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Competing Interests: Declaration of competing interest We have no financial or personal conflicts of interest to disclose.

Intraflagellar transport protein 88 (Ift88) is required for the formation of cilia in the thymus and non-ciliary dependent functions including T cell immune synapse formation. To test the role of Ift88 in T cell development, we performed flow cytometry analysis on thymus and spleen tissue isolated from mice lacking Ift88 in thymic epithelial cells (TECs) or T cells. Analyses indicated that TEC Ift88 deletion had no impact on thymic T cell development and minimal impact on splenic T cells. Analysis of T cells in CaggCre ERT2+ Ift88 tm1Bky mTmG mice indicate that approximately half of DN1 thymocytes are Ift88 deficient 3 weeks post-tamoxifen induction; Ift88 loss did not impact T cell development at the DN2-DN4 stage or the CD4+/CD8+ double-positive (DP) thymocyte stage. However, survival of Ift88 deficient T cells was significantly reduced at the single-positive (SP) thymocyte stage, as was the number of CD4+ and CD8+ T cells in spleen and kidney. Despite preferential survival of Ift88-proficient cells, the total number of T cells the in spleen and kidney was minimally impacted by Ift88 loss. These data suggest Ift88 is required for differentiation of DP thymocytes into SP thymocytes and that Ift88 proficient T cells can compensate for deficient cells to fill the open niche., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Ectomycorrhizal fungi in the genus Tuber form hypogeous fruiting bodies called truffles. Many Tuber species are highly prized due to their edible and aromatic ascomata. Historically, there has been attention on cultivating and selling European truffle species, but there is growing interest in cultivating, wild-harvesting, and selling species of truffles endemic to North America. North America has many endemic Tuber species that remain undescribed, including some that have favorable culinary qualities. Here, we describe two such Tuber species from eastern North America. Maximum likelihood and Bayesian phylogenetic analyses of ITS (internal transcribed spacer), tef1 (translation elongation factor 1-alpha), and rpb2 (second largest subunit of RNA polymerase II) sequences were used to place these species within a phylogenetic context. We coupled these data with morphological analyses and volatile analyses based on gas chromatography-mass spectrometry. Tuber cumberlandense , sp. nov. (previously referred to as Tuber sp. 66), is a member of the Rufum clade that has been opportunistically harvested for commercial sale from T. melanosporum orchards across eastern North America. Tuber canirevelatum , sp. nov. belongs in the Macrosporum clade and thus far is only known from eastern Tennessee, USA. Both new species were discovered with the assistance of trained truffle dogs. The volatile profiles of T. canirevelatum and T. cumberlandense were measured in order to characterize aromas based on the chemical compounds produced by these fungi. Ascomata from both species were enriched in acetone, dimethyl sulfide, 1-(methylthio)-1-propene, and 1-(methylthio)propane. In this work, we celebrate and encourage the use of trained truffle-hunting dogs for fungal biodiversity discovery and research.

Background: Risk score calculators are a widely developed tool to support clinicians in identifying and managing risk for certain diseases. However, little is known about physicians' applied experiences with risk score calculators and the role of risk score estimates in clinical decision making and patient communication., Methods: Physicians providing care in outpatient community-based clinical settings ( N  = 20) were recruited to participate in semi-structured individual interviews to assess their use of risk score calculators in practice. Two study team members conducted an inductive thematic analysis using a consensus-based coding approach., Results: Participants referenced at least 20 risk score calculators, the most common being the Atherosclerotic Cardiovascular Disease Risk Calculator. Ecological factors related to the clinical system (e.g., time), patient (e.g., receptivity), and physician (e.g., experience) influenced conditions and patterns of risk score calculator use. For example, compared with attending physicians, residents tended to use a greater variety of risk score calculators and with higher frequency. Risk score estimates were generally used in clinical decision making to improve or validate clinical judgment and in patient communication to serve as a motivational tool., Conclusions: The degree to which risk score estimates influenced physician decision making and whether and how these scores were communicated to patients varied, reflecting a nuanced role of risk score calculator use in clinical practice. The theory of planned behavior can help explain how attitudes, beliefs, and norms shape the use of risk score estimates in clinical decision making and patient communication. Additional research is needed to evaluate best practices in the use of risk score calculators and risk score estimates., Highlights: The risk score calculators and estimates that participants referenced in this study represented a range of conditions (e.g., heart disease, anxiety), levels of model complexity (e.g., probability calculations, scales of severity), and output formats (e.g., point estimates, risk intervals).Risk score calculators that are easily accessed, have simple inputs, and are trusted by physicians appear more likely to be used.Risk score estimates were generally used in clinical decision making to improve or validate clinical judgment and in patient communication to serve as a motivational tool.Risk score estimates helped participants manage the uncertainty and complexity of various clinical situations, yet consideration of the limitations of these estimates was relatively minimal.Developers of risk score calculators should consider the patient- (e.g., response to risk score estimates) and physician- (e.g., training status) related characteristics that influence risk score calculator use in addition to that of the clinical system., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: EMM is or has been a consultant to Amgen, Cytokinetics, PepGen, Pfizer, and Tenaya Therapeutics and is a founder of Ikaika Therapeutics. These activities are unrelated to the content of this article. All other authors declare no conflict of interest.

People spontaneously segment an observed everyday activity into discrete, meaningful events, but segmentation can be modified by task goals. Asking young adults to attend to event segmentation while watching movies of everyday actions improved their memory up to 1 month later (Flores et al., 2017). Does attending to event segmentation improve memory across the lifespan? Participants between the ages of 20 and 79 watched movies of actors performing everyday activities while intentionally encoding them for a recall and a recognition memory test 1 week (Experiment 1) or 1 month (Experiment 2) later. In addition to intentionally encoding the movies, half of the participants segmented the movies into fine-grained events. Young adults who segmented recalled more words in their recall responses than those who intentionally encoded 1 week and 1 month later. Middle-aged adults benefited from the intervention after a 1-week delay but not after a 1-month delay. Older adults over the age of 70 did not benefit from attending to segmentation. Of those who segmented, young and older adults showed similar agreement about the locations of event boundaries. Together, the results suggest that older adults are less able, compared to young adults, to maintain or retrieve well-encoded event memories after a delay. In addition, individual differences in segmentation agreement predicted memory up to 1 month later, regardless of age. These results suggest a practical and easy-to-implement intervention for improving recall of everyday events in young and middle-aged adults that is ineffective in older adults. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Cistaceae are shrubs, subshrubs and herbs that often occur in stressful, fire-prone or disturbed environments and form ectomycorrhizal (ECM) associations with symbiotic fungi. Although some Cistaceae are long-lived shrubs that grow to significant size, others are herbaceous annuals or short-lived plants. Thus, Cistaceae are atypical ECM hosts that are fundamentally different in their biology from trees that are the more typically studied ECM hosts. The Mediterranean region is the center of diversity for Cistaceae and the ectomycorrhizal fungi associated with Cistaceae hosts have primarily been studied in Europe, North Africa, and the Middle East. Mediterranean Cistaceae often host diverse communities of ECM fungi, but they also act as hosts for some ECM fungi that putatively show host-specificity or strong host preference for Cistaceae (including species of Delastria, Hebeloma, Terfezia, and Tirmania). The ECM associations of Cistaceae in North America, however, remain highly understudied. Here we use fungal DNA metabarcoding to document the ectomycorrhizal fungal communities associated with Crocanthemum and Lechea (Cistaceae) in open, fire-prone sandhill habitats in north Florida. At each site we also sampled nearby Pinus to determine whether small, herbaceous Cistaceae have specialized ECM fungi or whether they share their ECM fungal community with nearby pines. The ECM communities of Florida Cistaceae are dominated by Cenococcum (Ascomycota) and Russula (Basidiomycota) species but were also significantly associated with Delastria, an understudied genus of mostly truffle-like Pezizales (Ascomycota). Although many Cistaceae ECM fungi were shared with neighboring pines, the ECM communities with Cistaceae were nonetheless significantly different than those of pines., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Retraction is the removal of published material due to flaws in research that cannot be corrected. Our aim was to perform a systematic review of all retracted literature in Ear Nose and Throat to understand the characteristics of retraction and the citations of retracted literature., Methods: The Retraction Watch, EMBASE and MEDLINE databases were systematically searched to yield relevant retractions. Two independent authors performed abstract and full-text screening. Non-relevant texts, articles in non-English languages, and articles that were neither published (protocols) or retracted (expression of concern) were excluded., Results: We found 225 retractions in Ear Nose and Throat literature from 1992 to 2023. The number of retractions increased with time, and the average time-to-retraction was 1 year (range 0-29). Most articles were retracted due to misconduct (72%). In total, 191/225 of retractions were signposted with a retraction notice; 90.6% of notices were linked to the original manuscript; 96.9% specified the reason for retraction and 100% were freely accessible. Publications were cited more after retraction (median 2, range 0-215 vs median 0, range 0-78, Z -1.78, p = 0.075), however this was not significant, and appeared to improve with a shorter retraction time (RS 0.67, p < 0.001)., Conclusion: Retractions, although rare, are increasing across all scientific disciplines. Our data suggests that retractions are both efficiently and transparently publicised in the Ear Nose and Throat Literature. Investigators should be veracious when conducting their own research and regularly appraise manuscripts to ensure that misinformation is not perpetuated, remaining aware that retracted articles continue to be cited., (© 2024. Crown.)

Octacalcium phosphate (OCP, Ca 8 (PO 4 ) 4 (HPO 4 ) 2 ·5H 2 O) is a notable calcium phosphate due to its biocompatibility, making it a widely studied material for bone substitution. It is known to be a precursor of bone mineral, but its role in biomineralisation remains unclear. While the structure of OCP has been the subject of thorough investigations (including using Rietveld refinements of X-ray diffraction data, and NMR crystallography studies), important questions regarding the symmetry and H-bonding network in the material remain. In this study, it is shown that OCP undergoes a lowering of symmetry below 200 K, evidenced by 1 H, 17 O, 31 P and 43 Ca solid-state NMR experiments. Using ab initio molecular-dynamics (MD) simulations and gauge including projected augmented wave (GIPAW) DFT calculations of NMR parameters, the presence of rapid motions of the water molecules in the crystal cell at room temperature is proved. This information leads to an improved description of the OCP structure at both low and ambient temperatures, and helps explain long-standing issues of symmetry. Remaining challenges related to the understanding of the structure of OCP are then discussed.

Objective: The Society for Vascular Surgery (SVS) Wound, Ischemia, and foot Infection (WIfI) classification system aims to risk stratify patients with chronic limb-threatening ischemia (CLTI), predicting both amputation rates and the need for revascularization. However, real-world use of the system and whether it predicts outcomes accurately after open revascularization and peripheral interventions is unclear. Therefore, we sought to determine the adoption of the WIfI classification system within a contemporary statewide collaborative as well as the impact of patient factor, and WIfI risk assessment on short- and long-term outcomes., Methods: Using data from a large statewide collaborative, we identified patients with CLTI undergoing open surgical revascularization or peripheral vascular intervention (PVI) between 2016 and 2022. The primary exposure was preoperative clinical WIfI stage. Patients were categorized according to the SVS Lower Extremity Threatened Limb Classification System into clinical WIfI stages 1, 2, 3, or 4. The primary outcomes were 30-day and 1-year amputation and mortality rates. Multivariable logistic regression was performed to estimate the association of WIfI stage on postrevascularization outcomes., Results: In the cohort of 17,417 patients, 83.4% (n = 14,529) had WIfI stage documented. PVIs were performed on 57.6% of patients, and 42.4% underwent an open surgical revascularization. Of the patients, 49.5% were classified as stage 1, 19.3% stage 2, 12.8% stage 3, and 18.3% of patients met stage 4 criteria. Stage 3 and 4 patients had higher rates of diabetes, congestive heart failure, and renal failure, and were less likely to be current or former smokers. One-half of stage 3 patients underwent open surgical revascularization, whereas stage 1 patients were most likely to have received a PVI (64%). As WIfI stage increased from 1 to 4, 1-year mortality increased from 12% to 21% (P < .001), 30-day amputation rates increased from 5% to 38% (P < .001), and 1-year amputation rates increased from 15% to 55% (P < .001). Finally, patients who did not have WIfI scores classified had significantly higher 30-day and 1-year mortality rates, as well as higher 30-day and 1-year amputation rates., Conclusions: The SVS WIfI clinical stage is significantly associated with 1-year amputation rates in patients with CLTI after lower extremity revascularization. Because nearly 55% of stage 4 patients require a major amputation within 1 year of intervention, this finding study supports use of the WIfI classification system in clinical decision-making for patients with CLTI., Competing Interests: Disclosures None., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Subantarctic Nothofagus forests are the southernmost forests in the world, with negligible atmospheric nitrogen (N) deposition. Most paradigms about the role of ectomycorrhizal (ECM) fungi in N cycling and plant N uptake at high latitudes have been tested in boreal coniferous forests, while in the southern hemisphere, ECM hosts are primarily angiosperms. Using ITS1 meta-barcoding, we characterized ECM and saprotrophic fungal communities in evergreen and deciduous Nothofagus forests forming monodominant and mixed stands in the archipelago of Tierra del Fuego (Chile and Argentina). We assessed the N economy of Nothofagus by correlating host species with fungal relative abundances, edaphic variables, net N mineralization, microbial biomass N and the activity of eight extracellular soil enzymes activities. The N economy of deciduous N. pumilio forests was strikingly similar to boreal coniferous forests, with the lowest inorganic N availability and net N mineralization, in correlation to higher relative abundances of ECM fungi with enzymatic capacity for organic N mobilization (genus Cortinarius ). In contrast, the N economy of evergreen N. betuloides forests was predominantly inorganic and correlated with ECM lineages from the family Clavulinaceae, in acidic soils with poor drainage. Grassy understory vegetation in deciduous N. antarctica forests likely promoted saprotrophic fungi (i.e., genus Mortierella ) in correlation with higher activities of carbon-degrading enzymes. Differences between Nothofagus hosts did not persist in mixed forests, illustrating the range of soil fertility of these ECM angiosperms and the underlying effects of soil and climate on Nothofagus distribution and N cycling in southern Patagonia., Competing Interests: The authors have no conflict of interest to declare., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Chronic, low-grade inflammation increases with aging, contributing to functional declines and diseases that reduce healthspan. Growing evidence suggests that transcripts from repetitive elements (RE) in the genome contribute to this "inflammaging" by stimulating innate immune activation, but evidence of RE-associated inflammation with aging in humans is limited. Here, we present transcriptomic and clinical data showing that RE transcript levels are positively related to gene expression of innate immune sensors, and to serum interleukin 6 (a marker of systemic inflammation), in a large group of middle-aged and older adults. We also: (1) use transcriptomics and whole-genome bisulfite (methylation) sequencing to show that many RE may be hypomethylated with aging, and that aerobic exercise, a healthspan-extending intervention, reduces RE transcript levels and increases RE methylation in older adults; and (2) extend our findings in a secondary dataset demonstrating age-related changes in RE chromatin accessibility. Collectively, our data support the idea that age-related RE transcript accumulation may play a role in inflammaging in humans, and that RE dysregulation with aging may be due in part to upstream epigenetic changes., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

In the human brain, palmitic acid (16:0; PAM) comprises nearly half of total brain saturates and has been identified as the third most abundant fatty acid overall. Brain PAM supports the structure of membrane phospholipids, provides energy, and regulates protein stability. Sources underlying the origin of brain PAM are both diet and endogenous synthesis via de novo lipogenesis (DNL), primarily from glucose. However, studies investigating the origin of brain PAM are limited to tracer studies utilizing labelled ( 14 C/ 11 C/ 3 H/ 2 H) PAM, and results vary based on the model and tracer used. Nevertheless, there is evidence PAM is synthesized locally in the brain, in addition to obtained directly from the diet. Herein, we provide an overview of brain PAM origin, entry to the brain, metabolic fate, and factors influencing brain PAM kinetics and levels, the latter in the context of age, as well as neurological diseases and psychiatric disorders. Additionally, we briefly summarize the role of PAM in signaling at the level of the brain. We add to the literature a rudimentary summary on brain PAM metabolism., (Copyright © 2024. Published by Elsevier Ltd.)

Scene Perception and Event Comprehension Theory (SPECT) posits that understanding picture stories depends upon a coordination of two processes: (1) integrating new information into the current event model that is coherent with it (i.e., mapping) and (2) segmenting experiences into distinct event models (i.e., shifting). In two experiments, we investigated competing hypotheses regarding how viewers coordinate the mapping process of bridging inference generation and the shifting process of event segmentation by manipulating the presence/absence of Bridging Action pictures (i.e., creating coherence gaps) in wordless picture stories. The Computational Effort Hypothesis says that experiencing a coherence gap prompts event segmentation and the additional computational effort to generate bridging inferences. Thus, it predicted a positive relationship between event segmentation and explanations when Bridging Actions were absent. Alternatively, the Coherence Gap Resolution Hypothesis says that experiencing a coherence gap prompt generating a bridging inference to close the gap, which obviates segmentation. Thus, it predicted a negative relationship between event segmentation and the production of explanations. Replicating prior work, viewers were more likely to segment and generate explanations when Bridging Action pictures were absent than when they were present. Crucially, the relationship between explanations and segmentation was negative when Bridging Action pictures were absent, consistent with the Coherence Gap Resolution Hypothesis. Unexpectedly, the relationship was positive when Bridging Actions were present. The results are consistent with SPECT's assumption that mapping and shifting processes are coordinated, but how they are coordinated depends upon the experience of a coherence gap.

Individuals with serious mental illnesses (SMIs) face safety risks related to their mental health conditions that are often compounded by experiences of trauma, victimization, residence in impoverished neighborhoods, and histories of homelessness. Stigma and safety challenges significantly impact community integration for individuals with SMIs, particularly women, who often bear a disproportionate burden of vulnerability, gender-based stigma, violence, and other inequalities. This study investigates how women with SMIs engage in the meaning-making of their safety and stigma experiences that, in turn, influence their community integration. From a large multi-site study exploring community experiences of racially/ethnically diverse participants with SMIs, a subsample of 28 cis and trans-gender women, who reported experiencing gendered stigma and a lack of safety, were chosen for the current study. The interviews were analyzed using modified principles of Interpretive Phenomenological Analysis (IPA) to understand how women with SMIs made meaning of their safety and stigma encounters in their families, communities, and neighborhoods. IPA analysis resulted in the emergence of themes within a broad category of safety that represented participants' meaning-making about their physical safety and stigma experiences. Specifically, we used the broad themes from an existing framework of safety called 'Navigating Safety' model as sensitizing concepts for our analysis. Physical and psychological aspects of safety for this study were experienced in tandem whereby the women made sense of how their experiences of a lack of physical safety in multiple contexts shaped their sense of self, internalized stigma, and their social relationships. Within the broad theme of physical safety, participants described unsafe neighborhoods, exposure to domestic and intimate partner violence, and vulnerability to sexual violence. Additionally, under psychological safety, we identified how gender-based norms, race and ethnicity, sources of stigma (internalized, familial, and societal), and social isolation contributed to their mental health and social relationships (particularly with family). These findings highlight how the compounding influence of the intersection of multiple stigmatized identities exerts safety challenges on the lives and community experiences of women with SMIs. Focusing on access and affordability of appropriate gender-responsive resources for women, including trauma-informed care, could reduce hospitalizations, mental health symptoms, and stigma so they can safely integrate into their communities., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Miltefosine (MLT) is an alkylphosphocholine with clinical success as an anticancer and antiparasitic drug. Although the mechanism of action of MLT is highly debated, the interaction of MLT with the membrane, specifically lipid rafts of eukaryotes, is well-documented. Recent reports suggest MLT impacts the functional membrane microdomains in bacteria - regions of the membrane structurally and functionally similar to lipid rafts. There have been conflicting reports, however, as to whether MLT impacts the overall fluidity of cellular plasma membranes. Here, we apply steady-state fluorescence techniques, generalized polarization of laurdan and anisotropy of diphenylhexatriene, to discern how MLT impacts the global ordering and lipid packing of Staphylococcus aureus membranes. Additionally, we investigate how the transport of a range of small molecules is impacted by MLT for S. aureus and Bacillus subtilis by employing time-resolved second harmonic scattering. Overall, we observe MLT does not have an influence on the overall ordering and packing of S. aureus membranes. Additionally, we show that the transport of small molecules across the membrane can be significantly altered by MLT - although this is not the case for all molecules studied. The results presented here illustrate the potential use of MLT as an adjuvant to assist in the delivery of drug molecules in bacteria., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Pharmacologic immunosuppression regimes are commonly employed in stem cell clinical trials to mitigate host immune rejection and promote survival and viability of transplanted cells. Immunosuppression and cell survival has been extensively studied in retinal and spinal tissues. The applicability of stem cell therapy is rapidly expanding to other sensory organs such as the ear and hearing. As regenerative therapy is directed to new areas, a greater understanding of immunosuppression strategies and their efficacy is required to facilitate translation to organ-specific biologic microenvironments., Objective: This systematic review appraises the current literature regarding immunosuppression strategies employed in stem cell trials of retinal and neural cells., Methods: This systematic review was performed in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria included studies presenting data on neural or retinal cells as part of an in-human clinical trial that detailed the immunosuppression regime used. Exclusion criteria included non-English language studies, animal studies, review articles, case reports, editorials, and letters. The databases Medline, Embase, Scopus, Web of Science, and the Cochrane Library were searched from inception to February 2024. Risk of bias was evaluated using the ROBINS-I tool., Results: Eighteen articles fit the inclusion criteria. Nine articles concerned retinal cells, 5 concerned spinal cord injury, and 4 concerned amyotrophic lateral sclerosis. A multi-drug and short-term immunosuppression regime were commonly employed in the identified studies. Detected immune responses in treated patients were rare. Common immunosuppression paradigms included tacrolimus, mycophenolate mofetil and tapering doses of steroids. Local immunosuppression with steroids was employed in some studies concerning retinal diseases., Discussion: A short-term course of systemic immunosuppression seemed efficacious for most included studies, with some showing grafted cells viable months to years after immunosuppression had stopped. Longer-term follow-up is required to see if this remains the case. Side effects related to immunosuppression were uncommon., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gowrishankar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Spatial memory is important for supporting the successful completion of everyday activities and is a particularly vulnerable domain in late life. Grouping items together in memory, or chunking, can improve spatial memory performance. In memory for desktop scale spaces and well-learned large-scale environments, error patterns suggest that information is chunked in memory. However, the chunking mechanisms involved in learning new large-scale, navigable environments are poorly understood. In five experiments, two of which included young and older adult samples, participants watched movies depicting routes through building-sized environments while attempting to remember the locations of cued objects. We tested memory for the cued objects with virtual pointing, distance estimation, and map drawing tasks after participants viewed each route. Patterns of error failed to show consistent evidence of chunking in spatial memory across all experiments. One possibility is that chunking in spatial memory relies on visual perceptual grouping mechanisms that are not in play during encoding of large-scale spaces encountered through extended route experiences that do not afford concurrent viewing of target locations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Objectives: Nonselective laryngeal reinnervation is an effective procedure to improve voice quality after unilateral vocal fold paralysis. Few studies have captured long-term outcome data, and the revision rate for this operation is currently unknown. The objective of this study is to describe the long-term outcomes and revision rates of unilateral, nonselective reinnervation in pediatric and adult patients., Methods: Patients who underwent laryngeal reinnervation from 2000 to 2022 with a single surgeon were identified for inclusion. Patients who underwent bilateral, super selective, deinnervation and reinnervation, and/or concurrent arytenoid adduction procedures were excluded. Outcome measures included maximum phonation time [MPT], voice handicap index score [VHI], patient-reported percent normal voice, revision procedures, and complications. Data were compiled and analyzed using paired t-tests, repeated measures analysis of covariance, and binary logistic regression analysis., Results: One hundred thirty-two patients underwent unilateral, nonselective ansa-recurrent laryngeal nerve [RLN] laryngeal reinnervation. Reinnervation significantly improved MPT and patient-reported percentage of normal voice and significantly decreased VHI. Eleven patients underwent revision procedures, corresponding to a revision rate of 8.3%. Additional procedures included medialization laryngoplasty [n = 3], medialization laryngoplasty with arytenoid adduction [n = 3] and injection augmentation greater than 1 year after reinnervation [n = 5]. The only factor associated with the need for additional surgery was time lapse from nerve injury to reinnervation. The overall complication rate was 6.8%; no patient required reintubation or tracheostomy., Conclusion: Unilateral, nonselective laryngeal reinnervation can provide reliable improvement in vocal symptoms after recurrent laryngeal nerve injury. The revision rate after laryngeal reinnervation is favorable and comparable to framework surgery., Level of Evidence: 4 Laryngoscope, 134:3187-3192, 2024., (© 2024 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Decision-making regarding level of lower extremity amputation is sometimes challenging. Selecting an appropriate anatomic level for major amputation requires consideration of tradeoffs between postoperative function and risk of wound complications that may require additional operations, including debridement and/or conversion to above-knee amputation (AKA). We evaluated the utility of common, non-invasive diagnostic tests used in clinical practice to predict the need for reoperations among patients undergoing primary, elective, below knee-amputations (BKAs) by vascular surgeons., Methods: Patients undergoing elective BKA over a 5-year period were identified using Current Procedural Terminology codes. Medical records were reviewed to characterize demographics, pre-amputation testing transcutaneous oxygen tension (TcPO 2 ), and ankle-brachial index (ABI). The need for ipsilateral post-BKA reoperation (including BKA revision and/or conversion to AKA) regardless of indication was the primary outcome. Associations were evaluated using univariable and multivariable logistic regression models. Cutpoints for TcPO 2 values associated with amputation reoperation were evaluated using receiver operating characteristic curves., Results: We identified 175 BKAs, of which 46 (26.3%) required ipsilateral reoperation (18.9% BKA revisions and 14.3% conversions to AKA). The mean age was 63.3 ± 14.8 years. Most patients were male (65.1%) and White (72.0%). Mean pre-amputation calf TcPO 2 was 40.0 ± 20.5 mmHg, and mean ABI was 0.64 ± 0.45. In univariable models, post-BKA reoperation was associated with calf TcPO 2 (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.94-0.99; P = .013) but not ABI (OR, 0.53; 95% CI, 0.19-1.46; P = .217). Univariable associations with reoperation were also identified for age (OR, 0.97; 95% CI, 0.94-0.990; P = .003) and diabetes (OR, 0.43; 95% CI, 0.21-0.87; P = .019). No associations with amputation revision were identified for gender, race, end-stage renal disease, or preoperative antibiotics. Calf TcPO 2 remained associated with post-BKA reoperation in a multivariable model (OR, 0.97; 95% CI, 0.94-0.99; P = .022) adjusted for age (OR, 0.98; 95% CI, 0.94-1.01; P = .222) and diabetes (OR, 0.98; 95% CI, 0.94-1.01; P = .559). Receiver operating characteristic analysis suggested a TcPO 2 ≥38 mmHg as an appropriate cut-point for assessing risk for BKA revision (area under the curve = 0.682; negative predictive value, 0.91)., Conclusions: Reoperation after BKA is common, and reoperation risk was associated with pre-amputation TcPO 2 . For patients undergoing elective BKA, higher risk of reoperation should be discussed with patients with an ipsilateral TcPO 2  <38 mmHg., Competing Interests: Disclosures None., (Copyright © 2024 Society for Vascular Surgery. All rights reserved.)

Despite concerted and accelerated efforts to increase the knowledge of medicine and disease via clinical studies, clinical trials continue to face low enrollment for all patient groups. The dissemination of the availability of clinical trials to individuals with or at risk for hereditary disorders is critical. This study acts as a foundation in determining an unexplored role of clinical trial discussion in genetic counseling practice. Board-certified, patient-facing genetic counselors in the United States were invited to participate in an anonymous survey via the National Society of Genetic Counselors. Between February and April 2022, 157 participants (N = 157) completed the survey on clinical trial discussion with patients, barriers, and facilitators to discussing clinical trials with patients, research experience, and demographics. Survey results identified that most respondents have discussed the availability of clinical trials with a patient (85%). Almost one-third have previous research experience working for a clinical trial (30%). Most agreed that discussions of clinical trials are within the scope of genetic counseling (82%); however, one-third were not comfortable discussing them with patients (34%). Respondents who know how to find specific clinical trials (p < 0.001) were reportedly more likely to be comfortable discussing clinical trials with their patients. In addition to clinical research exposure, this study suggests that further education and training is necessary for genetic counselors to learn how to find and identify specific clinical trials for their patients. In turn, we hope for this to increase genetic counselors' comfort of clinical trial discussion., (© 2024 The Author(s). Journal of Genetic Counseling published by Wiley Periodicals LLC on behalf of National Society of Genetic Counselors.)

Objectives: To establish audiological and other outcomes following cochlear implantation in humans and animals with eluting electrodes., Methods: Systematic review and narrative synthesis. Databases searched (April 2023): MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov, and Web of Science. Studies reporting outcomes in either humans or animals following cochlear implantation with a drug-eluting electrode were included. No limits were placed on language or year of publication. Risk of bias assessment was performed on all included studies using either the Brazzelli or Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) assessment tools. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement., Results: Searches identified 146 abstracts and 108 full texts. Of these, 18 studies met the inclusion criteria, reporting outcomes in 523 animals (17 studies) and 24 humans (1 study). Eluting electrodes included dexamethasone (16 studies), aracytine (1 study), nicotinamide adenine dinucleotide (1 study), the growth factors insulin-like growth factor 1 (IGF1) and hepatocyte growth factor (HGF) (1 study), and neurotrophin-3 (1 study). All included studies compare outcomes following implantation with an eluting electrode with a control non-eluting electrode. In the majority of studies, audiological outcomes (e.g., auditory brainstem response threshold) were superior following implantation with an eluting electrode compared with a standard electrode. Most studies which investigated post-implantation impedance reported lower impedance following implantation with an eluting electrode. The influence of eluting electrodes on other reported outcomes (including post-implantation cochlear fibrosis and the survival of hair cells and spiral ganglion neurons) was more varied across the included studies., Conclusions: Eluting electrodes have shown promise in animal studies in preserving residual hearing following cochlear implantation and in reducing impedance, though data from human studies remain lacking. Further in-human studies will be required to determine the clinical usefulness of drug-eluting cochlear implants as a future treatment for sensorineural hearing loss., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Objective: Pure tone audiometry (PTA) is the gold standard for hearing assessment. However, it requires access to specialized equipment. Smartphone audiometry applications (apps) have been developed to perform automated threshold audiometry and could allow patients to perform self-administered screening or monitoring. This study aimed to assess the validity and feasibility of patients using apps to self-assess hearing thresholds at home, with comparison to PTA., Methods: A multi-center, prospective randomized study was conducted amongst patients undergoing PTA in clinics. Participants were randomly allocated to one of four publicly-available apps designed to measure pure tone thresholds. Participants used an app once in optimal sound-treated conditions and a further three times at home. Ear-specific frequency-specific thresholds and pure tone average were compared using Pearson correlation coefficient. The percentage of app hearing tests with results within ±10 dB of PTA was calculated. Patient acceptability was assessed via an online survey., Results: One hundred thirty-nine participants submitted data. The results of two at-home automated smartphone apps correlated strongly/very strongly with PTA average and their frequency-specific median was within ±10 dB accuracy. Smartphone audiometry performed in sound-treated and home conditions were very strongly correlated. The apps were rated as easy/very easy to use by 90% of participants and 90% would be happy/very happy to use an app to monitor their hearing., Conclusion: Judicious use of self-performed smartphone audiometry was both valid and feasible for two of four apps. It could provide frequency-specific threshold estimates at home, potentially allowing assessments of patients remotely or monitoring of fluctuating hearing loss., Level of Evidence: 2 Laryngoscope, 134:2864-2870, 2024., (© 2024 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Backpacks are common devices for carrying external posterior loads. However, relatively little is known about how these external loads affect the ability to recover from balance loss. In this exploratory investigation, 16 young adults (8 female, 8 male) performed forward and backward lean-and-release balance recovery trials, while wearing a backpack that was unloaded or loaded (at 15% of individual body weight). We quantified the effects of backpack loading on balance recovery in terms of maximum recoverable lean angles, center-of-mass kinematics, and temporal-spatial stepping characteristics. Mean values of maximum lean angles were 20° and 9° in response to forward and backward perturbations, respectively. These angles significantly decreased when wearing the additional load for only backward losses of balance. During backward losses of balance, the additional load decreased peak center-of-mass velocity and increased acceleration by ∼10 and 18% respectively, which was accompanied by ∼5% faster stepping responses and steps that were ∼9% longer, 11% higher, and had an ∼10% earlier onset. Thus, wearing a backpack decreases backward balance recovery ability and changes backward recovery stepping characteristics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Diversified crop rotations have been suggested to reduce grain yield losses from the adverse climatic conditions increasingly common under climate change. Nevertheless, the potential for climate change adaptation of different crop rotational diversity (CRD) remains undetermined. We quantified how climatic conditions affect small grain and maize yields under different CRDs in 32 long-term (10-63 years) field experiments across Europe and North America. Species-diverse and functionally rich rotations more than compensated yield losses from anomalous warm conditions, long and warm dry spells, as well as from anomalous wet (for small grains) or dry (for maize) conditions. Adding a single functional group or crop species to monocultures counteracted yield losses from substantial changes in climatic conditions. The benefits of a further increase in CRD are comparable with those of improved climatic conditions. For instance, the maize yield benefits of adding three crop species to monocultures under detrimental climatic conditions exceeded the average yield of monocultures by up to 553 kg/ha under non-detrimental climatic conditions. Increased crop functional richness improved yields under high temperature, irrespective of precipitation. Conversely, yield benefits peaked at between two and four crop species in the rotation, depending on climatic conditions and crop, and declined at higher species diversity. Thus, crop species diversity could be adjusted to maximize yield benefits. Diversifying rotations with functionally distinct crops is an adaptation of cropping systems to global warming and changes in precipitation., (Global Change Biology© 2024 His Majesty the King in Right of Canada and The Authors. Global Change Biology published by John Wiley & Sons Ltd. Reproduced with the permission of the Minister of Agriculture & Agri-Food Canada. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Starting in the fall of 2019, mortality, blight symptoms, and signs of white fungal mycelia were observed on external host tissues of non-native landscape trees as well as numerous native trees, understory shrubs, and vines throughout northern and central Florida, USA. We determined that the fungus is an undescribed species of Basidiomycota based on morphological characteristics and DNA sequence analysis. Phylogenetic analyses of the internal transcribed spacer (ITS), large subunit (LSU), and translation elongation factor 1-alpha (tef1) regions revealed that this novel plant pathogen is an undescribed taxon of the genus Parvodontia (Cystostereaceae, Agaricales). We propose the name Parvodontia relampaga sp. nov. which describes its unique morphological features and phylogenetic placement. We confirmed the pathogenicity of P. relampaga in greenhouse inoculations on host plants from which strains of this novel pathogen were isolated, including the non-native gymnosperm Afrocarpus falcatus, the non-native and commercially important Ligustrum japonicum, and the native tree Quercus hemisphaerica. P. relampaga was also detected on a total of 27 different species of woody host plants, including such economically and ecologically important hosts as Fraxinus, Ilex, Magnolia, Persea, Prunus, Salix, Vitis, and Vaccinium. For this new plant disease, we propose the name "relampago blight," which refers to the lightning-like rhizomorph growth (relámpago means 'lightning' in Spanish). This study presents a newly discovered fungal taxon with a wide host range on both angiosperms and gymnosperms that may be an emerging pathogen of concern in Florida and the Gulf Coast region., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024 British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

We have investigated the magnitude of circadian variation in Isokinetic and Isometric strength of the knee extensors and flexors, as well as back squat and bench press performance using the MuscleLab force velocity transducer. Ten resistance-trained males (mean±SD: age 21.5 ± 1.1 years; body mass 78.3 ± 5.2 kg; height 1.71 ± 0.07 m) underwent a) three to four familiarization sessions on each dynamometer and b) four sessions at different times of day (03:00, 09:00, 15:00 and 21:00 h). Each session was administered in a counterbalanced order and included a period when Perceived onset of mood states (POMS), then rectal and muscle temperature (T rec , T m ) was measured at rest, after which a 5-min standardized 150 W warm-up was performed on a cycle ergometer. Once completed, Isokinetic (60 and 240°·s -1 for extension and flexion) and Isometric dynamometry with peak torque (PT), time-to-peak-torque (tPT) and peak force (PF) and % activation was measured. Lastly, T rec and T m were measured before the bench press (at 30, 50 and 70 kg) and back squat (at 40, 60 and 80 kg) exercises. A linear encoder was attached to an Olympic bar used for the exercises and average force (AF), peak velocity (PV) and time-to-peak-velocity (tPV) were measured (MuscleLab software; MuscleLab Technology, Langesund, Norway) during the concentric phase of the movements. Five-min recovery was allowed between each set with three repetitions being completed. General linear models with repeated measures and cosinor analysis were used to analyse the data. Values for T rec and T m at rest were higher in the evening compared to morning values (Acrophase Φ: 16:35 and 17:03 h, Amplitude A: 0.30 and 0.23°C, Mesor M: 36.64 and 37.43°C, p  < 0.05). Vigor, happy and fatigue mood states responses showed Φ 16:11 and 16:03 h and 02:05 h respectively. Circadian rhythms were apparent for all variables irrespective of equipment used where AF, PF and PT values peaked between 16:18 and 18:34 h; PV, tPV and tPT peaked between 05:54 and 08:03 h ( p  < 0.05). In summary, circadian rhythms in force output (force, torque, power, and velocity) were shown for isokinetic, isometric dynamometers and complex multi-joint movements (using a linear encoder); where tPV and tPT occur in the morning compared to the evening. Circadian rhythms in strength can be detected using a portable, low-cost instrument that shows similar cosinor characteristics as established dynamometers. Hence, muscle-strength can be measured in a manner that is more directly transferable to the world of athletic and sports performance.

Background: Patients with severe-to-profound hearing loss may benefit from management with cochlear implants. These patients need a referral to a cochlear implant team for further assessment and possible surgery. The referral pathway may result in varied access to hearing healthcare. This study aimed to explore referral patterns and whether there were any socioeconomic or ethnic associations with the likelihood of referral. The primary outcome was to determine factors influencing referral for implant assessment. The secondary outcome was to identify factors impacting whether healthcare professionals had discussed the option of referral., Methods and Findings: A multicentre multidisciplinary observational study was conducted in secondary care Otolaryngology and Audiology units in Great Britain. Adults fulfilling NICE (2019) audiometric criteria for implant assessment were identified over a 6-month period between 1 July and 31 December 2021. Patient- and site-specific characteristics were extracted. Multivariable binary logistic regression was employed to compare a range of factors influencing the likelihood of implant discussion and referral including patient-specific (demographics, past medical history, and degree of hearing loss) and site-specific factors (cochlear implant champion and whether the hospital performed implants). Hospitals across all 4 devolved nations of the UK were invited to participate, with data submitted from 36 urban hospitals across England, Scotland, and Wales. Nine hospitals (25%) conducted cochlear implant assessments. The majority of patients lived in England (n = 5,587, 86.2%); the rest lived in Wales (n = 419, 6.5%) and Scotland (n = 233, 3.6%). The mean patient age was 72 ± 19 years (mean ± standard deviation); 54% were male, and 75·3% of participants were white, 6·3% were Asian, 1·5% were black, 0·05% were mixed, and 4·6% were self-defined as a different ethnicity. Of 6,482 submitted patients meeting pure tone audiometric thresholds for cochlear implantation, 311 already had a cochlear implant. Of the remaining 6,171, 35.7% were informed they were eligible for an implant, but only 9.7% were referred for assessment. When adjusted for site- and patient-specific factors, stand-out findings included that adults were less likely to be referred if they lived in more deprived area decile within Indices of Multiple Deprivation (4th (odds ratio (OR): 2·19; 95% confidence interval (CI): [1·31, 3·66]; p = 0·002), 5th (2·02; [1·21, 3·38]; p = 0·05), 6th (2·32; [1·41, 3·83]; p = 0.05), and 8th (2·07; [1·25, 3·42]; p = 0·004)), lived in London (0·40; [0·29, 0·57]; p < 0·001), were male (females 1·52; [1·27, 1·81]; p < 0·001), or were older (0·97; [0·96, 0·97]; p < 0·001). They were less likely to be informed of their potential eligibility if they lived in more deprived areas (4th (1·99; [1·49, 2·66]; p < 0·001), 5th (1·75; [1·31, 2·33], p < 0·001), 6th (1·85; [1·39, 2·45]; p < 0·001), 7th (1·66; [1·25, 2·21]; p < 0·001), and 8th (1·74; [1·31, 2·31]; p < 0·001) deciles), the North of England or London (North 0·74; [0·62, 0·89]; p = 0·001; London 0·44; [0·35, 0·56]; p < 0·001), were of Asian or black ethnic backgrounds compared to white patients (Asian 0·58; [0·43, 0·79]; p < 0·001; black 0·56; [0·34, 0·92]; p = 0·021), were male (females 1·46; [1·31, 1·62]; p < 0·001), or were older (0·98; [0·98, 0·98]; p < 0·001). The study methodology was limited by its observational nature, reliance on accurate documentation of the referring service, and potential underrepresentation of certain demographic groups., Conclusions: The majority of adults meeting pure tone audiometric threshold criteria for cochlear implantation are currently not appropriately referred for assessment. There is scope to target underrepresented patient groups to improve referral rates. Future research should engage stakeholders to explore the reasons behind the disparities. Implementing straightforward measures, such as educational initiatives and automated pop-up tools for immediate identification, can help streamline the referral process., Competing Interests: MB and MS have both been awarded grants from Advanced Bionics, Cochlear and MEDEL for other work. The other authors have no conflict of interest., (Copyright: © 2024 Swords et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Neonatal unilateral vocal fold paralysis may arise iatrogenically, idiopathically, or in the context of an underlying neurologic disorder. Management is often supportive, focusing on diet modification to allow for safe oral feeding. We describe the clinical course of six infants with unilateral vocal fold paralysis who developed predominantly unilateral laryngomalacia ipsilateral to the affected vocal fold with associated severe respiratory symptoms and feeding difficulty., Methods: Retrospective review of six infants with unilateral vocal fold paralysis and predominantly unilateral laryngomalacia. Charts were reviewed for etiology of vocal fold paralysis, presenting symptoms, operative details, postoperative course, and outcomes for breathing and swallowing., Results: Etiology of vocal fold paralysis included cardiac surgery in four patients, intubation-related in one, and idiopathic in one. Presenting symptoms included increased work of breathing, stridor, feeding difficulty, respiratory failure requiring noninvasive respiratory support, and weak cry. All infants were on nasogastric tube feedings. Direct microlaryngoscopy with unilateral or predominantly unilateral (conservative contralateral aryepiglottic fold division) supraglottoplasty was performed. Stridor and work of breathing improved in all six patients within 1 week postoperatively. Oral feeding improved in three patients within 2 weeks. Three patients had persistent feeding impairment with improvement within one year., Conclusions: Predominantly unilateral laryngomalacia may arise in the context of unilateral vocal fold paralysis. Addressing the ipsilateral cuneiform collapse can improve breathing and feeding. This may be an under-described phenomenon and represents an additional reason to include the otolaryngologist early in the care of infants with suspected possible new unilateral vocal fold paralysis. Breathing and swallow can improve post-operatively, but feeding may remain limited by the vocal fold paralysis and any medical comorbidities. Ongoing follow-up and collaboration with speech-language pathology to optimize feeding are important., Competing Interests: Declaration of competing interest none., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Nidulariaceae, also known as bird's nest fungi, is an understudied group of mushroom-forming fungi. The common name is derived from their nest-like morphology. Bird's nest fungi are ubiquitous wood decomposers or saprobes on dung. Recent studies showed that species in the Nidulariaceae form a monophyletic group with five sub-clades. However, phylogenetic relationships among genera and placement of Nidulariaceae are still unclear. We present phylogenomic analyses of bird's nest fungi and related Agaricales fungi to gain insight into the evolution of Nidulariaceae. A species tree with 17 newly generated genomes of bird's nest fungi and representatives from all major clades of Agaricales was constructed using 1044 single-copy genes to explore the intergeneric relationships and pinpoint the placement of Nidulariaceae within Agaricales. We corroborated the hypothesis that bird's nest fungi are sister to Squamanitaceae, which includes mushroom-shaped fungi with a stipe and pileus that are saprobes and mycoparasites. Lastly, stochastic character mapping of discrete traits on phylogenies (SIMMAP) suggests that the ancestor of bird's nest fungi likely possessed an evanescent, globose peridium without strings attaching to the spore packets (funiculi). This analysis suggests that the funiculus was gained twice and that the persistent, cupulate peridium form was gained at least four times and lost once. However, alternative coding schemes and datasets with a wider array of Agaricales produced conflicting results during ancestral state reconstruction, indicating that there is some uncertainty in the number of peridium transitions and that taxon sampling may significantly alter ancestral state reconstructions. Overall, our results suggest that several key morphological characters of Nidulariaceae have been subject to homoplasy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Data from DNA genotyping via a 96-SNP panel in a study of 25,015 clinical samples were utilized for quality control and tracking of sample identity in a clinical sequencing network. The study aimed to demonstrate the value of both the precise SNP tracking and the utility of the panel for predicting the sex-by-genotype of the participants, to identify possible sample mix-ups., Results: Precise SNP tracking showed no sample swap errors within the clinical testing laboratories. In contrast, when comparing predicted sex-by-genotype to the provided sex on the test requisition, we identified 110 inconsistencies from 25,015 clinical samples (0.44%), that had occurred during sample collection or accessioning. The genetic sex predictions were confirmed using additional SNP sites in the sequencing data or high-density genotyping arrays. It was determined that discrepancies resulted from clerical errors (49.09%), samples from transgender participants (3.64%) and stem cell or bone marrow transplant patients (7.27%) along with undetermined sample mix-ups (40%) for which sample swaps occurred prior to arrival at genome centers, however the exact cause of the events at the sampling sites resulting in the mix-ups were not able to be determined., (© 2024. The Author(s).)

People spontaneously segment continuous ongoing actions into sequences of events. Prior research found that gaze similarity and pupil dilation increase at event boundaries and that older adults segment more idiosyncratically than do young adults. We used eye tracking to explore age-related differences in gaze similarity (i.e., the extent to which individuals look at the same places at the same time as others) and pupil dilation at event boundaries. Older and young adults watched naturalistic videos of actors performing everyday activities while we tracked their eye movements. Afterward, they segmented the videos into subevents. Replicating prior work, we found that pupil size and gaze similarity increased at event boundaries. Thus, there were fewer individual differences in eye position at boundaries. We also found that young adults had higher gaze similarity than older adults throughout an entire video and at event boundaries. This study is the first to show that age-related differences in how people parse continuous everyday activities into events may be partially explained by individual differences in gaze patterns. Those who segment less normatively may do so because they fixate less normative regions. Results have implications for future interventions designed to improve encoding in older adults. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

AKI is characterized by a sudden, and usually reversible, decline in kidney function. In mice, ischemia-reperfusion injury (IRI) is commonly used to model the pathophysiologic features of clinical AKI. Macrophages are a unifying feature of IRI as they regulate both the initial injury response as well as the long-term outcome following resolution of injury. Initially, macrophages in the kidney take on a proinflammatory phenotype characterized by the production of inflammatory cytokines, such as CCL2 (monocyte chemoattractant protein 1), IL-6, IL-1 β , and TNF- α . Release of these proinflammatory cytokines leads to tissue damage. After resolution of the initial injury, macrophages take on a reparative role, aiding in tissue repair and restoration of kidney function. By contrast, failure to resolve the initial injury results in prolonged inflammatory macrophage accumulation and increased kidney damage, fibrosis, and the eventual development of CKD. Despite the extensive amount of literature that has ascribed these functions to M1/M2 macrophages, a recent paradigm shift in the macrophage field now defines macrophages on the basis of their ontological origin, namely monocyte-derived and tissue-resident macrophages. In this review, we focus on macrophage phenotype and function during IRI-induced injury, repair, and transition to CKD using both the classic (M1/M2) and novel (ontological origin) definition of kidney macrophages., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology.)

Idiopathic sudden sensorineural hearing loss (ISSNHL) is the rapid onset of reduced hearing due to loss of function of the inner ear or hearing nerve of unknown aetiology. Evidence supports improved hearing recovery with early steroid treatment, via oral, intravenous, intratympanic or a combination of routes. The STARFISH trial aims to identify the most clinically and cost-effective route of administration of steroids as first-line treatment for ISSNHL. STARFISH is a pragmatic, multicentre, assessor-blinded, three-arm intervention, superiority randomised controlled trial (1:1:1) with an internal pilot (ISRCTN10535105, IRAS 1004878). 525 participants with ISSNHL will be recruited from approximately 75 UK Ear, Nose and Throat units. STARFISH will recruit adults with sensorineural hearing loss averaging 30dBHL or greater across three contiguous frequencies (confirmed via pure tone audiogram), with onset over a ≤3-day period, within four weeks of randomisation. Participants will be randomised to 1) oral prednisolone 1mg/Kg/day up to 60mg/day for 7 days; 2) intratympanic dexamethasone: three intratympanic injections 3.3mg/ml or 3.8mg/ml spaced 7±2 days apart; or 3) combined oral and intratympanic steroids. The primary outcome will be absolute improvement in pure tone audiogram average at 12-weeks following randomisation (0.5, 1.0, 2.0 and 4.0kHz). Secondary outcomes at 6 and 12 weeks will include: Speech, Spatial and Qualities of hearing scale, high frequency pure tone average thresholds (4.0, 6.0 and 8.0kHz), Arthur Boothroyd speech test, Vestibular Rehabilitation Benefit Questionnaire, Tinnitus Functional Index, adverse events and optional weekly online speech and pure tone hearing tests. A health economic assessment will be performed, and presented in terms of incremental cost effectiveness ratios, and cost per quality-adjusted life-year. Primary analyses will be by intention-to-treat. Oral prednisolone will be the reference. For the primary outcome, the difference between group means and 97.5% confidence intervals at each time-point will be estimated via a repeated measures mixed-effects linear regression model., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Smith et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Palmitic acid (PAM) can be provided in the diet or synthesized via de novo lipogenesis (DNL), primarily, from glucose. Preclinical work on the origin of brain PAM during development is scarce and contrasts results in adults. In this work, we use naturally occurring carbon isotope ratios ( 13 C/ 12 C; δ 13 C) to uncover the origin of brain PAM at postnatal days 0, 10, 21 and 35, and RNA sequencing to identify the pathways involved in maintaining brain PAM, at day 35, in mice fed diets with low, medium, and high PAM from birth. Here we show that DNL from dietary sugars maintains the majority of brain PAM during development and is augmented in mice fed low PAM. Importantly, the upregulation of hepatic DNL genes, in response to low PAM at day 35, demonstrates the presence of a compensatory mechanism to maintain total brain PAM pools compared to the liver; suggesting the importance of brain PAM regulation., (© 2024. The Author(s).)

The complex evolutionary history of wheat has shaped its associated root microbial community. However, consideration of impacts from agricultural intensification has been limited. This study investigated how endogenous (genome polyploidization) and exogenous (introduction of chemical fertilizers) factors have shaped beneficial rhizobacterial selection. We combined culture-independent and -dependent methods to analyze rhizobacterial community composition and its associated functions at the root-soil interface from a range of ancestral and modern wheat genotypes, grown with and without the addition of chemical fertilizer. In controlled pot experiments, fertilization and soil compartment (rhizosphere, rhizoplane) were the dominant factors shaping rhizobacterial community composition, whereas the expansion of the wheat genome from diploid to allopolyploid caused the next greatest variation. Rhizoplane-derived culturable bacterial collections tested for plant growth-promoting (PGP) traits revealed that fertilization reduced the abundance of putative plant growth-promoting rhizobacteria in allopolyploid wheats but not in wild wheat progenitors. Taxonomic classification of these isolates showed that these differences were largely driven by reduced selection of beneficial root bacteria representative of the Bacteroidota phylum in allopolyploid wheats. Furthermore, the complexity of supported beneficial bacterial populations in hexaploid wheats was greatly reduced in comparison to diploid wild wheats. We therefore propose that the selection of root-associated bacterial genera with PGP functions may be impaired by crop domestication in a fertilizer-dependent manner, a potentially crucial finding to direct future plant breeding programs to improve crop production systems in a changing environment., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.)

Tinnitus is a common health condition, affecting approximately 15% of the UK population. The tinnitus treatment with the strongest evidence base is Cognitive Behavioural Therapy (CBT), with standard tinnitus therapy typically augmented with education, relaxation and other techniques. Availability of CBT and conventional tinnitus therapy more broadly is limited for tinnitus sufferers. The DEFINE trial aims to assess whether smartphone-delivered tinnitus therapy, the Oto app, is as effective as current standard care, one-to-one therapist-delivered tinnitus treatment for the treatment of tinnitus in adults. The trial is registered in the ISRCTN Registry: ISRCTN99577932. DEFINE is an open-label, non-inferiority, prospective, parallel design, randomised-controlled trial. Recruitment, interventions and assessments will be remote, enabling UK-wide participant involvement. 198 participants aged 18 years or more will be recruited via social media advertisement or via primary care physicians. A screening process will identify those with tinnitus that impacts health-related quality of life, and following consent smartphone-based audiometry will be performed. Randomisation 1:1 to the Oto app or one-to-one therapist-led tinnitus therapy will be performed centrally by computer, matching groups for age, sex and hearing level. Following participant allocation, the Oto app will be provided for immediate use, or a one-to-one remote therapy appointment booked to occur within approximately 1 week, with up to 6 sessions delivered. Participant outcomes will be collected at 4,12, 26 and 52 weeks via questionnaire and phone call. The primary outcome is the change in Tinnitus Functional Index (TFI) total score measured at 26 weeks following allocation. Adverse events will be recorded. A health economic evaluation in the form of a cost-utility analysis will be performed using data from participant submitted EuroQol 5D-5L and Health Utilities Index Mark 3 scores and resource use data. Trial results will be made publicly available, including a plain English summary., Competing Interests: The authors have read the journal’s policy and have the following competing interests: DS is the Founder’s Associate at Oto Health Ltd, JMuz is Chief Scientific Officer for Oto Health Ltd, and DS and JM have financial interests in Oto Health Ltd. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no products in development associated with this research to declare but the Oto app is commercially marketed by Oto Health Ltd., (Copyright: © 2024 Smith et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The UK Medical Licensing Assessment curriculum represents a consensus on core content, including ENT-related content for newly qualified doctors. No similar consensus exists as to how ENT content should be taught at medical school., Method: A virtual consensus forum was held at the 2nd East of England ENT Conference in April 2021. A syllabus of ENT-related items was divided into 'Presentations', 'Conditions' and 'Practical procedures'. Twenty-seven students, 11 foundation doctors and 7 other junior doctors voted via anonymous polling for the best three of nine methods for teaching each syllabus item., Results: For 'Presentations' and 'Conditions', work-based or clinical-based learning and small-group seminars were more popular than other teaching methods. For 'Practical procedures', practical teaching methods were more popular than theoretical methods., Conclusion: Students and junior doctors expressed a clear preference for clinical-based teaching and small-group seminars when learning ENT content. E-learning was poorly favoured despite its increasing use.

The synthesis rates of n-3 and n-6 polyunsaturated fatty acids (PUFAs) in rodents and humans are not agreed upon and depend on substrate availability independently of the capacity for synthesis. Therefore, we aimed to assess the activities of the enzymes for n-3 and n-6 PUFA synthesis pathways in liver, brain, testicle, kidney, heart, and lung, in relation to their protein concentration levels. Eight-week-old Balb/c mice (n = 8) were fed a standard chow diet (6.2% fat, 18.6% protein, and 44.2% carbohydrates) until 14 weeks of age, anesthetized with isoflurane and tissue samples were collected (previously perfused) and stored at -80°C. The protein concentration of the enzymes (Δ-6D, Δ-5D, Elovl2, and Elovl5) were assessed by ELISA kits; their activities were assayed using specific PUFA precursors and measuring the respective PUFA products as fatty acid methyl esters by gas chromatographic analysis. The liver had the highest capacity for PUFA biosynthesis, with limited activity in the brain, testicles, and kidney, while we failed to detect activity in the heart and lung. The protein concentration and activity of the enzymes were significantly correlated. Furthermore, Δ-6D, Δ-5D, and Elovl2 have a higher affinity for n-3 PUFA precursors compared to n-6 PUFA. The capacity for PUFA synthesis in mice mainly resides in the liver, with enzymes having preference for n-3 PUFAs., (© 2023 International Union of Biochemistry and Molecular Biology.)

Ahiflower® oil is high in α-linolenic and stearidonic acids, however, tissue/blood docosahexaenoic acid (DHA, 22:6n-3) turnover from dietary Ahiflower oil has not been investigated. In this study, we use compound-specific isotope analysis to determine tissue DHA synthesis/turnover from Ahiflower, flaxseed and DHA oils. Pregnant BALB/c mice (13-17 days) were placed on a 2 % algal DHA oil diet of high carbon-13 content (δ 13 C) and pups (n = 132) were maintained on the diet until 9 weeks old. Mice were then randomly allocated to a low δ 13 C-n-3 PUFA diet of either: 1) 4 % Ahiflower oil, 2) 4.35 % flaxseed oil or 3) 1 % fish DHA ethyl ester oil for 1, 3, 7, 14, 30, 60 or 120 days (n = 6). Serum, liver, adipose and brains were collected and DHA levels and δ 13 C were determined. DHA concentrations were highest (p < 0.05) in the liver and adipose of DHA-fed animals with no diet differences in serum or brain (p > 0.05). Based on the presence or absence of overlapping 95 % C.I.'s, DHA half-lives and synthesis/turnover rates were not different between Ahiflower and DHA diets in the liver, adipose or brain. DHA half-lives and synthesis/turnover rates from flaxseed oil were significantly slower than from the DHA diet in all serum/tissues. These findings suggest that the distinct Ahiflower oil n-3 PUFA composition could support tissue DHA needs at a similar rate to dietary DHA, making it a unique plant-based dietary option for maintaining DHA turnover comparably to dietary DHA., Competing Interests: Declaration of competing interest RPB has received research grants from Bunge Ltd., Arctic Nutrition, the Dairy Farmers of Canada and Nestle Inc., as well as travel support from Mead Johnson and mass spectrometry equipment and support from Sciex. In addition, RPB is on the executive board of the International Society for the Study of Fatty Acids and Lipids and held a meeting on behalf of Fatty Acids and Cell Signaling, both of which rely on corporate sponsorship. RPB has given expert testimony in relation to supplements and the brain. RPB also provides complimentary fatty acid analysis for farmers, food producers and others involved in the food industry, some of whom provide free food samples. GC is the Vice-President, Science & Regulatory at Natures Crops International, who funded this research and is the sole producer of Ahiflower oil world-wide. There are no other conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Here we present the results of taxonomic and systematic study of the rare truffle-forming genera Destuntzia and Kjeldsenia . Truffle-forming fungi are difficult to study due to their reduced morphological features and their cryptic, hypogeous fruiting habits. The rare occurrence of Destuntzia and Kjeldsenia further compounds these difficulties due to the lack of adequate material for study. Recent forays in North Carolina and Tennessee recovered new specimens of another rarely collected fungus, Octaviania purpurea . Morphological and phylogenetic analysis revealed that Octaviania purpurea is a member of the genus Destuntzia , and this led us to reevaluate the taxonomic status and systematic relationships of other Destuntzia species. We performed a multilocus phylogenetic analysis of Destuntzia specimens deposited in public fungaria, including all available type material, and environmental sequences from animal scat and soil. Our analyses indicate that Destuntzia is a member of the family Claustulaceae within the order Phallales and is a close relative of Kjeldsenia . Results of our phylogenetic analysis infer that three species originally described in the genus Destuntzia are members of the genus Kjeldsenia . We propose three new combinations in Kjeldsenia to accommodate these species as well as a new combination in Destuntzia to accommodate Octaviania purpurea . We also describe a new genus in Claustulaceae, Hosakaea , to accommodate a closely affiliated species, Octaviania violascens . Finally, we transfer the genus Destunzia into the family Claustulaceae and emend the description of the family. The newly proposed combinations in Destuntzia and Kjeldsenia significantly expand the known geographic ranges of both genera. The data from metabarcode analysis of scat and soil also reveal several additional undescribed species that expand these ranges well beyond those suggested by basidiomata collections. Systematic placement of Destuntzia in the saprotrophic order Phallales suggests that this genus is not ectomycorrhizal, and the ecological implications of this systematic revision are discussed.

Sound production capabilities and characteristics in Loricariidae, the largest catfish family, have not been well examined. Sounds produced by three loricariid catfish species, Otocinclus affinis, Pterygoplichthys gibbiceps, and Pterygoplichthys pardalis, were recorded. Each of these species produces pulses via pectoral-fin spine stridulation by rubbing the ridged condyle of the dorsal process of the pectoral-fin spine base against a matching groove-like socket in the pectoral girdle. Light and scanning electron microscopy were used to examine the dorsal process of the pectoral-fin spines of these species. Mean distances between dorsal process ridges of O. affinis, P. gibbiceps, and P. pardalis were 53, 161, and 329 μm, respectively. Stridulation sounds occurred during either abduction (type A) or adduction (type B). O. affinis produced sounds through adduction only and P. pardalis through abduction only, whereas P. gibbiceps often produced pulse trains alternating between abduction and adduction. In these species, dominant frequency was an inverse function of sound duration, fish total length, and inter-ridge distance on the dorsal process of the pectoral-fin spine and sound duration increased with fish total length. While stridulation sounds are used in many behavioral contexts in catfishes, the functional significance of sound production in Loricariidae is currently unknown., (© 2023 Acoustical Society of America.)

Background: V0v spinal interneurons are highly conserved, glutamatergic, commissural neurons that function in locomotor circuits. We have previously shown that Evx1 and Evx2 are required to specify the neurotransmitter phenotype of these cells. However, we still know very little about the gene regulatory networks that act downstream of these transcription factors in V0v cells., Methods: To identify candidate members of V0v gene regulatory networks, we FAC-sorted wild-type and evx1;evx2 double mutant zebrafish V0v spinal interneurons and expression-profiled them using microarrays and single cell RNA-seq. We also used in situ hybridization to compare expression of a subset of candidate genes in evx1;evx2 double mutants and wild-type siblings., Results: Our data reveal two molecularly distinct subtypes of zebrafish V0v spinal interneurons at 48 h and suggest that, by this stage of development, evx1;evx2 double mutant cells transfate into either inhibitory spinal interneurons, or motoneurons. Our results also identify 25 transcriptional regulator genes that require Evx1/2 for their expression in V0v interneurons, plus a further 11 transcriptional regulator genes that are repressed in V0v interneurons by Evx1/2. Two of the latter genes are hmx2 and hmx3a. Intriguingly, we show that Hmx2/3a, repress dI2 interneuron expression of skor1a and nefma, two genes that require Evx1/2 for their expression in V0v interneurons. This suggests that Evx1/2 might regulate skor1a and nefma expression in V0v interneurons by repressing Hmx2/3a expression., Conclusions: This study identifies two molecularly distinct subsets of zebrafish V0v spinal interneurons, as well as multiple transcriptional regulators that are strong candidates for acting downstream of Evx1/2 to specify the essential functional characteristics of these cells. Our data further suggest that in the absence of both Evx1 and Evx2, V0v spinal interneurons initially change their neurotransmitter phenotypes from excitatory to inhibitory and then, later, start to express markers of distinct types of inhibitory spinal interneurons, or motoneurons. Taken together, our findings significantly increase our knowledge of V0v and spinal development and move us closer towards the essential goal of identifying the complete gene regulatory networks that specify this crucial cell type., (© 2023. The Author(s).)

Objective: To establish outcomes following photobiomodulation therapy for tinnitus in humans and animal studies., Methods: A systematic review and narrative synthesis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The databases searched were: Medline, Embase, Cochrane Central Register of Controlled Trials ('Central'), ClinicalTrials.gov and Web of Science including the Web of Science Core collection. There were no limits on language or year of publication., Results: The searches identified 194 abstracts and 61 full texts. Twenty-eight studies met the inclusion criteria, reporting outcomes in 1483 humans (26 studies) and 34 animals (2 studies). Photobiomodulation therapy parameters included 10 different wavelengths, and duration ranged from 9 seconds to 30 minutes per session. Follow up ranged from 7 days to 6 months., Conclusion: Tinnitus outcomes following photobiomodulation therapy are generally positive and superior to no photobiomodulation therapy; however, evidence of long-term therapeutic benefit is deficient. Photobiomodulation therapy enables concentrated, focused delivery of light therapy to the inner ear through a non-invasive manner, with minimal side effects.

Background: Trichuris trichiura (whipworm) is one of the most prevalent soil transmitted helminths (STH) affecting 604-795 million people worldwide. Diagnostic tools that are affordable and rapid are required for detecting STH. Here, we assessed the performance of the near-infrared spectroscopy (NIRS) technique coupled with machine learning algorithms to detect Trichuris muris in faecal, blood, serum samples and non-invasively through the skin of mice., Methodology: We orally infected 10 mice with 30 T. muris eggs (low dose group), 10 mice with 200 eggs (high dose group) and 10 mice were used as the control group. Using the NIRS technique, we scanned faecal, serum, whole blood samples and mice non-invasively through their skin over a period of 6 weeks post infection. Using artificial neural networks (ANN) and spectra of faecal, serum, blood and non-invasive scans from one experiment, we developed 4 algorithms to differentiate infected from uninfected mice. These models were validated on mice from a second independent experiment., Principal Findings: NIRS and ANN differentiated mice into the three groups as early as 2 weeks post infection regardless of the sample used. These results correlated with those from concomitant serological and parasitological investigations., Significance: To our knowledge, this is the first study to demonstrate the potential of NIRS as a diagnostic tool for human STH infections. The technique could be further developed for large scale surveillance of soil transmitted helminths in human populations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kariyawasam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

As large-scale genomic screening becomes increasingly prevalent, understanding the influence of actionable results on healthcare utilization is key to estimating the potential long-term clinical impact. The eMERGE network sequenced individuals for actionable genes in multiple genetic conditions and returned results to individuals, providers, and the electronic health record. Differences in recommended health services (laboratory, imaging, and procedural testing) delivered within 12 months of return were compared among individuals with pathogenic or likely pathogenic (P/LP) findings to matched individuals with negative findings before and after return of results. Of 16,218 adults, 477 unselected individuals were found to have a monogenic risk for arrhythmia (n = 95), breast cancer (n = 96), cardiomyopathy (n = 95), colorectal cancer (n = 105), or familial hypercholesterolemia (n = 86). Individuals with P/LP results more frequently received services after return (43.8%) compared to before return (25.6%) of results and compared to individuals with negative findings (24.9%; p < 0.0001). The annual cost of qualifying healthcare services increased from an average of $162 before return to $343 after return of results among the P/LP group (p < 0.0001); differences in the negative group were non-significant. The mean difference-in-differences was $149 (p < 0.0001), which describes the increased cost within the P/LP group corrected for cost changes in the negative group. When stratified by individual conditions, significant cost differences were observed for arrhythmia, breast cancer, and cardiomyopathy. In conclusion, less than half of individuals received billed health services after monogenic return, which modestly increased healthcare costs for payors in the year following return., Competing Interests: Declaration of interests W.K.C. is on the board of directors of Prime Medicine and D.L.V. is a consultant for Illumina and has a funded project from GeneDx., (Copyright © 2023 American Society of Human Genetics. All rights reserved.)

A multigene phylogenetic assessment of North American species of Mallocybe is presented based on analyses of rpb1, rpb2, ITS, and 28S rDNA nucleotide data. This framework enables a systematic revision of the genus for 16 eastern North American species and captures taxonomic and phylogenetic diversity in a global context. A grade of two unusual and poorly known North American species stems from the most recent common ancestor of the genus that gives rise to three core subgroups named here as clades Unicolores, Nothosperma, and Mallocybe. The grade of taxa includes the poorly known Lepista praevillosa from Florida and a new species from the southern Appalachians, M. montana , both of which appear to be narrow-range endemics. Clade Nothosperma is characterized by Australian and New Zealand species, whereas clade Unicolores is composed of six species from eastern North America and East Asia. Clade Mallocybe is dominated by numerous north temperate taxa and constitutes the sister group to clade Nothosperma. These major clades are distinguished by a combination of phylogeny, morphology, geographic distribution, and ecology. In addition, four North American species are described as new: M. leucothrix, M. luteobasis, M. montana , and M. tomentella . Several names originating in North America, long ignored or misunderstood in the literature, are revitalized and established by type comparisons and modern reference material collected from or near type localities. In addition, 11 species were subjected to mass spectrometry muscarine assays, none of which contained detectable amounts of muscarine except for two: M. sabulosa and M. praevillosa . This confirms a diffuse phylogenetic distribution of muscarine within the genus. Taxonomic descriptions are presented for 16 species, several synonymies proposed, and four new combinations made. A key to species of eastern North American Mallocybe is presented, along with illustrations of important diagnostic features. Citation : Matheny PB, Kudzma LV, Graddy MG, Mardini SM, Noffsinger CR, Swenie RA, Walker NC, Campagna SR, Halling R, Lebeuf R, Kuo M, Lewis DP, Smith ME, Tabassum M, Trudell SA, Vauras J (2023). A phylogeny for North American Mallocybe (Inocybaceae) and taxonomic revision of eastern North American taxa. Fungal Systematics and Evolution 12: 153-201. doi: 10.3114/fuse.2023.12.09., (© 2023 Westerdijk Fungal Biodiversity Institute.)