Initiatives

In the phase-2 clinical trial (AIM) of venetoclax-ibrutinib, 24 patients with mantle cell lymphoma (MCL; 23 with relapsed/refractory [R/R] disease) received ibrutinib 560mg and venetoclax 400mg both once daily. High complete remission (CR) and measurable residual disease negative (MRD-negative) CR rates were previously reported. With median survivor follow-up now exceeding 7 years, we report long-term results. Treatment was initially continuous, with elective treatment interruption (ETI) allowed after protocol amendment for patients in MRD-negative CR...

BACKGROUND AND OBJECTIVES: The role of B cells in the pathogenic events leading to relapsing multiple sclerosis (R-MS) has only been recently elucidated. A pivotal step in defining this role has been provided by therapeutic efficacy of anti-CD20 monoclonal antibodies. Indeed, treatment with anti-CD20 can also alter number and function of other immune cells not directly expressing CD20 on their cell surface, whose activities can contribute to unknown aspects influencing therapeutic efficacy...

The therapeutic arsenal for the management of AML has expanded significantly in recent years. Before 2017, newly diagnosed AML was treated with either standard cytarabine- and anthracycline-based induction chemotherapy (for all fit patients) or a single-agent hypomethylating agent (in unfit patients or those 75 years and older). While assessing patient fitness remains important, characterizing the disease biology has become critical to select the optimal initial therapy for each patient with more options available...

No abstract text is available yet for this article.

An 8-year-old Leonberger receiving immunosuppressive treatment with clinical signs of acute dyspnea, cyanosis, and difficulty standing was referred to our institution (Day 1). Treatment including oxygen, clopidogrel, and low-molecular-weight heparin was initiated for suspected pulmonary thrombosis. However, exertional dyspnea persisted until Day 10, and increased tricuspid regurgitation velocity, pulmonary vascular resistance, and McConnell's signs also were observed. Thus, beraprost sodium was administered PO on Day 11 to treat suspected pulmonary hypertension...

PURPOSE: Pitch variations (tone productions) have been reported as a measure to differentiate Cantonese-speaking children with and without childhood apraxia of speech (CAS). This study aims to examine fundamental frequency ( F 0) changes within syllables and the effects of syllable structure, lexical status, and syllable positions on F 0 in Cantonese-speaking preschool children with and without CAS. METHOD: Six children with CAS, six children with non-CAS speech sound disorder plus language disorder (S&LD), 22 children with speech sound disorder only (SSD), and 63 children with typical speech-language development (TD) performed the tone sequencing task (TST)...

BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME) requires that all graduate medical education (GME) programs provide at least 6 paid weeks off for medical, parental, and caregiver leave to residents. However, it is unclear whether all orthopaedic residency programs have adapted to making specific parental leave policies web-accessible since the ACGME's mandate in 2022. This gap in policy knowledge leaves both prospective and current residents in the dark when it comes to choosing residency programs, and knowing what leave benefits they are entitled to when having children during training via birth, surrogacy, adoption, or legal guardianship...

Wildfire smoke (WFS) is a mixture of respirable particulate matter, environmental gases, and other hazardous pollutants that originate from the unplanned burning of arid vegetation during wildfires. The increasing size and frequency of recent wildfires has escalated public and occupational health concerns regarding WFS inhalation, by either individuals living nearby and downstream an active fire or wildland firefighters and other workers that face unavoidable exposure because of their profession. In this review, we first synthesize current evidence from environmental, controlled, and interventional human exposure studies, to highlight positive associations between WFS inhalation and cardiovascular morbidity and mortality...

BACKGROUND: Clinical practice guidelines recommend early serum electrolyte monitoring when starting antidepressants in older adults due to the increased risk of hyponatremia. It is unclear whether this monitoring improves outcomes. METHODS: Population-based, retrospective cohort study of Ontario adults aged ≥66 years who initiated therapy with a selective serotonin reuptake inhibitor (SSRI) or selective norepinephrine reuptake inhibitor (SNRI) between April 1, 2013, and January 31, 2020...

A deep-learning model reveals the rules that define transcription initiation.

Transcription initiation is a process that is essential to ensuring the proper function of any gene, yet we still lack a unified understanding of sequence patterns and rules that explain most transcription start sites in the human genome. By predicting transcription initiation at base-pair resolution from sequences with a deep learning-inspired explainable model called Puffin, we show that a small set of simple rules can explain transcription initiation at most human promoters. We identify key sequence patterns that contribute to human promoter activity, each activating transcription with distinct position-specific effects...

The signature feature of all plant viruses is the encoding of movement proteins (MPs) that supports the movement of the viral genome into adjacent cells and through the vascular system. The recent discovery of umbravirus-like viruses (ULVs), some of which only encode replication-associated proteins, suggested that they, as with umbraviruses that lack encoded capsid proteins (CPs) and silencing suppressors, would require association with a helper virus to complete an infection cycle. We examined the infection properties of 2 ULVs: citrus yellow vein associated virus 1 (CY1), which only encodes replication proteins, and closely related CY2 from hemp, which encodes an additional protein (ORF5CY2) that was assumed to be an MP...

BACKGROUND: Patients with atrial fibrillation (AF) have a high risk for recurrent clinical events after an ischemic stroke. Direct oral anticoagulants (DOAC) are prescribed for secondary prevention. Adherence to DOAC is crucial mainly because of their short elimination half-life. Non-adherence to DOAC can negatively impact patients' outcomes. The relationship between (non-)adherence and recurrent clinical events is unknown in AF patients after initial stroke. We investigated adherence to DOAC in stroke survivors with AF who were included in the MAAESTRO study at the University Hospital Basel, Switzerland, between 2008 and 2022...

The health risks that arise from environmental exposures vary widely within and across human populations, and these differences are largely determined by genetic variation and gene-by-environment (gene-environment) interactions. However, risk assessment in laboratory mice typically involves isogenic strains and therefore, does not account for these known genetic effects. In this context, genetically heterogenous cell lines from laboratory mice are promising tools for population-based screening because they provide a way to introduce genetic variation in risk assessment without increasing animal use...

Thousands of endoparasitoid wasp species in the families Braconidae and Ichneumonidae harbor "domesticated endogenous viruses" (DEVs) in their genomes. This study focuses on ichneumonid DEVs, named ichnoviruses (IVs). Large quantities of DNA-containing IV virions are produced in ovary calyx cells during the pupal and adult stages of female wasps. Females parasitize host insects by injecting eggs and virions into the body cavity. After injection, virions rapidly infect host cells which is followed by expression of IV genes that promote the successful development of wasp offspring...

Objective: Recurrent lumbar disc hernia (RLDH) is a common and challenging complication after an initial discectomy. This study aimed to investigate the relationship between the histopathologic outcomes of the initial and recurrent disc tissues. Methods: This study investigated 70 patients who underwent a microdiscectomy and subsequently developed same-level same-side lumbar disc herniation (LDH) recurrence. The clinic, western blot, and immunohistochemical evaluations of patients with initial LDH and RLDH were conducted and statistically analyzed...

Myosin motors use the energy of ATP to produce force and directed movement on actin by a swing of the lever arm. ATP is hydrolysed during the off-actin re-priming transition termed recovery stroke. To provide an understanding of chemo-mechanical transduction by myosin, it is critical to determine how the reverse swing of the lever arm and ATP hydrolysis are coupled. Previous studies concluded that the recovery stroke of myosin II is initiated by closure of the Switch II loop in the nucleotide-binding site. Recently, we proposed that the recovery stroke of myosin VI starts with the spontaneous re-priming of the converter domain to a putative pre-transition state (PTS) intermediate that precedes Switch II closing and ATPase activation...

Numerous recently introduced chaotic systems exhibit straightforward algebraic representations. In this study, we explore the potential for identifying a global analytic first integral in a generalized 3-dimensional chaotic system (2). Our work involves detailing the model of a new 3-D chaotic system characterized by three Lyapunov exponents-positive, zero, and negative. We depict the phase trajectories, illustrate bifurcation patterns, and visualize Lyapunov exponent graphs. The investigation encompasses both local and global analytic first integrals for the system, providing results on the existence and non-existence of these integrals for different parameter values...

Among the post-transcriptional modifications, m6A RNA methylation has gained significant research interest due to its critical role in regulating transcriptional expression. This modification affects RNA metabolism in several ways, including processing, nuclear export, translation, and decay, making it one of the most abundant transcriptional modifications and a crucial regulator of gene expression. The dysregulation of m6A RNA methylation-related proteins in many tumors has been shown to lead to the upregulation of oncoprotein expression, tumor initiation, proliferation, cancer cell progression, and metastasis...

Traditional medicinal knowledge and healing practices of indigenous spiritual healers play important roles in health care, and contribute towards achieving Universal Health Care. Traditional spiritual healers (TSHs) are grouped into three categories. One category of Baganda TSHs, Balubaale, engage ancestral spirits during health management. Balubaale are socially significant but not legally accepted. Their initiation and training practices have not been documented in Uganda. The study purpose was to understand and establish the training of traditional spiritual healers...