Benchmarking Cross-Docking Strategies in Kinase Drug Discovery.

In recent years, machine learning has transformed many aspects of the drug discovery process, including small molecule design, for which the prediction of bioactivity is an integral part. Leveraging structural information about the interactions between a small molecule and its protein target has great potential for downstream machine learning scoring approaches but is fundamentally limited by the accuracy with which protein-ligand complex structures can be predicted in a reliable and automated fashion. With the goal of finding practical approaches to generating useful kinase-inhibitor complex geometries for downstream machine learning scoring approaches, we present a kinase-centric docking benchmark assessing the performance of different classes of docking and pose selection strategies to assess how well experimentally observed binding modes are recapitulated in a realistic cross-docking scenario.

Percutaneous cryoablation in soft tissue tumor management: an educational review.

Background: Percutaneous cryoablation (PCA), having shown effectiveness in treating liver, lung, prostate, breast, and kidney tumors, is now gaining attention for the treatment of soft tissue tumors. PCA functions by freezing tissue, which induces ice crystal formation and cell death without damaging collagen structures. Technical considerations include the selection and handling of cryoprobes and cryogenic agents, procedural duration, and choice of image guidance for precision.

Aiming for zero: Success of the hysterectomy surgical site infection prevention bundle.

Background: The Center for Disease Control's National Healthcare Safety Network (NHSN) reported increased Standardized Infection Ratios (SIRs) for hysterectomy at a large community hospital.

Objective: To promote a surgical site infection (SSI) prevention bundle implemented to reduce hysterectomy-associated SSI.

Methods: A multidisciplinary Workgroup implemented the Hysterectomy SSI Prevention Bundle in 2020 to enforce standardization of perioperative techniques.

Aggressive Malignant Ossifying Fibromyxoid Tumor With a Rare Fusion: A Case Report and Literature Review.

Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm of uncertain origin, exhibiting a wide clinical and morphological spectrum. It ranges from benign forms, which typically behave indolently, to malignant lesions with significant recurrence and metastatic potential. The majority of OFMTs harbor gene rearrangements, with being the most common fusion partner.

Clinical benefit with tebentafusp in a patient with GNAQ mutant metastatic blue nevus-associated melanoma.

Melanoma arising in association with a blue nevus (BN) is rare but has molecular similarities to uveal melanoma (UM), including GNAQ/11 mutations. Tebentafusp was recently approved for UM based on improved overall survival in a phase 3 study. We hypothesized that tebentafusp may be active in BN-associated melanoma.

Single-cell and spatial transcriptomics identify COL6A3 as a prognostic biomarker in undifferentiated pleomorphic sarcoma.

Undifferentiated pleomorphic sarcoma (UPS) and related tumors are the most common type of soft tissue sarcoma. However, this spectrum of tumors has different etiologies with varying rates of metastasis and survival. Two dermal-based neoplasms in this class of pleomorphic sarcomas, atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS), are challenging to differentiate at initial biopsy but vary significantly in prognosis.

The effect of cancer and cancer treatment on attention control: evidence from anti-saccade performance.

Purpose: Cancer and cancer treatment have been associated with cognitive changes in survivorship, with forgetfulness and distractibility reported years post-treatment. Deficits in attention control may explain these difficulties. We assessed breast cancer survivors using a primary measure of attention control, the saccade/antisaccade task, to assess the effects of diagnosis and treatment.

Safety and efficacy of pembrolizumab, radiation therapy, and surgery versus radiation therapy and surgery for stage III soft tissue sarcoma of the extremity (SU2C-SARC032): an open-label, randomised clinical trial.

Background: Approximately half of patients with localised, high-risk soft tissue sarcoma of the extremity develop metastases. We aimed to assess whether the addition of pembrolizumab to preoperative radiotherapy and surgery would improve disease-free survival.

Methods: We completed an open-label, randomised clinical trial in patients with grade 2 or 3, stage III undifferentiated pleomorphic sarcoma or dedifferentiated or pleomorphic liposarcoma of the extremity and limb girdle.

IDH1/2 Mutations in Cancer: Unifying Insights and Unlocking Therapeutic Potential for Chondrosarcoma.

Chondrosarcomas, a rare form of bone sarcomas with multiple subtypes, pose a pressing clinical challenge for patients with advanced or metastatic disease. The lack of US Food and Drug Administration (FDA)-approved medications underscores the urgent need for further research and development in this area. Patients and their families face challenges as there are no systemic therapeutic options available with substantial effectiveness.

Architecture and activation of single-pass transmembrane receptor guanylyl cyclase.

The heart, in addition to its primary role in blood circulation, functions as an endocrine organ by producing cardiac hormone natriuretic peptides. These hormones regulate blood pressure through the single-pass transmembrane receptor guanylyl cyclase A (GC-A), also known as natriuretic peptide receptor 1. The binding of the peptide hormones to the extracellular domain of the receptor activates the intracellular guanylyl cyclase domain of the receptor to produce the second messenger cyclic guanosine monophosphate.

Exploring the Interplay Between Radioimmunoconjugates and Fcγ Receptors in Genetically Engineered Mouse Models of Cancer.

Fcγ receptors (FcγR) are responsible for many of the interactions between immunoglobulins (IgG) and immune cells. In biomedicine, this interplay is critical to the activity of several types of immunotherapeutics; however, relatively little is known about how FcγRs affect the in vivo performance of radiolabeled antibodies. A handful of recent preclinical studies suggest that binding by FcγR-and particularly FcγRI-can affect the pharmacokinetic profiles of Zr-labeled radioimmunoconjugates, but there are no extant studies in immunocompetent or genetically engineered mouse models of cancer.

A survey to determine the zone of equipoise for the Proximal FEmur Resection or Internal Fixation fOR Metastases (PERFORM) randomized controlled trial.

Objective: The objective of this study was to establish a zone of clinical equipoise for the Proximal FEmur Resection or Internal Fixation fOR Metastases (PERFORM) randomized controlled trial, which will compare resection and endoprosthetic reconstruction to internal fixation for skeletal metastases of the proximal femur.

Methods: A survey was developed, piloted, and distributed to self-declared interested stakeholders in the PERFORM trial. The survey targeted orthopedic oncologists and was designed to assess patient and bone lesion characteristics that drive surgical decision-making in the treatment of skeletal metastases in the proximal femur.

Fifteen-Year Experience of a Single Institution: Outcomes for Early-Stage Hodgkins Lymphoma Comparing Chemotherapy Alone Versus Combined Modality Therapy.

Purpose: Doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy is the current standard treatment for early-stage Hodgkins lymphoma (HL). The use of consolidative radiation therapy (RT) in addition to chemotherapy may lead to better survival rates but is controversial because of concerns about long-term toxicity. The aim of this study is to compare outcomes of patients receiving ABVD chemotherapy alone (CTX alone) versus ABVD with consolidative RT (CMT).

Treatment outcomes of non-curative endoscopic submucosal dissection for superficial gastric neoplasia: A retrospective study at a tertiary care center in the United States.

Objectives: Endoscopic submucosal dissection (ESD) is a minimally invasive treatment for early gastric cancer; additional treatment may be recommended for patients in whom resection is not curative per the American Society for Gastrointestinal Endoscopy guidelines. The aim of this study was to assess treatment outcomes of ESD for gastric neoplasia, with a focus on cases of non-curative resection.

Methods: This was a retrospective study of all individuals undergoing ESD for the treatment of gastric adenocarcinoma or dysplasia in a high-volume tertiary care center in the United States.

Shareable artificial intelligence to extract cancer outcomes from electronic health records for precision oncology research.

Databases that link molecular data to clinical outcomes can inform precision cancer research into novel prognostic and predictive biomarkers. However, outside of clinical trials, cancer outcomes are typically recorded only in text form within electronic health records (EHRs). Artificial intelligence (AI) models have been trained to extract outcomes from individual EHRs.

In vivo models of subclonal oncogenesis and dependency in hematopoietic malignancy.

Cancer evolution is a multifaceted process leading to dysregulation of cellular expansion and differentiation through somatic mutations and epigenetic dysfunction. Clonal expansion and evolution is driven by cell-intrinsic and -extrinsic selective pressures, which can be captured with increasing resolution by single-cell and bulk DNA sequencing. Despite the extensive genomic alterations revealed in profiling studies, there remain limited experimental systems to model and perturb evolutionary processes.