In vivo magnetogenetics for cell-type-specific targeting and modulation of brain circuits.

Neuromodulation technologies are crucial for investigating neuronal connectivity and brain function. Magnetic neuromodulation offers wireless and remote deep brain stimulations that are lacking in optogenetic- and wired-electrode-based tools. However, due to the limited understanding of working principles and poorly designed magnetic operating systems, earlier magnetic approaches have yet to be utilized.

Creating a win-win: A novel layered learning approach for assessing first-year pharmacy students' communication skills.

Background And Purpose: Individualized assessment of students in skills-based courses is essential for practice readiness, however recruiting evaluators is challenging. Our school of pharmacy offers a teaching certificate program for postgraduate year one pharmacy residents (PGY1 residents; PGY1s) which requires completion of a teaching experience. The longitudinal layered learning assessment experience (LLLAE) was designed to meet instructional needs for individualized assessment of first-year pharmacy students' communication skills and provide a meaningful teaching opportunity for PGY1s.

Post-translational regulation of proto-oncogene ZBTB7A expression by p53 status in cancer cells: HSP90-dependent stabilization vs. p53-KLHL20-ubiquitin proteasomal degradation.

ZBTB7A overexpressed in many human cancers is a major oncogenic driver. ZBTB7A promotes tumorigenesis by regulating transcription of the genes involved in cell survival and proliferation, apoptosis, invasion, and migration/metastasis. One unresolved issue is the mechanism underlying the aberrant overexpression of ZBTB7A in cancer cells.

One-Dimensional π-d Conjugated Coordination Polymer Intercalated MXene Compound for High-Performance Supercapacitor Electrode.

MXenes possess the characteristics required for high-performance supercapacitors, such as high metallic conductivity and electrochemical activity, but their full potential remains unrealized owing to their tendency to self-restack when fabricated into an electrode. Designing an MXene interlayer with an effective intercalant has, therefore, become an important criterion to alleviate the restacking issue while also synergistically interact with MXene to further improve its electrochemical activity. This study reports the intercalation of 1D π-d conjugated coordination polymer (Ni-BTA) within the Ti C T nanosheet for the fabrication of a highly efficient supercapacitor electrode.

An immunocompetent rectal cancer model to study radiation therapy.

We describe a mouse model of rectal cancer (RC) involving rapid tumor organoid engraftment via orthotopic transplantation in an immunocompetent setting. This approach uses simple mechanical disruption to allow engraftment, avoiding the use of dextran sulfate sodium. The resulting RC tumors invaded from the mucosal surface and metastasized to distant organs.

Risk Factors and Clinical Outcomes of Candidemia Associated With Severe COVID-19.

Unlabelled: COVID-19 can cause serious illness requiring multimodal treatment and is associated with secondary infections. Studies have suggested an increased risk of fungal infections, including candidemia following severe COVID-19 though understanding of risk factors and clinical outcomes remains unclear.

Objectives: To describe clinical characteristics, outcomes and risk factors of candidemia among patients hospitalized with severe COVID-19.

Genomic and transcriptomic determinants of response to neoadjuvant therapy in rectal cancer.

The incidence of rectal cancer is increasing in patients younger than 50 years. Locally advanced rectal cancer is still treated with neoadjuvant radiation, chemotherapy and surgery, but recent evidence suggests that patients with a complete response can avoid surgery permanently. To define correlates of response to neoadjuvant therapy, we analyzed genomic and transcriptomic profiles of 738 untreated rectal cancers.

A Post-Neurosurgical Infection due to KPC-Producing Klebsiella pneumoniae Treated with Meropenem-Vaborbactam: A Case Report.

This case report describes a patient with post-neurosurgical infection and bacteremia caused by Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae. There is limited evidence to guide antibiotic treatment decisions for such infections. The patient was treated with meropenem-vaborbactam (MEV).

Development of Certified Reference Material for Amino Acids in Dried Blood Spots and Accuracy Assessment of Disc Sampling.

To achieve the measurement reliability of amino acids used as diagnostic markers in clinical fields, establishing a reference measurement system is required, in which certified reference materials (CRMs) are an essential step in the hierarchy of measurement traceability. This study describes the development of dried blood spot (DBS) CRMs for amino acid analysis with complete measurement traceability to the International System of Units (SI). Six essential amino acids─proline, valine, isoleucine, leucine, phenylalanine, and tyrosine─were analyzed using isotope-dilution liquid chromatography-mass spectrometry (ID-MS).

KRAS Mutants Upregulate Integrin β4 to Promote Invasion and Metastasis in Colorectal Cancer.

Unlabelled: KRAS mutation in colorectal cancer is associated with aggressive tumor behavior through increased invasiveness and higher rates of lung metastases, but the biological mechanisms behind these features are not fully understood. In this study, we show that KRAS-mutant colorectal cancer upregulates integrin α6β4 through ERK/MEK signaling. Knocking-out integrin β4 (ITGB4) specifically depleted the expression of integrin α6β4 and this resulted in a reduction in the invasion and migration ability of the cancer cells.

Linking the Child Behavior Checklist to the Strengths and Difficulties Questionnaire.

The Child Behavior Checklist (CBCL) and Strengths and Difficulties Questionnaire (SDQ) both measure emotional and behavioral problems in children and adolescents, and scores on the two instruments are highly correlated. When administrative needs compel practitioners to change the instrument used or data from the two measures are combined to perform pooled analyses, it becomes necessary to compare scores on the two instruments. To enable such comparisons, we score linked three domains (Internalizing, Externalizing, and Total Problems) of the CBCL and SDQ in three age groups spanning 2-17 years.

An antibody against L1 cell adhesion molecule inhibits cardiotoxicity by regulating persistent DNA damage.

Targeting the molecular pathways underlying the cardiotoxicity associated with thoracic irradiation and doxorubicin (Dox) could reduce the morbidity and mortality associated with these anticancer treatments. Here, we find that vascular endothelial cells (ECs) with persistent DNA damage induced by irradiation and Dox treatment exhibit a fibrotic phenotype (endothelial-mesenchymal transition, EndMT) correlating with the colocalization of L1CAM and persistent DNA damage foci. We demonstrate that treatment with the anti-L1CAM antibody Ab417 decreases L1CAM overexpression and nuclear translocation and persistent DNA damage foci.

Proto-oncoprotein Zbtb7c and SIRT1 repression: implications in high-fat diet-induced and age-dependent obesity.

Zbtb7c is a proto-oncoprotein that controls the cell cycle and glucose, glutamate, and lipid metabolism. Zbtb7c expression is increased in the liver and white adipose tissues of aging or high-fat diet-fed mice. Knockout or knockdown of Zbtb7c gene expression inhibits the adipocyte differentiation of 3T3-L1 cells and decreases adipose tissue mass in aging mice.

Real-World Observational Review of Andexanet Alfa Prescribing and Utilization Outcomes at a Community Teaching Hospital.

Objectives: Andexanet alfa is the first approved antidote in the management of life-threatening bleeds in patients treated with Xa inhibitors. The ANNEXA-4 study was successful in reducing factor Xa levels during time of administration but lacked correlation to improved patient outcomes. Given its novel mechanism of action, U.

KRAS mutant rectal cancer cells interact with surrounding fibroblasts to deplete the extracellular matrix.

Somatic mutations in the KRAS oncogene are associated with poor outcomes in locally advanced rectal cancer but the underlying biologic mechanisms are not fully understood. We profiled mRNA in 76 locally advanced rectal adenocarcinomas from patients that were enrolled in a prospective clinical trial and investigated differences in gene expression between KRAS mutant (KRAS-mt) and KRAS-wild-type (KRAS-wt) patients. We found that KRAS-mt tumors display lower expression of genes related to the tumor stroma and remodeling of the extracellular matrix.

Posterior repair versus no posterior repair for posterior vaginal wall prolapse resolved under simulated apical support at the time of native tissue apical suspension.

Introduction And Hypothesis: The aim of this study was to evaluate the impact of an adjuvant posterior repair (PR) on treatment outcomes of native tissue apical suspension.

Materials And Methods: This retrospective cohort study included 194 women who underwent iliococcygeus or uterosacral ligament suspension with or without PR for Pelvic Organ Prolapse Quantification (POPQ) stage 2-4 posterior vaginal wall prolapse that resolved under simulated preoperative apical support and who completed a 1-year follow-up. The primary outcome was composite surgical failure defined as the presence of vaginal bulge symptoms, descent of the vaginal apex more than one-third of the way into the vaginal canal (apical recurrence), anterior or posterior vaginal wall descent beyond the hymen (anterior or posterior recurrence), or retreatment for prolapse.

Cell fate decisions by c-Myc depend on ZBTB5 and p53.

The oncoprotein, c-Myc, not only promotes cell proliferation, but can also induce or sensitize cells to apoptosis. However, how c-Myc decides cell fate and which c-Myc downstream target genes are involved remain unknown. Previously, we showed that ZBTB5 (zinc finger and BTB domain-containing 5) is a proto-oncogene that stimulates cell proliferation.

Pharmacologic Inhibition of HIF-1α Attenuates Radiation-Induced Pulmonary Fibrosis in a Preclinical Image Guided Radiation Therapy.

Purpose: Radiation-induced pulmonary fibrosis (RIPF) is a long-term side effect of thoracic radiation therapy. Hypoxia-induced vascular endothelial mesenchymal transition (EndMT) can occur during the development of RIPF. Here, we examined the direct contribution of endothelial HIF-1α (EC-HIF1α) on RIPF.

KLHL4, a novel p53 target gene, inhibits cell proliferation by activating p21.

KLHL4 is a member of the KLHL protein family, many of whom bind the Cul3 E3 ligase, and mediate the ubiquitination of interacting proteins. The KLHL4 gene, localized on the X chromosome, associates with a disorder known as X-linked cleft palate (CPX). However, the biological functions of KLHL4 are largely unknown.

Important Consideration in Choosing Antipsychotics in the Treatment of Patients with 22q11.2 Deletion Syndrome: Risk of Convulsion.

The prevalence of epilepsy and psychosis in 22q11.2 deletion syndrome (22q11.2DS) is higher than in the general population.

Endothelial-to-mesenchymal transition in anticancer therapy and normal tissue damage.

Endothelial-to-mesenchymal transition (EndMT) involves the phenotypic conversion of endothelial-to-mesenchymal cells, and was first discovered in association with embryonic heart development. EndMT can regulate various processes, such as tissue fibrosis and cancer. Recent findings have shown that EndMT is related to resistance to cancer therapy, such as chemotherapy, antiangiogenic therapy, and radiation therapy.

A rectal cancer organoid platform to study individual responses to chemoradiation.

Rectal cancer (RC) is a challenging disease to treat that requires chemotherapy, radiation and surgery to optimize outcomes for individual patients. No accurate model of RC exists to answer fundamental research questions relevant to patients. We established a biorepository of 65 patient-derived RC organoid cultures (tumoroids) from patients with primary, metastatic or recurrent disease.