The stabilization of visibility for sequentially presented, low-contrast objects: Experiments and neural field model.

In any environment, events transpire in temporal sequences. The general principle governing such sequences is that each instance of the event is influenced by its predecessors. It is shown here that this principle is true for a fundamental aspect of visual perception: visibility.

A nonrandomized phase I and biomarker trial of regorafenib in advanced myeloid malignancies.

We conducted a single-center, open-label, dose escalation, and expansion phase I trial of the antiangiogenic multikinase inhibitor regorafenib in patients with advanced myeloid neoplasms. We enrolled 16 patients with relapsed/refractory acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN), chronic myelomonocytic leukemia (CMML), or myelodysplastic syndrome (MDS). A 3 + 3 dose escalation design was used with two planned dose levels (120 or 160 mg daily) and one de-escalation level (80 mg daily).

Chemotherapy Resistance in B-ALL with Cryptic NUP214-ABL1 Is Amenable to Kinase Inhibition and Immunotherapy.

BCR-ABL1 kinase inhibitors have improved the prognosis of Philadelphia-chromosome-positive (Ph+)-acute lymphoblastic leukemia (ALL). Ph-like (or BCR-ABL1-like) ALL does not express BCR-ABL1 but commonly harbors other genomic alterations of signaling molecules that may be amenable to therapy. Here, we report a case with a NUP214-ABL1 fusion detected at relapse by multiplexed, targeted RNA sequencing.

Ixazomib in addition to chemotherapy for the treatment of acute lymphoblastic leukemia in older adults.

We sought to assess the safety of adding ixazomib, an oral proteasome inhibitor, to a multi-agent treatment regimen for older adults with acute lymphoblastic leukemia (ALL). Patients 51 to 75 years of age with newly diagnosed ALL were screened. Induction consisted of prednisone (P), vincristine (V), and doxorubicin (D).

The Second Oncogenic Hit Determines the Cell Fate of Positive Leukemia.

ETV6-RUNX1 is almost exclusively associated with childhood B-cell acute lymphoblastic leukemia (B-ALL), but the consequences of ETV6-RUNX1 expression on cell lineage decisions during B-cell leukemogenesis are completely unknown. Clinically silent ETV6-RUNX1 preleukemic clones are frequently found in neonatal cord blood, but few carriers develop B-ALL as a result of secondary genetic alterations. The understanding of the mechanisms underlying the first transforming steps could greatly advance the development of non-toxic prophylactic interventions.

Culture in the spotlight-cultural adaptation and content validity of the integrated palliative care outcome scale for dementia: A cognitive interview study.

Background: Dementia is a life-limiting disease with high symptom burden. The Integrated Palliative Care Outcome Scale for Dementia (IPOS-Dem) is the first comprehensive person-centered measure to identify and measure palliative care needs of people with dementia. However, such a measure is missing in the German health care system.

How does losing health insurance affect disability claims? Evidence from the Affordable Care Act's dependent care mandate.

We estimate the impacts of losing access to parental health insurance on Supplemental Security Income (SSI) participation, focusing on the age-26 limit for dependent coverage. We analyze the age pattern of SSI claims to develop counterfactual predictions that assume no change in access to insurance. Relative to this prediction, we find a 3.

Incidence of Invasive Fungal Infections in Acute Myeloid Leukemia Without Antifungal Prophylaxis.

Background: Antifungal prophylaxis during induction for acute myeloid leukemia (AML) varies according to local rates of invasive fungal infections (IFIs). We evaluated fluconazole prophylaxis and no antifungal prophylaxis, as a natural interrupted time-series study to assess survival and infection complications.

Patients And Methods: We identified patients with AML ≥ 18 years old undergoing induction chemotherapy during 2 time periods: period 1, fluconazole prophylaxis from August 1, 2013 to September 30, 2015, and period 2, no prophylaxis from October 1, 2015 to December 31, 2017.

Clinical response to larotrectinib in adult Philadelphia chromosome-like ALL with cryptic ETV6-NTRK3 rearrangement.

Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL) is a subtype of Ph-negative ALL that molecularly resembles Ph-positive ALL. It shares the adverse prognosis of Ph-positive ALL, but lacks the BCR-ABL1 fusion oncogene. Instead, Ph-like ALL is associated with alternative mutations in signaling pathways.

A phase 1 study of the antibody-drug conjugate brentuximab vedotin with re-induction chemotherapy in patients with CD30-expressing relapsed/refractory acute myeloid leukemia.

Background: Outcomes for patients with relapsed/refractory acute myeloid leukemia (R/R AML) remain poor. Novel therapies specifically targeting AML are of high interest. Brentuximab vedotin (BV) is an antibody-drug conjugate that is specific for human CD30.

Alisertib plus induction chemotherapy in previously untreated patients with high-risk, acute myeloid leukaemia: a single-arm, phase 2 trial.

Background: Increased aurora A kinase (AAK) expression occurs in acute myeloid leukaemia; AAK inhibition is a promising therapeutic target in this disease. We therefore aimed to assess the activity of alisertib combined with 7 + 3 induction chemotherapy in previously untreated patients with high-risk acute myeloid leukaemia.

Methods: We did a single-arm, phase 2 trial of patients recruited from the Dana-Farber/Harvard Cancer Center in the USA.

Inducible histone K-to-M mutations are dynamic tools to probe the physiological role of site-specific histone methylation in vitro and in vivo.

Development and differentiation are associated with profound changes to histone modifications, yet their in vivo function remains incompletely understood. Here, we generated mouse models expressing inducible histone H3 lysine-to-methionine (K-to-M) mutants, which globally inhibit methylation at specific sites. Mice expressing H3K36M developed severe anaemia with arrested erythropoiesis, a marked haematopoietic stem cell defect, and rapid lethality.

Comparison of Candida antarctica Lipase B Variants for Conversion of ε-Caprolactone in Aqueous Medium-Part 2.

Enzyme-catalyzed ring-opening polymerization of lactones is a method of increasing interest for the synthesis of polyesters. In the present work, we investigated which changes in the structure of lipase B (CaLB) shift the catalytic equilibrium between esterification and hydrolysis towards polymerization. Therefore, we present two concepts: (i) removing the glycosylation of CaLB to increase the surface hydrophobicity; and (ii) introducing a hydrophobic lid adapted from lipase (PsCL) to enhance the interaction of a growing polymer chain to the elongated lid helix.

Measuring the perceptual grouping of non-adjacent surfaces that are invisibly (amodally) or visibly connected.

Classic Gestalt examples of perceptual grouping entail arrays of disconnected surfaces that are grouped on the basis of the surfaces' relative similarity or proximity. However, most natural environments contain multiple objects, each with multiple, connected surfaces. Moreover, an object in a scene is likely to partially occlude other objects in the 2-dimensional retinal projection of the scene.

The Mst1 Kinase Is Required for Follicular B Cell Homing and B-1 B Cell Development.

The Mst1 and 2 cytosolic serine/threonine protein kinases are the mammalian orthologs of the Drosophila Hippo protein. Mst1 has been shown previously to participate in T-cell and B-cell trafficking and the migration of lymphocytes into secondary lymphoid organs in a cell intrinsic manner. We show here that the absence of Mst1 alone only modestly impacts B cell homing to lymph nodes.

Transcription factor Etv6 regulates functional differentiation of cross-presenting classical dendritic cells.

An IRF8-dependent subset of conventional dendritic cells (cDCs), termed cDC1, effectively cross-primes CD8 T cells and facilitates tumor-specific T cell responses. Etv6 is an ETS family transcription factor that controls hematopoietic stem and progenitor cell (HSPC) function and thrombopoiesis. We report that like HSPCs, cDCs express Etv6, but not its antagonist, ETS1, whereas interferon-producing plasmacytoid dendritic cells (pDCs) express both factors.

Activity-Induced Regulation of Synaptic Strength through the Chromatin Reader L3mbtl1.

Homeostatic synaptic downscaling reduces neuronal excitability by modulating the number of postsynaptic receptors. Histone modifications and the subsequent chromatin remodeling play critical roles in activity-dependent gene expression. Histone modification codes are recognized by chromatin readers that affect gene expression by altering chromatin structure.

Neurologic complications after allogeneic hematopoietic stem cell transplantation: risk factors and impact.

Neurologic complications (NCs) may be a significant source of morbidity and mortality after hematopoietic cell transplantation (HCT). We performed a retrospective study of 263 consecutive patients undergoing allogeneic HCT for hematological malignancies to determine the incidence, risk factors and clinical impact of NCs in the first 5 years after HCT. We determined the incidence of central nervous system (CNS) infection, intracranial hemorrhage, ischemic stroke, metabolic encephalopathy, posterior reversal encephalopathy syndrome, seizure and peripheral neuropathy.

ETV6 in hematopoiesis and leukemia predisposition.

The ETV6 (also known as TEL) gene encodes a transcriptional repressor that plays a critical role in hematopoiesis and in embryonic development. While somatic ETV6 translocations and missense mutations are frequently observed in human cancers, the role of ETV6 in malignant transformation was unclear. Recently, autosomal dominant germline ETV6 mutations were discovered in families with inherited thrombocytopenia and a propensity to develop hematological malignancy, unequivocally demonstrating a role for ETV6 in leukemogenesis.

CaLB Catalyzed Conversion of ε-Caprolactone in Aqueous Medium. Part 1: Immobilization of CaLB to Microgels.

The enzymatic ring-opening polymerization of lactones is a method of increasing interest for the synthesis of biodegradable and biocompatible polymers. In the past it was shown that immobilization of lipase B (CaLB) and the reaction medium play an important role in the polymerization ability especially of medium ring size lactones like ε-caprolactone (ε-CL). We investigated a route for the preparation of compartmentalized microgels based on poly(glycidol) in which CaLB was immobilized to increase its esterification ability.

Temporal Asymmetry in Dark-Bright Processing Initiates Propagating Activity across Primary Visual Cortex.

Unlabelled: Differences between visual pathways representing darks and lights have been shown to affect spatial resolution and detection timing. Both psychophysical and physiological studies suggest an underlying retinal origin with amplification in primary visual cortex (V1). Here we show that temporal asymmetries in the processing of darks and lights create motion in terms of propagating activity across V1.

Nonlinear dynamics in the perceptual grouping of connected surfaces.

Evidence obtained using the dynamic grouping method has shown that the grouping of an object's connected surfaces has properties characteristic of a nonlinear dynamical system. When a surface's luminance changes, one of its boundaries is perceived moving across the surface. The direction of this dynamic grouping (DG) motion indicates which of two flanking surfaces has been grouped with the changing surface.

Cognition and mood-related behaviors in L3mbtl1 null mutant mice.

Alterations in histone lysine methylation and epigenetic regulators of gene expression could play a role in the neurobiology and treatment of patients diagnosed with mood spectrum disorder, including depression and anxiety. Mutations and altered expression of various lysine methyltransferases (KMTs) and demethylases (KDMs) have been linked to changes in motivational and emotional behaviors in preclinical model systems. However, it is not known whether regulators operating downstream of histone lysine methylation could affect mood-related behavior.