Acute Extrinsic Activation of the RANKL Pathway Decreases Wound Healing and Functional Recovery After Spinal Cord Injury in Mice.

Manipulating wound healing-associated signaling after SCI presents a promising avenue for increasing the recovery of function after injury. This study explores the potential of targeting molecular regulators of wound healing, initially identified in nonneural tissues, to enhance outcomes after SCI. Astrocytes, pivotal in central nervous system wound healing, play a crucial role in tissue remodeling and recovery.

Strategies for automated affinity purification-resin screening for non-traditional biopharmaceuticals in the discovery space.

Biotherapeutics occupy a significant portion of the pharmaceutical pipeline and are projected to continue growing in sales and scope. Further, the field is advancing novel and more complex molecules beyond monoclonal antibodies including multi-target proteins, engineered proteins and bioconjugates. In this aspect, the development of increasingly advanced and challenging therapies necessitates a commiserate degree of innovation to develop automated methods for resin screening, purification, and analytics in the discovery space to quickly identify liabilities and rank candidates with minimal impact on developmental resources.

Combining Topic Modeling, Sentiment Analysis, and Corpus Linguistics to Analyze Unstructured Web-Based Patient Experience Data: Case Study of Modafinil Experiences.

Background: Patient experience data from social media offer patient-centered perspectives on disease, treatments, and health service delivery. Current guidelines typically rely on systematic reviews, while qualitative health studies are often seen as anecdotal and nongeneralizable. This study explores combining personal health experiences from multiple sources to create generalizable evidence.

Innovations in Amputation Rehabilitation and Prosthetic Design.

This article reviews emerging surgical techniques and prosthetic innovations related to amputation rehabilitation. Osseointegration is discussed from conception to modern implant designs. Motor and sensory reinnervation techniques are reviewed and compared.

A Minimal PBPK Model Describes the Differential Disposition of Silica Nanoparticles In Vivo.

Nanoparticles (NPs) have emerged as promising candidates for drug delivery due to their tunable physical and chemical properties. Among these, silica nanoparticles (SiNPs) are particularly valued for their biocompatibility and adaptability in applications like drug delivery and medical imaging. However, predicting SiNP biodistribution and clearance remains a significant challenge.

Iatrogenic Sciatic Nerve Injury in Posterior Acetabular Surgery: Surgeon More Predictive Than Position.

Objectives: To identify factors that contribute to iatrogenic sciatic nerve palsy during acetabular surgery through a Kocher-Langenbeck approach and to evaluate if variation among individual surgeons exists.

Design: Retrospective cohort.

Setting: Level I trauma center.

Translational modeling-based evidence for enhanced efficacy of standard-of-care drugs in combination with anti-microRNA-155 in non-small-cell lung cancer.

Background: Elevated microRNA-155 (miR-155) expression in non-small-cell lung cancer (NSCLC) promotes cisplatin resistance and negatively impacts treatment outcomes. However, miR-155 can also boost anti-tumor immunity by suppressing PD-L1 expression. Therapeutic targeting of miR-155 through its antagonist, anti-miR-155, has proven challenging due to its dual molecular effects.

Translational modeling-based evidence for enhanced efficacy of standard-of-care drugs in combination with anti-microRNA-155 in non-small-cell lung cancer.

Elevated microRNA-155 (miR-155) expression in non-small-cell lung cancer (NSCLC) promotes cisplatin resistance and negatively impacts treatment outcomes. However, miR-155 can also boost anti-tumor immunity by suppressing PD-L1 expression. We developed a multiscale mechanistic model, calibrated with data and then extrapolated to humans, to investigate the therapeutic effects of nanoparticle-delivered anti-miR-155 in NSCLC, alone or in combination with standard-of-care drugs.

Impact of the COVID-19 pandemic on the rate of lower limb amputation in Veterans.

Background: The COVID-19 pandemic led to changes in health care, including postponement of nonurgent appointments. These changes, combined with overall decreased activity levels, may have placed individuals with vascular disease at increased risk for skin ulceration and amputation.

Objective: To determine the rates of lower limb amputation in Veterans due to complications of diabetes and/or vascular disease in the year following onset of the COVID-19 pandemic (March 2020-March 2021) compared to the previous 3 years (March 2017-March 2020).

Mechanistic modeling of anti-microRNA-155 therapy combinations in lung cancer.

To improve treatment outcomes in non-small cell lung cancer (NSCLC), it is crucial to identify treatment strategies with the potential to exhibit drug synergism. This can lower the required effective dose, reducing exposure to drugs and associated toxicities, while improving treatment efficacy. In previous studies, drugs targeting the microRNA-155 or PD-L1 have been promising in restraining NSCLC tumor growth.

Evaluating niraparib versus active symptom control in patients with previously treated mesothelioma (NERO): a study protocol for a multicentre, randomised, two-arm, open-label phase II trial in UK secondary care centres.

Background: Malignant mesothelioma is a rapidly lethal cancer that has been increasing at an epidemic rate over the last three decades. Targeted therapies for mesothelioma have been lacking. A previous study called MiST1 (NCT03654833), evaluated the efficacy of Poly (ADP-ribose) polymerase (PARP) inhibition in mesothelioma.

Organizational Supports for Nurse Managers in a North American Context: A Scoping Review.

Organizational support for nurse managers (NMs) is not a new phenomenon. However, generally speaking, NMs are not well supported in their roles. This lack of support is burdensome to NMs' role functioning and has impacts on NM recruitment and retention; NM job satisfaction; and outcomes for front-line nurses and patients.

Validation of Proprietary and Novel Step-counting Algorithms for Individuals Ambulating With a Lower Limb Prosthesis.

Objective: To compare the accuracy and reliability of 10 different accelerometer-based step-counting algorithms for individuals with lower limb loss, accounting for different clinical characteristics and real-world activities.

Design: Cross-sectional study.

Setting: General community setting (ie, institutional research laboratory and community free-living).

Immunotherapy-related adverse events in real-world patients with advanced non-small cell lung cancer on chemoimmunotherapy: a Spinnaker study sub-analysis.

Background: The Spinnaker study evaluated survival outcomes and prognostic factors in patients with advanced non-small-cell lung cancer receiving first-line chemoimmunotherapy in the real world. This sub-analysis assessed the immunotherapy-related adverse effects (irAEs) seen in this cohort, their impact on overall survival (OS) and progression-free survival (PFS), and related clinical factors.

Methods: The Spinnaker study was a retrospective multicentre observational cohort study of patients treated with first-line pembrolizumab plus platinum-based chemotherapy in six United Kingdom and one Swiss oncology centres.

NET-02: a randomised, non-comparative, phase II trial of nal-IRI/5-FU or docetaxel as second-line therapy in patients with progressive poorly differentiated extra-pulmonary neuroendocrine carcinoma.

Background: The prognosis for patients with poorly-differentiated extra-pulmonary neuroendocrine carcinoma (PD-EP-NEC) is poor. A recognised first-line (1L) treatment for advanced disease is etoposide/platinum-based chemotherapy with no standard second-line (2L) treatment.

Methods: Patients with histologically-confirmed PD-EP-NEC (Ki-67 > 20%; Grade 3) received IV liposomal irinotecan (nal-IRI) (70 mg/m free base)/5-FU (2400 mg/m)/folinic acid, Q14 days (ARM A), or IV docetaxel (75 mg/m), Q21 days (ARM B), as 2L therapy.

An Exploratory Study of Health-related Quality of Life and Care Experiences in Older Adults with Inflammatory Bowel Disease.

Canada has one of the highest rates of inflammatory bowel disease (IBD), with older adults as the fastest-growing group of individuals affected. This exploratory mixed methods study aimed to understand perceived health-related quality of life and care experiences in older adults with IBD. Participants greater than 60 years of age, who were diagnosed with IBD, and who lived in Saskatchewan, Canada were invited to participate in both an online survey and telephone interview.

The evolution of lung cancer and impact of subclonal selection in TRACERx.

Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome.

The evolution of non-small cell lung cancer metastases in TRACERx.

Metastatic disease is responsible for the majority of cancer-related deaths. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis.

The Effects of GCSF Primary Prophylaxis on Survival Outcomes and Toxicity in Patients with Advanced Non-Small Cell Lung Cancer on First-Line Chemoimmunotherapy: A Sub-Analysis of the Spinnaker Study.

GCSF prophylaxis is recommended in patients on chemotherapy with a >20% risk of febrile neutropenia and is to be considered if there is an intermediate risk of 10−20%. GCSF has been suggested as a possible adjunct to immunotherapy due to increased peripheral neutrophil recruitment and PD-L1 expression on neutrophils with GCSF use and greater tumour volume decrease with higher tumour GCSF expression. However, its potential to increase neutrophil counts and, thus, NLR values, could subsequently confer poorer prognoses on patients with advanced NSCLC.