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Abstract Serious infection is common in patients with multiple myeloma due to immune deficiency from the underlying disease and/or its treatment. Immunoglobulin replacement is one approach to reduce infection risk in these patients. However, few real‐world data exist on its use in patients with myeloma. We investigated immunoglobulin use in Australia, New Zealand and Asia‐Pacific using registry data and explored its association with survival outcomes. A total of 2374 patients with a median follow‐up time of 29.5 months (interquartile range 13.3–54.3 months) were included in the analysis – 1673 from Australia, 313 Korea, 281 New Zealand and 107 Singapore. Overall, 7.1% of participants received immunoglobulin replacement within 24 months of diagnosis. Patients who received immunoglobulin replacement were likely to be younger, had lower baseline IgG levels (excluding paraprotein), were more likely to have baseline hypogammaglobulinaemia, baseline severe hypogammaglobulinaemia and abnormal baseline fluorescent in‐situ hybridisation status, receive first‐line myeloma treatment with immunomodulatory drugs or anti‐CD38 therapy and undergo upfront autologous stem cell transplant. In our patient cohort, the use of immunoglobulin was not associated with overall survival benefit at the time of last follow‐up (adjusted hazard ratio 0.72, 95% CI 0.46–1.14, p = 0.16). Understanding treatment approaches in clinical practice can help support future planning and provision of immunoglobulin resources.

Abstract Background Patients with opioid use disorder (OUD) experience various forms of stigma at the individual, public, and structural levels that can affect how they access and engage with healthcare, particularly with medications for OUD treatment. Telehealth is a relatively new form of care delivery for OUD treatment. As reducing stigma surrounding OUD treatment is critical to address ongoing gaps in care, the aim of this study was to explore how telehealth impacts patient experiences of stigma. Methods In this qualitative study, we interviewed patients with OUD at a single urban academic medical center consisting of multiple primary care and addiction clinics in Oregon, USA. Participants were eligible if they had (1) at least one virtual visit for OUD between March 2020 and December 2021, and (2) a prescription for buprenorphine not exclusively used for chronic pain. We conducted phone interviews between October and December 2022, then recorded, transcribed, dual-coded, and analyzed using reflexive thematic analysis. Results The mean age of participants (n = 30) was 40.5 years (range 20–63); 14 were women, 15 were men, and two were transgender, non-binary, or gender-diverse. Participants were 77% white, and 33% had experienced homelessness in the prior six months. We identified four themes regarding how telehealth for OUD treatment shaped patient perceptions of and experiences with stigma at the individual (1), public (2–3), and structural levels (4): (1) Telehealth offers wanted space and improved control over treatment setting; (2) Public stigma and privacy concerns can impact both telehealth and in-person encounters, depending on clinical and personal circumstances; (3) The social distance of telehealth could mitigate or exacerbate perceptions of clinician stigma, depending on both patient and clinician expectations; (4) The increased flexibility of telehealth translated to perceptions of increased clinician trust and respect. Conclusions The forms of stigma experienced by individuals with OUD are complex and multifaceted, as are the ways in which those experiences interact with telehealth-based care. The mixed results of this study support policies allowing for a more individualized, patient-centered approach to care delivery that allows patients a choice over how they receive OUD treatment services.

Abstract In striated muscle, the sarcomeric protein myosin-binding protein-C (MyBP-C) is bound to the myosin thick filament and is predicted to stabilize myosin heads in a docked position against the thick filament, which limits crossbridge formation. Here, we use the homozygous Mybpc2 knockout (C2-/-) mouse line to remove the fast-isoform MyBP-C from fast skeletal muscle and then conduct mechanical functional studies in parallel with small-angle X-ray diffraction to evaluate the myofilament structure. We report that C2−/− fibers present deficits in force production and calcium sensitivity. Structurally, passive C2-/- fibers present altered sarcomere length-independent and -dependent regulation of myosin head conformations, with a shift of myosin heads towards actin. At shorter sarcomere lengths, the thin filament is axially extended in C2-/-, which we hypothesize is due to increased numbers of low-level crossbridges. These findings provide testable mechanisms to explain the etiology of debilitating diseases associated with MyBP-C.

The purpose of this Delphi study was to identify the competencies needed by first-year, tenure-track faculty in the profession of agricultural education and its related specializations (i.e., teacher education, Extension education, leadership development, and agricultural communication) as perceived by hiring authorities. The expert panel was composed of 31 individuals across 25 states who were hiring authorities of agricultural education faculty. At the completion of the third round, there were a total of 52 competencies that reached consensus with the panel. The competencies were situated into three thematic categories: (a) professional skills, (b) technical skills, and (c) personal attributes. A visual framework, including the competencies, categories, and subcategories is presented. We recommend that this framework be used by graduate programs of agricultural education and related specializations as a potential framework for evaluating their programming. The time is ripe for a profession-wide conversation around the development and preparation of future faculty, and how to establish a community of scholars. Future research should be conducted to examine the best practices, such as mentorship and collaboration, to sustain and support faculty over their career and how such practices may be effectively implemented across the agricultural education professorate.

Abstract The early stages of mussel farming are often inefficient with a large proportion of seed (spat) typically lost early in the production cycle. An effective approach for decreasing such losses is to grow spat to larger sizes in nursery systems prior to seeding. However, for such an approach to be commercially viable, spat must first be separated from their settlement substrates into a single seed format, that is, singulated. This study investigated the efficacy of three commercial protease enzymes (Enzidase PAP, PXT and BAP) and chlorine (NaOCl) in singulating Greenshell mussel (Perna canaliculus) spat from spat‐collector ropes. Two distinct experiments involved immersing segments of spat collector rope in seawater solutions with varying concentrations (2.5% or 5%) of each enzyme or chlorine (NaOCl) for different exposure times (10, 30 and 60 min for enzymes; 2 and 5 min for chlorine). After the singulation experiments, all spat were recovered with sieves and reintroduced into the tanks with renewed seawater. After 24 h of rearing, the recovery of alive spat was measured. Results indicate that in Experiment 1, involving spat ∼5 mm in size, the singulation rate was up to 65% for protease enzymes (i.e., in the case of 5% PAP at 30 min) and 61% for chlorine (i.e., at 5% for 2 min). In Experiment 2, involving spat ∼1.5 mm in size, the singulation rate was up to 85% for protease enzymes (i.e., in the case of 5% PXT for 60 min) and 78% for chlorine (i.e., of 2.5% for 5 min). However, these treatments generally resulted in elevated spat mortality, which was exacerbated by increasing concentrations and exposure times, resulting in recovery rates of up to 35% (i.e., for 2.5% PAP for 30 min) in Experiment 1 and 26.0% (i.e., for 5% chlorine for 2 min) in Experiment 2. These findings emphasise the necessity for consideration of chemical concentrations and exposure times to optimise the singulation process while highlighting challenges in achieving high post‐singulation survival rates. These insights contribute to ongoing efforts aimed at improving the efficiency and sustainability of mussel farming practices, demonstrating the potential utility of protease enzymes and chlorination in singulating spat from settlement substrate prior to their transfer to nursery systems for further ongrowing.

Esophageal dysmotility is identified as a contraindication to lung transplantation at some centers due to increased risks of acute rejection, pulmonary infection, and chronic lung allograft dysfunction. Phosphodiesterase-type 5 inhibitors (PDE5i) are a cornerstone pharmacotherapy for pulmonary arterial hypertension (PAH) and are known to exert off-target effects that may impact lung transplant candidacy, including impaired esophageal contractility and decreased lower esophageal sphincter tone. We report 2 patients with PAH who were initially declined listing for lung transplantation due to iatrogenic esophageal dysmotility induced by PDE5is. Upon discontinuation of PDE5i therapy, these patients experienced significant improvement in esophageal motility within 14 days and met the criteria for transplant listing at their centers. Recognizing and mitigating the off-target effects of PDE5i medications is critical for maximizing access to transplant for patients with PAH.

Abstract Background Past research describes robust associations between education and health, yet findings have generally been limited to the examination of education as the number of years of education or educational attainment. Little is known about the specific features or processes underpinning education that are health protective. The objective of the current study was to address this gap by examining specific aspects of early education pertaining to student characteristics and experiences, as well as features of the classroom environment, in predicting cardiometabolic health in adulthood. Methods Subjects were 1364 participants in the NICHD Study of Early Child Care and Youth Development (SECCYD, 1991–2009) and recent SECCYD 30-year follow-up, the Study of Health in Early and Adult Life (SHINE, 2018–2022). Models examined individual education indicators (student social skills, student-teacher relationship quality, and classroom emotional and instructional quality in the period of elementary school and student academic performance between ages 54 months and 15 years) in relation to a composite of cardiometabolic risk in adulthood (ages 26–31), reflecting central adiposity, blood pressure, insulin resistance, inflammation, and dyslipidemia. Models were adjusted for key explanatory factors including socio-demographics, infant characteristics, parental socioeconomic status (SES), and child health status. Follow-up analyses were performed to test potential mediators of early education effects on adult health, including adult SES (educational attainment, household income) and health behaviors (diet quality, activity level, sleep duration, smoking). Results In adjusted models, results showed greater student social skills, indexed by a mean of annual teacher ratings between kindergarten and 6th grade, predicted lower cardiometabolic risk in adulthood (β=-0.009, p 0.05). Conclusions Findings point to the potential significance of early student social competence as a link to long-term health, possibly via the acquisition of resources needed for the maintenance of health, as well as through engagement in health behaviors supporting healthy eating. However, more research is needed to replicate these findings and to elaborate on the role of early student social competence and the pathways explaining its effects on cardiometabolic health in adulthood.

Abstract 2D materials have important fundamental properties allowing for their use in many potential applications, including quantum computing. Various Van der Waals materials, including Tungsten disulfide (WS2), have been employed to showcase attractive device applications such as light emitting diodes, lasers and optical modulators. To maximize the utility and value of integrated quantum photonics, the wavelength, polarization and intensity of the photons from a quantum emission (QE) must be stable. However, random variation of emission energy, caused by the inhomogeneity in the local environment, is a major challenge for all solid-state single photon emitters. In this work, we assess the random nature of the quantum fluctuations, and we present time series forecasting deep learning models to analyse and predict QE fluctuations for the first time. Our trained models can roughly follow the actual trend of the data and, under certain data processing conditions, can predict peaks and dips of the fluctuations. The ability to anticipate these fluctuations will allow physicists to harness quantum fluctuation characteristics to develop novel scientific advances in quantum computing that will greatly benefit quantum technologies.

The neutral organosilicon(IV) complex, (C6F5)2Si(OPO)2 (OPO = 1-oxopyridin-2-one, C5H4NO2), was synthesized from (C6F5)2Si(OCH3)2 and 2 equiv. of 1-hydroxypyridin-2-one in tetrahydrofuran (THF). Single crystals grown from the diffusion of n-pentane into a THF solution were identified as a THF hemisolvate and an n-pentane hemisolvate, (C6F5)2Si(OPO)2·0.5THF·0.5C5H12 (1). p-Tolyl2Si(OPO)2 (2) and mesityl2Si(OPO)2 (3) crystallized directly from reaction mixtures of 2 equiv. of Me3Si(OPO) with p-tolyl2SiCl2 and mesityl2SiCl2, respectively, in acetonitrile. The oxygen-bonded carbon and nitrogen atoms of the OPO ligands in 1, 2, and 3 were modeled as disordered indicating co-crystallization of up to three possible diastereomers in each. Solution NMR studies support the presence of exclusively the all-cis isomer in 1 and multiple isomers in 2. Poor solubility of 3 limited its characterization in solution.

Abstract In the United States, catfish are primarily farmed in earthen ponds, resulting in an aquatic environment influenced both by management practices and natural ecological processes. Profiling pond water microbiota can be useful for understanding what conditions may lead to microbial communities associated with production issues and could inform management practices. The aim of this study was to identify appropriate methods for bacterial community profiling of catfish pond water with nanopore sequencing of the 16S rRNA gene. To this end, two forward primers, two reverse primers, and three different polymerase chain reaction (PCR) cycle numbers were tested on a mock community consisting of aquaculture‐relevant bacteria. The optimized protocol was applied to water samples obtained from three experimental catfish ponds sampled in May, June, August, and September 2020. Applying these methods to pond samples allowed for the identification of 1488 genera, primarily within four dominating phyla: Actinobacteriota, Bacteroidota, Cyanobacteria, and Firmicutes. High variation was observed between individual ponds and sampling timepoints; only 18 of the 1488 genera were found in relative abundances ≥1% in all ponds from at least one sampling point. Despite this variation, consistent results could be observed. Samples obtained from the month of September had the highest number of observed genera, and samples from June had the lowest. Overall, these data demonstrated individual ponds represent distinct microcosms composed of unique bacterial communities, although this pond effect was secondary to the influence of sampling month on pond community composition.

We describe the evolution of low mass planets in a dispersing protoplanetary disk around a Solar mass star. The disk model is based on the results of \cite{YHH23}, which describes a region of the inner disk where the direction of the migration torque is outwards due to the diffusion of the stellar magnetic field into the disk and the resultant gradual increase in surface density outwards. We demonstrate that the magnetospheric rebound phase in such a disk leads to diverging orbits for double and triple planet systems, and the disruption of a high fraction of the initial resonant chains. We present simulations of three planet systems, with masses based on the observed triple planet systems observed by the Kepler satellite, within the context of this model. The final distribution of nearest neighbour period ratios provides an excellent fit to the observations, provided that the initial configurations {\bf contain a significant fraction of pairs whose period ratios are less than 2:1}. The occurrence rate of planets as a function of orbital period also provides a good match to the observations, for final orbital periods $P

Background: Engaging diverse populations in clinical trials is vital to research. This study evaluated the effects of varying recruitment messages for a clinical trial. Methods: The messages were evaluated in a randomly assigned, factorial design that tested enhanced trust (vs. standard) and participant endorsement (vs. standard) messaging.Four postcards were developed and randomly assigned to 4000 potential participants' addresses. Except for the messages of interest, the cards were identical, and participants were directed to four identical study websites and screening forms. Outcomes include unique website visits, visit conversion rate, screening forms completed, and participants randomized into the parent study. Results: Study websites received 74 visits (range by message type 9 to 34). There was no significant difference by message type (p = 0.79). Online screening forms were completed by 15 participants (range by message type 0–6), representing a conversion rate of 20.3% of website visits. Seven participants were randomized into the study in response to the postcards (range by message type 0 to 3; 46.7% of screenings). Overall, 0.2% of individuals who received a postcard were randomized into the study. Conclusion: Despite developing recruitment messages with participant input, the enhanced messages did not yield a greater response than standard messages. However, this method of evaluating recruitment messages shows promise.

Neuromusculoskeletal (NMS) models enable non-invasive estimation of clinically important internal biomechanics. A critical part of NMS modelling is the estimation of musculotendon kinematics, which comprise musculotendon unit lengths, moment arms, and lines of action. Musculotendon kinematics, which are partially dependent on joint angles, define the non-linear mapping of muscle forces to joint moments and contact forces. Currently, real-time computation of musculotendon kinematics requires creation of a per-individual surrogate model. The computational speed and accuracy of these surrogates degrade with increasing number of coordinates. We developed a feed-forward neural network that completely encodes musculotendon kinematics of a target model across a wide anthropometric range, enabling accurate real-time estimates of musculotendon kinematics without need for a priori creation of a per-individual surrogate model. Compared to reference, the neural network had median normalized errors ~0.1% for musculotendon lengths, $1.23\pm 0.15$ %) compared to using reference musculotendon kinematics. Finally, execution time was

Remodeling of the Achilles tendon (AT) is partly driven by its mechanical environment. AT force can be estimated with neuromusculoskeletal (NMSK) modeling; however, the complex experimental setup required to perform the analyses confines use to the laboratory. We developed task-specific long short-term memory (LSTM) neural networks that employ markerless video data to predict the AT force during walking, running, countermovement jump, single-leg landing, and single-leg heel rise. The task-specific LSTM models were trained on pose estimation keypoints and corresponding AT force data from 16 subjects, calculated via an established NMSK modeling pipeline, and cross-validated using a leave-one-subject-out approach. As proof-of-concept, new motion data of one participant was collected with two smartphones and used to predict AT forces. The task-specific LSTM models predicted the time-series AT force using synthesized pose estimation data with root mean square error (RMSE) $\le 526$ N, normalized RMSE (nRMSE) $\le 0.21$ , R $^{{2}} \ge 0.81$ . Walking task resulted the most accurate with RMSE $= 189\pm 62$ N; nRMSE $= 0.11\pm 0.03$ , R $^{{2}}= 0.92\pm 0.04$ . AT force predicted with smartphones video data was physiologically plausible, agreeing in timing and magnitude with established force profiles. This study demonstrated the feasibility of using low-cost solutions to deploy complex biomechanical analyses outside the laboratory.

Abstract Growing seed mussels (spat) to larger sizes in single‐seed nursery culture systems prior to seeding onto coastal mussel farms is an effective approach for greatly reducing costly spat losses during this stage of mussel aquaculture. However, the production of single‐seed mussel spat in nursery culture systems relies on first separating spat from the settlement substrata to which they are attached, whether spat are settled in a hatchery or gathered from the wild. This study sought to determine whether chlorination could be an effective approach for separating wild Greenshell mussel (Perna canaliculus) spat from beachcast macroalgal material (Kaitaia spat material) harvested from a beach in northern New Zealand. The results demonstrate that chlorination (i.e. in solutions of up to 0.625% sodium hypochlorite) is a highly effective approach for separating spat, resulting in the detachment of up to 94.6% in one treatment without increasing mortality relative to controls. The effectiveness of chlorination was modulated by spat density, with increasing spat densities, lowering rates of detachment. While chlorination is effective at separating small spat (i.e. successfully separating 72.4% of spat 750 μm). The high survival (relative to the control treatments) also suggests that chlorine concentrations and exposure durations could be increased from those used in this study. These results demonstrate that chlorination can be used to separate spat from substrate prior to their transfer to nursery systems for ongrowing, paving the way for such approaches for reducing spat losses to be integrated into the aquaculture production cycle.

Abstract Mitigation actions and regulations to meet critical 2030 methane reduction targets under the Global Methane Pledge are hampered by uncertainty in true levels of emissions and source breakdowns. Here we present a measurement-based, source-resolved, hybrid top-down/bottom-up methane inventory for conventional upstream oil and gas operations in Canada’s largest oil and gas-producing province, Alberta. The derived 2021 inventory of 1337 kt/y is approximately 1.5× the official federal inventory and matches independent top-down aerial mass-balance and satellite estimates within uncertainties. Major sources are starkly different from official estimates, with venting (e.g., uncontrolled tanks, pneumatics, unlit flares) comprising almost two-thirds of emissions implying important mitigation opportunities. Derived methane intensities, while similar to U.S. basins, are approximately 4× those in neighbouring British Columbia and further reveal order-of-magnitude differences among individual anonymized companies at directly comparable facility types. This highlights the importance of independent monitoring, reporting, and verification to ensure collective success in reducing emissions.

Abstract The Society for Ecological Restoration defines restoration as “the process of assisting the recovery of an ecosystem that has been degraded, damaged, or destroyed.” The United Nations Decade on Ecosystem Restoration is an “all‐hands‐on‐deck” call to revive imperilled ecosystems around the world. The task at hand is more than professional practitioners and organizations can handle alone. Volunteers play a critically important role in restoring the structure and function of the world's most degraded ecosystems. The 485 ha University of Wisconsin–Madison Arboretum is the site of some of the oldest restored ecological communities in the world. Like many restoration sites, long‐term management of these communities requires expertise and sustained volunteer engagement. The Arboretum fosters expertise and engagement with a two‐pronged approach. This includes (1) the Arboretum's Restoration Team Leader Program, which trains and empowers restoration volunteers to lead community members in on‐the‐ground restoration, and (2) the Restoration Managers Who Work with Volunteers group that convenes restoration managers from multiple organizations for collaborative projects. These programs facilitate ecological restoration by working directly with volunteers and are models of participatory leadership and communities of practice. Here, we share the principles, practices and frameworks behind these programs and illustrate how this model can be replicated to strengthen community‐based restoration around the globe.

Tibial-sided posterior cruciate ligament avulsion fractures are challenging injuries that often occur concomitantly in the setting of multiligament knee and other soft-tissue injuries. There is no consensus on the optimal surgical approach or timing of treatment for these injuries. This Technical Note describes the fixation of a displaced posterior cruciate ligament avulsion fracture with concomitant grade 3 medial collateral ligament injuries and bucket-handle lateral meniscus tears using open and arthroscopic techniques. This method allows the surgeon to address multiple pathologies in a single stage, although it requires strategic planning and rehabilitation considerations.

Circadian clocks are composed of transcription-translation negative feedback loops that pace rhythms of gene expression to the diurnal cycle. In the filamentous fungus Neurospora crassa, the proteins Frequency (FRQ), the FRQ-interacting RNA helicase (FRH), and Casein-Kinase I (CK1) form the FFC complex that represses expression of genes activated by the white-collar complex (WCC). FRQ orchestrates key molecular interactions of the clock despite containing little predicted tertiary structure. Spin labeling and pulse-dipolar electron spin resonance spectroscopy provide domain-specific structural insights into the 989-residue intrinsically disordered FRQ and the FFC. FRQ contains a compact core that associates and organizes FRH and CK1 to coordinate their roles in WCC repression. FRQ phosphorylation increases conformational flexibility and alters oligomeric state, but the changes in structure and dynamics are non-uniform. Full-length FRQ undergoes liquid–liquid phase separation (LLPS) to sequester FRH and CK1 and influence CK1 enzymatic activity. Although FRQ phosphorylation favors LLPS, LLPS feeds back to reduce FRQ phosphorylation by CK1 at higher temperatures. Live imaging of Neurospora hyphae reveals FRQ foci characteristic of condensates near the nuclear periphery. Analogous clock repressor proteins in higher organisms share little position-specific sequence identity with FRQ; yet, they contain amino acid compositions that promote LLPS. Hence, condensate formation may be a conserved feature of eukaryotic clocks.

Cardiac microtubules have recently been implicated in mechanical dysfunction during heart failure. However, systemic intolerance and non-cardiac effects of microtubule-depolymerizing compounds have made it challenging to determine the effect of microtubules on myocardial performance. Herein, we leverage recent advancements in living myocardial slices to develop a stable working preparation that recapitulates the complexity of diastole by including early and late phases of diastolic filling. To determine the effect of cardiac microtubule depolymerization on diastolic performance, myocardial slices were perfused with oxygenated media to maintain constant isometric twitch forces for more than 90 min. Force-length work loops were collected before and after 90 min of treatment with either DMSO (vehicle) or colchicine (microtubule depolymerizer). A trapezoidal stretch was added prior to the beginning of ventricular systole to mimic late-stage-diastolic filling driven by atrial systole. Force-length work loops were obtained at fixed preload and afterload, and tissue velocity was obtained during diastole as an analog to trans-mitral Doppler. In isometric twitches, microtubule destabilization accelerated force development, relaxation kinetics, and decreased end diastolic stiffness. In work loops, microtubule destabilization increased stroke length, myocardial output, accelerated isometric contraction and relaxation, and increased the amplitude of early filling. Taken together, these results indicate that the microtubule destabilizer colchicine can improve diastolic performance by accelerating isovolumic relaxation and early filling leading to increase in myocardial work output.

Abstract The nutritional condition of seed mussels (spat) at the time of seeding is thought to play a major role in influencing spat losses on mussel farms, with nutritionally compromised spat thought to be more likely to be lost from aquaculture substrata than those in good condition. New Zealand's Greenshell™ mussel (Perna canaliculus) aquaculture industry relies almost exclusively (∼85%) on wild caught spat, with the vast majority, typically > 90%, lost shortly after being seeded onto coastal mussel farms. This study sought to quantify the extent of the variability in the nutritional condition (i.e., calorific, protein, lipid and carbohydrate content) of samples of spat used by the Greenshell™ industry between 2014 and 2021 (i.e., wild caught and hatchery produced) as a first step towards determining whether variability in nutritional condition may be a significant contributor to the marked variation observed in spat performance after it is seeded onto coastal farms. All parameters measured were highly variable among wild spat samples, with all but lipid content varying, including for samples of wild spat harvested at different times within the same month. Furthermore, there were no clear patterns in the nutritional condition of spat across months or years, suggesting environmental factors that limit feeding during the harvest and transport of spat may be contributing to marked differences in the quality of spat being used by the industry to seed farms. These results provide a baseline for assessing the nutritional condition of Greenshell™ spat and point towards a need to develop interventions to improve the quality of wild spat supply for this industry to help and prevent the ongoing massive losses of spat from farms. These measures could include, testing nutritional condition of spat at harvest or prior to seeding, development of nursery culture methods and development of artificial spat feeds that have the potential to replace live phytoplankton during nursery culture.

Abstract Bolbophorus damnificus is a digenetic trematode causing significant economic losses within the United States commercial catfish industry. The indirect life cycle is complex, requiring piscivorous birds, aquatic snails, and fish to complete. With federal protections on many piscivorous birds and no FDA‐approved therapeutic treatment for trematode infections in fish, management within the catfish industry is primarily limited to controlling the snail host. Planorbella trivolvis and Biomphalaria havanensis are snails commonly found in commercial catfish ponds and known to transmit B. damnificus. This study evaluated a low‐cost snail trap prototype for monitoring populations of these snails in efforts to better inform treatment regimes. Snail traps were deployed into ponds on a commercial catfish farm and checked weekly throughout the production season. All snails were identified and counted to evaluate trap efficacy. Traps captured significantly more snails in foodfish ponds than in fingerling ponds; however, this trend was not present in monthly box samples. B. havanensis was rarely collected and was only found consistently within one pond, while P. trivolvis was routinely collected from all ponds, although abundance varied widely among ponds. Snail traps could be a useful, low‐cost method to monitor snail populations within ponds and better inform control treatments.

The title compound, systematic name 4,4′,6,6′-tetrachloro-2,2′-{[(2-methoxyethyl)azanediyl]bis(methylene)}diphenol (C17H17Cl4NO, 1), was prepared via a modified Mannich reaction between 2-methoxyethylamine, 2,4-dichlorophenol, and aqueous formaldehyde. The resulting amine bis(phenol) provides an interesting comparison to related species as a result of the electron-withdrawing substituents on the phenol rings, in combination with similar steric parameters. One of the Cl atoms was modeled as a two-component disorder with partial occupancies of 0.49 (3) and 0.51 (3), while the pendant ether group was modeled as a two-component disorder with partial occupancies of 0.867 (3) and 0.133 (3). A comparison of metrical parameters for the title compound and closely related structures provides insight into the use of these species as ligands to support transition-metal complexes for applications as homogeneous catalysts.

Cutaneous T‐cell lymphoma (CTCL) encompasses two main subtypes: mycosis fungoides and Sezary syndrome. Global response rates for the systemic treatment of mycosis fungoides and Sezary syndrome are approximately 30%, and none of these treatments are thought to be curative. C–C chemokine receptor type 4 (CCR4) and CD25 are encouraging targets for the treatment of CTCL and are individually targeted by mogamulizumab and denileukin diftitox, respectively. We developed a novel CCR4‐IL2 bispecific immunotoxin (CCR4‐IL2 IT) targeting both CCR4 and CD25. CCR4‐IL2 IT demonstrated superior efficacy against CCR4+CD25+CD30+ CTCL in an immunodeficient NSG mouse tumor model. Investigative New Drug‐enabling studies of CCR4–IL2 IT are ongoing, including Good Manufacturing Practice production and toxicology studies. In this study, we compared the in vivo efficacy of CCR4‐IL2 IT versus the US Food and Drug Administration–approved drug, brentuximab, using an immunodeficient mouse CTCL model. We demonstrated that CCR4–IL2 IT was significantly more effective in prolonging survival than brentuximab, and combination treatment of CCR4–IL2 IT and brentuximab was more effective than brentuximab or CCR4–IL2 IT alone in an immunodeficient NSG mouse CTCL model. Thus, CCR4–IL2 IT is a promising novel therapeutic drug candidate for CTCL treatment.

Abstract Multiple studies have shown that extracellular vesicles (EVs) play a key role in the process of information transfer and material transport between cells. EVs are classified into different types according to their sizes, which includes the class of exosomes. In comparison to normal EVs, tumor-derived EVs (TDEs) have both altered components and quantities of contents. TDEs have been shown to help facilitate an environment conducive to the occurrence and development of tumor by regulation of glucose, lipids and amino acids. Furthermore, TDEs can also affect the host metabolism and immune system. EVs have been shown to have multiple clinically useful properties, including the use of TDEs as biomarkers for the early diagnosis of diseases and using the transport properties of exosomes for drug delivery. Targeting the key bioactive cargoes of exosomes could be applied to provide new strategies for the treatment of tumors. In this review, we summarize the finding of studies focused on measuring the effects of TDE on tumor-related microenvironment and systemic metabolism. Video Abstract

Abstract Objective Men who work in skilled and unskilled trades and labor occupations (i.e., blue‐collar occupations), have high rates of obesity and associated comorbidities but are underrepresented in weight loss programs. A first step in engaging this group is to better understand their preferences for weight loss programs. Methods Respondents were men working in trade and labor occupations, with overweight/obesity, and an interest in losing weight. A discrete choice experiment was developed, and the data were analyzed using mixed logit model. Respondent characteristics were tested as effect modifiers. Results Respondents (N = 221, age (M ± SD) 45.0 ± 12.6, BMI 33.3 ± 6.3, 77% non‐Hispanic white) working in a variety of occupations (construction 31%, manufacturing 30%, transportation 25%, maintenance/repair 14%) participated in this study. Results indicate preferences for programs that encourage making smaller dietary changes, are delivered online, and do not incorporate competition. Results were consistent across sensitivity analyses and most respondent groups. Conclusions The results suggest specific ways to make weight loss programs more appealing to men in trade and labor occupations. Using experimental methods to quantify preferences using larger, more representative samples would further assist in tailoring behavioral weight loss programs for under‐reached populations.

Abstract We recently introduced an absolute and physical quantitative scale for chromatin immunoprecipitation followed by sequencing (ChIP-seq). The scale itself was determined directly from measurements routinely made on sequencing samples without additional reagents or spike-ins. We called this approach sans spike-in quantitative ChIP, or siQ-ChIP. Herein, we extend those results in several ways. First, we simplified the calculations defining the quantitative scale, reducing practitioner burden. Second, we reveal a normalization constraint implied by the quantitative scale and introduce a new scheme for generating ‘tracks’. The constraint requires that tracks are probability distributions so that quantified ChIP-seq is analogous to a mass distribution. Third, we introduce some whole-genome analyses that allow us, for example, to project the IP mass (immunoprecipitated mass) onto the genome to evaluate how much of any genomic interval was captured in the IP. We applied siQ-ChIP to p300/CBP inhibition and compare our results to those of others. We detail how the same data-level observations are misinterpreted in the literature when tracks are not understood as probability densities and are compared without correct quantitative scaling, and we offer new interpretations of p300/CBP inhibition outcomes.

Most, if not all, Sun-like stars host one or more planets, making multiplanetary systems commonplace in our Galaxy. We utilize hundreds of multiplanet simulations to explore the origin of such systems, focusing on their orbital architecture. The first set of simulations assumes in situ assembly of planetary embryos, while the second explores planetary migration. After applying observational biases to the simulations, we compare them to 250+ observed multiplanetary systems, including 13 systems with planets in the habitable zone. For all of the systems, we calculate two of the so-called statistical measures: the mass concentration ( S _c ) and orbital spacing ( S _s ). After analytic and empirical analyses, we find that the measures are related to first order with a power law: ${S}_{c}\sim {S}_{s}^{\beta }$ . The in situ systems exhibit steeper power-law relations relative to the migration systems. We show that different formation scenarios cover different regions in the S _s – S _c diagram with some overlap. Furthermore, we discover that observed systems with S _s < 30 are likely dominated by the migration scenario, while those with S _s ≥ 30 are likely dominated by the in situ scenario. We apply these criteria to determine that a majority (62%) of observed multiplanetary systems formed via migration, whereas most systems with currently observed habitable planets formed via in situ assembly. This work provides methods of leveraging the statistical measures ( S _s and S _c ) to disentangle the formation history of observed multiplanetary systems based on their present-day architectures.

Knee function is rarely measured objectively during functional tasks following total knee arthroplasty. Inertial measurement units (IMU) can measure knee kinematics and range of motion (ROM) during dynamic activities and offer an easy-to-use system for knee function assessment post total knee arthroplasty. However, IMU must be validated against gold standard three-dimensional optical motion capture systems (OMC) across a range of tasks if they are to see widespread uptake. We computed knee rotations and ROM from commercial IMU sensor measurements during walking, squatting, sit-to-stand, stair ascent, and stair descent in 21 patients one-year post total knee arthroplasty using two methods: direct computation using segment orientations (r_IMU), and an IMU-driven iCloud-based interactive lower limb model (m_IMU). This cross-sectional study compared computed knee angles and ROM to a gold-standard OMC and inverse kinematics method using Pearson's correlation coefficient (R) and root-mean-square-differences (RMSD). The r_IMU and m_IMU methods estimated sagittal plane knee angles with excellent correlation (>0.95) compared to OMC for walking, squatting, sit-to-stand, and stair-ascent, and very good correlation (>0.90) for stair descent. For squatting, sit-to-stand, and walking, the mean RMSD for r_IMU and m_IMU compared to OMC were

In this study, our goal was to determine probe-specific thresholds for identifying aberrant, or outlying, DNA methylation and to provide guidance on the relative merits of using continuous or outlier methylation data. To construct a reference database, we downloaded Illumina Human 450K array data for more than 2,000 normal samples, characterized the distribution of DNA methylation and derived probe-specific thresholds for identifying aberrations. We made the decision to restrict our reference database to solid normal tissue and morphologically normal tissue found adjacent to solid tumours, excluding blood which has very distinctive patterns of DNA methylation. Next, we explored the utility of our outlier thresholds in several analyses that are commonly performed on DNA methylation data. Outliers are as effective as the full continuous dataset for simple tasks, like distinguishing tumour tissue from normal, but becomes less useful as the complexity of the problem increases. We developed an R package called OutlierMeth containing our thresholds, as well as functions for applying them to data.

Decision-making is an executive function, tapping into cognitive, emotional, and personality-based components. This complexity, and the varying operational definitions of the construct, is reflected in the rich array of behavioral decision-making tasks available for use in research and clinical settings. In many cases, these tasks are “subfield-specific,” with tasks developed by cognitive psychologists focusing on cognitive aspects of decision-making and tasks developed by clinical psychologists focusing on interactions between emotional and cognitive aspects. Critically, performance across different tasks does not consistently correlate, obfuscating the ability to compare scores between measures and detect changes over time. Differing theories as to what cognitive and/or emotional aspects affect decision-making likely contribute to this lack of consistency across measures. The low criterion-related validity among decision-making tasks and lack of consistent measurement of the construct presents challenges for emotion and decision-making scholars. In this perspective, we provide several recommendations for the field: (a) assess decision-making as a specific cognitive ability versus a taxonomy of cognitive abilities; (b) a renewed focus on convergent validity across tasks; (c) further assessment of test–retest reliability versus practice effects on tasks; and (d) reimagine future decision-making research to consider the research versus clinical implications. We discuss one example of decision-making research applied to clinical settings, acquired brain injury recovery, to demonstrate how some of these concerns and recommendations can affect the ability to track changes in decision-making across time.

Abstract Critical mitigation of methane emissions from the oil and gas (OG) sector is hampered by inaccurate official inventories and limited understanding of contributing sources. Here we present a framework for incorporating aerial measurements into comprehensive OG sector methane inventories that achieves robust, independent quantification of measurement and sample size uncertainties, while providing timely source-level insights. This hybrid inventory combines top-down, source-resolved, multi-pass aerial measurements with bottom-up estimates of unmeasured sources leveraging continuous probability of detection and quantification models for a chosen aerial technology. Notably, the technique explicitly considers skewed source distributions and finite facility populations that have not been previously addressed. The protocol is demonstrated to produce a comprehensive upstream OG sector methane inventory for British Columbia, Canada, which while approximately 1.7 times higher than the most recent official bottom-up inventory, reveals a lower methane intensity of produced natural gas (

Over the past decade, there have been reports of short novel functional peptides (less than 100 aa in length) translated from so-called non-coding RNAs (ncRNAs) that have been characterized using mass spectrometry (MS) and large-scale proteomics studies. Therefore, understanding the bivalent functions of some ncRNAs as transcripts that encode both functional RNAs and short peptides, which we named ncPEPs, will deepen our understanding of biology and disease. In 2020, we published the first database of functional peptides translated from non-coding RNAs—FuncPEP. Herein, we have performed an update including the newly published ncPEPs from the last 3 years along with the categorization of host ncRNAs. FuncPEP v2.0 contains 152 functional ncPEPs, out of which 40 are novel entries. A PubMed search from August 2020 to July 2023 incorporating specific keywords was performed and screened for publications reporting validated functional peptides derived from ncRNAs. We did not observe a significant increase in newly discovered functional ncPEPs, but a steady increase. The novel identified ncPEPs included in the database were characterized by a wide array of molecular and physiological parameters (i.e., types of host ncRNA, species distribution, chromosomal density, distribution of ncRNA length, identification methods, molecular weight, and functional distribution across humans and other species). We consider that, despite the fact that MS can now easily identify ncPEPs, there still are important limitations in proving their functionality.

Purpose: The purposes of this study were to determine the incidence and key characteristics of meniscus injuries in professional baseball players, assess current treatment strategies, determine the return to play rates at any level (RTP) and at the same level (RSL), and identify prognostic factors that predict injury severity. Methods: After approval from the Major League Baseball (MLB) Research Committee and our institutional review board, the MLB Health and Injury Tracking System was used to identify meniscus injuries occurring across MLB and Minor League Baseball (MiLB) from 2011 to 2017. Analyzed injuries occurred during normal baseball activity in a player who was active on an MLB or MiLB roster and resulted in at least 1 day missed. Results: A total of 293 professional baseball players sustained 314 meniscus injuries from 2011 to 2017 (7 years) for a mean of 44.9 injuries/y. Pitchers were the most injured position (31.8%), followed by infielders (26.4%). Catchers and infielders missed the most median number of days (50 days). When comparing injuries to landing leg vs push-off leg in pitchers, injury to the push-off leg resulted in significantly more days missed per injury compared to the lead leg (59.6 vs 39.9 days, P = .048). Overall, RTP was 93.0%, while RSL was 84.4%. Conclusions: Over 7 professional baseball seasons, 314 meniscus injuries occurred in 293 players. Pitchers and catchers were most injured, and overall, the number of meniscal injuries per year declined while the percentage of injuries that required surgery increased over time. High rates of RTP were observed. Level of Evidence: Level IV, therapeutic case series.

The preparatory experiences leading up to student teaching vary greatly. Understanding the evolution of the student teaching block can provide key guidance on what is needed for the student teacher of today and the student teacher of tomorrow. A historical narrative approach was used to understand the student teaching block as it has been developed and implemented historically in agricultural education. Six semi-structured interviews were conducted with participants who were current faculty at the rank of Professor in agricultural education and had been involved in agricultural education for at least 25 years. Four themes emerged through our analysis: (a) origins, (b) purpose and philosophy, (c) structural elements of the block, and (d) limitations and forward-thinking. Based on the findings, the purpose of the block as it relates to the agricultural education profession is to provide an intensive, immersive experience to prepare soon-to-be student teachers in an environment that provides an opportunity for practice and reflection before entering the classroom. It is recommended that periodic check-ins or seminars with student teachers be done to ensure they can reflect, share experiences, exchange ideas, discuss best practices, and learn from each other as they experience student teaching.

The Achilles tendon (AT) is sensitive to mechanical loading, with appropriate strain improving tissue mechanical and material properties. Estimating free AT strain is currently possible through personalized neuromusculoskeletal (NMSK) modeling; however, this approach is time-consuming and requires extensive laboratory data. To enable in-field assessments, we developed an artificial intelligence (AI) workflow to predict free AT strain during running from motion capture data. Ten keypoints commonly used in pose estimation algorithms (e.g., OpenPose) were synthesized from motion capture data and noise was added to represent real-world data obtained using video cameras. Two AI workflows were compared: (1) a Long Short-Term Memory (LSTM) neural network that predicted free AT strain directly (called LSTM only workflow); and (2) an LSTM neural network that predicted AT force which was subsequently converted to free AT strain using a personalized force-strain curve (called LSTM+ workflow). AI models were trained and evaluated using estimates of free AT strain obtained from a validated NMSK model with personalized AT force-strain curve. The effect of using different input features (position, velocity, and acceleration of keypoints, height and mass) on free AT strain predictions was also assessed. The LSTM+ workflow significantly improved the predictions of free AT strain compared to the LSTM only workflow (p < 0.001). The best free AT strain predictions were obtained using positions and velocities of keypoints as well as the height and mass of the participants as input, with average time-series root mean square error (RMSE) of 1.72±0.95% strain and r2 of 0.92±0.10, and peak strain RMSE of 2.20% and r2 of 0.54. In conclusion, we showed feasibility of predicting accurate free AT strain during running using low fidelity pose estimation data.

Abstract Background Both short sleep duration and circadian rhythm misalignment are risk factors for metabolic dysfunction, but the underlying mechanisms are unknown. The goal of this study is to examine how sleep duration and circadian alignment predict changes in cardiometabolic risk factors over a 12-month period, and test cognitive function and hedonic eating tendencies as potential mechanisms. Methods We will recruit a sample of 120 working aged adults with BMI 25–35 kg/m2 (overweight to class I obesity). The protocol includes 5 visits over a 12-month period. Study visits include wrist actigraphy to measure sleep behaviors, 24-h diet recalls, dim light melatonin collection, a computerized neurobehavioral assessment, eating in the absence of hunger task, and frequently sampled IV glucose tolerance test. Discussion The results of the TIME study will advance the understanding of how both short sleep duration and circadian misalignment contribute to behavioral aspects of obesity and metabolic dysfunction. Trial registration ClinicalTrials.Gov, NCT04759755 , registered retrospectively February 13, 2021.

Abstract Computer vision algorithms can quickly analyze numerous images and identify useful information with high accuracy. Recently, computer vision has been used to identify 2D materials in microscope images. 2D materials have important fundamental properties allowing for their use in many potential applications, including many in quantum information science and engineering. One such material is hexagonal boron nitride (hBN), an isomorph of graphene with a very indistinguishable layered structure. In order to use these materials for research and product development, the most effective method is mechanical exfoliation where single-layer 2D crystallites must be prepared through an exfoliation procedure and then identified using reflected light optical microscopy. Performing these searches manually is a time-consuming and tedious task. Deploying deep learning-based computer vision algorithms for 2D material search can automate the flake detection task with minimal need for human intervention. In this work, we have implemented a new deep learning pipeline to classify crystallites of hBN based on coarse thickness classifications in reflected-light optical micrographs. We have used DetectoRS as the object detector and trained it on 177 images containing hexagonal boron nitride (hBN) flakes of varying thickness. The trained model achieved a high detection accuracy for the rare category of thin flakes ( $$

Abstract Foraging behavior and interaction with prey is an integral component of the ecological niche of predators but is inherently difficult to observe for highly mobile animals in the marine environment. Billfishes have been described as energy speculators, expending a large amount of energy foraging, expecting to offset high costs with periodic high energetic gain. Surface-based group feeding of sailfish, Istiophorus platypterus, is commonly observed, yet sailfish are believed to be largely solitary roaming predators with high metabolic requirements, suggesting that individual foraging also represents a major component of predator–prey interactions. Here, we use biologging data and video to examine daily activity levels and foraging behavior, estimate metabolic costs, and document a solitary predation event for a 40 kg sailfish. We estimate a median active metabolic rate of 218.9 ± 70.5 mgO2 kg−1 h−1 which increased to 518.8 ± 586.3 mgO2 kg−1 h−1 during prey pursuit. Assuming a successful predation, we estimate a daily net energy gain of 2.4 MJ (5.1 MJ acquired, 2.7 MJ expended), supporting the energy speculator model. While group hunting may be a common activity used by sailfish to acquire energy, our calculations indicate that opportunistic individual foraging events offer a net energy return that contributes to the fitness of these highly mobile predators.

Abstract Lysine methylation modulates the function of histone and non-histone proteins, and the enzymes that add or remove lysine methylation—lysine methyltransferases (KMTs) and lysine demethylases (KDMs), respectively—are frequently mutated and dysregulated in human diseases. Identification of lysine methylation sites proteome-wide has been a critical barrier to identifying the non-histone substrates of KMTs and KDMs and for studying functions of non-histone lysine methylation. Detection of lysine methylation by mass spectrometry (MS) typically relies on the enrichment of methylated peptides by pan-methyllysine antibodies. In this study, we use peptide microarrays to show that pan-methyllysine antibodies have sequence bias, and we evaluate how the differential selectivity of these reagents impacts the detection of methylated peptides in MS-based workflows. We discovered that most commercially available pan-Kme antibodies have an in vitro sequence bias, and multiple enrichment approaches provide the most comprehensive coverage of the lysine methylome. Overall, global lysine methylation proteomics with multiple characterized pan-methyllysine antibodies resulted in the detection of 5089 lysine methylation sites on 2751 proteins from two human cell lines, nearly doubling the number of reported lysine methylation sites in the human proteome.

Abstract The previously uncultured phylum “Candidatus Eremiobacterota” is globally distributed and often abundant in oligotrophic environments. Although it includes lineages with the genetic potential for photosynthesis, one of the most important metabolic pathways on Earth, the absence of pure cultures has limited further insights into its ecological and physiological traits. We report the first successful isolation of a “Ca. Eremiobacterota” strain from a fumarolic ice cave on Mt. Erebus volcano (Antarctica). Polyphasic analysis revealed that this organism is an aerobic anoxygenic photoheterotrophic bacterium with a unique lifestyle, including bacteriochlorophyll a production, CO2 fixation, a high CO2 requirement, and phototactic motility using type IV-pili, all of which are highly adapted to polar and fumarolic environments. The cells are rods or filaments with a vesicular type intracytoplasmic membrane system. The genome encodes novel anoxygenic Type II photochemical reaction centers and bacteriochlorophyll synthesis proteins, forming a deeply branched monophyletic clade distinct from known phototrophs. The first cultured strain of the eighth phototrophic bacterial phylum which we name Vulcanimicrobium alpinus gen. nov., sp. nov. advances our understanding of ecology and evolution of photosynthesis.

Tenalisib, a selective phosphoinositide-3-kinase δ/γ, and salt-inducible-kinase-3 inhibitor has shown efficacy and was well-tolerated in patients with T-cell lymphoma (TCL). In vitro studies suggest a synergistic anti-tumor potential for the combination of tenalisib with the histone-deacetylase inhibitor, romidepsin. This multicenter, open-label, phase I/II study was designed to characterize the safety, efficacy and pharmacokinetics of oral tenalisib twice-daily and intravenous romidepsin administered on days 1, 8 and 15 in 28-day cycles in adults with relapsed/refractory TCL. Phase I/dose escalation determined the maximum tolerated dose (MTD)/optimal doses of tenalisib and romidepsin. The phase II/dose expansion assessed the safety and anti-tumor activity of the combination at MTD/optimal dose. Overall, 33 patients were enrolled. In dose escalation, no dose-limiting toxicity was identified. Hence, the recommended doses for dose expansion were tenalisib 800 mg twice daily orally, and romidepsin 14 mg/m2 intravenous. Overall treatment-emergent adverse events of any grade reported in >15% of patients were nausea, thrombocytopenia, increased aspartate aminotransferase, increased alanine aminotransferase, decreased appetite, neutropenia, vomiting, fatigue, anemia, dysgeusia, weight loss, diarrhea, and hypokalemia. Twenty-three patients (69.7%) had related grade ≥3 treatment-emergent adverse events. The overall objective response rate in evaluable patients was 63.0% (peripheral TCL: 75% and cutaneous TCL: 53.3%), with a complete response and partial response of 25.9% and 37.0% respectively. The median duration of response was 5.03 months. Co-administration of tenalisib and romidepsin did not significantly alter the pharmacokinetics of romidepsin. Overall, tenalisib and romidepsin combination demonstrated a favorable safety and efficacy profile supporting its further development for relapsed/refractory TCL (clinicaltrials gov. Identifier: NCT03770000).

Background: Depression is prevalent among adolescents and young adults and is associated with experiencing increased negative alcohol-related consequences; thus, it is imperative to identify malleable protective factors for alcohol risks in young adults experiencing elevated depressive symptoms. The current study longitudinally explored the effects of perceived parental alcohol-related discipline on the relationship between depressive symptoms, alcohol use, and negative drinking consequences during the transition into college. Methods: Incoming college students (N = 272, 63.2% female) completed web-based surveys before (July, T1) and after (October, T2) the transition into college and reported depressive symptoms, perceived alcohol-related discipline, alcohol use, and consequences of drinking experienced in the past 30 days. Results: The moderated mediation model revealed that at above average perceptions of alcohol-related discipline, depressive symptoms were negatively associated with alcohol use, which in turn was associated with experiencing fewer negative consequences of drinking. Limitations: The current study did not measure a diagnosis of major depressive disorder, and therefore our results may differ among clinical populations. In addition, we did not measure other parenting constructs shown to protect students with elevated levels of depressive symptoms from experiencing consequences (i.e., monitoring). Conclusions: The present findings suggest perceptions of parental alcohol-related discipline measured here (e.g., having a privilege taken away, being scolded or grounded) can be protective against alcohol risks among college students experiencing above average depressive symptoms. Parent-based alcohol interventions administered prior to matriculation should encourage parents of depressed students to clearly communicate consequences for drinking to their child.

Sensory feedback is required for the stable execution of learned motor skills, and its loss can severely disrupt motor performance. The neural mechanisms that mediate sensorimotor stability have been extensively studied at systems and physiological levels, yet relatively little is known about how disruptions to sensory input alter the molecular properties of associated motor systems. Songbird courtship song, a model for skilled behavior, is a learned and highly structured vocalization that is destabilized following deafening. Here, we sought to determine how the loss of auditory feedback modifies gene expression and its coordination across the birdsong sensorimotor circuit. To facilitate this system-wide analysis of transcriptional responses, we developed a gene expression profiling approach that enables the construction of hundreds of spatially-defined RNA-sequencing libraries. Using this method, we found that deafening preferentially alters gene expression across birdsong neural circuitry relative to surrounding areas, particularly in premotor and striatal regions. Genes with altered expression are associated with synaptic transmission, neuronal spines, and neuromodulation and show a bias toward expression in glutamatergic neurons and Pvalb/Sst-class GABAergic interneurons. We also found that connected song regions exhibit correlations in gene expression that were reduced in deafened birds relative to hearing birds, suggesting that song destabilization alters the inter-region coordination of transcriptional states. Finally, lesioning LMAN, a forebrain afferent of RA required for deafening-induced song plasticity, had the largest effect on groups of genes that were also most affected by deafening. Combined, this integrated transcriptomics analysis demonstrates that the loss of peripheral sensory input drives a distributed gene expression response throughout associated sensorimotor neural circuitry and identifies specific candidate molecular and cellular mechanisms that support the stability and plasticity of learned motor skills.

Concerns about decreases in insect population and biodiversity, in addition to the need for monitoring insects in agriculture and disease control, have led to an increased need for automated, non-invasive monitoring techniques. To this end, entomological lidar systems have been developed and successfully used for detecting and classifying insects. However, the data produced by these lidar systems create several problems from a data analysis standpoint: the data can contain millions of observations, very few observations contain insects, and the background environment is non-stationary. This study compares the insect-detection performance of various supervised machine learning and unsupervised changepoint detection algorithms and provides commentary on the relative strengths of each method. We found that the supervised methods generally perform better than the changepoint detection methods, at the cost of needing labeled data. The supervised learning method with the highest Matthew’s Correlation Coefficient score on the testing set correctly identified 99.5% of the insect-containing images and 83.7% of the non-insect images; similarly, the best changepoint detection method correctly identified 83.2% of the insect-containing images and 84.2% of the non-insect images. Our results show that both types of methods can reduce the need for manual data analysis.

Abstract Atrial fibrillation (AF) is the most common cardiac tachyarrhythmia and has a rising global prevalence. Given the increasing burden of AF-related symptoms and complications, new approaches to management are required. Anemia and iron deficiency are common conditions in patients with AF. Furthermore, emerging evidence suggests that the presence of anemia may be associated with worse outcome in these patients. The role of anemia and iron deficiency has been extensively explored in other cardiovascular states, such as heart failure and ischemic heart disease. In particular, the role of iron repletion amongst patients with heart failure is now an established treatment modality. However, despite the strong bidirectional inter-relationship between AF and heart failure, the implications of anemia and iron-deficiency in AF have been scarcely studied. This area is of mechanistic and clinical relevance given the potential that treatment of these conditions may improve symptoms and prognosis in the increasing number of individuals with AF. In this review, we summarise the current published literature on anemia and iron deficiency in patients with AF. We discuss AF complications such as stroke, bleeding, and heart failure, in addition to AF-related symptoms such as exercise intolerance, and the potential impact of anemia and iron deficiency on these. Finally, we summarize current research gaps on anemia, iron deficiency, and AF, and underscore potential research directions.