Understanding the genetic complexity of puberty timing across the allele frequency spectrum.

Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, which amplified the signaling of MC3R, a key nutritional sensor. Shared signals with menopause timing at genes involved in DNA damage response suggest that the ovarian reserve might signal centrally to trigger puberty. We also highlight body size-dependent and independent mechanisms that potentially link reproductive timing to later life disease.

Increases in Global and East Asian Nitrogen Trifluoride (NF3) Emissions Inferred from Atmospheric Observations.

Nitrogen trifluoride (NF3) is a potent and long-lived greenhouse gas that is widely used in the manufacture of semiconductors, photovoltaic cells, and flat panel displays. Using atmospheric observations from eight monitoring stations from the Advanced Global Atmospheric Gases Experiment (AGAGE) and inverse modeling with a global 3-D atmospheric chemical transport model (GEOS-Chem), we quantify global and regional NF3 emission from 2015 to 2021. We find that global emissions have grown from 1.93 ± 0.58 Gg yr-1 (± one standard deviation) in 2015 to 3.38 ± 0.61 Gg yr-1 in 2021, with an average annual increase of 10% yr-1. The available observations allow us to attribute significant emissions to China (0.93 ± 0.15 Gg yr-1 in 2015 and 1.53 ± 0.20 Gg yr-1 in 2021) and South Korea (0.38 ± 0.07 Gg yr-1 to 0.65 ± 0.10 Gg yr-1). East Asia contributes around 73% of the global NF3 emission increase from 2015 to 2021: approximately 41% of the increase is from emissions from China (with Taiwan included), 19% from South Korea, and 13% from Japan. For Japan, which is the only one of these three countries to submit annual NF3 emissions to UNFCCC, our bottom-up and top-down estimates are higher than reported. With increasing demand for electronics, especially flat panel displays, emissions are expected to further increase in the future.

Radiographic Findings Associated With Mild Hip Dysplasia in 3869 Patients Using a Deep Learning Measurement Tool.

Background: Hip dysplasia is considered one of the leading etiologies contributing to hip degeneration and the eventual need for total hip arthroplasty (THA). We validated a deep learning (DL) algorithm to measure angles relevant to hip dysplasia and applied this algorithm to determine the prevalence of dysplasia in a large population based on incremental radiographic cutoffs. Methods: Patients from the Osteoarthritis Initiative with anteroposterior pelvis radiographs and without previous THAs were included. A DL algorithm automated 3 angles associated with hip dysplasia: modified lateral center-edge angle (LCEA), Tönnis angle, and modified Sharp angle. The algorithm was validated against manual measurements, and all angles were measured in a cohort of 3869 patients (61.2 ± 9.2 years, 57.1% female). The percentile distributions and prevalence of dysplastic hips were analyzed using each angle. Results: The algorithm had no significant difference (P > .05) in measurements (paired difference: 0.3°-0.7°) against readers and had excellent agreement for dysplasia classification (kappa = 0.78-0.88). In 140 minutes, 23,214 measurements were automated for 3869 patients. LCEA and Sharp angles were higher and the Tönnis angle was lower (P < .01) in females. The dysplastic hip prevalence varied from 2.5% to 20% utilizing the following cutoffs: 17.3°-25.5° (LCEA), 9.4°-15.6° (Tönnis), and 41.3°-45.9° (Sharp). Conclusions: A DL algorithm was developed to measure and classify hips with mild hip dysplasia. The reported prevalence of dysplasia in a large patient cohort was dependent on both the measurement and threshold, with 12.4% of patients having dysplasia radiographic indices indicative of higher THA risk.

[Top 4 Research Studies of the month for Italian Primary Care Physicians: June 2024.] / La Top 4 di giugno 2024. Gli studi clinici che vale la pena conoscere se lavori nelle cure primarie in Italia.

This monthly article provides a collection of summaries of the most relevant studies identified as POEMs (patient-oriented evidence that matters) for Italian primary care physicians. 1) Although bleeding risk scores such as HAS-BLED and HEMORR2HAGE are widely recommended by guidelines for decision-making regarding long-term anticoagulation, their accuracy in primary care patients seems to be pretty terrible. Studies in the primary care setting that derive and then externally validate simple, pragmatic risk scores are needed. 2) Point-of-care ultrasound is increasingly finding a role at the bedside, and this study adds to that evidence base. In the patient with acute abdominal pain, point-of-care ultrasound has been shown to be highly accurate for diagnosis of appendicitis, small bowel obstruction, aneurysm - and now, acute diverticulitis. 3) According to a recent meta-analysis, rhythm control is associated with a lower risk of dementia and cognitive dysfunction than rate control. Most of the data come from middling quality studies, which likely overestimate the purported protective effects. 4) Limited quality research finds no difference in outcomes among common treatments for acute otitis externa, including antibiotic, steroid, antiseptic, or nonpharmacologic treatment. Given the low quality of trials conducted so far, it remains to be seen if larger, better studies will find out a difference, but for now the existing literature gives us little guidance.

Improving Social and Personal Rhythm Dysregulation in Young and Old Adults with Bipolar Disorder: Post-Hoc Analysis of a Feasibility Randomized Controlled Trial Using Virtual Reality-Based Intervention.

Introduction: Rehabilitative interventions employing technology play a crucial role in bipolar disorder (BD) treatment. The study aims to appraise the virtual reality (VR)-based cognitive remediation (CR) and the interpersonal rhythm approaches to treatment outcomes of BD across different age groups. Methods: Post-hoc analysis of a 12-week randomizedcontrolled cross-over feasibility trial involving people with mood disorders (BD, DSM-IV) aged 18-75 years old: thirty-nine exposed to the experimental VR-based CR vs 25 waiting list controls. People with BD relapse, epilepsy or severe eye diseases (due to the potential VR risks exposure) were excluded. Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) was used to measure the outcome. Results: Cases and controls did not statistically significantly differ in age and sex distributions. Personal rhythm scores improved over the study follow-up in the experimental vs the control group (APC = 8.7%; F = 111.9; p < 0.0001), both in young (18-45 years) (APC = 5.5%; F = 70.46; p < 0.0001) and, to a lesser extent, older (>46 years) adults (APC = 10.5%; F = 12.110; p = 0.002). Conclusions: This study observed improved synchronization of personal and social rhythms in individuals with BD after a virtual reality cognitive remediation intervention, particularly in social activity, daily activities, and chronotype, with greater benefits in the younger population.

Fluid inertia controls mineral precipitation and clogging in pore to network-scale flows.

Mineral precipitation caused by fluid mixing presents complex control and predictability challenges in a variety of natural and engineering processes, including carbon mineralization, geothermal energy, and microfluidics. Precipitation dynamics, particularly under the influence of fluid flow, remain poorly understood. Combining microfluidic experiments and three-dimensional reactive transport simulations, we demonstrate that fluid inertia controls mineral precipitation and clogging at flow intersections, even in laminar flows. We observe distinct precipitation regimes as a function of Reynolds number (Re). At low Reynolds numbers (Re < 10), precipitates form a thin, dense layer along the mixing interface, which shuts precipitation off, while at high Reynolds numbers (Re > 50), strong three-dimensional flows significantly enhance precipitation over the entire intersection, resulting in rapid clogging. When injection rates from two inlets are uneven, flow symmetry-breaking leads to unexpected flow bifurcation phenomena, which result in enhanced concurrent precipitation in both downstream channels. Finally, we extend our findings to rough channel networks and demonstrate that the identified inertial effects on precipitation at the intersection scale are also present and even more dramatic at the network scale. This study sheds light on the fundamental mechanisms underlying mixing-induced mineral precipitation and provides a framework for designing and optimizing processes involving mineral precipitation.

Modern multiligament knee injury surgical reconstruction techniques can achieve excellent knee function and patient satisfaction, with low complication rates.

PURPOSE: To report on the recovery of strength and functional capacity symmetry following multiligament knee surgical reconstruction (MLKR), as well as the capacity of athletes to return to sport. METHODS: This prospective cohort study recruited 47 patients undergoing MLKR between February 2018 and July 2021. Forty patients had full outcome assessment postoperatively at 6, 12 and 24 months and were included in the analysis, 75% were knee dislocation one injuries and 60% were injured playing sport. Patient-reported outcome measures (PROMs) assessed included the International Knee Documentation Committee score, the Knee Outcome Survey, the Lysholm Knee Score and the Tegner Activity Scale (TAS). Patient satisfaction was also assessed. Objective assessment included assessment of active knee flexion and extension range of motion (ROM), the single (single horizontal hop for distance [SHD]) and triple (triple horizontal hop for distance [THD]) hop tests for distance and peak isokinetic knee flexor/extensor torque. RESULTS: All PROMs significantly improved (p < 0.001) from presurgery to 24 months postsurgery. At 24 months, 70% of patients were satisfied with their sports participation. Active knee flexion (p < 0.0001) and extension (p < 0.0001) ROM significantly improved over time, as did the limb symmetry indices (LSIs) for the SHD (p < 0.0001), THD (p < 0.0001), peak knee extensor (p < 0.0001) and flexor (p = 0.012) torque. While LSIs for the SHD, THD and knee flexor strength tended to plateau by 12 months, knee extensor strength continued to improve from 12 to 24 months. CONCLUSIONS: The majority of patients undergoing modern MLKR surgical techniques and rehabilitation can achieve excellent knee function, with low complication rates. LEVEL OF EVIDENCE: Level IV.

Increasing aggregate size reduces single-cell organic carbon incorporation by hydrogel-embedded wetland microbes.

Microbial degradation of organic carbon in sediments is impacted by the availability of oxygen and substrates for growth. To better understand how particle size and redox zonation impact microbial organic carbon incorporation, techniques that maintain spatial information are necessary to quantify elemental cycling at the microscale. In this study, we produced hydrogel microspheres of various diameters (100, 250, and 500 µm) and inoculated them with an aerobic heterotrophic bacterium isolated from a freshwater wetland (Flavobacterium sp.), and in a second experiment with a microbial community from an urban lacustrine wetland. The hydrogel-embedded microbial populations were incubated with 13C-labeled substrates to quantify organic carbon incorporation into biomass via nanoSIMS. Additionally, luminescent nanosensors enabled spatially explicit measurements of oxygen concentrations inside the microspheres. The experimental data were then incorporated into a reactive-transport model to project long-term steady-state conditions. Smaller (100 µm) particles exhibited the highest microbial cell-specific growth per volume, but also showed higher absolute activity near the surface compared to the larger particles (250 and 500 µm). The experimental results and computational models demonstrate that organic carbon availability was not high enough to allow steep oxygen gradients and as a result, all particle sizes remained well-oxygenated. Our study provides a foundational framework for future studies investigating spatially dependent microbial activity in aggregates using isotopically labeled substrates to quantify growth.

Malnutrition in hospitalized adults in the United States, 2016-2019.

BACKGROUND: Malnutrition in hospitalized patients is associated increased length of stay, cost, readmission, and death. No recent studies have examined trends in prevalence or outcomes of hospitalized patients with a diagnosis of malnutrition. OBJECTIVES: To study the prevalence of malnutrition diagnostic codes and associated hospital outcomes in the United States between 2016 and 2019. METHODS: We conducted a retrospective trends study to identify use of malnutrition codes in hospitalizations in the National Inpatient Sample between 2016 and 2019. We used direct standardization by logistic regression to adjust outcomes of percutaneous gastrostomy tube placement, mechanical ventilation, and death for age, Gagne comorbidity score, and sex. We then used linear regression to test for trends over time by malnutrition type. RESULTS: Across all hospitalizations, codes for diagnoses of non-severe malnutrition and severe malnutrition were present in 3.7% and 4.1% of hospitalizations, respectively. Codes for any malnutrition increased over time, from 6.6% in 2016 to 8.6% in 2018 (p = .03). Codes for severe malnutrition increased from 3.3% to 4.7% (p = .01). Among hospitalizations with coded severe malnutrition diagnoses, there was a statistically significant decrease in adjusted rate of death over time (-0.54% per year, p = .03) which was not seen in hospitalizations without coded malnutrition diagnoses. CONCLUSIONS: Use of malnutrition diagnosis codes increased significantly from 2016 to 2019. During this time, mortality among hospitalizations with a diagnosis code for severe malnutrition decreased. Though the increased prevalence of malnutrition codes may represent a change in the clinical characteristics of hospitalized patients, the decline in mortality suggests some of the increase may be due to lower threshold for coding and assignment of the diagnosis to less ill patients.

Synchronized Temporal-spatial Analysis via Microscopy and Phoshoproteomics (STAMP) of Quiescence.

Tightly coordinated cell cycle regulation is essential for homeostasis. G 0 , or quiescence, is especially crucial for cells to respond to extracellular stimuli. Little is known about the mechanisms that establish the G 0 program, though the primary cilium (a key signaling hub formed only in G 0 ) is the most widely recognized marker. The study of ciliogenesis is challenging due to its small size, relative to the cell body. To address this gap in our understanding, we developed STAMP (Spatio-Temporal Analysis via Microscopy and Proteomics) to temporally map the changes in cellular landscape occurring in G 0 and ciliogenesis. Using synchronized RPE cells, we used fixed and live cell imaging combined with phosphoproteomics to uncover new signals and order them in these processes, which also allows further, more targeted, analyses (e.g., using genetic and pharmacological perturbations). We propose that STAMP is broadly applicable for studying temporal-spatial signaling processes and the underlying mechanisms in various biological contexts and cell types.

Sharing Data from the Human Tumor Atlas Network through Standards, Infrastructure, and Community Engagement.

The Data Coordinating Center (DCC) of the Human Tumor Atlas Network (HTAN) has played a crucial role in enabling the broad sharing and effective utilization of HTAN data within the scientific community. Data from the first phase of HTAN are now available publicly. We describe the diverse datasets and modalities shared, multiple access routes to HTAN assay data and metadata, data standards, technical infrastructure and governance approaches, as well as our approach to sustained community engagement. HTAN data can be accessed via the HTAN Portal, explored in visualization tools-including CellxGene, Minerva, and cBioPortal-and analyzed in the cloud through the NCI Cancer Research Data Commons nodes. We have developed a streamlined infrastructure to ingest and disseminate data by leveraging the Synapse platform. Taken together, the HTAN DCC's approach demonstrates a successful model for coordinating, standardizing, and disseminating complex cancer research data via multiple resources in the cancer data ecosystem, offering valuable insights for similar consortia, and researchers looking to leverage HTAN data.

Decreased "Polar Axis Angle" is Associated with Instability after Total Hip Arthroplasty: A New Method to Assess Functional Component Position on Lateral Seated Radiographs.

BACKGROUND: Research on hip instability has focused on establishing "safe" ranges of combined component position in supine posture or functional placement of the acetabular component based on the hip-spine relationship. A new angle, the polar axis angle (PAA), of the total hip arthroplasty (THA) components describes the concentricity of both components and can be evaluated in functional positions that confer a greater risk of instability (i.e., sitting). The goal of this study was to compare the polar axis angle in functional positions between patients who experienced a postoperative dislocation, and a matched control group who did not have a dislocation. METHODS: An institutional database was searched for patients experiencing a dislocation after primary THA. Patients who had postoperative full-length standing and seated lateral radiographs were included in the dislocator group. A control group of non-dislocator patients was matched 2:1 by age, body mass index (BMI), sex, and hip-spine classification. Radiographic measurements of the neck angle, acetabular ante-inclination, and polar axis angle (PAA) were performed by two separate blinded, trained reviewers. RESULTS: The lateral seated neck angle and lateral seated polar axis angle measurements were significantly lower in the dislocator groups (n = 37) when compared with the control group (n = 74) (23 versus 33 degrees, P < 0.001; 74 versus 83 degrees, P = 0.012, respectively). Significant differences were also observed in changes in the polar axes and neck angles between standing and seated positions (P < 0.001 and P < 0.001, respectively). When comparing patients who have mobile spines versus stiff spines within the dislocator group, there were no differences in the acetabular, neck, or polar axis angles. The effect of neck angle on the polar axis angle showed a linear trend across cohorts. CONCLUSIONS: Patients who experience postoperative instability have a significantly lower polar axis angle on lateral seated radiographs when matched for age, sex, BMI, and hip-spine classification. In addition, the lower seated polar axis angle is driven more strongly by decreased functional femoral anteversion, which emphasizes the role of functional femoral version on stability in THA.

Public Perception of Scrub Color and Style in Plastic Surgery.

Background: Scrubs have become widespread office attire for plastic surgeons. The purpose of this study is to evaluate the public perception of scrub color and style for plastic surgeons. Methods: A crowdsourced survey was performed via MTurk. Respondents were asked to rate images of a surgeon dressed in black, navy, blue, and green scrubs as well as traditional or fitted scrubs. Qualities including representativeness, skill, trustworthiness, knowledge, and compassion were rated on a Likert scale across all images. Analysis of variance and one-sided t test were used to analyze differences in means. Results: In total, 562 responses were collected. For female plastic surgeons, navy and blue scrubs were perceived to be superior to those wearing black for skill, representativeness, trustworthiness, and compassion (P < 0.05). For male plastic surgeons, navy and blue scrubs were superior to black for knowledge, skill, representativeness, trustworthiness, and compassion (P < 0.05). For skill and representativeness, navy was superior to green (P < 0.05). For representativeness, blue was superior to green (P < 0.05). For trustworthiness and compassion, green was superior to black (P < 0.05). Fitted scrubs were significantly preferred (P < 0.05) across all characteristics with the exception of representativeness in the subgroup of male plastic surgeons. Conclusions: Black scrubs are associated with more negative characteristics than navy or blue scrubs, which were found to be the most positively perceived. Fitted scrubs were associated with positive characteristics for both male and female surgeons. The purchase of fitted scrubs may be a worthwhile purchase to maximize the patient-physician relationship.

Anterior-Posterior Laxity in Midflexion After Posterior-Stabilized TKA Is Sensitive to MCL Tension in Passive Flexion: An in Vitro Biomechanical Study.

BACKGROUND: Knee instability in midflexion may contribute to patient dissatisfaction following total knee arthroplasty (TKA). Midflexion instability involves abnormal motions and tissue loading in multiple planes. Therefore, we quantified and compared the tensions carried by the medial and lateral collateral ligaments (MCL and LCL) following posterior-stabilized (PS) TKA through knee flexion, and then compared these tensions with those carried by the native knee. Finally, we examined the relationships between collateral ligament tensions and anterior tibial translation (ATT). METHODS: Eight cadaveric knees (from 5 male and 3 female donors with a mean age of 62.6 years and standard deviation of 10.9 years) underwent PS TKA. Each specimen was mounted to a robotic manipulator and flexed to 90°. ATT was quantified by applying 30 N of anterior force to the tibia. Tensions carried by the collateral ligaments were determined via serial sectioning. Robotic testing was also conducted on a cohort of 15 healthy native cadaveric knees (from 9 male and 6 female donors with a mean age of 36 years and standard deviation of 11 years). Relationships between collateral ligament tensions during passive flexion and ATT were assessed via linear and nonlinear regressions. RESULTS: MCL tensions were greater following PS TKA than in the native knee at 15° and 30° of passive flexion, by a median of ≥27 N (p = 0.002), while the LCL tensions did not differ. Median tensions following PS TKA were greater in the MCL than in the LCL at 15°, 30°, and 90° of flexion, by ≥4 N (p ≤ 0.02). Median tensions in the MCL of the native knee were small (≤11 N) and did not exceed those in the LCL (p ≥ 0.25). A logarithmic relationship was identified between MCL tension and ATT following TKA. CONCLUSIONS: MCL tensions were greater following PS TKA with this typical nonconforming PS implant than in the native knee. Anterior laxity at 30° of flexion was highly sensitive to MCL tension during passive flexion following PS TKA but not in the native knee. CLINICAL RELEVANCE: Surgeons face competing objectives when performing PS TKA: they can either impart supraphysiological MCL tension to reduce anterior-posterior laxity or maintain native MCL tensions that lead to heightened anterior-posterior laxity, as shown in this study.

Development and utility of a SARS-CoV-2 pseudovirus assay for compound screening and antibody neutralization assays.

Background: The highly infectious nature of SARS-CoV-2 necessitates using bio-containment facilities to study viral pathogenesis and identify potent antivirals. However, the lack of high-level bio-containment laboratories across the world has limited research efforts into SARS-CoV-2 pathogenesis and the discovery of drug candidates. Previous research has reported that non-replicating SARS-CoV-2 Spike-pseudotyped viral particles are effective tools to screen for and identify entry inhibitors and neutralizing antibodies. Methods: To generate SARS-CoV-2 pseudovirus, a lentiviral packaging plasmid p8.91, a luciferase expression plasmid pCSFLW, and SARS-CoV-2 Spike expression plasmids (Wild-type (D614G) or Delta strain) were co-transfected into HEK293 cells to produce a luciferase-expressing non-replicating pseudovirus which expresses SARS-CoV-2 spike protein on the surface. For relative quantitation, HEK293 cells expressing ACE2 (ACE2-HEK293) were infected with the pseudovirus, after which luciferase activity in the cells was measured as a relative luminescence unit. The ACE2-HEK293/Pseudovirus infection system was used to assess the antiviral effects of some compounds and plasma from COVID-19 patients to demonstrate the utility of this assay for drug discovery and neutralizing antibody screening. Results: We successfully produced lentiviral-based SARS-CoV2 pseudoviruses and ACE2-expressing HEK293 cells. The system was used to screen compounds for SARS-CoV-2 entry inhibitors and identified two compounds with potent activity against SARS-CoV-2 pseudovirus entry into cells. The assay was also employed to screen patient plasma for neutralizing antibodies against SARS-CoV-2, as a precursor to live virus screening, using successful hits. Significance: This assay is scalable and can perform medium-to high-throughput screening of antiviral compounds with neither severe biohazard risks nor the need for higher-level containment facilities. Now fully deployed in our resource-limited laboratory, this system can be applied to other highly infectious viruses by swapping out the envelope proteins in the plasmids used in pseudovirus production.

Functional remodeling of presynaptic voltage-gated calcium channels in superficial layers of the dorsal horn during neuropathic pain.

N- and P/Q-type voltage-gated Ca2+ channels are critical for synaptic transmission. While their expression is increased in the dorsal root ganglion (DRG) neuron cell bodies during neuropathic pain conditions, less is known about their synaptic remodeling. Here, we combined genetic tools with 2-photon Ca2+ imaging to explore the functional remodeling that occurs in central presynaptic terminals of DRG neurons during neuropathic pain. We imaged GCaMP6s fluorescence responses in an ex vivo spinal cord preparation from mice expressing GCaMP6s in Trpv1-Cre lineage nociceptors. We show that Ca2+ transient amplitude is increased in central terminals of these neurons after spared nerve injury, and that this increase is mediated by both N- and P/Q-type channels. We found that GABA-B receptor-dependent inhibition of Ca2+ transients was potentiated in the superficial layer of the dorsal horn. Our results provide direct evidence toward nerve injury-induced functional remodeling of presynaptic Ca2+ channels in Trpv1-lineage nociceptor terminals.

JWST detection of a supernova associated with GRB 221009A without an r-process signature.

Identifying the sites of r-process nucleosynthesis, a primary mechanism of heavy element production, is a key goal of astrophysics. The discovery of the brightest gamma-ray burst (GRB) to date, GRB 221009A, presented an opportunity to spectroscopically test the idea that r-process elements are produced following the collapse of rapidly rotating massive stars. Here we present James Webb Space Telescope observations of GRB 221009A obtained +168 and +170 rest-frame days after the gamma-ray trigger, and demonstrate that they are well described by a SN 1998bw-like supernova (SN) and power-law afterglow, with no evidence for a component from r-process emission. The SN, with a nickel mass of approximately 0.09 M ⊙, is only slightly fainter than the brightness of SN 1998bw at this phase, which indicates that the SN is not an unusual GRB-SN. This demonstrates that the GRB and SN mechanisms are decoupled and that highly energetic GRBs are not likely to produce significant quantities of r-process material, which leaves open the question of whether explosions of massive stars are key sources of r-process elements. Moreover, the host galaxy of GRB 221009A has a very low metallicity of approximately 0.12 Z ⊙ and strong H2 emission at the explosion site, which is consistent with recent star formation, hinting that environmental factors are responsible for its extreme energetics.

Five-Year Incidence of Progression to Osteoarthritis and Total Joint Arthroplasty in Patients Prescribed Glucagon-Like Peptide 1 Receptor Agonists.

BACKGROUND: Research has suggested that glucagon-like peptide-1 receptor agonists (GLP-1-RAs) may have therapeutic effects on osteoarthritis of the hip and knee, in addition to managing diabetes and obesity. However, there is a lack of understanding regarding the association between GLP-1-RA use and the diagnosis of osteoarthritis (OA) of the hip and knee. METHODS: A collaborative network analytics platform was queried for obese diabetic (n = 1,094,198), obese nondiabetic (n = 916,235), and nonobese diabetic (n = 157,305) patients who had an index visit between 2015 and 2017. Patients who had pre-existing hip and/or knee OA were excluded. A 1:1 propensity score matching was used to balance GLP-1-RA use in stratified cohorts for age, sex, race, body mass index, and hemoglobin A1c. The primary outcomes were rates of progression to hip OA, knee OA, major joint injections, total hip arthroplasty, and total knee arthroplasty. Cox proportional hazards models determined hazard ratios (HRs) between cohorts prescribed and not prescribed GLP-1-RAs. RESULTS: All patients had a five-year follow-up. Rates of progression to hip and knee OA were higher among the GLP-1-RA users in both obese diabetic (hip HR: 1.63, 95% confidence interval [CI]: 1.46 to 1.82; knee HR: 1.52, CI: 1.41 to 1.64) and nonobese diabetic (hip HR: 1.78, CI: 1.50 to 2.10; knee HR: 1.58, CI: 1.39 to 1.80) cohorts. These diabetic cohorts received higher rates of major joint injections, though there was no difference in rates of total hip arthroplasty or total knee arthroplasty. No differences in five-year outcomes were seen when comparing obese, nondiabetic patients who were prescribed GLP-1-RAs with obese, nondiabetic patients not exposed to GLP-1-RAs. CONCLUSIONS: This five-year analysis found a greater risk of progression to hip and knee OA among obese and non-obese diabetic GLP-1-RA users. Further studies should explore GLP-1-RA effects upon glucose management, weight loss, and lower extremity arthritis development. LEVEL OF EVIDENCE: III, retrospective cohort study.

SCIMAP: A Python Toolkit for Integrated Spatial Analysis of Multiplexed Imaging Data.

Multiplexed imaging data are revolutionizing our understanding of the composition and organization of tissues and tumors ("Catching up with Multiplexed Tissue Imaging," 2022). A critical aspect of such "tissue profiling" is quantifying the spatial relationships among cells at different scales from the interaction of neighboring cells to recurrent communities of cells of multiple types. This often involves statistical analysis of 107 or more cells in which up to 100 biomolecules (commonly proteins) have been measured. While software tools currently cater to the analysis of spatial transcriptomics data (Liu et al., 2022), there remains a need for toolkits explicitly tailored to the complexities of multiplexed imaging data including the need to seamlessly integrate image visualization with data analysis and exploration. We introduce SCIMAP, a Python package specifically crafted to address these challenges. With SCIMAP, users can efficiently preprocess, analyze, and visualize large datasets, facilitating the exploration of spatial relationships and their statistical significance. SCIMAP's modular design enables the integration of new algorithms, enhancing its capabilities for spatial analysis.