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Clostridioides difficile is a bacterial pathogen that has been implicated in severe gastrointestinal infections. C. difficile has intrinsic green autofluorescence and the level of this autofluorescence is known to be increased by growth time and oxygen. Currently, it is unclear if dietary compounds or metabolites from the gut microbiota are able to enhance C. difficile autofluorescence. Here, we aimed to determine potential factors that affect C. difficile autofluorescence. After screening a large repertoire of compounds, we identified several substances, like L-lysine and pantothenate, that led to an increased C. difficile autofluorescence. We also found that several members of the gut microbiota, such as Enterococcus faecalis, Klebsiella aerogenes and K. pneumoniae, can increase C. difficile autofluorescence through their secreted compounds. We further focused on the effect of K. pneumoniae on C. difficile autofluorescence and found that multiple enteric strains of K. pneumoniae could enhance C. difficile’s autofluorescence. We used this enhanced autofluorescence to identify C. difficile in K. pneumoniae co-cultures by flow cytometry. Our findings shed light on the relationship between C. difficile and other members of the gut microbiota, as well as different factors that can affect C. difficile autofluorescence.

The choice of deposition technique and post deposition treatment can significantly influence the performance of organic electronic devices by altering the complex relationship between film properties and charge transport. Herein, the influence of deposition method and post deposition thermal annealing on the thin‐film properties of an emerging semiconductor, bis(tri‐n‐propylsilyl oxide) SiPc ((3PS)2‐SiPc), is examined by polarized Raman microscopy. Comparing physical vapor deposition (PVD) and spin‐coating, the orientation of (3PS)2‐SiPc molecules in films is determined and further characterized by X‐ray diffraction to assess variations in microstructure and morphology due to thermal annealing. Despite differences in film formation, non‐annealed organic thin‐film transistors (OTFTs) fabricated by PVD and spin‐coating resulted in similar electron mobilities (μe) on the order of 10−2 cm2 V−1 s−1 and threshold voltages (VT) of 10–20 V. Films fabricated by PVD annealed at 175 °C transition to a new polymorphic form with molecules aligned at a higher angle to the substrate and exhibiting reduced device performance. Conversely, spin‐coated films do not undergo any new polymorph formation or structural reorganization with thermal annealing. PVD fabricated films are thus more readily able to undergo transformations to structure and morphology with post deposition processing, while the microstructure of spin‐coated films is established at the time of deposition.

Objective: Low vagal tone is common in osteoarthritis (OA) comorbidities and results in greater peripheral inflammation. Characterizing vagal tone's role in OA pathogenesis may offer insights into OA's influences beyond the articular joint. We hypothesized that low vagal tone would accelerate onset of OA-related gait changes and worsen joint damage in a rat knee OA model. Methods: Knee OA was induced in male Sprague Dawley rats by transecting the medial collateral ligament and medial meniscus. Then, left cervical vagus nerve transection (VGX, n ​= ​9) or sham VGX (non-VGX, n ​= ​6) was performed. Gait and tactile sensitivity were assessed at baseline and across 12 weeks, with histology and systemic inflammation evaluated at endpoint. Results: At week 4, VGX animals showed limping gait characteristics through shifted stance times from their OA to non-OA limb (p ​= ​0.055; stance time imbalance ​= ​1.6 ​± ​1.6%) and shifted foot strike locations (p ​

Abstract Here, four MOFs, namely Sc-TBAPy, Al-TBAPy, Y-TBAPy, and Fe-TBAPy (TBAPy: 1,3,6,8-tetrakis(p-benzoic acid)pyrene), were characterized and evaluated for their ability to remediate glyphosate (GP) from water. Among these materials, Sc-TBAPy demonstrates superior performance in both the adsorption and degradation of GP. Upon light irradiation for 5 min, Sc-TBAPy completely degrades 100% of GP in a 1.5 mM aqueous solution. Femtosecond transient absorption spectroscopy reveals that Sc-TBAPy exhibits enhanced charge transfer character compared to the other MOFs, as well as suppressed formation of emissive excimers that could impede photocatalysis. This finding was further supported by hydrogen evolution half-reaction (HER) experiments, which demonstrated Sc-TBAPy’s superior catalytic activity for water splitting. In addition to its faster adsorption and more efficient photodegradation of GP, Sc-TBAPy also followed a selective pathway towards the oxidation of GP, avoiding the formation of toxic aminomethylphosphonic acid observed with the other M3+-TBAPy MOFs. To investigate the selectivity observed with Sc-TBAPy, electron spin resonance, depleted oxygen conditions, and solvent exchange with D2O were employed to elucidate the role of different reactive oxygen species on GP photodegradation. The findings indicate that singlet oxygen (1O2) plays a critical role in the selective photodegradation pathway achieved by Sc-TBAPy.

Vesicular stomatitis (VS) is a viral disease that affects horses, cattle, and swine that is transmitted by direct contact and hematophagous insects. In 2023, a multi-state outbreak of vesicular stomatitis New Jersey virus (VSNJV) occurred in California, Nevada, and Texas, infecting horses, cattle, and rhinoceros. To identify possible insect vectors, we conducted insect surveillance at various locations in San Diego County, CA, including at a wildlife park. CO2 baited traps set from mid-May to mid-August 2023 collected 2357 Culicoides biting midges and 1215 Simulium black flies, which are insect genera implicated in VSNJV transmission. Insects were pooled by species, location, and date, then tested for viral RNA. Nine RNA-positive pools of Culicoides spp. and sixteen RNA-positive pools of Simulium spp were detected. Infectious virus was detected by cytopathic effect in 96% of the RNA-positive pools. This is the first report of VSNJV in wild-caught C. bergi, C. freeborni, C. occidentalis, S. argus, S. hippovorum, and S. tescorum. The vector competency of these species for VSNJV has yet to be determined but warrants examination. Active vector surveillance and testing during disease outbreaks increases our understanding of the ecology and epidemiology of VS and informs vector control efforts.

IntroductionLow back pain is the most common type of chronic pain. We examined pain-related behaviors across 18 weeks in rats that received injury to one or two lumbar intervertebral discs (IVD) to determine if multi-level disc injuries enhance/prolong pain.MethodsTwenty-three Sprague-Dawley adult female rats were used: 8 received disc puncture (DP) of one lumbar IVD (L5/6, DP-1); 8 received DP of two lumbar IVDs (L4/5 & L5/6, DP-2); 8 underwent sham surgery.ResultsDP-2 rats showed local (low back) sensitivity to pressure at 6- and 12-weeks post-injury, and remote sensitivity to pressure (upper thighs) at 12- and 18-weeks and touch (hind paws) at 6, 12 and 18-weeks. DP-1 rats showed local and remote pressure sensitivity at 12-weeks only (and no tactile sensitivity), relative to Sham DP rats. Both DP groups showed reduced distance traveled during gait testing over multiple weeks, compared to pre-injury; only DP-2 rats showed reduced distance relative to Sham DP rats at 12-weeks. DP-2 rats displayed reduced positive interactions with a novel adult female rat at 3-weeks and hesitation and freezing during gait assays from 6-weeks onwards. At study end (18-weeks), radiological and histological analyses revealed reduced disc height and degeneration of punctured IVDs. Serum BDNF and TNFα levels were higher at 18-weeks in DP-2 rats, relative to Sham DP rats, and levels correlated positively with remote sensitivity in hind paws (tactile) and thighs (pressure).DiscussionThus, multi-level disc injuries resulted in earlier, prolonged and greater discomfort locally and remotely, than single-level disc injury. BDNF and TNFα may have contributing roles.

Sarah Candy,1,2 Julie Reeve,2 Rosie Dobson,3,4 Robyn Whittaker,3,4 Jeffrey Garrett,1 Jim Warren,5 Amanda Calder,3 Taria Tane,3 Trina Robertson,4 Usman Rashid,2 Denise Taylor2 1Te Whatu Ora Counties Manukau Health, Auckland, New Zealand; 2Health & Rehabilitation Research Institute, Auckland University of Technology, Auckland, New Zealand; 3National Institute for Health Innovation, University of Auckland, Auckland, New Zealand; 4Te Whatu Ora Waitematā, Auckland, New Zealand; 5School of Computer Science, University of Auckland, Auckland, New ZealandCorrespondence: Sarah Candy, Department of Respiratory Medicine, Te Whatu Ora Counties Manukau, Private Bag 93311, Otahuhu, Auckland, 1640, New Zealand, Tel +64274363116, Email scandy@middlemore.co.nzPurpose: Pulmonary rehabilitation (PR) is vital in the management of chronic respiratory disorders (CRDs) although uptake, attendance and completion are poor. Differing models of delivering PR are emerging in an attempt to increase the uptake and completion of this intervention. This study aimed to evaluate participant rate of attendance and completion of PR when given a preference regarding model of delivery (centre-based and mPR). Secondary aims were to evaluate the factors affecting patient preference for model of delivery and determine whether mPR is non-inferior to centre-based PR in health outcomes.Methods: A multi-centre non-inferiority preference based clinical trial in Auckland, New Zealand. Participants with a CRD referred for PR were offered the choice of centre-based or mHealth PR (mPR). The primary outcome was completion rate of chosen intervention.Results: A total of 105 participants were recruited to the study with 67 (64%) preferring centre-based and 38 (36%) mPR. The odds of completing the PR programme were higher in the centre-based group compared to mPR (odds ratio 1.90 95% CI [0.83– 4.35]). Participants opting for mPR were significantly younger (p = 0.002) and significantly more likely to be working (p = 0.0001). Results showed that mPR was not inferior to centre-based regarding changes in symptom scores (CAT) or time spent in sedentary behaviour (SBQ). When services were forced to transition to telehealth services during COVID-19 restrictions, the attendance and completion rates were higher with telephone calls and video conferencing compared to mPR – suggesting that synchronous interpersonal interactions with clinicians may facilitate the best attendance and completion rates.Conclusion: When offered the choice of PR delivery method, the majority of participants preferred centre-based PR and this facilitated the best completion rates. mPR was the preferred choice for younger, working participants suggesting that mPR may offer a viable alternative to centre-based PR for some participants, especially younger, employed participants.Keywords: chronic respiratory disorder, mHealth, preference, pulmonary rehabilitation, telehealth, telerehabilitation

ObjectiveTo investigate the relationship between corneal diameter and internal corneal span determined from angle-to-angle distance using ultrasound biomicroscopy (UBM) in an observational cross-sectional patient population comprised of 54 eyes (28 healthy control eyes, ages 0.1 to 11.3 years; 26 eyes with primary congenital glaucoma, ages 0.1 to 3.5 years) from 41 pediatric participants ages 0.1 to 11.3 years (mean age: 3±3 years, median age: 2 years).MethodsForty cornea photographs with reference ruler and 110 UBM images were obtained. Three observers measured horizontal and vertical corneal diameter and angle-to-angle distance in each cornea photo and UBM image using ImageJ and the average values were used. Main outcome measures were Pearson correlation coefficient, linear regression, mean difference between corneal diameter and angle-to-angle distance, and intra-class correlation coefficients among measurements from all three observers for each parameter.ResultsCorneal diameter and angle-to-angle distance had a strong positive correlation horizontally (Pearson r = 0.89, pConclusionsBased on the strong positive correlation found between corneal diameter and angle-to-angle distance in our study population, UBM image analysis can be used to accurately estimate corneal diameter from angle-to-angle distance in children with healthy eyes and primary congenital glaucoma. UBM may provide a useful intraocular alternative for estimating corneal diameter and monitoring diseases that affect the cornea in infants and children, such as congenital glaucoma.

Abstract Objective: This comprehensive literature scoping review outlines available infection prevention and control (IPC) methods for viral-mediated gene therapies and provides one IPC strategy for the healthcare setting based on a single-center recommendation. Methods: A team of experts in pharmacy, healthcare epidemiology, and biosafety with experience in viral-mediated gene therapy was assembled within a pediatric hospital to conduct a comprehensive literature scoping review. The comprehensive review included abstracts and full-text articles published since 2009 and utilized prespecified search terms of the five viral vectors of interest: adenovirus (AV), retrovirus (RV), adeno-associated virus (AAV), lentivirus (LV), and herpes simplex virus (HSV). Case reports, randomized controlled trials, and bench research studies were all included, while systematic reviews were excluded. Results: A total of 4473 case reports, randomized control trials, and benchtop research studies were identified using the defined search criteria. Chlorine compounds were found to inactivate AAV and AV, while alcohol-based disinfectants were ineffective. There was a relative paucity of studies investigating surface-based disinfection for HSV, however, alcohol-based disinfectants were effective in one study. Ultraviolent irradiation was also found to inactivate HSV in numerous studies. No studies investigated disinfection for LV and RV vectors. Conclusions: The need to define IPC methods is high due to the rapid emergence of viral-mediated gene therapies to treat rare diseases, but published clinical guidance remains scarce. In the absence of these data, our center recommends a 1:10 sodium hypochlorite solution in clinical and academic environments to ensure complete germicidal activity of viral-mediated gene therapies.

Photochromic fluorescent proteins (FPs) have proved to be indispensable luminous probes for sophisticated and advanced bioimaging techniques. Among them, an interplay between photoswitching and photoconversion has only been observed in a limited subset of Kaede-like FPs that show potential for discovering the key mechanistic steps during green-to-red photoconversion. Various spectroscopic techniques including femtosecond stimulated Raman spectroscopy (FSRS), X-ray crystallography, and femtosecond transient absorption were employed on a set of five related FPs with varying photoconversion and photoswitching efficiencies. A 3-methyl-histidine chromophore derivative, incorporated through amber suppression using orthogonal aminoacyl tRNA synthetase/tRNA pairs, displays more dynamic photoswitching but greatly reduced photoconversion versus the least-evolved ancestor (LEA). Excitation-dependent measurements of the green anionic chromophore reveal that the varying photoswitching efficiencies arise from both the initial transient dynamics of the bright cis state and the final trans-like photoswitched off state, with an exocyclic bridge H-rocking motion playing an active role during the excited-state energy dissipation. This investigation establishes a close-knit feedback loop between spectroscopic characterization and protein engineering, which may be especially beneficial to develop more versatile FPs with targeted mutations and enhanced functionalities, such as photoconvertible FPs that also feature photoswitching properties.

Background: Transcranial focused ultrasound has the potential to noninvasively modulate deep brain circuits and impart sustained, neuroplastic effects. Objective: Bring the approach closer to translations by demonstrating sustained modulation of deep brain circuits and choice behavior in task-performing non-human primates. Methods: Low-intensity transcranial ultrasound of 30 s in duration was delivered in a controlled manner into deep brain targets (left or right lateral geniculate nucleus; LGN) of non-human primates while the subjects decided whether a left or a right visual target appeared first. While the animals performed the task, we recorded intracranial EEG from occipital screws. The ultrasound was delivered into the deep brain targets daily for a period of more than 6 months. Results: The brief stimulation induced effects on choice behavior that persisted up to 15 minutes and were specific to the sonicated target. Stimulation of the left/right LGN increased the proportion of rightward/leftward choices. These effects were accompanied by an increase in gamma activity over visual cortex. The contralateral effect on choice behavior and the increase in gamma, compared to sham stimulation, suggest that the stimulation excited the target neural circuits. There were no detrimental effects on the animals' discrimination performance over the months-long course of the stimulation. Conclusion: This study demonstrates that brief, 30-s ultrasonic stimulation induces neuroplastic effects specifically in the target deep brain circuits, and that the stimulation can be applied daily without detrimental effects. These findings encourage repeated applications of transcranial ultrasound to malfunctioning deep brain circuits in humans with the goal of providing a durable therapeutic reset.

Hava Izci,1 Gilles Macq,2 Tim Tambuyzer,2 Harlinde De Schutter,2 Hans Wildiers,1,3 Francois P Duhoux,4 Evandro de Azambuja,5 Donatienne Taylor,6 Gracienne Staelens,7 Guy Orye,8 Zuzana Hlavata,9 Helga Hellemans,10 Carine De Rop,11 Patrick Neven,1,3 Freija Verdoodt2 1KU Leuven - University of Leuven, Department of Oncology, Leuven, B-3000, Belgium; 2Belgian Cancer Registry, Research Department, Brussels, Belgium; 3University Hospitals Leuven, Multidisciplinary Breast Center, Leuven, B-3000, Belgium; 4Department of Medical Oncology, King Albert II Cancer Institute, Cliniques Universitaires Saint-Luc, Brussels, Belgium; 5Institut Jules Bordet and l’Université Libre de Bruxelles (U.L.B), Brussels, Belgium; 6CHU UCL Namur, Site Sainte-Elisabeth, Namur, Belgium; 7Multidisciplinary Breast Center, General Hospital Groeninge, Kortrijk, Belgium; 8Department of Obstetrics and Gynecology, Jessa Hospital, Hasselt, Belgium; 9Department of Medical Oncology, CHR Mons-Hainaut, Mons, Hainaut, Belgium; 10Department of Obstetrics and Gynaecology, AZ Delta, Roeselaere, Belgium; 11Department of Obstetrics and Gynaecology, Imelda Hospital, Bonheiden, BelgiumCorrespondence: Hava Izci, KU Leuven, Department of oncology, Herestraat 49 Box 7003-06, Leuven, 3000, Belgium, Email hava.izci@kuleuven.bePurpose: High-quality population-based cancer recurrence data are scarcely available, mainly due to complexity and cost of registration. For the first time in Belgium, we developed a tool to estimate distant recurrence after a breast cancer diagnosis at the population level, based on real-world cancer registration and administrative data.Methods: Data on distant cancer recurrence (including progression) from patients diagnosed with breast cancer between 2009– 2014 were collected from medical files at 9 Belgian centers to train, test and externally validate an algorithm (i.e., gold standard). Distant recurrence was defined as the occurrence of distant metastases between 120 days and within 10 years after the primary diagnosis, with follow-up until December 31, 2018. Data from the gold standard were linked to population-based data from the Belgian Cancer Registry (BCR) and administrative data sources. Potential features to detect recurrences in administrative data were defined based on expert opinion from breast oncologists, and subsequently selected using bootstrap aggregation. Based on the selected features, classification and regression tree (CART) analysis was performed to construct an algorithm for classifying patients as having a distant recurrence or not.Results: A total of 2507 patients were included of whom 216 had a distant recurrence in the clinical data set. The performance of the algorithm showed sensitivity of 79.5% (95% CI 68.8– 87.8%), positive predictive value (PPV) of 79.5% (95% CI 68.8– 87.8%), and accuracy of 96.7% (95% CI 95.4– 97.7%). The external validation resulted in a sensitivity of 84.1% (95% CI 74.4– 91.3%), PPV of 84.1% (95% CI 74.4– 91.3%), and an accuracy of 96.8% (95% CI 95.4– 97.9%).Conclusion: Our algorithm detected distant breast cancer recurrences with an overall good accuracy of 96.8% for patients with breast cancer, as observed in the first multi-centric external validation exercise.Keywords: machine learning, breast cancer, distant metastases, recurrences, algorithm, administrative data

Abstract This work presents a new method for processing single-crystal semiconductors designed by a computational method to lower the process temperature. This research study is based on a CALPHAD approach (ThermoCalc) to theoretically design processing parameters by utilizing theoretical phase diagrams. The targeted material composition consists of Bi–Se2–Te–Sb (BSTS). The semiconductor alloy contains three phases, hexagonal, rhombohedral-1, and rhombohedral-2 crystal structures, that are presented in the phase field of the theoretical pseudo-binary phase diagram. The semiconductor is also evaluated by applying Hume–Rothery rules along with the CALPHAD approach. Thermodynamic modelling suggests that single-crystals of BSTS can be grown at significantly lower temperatures and this is experimentally validated by low-temperature growth of single crystalline samples followed by exfoliation, compositional analysis, and diffraction.

Background:. Secondary Furlow (Furlow) and buccal myomucosal flaps (BMMF) treat velopharyngeal insufficiency by lengthening the palate and retropositioning the levator veli palatini muscles. The criteria for choosing one operation over the other remain unclear. Methods:. A single-center retrospective cohort study was conducted. Thirty-two patients with nonsyndromic, repaired cleft palate were included. All patients underwent a Furlow or BMMF. Outcome measures included (1) resolution of hypernasality 12 months postoperatively, (2) degree of improvement of hypernasality severity; and (3) change in velar length, as measured on magnetic resonance imaging scans obtained preoperatively and 12 months postoperatively. All measures were performed by raters blinded to participants’ medical and surgical history. Results:. Hypernasality was corrected to normal in 80% of the Furlow group and in 56% of the BMMF group. Patients receiving BMMF had more severe hypernasality during preoperative speech evaluation. Both groups had a median decrease of two scalar rating points for severity of hypernasality (P = 0.58). On postoperative magnetic resonance imaging, patients who underwent Furlow had a median increased velar length of 6.9 mm. Patients who received BMMF had a median increased velar length of 7.5 mm. There was no statistically significant difference between groups regarding increase in velar length (P = 0.95). Conclusions:. Furlow and BMMF procedures increase velar length with favorable speech outcomes. The same degree of improvement for hypernasality was observed across groups, likely explained by the similar increase in velar length achieved. Anatomic changes in palate length and levator veli palatini retropositioning persist 1 year after surgery.

In scientific disciplines, benchmarks play a vital role in driving progress forward. For a benchmark to be effective, it must closely resemble real-world tasks. If the level of difficulty or relevance is inadequate, it can impede progress in the field. Moreover, benchmarks should have low computational overhead to ensure accessibility and repeatability. The objective is to achieve a kind of ``Turing test'' by creating a surrogate model that is practically indistinguishable from the ground truth observation, at least within the dataset's explored boundaries. This objective necessitates a large quantity of data. This data encompasses numerous features that are characteristic of chemistry and materials science optimization tasks that are relevant to industry. These features include high levels of noise, multiple fidelities, multiple objectives, linear constraints, non-linear correlations, and failure regions. We performed 494498 random hard-sphere packing simulations representing 206 CPU days’ worth of computational overhead. Simulations required nine input parameters with linear constraints and two discrete fidelities each with continuous fidelity parameters. The data was logged in a free-tier shared MongoDB Atlas database, producing two core tabular datasets: a failure probability dataset and a regression dataset. The failure probability dataset maps unique input parameter sets to the estimated probabilities that the simulation will fail. The regression dataset maps input parameter sets (including repeats) to particle packing fractions and computational runtimes for each of the two steps. These two datasets were used to create a surrogate model as close as possible to running the actual simulations by incorporating simulation failure and heteroskedastic noise. In the regression dataset, percentile ranks were calculated for each group of identical parameter sets to account for heteroskedastic noise, thereby ensuring reliable and accurate data. This differs from the conventional approach that imposes a-priori assumptions, such as Gaussian noise, by specifying mean and standard deviation. This technique can be extended to other benchmark datasets to bridge the gap between optimization benchmarks with low computational overhead and the complex optimization scenarios encountered in the real world.

Nickel- and cobalt-based superalloys are commonly used as turbine materials for high-temperature applications. However, their maximum operating temperature is limited to about 1100 °C. Therefore, to improve turbine efficiency, current research is focused on designing materials that can withstand higher temperatures. Niobium-based alloys can be considered as promising candidates because of their exceptional properties at elevated temperatures. The conventional approach to alloy design relies on phase diagrams and structure–property data of limited alloys and extrapolates this information into unexplored compositional space. In this work, we harness machine learning and provide an efficient design strategy for finding promising niobium-based alloy compositions with high yield and ultimate tensile strength. Unlike standard composition-based features, we use domain knowledge-based custom features and achieve higher prediction accuracy. We apply Bayesian optimization to screen out novel Nb-based quaternary and quinary alloy compositions and find these compositions have superior predicted strength over a range of temperatures. We develop a detailed design flow and include Python programming code, which could be helpful for accelerating alloy design in a limited alloy data regime.

Abstract Background Hypertension is a common comorbidity of osteoarthritis (OA) with known autonomic dysregulation; thus, the autonomic nervous system may provide a shared underlying mechanism. The objective of this study was to examine the role of the autonomic nervous system in a preclinical model of OA and hypertension. Methods Experiments were conducted in spontaneously hypertensive rats and a normotensive control strain, including male and female rats. OA was surgically induced via medial meniscus transection with skin incision used as a sham control (n = 7–8/strain/sex/surgery). Tactile sensitivity, anxiety-related behavior, and serum corticosterone were measured at baseline then bi-weekly across 8 weeks. At weeks 9–10, cardiovascular responses to a chemical vagal nerve agonist were determined to indirectly evaluate vagus nerve function. The joint structure was assessed via grading of histological sections. Results In males, OA resulted in thinner cartilage in both hypertensive (OA vs. non-OA p < 0.001) and normotensive (OA vs. non-OA p < 0.001). Only females with comorbid hypertension and OA displayed thinner cartilage (p = 0.013). Male hypertensive OA animals had increased calcified subchondral bone compared to normotensive OA animals (p = 0.043) while female hypertensive OA animals had increased calcified subchondral bone compared to hypertensive sham animals (p < 0.001). All MCLT+MMT groups developed low-grade synovitis; interestingly, hypertensive OA females had higher synovitis scores than normotensive OA females (p = 0.046). Additionally, hypertension led to larger drops in blood pressure with vagal activation in both OA (hypertensive vs. normotensive p = 0.018) and sham (hypertensive vs. normotensive p < 0.001) male animals. In females, this trend held true only in OA animals (normotensive vs. hypertensive p = 0.005). Conclusion These data provide preliminary evidence that hypertension influences OA progression and encourages further study into the autonomic nervous system as a possible mechanism.

As the thickness of a three-dimensional (3D) topological insulator (TI) becomes comparable to the penetration depth of surface states, hybridization turns their gapless Dirac electronic structure into a gapped spectrum. Here, authors show that 2D topological states can exist in the 3D TI BiSbTeSe2 when the Fermi level is inside the hybridization gap.

Summary: Learn how to build a Closed-loop Spectroscopy Lab: Light-mixing demo (CLSLab:Light) to perform color matching via RGB LEDs and a light sensor for under 100 USD and less than an hour of setup. Our tutorial covers ordering parts, verifying prerequisites, software setup, sensor mounting, testing, and an optimization algorithm comparison tutorial. We use secure IoT-style communication via MQTT, MicroPython firmware on a pre-soldered Pico W microcontroller, and the self-driving-lab-demo Python package. A video tutorial is available at https://youtu.be/D54yfxRSY6s.For complete details on the use and execution of this protocol, please refer to Baird et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Transcranial focused ultrasound with the InSightec Exablate system uses thermal ablation for the treatment of movement and mood disorders and blood brain barrier disruption for tumor therapy. The system uses computed tomography (CT) images to calculate phase corrections that account for aberrations caused by the human skull. This work investigates whether magnetic resonance (MR) images can be used as an alternative to CT images to calculate phase corrections. Phase corrections were calculated using the gold standard hydrophone method and the standard of care InSightec ray tracing method. MR binary image mask, MR-simulated-CT (MRsimCT), and CT images of three ex vivo human skulls were supplied as inputs to the InSightec ray tracing method. The degassed ex vivo human skulls were sonicated with a 670 kHz hemispherical phased array transducer (InSightec Exablate 4000). 3D raster scans of the beam profiles were acquired using a hydrophone mounted on a 3-axis positioner system. Focal spots were evaluated using six metrics: pressure at the target, peak pressure, intensity at the target, peak intensity, positioning error, and focal spot volume. Targets at the geometric focus and 5 mm lateral to the geometric focus were investigated. There was no statistical difference between any of the metrics at either target using either MRsimCT or CT for phase aberration correction. As opposed to the MRsimCT, the use of CT images for aberration correction requires registration to the treatment day MR images; CT misregistration within a range of ± 2 degrees of rotation error along three dimensions was shown to reduce focal spot intensity by up to 9.4%. MRsimCT images used for phase aberration correction for the skull produce similar results as CT-based correction, while avoiding both CT to MR registration errors and unnecessary patient exposure to ionizing radiation.

Nanoscale emitters are useful for measuring biomolecular interactions, but are limited by weak signals. Here, the authors use a photonic crystal surface for 3000-fold signal enhancement, achieving single emitter sensitivity with extended on-time, and demonstrate its application in miRNA biomarker sensing.

IntroductionHolstein steers (n = 32) were used to determine if the ergot analog, bromocriptine decreases muscle protein synthesis through inhibitory action on the mTOR pathway via a direct effect on signal proteins, and if these negative effects can be alleviated with anabolic agents.MethodsSteers were treated with intramuscular administration of bromocriptine (vehicle or 0.1 mg/kg BW) and a subdermal commercial steroidal implant containing trenbolone acetate (TBA) and estradiol 17β (with or without), in a 2×2 factorial design. During the 35 day experiment, intake was restricted to 1.5 times maintenance energy requirement. On days 27 through 32, steers were moved to metabolism stalls for urine collection, and whole-body protein turnover was determined using a single pulse dose of [15N] glycine into the jugular vein on day 28. On day 35, skeletal muscle samples were collected before (basal state) and 60 min after (stimulated state) an i.v. glucose challenge (0.25 g glucose/kg). Blood samples were collected at regular intervals before and after glucose infusion for determination of circulating concentrations of glucose and insulin.ResultsBromocriptine reduced insulin and glucose clearance following the glucose challenge, indicating decreased insulin sensitivity and possible disruption of glucose uptake and metabolism in the skeletal muscle. Conversely, analysis of whole-body protein turnover demonstrated that bromocriptine does not appear to affect protein synthesis or urea excretion. Western immunoblot analysis of skeletal muscle showed that it did not affect abundance of S6K1 or 4E-BP1, so bromocriptine does not appear to inhibit activation of the mTOR pathway or protein synthesis. Estradiol/TBA implant decreased urea excretion and protein turnover but had no effect on protein synthesis, suggesting that steroidal implants promote protein accretion through unchanged rates of synthesis and decreased degradation, even in the presence of bromocriptine, resulting in improved daily gains. Implanted steers likely experienced increased IGF-1 signaling, but downstream activation of mTOR, S6K and 4E-BP1, and thus increased protein synthesis did not occur as expected.ConclusionsOverall, this data suggests that bromocriptine does not have a negative impact on muscle protein synthetic pathways independent of DMI.

Abstract Mucin-degrading microbes are known to harbor glycosyl hydrolases (GHs) which cleave specific glycan linkages. Although several microbial species have been identified as mucin degraders, there are likely many other members of the healthy gut community with the capacity to degrade mucins. The aim of the present study was to systematically examine the CAZyme mucin-degrading profiles of the human gut microbiota. Within the Verrucomicrobia phylum, all Akkermansia glycaniphila and muciniphila genomes harbored multiple gene copies of mucin-degrading GHs. The only representative of the Lentisphaerae phylum, Victivallales, harbored a GH profile that closely mirrored Akkermansia. In the Actinobacteria phylum, we found several Actinomadura, Actinomyces, Bifidobacterium, Streptacidiphilus and Streptomyces species with mucin-degrading GHs. Within the Bacteroidetes phylum, Alistipes, Alloprevotella, Bacteroides, Fermenitomonas Parabacteroides, Prevotella and Phocaeicola species had mucin degrading GHs. Firmicutes contained Abiotrophia, Blautia, Enterococcus, Paenibacillus, Ruminococcus, Streptococcus, and Viridibacillus species with mucin-degrading GHs. Interestingly, far fewer mucin-degrading GHs were observed in the Proteobacteria phylum and were found in Klebsiella, Mixta, Serratia and Enterobacter species. We confirmed the mucin-degrading capability of 23 representative gut microbes using a chemically defined media lacking glucose supplemented with porcine intestinal mucus. These data greatly expand our knowledge of microbial-mediated mucin degradation within the human gut microbiota.

A novel design and fabrication technique for complex microwave waveguide components has been developed. Open cellular structures, characterized by effective medium theory, are used as a replacement for conventional highly-conductive materials. The fabrication is enabled by advancements in additive manufacturing and metal deposition techniques. Components that can be fabricated by vat polymerization followed by electroless deposition of copper, are specifically addressed. The open cellular structure allows fluid penetration to the internal surfaces, allowing for more uniform deposition of metal throughout the part. This makes it feasible to fabricate electrically conductive, complex, multi-function, monolithic parts, something which has proven to be difficult with conventional fabrication techniques, even with recent developments in additive manufacturing. Effective conductivity values are reported for cellular structures that can be practically fabricated. The characterization as a meta surface, not only allows for the easy adoption into existing design work flows, but also enables the exploration of new designs, since the properties of the material can be easily manipulated by changing the fine details of the cellular mesh. Because of the extra degrees of freedom offered in the new process, it is possible to improve performance of secondary properties such as: size, weight, and thermal management characteristics.

Summary: Background: Melioidosis is a neglected tropical infection caused by the environmental saprophyte Burkholderia pseudomallei. Methods: We conducted a prospective, observational study at nine hospitals in northeastern Thailand, a hyperendemic melioidosis zone, to define current characteristics of melioidosis patients and quantify outcomes over one year. Findings: 2574 individuals hospitalised with culture-confirmed melioidosis were screened and 1352 patients were analysed. The median age was 55 years, 975 (72%) were male and 951 (70%) had diabetes. 561 (42%) patients presented with lung infection, 1042 (77%) were bacteraemic, 442 (33%) received vasopressors/inotropes and 547 (40%) received mechanical ventilation. 1307 (97%) received an intravenous antibiotic against B. pseudomallei. 335/1354 (25%) patients died within one month and 448/1331 (34%) of patients died within one year. Most patients had risk factors for melioidosis, but patients without identified risk factors did not have a reduced risk of death. Of patients discharged alive, most received oral trimethoprim-sulfamethoxazole, which was associated with decreased risk of post-discharge death; 235/970 (24%) were readmitted, and 874/1015 (86%) survived to one year. Recurrent infection was detected in 17/1018 patients (2%). Patients with risk factors other than diabetes had increased risk of death and increased risk of hospital readmission. Interpretation: In northeastern Thailand patients with melioidosis experience high rates of bacteraemia, organ failure and death. Most patients discharged alive survive one year although all-cause readmission is common. Recurrent disease is rare. Strategies that emphasize prevention, rapid diagnosis and intensification of early clinical management are likely to have greatest impact in this and other resource-restricted regions. Funding: US NIH/NIAID U01AI115520.

Abstract Seasonal subsidence induced by ground ice melt can be measured by interferometric synthetic aperture radar (InSAR) techniques to infer active layer thickness (ALT) in permafrost regions. The magnitude of subsidence depends on both how deep the soil thawed and how much ice/water content existed in the active layer soil. To provide the later, P‐band polarimetric synthetic aperture radar (PolSAR) backscatter is used due to its sensitivity to subsurface soil moisture and freeze/thaw conditions. In this study, which is the second in a two‐part series of Permafrost Dynamics Observatory (PDO), we exploit L‐band InSAR subsidence and P‐band PolSAR backscatter in a joint retrieval scheme to simultaneously estimate ALT and soil moisture profile of permafrost active layer. Both subsidence and backscatter are explicitly characterized by physics‐based models and share a common set of soil parameters including porosity and water saturation profiles. The PDO joint retrieval has been applied to the L‐ and P‐band SAR data acquired by National Aeronautics and Space Administration/Jet Propulsion Laboratory's Uninhabited Aerial Vehicle Synthetic Aperture Radar over Alaska and western Canada during the 2017 Arctic‐Boreal Vulnerability Experiment (ABoVE) airborne campaign. This high‐resolution (30 m) regional estimates of ALT and soil moisture profile spanning over the ABoVE study domain can help link the ground‐based field surveys with satellite observations to further understand the permafrost and active layer soil process dynamics to disturbances and climate change occurring across the northern circumpolar region.

IntroductionHigh quality semen is essential for reproductive efficiency. Nutrition and environmental factors impact the ejaculate components, like cytokines, that are essential for pregnancy establishment. We hypothesized that differing nutritional periods and body condition scores would affect seminal plasma cytokine concentrations of bulls.MethodsMature Angus bulls (n=11) were individually housed and randomly assigned to either over-fed (n=5) or restricted (n=6) treatment pathways. Bulls were fed different volumes of a single ration creating 8 individual treatment periods. Body weight and body condition scores were taken every 14 d to manage intake volumes. Ejaculates were collected every 84 d to determine seminal plasma cytokine profiles. A complete randomized design was used to evaluate seminal plasma cytokines after each nutritional treatment. Initial cytokine concentrations and volume of the ejaculate were included as covariates.ResultsAll cytokines returned to initial concentrations following maintenance treatments at an ideal body condition score of 6. Nutritional treatments affected (P ≤ 0.05) IFN-γ, IL-8, MIP-1α, MIP-1β, TNF-α, IL-1β, and VEGF-A. However, TNF-α, IFN-γ, and MIP-1α had the greatest impact on cytokine profile.DiscussionNutritional levels and adiposity altered seminal plasma cytokine concentrations which could potentially impact the inflammatory balance of the uterus and the immune responses necessary for pregnancy establishment.

Background: Following orthopedic surgery, patients with Parkinson's disease (PD) have been shown to have high rates of surgical complications, and some studies suggest that PD may be associated with greater risk for postoperative medical complications. As complication rates are critical to consider for elective surgery planning, the current study aimed to describe the association of PD with medical complications following anterior cervical discectomy and fusion (ACDF), the most commonly performed procedure to treat cervical degenerative pathology. Methods: The 2008-2018 National Inpatient Sample database was queried for cases involving elective ACDF. Demographics and comorbidities were extracted using ICD codes. Cases were propensity matched based on demographic and comorbidity burden, and logistic regression was used to compare in-hospital complications between patients with and without PD. Results: After weighting, a total of 1,273,437 elective ACDF cases were identified, of which 3948 (0.31%) involved cases with PD. After 1:1 propensity score matching by demographic and comorbidity variables, there were no differences between the PD and non-PD cohorts. Logistic regression models constructed for the matched and unmatched populations showed that PD cases have greater odds of in-hospital minor adverse events with no differences in odds of serious adverse events or mortality. Conclusions: After matching for demographics and comorbidity burden, PD cases undergoing elective ACDF had slightly longer length of stay and greater risk for minor adverse events but had similar rates of serious adverse events and mortality. These findings are important for surgeons and patients to consider when making decisions about surgical intervention.

Summary: Transcranial-focused ultrasound brings personalized medicine to the human brain. Ultrasound can modulate neural activity or release drugs in specific neural circuits but this personalized approach requires a system that delivers ultrasound into specified targets flexibly and on command. We developed a remote ultrasound system (Remus) that programmatically targets deep brain regions with high spatiotemporal precision and in a multi-focal manner. We validated these functions by modulating two deep brain nuclei—the left and right lateral geniculate nucleus—in a task-performing nonhuman primate. This flexible system will enable researchers and clinicians to diagnose and treat specific deep brain circuits in a noninvasive yet targeted manner, thus embodying the promise of personalized treatments of brain disorders.

Abstract In this paper, we demonstrate an application of the Transformer self-attention mechanism in the context of materials science. Our network, the Compositionally Restricted Attention-Based network (CrabNet), explores the area of structure-agnostic materials property predictions when only a chemical formula is provided. Our results show that CrabNet’s performance matches or exceeds current best-practice methods on nearly all of 28 total benchmark datasets. We also demonstrate how CrabNet’s architecture lends itself towards model interpretability by showing different visualization approaches that are made possible by its design. We feel confident that CrabNet and its attention-based framework will be of keen interest to future materials informatics researchers.

Abstract Electrochromic materials and devices are enabling a variety of advanced technologies. Gel-based organic electrochromic molecules such as ethyl viologen diperchlorate are attractive options due to their simple device design and low cost processing options relative to the more expensive and complex transition metal oxide films. However, electrochromic devices are subject to extensive cycling in which failure and fatigue can eventually occur. This work presents the lifetime cycling performance of ethyl viologen diperchlorate-based electrochromic devices using two different anodic compounds, hydroquinone and ferrocene, which are cycled at different voltages, 3 V and 1.2 V, respectively. Multiple devices are cycled until failure with periodic device characterization via UV–Vis spectroscopy, electrical resistance and power measurement, and transition duration measurement. Devices with hydroquinone can transition quickly. Cycle times are $$\sim$$ ∼ 30 s in these samples, however, these samples also typically fail before 3000 cycles. On the other hand, devices using ferrocene transition more slowly (total cycle time $$\sim$$ ∼ 2 min), but have superior cycling performance with all samples surviving beyond 10,000 cycles while complying with ASTM E2141-14 standard.

Abstract The InSightec Exablate system is the standard of care used for transcranial focused ultrasound ablation treatments in the United States. The system calculates phase corrections that account for aberrations caused by the human skull. This work investigates whether skull aberration correction can be improved by comparing the standard of care InSightec ray tracing method with the hybrid angular spectrum (HAS) method and the gold standard hydrophone method. Three degassed ex vivo human skulls were sonicated with a 670 kHz hemispherical phased array transducer (InSightec Exablate 4000). Phase corrections were calculated using four different methods (straight ray tracing, InSightec ray tracing, HAS, and hydrophone) and were used to drive the transducer. 3D raster scans of the beam profiles were acquired using a hydrophone mounted on a 3-axis positioner system. Focal spots were evaluated using six metrics: pressure at the target, peak pressure, intensity at the target, peak intensity, positioning error, and focal spot volume. For three skulls, the InSightec ray tracing method achieved 52 ± 21% normalized target intensity (normalized to hydrophone), 76 ± 17% normalized peak intensity, and 0.72 ± 0.47 mm positioning error. The HAS method achieved 74 ± 9% normalized target intensity, 81 ± 9% normalized peak intensity, and 0.35 ± 0.09 mm positioning error. The InSightec-to-HAS improvement in focal spot targeting provides promise in improving treatment outcomes. These improvements to skull aberration correction are also highly relevant for the applications of focused ultrasound neuromodulation and blood brain barrier opening, which are currently being translated for human use.

Here, the authors present photonic resonator interferometric scattering microscopy, which utilises a dielectric photonic crystal as the sample substrate. The resonant near-field enhancement leads to improved signal to noise ratio without increasing illumination intensity.

Few studies have examined the time-dependent effects of stress on fear learning. Previously, we found that stress immediately before fear conditioning enhanced fear learning. Here, we aimed to extend these findings by assessing the effects of stress 30 min prior to fear conditioning on fear learning and fear generalization. Two hundred and twenty-one healthy adults underwent stress (socially evaluated cold pressor test) or a control manipulation 30 min before completing differential fear conditioning in a fear-potentiated startle paradigm. One visual stimulus (CS+), but not another (CS−), was associated with an aversive airblast to the throat (US) during acquisition. The next day, participants were tested for their fear responses to the CS+, CS−, and several generalization stimuli. Stress impaired the acquisition of fear on Day 1 but had no significant impact on fear generalization. The stress-induced impairment of fear learning was particularly evident in participants who exhibited a robust cortisol response to the stressor. These findings are consistent with the notion that stress administered 30 min before learning impairs memory formation via corticosteroid-related mechanisms and may help us understand how fear memories are altered in stress-related psychological disorders.

Proton transfer processes of organic molecules are key to charge transport and photoprotection in biological systems. Among them, excited-state intramolecular proton transfer (ESIPT) reactions are characterized by quick and efficient charge transfer within a molecule, resulting in ultrafast proton motions. The ESIPT-facilitated interconversion between two tautomers (PS and PA) comprising the tree fungal pigment Draconin Red in solution was investigated using a combination of targeted femtosecond transient absorption (fs-TA) and excited-state femtosecond stimulated Raman spectroscopy (ES-FSRS) measurements. Transient intensity (population and polarizability) and frequency (structural and cooling) dynamics of –COH rocking and –C=C, –C=O stretching modes following directed stimulation of each tautomer elucidate the excitation-dependent relaxation pathways, particularly the bidirectional ESIPT progression out of the Franck–Condon region to the lower-lying excited state, of the intrinsically heterogeneous chromophore in dichloromethane solvent. A characteristic overall excited-state PS-to-PA transition on the picosecond timescale leads to a unique “W”-shaped excited-state Raman intensity pattern due to dynamic resonance enhancement with the Raman pump–probe pulse pair. The ability to utilize quantum mechanics calculations in conjunction with steady-state electronic absorption and emission spectra to induce disparate excited-state populations in an inhomogeneous mixture of similar tautomers has broad implications for the modeling of potential energy surfaces and delineation of reaction mechanisms in naturally occurring chromophores. Such fundamental insights afforded by in-depth analysis of ultrafast spectroscopic datasets are also beneficial for future development of sustainable materials and optoelectronics.

People with disabilities in the United States have access to a fraction of engaging play experiences available to others due to playground design choices, minimal legal requirements, and societal acceptance of the status quo. PlayGrand Adventures, the first and largest all-abilities playground in North Texas, meets this need by providing engaging play opportunities for everyone. This qualitative case study explores and describes community engagement at PlayGrand Adventures, informed by principles of environmental reciprocity supported by Bandura’s Social Cognitive Theory (1986) and Gibson’s Affordance Theory (1979). The researcher collected data on community perception and engagement via a questionnaire, semi-structured interviews, and playground observations. The study fills a gap in academic research on all-abilities playgrounds in the United States to increase awareness of the systemic underserving of people with disabilities in this country and provides a potential solution. The researcher offers initial recommendations for PlayGrand Adventures’ future development and implementation with implications for replication in other cities.

Background: The gastrointestinal tract has been speculated to serve as a reservoir for Acinetobacter, however little is known about the ecological fitness of Acinetobacter strains in the gut. Likewise, not much is known about the ability of Acinetobacter to consume dietary, or host derived nutrients or their capacity to modulate host gene expression. Given the increasing prevalence of Acinetobacter in the clinical setting, we sought to characterize how A. calcoaceticus responds to gut-related stressors and identify potential microbe-host interactions.Materials and Methods: To accomplish these aims, we grew clinical isolates and commercially available strains of A. calcoaceticus in minimal media with different levels of pH, osmolarity, ethanol and hydrogen peroxide. Utilization of nutrients was examined using Biolog phenotypic microarrays. To examine the interactions of A. calcoaceticus with the host, inverted murine organoids where the apical membrane is exposed to bacteria, were incubated with live A. calcoaceticus, and gene expression was examined by qPCR.Results: All strains grew modestly at pH 6, 5 and 4; indicating that these strains could tolerate passage through the gastrointestinal tract. All strains had robust growth in 0.1 and 0.5 M NaCl concentrations which mirror the small intestine, but differences were observed between strains in response to 1 M NaCl. Additionally, all strains tolerated up to 5% ethanol and 0.1% hydrogen peroxide. Biolog phenotypic microarrays revealed that A. calcoaceticus strains could use a range of nutrient sources, including monosaccharides, disaccharides, polymers, glycosides, acids, and amino acids. Interestingly, the commercially available A. calcoaceticus strains and one clinical isolate stimulated the pro-inflammatory cytokines Tnf, Kc, and Mcp-1 while all strains suppressed Muc13 and Muc2.Conclusion: Collectively, these data demonstrate that A. calcoaceticus is well adapted to dealing with environmental stressors of the gastrointestinal system. This data also points to the potential for Acinetobacter to influence the gut epithelium.

BackgroundChildhood adversity is linked to adverse health in adulthood. One posited mechanistic pathway is through physiological responses to acute stress. Childhood adversity has been previously related to both exaggerated and blunted physiological responses to acute stress, however, less is known about the psychological mechanisms which may contribute to patterns of physiological reactivity linked to childhood adversity.ObjectiveIn the current work, we investigated the role of challenge and threat stress appraisals in explaining relationships between childhood adversity and cortisol reactivity in response to an acute stressor.MethodsUndergraduate students (n = 81; 61% female) completed an online survey that included general demographic information and the Risky Families Questionnaire 24 h before a scheduled lab visit. In the lab, a research assistant collected a baseline salivary cortisol sample. Following the baseline period, participants were read instructions for the Trier Social Stress Test (TSST), a validated psychological lab stressor. Next, they completed a challenge vs. threat task appraisal questionnaire and completed the speech and math portion of the TSST. Twenty minutes following the start of the TSST, a second salivary sample was collected to measure changes in salivary cortisol following the TSST.ResultsLinear regression analyses adjusted for age, sex, childhood socioeconomic status (SES), and baseline cortisol levels, showed childhood adversity associated with changes in cortisol levels [B = –0.29 t(73) = –2.35, p = 0.02, R2=0.07]. Linear regression analyses controlling for age, sex, and childhood SES showed childhood adversity associated with both challenge [B = –0.52 t(74) = –5.04, p < 0.001, R2=0.24] and threat [B = 0.55 t(74) = 5.40, p < 0.001, R2=0.27] appraisals. Significant indirect effects of childhood trauma on cortisol reactivity were observed through challenge appraisals [B = –0.01 (95% confidence interval = –0.02, –0.003)], and threat appraisals [B = –0.01 (95% confidence interval = –0.01, –0.003)].ConclusionChildhood adversity may contribute to blunted cortisol reactivity, a pattern of response which is linked to obesity, addiction, and other behavior-related diseases. Our findings suggest that this relationship is in part a product of stress appraisals.

Abstract Background Thymidine kinase 1 (TK1) is a pyrimidine salvage pathway enzyme that is up-regulated in malignant tissues and elevated in the serum of cancer patients. While TK1 has been well established as a tumor biomarker, little has been done to explore its potential as a tumor target. Recently, we reported the membrane expression of TK1 on malignant cells, but not on normal cells. This study explores the possible use of monoclonal antibodies for the targeting of membrane associated TK1 in lung, breast, colon and prostate cancer cells. Methods We generated and evaluated a panel of monoclonal antibodies against six different epitopes exposed in the tetrameric form of TK1. Antibodies were developed with hybridoma technology and validated with Western blot, siRNA TK1 knockdown, enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The therapeutic potential of the antibodies was evaluated in vitro in antibody-dependent cell-mediated-cytotoxicity (ADCC) experiments. Results Binding of the antibodies to TK1 was confirmed by Western blot in purified recombinant protein, cancer serum, and cell lysate. After a TK1 knockdown was performed, a reduction of TK1 expression was observed with five antibodies. Using indirect ELISA, we identified 3B2E11, 9C10, 7H2, 3B4, 8G2 among the most sensitive antibodies (LOD = 10.73–66.9 pg/ml). Surface expression of TK1 on the membrane of various cancer cell lines was analyzed with flow cytometry. Antibodies 8G2, 3B4, 7HD and 5F7G11 detected TK1 on the membrane of various cancer cell lines, including lung, prostate, colon and breast. No significant binding was detected on normal lymphocytes. Increased cytolysis of lung (~ 70%. p = 0.0001), breast (~ 70%, p = 0.0461) and colon (~ 50% p = 0.0216) cancer cells by effector cells was observed when anti-TK1 antibodies were added during ADCC experiments. Conclusions The antibodies developed showed potential to be used to detect and target TK1 on the membrane of various tumor cells. The targeting of TK1 in malignant cells using monoclonal antibodies may be a feasible approach for the elimination of high TK1 expressing tumor cells.

Hydropower production is one of the greatest threats to fluvial ecosystems and freshwater biodiversity. Now that we have entered the Anthropocene, there is an opportunity to reflect on what might constitute a ‘sustainable’ Anthropocene in the context of hydropower and riverine fish populations. Considering elements of existing practices that promote favorable social-ecological outcomes (i.e., ‘bright spots’) is timely given that there are plans to expand hydropower capacity in previously undammed rivers, intensify dam development in some of the world's largest river systems, and re-license existing facilities. We approach this from a pragmatic perspective: for the foreseeable future, hydropower will likely remain an important source of renewable electricity. To offer support for moving toward a more ‘sustainable’ Anthropocene, we provide syntheses of best practices during the siting, design, construction, operation, and compensation phases of hydropower development to minimize impacts on inland fish. For each phase, we offer positive examples (or what might be considered ‘bright spots’) pertaining to some of the approaches described within our syntheses, acknowledging that these projects may not be viewed as without ecological and (or) societal detriment by all stakeholders. Our findings underscore the importance of protecting critical habitat and free-flowing river reaches through careful site selection and basin-scale planning, infrastructure designs that minimize reservoir effects and facilitate safe passage of fish, construction of hydropower plants using best practices that minimize long-term damage, operating guidelines that mimic natural flow conditions, and compensation that is lasting, effective, inclusive, and locally relevant. Learning from these ‘bright spots’ may require engagement of diverse stakeholders, professionals, and governments at scales that extend well beyond a given site, river, or even basin. Indeed, environmental planning that integrates hydropower development into broader discussions of conserving regional biodiversity and ecosystem services will be of utmost importance.

Summary: Human analysis of research data is slow and inefficient. In recent years, machine learning tools have advanced our capability to perform tasks normally carried out by humans, such as image segmentation and classification. In this work, we seek to further improve binary classification models for high-throughput identification of different microstructural morphologies. We utilize a dataset with limited observations (133 dendritic structures, 444 non-dendritic) and employ data augmentation via rotation and translation to enhance the dataset six-fold. Then, transfer learning is carried out using pre-trained networks VGG16, InceptionV3, and Xception achieving only moderate F1 scores (0.801–0.822). We hypothesize that feature engineering could yield better results than transfer learning alone. To test this, we employ a new nature-inspired feature optimization algorithm, the Binary Red Deer Algorithm (BRDA), to carry out binary classification and observe F1 scores in the range of 0.96.

IntroductionChondrosarcoma, although relatively uncommon, represents a significant percentage of primary osseous tumors. Nonetheless, there are few large-cohort, longitudinal studies of long-term survival and treatment outcomes of chondrosarcoma patients and none using the National Cancer Database (NCDB).MethodsChondrosarcoma patients were identified from the 2004-2015 NCDB datasets and divided on three primary tumor sites: appendicular, axial, and other. Demographic, treatment, and long-term survival data were determined for each group. Multivariate Cox analysis and Kaplan-Meier survival curves were generated to assess long-term survival over time for each.ResultsIn total, 5,329 chondrosarcoma patients were identified, of which 2,686 were appendicular and 1,616 were axial. Survival was higher among the appendicular cohort than axial at 1-year, 5-year, and 10-year (89.52%, 75.76%, and 65.24%, respectively). Multivariate Cox analysis identified patients in the appendicular cohort to have significantly greater likelihood of death with increasing age category, distant metastases at presentation, and male sex (pConclusionsFor both appendicular and axial chondrosarcomas, surgical treatment remains the mainstay of treatment due to its continued superiority for the long-term survival of patients, although advancements in survival over the last decade have been insignificant. Presence of distant metastases and axial involvement are significant, poor prognostic factors perhaps because of difficulty in surgical excision or extent of disease.

IntroductionAmerican orthopaedists are increasingly seeking fellowship sub-specialization. One proposed benefit of fellowship training is decrease in complications, however, few studies have investigated the rates of medical and surgical complications for hip fracture patients between orthopedists from different fellowship backgrounds. This study aims to investigate the effect of fellowship training and case volume on medical and surgical outcomes of patient following hip fracture surgical intervention.Methods1999-2016 American Board of Orthopedic Surgery (ABOS) Part II Examination Case List data were used to assess patients treated by trauma or adult reconstruction fellowship-trained orthopedists versus all-other orthopaedists. Rates of surgeon-reported medical and surgical adverse events were compared between the three surgeon cohorts. Using binary multivariate logistic regression to control of demographic factors, independent factors were evaluated for their effect on surgical complications.ResultsData from 73,427 patients were assessed. An increasing number of hip fractures are being treated by trauma fellowship trained surgeons (9.43% in 1999-2004 to 60.92% in 2011-2016). In multivariate analysis, there was no significant difference in type of fellowship, however, surgeons with increased case volume saw significantly decreased odds of complications (16-30 cases: OR = 0.91; 95% CI: 0.85-0.97; p = 0.003; 31+ cases: OR = 0.68; 95% CI: 0.61-0.76; pDiscussionDespite minor differences in incidence of surgical complications between different fellowship trained orthopaedists, there is no major difference in overall risk of surgical complications for hip fracture patients based on fellowship status of early orthopaedic surgeons. However, case volume does significantly decrease the risk of surgical complications among these patients and may stand as a proxy for fellowship training. Fellows required to take hip fracture call as part of their training regardless of fellowship status exhibited decreased complication risk for hip fracture patients, thus highlighting the importance of additional training.

Fluorescent proteins (FPs) are indispensable tools for noninvasive bioimaging and sensing. Measuring the free cellular calcium (Ca2+) concentrations in vivo with genetically encodable FPs can be a relatively direct measure of neuronal activity due to the complex signaling role of these ions. REX-GECO1 is a recently developed red-green emission and excitation ratiometric FP-based biosensor that achieves a high dynamic range due to differences in the chromophore response to light excitation with and without calcium ions. Using steady-state electronic measurements (UV/Visible absorption and emission), along with time-resolved spectroscopic techniques including femtosecond transient absorption (fs-TA) and femtosecond stimulated Raman spectroscopy (FSRS), the potential energy surfaces of these unique biosensors are unveiled with vivid details. The ground-state structural characterization of the Ca2+-free biosensor via FSRS reveals a more spacious protein pocket that allows the chromophore to efficiently twist and reach a dark state. In contrast, the more compressed cavity within the Ca2+-bound biosensor results in a more heterogeneous distribution of chromophore populations that results in multi-step excited state proton transfer (ESPT) pathways on the sub-140 fs, 600 fs, and 3 ps timescales. These results enable rational design strategies to enlarge the spectral separation between the protonated/deprotonated forms and the Stokes shift leading to a larger dynamic range and potentially higher fluorescence quantum yield, which should be broadly applicable to the calcium imaging and biosensor communities.

Nitrophenols are a group of small organic molecules with significant environmental implications from the atmosphere to waterways. In this work, we investigate a series of nitrophenols and nitrophenolates, with the contrasting ortho-, meta-, and para-substituted nitro group to the phenolic hydroxy or phenolate oxygen site (2/3/4NP or NP−), implementing a suite of steady-state and time-resolved spectroscopic techniques that include UV/Visible spectroscopy, femtosecond transient absorption (fs-TA) spectroscopy with probe-dependent and global analysis, and femtosecond stimulated Raman spectroscopy (FSRS), aided by quantum calculations. The excitation-dependent (400 and 267 nm) electronic dynamics in water and methanol, for six protonated or deprotonated nitrophenol molecules (three regioisomers in each set), enable a systematic investigation of the excited-state dynamics of these functional “nanomachines” that can undergo nitro-group twisting (as a rotor), excited-state intramolecular or intermolecular proton transfer (donor–acceptor, ESIPT, or ESPT), solvation, and cooling (chromophore) events on molecular timescales. In particular, the meta-substituted compound 3NP or 3NP− exhibits the strongest charge-transfer character with FSRS signatures (e.g., C–N peak frequency), and thus, does not favor nitroaromatic twist in the excited state, while the ortho-substituted compound 2NP can undergo ESIPT in water and likely generate nitrous acid (HONO) after 267 nm excitation. The delineated mechanistic insights into the nitro-substituent-location-, protonation-, solvent-, and excitation-wavelength-dependent effects on nitrophenols, in conjunction with the ultraviolet-light-induced degradation of 2NP in water, substantiates an appealing discovery loop to characterize and engineer functional molecules for environmental applications.

Endophyte-infected fescue is a major cool season forage used for livestock production in the United States and through other areas of the world. A unique aspect of this forage resource is the symbiotic relationship with an endophytic fungus (Epichloë coenophiala) that has detrimental impact on herbivores due to toxic ergot alkaloids. Research over the past 50 years has unveiled details regarding this symbiotic relationship. This review focuses on the origin of tall fescue in the United States and the consequences of its wide-spread utilization as a livestock forage, along with the discovery and toxicodynamics of ergot alkaloids produced by E. coenophiala. The majority of past ergot alkaloid research has focused on observing phenotypic changes that occur in livestock affected by ergot alkaloids, but recent investigation of the metabolome, transcriptome, and proteome have shown that fescue toxicity-related illnesses are much more complex than previous research suggests.