C-terminal binding protein 2 is a novel tumor suppressor targeting the MYC-IRF4 axis in multiple myeloma.

Multiple myeloma (MM) cells are addicted to MYC and its direct transactivation targets IRF4 for proliferation and survival. MYC and IRF4 are still considered "undruggable," as most small-molecule inhibitors suffer from low potency, suboptimal pharmacokinetic properties, and undesirable off-target effects. Indirect inhibition of MYC/IRF4 emerges as a therapeutic vulnerability in MM.

SPINK2 Protein Expression Is an Independent Adverse Prognostic Marker in AML and Is Potentially Implicated in the Regulation of Ferroptosis and Immune Response.

There is an urgent need for the identification as well as clinicopathological and functional characterization of potent prognostic biomarkers and therapeutic targets in acute myeloid leukemia (AML). Using immunohistochemistry and next-generation sequencing, we investigated the protein expression as well as clinicopathological and prognostic associations of serine protease inhibitor Kazal type 2 (SPINK2) in AML and examined its potential biological functions. High SPINK2 protein expression was an independent adverse biomarker for survival and an indicator of elevated therapy resistance and relapse risk.

Deep genomic characterization highlights complexities and prognostic markers of pediatric acute myeloid leukemia.

Pediatric acute myeloid leukemia (AML) is an uncommon but aggressive hematological malignancy. The poor outcome is attributed to inadequate prognostic classification and limited treatment options. A thorough understanding on the genetic basis of pediatric AML is important for the development of effective approaches to improve outcomes.

Mutational spectrum and prognosis in Chinese patients with prefibrotic primary myelofibrosis.

Prefibrotic primary myelofibrosis (Pre-PMF) has been classified as a separate entity of myeloproliferative neoplasms (MPNs). Pre-PMF is clinically heterogeneous but a specific prognostic model is lacking. Gene mutations have emerged as useful tools for stratification of myelofibrosis patients.

A novel NUP98-JADE2 fusion in a patient with acute myeloid leukemia resembling acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a specific subtype of acute myeloid leukemia (AML) characterized by block of differentiation at the promyelocytic stage and the presence of PML-RARA fusion. In rare instances, RARA is fused with other partners in variant APL. More infrequently, non-RARA genes are rearranged in AML patients resembling APL.

Structure of an activated DNA-PK and its implications for NHEJ.

DNA-dependent protein kinase (DNA-PK), like all phosphatidylinositol 3-kinase-related kinases (PIKKs), is composed of conserved FAT and kinase domains (FATKINs) along with solenoid structures made of HEAT repeats. These kinases are activated in response to cellular stress signals, but the mechanisms governing activation and regulation remain unresolved. For DNA-PK, all existing structures represent inactive states with resolution limited to 4.

Impact of COVID-19 pandemic on international higher education and student mobility: Student perspectives from mainland China and Hong Kong.

The study critically examines how students in Mainland China and Hong Kong conceive overseas studies plans against the COVID-19 crisis. Amongst the 2739 respondents, 84 % showed no interest to study abroad after the pandemic. For those respondents who will continue to pursue further degrees abroad, Asian regions and countries, specifically Hong Kong, Japan and Taiwan, are listed in the top five, apart from the US and the UK.

Looking Beyond the Cell in Cellulitis.

Background: Patients with erythematous skin are likely to receive a diagnosis of cellulitis; however, the accuracy of this diagnosis is approximately only 33%. The diagnosis of cellulitis should be made only after a thorough evaluation of all possible differential diagnoses. Cellulitis may be a primary process (superficial spreading infective process involving only the epidermis and dermis) versus a secondary (reactive) process incited by a subcutaneous process, such as an abscess, tenosynovitis, necrotizing fasciitis, and osteomyelitis.

Purposeful Activity in Psychiatric Rehabilitation: Is Neurogenesis a Key Player?

Adult neurogenesis, defined as the generation of new neurons in adulthood, has been a fascinating discovery in neuroscience, as the continuously replenishing neuronal population provides a new perspective to understand neuroplasticity. Besides maintaining normal physiological function, neurogenesis also plays a key role in pathophysiology and symptomatology for psychiatric conditions. In the past decades, extensive effort has been spent on the understanding of the functional significance of neurogenesis in psychiatric conditions, mechanisms of pharmacological treatment, and discovery of novel drug candidates for different conditions.

Combined effects of sensory cueing and limb activation on unilateral neglect in subacute left hemiplegic stroke patients: a randomized controlled pilot study.

Objective: To compare the effects of contralesional sensory cueing and limb activation with that of sham control in the treatment of unilateral neglect after stroke.

Design: A randomized, single-blinded, sham-controlled pilot study.

Setting: Two rehabilitation hospitals.

The difference between critical care initiation anion gap and prehospital admission anion gap is predictive of mortality in critical illness.

Objective: We hypothesized that the delta anion gap defined as difference between critical care initiation standard anion gap and prehospital admission standard anion gap is associated with all cause mortality in the critically ill.

Design: Observational cohort study.

Setting: Two hundred nine medical and surgical intensive care beds in two hospitals in Boston, MA.

Anxiety and mood disorders and cannabis use.

Background: Cannabis use has been linked to anxiety and mood disorders (AMD) in clinical cases, but little research on this relationship has been reported at the epidemiological level.

Objectives: We examined the relationship between self-reported frequency of cannabis use and risk for AMD in the general Ontario adult population.

Methods: Data were based on the CAMH Monitor survey of Ontario adults from 2001 to 2006 (n = 14,531).

Evidence for an inositol hexakisphosphate-dependent role for Ku in mammalian nonhomologous end joining that is independent of its role in the DNA-dependent protein kinase.

Nonhomologous end-joining (NHEJ) is an important pathway for the repair of DNA double-strand breaks (DSBs) and plays a critical role in maintaining genomic stability in mammalian cells. While Ku70/80 (Ku) functions in NHEJ as part of the DNA-dependent protein kinase (DNA-PK), genetic evidence indicates that the role of Ku in NHEJ goes beyond its participation in DNA-PK. Inositol hexakisphosphate (IP(6)) was previously found to stimulate NHEJ in vitro and Ku was identified as an IP(6)-binding factor.

Attitudes, knowledge, and actions with regard to organ donation among Hong Kong medical students.

Objective: To study attitudes, knowledge, and actions of local medical students with regard to organ donation and self-perceived confidence and competence in approaching potential organ donors.

Design: Cross-sectional questionnaire survey.

Setting: Faculty of Medicine, The University of Hong Kong, Hong Kong.

End modification of a linear DNA duplex enhances NER-mediated excision of an internal Pt(II)-lesion.

The study of DNA repair has been facilitated by the development of extract-based in vitro assay systems and the use of synthetic DNA duplexes that contain site-specific lesions as repair substrates. Unfortunately, exposed DNA termini can be a liability when working in crude cell extracts because they are targets for DNA end-modifying enzymes and binding sites for proteins that recognize DNA termini. In particular, the double-strand break repair protein Ku is an abundant DNA end-binding protein that has been shown to interfere with nucleotide excision repair (NER) in vitro.

A role for the HOXB7 homeodomain protein in DNA repair.

Homeobox genes encode transcription factors which function in body axis patterning in the developing embryo. Recent evidence suggests that the maintenance of specific HOX expression patterns is necessary for regulating the homeostasis of adult tissues as well. In this study, HOXB7 transformed human mammary epithelial cells, MCF10A, to grow in minimally supplemented medium, to form colonies in Matrigel, and display resistance to ionizing radiation.

A small-scale serum-free liquid cell culture model of erythropoiesis to assess the effects of exogenous factors.

Anaemia is an important global health problem. Therefore, it is crucial to understand its pathophysiology in various genetic or infectious diseases where dyserythropoiesis is a key pathological feature. To this effect, reproducible and reliable models of erythropoiesis in vitro are much needed as investigative tools.

Suppression of erythropoiesis in malarial anemia is associated with hemozoin in vitro and in vivo.

Malarial anemia is a global public health problem and is characterized by a low reticulocyte response in the presence of life-threatening hemolysis. Although cytokines, in particular tumor necrosis factor-alpha (TNF-alpha), can suppress erythropoiesis, the grossly abnormal bone marrow morphology indicates that other factors may contribute to ineffective erythropoiesis. We hypothesized that the cytotoxic hemozoin (Hz) residues from digested hemoglobin (Hb) significantly contribute to abnormal erythropoiesis.

Epitope-dependent localization of estrogen receptor-alpha, but not -beta, in en face arterial endothelium.

Rapid, nongenomic effects of 17 beta-estradiol (E(2)) in endothelial cells are postulated to arise from membrane-associated estrogen receptors (ERs), which have not been visualized in vascular tissue. To identify membrane ERs, we used multiple site-directed ER alpha or ER beta antibodies to label en face rat cerebral and coronary arterial endothelia. Western blots revealed a novel 55-kDa ER alpha isoform.