The effect of attentional cues on mechanical efficiency and movement smoothness in running gait: An interdisciplinary investigation.

The aim was to examine the effect of focus of attention cues on foot angle for retraining movement purposes. Twenty (females: 8) rearfoot-striking recreational runners (mass: 72.5 ± 11.8 kg; height: 1.73 ± 0.09 m; age: 32.9 ± 11.3 years) were randomly assigned to an internal focus (IF) (n = 10) or external focus (EF) (n = 10) verbal cue group. Participants performed 5 × 6 minute blocks of treadmill running (control run, 3 × cued running, retention run) at a self-selected running velocity (9.4 ± 1.1 km∙h-1) during a single laboratory visit. Touchdown foot angle, mechanical efficiency, internal and external work were calculated and, centre of mass (COM) and foot movement smoothness was quantified. Linear-mixed effect models showed an interaction for foot angle (p < 0.001, ηp2 = 0.35) and mechanical efficiency (p < 0.001, ηp2 = 0.40) when comparing the control to the cued running. Only the IF group reduced foot angle and mechanical efficiency during cued running, but not during the retention run. The IF group produced less external work during the 1st cued run than the control run. COM and foot smoothness were unaffected by cueing. Only an IF produced desired technique changes but at the cost of reduced mechanical efficiency. Movement smoothness was unaffected by cue provision. Changes to foot angle can be achieved within 6 minutes of gait retraining.

Detecting Psychological Interventions Using Bilateral Electromyographic Wearable Sensors.

This study investigated the impact of auditory stimuli on muscular activation patterns using wearable surface electromyography (EMG) sensors. Employing four key muscles (Sternocleidomastoid Muscle (SCM), Cervical Erector Muscle (CEM), Quadricep Muscles (QMs), and Tibialis Muscle (TM)) and time domain features, we differentiated the effects of four interventions: silence, music, positive reinforcement, and negative reinforcement. The results demonstrated distinct muscle responses to the interventions, with the SCM and CEM being the most sensitive to changes and the TM being the most active and stimulus dependent. Post hoc analyses revealed significant intervention-specific activations in the CEM and TM for specific time points and intervention pairs, suggesting dynamic modulation and time-dependent integration. Multi-feature analysis identified both statistical and Hjorth features as potent discriminators, reflecting diverse adaptations in muscle recruitment, activation intensity, control, and signal dynamics. These features hold promise as potential biomarkers for monitoring muscle function in various clinical and research applications. Finally, muscle-specific Random Forest classification achieved the highest accuracy and Area Under the ROC Curve for the TM, indicating its potential for differentiating interventions with high precision. This study paves the way for personalized neuroadaptive interventions in rehabilitation, sports science, ergonomics, and healthcare by exploiting the diverse and dynamic landscape of muscle responses to auditory stimuli.

Rothia in Nonsmall Cell Lung Cancer is Associated With Worse Survival.

INTRODUCTION: The microbiome is known to play a significant role in cancer biology; however, few studies have elucidated its relationship with Nonsmall Cell Lung Cancer (NSCLC) patient outcomes. We hypothesized that there are specific microorganisms that are closely related with NSCLC patient survival. METHODS: Total of 647 NSCLC (Adenocarcinoma and Squamous Cell Carcinoma combined) patients in The Cancer Genome Atlas (TCGA) were analyzed using the R software. RESULTS: A Volcano Plot was analyzed with the patients divided into Short and Long Survivors by overall survival of 0.9 years, and we found that a bacterium Rothia was significantly abundant in Short Survivors, and Blastococcus, Leptospira, and Haematobacter in Long Survivors, but presence of Rothia alone was associated with overall survival. The age, race, subtype, and sex were not significantly different by the presence of Rothia in NSCLC. Unexpectedly, Rothia-positive NSCLC was associated with less cell proliferation by gene set enrichment analysis, Mki67 expression, proliferation score, with less fraction altered and homologous recombination deficiency, and with high infiltration of stromal cells, indicating favorable oncological characteristics. Further, Rothia-positive tumors were associated with significantly higher infiltration of CD8 T cells, CD4 T cells, Monocytes, and NK cells, and high interferon-gamma response, T-cell receptor richness, cytolytic activity, indicating favorable tumor immune microenvironment. CONCLUSIONS: NSCLC with Rothia was associated with worse survival but also with favorable oncological characteristics such as less cell proliferation and favorable tumor immune microenvironment. We cannot help but speculate that Rothia in NSCLC is associated with mortality unrelated to oncological characteristics.

Using wearable technology data to explain recreational running injury: A prospective longitudinal feasibility study.

OBJECTIVES: Investigate 1) if collecting and analysing wristwatch inertial measurement unit (IMU) and global positioning system (GPS) data using a commercially-available training platform was feasible in recreational runners and 2) which variables were associated with subsequent injury. DESIGN: Prospective longitudinal cohort. PARTICIPANTS: Healthy recreational runners. MAIN OUTCOME MEASURES: We set a priori feasibility thresholds for recruitment (maximum six-months), acceptance (minimum 80%), adherence (minimum 70%), and data collection (minimum 80%). Participants completed three patient-reported outcome measures (PROMS) detailing their psychological health, sleep quality, and intrinsic motivation to run. We extracted baseline anthropometric, biomechanical, metabolic, and training load data from their IMU/GPS wristwatch for analysis. Participants completed a weekly injury status surveillance questionnaire over the next 12-weeks. Feasibility outcomes were analysed descriptively and injured versus non-injured group differences with 95% confidence intervals were calculated for PROM/IMU/GPS data. RESULTS: 149 participants consented; 86 participants completed (55 men, 31 women); 21 developed an injury (0.46 injuries/1000km). Feasibility outcomes were satisfied (recruitment = 47 days; acceptance = 133/149 [89%]; adherence = 93/133 [70%]; data collection = 86/93 [92%]). Acute load by calculated effort was associated with subsequent injury (mean difference -562.14, 95% CI -1019.42, -21.53). CONCLUSION: Collecting and analysing wristwatch IMU/GPS data using a commercially-available training platform was feasible in recreational runners.

Wide-Area Debris Field and Seabed Characterization of a Deep Ocean Dump Site Surveyed by Autonomous Underwater Vehicles.

Disposal of industrial and hazardous waste in the ocean was a pervasive global practice in the 20th century. Uncertainty in the quantity, location, and contents of dumped materials underscores ongoing risks to marine ecosystems and human health. This study presents an analysis of a wide-area side-scan sonar survey conducted with autonomous underwater vehicles (AUVs) at a dump site in the San Pedro Basin, California. Previous camera surveys located 60 barrels and other debris. Sediment analysis in the region showed varying concentrations of the insecticidal chemical dichlorodiphenyltrichloroethane (DDT), of which an estimated 350-700 t were discarded in the San Pedro Basin between 1947 and 1961. A lack of primary historical documents specifying DDT acid waste disposal methods has contributed to the ambiguity surrounding whether dumping occurred via bulk discharge or containerized units. Barrels and debris observed during previous surveys were used for ground truth classification algorithms based on size and acoustic intensity characteristics. Image and signal processing techniques identified over 74,000 debris targets within the survey region. Statistical, spectral, and machine learning methods characterize seabed variability and classify bottom-type. These analytical techniques combined with AUV capabilities provide a framework for efficient mapping and characterization of uncharted deep-water disposal sites.

Diverse heterochromatin states restricting cell identity and reprogramming.

Heterochromatin is defined as a chromosomal domain harboring repressive H3K9me2/3 or H3K27me3 histone modifications and relevant factors that physically compact the chromatin. Heterochromatin can restrict where transcription factors bind, providing a barrier to gene activation and changes in cell identity. While heterochromatin thus helps maintain cell differentiation, it presents a barrier to overcome during efforts to reprogram cells for biomedical purposes. Recent findings have revealed complexity in the composition and regulation of heterochromatin, and shown that transiently disrupting the machinery of heterochromatin can enhance reprogramming. Here, we discuss how heterochromatin is established and maintained during development, and how our growing understanding of the mechanisms regulating H3K9me3 heterochromatin can be leveraged to improve our ability to direct changes in cell identity.

A pioneer factor locally opens compacted chromatin to enable targeted ATP-dependent nucleosome remodeling.

To determine how different pioneer transcription factors form a targeted, accessible nucleosome within compacted chromatin and collaborate with an ATP-dependent chromatin remodeler, we generated nucleosome arrays in vitro with a central nucleosome containing binding sites for the hematopoietic E-Twenty Six (ETS) factor PU.1 and Basic Leucine Zipper (bZIP) factors C/EBPα and C/EBPß. Our long-read sequencing reveals that each factor can expose a targeted nucleosome on linker histone-compacted arrays, but with different nuclease sensitivity patterns. The DNA binding domain of PU.1 binds mononucleosomes, but requires an additional intrinsically disordered domain to bind and open compacted chromatin. The canonical mammalian SWI/SNF (cBAF) remodeler was unable to act upon two forms of locally open chromatin unless cBAF was enabled by a separate transactivation domain of PU.1. cBAF potentiates the PU.1 DNA binding domain to weakly open chromatin in the absence of the PU.1 disordered domain. Our findings reveal a hierarchy by which chromatin is opened and show that pioneer factors can provide specificity for action by nucleosome remodelers.

Identifying Individuals Who Currently Report Feelings of Anxiety Using Walking Gait and Quiet Balance: An Exploratory Study Using Machine Learning.

Literature suggests that anxiety affects gait and balance among young adults. However, previous studies using machine learning (ML) have only used gait to identify individuals who report feeling anxious. Therefore, the purpose of this study was to identify individuals who report feeling anxious at that time using a combination of gait and quiet balance ML. Using a cross-sectional design, participants (n = 88) completed the Profile of Mood Survey-Short Form (POMS-SF) to measure current feelings of anxiety and were then asked to complete a modified Clinical Test for Sensory Interaction in Balance (mCTSIB) and a two-minute walk around a 6 m track while wearing nine APDM mobility sensors. Results from our study finds that Random Forest classifiers had the highest median accuracy rate (75%) and the five top features for identifying anxious individuals were all gait parameters (turn angles, variance in neck, lumbar rotation, lumbar movement in the sagittal plane, and arm movement). Post-hoc analyses suggest that individuals who reported feeling anxious also walked using gait patterns most similar to older individuals who are fearful of falling. Additionally, we find that individuals who are anxious also had less postural stability when they had visual input; however, these individuals had less movement during postural sway when visual input was removed.

Movement strategy correspondence across jumping and cutting tasks after anterior cruciate ligament reconstruction.

There are currently a multitude of tests used to assess readiness to return to sport (RTS) following anterior cruciate ligament reconstruction (ACLR). The aim of this study was to establish the extent to which movement strategies transfer between three common assessment tasks to help improve design of athlete testing batteries following ACLR. A cohort of 127 male patients 8-10 months post-ACLR and 45 non-injured controls took part in the study. Three movement tasks were completed (unilateral and bilateral drop jump, and 90° pre-planned cut), while ground reaction forces and three-dimensional kinematics (250 Hz) were recorded. Compared to the bilateral drop jump and cut, the unilateral drop jump had a higher proportion of work done at the ankle (d = 0.29, p < 0.001 and d = -1.87, p < 0.001, respectively), and a lower proportion of work done at the knee during the braking phase of the task (d = 0.447, p < 0.001 and d = 1.56, p < 0.001, respectively). The ACLR group had higher peak hip moments than the non-injured controls, although the proportion of work done at the ankle, knee and hip joints were similar. Movement strategies were moderately and positively related at the ankle (rs  = 0.728, p < 0.001), knee (rs  = 0.638, p < 0.001) and hip (rs  = 0.593, p < 0.001) between the unilateral and bilateral drop jump, but there was no relationship at the ankle (rs  = 0.10, p = 0.104), knee (rs  = 0.106, p = 0.166) and hip (rs  = -0.019, p = 0.808) between the unilateral drop jump and the cut. Clinicians could therefore consider omitting one of the drop jumps from assessment batteries but should include both jumping and cutting tasks.

Autonomous learning and interpretation of channel multipath scattering using braid manifolds in underwater acoustic communications.

In this work, we explore machine learning through a model-agnostic feature representation known as braiding, that employs braid manifolds to interpret multipath ray bundles. We generate training and testing data using the well-known BELLHOP model to simulate shallow water acoustic channels across a wide range of multipath scattering activity. We examine three different machine learning techniques-k-nearest neighbors, random forest tree ensemble, and a fully connected neural network-as well as two machine learning applications. The first application applies known physical parameters and braid information to determine the number of reflections the acoustic signal may undergo through the environment. The second application applies braid path information to determine if a braid is an important representation of the channel (i.e., evolving across bands of higher amplitude activity in the channel). Testing accuracy of the best trained machine learning algorithm in the first application was 86.70% and the testing accuracy of the second application was 99.94%. This work can be potentially beneficial in examining how the reflectors in the environment changeover time while also determining relevant braids for faster channel estimation.

Diverse heterochromatin-associated proteins repress distinct classes of genes and repetitive elements.

Heterochromatin, typically marked by histone H3 trimethylation at lysine 9 (H3K9me3) or lysine 27 (H3K27me3), represses different protein-coding genes in different cells, as well as repetitive elements. The basis for locus specificity is unclear. Previously, we identified 172 proteins that are embedded in sonication-resistant heterochromatin (srHC) harbouring H3K9me3. Here, we investigate in humans how 97 of the H3K9me3-srHC proteins repress heterochromatic genes. We reveal four groups of srHC proteins that each repress many common genes and repeat elements. Two groups repress H3K9me3-embedded genes with different extents of flanking srHC, one group is specific for srHC genes with H3K9me3 and H3K27me3, and one group is specific for genes with srHC as the primary feature. We find that the enhancer of rudimentary homologue (ERH) is conserved from Schizosaccharomyces pombe in repressing meiotic genes and, in humans, now represses other lineage-specific genes and repeat elements. The study greatly expands our understanding of H3K9me3-based gene repression in vertebrates.

Employing and Interpreting a Machine Learning Target-Cognizant Technique for Analysis of Unknown Signals in Multiple Reaction Monitoring.

The aim of this interdisciplinary work is a robust signal processing and autonomous machine learning framework to associate well-known (target) as well as any potentially unknown (non-target) peaks present within gas chromatography-mass spectrometry (GC/MS/MS) raw instrument signal. Particularly, this work evaluates three machine learning algorithms abilities to autonomously associate raw signal peaks based on accuracy in training and testing. A target is a known congener that is expected to be present within the raw instrument signal and a non-target is an unknown or unexpected compound. Autonomously identifying target peaks within the GC/MS/MS and associating them with non-target peaks can help improve the analysis of collected samples. Association of peaks refers to classifying peaks as known congeners regardless if the peak is a target or non-target. Uncertainty of peaks fitted and discovered through raw instrument signals from GC/MS/MS data is assessed to create topographical illustrations of target annotated peaks among sample raw instrument signals collected across diverse locations in the Chicago area. The term "annotated peak" is used to assign peaks found at specific retention times as a known congener. Adaptive signal processing techniques are utilized to smooth data and correct baseline drifts as well as detect and separate coeluted (overlapped) peaks in the raw instrument signal to provide key feature extraction. 150 air samples are analyzed for individual polychlorinated biphenyls (PCB) with GC/MS/MS across Chicago, IL. 80% of the data is used for training classification of target PCBs and 20% of the data is evaluated to identify and associate consistently occurring non-target peaks with target PCBs. A random forest classifier is used to associate identified peaks to target PCB peaks. Geographical topographical representations of target PCBs in the raw instrument signal demonstrates how PCBs accumulate and degrade in certain locations.

Massive Gasoline Ingestion in a 64-Year-Old Female: An Explosive Situation.

Hydrocarbons from gasoline are toxins that can affect a multitude of organ systems based on the route of chemical intoxication exposure, with a majority involving oral ingestion or inhalation. Data is still incomplete concerning the systemic complications of gasoline ingestion due in part to variability in the chemical composition of various gasoline products. A 64-year-old female presented to her local emergency department following the ingestion of gasoline in a suicide attempt with altered mental status, hypotension, shortness of breath, tachypnea, sinus tachycardia, coarse rhonchi bilaterally, and hyperactive bowel sounds. Treatment upon admission included intravenous ampicillin/sulbactam, intubation, an intravenous fluid bolus, and ketamine to address the developing hypotension. The patient developed multiorgan failure and acute toxic encephalopathy despite medical interventions and hemodialysis. After four days, comfort care measures were initiated, and the patient passed away. Gasoline toxicity can have a profound effect on multiple organs based on the chemical properties and the route of exposure. These sequelae can be monitored through patient symptoms as well as radiologic imaging. Early supportive therapy and decontamination are vital in decreasing the morbidity and mortality associated with gasoline ingestion.

Modern Medical Miracle: Matched Unrelated Donor Hematopoietic Stem Cell Transplant After Aplastic Anemia.

Aplastic anemia is a hematological disease with deadly complications related to pancytopenia if not treated in a timely manner. First-line treatment consists of immunosuppressive therapy or matched sibling donor (MSD) hematopoietic stem cell transplant. Step up treatment involves a matched unrelated donor (MUD) hematopoietic stem cell transplant (HSCT) alongside immunosuppressant conditioning. However, recent research suggests that there is improved success of MUD HSCT for severe aplastic anemia compared to immunosuppressive therapy. We present a case of an 18-year-old who was diagnosed with severe aplastic anemia who received numerous immunosuppressive therapy regimens prior to obtaining a MUD HSCT. Over a year after bone marrow transplant, the patient is doing well with no signs of rejection. This case creates an argument for the use of upfront MUD HSCT as a curative treatment for acquired aplastic anemia rather than initial treatment with immunosuppressive agents.

Signal Processing Methods to Interpret Polychlorinated Biphenyls in Airborne Samples.

The main contribution of this interdisciplinary work is a robust computational framework to autonomously discover and quantify previously unknown associations between well-known (target) and potentially unknown (non-target) toxic industrial air pollutants. In this work, the variability of polychlorinated biphenyl (PCB) data is evaluated using a combination of statistical, signal processing, and graph-based informatics techniques to interpret the raw instrument signal from gas chromatography-mass spectrometry (GC/MS/MS) data sets. Specifically, minimum mean-squared techniques from the adaptive signal processing literature are extended to detect and separate coeluted (overlapped) peaks in the raw instrument signal. A graph-based visualization is provided which bridges two complementary approaches to quantitative pollution studies: (i) peak-cognizant target analysis (limits data analysis to few well-known compounds) and (ii) chemometric analysis (statistical large-scale data analysis) that is agnostic of specific compounds. Further, peak fitting techniques based on L2 error minimization are employed to autonomously calculate the amount of each PCB present with a normalized mean square error of -18.4851 dB. Graph-based visualization of associations between known and unknown compounds are developed through principal component analysis and both fuzzy c-means (FCM) and k-means clustering techniques are implemented and compared. The efficiency of these methods are compared using 150 air samples analyzed for individual PCBs with GC/MS/MS against traditional target-only techniques that perform analysis across only the known (target) PCBs. Parameter optimization techniques are employed to evaluate the relative contribution of PCB signals against ten potential source signals representing legacy signatures from historical manufacture of Aroclors and modern sources of PCBs produced as by products of pigment and polymer manufacturing. Aroclors 1232, 1254, 1016, and 1221 as well as non-Aroclor 3, 3', dichlorobiphenyl (PCB 11) were found in many of the samples as unique source signals that describe PCB mixtures in air samples collected from Chicago, IL.

Jaw Pain and Profound Bradycardia - An Atypical Presentation of Lyme Carditis.

In 2018, 23,558 confirmed cases and 10,108 probable cases of Lyme disease were reported in the United States, with 96% of all cases coming from 14 states. Lyme carditis is well described, occurring in less than 1% of Lyme disease. High-grade heart block is uncommon in early disseminated Lyme disease. In Lyme carditis due to sinus node dysfunction and/or high grade atrioventricular block, the pulse rates are significantly lower which can lead to syncope. This can happen in the setting of an unstable ventricular escape rhythm with pulse rates ranging around 30 beats per minute or lower. In patients with low cardiovascular reserve, high-degree AV block can cause sudden death. Here we describe a rare case of profound bradycardia in disseminated Lyme disease. The patient's only two symptoms are bradycardia and jaw pain. He lacks erythema migrans, neurological symptoms or syncope - despite having high-degree AV block. Initially prescribed doxycycline 100mg BID, his PR interval begins to normalize, but once a Lyme titre was positive for IgM (p41, p39, p23) and IgG (p66, p45, p41, p39, p23, p18), the patient was switched to 2g ceftriaxone IV Q 24h, per Infectious Disease Society of America (IDSA) guidelines. After several days he feels better and was discharged home to complete antibiotics and wear a cardiac event monitor. Lyme disease has three distinct stages that include early localized infection, early disseminated disease, and late infection. At the time of Lyme carditis diagnosis, common symptoms include erythema migrans, malaise, polyarthritis, Bell's palsy and other neurological symptoms - all of which were lacking in our patient. The prognosis for Lyme carditis is generally good, despite disagreement over the incidence of persistent B. burgdorferi infection. This patient's unique presentation of Lyme carditis is further evidence of variability in cardiac symptoms depending on one's immunological and physiological ability to combat acute spirochete infection.

Two-parameter single-molecule analysis for measurement of chromatin mobility.

This protocol provides a two-parameter analysis of single-molecule tracking (SMT) trajectories of Halo-tagged histones in living adherent cell lines and unveils a chromatin mobility landscape composed of five chromatin types, ranging from low to high mobility. When the analysis is applied to Halo-tagged, chromatin-binding proteins, it associates chromatin interaction properties with known functions in a way that previously used SMT parameters did not. For complete information on the use and execution of this protocol, please refer to Lerner et al. (2020).

Two-Parameter Mobility Assessments Discriminate Diverse Regulatory Factor Behaviors in Chromatin.

Enzymatic probes of chromatin structure reveal accessible versus inaccessible chromatin states, while super-resolution microscopy reveals a continuum of chromatin compaction states. Characterizing histone H2B movements by single-molecule tracking (SMT), we resolved chromatin domains ranging from low to high mobility and displaying different subnuclear localizations patterns. Heterochromatin constituents correlated with the lowest mobility chromatin, whereas transcription factors varied widely with regard to their respective mobility with low- or high-mobility chromatin. Pioneer transcription factors, which bind nucleosomes, can access the low-mobility chromatin domains, whereas weak or non-nucleosome binding factors are excluded from the domains and enriched in higher mobility domains. Nonspecific DNA and nucleosome binding accounted for most of the low mobility of strong nucleosome interactor FOXA1. Our analysis shows how the parameters of the mobility of chromatin-bound factors, but not their diffusion behaviors or SMT-residence times within chromatin, distinguish functional characteristics of different chromatin-interacting proteins.

Phase 1 study to evaluate safety, tolerability and pharmacokinetics of a novel intra-tympanic administered thiosulfate to prevent cisplatin-induced hearing loss in cancer patients.

Cisplatin is a widely used chemotherapy for the treatment of certain solid tumors. Ototoxicity and subsequent permanent hearing loss remain a serious dose-limiting side effect associated with cisplatin treatment. To date, no therapies have been approved to prevent or treat cisplatin-induced hearing loss (CIHL). Sodium thiosulfate effectively inactivates cisplatin through covalent binding and may provide protection against cisplatin-induced ototoxicity. DB-020 is being developed as a novel formulation of sodium thiosulfate pentahydrate in 1% sodium hyaluronate for intratympanic injection (IT), enabling the delivery of high concentrations of thiosulfate into the cochlea prior to cisplatin administration. In the DB-020-002 phase 1a single-ascending dose study, healthy volunteers were enrolled into 5 cohorts to receive different doses of DB-020 via IT injection. Cohorts 1-4 received unilateral injections while Cohort 5 received bilateral injections. Plasma thiosulfate pharmacokinetics was measured, and safety and audiometric data were collected throughout the study. This study has demonstrated that intratympanic administration of DB-020 results in nominal systemic increases in thiosulfate levels, hence it should not compromise cisplatin anti-tumor efficacy. Furthermore, DB-020 was safe and well tolerated with most adverse events reported as transient, of mild-to-moderate severity and related to the IT administration procedure. These results support the design and execution of the ongoing proof-of-concept study, DB-020-002, to assess otoprotection using DB-020 in cancer patients receiving cisplatin without negatively impacting cisplatin anti-tumor efficacy.