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Single-neuron spiking variability in hippocampus dynamically tracks sensory content during memory formation in humans
AbstractDuring memory formation, the hippocampus is presumed to represent the content of stimuli, but how it does so is unknown. Using computational modelling and human single-neuron recordings, we show that the more precisely hippocampal spiking variability tracks the composite features of each individual stimulus, the better those stimuli are later remembered. We propose that moment-to-moment spiking variability may provide a new window into how the hippocampus constructs memories from the building blocks of our sensory world.
Dexamethasone dose intensity does not impact outcomes in newly diagnosed multiple myeloma: a secondary SWOG analysis
Abstract Dexamethasone is a key component of induction for newly diagnosed multiple myeloma (NDMM), despite common toxicities, including hyperglycemia and insomnia. In the randomized ECOG E4A03 trial, dexamethasone 40 mg once weekly was associated with lower mortality than higher doses. However, the performance of dexamethasone dose reductions below this threshold with regard to progression-free survival (PFS) and overall survival (OS) in NDMM has not been fully characterized. We conducted a secondary pooled analysis of the SWOG 0777 and SWOG 1211 studies of NDMM, which used lenalidomide and dexamethasone (Rd) alone, with or without bortezomib, and with or without elotuzumab. The planned dexamethasone intensity was 40 to 60 mg weekly in all arms. Patients were categorized into FD-DEX (full-dose dexamethasone maintained throughout induction) or LD-DEX (lowered-dose dexamethasone or discontinuation; only permitted for grade 3+ toxicities per both study protocols). Of the 541 evaluated patients, the LD-DEX group comprised 373 patients (69%). There were no differences in PFS or OS between the FD-DEX and LD-DEX groups, which were balanced in terms of age, stage, and performance status. Predictors of PFS and OS in the multivariate models were treatment arm, age ≥70 years, and thrombocytopenia. FD-DEX did not significantly improve either outcome. Our study suggests that dexamethasone dose reductions are common in multiple myeloma, even within clinical trials. Given the many toxicities and unclear benefits of dexamethasone in the era of modern treatment regimens, dexamethasone dose reduction during NDMM induction warrants further prospective studies. These trials were registered at www.clinicaltrials.gov as #NCT00644228 and NCT01668719.
Cep78 knockout causes sterility and oligoasthenoteratozoospermia in male mice
Development and preliminary validation of five miRNAs for lung adenocarcinoma prognostic model associated with immune infiltration
Effect of nanoparticulate CaCO3 on the biological properties of calcium silicate cement
Noradrenergic inputs from the locus coeruleus to anterior piriform cortex and the olfactory bulb modulate olfactory outputs
Down with dex!
A recurrent sigma pi sigma neural network
Effects of linsitinib on M22 and IGF:1-treated 3D spheroids of human orbital fibroblasts
Association between the triglyceride glucose index and acute kidney injury following traumatic brain injury
Respiratory processes of early-evolved hyperthermophiles in sulfidic and low-oxygen geothermal microbial communities
Parvovirus B19-induced autoimmune hemolytic anemia in hereditary elliptocytosis
Analysis of ICIs alone or in combination rechallenged outcomes after progression from first-line ICIs plus chemotherapy in patients with advanced non-small cell lung cancer
Ovarian steroids modulate mRNA expression of ECM associated genes and collagen deposition induced by TGF β1 in equine endometrium in vitro
A comparative analysis of L-moments, maximum likelihood, and maximum product of spacing methods for the four-parameter kappa distribution in extreme value analysis
Feshbach hypothesis of high-Tc superconductivity in cuprates
AbstractResonant interactions associated with the emergence of a bound state constitute one of the cornerstones of modern many-body physics. Here we present a Feshbach perspective on the origin of strong pairing in Fermi-Hubbard type models. We perform a theoretical analysis of interactions between spin-polaron charge carriers in doped Mott insulators, modeled by a near-resonant two-channel scattering problem, and report evidence for Feshbach-type interactions in the $${d}_{{x}^{2}-{y}^{2}}$$ d x 2 − y 2 channel, consistent with the established phenomenology of cuprates. Existing experimental and numerical results on hole-doped cuprates lead us to conjecture the existence of a light, long-lived, low-energy excited state of two holes, which enables near-resonant interactions. To put our theory to a test we suggest to use coincidence angle-resolved photoemission spectroscopy (cARPES), pair-tunneling measurements or pump-probe experiments. The emergent Feshbach resonance among spin-polarons could also underlie superconductivity in other doped antiferromagnetic Mott insulators highlighting its potential as a unifying strong-coupling pairing mechanism rooted in quantum magnetism.
How I treat Philadelphia chromosome–like acute lymphoblastic leukemia in children, adolescents, and young adults
Abstract Philadelphia chromosome–like acute lymphoblastic leukemia (Ph-like ALL) represents a high-risk B-lineage ALL subtype characterized by adverse clinical features and poor relapse-free survival despite risk–adapted multiagent chemotherapy regimens. The advent of next-generation sequencing has unraveled the diversity of kinase-activating genetic drivers in Ph-like ALL that are potentially amenable to personalized molecularly-targeted therapies. Based upon robust preclinical data and promising case series of clinical activity of tyrosine kinase inhibitor (TKI)–based treatment in adults and children with relevant genetic Ph-like ALL subtypes, several clinical trials have investigated the efficacy of JAK- or ABL-directed TKIs in cytokine receptor-like factor 2 (CRLF2)/JAK pathway-mutant or ABL-class Ph-like ALL, respectively. The final results of these trials are pending, and standard-of-care therapeutic approaches for patients with Ph-like ALL have yet to be defined. In this How I Treat perspective, we review recent literature to guide current evidence-based treatment recommendations via illustrative clinical vignettes of children, adolescents, and young adults with newly diagnosed or relapsed/refractory Ph-like ALL, and we further highlight open and soon-to-open trials investigating immunotherapy and TKIs specifically for this high-risk patient population.