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Given the paucity of data surrounding the prognostic relevance of circulating lymphoma (CL) in Waldenström macroglobulinemia (WM), we sought to evaluate the impact of CL at diagnosis on outcomes in patients with WM. Patients were divided into CL+ and CL-based on the results of flow cytometry. The endpoints included assessing progression-free survival (PFS), overall survival (OS), and diagnosis-to-treatment interval (DTI) between the two groups. Among the 308 patients with WM, 69 met the eligibility criteria with 42 and 27 in CL+ and CLgroups, respectively. The two groups were well balanced in regard to all the baseline characteristics. The ORR was numerically higher in the CL+ group compared to the CL-group (81% versus 61%, respectively), however, the CR +VGPR rates were similar between the two groups. The median PFS was not significantly different between the two groups (6.3 years in the CL- group versus not reached [NR] in the CL+ group) regardless of the first-line therapy. There was no significant difference in median OS between the CL- and CL+ groups (13 years versus NR). Although the median DTI was shorter in the CL+ group compared to CL- group, the significance was lost in the multivariable analysis. In this study (largest-to-date) evaluating the impact of CL on outcomes in patients with newly diagnosed WM, we did not find the prognostic utility of CL in WM. Future studies should explore the correlation of CL with other biological factors that impact the outcomes in WM patients. [ABSTRACT FROM AUTHOR]

Cognitive dysfunction and brain white matter (WM) injury have been found in adults exposed to hypoxia. However, the mechanisms underlying these impairments remain unclear, and moreover, it is also unclear whether these impairments are reversible after reoxygenation. In this study, adult male mice were exposed to hypoxia for 15 days at a simulated altitude of 4300 m and then reoxygenated for 2 months. Control mice were raised under normoxic conditions. Mice showed a significant decrease in arterial oxygen saturation (SaO2) and an increase in heart rate and breath rate after hypoxic exposure, and they displayed anxiety-like emotion and impaired cognitions. Hypoxic mice showed decreased brain WM fractional anisotropy (FA) and increased mean diffusion (MD) mainly in the corpus callosum and internal capsule. The reason for the adult brain WM injury was myelin rather than axon. Further, the myelin injury was due to the obstruction of oligodendrocyte precursor cells (OPCs) differentiation and eventually led to behavioral deficits. More importantly, the changes in physiological indicators, behavioral disorders, and WM injury caused by hypoxia can be recovered after reoxygenation. Taken together, our data indicate that adult brain WM injury caused by hypoxia is reversible after reoxygenation and enhancing OPCs differentiation may be a promising therapy for clinical hypoxic diseases associated with brain injury. Schematic diagram of brain WM and behavioral changes induced by hypoxia/reoxygenation in adult mice [ABSTRACT FROM AUTHOR]

Given the paucity of data surrounding the prognostic relevance of circulating lymphoma (CL) in Waldenström macroglobulinemia (WM), we sought to evaluate the impact of CL at diagnosis on outcomes in patients with WM. Patients were divided into CL+ and CL- based on the results of flow cytometry. The endpoints included assessing progression-free survival (PFS), overall survival (OS), and diagnosis-to-treatment interval (DTI) between the two groups. Among the 308 patients with WM, 69 met the eligibility criteria with 42 and 27 in CL+ and CL- groups, respectively. The two groups were well balanced in regard to all the baseline characteristics. The ORR was numerically higher in the CL+ group compared to the CL-group (81% versus 61%, respectively), however, the CR+VGPR rates were similar between the two groups. The median PFS was not significantly different between the two groups (6.3 years in the CL- group versus not reached [NR] in the CL+ group) regardless of the first-line therapy. There was no significant difference in median OS between the CL- and CL+ groups (13 years versus NR). Although the median DTI was shorter in the CL+ group compared to CL- group, the significance was lost in the multivariable analysis. In this study (largest-to-date) evaluating the impact of CL on outcomes in patients with newly diagnosed WM, we did not find the prognostic utility of CL in WM. Future studies should explore the correlation of CL with other biological factors that impact the outcomes in WM patients.

A 65-year-old woman was referred to the hospital for further investigation of weight loss, hyperproteinemia, and anemia. Serum immunofixation electrophoresis revealed IgM-κ M protein. Bone marrow examination revealed an increase in the number of B -cells with immunoglobulin kappa light-chain restriction. Although the MYD88 L265P mutation was identified in bone marrow mononuclear cells, which suggested the diagnosis of Waldenstrom's macroglobulinemia (WM), a fusion signal of IgH-MALT1, which is commonly observed in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma, was also identified. Here, we describe a rare case of low-grade B-cell lymphoma with MYD88 L265P mutations accompanying IgH-MALT1.

The present study investigated the differential effects of explicit corrections, meta-linguistic corrective feedback (CF), and analogy-based CF on L2 learners' acquisition of English third-person singular form -s and whether and how individual differences in working memory (WM) mediate such effects. One hundred secondary school English-as-a-foreign-language (EFL) learners at a junior middle school in inland China were randomly assigned to the explicit correction group (EG), the meta-linguistic CF group (MG), the analogy-based CF group (AG), and the control group (CG). Learners performed both an information-gap activity and a picture-description activity where their errors on target structure were treated according to their group assignment. The Untimed Grammatical Judgement Test (UGJT) and the Elicited Oral Production Test (EOPT) were used tomeasure learners' resulting performance. Learners' WM was measured with operation span test. Results revealed that (1) compared to the control group, all the CF groups significantly improved their performance of English third-person singular form -s over time; (2) explicit corrections and meta-linguistic CF displayed superior advantages over analogy-based CF on the immediate posttest. However, the three CF groups demonstrated no significant difference in their performance of English third-person singular form -s on the delayed posttest; (3) WM was only able to predict the effects of analogy-based CF but not explicit corrections and meta-linguistic CF; and (4) analogy-based CF was more favorable to learners with higher WM who can regulate their limited attentional resources more efficiently, whereas explicit corrections and meta-linguistic CF equalize learning opportunities for all learners with different levels of WM. The findings of this study suggest optimal, profile-matched pedagogical options for L2 learning through identifying CF conditions that cater to the needs of young learners with different levels of WM. [ABSTRACT FROM AUTHOR]

Waldenström's Macroglobulinemia (WM) is a clonal B-lymphocyte neoplasm characterized by the presence of IgM monoclonal protein and ≥ 10% bone marrow involvement with lymphoplasmacytic cells. Several mature B-cell and plasma cell disorders can potentially produce monoclonal IgM immunoglobulin and hence, careful consideration of the differential diagnosis is vital. Clinico-pathological features, immunophenotype, and MYD88 mutation status help distinguish WM from other plasma cell and lymphoproliferative disorders. Treatment is only indicated in patients symptomatic from adenopathy or organomegaly, neuropathy, hyper viscosity, cryoglobulinemia, cold agglutinin disease, cytopenia's or amyloidosis. Alkylators (cyclophosphamide, bendamustine) in combination with anti-CD20 antibodies and novel targeted agents including Bruton tyrosine kinase (BTK) inhibitors like ibrutinib are the mainstay of frontline treatment in symptomatic WM. [ABSTRACT FROM AUTHOR]

A clinical diagnosis of primary progressive aphasia relies on behavioral characteristics and patterns of atrophy to determine a variant: logopenic; nonfluent/agrammatic; or semantic. The dual stream model is a contemporary paradigm that has been applied widely to understand brain-behavior relationships; however, applications to neurodegenerative diseases like primary progressive aphasia are limited. The primary aim of this study is to determine if the dual stream model can be applied to a neurodegenerative disease, such as primary progressive aphasia, using both behavioral and neuroimaging data. We analyzed behavioral and neuroimaging data to apply a multivariate classification tool (support vector machines) to determine if the dual stream model extends to primary progressive aphasia. Sixty-four individuals with primary progressive aphasia were enrolled (26 logopenic variant, 20 nonfluent/agrammatic variant, and 18 semantic variant) and administered four behavioral tasks to assess three linguistic domains (naming, repetition, and semantic knowledge). We used regions of interest from the dual stream model and calculated the cortical volume for gray matter regions and white matter structural volumes and fractional anisotropy. We applied a multivariate classification tool (support vector machines) to distinguish variants based on behavioral performance and patterns of atrophy. Behavioral performance discriminates logopenic from semantic variant and nonfluent/agrammatic from semantic variant. Cortical volume distinguishes all three variants. White matter structural volumes and fractional anisotropy primarily distinguish nonfluent/agrammatic from semantic variant. Regions of interest that contribute to each classification in cortical and white matter analyses demonstrate alignment of logopenic and nonfluent/agrammatic variants to the dorsal stream, while the semantic variant aligns with the ventral stream. A novel implementation of an automated multivariate classification suggests that the dual stream model can be extended to primary progressive aphasia. Variants are distinguished by behavioral and neuroanatomical patterns and align to the dorsal and ventral streams of the dual stream model. Application of the dual stream model to PPA [ABSTRACT FROM AUTHOR]

Waldenström Macroglobulinemia (WM) is an indolent lymphoplasmacytic lymphoma, characterized by the production of excess immunoglobulin M monoclonal protein. WM belongs to the spectrum of IgM gammopathies, ranging from asymptomatic IgM monoclonal gammopathy of undetermined significance (IgM-MGUS), through IgM-related disorders and asymptomatic WM to symptomatic WM. In recent years, its complex genomic and transcriptomic landscape has been extensively explored, hereby elucidating the biological mechanisms underlying disease onset, progression and therapy response. An increasing number of mutations, cytogenetic abnormalities, and molecular signatures have been described that have diagnostic, phenotype defining or prognostic implications. Moreover, cell-free nucleic acid biomarkers are increasingly being investigated, benefiting the patient in a minimally invasive way. This review aims to provide an extensive overview of molecular biomarkers in WM and IgM-MGUS, considering current shortcomings, as well as potential future applications in a precision medicine approach. [ABSTRACT FROM AUTHOR]

Using quantitative T2* at 7 Tesla (T) magnetic resonance imaging, we investigated whether impairment in selective cognitive functions in multiple sclerosis (MS) can be explained by pathology in specific areas and/or layers of the cortex. Thirty-one MS patients underwent neuropsychological evaluation, acquisition of 7 T multi-echo T2* gradient-echo sequences, and 3 T anatomical images for cortical surfaces reconstruction. Seventeen age-matched healthy subjects served as controls. Cortical T2* maps were sampled at various depths throughout the cortex and juxtacortex. Relation between T2*, neuropsychological scores and a cognitive index (CI), calculated from a principal component analysis on the whole battery, was tested by a general linear model. Cognitive impairment correlated with T2* increase, independently from white matter lesions and cortical thickness, in cortical areas highly relevant for cognition belonging to the default-mode network (p

This paper presents a process voltage temperature (PVT)‐variation‐tolerant Schmitt‐trigger‐based 12T SRAM cell at 32 nm. The cell uses a modified Schmitt‐trigger action in all operating modes for performance improvement, a characteristic that is not exhibited by existing SRAM cells. The action improves the stability of stored data in read and hold modes and assists the write process to enable a faster and low‐voltage write operation. Additionally, the cell uses negative bitline technique and fully‐gated grounded scheme for achieving further improvement in write ability and ION/IOFF ratio. The proposed cell shows 34.9% reduced deviation in switching threshold voltage in comparison to conventional structure. Further, improvement of up to 211% in write ability and 169% in ION/IOFF ratio is obtained over existing SRAM cells operating in sub‐threshold region. The cell takes up to 86% and 99% lesser read and write access time, respectively. The Monte‐Carlo simulations show the robust performance of proposed cell. The cell has reduced write, read, and hold failure probabilities resulting in overall Vmin of 425 mV, which is the least among the cells considered for comparison, thus making it an amenable design suitable for sub‐threshold operation under PVT‐variations. [ABSTRACT FROM AUTHOR]

Background: Impairments in various subdomains of memory have been associated with chronic cannabis use, but less is known about their neural underpinnings, especially in the domain of the brain's oscillatory activity. Aims: To investigate neural oscillatory activity supporting working memory (WM) in regular cannabis users and non-using controls. We focused our analyses on frontal midline theta and posterior alpha asymmetry as oscillatory fingerprints for the WM's maintenance process. Methods: 30 non-using controls (CG) and 57 regular cannabis users—27 exclusive cannabis users (CU) and 30 polydrug cannabis users (PU) completed a Sternberg modified WM task with a concurrent electroencephalography recording. Theta, alpha and beta frequency bands were examined during WM maintenance. Results: When compared to non-using controls, the PU group displayed increased frontal midline theta (FMT) power during WM maintenance, which was positively correlated with RT. The posterior alpha asymmetry during the maintenance phase, on the other hand, was negatively correlated with RT in the CU group. WM performance did not differ between groups. Conclusions: Both groups of cannabis users (CU and PU), when compared to the control group, displayed differences in oscillatory activity during WM maintenance, unique for each group (in CU posterior alpha and in PU FMT correlated with performance). We interpret those differences as a reflection of compensatory strategies, as there were no differences between groups in task performance. Understanding the psychophysiological processes in regular cannabis users may provide insight on how chronic use may affect neural networks underlying cognitive processes, however, a polydrug use context (i.e., combining cannabis with other illegal substances) seems to be an important factor. [ABSTRACT FROM AUTHOR]

Background: Impairments in various subdomains of memory have been associated with chronic cannabis use, but less is known about their neural underpinnings, especially in the domain of the brain’s oscillatory activity.Aims: To investigate neural oscillatory activity supporting working memory (WM) in regular cannabis users and non-using controls. We focused our analyses on frontal midline theta and posterior alpha asymmetry as oscillatory fingerprints for the WM’s maintenance process.Methods: 30 non-using controls (CG) and 57 regular cannabis users—27 exclusive cannabis users (CU) and 30 polydrug cannabis users (PU) completed a Sternberg modified WM task with a concurrent electroencephalography recording. Theta, alpha and beta frequency bands were examined during WM maintenance.Results: When compared to non-using controls, the PU group displayed increased frontal midline theta (FMT) power during WM maintenance, which was positively correlated with RT. The posterior alpha asymmetry during the maintenance phase, on the other hand, was negatively correlated with RT in the CU group. WM performance did not differ between groups.Conclusions: Both groups of cannabis users (CU and PU), when compared to the control group, displayed differences in oscillatory activity during WM maintenance, unique for each group (in CU posterior alpha and in PU FMT correlated with performance). We interpret those differences as a reflection of compensatory strategies, as there were no differences between groups in task performance. Understanding the psychophysiological processes in regular cannabis users may provide insight on how chronic use may affect neural networks underlying cognitive processes, however, a polydrug use context (i.e., combining cannabis with other illegal substances) seems to be an important factor.

Despite the success of antiretroviral therapy (ART), perinatally infected HIV remains a major health problem worldwide. Although advance neuroimaging studies have investigated structural brain changes in HIV-infected adults, regional gray matter (GM) and white matter (WM) volume changes have not been reported in perinatally HIV-infected adolescents and young adults. In this cross-sectional study, we investigated regional GM and WM changes in 16 HIV-infected youths receiving ART (age 17.0 ± 2.9 years) compared with age-matched 14 healthy controls (age 16.3 ± 2.3 years) using magnetic resonance imaging (MRI)-based high-resolution T1-weighted images with voxel based morphometry (VBM) analyses. White matter atrophy appeared in perinatally HIV-infected youths in brain areas including the bilateral posterior corpus callosum (CC), bilateral external capsule, bilateral ventral temporal WM, mid cerebral peduncles, and basal pons over controls. Gray matter volume increase was observed in HIV-infected youths for several regions including the left superior frontal gyrus, inferior occipital gyrus, gyrus rectus, right mid cingulum, parahippocampal gyrus, bilateral inferior temporal gyrus, and middle temporal gyrus compared with controls. Global WM and GM volumes did not differ significantly between groups. These results indicate WM injury in perinatally HIV-infected youths, but the interpretation of the GM results, which appeared as increased regional volumes, is not clear. Further longitudinal studies are needed to clarify if our results represent active ongoing brain infection or toxicity from HIV treatment resulting in neuronal cell swelling and regional increased GM volume. Our findings suggest that assessment of regional GM and WM volume changes, based on VBM procedures, may be an additional measure to assess brain integrity in HIV-infected youths and to evaluate success of current ART therapy for efficacy in the brain.

Despite the success of antiretroviral therapy (ART), perinatally infected HIV remains a major health problem worldwide. Although advance neuroimaging studies have investigated structural brain changes in HIV-infected adults, regional gray matter (GM) and white matter (WM) volume changes have not been reported in perinatally HIV-infected adolescents and young adults. In this cross-sectional study, we investigated regional GM and WM changes in 16 HIV-infected youths receiving ART (age 17.0 ± 2.9 years) compared with age-matched 14 healthy controls (age 16.3 ± 2.3 years) using magnetic resonance imaging (MRI)-based high-resolution T1-weighted images with voxel based morphometry (VBM) analyses. White matter atrophy appeared in perinatally HIV-infected youths in brain areas including the bilateral posterior corpus callosum (CC), bilateral external capsule, bilateral ventral temporal WM, mid cerebral peduncles, and basal pons over controls. Gray matter volume increase was observed in HIV-infected youths for several regions including the left superior frontal gyrus, inferior occipital gyrus, gyrus rectus, right mid cingulum, parahippocampal gyrus, bilateral inferior temporal gyrus, and middle temporal gyrus compared with controls. Global WM and GM volumes did not differ significantly between groups. These results indicate WM injury in perinatally HIV-infected youths, but the interpretation of the GM results, which appeared as increased regional volumes, is not clear. Further longitudinal studies are needed to clarify if our results represent active ongoing brain infection or toxicity from HIV treatment resulting in neuronal cell swelling and regional increased GM volume. Our findings suggest that assessment of regional GM and WM volume changes, based on VBM procedures, may be an additional measure to assess brain integrity in HIV-infected youths and to evaluate success of current ART therapy for efficacy in the brain.

Waldenström Macroglobulinemia (WM) is an indolent lymphoplasmacytic lymphoma, characterized by the production of excess immunoglobulin M monoclonal protein. WM belongs to the spectrum of IgM gammopathies, ranging from asymptomatic IgM monoclonal gammopathy of undetermined significance (IgM-MGUS), through IgM-related disorders and asymptomatic WM to symptomatic WM. In recent years, its complex genomic and transcriptomic landscape has been extensively explored, hereby elucidating the biological mechanisms underlying disease onset, progression and therapy response. An increasing number of mutations, cytogenetic abnormalities, and molecular signatures have been described that have diagnostic, phenotype defining or prognostic implications. Moreover, cell-free nucleic acid biomarkers are increasingly being investigated, benefiting the patient in a minimally invasive way. This review aims to provide an extensive overview of molecular biomarkers in WM and IgM-MGUS, considering current shortcomings, as well as potential future applications in a precision medicine approach.

Recent contributions to the body of knowledge on traumatic brain injury (TBI) favor the view that multimodal neuroimaging using structural and functional magnetic resonance imaging (MRI and fMRI, respectively) as well as diffusion tensor imaging (DTI) has excellent potential to identify novel biomarkers and predictors of TBI outcome. This is particularly the case when such methods are appropriately combined with volumetric/morphometric analysis of brain structures and with the exploration of TBI-related changes in brain network properties at the level of the connectome. In this context, our present review summarizes recent developments on the roles of these two techniques in the search for novel structural neuroimaging biomarkers that have TBI outcome prognostication value. The themes being explored cover notable trends in this area of research, including (1) the role of advanced MRI processing methods in the analysis of structural pathology, (2) the use of brain connectomics and network analysis to identify outcome biomarkers, and (3) the application of multivariate statistics to predict outcome using neuroimaging metrics. The goal of the review is to draw the community's attention to these recent advances on TBI outcome prediction methods and to encourage the development of new methodologies whereby structural neuroimaging can be used to identify biomarkers of TBI outcome.

During aging, human white matter (WM) is subject to dynamic structural changes which have a deep impact on healthy and pathological evolution of the brain through the lifespan; characterizing this pattern is of key importance for understanding brain development, maturation, and aging as well as for studying its pathological alterations. Diffusion magnetic resonance imaging (MRI) can provide a quantitative assessment of the white-matter microstructural organization that characterizes these trajectories. Here, we use both conventional and advanced diffusion MRI in a cohort of 91 individuals (age range: 13–62 years) to study region- and sex-specific features of WM microstructural integrity in healthy aging. We focus on the age at which microstructural imaging parameters invert their development trend as the time point which marks the onset of microstructural decline in WM. Importantly, our results indicate that age-related brain changes begin earlier in males than females and affect more frontal regions—in accordance with evolutionary theories and numerous evidences across non-MRI domains. Advanced diffusion MRI reveals age-related WM modification patterns which cannot be detected using conventional diffusion tensor imaging. • Age-related WM changes begin earlier in males than in females. • Advanced MRI is more sensitive to age-related alterations in the brain. • Early WM modifications can be detected sooner using advanced diffusion MRI. [ABSTRACT FROM AUTHOR]

Comparisons of white matter (WM) fractional anisotropy (FA) values between mild traumatic brain injury (mTBI) patients and controls have revealed inconsistencies in the directions of the resulting FA changes. To address these discrepancies, we examined hemispheric FA symmetry levels across WM tracts in 150 mTBI patients relative to 96 military controls. Automated fiber quantification was used to extract 18 WM tracts with 100 FA values, which were used to compute correlation strengths between the nine bilateral tract pairs. The Fisher z-transformed Pearson's r values were entered into an analysis of covariance examining the effects of group (mTBI and controls) and age on symmetry levels within each tract pair. The mTBI group displayed lower symmetry levels in the corticospinal tract and the inferior longitudinal fasciculus. Interactions between age and group were detected in the inferior fronto-occipital (IFOF), uncinate (UF), and superior longitudinal fasciculi (SLF). A similar pattern emerged in the IFOF and the UF, revealing age-related symmetry decreases in the mTBI patients despite stable levels of symmetry across ages in controls. In contrast, although the control group's symmetry levels actually increased with age in the SLF, no age-related symmetry changes were detected across the mTBI participants. Here, we proposed WM symmetry measures as a potential means of circumventing directional inconsistencies of trauma-related FA changes, as well as capturing more within-tract and within-subject variances of diffusion tensor imaging (DTI) metrics. Further, we demonstrated the method's utility in detecting mTBI-specific effects and their associated interactions with age. [ABSTRACT FROM AUTHOR]

• Verbal working memory is significantly better in the pathological smartphone users than in the control group. • Verbal working memory advantage of the pathological smartphone users is transferred from the network-related stimulus to the neutral stimulus. • The advantages of network stimulus were related to bidirectional connectivity between frontopolar and right-dorsolateral. • The left-dorsolateral prefrontal cortex and frontopolar are associated with the cross-material consistency of working memory. Previous studies have found working memory (WM) advantages of the pathological smartphone use (PSU) group, but most of which were emphasized in the network-related domain. Whether the advantages can transfer to other domains has yet to be confirmed. In particular, exploring from a brain mechanism perspective is necessary. Using the classical N-back paradigm, this study selected network-related words and neutral words as materials combined with fNIRS to probe the verbal WM characteristics of the PSU group. The results showed that β in channel 3, channel 4, and channel 5 were significantly lower in the PSU group than those in the control group The analysis of the region of interest revealed that the PSU group showed significantly lower β in the l -DLPFC and frontopolar. Granger Causality results showed that functional connectivity between frontopolar and R-DLPFC for the PSU group was significantly higher than for the control group in the network word condition. These results demonstrate that the PSU group has an advantage in WM, transferring from the network-related stimulus to the neutral stimulus. The advantages of network stimulus were related to bidirectional connectivity between frontopolar and R-DLPFC. Also, the l -DLPFC and frontopolar are associated with the cross-material consistency of WM. [ABSTRACT FROM AUTHOR]

In IgM monoclonal gammopathies MYD88L265P is a prognostic and predictive biomarker of therapy response. MYD88L265P detection is mainly performed by allele-specific quantitative PCR (ASqPCR), however recently, droplet digital PCR (ddPCR) has been proved to be suitable for MYD88L265P screening and minimal residual disease monitoring (MRD). This study compared ASqPCR and ddPCR to define the most sensitive method for MYD88L265P detection in bone marrow (BM), peripheral blood (PB) sorted or unsorted CD19+ cells, and in plasma cell-free DNA (cfDNA). Overall, the analysis showed a good concordance rate (74%) between the two methods, especially in BM samples, while discordances (26%) were mostly in favor of ddPCR (ddPCR+ vs. ASqPCR-) and were particularly evident in samples with low mutational burden, such as PB and cfDNA. This study highlights ddPCR as a feasible approach for MYD88L265P detection across different specimen types (including cfDNA). Interestingly, its high sensitivity makes CD19+ selection dispensable. On the other hand, our results showed that MYD88L265P detection on PB samples, especially with ASqPCR, is suboptimal for screening and MRD analysis. Finally, significantly different MYD88L265P mutational levels observed between Waldenström Macroglobulinemia and IgM monoclonal gammopathy of undetermined significance patients suggest the need for further studies in order to identify possible correlations between mutational levels and risk of progression to Waldenström.

There are no studies to date,describing changes in the diffusion tensor imaging (DTI) metrics of the white matter (WM) regions of the entire cervical and thoracic spinal cord (SC) remote from the lesion in pediatric spinal cord injury (SCI) subjects. The purpose of this study was to determine whether DTI at sites cephalad and caudal to a lesion provides measures of cord abnormalities in children with chronic SCI. A retrospective study included 10 typically developing subjects (TD) and 10 subjects with chronic SCI who underwent SC imaging in 2014–2017. Axial diffusion tensor images using an inner field of view DTI sequence were acquired to cover the entire cervical and thoracic SC. Regions of interest were drawn on the SC WM: right and left lateral (motor), ventral (motor), and dorsal (sensory) tracts. To detect differences in DTI metrics between TD and SCI of the cord, a one way analysis of variance with pooled t test was performed. A stepwise regression analysis was performed to assess the correlation between DTI metrics and clinical scores. In motor and sensory tracts, fractional anisotropy (FA) and axial diffusivity (AD) were significantly decreased in the proximal segments of the caudal cord. In motor tracts cephalad to the lesion, FA was significantly decreased whereas AD was significantly increased in the proximal segment; however, AD was decreased in the distal and middle segments. International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) total score was significantly correlated with FA and AD of the motor and sensory tracts cephalad to the lesion. This study demonstrates that FA and AD have the potential to be sensitive biomarkers of the full extent of cord injury and might be useful in detecting remote injuries to the SC and in guiding new treatments. [ABSTRACT FROM AUTHOR]

Segmentation of brain MR images for the detection of various healthy brain tissues such as white matter, gray matter, and cerebrospinal fluid is of immense interest to detect and to diagnose different brain-related disorders at the primitive level. MR image segmentation becomes a difficult task owing to the presence of intensity inhomogeneity (IIH), noise, partial volume effects, and intrinsic nature of the MR images. This paper proposes an efficient, region-based, energy minimization technique named as anisotropic multiplicative intrinsic component optimization (AMICO) to segment the brain image in the presence of IIH and noise and to detect different healthy brain tissues. The proposed algorithm utilizes a powerful anisotropic diffusion filter to denoise the image. The MICO algorithm segment the denoised image after correcting IIH. In the proposed technique, MR brain image is decomposed into two multiplicative and intrinsic components, such as the true image component and the bias field component. Brain tissue physical properties are represented by the component of true image and the IIH is characterized by the bias field component. Optimization of these two multiplicative and intrinsic components by employing the proposed effective energy minimization process, result in IIH correction and tissue segmentation simultaneously. The pursuance of the proposed technique is compared with some other existing techniques using the parameters, dice similarity coefficient, sensitivity, specificity, and segmentation accuracy. The results validated the excellent performance of the AMICO in detecting various brain tissues consisting of various levels of IIH and noise. [ABSTRACT FROM AUTHOR]

Abstract Background and purpose The stiffness of large arteries and increased pulsatility can have an impact on the brain white matter (WM) microstructure, however those mechanisms are still poorly understood. The aim of this study was to investigate the association between central artery stiffness, axonal and myelin integrity in 54 cognitively unimpaired elderly subjects (65–75 years old). Methods The neuronal fiber integrity of brain WM was assessed using diffusion tensor metrics and magnetization transfer imaging as measures of axonal organization (Fractional anisotropy, Radial diffusivity) and state of myelination (Myelin volume fraction). Central artery stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). Statistical analyses included 4 regions (the corpus callosum, the internal capsule, the corona radiata and the superior longitudinal fasciculus) which have been previously denoted as vulnerable to increased central artery stiffness. Results cfPWV was significantly associated with fractional anisotropy and radial diffusivity (p < 0.05, corrected for multiple comparisons) but not with myelin volume fraction. Findings from this study also show that improved executive function performance correlates with Fractional anisotropy positively (p < 0.05 corrected) as well as with myelin volume fraction and radial diffusivity negatively (p < 0.05 corrected). Conclusions These findings suggest that arterial stiffness is associated with axon degeneration rather than demyelination. Controlling arterial stiffness may play a role in maintaining the health of WM axons in the aging brain. [ABSTRACT FROM AUTHOR]

Sub-Saharan Africa is home to 90% of HIV infected (HIV+) children. Since the advent of antiretroviral therapy (ART), HIV/AIDS has transitioned to a chronic condition where central nervous system (CNS) damage may be ongoing. Although, most guidelines recommend early ART to reduce CNS viral reservoirs, the brain may be more vulnerable to potential neurotoxic effects of ART during the rapid development phase in the first years of life. Here we investigate differences in subcortical volumes between 5-year-old HIV+ children who received early ART (before age 18 months) and uninfected children using manual tracing of Magnetic Resonance Images. Participants included 61 Xhosa children (43 HIV+/18 uninfected, mean age = 5.4 ± 0.3 years, 25 male) from the children with HIV early antiretroviral (CHER) trial; 27 children initiated ART before 12 weeks of age (ART-Before12Wks) and 16 after 12 weeks (ART-After12Wks). Structural images were acquired on a 3T Allegra MRI in Cape Town and manually traced using MultiTracer. Volumetric group differences (HIV+ vs. uninfected; ART-Before12Wks vs. ART-After12Wks) were examined for the caudate, nucleus accumbens (NA), putamen (Pu), globus pallidus (GP), and corpus callosum (CC), as well as associations within infected children of structure volumes with age at ART initiation and CD4/CD8 as a proxy for immune health. HIV+ children had significantly larger NA and Pu volumes bilaterally and left GP volumes than controls, whilst CC was smaller. Bilateral Pu was larger in both treatment groups compared to controls, while left GP and bilateral NA were enlarged only in ART-After12Wks children. CC was smaller in both treatment groups compared to controls, and smaller in ART-After12Wks compared to ART-Before12Wks. Within infected children, delayed ART initiation was associated with larger Pu volumes, effects that remained significant when controlling for sex and duration of treatment interruption (left β = 0.447, p = 0.005; right β = 0.325, p = 0.051), and lower CD4/CD8 with larger caudates controlling for sex (left β = −0.471, p = 0.002; right β = −0.440, p = 0.003). Volumetric differences were greater in children who initiated ART after 12 weeks. Results suggest damage is ongoing despite early ART and viral load suppression; however, earlier treatment is neuroprotective.

Background Glatiramer acetate (GA) 40 mg × 3/weekly was approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). While the beneficial effect of GA 20 mg/daily in MS patients on non-conventional MRI measures has been demonstrated, the effect of GA 40 mg × 3/weekly at the microstructural tissue level has yet to be explored. Objective To investigate the effect of switching from GA 20 mg/daily to GA 40 mg × 3/weekly on the evolution of microstructural changes in the thalamus and normal appearing white matter (NAWM), using diffusion tensor imaging (DTI). Methods In this observational, longitudinal, cross-over, 34-month MRI study, we recruited 150 RRMS patients that underwent MRI 12–18 months before switching (pre-index), during the switch (index) and 12–18 months after switching (post-index) from GA 20 mg/daily to GA 40 mg × 3/weekly. Regional DTI metrics and tract-based spatial statistics (TBSS) analyses were performed. Mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) and fractional anisotropy (FA) were measured in thalamus and NAWM. Results Regional DTI measures, measures of whole brain, white and gray matter, and thalamus volumes, as well as lesion volume, showed no significant changes. However, the voxel-wise TBSS analysis showed increased FA both in the NAWM and thalamus, as well as increased MD and AD in NAWM, and decreased RD in NAWM (p < .05). Areas of increased FA and MD as well as decreased RD in the NAWM, and increased AD both in the NAWM and thalamus were detected between index to post-index (p < .05). Conclusions This study confirms a comparable effect of GA 40 mg × 3/weekly to GA 20 mg/daily on DTI measures over 34 months. [ABSTRACT FROM AUTHOR]

Turkish Woodworking Machinery (WM) Industry has become an important market in line with the developments in furniture and other forest products industries. In spite of the developments in WM industry of Turkey, the sector is yet to be developed in terms of competitiveness, especially given the fact that the sector still fails to satisfy the domestic demand. WM foreign trade of Turkey changes on an annual basis, and according to recent trade data, export volume reached 1% of global market with 90 million USD and import volume reached 2% of global market with 200 million$. The majority of imported goods are supplied from developed countries such as Germany, Italy and China, whereas developing countries such as Russia, Iraq and Libya purchase most of the exported goods. In recent years the negative trend in the balance of foreign trade declined to 110 million $ levels, resulting in a rapid decline in foreign trade deficit. The aim of the present study was to determine the position and international competitiveness of Turkish WM industry. For this purpose, the definitions as to the competitiveness of the sector and evaluation methodology for international competitiveness were initially provided. 2004-2015 foreign trade data of International Trade Center (ITC) and Turkish Statistical Institute (TUIK in Turkish) were used to estimate the Revealed Comparative Advantage Index. Afterwards, other indices for competitiveness, adopted in the literature, were used to determine the international competitiveness of the sector among global markets. [ABSTRACT FROM AUTHOR]

MYD88 L265P is a gain-of-function mutation, arising from the missense alteration c.794T>C, that frequently occurs in B-cell malignancies such as Waldenstrom macroglobulinemia and less frequently in IgM monoclonal gammopathy of undetermined significance (IgM-MGUS) or other lymphomas. MYD88 L265P has been recognized as a relevant diagnostic flag, but also as a valid prognostic and predictive biomarker, as well as an investigated therapeutic target. Up until now, allele-specific quantitative PCR (ASqPCR) has been widely used for MYD88 L265P detection providing a higher level of sensitivity than Sanger sequencing. However, the recently developed droplet digital PCR (ddPCR) shows a deeper sensitivity, compared to ASqPCR, that is necessary for screening low infiltrated samples. Actually, ddPCR could represent an improvement in daily laboratory practice since it allows mutation detection in unselected tumor cells, allowing to bypass the time-consuming and costly B-cell selection procedure. ddPCR accuracy has been recently proved to be suitable also for mutation detection in "liquid biopsy" samples that might be used as a noninvasive and patient-friendly alternative to bone marrow aspiration especially during the disease monitoring. The relevance of MYD88 L265P , both in daily management of patients and in prospective clinical trials investigating the efficacy of novel agents, makes crucial to find a sensitive, accurate, and reliable molecular technique for mutation detection. Here, we propose a protocol for MYD88 L265P detection by ddPCR., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The aim of this study is to investigate and describe the barriers system that precludes the feasibility, or limits the performance of the waste management projects through the analysis of which are the declared barriers at the 432 large waste management projects registered as CDM during the period 2004–2014. The final product is a waste management barriers conceptual model proposal (STAR), supported by literature and corroborated by projects design documents. This paper uses the computer assisted qualitative content analysis (CAQCA) methodology with the qualitative data analysis (QDA) software NVivo®, by 890 fragments, to investigate the motives to support our conclusions. Results suggest the main barriers classification in five types: sociopolitical, technological, regulatory, financial, and human resources constraints. Results also suggest that beyond the waste management industry, projects have disadvantages added related to the same barriers inherent to others renewable energies initiatives. The STAR model sheds some light over the interactivity and dynamics related to the main constraints of the industry, describing the mutual influences and relationships among each one. Future researches are needed to better and comprehensively understand these relationships and ease the development of tools to alleviate or eliminate them. [ABSTRACT FROM AUTHOR]

The present study examined the relations of general, fluid and crystallized intelligence with three cognitive functions – speed of processing, attention and working memory (WM) – in 158 7- to 18-year-old children and adolescents. Multiple measures of each of these cognitive functions were obtained. Intelligence was assessed using the Wechsler Abbreviated Scale of Intelligence (WASI). Structural equation modeling was performed to determine which cognitive function served as the best predictor of intelligence. The results showed that only WM predicted general, fluid and crystallized intelligence when controlling for the other two cognitive functions. Neither processing speed nor attention significantly predicted intelligence. These findings indicate that WM is the main cognitive function underlying general, fluid and crystallized intelligence in children and adolescents. Moreover, results indicated that age-related changes in WM lead directly to developmental changes in intelligence (general, fluid and crystallized). [ABSTRACT FROM AUTHOR]