Comparative Effectiveness of Antivirals and Monoclonal Antibodies for Treating COVID-19 Patients Infected With Omicron Variant: A Systematic Review and Network Meta-Analysis.

Antiviral drugs likely remain effective against the SARS-CoV-2 Omicron variant, while monoclonal antibody (mAb) therapies have experienced drops in neutralizing ability. This systematic review and network meta-analysis aims to estimate the comparative effectiveness of antivirals and mAb therapies for treating COVID-19 patients infected with Omicron, capturing primarily acute outcomes. We searched multiple databases from July 4 to July 19, 2022, with updates through November 4, 2022.

Temporal Changes in PROMs Improvement and Recovery Kinetics Following Transforaminal Endoscopic Lumbar Discectomy.

Study Design: Retrospective cohort study.

Objective: to analyze trends in PROMs improvement and recovery kinetics following transforaminal endoscopic lumbar discectomy and foraminotomy (TELD).

Summary Of Background Data: As TELDs become an increasingly common alternative to fusions for lateral disc herniations, it is important to understand patients' postoperative recovery timelines to manage patient expectations.

Covalent Attachment of Horseradish Peroxidase to Single-Walled Carbon Nanotubes for Hydrogen Peroxide Detection.

Single-walled carbon nanotubes (SWCNTs) are desirable nanoparticles for sensing biological analytes due to their photostability and intrinsic near-infrared fluorescence. Previous strategies for generating SWCNT nanosensors have leveraged nonspecific adsorption of sensing modalities to the hydrophobic SWCNT surface that often require engineering new molecular recognition elements. An attractive alternate strategy is to leverage pre-existing molecular recognition of proteins for analyte specificity, yet attaching proteins to SWCNT for nanosensor generation remains challenging.

: Integrative Module Analysis for Multi-omics Data.

Summary: The integration of metabolomics with other omics ("multi-omics") offers complementary insights into disease biology. However, this integration remains challenging due to the fragmented landscape of current methodologies, which often require programming experience or bioinformatics expertise. Moreover, existing approaches are limited in their ability to accommodate unidentified metabolites, resulting in the exclusion of a significant portion of data from untargeted metabolomics experiments.

Small Molecule Inhibitor of Protein Kinase C DeltaI (PKCδI) Decreases Inflammatory Pathways and Gene Expression and Improves Metabolic Function in Diet-Induced Obese Mouse Model.

Obesity promotes metabolic diseases such as type 2 diabetes and cardiovascular disease. PKCδI is a serine/threonine kinase which regulates cell growth, differentiation, and survival. Caspase-3 cleavage of PKCδI releases the C-terminal catalytic fragment (PKCδI_C), which promotes inflammation and apoptosis.

Impaired Pre-operative Ambulatory Capacity in Patients Undergoing Elective Endovascular Infrarenal Abdominal Aortic Aneurysm Repair is Associated with Increased Peri-operative Death.

Objective: While ambulatory capacity is a readily assessable clinical indicator of functional status, its association with outcomes after endovascular aneurysm repair (EVAR) remains underexplored. This study aimed to investigate the association between pre-operative ambulatory status and outcomes following elective EVAR.

Methods: A retrospective review of the multi-institutional Vascular Quality Initiative database was conducted for all patients who underwent elective infrarenal EVAR from 2009 - 2022.

Combination of MDM2 and Targeted Kinase Inhibitors Results in Prolonged Tumor Control in Lung Adenocarcinomas With Oncogenic Tyrosine Kinase Drivers and Amplification.

Purpose: MDM2, a negative regulator of the TP53 tumor suppressor, is oncogenic when amplified. amplification (MDM2amp) is mutually exclusive with mutation and is seen in 6% of patients with lung adenocarcinoma (LUAD), with significant enrichment in subsets with receptor tyrosine kinase (RTK) driver alterations. Recent studies have shown synergistic activity of MDM2 and MEK inhibition in patient-derived LUAD models with MDM2amp and RTK driver alterations.

Glioblastoma induces the recruitment and differentiation of dendritic-like "hybrid" neutrophils from skull bone marrow.

Tumor-associated neutrophil (TAN) effects on glioblastoma (GBM) biology remain under-characterized. We show here that neutrophils with dendritic features-including morphological complexity, expression of antigen presentation genes, and the ability to process exogenous peptide and stimulate major histocompatibility complex (MHC)II-dependent T cell activation-accumulate intratumorally and suppress tumor growth in vivo. Trajectory analysis of patient TAN scRNA-seq identifies this "hybrid" dendritic-neutrophil phenotype as a polarization state that is distinct from canonical cytotoxic TANs, and which differentiates from local precursors.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with biliary tract cancer.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with biliary tract cancer (BTC), published in late 2022 were adapted in December 2023, according to established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with BTC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with BTC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Taiwan Oncology Society (TOS). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different regions of Asia.

HER2 Antibody-Drug Conjugates Are Active against Desmoplastic Small Round Cell Tumor.

Purpose: Desmoplastic small round cell tumor (DSRCT) is a rare but highly aggressive soft tissue sarcoma that arises in the abdominopelvic cavity of young males. Since the discovery of EWSR1::WT1 fusion as the driver of DSRCT, no actionable genomic alterations have been identified, limiting disease management to a combination of surgery, chemotherapy, and radiation, with very poor outcomes. Herein, we evaluated ERBB2/HER2 expression in DSRCT as a therapeutic target.

Comparative Review of the Socioeconomic Burden of Lower Back Pain in the United States and Globally.

Internationally, the United States (U.S.) cites the highest cost burden of low back pain (LBP).

Clinical Impact of Contouring Variability for Prostate Cancer Tumor Boost.

Purpose: The focal radiation therapy (RT) boost technique was shown in a phase III randomized controlled trial (RCT) to improve prostate cancer outcomes without increasing toxicity. This technique relies on the accurate delineation of prostate tumors on MRI. A recent prospective study evaluated radiation oncologists' accuracy when asked to delineate prostate tumors on MRI and demonstrated high variability in tumor contours.

Healthy lifestyle and prostate cancer risk in the Million Veteran Program.

Background: This study aims to assess the impact of healthy lifestyle on prostate cancer (PCa) risk in a diverse population.

Methods: Data for 281,923 men from the Million Veteran Program (MVP), a nationwide, health system-based cohort study, were analyzed. Self-reported information at enrollment included smoking status, exercise, diet, family history of PCa, and race/ethnicity.

Agent orange exposure and prostate cancer risk in the million veteran program.

Background: The US government considers veterans to have been exposed to Agent Orange if they served in Vietnam while the carcinogen was in use, and these veterans are often deemed at high risk of prostate cancer (PCa). Here, we assess whether presumed Agent Orange exposure is independently associated with increased risk of any metastatic or fatal PCa in a diverse Veteran cohort still alive in the modern era (at least 2011), when accounting for race/ethnicity, family history, and genetic risk.

Patients And Methods: Participants in the Million Veteran Program (MVP; enrollment began in 2011) who were on active duty during the Vietnam War era (August 1964-April 1975) were included (n = 301,470).

Tumor Suppressor MicroRNAs in Clinical and Preclinical Trials for Neurological Disorders.

Cancers and neurological disorders are two major types of diseases in humans. We developed the concept called the "Aberrant Cell Cycle Disease (ACCD)" due to the accumulating evidence that shows that two different diseases share the common mechanism of aberrant cell cycle re-entry. The aberrant cell cycle re-entry is manifested as kinase/oncoprotein activation and tumor suppressor (TS) inactivation, which are associated with both tumor growth in cancers and neuronal death in neurological disorders.

Nationwide Incidence and Trends in Central Retinal Arterial Occlusion Management: A 5000-Patient Analysis.

Central retinal artery occlusion (CRAO) is a rare and visually debilitating vascular condition characterized by sudden and severe vision loss. CRAO is a compelling target for intravenous alteplase (tPA) and endovascular mechanical thrombectomy (MT) due to pathophysiological similarities with acute ischemic stroke; however, the utility of these interventions in CRAO remains dubious due to limited sample sizes and potential risks. To assess usage and outcomes of tPA and MT in CRAO, we queried the National Inpatient Sample database using International Classification of Disease, Ninth and Tenth edition for patients with CRAO and acute ischemic stroke between 2010 and 2019.

Development and external validation of a dynamic risk score for early prediction of cardiogenic shock in cardiac intensive care units using machine learning.

Aims: Myocardial infarction and heart failure are major cardiovascular diseases that affect millions of people in the USA with morbidity and mortality being highest among patients who develop cardiogenic shock. Early recognition of cardiogenic shock allows prompt implementation of treatment measures. Our objective is to develop a new dynamic risk score, called CShock, to improve early detection of cardiogenic shock in the cardiac intensive care unit (ICU).

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with gastric cancer.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with gastric cancer (GC), published in late 2022 and the updated ESMO Gastric Cancer Living Guideline published in July 2023, were adapted in August 2023, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with GC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with GC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), coordinated by ESMO and the Japanese Society of Medical Oncology (JSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian regions represented by the 10 oncological societies.

Utilization of Tenting Pole Abutments for the Reconstruction of Severely Resorbed Alveolar Bone: Technical Considerations and Case Series Reports.

Introduction: Although various surgical techniques have been utilized in the reconstruction of severely resorbed alveolar bone, its regeneration is still regarded as a major challenge. Most of the surgical techniques used in advanced ridge augmentation have the disadvantages of prolonging the patient's edentulous healing and increasing the need for surgical revisits because simultaneous implant placement is not allowed. This report presents a new and simplified method for advanced ridge augmentation, which utilizes a vertical tenting device.

Nudix hydrolase 23 post-translationally regulates carotenoid biosynthesis in plants.

Carotenoids are essential for photosynthesis and photoprotection. Plants must evolve multifaceted regulatory mechanisms to control carotenoid biosynthesis. However, the regulatory mechanisms and the regulators conserved among plant species remain elusive.

Biomimetic Synthesis and Chemical Proteomics Reveal the Mechanism of Action and Functional Targets of Phloroglucinol Meroterpenoids.

Natural products perennially serve as prolific sources of drug leads and chemical probes, fueling the development of numerous therapeutics. Despite their scarcity, natural products that modulate protein function through covalent interactions with lysine residues hold immense potential to unlock new therapeutic interventions and advance our understanding of the biological processes governed by these modifications. Phloroglucinol meroterpenoids constitute one of the most expansive classes of natural products, displaying a plethora of biological activities.

Multifunctional 5-hydroxyconiferaldehyde O-methyltransferases (CAldOMTs) in plant metabolism.

Lignin, flavonoids, melatonin, and stilbenes are plant specialized metabolites with diverse physiological and biological functions, supporting plant growth and conferring stress resistance. Their biosynthesis requires O-methylations catalyzed by 5-hydroxyconiferaldehyde O-methyltransferase (CAldOMT; also called caffeic acid O-methyltransferase, COMT). CAldOMT was first known for its roles in syringyl (S) lignin biosynthesis in angiosperm cell walls and later found to be multifunctional.