Treatment of type 2 diabetes with the designer cytokine IC7Fc.

The gp130 receptor cytokines IL-6 and CNTF improve metabolic homeostasis but have limited therapeutic use for the treatment of type 2 diabetes. Accordingly, we engineered the gp130 ligand IC7Fc, in which one gp130-binding site is removed from IL-6 and replaced with the LIF-receptor-binding site from CNTF, fused with the Fc domain of immunoglobulin G, creating a cytokine with CNTF-like, but IL-6-receptor-dependent, signalling. Here we show that IC7Fc improves glucose tolerance and hyperglycaemia and prevents weight gain and liver steatosis in mice. In addition, IC7Fc either increases, or prevents the loss of, skeletal muscle mass by activation of the transcriptional regulator YAP1. In human-cell-based assays, and in non-human primates, IC7Fc treatment results in no signs of inflammation or immunogenicity. Thus, IC7Fc is a realistic next-generation biological agent for the treatment of type 2 diabetes and muscle atrophy, disorders that are currently pandemic.

Definitions of massive transfusion in adults with critical bleeding: a systematic review.

BACKGROUND: Definitions for massive transfusion (MT) vary widely between studies, contributing to challenges in interpretation of research findings and practice evaluation. In this first systematic review, we aimed to identify all MT definitions used in randomised controlled trials (RCTs) to date to inform the development of consensus definitions for MT. METHODS: We systematically searched the following databases for RCTs from inception until 11 August 2022: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Cumulative Index to Nursing and Allied Health Literature, and Transfusion Evidence Library. Ongoing trials were sought from CENTRAL, ClinicalTrials.gov, and World Health Organisation International Clinical Trials Registry Platform. To be eligible for inclusion, studies had to fulfil all the following three criteria: (1) be an RCT; (2) include an adult patient population with major bleeding who had received, or were anticipated to receive, an MT in any clinical setting; and (3) specify a definition for MT as an inclusion criterion or outcome measure. RESULTS: Of the 8,458 distinct references identified, 30 trials were included for analysis (19 published, 11 ongoing). Trauma was the most common clinical setting in published trials, while for ongoing trials, it was obstetrics. A total of 15 different definitions of MT were identified across published and ongoing trials, varying greatly in cut-offs for volume transfused and time period. Almost all definitions specified the number of red blood cells (RBCs) within a set time period, with none including plasma, platelets or other haemostatic agents that are part of contemporary transfusion resuscitation. For completed trials, the most commonly used definition was transfusion of ≥ 10 RBC units in 24 h (9/19, all in trauma), while for ongoing trials it was 3-5 RBC units (n = 7), with the timing for transfusion being poorly defined, or in some trials not provided at all (n = 5). CONCLUSIONS: Transfusion of ≥ 10 RBC units within 24 h was the most commonly used definition in published RCTs, while lower RBC volumes are being used in ongoing RCTs. Any consensus definitions should reflect the need to incorporate different blood components/products for MT and agree on whether a 'one-size-fits-all' approach should be used across different clinical settings.

Survival in Huntington's disease and other young-onset dementias.

OBJECTIVES: To compare survival and risk factors associated with mortality in common young-onset dementias (YOD) including Huntington's disease. METHODS: This retrospective cohort study included inpatients from an Australian specialist neuropsychiatry service, over 20 years. Dementia diagnoses were based on consensus criteria and Huntington's disease (HD) was confirmed genetically. Mortality and cause of death were determined using linkage to the Australian Institute of Health and Welfare National Death Index. RESULTS: There were 386 individuals with YOD included. The dementia types included frontotemporal dementia (FTD) (24.5%), HD (21.2%) and Alzheimer's disease (AD) (20.5%). 63% (n = 243) individuals had died. The longest median survival was for those who had HD, 18.8 years from symptom onset and with a reduced mortality risk compared to AD and FTD (hazard ratio 0.5). Overall, people with YOD had significantly increased mortality, of 5-8 times, compared to the general population. Females with a YOD had higher standardised mortality ratio compared to males (9.3 vs. 4.9) overall. The most frequent cause of death in those with HD was reported as HD, with other causes of death in the other YOD-subtypes related to dementia and mental/behavioural disorders. DISCUSSION: This is the first Australian study to investigate survival and risk factors of mortality in people with YOD. YOD has a significant risk of death compared to the general population. Our findings provide useful clinical information for people affected by YOD as well as future planning and service provision.

Baseline Characteristics and Clinical Presentation of Biopsy-Proven Giant Cell Arteritis in White Compared with Black Patients.

BACKGROUND: Giant cell arteritis (GCA) is the most prevalent systemic vasculitis in the elderly and can lead to permanent vision loss if left untreated. Most earlier studies have evaluated GCA in primarily white populations, and GCA was traditionally thought to occur at nearly negligible frequency in black populations. Our previous study showed that GCA may occur at similar rates in white and black patients, but little is known about the presentation of GCA in black patients. The purpose of this study is to examine baseline presentation of biopsy-proven GCA (BP-GCA) in a tertiary care center-based population with a sizeable proportion of black patients. METHODS: Retrospective study from a single academic institution of a previously described cohort of BP-GCA. Presenting symptoms, laboratory findings, and GCA Calculator Risk score were compared in black and white patients with BP-GCA. RESULTS: Among 85 patients with biopsy-proven GCA, 71 (84%) were white and 12 (14%) were black. White patients had higher rates of elevated platelet count (34% vs 0%, P = 0.04), whereas black patients had higher rates of diabetes mellitus (67% vs 12%, P < 0.001). There were no statistically significant differences in age, gender, biopsy classification (active vs healed arteritis), cranial symptoms, visual symptoms/ophthalmic findings, rates of abnormal erythrocyte sedimentation rate or C-reactive protein, unintentional weight loss, polymyalgia rheumatica, or GCA risk calculator score. CONCLUSIONS: Presenting features of GCA were similar between white and black patients in our cohort, except for rates of abnormal platelet level and diabetes. Physicians should feel comfortable relying on the usual clinical features for the diagnosis of GCA independent of race.

Presenting Features of Giant Cell Arteritis with Active Versus Healed Arteritis on Biopsy.

Giant cell arteritis (GCA) is often categorised as "active" or "healed" on temporal artery biopsy (TAB). The purpose of this study was to compare the initial clinical presentation of patients with GCA according to active versus healed arteritis on TAB. A retrospective chart review was performed for patients with biopsy-proven GCA (BP-GCA) at a single academic medical institution from a previously reported cohort. The arteritis on TAB was categorised as "active" or "healed" based on the pathological reports. Demographic information, clinical presentation, past medical history, and test results were collected from the date of TAB. These baseline characteristics were entered into the GCA Risk Calculator. Of 85 patients with BP-GCA, 80% had active and 20% had healed disease according to histopathology. A higher percentage of those with active arteritis had ischaemic optic neuropathy (ION) (36% versus 6%, p = .03), elevated erythrocyte sedimentation rates (92% versus 63%, p = .01), elevated C-reactive protein levels (79% versus 46%, p = .049), GCA risk score > 7.5% (99% sensitivity, 100% versus 71%, p < .001), higher mean GCA risk calculator scores (neural network p = .001; logistic regression p = .002). Patients with healed arteritis were less likely to have visual manifestations than the active arteritis group (38% versus 71%, p = .04). Patients with active vasculitis on biopsy had higher rates of ION and elevated inflammatory markers, as well as higher predictive scores from the GCA risk calculator. Further research is needed regarding correlation of biopsy findings and risk of complications or relapses.

A Gut-Intrinsic Melanocortin Signaling Complex Augments L-Cell Secretion in Humans.

OBJECTIVE: Hypothalamic melanocortin 4 receptors (MC4R) are a key regulator of energy homeostasis. Brain-penetrant MC4R agonists have failed, as concentrations required to suppress food intake also increase blood pressure. However, peripherally located MC4R may also mediate metabolic benefits of MC4R activation. Mc4r transcript is enriched in mouse enteroendocrine L cells and peripheral administration of the endogenous MC4R agonist, α-melanocyte stimulating hormone (α-MSH), triggers the release of the anorectic hormones Glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) in mice. This study aimed to determine whether pathways linking MC4R and L-cell secretion exist in humans. DESIGN: GLP-1 and PYY levels were assessed in body mass index-matched individuals with or without loss-of-function MC4R mutations following an oral glucose tolerance test. Immunohistochemistry was performed on human intestinal sections to characterize the mucosal MC4R system. Static incubations with MC4R agonists were carried out on human intestinal epithelia, GLP-1 and PYY contents of secretion supernatants were assayed. RESULTS: Fasting PYY levels and oral glucose-induced GLP-1 secretion were reduced in humans carrying a total loss-of-function MC4R mutation. MC4R was localized to L cells and regulates GLP-1 and PYY secretion from ex vivo human intestine. α-MSH immunoreactivity in the human intestinal epithelia was predominantly localized to L cells. Glucose-sensitive mucosal pro-opiomelanocortin cells provide a local source of α-MSH that is essential for glucose-induced GLP-1 secretion in small intestine. CONCLUSION: Our findings describe a previously unidentified signaling nexus in the human gastrointestinal tract involving α-MSH release and MC4R activation on L cells in an autocrine and paracrine fashion. Outcomes from this study have direct implications for targeting mucosal MC4R to treat human metabolic disorders.

The gut microbiome regulates host glucose homeostasis via peripheral serotonin.

The gut microbiome is an established regulator of aspects of host metabolism, such as glucose handling. Despite the known impacts of the gut microbiota on host glucose homeostasis, the underlying mechanisms are unknown. The gut microbiome is also a potent mediator of gut-derived serotonin synthesis, and this peripheral source of serotonin is itself a regulator of glucose homeostasis. Here, we determined whether the gut microbiome influences glucose homeostasis through effects on gut-derived serotonin. Using both pharmacological inhibition and genetic deletion of gut-derived serotonin synthesis, we find that the improvements in host glucose handling caused by antibiotic-induced changes in microbiota composition are dependent on the synthesis of peripheral serotonin.

The Pivotal Role of NF-kB in the Pathogenesis and Therapeutics of Alzheimer's Disease.

Alzheimer's Disease (AD) is the most common neurodegenerative disease worldwide, with a high prevalence that is expected to double every 20 years. Besides the formation of Aß plaques and neurofibrillary tangles, neuroinflammation is one the major phenotypes that worsens AD progression. Indeed, the nuclear factor-κB (NF-κB) is a well-established inflammatory transcription factor that fuels neurodegeneration. Thus, in this review, we provide an overview of the NF-κB role in the pathogenesis of AD, including its interaction with various molecular factors in AD mice models, neurons, and glial cells. Some of these cell types and molecules include reactive microglia and astrocytes, ß-secretase, APOE, glutamate, miRNA, and tau protein, among others. Due to the multifactorial nature of AD development and the failure of many drugs designed to dampen AD progression, the pursuit of novel targets for AD therapeutics, including the NF-κB signaling pathway, is rising. Herein, we provide a synopsis of the drug development landscape for AD treatment, offering the perspective that NF-κB inhibitors may generate widespread interest in AD research in the future. Ultimately, the additional investigation of compounds and small molecules that target NF-κB signaling and the complete understanding of NF-κB mechanistic activation in different cell types will broaden and provide more therapeutic options for AD patients.

Shifting attention to an undervalued asset; the emergency department technician.

US emergency departments are facing a number of operational challenges related to chronic shortages of registered nurses. Many of the tasks done by registered nurses can be safely and successfully delegated to the emergency department technician (EDT), particularly if a hospital's nursing and administrative leadership are affirmatively engaged in a process to professionalize and train their EDT workforce. This paper examines the state, Joint Commission on Accreditation of Healthcare Organizations, and Centers for Medicare & Medicaid Services regulatory landscape for the EDT, reviews the literature on how hospital's utilize EDT's, discusses approaches to skills training, and examines the need for profession standardization that enables job role expansion.

Augmented capacity for peripheral serotonin release in human obesity.

BACKGROUND/OBJECTIVES: Evidence from animal studies highlights an important role for serotonin (5-HT), derived from gut enterochromaffin (EC) cells, in regulating hepatic glucose production, lipolysis and thermogenesis, and promoting obesity and dysglycemia. Evidence in humans is limited, although elevated plasma 5-HT concentrations are linked to obesity. SUBJECTS/METHODS: We assessed (i) plasma 5-HT concentrations before and during intraduodenal glucose infusion (4 kcal/min for 30 min) in non-diabetic obese (BMI 44 ± 4 kg/m2, N = 14) and control (BMI 24 ± 1 kg/m2, N = 10) subjects, (ii) functional activation of duodenal EC cells (immunodetection of phospho-extracellular related-kinase, pERK) in response to glucose, and in separate subjects, (iii) expression of tryptophan hydroxylase-1 (TPH1) in duodenum and colon (N = 39), and (iv) 5-HT content in primary EC cells from these regions (N = 85). RESULTS: Plasma 5-HT was twofold higher in obese than control responders prior to (P = 0.025), and during (iAUC, P = 0.009), intraduodenal glucose infusion, and related positively to BMI (R2 = 0.334, P = 0.003) and HbA1c (R2 = 0.508, P = 0.009). The density of EC cells in the duodenum was twofold higher at baseline in obese subjects than controls (P = 0.023), with twofold more EC cells activated by glucose infusion in the obese (EC cells co-expressing 5-HT and pERK, P = 0.001), while the 5-HT content of EC cells in duodenum and colon was similar; TPH1 expression was 1.4-fold higher in the duodenum of obese subjects (P = 0.044), and related positively to BMI (R2 = 0.310, P = 0.031). CONCLUSIONS: Human obesity is characterized by an increased capacity to produce and release 5-HT from the proximal small intestine, which is strongly linked to higher body mass, and glycemic control. Gut-derived 5-HT is likely to be an important driver of pathogenesis in human obesity and dysglycemia.

Nuclear receptor TLX stimulates hippocampal neurogenesis and enhances learning and memory in a transgenic mouse model.

The role of the nuclear receptor TLX in hippocampal neurogenesis and cognition has just begun to be explored. In this study, we generated a transgenic mouse model that expresses TLX under the control of the promoter of nestin, a neural precursor marker. Transgenic TLX expression led to mice with enlarged brains with an elongated hippocampal dentate gyrus and increased numbers of newborn neurons. Specific expression of TLX in adult hippocampal dentate gyrus via lentiviral transduction increased the numbers of BrdU(+) cells and BrdU(+)NeuN(+) neurons. Furthermore, the neural precursor-specific expression of the TLX transgene substantially rescued the neurogenic defects of TLX-null mice. Consistent with increased neurogenesis in the hippocampus, the TLX transgenic mice exhibited enhanced cognition with increased learning and memory. These results suggest a strong association between hippocampal neurogenesis and cognition, as well as significant contributions of TLX to hippocampal neurogenesis, learning, and memory.

Using Twitter to Understand Public Perceptions Regarding the #HPV Vaccine: Opportunities for Public Health Nurses to Engage in Social Marketing.

OBJECTIVES: Given the degree of public mistrust and provider hesitation regarding the human papillomavirus (HPV) vaccine, it is important to explore how information regarding the vaccine is shared online via social media outlets. The purpose of this study was to evaluate the content of messaging regarding the HPV vaccine on the social media and microblogging site Twitter, and describe the sentiment of those messages. DESIGN AND SAMPLE: This study utilized a cross-sectional descriptive approach. Over a 2-week period, Twitter content was searched hourly using key terms "#HPV and #Gardasil," which yielded 1,794 Twitter posts for analysis. Each post was then analyzed individually using an a priori coding strategy and directed content analysis. RESULTS: The majority of Twitter posts were written by lay consumers and were sharing commentary about a media source. However, when actual URLs were shared, the most common form of share was linking back to a blog post written by lay users. The vast majority of content was presented as polarizing (either as a positive or negative tweet), with 51% of the Tweets representing a positive viewpoint. CONCLUSIONS: Using Twitter to understand public sentiment offers a novel perspective to explore the context of health communication surrounding certain controversial issues.

Incivility Across the Nursing Continuum.

Incivility affects nurses throughout education and practice; it directly affects patient safety as well as nurses' decisions to remain in academia and clinical practice. This article reviews the current literature on incivility and proposes the application of social learning theory to evidence-based strategies that can be implemented to combat incivility.

Homologous recombination is a primary pathway to repair DNA double-strand breaks generated during DNA rereplication.

Re-initiation of DNA replication at origins within a given cell cycle would result in DNA rereplication, which can lead to genome instability and tumorigenesis. DNA rereplication can be induced by loss of licensing control at cellular replication origins, or by viral protein-driven multiple rounds of replication initiation at viral origins. DNA double-strand breaks (DSBs) are generated during rereplication, but the mechanisms of how these DSBs are repaired to maintain genome stability and cell viability are poorly understood in mammalian cells. We generated novel EGFP-based DSB repair substrates, which specifically monitor the repair of rereplication-associated DSBs. We demonstrated that homologous recombination (HR) is an important mechanism to repair rereplication-associated DSBs, and sister chromatids are used as templates for such HR-mediated DSB repair. Micro-homology-mediated non-homologous end joining (MMEJ) can also be used but to a lesser extent compared to HR, whereas Ku-dependent classical non-homologous end joining (C-NHEJ) has a minimal role to repair rereplication-associated DSBs. In addition, loss of HR activity leads to severe cell death when rereplication is induced. Therefore, our studies identify HR, the most conservative repair pathway, as the primary mechanism to repair DSBs upon rereplication.

Impact of Gender and Underrepresented in Medicine Status on Research Productivity Among Ophthalmology Residency Applicants.

PURPOSE: Insufficient representation of women and underrepresented in medicine (URiM) students remains a problem among the ophthalmology workforce. In the residency selection process, research productivity is an important factor. We aimed to determine the average research output listed by applicants and assess for differences by gender and race. DESIGN: Retrospective cohort study. METHODS: All San Francisco Match applications to the Wilmer Eye Institute for the 2019, 2020, and 2021 ophthalmology residency cycles were retrospectively reviewed. Each applicant's number of published research articles was recorded and subclassified into first-author publications in any field, publications in ophthalmology, and first-author publications in ophthalmology. Multivariable logistic regression was performed to determine factors associated with successful publication. RESULTS: A total of 1376 applications were reviewed. On average, women had a greater number of publications in ophthalmology (2.08 vs 1.73, P = .05) and presentations (4.52 vs 4.09, P = .01) compared with men. Self-identified URiMs were less likely to list publications in ophthalmology (odds ratio [OR] 0.650, P = .05) and first-author publications in ophthalmology (OR 0.570, P = .02) compared to non-URiMs. CONCLUSIONS: Our findings highlight disparities in research productivity by self-identified URiM status. On the other hand, women had similar if not higher research outputs than men. Greater research mentorship and opportunities to support URiM students may facilitate the recruitment of diverse trainees to ophthalmology programs.

The Specialist Treatment of Inpatients: Caring for Diabetes in Surgery (STOIC-D Surgery) Trial: A Randomized Controlled Trial of Early Intervention With an Electronic Specialist-Led Model of Diabetes Care.

OBJECTIVE: To investigate the effect of early intervention with an electronic specialist-led "proactive" model of care on glycemic and clinical outcomes. RESEARCH DESIGN AND METHODS: The Specialist Treatment of Inpatients: Caring for Diabetes in Surgery (STOIC-D Surgery) randomized controlled trial was performed at the Royal Melbourne Hospital. Eligible participants were adults admitted to a surgical ward during the study with either known diabetes or newly detected hyperglycemia (at least one random blood glucose result ≥11.1 mmol/L). Participants were randomized 1:1 to standard diabetes care or the intervention consisting of an early consult by a specialist inpatient diabetes team using electronic tools for patient identification, communication of recommendations, and therapy intensification. The primary outcome was median patient-day mean glucose (PDMG). The key secondary outcome was incidence of health care-associated infection (HAI). RESULTS: Between 12 February 2021 and 17 December 2021, 1,371 admissions met inclusion criteria, with 680 assigned to early intervention and 691 to standard diabetes care. Baseline characteristics were similar between groups. The early intervention group achieved a lower median PDMG of 8.2 mmol/L (interquartile range [IQR] 6.9-10.0 mmol/L) compared with 8.6 mmol/L (IQR 7.2-10.3 mmol/L) in the control group for an estimated difference of -0.3 mmol/L (95% CI -0.4 to -0.2 mmol/L, P < 0.0001). The incidence of HAI was lower in the intervention group (77 [11%] vs. 110 [16%]), for an absolute risk difference of -4.6% (95% CI -8.2 to -1.0, P = 0.016). CONCLUSIONS: In surgical inpatients, early diabetes management intervention with an electronic specialist-led diabetes model of care reduces glucose and HAI.

A web-based tool for real-time adequacy assessment of kidney biopsies.

The escalating incidence of kidney biopsies providing insufficient tissue for diagnosis poses a dual challenge, straining the healthcare system and jeopardizing patients who may require rebiopsy or face the prospect of an inaccurate diagnosis due to an unsampled disease. Here, we introduce a web-based tool that can provide real-time, quantitative assessment of kidney biopsy adequacy directly from photographs taken with a smartphone camera. The software tool was developed using a deep learning-driven automated segmentation technique, trained on a dataset comprising nephropathologist-confirmed annotations of the kidney cortex on digital biopsy images. Our framework demonstrated favorable performance in segmenting the cortex via 5-fold cross-validation (Dice coefficient: 0.788±0.130) (n=100). Offering a bedside tool for kidney biopsy adequacy assessment has the potential to provide real-time guidance to the physicians performing medical kidney biopsies, reducing the necessity for re-biopsies. Our tool can be accessed through our web-based platform: http://www.biopsyadequacy.org.

The Ophthalmic Manifestations of Down Syndrome.

Down Syndrome is one of the most common chromosomal conditions in the world, affecting an estimated 1:400-1:500 births. It is a multisystem genetic disorder but has a wide range of ophthalmic findings. These include strabismus, amblyopia, accommodation defects, refractive error, eyelid abnormalities, nasolacrimal duct obstruction, nystagmus, keratoconus, cataracts, retinal abnormalities, optic nerve abnormalities, and glaucoma. These ophthalmic conditions are more prevalent in children with Down Syndrome than the general pediatric population, and without exception, early identification with thoughtful screening in this patient population can drastically improve prognosis and/or quality of life.

Impact of organic solutes on capillary phenomena in water-CO2-quartz systems.

HYPOTHESIS: The migration of supercritical CO2 (scCO2) injected into underground reservoirs as part of carbon capture and storage is influenced by organic contamination affecting mineral wettability. Molecular dynamics (MD) simulations of relevant systems that incorporate representative organic solutes allow detailed investigation of changes in fundamental interfacial and capillary properties. EXPERIMENTS: We use MD simulations to explore the effects of four organic solutes (quinoline, decanoic acid, coronene, sorgoleone) on the wettability of quartz by water in the presence of scCO2. We examine the impacts of polar, alkyl, and aromatic moieties as well as fluid flow velocity at elevated temperatures and pressures. FINDINGS: Organic molecules accumulate at the water-CO2 interface, where they distribute according to their size and functional groups. Certain organics penetrate the adsorbed water film at the quartz-CO2 interface, revealing two modes of hydrogen bonding between polar organic functional group, water, and quartz surface -OH groups. Interfacial energies and contact angles are minimally impacted by organic adsorption at the water-CO2 interface, possibly due to simultaneous CO2 desorption. Non-equilibrium MD simulations reveal that flow-induced redistribution of organic compounds modulates the radii of curvature of the advancing and receding water-CO2 interfaces. Our results indicate that organic adsorption on water surfaces is likely ubiquitous during multi-phase flow in soils and sedimentary rocks, with implications for the mobilization and transport of organic compounds.

Fate of Research Articles Reported by Ophthalmology Residency Applicants: What Happens to "Submitted" and "In Preparation" Articles?

OBJECTIVE: As coronavirus disease 2019 affects clinical training opportunities and with the transition of U.S. Medical Licensing Examination Step 1 to pass-fail, research may become increasingly important for evaluating ophthalmology residency applicants. Though publication misrepresentation has been studied among ophthalmology residency applicants, eventual publication rates of incomplete articles remain unknown. We aimed to determine publication rates for manuscripts listed as "submitted" or "in preparation" on ophthalmology residency applications and identify factors associated with unpublished manuscripts. DESIGN: San Francisco Match applications to the Wilmer Eye Institute for the 2019 ophthalmology residency cycle were retrospectively reviewed. Each applicant's number of "published," "submitted," and "in preparation" manuscripts was recorded, then verified 1.5 years later through PubMed, Google Scholar, or journal websites. Unverifiable manuscripts were deemed "unpublished." SETTING: Single academic institution (Wilmer Eye Institute, Baltimore, MD, USA) PARTICIPANTS: All 458 medical students who applied to the Wilmer Eye Institute for the 2019 ophthalmology residency cycle through the San Francisco Match. RESULTS: A total of 458 applications were reviewed. Of 428 "submitted" publications, 126 (29.4%) remained unpublished after 1.5 years. Of 324 manuscripts "in preparation," 215 (66.4%) remained unpublished. In a multivariate model, AOA was associated with not having an unpublished manuscript compared to applicants without AOA (OR: 0.423, p = 0.0163). Gender, Step 1 score, additional degrees, and a research year had no association. CONCLUSIONS: Nearly two-thirds of manuscripts listed as "in preparation" remained unpublished. Specific guidance from research mentors may help applicants better represent their publications in residency applications.