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Gross anatomy is a crucial course in medical school; it sets the foundation for future coursework and is highly valued by clinicians. While both medical students and faculty recognize the importance of pre-medical school anatomy experience, few medical schools require it as a prerequisite. Consequently, medical school gross anatomy courses have a diverse range of prior anatomy experience among students. Prior studies have shown mixed results regarding the impact of pre-medical school anatomy experience on medical school gross anatomy performance, often using final exam scores as the metric of analysis. In this study, we investigated the relationship between pre-medical school anatomy experience and medical school gross anatomy performance among students at New York Institute of Technology, College of Osteopathic Medicine. We surveyed students from all four matriculated years and analyzed their individual anatomy laboratory exam scores and final anatomy laboratory course scores. We found that students with prior anatomy experience performed significantly better on the first anatomy laboratory exam, leading to an overall positive effect on their final anatomy laboratory score. However, this advantage seemed to diminish in subsequent exams, suggesting that students without prior experience rapidly adjusted to the course challenges. Students with prior anatomy experience felt more prepared for the anatomy course, reported lower stress levels, and believed they had an advantage over peers without prior experience. Our study highlights the importance of pre-medical school anatomy experience, particularly for early performance in the anatomy course.

Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a type I transmembrane protein initially identified in nonmetastatic melanomas and has been associated with human heart failure; however, its role in cardiac injury and function remains unclear. Here we show that GPNMB expression is elevated in failing human and mouse hearts after myocardial infarction (MI). Lineage tracing and bone-marrow transplantation reveal that bone-marrow-derived macrophages are the main source of GPNMB in injured hearts. Using genetic loss-of-function models, we demonstrate that GPNMB deficiency leads to increased mortality, cardiac rupture and rapid post-MI left ventricular dysfunction. Conversely, increasing circulating GPNMB levels through viral delivery improves heart function after MI. Single-cell transcriptomics show that GPNMB enhances myocyte contraction and reduces fibroblast activation. Additionally, we identified GPR39 as a receptor for circulating GPNMB, with its absence negating the beneficial effects. These findings highlight a pivotal role of macrophage-derived GPNMBs in post-MI cardiac repair through GPR39 signaling.

Quasi-periodic eruptions (QPEs) are luminous bursts of soft X-rays from the nuclei of galaxies, repeating on timescales of hours to weeks1-5. The mechanism behind these rare systems is uncertain, but most theories involve accretion disks around supermassive black holes (SMBHs) undergoing instabilities6-8 or interacting with a stellar object in a close orbit9-11. It has been suggested that this disk could be created when the SMBH disrupts a passing star8,11, implying that many QPEs should be preceded by observable tidal disruption events (TDEs). Two known QPE sources show long-term decays in quiescent luminosity consistent with TDEs4,12 and two observed TDEs have exhibited X-ray flares consistent with individual eruptions13,14. TDEs and QPEs also occur preferentially in similar galaxies15. However, no confirmed repeating QPEs have been associated with a spectroscopically confirmed TDE or an optical TDE observed at peak brightness. Here we report the detection of nine X-ray QPEs with a mean recurrence time of approximately 48 h from AT2019qiz, a nearby and extensively studied optically selected TDE16. We detect and model the X-ray, ultraviolet (UV) and optical emission from the accretion disk and show that an orbiting body colliding with this disk provides a plausible explanation for the QPEs.

The gastrointestinal system is a hollow organ affected by fibrostenotic diseases that cause volumetric compromise of the lumen via smooth muscle hypertrophy and fibrosis. Many of the driving mechanisms remain unclear. Yes-associated protein-1 (YAP) is a critical mechanosensory transcriptional regulator that mediates cell hypertrophy in response to elevated extracellular rigidity. In the type 2 inflammatory disorder, eosinophilic esophagitis (EoE), phospholamban (PLN) can induce smooth muscle cell hypertrophy. We used EoE as a disease model for understanding a mechanistic pathway in which PLN and YAP interact in response to rigid extracellular substrate to induce smooth muscle cell hypertrophy. PLN-induced YAP nuclear sequestration in a feed-forward loop caused increased cell size in response to a rigid substrate. This mechanism of rigidity sensing may have previously unappreciated clinical implications for PLN-expressing hollow systems such as the esophagus and heart.

Abstract There are differences within the literature regarding the upper frequency cut‐off point of the dynamic cerebral autoregulation (CA) high‐pass filter. The projection pursuit regression approach has demonstrated that the upper frequency limit is ∼0.07 Hz, whereas another approach [transfer function analysis (TFA) phase approaching zero] indicated a theoretical upper frequency limit for the high‐pass filter of 0.24 Hz. We investigated how these limits accurately represent the CA upper frequency limit, in addition to extending earlier findings with respect to biological sexes and across the cardiac cycle. Sixteen participants (nine females and seven males) performed repeated squat–stand manoeuvres at frequencies of 0.05, 0.10, 0.15, 0.20 and 0.25 Hz, with insonation of the middle and posterior cerebral arteries. Linear regression modelling with adjustment for sex and order of squat completion was used to compared TFA gain and phase with 0.25 Hz (above the theoretical limit of CA). The upper frequency limit of CA with TFA gain was within the range of 0.05–0.10 Hz, whereas TFA phase was within the range of 0.20–0.25 Hz, and consistent between vessels, between sexes and across the cardiac cycle. Females displayed greater middle cerebral artery gain compared with males (all P 0.072). Although sex‐specific differences were present for specific TFA metrics at a given frequency, the upper frequency limit of autoregulation was similar between cerebral conduit vessels, cardiac cycle phase and biological sex. Future work is warranted to determine whether an upper frequency limit exists with respect to hysteresis analyses.

Abstract Background Brain-computer interfaces (BCIs) can restore communication for movement- and/or speech-impaired individuals by enabling neural control of computer typing applications. Single command click detectors provide a basic yet highly functional capability. Methods We sought to test the performance and long-term stability of click decoding using a chronically implanted high density electrocorticographic (ECoG) BCI with coverage of the sensorimotor cortex in a human clinical trial participant (ClinicalTrials.gov, NCT03567213) with amyotrophic lateral sclerosis. We trained the participant’s click detector using a small amount of training data (

Objective: Examine how changes in sleep duration, objectively measured by activity trackers, impact weight gain in incoming college freshman. Participants: Incoming college freshmen, age [greater than equal to] 18. Methods: We measured weight and daily sleep duration before college entry and through the 1st college quarter. Additionally, we examined changes in sleep variability, activity levels and smartphone screen time use as possible predictors of weight gain. Results: 75 participants completed the study. Total sleep duration decreased from 437.9 ± SD 57.3 minutes at baseline to 416.5 ± SD 68.6 minutes by the end of the first quarter (p = 6.6 × 10[superscript -3]). (BMI) did not change significantly in this cohort. Higher sleep variability at baseline and an increase in sleep variability were associated with increases in BMI. Smartphone screen use was note to be high (235.2 ± SD 110.3 minutes/day) at the end of the first quarter. Conclusions: College weight gain may be affected by factors other than sleep duration, including sleep variability.

Near-peer tutoring (NPT) programs are popular vehicles to supplement traditional delivery of medical school curricula, including for anatomy laboratory (AL) content. While NPT programs can result in improved preclinical coursework performance for tutees, little to no data specifically show a benefit of NPT in AL course performance. In 2021, NYIT College of Osteopathic Medicine launched an NPT program where qualified second-year students led group tutoring sessions for first-year students. This study investigated whether participation and level of attendance in AL NPT sessions were associated with greater examination-to-examination improvement in AL performance. Student attendance at AL sessions in the NPT program was categorized as either regular (10 or more sessions), moderate (5-9 sessions), infrequent (1-4 sessions), or never during one semester. For the first 2 years of the NPT program, attendance frequency at AL tutoring sessions had a significant impact on average exam-to-exam improvement (p < 0.05). Overall, students who attended tutoring at any frequency had greater exam-to-exam improvement than students who never attended (p < 0.05). However, this trend was only significant in 1 of 2 years investigated. These data show that NPT programs can, though not uniformly, benefit student outcomes in AL coursework. With these data, this study provides additional details on the level of attendance necessary for expected improvements in AL coursework.

The El Niño—Southern Oscillation (ENSO) is an important mode of tropical Pacific atmosphere-ocean variability that drives teleconnections with weather and climate globally. However, prior studies using state-of-the-art climate models lack consensus regarding future ENSO projections and are often impacted by tropical Pacific sea-surface temperature (SST) biases. We used 173 simulations from 29 climate models participating in the Coupled Model Intercomparison Project, version 6 (CMIP6) to analyze model biases and future ENSO projections. We analyzed two ENSO indices, namely the ENSO Longitude Index (ELI), which measures zonal shifts in tropical Pacific deep convection and accounts for changes in background SST, and the Niño 3.4 index, which measures SST anomalies in the central-eastern equatorial Pacific. We found that the warm eastern tropical-subtropical Pacific SST bias typical of previous generations of climate models persists into many of the CMIP6 models. Future projections of ENSO shift toward more El Niño-like conditions based on ELI in 48% of simulations and 55% of models, in association with a future weakening of the zonal equatorial Pacific SST gradient. On the other hand, none of the models project a significant shift toward La Niña-like conditions. The standard deviation of the Niño 3.4 index indicates a lack of consensus on whether an increase or decrease in ENSO variability is expected in the future. Finally, we found a possible relationship between historical SST and low-level cloud cover biases in the ENSO region and future changes in ELI; however, this result may be impacted by limitations in data availability.

Abstract Historically, eloquent functions have been viewed as localized to focal areas of human cerebral cortex, while more recent studies suggest they are encoded by distributed networks. We examined the network properties of cortical sites defined by stimulation to be critical for speech and language, using electrocorticography from sixteen participants during word-reading. We discovered distinct network signatures for sites where stimulation caused speech arrest and language errors. Both demonstrated lower local and global connectivity, whereas sites causing language errors exhibited higher inter-community connectivity, identifying them as connectors between modules in the language network. We used machine learning to classify these site types with reasonably high accuracy, even across participants, suggesting that a site’s pattern of connections within the task-activated language network helps determine its importance to function. These findings help to bridge the gap in our understanding of how focal cortical stimulation interacts with complex brain networks to elicit language deficits.

Evidence suggests that sleep is a vital component of physical and health well-being. However, while sleep problems are present in individuals with mental health problems such as depression, it has not been clear whether these conditions are independent or whether they might be causally related. Indeed, if sleep or sleep disorders predispose or modify onset and outcomes of mental health issues, treatment of these factors could be explored as new mental health prevention or treatment options. The aim of this review was to examine in detail the bidirectional relationship between sleep, sleep disorders, and mental and physical health and well-being. It has considered the evidence that sleep architecture disruption, occurring through both quantity, quality, and timing of sleep as well as through the presence of sleep disorders may both influence mental health and well-being as well as be disrupted by both physical and mental health conditions. Also, the review has explored the effects of sleep disruption on mental health and performance through fatigue, mood, and vigilance. The review has considered the bidirectionality between sleep, sleep disorders, and mental health to examine how these may lead to or exacerbate mental health disorders such as affective, anxiety, autism, depressive and schizophrenia disorders but also considers how these conditions can affect sleep. The review highlights that poor sleep or the presence of a sleep disorder can increase the risks from mental health conditions such as suicidality. Furthermore, mental health conditions such as anxiety and worry can cause racing or repetitive thoughts that can keep an individual awake, leading to shortened sleep. It is important that sleep and sleep disorders are considered potential modifiable factors that could improve mental health outcomes. The important interconnect between both physical and mental health and sleep, in patient evaluations, also needs to be considered as these may affect treatment pathways and patient outcomes. Further, more robust and perspective research is required to establish the triad relationship of physical, mental health, and sleep.

Abstract Cancer genomes are composed of many complex structural alterations on chromosomes and extrachromosomal DNA (ecDNA), making it difficult to identify non-coding enhancer regions that are hijacked to activate oncogene expression. Here, we describe a 3D genomics-based analysis called HAPI (Highly Active Promoter Interactions) to characterize enhancer hijacking. HAPI analysis of HiChIP data from 34 cancer cell lines identified enhancer hijacking events that activate both known and potentially novel oncogenes such as MYC, CCND1, ETV1, CRKL, and ID4. Furthermore, we found enhancer hijacking among multiple oncogenes from different chromosomes, often including MYC, on the same complex amplicons such as ecDNA. We characterized a MYC-ERBB2 chimeric ecDNA, in which ERBB2 heavily hijacks MYC’s enhancers. Notably, CRISPRi of the MYC promoter led to increased interaction of ERBB2 with MYC enhancers and elevated ERBB2 expression. Our HAPI analysis tool provides a robust strategy to detect enhancer hijacking and reveals novel insights into oncogene activation.

Organisms living in mountains contend with extreme climatic conditions, including short growing seasons and long winters with extensive snow cover. Anthropogenic climate change is driving unprecedented, rapid warming of montane regions across the globe, resulting in reduced winter snowpack. Loss of snow as a thermal buffer may have serious consequences for animals overwintering in soil, yet little is known about how variability in snowpack acts as a selective agent in montane ecosystems. Here, we examine genomic variation in California populations of the leaf beetle Chrysomela aeneicollis, an emerging natural model system for understanding how organisms respond to climate change. We used a genotype-environment association approach to identify genomic signatures of local adaptation to microclimate in populations from three montane regions with variable snowpack and a coastal region with no snow. We found that both winter-associated environmental variation and geographical distance contribute to overall genomic variation across the landscape. We identified non-synonymous variation in novel candidate loci associated with cytoskeletal function, ion transport and membrane stability, cellular processes associated with cold tolerance in other insects. These findings provide intriguing evidence that variation in snowpack imposes selective gradients in montane ecosystems.

Electrochemically derived multicarbon products are a golden target for valorization of captured carbon dioxide due to the potential of turning a waste product into useful commodity chemicals with renewable energy sources. As a tantalizing approach toward their synthesis, the formose reaction utilizes catalytic condensation of formaldehyde to generate carbohydrates. While a sustainable approach to artificial carbohydrate production through electrochemical generation of formaldehyde is desirable, to date, it has not been fully realized. Here, we study the electrocatalytic conversion of methanol to formaldehyde on palladium with faradaic efficiency of over 90% at 0.9 V vs Ag/AgCl and with the partial current density of nearly 3 mA cm-2 at 1.6 V vs Ag/AgCl. We observe the concurrent generation of palladium oxides as a consequence of the high overpotentials employed, which may partially explain the higher selectivity toward the partial oxidation product. Moreover, we demonstrate that formaldehyde produced electrochemically from methanol is feasible for formose reactions without the need for further purification, achieving 21-28% carbon conversion to carbohydrates. This process, therefore, represents a potential avenue for the electrochemical generation of formaldehyde and its utilization in generating multicarbon products inaccessible by other electrocatalytic means.

In Utah, deaf and hard of hearing elementary school students can access their education--in American Sign Language (ASL) and spoken and written English--from their devices at home. Many secondary students can access online coursework as well. This is thanks to a four-year project undertaken by the Utah School for the Deaf (USD). The goal was to provide online services--even an online school--for deaf and hard of hearing students, for both those in deaf schools and those in mainstream programs. Today, any deaf or hard of hearing student in Utah can take advantage of the USD Online School. Deaf and hard of hearing students can elect to work entirely from home or make up a single high school course for credit. Students in the mainstream can sign onto courses in ASL and see other courses in written and spoken English. A shift in thinking has occurred. Many teachers have re-evaluated traditional notions of what school means and looks like.

Introduction Injury rates in competitive alpine skiing are high. With current methods, identifying people at risk is expensive and thus often not feasible at the youth level. The aims of this study were (1) to describe the jump performance and movement quality of youth competitive alpine skiers according to age and sex, (2) to compare the jump distance among skiers of different sexes and movement quality grades, and (3) to assess the inter-rater grading reliability of the qualitative visual movement quality classification of such jumps and the agreement between live and video-based post-exercise grading.Materials and Methods This cross-sectional study is based on an anonymized dataset of 301 7- to 15-year-old competitive alpine skiers. The skiers performed two-legged forward triple jumps, whereby the jump distance was measured, and grades were assigned by experienced raters from the frontal and sagittal perspectives depending on the execution quality of the jumps. Furthermore, jumps were filmed and ultimately rated post-exercise. Differences in jump distance between various groups were assessed by multivariate analyses of variance (MANOVAs). Reliability was determined using Kendall’s coefficient of concordance.Results The jump distance was significantly greater in U16 skiers than in U11 skiers of both sexes and in skiers with good execution quality than in those with reduced or poor execution quality. Overall, jump distance in U16 skiers significantly differed between female (5.37 m with 95% CI [5.21, 5.53]) and male skiers (5.90 m with 95%CI [5.69, 6.10]). Slightly better inter-rater grading reliability was observed for video-based post-exercise (strong agreement) ratings than for live ratings (moderate agreement).Conclusion In competitive alpine skiers aged 7 to 15 years, jump performance increases with age, and around puberty, sex differences start to manifest. Our results highlight the importance of evaluating both jump distance and movement quality in youth skiers. To improve test-retest reliability, however, a video-based post-exercise evaluation is recommended.

IntroductionAttention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by attention problems, excessive activity, and impulsivity - occurring in approximately 13% of children 12–17 years of age, and as many as 16% of older adolescents 18–22 years of age, with a greater prevalence in boys than girls. ADHD frequently co-occurs with specific learning disorder (LD), a neurodevelopmental disorder characterized by difficulties learning and using academic skills, such as reading, writing, and mathematics. Taken together, ADHD and/or LD are common among high school students and college students and can influence performance on computerized tests used in concussion management. However, normative data for widely used computer-based measures used in concussion management do not include reference samples with ADHD and/or LD. Previous research has documented the expected frequency of obtaining low scores on computer-based neuropsychological test measures among healthy, uninjured individuals, but few studies have examined the frequency of obtaining low scores in athletes with neurodevelopmental diagnoses, such as ADHD and/or LD. This study examined the frequency of low scores (i.e., multivariate base rates) on the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT) for youth and young adults with self-reported ADHD and/or LD.MethodsThe sample included 174,878 adolescent and young adult student-athletes who completed pre-season baseline neurocognitive assessments, who were assigned to the following independent groups: ADHD only (n = 45,215), LD only (n = 54,223), ADHD and LD (n = 45,737), No ADHD or LD (n = 47,684; “control athletes”).ResultsBase rates of low scores were stratified by high school (e.g., 13–18) and collegiate age (e.g., 19–22) and sex. It was common for student athletes (all ages) with LD alone (i.e., 30–37%), or with both ADHD and LD (i.e., 24–31%), to obtain at least two low ImPACT composite scores, but not three low composite scores. However, it was relatively uncommon for control athletes (those without ADHD or LD) (i.e., 12–14%) or older athletes (ages 19–22) with ADHD (i.e., 14–15%) to obtain two (or more) low scores.DiscussionHaving information relating to the base rates of low scores among uninjured athletes enhances the interpretation of ImPACT results among the broader population of student-athletes with and without neurodevelopmental disorders.

Gene activity defines cell identity, drives intercellular communication, and underlies the functioning of multicellular organisms. We present the single-cell resolution atlas of gene activity of a fertile adult metazoan: Caenorhabditis elegans. This compendium comprises 180 distinct cell types and 19,657 expressed genes. We predict 7541 transcription factor expression profile associations likely responsible for defining cellular identity. We predict thousands of intercellular interactions across the C. elegans body and the ligand-receptor pairs that mediate them, some of which we experimentally validate. We identify 172 genes that show consistent expression across cell types, are involved in basic and essential functions, and are conserved across phyla; therefore, we present them as experimentally validated housekeeping genes. We developed the WormSeq application to explore these data. In addition to the integrated gene-to-systems biology, we present genome-scale single-cell resolution testable hypotheses that we anticipate will advance our understanding of the molecular mechanisms, underlying the functioning of a multicellular organism and the perturbations that lead to its malfunction.

BackgroundDisabling pansclerotic morphea (DPM) is a rare systemic inflammatory disorder, characterized by poor wound healing, fibrosis, cytopenias, hypogammaglobulinemia, and squamous-cell carcinoma. The cause is unknown, and mortality is high.MethodsWe evaluated four patients from three unrelated families with an autosomal dominant pattern of inheritance of DPM. Genomic sequencing independently identified three heterozygous variants in a specific region of the gene that encodes signal transducer and activator of transcription 4 (STAT4). Primary skin fibroblast and cell-line assays were used to define the functional nature of the genetic defect. We also assayed gene expression using single-cell RNA sequencing of peripheral-blood mononuclear cells to identify inflammatory pathways that may be affected in DPM and that may respond to therapy.ResultsGenome sequencing revealed three novel heterozygous missense gain-of-function variants in STAT4. In vitro, primary skin fibroblasts showed enhanced interleukin-6 secretion, with impaired wound healing, contraction of the collagen matrix, and matrix secretion. Inhibition of Janus kinase (JAK)-STAT signaling with ruxolitinib led to improvement in the hyperinflammatory fibroblast phenotype in vitro and resolution of inflammatory markers and clinical symptoms in treated patients, without adverse effects. Single-cell RNA sequencing revealed expression patterns consistent with an immunodysregulatory phenotype that were appropriately modified through JAK inhibition.ConclusionsGain-of-function variants in STAT4 caused DPM in the families that we studied. The JAK inhibitor ruxolitinib attenuated the dermatologic and inflammatory phenotype in vitro and in the affected family members. (Funded by the American Academy of Allergy, Asthma, and Immunology Foundation and others.).

ImportanceEvidence is lacking from randomized clinical trials of hypoglossal nerve stimulation in obstructive sleep apnea (OSA).ObjectiveTo evaluate the safety and effectiveness of targeted hypoglossal nerve stimulation (THN) of the proximal hypoglossal nerve in patients with OSA.Design, setting, and participantsThis randomized clinical trial (THN3) was conducted at 20 centers and included 138 patients with moderate to severe OSA with an apnea-hypopnea index (AHI) of 20 to 65 events per hour and body mass index (calculated as weight in kilograms divided by height in meters squared) of 35 or less. The trial was conducted from May 2015 through June 2018. Data were analyzed from January 2022 through January 2023.InterventionImplant with THN system; randomized 2:1 to activation at month 1 (treatment) or month 4 (control). All received 11 months of THN with follow-up at months 12 and 15, respectively.Main outcomes and measuresPrimary effectiveness end points comprised AHI and oxygen desaturation index (ODI) responder rates (RRs). Treatment responses at months 4 and 12/15 were defined as a 50% or greater reduction in AHI to 20 or less per hour and an ODI decrease of 25% or greater. Coprimary end points comprised (1) month 4 AHI and ODI RR in the treatment greater than the control group and (2) month 12/15 AHI and ODI RR in the entire cohort exceeding 50%. Secondary end points included sleep apnea severity (AHI and ODI) and patient-reported outcomes (Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, and EQ-5D visual analog scale).ResultsAmong 138 participants, the mean (SD) age was 56 (9) years, and 19 (13.8%) were women. Month 4 THN RRs were substantially greater in those in the treatment vs control group (AHI, 52.3% vs 19.6%; ODI, 62.5% vs 41.3%, respectively) with treatment-control standardized mean differences of 0.725 (95% CI, 0.360-1.163) and 0.434 (95% CI, 0.070-0.843) for AHI and ODI RRs, respectively. Months 12/15 RRs were 42.5% and 60.4% for AHI and ODI, respectively. Improvements in AHI, ODI, Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, and EQ-5D visual analog scale scores were all clinically meaningful (medium to large effect size). Two serious adverse events and 100 nonserious related adverse events were observed from the implant procedure or study protocol.Conclusions and relevanceThis randomized clinical trial found that THN demonstrated improvements in sleep apnea, sleepiness, and quality of life in patients with OSAs over an extended AHI and body mass index range without prior knowledge of pharyngeal collapse pattern. Clinically meaningful improvements in AHI and patient-reported responses compared favorably with those of distal hypoglossal nerve stimulation trials, although clinically meaningful differences were not definitive for ODI.Trial registrationClinicalTrials.gov Identifier: NCT02263859.

GlyCompareCT is a portable command-line tool to facilitate downstream glycomic data analyses, by addressing data inherent sparsity and non-independence. Inputting glycan abundances, users can run GlyCompareCT with one line of code to obtain the abundances of a minimal substructure set, named glycomotif, thereby quantifying hidden biosynthetic relationships between measured glycans. Optional parameters tuning and annotation are supported for personal preference. For complete details on the use and execution of this protocol, please refer to Bao et al. (2021).1.

Variations in N-glycosylation, which is crucial to glycoprotein functions, impact many diseases and the safety and efficacy of biotherapeutic drugs. Here, we present a protocol for using GlycoMME (Glycosylation Markov Model Evaluator) to study N-glycosylation biosynthesis from glycomics data. We describe steps for annotating glycomics data and quantifying perturbations to N-glycan biosynthesis with interpretable models. We then detail procedures to predict the impact of mutations in disease or potential glycoengineering strategies in drug development. For complete details on the use and execution of this protocol, please refer to Liang et al. (2020).1.