide positions 18 and 31 within P block. The mutation at position 31 involved the nuclear factor‐1 site. Sequencing of the VP1 region revealed a subtype I/subgroup b‐1. Highlights: Uncontrolled replication of BKPyV can cause PyVAN in Kidney transplant patients.Reduction of immunosuppressive therapy usually allows to control BKPyV replication.Here, PyVAN develops despite reduction of immunosuppressive therapy.No significant genetic changes were found in VP1 gene and NCCR of the virus. [ABSTRACT FROM AUTHOR]

During the past two decades, esca disease has emerged as one of the most important diseases of grapevines. Esca is caused by complex of fungal pathogens, one of the main being Phaeomoniella chlamydospora (Pch). Since propagation material is considered one of the main infection sources of this fungus, most studies on Pch detection have focused on plant tissues and nursery soils. Conversely, due to methodological limitations encountered in retrieving this slow‐growing fungus, little is known about its true occurrence in vineyard soils. This study presents the adaptation of a molecular‐based methodology for the detection and quantification of Pch in soil samples. For this purpose, soil from the root‐explored area of esca‐foliar symptomatic and asymptomatic plants was sampled in 17 adult vineyards in two different climatic regions. Qualitative and quantitative nested PCR assays indicated the presence of Pch DNA in soil, differentiating between vineyards and regions, regardless of esca symptoms. The number of positive samples (32%) detected in the vineyards indicates that Pch can be recovered in natural soils, thus opening perspectives for the use of molecular tools in the study of the ecology and epidemiology of this fungus in soil. [ABSTRACT FROM AUTHOR]

Introduction: Despite neurological patients show frequent physical impairment, timed neuropsychological tests do not take this into account during scoring procedures. Objective: We propose a normalization method based on the PATA Rate Task (PRT) and on the nine‐hole pegboard test (9HPT) as a measure of dysarthria and upper limb dysfunction. Methods: We tested 65 healthy controls on timed neuropsychological tests (Attentional Matrices [AM], Trail Making Test, Symbol Digit Modalities Test, Verbal Fluencies) to determine the time spent on phonation or on hand movement during test execution. We developed correction formulas to normalize test times considering the patient's PRT/9HPT, their normality limits, and the test timing. We tested the method on 24 patients with Friedreich Ataxia (FRDA), as a model of motor and speech impairment. Results: In healthy controls, phonation or hand movement is 13.5–61.7% of total test time. In FRDA patients, the effect of normalization improved all test results (range: 0.51–48.4%; p < .001). FRDA patients had worst scores in all tests when compared to controls, and the difference remained significant after correction except for the AM. At the individual level, the normalization method improved equivalent scores with fever patients showing impaired scores after correction. Conclusions: We propose an innovative normalization method to reduce the impact of neurological disability on timed neuropsychological tests. This could be easily integrated in a clinical setting, as it requires a simple preliminary test with the PRT and 9HPT. [ABSTRACT FROM AUTHOR]

Cybersecurity compliance analysis is the process of assessing whether the behavior of an IT system or application conforms to the cybersecurity rules and regulations in force. This assessment can be offered as a service by exploiting available cloud technologies, and, indeed, it is one of the services classified by the Cloud Security Alliance (CSA) as part of the security information and event management (SIEM) category of the SecaaS (security as a service) domain. The definition and implementation of this typology of cloud services are challenging activities due to the complexity of both the reference business domain and the compliance analysis services to be provided themselves. The paper exploits a recently proposed requirements methodology, called GOReM(goal-oriented requirements methodology), to support the conceptualization and subsequent implementation of cybersecurity compliance analysis services. In particular, two different application scenarios regarding compliance analysis of an existing or under development IT system/ application are presented and discussed. In both the scenarios, GOReM allows to grasp and understand the many and complex issues to address for providing secure cloud services toworldwide customers, also due to the numerous, different and ever changing legal aspects, which have to be taken into account by service providers. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of this study was to perform the first resting‐state functional MRI (RS‐fMRI) analysis in Friedreich's ataxia (FRDA) patients to assess possible brain functional connectivity (FC) differences in these patients, and test their correlations with neuropsychological performances. Methods: In total, 24 FRDA patients (M/F: 15/9, mean age 31.3 ± 15.0) and 24 healthy controls (HC; M/F: 15/9, mean age 30.7 ± 15.5) were enrolled in this cross‐sectional study. All patients underwent a thorough neuropsychological battery, investigating different cognitive domains. RS‐fMRI data were analyzed using a seed‐based approach, probing the FC of cortical areas potentially referable to specific executive and cognitive functions compromised in FRDA. Results: Compared to HC, FRDA patients showed overall worse neuropsychological scores in several domains, including global cognitive assessment, spatial memory, visuoperception and visuospatial functions, and executive functions. Analysis of RS‐fMRI data showed a higher FC in FRDA patients compared to HC between paracingulate gyri and the medial frontal gryrus, between the superior frontal gyrus and bilateral angular gyri, and between the middle temporal gyrus and the cingulate gyrus, with a reduced FC between the medial frontal gryrus and the cerebellum. Interpretation: We found a reduction in FC between frontal areas and the contralateral cerebellar cortex in FRDA, in line with the known alteration in cerebello‐cortical pathway in this condition. On the other hand, a higher FC between different cortical areas was shown, possibly reflecting a compensatory phenomenon. These results, in conjunction with clinical findings, may shed new light on the pattern of supratentorial and infratentorial involvement, and on dynamics of brain plasticity in this disease. [ABSTRACT FROM AUTHOR]

Abstract: Aim of the study was to evaluate the presence of Default Mode Network (DMN) modifications in Fabry Disease (FD), and their possible correlations with structural alterations and neuropsychological scores. Thirty‐two FD patients with a genetically confirmed diagnosis of classical FD (12 males, mean age 43.3 ± 12.2) were enrolled, along with 35 healthy controls (HC) of comparable age and sex (14 males, mean age 42.1 ± 14.5). Resting‐State fMRI data were analyzed using a seed‐based approach, with six different seeds sampling the main hubs of the DMN. Structural modifications were assessed by means of Voxel‐Based Morphometry (VBM) and Tract‐Based Spatial Statistics analyses. Between‐group differences and correlations with neuropsychological variables were probed voxelwise over the whole brain. Possible correlations between FC modifications and global measures of microstructural alteration were also tested in FD patients with a partial correlation analysis. In the FD group, clusters of increased functional connectivity involving both supratentorial and infratentorial regions emerged, partially correlated to the widespread white matter (WM) damage found in these patients. No gray matter volume differences were found at VBM between the two groups. The connectivity between right inferior frontal gyrus and precuneus was significantly correlated with the Corsi block‐tapping test results (p = .0001). Widespread DMN changes are present in FD patients that correlate with WM alterations and cognitive performance. Our results confirm the current view of a cerebral involvement in FD patients not simply associated to major cerebrovascular events, but also related to significant and diffuse microstructural and functional changes. [ABSTRACT FROM AUTHOR]

Abstract: BACKGROUND: One of the main constraints established by organic legislation that limits the development of the rearing of young bulls is the ban on the use of genetically modified organisms (GMO). Most of the worldwide cultivated soybean is GMO, therefore the use of alternative protein sources should be evaluated. In this study, the effect of dietary substitution of soybean with pea (Pisum sativum L.) on carcass characteristics and meat quality of dual purpose young bulls reared following the organic method was investigated. RESULTS: Twenty‐four young bulls of Rendena breed were randomly assigned to two diet treatments differing in protein supplement (soybean (SB) or field pea (FP)). Carcass characteristics and meat chemical composition, colour, cooking loss and Warner–Bratzler shear force did not differ between groups. Regarding meat fatty acid composition, SB showed higher concentrations of C18:0 and C18:1 t and lower C16:1n‐9c, C14:0, C17:1n‐9c and C18:1n‐9c than FP. In descriptive sensory analysis, trained judges were not able to differentiate meats from SB and FP, which also had similar overall liking expressed by consumers. CONCLUSION: The results of this study indicate that FP can replace SB in the diet of dual purpose young bulls with only a minor influence on fatty acid composition and no effect on carcass characteristics and meat quality. © 2017 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

In recent years, the poorly remarkable goals achieved in terms of patients’ important outcomes for ovarian cancer have fueled our interest toward the study of its metabolic roots. Within this research pipeline, we assessed the association between the expression of the glucose transporter GLUT1, as expressed at the tumor tissue level, and circulating pre-surgical levels of fasting glucose in a case series including data from 40 patients with high FIGO stage serous ovarian cancer. Patients who provided data to the current analysis were randomly selected from a larger cohort. To our purposes, the procedures related to serum and tissue collection, storage and biomarker assessment were highly standardized and centralized at the institutional laboratories. The GLUT1 antibody SPM498 SPRING (REF. E13810) was used at a 1:500 dilution in 2 μmslides. Staining for GLUT1 was observed at the cell membrane level in all the cases assessed, but strong staining was described in 29 (72.5%) of them. The agreement between the two independent reviewers was 100%. Strong GLUT1 staining was inversely associated with circulating levels of fasting glucose, with a particularly striking difference for patients in the lowest fasting glucose tertile (p = 0.044). These results support the biological plausibility of the association of interest. If confirmed in larger studies, our findings may help clarify the potentials of biomarkers related to energy metabolism in terms of prognosis definition, treatment assignment, and outcome interpretation for patients with high FIGO stage serous ovarian cancer. [ABSTRACT FROM AUTHOR]

This narrative review aims to provide an objective view of the noninvasive neuromodulation (NINM) protocols available for treating spasticity, including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). On the basis of the relevant randomized controlled trials, we infer that NINM is more effective in reducing spasticity when combined with the conventional therapies than used as a stand-alone treatment. However, the magnitude of NINM after-effects depends significantly on the applied hemisphere and the underlying pathology. Being in line with these arguments, low-frequency rTMS and cathodal-tDCS over the unaffected hemisphere are more effective in reducing spasticity than high-frequency rTMS and anodal-tDCS over the affected hemisphere in chronic poststroke. However, most of the studies are heterogeneous in the stimulation setup, patient selection, follow-up duration, and the availability of the sham operation. Therefore, the available data on the usefulness of NINM in reducing spasticity need to be confirmed by larger and multicentric randomized controlled trials to gather evidence on the efficiency of NINM regimens in reducing spasticity in various neurologic conditions.Level Of Evidence: V. [ABSTRACT FROM AUTHOR]

Background Different retrospective studies compared natalizumab and fingolimod in relapsing-remitting multiple sclerosis ( RRMS), with conflicting results. We aimed to explore the prescriptive attitude and the clinical outcome of the two therapies. Methods We retrospectively included all RRMS patients treated with natalizumab (n=101) or fingolimod (n=78) as their first second-line therapy with at least 24-month follow-up. Demographic and clinical features were recorded to calculate the propensity score ( PS). Outcomes of interest were annualized relapse rate ( ARR), risk of relapse, and change in the EDSS Results At baseline, natalizumab patients were younger and had a shorter disease duration, a higher number of relapse in 1 year (1yR) and 2 years (2yR) and overall ( ARR- PT) pretherapy, compared to fingolimod patients. On therapy, the proportion of relapsing patients and the mean RR were similar in the two groups. However, the change in the ARR was higher in natalizumab than in fingolimod group ( P<.002), but, using PS as a covariate, it was comparable ( P=.960). Similarly, the change in EDSS was significantly different for the two groups ( P<.004), but not after adjusting for the PS ( P=.321). Conclusion We observed a comparable efficacy on ARR reduction and on EDSS progression with natalizumab and fingolimod correcting through PS, suggesting that the efficacy difference observed before correction might derive from the clinical attitude in prescribing natalizumab in more active MS patients in real life. [ABSTRACT FROM AUTHOR]

Spinocerebellar ataxia type 2 ( SCA2) is among the most common forms of autosomal dominant ataxias, accounting for 15% of the total families. Occurrence is higher in specific populations such as the Cuban and Southern Italian. The disease is caused by a CAG expansion in ATXN2 gene, leading to abnormal accumulation of the mutant protein, ataxin-2, in intracellular inclusions. The clinical picture is mainly dominated by cerebellar ataxia, although a number of other neurological signs have been described, ranging from parkinsonism to motor neuron involvement, making the diagnosis frequently challenging for neurologists, particularly when information about the family history is not available. Although the functions of ataxin-2 have not been completely elucidated, the protein is involved in mRNA processing and control of translation. Recently, it has also been shown that the size of the CAG repeat in normal alleles represents a risk factor for ALS, suggesting that ataxin-2 plays a fundamental role in maintenance of neuronal homeostasis. [ABSTRACT FROM AUTHOR]

Male breast cancer (MBC) is an uncommon malignancy. We have previously reported that the expression of the Hippo transducers TAZ/YAP and their target CTGF was associated with inferior survival in MBC patients. Preclinical evidence demonstrated that Axl is a transcriptional target of TAZ/YAP. Thus, we herein assessed AXL expression to further investigate the significance of active TAZ/YAP-driven transcription in MBC. For this study, 255 MBC samples represented in tissue microarrays were screened for AXL expression, and 116 patients were included. The association between categorical variables was verified by the Pearson's Chi-squared test of independence (2-tailed) or the Fisher Exact test. The relationship between continuous variables was tested with the Pearson's correlation coefficient. The Kaplan-Meier method was used for estimating survival curves, which were compared by log-rank test. Factors potentially impacting 10-year and overall survival were verified in Cox proportional regression models. AXL was positively associated with the TAZ/CTGF and YAP/CTGF phenotypes ( P = 0.001 and P = 0.002, respectively). Patients with TAZ/CTGF/AXL- or YAP/CTGF/AXL-expressing tumors had inferior survival compared with non-triple-positive patients (log rank P = 0.042 and P = 0.048, respectively). The variables TAZ/CTGF/AXL and YAP/CTGF/AXL were adverse factors for 10-year survival in the multivariate Cox models (HR 2.31, 95%CI:1.02-5.22, P = 0.045, and HR 2.27, 95%CI:1.00-5.13, P = 0.050). Nearly comparable results were obtained from multivariate analyses of overall survival. The expression pattern of AXL corroborates the idea of the detrimental role of TAZ/YAP activation in MBC. Overall, Hippo-linked biomarkers deserve increased attention in this rare disease. J. Cell. Physiol. 232: 2246-2252, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Bevacizumab in combination with taxanes in HER2-negative metastatic breast cancer (MBC) patients has shown improved progression-free survival (PFS), despite the lack of clear overall survival (OS) benefit. We performed a retrospective analysis to evaluate the impact of paclitaxel-bevacizumab and of maintenance therapy with bevacizumab (BM) and endocrine therapy (ET) in the real-world practice. We identified 314 HER2-negative MBC patients treated in 12 cancer centers. Overall, the median PFS and OS were 14 and 40 months, respectively. Among the 254 patients potentially eligible for BM, 183 received BM after paclitaxel discontinuation until progression/toxicity. PFS and OS were improved in patients who had received BM in comparison with those potentially eligible but who did not receive BM ( P< 0.0001 and P = 0.001, respectively). Results were confirmed when adjusting for propensity score. Among the 216 hormone-receptor positive patients eligible for BM, a more favorable PFS and OS were observed when maintenance ET was administered ( P < 0.0001). Multivariate analysis showed that PS, BM, number of disease sites and maintenance ET were related to PFS, while response and maintenance ET were related to OS. In hormone-receptor positive patients, BM produced a significant PFS and a trend towards OS benefit only in absence of maintenance ET ( P = 0.0007 and P = 0.06, respectively). In the triple-negative subgroup, we observed a trend towards a better OS for patients who received BM ( P = 0.06), without differences in PFS ( P = 0.21). Our results confirmed the efficacy of first-line paclitaxel-bevacizumab in real-world practice; both BM and maintenance ET significantly improved PFS and OS compared to no maintenance therapies. J. Cell. Physiol. 232: 1571-1578, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Biomass estimation is central in most microbial plankton ecology studies. Numerous advances have been made that rendered this task more and more effective, from the introduction of allometric volume-to-carbon conversion factors to the development of submersible flow-through imaging devices. Although several ingenious methods have been suggested for this purpose, the problem of biovolume extrapolation from two-dimensional pictures remains. This study offers a historical and critical review of the methods for the estimation of the biovolume of microorganisms that have been proposed throughout the last four decades. It covers three main approaches-respectively based on a single equation, a set of simple or composite geometric shapes or a computational algorithm-as well as several methods featuring exclusive characteristics. Both strengths and shortcomings of each technique are analyzed, with particular emphasis on compatibility with the most recent flow-through devices coupled with in situ imaging systems. A composite picture emerges with no such unique method, at present, suitable for every situation. This review can thus be a valuable guide for the microbial plankton ecologist who seeks the most suitable technique for a specific circumstance. [ABSTRACT FROM AUTHOR]

View Supplementary Video 1 [ABSTRACT FROM AUTHOR]

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an inherited neurodegenerative disorder characterized by early-onset, spastic ataxia and peripheral neuropathy. It was originally described in an inbred population of Quebec and later in some other countries. We report a new missense SACS mutation (7848C>T) in a Spanish family whose phenotype is similar to that of the previously described ARSACS patients. 7848C>T is the first SACS mutation reported in Spain confirming worldwide distribution of the disease. [ABSTRACT FROM AUTHOR]

Background and purpose Growth hormone (GH)/insulin-like growth factor 1 ( IGF-1) axis abnormalities in multiple sclerosis ( MS) suggest their role in its pathogenesis. Interferon β ( IFN-β) efficacy could be mediated also by an increase of IGF-1 levels. A 2-year longitudinal study was performed to estimate the prevalence of GH and/or IGF-1 deficiency in clinically isolated syndrome ( CIS) patients and their correlation with conversion to MS in IFN treated patients. Methods Clinical and demographic features of CIS patients were collected before the start of IFN-β-1b. IGF-1 levels and GH response after arginine and GH releasing hormone + arginine stimulation tests were assessed. Clinical and magnetic resonance imaging evaluations were performed at baseline, 1 year and 2 years. Results Thirty CIS patients (24 female) were enrolled. At baseline, four patients (13%) showed a hypothalamic GH deficiency ( GHD), whilst no one had a pituitary GHD. Baseline demographic, clinical and radiological data were not related to GHD, whilst IGF-1 levels were inversely related to age ( P < 0.001) and GH levels ( P = 0.03). GH and IGF-1 serum mean levels were not significantly modified after 1 and 2 years of treatment in the whole group, although 3/4 GHD patients experienced a normalization of GH levels, whilst one dropped out. After 2 years of treatment 13/28 (46%) patients converted to MS. The presence of GHD and GH and IGF-1 levels were not predictive of relapses, new T2 lesions or conversion occurrence. Conclusions Growth hormone/ IGF-1 axis function was found to be frequently altered in CIS patients, but this was not related to MS conversion. Patients experienced an improvement of GHD during IFN therapy. Longer follow-up is necessary to assess its impact on disease progression. [ABSTRACT FROM AUTHOR]

To report the results of the DECT trial, a phase II study of locally advanced or operable HER2-positive breast cancer (BC) treated with taxanes and concurrent anthracyclines and trastuzumab. Eligible patients (stage IIA-IIIB HER2-positive BC, 18-75 years, normal organ functions, ECOG ≤1, and left ventricular ejection fraction (LVEF) ≥55%) received four cycles of neoadjuvant docetaxel, 100 mg/m2 intravenously, plus trastuzumab 6 mg/kg (loading dose 8 mg/kg) every 3 weeks, followed by four 3-weekly cycles of epirubicin 120 mg/m2 and cyclophosphamide, 600 mg/m2, plus trastuzumab. Primary objective was pathologic complete response (pCR) rate, defined as ypT0/is ypN0 at definitive surgery. We enrolled 45 consecutive patients. All but six patients (13.3%) completed chemotherapy and all underwent surgery. pCR was observed in 28 patients (62.2%) overall and in 6 (66.7%) from the inflammatory subgroup. The classification and regression tree analysis showed a 100% pCR rate in patients with BMI ≥25 and with hormone negative disease. The median follow up was 46 months (8-78). Four-year recurrence-free survival was 74.7% (95%CI, 58.2-91.2). Seven patients (15.6%) recurred and one died. Treatment was well tolerated, with limiting toxicity being neutropenia. No clinical cardiotoxicity was observed. Six patients (13.4%) showed a transient LVEF decrease (<10%). In one patient we observed a ≥10% asymptomatic LVEF decrease persisting after surgery. Notwithstanding their limited applicability due to the current guidelines, our findings support the efficacy of the regimen of interest in the neoadjuvant setting along with a fairly acceptable toxicity profile, including cardiotoxicity. Results on BMI may invite further assessment in future studies. J. Cell. Physiol. 231: 2541-2547, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The trabecular meshwork (TM) plays an important role in high-tension glaucomas. Indeed, the TM is a true organ, through which the aqueous humor flows from the anterior chamber to Schlemm's canal (SC). Until recently, the TM, which is constituted by endothelial-like cells, was described as a kind of passive filter. In reality, it is much more. The cells delineating the structures of the collagen framework of the TM are endowed with a cytoskeleton, and are thus able to change their shape. These cells also have the ability to secrete the extracellular matrix, which expresses proteins and cytokines, and are capable of phagocytosis and autophagy. The cytoskeleton is attached to the nuclear membrane and can, in millionths of a second, send signals to the nucleus in order to alter the expression of genes in an attempt to adapt to biomechanical insult. Oxidative stress, as happens in aging, has a deleterious effect on the TM, leading eventually to cell decay, tissue malfunction, subclinical inflammation, changes in the extracellular matrix and cytoskeleton, altered motility, reduced outflow facility, and (ultimately) increased IOP. TM failure is the most relevant factor in the cascade of events triggering apoptosis in the inner retinal layers, including ganglion cells. J. Cell. Physiol. 231: 1876-1893, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Species determination is crucial in biodiversity research. In tintinnids, identification is based almost exclusively on the lorica, despite its frequent intraspecific variability and interspecific similarity. We suggest updated procedures for identification and, depending on the aim of the study, further steps to obtain morphological, molecular, and ecological data. Our goal is to help improving the collection of information (e.g. species re-/descriptions and DNA barcodes) that is essential for generating a natural tintinnid classification and a reliable reference for environmental surveys. These suggestions are broadly useful for protistologists because they exemplify data integration, quality/effort compromise, and the need for scientific collaborations. [ABSTRACT FROM AUTHOR]

Background: Friedreich ataxia is an autosomal recessive disease with no available therapy. Clinical trials with erythropoietin in Friedreich ataxia patients have yielded conflicting results, and the long-term effect of the drug remains unknown.Methods: We designed a double-blind, placebo-controlled, multicenter trial to test the efficacy of epoetin alfa on 56 patients with Friedreich ataxia. The primary endpoint of the study was the effect of epoetin alfa on peak oxygen uptake (VO2 max) at the cardiopulmonary exercise test. Secondary endpoints were frataxin levels in peripheral blood mononuclear cells, improvement in echocardiography findings, vascular reactivity, neurological progression, upper limb dexterity, safety, and quality of life. Epoetin alfa or placebo (1:1 ratio) was administered subcutaneously at a dose of 1200 IU/Kg of body weight every 12 weeks for 48 weeks.Results: A total of 56 patients were randomized; 27 completed the study in the active treatment group, and 26 completed the study in the placebo group[KG1]. VO2 max was not modified after treatment (0.01 [-0.04 to 0.05]; P = .749), as well as most of the secondary endpoint measures, including frataxin. The 9-hole peg test showed a significant amelioration in the treatment group (-17.24 sec. [-31.5 to -3.0]; P = .018). The treatment was safe and well tolerated.Conclusions: Although results are not in favor of an effect of epoetin alfa in Friedreich ataxia, this is the largest trial testing its effect. It is still possible that epoetin alfa may show some symptomatic effect on upper-limb performance. This study provides class I evidence that erythropoietin does not ameliorate VO2 max in patients with Friedreich ataxia. © 2016 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Spermatozoa can be retrieved in non-obstructive azoospermia ( NOA) patients despite the absence of ejaculated spermatozoa in their semen because of the presence of isolated foci with active spermatogenesis. Conventional testicular sperm extraction (c- TESE) in patients with NOA has been partially replaced by micro- TESE. It is still under debate the problem regarding the higher costs related to micro- TESE when compared with c- TESE. In this study, we evaluated sperm retrieval rate ( SRR) of c- TESE in naive NOA patients. Sixty-three NOA patients were referred to our centre for a c- TESE. For every subject, we collected demographic data, cause of infertility, time to first infertility diagnosis, serum levels of LH, FSH, total testosterone and prolactin. A statistical analysis was conducted to correlate all the clinical variables, the histology and the Johnsen score with the SRR. Sixty-three consecutive NOA patients with a mean age of 37.3 years were included. The positive SRR was 47.6%. No statistical differences were observed between positive vs. negative SRR regarding mean FSH (17.12 vs. 19.03 mUI/ mL; p = 0.72), and LH (9.72 vs. 6.92 mUI/ mL; p = 0.39) values. Interestingly, we found a statistically significant difference in terms of time to first infertility diagnosis (+ SRR vs. − SRR; 44.5 vs. 57 months; p = 0.02) and regarding to age (+ SSR vs. − SRR; 40.1 vs. 35.3; p = 0.04). There was a statistically significant decrease in SRRs with the decline in testicular histopathology from hypospermatogenesis to maturation arrest, and SCO. The mean Johnsen score was 5.9 with a mean percentage of Johnsen score ≥8 tubules equal to 19%. The overall pregnancy rate was 26.6%. In our prospective cohort of patients successful SRR with c- TESE was 47.6%. Lower costs and high reproducibility of this technique still support this procedure as an actual reliable option in NOA patients for sperm retrieval. [ABSTRACT FROM AUTHOR]

The activities of calpain and caspase systems during ageing in Longissimus lumborum (LL) and Infraspinatus (IS) muscles of Italian Simmental young bulls ( Bos taurus) were assessed. Samples from 10 animals were collected within 20 min of exsanguination (T0), after 48 h (T1) and 7 days (T2) post mortem. Calpain and caspase activity were evaluated based on the formation of αII spectrin cleavage products of 145 kDa (SBDP145) and 120 kDa (SBDP120), respectively. Caspase activity was also assessed by the presence of poly (adenosine diphosphate-ribose) polymerase-1 (PARP-1) cleavage product. At T0, LL showed higher levels of SBDP145 than IS ( P < 0.01), while SBDP120 and PARP-1 degradation products were similar between muscles. At T1, no difference was found in the level of SBDP145 between muscles, while SBDP120 and PARP-1 cleavage products were not detected. At T2 neither αII spectrin nor PARP-1 cleavage products were found. LL and IS showed different proteolysis after slaughter that was influenced more by calpain than caspase activity, which was detectable only in the early post mortem period. [ABSTRACT FROM AUTHOR]

The early post mortem expression of eight genes potentially involved in meat ageing process and the tenderness of two Italian Simmental young bulls' ( Bos taurus) skeletal muscles differing in their contractile type were evaluated. Samples of Longissimus lumborum ( LL) and Infraspinatus ( IS) muscles were collected from 17 bulls. The messenger RNA ( mRNA) abundances of calpain-1, calpain-2, calpastatin, caspase 3, caspase 9, heat shock p rotein 27 (Hsp27), Hsp40 and Hsp70 were detected by quantitative PCR. The myosin heavy chain-slow and -fast isoform content, the pH48h and the lipid content of the muscles were in line with the contractile and metabolic type. In comparison with the fast LL, the slow IS showed a lower calpain-1/calpastatin mRNA content ratio after slaughtering and a higher Warner- Bratzler Initial Yield value after 7 days of ageing. Hsp27 and Hsp70 mRNA abundances were significantly lower in LL than IS, highlighting their potential role in the ageing process of bovine muscles. [ABSTRACT FROM AUTHOR]

Two-dimensional DNA lattices have been assembled from DNA double-crossover (DX) motifs on DNA-encoded surfaces in a site-specific manner. The lattices contained two types of single-stranded protruding arms pointing into opposite directions of the plane. One type of these protruding arms served to anchor the DNA lattice on the solid support through specific hybridization with surface-bound, complementary capture oligomers. The other type of arms allowed for further attachment of DNA-tethered probe molecules on the opposite side of the lattices exposed to the solution. Site-specific lattice assembly and attachment of fluorophore-labeled oligonucleotides and DNA-protein conjugates was demonstrated using DNA microarrays on flat, transparent mica substrates. Owing to their programmable orientation and addressability over a broad dynamic range from the nanometer to the millimeter length scale, such supramolecular architecture might be used for presenting biomolecules on surfaces, for instance, in biosensor applications. [ABSTRACT FROM AUTHOR]

Purpose We aimed to investigate the integrity of the Resting State Networks in spinocerebellar ataxia type 2 (SCA2) and the correlations between the modification of these networks and clinical variables. Methods Resting-state functional magnetic resonance imaging (RS-fMRI) data from 19 SCA2 patients and 29 healthy controls were analyzed using an independent component analysis and dual regression, controlling at voxel level for the effect of atrophy by co-varying for gray matter volume. Correlations between the resting state networks alterations and disease duration, age at onset, number of triplets, and clinical score were assessed by Spearman's coefficient, for each cluster which was significantly different in SCA2 patients compared with healthy controls. Results In SCA2 patients, disruption of the cerebellar components of all major resting state networks was present, with supratentorial involvement only for the default mode network. When controlling at voxel level for gray matter volume, the reduction in functional connectivity in supratentorial regions of the default mode network, and in cerebellar regions within the default mode, executive and right fronto-parietal networks, was still significant. No correlations with clinical variables were found for any of the investigated resting state networks. Conclusions The SCA2 patients show significant alterations of the resting state networks, only partly explained by the atrophy. The default mode network is the only resting state network that shows also supratentorial changes, which appear unrelated to the cortical gray matter volume. Further studies are needed to assess the clinical significance of these changes. © 2015 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Genomic and trascriptomic profiling has recently contributed details to the characterization of luminal B breast cancer. We explored the contribution of anthropometric, metabolic, and molecular determinants to the multifaceted heterogeneity of this breast cancer subtype, with a specific focus on the association between body mass index (BMI), pre-treatment fasting glucose, hormone receptors, and expression of human epidermal growth factor receptor 2 (HER2). Extensively annotated specimens were obtained from 154 women with luminal B breast cancer diagnosed at two Italian comprehensive cancer centres. Participants' characteristics were descriptively analyzed overall and by HER2 status (positive vs. negative). BMI (<25 vs ≥25), pre-treatment fasting glucose (