Algorithm for Rapid Exclusion of Clinically Relevant Plasma Levels of Direct Oral Anticoagulants in Patients Using the DOAC Dipstick: An Expert Consensus Paper.

Background:  With the widespread use of direct oral anticoagulants (DOACs), there is an urgent need for a rapid assay to exclude clinically relevant plasma levels. Accurate and rapid determination of DOAC levels would guide medical decision-making to (1) determine the potential contribution of the DOAC to spontaneous or trauma-induced hemorrhage; (2) identify appropriate candidates for reversal, or (3) optimize the timing of urgent surgery or intervention.

Methods And Results:  The DOAC Dipstick test uses a disposable strip to identify factor Xa- or thrombin inhibitors in a urine sample.

JAK1 Is a Novel Target of Tumor- and Invasion-Suppressive microRNA 494-5p in Colorectal Cancer.

MiR-494-5p expression has been suggested to be associated with colorectal cancer (CRC) and its metastases in our previous studies. However, functional investigations on the molecule-mediating actions of this miR in CRC are lacking. In silico analysis in the present study revealed a putative binding sequence within the 3'UTR of JAK1.

Epigenetically Downregulated Breast Cancer Gene 2 through Acetyltransferase Lysine Acetyltransferase 2B Increases the Sensitivity of Colorectal Cancer to Olaparib.

Olaparib suppresses DNA damage repair by inhibiting the poly ADP ribose polymerase (PARP), especially in cancers with mutations or the BRCA-ness phenotype. However, the first trials showed that some patients with defective DNA damage repair are still resistant to olaparib. The recovery of the wildtype BRCA is a prominent mechanism of PARP inhibitor (PARPi) resistance in BRCA-deficient tumors, but additional molecular features of olaparib resistance remain poorly understood.

An ex-vivo and in-vitro dynamic simulator for surgical and transcatheter mitral valve interventions.

Purpose: Minimally invasive mitral valve surgery (MIMVS) and transcatheter edge-to-edge repair (TEER) are complex procedures used to treat mitral valve (MV) pathologies, but with limited training opportunities available. To enable training, a realistic hemodynamic environment is needed. In this work we aimed to develop and validate a simulator that enables investigation of MV pathologies and their repair by MIMVS and TEER in a hemodynamic setting.

An update on the secretory functions of brown, white, and beige adipose tissue: Towards therapeutic applications.

Adipose tissue, including white adipose tissue (WAT), brown adipose tissue (BAT), and beige adipose tissue, is vital in modulating whole-body energy metabolism. While WAT primarily stores energy, BAT dissipates energy as heat for thermoregulation. Beige adipose tissue is a hybrid form of adipose tissue that shares characteristics with WAT and BAT.

Beyond the Operating Room: Exploring Gender Bias in Leadership Positions in German Plastic Surgery.

Background: Despite efforts to promote gender equity in medicine, gender disparities persist in various medical specialties, including plastic surgery. This study aimed to investigate the representation of female physicians in leadership positions in German plastic surgery departments.

Methods: This cross-sectional study collected data about the physician workforce in the German plastic surgery field.

Application of a Deep Learning System to Detect Papilledema on Nonmydriatic Ocular Fundus Photographs in an Emergency Department.

Purpose: The Fundus photography vs Ophthalmoscopy Trial Outcomes in the Emergency Department (FOTO-ED) studies showed that ED providers poorly recognized funduscopic findings in patients in the ED. We tested a modified version of the Brain and Optic Nerve Study Artificial Intelligence (BONSAI) deep learning system on nonmydriatic fundus photographs from the FOTO-ED studies to determine if the deep learning system could have improved the detection of papilledema had it been available to ED providers as a real-time diagnostic aid.

Design: Retrospective secondary analysis of a cohort of patients included in the FOTO-ED studies.

Management of congenital urogenital and perineal vascular malformations: correlation of clinical findings with diagnostic imaging for treatment decision.

Purpose: Analysis of clinical and diagnostic findings in rare urogenital and perineal vascular malformations only occurring in 2-3 % of vascular anomalies with regard to clinical symptoms and treatment decisions.

Materials And Methods: All 25 out of 537 patients presenting with congenital urogenital and perineal vascular malformations at our institution from 2014 to 2021 were included. Vascular anomaly classification, anatomical location, clinical symptoms at presentation, diagnostic imaging, and pain intensity were retrospectively assessed from the patient record and therapy management was evaluated.

My virtual home: needs of patients in palliative cancer care and content effects of individualized virtual reality - a mixed methods study protocol.

Background: The desire to be at home is one of the most important needs of patients with advanced, incurable cancers. However, palliative cancer patients may require inpatient hospital care for medical reasons. Virtual reality (VR) could provide an approximation to the individuals' home environment.

The Relationship Between Fear and Anxiety Among Chinese Uninfected Residents During the Pandemic: A Conditional Process Analysis.

Background: This study aimed to explore the relationship between residents' COVID-19 fear and anxiety, consider whether this relationship is mediated through obsessions and the moderating role of self-efficacy on this mediating pathway.

Methods: This study used an online questionnaire to obtain and assess fear, obsession, anxiety and self-efficacy in 1589 Chinese COVID-19 uninfected residents. A conditional process model was used to examine the relationships between variables.

Halide-Coupled Double Electron Transfer with Electron-Rich Diboranes.

The ditriflato-diborane B (μ-hpp) (OTf) (hpp=1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidinate) acts as a stable surrogate of the elusive dication [B (hpp) ] , being both electrophilic (vacant boron p orbitals) and nucleophilic (filled B-B bond orbital). This combination of seemingly contrasting behaviors could be used to develop a metallomimetic diborane chemistry, with Lewis σ-basic and π-acidic substrates being bound and reduced at the diborane. Here, we report on a novel reaction type within this general theme, in which double electron transfer from the diboron unit to the boron-bound organic substrate is coupled with halide transfer in the other direction.

Implementation behavior of communities regarding relatives caring for people with dementia : A quantitative study among German communities.

Background: Actors from the community (CAs) play a fundamental role in the support of caring relatives (CRs) of people with dementia (PWD). As their support is not sufficient, the implementation of support services needs to be optimized; however, little is known about the factors associated with the implementation behavior of CAs.

Aim: This study aimed to investigate the association of person-related factors with the implementation behavior of CAs.

Functionally distinct cancer-associated fibroblast subpopulations establish a tumor promoting environment in squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is a serious public health problem due to its high incidence and metastatic potential. It may progress from actinic keratosis (AK), a precancerous lesion, or the in situ carcinoma, Bowen's disease (BD). During this progression, malignant keratinocytes activate dermal fibroblasts into tumor promoting cancer-associated fibroblasts (CAFs), whose origin and emergence remain largely unknown.

Cas9-mediated knockout of Ndrg2 enhances the regenerative potential of dendritic cells for wound healing.

Chronic wounds impose a significant healthcare burden to a broad patient population. Cell-based therapies, while having shown benefits for the treatment of chronic wounds, have not yet achieved widespread adoption into clinical practice. We developed a CRISPR/Cas9 approach to precisely edit murine dendritic cells to enhance their therapeutic potential for healing chronic wounds.

Interleukin 17 signaling supports clinical benefit of dual CTLA-4 and PD-1 checkpoint inhibition in melanoma.

Recent studies suggest that BRAF-mutated melanomas in particular respond to dual anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) immune checkpoint inhibition (ICI). Here we identified an over-representation of interleukin (IL)-17-type 17 helper T (T17) gene expression signatures (GES) in BRAF-mutated tumors. Moreover, high baseline IL-17 GES consistently predicted clinical responses in dual-ICI-treated patient cohorts but not in mono anti-CTLA-4 or anti-PD-1 ICI cohorts.

Enhancing immunotherapy response in melanoma: myeloid-derived suppressor cells as a therapeutic target.

Despite the remarkable success of immune checkpoint inhibitors (ICIs) in melanoma treatment, resistance to them remains a substantial clinical challenge. Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of myeloid cells that can suppress antitumor immune responses mediated by T and natural killer cells and promote tumor growth. They are major contributors to ICI resistance and play a crucial role in creating an immunosuppressive tumor microenvironment.

Changes in the expression of cancer- and metastasis-related genes and proteins after metformin treatment under different metabolic conditions in endometrial cancer cells.

Research Question: Hyperinsulinemia and elevated estrogen levels are known risk factors for endometrial cancer (EC) development and are associated with obesity, type 2 diabetes mellitus (T2DM), insulin resistance, among others. Metformin, an insulin-sensitizing drug, displays anti-tumor effects in cancer patients, including EC, but the mechanism of action is still not completely understood. In the present study, the effects of metformin on gene and protein expression were investigated in pre- and postmenopausal EC models in order to identify candidates that are potentially involved in the drug's anti-cancer mechanism.

Translatability scoring in prospective and retrospective COVID drug development cases.

Background: The ongoing pandemic of severe acute respiratory syndrome coronavirus 2 has led to an enormous surge of clinical research. So far, the speed and success rate of related drug development projects, especially of vaccines, is unprecedented. For the first time, this situation allowed for the opportunistic evaluation of a translatability score, originally proposed in 2009, in a prospective manner.

Detection Rate of Prostate Cancer in Repeat Biopsy after an Initial Negative Magnetic Resonance Imaging/Ultrasound-Guided Biopsy.

A negative multiparametric magnetic resonance imaging (mpMRI)-guided prostate biopsy in patients with suspected prostate cancer (PC) results in clinical uncertainty, as the biopsy can be false negative. The clinical challenge is to determine the optimal follow-up and to select patients who will benefit from repeat biopsy. In this study, we evaluated the rate of significant PC (sPC, Gleason score ≥7) and PC detection in patients who received a follow-up mpMRI/ultrasound-guided biopsy for persistent PC suspicion after a negative mpMRI/ultrasound-guided biopsy.

Noxious radiant heat evokes bi-component nociceptive withdrawal reflexes in spinal cord injured humans-A clinical tool to study neuroplastic changes of spinal neural circuits.

Investigating nocifensive withdrawal reflexes as potential surrogate marker for the spinal excitation level may widen the understanding of maladaptive nociceptive processing after spinal cord injury (SCI). The aim of this prospective, explorative cross-sectional observational study was to investigate the response behavior of individuals with SCI to noxious radiant heat (laser) stimuli and to assess its relation to spasticity and neuropathic pain, two clinical consequences of spinal hyperexcitability/spinal disinhibition. Laser stimuli were applied at the sole and dorsum of the foot and below the fibula head.

An artificial intelligence-based chatbot for prostate cancer education: Design and patient evaluation study.

Introduction: Artificial intelligence (AI) is increasingly used in healthcare. AI-based chatbots can act as automated conversational agents, capable of promoting health and providing education at any time. The objective of this study was to develop and evaluate a user-friendly medical chatbot (prostate cancer communication assistant (PROSCA)) for provisioning patient information about early detection of prostate cancer (PC).