Study protocol: multi-centre, randomised controlled clinical trial exploring stromal targeting in locally advanced pancreatic cancer; STARPAC2.

Background: Pancreatic cancer (PDAC: pancreatic ductal adenocarcinoma, the commonest form), a lethal disease, is best treated with surgical excision but is feasible in less than a fifth of patients. Around a third of patients presentlocally advanced, inoperable, non-metastatic (laPDAC), whose stadrd of care is palliative chemotherapy; a small minority are down-sized sufficiently to enable surgical excision. We propose a phase II clinical trial to test whether a combination of standard chemotherapy (gemcitabine & nab-Paclitaxel: GEM-NABP) and repurposing All Trans Retinoic Acid (ATRA) to target the stroma may extend progression-free survival and enable successful surgical resection for patients with laPDAC, since data from phase IB clinical trial demonstrate safety of GEM-NABP-ATRA combination to patients with advanced PDAC with potential therapeutic benefit.

The impact of gender-affirming interventions on eating disorder diagnosis risk among transgender and gender-diverse individuals.

Background: The objective of this study is to evaluate the risk of being diagnosed with an eating disorder among transgender and gender-diverse (TGD) individuals, specifically examining how this risk differs following gender-affirming medical therapy (GAMT).

Methods: The study utilizes electronic medical record (EMR) data from the TriNetX database. A total of 90,955 TGD individuals were identified in the TriNetX database.

Efficacy of traditional and gamified attention bias modification for depression: Study protocol for a randomized controlled trial.

Cognitive models posit that negatively biased attention toward dysphoric information has a causal role in the maintenance of depression-related psychopathology. Attention bias modification (ABM) tests this idea by altering an attentional bias and examining subsequent effects on depression. Prior work finds that ABM alters negatively biased attention for dysphoric information and reduces depression; however, a number of studies have failed to show these effects.

Adjuvant Therapy after Esophagectomy for Esophageal Cancer: Who Needs It?: Multi-institution Worldwide Observational Study.

Objective: Based on current practice guidelines, we hypothesized that most patients with esophageal cancer, particularly those with locally advanced cancer, would benefit from adjuvant therapy after esophagectomy esophagectomy alone. We sought to obtain a granular estimate of patient-level risk-adjusted survival for each therapeutic option by cancer histopathology and stage.

Background: Although esophagectomy alone is now an uncommon therapy for treating locally advanced esophageal cancer, the value of adjuvant therapy after esophagectomy is unknown.

Stef M. Shuster and Meredithe McNamara reply.

This letter responds to a letter by Moti Gorin in the same issue, September-October 2024, of the Hastings Center Report.

Impact of mild hypercapnia in critically ill patients with metabolic acidosis.

Purpose: Clinical trials focusing on critically ill patients with metabolic acidosis, a common exclusion criterion is the presence of a PaCO > 45 mmHg. The aim of this study was to assess the impact of mild hypercapnia on patient characteristics, severity, and clinical outcomes in critically ill patients with metabolic acidosis.

Material And Methods: Multicentre, retrospective, observational study conducted in 12 intensive care units (ICUs) in Queensland, Australia.

Antibody-Drug Conjugates and Their Potential in the Treatment of Patients with Biliary Tract Cancer.

Biliary tract cancers (BTCs) are aggressive in nature, often presenting asymptomatically until they are diagnosed at an advanced stage. Surgical resection or liver transplantation are potential curative options. However, a large proportion of patients present with incurable locally advanced or metastatic disease and most of these patients are only eligible for palliative chemotherapy or best supportive care.

Understanding and Addressing Disinformation in Gender-Affirming Health Care Bans.

Legislation undermining the human rights of transgender and gender-expansive (TGE) people is on the rise. Many U.S.

The burden of chronic pain in transgender and gender diverse populations: Evidence from a large US clinical database.

Background: Chronic pain, affecting approximately 20% of the global population, is the leading cause of disability worldwide. Transgender individuals are disproportionately exposed to chronic pain risk factors compared with the cisgender population. This study compares the incidence of chronic pain between transgender and cisgender individuals and examines the impact of gender affirming hormone therapy, anxiety, and depression on chronic pain.

Negative self-referent cognition predicts future depression symptom change: an intensive sampling approach.

Cognitive theories of depression assert that negative self-referent cognition has a causal role in the development and maintenance of depression symptoms, but few studies have examined temporal associations between these constructs using intensive, longitudinal sampling strategies. In three samples of undergraduate students, we examined associations between change in self-referent processing and depression across 5 daily assessments (Sample 1, = 303, 1,194 measurements, 79% adherence), 7 daily assessments (Sample 2, = 313, 1,784 measurements, 81% adherence), and 7 weekly assessments (Sample 3; = 155, 833 measurements, 81% adherence). Random intercept cross-lagged panel models indicated large cross-lagged effects in two of the three samples (Samples 1 and 3 but not Sample 2), such that more negative self-referent thinking than usual was significantly associated with a subsequent increase in depression symptoms at the next time lag.

Assessment of clinical depression metrics in cardiac patients using the patient health Questionnaire-9 before and after phase-II cardiac rehabilitation.

Cardiovascular disease remains a leading cause of morbidity and mortality, a fact that is commonly associated with co-morbidities such as clinical depression. While phase II cardiac rehabilitation is an established intervention for those with cardiovascular disease, its effect on patients who also suffer from depression are under studied. Aim: To quantify Pre- and Post-cardiac rehabilitation questionnaire scores collected from a large patient data registry.

A new non-destructive method to decipher the origin of organic matter in fossils using Raman spectroscopy.

Ancient biomolecules provide a unique perspective on the past but are underutilized in paleontology because of challenges in interpreting the chemistry of fossils. Most organically preserved soft tissues in fossils have been altered by thermal maturation during the fossilization process, obscuring original chemistry. Here, we use a comprehensive program of thermal maturation experiments on soft tissues from diverse extant organisms to systematically test whether thermally altered biosignatures can be discriminated using Raman spectroscopy.

A distinctive profession? Building professional identity and knowledge for intellectual disability nursing education.

Intellectual disability nursing students can struggle to build a professional identity and make sense of their extensive curriculum and its application to practice. In this article Legitimation Code Theory (LCT) and Critical Discourse Analysis (CDA) are used to facilitate an examination of the organising principles underlying intellectual disability nursing and the relationships agents construct between intellectual disability and other nursing divisions. In particular this paper explores the relationship with general nursing, and examines the connections and boundaries that intellectual disability nursing builds with general nursing, and their implications.

Causes of death and patterns of metastatic disease at the end of life for patients with advanced melanoma in the immunotherapy era.

Despite remarkable advances in immunotherapy, melanoma remains a significant cause of cancer mortality. Many factors concerning melanoma mortality are poorly understood, posing an obstacle to optimal care. We conducted a retrospective observational cohort study of 183 patients with metastatic melanoma who died following immunotherapy treatment to investigate sites of metastases at death, settings of death, and mechanisms of death.

A Realist Review Protocol into the Contexts and Mechanisms That Enable the Inclusion of Environmental Sustainability Outcomes in the Design of Lean Healthcare Improvement Interventions.

Healthcare makes a significant contribution to the social, economic and environmental benefits of communities. It is correspondingly a significant employer and consumer of both energy and consumables, often at high costs. Lean, a quality improvement methodology focuses on the elimination of non-value add (NVA) activities (steps that do not add value from the perspective of the customer) to improve the flow of people, information or goods.

Mental Health, Climate Change, and Bodily Autonomy: An Analysis of Adolescent Health Policy in the Post-Pandemic Climate.

The COVID-19 pandemic exacerbated the vulnerability of adolescents and young adults (AYAs) who face economic disadvantage, depend on social safety net resources, have politically targeted identities, are geopolitically displaced, and/or are racially or ethnically marginalized. A rapid change in social safety net policies has impacts that reverberate throughout interrelated domains of AYA health, especially for vulnerable AYAs. The authors analyze policy-related changes in mental health, climate change, and bodily autonomy to offer a paradigm for an equitable path forward.

The Role of Aging and Senescence in Immune Checkpoint Inhibitor Response and Toxicity.

Cellular senescence accumulates with age and has been shown to impact numerous physiological and pathological processes, including immune function. The role of cellular senescence in cancer is multifaceted, but the impact on immune checkpoint inhibitor response and toxicity has not been fully evaluated. In this review, we evaluate the impact of cellular senescence in various biological compartments, including the tumor, the tumor microenvironment, and the immune system, on immune checkpoint inhibitor efficacy and toxicity.

Long-term NMN treatment increases lifespan and healthspan in mice in a sex dependent manner.

Nicotinamide adenine dinucleotide (NAD) is essential for many enzymatic reactions, including those involved in energy metabolism, DNA repair and the activity of sirtuins, a family of defensive deacylases. During aging, levels of NAD can decrease by up to 50% in some tissues, the repletion of which provides a range of health benefits in both mice and humans. Whether or not the NAD precursor nicotinamide mononucleotide (NMN) extends lifespan in mammals is not known.