Molecular Imaging in Gynecology: Beyond Cancer.

Gynecological pathologies account for approximately 4.5% of the overall global disease burden. Although cancers of the female reproductive system have understandably been the focus of a great deal of research, benign gynecological conditions-such as endometriosis, polycystic ovary syndrome, and uterine fibroids-have remained stubbornly understudied despite their astonishing ubiquity and grave morbidity. This historical inattention has frequently become manifested in flawed diagnostic and treatment paradigms. Molecular imaging could be instrumental in improving patient care on both fronts. In this Focus on Molecular Imaging review, we will examine recent advances in the use of PET, SPECT, MRI, and fluorescence imaging for the diagnosis and management of benign gynecological conditions, with particular emphasis on recent clinical reports, areas of need, and opportunities for growth.

Site-specific bioconjugation and nuclear imaging.

Monoclonal antibodies and antibody fragments have proven to be highly effective vectors for the delivery of radionuclides to target tissues for positron emission tomography (PET) and single-photon emission computed tomography (SPECT). However, the stochastic methods that have traditionally been used to attach radioisotopes to these biomolecules inevitably produce poorly defined and heterogeneous probes and can impair the ability of the immunoglobulins to bind their molecular targets. In response to this challenge, an array of innovative site-specific and site-selective bioconjugation strategies have been developed, and these approaches have repeatedly been shown to yield better-defined and more homogeneous radioimmunoconjugates with superior in vivo performance than their randomly modified progenitors. In this Current Opinion in Chemical Biology review, we will examine recent advances in this field, including the development - and, in some cases, clinical translation - of nuclear imaging agents radiolabeled using strategies that target the heavy chain glycans, peptide tags, and unnatural amino acids.

Spatially resolved cell atlas of the teleost telencephalon and deep homology of the vertebrate forebrain.

The telencephalon has undergone remarkable diversification and expansion throughout vertebrate evolution, exhibiting striking variations in structural and functional complexity. Nevertheless, fundamental features are shared across vertebrate taxa, such as the presence of distinct regions including the pallium, subpallium, and olfactory structures. Teleost fishes have a uniquely "everted" telencephalon, which has confounded comparisons of their brain regions to other vertebrates. Here we combine spatial transcriptomics and single nucleus RNA-sequencing to generate a spatially-resolved transcriptional atlas of the Mchenga conophorus cichlid fish telencephalon. We then compare cell-types and anatomical regions in the cichlid telencephalon with those in amphibians, reptiles, birds, and mammals. We uncover striking transcriptional similarities between cell-types in the fish telencephalon and subpallial, hippocampal, and cortical cell-types in tetrapods, and find support for partial eversion of the teleost telencephalon. Ultimately, our work lends new insights into the organization and evolution of conserved cell-types and regions in the vertebrate forebrain.

Interrogating the Theranostic Capacity of a MUC16-Targeted Antibody for Ovarian Cancer.

Aberrantly expressed glycans on mucins such as mucin-16 (MUC16) are implicated in the biology that promotes ovarian cancer (OC) malignancy. Here, we investigated the theranostic potential of a humanized antibody, huAR9.6, targeting fully glycosylated and hypoglycosylated MUC16 isoforms. Methods: In vitro and in vivo targeting of the diagnostic radiotracer [89Zr]Zr-DFO-huAR9.6 was investigated via binding experiments, immuno-PET imaging, and biodistribution studies on OC mouse models. Ovarian xenografts were used to determine the safety and efficacy of the therapeutic version, [177Lu]Lu-CHX-A″-DTPA-huAR9.6. Results: In vivo uptake of [89Zr]Zr-DFO-huAR9.6 supported in vitro-determined expression levels: high uptake in OVCAR3 and OVCAR4 tumors, low uptake in OVCAR5 tumors, and no uptake in OVCAR8 tumors. Accordingly, [177Lu]Lu-CHX-A″-DTPA-huAR9.6 displayed strong antitumor effects in the OVCAR3 model and improved overall survival in the OVCAR3 and OVCAR5 models in comparison to the saline control. Hematologic toxicity was transient in both models. Conclusion: PET imaging of OC xenografts showed that [89Zr]Zr-DFO-huAR9.6 delineated MUC16 expression levels, which correlated with in vitro results. Additionally, we showed that [177Lu]Lu-CHX-A″-DTPA-huAR9.6 displayed strong antitumor effects in highly MUC16-expressing tumors. These findings demonstrate great potential for 89Zr- and 177Lu-labeled huAR9.6 as theranostic tools for the diagnosis and treatment of OC.

Dynamic Computed Tomography of the Distal Radioulnar Joint Versus Magnetic Resonance Imaging in Detecting Foveal Tears of the Triangular Fibrocartilage Complex.

BACKGROUND: Diagnosis of foveal triangular fibrocartilage complex (TFCC) tears remains difficult. The purpose of this study was to evaluate whether dynamic computed tomography (CT) of the distal radioulnar joint (DRUJ) has a higher sensitivity in detecting foveal tears of the TFCC when compared with magnetic resonance imaging (MRI). METHODS: A database query identified all patients above the age of 18 years with suspected foveal TFCC injuries who underwent bilateral dynamic CT imaging of the DRUJ, static 3T MRI, and subsequent wrist arthroscopy. All patients had evidence of foveal tenderness on clinical examination. The imaging results were validated with wrist arthroscopy. RESULTS: Twelve patients with a mean age of 31 years (range, 18-53 years) were identified. Eight patients were diagnosed with a complete foveal detachment of the TFCC on wrist arthroscopy. Of the 8 patients with a foveal tear on DRUJ arthroscopy, only 3 had a preoperative physical examination suggestive of DRUJ instability. Magnetic resonance imaging identified foveal injuries in 4 of these 8 patients (sensitivity, 50%), and 3 of these were identified as only partial tears. Dynamic CT identified instability of DRUJ in 6 of 8 patients (sensitivity, 75%). Seven of 8 patients had imaging findings suggestive of a foveal tear when including either MRI or CT imaging (sensitivity, 88%). Of the 4 patients with an intact foveal attachment on arthroscopy, 3 (specificity, 75%) had a stable DRUJ on CT and all 4 (specificity, 100%) had an intact foveal attachment on MRI. CONCLUSION: Sixty-two percent of patients with foveal tears on arthroscopy have a stable DRUJ on clinical examination. When combining MRI and dynamic CT imaging of the DRUJ, the sensitivity of detecting a foveal TFCC tear approaches 88% compared with a gold standard of wrist arthroscopy.

Adult sex change leads to extensive forebrain reorganization in clownfish.

Sexual differentiation of the brain occurs in all major vertebrate lineages but is not well understood at a molecular and cellular level. Unlike most vertebrates, sex-changing fishes have the remarkable ability to change reproductive sex during adulthood in response to social stimuli, offering a unique opportunity to understand mechanisms by which the nervous system can initiate and coordinate sexual differentiation. This study explores sexual differentiation of the forebrain using single nucleus RNA-sequencing in the anemonefish Amphiprion ocellaris, producing the first cellular atlas of a sex-changing brain. We uncover extensive sex differences in cell type-specific gene expression, relative proportions of cells, baseline neuronal excitation, and predicted inter-neuronal communication. Additionally, we identify the cholecystokinin, galanin, and estrogen systems as central molecular axes of sexual differentiation. Supported by these findings, we propose a model of neurosexual differentiation in the conserved vertebrate social decision-making network spanning multiple subtypes of neurons and glia, including neuronal subpopulations within the preoptic area that are positioned to regulate gonadal differentiation. This work deepens our understanding of sexual differentiation in the vertebrate brain and defines a rich suite of molecular and cellular pathways that differentiate during adult sex change in anemonefish.

The Impact of COVID-19 on the Cardiovascular Health of Emerging Adults Aged 18-25: Findings From a Scoping Review.

There is limited knowledge regarding the cardiovascular impact of coronavirus disease 2019 (COVID-19) on emerging adults aged 18-25, a group that disproportionately contracts COVID-19. To guide future cardiovascular disease (CVD) research, policy, and practice, a scoping review was conducted to: (i) examine the impact of the COVID-19 pandemic on the cardiovascular health of emerging adults; and (ii) identify strategies to screen for and manage COVID-19-related cardiovascular complications in this age group. A comprehensive search strategy was applied to several academic databases and grey literature sources. An updated search yielded 6738 articles, 147 of which were extracted and synthesized. Reports identified COVID-19-associated cardiac abnormalities, vascular alterations, and multisystem inflammatory syndrome in emerging adults; based on data from student-athlete samples, prevalence estimates of myocarditis and cardiac abnormalities were 0.5%-3% and 0%-7%, respectively. Obesity, hypertension, CVD, congenital heart disease, and marginalization are potential risk factors for severe COVID-19, related cardiovascular complications, and mortality in this age group. As a screening modality for COVID-19-associated cardiac involvement, it is recommended that cardiac magnetic resonance imaging be indicated by a positive cardiac history and/or abnormal "triad" testing (cardiac troponin, electrocardiogram, and transthoracic echocardiogram) to improve diagnostic utility. To foster long-term cardiovascular health among emerging adults, cardiorespiratory fitness, health literacy and education, and telehealth accessibility should be priorities of health policy and clinical practice. Ultimately, surveillance data from the broader emerging adult population will be crucial to assess the long-term cardiovascular impact of both COVID-19 infection and vaccination, guide screening and management protocols, and inform CVD prevention efforts.

Il existe peu de données portant sur les répercussions de la maladie à coronavirus 2019 (COVID-19) sur le plan cardiovasculaire chez les jeunes adultes âgés de 18 à 25 ans, un groupe contractant la COVID-19 de façon disproportionnée. Afin d'orienter la recherche, les poli-tiques et les pratiques en matière de maladies cardiovasculaires (MCV), un examen exploratoire a été réalisé dans le but i) d'examiner les conséquences de la pandémie de la COVID-19 sur la santé cardiovasculaire des jeunes adultes, et ii) de proposer des stratégies de dépistage et de prise en charge des complications cardiovasculaires associées à la COVID-19 chez les personnes de cette tranche d'âge. Une recherche initiale exhaustive a été réalisée dans plusieurs bases de données universitaires et sources de littérature grise. Les résultats actualisés de cette recherche ont permis de recenser 6 738 articles, dont 147 ont été extraits et synthétisés. Les rapports faisaient état d'anomalies cardiaques, d'altérations vasculaires et de cas du syndrome inflammatoire multisystémique, tous associés à la COVID-19 chez les jeunes adultes. À la lumière des données sur les échantillons d'étudiants-athlètes, la prévalence des myocardites et des anomalies cardiaques se situait respectivement entre 0,5 et 3 %, et entre 0 et 7 % environ. Chez ce même groupe d'âge, l'obésité, l'hypertension, les MCV, les cardiopathies congénitales et la marginalisation constituent des facteurs de risque de COVID-19 sévère, de complications cardiovasculaires associées à la COVID-19 et de mortalité. Dans le cadre du dépistage des atteintes cardiaques associées à la COVID-19, il est recommandé, pour améliorer l'utilité diagnostique, d'indiquer l'imagerie par résonance magnétique cardiaque lors de l'existence d'antécédents cardiaques ou à la suite d'une « triade ¼ de dépistages anormaux (la troponine cardiaque, l'électrocardiogramme et l'échocardiographie transthoracique). Afin de favoriser une bonne santé cardiovasculaire à long terme chez les jeunes adultes, il est recommandé que la capacité cardiorespiratoire, la littératie dans le domaine de la santé, l'éducation et l'accès à la télésanté soient intégrés à titre de priorités dans les politiques de santé et la pratique clinique. En définitive, les données de surveillance portant sur cette large tranche d'âge seront essentielles pour évaluer les répercussions cardiovasculaires à long terme (autant celles d'infections à la COVID-19 que celles de la vaccination), pour orienter les protocoles de dépistage et de prise en charge, ainsi que pour éclairer les efforts de prévention des MCV.

Natural variation in oxytocin receptor signaling causes widespread changes in brain transcription: a link to the natural killer gene complex.

Oxytocin (OXT) is a highly conserved neuropeptide that modulates social cognition, and variation in its receptor gene (Oxtr) is associated with divergent social phenotypes. The cellular mechanisms connecting Oxtr genotype to social phenotype remain obscure. We exploit an association between Oxtr polymorphisms and striatal-specific OXTR density in prairie voles to investigate how OXTR signaling influences the brain transcriptome. We discover widespread, OXTR signaling-dependent transcriptomic changes. Interestingly, OXTR signaling robustly modulates gene expression of C-type lectin-like receptors (CTLRs) in the natural killer gene complex, a genomic region associated with immune function. CTLRs are positioned to control microglial synaptic pruning; a process important for shaping neural circuits. Similar relationships between OXTR RNA and CTLR gene expression were found in human striatum. These data suggest a potential molecular mechanism by which variation in OXTR signaling due to genetic background and/or life-long social experiences, including nurturing/neglect, may affect circuit connectivity and social behavior.

Cellular profiling of a recently-evolved social behavior in cichlid fishes.

Social behaviors are diverse in nature, but it is unclear how conserved genes, brain regions, and cell populations generate this diversity. Here we investigate bower-building, a recently-evolved social behavior in cichlid fishes. We use single nucleus RNA-sequencing in 38 individuals to show signatures of recent behavior in specific neuronal populations, and building-associated rebalancing of neuronal proportions in the putative homolog of the hippocampal formation. Using comparative genomics across 27 species, we trace bower-associated genome evolution to a subpopulation of glia lining the dorsal telencephalon. We show evidence that building-associated neural activity and a departure from quiescence in this glial subpopulation together regulate hippocampal-like neuronal rebalancing. Our work links behavior-associated genomic variation to specific brain cell types and their functions, and suggests a social behavior has evolved through changes in glia.

Direct speech reconstruction from sensorimotor brain activity with optimized deep learning models.

Objective.Development of brain-computer interface (BCI) technology is key for enabling communication in individuals who have lost the faculty of speech due to severe motor paralysis. A BCI control strategy that is gaining attention employs speech decoding from neural data. Recent studies have shown that a combination of direct neural recordings and advanced computational models can provide promising results. Understanding which decoding strategies deliver best and directly applicable results is crucial for advancing the field.Approach.In this paper, we optimized and validated a decoding approach based on speech reconstruction directly from high-density electrocorticography recordings from sensorimotor cortex during a speech production task.Main results.We show that (1) dedicated machine learning optimization of reconstruction models is key for achieving the best reconstruction performance; (2) individual word decoding in reconstructed speech achieves 92%-100% accuracy (chance level is 8%); (3) direct reconstruction from sensorimotor brain activity produces intelligible speech.Significance.These results underline the need for model optimization in achieving best speech decoding results and highlight the potential that reconstruction-based speech decoding from sensorimotor cortex can offer for development of next-generation BCI technology for communication.

Spatially resolved cell atlas of the teleost telencephalon and deep homology of the vertebrate forebrain.

The telencephalon has undergone remarkable diversification and expansion throughout vertebrate evolution, exhibiting striking differences in structural and functional complexity. Nevertheless, fundamental features are shared across vertebrate taxa, such as the presence of distinct regions including the pallium, subpallium, and olfactory structures. Teleost fishes have a uniquely 'everted' telencephalon, which has made it challenging to compare brain regions in fish to those in other vertebrates. Here we combine spatial transcriptomics and single-nucleus RNA-sequencing to generate a spatially-resolved transcriptional atlas of the cichlid fish telencephalon. We then compare cell-types and anatomical regions in the cichlid telencephalon with those in amphibians, reptiles, birds, and mammals. We uncover striking transcriptional similarities between cell populations in the fish telencephalon and subpallial, hippocampal, and cortical cell populations in tetrapods. Ultimately, our work lends new insights into the organization and evolution of conserved cell-types and regions in the vertebrate forebrain.

Development and Validation of Nerve-Targeted Bacteriochlorin Sensors.

We report an innovative approach to producing bacteriochlorins (bacs) via formal cycloaddition by subjecting a porphyrin to a trimolecular reaction. Bacs are near-infrared probes with the intrinsic ability to serve in multimodal imaging. However, despite their ability to fluoresce and chelate metal ions, existing bacs have thus offered limited ability to label biomolecules for target specificity or have lacked chemical purity, limiting their use in bio-imaging. In this work, bacs allowed a precise and controlled appending of clickable linkers, lending the porphyrinoids substantially more chemical stability, clickability, and solubility, rendering them more suitable for preclinical investigation. Our bac probes enable the targeted use of biomolecules in fluorescence imaging and Cerenkov luminescence for guided intraoperative imaging. Bacs' capacity for chelation provides opportunities for use in non-invasive positron emission tomography/computed tomography. Herein, we report the labeling of bacs with Hs1a, a (NaV1.7)-sodium-channel-binding peptide derived from the Chinese tarantula Cyriopagopus schmidti to yield Bac-Hs1a and radiolabeled Hs1a, which shuttles our bac sensor(s) to mouse nerves. In vivo, the bac sensor allowed us to observe high signal-to-background ratios in the nerves of animals injected with fluorescent Bac-Hs1a and radiolabeled Hs1a in all imaging modes. This study demonstrates that Bac-Hs1a and [64Cu]Cu-Bac-Hs1a accumulate in peripheral nerves, providing contrast and utility in the preclinical space. For the chemistry and bio-imaging fields, this study represents an exciting starting point for the modular manipulation of bacs, their development and use as probes for diagnosis, and their deployment as formidable multiplex nerve-imaging agents for use in routine imaging experiments.

Osteochondritis Dissecans of the Capitellum of the Elbow: Improved Outcomes in Surgically Treated Versus Nonoperatively Treated Patients at Long-Term Follow-up.

Purpose: To (1) report the long-term outcomes associated with both operative and nonoperative management of capitellar osteochondritis dissecans (OCD), (2) identify factors associated with failure of nonoperative management, and (3) determine whether delay in surgery affects final outcomes. Methods: All patients who received a diagnosis of capitellar OCD from 1995-2020 within a geographic cohort were included. Medical records, imaging studies, and operative reports were manually reviewed to record demographic data, treatment strategies, and outcomes. The cohort was divided into 3 groups: (1) nonoperative management, (2) early surgery, and (3) delayed surgery. Delayed surgery (surgery ≥6 months after symptom onset) was considered failure of nonoperative management. Results: Fifty elbows with a mean follow-up period of 10.5 years (median, 10.3 years; range, 1-25 years) were studied. Of these, 7 (14%) were definitively treated nonoperatively, 16 (32%) underwent delayed surgery after at least 6 months of failed nonoperative treatment, and 27 (54%) underwent early surgical intervention. When compared with nonoperative management, surgical management resulted in superior Mayo Elbow Performance Index pain scores (40.1 vs 33, P = .04), fewer mechanical symptoms (9% vs 50%, P < .01), and better elbow flexion (141° vs 131°, P = .01) at long-term follow-up. Older patients trended toward increased failure of nonoperative management (P = .06). The presence of an intra-articular loose body predicted failure of nonoperative management (P = .01; odds ratio, 13). Plain radiography and magnetic resonance imaging had poor sensitivities for identifying loose bodies (27% and 40%, respectively). Differences in outcomes after early versus delayed surgical management were not observed. Conclusions: Nonoperative management of capitellar OCD failed 70% of the time. Elbows that did not undergo surgery had slightly more symptoms and decreased functional outcomes compared with those treated surgically. The greatest predictors of failure of nonoperative treatment were older age and presence of a loose body; however, an initial trial of nonoperative treatment did not adversely impact the success of future surgery. Level of Evidence: Level III, retrospective cohort study.

Bedside hip aspiration results in decrease in total general anesthesia time in pediatric patients: A multicenter study.

Purpose: The purpose of this study is to compare pediatric hip aspiration in the operating room under general anesthesia or via bedside aspiration under moderate sedation and delineate the anesthetic time required. Methods: A database query conducted at two academic institutions identified all patients under the age of 17 who underwent hip aspiration between 2000 and 2017. At one institution, aspiration was performed in the operating room under general anesthesia. Patients were kept anesthetized until cell count was complete. At the second institution, aspiration was performed in the emergency room at bedside under sedation. The medical record was reviewed for demographic data, hip aspiration results, diagnoses, treatment, and anesthesia time. Results: A total of 233 patients (233 hips) with a mean age of 7.2 years were identified. Seventy-five patients underwent aspiration in the operating room, and 158 patients underwent bedside aspiration. Patients with a negative aspiration averaged 87 min under anesthesia when performed in the operating room and 29 min under sedation when performed at bedside. Patients with a negative aspiration performed in the operating room after 5 pm averaged 99 min under anesthesia, and 73 min under anesthesia when performed between 7 am and 5 pm (p < 0.01). Seventy-eight (49%) patients who underwent bedside aspiration did not require operative intervention and therefore avoided general anesthesia. Conclusion: Pediatric hip aspiration performed in the operating room results in prolonged anesthesia times while synovial fluid is transported and processed. Anesthesia times are significantly longer after 5 pm. Bedside aspiration resulted in significantly less anesthesia exposure, with half of patients undergoing bedside aspiration avoiding general anesthesia altogether. Level of evidence: Level III.

Incidence and Epidemiology of Symptomatic Capitellar Osteochondritis Dissecans of the Elbow: A United States Population-Based Study Over a 25-Year Period.

Background: There are limited data on the incidence of capitellar osteochondritis dissecans (OCD) in the United States (US) population. Purpose: To determine the incidence of symptomatic capitellar OCD in a representative US subpopulation and identify changes in its incidence over time and to investigate the relationship between the incidence of capitellar OCD and patient sex and age. Study Design: Descriptive epidemiology study. Methods: A retrospective review was performed of patients aged ≤24 years from Olmsted County, Minnesota, with symptomatic capitellar OCD over a 25-year period (1995-2019). Patients with acute osteochondral injuries, Panner disease, and hereditary arthropathy were excluded. Poisson regression was utilized to identify the predictors of a capitellar OCD diagnosis. Incidence rates (per 100,000) were assessed for changes over time. Age groups of younger (10-15 years) versus older (16-24 years) patients were compared. Results: A total of 45 patients (78% male) were identified. The mean age was 14.5 years (range, 10-24 years); 31 patients were in the younger group, and 14 patients were in the older group. Sport participation was seen in 89%of patients; 90% were overhead athletes, and 58% were throwing athletes. The incidence of capitellar OCD was 6.0 per 100,000 overall, 9.5 per 100,000 for male patients, and 2.6 per 100,000 for female patients. The incidence was highest for male patients in the younger group (15.3/100,000) and lowest for female patients in the older group (0.8/100,000). The estimated incidence rate ratio for younger versus older patients was 3.3 (P < .001), and the incidence rate ratio for male versus female patients was 3.5 (P < .001). There were no changes in the incidence of capitellar OCD over time as a continuous or 5-year categorical variable (P = .290 and P = .460, respectively). Overall, 82% of patients were treated surgically. There were no significant changes in surgical rates over time. Conclusion: In this US subpopulation, the overall incidence of symptomatic capitellar OCD between the ages of 10 and 24 years was 6.0 per 100,000 over the 25-year period studied, which is higher than previously reported US estimates. Incidence rates and treatment strategies did not change significantly over time.

Mapping Acoustics to Articulatory Gestures in Dutch: Relating Speech Gestures, Acoustics and Neural Data.

Completely locked-in patients suffer from paralysis affecting every muscle in their body, reducing their communication means to brain-computer interfaces (BCIs). State-of-the-art BCIs have a slow spelling rate, which inevitably places a burden on patients' quality of life. Novel techniques address this problem by following a bio-mimetic approach, which consists of decoding sensory-motor cortex (SMC) activity that underlies the movements of the vocal tract's articulators. As recording articulatory data in combination with neural recordings is often unfeasible, the goal of this study was to develop an acoustic-to-articulatory inversion (AAI) model, i.e. an algorithm that generates articulatory data (speech gestures) from acoustics. A fully convolutional neural network was trained to solve the AAI mapping, and was tested on an unseen acoustic set, recorded simultaneously with neural data. Representational similarity analysis was then used to assess the relationship between predicted gestures and neural responses. The network's predictions and targets were significantly correlated. Moreover, SMC neural activity was correlated to the vocal tract gestural dynamics. The present AAI model has the potential to further our understanding of the relationship between neural, gestural and acoustic signals and lay the foundations for the development of a bio-mimetic speech BCI. Clinical Relevance- This study investigates the relationship between articulatory gestures during speech and the underlying neural activity. The topic is central for development of brain-computer interfaces for severely paralysed individuals.

Towards predicting ECoG-BCI performance: assessing the potential of scalp-EEG.

Objective. Implanted brain-computer interfaces (BCIs) employ neural signals to control a computer and may offer an alternative communication channel for people with locked-in syndrome (LIS). Promising results have been obtained using signals from the sensorimotor (SM) area. However, in earlier work on home-use of an electrocorticography (ECoG)-based BCI by people with LIS, we detected differences in ECoG-BCI performance, which were related to differences in the modulation of low frequency band (LFB) power in the SM area. For future clinical implementation of ECoG-BCIs, it will be crucial to determine whether reliable performance can be predicted before electrode implantation. To assess if non-invasive scalp-electroencephalography (EEG) could serve such prediction, we here investigated if EEG can detect the characteristics observed in the LFB modulation of ECoG signals.Approach. We included three participants with LIS of the earlier study, and a control group of 20 healthy participants. All participants performed a Rest task, and a Movement task involving actual (healthy) or attempted (LIS) hand movements, while their EEG signals were recorded.Main results.Data of the Rest task was used to determine signal-to-noise ratio, which showed a similar range for LIS and healthy participants. Using data of the Movement task, we selected seven EEG electrodes that showed a consistent movement-related decrease in beta power (13-30 Hz) across healthy participants. Within the EEG recordings of this subset of electrodes of two LIS participants, we recognized the phenomena reported earlier for the LFB in their ECoG recordings. Specifically, strong movement-related beta band suppression was observed in one, but not the other, LIS participant, and movement-related alpha band (8-12 Hz) suppression was practically absent in both. Results of the third LIS participant were inconclusive due to technical issues with the EEG recordings.Significance. Together, these findings support a potential role for scalp EEG in the presurgical assessment of ECoG-BCI candidates.

Delta-like ligand 3-targeted radioimmunotherapy for neuroendocrine prostate cancer.

Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer with limited meaningful treatment options. NEPC lesions uniquely express delta-like ligand 3 (DLL3) on their cell surface. Taking advantage of DLL3 overexpression, we developed and evaluated lutetium-177 (177Lu)-labeled DLL3-targeting antibody SC16 (177Lu-DTPA-SC16) as a treatment for NEPC. SC16 was functionalized with DTPA-CHX-A" chelator and radiolabeled with 177Lu to produce 177Lu-DTPA-SC16. Specificity and selectivity of 177Lu-DTPA-SC16 were evaluated in vitro and in vivo using NCI-H660 (NEPC, DLL3-positive) and DU145 (adenocarcinoma, DLL3-negative) cells and xenografts. Dose-dependent treatment efficacy and specificity of 177Lu-DTPA-SC16 radionuclide therapy were evaluated in H660 and DU145 xenograft-bearing mice. Safety of the agent was assessed by monitoring hematologic parameters. 177Lu-DTPA-SC16 showed high tumor uptake and specificity in H660 xenografts, with minimal uptake in DU145 xenografts. At all three tested doses of 177Lu-DTPA-SC16 (4.63, 9.25, and 27.75 MBq/mouse), complete responses were observed in H660-bearing mice; 9.25 and 27.75 MBq/mouse doses were curative. Even the lowest tested dose proved curative in five (63%) of eight mice, and recurring tumors could be successfully re-treated at the same dose to achieve complete responses. In DU145 xenografts, 177Lu-DTPA-SC16 therapy did not inhibit tumor growth. Platelets and hematocrit transiently dropped, reaching nadir at 2 to 3 wk. This was out of range only in the highest-dose cohort and quickly recovered to normal range by week 4. Weight loss was observed only in the highest-dose cohort. Therefore, our data demonstrate that 177Lu-DTPA-SC16 is a potent and safe radioimmunotherapeutic agent for testing in humans with NEPC.

Kickstand Technique for Intraoperative Reduction of Fifth Metacarpal Neck Fractures.

This article reports a novel intraoperative technique for the reduction of angulated metacarpal neck fractures undergoing retrograde headless intramedullary screw fixation. This technique is a useful reduction maneuver, especially for hand surgeons operating without a first assistant, because it eliminates the need to hold manual reduction during implant placement.

Personalized medicine: From diagnostic to adaptive.

Personalized therapy has made great strides but suffers from the lack of companion diagnostics. With the dawn of extracellular vesicle (EV) based liquid biopsies fast approaching, this article proposes a novel approach to cancer treatment - adaptive therapy. Already being implemented in the field of radiation oncology, adaptive radiation therapy utilizes cutting-edge imaging techniques as a viable means to monitor a patient's tumor throughout the entire treatment cycle by adapting the dosage and alignment to match the dynamic tumor. Through an EV liquid biopsy, medical oncologists will also soon have the means to continuously monitor a patient's tumor as it changes over time. With this information, physicians will be able to "adapt" pre-planned therapies concurrently with the fluctuating tumor environment, thus creating a more precise personalized medicine. In this article, a theory for adaptive medicine and the current state of the field with an outlook on future challenges are discussed.