Enhancing Meibography Image Analysis Through Artificial Intelligence-Driven Quantification and Standardization for Dry Eye Research.

Purpose: This study enhances Meibomian gland (MG) infrared image analysis in dry eye (DE) research through artificial intelligence (AI). It is comprised of two main stages: automated eyelid detection and tarsal plate segmentation to standardize meibography image analysis. The goal is to address limitations of existing assessment methods, bridge the curated and real-world dataset gap, and standardize MG image analysis. Methods: The approach involves a two-stage process: automated eyelid detection and tarsal plate segmentation. In the first stage, an AI model trained on curated data identifies relevant eyelid areas in non-curated datasets. The second stage refines the eyelid area in meibography images, enabling precise comparisons between normal and DE subjects. This approach also includes specular reflection removal and tarsal plate mask refinement. Results: The methodology achieved a promising instance-wise accuracy of 80.8% for distinguishing meibography images from 399 DE and 235 non-DE subjects. By integrating diverse datasets and refining the area of interest, this approach enhances meibography feature extraction accuracy. Dimension reduction through Uniform Manifold Approximation and Projection (UMAP) allows feature visualization, revealing distinct clusters for DE and non-DE phenotypes. Conclusions: The AI-driven methodology presented here quantifies and classifies meibography image features and standardizes the analysis process. By bootstrapping the model from curated datasets, this methodology addresses real-world dataset challenges to enhance the accuracy of meibography image feature extraction. Translational Relevance: The study presents a standardized method for meibography image analysis. This method could serve as a valuable tool in facilitating more targeted investigations into MG characteristics.

Scottish Intercollegiate Guidelines Network Guidance on Dementia: The Investigation of Suspected Dementia (SIGN 168) with Focus on Biomarkers-Executive Summary.

This is an executive summary of the recent guidance produced by the Scottish Intercollegiate Guidelines Network (SIGN) dementia guideline group with regards to the investigation of suspected dementia. This is a sub-section of the broader SIGN 168 guideline released in November 2023. The guideline group included clinicians with expertise in Old Age Psychiatry, Neurology, Radiology, and Nuclear Medicine supported by colleagues from the SIGN and Healthcare Improvement Scotland teams. There was representation from carers and support organizations with experience of dementia, to ensure the recommendations were appropriate from the perspective of the people being assessed for possible dementia and their carers. As the 2018 National Institute for Health and Clinical Excellence (NICE) dementia review included a review of the evidenced investigation of dementia, the SIGN guideline development group decided to focus on a review on the up-to-date evidence regarding the role of imaging and fluid biomarkers in the diagnosis of dementia. To give context to the consideration of more advanced diagnostic biomarker investigations, the guideline and this summary include the NICE guidance on the use of standard investigations as well as more specialist investigations. The evidence review supports consideration of the use of structural imaging, nuclear medicine imaging, and established Alzheimer's cerebrospinal fluid biomarkers (amyloid and tau) in the diagnosis of dementia. Although routine use of amyloid positron emission tomography imaging was not recommended, its potential use, under specialist direction, in patients with atypical or young-onset presentations of suspected Alzheimer's dementia was included as a clinical good practice point.

Poly(acrylic acid)/Poly(vinyl alcohol) Microarray Patches for Continuous Transdermal Delivery of Levodopa and Carbidopa: In Vitro and In Vivo Studies.

Levodopa (LD) has been the most efficacious medication and the gold standard therapy for Parkinson's disease (PD) for decades. However, its long-term administration is usually associated with motor complications, which are believed to be the result of the fluctuating pharmacokinetics of LD following oral administration. Duodopa® is the current option to offer a continuous delivery of LD and its decarboxylase inhibitor carbidopa (CD); however, its administration involves invasive surgical procedures, which could potentially lead to lifelong complications, such as infection. Recently, dissolving microarray patches (MAPs) have come to the fore as an alternative that can bypass the oral administration route in a minimally invasive way. This work explored the potential of using dissolving MAPs to deliver LD and CD across the skin. An acidic polymer poly(acrylic acid) (PAA) was used in the MAP fabrication to prevent the potential oxidation of LD at neutral pH. The drug contents of LD and CD in the formulated dissolving MAPs were 1.82 ± 0.24 and 0.47 ± 0.04 mg/patch, respectively. The in vivo pharmacokinetic study using female Sprague-Dawley® rats (Envigo RMS Holding Corp, Bicester, UK) demonstrated a simultaneous delivery of LD and CD and comparable AUC values between the dissolving MAPs and the oral LD/CD suspension. The relative bioavailability for the dissolving MAPs was calculated to be approximately 37.22%. Accordingly, this work highlights the use of dissolving MAPs as a minimally invasive approach which could potentially bypass the gastrointestinal pathway and deliver both drugs continuously without surgery.

The Intellectual Disability Risk Gene Kdm5b Regulates Long-Term Memory Consolidation in the Hippocampus.

The histone lysine demethylase KDM5B is implicated in recessive intellectual disability disorders, and heterozygous, protein-truncating variants in KDM5B are associated with reduced cognitive function in the population. The KDM5 family of lysine demethylases has developmental and homeostatic functions in the brain, some of which appear to be independent of lysine demethylase activity. To determine the functions of KDM5B in hippocampus-dependent learning and memory, we first studied male and female mice homozygous for a Kdm5b Δ ARID allele that lacks demethylase activity. Kdm5b Δ ARID/ Δ ARID mice exhibited hyperactivity and long-term memory deficits in hippocampus-dependent learning tasks. The expression of immediate early, activity-dependent genes was downregulated in these mice and hyperactivated upon a learning stimulus compared with wild-type (WT) mice. A number of other learning-associated genes were also significantly dysregulated in the Kdm5b Δ ARID/ Δ ARID hippocampus. Next, we knocked down Kdm5b specifically in the adult, WT mouse hippocampus with shRNA. Kdm5b knockdown resulted in spontaneous seizures, hyperactivity, and hippocampus-dependent long-term memory and long-term potentiation deficits. These findings identify KDM5B as a critical regulator of gene expression and synaptic plasticity in the adult hippocampus and suggest that at least some of the cognitive phenotypes associated with KDM5B gene variants are caused by direct effects on memory consolidation mechanisms.

The Test-retest Reliability of Pain Outcome Measures in People with Phantom Limb Pain.

OBJECTIVES: To quantify the test-retest reliability of three patient-reported outcome measures of pain for people living with phantom limb pain (PLP) and assess impact of test-retest errors on future research and clinical decisions. METHODS: Thirty-nine participants (30 males), mean (SD) age: 55 (16), mean (SD) years post amputation: 6.8 (8.3), reported their PLP levels on a Visual Analogue Scale (VAS) for pain intensity, the revised Short Form McGill Pain Questionnaire (SF-MPQ-2), and a pain diary, on two occasions 7-14 days apart. Mean systematic change, within-subjects SD, limits of agreement (LOA), coefficient of variation and the intraclass correlation coefficient (ICC) were quantified alongside their respective 95% confidence intervals (95%CI). RESULTS: Systematic learning effects (mean changes) were not clinically relevant across the VAS, SF-MPQ-2 and pain diary. Within-subjects SDs (95%CI) were 11.8 (9.6-15.3), 0.9 (0.7-1.2), and 8.6 (6.9-11.5), respectively. LOA (95%CI) were 32.6 (26.5-42.4), 2.5 (2-3.3), and 23.9 (19.2-31.8), respectively. ICCs (95%CI) were 0.8 (0.6-0.9), 0.8 (0.7-0.9), and 0.9 (0.8-0.9), respectively, but may have been inflated by sample heterogeneity. The test-retest errors allowed detection of clinically relevant effect sizes with feasible sample sizes in future studies, but individual errors were large. DISCUSSION: For people with PLP, a pain intensity VAS, the SF-MPQ-2, and a pain diary show an acceptable level of inter-session reliability for use in future clinical trials with feasible sample sizes. Nevertheless, the random error observed for all three of the pain outcome measures suggests they should be interpreted with caution in case studies and when monitoring individuals' clinical status and progress.

Chronic effects of stretching on range of motion with consideration of potential moderating variables: A systematic review with meta-analysis.

BACKGROUND: It is well known that stretch training can induce prolonged increases in joint range of motion (ROM). However, to date more information is needed regarding which training variables might have greater influence on improvements in flexibility. Thus, the purpose of this meta-analysis was to investigate the effects of stretch training on ROM in healthy participants by considering potential moderating variables, such as stretching technique, intensity, duration, frequency, and muscles stretched, as well as sex-specific, age-specific, and/or trained state-specific adaptations to stretch training. METHODS: We searched through PubMed, Scopus, Web of Science, and SportDiscus to find eligible studies and, finally, assessed the results from 77 studies and 186 effect sizes by applying a random-effect meta-analysis. Moreover, by applying a mixed-effect model, we performed the respective subgroup analyses. To find potential relationships between stretch duration or age and effect sizes, we performed a meta-regression. RESULTS: We found a significant overall effect, indicating that stretch training can increase ROM with a moderate effect compared to the controls (effect size = -1.002; Z = -12.074; 95% confidence interval: -1.165 to -0.840; p < 0.001; I2 = 74.97). Subgroup analysis showed a significant difference between the stretching techniques (p = 0.01) indicating that proprioceptive neuromuscular facilitation and static stretching produced greater ROM than did ballistic/dynamic stretching. Moreover, there was a significant effect between the sexes (p = 0.04), indicating that females showed higher gains in ROM compared to males. However, further moderating analysis showed no significant relation or difference. CONCLUSION: When the goal is to maximize ROM in the long term, proprioceptive neuromuscular facilitation or static stretching, rather than ballistic/dynamic stretching, should be applied. Something to consider in future research as well as sports practice is that neither volume, intensity, nor frequency of stretching were found to play a significant role in ROM yields.

Maximal and Submaximal Intensity Isometric Knee Extensions Induce an Underestimation of Time Estimates with Both Younger And Older Adults: A Randomized Crossover Trial.

Our perception of time plays a critical role in nearly all daily activities and especially in sports. There are no studies that have investigated and compared time perception during exercise in young and older adults. Thus, this study aimed to compare the effects of exercise on time perception between younger and older adult populations. Thirty-three recreationally active participants were recruited and assigned to either the younger (university students, 9 males and 10 females) or older adults (>60 years, 8 males and 6 females). All participants completed four exercise conditions over two sessions on separate days: approximately 30-seconds of knee extensors 100%, 60% and 10% of maximum voluntary isometric contraction (MVIC), and control (no contractions). Prospective time perception was estimated (at 5-, 10-, 20-, and 30-seconds) at the beginning of each session and while performing the exercise. A main effect for condition (p < 0.001, d = 1.06) with subsequent post-hoc tests indicated participants significantly underestimated (estimated time was shorter than chronological time) time in all three exercise conditions compared to the control. There were no significant age group differences. In conclusion, exercise underestimated time estimates regardless of intensity or age. This questions the postulated intensity-dependent relationship between exercise and time perception. While older adults were expected to be less accurate in their time estimates, they may have been able to adopt alternative strategies for age-related changes in their internal clock, resulting in no significant age group differences.

Temporal perception is distorted by submaximal and maximal isometric contractions of the knee extensors in young healthy males and females.

Introduction: The estimate of time (temporal perception) is important for activities of daily living, sports and even survival, however time perception research needs greater scrutiny. Time estimation can influence movement decisions and determine whether the individual is successful at their goal, The objectives of this study were to examine participants perception of time at 5-, 10-, 20-, and 30-s intervals to determine possible distortions of time estimates caused by varying intensity isometric contractions, and sex differences. Methods: In this repeated measures study, 19 participants (10 females, 9 males) endured two sessions, which consisted of a cognitive task of estimating time intervals while performing an isometric knee extension at maximal, submaximal (60%), and distraction (10%) intensities and a non-active control. In addition to time estimates; heart rate (HR), tympanic temperatures and electromyography during the intervention contractions were monitored. Maximal contractions induced significantly greater time underestimations at 5-s (4.43 ± 0.93, p = 0.004), 20-s (18.59 ± 2.61-s, p = 0.03), and 30-s (27.41 ± 4.07-s, p = 0.004) than control. Submaximal contractions contributed to time underestimation at 30-s (27.38 ± 3.17-s, p = 0.001). Females demonstrated a greater underestimation of 5-s during the interventions than males (p = 0.02) with 60% submaximal (-0.64-s ± 0.26) and distraction (-0.53-s ± 0.22) conditions. For the other 10-, 20-, 30-s intervals, there was no significant time perception sex differences. The control condition exhibited lower HR (75.3 ± 11.6) than the maximal (92.5 ± 13.9), 60% submaximal (92.2 ± 14.4) or distraction (90.5 ± 14.7) conditions. Tympanic temperatures were not influenced by the contraction intensities. Discussion: There was greater integrated knee extensor electromyographic activity during the maximal contractions to suggest greater neuromuscular activation that may influence time perception. However, there was no consistent effect of changes in HR or temperature on time estimates. This work adds to the growing literature of time perception during exercise to state that time is significantly underestimated when performing moderate to vigorous intensity exercise.

Surgical pit crew: initiative to optimise measurement and accountability for operating room turnover time.

BACKGROUND AND OBJECTIVES: Turnover time (TOT), defined as the time between surgical cases in the same operating room (OR), is often perceived to be lengthy without clear cause. With the aim of optimising and standardising OR turnover processes and decreasing TOT, we developed an innovative and staff-interactive TOT measurement method. METHODS: We divided TOT into task-based segments and created buttons on the electronic health record (EHR) default prelogin screen for appropriate staff workflows to collect more granular data. We created submeasures, including 'clean-up start', 'clean-up complete', 'set-up start' and 'room ready for patient', to calculate environmental services (EVS) response time, EVS cleaning time, room set-up response time, room set-up time and time to room accordingly. RESULTS: Since developing and implementing these workflows, measures have demonstrated excellent staff adoption. Median times of EVS response and cleaning have decreased significantly at our main hospital ORs and ambulatory surgery centre. CONCLUSION: OR delays are costly to hospital systems. TOT, in particular, has been recognised as a potential dissatisfier and cause of delay in the perioperative environment. Viewing TOT as one finite entity and not a series of necessary tasks by a variety of team members limits the possibility of critical assessment and improvement. By dividing the measurement of TOT into respective segments necessary to transition the room at the completion of one case to the onset of another, valuable insight was gained into the causes associated with turnover delays, which increased awareness and improved accountability of staff members to complete assigned tasks efficiently.

Optimizing opioid prescribing practices after minimally invasive lung resection through a quality-improvement intervention.

BACKGROUND: In their 2019 guideline on the prescribing and management of opioids after elective ambulatory thoracic surgery, the Canadian Association of Thoracic Surgeons (CATS) recommended 120 morphine milligram equivalents (MME) after minimally invasive (video-assisted thoracoscopic surgery [VATS]) lung resection. We conducted a quality-improvement project to optimize opioid prescribing after VATS lung resection. METHODS: We assessed baseline prescribing practices for opioid-naive patients. Using a mixed-methods approach, we selected 2 quality-improvement interventions: formal incorporation of the CATS guideline into our postoperative care pathway, and development of a patient information handout regarding opioids. The intervention was initiated on Oct. 1, 2020, and was formally implemented on Dec. 1, 2020. The outcome measure was average MME of discharge opioid prescriptions, the process measure was proportion of discharge prescriptions exceeding the recommended dosage, and the balancing measure was opioid prescription refills. We analyzed the data using control charts, and compared all measures between the pre-intervention (12 mo before) and postintervention (12 mo after) groups. RESULTS: A total of 348 patients who underwent VATS lung resection were identified, 173 before the intervention and 175 after the intervention. Significantly less MME was prescribed after the intervention (100 v. 158, p < 0.001), and a lower proportion of prescriptions were nonadherent to the guideline (18.9% v. 50.9%, p < 0.001). Control charts showed special cause variation corresponding with the intervention, and system stability existed after the intervention. There was no statistically significant difference in the proportion or dosage of opioid prescription refills after the intervention. CONCLUSION: After implementation of the CATS opioid guideline, there was a significant reduction in opioids prescribed at discharge and no increase in opioid prescription refills. Control charts are a valuable resource for monitoring outcomes on an ongoing basis and for assessing the effects of an intervention.

Tear-film evaporation flux and its relationship to tear properties in symptomatic and asymptomatic soft-contact-lens wearers.

PURPOSE: With soft-contact-lens wear, evaporation of the pre-lens tear film affects the osmolarity of the post-lens tear film and this can introduce a hyperosmotic environment at the corneal epithelium, leading to discomfort. The purposes of the study are to ascertain whether there are differences in evaporation flux (i.e., the evaporation rate per unit area) between symptomatic and asymptomatic soft-contact-lens wearers, to assess the repeatability of a flow evaporimeter, and to assess the relationship between evaporation fluxes, tear properties, and environmental conditions. METHODS: Closed-chamber evaporimeters commonly used in ocular-surface research do not control relative humidity and airflow, and, therefore, misestimate the actual tear-evaporation flux. A recently developed flow evaporimeter overcomes these limitations and was used to measure accurate in-vivo tear-evaporation fluxes with and without soft-contact-lens wear for symptomatic and asymptomatic habitual contact-lens wearers. Concomitantly, lipid-layer thickness, ocular-surface-temperature decline rate (i.e., °C/s), non-invasive tear break-up time, tear-meniscus height, Schirmer tear test, and environmental conditions were measured in a 5 visit study. RESULTS: Twenty-one symptomatic and 21 asymptomatic soft-contact-lens wearers completed the study. A thicker lipid layer was associated with slower evaporation flux (p < 0.001); higher evaporation flux was associated with faster tear breakup irrespective of lens wear (p = 0.006). Higher evaporation flux was also associated with faster ocular-surface-temperature decline rate (p < 0.001). Symptomatic lens wearers exhibited higher evaporation flux than did asymptomatic lens wearers, however, the results did not reach statistical significance (p = 0.053). Evaporation flux with lens wear was higher than without lens wear but was also not statistically significant (p = 0.110). CONCLUSIONS: The repeatability of the Berkeley flow evaporimeter, associations between tear characteristics and evaporation flux, sample-size estimates, and near statistical significance in tear-evaporation flux between symptomatic and asymptomatic lens wearers all suggest that with sufficient sample sizes, the flow evaporimeter is a viable research tool to understand soft-contact-lens wear comfort.

(The shift to) online delivery of a rural faculty development program in research skills: lessons learned.

BACKGROUND: While rural physicians are the ideal candidates to investigate health and healthcare issues in rural communities, they often lack the required skills, competencies, and resources. As a result, research skills development programs are crucial to help ensure communities receive the quality of care they deserve. Memorial University of Newfoundland created a research skills development program called 6for6 to empower and enable rural physicians to research solutions to community-specific health needs. 6for6 program delivery was exclusively in-person until 2019. However, with limitations introduced due to the COVID-19 pandemic, organizations around the globe needed to respond quickly. As we work to return to a post-pandemic environment, program administrators and educators worldwide are unsure whether to retain or remove the changes made to programs to adapt to the pandemic restrictions. Therefore, this work addresses the impact of the online delivery model in two areas: 1) attainment of competencies (specifically research skills, knowledge, and attitudes); and 2) participant experiences, defined as the ease of attendance, the capacity to interact with team members and peers, and challenges or barriers associated with navigating program resources. METHODS: We compared the effect of an online delivery model pivoted to adapt pandemic restrictions with the original model (primarily face-to-face) on the acquisition of learning competencies and participant experience using a mixed-methods study. Various data collection methods, such as a pre-post program survey, post-program focus group, and structured observation, were utilized. RESULTS: From 2014 to 2021, 35 physicians attended the program (30 face-to-face and five online). The Wilcoxon-sign-rank test did not show any significant differences in the participants' median change of research competency scores who attended face-to-face and online learning, respectively: knowledge (32.6, 26.8), attitudes (3.8, 3.5), and skills (32.4, 20.0). Flexibility and accessibility were key aspects of participants' experiences during the online model. Comparison with previous years demonstrated no significant challenges with the virtual delivery model, yet participants struggled with mentorship challenges and learning-life balance. CONCLUSIONS: Although presenting some unique challenges, the online model did not negatively affect learner competencies. Likewise, it provided opportunities for rural physicians to attend learning sessions and interact with experts and peers while remaining in their communities.

Predicting demographics from meibography using deep learning.

This study introduces a deep learning approach to predicting demographic features from meibography images. A total of 689 meibography images with corresponding subject demographic data were used to develop a deep learning model for predicting gland morphology and demographics from images. The model achieved on average 77%, 76%, and 86% accuracies for predicting Meibomian gland morphological features, subject age, and ethnicity, respectively. The model was further analyzed to identify the most highly weighted gland morphological features used by the algorithm to predict demographic characteristics. The two most important gland morphological features for predicting age were the percent area of gland atrophy and the percentage of ghost glands. The two most important morphological features for predicting ethnicity were gland density and the percentage of ghost glands. The approach offers an alternative to traditional associative modeling to identify relationships between Meibomian gland morphological features and subject demographic characteristics. This deep learning methodology can currently predict demographic features from de-identified meibography images with better than 75% accuracy, a number which is highly likely to improve in future models using larger training datasets, which has significant implications for patient privacy in biomedical imaging.

Whole genome analysis in APOE4 homozygotes identifies the DAB1-RELN pathway in Alzheimer's disease pathogenesis.

The APOE-ε4 allele is known to predispose to amyloid deposition and consequently is strongly associated with Alzheimer's disease (AD) risk. There is debate as to whether the APOE gene accounts for all genetic variation of the APOE locus. Another question which remains is whether APOE-ε4 carriers have other genetic factors influencing the progression of amyloid positive individuals to AD. We conducted a genome-wide association study in a sample of 5,390 APOE-ε4 homozygous (ε4ε4) individuals (288 cases and 5102 controls) aged 65 or over in the UK Biobank. We found no significant associations of SNPs in the APOE locus with AD in the sample of ε4ε4 individuals. However, we identified a novel genome-wide significant locus associated to AD, mapping to DAB1 (rs112437613, OR = 2.28, CI = 1.73-3.01, p = 5.4 × 10-9). This identification of DAB1 led us to investigate other components of the DAB1-RELN pathway for association. Analysis of the DAB1-RELN pathway indicated that the pathway itself was associated with AD, therefore suggesting an epistatic interaction between the APOE locus and the DAB1-RELN pathway.

Sensory discrimination training for adults with chronic musculoskeletal pain: a systematic review.

BACKGROUND: Sensory discrimination training (SDT) is a form of feedback guided sensory training used in the treatment of chronic musculoskeletal pain (CMP). OBJECTIVE: This systematic review aimed to investigate the efficacy and safety of SDT for CMP. METHODS: MEDLINE, CINAHL, EMBASE, AMED, CENTRAL, PsycINFO, Scopus, OT Seeker, PEDro, ETHOS, Web of Science, and Open Grey were searched for appropriate randomized controlled trials (RCTs). Included papers were assessed for risk of bias, and evidence was graded using the GRADE approach. The protocol was published on PROSPERO (anonymized). RESULTS: Ten RCTs met the inclusion/exclusion criteria. There was conflicting evidence from seven RCTs for the efficacy of SDT for chronic low back pain (CLBP). There was very low-quality evidence from two studies supporting the efficacy of SDT for phantom limb pain (PLP). There was very low-quality evidence from one RCT for the efficacy of SDT for Fibromyalgia. No adverse effects of SDT were identified. CONCLUSIONS: SDT has been delivered in multiple forms in the literature. SDT does not appear to be associated with any adverse effects and shows potential regarding its clinical efficacy. However, there is a lack of high-quality evidence upon which to make any firm clinical recommendations.

A genetic link between risk for Alzheimer's disease and severe COVID-19 outcomes via the OAS1 gene.

Recently, we reported oligoadenylate synthetase 1 (OAS1) contributed to the risk of Alzheimer's disease, by its enrichment in transcriptional networks expressed by microglia. However, the function of OAS1 within microglia was not known. Using genotyping from 1313 individuals with sporadic Alzheimer's disease and 1234 control individuals, we confirm the OAS1 variant, rs1131454, is associated with increased risk for Alzheimer's disease. The same OAS1 locus has been recently associated with severe coronavirus disease 2019 (COVID-19) outcomes, linking risk for both diseases. The single nucleotide polymorphisms rs1131454(A) and rs4766676(T) are associated with Alzheimer's disease, and rs10735079(A) and rs6489867(T) are associated with severe COVID-19, where the risk alleles are linked with decreased OAS1 expression. Analysing single-cell RNA-sequencing data of myeloid cells from Alzheimer's disease and COVID-19 patients, we identify co-expression networks containing interferon (IFN)-responsive genes, including OAS1, which are significantly upregulated with age and both diseases. In human induced pluripotent stem cell-derived microglia with lowered OAS1 expression, we show exaggerated production of TNF-α with IFN-γ stimulation, indicating OAS1 is required to limit the pro-inflammatory response of myeloid cells. Collectively, our data support a link between genetic risk for Alzheimer's disease and susceptibility to critical illness with COVID-19 centred on OAS1, a finding with potential implications for future treatments of Alzheimer's disease and COVID-19, and development of biomarkers to track disease progression.

Two-Year Follow-Up of a Randomized Controlled Study of Integrated Smoking Cessation in a Lung Cancer Screening Program.

INTRODUCTION: Smoking cessation activities incorporated into lung cancer screening programs have been broadly recommended, but studies to date have not exhibited increased quit rates associated with cessation programs in this setting. We aimed to determine the long-term effectiveness of smoking cessation counseling in smokers presenting for lung cancer screening. METHODS: This was a randomized control trial of an intensive, telephone-based smoking cessation counseling intervention incorporating lung cancer screening results versus usual care (information pamphlet). This analysis reports on the long-term impact (24-mo) of the intervention on abstinence from smoking. RESULTS: A total of 337 active smokers who participated in the screening study were randomized to active smoking cessation counseling (n = 171) or control arm (n = 174) and completed a 24-month assessment. The 30-day smoking abstinence rates at 24 months postrandomization was 18.3% and 21.4% in the control and intervention arms, respectively-a 3.1% difference (95% confidence interval: -5.4 to 11.6, p = 0.48). No statistically significant differences in the 7-day abstinence, the use of pharmacologic cessation aids, nicotine replacement therapies, nor intent to quit in the following 30 days were noted (p > 0.05). The abstinence rates at 24-months were higher overall than at 12-months (19.9% versus 13.3%, p < 0.001), and smoking intensity was lower than at baseline for ongoing smokers. CONCLUSIONS: A telephone-based smoking cessation counseling intervention incorporating lung cancer screening results did not result in increased long-term cessation rates versus written information alone in unselected smokers undergoing lung cancer screening. Overall, quit rates were high and continued to improve throughout participation in the screening program. (ClinicalTrials.govNCT02431962).

Quantifying Meibomian Gland Morphology Using Artificial Intelligence.

SIGNIFICANCE: Quantifying meibomian gland morphology from meibography images is used for the diagnosis, treatment, and management of meibomian gland dysfunction in clinics. A novel and automated method is described for quantifying meibomian gland morphology from meibography images. PURPOSE: Meibomian gland morphological abnormality is a common clinical sign of meibomian gland dysfunction, yet there exist no automated methods that provide standard quantifications of morphological features for individual glands. This study introduces an automated artificial intelligence approach to segmenting individual meibomian gland regions in infrared meibography images and analyzing their morphological features. METHODS: A total of 1443 meibography images were collected and annotated. The dataset was then divided into development and evaluation sets. The development set was used to train and tune deep learning models for segmenting glands and identifying ghost glands from images, whereas the evaluation set was used to evaluate the performance of the model. The gland segmentations were further used to analyze individual gland features, including gland local contrast, length, width, and tortuosity. RESULTS: A total of 1039 meibography images (including 486 upper and 553 lower eyelids) were used for training and tuning the deep learning model, whereas the remaining 404 images (including 203 upper and 201 lower eyelids) were used for evaluations. The algorithm on average achieved 63% mean intersection over union in segmenting glands, and 84.4% sensitivity and 71.7% specificity in identifying ghost glands. Morphological features of each gland were also fed to a support vector machine for analyzing their associations with ghost glands. Analysis of model coefficients indicated that low gland local contrast was the primary indicator for ghost glands. CONCLUSIONS: The proposed approach can automatically segment individual meibomian glands in infrared meibography images, identify ghost glands, and quantitatively analyze gland morphological features.