The use of investigator-assigned subjective or judgmental efficacy and toxicity reporting in early phase clinical trials of lung cancer treatments.

Introduction: Investigator-assigned Subjective or Judgmental Efficacy and Toxicity (ISJET) reporting represents language used to contextualize efficacy or toxicity data in clinical trials that may be inappropriate or misleading. In addition, pooling of grade 1 and 2 adverse events (AEs) may reflect a practice based on acute chemotherapy treatments rather than the expansion of chronic treatments that are now commonplace for many lung cancer patients. In this study, we set out to evaluate the use of ISJETs and combined grade 1 and 2 reporting in early phase clinical trials of lung treatments at the 2024 ASCO Annual Meeting.

Nasal lymphatic obstruction of CSF drainage as a possible cause of Alzheimer's disease and dementia.

Alzheimer's disease, the most common form of dementia among older adults, slowly destroys memory and thinking skills. In recent years, scientists have made tremendous progress in understanding Alzheimer's disease, still, they do not yet fully understand what causes the disease. This article proposes a novel etiology for Alzheimer's disease.

Cellular psychology: relating cognition to context-sensitive pyramidal cells.

'Cellular psychology' is a new field of inquiry that studies dendritic mechanisms for adapting mental events to the current context, thus increasing their coherence, flexibility, effectiveness, and comprehensibility. Apical dendrites of neocortical pyramidal cells have a crucial role in cognition - those dendrites receive input from diverse sources, including feedback, and can amplify the cell's feedforward transmission if relevant in that context. Specialized subsets of inhibitory interneurons regulate this cooperative context-sensitive processing by increasing or decreasing amplification.

A Retrospective Analysis of the Diagnosis of Gastroenteropancreatic Neuroendocrine Tumors at The Ottawa Hospital Cancer Center over the Last Decade Including COVID-19 Pandemic Period.

Introduction: The incidence of neuroendocrine tumors (NETs) is rising. Our objective was to assess trends in gastroenteropancreatic (GEP)-NETs diagnosis (June 2010 to June 2021) at TOHCC and to explore whether early COVID-19 pandemic data impacted these trends.

Methods: This was a single-center retrospective chart review of data collected from June 2010 to June 2021.

Utilization and engagement with an employer-provided digital mental health platform: An international perspective.

Objective: This retrospective study (2020-2022) compared the usage patterns across international regions of an employer-provided digital mental health platform, which is available in native languages and offers both self-guided digital activities and one-on-one sessions.

Methods: Routine data from the platform were analyzed by describing the demographic profile of 178,119 users from different geographical regions, their baseline mental health status and burnout levels, as well as patterns of engagement. Statistical analyses were conducted using logistic and ordered logit models to examine the association between cumulative engagement with the platform over time and baseline characteristics.

Nasal turbinate lymphatic obstruction: a proposed new paradigm in the etiology of essential hypertension.

Hypertension affects an estimated 1.3 billion people worldwide and is considered the number one contributor to mortality via stroke, heart failure, renal failure, and dementia. Although the physiologic mechanisms leading to the development of essential hypertension are poorly understood, the regulation of cerebral perfusion has been proposed as a primary cause.

The Consensus Reporting Items for Studies in Primary Care (CRISP) checklist - the first research reporting guideline made by and for primary care.

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Surgical management of native aortic valve leaflet avulsion during TAVR.

Background: Transcatheter aortic valve replacement (TAVR) has increased in utilization since its approval for management of aortic stenosis patients across all risk strata. We report a rare case of aortic valve leaflet avulsion after balloon expandable TAVR managed with urgent surgery.

Case Presentation: A 78-year-old male underwent TAVR complicated by avulsion of the native aortic valve leaflet's left coronary cusp.

HYENA detects oncogenes activated by distal enhancers in cancer.

Somatic structural variations (SVs) in cancer can shuffle DNA content in the genome, relocate regulatory elements, and alter genome organization. Enhancer hijacking occurs when SVs relocate distal enhancers to activate proto-oncogenes. However, most enhancer hijacking studies have only focused on protein-coding genes.

Image-guided patient-specific optimization of catheter placement for convection-enhanced nanoparticle delivery in recurrent glioblastoma.

Background: Proper catheter placement for convection-enhanced delivery (CED) is required to maximize tumor coverage and minimize exposure to healthy tissue. We developed an image-based model to patient-specifically optimize the catheter placement for rhenium-186 (Re)-nanoliposomes (RNL) delivery to treat recurrent glioblastoma (rGBM).

Methods: The model consists of the 1) fluid fields generated via catheter infusion, 2) dynamic transport of RNL, and 3) transforming RNL concentration to the SPECT signal.

Scalable purification of extracellular vesicles with high yield and purity using multimodal flowthrough chromatography.

Extracellular vesicles (EVs) are cell derived membranous nanoparticles. EVs are important mediators of cell-cell communication via the transfer of bioactive content and as such they are being investigated for disease diagnostics as biomarkers and for potential therapeutic cargo delivery to recipient cells. However, existing methods for isolating EVs from biological samples suffer from challenges related to co-isolation of unwanted materials such as proteins, nucleic acids, and lipoproteins.

Musculoskeletal Issues in Pediatric Burn Patients.

A burn injury affects virtually every organ system. The purpose of this article is to review musculoskeletal issues in children with burn injuries. Both acute and long-term problems will be discussed.

Dysfunctions of cellular context-sensitivity in neurodevelopmental learning disabilities.

Pyramidal neurons have a pivotal role in the cognitive capabilities of neocortex. Though they have been predominantly modeled as integrate-and-fire point processors, many of them have another point of input integration in their apical dendrites that is central to mechanisms endowing them with the sensitivity to context that underlies basic cognitive capabilities. Here we review evidence implicating impairments of those mechanisms in three major neurodevelopmental disabilities, fragile X, Down syndrome, and fetal alcohol spectrum disorders.

Cellular mechanisms of cooperative context-sensitive predictive inference.

We argue that prediction success maximization is a basic objective of cognition and cortex, that it is compatible with but distinct from prediction error minimization, that neither objective requires subtractive coding, that there is clear neurobiological evidence for the amplification of predicted signals, and that we are unconvinced by evidence proposed in support of subtractive coding. We outline recent discoveries showing that pyramidal cells on which our cognitive capabilities depend usually transmit information about input to their basal dendrites and amplify that transmission when input to their distal apical dendrites provides a context that agrees with the feedforward basal input in that both are depolarizing, i.e.

Storylines of family medicine V: ways of thinking-honing the therapeutic self.

is a 12-part series of thematically linked essays with accompanying illustrations that explore the many dimensions of family medicine, as interpreted by individual family physicians and medical educators in the USA and elsewhere around the world. In 'V: ways of thinking-honing the therapeutic self', authors present the following sections: 'Reflective practice in action', 'The doctor as drug-Balint groups', 'Cultivating compassion', 'Towards a humanistic approach to doctoring', 'Intimacy in family medicine', 'The many faces of suffering', 'Transcending suffering' and 'The power of listening to stories.' May readers feel a deeper sense of their own therapeutic agency by reflecting on these essays.

Real-World Evaluation of Primary Versus Secondary Prevention of Skeletal-Related Events in Metastatic Castration-Resistant Prostate Cancer.

Introduction: Anti-osteoclast treatment with denosumab or zoledronate is known to effectively reduce the need for radiotherapy to bone and other skeletal-related events (SREs) in patients with metastatic castration-resistant prostate cancer (mCRPC). In this study, we analyze primary versus secondary initiation of bone-targeting agents (BTAs) relative to first palliative bone radiotherapy in patients dying of mCRPC.

Methods: Provincial administrative databases from Ontario, Canada identified patients with prostate cancer (2007-2018, n = 98 646) who received continuous androgen deprivation therapy (n = 29 453), died of prostate cancer (2013-2018, n = 3864), and received life-prolonging therapy for mCRPC (n = 1850).

Variation in Access to Palliative Radiotherapy in Prostate Cancer: A Population-Based Study in Canada.

Background: As a result of improvements in cancer therapies, patients with metastatic malignancies are living longer, and the role of palliative radiotherapy has become increasingly recognized. However, access to adequate palliative radiotherapy may continue to be a challenge, as is evident from the high proportion of patients dying of prostate cancer who never receive palliative radiotherapy. The main objective of this investigation is to identify and describe the factors associated with the receipt of palliative radiation treatment in a decedent cohort of prostate cancer patients in Ontario.

Development of a mentor training curriculum to support LGBTQIA+ health professionals.

While mentors can learn general strategies for effective mentoring, existing mentorship curricula do not comprehensively address how to support marginalized mentees, including LGBTQIA+ mentees. After identifying best mentoring practices and existing evidence-based curricula, we adapted these to create the Harvard Sexual and Gender Minority Health Mentoring Program. The primary goal was to address the needs of underrepresented health professionals in two overlapping groups: (1) LGBTQIA+ mentees and (2) any mentees focused on LGBTQIA+ health.

Wellbeing Impact Study of High-Speed 2 (WISH2): Protocol for a mixed-methods examination of the impact of major transport infrastructure development on mental health and wellbeing.

Although research has demonstrated that transport infrastructure development can have positive and negative health-related impacts, most of this research has not considered mental health and wellbeing separately from physical health. There is also limited understanding of whether and how any effects might be experienced differently across population groups, whether this differs according to the stage of development (e.g.