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Jacob T Martin,1 Marc Douaisi,2 Ammar Arsiwala,3 Manish Arha,2 Ravi S Kane3 1Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; 2Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA; 3School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA Purpose: We are interested in designing a modular strategy for creating potent multivalent ligands, which frequently can be used as effective inhibitors of undesired biomolecular interactions. For example, such inhibitors might prevent the self-assembly of bacterial toxins or the attachment of a virus to its host cell receptors. Methods: We used a biocompatible polyamino acid polymer as a scaffold for grafting multiple copies of an oligonucleotide aptamer (OA). Specifically, the carboxylates on the side chains of polyglutamic acid (PGA) were modified with a thiol-reactive linker, N-aminoethyl maleimide (AEM), and thiol-functionalized OAs were attached to the maleimide moieties. The resulting conjugates were tested for their ability to compete with and inhibit the binding of unconjugated monovalent OAs to the target cell receptor. Results: Multivalent PGA–OA conjugates with low, medium, and high valency were successfully prepared. The varying valency and successful purification to remove unconjugated OAs were confirmed by polyacrylamide gel electrophoresis. The resulting purified conjugates inhibited the binding of unconjugated monovalent OAs, and the measured half maximal inhibitory concentration (IC50) values corresponded to a 38–88-fold enhancement of potency on a per-aptamer basis, relative to OA alone. Conclusion: Multivalent conjugation of OA ligands has potential as a generally useful way to improve the potency of the interaction between the ligand and its target receptor. We have demonstrated this principle with a known OA as a proof of concept as well a synthetic strategy that can be used to synthesize multivalent conjugates of other OAs. Keywords: polyvalency, grafting, oligonucleotide, polyglutamic acid

A number of manufacturing processes are adversely affected by the presence of trace amounts of water vapour in purge and process gases. It is important for the operators of such processes to monitor the levels of water vapour in these gases continuously. There are many analytical methods for determination of trace water vapour which all require regular, traceable calibration. In this paper, a new standard facility for generating an adjustable level of trace water vapour is described. It uses continuous accurate measurements of the mass loss from a permeation device coupled with a dilution system based on an array of critical flow orifices. Details of the verification of the facility are presented along with results of comparisons with the National Physical Laboratory thermally-based dew/frost point humidity standards facility.

Abstract Background Allyl isothiocyanate (AITC) from mustard is cytotoxic; however the mechanism of its toxicity is unknown. We examined the effects of AITC on heat shock protein (HSP) 70 expression in Caenorhabditis elegans. We also examined factors affecting the production of AITC from its precursor, sinigrin, a glucosinolate, in ground Brassica juncea cv. Vulcan seed as mustard has some potential as a biopesticide. Findings An assay to determine the concentration of AITC in ground mustard seed was improved to allow the measurement of AITC release in the first minutes after exposure of ground mustard seed to water. Using this assay, we determined that temperatures above 67°C decreased sinigrin conversion to AITC in hydrated ground B. juncea seed. A pH near 6.0 was found to be necessary for AITC release. RT-qPCR revealed no significant change in HSP70A mRNA expression at low concentrations of AITC (< 0.1 μM). However, treatment with higher concentrations (> 1.0 μM) resulted in a four- to five-fold increase in expression. A HSP70 ELISA showed that AITC toxicity in C. elegans was ameliorated by the presence of ground seed from low sinigrin B. juncea cv. Arrid. Conclusions • AITC induced toxicity in C. elegans, as measured by HSP70 expression. • Conditions required for the conversion of sinigrin to AITC in ground B. juncea seed were determined. • The use of C. elegans as a bioassay to test AITC or mustard biopesticide efficacy is discussed.

Family physicians commonly encounter patients with dental infections, such as dental caries and periodontal disease. Dental caries is caused by bacteria that destroy the enamel and dentin; it can be detected by an oral examination that shows stained pits or fissures on the tooth surface. Use of fluoride is the most effective prevention measure for dental caries. Untreated caries may progress to pulpitis and, eventually, to necrosis of the pulp. In irreversible pulpitis, the tooth dies and the patient may have a localized abscess that can spread to surrounding tissue. Periodontal infections are caused by bacteria in the subgingival dental plaque. In gingivitis, the inflamed gums bleed easily with brushing or flossing; the condition can be controlled with good oral hygiene. Periodontitis is characterized by a loss of supportive bone structure caused by chronic gingivitis; it is also associated with some systemic diseases. Localized periodontitis is treated with mechanical debridement and good oral hygiene, whereas generalized periodontitis requires adjunct antibiotic therapy. Pericoronitis results when food particles become trapped under the gum of an impacted tooth. This condition can be controlled by removal of food debris and good oral hygiene. For patients in whom dental infections are disseminated and have invaded the deeper oral spaces, antibiotic treatment should be initiated at the time of referral. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine compliance with follow-up serial Papanicolaou smears after the completion of colposcopic examination and treatment as required in women with abnormal Papanicolaou smears. Following a retrospective chart review, data were selected from 103 charts of women who had undergone colposcopy. Patient compliance with the treatment plan was tracked for 18 months. Compliance was defined as having at least two cervical cancer screenings performed in the year and a half following colposcopy. Thirty-two percent of the study population complied with the plan of care. Eighty-six percent of those patients who had at least one Papanicolaou smear in the 18 months following colposcopy had no progression of dysplasia. Less than one-third of the patients in this study population followed the recommendations given to them after their colposcopic examination and treatment. Health care providers will be aware of the low percentage of patient follow-up as well as the importance of educating patients about prevention of cervical cancer and reducing risk of cervical dysplasia. [ABSTRACT FROM AUTHOR]

Much progress has been made in understanding how the brain combines signals from the two eyes. However, most of this work has involved achromatic (black and white) stimuli, and it is not clear if the same processes apply in color-sensitive pathways. In our first experiment, we measured contrast discrimination ("dipper") functions for four key ocular configurations (monocular, binocular, half-binocular, and dichoptic), for achromatic, isoluminant L-M and isoluminant S-(L+M) sine-wave grating stimuli (L: long-, M: medium-, S: short-wavelength). We find a similar pattern of results across stimuli, implying equivalently strong interocular suppression within each pathway. Our second experiment measured dichoptic masking within and between pathways using the method of constant stimuli. Masking was strongest within-pathway and weakest between S-(L+M) and achromatic mechanisms. Finally, we repeated the dipper experiment using temporal luminance modulations, which produced slightly weaker interocular suppression than for spatially modulated stimuli. We interpret our results in the context of a contemporary two-stage model of binocular contrast gain control, implemented here using a hierarchical Bayesian framework. Posterior distributions of the weight of interocular suppression overlapped with a value of 1 for all dipper data sets, and the model captured well the pattern of thresholds from all three experiments.

Objective: Chronic low back pain (cLBP) is a complex disease with biological, psychological, and social components and the complex interactions of these components are poorly understood. Chronic psychological stress (CPS) (anxiety, depression, etc.) and pathological changes in spinal tissue (osteoporosis, disc degeneration, etc.) are frequently and independently associated with cLBP, yet their explicit relationship has not been collectively reviewed. The objective of this scoping review is to investigate the current state of research on how CPS may impact spinal tissue pathology., Design: Five steps were utilized to conduct this scoping review: 1) identify a research objective and establish a search strategy, 2) identify research articles, 3) select research articles that meet search criteria, 4) extract data, 5) summarize and report results., Results: We identified N ​= ​56 articles relating CPS to spinal pathology. Of those that identified a relationship between CPS and spine pathology (N ​= ​39), most (N ​= ​24) described decreased lumbar vertebral bone mineral density (BMD) between depression and control groups. Animal studies (N ​= ​8) were limited to mice and confirmed a causal relationship between CPS and lower vertebral BMD. Only a few additional human studies (N ​= ​9) documented relationships between other various forms of CPS and spinal tissue pathologies., Conclusion: This scoping review documents evidence of a relationship between CPS and decreased spine health in humans as well as a causal relationship between the initiation of CPS and decreased BMD in animals. As few studies evaluated disease in other spinal anatomy in relationship to CPS, future work in this area is warranted. Further exploration of CPS beyond depression is warranted as well., Competing Interests: None to disclose., (© 2024 The Authors.)

Background: Lumbar degenerative spondylolisthesis (LDS), characterized as degeneration of the intervertebral disc and structural changes of the facet joints, is a condition with varying degrees of instability that may lead to pain, canal stenosis, and subsequent surgical intervention. However, the etiology of LDS remains inconclusive. Gut microbiome dysbiosis may stimulate systemic inflammation in various disorders. However, the role of such dysbiosis upon spine health remains under-studied. The current study assessed the association of gut microbiome dysbiosis in symptomatic patients with or without LDS., Methods: A cross-sectional analysis within the framework of a prospective study was performed. DNA was extracted from fecal samples collected from adult symptomatic patients with ( n  = 21) and without LDS ( n  = 12). Alpha and beta diversity assessed differences in fecal microbial community between groups. Taxon-by-taxon analysis identified microbial features with differential relative abundance between groups. Subject demographics and imaging parameters were also assessed., Results: There was no significant group differences in age, sex, race, body mass index, smoking/alcohol history, pain profiles, spinopelvic alignment, and Modic changes ( p  >0.05). LDS subjects had significantly higher disc degeneration severity ( p  = 0.018) and alpha diversity levels compared to non-LDS subjects ( p  = 0.002-0.003). Significant differences in gut microbial community structure were observed between groups ( p  = 0.046). Subjects with LDS exhibited distinct differences at the phylum level, with a significantly higher Firmicutes to Bacteroidota ratio compared to non-LDS ( p  = 0.003). Differential relative abundance analysis identified six taxa with significant differences between the two groups, with LDS demonstrating an increase in putative pro-inflammatory bacteria ( Dialister, CAG-352 ) and a decrease in anti-inflammatory bacteria ( Slackia , Escherichia-Shigella )., Conclusion: This study is the first to report a significant association of gut microbiome dysbiosis and LDS in symptomatic patients, noting pro-inflammatory bacterial taxa. This work provides a foundation for future studies addressing the role of the gut microbiome in association with spine health and disease., (© 2024 The Author(s). JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Oil sands process-affected water (OSPW), generated by surface mining in Canada's oil sands, require treatment of environmentally persistent dissolved organic compounds before release to the watershed. Conventional chemical and mechanical treatments have not proved suitable for treating the large quantities of stored OSPW, and the biological recalcitrance of some dissolved organics may not be adequately addressed by conventional passive treatment systems. Previous work has evaluated photocatalytic treatment as a passive advanced oxidation process (P-AOP) for OSPW remediation. This work expands upon this prior research to further characterize the effects of water chemistry on the treatment rate and detoxification threshold. Under artificial sunlight, buoyant photocatalysts (BPCs) detoxified all OSPW samples within 1 week of treatment time with simultaneous treatment of polycyclic aromatic hydrocarbons, naphthenic acid fraction components (NAFCs), and un-ionized ammonia. Overall, these results further demonstrate passive photocatalysis as an effective method for treatment of OSPW contaminants of potential concern (COPCs)., Competing Interests: Declaration of competing interest T.M.C.L., Z.W.Y., and F.G. declare ownership stakes in H2nanO Inc., a company with financial interest in the subject matter of this work, as well as inventorship on a BPC patent application (PCT/IB2017/056505, US16/343,298) assigned to H2nanO. T.P., A.B., and T.W. work for COSIA member companies that produce materials and waste streams that are represented by the ones reported in this research. The other authors declare no potentially competing conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Academic researchers faced a multitude of challenges posed by the COVID-19 pandemic, including widespread shelter-in-place orders, workplace closures, and cessation of in-person meetings and laboratory activities. The extent to which these challenges impacted musculoskeletal researchers, specifically, is unknown. We developed an anonymous web-based survey to determine the pandemic's impact on research productivity and career prospects among musculoskeletal research trainees and faculty. There were 116 musculoskeletal (MSK) researchers with varying demographic backgrounds who completed the survey. Of respondents, 48.3% (n = 56) believed that musculoskeletal funding opportunities decreased because of COVID-19, with faculty members more likely to hold this belief compared to nonfaculty researchers (p = 0.008). Amongst MSK researchers, 88.8% (n = 103) reported research activity was limited by COVID-19, and 92.2% (n = 107) of researchers reported their research was not able to be refocused on COVID-19-related topics, with basic science researchers less likely to be able to refocus their research compared to clinical researchers (p = 0.030). Additionally, 47.4% (n = 55) reported a decrease in manuscript submissions since the onset of the pandemic. Amongst 51 trainee researchers, 62.8% (n = 32) reported a decrease in job satisfaction directly attributable to the COVID-19 pandemic. In summary, study findings indicated that MSK researchers struggled to overcome challenges imposed by the pandemic, reporting declines in funding opportunities, research productivity, and manuscript submission. Trainee researchers experienced significant disruptions to critical research activities and worsening job satisfaction. Our findings motivate future efforts to support trainees in developing their careers and target the recovery of MSK research from the pandemic stall., (© 2024 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

With the intensity and frequency of wildfires increasing rapidly, the need to study the ecological effects of these wildfires is also growing. An understudied aspect of fire ecology is the effect fires have on parasite-host interactions, including ectoparasites that might be pathogen vectors. Although some studies have examined the impacts of fire on ticks, studies on other ectoparasites, including pathogen vectors, are rare. To help address this knowledge gap, we examined the abiotic and biotic factors that predict the likelihood and extent of parasitism of deer mice (Peromyscus maniculatus) by fleas within a landscape of unburned and recovering burned (>9 yr postfire) mixed conifer forests. We sampled 227 individual deer mice across 27 sites within the Jemez Mountains of northern New Mexico in 2022 and quantified measures of parasitism by fleas (primarily Aetheca wagneri). These sites were distributed in both unburned areas (n = 15) and recovering burned areas (n = 12), with the latter derived from 2 large fires, the Las Conchas fire (2011) and the Thompson Ridge fire (2013). Using these data, we tested for differences in prevalence, mean abundance, and mean intensity of fleas on deer mice, focusing on the predictive importance of host sex and fire history. We also created generalized linear mixed-effects models to investigate the best host and environmental predictors of parasitism by fleas. Approximately a decade postfire, we found minimal evidence to suggest that fire history influenced either the presence or intensity of fleas on deer mice. Rather, at the current forest-regeneration stage, the extent of parasitism by fleas was best predicted by measures of host sex, body condition, and the trapline's ability to accumulate water, as measured through topography. As host body condition increased, the probability of males being parasitized increased, whereas the opposite pattern was seen for females. Male mice also had significantly greater flea loads. Among potential abiotic predictors, the topographic wetness index or compound topographic index (a proxy for soil moisture) was positively related to flea intensity, suggesting larger flea populations in burrows with higher relative humidity. In summary, although fire may potentially have short-term impacts on the likelihood and extent of host parasitism by fleas, in this recovering study system, host characteristics and topographic wetness index are the primary predictors of parasitism by fleas., (© American Society of Parasitologists 2024.)

Timely detection and treatment of postpartum hemorrhage (PPH) are crucial to prevent complications or death. A calibrated blood-collection drape can help provide objective, accurate and early diagnosis of PPH, and a treatment bundle can address delays or inconsistencies in the use of effective interventions. Here we conducted an economic evaluation alongside the E-MOTIVE trial, an international, parallel cluster-randomized trial with a baseline control phase involving 210,132 women undergoing vaginal delivery across 78 secondary-level hospitals in Kenya, Nigeria, South Africa and Tanzania. We aimed to assess the cost-effectiveness of the E-MOTIVE intervention, which included a calibrated blood-collection drape for early detection of PPH and a bundle of first-response treatments (uterine massage, oxytocic drugs, tranexamic acid, intravenous fluids, examination and escalation), compared with usual care. We used multilevel modeling to estimate incremental cost-effectiveness ratios from the perspective of the public healthcare system for outcomes of cost per severe PPH (blood loss ≥1,000 ml) avoided and cost per disability-adjusted life-year averted. Our findings suggest that the use of a calibrated blood-collection drape for early detection of PPH and bundled first-response treatment is cost-effective and should be perceived by decision-makers as a worthwhile use of healthcare budgets. ClinicalTrials.gov identifier: NCT04341662 ., (© 2024. The Author(s).)

Intratumoral heterogeneity is common in cancer, particularly in sarcomas like undifferentiated pleomorphic sarcoma (UPS), where individual cells demonstrate a high degree of cytogenic diversity. Previous studies showed that a small subset of cells within UPS, known as the metastatic clone (MC), as responsible for metastasis. Using a CRISPR-based genomic screen in-vivo , we identified the COMPASS complex member Setd1a as a key regulator maintaining the metastatic phenotype of the MC in murine UPS. Depletion of Setd1a inhibited metastasis development in the MC. Transcriptome and chromatin sequencing revealed COMPASS complex target genes in UPS, such as Cxcl10 , downregulated in the MC. Deleting Cxcl10 in non-MC cells increased their metastatic potential. Treating mice with human UPS xenografts with a COMPASS complex inhibitor suppressed metastasis without affecting tumor growth in the primary tumor. Our data identified an epigenetic program in a subpopulation of sarcoma cells that maintains metastatic potential., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

The current study evaluated the use of a machine learning model to determine benefit of medical record variables in predicting geriatric clinic communication requirements. Patient behavioral symptoms and global cognition, medical information, and caregiver intake assessments were extracted from 557 patient records. Two independent raters reviewed the subsequent 12 months for documented (1) incoming caregiver contacts, (2) outgoing clinic contacts, and (3) clinic communications. Random forest models' average explained variance in training sets for incoming, outgoing, and clinic communications were 7.42%, 3.65%, and 6.23%, respectively. Permutation importances revealed the strongest predictors across outcomes were patient neuropsychiatric symptoms, global cognition, and body mass, caregiver burden, and age (caregiver and patient). Average explained variance in out-of-sample test sets for incoming, outgoing, clinic communications were 6.17%, 2.78%, and 4.28%, respectively. Findings suggest patient neuropsychiatric symptoms, caregiver burden, caregiver and patient age, patient body mass index, and global cognition may be useful predictors of communication requirements for patient care in a geriatric clinic. Future studies should consider additional caregiver variables, such as personality characteristics, and explore modifiable factors longitudinally., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Bot flies (Oestridae: Cuterebrinae) are obligate mammalian parasites that complete the larval stage of their life cycle under the skin of their host. Most detailed studies of bot fly larval disease ecology have been conducted in temperate deciduous zone rodent systems. To understand the relative importance of seasonal and spatial factors, as well as factors intrinsic to the host, in underpinning the likelihood and extent of parasitism by bot flies in non-rodent hosts as well as in arid-land ecosystems, we examined the dynamic for black-tailed jackrabbit (Lepus californicus) and desert cottontail (Sylvilagus audubonii) parasitism by bot fly larvae (Cuterebra spp.) across 7 repeatedly sampled sites spread across approximately 500 km of the Chihuahuan Desert ecoregion of southern New Mexico. This environment is characterized by a climate that includes hot dry summers and cool to cold dry winters, as well as strongly seasonal summer monsoonal rains. Lagomorphs are a common mid-sized mammal in these landscapes. Bot fly parasitism was strongly seasonal, with peak prevalence and abundance in the spring, and there was spatial variation in the extent of parasitism between collection sites. Additionally, jackrabbits in better body condition were less likely to be parasitized (as indicated by kidney fat index). We did not find sex-based differences in bot fly parasitism between male and female jackrabbits. Thus, in arid-land ecoregions, abiotic factors are likely the primary driver of the bot fly-host interaction, whereas factors intrinsic to the host were of secondary importance for characterizing the interactions of bot flies and lagomorphs., (© American Society of Parasitologists 2023.)

How does the human brain combine information across the eyes? It has been known for many years that cortical normalization mechanisms implement 'ocularity invariance': equalizing neural responses to spatial patterns presented either monocularly or binocularly. Here, we used a novel combination of electrophysiology, psychophysics, pupillometry, and computational modeling to ask whether this invariance also holds for flickering luminance stimuli with no spatial contrast. We find dramatic violations of ocularity invariance for these stimuli, both in the cortex and also in the subcortical pathways that govern pupil diameter. Specifically, we find substantial binocular facilitation in both pathways with the effect being strongest in the cortex. Near-linear binocular additivity (instead of ocularity invariance) was also found using a perceptual luminance matching task. Ocularity invariance is, therefore, not a ubiquitous feature of visual processing, and the brain appears to repurpose a generic normalization algorithm for different visual functions by adjusting the amount of interocular suppression., Competing Interests: FS, AB, JM, MA, AW, DB No competing interests declared, (© 2023, Segala et al.)

The normal human retina contains several classes of photosensitive cell-rods for low-light vision, three cone classes for daylight vision, and intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing melanopsin for non-image-forming functions, including pupil control, melatonin suppression, and circadian photoentrainment. The spectral sensitivities of the photoreceptors overlap significantly, which means that most lights will stimulate all photoreceptors to varying degrees. The method of silent substitution is a powerful tool for stimulating individual photoreceptor classes selectively and has found much use in research and clinical settings. The main hardware requirement for silent substitution is a spectrally calibrated light stimulation system with at least as many primaries as there are photoreceptors under consideration. Device settings that will produce lights to selectively stimulate the photoreceptor(s) of interest can be found using a variety of analytic and algorithmic approaches. Here we present PySilSub (https://github.com/PySilentSubstitution/pysilsub), a novel Python package for silent substitution featuring flexible support for individual colorimetric observer models (including human and mouse observers), multiprimary stimulation devices, and solving silent substitution problems with linear algebra and constrained numerical optimization. The toolbox is registered with the Python Package Index and includes example data sets from various multiprimary systems. We hope that PySilSub will facilitate the application of silent substitution in research and clinical settings.

Background: Cartilaginous neoplasms can be challenging to grade; there is a need to create an evidence-based rubric for grading. The goal of this study was to identify histopathologic features of chondrosarcoma that were associated with 5-year survival and to compare these to traditional patient, tumor and treatment variables., Methods: This was a retrospective review of all patients undergoing surgical resection of a primary chondrosarcoma with at least 2 years of follow up. All specimens were independently reviewed by two pathologists and histopathologic features scored. Univariate and multivariate analyses were performed utilizing Kaplan Meier and proportional hazards methods to identify variables associated with 5-year disease specific survival (DSS) and disease free survival (DFS)., Results: We identified 51 patients with an average follow up of 49 months eligible for inclusion. 30% of tumors were low grade, 45% were intermediate grade, and 25% were high grade. In a univariate analysis considering histopathologic factors, higher tumor mitotic rate (HR 8.9, p < 0.001), tumor dedifferentiation (HR 7.3, p < 0.001), increased tumor cellularity (HR 5.8, p = 0.001), increased tumor atypia (HR 5.8, p = 0.001), LVI (HR 4.7, p = 0.04) and higher tumor necrosis (HR 3.7, p = 0.02) were all associated with worse 5-year DSS. In a multivariate analysis controlling for potentially confounding variables, higher tumor necrosis was significantly associated with disease specific survival survival (HR 3.58, p = 0.035); none of the factors were associated with DFS., Conclusions: This study provides an evidence-based means for considering histopathologic markers and their association with prognosis in chondrosarcoma. Our findings suggest that necrosis and LVI warrant further study., (© 2023. The Author(s).)

Purpose: Bullying, harassment, and discrimination (BHD) are prevalent in academic, scientific, and clinical departments, particularly orthopedic surgery, and can have lasting effects on victims. As it is unclear how BHD affects musculoskeletal (MSK) researchers, the following study assessed BHD in the MSK research community and whether the COVID-19 pandemic, which caused hardships in other industries, had an impact., Methods: A web-based anonymous survey was developed in English by ORS Spine Section members to assess the impact of COVID-19 on MSK researchers in North America, Europe, and Asia, which included questions to evaluate the personal experience of researchers regarding BHD., Results: 116 MSK researchers completed the survey. Of respondents, 34.5% (n = 40) focused on spine, 30.2% (n = 35) had multiple areas of interest, and 35.3% (n = 41) represented other areas of MSK research. BHD was observed by 26.7% (n = 31) of respondents and personally experienced by 11.2% (n = 13), with mid-career faculty both observing and experiencing the most BHD. Most who experienced BHD (53.8%, n = 7) experienced multiple forms. 32.8% (n = 38) of respondents were not able to speak out about BHD without fear of repercussions, with 13.8% (n = 16) being unsure about this. Of those who observed BHD, 54.8% (n = 17) noted that the COVID-19 pandemic had no impact on their observations., Conclusions: To our knowledge, this is the first study to address the prevalence and determinants of BHD among MSK researchers. MSK researchers experienced and observed BHD, while many were not comfortable reporting and discussing violations to their institution. The COVID-19 pandemic had mixed-effects on BHD. Awareness and proactive policy changes may be warranted to reduce/eliminate the occurrence of BHD in this community., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: An acceptance and commitment training (ACT) educational program targeting reaction to difficult client interactions recently demonstrated efficacy in reducing burden transfer, stress, and burnout in veterinary healthcare teams. The current noninferiority trial compared effectiveness of the original program with a self-paced version., Sample: Employees of 2 corporate veterinary groups were randomized to live (n = 128) or self-paced (124) conditions. The workshop and assessments were completed by 137 (55 live and 82 self-paced)., Procedures: Asynchronous modules containing the same content as the original program were placed on in-house veterinary clinic learning systems. Participants of this parallel arms trial completed pretest measures of burden transfer, stress, and burnout. Following assessment, the 3-week ACT program was delivered via videoconferencing (live) or asynchronous modules (self-paced). At post-test and 1-month follow-up, measures were repeated, with added assessment of knowledge, helpfulness ratings, and usage of techniques. A subset (n = 33) of participants repeated measures 9 to 12 months as an extended follow-up., Results: Program helpfulness was rated more highly by live versus self-paced participants. Self-paced showed better program retention. No differences in knowledge or use of program techniques (> 5 times daily) emerged. Relative to pretest, both conditions showed reduced burden transfer, stress, and burnout at post-test and follow-up; no differences by condition emerged. Participants completing extended follow-up maintained improvement from baseline., Clinical Relevance: Findings suggest a learning system-based version of this program can improve occupational distress in veterinary healthcare teams, with gains maintained over time. The flexibility of this format promotes program completion and allows broader dissemination.

Biological selenium reduction processes are commonly employed as the best available technology (BAT) for selenium removal; however, as a by-product they produce trace amounts of organoselenium compounds with orders of magnitude greater bioaccumulation potential and toxicity. Here, we assessed buoyant photocatalysts (BPCs) as a potential passive advanced oxidation process (P-AOP) for organoselenium treatment. Using a synthetic mine-impacted water solution, spiked with selenomethionine (96 μg/L) as a representative organoselenium compound, photocatalysis with BPCs fully eliminated selenomethionine to <0.01 μg/L with conversion to selenite and selenate. A theoretical reaction pathway was inferred, and a kinetics model developed to describe the treatment trends and intermediates. Given the known toxic responses of Lepomis macrochirus and Daphnia magna to organoselenium, it was estimated that photocatalysis could effectively eliminate organoselenium acute toxicity within a UV dose of 8 kJ/L (1-2 days solar equivalent exposure), by transformation of selenomethionine to less hazardous oxidized Se species. Solar photocatalysis may therefore be a promising passive treatment technology for selenium-impacted mine water management.

Background: Low back pain (LBP) is a heterogeneous disease with biological, physical, and psychosocial etiologies. Models for predicting LBP severity and chronicity have not made a clinical impact, perhaps due to difficulty deciphering multidimensional phenotypes. In this study, our objective was to develop a computational framework to comprehensively screen metrics related to LBP severity and chronicity and identify the most influential., Methods: We identified individuals from the observational, longitudinal Osteoarthritis Initiative cohort ( N  = 4796) who reported LBP at enrollment ( N  = 215). OAI descriptor variables ( N  = 1190) were used to cluster individuals via unsupervised learning and uncover latent LBP phenotypes. We also developed a dimensionality reduction algorithm to visualize clusters/phenotypes using Uniform Manifold Approximation and Projection (UMAP). Next, to predict chronicity, we identified those with acute LBP ( N  = 40) and persistent LBP over 8 years of follow-up ( N  = 66) and built logistic regression and supervised machine learning models., Results: We identified three LBP phenotypes: a "high socioeconomic status, low pain severity group", a "low socioeconomic status, high pain severity group", and an intermediate group. Mental health and nutrition were also key clustering variables, while traditional biomedical factors (e.g., age, sex, BMI) were not. Those who developed chronic LBP were differentiated by higher pain interference and lower alcohol consumption (a correlate to poor physical fitness and lower soceioeconomic status). All models for predicting chronicity had satisfactory performance (accuracy 76%-78%)., Conclusions: We developed a computational pipeline capable of screening hundreds of variables and visualizing LBP cohorts. We found that socioeconomic status, mental health, nutrition, and pain interference were more influential in LBP than traditional biomedical descriptors like age, sex, and BMI., Competing Interests: John T. Martin is a consultant for DiscGenics Inc. ZeYu Huang is a consultant for DePuy Synthes. Neither these companies nor the funding sources for this work contributed to the study design, data collection, data analysis, manuscript preparation, or decision to submit this manuscript., (© 2023 The Authors. JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

We introduce PyPlr-a versatile, integrated system of hardware and software to support a broad spectrum of research applications concerning the human pupillary light reflex (PLR). PyPlr is a custom Python library for integrating a research-grade video-based eye-tracker system with a light source and streamlining stimulus design, optimisation and delivery, device synchronisation, and extraction, cleaning, and analysis of pupil data. We additionally describe how full-field, homogenous stimulation of the retina can be realised with a low-cost integrating sphere that serves as an alternative to a more complex Maxwellian view setup. Users can integrate their own light source, but we provide full native software support for a high-end, commercial research-grade 10-primary light engine that offers advanced control over the temporal and spectral properties of light stimuli as well as spectral calibration utilities. Here, we describe the hardware and software in detail and demonstrate its capabilities with two example applications: (1) pupillometer-style measurement and parametrisation of the PLR to flashes of white light, and (2) comparing the post-illumination pupil response (PIPR) to flashes of long and short-wavelength light. The system holds promise for researchers who would favour a flexible approach to studying the PLR and the ability to employ a wide range of temporally and spectrally varying stimuli, including simple narrowband stimuli., (© 2021. The Author(s).)

Increasing incidence of tick-borne human diseases and geographic range expansion of tick vectors elevates the importance of research on characteristics of tick species that transmit pathogens. Despite their global distribution and role as vectors of pathogens such as Rickettsia spp., ticks in the genus Dermacentor Koch, 1844 (Acari: Ixodidae) have recently received less attention than ticks in the genus Ixodes Latreille, 1795 (Acari: Ixodidae). To address this knowledge gap, we compiled an extensive database of Dermacentor tick traits, including morphological characteristics, host range, and geographic distribution. Zoonotic vector status was determined by compiling information about zoonotic pathogens found in Dermacentor species derived from primary literature and data repositories. We trained a machine learning algorithm on this data set to assess which traits were the most important predictors of zoonotic vector status. Our model successfully classified vector species with ~84% accuracy (mean AUC) and identified two additional Dermacentor species as potential zoonotic vectors. Our results suggest that Dermacentor species that are most likely to be zoonotic vectors are broad ranging, both in terms of the range of hosts they infest and the range of ecoregions across which they are found, and also tend to have large hypostomes and be small-bodied as immature ticks. Beyond the patterns we observed, high spatial and species-level resolution of this new, synthetic dataset has the potential to support future analyses of public health relevance, including species distribution modeling and predictive analytics, to draw attention to emerging or newly identified Dermacentor species that warrant closer monitoring for zoonotic pathogens., (© The Author(s) 2022. Published by Oxford University Press on behalf of Entomological Society of America.)