The increasing incidence and mortality of bacteremia in Denmark from 2010 to 2022: a population-based nationwide cohort study.

Objectives: An increasing incidence of positive blood cultures has been reported in several countries. This represents an important challenge for public health due to the large number of hospital admissions with high mortality among these patients. This study aims to characterize the epidemiology and mortality associated with positive blood cultures.

Development of DuoMYC: a synthetic cell penetrant miniprotein that efficiently inhibits the oncogenic transcription factor MYC.

The master regulator transcription factor MYC is implicated in numerous human cancers, and its targeting is a long-standing challenge in drug development. MYC is a typical 'undruggable' target, with no binding pockets on its DNA binding domain and extensive intrinsically disordered regions. Rather than trying to target MYC directly with classical modalities, here we engineer synthetic miniproteins that can bind to MYC's target DNA, the enhancer box (E-Box), and potently inhibit MYC-driven transcription.

Phosphinate Esters as Novel Warheads for Quenched Activity-Based Probes Targeting Serine Proteases.

Quenched activity-based probes (qABP) are invaluable tools to visualize aberrant protease activity. Unfortunately, most studies so far have only focused on cysteine proteases, and only a few studies describe the synthesis and use of serine protease qABPs. We recently used phosphinate ester electrophiles as a novel type of reactive group to construct ABPs for serine proteases.

Synthetic Peptides: Promising Modalities for the Targeting of Disease-Related Nucleic Acids.

DNA and RNA play pivotal roles in life processes by storing and transferring genetic information, modulating gene expression, and contributing to essential cellular machinery such as ribosomes. Dysregulation and mutations in nucleic acid-related processes are implicated in numerous diseases. Despite the critical impact on health of nucleic acid mutations or dysregulation, therapeutic compounds addressing these biomolecules remain limited.

Comparison of morbidity and mortality after bloodstream infection with vancomycin-resistant versus -susceptible nationwide cohort study in Denmark, 2010-2019.

The emergence of bloodstream infections (BSI) caused by vancomycin-resistant Enterococci (VRE) has caused concern. Nonetheless, it remains unclear whether these types are associated with an excess risk of severe outcomes when compared with infections caused by vancomycin-susceptible Enterococci (VSE). This cohort study included hospitalized patients in Denmark with -positive blood cultures collected between 2010 and 2019 identified in the Danish Microbiology Database.

Rapid on-site evaluation (ROSE) of image-guided FNA specimens improves subsequent core biopsy adequacy in clinical trial patients: The impact of preanalytical factors and its correlation with survival.

Background: Sufficient tumor collection has become of utmost importance in therapeutic experimental protocols. Rapid on-site evaluation (ROSE) ensures adequate sampling for quantification of biomarkers, molecular analyses, and other ancillary studies. The objectives of this study were to evaluate the role of ROSE in trial-associated fine-needle aspiration (FNA) and to analyze predictors of adequacy and cumulative survival from in-house FNA cases used in clinical trials.

Predicting COVID-19 Incidence Using Wastewater Surveillance Data, Denmark, October 2021-June 2022.

Analysis of wastewater is used in many settings for surveillance of SARS-CoV-2, but it remains unclear how well wastewater testing results reflect incidence. Denmark has had an extensive wastewater analysis system that conducts 3 weekly tests in ≈200 sites and has 85% population coverage; the country also offers free SARS-CoV-2 PCR tests to all residents. Using time series analysis for modeling, we found that wastewater data, combined with information on circulating variants and the number of human tests performed, closely fitted the incidence curve of persons testing positive.

Duodenal macrophages control dietary iron absorption via local degradation of transferrin.

Iron is an essential cellular metal that is important for many physiological functions including erythropoiesis and host defense. It is absorbed from the diet in the duodenum and loaded onto transferrin (Tf), the main iron transport protein. Inefficient dietary iron uptake promotes many diseases, but mechanisms regulating iron absorption remain poorly understood.

Clotrimazole-Based Modulators of the TRPM3 Ion Channel Reveal Narrow Structure-Activity Relationship.

TRPM3 is an ion channel that is highly expressed in nociceptive neurons and plays a key role in pain perception. In the presence of the endogenous TRPM3 ligand, pregnenolone sulfate (PS), the antifungal compound clotrimazole (Clt) augments Ca signaling and opens a non-canonical pore, permeable to Na, which aggravates TRPM3-induced pain. To date, little is known about structural features that govern the Clt modulatory effect of TRPM3.

Atypia of undetermined significance in the Milan System for Reporting Salivary Gland Cytopathology: Cystic versus non-cystic masses.

The term "Atypia" has been employed to describe a wide spectrum of cytomorphologic features associated with reactive/inflammatory processes as well as those suspicious for neoplasms in cytology. Similar to other cytopathology reporting systems, the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has reserved the atypical category for cytology specimens lacking quantitative and/or qualitative cytomorphologic features to be diagnosed with confidence as either non-neoplastic or neoplastic. In MSRSGC, the atypical category is associated with a risk of malignancy and recommendation for clinical management.

An evaluation of common risk factors for prolonged grief disorder using the international classification of diseases-11 criteria.

Objectives: Inclusion of Prolonged Grief Disorder (PGD) in the ICD-11 warrants examination of risk factors using diagnostic criteria as there is a paucity of research that has examined risk factors of PGD using the diagnostic criteria. This study examines if the identified risk factors for prolonged grief predict PGD using the diagnostic criteria across three samples.

Methods: A cross-sectional survey design was used to assess risk factors and PG-13 in three distinct samples of bereaved adults.

The Value of Second-Opinion Consultation in Nongynecologic Cytopathology.

Objectives: The value of consultation in pathology has been well documented in surgical pathology, but there are few comprehensive studies of consultation cases in cytopathology. Here we report our experience with cytopathology consultation cases at a large academic center.

Methods: A review of consultation cases at our institution was performed by searching our laboratory information system.

Perception of grief responses: Are maladaptive grief responses and the stages of grief considered ?

Literature indicates laypeople hold strong opinions about how persons should grieve. This study examined how individuals perceive grief. Participants across two distinct samples (Study 1:  = 510 via MTurk; Study 2:  = 210 via Qualtrics panels) completed the Perception of Grief Scale and Grief Expectations Questionnaire.

Phosphinate esters as novel warheads for activity-based probes targeting serine proteases.

Activity-based protein profiling enables the specific detection of the active fraction of an enzyme and is of particular use for the profiling of proteases. The technique relies on a mechanism-based reaction between small molecule activity-based probes (ABPs) with the active enzyme. Here we report a set of new ABPs for serine proteases, specifically neutrophil serine proteases.

Atrial natriuretic peptide (ANP) as an endogenous anxiolytic in patients with heart failure? - No replication of previous results showing an inverse association of anxiety and plasma ANP parameters.

Objective: An acute anxiolytic-like effect of atrial natriuretic peptide (ANP) has been demonstrated in several preclinical and clinical studies. In a so far singular study (Herrmann-Lingen et al., 2003), patients with congestive heart failure, who pathognomonicly display increased plasma ANP, showed a significant inverse association of anxiety symptoms and pro-ANP levels, giving rise to speculations about ANP as an endogenous anxiolytic.

"It may help you to know…": The Early-phase Qualitative Development of a Rheumatoid Arthritis Goal Elicitation Tool.

Objective: Treatment guidelines for rheumatoid arthritis (RA) include a patient-centered approach and shared decision making, which includes a discussion of patient goals. We describe the iterative early development of a structured goal elicitation tool to facilitate goal communication for persons with RA and their clinicians.

Methods: Tool development occurred in 3 phases: (1) clinician feedback on the initial prototype during a communication training session; (2) semistructured interviews with RA patients; and (3) community stakeholder feedback on elements of the goal elicitation tool in a group setting and electronically.

Development of Highly Optimized Antibody-Drug Conjugates against CD33 and CD123 for Acute Myeloid Leukemia.

Purpose: Mortality due to acute myeloid leukemia (AML) remains high, and the management of relapsed or refractory AML continues to be therapeutically challenging. The reapproval of Mylotarg, an anti-CD33-calicheamicin antibody-drug conjugate (ADC), has provided a proof of concept for an ADC-based therapeutic for AML. Several other ADCs have since entered clinical development of AML, but have met with limited success.

Fracture of an S-ICD lead after two prior transvenous lead-related complications with conventional defibrillators.

Six months after subcutaneous implantable cardioverter defibrillator (S-ICD) implantation a 26-year-old Brugada patient presented because of a beeping tone emitted by his device. Chest X-ray displayed two functionless transvenous shock leads and the S-ICD system with a lead fracture. During lead revision procedure, extensive preparation of the lead from unexpectedly firm surrounding fibrous tissue encapsulating the lead was necessary before it could be removed, and a new shock lead could be implanted.

Evaluating the empirical evidence for three transdiagnostic mechanisms in anxiety and mood disorders.

High co-morbidity among mental disorders indicates that common transdiagnostic mechanisms underlie various psychopathology, yet there has been little research effort to empirically explicate transdiagnostic processes. A few existing studies are limited in the number of transdiagnostic mechanisms and mental disorder categories explored. The current study addresses these limitations by examining the relationship between three transdiagnostic processes (experiential avoidance, rumination, and emotion dysregulation) and symptom severity of five mental disorders (generalized anxiety disorder, panic disorder, social anxiety disorder, specific phobia, and depression) in a college sample (N = 266).

Feasibility, Safety, and Clinical Performance of Self-apposing Stents for Left Main Stenosis.

Drug-eluting stents (DES) are the gold standard for percutaneous coronary interventions (PCI); however, technical and anatomical challenges need to be addressed to ensure optimal apposition and prevent late adverse events. Complex vessel anatomies, including ectatic or aneurysmatic vessels, or significant differences in diameter in left main stenosis of the coronary artery, are clinical indications in which current PCI techniques attempt to shape conventional DES to follow vessel anatomy, thus modifying the original stent scaffold and its properties. However, due to their design, balloon-expandable cobalt-chromium and cobalt-nickel DES have limitations regarding their expansion capacity, which can result in undersizing and malapposition.

Facile Synthesis of Aminomethyl Phosphinate Esters as Serine Protease Inhibitors with Primed Site Interaction.

Serine proteases comprise about one-third of all proteases, and defective regulation of serine proteases is involved in numerous diseases. Therefore, serine protease inhibitors are promising drug candidates. Aminomethyl diphenyl phosphonates have been regularly used as scaffolds for covalent serine protease inhibition and the design of activity-based probes.

Heterogeneous nuclear ribonucleoprotein K is overexpressed and contributes to radioresistance irrespective of HPV status in head and neck squamous cell carcinoma.

Radiotherapy is a major treatment option for head and neck squamous cell carcinoma (HNSCC). However, the success of radiotherapy is limited by tumor cell resistance to ionizing radiation (IR). Clinical studies have demonstrated an overall improved prognosis and higher susceptibility to radiotherapy of high‑risk human papillomavirus (HPV)‑associated HNSCC compared with classic HNSCC, as well as worse overall survival for male HNSCC patients.