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BACKGROUND: Degenerative cervical myelopathy (DCM) is a progressive chronic spinal cord injury estimated to affect 1 in 50 adults. Without standardised guidance, clinical research studies have selected outcomes at their discretion, often underrepresenting the disease and limiting comparability between studies. Utilising a standard minimum data set formed via multi-stakeholder consensus can address these issues. This combines processes to define a core outcome set (COS)-a list of key outcomes-and core data elements (CDEs), a list of key sampling characteristics required to interpret the outcomes. Further how these outcomes should be measured and/or reported is then defined in a core measurement set (CMS). This can include a recommendation of a standardised time point at which outcome data should be reported. This study defines a COS, CDE, and CMS for DCM research. METHODS AND FINDINGS: A minimum data set was developed using a series of modified Delphi processes. Phase 1 involved the setup of an international DCM stakeholder group. Phase 2 involved the development of a longlist of outcomes, data elements, and formation into domains. Phase 3 prioritised the outcomes and CDEs using a two-stage Delphi process. Phase 4 determined the final DCM minimal data set using a consensus meeting. Using the COS, Phase 5 finalised definitions of the measurement construct for each outcome. In Phase 6, a systematic review of the literature was performed, to scope and define the psychometric properties of measurement tools. Phase 7 used a modified Delphi process to inform the short-listing of candidate measurement tools. The final measurement set was then formed through a consensus meeting (Phase 8). To support implementation, the data set was then integrated into template clinical research forms (CRFs) for use in future clinical trials (Phase 9). In total, 28 outcomes and 6 domains (Pain, Neurological Function, Life Impact, Radiology, Economic Impact, and Adverse Events) were entered into the final COS. Thirty two outcomes and 4 domains (Individual, Disease, Investigation, and Intervention) were entered into the final CDE. Finally, 4 outcome instruments (mJOA, NDI, SF-36v2, and SAVES2) were identified for the CMS, with a recommendation for trials evaluating outcomes after surgery, to include baseline measurement and at 6 months from surgery. CONCLUSIONS: The AO Spine RECODE-DCM has produced a minimum data set for use in DCM clinical trials today. These are available at https://myelopathy.org/minimum-dataset/. While it is anticipated the CDE and COS have strong and durable relevance, it is acknowledged that new measurement tools, alongside an increasing transition to study patients not undergoing surgery, may necessitate updates and adaptation, particularly with respect to the CMS.

Abstract: Time series similarity matrices (informally, recurrence plots or dot-plots), are useful tools for time series data mining. They can be used to guide data exploration, and various useful features can be derived from them and then fed into downstream analytics. However, time series similarity matrices suffer from very poor scalability, taxing both time and memory requirements. In this work, we introduce novel ideas that allow us to scale the largest time series similarity matrices that can be examined by several orders of magnitude. The first idea is a novel algorithm to compute the matrices in a way that removes dependency on the subsequence length. This algorithm is so fast that it allows us to now address datasets where the memory limitations begin to dominate. Our second novel contribution is a multiscale algorithm that computes an approximation of the matrix appropriate for the limitations of the user’s memory/screen-resolution, then performs a local, just-in-time recomputation of any region that the user wishes to zoom-in on. Given that this largely removes time and space barriers, human visual attention then becomes the bottleneck. We further introduce algorithms that search massive matrices with quadrillions of cells and then prioritize regions for later examination by either humans or algorithms. We will demonstrate the utility of our ideas for data exploration, segmentation, and classification in domains as diverse as astronomy, bioinformatics, entomology, and wildlife monitoring.

Neurologic events (NEs) have been reported during treatment with blinatumomab, a bispecific T cell engager (BiTE®) construct. We evaluated the occurrence, severity, and management of NEs; the relationship between NEs and blinatumomab dose; and the potential clinical risk factors in an open-label, single-arm, phase 2 study (N = 189). Patients had Philadelphia chromosome-negative, relapsed/refractory acute lymphoblastic leukemia (ALL) and ≥ 10% bone marrow blasts. The relationship between blinatumomab exposure and NE incidence and severity was assessed. Clinical risk factors for NEs were assessed in a post hoc multivariate analysis. Overall, 98 patients (52%) experienced NEs: most frequently, dizziness, tremor, confusional state, and encephalopathy. NEs occurred predominantly during cycle 1 (median onset, 9 days) and were usually grades 1 or 2. Grade ≥ 3 NEs (13-17% incidence), serious NEs (16-19% incidence), and recurring NEs were managed with infusion interruptions or dexamethasone treatment. The incidence of NEs increased with increasing blinatumomab exposure at a given dose, but exposure appeared unrelated to NE severity. NEs were more frequent in patients ≥ 65 years than  2 prior salvage therapies (HR, 2.48; P = 0.006), and prior NEs (HR, 1.65; P = 0.020) were risk factors for time to first on-study NE. Although the mechanism underlying NEs associated with blinatumomab treatment in patients with relapsed/refractory ALL remains unclear, NEs tended to occur early during treatment and were often resolved by interrupting treatment and with dexamethasone. Additional research is warranted to investigate the risk factors for NEs.

Time series motifs are approximately repeated subsequences found within a longer time series. They have been in the literature since 2002, but recently they have begun to receive significant attention in research and industrial communities. This is perhaps due to the growing realization that they implicitly offer solutions to a host of time series problems, including rule discovery, anomaly detection, density estimation, semantic segmentation, summarization, etc. Recent work has improved the scalability so exact motifs can be computed on datasets with up to a million data points in tenable time. However, in some domains, for example seismology or climatology, there is an immediate need to address even larger datasets. In this work, we demonstrate that a combination of a novel algorithm and a high-performance GPU allows us to significantly improve the scalability of motif discovery. We demonstrate the scalability of our ideas by finding the full set of exact motifs on a dataset with one hundred and forty-three million subsequences, which is by far the largest dataset ever mined for time series motifs/joins; it requires ten quadrillion pairwise comparisons. Furthermore, we demonstrate that our algorithm can produce actionable insights into seismology and ethology.

This paper introduces a multiterminal escape routing algorithm for the design of printed circuit boards (PCBs) that control digital microfluidic biochips (DMFBs). The new algorithm extends a negotiated congestion-based single-terminal escape router that has been shown to be superior to previous methods. It relaxes the pin assignment to allow pin groups to be broken up when doing so can reduce the number of PCB layers. Experimental results indicate that the improved method can reduce both the number of PCB layers and average wirelength compared to existing DMFB escape routers.

Introduction: Glucocorticoids (GCs) are commonly prescribed for laryngeal indications due to their potent anti‐inflammatory properties. However, GCs effect on vocal fold (VF) epithelial morphology and barrier function following injury is overlooked and may be key to efficacy. In this study, the effects of GCs on epithelial morphology and barrier function were quantified in injured VFs. We seek to increase our understanding of biochemical processes underlying GC mechanisms to refine therapeutic strategies. Methods: Microflap injury was induced in 65 rabbits. Seven days after injury, animals received bilateral 20 μL intracordal injections of saline, dexamethasone, methylprednisolone, or triamcinolone (n = 15 per condition). Five rabbits in each condition were euthanized 1, 7, or 60 days following treatment. An additional five animals served as non‐injured/untreated controls. To quantify transepithelial electrical resistance (TEER), 1 mm epithelial biopsies were placed in an Ussing chamber. The contralateral VF was processed for transmission electron microscopy and epithelial depth analysis. Results: At 60 days, GC treatment maintained TEER levels similar to non‐injured/untreated controls. However, triamcinolone reduced TEER compared with saline‐treated conditions. Acutely, epithelial hyperplasia typically persisted in all injured VFs. At 60 days, only dexamethasone and triamcinolone increased epithelial depth in injured VFs; all GCs increased epithelial depth compared with non‐injured/untreated controls. Conclusion: Acutely, GCs did not alter TEER. Additionally, GCs did not alter epithelial depth compared with saline treatment, indicating alignment with natural healing responses. At 60 days, GCs exhibited varying degrees of TEER restoration and epithelial hyperplasia, possibly due to distinct pharmacodynamic profiles. Level of Evidence: NA Laryngoscope, 135:206–212, 2025 [ABSTRACT FROM AUTHOR]

Time series motifs have been in the literature for about fifteen years, but have only recently begun to receive significant attention in the research community. This is perhaps due to the growing realization that they implicitly offer solutions to a host of time series problems, including rule discovery, anomaly detection, density estimation, semantic segmentation, etc. Recent work has improved the scalability to the point where exact motifs can be computed on datasets with up to a million data points in tenable time. However, in some domains, for example seismology, there is an insatiable need to address even larger datasets. In this work we show that a combination of a novel algorithm and a high-performance GPU allows us to significantly improve the scalability of motif discovery. We demonstrate the scalability of our ideas by finding the full set of exact motifs on a dataset with one hundred million subsequences, by far the largest dataset ever mined for time series motifs. Furthermore, we demonstrate that our algorithm can produce actionable insights in seismology and other domains.

This paper describes a publicly available, open source software framework designed to support research efforts on algorithms and control for digital microfluidic biochips (DMFBs), an emerging laboratory-on-a-chip (LoC) technology. The framework consists of two parts: a compiler, which converts an assay, specified using the BioCoder language, into a sequence of electrode activations that execute out the assay on the DMFB; and a printed circuit board (PCB) layout tool, which includes algorithms to reduce the number of control pins and PCB layers required to drive the chip from an external source. The framework also includes a suite of visualization tools for debugging, and a collection of front-end algorithms that generate mixing/dilution trees for sample preparation.

Objectives/Hypothesis: Systemic glucocorticoids (GC)s are employed to treat various voice disorders. However, GCs have varying pharmacodynamic properties with adverse effects ranging from changes in epithelial integrity, skeletal muscle catabolism, and altered body weight. We sought to characterize the acute temporal effects of systemic dexamethasone and methylprednisolone on vocal fold (VF) epithelial glucocorticoid receptor (GR) nuclear translocation, epithelial tight junction (ZO-1) expression, thyroarytenoid (TA) muscle fiber morphology, and body weight using an established pre-clinical model. We hypothesized dexamethasone and methylprednisolone will elicit changes in VF epithelial GR nuclear translocation, epithelial ZO-1 expression, TA muscle morphology, and body weight compared to placebo-treated controls. Methods: Forty-five New Zealand white rabbits received intramuscular injections of methylprednisolone (4.5 mg; n = 15), dexamethasone (450 µg; n = 15), or volume matched saline (n = 15) into the iliocostalis/longissimus muscle for 6 consecutive days. Vocal folds from 5 rabbits from each treatment group were harvested at 1-, 3-, or 7 days following the final injection and subjected to immunohistochemistry for ZO-1 and GR as well as TA muscle fiber cross-sectional area (CSA) measures. Results: Dexamethasone increased epithelial GR nuclear translocation and ZO-1 expression 1-day following injections compared to methylprednisolone (P =.024; P =.012). Dexamethasone and methylprednisolone increased TA CSA 1-day following injections (P =.011). Methylprednisolone decreased body weight 7 days following injections compared to controls (P =.004). Conclusions: Systemic dexamethasone may more efficiently activate GR in the VF epithelium with a lower risk of body weight loss, suggesting a role for more refined approaches to GC selection for laryngeal pathology. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: Glucocorticoids (GC)s are commonly employed to treat vocal fold (VF) pathologies. However, VF atrophy has been associated with intracordal GC injections. Dexamethasone‐induced skeletal muscle atrophy is well‐documented in other tissues and believed to be mediated by increased muscle proteolysis via upregulation of Muscle Ring Finger (MuRF)‐1 and Atrogin‐1. Mechanisms of dexamethasone‐mediated VF atrophy have not been described. This pilot study employed in vitro and in vivo models to investigate the effects of dexamethasone on VF epithelium, thyroarytenoid (TA) muscle, and TA‐derived myoblasts. We hypothesized that dexamethasone will increase atrophy‐associated gene expression in TA muscle and myoblasts and decrease TA muscle fiber size and epithelial thickness. Study Design: In vitro, pre‐clinical. Methods: TA myoblasts were isolated from a female Sprague–Dawley rat and treated with 1 μM dexamethasone for 24‐h. In vivo, 15 New Zealand white rabbits were randomly assigned to three treatment groups: (1) bilateral intracordal injection of 40 μL dexamethasone (10 mg/ml; n = 5), (2) volume‐matched saline (n = 5), and (3) untreated controls (n = 5). Larynges were harvested 7‐days post‐injection. Across in vivo and in vitro experimentation, MuRF‐1 and Atrogin‐1 mRNA expression were measured via RT‐qPCR. TA muscle fiber cross‐sectional area (CSA) and epithelial thickness were also quantified in vivo. Results: Dexamethasone increased MuRF‐1 gene expression in TA myoblasts. Dexamethasone injection, however, did not alter atrophy‐associated gene expression, TA CSA, or epithelial thickness in vivo. Conclusion: Dexamethasone increased atrogene expression in TA myoblasts, providing foundational insight into GC induced atrophic gene transcription. Repeated dexamethasone injections may be required to elicit atrophy in vivo. Level of Evidence: NA Laryngoscope, 133:2264–2270, 2023 [ABSTRACT FROM AUTHOR]

Objectives: Functional outcomes following microflap surgery for vocal fold pathology are favorable. Although the stratified squamous epithelium appears to heal rapidly, persistent physiologic tissue alterations are likely. We sought to elucidate key biochemical processes including recruitment of immune cells, regulation of cellular junction proteins, and long‐term alterations to epithelial tissue permeability following microflap with an eye toward enhanced clinical outcomes. Methods: Forty New Zealand rabbits were assigned to eight groups (n = 5/group): no‐injury control or bilateral microflap with survival for 0 h, 12 h, 1 day, 3 days, 7 days, 30 days, and 60 days post‐microflap. The epithelium was dissected from one vocal fold and transepithelial resistance was quantified. The contralateral fold was subjected to transmission electron microscopy. Images were evaluated by a blinded rater and paracellular space dilation was quantified using ImageJ. Immune cell infiltration was evaluated and recorded qualitatively. Results: Increased innate immune response was observed 12 h as well as 7 and 30 days after microflap. At 60 days following injury, decreased epithelial resistance was observed. Paracellular spaces were dilated at all time‐points following injury. Conclusions: The vocal fold epithelium was significantly altered at 60 days following microflap. The implications for this tissue phenotype are unclear. However, compromised epithelial barrier function is implicated in various diseases and may increase the risk of subsequent injury. Level of Evidence: NA Laryngoscope, 133:350–356, 2023 [ABSTRACT FROM AUTHOR]