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The effect associated with productivity movements about As well as pollution levels within Turkey: testing EKC speculation using Fourier stationarity check.
Since the introduction of an alkylator to the treatment of multiple myeloma (MM), new effective agents have been developed, such as immunomodulatory drugs including thalidomide, lenalidomide, and pomalidomide; proteasome inhibitors including bortezomib, carfilzomib, and ixazomib; monoclonal antibodies including daratumumab and elotuzumab; and deacetylase inhibitors including panobinostat. Numerous regimens with these new agents have been developed and they have contributed in improving survival outcomes in MM patients. In addition, the recommended therapies for newly diagnosed MM change every year based on the results of clinical trials. This review will discusses the appropriate induction therapies based on recent clinical trials for patients with newly diagnosed MM.Acute lymphoblastic leukemia (ALL) is an aggressive hematological disease. The incorporation of tyrosine kinase inhibitors (TKIs) into the standard treatment regimen for Philadelphia (Ph)-positive ALL significantly improved clinical outcomes. TKI-based induction chemotherapy, followed by allogeneic hematopoietic cell transplantation (HCT) during the first complete remission (CR), is the standard of care for ALL patients. However, treatment with TKIs alone or TKIs plus low-intensity chemotherapy can achieve CR in some patients. Although this strategy is not enough to induce a deeper molecular response, it can reduce the incidence of treatment-related mortality. Despite promising results from pediatric trials, allogeneic HCT remains an important component of the treatment strategy for Ph-positive adult ALL. However, improving the highly sensitive BCR-ABL1 assays and introducing immunotherapy may decrease the demand for allogeneic HCT. Nevertheless, the treatment of Ph-positive ALL is still challenging, especially in cases with relapsed and refractory disease. Potent TKIs and monoclonal antibodies, such as blinatumomab and inotuzumab, have improved patient outcomes in relapse and refractory cases of ALL. The introduction of effective agents, such as potent TKIs and monoclonal antibodies, may improve the possibility of remission in Ph-positive ALL patients and hopefully cure this disease.Adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) have worse prognosis than children. Differing biology of ALL may account for some of this disparity in outcome, with AYA patients having far lower incidence of good risk cytogenetic abnormalities, and higher proportion of patients with genetic lesions associated with inferior survival such as Ph-like ALL. Actual chemotherapy may also contribute to differences in outcome. Retrospective studies have shown that AYA patients treated on pediatric-based regimens had higher survival than those treated with adult regimens; the superiority of pediatric protocols has also been proven in several prospective comparative trials. Increase in rate of enrollment of AYA patients in clinical trials may further improve outcome. Cure based on chemotherapy may further limit the role of allogeneic hematopoietic cell transplantation (HCT) in AYA patients. The unique biology of AYA ALL may allow for novel methods of targeted therapy, while immunotherapy, the efficacy of which has been proven for both children and adults, may also play a major role in the treatment of relapsed/refractory ALL.Minimal residual disease (MRD) monitoring has proven to be one of the fundamental independent prognostic factors for patients with acute lymphoblastic leukemia (ALL). Sequential monitoring of MRD using sensitive and specific methods, such as real-time quantitative polymerase chain reaction (qPCR) or flow cytometry (FCM), has improved the assessment of treatment response and is currently used for therapeutic stratification and early detection. Although both FCM and qPCR yield highly consistent results with sensitivities of 10‒4, each method has several limitations. For example, qPCR is time-consuming and laborious designing primers that correspond to the immunoglobulin (IG) and T-cell receptor (TCR) gene rearrangements at diagnosis can take 3‒4 weeks. In addition, the evolution of additional clones beyond the first or index clone during therapy cannot be detected, which might lead to false-negative results. FCM requires experienced technicians and sometimes does not achieve a sensitivity of 10‒4. Accordingly, a next generation sequencing (NGS)-based method has been developed in an attempt to overcome these limitations. With the advent of high-throughput NGS technologies, a more in-depth analysis of IG and/or TCR gene rearrangements is now within reach, which impacts all applications of IG/TR analysis. However, standardization, quality control, and validation of this new technology are warranted prior to its incorporation into routine practice.Despite expanding knowledge in the molecular landscape of acute myeloid leukemia (AML) and an increasing understanding of leukemogenic pathways, little has changed in the treatment of AML in the last 40 years. Since introduction in the 1970s, combination chemotherapy consisting of anthracycline and cytarabine has been the mainstay of treatment, with major therapeutic advances based on improving supportive care rather than the introduction of novel therapeutics. Over the last decades, there have been extensive efforts to identify specific target mutations or pathways with the aim of improving clinical outcomes. Finally, after a prolonged wait, we are witnessing the next wave of AML treatment, characterized by a more "precise" and "personalized" understanding of the unique molecular or genetic mapping of individual patients. This new trend has since been further facilitated, with four new FDA approvals granted in 2017 in AML therapeutics. Currently, a total of eight targeted agents have been approved since 2017 (as of Jan. 2020). In this review, we will briefly discuss these newer agents in the context of their indication and the basis of their approval.In recent decades, survival rates for childhood acute myeloid leukemia have remarkably improved, owing to chemotherapy intensification, allogeneic hematopoietic stem cell transplantation, and improved supportive care. Furthermore, treatment protocols have evolved and are currently better matched to prognostic factors and treatment responses. Recently, new molecular prognostic factors were discovered via leukemia genomic studies. Moreover, new tumor subtypes with independent gene expression profiles have been characterized. To broaden the therapeutic options for patients with poor prognoses, therapies that target specific candidate mutations are being identified. Additionally, new drugs are undergoing clinical trials, and immunotherapy is attracting significant interest as a treatment option for recurrent or refractory childhood acute myeloid leukemia.The World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues was revised in 2017 on the basis of recent high-throughput sequencing and gene expression data on hematologic malignancies. This review explores the current WHO classification of acute myeloid leukemia (AML) and related precursor neoplasms, highlighting the changes made in the current edition and focusing on the diagnosis of AML.Temporary stent-assisted coiling is an eligible approach for the treatment of acutely ruptured complex cerebral aneurysms. Improved material properties and industrial advances in braiding technology have led to the introduction of new stent-like devices to augment endovascular coil embolization. Such technology includes the Cascade and Comaneci neck-bridging devices. Both devices are manually controlled, non-occlusive and fully retrievable neck-bridging temporary implants. The braided nature and the ultra-thin wire, compliant structure of their bridging meshes helps maintain target vessel patency during coil embolization. In this video (video 1) we demonstrate the straightforward combination of two temporary neck-bridging devices for the embolization of an acutely ruptured aneurysm of the basilar artery. Technical success and complete embolization of the aneurysm were recorded at the final angiography. In this technical video we discuss the technical nuances of the Comaneci and Cascade coil embolization. neurintsurg;13/2/196/V1F1V1Video 1.
Wide-necked bifurcation aneurysms (WNBAs) present unique challenges for endovascular treatment. The Woven EndoBridge (WEB) device is an intrasaccular braided device, recently approved by the FDA for treatment of WNBAs. While treatment of intracranial aneurysms with the WEB device has been shown to yield an adequate occlusion rate of 85% at 1 year, few data have been published for patients with ruptured aneurysms.

To present a multi-institutional series depicting the safety and efficacy of using the WEB device as the primary treatment modality in ruptured intracranial aneurysms.

A multi-institutional retrospective analysis was conducted, assessing patients presenting with aneurysmal subarachnoid hemorrhage treated with the WEB between January 2014 and April 2020. Baseline demographics, aneurysm characteristics, adverse events, and long-term outcomes (occlusion, re-treatment, functional status) were collected. A descriptive analysis was performed, and variables potentially associated with aneurysm recurreeatment of acutely ruptured aneurysms with the WEB device demonstrates both safety and efficacy on par with rates of conventional treatment strategies.Decisions under threat are crucial to survival and require integration of distinct situational features, such as threat probability and magnitude. Recent evidence from human lesion and neuroimaging studies implicated anterior hippocampus (aHC) and amygdala in approach-avoidance decisions under threat, and linked their integrity to cautious behavior. Here we sought to elucidate how threat dimensions and behavior are represented in these structures. Twenty human participants (11 female) completed an approach-avoidance conflict task during high-resolution fMRI. Participants could gather tokens under threat of capture by a virtual predator, which would lead to token loss. Threat probability (predator wake-up rate) and magnitude (amount of token loss) varied on each trial. To disentangle effects of threat features, and ensuing behavior, we performed a multifold parametric analysis. We found that high threat probability and magnitude related to BOLD signal in left aHC/entorhinal cortex. However, BOLD signal in thisOur results disclose the human anterior hippocampus as a likely arbiter of approach-avoidance decisions harnessing compound environmental information while partially replicating previous findings and blending into recent efforts to illuminate the neural basis of approach-avoidance conflict in humans.Brain responses vary considerably from moment to moment, even to identical sensory stimuli. This has been attributed to changes in instantaneous neuronal states determining the system's excitability. Yet the spatiotemporal organization of these dynamics remains poorly understood. Here we test whether variability in stimulus-evoked activity can be interpreted within the framework of criticality, which postulates dynamics of neural systems to be tuned toward the phase transition between stability and instability as is reflected in scale-free fluctuations in spontaneous neural activity. Using a novel noninvasive approach in 33 male human participants, we tracked instantaneous cortical excitability by inferring the magnitude of excitatory postsynaptic currents from the N20 component of the somatosensory evoked potential. Fluctuations of cortical excitability demonstrated long-range temporal dependencies decaying according to a power law across trials, a hallmark of systems at critical states. As these dynamics covaried with changes in prestimulus oscillatory activity in the alpha band (8-13 Hz), we establish a mechanistic link between ongoing and evoked activity through cortical excitability and argue that the co-emergence of common temporal power laws may indeed originate from neural networks poised close to a critical state.
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