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Objective Individuals with a history of suicidality may be especially vulnerable to the adverse impact of COVID‐related stressors, but this vulnerability has not been demonstrated. This study examined the longitudinal effects of suicidality history (ideation only or attempt vs. none) and interactions with COVID‐related stressors (e.g., work interruptions, childcare challenges, and financial stress) on anxiety symptoms, depressive symptoms, and problematic drinking. Methods Longitudinal data from 517 participants were drawn from the National Institute on Alcohol Abuse and Alcoholism Natural History Protocol and COVID‐19 Pandemic Impact on Alcohol Study. Lifetime history of suicidality was assessed using the clinician administered Columbia‐Suicide Severity Rating Scale. Multiple regressions tested the interaction between suicidality history and COVID‐related stressors on clinical outcomes. Results Compared to individuals without any history of suicidality (79.9%; n = 413), individuals with a history of suicide ideation only (14.5%; n = 75) and suicide attempt (5.6%; n = 29) had higher anxiety symptoms, depressive symptoms, and problematic drinking during the pandemic. Significant interaction effects showed the associations between COVID‐related stressors and mental disorder symptoms were stronger among individuals with suicide attempt history than individuals without suicidality history. Conclusions History of suicide attempt in combination with high COVID‐related stressors put individuals at the greatest risk for pandemic mental disorder symptoms. Individuals with suicide attempt history may have lower coping resources to handle COVID‐related stressors. Suicide risk assessment and intervention to increase cognitive flexibility and emotional regulation skills may help these individuals manage emotional distress experienced during the COVID‐19 pandemic and beyond.

Abstract We describe the case of an 87‐year‐old gentleman referred to a metropolitan hospital in Sydney with pneumomediastinum complicating immunotherapy associated pneumonitis and recent bronchoscopic intervention. The contribution of pneumonitis in the setting of interstitial lung disease has been well described to developing pneumomediastinum however this is less clear in the setting of immunotherapy associated pneumonitis and to what extent bronchoscopic intervention compounds this risk.

Objective To assess outcomes related to Lupus Therapeutics’ Patient Advocates for Lupus Studies (LT‐PALS), a peer‐to‐peer lupus clinical trial (LCT) education program designed to improve representation of diverse groups in LCTs. Patients with lupus and clinical trial participation experience were trained as peer educators (PALs) providing trial‐agnostic education to trial‐naive patients with lupus. Methods We used a two‐arm, randomized pretest/posttest study design to evaluate outcomes related to LCT participation: knowledge, attitudes, self‐efficacy, and intentions to participate in an LCT. Five academic medical centers piloted the program. The intervention group (IG) individually received peer‐to‐peer education sessions with trained PALs, primarily via telephone; the control group (CG) received a 3‐week waiting period. We conducted within/between‐group t‐tests and multiple linear regressions with posttest scores as dependent variables and participation in LT‐PALS as the exposure variable. Results The sample (n = 136) included 64 IG and 72 CG participants, with 67.7% identifying as Black. At posttest, IG participants had higher knowledge (P

Abstract The hyporheic zone is a hotspot for biogeochemical cycling where interactions with mineral metals preserve the release and biodegradation of organic matter (OM). A small fraction of OM can still be exchanged between localized sediments and the overlying water column, and recent evidence suggests there exists a longitudinal structuring in sediment dissolved OM (DOM) chemistry across the continental United States (CONUS). In this study, we tested a hypothesis that water extractable sediment DOM chemistry could be explained by sediment metal contents and integrative watershed scale features at the CONUS scale. Crowdsourced samples were characterized for high resolution mass spectrometry and coupled with sediment metals determined via x‐ray fluorescence as well as with land cover and soil elemental information obtained from national databases. Our results highlight weak relationships between DOM chemistry and elemental composition at the CONUS scale indicating limited transferability of organo‐metal linkages into multi‐scale hydrobiogeochemical models.

Key Clinical Message Diffuse idiopathic skeletal hyperostosis (DISH) involves spine ligament ossification. Computer‐assisted navigation (CAN) effectively aids complex surgeries, such as anterior cervical osteotomy, to alleviate progressive DISH‐related dysphagia. Abstract We describe a 68‐year‐old man with sudden onset dysphagia to both solids and liquids. Radiographic Imaging revealed DISH lesions from C2 down to the thoracic spine. The patient was successfully treated with CAN anterior osteotomy and resection of DISH lesions from C3–C6 and had complete symptom relief within 2 weeks post‐operatively.

Abstract Background Melanoma mortality rates in the US are highest among older men, individuals of lower socioeconomic status (SES), and people of color. To better understand these inequities, a qualitative exploratory study was conducted in Northern and Southern California to generate knowledge about barriers and facilitators of awareness, prevention, and early detection of melanoma in lower SES Latinx and non‐Latinx White (NLW) individuals living in urban and semi‐rural areas. Methods Nineteen focus groups were conducted (N = 176 adult participants), stratified by race/ethnicity (Latinx, low‐income NLW), geography (semi‐rural, urban), and language (English and Spanish). Inductive and deductive thematic analysis was conducted, and the findings were organized using the socioecological model framework: individual, interpersonal, community, and health system/policy levels. Results Four socioecological themes describe how key factors affect knowledge, perceived risk, preventive behaviors, and melanoma screening. Individual level findings revealed that many participants were not familiar with melanoma, yet were willing to learn through trusted sources. Having brown or darker skin tone was perceived as being associated with lower risk for skin cancer. Interpersonally, social relationships were important influences for skin cancer prevention practice. However, for several Latinx and semi‐rural participants, conversations about melanoma prevention did not occur with family and peers. At the community level, semi‐rural participants reported distance or lack of transportation to a clinic as challenges for accessing dermatology care. Healthcare systems barriers included burdens of additional healthcare costs for dermatology visits and obtaining referral. Conclusions Varying factors influence the awareness levels, beliefs, and behaviors associated with knowledge, prevention, and early detection of melanoma among low‐income Latinx and NLW individuals and in semi‐rural areas. Results have implications for health education interventions. Navigation strategies that target individuals, families, and health care settings can promote improved prevention and early detection of melanoma in these communities.

Objective Quality of life (QoL) is inversely associated with alcohol misuse and is a key measure by which recovery from alcohol use disorder (AUD) might be assessed. Yet, the determinants of QoL are scarcely known. The authors examined three ways through which demographic characteristics, familial and early life factors, and psychopathology conferred risks for QoL, including unique direct effects, developmental pathways, and clinical risk Profiles. Methods Cross‐sectional data from 1095 adults (50.4% without AUD; 49.6% with AUD) who participated in the NIAAA Natural History Protocol from January 2015 to March 2022 were analyzed. Multivariable regressions, path analysis, and latent Profile analysis were conducted. Results AUD was uniquely associated with lower QoL, and adverse effects of child maltreatment history and psychopathology symptoms on QoL were of similar or larger magnitudes. Mediation analysis indicated family history of AUD and child maltreatment history were indirectly associated with lower QoL through higher attention‐deficit/hyperactivity disorder symptoms, higher depressive symptoms, and positive AUD diagnosis. Latent Profile analysis of an enriched set of clinical characteristics identified four latent Profiles capturing the full range of alcohol use behavior. Latent Profiles with greater severity of familial and early life factors, psychopathology, and problematic drinking showed dose‐response associations with lower levels of physical, psychological, social, and environment QoL. Conclusions A constellation of developmental and clinical characteristics disproportionately affects individuals with AUD and is negatively associated with QoL domains. To improve QoL, prevention and intervention need to target multiple factors, including history of child maltreatment, comorbid psychopathology, and problematic drinking itself.

Abstract Standard occupancy models enable unbiased estimation of occupancy by accounting for observation errors such as missed detections (false negatives) and, less commonly, incorrect detections (false positives). Occupancy models are fitted to data from repeated site visits in which surveyors record evidence of species presence. Use of indirect sign (e.g., scat, tracks) as evidence of presence can vastly improve survey efficiency for inconspicuous species but can also introduce additional sources of error. We developed a “multi‐sign” occupancy approach to model the detection process separately for unique sign types and used this method to improve estimates of occupancy dynamics for an inconspicuous species, the American pika (Ochotona princeps). We investigated how estimates of pika occupancy and environmental drivers differed under four increasingly realistic representations of the observation process: (1) perfect detection (commonly assumed for modeling pika occupancy), (2) standard occupancy model (single observation process without possibility of false detection), (3) multi‐sign with no false detections (non‐false positive model), and (4) multi‐sign with false detections (full model). For the multi‐sign occupancy models, we modeled the detection of each sign type (fresh scat, fresh haypiles, pika calls, and pika sightings) separately as a function of climatic and environmental covariates. Estimates of occupancy processes and inferences about environmental drivers were sensitive to different detection models. Simplified representations of the detection processes generally resulted in higher occupancy estimates and higher turnover rates than the full multi‐sign model. Environmental drivers also varied in their influence on occupancy models, where (e.g.) forb cover was estimated to more strongly influence occupancy in the full multi‐sign model than the simpler models. As has been reported previously in other contexts, unmodeled heterogeneity in the observation process can lead to biases in occupancy processes and uncertainty in the relationships between occupancy and environmental covariates. Overall, our multi‐sign approach to dynamic occupancy modeling, which accounts for spatio‐temporal variation in reliability among sign types, has strong potential to generate more realistic estimates of occupancy dynamics for inconspicuous species.

Background Acute ischemic stroke attributed to basilar artery occlusion (BAO) results in high rates of death and significant morbidity. Endovascular thrombectomy an effective treatment for BAO, but imaging parameters that predict a favorable response to thrombectomy are not well defined. We determined which imaging parameters were associated with poor outcome in patients with BAO treated by thrombectomy. Methods We performed a retrospective cohort study of patients with BAO who underwent thrombectomy at multiple international stroke centers. All patients underwent computed tomography or magnetic resonance perfusion imaging before treatment. Clinical and imaging variables were measured and correlated to poor functional outcomes (modified Rankin scale score ≥4) after thrombectomy. Imaging variables included the following: Critical Area Perfusion Score, Posterior Circulation Alberta Stroke Program Early Computed Tomography Score, ischemic core volume (30% cerebral blood flow on computed tomography perfusion or diffusion‐weighted imaging), and volume of time to maximum >10 seconds. Clinical and imaging variables associated with poor functional outcome were assessed by a multivariable binary logistic regression analysis. Results A total of 102 patients were included in the study. Median patient age was 66.5 years (interquartile range [IQR], 55–78), median presentation National Institutes of Health Stroke Scale score was 14 (IQR, 7–23), and the median time from last seen normal was 4 hours (IQR, 1:52–9:20). Patient age (odds ratio [OR], 1.37 per 5‐year increment [95% CI, 1.08–1.72]; P=0.008), presentation National Institutes of Health Stroke Scale score (OR, 1.11 [95% CI, 1.04–1.18]; P=0.001), successful reperfusion after thrombectomy (OR, 0.03 [95% CI, 0.003–0.25]; P=0.002), Posterior Circulation Alberta Stroke Program Early Computed Tomography Score ≤6 (OR, 11.40 [95% CI, 1.73–75]; P=0.011), and Critical Area Perfusion Score >3 (OR, 26.22 [95% CI, 1.07–642]; P=0.045) independently predicted poor outcome after BAO thrombectomy. Ischemic core volume (30% cerebral blood flow) and volume of time to maximum >10 seconds did not predict poor outcome. Conclusion Age, National Institutes of Health Stroke Scale presentation, unsuccessful reperfusion, Critical Area Perfusion Score >3, and Posterior Circulation Alberta Stroke Program Early Computed Tomography Score ≤6 are independently associated with poor outcome after BAO thrombectomy.

Abstract Purpose This study aimed to develop and characterize a closed intra‐articular fracture (IAF) mediated post‐traumatic osteoarthritis (PTOA) model in rats to serve as a testbed for putative disease modifying interventions. Methods Male rats were subject to a 0 Joule (J), 1 J, 3 J, or 5 J blunt‐force impact to the lateral aspect of the knee and allowed to heal for 14 and 56 days. Micro‐CT was performed at time of injury and at the specified endpoints to assess bone morphometry and bone mineral density measurements. Cytokines and osteochondral degradation markers were assayed from serum and synovial fluid via immunoassays. Histopathological analyses were performed on decalcified tissues and assessed for evidence of osteochondral degradation. Results High‐energy (5 J) blunt impacts consistently induced IAF to the proximal tibia, distal femur, or both while lower energy (1 J and 3 J) impacts did not. CCL2 was found to be elevated in the synovial fluid of rats with IAF at both 14‐ and 56‐days post‐injury while COMP and NTX‐1 were upregulated chronically relative to sham controls. Histological analysis showed increased immune cell infiltration, increased osteoclasts and osteochondral degradation with IAF relative to sham. Conclusion Based on results from the current study, our data indicates that a 5 J blunt‐forced impact adequately and consistently induces hallmark osteoarthritic changes to the articular surface and subchondral bone at 56 days after IAF. Marked development of PTOA pathobiology suggest this model will provide a robust testbed for screening putative disease modifying interventions that might be translated to the clinic for militarily relevant, high‐energy joint injuries.

Abstract The regulatory path for drug approval is increasingly well defined. Drugs for the treatment of Alzheimer disease (AD) need to show statistically significant benefit over placebo with respect to cognitive and functional measures, with the Clinical Dementia Rating scale and Alzheimer's Disease Assessment Scale–Cognitive Subscale being among the most often used instruments in AD clinical trials. In contrast, there are no validated instruments for use in clinical trials of drugs for the treatment of dementia with Lewy bodies. This poses challenges for drug development because the regulatory pathway to drug approval requires demonstrable efficacy measures. In December 2021, the Lewy Body Dementia Association advisory group met with representatives from the US Food and Drug Administration to discuss the lack of approved drugs and treatments, discernment of efficacy measures, and identification of biomarkers. Highlights The Lewy Body with Dementia Association convened a listening session with the US Food and Drug Administration on dementia with Lewy bodies (DLB) and clinical trial design. Gaps include DLB‐specific measures, alpha synuclein biomarkers, and coexisting pathologies. DLB clinical trial design should focus on clinical value and disease specificity.

Terrain irregularities in natural environments present mobility challenges for autonomous robots and vehicles. Loosely consolidated sandy slopes flow unpredictably when perturbed, often leading to locomotion failure. Systematic experiments with various robot morphologies on flowable terrains feature open‐loop quasistatic gait strategies that remodel the terrain to aid locomotor kinematics. On a sloped terrain of granular media near the critical angle, a laboratory‐scale rover robot induces a flow via a localized fluidization gait to remodel local terrain and succeed in locomotion. A Bayesian optimization machine learning approach that modulates this gait strategy then finds a pattern of selectively fluidizing and solidifying terrain to climb slopes rapidly. In a biped walker robot, a cleated foot design dynamically manipulates the stress fields of flowable slopes. The deeply submerged cleats remodel the shear response of the material by creating jammed regions behind them which then improve forward progression by reducing slip when compared to a flat foot. The “robophysics” approach of systematic experiments exploring terrain reconfiguration combined with future machine learning models of flowable terrain evolution can augment gait discovery for future robots.

Abstract Background To reduce suicide in females with mood disorders, it is critical to understand brain substrates underlying their vulnerability to future suicidal ideation and behaviors (SIBs) in adolescence and young adulthood. In an international collaboration, grey and white matter structure was investigated in adolescent and young adult females with future suicidal behaviors (fSB) and ideation (fSI), and without SIBs (fnonSIB). Methods Structural (n = 91) and diffusion‐weighted (n = 88) magnetic resonance imaging scans at baseline and SIB measures at follow‐up on average two years later (standard deviation, SD = 1 year) were assessed in 92 females [age(SD) = 16.1(2.6) years] with bipolar disorder (BD, 28.3%) or major depressive disorder (MDD, 71.7%). One‐way analyses of covariance comparing baseline regional grey matter cortical surface area, thickness, subcortical grey volumes, or white matter tensor‐based fractional anisotropy across fSB (n = 40, 43.5%), fSI (n = 33, 35.9%) and fnonSIB (n = 19, 20.6%) groups were followed by pairwise comparisons in significant regions (p

Background We characterized the treatment preferences, care setting, and end‐of‐life outcomes among patients with advanced heart failure supported by a collaborative home‐based model of palliative care. Methods and results This decedent cohort study included 250 patients with advanced heart failure who received collaborative home‐based palliative care for a median duration of 1.9 months of follow‐up in Ontario, Canada, from April 2013 to July 2019. Patients were categorized into 1 of 4 groups according to their initial treatment preferences. Outcomes included location of death (out of hospital versus in hospital), changes in treatment preferences, and health service use. Among patients who initially prioritized quantity of life, 21 of 43 (48.8%) changed their treatment preferences during follow‐up (mean 0.28 changes per month). The majority of these patients changed their preferences to avoid hospitalization and focus on comfort at home (19 of 24 changes, 79%). A total of 207 of 250 (82.8%) patients experienced an out‐of‐hospital death. Patients who initially prioritized quantity of life had decreased odds of out‐of‐hospital death (versus in‐hospital death; adjusted odds ratio, 0.259 [95% CI, 0.097–0.693]) and more frequent hospitalizations (mean 0.45 hospitalizations per person‐month) compared with patients who initially prioritized quality of life at home. Conclusions Our results yield a more detailed understanding of the interaction of advanced care planning and patient preferences. Shared decision making for personalized treatment is dynamic and can be enacted earlier than at the very end of life.

Summary Lactiplantibacillus plantarum (formerly Lactobacillus plantarum) is a lactic acid bacteria species found on plants that is essential for many plant food fermentations. In this study, we investigated the intraspecific phenotypic and genetic diversity of 13 L. plantarum strains isolated from different plant foods, including fermented olives and tomatoes, cactus fruit, teff injera, wheat boza and wheat sourdough starter. We found that strains from the same or similar plant food types frequently exhibited similar carbohydrate metabolism and stress tolerance responses. The isolates from acidic, brine‐containing ferments (olives and tomatoes) were more resistant to MRS adjusted to pH 3.5 or containing 4% w/v NaCl, than those recovered from grain fermentations. Strains from fermented olives grew robustly on raffinose as the sole carbon source and were better able to grow in the presence of ethanol (8% v/v or sequential exposure of 8% (v/v) and then 12% (v/v) ethanol) than most isolates from other plant types and the reference strain NCIMB8826R. Cell free culture supernatants from the olive‐associated strains were also more effective at inhibiting growth of an olive spoilage strain of Saccharomyces cerevisiae. Multi‐locus sequence typing and comparative genomics indicated that isolates from the same source tended to be genetically related. However, despite these similarities, other traits were highly variable between strains from the same plant source, including the capacity for biofilm formation and survival at pH 2 or 50°C. Genomic comparisons were unable to resolve strain differences, with the exception of the most phenotypically impaired and robust isolates, highlighting the importance of utilizing phenotypic studies to investigate differences between strains of L. plantarum. The findings show that L. plantarum is adapted for growth on specific plants or plant food types, but that intraspecific variation may be important for ecological fitness and strain coexistence within individual habitats.

Abstract The availability of genomic and proteomic data from across the tree of life has made it possible to infer features of the genome and proteome of the last universal common ancestor (LUCA). A number of studies have done so, all using a unique set of methods and bioinformatics databases. Here, we compare predictions across eight such studies and measure both their agreement with one another and with the consensus predictions among them. We find that some LUCA genome studies show a strong agreement with the consensus predictions of the others, but that no individual study shares a high or even moderate degree of similarity with any other individual study. From these observations, we conclude that the consensus among studies provides a more accurate depiction of the core proteome of the LUCA and its functional repertoire. The set of consensus LUCA protein family predictions between all of these studies portrays a LUCA genome that, at minimum, encoded functions related to protein synthesis, amino acid metabolism, nucleotide metabolism, and the use of common, nucleotide‐derived organic cofactors.

Objective Interindividual variation in responses to alcohol is substantial, posing challenges for medical management and for understanding the biological underpinnings of alcohol use disorders (AUD). It is important to understand whether diverse alcohol responses such as sedation, which is predictive of risk and partly heritable, occur concurrently or independently from responses such as blackouts and withdrawal. We hypothesized that latent factors accounting for sources of variance in diverse alcohol response phenotypes could be identified in a large, deeply phenotyped sample of patients with AUD. Methods We factor analyzed 17 alcohol response related items from the Alcohol Dependence Scale (ADS) in 938 individuals diagnosed with AUD via structured clinical interviews. Demographic, genetic, and clinical characteristics were tested as predictors of the latent factors by multiple indicators, multiple causes analysis. Results The final factor solution included three alcohol response factors: Physical Symptoms, Perceptual Disturbances, and Neurobiological Effects. Both gender and genetic ancestry were identified as variables influencing alcohol response. Major depressive disorder positively predicted physical symptoms and aggression negatively predicted physical symptoms. Barratt's Impulsivity Scale total score predicted the Physical and Perceptual domains. Family history, average drinks per drinking day, and negative urgency (an impulsivity measure) predicted all three domains. Conclusions Diverse items from the ADS concurrently load onto three correlated alcohol response factors rather than loading independently. Genetic ancestry and clinical characteristics predicted the severity of items that define the alcohol response factors even after accounting for degree of alcohol consumption. Co‐occurring phenotypes point towards an underlying shared physiology of diverse alcohol responses.

Small cell lung cancer (SCLC) is a leading cause of cancer death worldwide, with few treatment options. Rovalpituzumab tesirine (Rova‐T) is an antibody‐drug conjugate that targets delta‐like 3 on SCLC cells to deliver a cytotoxic payload directly to tumor cells. In this study, the cardiac safety profile of Rova‐T was assessed by evaluating changes in QT interval, electrocardiogram (ECG) waveform, heart rate, and proarrhythmic adverse events (AEs) after treatment with Rova‐T in patients with previously treated extensive‐stage SCLC. Patients underwent ECG monitoring for 2 weeks after each of 2 i.v. infusions of 0.3 mg/kg Rova‐T over 30 minutes, administered 6 weeks apart. Forty‐six patients received at least one dose of Rova‐T. At the geometric mean Rova‐T maximum serum concentration of 7,940 ng/mL, ECG monitoring showed no significant changes in the Fridericia‐corrected QT (QTcF) interval; the upper limit of the 2‐sided 90% confidence interval did not exceed 10 msec for any time point. There were no clinically significant changes in QRS or PR intervals, ECG waveforms, or heart rate after Rova‐T administration. All patients experienced a treatment‐emergent AE (TEAE); 78% had a grade ≥ 3 TEAE, 59% had a serious TEAE, and 41% had a cardiac‐related TEAE. The TEAEs that might signal proarrhythmia tendencies were uncommon. Confirmed partial responses were observed in 24% of patients. Based on the evaluation of ECG data collected in this study from patients treated with Rova‐T at 0.3 mg/kg i.v. administered every 6 weeks, a QTcF effect of clinical concern can be excluded.

Objective To evaluate the usefulness of biomarkers to predict the evolution of patients suspected of systemic lupus erythematosus (SLE), designated as probable SLE (pSLE), into classifiable SLE according to the American College of Rheumatology (ACR) classification criteria. Methods Patients suspected of SLE were enrolled by lupus experts if they fulfilled three ACR criteria for SLE and were followed for approximately 1‐3 years to evaluate transition into ACR‐classifiable SLE. Individual cell‐bound complement activation products (CB‐CAPs), serum complement proteins (C3 and C4), and autoantibodies were measured by flow cytometry, turbidimetry, and enzyme‐linked immunosorbent assay, respectively. Blood levels of hydroxychloroquine (HCQ) were measured by mass spectrometry. A multianalyte assay panel (MAP), which includes CB‐CAPs, was also evaluated. A MAP of greater than 0.8 reflected the optimal cutoff for transition to SLE. Time to fulfillment of ACR criteria was evaluated by Kaplan‐Meier analysis and Cox proportional hazards model. Results Of the 92 patients with pSLE enrolled, 74 had one or two follow‐up visits 9‐35 months after enrollment for a total of 128 follow‐up visits. Overall, 28 patients with pSLE (30.4%) transitioned to ACR‐classifiable SLE, including 16 (57%) in the first year and 12 (43%) afterwards. A MAP score of greater than 0.8 at enrollment predicted transition to classifiable SLE during the follow‐up period (hazard ratio = 2.72; P = 0.012), whereas individual biomarkers or fulfillment of Systemic Lupus International Collaborating Clinics criteria did not. HCQ therapy was not associated with the prevention of transition to SLE. Conclusion Approximately one‐third of patients with pSLE transitioned within the study period. MAP of greater than 0.8 predicted disease evolution into classifiable SLE.

Abstract Objective Friedreich ataxia (FRDA) is the commonest hereditary ataxia in Caucasians. Most patients are homozygous for expanded GAA triplet repeats in the first intron of the frataxin (FXN) gene, involved in mitochondrial iron metabolism. Here, we used magnetoencephalography (MEG) to characterize the main determinants of FRDA‐related changes in intrinsic functional brain architecture. Methods Five minutes of MEG signals were recorded at rest from 18 right‐handed FRDA patients (mean age 27 years, 9 females; mean SARA score: 21.4) and matched healthy individuals. The MEG connectome was estimated as resting‐state functional connectivity (rsFC) matrices involving 37 nodes from six major resting state networks and the cerebellum. Source‐level rsFC maps were computed using leakage‐corrected broad‐band (3–40 Hz) envelope correlations. Post hoc median‐split was used to contrast rsFC in FRDA patients with different clinical characteristics. Nonparametric permutations and Spearman rank correlation test were used for statistics. Results High rank correlation levels were found between rsFC and age of symptoms onset in FRDA mostly between the ventral attention, the default‐mode, and the cerebellar networks; patients with higher rsFC developing symptoms at an older age. Increased rsFC was found in FRDA with later age of symptoms onset compared to healthy subjects. No correlations were found between rsFC and other clinical parameters. Conclusion Age of symptoms onset is a major determinant of FRDA patients' intrinsic functional brain architecture. Higher rsFC in FRDA patients with later age of symptoms onset supports compensatory mechanisms for FRDA‐related neural network dysfunction and position neuromagnetic rsFC as potential marker of FRDA neural reserve.

Abstract This case report demonstrates the possible subclinical adrenal and pancreatic involvement in immunocompromised patients (in particular those with lymphoma) with a CMV infection and the role of whole‐body 18F‐FDG PET/CT in detecting these lesions.