MicroRNA-34a suppresses KLF2 to promote pathological angiogenesis through the CXCR4/CXCL12 pathway in age-related macular degeneration.

Unlabelled: Age-related macular degeneration (AMD), characterized by pathologic choroidal neovascularization (CNV), is a leading cause of vision loss in the elderly. Vascular endothelial growth factor A (VEGFa) antagonists can prevent acute vision loss, but high treatment burden and loss of efficacy with chronic therapy highlight the need to explore alternative mechanisms. Recently, microRNA-34a (miR-34a) has emerged as a key regulator in aging and age-related diseases, but its role in neovascular AMD is unclear.

Targeting the USP7-CDK1 axis suppresses estrogen receptor-positive breast cancer progression.

Estrogen receptor-positive breast cancer (ERPBC) accounts for approximately 70% of breast cancers in women worldwide. The therapeutic strategy process for ERPBC is well-established and significantly reduces the mortality rate. The discovery of new therapeutic targets remains essential for ERPBC patients with metastasis or endocrine resistance.

The Landscape of Vascular Endothelial Growth Factor Inhibition in Retinal Diseases.

Ever since the US Food and Drug Administration (FDA) approved the first vascular endothelial growth factor (VEGF) antagonist 2 decades ago, inhibitors of VEGF have revolutionized the treatment of a variety of ocular disorders involving pathologic neovascularization and retinal exudation. In this perspective, we evaluate the current status of anti-VEGF therapies and the real-world challenges encountered with maintaining therapeutic outcomes. Finally, we describe novel VEGF-based and combinatorial approaches that are in clinical development.

Cholesterol Accumulation Promotes Photoreceptor Senescence and Retinal Degeneration.

Purpose: Dysregulated cholesterol metabolism is critical in the pathogenesis of AMD. Cellular senescence contributes to the development of numerous age-associated diseases. In this study, we investigated the link between cholesterol burden and the cellular senescence of photoreceptors.

Evaluating the Margins of Breast Cancer Tumors by Using Digital Breast Tomosynthesis with Deep Learning: A Preliminary Assessment.

Background: The assessment information of tumor margins is extremely important for the success of the breast cancer surgery and whether the patient undergoes a second operation. However, conducting surgical margin assessments is a time-consuming task that requires pathology-related skills and equipment, and often cannot be provided in a timely manner. To address this challenge, digital breast tomosynthesis technology was utilized to generate detailed cross-sectional images of the breast tissue and integrate deep learning algorithms for image segmentation, achieving an assessment of tumor margins during surgery.

Identifying Novel Inhibitors of Workplace Support and the Importance of Value Congruence and Feeling Valued in General Surgery Residency Training.

Objective: To explore residents' perceptions of workplace support inhibitors and their relationship to resident wellbeing. We aim to provide evidence-based targets to inform future work operationalizing support in surgical training.

Design: This is a 2-part mixed-methods cross-sectional study.

Aqueous Macrophages Contribute to Conserved CCL2 and CXCL10 Gradients in Uveitis.

Purpose: Uveitis is a heterogenous group of inflammatory eye disease for which current cytokine-targeted immune therapies are effective for only a subset of patients. We hypothesized that despite pathophysiologic nuances that differentiate individual disease states, all forms of eye inflammation might share common mechanisms for immune cell recruitment. Identifying these mechanisms is critical for developing novel, broadly acting therapeutic strategies.

LXR/CD38 activation drives cholesterol-induced macrophage senescence and neurodegeneration via NAD depletion.

Although dysregulated cholesterol metabolism predisposes aging tissues to inflammation and a plethora of diseases, the underlying molecular mechanism remains poorly defined. Here, we show that metabolic and genotoxic stresses, convergently acting through liver X nuclear receptor, upregulate CD38 to promote lysosomal cholesterol efflux, leading to nicotinamide adenine dinucleotide (NAD) depletion in macrophages. Cholesterol-mediated NAD depletion induces macrophage senescence, promoting key features of age-related macular degeneration (AMD), including subretinal lipid deposition and neurodegeneration.

Cell-specific Systemic Immune Signatures Associated with Treatment Burden in Neovascular Age-related Macular Degeneration.

Purpose: Choroidal neovascularization (CNV) accounts for the majority of severe vision loss in neovascular age-related macular degeneration (AMD). Despite therapies that target VEGF, patients are often under-responsive, require frequent eye injections to control disease, and eventually lose some vision despite chronic therapy implicating a multifactorial etiology in treatment response. Genetic studies implicate systemic immunity in AMD and systemic immune cells accumulate within CNV lesions, yet a role for these cells in anti-VEGF response remains undetermined.

Investigating Workplace Support and the Importance of Psychological Safety in General Surgery Residency Training.

Objective: Workplace interventions that increase support can mitigate burnout, improve workplace satisfaction, and increase well-being. Our aim is to provide evidence-based targets to inform future work for operationalizing support in general surgery residency.

Design: This is a 2-part mixed-methods cross-sectional study.

"It Gives Me Peace of Mind So I Can Focus on Healing": Views on Advance Care Planning for Older Surgical Patients.

The period of time before an elective operation may be an opportune time to engage older adults in advance care planning (ACP). Past interventions have not been readily incorporated into surgical workflows leaving a need for ACP tools that are generalizable, easy to implement, and effective. This is a qualitative study.

Targeting cell-type-specific, choroid-peripheral immune signaling to treat age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness featuring pathogenic neovascularization of the choroidal vasculature (CNV). Although systemic immunity plays a role in AMD, the ocular signals that recruit and activate immune cells remain poorly defined. Using single-cell RNA sequencing, we prospectively profile peripheral blood mononuclear cells from 65 individuals including AMD and controls, which we integrate with existing choroid data.

Catalytic isoforms of AMP-activated protein kinase differentially regulate IMPDH activity and photoreceptor neuron function.

AMP-activated protein kinase (AMPK) plays a crucial role in maintaining ATP homeostasis in photoreceptor neurons. AMPK is a heterotrimeric protein consisting of α, β, and γ subunits. The independent functions of the 2 isoforms of the catalytic α subunit, PRKAA1 and PRKAA2, are uncharacterized in specialized neurons, such as photoreceptors.

Dysregulated CD200-CD200R signaling in early diabetes modulates microglia-mediated retinopathy.

Diabetic retinopathy (DR) is a neurovascular complication of diabetes. Recent investigations have suggested that early degeneration of the neuroretina may occur prior to the appearance of microvascular changes; however, the mechanisms underlying this neurodegeneration have been elusive. Microglia are the predominant resident immune cell in the retina and adopt dynamic roles in disease.

Loss of stearoyl-CoA desaturase 2 disrupts inflammatory response in macrophages.

Macrophages are innate immune cells that patrol tissues and are the first responders to detect infection. They orchestrate the host immune response in eliminating invading pathogens and the subsequent transition from inflammation to tissue repair. Macrophage dysfunction contributes to age-related pathologies, including low-grade inflammation in advanced age that is termed "inflammaging.

Time is Short: Tools to Integrate Palliative Care and Communication Skills Education into Your Surgical Residency.

The need to integrate palliative care (PC) training into surgical education has been increasingly recognized. Our aim is to describe a set of PC educational strategies, with a range of requisite resources, time, and prior expertise, to provide options that surgical educators can tailor for different programs. Each of these strategies has been successfully employed individually or in some combination at our institutions, and components can be generalized to other training programs.

Histamine-releasing factor in severe asthma and rhinovirus-associated asthma exacerbation.

Background: Histamine-releasing factor (HRF) is implicated in allergic diseases. We previously showed its pathogenic role in murine models of asthma.

Objective: We aim to present data analysis from 3 separate human samples (sera samples from asthmatic patients, nasal washings from rhinovirus [RV]-infected individuals, and sera samples from patients with RV-induced asthma exacerbation) and 1 mouse sample to investigate correlates of HRF function in asthma and virus-induced asthma exacerbations.

Disparities in advance care planning rates persist among emergency general surgery patients: Current state and recommendations for improvement.

Background: Unanticipated changes in health status and worsening of chronic conditions often prompt the need to consider emergency general surgery (EGS). Although discussions about goals of care may promote goal-concordant care and reduce patient and caregiver depression and anxiety, these conversations, as well as standardized documentation, remain infrequent for EGS patients.

Methods: We conducted a retrospective cohort study using electronic health record data from patients admitted to an EGS service at a tertiary academic center to determine the prevalence of clinically meaningful advance care planning (ACP) documentation (conversations and legal ACP forms) during the EGS hospitalization.

Experiences with targeting inpatient advance care planning for emergency general surgery patients: A resident-led quality improvement project.

Background: For patients who may permanently or temporarily lose their ability to communicate preferences, advance care planning is a critical mechanism to guide medical decision-making but is currently underused among surgical patients.

Methods: A resident-led quality improvement project, including education and performance measurement, was conducted on an emergency general surgery service to increase the completion of inpatient advance care planning notes using a specialized template in the electronic health record. Advance care planning documentation was defined as either preadmission advance care planning documentation (eg, advance directive) or inpatient advance care planning (use of the electronic health record template).

Saline irrigation versus gauze wiping and suction only for peritoneal decontamination during laparoscopic repair for perforated peptic ulcer disease.

The aim of current single-center study was to compare the short-term outcome of suction and gauze wiping alone versus the irrigation and suction technique for peritoneal decontamination among patients who underwent laparoscopic repair of PPU. Using data from our institution's prospectively maintained database, 105 patients who underwent laparoscopic repair were enrolled in this study. The participants were further divided into the group who received peritoneal irrigation (irrigation group, n = 67) and group who received gauze wiping and suction only (suction only group, n = 38).

Dry eye disease in mice activates adaptive corneal epithelial regeneration distinct from constitutive renewal in homeostasis.

Many epithelial compartments undergo constitutive renewal in homeostasis but activate unique regenerative responses following injury. The clear corneal epithelium is crucial for vision and is renewed from limbal stem cells (LSCs). Using single-cell RNA sequencing, we profiled the mouse corneal epithelium in homeostasis, aging, diabetes, and dry eye disease (DED), where tear deficiency predisposes the cornea to recurrent injury.