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The document discusses the safety and tolerability of ultrasound-guided fine-needle aspiration (FNA) in pediatric patients with thyroid nodules. The study conducted at Boston Children's Hospital and Brigham & Women's Hospital over 26 years found that FNA was performed without sedation in over 97% of cases, with minimal complications and mild patient-reported pain. Sedation was primarily used for young children, those with developmental delays, or for repeat FNA procedures. The study suggests that sedation may not be necessary for routine pediatric thyroid FNA, as most procedures can be safely performed without sedation. [Extracted from the article]

The article discusses the diagnostic accuracy of MRI in identifying Creutzfeldt‐Jakob Disease (CJD), a rare prion infection. MRI has been found to be more effective than CSF testing in diagnosing CJD, with a high negative predictive value. The study suggests that patients without suggestive MRI findings are unlikely to have CJD confirmed through lumbar puncture, highlighting the potential of MRI as a screening tool to avoid unnecessary invasive procedures. [Extracted from the article]

Laying hens usually have 16 h of light and 8 h of darkness during egg laying, with eggshell formation primarily occurring during darkness when dietary calcium is lacking, leading to bone calcium resorption and osteoporosis. This study examined how interrupting the dark phase affects bone health in 396 Hy-line W36 hens assigned to control (C) or treatment groups (W1 and W2). All hens received 16 h of light and 8 h of darkness daily in different variations of scotophase interruption. Blood samples were taken at weeks 20, 30, 50, and 70, serum calcium was measured during darkness at two timepoints (SRT and END), and bone demineralization markers were examined using enzyme concentrations (TRACP-5b and CTX-I). Across weeks, tibias were CT-scanned for density (mg/cm3) and area (mm2), then used for breakage strength analysis (N) and ash%. No SRT Ca level differences emerged, but C hens had lower END Ca levels compared to W1 and W2 hens across all weeks, while W1 and W2 hens showed no significant differences. C hens displayed higher TRACP-5b and CTX-I concentrations across all weeks compared to W1 and W2 (all p ≤ 0.05). At week 70, C hens had the lowest cortical bone cross-sectional area and mineral density compared to W1 and W2 (all p ≤ 0.05). Tibiotarsi bone breakage strength was lower in C hens compared to W1 and W2. C hens had significantly lower ash% than treatment birds. Interrupting the scotophase period improved overall bone health in Hy-line W36 laying hens. [ABSTRACT FROM AUTHOR]

Background: We aimed to compare cone beam computed tomography (CBCT) utilization and radiation exposure during prostatic artery embolization (PAE) procedures on two different angiography systems. Methods: PAEs performed by a single interventionalist between January 2018 and October 2020 on two multivendor angiography systems (AS1 and AS2) at a single center were retrospectively evaluated. Imaging techniques included CBCT acquisition when possible, predominantly from the distal aorta in AS1 and from the bilateral internal iliac arteries in AS2 (Discovery IGS 740, GE HealthCare, Chicago, IL). Baseline demographics, CBCT utilization and radiation doses, and total procedure radiation metrics for each group were collected and compared. Results: One hundred and twenty patients were analyzed in this study, with fifty-three patients (n = 25 in AS1, 28 in AS2) included as embolized bilaterally using CBCT. CBCT was acquired in 31% of the cases in AS1 and in 85% of the cases in AS2. Mean prostate volume was similar in both groups (103.0 mL vs. 130.1 mL, p = 0.23). There was no difference in fluoroscopy time, while the number of DSA series and CBCTs per case did differ in AS1 and AS2 (37.3 min vs. 32.1 min, p = 0.13, 19.8 vs. 8.0, p ≤ 0.001, 1.3 vs. 2.1 p ≤ 0.001). The mean total air kerma, total kerma area product and air kerma per CBCT were higher in AS1 compared to AS2 (2020.4 mGy vs. 490.3 mGy, p ≤ 0.001, 259.3 Gy*cm2 vs. 72.7 Gy*cm2, p ≤ 0.001 and 217.8 mGy vs. 45.8 mGy, p ≤ 0.001 respectively). To prevent confounding from a mean difference in body mass index, the data were adjusted using log outcome means, which corroborated the raw data findings. Conclusions: The mean procedural total kerma area product from AS1 was similar to that reported in other PAE studies, but it was substantially lower in AS2. The angiography system used has a significant impact on the ability to leverage CBCT and on overall patient and thus staff radiation exposure. [ABSTRACT FROM AUTHOR]

Chronic demyelination and oligodendrocyte loss deprive neurons of crucial support. It is the degeneration of neurons and their connections that drives progressive disability in demyelinating disease. However, whether chronic demyelination triggers neurodegeneration and how it may do so remain unclear. We characterize two genetic mouse models of inducible demyelination, one distinguished by effective remyelination and the other by remyelination failure and chronic demyelination. While both demyelinating lines feature axonal damage, mice with blocked remyelination have elevated neuronal apoptosis and altered microglial inflammation, whereas mice with efficient remyelination do not feature neuronal apoptosis and have improved functional recovery. Remyelination incapable mice show increased activation of kinases downstream of dual leucine zipper kinase (DLK) and phosphorylation of c-Jun in neuronal nuclei. Pharmacological inhibition or genetic disruption of DLK block c-Jun phosphorylation and the apoptosis of demyelinated neurons. Together, we demonstrate that remyelination is associated with neuroprotection and identify DLK inhibition as protective strategy for chronically demyelinated neurons. The mechanisms that trigger neurodegeneration in demyelinating disease are unclear. Here, the authors find that impaired remyelination induces a DLK-mediated loss of retinal ganglion cells (RGCs), and that efficient remyelination or DLK inhibition block RGC death. [ABSTRACT FROM AUTHOR]

Consequences are presented from flume experiments regarding bed scour at rock vanes and bendway weirs constructed of loose rock placed on sand bed channels. The experiments involved three flow discharges adjusted to replicate approximately the rising limb of a hydrograph and two bed-material sizes (a medium sand and a very coarse sand) subject to live-bed and clearwater scour. Observations show that these structures shortened due to rock dislodgement triggered by relatively modest contraction scour, which undermined the toe of the crest tip of these loose rock structures, causing the tips to become geotechnically unstable. Additionally, flow dislodgment of rock destabilized by tip slope failure further shortened the crest length of these structures and decreased tip slope. Displaced rock partially armored the scour zone and, thereby, affected scour depth and thalweg development. The experiments illustrated thalweg development as flow rate increased. Design dimensions are given for rock vanes and bendway weirs. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic and debilitating neurological disease that results in inflammatory demyelination. While endogenous remyelination helps to recover function, this restorative process tends to become less efficient over time. Currently, intense efforts aimed at the mechanisms that promote remyelination are being considered promising therapeutic approaches. The M1 muscarinic acetylcholine receptor (M1R) was previously identified as a negative regulator of oligodendrocyte differentiation and myelination. Here, we validate M1R as a target for remyelination by characterizing expression in human and rodent oligodendroglial cells (including those in human MS tissue) using a highly selective M1R probe. As a breakthrough to conventional methodology, we conjugated a fluorophore to a highly M1R selective peptide (MT7) which targets the M1R in the subnanomolar range. This allows for exceptional detection of M1R protein expression in the human CNS. More importantly, we introduce PIPE-307, a brain-penetrant, small-molecule antagonist with favorable drug-like properties that selectively targets M1R. We evaluate PIPE-307 in a series of in vitro and in vivo studies to characterize potency and selectivity for M1R over M2-5R and confirm the sufficiency of blocking this receptor to promote differentiation and remyelination. Further, PIPE-307 displays significant efficacy in the mouse experimental autoimmune encephalomyelitis model of MS as evaluated by quantifying disability, histology, electron microscopy, and visual evoked potentials. Together, these findings support targeting M1R for remyelination and support further development of PIPE-307 for clinical studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related deaths worldwide. While there has been an improvement in detecting this cancer earlier on, progression rates have remained consistent. Patients with early-stage HCC are first treated with liver-directed therapies before they are eligible to undergo liver transplantation (LT). The success of liver-directed therapy (LDT) is measured by follow-up imaging and is crucial to the success of overall outcomes in HCC. In this study, we investigated the impact of HCC care delay, specifically delays in follow-up imaging studies, on tumor progression in patients with early-stage HCC. The results demonstrate a need to optimize the scheduling of post-treatment appointments to decrease HCC care delay and improve progression rates. Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related deaths in the world. Patients with early-stage HCC are treated with liver-directed therapies to bridge or downstage for liver transplantation (LT). In this study, the impact of HCC care delay on HCC progression among early-stage patients was investigated. Early-stage HCC patients undergoing their first cycle of liver-directed therapy (LDT) for bridge/downstaging to LT between 04/2016 and 04/2022 were retrospectively analyzed. Baseline variables were analyzed for risk of disease progression and time to progression (TTP). HCC care delay was determined by the number of rescheduled appointments related to HCC care. The study cohort consisted of 316 patients who received first-cycle LDT. The HCC care no-show rate was associated with TTP (p = 0.004), while the overall no-show rate was not (p = 0.242). The HCC care no-show rate and HCC care delay were further expanded as no-show rates and rescheduled appointments for imaging, laboratory, and office visits, respectively. More than 60% of patients experienced HCC care delay for imaging and laboratory appointments compared to just 8% for office visits. Multivariate analysis revealed that HCC-specific no-show rates and HCC care delay for imaging (p < 0.001) were both independently associated with TTP, highlighting the importance of minimizing delays in early-stage HCC imaging surveillance to reduce disease progression risk. [ABSTRACT FROM AUTHOR]

As aging and tumorigenesis are tightly interconnected biological processes, targeting their common underlying driving pathways may induce dual‐purpose anti‐aging and anti‐cancer effects. Our transcriptomic analyses of 16,740 healthy samples demonstrated tissue‐specific age‐associated gene expression, with most tumor suppressor genes downregulated during aging. Furthermore, a large‐scale pan‐cancer analysis of 11 solid tumor types (11,303 cases and 4431 control samples) revealed that many cellular processes, such as protein localization, DNA replication, DNA repair, cell cycle, and RNA metabolism, were upregulated in cancer but downregulated in healthy aging tissues, whereas pathways regulating cellular senescence were upregulated in both aging and cancer. Common cancer targets were identified by the AI‐driven target discovery platform—PandaOmics. Age‐associated cancer targets were selected and further classified into four groups based on their reported roles in lifespan. Among the 51 identified age‐associated cancer targets with anti‐aging experimental evidence, 22 were proposed as dual‐purpose targets for anti‐aging and anti‐cancer treatment with the same therapeutic direction. Among age‐associated cancer targets without known lifespan‐regulating activity, 23 genes were selected based on predicted dual‐purpose properties. Knockdown of histone demethylase KDM1A, one of these unexplored candidates, significantly extended lifespan in Caenorhabditis elegans. Given KDM1A's anti‐cancer activities reported in both preclinical and clinical studies, our findings propose KDM1A as a promising dual‐purpose target. This is the first study utilizing an innovative AI‐driven approach to identify dual‐purpose target candidates for anti‐aging and anti‐cancer treatment, supporting the value of AI‐assisted target identification for drug discovery. [ABSTRACT FROM AUTHOR]

Translational strategies to characterize and monitor extracellular vesicles such as exosome (EX) shedding and the clinical impact of this data within hepatocellular carcinoma (HCC) remains unclear. In this study, EX shedding was assessed in early-stage HCC and evaluated as a stratification factor for time to progression (TTP) following first-cycle liver-directed therapy (LDT). Plasma EXs were isolated from HCC patients undergoing LDT using ultracentrifugation. Purified EXs were stained using markers CD9 and CD63 and quantified using an ImageStreamX flow cytometer. Circulating EXs expressing CD9 were isolated at 10-fold higher levels compared to CD63. The intensity of CD9+ EX shedding following LDT was positively correlated with treatment response. High post-LDT CD9+ EX shedding stratified TTP risk with a 30% lower frequency of disease progression at 1 year following LDT. Post-LDT high CD9+ EX shedding was observed in 100% (10/10) of patients successfully bridged to liver transplantation while only 22% (2/9) of patients with tumor progression had high CD9+ EX shedding post-LDT. CD9+ EX shedding also stratified TTP risk within the first cycle objective response rate (ORR) group, identifying patients still at higher disease progression. EX shedding was concordant with imaging response rate, stratified TTP in early-stage HCC, and may have important implications for assessing post-LDT viable, biologically aggressive HCC. [ABSTRACT FROM AUTHOR]

The popularity of Mimi Peri as a queer micro-celebrity on Instagram shows a paradox in the Indonesian digital society, widely known for being very heteronormative towards gender and sexual identities. Despite the controversy over their queer performance and identity, Mimi Peri's positive image as a "kind-hearted" and funny micro-celebrity managed to attract the attention of 1.9 million followers on Instagram. By using a virtual ethnographic paradigm within the framework of queer studies, this research examines how queer performativity in the @mimi.peri Instagram account during the periode between 2017 and 2018 presented and related to the Camp strategy. Switching their virtual identity, playing a role as a "female fairy", parodying, and representing it as a comic figure have been identified as Mimi Peri's practice and strategy to effectively gain the attention and acceptance of their followers. While there are established assumptions of queer subjects as fun and funny, we also argue that the strategy to commodify their comical performance can be seen as a form of negotiation to the predominant gender norms on Instagram. [ABSTRACT FROM AUTHOR]

All patients completed double induction with FLAG-IDA, and 27/30 (90%) patients completed all planned therapy (persistent thrombocytopenia, early relapse post-consolidation I, physician discretion). Of the 1096 patients enrolled in the COG trial AAML1031, MRD was available in 95% of patients and was negative (<0.05%) post-Induction I in only 75% of patients. Abbreviations AML Acute myeloid leukaemia ANC Absolute neutrophil count CNS Central nervous system COG Children's Oncology Group CR1 First complete remission EFS Event-free survival FLAG-IDA Fludarabine, cytarabine, idarubicin and G-CSF GO Gemtuzumab ozogamicin GCSF G-colony stimulating factor HDAc High-dose cytarabine HSCT Haematopoietic stem cell transplant IFI Invasive fungal infection LVSF Left ventricular shortening fraction MRC Medical Research Council MRD Minimal residual disease OS Overall survival TKI Tyrosine kinase inhibitor TRM Treatment-related mortality UK United Kingdom WBC White blood cell count DATA AVAILABILITY STATEMENT The data that support the findings of this study are available from the corresponding author upon reasonable request. [Extracted from the article]

Background: The N-MOmentum trial investigated safety and efficacy of inebilizumab in participants with neuromyelitis optica spectrum disorder (NMOSD). Objective: Evaluate the attack identification process and adjudication committee (AC) performance in N-MOmentum. Methods: Adults (n = 230) with NMOSD and Expanded Disability Status Scale score ⩽8 were randomized (3:1) to inebilizumab 300 mg or placebo. The randomized controlled period was 28 weeks or until adjudicated attack. Attacks were adjudicated according to 18 predefined criteria. Magnetic resonance imaging (MRI) and biomarker (serum glial fibrillary acidic protein [sGFAP]) analyses were performed. Results: A total of 64 participant-reported neurological events occurred; 51 (80%) were investigator-determined to be attacks. The AC confirmed 43 of the investigator-determined attacks (84%). There was high inter- and intra-AC-member agreement. In 25/64 events (39%) and 14/43 AC-adjudicated attacks (33%), MRI was reviewed during adjudication. Retrospective analysis revealed new domain-specific T1 and T2 MRI lesions in 90% of adjudicated attacks. Increased mean sGFAP concentrations (>2-fold change) from baseline were observed in 56% of adjudicated attacks versus 14% of investigator-determined attacks rejected by the AC and 31% of participant-reported events determined not to be attacks. Conclusion: AC adjudication of NMOSD attacks according to predefined criteria appears robust. MRI lesion correlates and sGFAP elevations were found in most adjudicated attacks. [ABSTRACT FROM AUTHOR]

Myelin repair is an unrealized therapeutic goal in the treatment of multiple sclerosis (MS). Uncertainty remains about the optimal techniques for assessing therapeutic efficacy and imaging biomarkers are required to measure and corroborate myelin restoration. We analyzed myelin water fraction imaging from ReBUILD, a double-blind, randomized placebo-controlled (delayed treatment) remyelination trial, that showed a significant reduction in VEP latency in patients with MS. We focused on brain regions rich in myelin. Fifty MS subjects in two arms underwent 3T MRI at baseline and months 3 and 5. Half of the cohort was randomly assigned to receive treatment from baseline through 3 mo, whereas the other half received treatment from 3 mo to 5 mo post-baseline. We computed myelin water fraction changes occurring in normal-appearing white matter of corpus callosum, optic radiations, and corticospinal tracts. An increase in myelin water fraction was documented in the normal-appearing white matter of the corpus callosum, in correspondence with the administration of the remyelinating treatment clemastine. This study provides direct, biologically validated imaging-based evidence of medically induced myelin repair. Moreover, our work strongly suggests that significant myelin repair occurs outside of lesions. We therefore propose myelin water fraction within the normal-appearing white matter of the corpus callosum as a biomarker for clinical trials looking at remyelination. [ABSTRACT FROM AUTHOR]

Objective: To develop a machine learning framework to forecast emergency department (ED) crowding and to evaluate model performance under spatial and temporal data drift.Materials and Methods: We obtained four datasets, identified by the location: 1-large academic hospital and 2-rural hospital, and time period: pre-COVID (Jan 1, 2019-Feb 1, 2020) and COVID-era (May 15, 2020-Feb 1, 2021). Our primary target was a binary outcome that is equal to 1 if the number of patients with acute respiratory illness that were ED boarding for more than four hours was above a prescribed historical percentile. We trained a random forest and used the area under the curve (AUC) to evaluate out-of-sample performance for two experiments: 1) we evaluated the impact of sudden temporal drift by training models using pre-COVID data and testing them during the COVID-era, 2) we evaluated the impact of spatial drift by testing models trained at Location 1 on data from Location 2, and vice versa.Results: The baseline AUC values for ED boarding ranged from 0.54 (pre-COVID at Location 2) to 0.81 (COVID-era at Location 1). Models trained with pre-COVID data performed similarly to COVID-era models (0.82 vs. 0.78 at Location 1). Models that were transferred from Location 2 to Location 1 performed worse than models trained at Location 1 (0.51 vs. 0.78).Discussion and Conclusion: Our results demonstrate that ED boarding is a predictable metric for ED crowding, models were not significantly impacted by temporal data drift, and any attempts at implementation must consider spatial data drift. [ABSTRACT FROM AUTHOR]

We describe the newest generation of the SLAC Microresonator RF (SMuRF) electronics, a warm digital control and readout system for microwave-frequency resonator-based cryogenic detector and multiplexer systems, such as microwave superconducting quantum interference device multiplexers (μmux) or microwave kinetic inductance detectors. Ultra-sensitive measurements in particle physics and astronomy increasingly rely on large arrays of cryogenic sensors, which in turn necessitate highly multiplexed readout and accompanying room-temperature electronics. Microwave-frequency resonators are a popular tool for cryogenic multiplexing, with the potential to multiplex thousands of detector channels on one readout line. The SMuRF system provides the capability for reading out up to 3328 channels across a 4–8 GHz bandwidth. Notably, the SMuRF system is unique in its implementation of a closed-loop tone-tracking algorithm that minimizes RF power transmitted to the cold amplifier, substantially relaxing system linearity requirements and effective noise from intermodulation products. Here, we present a description of the hardware, firmware, and software systems of the SMuRF electronics, comparing achieved performance with science-driven design requirements. In particular, we focus on the case of large-channel-count, low-bandwidth applications, but the system has been easily reconfigured for high-bandwidth applications. The system described here has been successfully deployed in lab settings and field sites around the world and is baselined for use on upcoming large-scale observatories. [ABSTRACT FROM AUTHOR]

Many biomarkers in clinical neuroscience lack pathological certification. This issue is potentially a significant contributor to the limited success of neuroprotective and neurorestorative therapies for human neurological disease-and is evident even in areas with therapeutic promise such as myelin repair. Despite the identification of promising remyelinating candidates, biologically validated methods to demonstrate therapeutic efficacy or provide robust preclinical evidence of remyelination in the CNS are lacking. Therapies with potential to remyelinate the CNS constitute one of the most promising and highly anticipated therapeutic developments in the pipeline to treat multiple sclerosis and other demyelinating diseases. The optic nerve has been proposed as an informative pathway to monitor remyelination in animals and human subjects. Recent clinical trials using visual evoked potential have had promising results, but without unequivocal evidence about the cellular and molecular basis for signal changes on visual evoked potential, the interpretation of these trials is constrained. The visual evoked potential was originally developed and used in the clinic as a diagnostic tool but its use as a quantitative method for assessing therapeutic response requires certification of its biological specificity. Here, using the tools of experimental pathology we demonstrate that quantitative measurements of myelination using both histopathological measures of nodal structure and ultrastructural assessments correspond to visual evoked potential latency in both inflammatory and chemical models of demyelination. Visual evoked potential latency improves after treatment with a tool remyelinating compound (clemastine), mirroring both quantitative and qualitative myelin assessment. Furthermore, clemastine does not improve visual evoked potential latency following demyelinating injury when administered to a transgenic animal incapable of forming new myelin. Therefore, using the capacity for therapeutic enhancement and biological loss of function we demonstrate conclusively that visual evoked potential measures myelin status and is thereby a validated tool for preclinical verification of remyelination. [ABSTRACT FROM AUTHOR]

Background: Recurrent head and neck squamous cell carcinoma (HNSCC) is associated with poor overall survival (OS). Prior studies suggested incorporation of nab-paclitaxel (A) may improve outcomes in recurrent HNSCC.Methods: This Phase I study evaluated induction with carboplatin and A followed by concomitant FHX (infusional 5-fluorouracil, hydroxyurea and twice-daily radiation therapy administered every other week) plus A with cohort dose escalation ranging from 10-100 mg/m2 in recurrent HNSCC. The primary endpoint was maximally tolerated dose (MTD) and dose-limiting toxicity (DLT) of A when given in combination with FHX (AFHX).Results: Forty-eight eligible pts started induction; 28 pts started AFHX and were evaluable for toxicity. Two DLTs occurred (both Grade 4 mucositis) at a dose level 20 mg/m2. No further DLTs were observed with subsequent dose escalation. The MTD and recommended Phase II dose (RP2D) of A was 100 mg/m2.Conclusions: In this Phase I study, the RP2D of A with FHX is 100 mg/m2 (AFHX). The role of re-irradiation with immunotherapy warrants further investigation.Clinical Trial Information: This clinical trial was registered with ClinicalTrials.gov identifier: NCT01847326. [ABSTRACT FROM AUTHOR]

Background: It is uncertain whether the presence of autoimmune thyroiditis (AIT) increases the risk of thyroid cancer in children with thyroid nodules. This study evaluated the association between AIT and thyroid cancer in pediatric patients with thyroid nodules. Methods: A cross-sectional study was performed of pediatric patients (<19 years old) with a thyroid nodule (≥1 cm) who underwent fine-needle aspiration in an academic pediatric thyroid center. AIT was defined by the presence of thyroid autoantibodies or diffusely heterogeneous sonographic echotexture. The primary outcome was diagnosis of thyroid cancer. The association of AIT with thyroid cancer was evaluated with univariable and multivariable logistic regression. Associations of AIT with subject and nodule characteristics were also assessed. Results: Four hundred fifty-eight thyroid nodules in 385 patients (81% female) were evaluated at a median age of 15.5 years (interquartile range 13.5–17.0). Thyroid cancer was present in 108 nodules (24%). AIT was present in 95 subjects (25%) and was independently associated with an increased risk of thyroid cancer (multivariable odds ratio [OR] 2.19, 95% confidence interval [CI] 1.32–3.62). Thyroid cancer was also independently associated with younger age, nodule size, and solitary nodules, but was not associated with serum thyrotropin concentration. AIT was not associated with the likelihood of subjects undergoing thyroid surgery (p = 0.17). AIT was less commonly associated with follicular thyroid carcinoma than with papillary thyroid carcinoma (OR 0.22, CI 0.05–1.06). Among papillary thyroid carcinomas, AIT was strongly associated with the diffuse sclerosing variant (OR 4.74, CI 1.33–16.9). AIT was not associated with the extent of local, regional, or distant disease at thyroid cancer diagnosis. Conclusions: AIT is independently associated with an increased risk of thyroid cancer in children with thyroid nodules. These findings suggest that the evaluation of thyroid autoantibodies and thyroid echotexture may inform thyroid cancer risk assessment and surgical decision-making in children with thyroid nodules. [ABSTRACT FROM AUTHOR]

NBTXR3 nanoparticle injection is a relatively novel radioenhancer for treatment of various cancers. CT scans following NBTXR3 injection of metastatic lymph nodes from head and neck squamous cell carcinoma were reviewed in a small series of patients. The radioenhancing appears as hyperattenuating, with a mean attenuation of the injected material of 1516 HU. The material was found to leak beyond the margins of the tumor in some cases. [ABSTRACT FROM AUTHOR]

Let Ω ⊂ R 2 be an unbounded convex domain. It is proven in López (J Diff Equ 171:54–62, 2001) and Ripoll (Pac J Math 198(1):175–196, 2001) that, given H > 0 , there exists a graph G ⊂ R 3 of constant mean curvature H over Ω with ∂ G = ∂ Ω if and only if Ω is included in a strip of width 1/H. In this paper we obtain results in H 2 × R in the same direction: given H ∈ 0 , 1 / 2 , if Ω is included in a region of H 2 × 0 bounded by two hypercircles equidistant ℓ (H) to a same geodesic, we show that, if the geodesic curvature of ∂ Ω is bounded from below by - 1 , then there is an H-graph G over Ω with ∂ G = ∂ Ω . We also present more refined existence results involving the curvature of ∂ Ω , which can also be less than - 1. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma is a heterogeneous tumor that accumulates a mutational burden and dysregulated signaling pathways that differ from early to advanced stages. Liver transplant candidates with early-stage hepatocellular carcinoma (HCC) undergo liver-directed therapy (LDT) to delay disease progression and serve as a bridge to liver transplantation (LT). Unfortunately, >80% of LDT-treated patients have viable HCC in the explant liver, dramatically increasing recurrence risk. Understanding the effect of LDT on early-stage HCC could help identify therapeutic targets to promote complete pathologic necrosis and improve recurrence-free survival. In this study, transcriptomic data from viable HCC in LDT-treated bridged to transplant patients were investigated to understand how treatment may affect tumor signaling pathways. Methods: Multiplex transcriptomic gene analysis was performed with mRNA extracted from viable tumors of HCC patients bridged to transplant using LDT. The NanoString nCounter® Tumor Signaling 360 panel was used that contained 780 genes from 48 pathways involved in tumor biology within the microenvironment as well as antitumoral immune responses. Results: Hierarchical clustering separated tumors into three subtypes (HCC-1, HCC-2, and HCC-3) each with distinct differences in anti-tumoral signaling and immune infiltration within the tumor microenvironment. Immune infiltration (neutrophils, T cells, and macrophages) were all lowest in subtype HCC-3. The tumor inflammatory signature consisting of 18 genes associated with PD-1/PD-L1 inhibition, antigen presentation, chemokine secretion, and adaptive immune responses was highest in subtype HCC-1 and lowest in HCC-3. History of decompensation and etiology were associated with HCC subtype favoring downregulations in inflammation and immune infiltration with upregulation of lipid metabolism. Gene expression among intrahepatic lesions was remarkably similar with >85% of genes expressed in both lesions. Genes differentially expressed (<8 genes per patient) in multifocal disease were all upregulated in LDT-treated tumors from pathways involving epithelial mesenchymal transition, extracellular matrix remodeling, and/or inflammation potentially implicating intrahepatic metastases. Conclusion: Incomplete response to LDT may drive expression patterns that inhibit an effective anti-tumoral response through immune exclusion and induce intrahepatic spread. [ABSTRACT FROM AUTHOR]

There is substantial interest in the potential for traumatic brain injury to result in progressive neurological deterioration. While blood biomarkers such as glial fibrillary acid protein (GFAP) and neurofilament light have been widely explored in characterizing acute traumatic brain injury (TBI), their use in the chronic phase is limited. Given increasing evidence that these proteins may be markers of ongoing neurodegeneration in a range of diseases, we examined their relationship to imaging changes and functional outcome in the months to years following TBI. Two-hundred and three patients were recruited in two separate cohorts; 6 months post-injury (n = 165); and >5 years post-injury (n = 38; 12 of whom also provided data ∼8 months post-TBI). Subjects underwent blood biomarker sampling (n = 199) and MRI (n = 172; including diffusion tensor imaging). Data from patient cohorts were compared to 59 healthy volunteers and 21 non-brain injury trauma controls. Mean diffusivity and fractional anisotropy were calculated in cortical grey matter, deep grey matter and whole brain white matter. Accelerated brain ageing was calculated at a whole brain level as the predicted age difference defined using T1-weighted images, and at a voxel-based level as the annualized Jacobian determinants in white matter and grey matter, referenced to a population of 652 healthy control subjects. Serum neurofilament light concentrations were elevated in the early chronic phase. While GFAP values were within the normal range at ∼8 months, many patients showed a secondary and temporally distinct elevations up to >5 years after injury. Biomarker elevation at 6 months was significantly related to metrics of microstructural injury on diffusion tensor imaging. Biomarker levels at ∼8 months predicted white matter volume loss at >5 years, and annualized brain volume loss between ∼8 months and 5 years. Patients who worsened functionally between ∼8 months and >5 years showed higher than predicted brain age and elevated neurofilament light levels. GFAP and neurofilament light levels can remain elevated months to years after TBI, and show distinct temporal profiles. These elevations correlate closely with microstructural injury in both grey and white matter on contemporaneous quantitative diffusion tensor imaging. Neurofilament light elevations at ∼8 months may predict ongoing white matter and brain volume loss over >5 years of follow-up. If confirmed, these findings suggest that blood biomarker levels at late time points could be used to identify TBI survivors who are at high risk of progressive neurological damage. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) patients undergo liver-directed therapy (LDT) to control tumor burden while awaiting liver transplantation with response impacting waitlist survival. In this study, we investigate the link between absolute lymphocyte count (ALC) and PD-1 expression with response to LDT and bridge-to-transplant survival. Methods: Treatment-naïve HCC patients (n = 86) undergoing LDT were enrolled at a single center from August 2016–March 2020. Response to LDT was determined using mRECIST. Blood samples were collected on the day of LDT and at follow-up. Cells were analyzed for phenotype by flow cytometry. Outcomes were liver transplantation or tumor progression. Results: Incomplete response to initial LDT was associated with tumor progression precluding liver transplantation (OR: 7.6, 1.7 – 33.3, P < 0.001). Univariate analysis of baseline T cell phenotypes revealed ALC (OR: 0.44, 0.24–0.85, P = 0.009) as well as intermediate expression of PD-1 on CD4 (OR: 3.3, 1.03–10.3, P = 0.034) and CD8 T cells (OR: 3.0, 0.99–8.8 P = 0.043) associated with incomplete response to LDT. Elevations in PD-1 expression were associated with increased risk of bridge-to-transplant tumor progression (HR: 3.2, 1.2–9.4). In patients successfully bridged to liver transplantation, pre-treatment peripheral PD-1 profile was associated with advanced tumor staging (P < 0.005) with 2/4 of patients with elevations in PD-1 having T3-T4 TNM staging compared to 0 with low PD-1 expression. Conclusion: Low lymphocyte count or elevated expression of the PD-1 checkpoint inhibitor is associated with incomplete response to LDT and increased risk of bridge-to-transplant tumor progression. Patients with impaired T cell homeostasis may benefit from PD-1 immunotherapy to improve response to LDT and improve bridge-to-transplant outcomes. [ABSTRACT FROM AUTHOR]

Diffuse axonal injury (DAI) is a common neuropathological manifestation of traumatic brain injury (TBI), presenting as traumatic alterations in the cerebral white matter (WM) microstructure and often leading to long-term neurocognitive impairment. These WM alterations can be assessed using diffusion tensor imaging (DTI). Cerebral microbleeds (CMBs) are a common finding on head imaging in TBI and are often considered a visible sign of DAI, although they represent diffuse vascular injury. It is poorly known how they associate with long-term white matter integrity. This study included 20 patients with TBI and CMBs, 34 patients with TBI without CMBs, and 11 controls with orthopedic injuries. DTI was used to assess microstructural WM alterations. CMBs were detected using susceptibility-weighted imaging (SWI) and graded according to their location in the WM and total lesion load was counted. Patients underwent SWI within 2 months after injury. DTI and clinical outcome assessment were performed at an average of eight months after injury. Outcome was assessed using the extended Glasgow Outcome Scale (GOSe). The Glasgow Coma Scale (GCS) and length of post-traumatic amnesia (PTA) were used to assess clinical severity of the injury. We found that CMB grading and total lesion load were negatively associated with fractional anisotropy (FA) and positively associated with mean diffusivity (MD). Patients with TBI and CMBs had decreased FA and increased MD compared with patients with TBI without CMBs. CMBs were also associated with worse clinical outcome. When adjusting for the clinical severity of the injury, none of the mentioned associations were found. Thus, the difference in FA and MD is explained by patients with TBI and CMBs having more severe injuries. Our results suggest that CMBs are not associated with greater WM alterations when adjusting for the clinical severity of TBI. Thus, CMBs and WM alterations may not be strongly associated pathologies in TBI. [ABSTRACT FROM AUTHOR]

BACKGROUND: Thyroid nodules with atypia of undetermined significance (AUS) are challenging to manage because of their intermediate risk of malignancy. Subclassification of atypia can refine malignancy risk in adult AUS nodules but has not been evaluated in children. METHODS: This was a retrospective cohort study of pediatric patients (<19 years old) who underwent fine‐needle aspiration (FNA) of a thyroid nodule with resulting AUS cytology. Atypia was subclassified as nuclear only, architectural only, nuclear and architectural, or oncocytic. The primary outcome was the association between atypia subtype and malignancy. A secondary outcome was the association of atypia subtype with repeat FNA cytology. RESULTS: Sixty‐eight AUS nodules in 61 patients were analyzed. The median age at FNA was 16.2 years (range, 9.8‐18.9 years). Twenty‐four nodules (35%) were malignant. Nuclear atypia only was present in 17 nodules (25%), architectural atypia only was present in 27 nodules (40%), nuclear and architectural atypia was present in 20 nodules (29%), and predominantly oncocytic features were present in 4 nodules (6%). The presence of nuclear atypia was associated with a significantly increased rate of malignancy (22 of 37 [59%] vs 2 of 31 [6.5%]; P <.001), whereas architectural atypia was not associated with malignancy (P =.8). Repeat FNA was performed in 42 of 68 nodules (62%). In nodules with initial nuclear and architectural atypia, benign repeat cytology had a high false‐negative rate (3 of 6; 50%). CONCLUSIONS: Pediatric AUS nodules with nuclear atypia have a high rate of malignancy, but architectural atypia is not associated with malignancy. In nodules with nuclear atypia, repeat FNA may inform clinical decisions regarding the need for resection. In the absence of suspicious clinical features, nodules without nuclear atypia might be considered for observation rather than resection or repeat FNA. The subclassification of atypia on fine‐needle aspiration cytology is useful for guiding the management of pediatric thyroid nodules with atypia of undetermined significance. Nodules with nuclear atypia have a high risk of malignancy, whereas nodules with architectural atypia alone are unlikely to be malignant and may be considered for observation rather than resection. [ABSTRACT FROM AUTHOR]

Purpose Multigene panels allow simultaneous testing of genes involved in cancer predisposition. Thyroid cancer (TCa) is a component tumor of several cancer predisposition syndromes, but the complete landscape of germline variants predisposing to TCa remains to be determined. Methods: Clinical information and genetic test results were reviewed from over 170,000 individuals who had multigene panel testing for hereditary cancer at a single diagnostic laboratory. Germline pathogenic and likely pathogenic variants ("pathogenic variants") were examined among individuals with TCa. A cohort with breast cancer (BCa) was examined to serve as a comparison group and to determine the added contribution of TCa to the ascertainment of genetic risk. Results: Of 3134 individuals with TCa, 291 (9.3%) were found to have one or more pathogenic variant(s). Among 904 individuals with TCa alone, 7.5% had one or more pathogenic variant(s), similar to those with BCa alone (8.4%). In all groups, CHEK2 was the gene with the highest number of pathogenic variants identified, with a significantly increased frequency among individuals with a history of both thyroid and BCa compared to BCa alone. Conclusions: A high prevalence of germline pathogenic variants was observed among individuals with TCa referred for hereditary cancer genetic testing, even in the absence of other cancer diagnoses. These data suggest that TCa may be an under‐recognized component of cancer predisposition syndromes. [ABSTRACT FROM AUTHOR]

Simple Summary: With the increasing rates of early-stage hepatocellular carcinoma (HCC) diagnosis, patients are being diagnosed with less tumor burden and low biomarker levels. Assessing HCC prognosis in these patients is challenging as most prognosis strategies are based on elevated tumor burden and biomarkers. In this study we focus on albumin levels prior to HCC treatment based on the established roles of albumin in HCC incidence and overall survival outcomes. The role of albumin as a risk factor for HCC progression was investigated with the goal of demonstrating that albumin could identify optimal candidates for treatment in early-stage HCC. These results may also impact the field by identifying patients with advancing cirrhotic disease who require more aggressive approaches to HCC treatment. Due to active hepatocellular carcinoma (HCC) surveillance, many patients are diagnosed with early-stage disease and are usually amendable to curative treatments. These patients lack poor prognostic factors associated with Milan Criteria and alpha fetoprotein (AFP) biomarker levels. There are currently limited strategies to assess prognosis in the patients who remain at risk of post-treatment HCC progression. In a cohort of liver transplant (LT) candidates with HCC, this study seeks to identify factors prior to liver-directed therapy (LDT) associated with time to progression (TTP). This is a retrospective analysis of prospectively collected data from LT candidates with recently diagnosed HCC and receiving LDT as a bridge to LT at three interventional oncology programs within a single system (n = 373). Demographics, clinical hepatology and serology, and factors related to HCC burden were extracted and analyzed for associations with TTP risk. Albumin level below the cohort median (3.4 g/dL) emerged as an independent risk factor for TTP controlling for AFP > 20 ng/mL as well as Milan, T-stage, and Barcelona Clinic Liver Cancer (BCLC) stage individually. In modality-specific subgroup survival analysis, albumin-based TTP stratification was restricted to patients receiving first cycle microwave ablation (p = 0.007). In n = 162 patients matching all low-risk criteria for Milan, T-stage, BCLC stage, and AFP, the effect of albumin < 3.4 g/dL remained significant for TTP (p = 0.004) with 2-year TTP rates of 68% (<3.4 g/dL) compared to 95% (≥3.4 g/dL). In optimal bridge to LT candidates with small HCC and low AFP biomarker levels, albumin level at treatment baseline provides an HCC-independent positive prognostic factor for risk of HCC progression prior to LT. [ABSTRACT FROM AUTHOR]

Ice friction plays an important role in many engineering applications, e.g., tires on icy roads, ice breaker ship motion, or winter sports equipment. Although numerous experiments have already been performed to understand the effect of various conditions on ice friction, to reveal the fundamental frictional mechanisms is still a challenging task. This study uses in situ white light interferometry to analyze ice surface topography during linear friction testing with a rubber slider. The method helps to provide an understanding of the link between changes in the surface topography and the friction coefficient through direct visualization and quantitative measurement of the morphologies of the ice surface at different length scales. Besides surface polishing and scratching, it was found that ice melts locally even after one sweep showing the refrozen droplets. A multi-scale rubber friction theory was also applied to study the contribution of viscoelasticity to the total friction coefficient, which showed a significant level with respect to the smoothness of the ice; furthermore, the theory also confirmed the possibility of local ice melting. [ABSTRACT FROM AUTHOR]

Single ventricle patients typically undergo some form of advanced diagnostic imaging prior to superior cavopulmonary connection (SCPC). We sought to evaluate variability of diagnostic practice and associated comprehensive risk. A retrospective evaluation across 4 institutions was performed (1/1/2010–9/30/2016) comparing the primary modalities of cardiac catheterization (CC), cardiac magnetic resonance (CMR), and cardiac computed tomography (CT). Associated risks included anesthesia/sedation, vascular access, total room time, contrast agent usage, radiation exposure, and adverse events (AEs). Of 617 patients undergoing SCPC, 409 (66%) underwent at least one advanced diagnostic imaging study in the 60 days prior to surgery. Seventy-eight of these patients (13%) were analyzed separately because of a concomitant cardiac intervention during CC. Of 331 (54%) with advanced imaging and without catheterization intervention, diagnostic CC was most common (59%), followed by CT (27%) and CMR (14%). Primary modality varied significantly by institution (p < 0.001). Median time between imaging and SCPC was 13 days (IQR 3–33). Anesthesia/sedation varied significantly (p < 0.001). Pre-procedural vascular access did not vary significantly across modalities (p = 0.111); procedural access varied between CMR/CT and CC, in which central access was used in all procedures. Effective radiation dose was significantly higher for CC than CT (p < 0.001). AE rate varied significantly, with 12% CC, 6% CMR, and 1% CT (p = 0.004). There is significant practice variability in the use of advanced diagnostic imaging prior to SCPC, with important differences in associated procedural risk. Future studies to identify differences in diagnostic accuracy and long-term outcomes are warranted to optimize diagnostic protocols. [ABSTRACT FROM AUTHOR]

Background: There is substantial interest in blood biomarkers as fast and objective diagnostic tools for traumatic brain injury (TBI) in the acute setting.Methods: Adult patients (≥18) with TBI of any severity and indications for CT scanning and orthopaedic injury controls were prospectively recruited during 2011-2013 at Turku University Hospital, Finland. The severity of TBI was classified with GCS: GCS 13-15 was classified as mild (mTBI); GCS 9-12 as moderate (moTBI) and GCS 3-8 as severe (sTBI). Serum samples were collected within 24 hours of admission and biomarker levels analysed with high-performance kits. The ability of biomarkers to distinguish between severity of TBI and CT-positive and CT-negative patients was assessed.Results: Among 189 patients recruited, neurofilament light (NF-L) was obtained from 175 patients with TBI and 40 controls. S100 calcium-binding protein B (S100B), heart fatty-acid binding protein (H-FABP) and interleukin-10 (IL-10) were analysed for 184 patients with TBI and 39 controls. There were statistically significant differences between levels of all biomarkers between the severity classes, but none of the biomarkers distinguished patients with moTBI from patients with sTBI. Patients with mTBI discharged from the ED had lower levels of IL-10 (0.26, IQR=0.21, 0.39 pg/mL), H-FABP (4.15, IQR=2.72, 5.83 ng/mL) and NF-L (8.6, IQR=6.35, 15.98 pg/mL) compared with those admitted to the neurosurgical ward, IL-10 (0.55, IQR=0.31, 1.42 pg/mL), H-FABP (6.022, IQR=4.19, 20.72 ng/mL) and NF-L (13.95, IQR=8.33, 19.93 pg/mL). We observed higher levels of H-FABP and NF-L in older patients with mTBI. None of the biomarkers or their combinations was able to distinguish CT-positive (n=36) or CT-negative (n=58) patients with mTBI from controls.Conclusions: S100B, H-FABP, NF-L and IL-10 levels in patients with mTBI were significantly lower than in patients with moTBI and sTBI but alone or in combination, were unable to distinguish patients with mTBI from orthopaedic controls. This suggests these biomarkers cannot be used alone to diagnose mTBI in trauma patients in the acute setting. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is a molecularly heterogeneous disease, with a 5-year survival rate that still hovers at ~60% despite recent advancements. The advanced stage upon diagnosis, limited success with effective targeted therapy and lack of reliable biomarkers are among the key factors underlying the marginally improved survival rates over the decades. Prevention, early detection and biomarker-driven treatment adaptation are crucial for timely interventions and improved clinical outcomes. Liquid biopsy, analysis of tumour-specific biomarkers circulating in bodily fluids, is a rapidly evolving field that may play a striking role in optimising patient care. In recent years, significant progress has been made towards advancing liquid biopsies for non-invasive early cancer detection, prognosis, treatment adaptation, monitoring of residual disease and surveillance of recurrence. While these emerging technologies have immense potential to improve patient survival, numerous methodological and biological limitations must be overcome before their implementation into clinical practice. This review outlines the current state of knowledge on various types of liquid biopsies in HNSCC, and their potential applications for diagnosis, prognosis, grading treatment response and post-treatment surveillance. It also discusses challenges associated with the clinical applicability of liquid biopsies and prospects of the optimised approaches in the management of HNSCC. [ABSTRACT FROM AUTHOR]

Oral cavity squamous cell carcinoma (OSCC) affects more than 30 000 individuals in the United States annually, with smoking and alcohol consumption being the main risk factors. Management of early‐stage tumors usually includes surgical resection followed by postoperative radiotherapy in certain cases. The cervical lymph nodes (LNs) are the most common site for local metastasis, and elective neck dissection is usually performed if the primary tumor thickness is greater than 3.5 mm. However, postoperative histological examination often reveals that many patients with early‐stage disease are negative for neck nodal metastasis, posing a pressing need for improved risk stratification to either avoid overtreatment or prevent the disease progression. To this end, we aimed to identify a primary tumor gene signature that can accurately predict cervical LN metastasis in patients with early‐stage OSCC. Using gene expression profiles from 189 samples, we trained K‐top scoring pairs models and identified six gene pairs that can distinguish primary tumors with nodal metastasis from those without metastasis. The signature was further validated on an independent cohort of 35 patients using real‐time polymerase chain reaction (PCR) in which it achieved an area under the receiver operating characteristic (ROC) curve and accuracy of 90% and 91%, respectively. These results indicate that such signature holds promise as a quick and cost effective method for detecting patients at high risk of developing cervical LN metastasis, and may be potentially used to guide the neck treatment regimen in early‐stage OSCC. What's new? In oral squamous cell carcinoma (OSCC), early diagnosis of lymph‐node metastasis is essential for successful treatment. However, there is a pressing need for techniques that can improve risk stratification, in order to spare patients without metastases from further invasive surgery. In this study, the authors used a computer model to identify a simple, clinic‐friendly gene panel that can predict which OSCC tumors will likely spread to the lymph nodes. The reliability of this panel underscores the importance of embedding biological knowledge in the training process of cancer predictive models. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is a molecularly heterogeneous disease, with a 5-year survival rate that still hovers at ~60% despite recent advancements. The advanced stage upon diagnosis, limited success with effective targeted therapy and lack of reliable biomarkers are among the key factors underlying the marginally improved survival rates over the decades. Prevention, early detection and biomarker-driven treatment adaptation are crucial for timely interventions and improved clinical outcomes. Liquid biopsy, analysis of tumour-specific biomarkers circulating in bodily fluids, is a rapidly evolving field that may play a striking role in optimising patient care. In recent years, significant progress has been made towards advancing liquid biopsies for non-invasive early cancer detection, prognosis, treatment adaptation, monitoring of residual disease and surveillance of recurrence. While these emerging technologies have immense potential to improve patient survival, numerous methodological and biological limitations must be overcome before their implementation into clinical practice. This review outlines the current state of knowledge on various types of liquid biopsies in HNSCC, and their potential applications for diagnosis, prognosis, grading treatment response and post-treatment surveillance. It also discusses challenges associated with the clinical applicability of liquid biopsies and prospects of the optimised approaches in the management of HNSCC. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) has a favorable prognosis which has led to efforts to de-intensify treatment. Response-adaptive de-escalated treatment is promising, however improved biomarkers are needed. Quantitative cell-free HPV-DNA (cfHPV-DNA) in plasma represents an attractive non-invasive biomarker for grading treatment response and post-treatment surveillance. This prospective study evaluates dynamic changes in cfHPV-DNA during induction therapy, definitive (chemo)radiotherapy, and post-treatment surveillance in the context of risk and response-adaptive treatment for HPV + OPC.Methods: Patients with locoregional HPV + OPC are stratified into two cohorts: High risk (HR) (T4, N3, [Formula: see text] 20 pack-year smoking history (PYH), or non-HPV16 subtype); Low risk (LR) (all other patients). All patients receive induction chemotherapy with three cycles of carboplatin and paclitaxel. LR with ≥ 50% response receive treatment on the single-modality arm (minimally-invasive surgery or radiation alone to 50 Gy). HR with ≥ 50% response or LR with ≥ 30% and < 50% response receive treatment on the intermediate de-escalation arm (chemoradiation to 50 Gy with cisplatin). All other patients receive treatment on the regular dose arm with chemoradiation to 70 Gy with concurrent cisplatin. Plasma cfHPV-DNA is assessed during induction, (chemo)radiation, and post-treatment surveillance. The primary endpoint is correlation of quantitative cfHPV-DNA with radiographic response.Discussion: A de-escalation treatment paradigm that reduces toxicity without compromising survival outcomes is urgently needed for HPV + OPC. Response to induction chemotherapy is predictive and prognostic and can select candidates for de-escalated definitive therapy. Assessment of quantitative cfHPV-DNA in the context of response-adaptive treatment of represents a promising reliable and convenient biomarker-driven strategy to guide personalized treatment in HPV + OPC.Trial Registration: This trial is registered with ClinicalTrials.gov on October 1st, 2020 with Identifier: NCT04572100 . [ABSTRACT FROM AUTHOR]

Introduction: Development of novel diagnostic tools is a top research priority in vascular dementia. A major obstacle is the lack of a simple, non‐invasive method to visualize cerebral arteriolar walls in vivo. Retinal arterioles offer a window into the cerebral circulation. Methods: Intensity‐based retinal arteriolar visualization in optical coherence tomography (I‐bRAVO) was applied to evaluate mean wall thickness (MWT) and wall‐to‐lumen ratio (WLR) in 250 subjects with sporadic and genetic cerebral small vessel disease (CSVD), non‐vascular neurodegenerative diseases (NVND), and healthy controls (HC) in association with imaging and cognitive markers. Results: MWT and WLR were higher in CSVD, associated with severity of vascular white matter lesions, and correlated with magnetic resonance imaging‐based intracranial arteriolosclerosis score. WLR correlated with gray and white matter volume and differentiated asymptomatic sporadic CSVD from HC (area under the curve = 0.82). Discussion: I‐bRAVO is a rapid, non‐invasive tool. MWT and WLR were associated with imaging markers of CSVD and could contribute to early identification of sporadic CSVD. [ABSTRACT FROM AUTHOR]