Insulin Resistance Increases TNBC Aggressiveness and Brain Metastasis via Adipocyte-derived Exosomes.

Patients with triple negative breast cancer (TNBC) and comorbid Type 2 Diabetes (T2D), characterized by insulin resistance of adipose tissue, have higher risk of metastasis and shorter survival. Adipocytes are the main non-malignant cells of the breast tumor microenvironment (TME). However, adipocyte metabolism is usually ignored in oncology and mechanisms that couple T2D to TNBC outcomes are poorly understood. Here we hypothesized that exosomes, small vesicles secreted by TME breast adipocytes, drive epithelial-to-mesenchymal transition (EMT) and metastasis in TNBC via miRNAs. Exosomes were purified from conditioned media of 3T3-L1 mature adipocytes, either insulin-sensitive (IS) or insulin-resistant (IR). Murine 4T1 cells, a TNBC model, were treated with exosomes in vitro (72h). EMT, proliferation and angiogenesis were elevated in IR vs. control and IS. Brain metastases showed more mesenchymal morphology and EMT enrichment in the IR group. MiR-145a-3p is highly differentially expressed between IS and IR, and potentially regulates metastasis. Significance: IR adipocyte exosomes modify TME, increase EMT and promote metastasis to distant organs, likely through miRNA pathways. We suggest metabolic diseases such as T2D reshape the TME, promoting metastasis and decreasing survival. Therefore, TNBC patients with T2D should be closely monitored for metastasis, with metabolic medications considered.

Predictors of Substance Use Initiation by Early Adolescence.

OBJECTIVE: Substance use initiation during early adolescence is associated with later development of substance use and mental health disorders. This study used various domains to predict substance use initiation, defined as trying any nonprescribed substance (e.g., alcohol, tobacco, cannabis), by age 12, using a large longitudinal data set. METHODS: Substance-naive youths from the Adolescent Brain Cognitive Development Study (ages 9-10; N=6,829) were followed for 3 years. A total of 420 variables were examined as predictors of substance use initiation, using a penalized logistic regression with elastic net; domains spanned demographic characteristics, self and peer involvement with substance use, parenting behaviors, mental and physical health, culture and environment, hormones, neurocognitive functioning, and structural neuroimaging. RESULTS: By age 12, 982 (14.4%) children reported substance initiation, with alcohol being the most common. Models with only self-report predictors had similar prediction performance to models adding hormones, neurocognitive factors, and neuroimaging predictors (AUCtest=0.66). Sociodemographic factors were the most robust predictors, followed by cultural and environmental factors, physical health factors, and parenting behaviors. The top predictor was a religious preference of Mormon (coefficient=-0.87), followed by a religious preference for Jewish (coefficient=0.32), and by Black youths (coefficient=-0.32). CONCLUSIONS: Sociodemographic variables were the most robust predictors of substance use initiation. Adding resource-intensive measures, including hormones, neurocognitive assessment, and structural neuroimaging, did not improve prediction of substance use initiation. The application of these large-scale findings in clinical settings could help to streamline and tailor prevention and early intervention efforts.

An evaluation of the COVID-19 self-service digital contact tracing system in New Zealand.

BACKGROUND: Digital contact tracing (DCT) aims to improve time-to-isolation (timeliness) and find more potentially exposed individuals (sensitivity) to enhance the utility of contact tracing. The aim of this study was to evaluate the public uptake of a DCT self-service survey and its integration with the Bluetooth exposure notification system within the New Zealand Covid Tracer App (NZCTA). METHODS: We adopted a retrospective cohort study design using community COVID-19 cases from February 2022 to August 2022 in New Zealand (1.2 million cases). We examined the proportion of cases completing a self-service survey and the time to complete the survey by age, sex and ethnicity. RESULTS: Overall, 66 % of cases completed their self-service survey. Completion was influenced by age, sex and ethnicity. The median completion time was 1.8 h (IQR 0.2, 17.2), with 95 % of those completing this survey doing so within 48 h of case identification. Around 13 % of all survey completers also uploaded their Bluetooth data, which resulted in an average of 663 cases per day notifying 4.5 contacts per case. CONCLUSION: The combination of high public uptake and rapid response times suggest self-service DCT could be a useful tool for future outbreaks, particularly if implemented in conjunction with manual processes and other DCT tools (e.g. Bluetooth) to address issues related to performance (sensitivity, timeliness), effectiveness, and health equity.

A case report of a distal radius fracture treated with a dorsal spanning plate augmented with fragment specific fixation.

Dorsal spanning plates are frequently utilized to manage comminuted intra-articular distal radius fractures, but there is little literature on combining them with augmented fixation in complex cases. We present a 43-year-old man who fell 5 ft onto his outstretched right hand. On examination, there was gross swelling and tenderness of the right wrist with no neurovascular deficit. Radiographs confirmed a comminuted intra-articular displaced distal radius fracture. He was treated with a dorsal spanning plate fixation combined with radiostyloid and volar buttress plates. Follow-up at 2 months showcased intact hardware with good fracture healing. The dorsal spanning plate was removed 4 months after the procedure with radiographs demonstrating adequate alignment and healing without failure. The patient reported no complaints and minimal functional disability. We highlight a case of augmenting a dorsal spanning plate with fragment-specific plate fixation for a comminuted intra-articular displaced distal radius fracture.

Functional connectivity development along the sensorimotor-association axis enhances the cortical hierarchy.

Human cortical maturation has been posited to be organized along the sensorimotor-association axis, a hierarchical axis of brain organization that spans from unimodal sensorimotor cortices to transmodal association cortices. Here, we investigate the hypothesis that the development of functional connectivity during childhood through adolescence conforms to the cortical hierarchy defined by the sensorimotor-association axis. We tested this pre-registered hypothesis in four large-scale, independent datasets (total n = 3355; ages 5-23 years): the Philadelphia Neurodevelopmental Cohort (n = 1207), Nathan Kline Institute-Rockland Sample (n = 397), Human Connectome Project: Development (n = 625), and Healthy Brain Network (n = 1126). Across datasets, the development of functional connectivity systematically varied along the sensorimotor-association axis. Connectivity in sensorimotor regions increased, whereas connectivity in association cortices declined, refining and reinforcing the cortical hierarchy. These consistent and generalizable results establish that the sensorimotor-association axis of cortical organization encodes the dominant pattern of functional connectivity development.

Population and contact tracer uptake of New Zealand's QR-code-based digital contact tracing app for COVID-19.

This study aimed to understand the population and contact tracer uptake of the quick response (QR)-code-based function of the New Zealand COVID Tracer App (NZCTA) used for digital contact tracing (DCT). We used a retrospective cohort of all COVID-19 cases between August 2020 and February 2022. Cases of Asian and other ethnicities were 2.6 times (adjusted relative risk (aRR) 2.58, 99 per cent confidence interval (95% CI) 2.18, 3.05) and 1.8 times (aRR 1.81, 95% CI 1.58, 2.06) more likely than Maori cases to generate a token during the Delta period, and this persisted during the Omicron period. Contact tracing organization also influenced location token generation with cases handled by National Case Investigation Service (NCIS) staff being 2.03 (95% CI 1.79, 2.30) times more likely to generate a token than cases managed by clinical staff at local Public Health Units (PHUs). Public uptake and participation in the location-based system independent of contact tracer uptake were estimated at 45%. The positive predictive value (PPV) of the QR code system was estimated to be close to nil for detecting close contacts but close to 100% for detecting casual contacts. Our paper shows that the QR-code-based function of the NZCTA likely made a negligible impact on the COVID-19 response in New Zealand (NZ) in relation to isolating potential close contacts of cases but likely was effective at identifying and notifying casual contacts.

Combination radiofrequency ablation and vertebral cement augmentation for spinal metastatic tumors: A systematic review and meta-analysis of safety and treatment outcomes.

Background: The treatment of spine metastases continues to pose a significant clinical challenge, requiring the integration of multiple therapeutic modalities to address the multifactorial aspects of this disease process. Radiofrequency ablation (RFA) and vertebral cement augmentation (VCA) are 2 less invasive modalities compared to open surgery that have emerged as promising strategies, offering the potential for both pain relief and preservation of vertebral stability. The utility of these approaches, however, remains uncertain and subject to ongoing investigation.This systematic review and meta-analysis evaluates the available evidence and synthesize the results of studies that have investigated the combination of RFA and VCA for the treatment of spinal metastases, with the goal of providing a comprehensive and up-to-date assessment of the efficacy and safety of this therapeutic approach. Methods: A literature search was conducted using the electronic databases PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus from their inception to May 4th, 2022 in accordance with PRISMA guidelines. Studies were included if they met the following criteria: 1) spine metastases treated with RFA in combination with VCA, 2) available data on at least one outcome (i.e., pain palliation, complications, local tumor control), 3) prospective or retrospective studies with at least 10 patients, and 4) English language. Meta-analyses were conducted in R (R Foundation for Statistical Computing; Vienna, Austria), using the meta package. Results: In the 25 included studies, a total of 947 patients (females=53.9%) underwent RFA + VCA for spinal metastatic tumors. Out of 1,163 metastatic lesions, the majority were located in the lumbar region (585/1,163 [50.3%]) followed by thoracic (519/1,163 [44.6%]), sacrum (39/1,163 [3.4%]), and cervical (2/1,163 [0.2%]). 48/72 [66.7%] metastatic lesions expanded into the posterior elements. Preoperative pathologic vertebral fractures were identified in 115/176 [65.3%] patients. Between pre-procedure pain scores and postprocedure pain scores, average follow-up (FU) was 4.41±2.87 months. Pain scores improved significantly at a short-term FU (1-6 months), with a pooled mean difference (MD) from baseline of 4.82 (95% CI, 4.48-5.16). The overall local tumor progression (LTP) rate at short-term FU (1-6 months) was 5% (95% CI, 1%-8%), at mid-term FU (6-12 months) was 22% (95% CI, 0%-48%), and at long-term FU (>12 months) was 5% (95% CI, 0%-11%). The pooled incidence of total complications was 1% (95% CI, 0%-1%), the most frequent of which were transient radicular pain and asymptomatic cement extravasation. Conclusions: The findings of this meta-analysis reveal that the implementation of RFA in conjunction with VCA for the treatment of spinal metastatic tumors resulted in a significant short-term reduction of pain, with minimal total complications. The LTP rate was additionally low. The clinical efficacy and safety of this technique are established, although further exploration of the long-term outcomes of RFA+VCA is warranted.

Generalizable Links Between Borderline Personality Traits and Functional Connectivity.

BACKGROUND: Symptoms of borderline personality disorder (BPD) often manifest during adolescence, but the underlying relationship between these debilitating symptoms and the development of functional brain networks is not well understood. Here, we aimed to investigate how multivariate patterns of functional connectivity are associated with borderline personality traits in large samples of young adults and adolescents. METHODS: We used functional magnetic resonance imaging data from young adults and adolescents from the HCP-YA (Human Connectome Project Young Adult) (n = 870, ages 22-37 years, 457 female) and the HCP-D (Human Connectome Project Development) (n = 223, ages 16-21 years, 121 female). A previously validated BPD proxy score was derived from the NEO Five-Factor Inventory. A ridge regression model with cross-validation and nested hyperparameter tuning was trained and tested in HCP-YA to predict BPD scores in unseen data from regional functional connectivity. The trained model was further tested on data from HCP-D without further tuning. Finally, we tested how the connectivity patterns associated with BPD aligned with age-related changes in connectivity. RESULTS: Multivariate functional connectivity patterns significantly predicted out-of-sample BPD scores in unseen data in young adults (HCP-YA ppermuted = .001) and older adolescents (HCP-D ppermuted = .001). Regional predictive capacity was heterogeneous; the most predictive regions were found in functional systems relevant for emotion regulation and executive function, including the ventral attention network. Finally, regional functional connectivity patterns that predicted BPD scores aligned with those associated with development in youth. CONCLUSIONS: Individual differences in functional connectivity in developmentally sensitive regions are associated with borderline personality traits.

Variation in Defining Retention After Onabotulinum Toxin A for Overactive Bladder: A Systematic Review.

IMPORTANCE: Urinary retention is a common adverse effect after intravesical injection of onabotulinum toxin A (BTX) for overactive bladder (OAB). Reported retention rates range from 1.6% to more than 40%. This variation may be due to varying definitions of retention in the literature. OBJECTIVE: We aimed to assess the variation in definitions of urinary retention across studies of BTX for the treatment of OAB. STUDY DESIGN: We performed a systematic review of studies of BTX for OAB by querying MEDLINE and EMBASE according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included original research studies on adults with overactive bladder treated with BTX and urinary retention reported as an outcome from January 2000 to December 2020. RESULTS: From 954 results, we identified 53 articles that met inclusion criteria. There were 6 definitions for urinary retention. The majority of studies (60.4%) reported initiating clean intermittent catheterization (CIC) as the metric for retention. Five (9.5%) studies provided no definition despite reporting retention as an adverse event. Twenty studies (37.7%) specified a postvoid residual volume (PVR) threshold for initiating CIC in asymptomatic patients; 19 (35.8%) specified a PVR threshold for CIC in symptomatic patients. The PVR thresholds ranged from 100 to 400 mL. Twenty-three studies (43.4%) did not address asymptomatic elevation of PVR, and 22 (41.5%) did not address how symptomatic patients were managed. CONCLUSIONS: Urinary retention after BTX injection is inconsistently defined in the literature. Lack of standardization in reporting retention after intravesical BTX prevents accurate assessment of the risk of urinary retention and comparison of outcomes between studies.

Patient-reported hip pain and function are worse among elite Nordic ski athletes competing in ski jumping versus Nordic combined: a cross-sectional analysis.

OBJECTIVES: Nordic ski athletes are at increased risk of developing hip pain and dysfunction secondary to femoroacetabular impingement syndrome (FAIS), but it is unclear whether hip symptomatology differs between ski jumping (SJ) and Nordic combined (NC) athletes. The purpose of this study was to compare patient-reported hip pain and dysfunction between elite Nordic ski athletes participating in SJ versus NC. METHODS: A cross-sectional study was conducted involving SJ and NC athletes who competed at the international and U.S. national levels during the 2021-2022 season. Subjects were excluded if they had hip surgery within two years prior to enrollment. Subjects were asked to undergo diagnostic workups for FAIS, including physical examination and plain radiographic imaging. Subjects were asked to complete a survey that collected information on athletic and training history and to complete the hip disability and osteoarthritis outcome score (HOOS). Demographics, athletic/training history, and HOOS sub-scores were compared between the SJ and NC groups using the Student's t-test, Wilcoxon rank-sum test, or Fisher's exact test, as appropriate. p-values < 0.05 were considered significant. RESULTS: Twenty-four athletes (13 SJ, 11 NC) were included in the study. There were no statistically significant differences in age, sex, BMI, or age of menarche between the two groups (all p â€‹> â€‹0.05). There were also no statistically significant differences in the number of prior sports participated in, total hours of participation in prior sports, or total hours of training in Nordic specialization (all p â€‹> â€‹0.05). Among the 18 athletes who underwent physical examination (9 SJ, 9 NC), there were no statistically significant inter-group differences in hip range of motion or incidence of positive impingement tests (all p â€‹> â€‹0.05). Among the 19 athletes who underwent imaging (9 SJ, 10 NC), there were no statistically significant inter-group differences in the incidence of cam or pincer morphology in at least one hip (all p â€‹> â€‹0.05). SJ athletes had statistically significantly worse HOOS sub-scores for hip symptoms and stiffness, hip function in sports/recreational activities, and hip-related quality of life compared to NC athletes (all p â€‹< â€‹0.05). CONCLUSION: Elite SJ athletes have worse self-reported hip function compared to elite NC athletes, despite comparable demographics, athletic history, and duration of ski training. LEVEL OF EVIDENCE: IV.

Evidence-Based Performance Measures for Reconstruction after Skin Cancer Resection: A Multidisciplinary Performance Measure Set.

BACKGROUND: The American Society of Plastic Surgeons commissioned the multidisciplinary Performance Measure Development Work Group on Reconstruction after Skin Cancer Resection to identify and draft quality measures for the care of patients undergoing skin cancer reconstruction. Included stakeholders were the American Academy of Otolaryngology-Head and Neck Surgery, the American Academy of Facial Plastic and Reconstructive Surgery, the American Academy of Dermatology, the American Society of Dermatologic Surgery, the American College of Mohs Surgery, the American Society for Mohs Surgery, and a patient representative. METHODS: Two outcome measures and five process measures were identified. The outcome measures included the following: (1) patient satisfaction with information provided by their surgeon before their facial procedure, and (2) postprocedural urgent care or emergency room use. The process measures focus on antibiotic stewardship, anticoagulation continuation and/or coordination of care, opioid avoidance, and verification of clear margins. RESULTS: All measures in this report were approved by the American Society of Plastic Surgeons Quality and Performance Measures Work Group and Executive Committee, and the stakeholder societies. CONCLUSION: The work group recommends the use of these measures for quality initiatives, Continuing Medical Education, Continuous Certification, Qualified Clinical Data Registry reporting, and national quality reporting programs.

Artificial intelligence and urology: ethical considerations for urologists and patients.

The use of artificial intelligence (AI) in medicine and in urology specifically has increased over the past few years, during which time it has enabled optimization of patient workflow, increased diagnostic accuracy and enhanced computer analysis of radiological and pathological images. However, before further use of AI is undertaken, possible ethical issues need to be evaluated to improve understanding of this technology and to protect patients and providers. Possible ethical issues that require consideration when applying AI in clinical practice include patient safety, cybersecurity, transparency and interpretability of the data, inclusivity and equity, fostering responsibility and accountability, and the preservation of providers' decision-making and autonomy. Ethical principles for the application of AI to health care and in urology are proposed to guide urologists, patients and regulators to improve use of AI technologies and guide policy-making.

Sensitive MRD Detection from Lymphatic Fluid after Surgery in HPV-Associated Oropharyngeal Cancer.

PURPOSE: Our goal was to demonstrate that lymphatic drainage fluid (lymph) has improved sensitivity in quantifying postoperative minimal residual disease (MRD) in locally advanced human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) compared with plasma, and leverage this novel biofluid for patient risk stratification. EXPERIMENTAL DESIGN: We prospectively collected lymph samples from neck drains of 106 patients with HPV (+) OPSCC, along with 67 matched plasma samples, 24 hours after surgery. PCR and next-generation sequencing were used to quantify cancer-associated cell-free HPV (cf-HPV) and tumor-informed variants in lymph and plasma. Next, lymph cf-HPV and variants were compared with TNM stage, extranodal extension (ENE), and composite definitions of high-risk pathology. We then created a machine learning model, informed by lymph MRD and clinicopathologic features, to compare with progression-free survival (PFS). RESULTS: Postoperative lymph was enriched with cf-HPV compared with plasma (P < 0.0001) and correlated with pN2 stage (P = 0.003), ENE (P < 0.0001), and trial-defined pathologic risk criteria (mean AUC = 0.78). In addition, the lymph mutation number and variant allele frequency were higher in pN2 ENE (+) necks than in pN1 ENE (+) (P = 0.03, P = 0.02) or pN0-N1 ENE (-) (P = 0.04, P = 0.03, respectively). The lymph MRD-informed risk model demonstrated inferior PFS in high-risk patients (AUC = 0.96, P < 0.0001). CONCLUSIONS: Variant and cf-HPV quantification, performed in 24-hour postoperative lymph samples, reflects single- and multifeature high-risk pathologic criteria. Incorporating lymphatic MRD and clinicopathologic feature analysis can stratify PFS early after surgery in patients with HPV (+) head and neck cancer. See related commentary by Shannon and Iyer, p. 1223.

Does Anterior Plating of Pelvic Ring Fractures Increase Infection Risk in Patients With Bladder or Urethral Injuries?

OBJECTIVES: Evaluate the effect of anterior fixation on infection in patients with operative pelvic fractures and bladder or urethral injuries. DESIGN: Retrospective. SETTING: Eight centers. PATIENT SELECTION CRITERIA: Adult patients with closed pelvic fractures with associated bladder or urethral injuries treated with anterior plating (AP), intramedullary screw (IS), or no anterior internal fixation (NAIF, including external fixation or no fixation). OUTCOME MEASURES AND COMPARISONS: Deep infection. RESULTS: There were 81 extraperitoneal injuries and 57 urethral injuries. There was no difference in infection between fixation groups across all urologic injuries (AP: 10.8%, IS: 0%, NAIF: 4.9%, P = 0.41). There was a higher rate of infection in the urethral injury group compared with extraperitoneal injuries (14.0% vs. 2.5%, P = 0.016). Among extraperitoneal injuries, specifically, there was no difference in deep infection related to fixation (AP: 2.6%, IS 0%, NAIF: 2.9%, P = 0.99). Among urethral injuries, there was no statistical difference in deep infection related to fixation (AP: 23.1%, IS: 0%, NAIF: 7.4%, P = 0.21). There was a higher rate of suprapubic catheter (SPC) use in urethral injuries compared with extraperitoneal injuries (57.9% vs. 4.9%, P < 0.0001). In the urethral injury group, SPC use did not have a statistically significant difference in infection rate (SPC: 18.2% vs. No SPC: 8.3%, P = 0.45). Early removal of the SPC before or during the definitive orthopaedic intervention did not significantly affect infection rate (early: 0% vs. delayed: 25.0%, P = 0.16). CONCLUSIONS: Surgeons should approach operative pelvic fractures with associated urologic injuries with caution given the high risk of infection. Further work must be done to elucidate the effect of anterior implants and SPC use and duration. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Outcomes of Humerus Nonunion Surgery in Patients With Initial Operative Fracture Fixation.

OBJECTIVES: To describe outcomes following humerus aseptic nonunion surgery in patients whose initial fracture was treated operatively and to identify risk factors for nonunion surgery failure in the same population. DESIGN: Retrospective case series. SETTING: Eight, academic, level 1 trauma centers. PATIENTS SELECTION CRITERIA: Patients with aseptic humerus nonunion (OTA/AO 11 and 12) after the initial operative management between 1998 and 2019. OUTCOME MEASURES AND COMPARISONS: Success rate of nonunion surgery. RESULTS: Ninety patients were included (56% female; median age 50 years; mean follow-up 21.2 months). Of 90 aseptic humerus nonunions, 71 (78.9%) united following nonunion surgery. Thirty patients (33.3%) experienced 1 or more postoperative complications, including infection, failure of fixation, and readmission. Multivariate analysis found that not performing revision internal fixation during nonunion surgery (n = 8; P = 0.002) and postoperative de novo infection (n = 9; P = 0.005) were associated with an increased risk of recalcitrant nonunion. Patient smoking status and the use of bone graft were not associated with differences in the nonunion repair success rate. CONCLUSIONS: This series of previously operated aseptic humerus nonunions found that more than 1 in 5 patients failed nonunion repair. De novo postoperative infection and failure to perform revision internal fixation during nonunion surgery were associated with recalcitrant nonunion. Smoking and use of bone graft did not influence the success rate of nonunion surgery. These findings can be used to give patients a realistic expectation of results and complications following humerus nonunion surgery. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

ACR Appropriateness Criteria® Breast Implant Evaluation: 2023 Update.

This document discusses the appropriate initial imaging in both asymptomatic and symptomatic patients with breast implants. For asymptomatic patients with saline implants, no imaging is recommended. If concern for rupture exists, ultrasound is usually appropriate though saline rupture is often clinically evident. The FDA recently recommended patients have an initial ultrasound or MRI examination 5 to 6 years after initial silicone implant surgery and then every 2 to 3 years thereafter. In a patient with unexplained axillary adenopathy with current or prior silicone breast implants, ultrasound and/or mammography are usually appropriate, depending on age. In a patient with concern for silicone implant rupture, ultrasound or MRI without contrast is usually appropriate. In the setting of a patient with breast implants and possible implant-associated anaplastic large cell lymphoma, ultrasound is usually appropriate as the initial imaging. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Similarity-based multimodal regression.

To better understand complex human phenotypes, large-scale studies have increasingly collected multiple data modalities across domains such as imaging, mobile health, and physical activity. The properties of each data type often differ substantially and require either separate analyses or extensive processing to obtain comparable features for a combined analysis. Multimodal data fusion enables certain analyses on matrix-valued and vector-valued data, but it generally cannot integrate modalities of different dimensions and data structures. For a single data modality, multivariate distance matrix regression provides a distance-based framework for regression accommodating a wide range of data types. However, no distance-based method exists to handle multiple complementary types of data. We propose a novel distance-based regression model, which we refer to as Similarity-based Multimodal Regression (SiMMR), that enables simultaneous regression of multiple modalities through their distance profiles. We demonstrate through simulation, imaging studies, and longitudinal mobile health analyses that our proposed method can detect associations between clinical variables and multimodal data of differing properties and dimensionalities, even with modest sample sizes. We perform experiments to evaluate several different test statistics and provide recommendations for applying our method across a broad range of scenarios.

Cryptogenic pyogenic liver abscess caused by Fusobacterium necrophorum in an immunocompetent patient.

Pyogenic liver abscesses are potentially fatal conditions that require prompt treatment with drainage and appropriate antimicrobial therapy. Fusobacterium necrophorum is a gram-negative rod that is found in the oral cavity, gastrointestinal tract and female genital tract. It is an extremely rare cause of liver abscess, particularly in the absence of risk factors or exposures. We describe an unusual case of a cryptogenic F. necrophorum hepatic abscess without a clear source despite extensive investigation in a young, immunocompetent patient without known risk factors or exposures for such an infection.

Personalized functional brain network topography is associated with individual differences in youth cognition.

Individual differences in cognition during childhood are associated with important social, physical, and mental health outcomes in adolescence and adulthood. Given that cortical surface arealization during development reflects the brain's functional prioritization, quantifying variation in the topography of functional brain networks across the developing cortex may provide insight regarding individual differences in cognition. We test this idea by defining personalized functional networks (PFNs) that account for interindividual heterogeneity in functional brain network topography in 9-10 year olds from the Adolescent Brain Cognitive Development℠ Study. Across matched discovery (n = 3525) and replication (n = 3447) samples, the total cortical representation of fronto-parietal PFNs positively correlates with general cognition. Cross-validated ridge regressions trained on PFN topography predict cognition in unseen data across domains, with prediction accuracy increasing along the cortex's sensorimotor-association organizational axis. These results establish that functional network topography heterogeneity is associated with individual differences in cognition before the critical transition into adolescence.

Harmonization of multi-site diffusion tensor imaging data for cervical and thoracic spinal cord at 1.5 T and 3 T using longitudinal ComBat.

MRI scanner hardware, field strengths, and sequence parameters are major variables in diffusion studies of the spinal cord. Reliability between scanners is not well known, particularly for the thoracic cord. DTI data was collected for the entire cervical and thoracic spinal cord in thirty healthy adult subjects with different MR vendors and field strengths. DTI metrics were extracted and averaged for all slices within each vertebral level. Metrics were examined for variability and then harmonized using longitudinal ComBat (longComBat). Four scanners were used: Siemens 3 T Prisma, Siemens 1.5 T Avanto, Philips 3 T Ingenia, Philips 1.5 T Achieva. Average full cord diffusion values/standard deviation for all subjects and scanners were FA: 0.63, σ = 0.10, MD: 1.11, σ = 0.12 × 10-3 mm2/s, AD: 1.98, σ = 0.55 × 10-3 mm2/s, RD: 0.67, σ = 0.31 × 10-3 mm2/s. FA metrics averaged for all subjects by level were relatively consistent across scanners, but large variability was found in diffusivity measures. Coefficients of variation were lowest in the cervical region, and relatively lower for FA than diffusivity measures. Harmonized metrics showed greatly improved agreement between scanners. Variability in DTI of the spinal cord arises from scanner hardware differences, pulse sequence differences, physiological motion, and subject compliance. The use of longComBat resulted in large improvement in agreement of all DTI metrics between scanners. This study shows the importance of harmonization of diffusion data in the spinal cord and potential for longitudinal and multisite clinical research and clinical trials.