Mutational profile in previously treated patients with chronic lymphocytic leukemia progression on acalabrutinib or ibrutinib.

Chronic lymphocytic leukemia (CLL) progression during Bruton tyrosine kinase (BTK) inhibitor treatment is typically characterized by emergent B-cell receptor pathway mutations. Using peripheral blood samples from patients with relapsed/refractory CLL in ELEVATE-RR (NCT02477696; median 2 prior therapies), we report clonal evolution data for patients progressing on acalabrutinib or ibrutinib (median follow-up, 41 months). Paired (baseline and progression) samples were available for 47 (excluding 1 Richter) acalabrutinib-treated and 30 (excluding 6 Richter) ibrutinib-treated patients.

Safety and efficacy of peptide receptor radionuclide therapy in neuroendocrine tumors: A single center experience.

Peptide receptor radionucleotide therapy (PRRT) with 177Lu-dotatate is widely used for the treatment of patients with neuroendocrine tumors (NETs). We analyzed data from 104 patients with NETs treated with 177Lu -dotatate at a US academic center between December 2017 and October 2020 to better understand patterns of long-term efficacy, safety, and toxicity in the real-world setting. 177Lu-dotatate (200 mCi) was administered every eight weeks for four doses.

The longitudinal mediating role of sleep in associations between COVID-19 stressors predicting mental and physical health outcomes among emerging adult college students.

The current study tested a longitudinal mediation model throughout the COVID-19 pandemic focused on whether students' housing instability stress and food/financial instability stress at the beginning of the pandemic in spring 2020 (T1) informed sleep dissatisfaction and duration in fall 2020 (T2) and, in turn, physical and mental health in spring 2021 (T3). Further, we tested whether relations varied based on students' ethnic-racial backgrounds. Participants included 879 Asian, Black, Latine, Multiracial, and White emerging adult college students (Mage = 19.

"Minimally symptomatic" congenital cytomegalovirus infection: latest data and emerging concepts.

Purpose Of Review: Universal and targeted screening of newborns for congenital cytomegalovirus (CMV) infection is increasing globally. Questions remain concerning the management of infants who have been identified with congenital CMV infection, especially those with "minimally symptomatic" or clinically inapparent infection. Our objective is to discuss current management of CMV-infected neonates with a focus on less affected infants with or without sensorineural hearing loss (SNHL).

Open-label extension of a randomized trial investigating safety and efficacy of rhPTH(1-84) in hypoparathyroidism.

Unlabelled: Hypoparathyroidism (HypoPT) is a rare disease, often inadequately controlled by conventional treatment. PARALLAX was a mandatory post-marketing trial assessing pharmacokinetics and pharmacodynamics of different dosing regimens of recombinant human parathyroid hormone 1-84 (rhPTH[1-84]) for treating HypoPT. The present study (NCT03364738) was a phase 4, 1-yr open-label extension of PARALLAX.

Description of swine producer biosecurity planning for foreign animal disease preparedness using the Secure Pork Supply framework.

Introduction: Preventing potential foreign animal diseases is a high priority, with re-emerging threats such as African Swine Fever emerging close to North American borders. The Secure Pork Supply (SPS) plan provides a voluntary framework for swine producer biosecurity planning and disease outbreak preparedness. However, biosecurity knowledge varies greatly among swine veterinarians, managers, and caretakers within the industry, which impacts the understanding, quality, implementation and biosecurity plan agreements with the SPS guidelines unless review procedures and quality control mechanisms are in place.

FOXK2 targeting by the SCF-E3 ligase subunit FBXO24 for ubiquitin mediated degradation modulates mitochondrial respiration.

FOXK2 is a crucial transcription factor implicated in a wide array of biological activities and yet understanding of its molecular regulation at the level of protein turnover is limited. Here, we identify that FOXK2 undergoes degradation in lung epithelia in the presence of the virulent pathogens Pseudomonas aeruginosa and Klebsiella pneumoniae through ubiquitin-proteasomal processing. FOXK2 through its carboxyl terminus (aa 428-478) binds the Skp-Cullin-F-box ubiquitin E3 ligase subunit FBXO24 that mediates multisite polyubiquitylation of the transcription factor resulting in its nuclear degradation.

American Society of Pain and Neuroscience Best Practice (ASPN) Guideline for the Treatment of Sacroiliac Disorders.

Clinical management of sacroiliac disease has proven challenging from both diagnostic and therapeutic perspectives. Although it is widely regarded as a common source of low back pain, little consensus exists on the appropriate clinical management of sacroiliac joint pain and dysfunction. Understanding the biomechanics, innervation, and function of this complex load bearing joint is critical to formulating appropriate treatment algorithms for SI joint disorders.

Crop rotational diversity can mitigate climate-induced grain yield losses.

Diversified crop rotations have been suggested to reduce grain yield losses from the adverse climatic conditions increasingly common under climate change. Nevertheless, the potential for climate change adaptation of different crop rotational diversity (CRD) remains undetermined. We quantified how climatic conditions affect small grain and maize yields under different CRDs in 32 long-term (10-63 years) field experiments across Europe and North America.

Small-molecule-induced epigenetic rejuvenation promotes SREBP condensation and overcomes barriers to CNS myelin regeneration.

Remyelination failure in diseases like multiple sclerosis (MS) was thought to involve suppressed maturation of oligodendrocyte precursors; however, oligodendrocytes are present in MS lesions yet lack myelin production. We found that oligodendrocytes in the lesions are epigenetically silenced. Developing a transgenic reporter labeling differentiated oligodendrocytes for phenotypic screening, we identified a small-molecule epigenetic-silencing-inhibitor (ESI1) that enhances myelin production and ensheathment.

Angiogenic Gene Therapy for Refractory Angina: Results of the EXACT Phase 2 Trial.

Background: XC001 is a novel adenoviral-5 vector designed to express multiple isoforms of VEGF (vascular endothelial growth factor) and more safely and potently induce angiogenesis. The EXACT trial (Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment) assessed the safety and preliminary efficacy of XC001 in patients with no option refractory angina.

Methods: In this single-arm, multicenter, open-label trial, 32 patients with no option refractory angina received a single treatment of XC001 (1×10 viral particles) via transepicardial delivery.

Brentuximab Vedotin Plus Ibrutinib in Relapsed and Refractory Hodgkin Lymphoma.

Introduction: Brentuximab vedotin (BV) is an antibody-drug conjugate that delivers monomethyl auristatin E (MMAE) to CD30+ cells and is safe and effective in relapsed/refractory (r/r) Hodgkin lymphoma (HL). Although most patients respond to BV, only a minority will obtain a complete response (CR), and almost all patients eventually progress. Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor highly active in multiple subtypes of non-Hodgkin lymphoma; limited data exist regarding its use in HL.

Failure to Undergo Resection Following Neoadjuvant Therapy for Resectable Pancreatic Cancer: A Secondary Analysis of SWOG S1505.

Background: Neoadjuvant therapy (NT) is increasingly used for patients with pancreatic ductal adenocarcinoma (PDAC), and yet reasons for not undergoing subsequent pancreatectomy are poorly understood. Given the importance of completing multimodality therapy, we investigated factors associated with failure to undergo surgical resection following NT for PDAC.

Methods: SWOG S1505 was a multicenter phase II randomized trial of preoperative mFOLFIRINOX or gemcitabine/nab-paclitaxel prior to planned pancreatectomy for patients with potentially resectable PDAC.

Hedgehog pathway inhibitors for locally advanced and metastatic basal cell carcinoma: A real-world single-center retrospective review.

Basal cell carcinoma (BCC) is highly curable by surgical excision or radiation. In rare cases, BCC can be locally destructive or difficult to surgically remove. Hedgehog inhibition (HHI) with vismodegib or sonidegib induces a 50-60% response rate.

Delta-8 tetrahydrocannabinol, delta-10 tetrahydrocannabinol, and tetrahydrocannabinol-O acetate exposures reported to America's Poison Centers.

Introduction: Since the passage of the Farm Bill in 2018, the availability of synthetic tetrahydrocannabinols has increased, including delta-8 tetrahydrocannabinol, delta-10 tetrahydrocannabinol, and tetrahydrocannabinol-O acetate. The objective of this study is to investigate the characteristics of delta-8 tetrahydrocannabinol, delta-10 tetrahydrocannabinol, and tetrahydrocannabinol-O acetate exposures reported to United States poison centers from 2021 to 2022.

Methods: National Poison Data System data were analyzed, including year, individual demographics, substance category and type, reason for exposure, highest level of health care received, and medical outcome.

Inhibition of SRC-3 as a potential therapeutic strategy for aggressive mantle cell lymphoma.

Mantle cell lymphoma (MCL) has a poor prognosis and high relapse rates despite current therapies, necessitating novel treatment regimens. Inhibition of SRC-3 show effectiveness in vivo and in vitro in other B cell lymphomas. Additionally, previous studies have shown that SRC-3 is highly expressed in the lymph nodes of B cell non-Hodgkin's lymphoma patients, suggesting SRC-3 may play a role in the progression of B cell lymphoma.

Increased Dietary Trp, Thr, and Met Supplementation Improves Performance, Health, and Protein Metabolism of Weaned Piglets under Mixed Management and Poor Housing Conditions.

A sanitary challenge was carried out to induce suboptimal herd health while investigating the effect of amino acids supplementation on piglet responses. Weaned piglets of high sanitary status (6.33 ± 0.

Epigallocatechin gallate regulates the myeloid-specific transcription factor PU.1 in macrophages.

Our previous research demonstrated that PU.1 regulates expression of the genes involved in inflammation in macrophages. Selective knockdown of PU.

Safety and efficacy of losmapimod in facioscapulohumeral muscular dystrophy (ReDUX4): a randomised, double-blind, placebo-controlled phase 2b trial.

Background: Facioscapulohumeral muscular dystrophy is a hereditary progressive myopathy caused by aberrant expression of the transcription factor DUX4 in skeletal muscle. No approved disease-modifying treatments are available for this disorder. We aimed to assess the safety and efficacy of losmapimod (a small molecule that inhibits p38α MAPK, a regulator of DUX4 expression, and p38β MAPK) for the treatment of facioscapulohumeral muscular dystrophy.

Preventative Effects of Milk Fat Globule Membrane Ingredients on DSS-Induced Mucosal Injury in Intestinal Epithelial Cells.

The goblet cells of the gastrointestinal tract (GIT) produce glycoproteins called mucins that form a protective barrier from digestive contents and external stimuli. Recent evidence suggests that the milk fat globule membrane (MFGM) and its milk phospholipid component (MPL) can benefit the GIT through improving barrier function. Our objective was to compare the effects of two digested MFGM ingredients with or without dextran sodium sulfate (DSS)-induced barrier stress on mucin proteins.

Single-molecule epitranscriptomic analysis of full-length HIV-1 RNAs reveals functional roles of site-specific mAs.

Although the significance of chemical modifications on RNA is acknowledged, the evolutionary benefits and specific roles in human immunodeficiency virus (HIV-1) replication remain elusive. Most studies have provided only population-averaged values of modifications for fragmented RNAs at low resolution and have relied on indirect analyses of phenotypic effects by perturbing host effectors. Here we analysed chemical modifications on HIV-1 RNAs at the full-length, single RNA level and nucleotide resolution using direct RNA sequencing methods.

The Utility of Prostate-Specific Membrane Antigen-11 PET in Detection and Management of Central Nervous System Neoplasms.

We present a case series of 5 patients diagnosed with schwannoma and 1 patient diagnosed with astrocytoma who underwent PSMA PET imaging for tumor detection. We retrospectively analyzed the records of 4 male and 2 female patients (mean age, 53.2 ± 13.

Combined Motivational Interviewing and Ecological Momentary Intervention to Reduce Hazardous Alcohol Use Among Sexual Minority Cisgender Men and Transgender Individuals: Protocol for a Randomized Controlled Trial.

Background: Sexual minority cisgender men and transgender (SMMT) individuals, particularly emerging adults (aged 18-34 years), often report hazardous drinking. Given that alcohol use increases the likelihood of HIV risk behaviors, and HIV disproportionately affects SMMT individuals, there is a need to test interventions that reduce hazardous alcohol use and subsequent HIV risk behaviors among this population. Ecological momentary interventions (EMIs), which use mobile phones to deliver risk reduction messages based on current location and behaviors, can help to address triggers that lead to drinking in real time.

Genetic structure and landscape effects on gene flow in the Neotropical lizard Norops brasiliensis (Squamata: Dactyloidae).

One key research goal of evolutionary biology is to understand the origin and maintenance of genetic variation. In the Cerrado, the South American savanna located primarily in the Central Brazilian Plateau, many hypotheses have been proposed to explain how landscape features (e.g.