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IntroductionThe 2024 Voice AI Symposium, hosted by the Bridge2AI-Voice Consortium in Tampa, FL, featured two keynote speeches that addressed the intersection of voice AI, healthcare, ethics, and law. Dr. Rupal Patel and Dr. Nicholson Price provided insights into the advancements, applications, and challenges of AI-driven voice tools in healthcare. The symposium aimed to advance cross-disciplinary collaboration and establish frameworks for the ethical use of AI technologies in healthcare.MethodsThe keynote speeches, delivered on May 1st and 2nd, were 30 minutes each, followed by 10-minutes Q&A sessions. The audio was recorded and transcribed using Whisper (v7.13.1). Content summaries were generated with the aid of ChatGPT (v4.0), and the authors reviewed and edited the final transcripts to ensure accuracy and clarity.ResultsDr. Rupal Patel’s keynote, “Reflections and New Frontiers in Voice AI”, explored the potential of voice AI for early detection of health conditions, monitoring disease progression, and promoting non-invasive global health management. She highlighted innovative uses beyond traditional applications, such as examining menopause-related symptoms. Dr. Nicholson Price’s keynote, “Governance for Clinical Voice AI”, addressed the regulatory and ethical challenges posed by AI in healthcare. He stressed the need for context-aware systems and dynamic legal frameworks to address liability and accountability.ConclusionsThe 2024 Voice AI Symposium highlighted the transformative potential of voice AI for early detection, health monitoring, and reducing healthcare disparities. It also underscored the importance of dynamic governance to address the ethical and regulatory challenges of deploying AI in clinical settings.

IntroductionThe 2024 Voice AI Symposium, presented by the Bridge2AI-Voice Consortium, featured deep-dive educational workshops conducted by experts from diverse fields to explore the latest advancements in voice biomarkers and artificial intelligence (AI) applications in healthcare. Through five workshops, attendees learned about topics including international standardization of vocal biomarker data, real-world deployment of AI solutions, assistive technologies for voice disorders, best practices for voice data collection, and deep learning applications in voice analysis. These workshops aimed to foster collaboration between academia, industry, and healthcare to advance the development and implementation of voice-based AI tools.MethodsEach workshop featured a combination of lectures, case studies, and interactive discussions. Transcripts of audio recordings were generated using Whisper (Version 7.13.1) and summarized by ChatGPT (Version 4.0), then reviewed by the authors. The workshops covered various methodologies, from signal processing and machine learning operations (MLOps) to ethical concerns surrounding AI-powered voice data collection. Practical demonstrations of AI-driven tools for voice disorder management and technical discussions on implementing voice AI models in clinical and non-clinical settings provided attendees with hands-on experience.ResultsKey outcomes included the discussion of international standards to unify stakeholders in vocal biomarker research, practical challenges in deploying AI solutions outside the laboratory, review of Bridge2AI-Voice data collection processes, and the potential of AI to empower individuals with voice disorders. Additionally, presenters shared innovations in ethical AI practices, scalable machine learning frameworks, and advanced data collection techniques using diverse voice datasets. The symposium highlighted the successful integration of AI in detecting and analyzing voice signals for various health applications, with significant advancements in standardization, privacy, and clinical validation processes.DiscussionThe symposium underscored the importance of interdisciplinary collaboration to address the technical, ethical, and clinical challenges in the field of voice biomarkers. While AI models have shown promise in analyzing voice data, challenges such as data variability, security, and scalability remain. Future efforts must focus on refining data collection standards, advancing ethical AI practices, and ensuring diverse dataset inclusion to improve model robustness. By fostering collaboration among researchers, clinicians, and technologists, the symposium laid a foundation for future innovations in AI-driven voice analysis for healthcare diagnostics and treatment.

Monitoring population size at ecosystem scales is difficult for most species of conservation concern. While assessing site occupancy at broad scales has proven feasible, rigorous tracking of changes in population size over time has not – even though it can provide a stronger basis for assessing population status and conservation-decision making. Therefore, we demonstrate how relatively low-intensity, ecosystem-scale passive acoustic monitoring (PAM) can be linked to local-density monitoring to estimate the population size of native California spotted owls (Strix occidentalis occidentalis) and invasive barred owls (S. varia) across the western Sierra Nevada, California. Based on a PAM sampling grid with 400 ha cells (the approximate home range size of these species), we estimated site occupancy to be between 0.42 (SE = 0.02) and 0.30 (SE = 0.02) for California spotted owls using relatively liberal and strict criteria, respectively, for considering a cell occupied. PAM-based site occupancy estimates within local-scale density monitoring study areas (range = 0.41–0.78 and 0.28–0.76 for liberal and strict criteria, respectively) were strongly and positively correlated with local density (range = 0.08–0.31 owl/km2) for this species. In contrast, ecosystem-wide site occupancy of barred owls was very low based on PAM (0.034, SE

The leafminers on gymnosperms receive much less attention than those on either angiosperms or ferns. Given the distinctly different leaf shape and leaf venation found in gymnosperms, they would be expected to host significantly different leafminer groups. Very few comprehensive reports on gymnosperm-feeding leafminers have been presented.Based on the well-studied fauna in North America and Europe, we compiled a list of 133 species, 30 genera and 13 families of gymnosperm-feeding leafminers. The gymnosperm-mining families (in descending order of leafminer number) included Tortricidae, Gelechiidae, Argyresthiidae, Yponomeutidae, Batrachedridae, Pyralidae, Adelidae, Agromyzidae, Blastobasidae, Bucculatricidae, Coleophoridae, Curculionidae and Noctuidae. There were 109 species, 22 genera and ten families in North America and 34 species, 19 genera and nine families in Europe. We compiled a list of 102 species and 16 genera of host plants, belonging to four families: Pinaceae, Cupressaceae, Taxaceae and Zamiaceae. There were 84 host species, 15 genera and three host families in North America and 46 host species, ten genera and three host families in Europe. Dominant gymnosperm-mining families and dominant host families were generally the same in the two continents.

PurposeOnly one chemical class of topoisomerase I (TOP1) inhibitors is FDA approved, the camptothecins with irinotecan and topotecan widely used. Because of their limitations (chemical instability, drug efflux-mediated resistance, and diarrhea), novel TOP1 inhibitors are warranted. Indenoisoquinoline non-camptothecin topoisomerase I (TOP1) inhibitors overcome chemical instability and drug resistance that limit camptothecin use. Three indenoisoquinolines, LMP400 (indotecan), LMP776 (indimitecan), and LMP744, were examined in a phase I study for lymphoma-bearing dogs to evaluate differential efficacy, pharmacodynamics, toxicology, and pharmacokinetics.Experimental designEighty-four client-owned dogs with lymphomas were enrolled in dose-escalation cohorts for each indenoisoquinoline, with an expansion phase for LMP744. Efficacy, tolerability, pharmacokinetics, and target engagement were determined.ResultsThe MTDs were 17.5 mg/m2 for LMP 776 and 100 mg/m2 for LMP744; bone marrow toxicity was dose-limiting; up to 65 mg/m2 LMP400 was well-tolerated and MTD was not reached. None of the drugs induced notable diarrhea. Sustained tumor accumulation was observed for LMP744; γH2AX induction was demonstrated in tumors 2 and 6 hours after treatment; a decrease in TOP1 protein was observed in most lymphoma samples across all compounds and dose levels, which is consistent with the fact that tumor response was also observed at low doses LMP744. Objective responses were documented for all indenoisoquinolines; efficacy (13/19 dogs) was greatest for LMP744.ConclusionsThese results demonstrate proof-of-mechanism for indenoisoquinoline TOP1 inhibitors supporting their further clinical development. They also highlight the value of the NCI Comparative Oncology Program (https://ccr.cancer.gov/Comparative-Oncology-Program) for evaluating novel therapies in immunocompetent pets with cancers.

Hedgehog signaling is essential for bone formation. Here, the authors show that the transmembrane protein SLITRK5 is a negative regulator of hedgehog signaling in osteoblasts, suggesting it may be a potential therapeutic target to enhance bone formation.

PurposeThe oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) promotes gene transcription involved in cancer, and its activation by IL-6 is found in head and neck squamous cell carcinoma. Four triazolothiadizine STAT3 pathway inhibitors were evaluated to prioritize a single compound for in vivo examination.MethodsMetabolic stability in mouse liver microsome incubation was used to evaluate four triazolothiadizine analogues, and UPCDC-10205 was administered to mice IV as single or multiple doses to evaluate toxicity. Single-dose pharmacokinetics (PK), bioavailability and metabolism were studied after IV 4 mg/kg, PO 4 mg/kg, or PO 30 mg/kg suspension in 1% carboxymethyl cellulose. Mice were euthanized between 5 min to 24 h after dosing, and plasma and tissues were analyzed by LC-MS. Non-compartmental PK parameters were determined.ResultsOf the four triazolothiadizine analogues evaluated, UPCDC-10205 was metabolically most stable. The maximum soluble dose of 4 mg/kg in 10% Solutol™ was not toxic to mice after single and multiple doses. PK analysis showed extensive tissue distribution and rapid plasma clearance. Bioavailability was ~5%. A direct glucuronide conjugate was identified as the major metabolite which was recapitulated in vitro.ConclusionsRapid clearance of UPCDC-10205 was thought to be the result of phase II metabolism despite its favorable stability in a phase I in vitro metabolic stability assay. The direct glucuronidation explains why microsomal stability (reflective of phase I metabolism) did not translate to in vivo metabolic stability. UPCDC-10205 did not demonstrate appropriate exposure to support efficacy studies in the current formulation.

Neurofibromatosis type I (NF1) is characterized by prominent skeletal abnormalities mediated in part by aberrant ERK pathway activation due to NF1 loss-of-function. Here, the authors report the MEKK2 is a key mediator of this aberrant ERK activation and that MEKK2 inhibitors, including ponatinib, ameliorate skeletal defects in a mouse model of NF1.

Stephanie B Terrill,1 Hyelin You,2 Heidi Eiseman,1 Michael E Rauser1 1Department of Ophthalmology, Loma Linda University Eye Institute, Loma Linda, CA, USA; 2Department of Ophthalmology, Loma Linda University School of Medicine, Loma Linda, CA, USACorrespondence: Michael E RauserLoma Linda University Eye Institute, 11370 Anderson Street, Suite 1800, Loma Linda, CA 92354, USATel +1 909 558 2112Email mrauser@llu.eduPurpose: The purpose of this study was to determine the incidence of minor and major ocular injuries in patients with orbital wall fractures at Loma Linda University Health, a level-one trauma center, to help determine the most appropriate setting for the initial dilated fundus examination by ophthalmologists.Methods: A retrospective study was performed from January 2008 to January 2013 of patients diagnosed with orbital wall fracture secondary to trauma. Exclusion criteria included unknown mechanism of injury, the absence of ophthalmology consultation, or absence of imaging. Data collected included age, gender, mechanism of injury, visual acuity, and anterior/posterior segment findings. Ocular injuries were categorized as either minor or major.Results: Of 567 charts reviewed, 460 met criteria and were included for analysis. In the analysis, 86.5% of patients were male, and 81.3% were Caucasian. The most common mechanism of orbital fracture was blunt injury. Visual acuity was better than 20/100 in 82.4% of patients. On chart review, 81.1% of patients were found to have either a minor injury, a major injury, or both. The most common injury was subconjunctival hemorrhage (53.5%). Globe rupture (2.9%) and vision-threatening posterior segment findings such as retinal tear and choroidal rupture (1.3%) were relatively rare. Only one retinal detachment (0.2%) was found, specifically in the setting of severe injury with concomitant globe rupture.Conclusion: Knowledge of the common ocular injuries associated with orbital fractures will help emergency department (ED) physicians and ophthalmologists provide the dilated fundus exam in the most appropriate setting. The most frequent injuries identified were non-vision threatening, and visually significant posterior segment findings were relatively rare (1.3%). Thus, for the majority of patients presenting to the ED with orbital fracture, a dilated fundus exam can be performed at a later date in the outpatient clinic setting, unless urgent orbital fracture surgery is planned.Keywords: ocular trauma, orbital wall fracture, subconjunctival hemorrhage, globe rupture, entrapment, vision loss

The new genus Aspilanta gen. n. is described to harbour Nearctic heliozelid moths with reduced venation, previously placed in Antispila Hübner, 1825, with type species Antispila oinophylla van Nieukerken & Wagner, 2012. The erection of this genus has become possible now that monophyly has been supported by a recent phylotranscriptomics analysis. Six species are combined in this genus: Aspilanta oinophylla (van Nieukerken & Wagner, 2012), comb. n., A. hydrangaeella (Chambers, 1874), comb. n., A. ampelopsifoliella (Chambers, 1874), comb. n., A. voraginella (Braun, 1927), comb. n., A. argentifera (Braun, 1927), comb. n., A. viticordifoliella (Clemens, 1860), comb. n. and two candidate species are recognised. DNA barcode COI sequences of Malaise trapped specimens suggest a rich fauna of Aspilanta in Central America. All are leafminers, with Vitaceae as main host family, and single species feeding respectively on Hydrangeaceae and Myricaceae. The species are briefly diagnosed, and data on biology, DNA barcodes and distribution are provided. To place the genus in context, a review of heliozelid morphology and phylogeny is presented and a key to Nearctic genera is given. The genus is confined to North and Central America, possibly also occurring in South America. Aspilanta oinophylla is also an invasive species on grapevine in Italy. The genus is sister to Coptodisca Walsingham, 1895. Another species is removed from Antispila: Heliozela eugeniella (Busck, 1900), comb. n., feeding on Eugenia (Myrtaceae), from Florida.

Most leadership programs emphasize knowledge over skills, being skillful over how to be skillful, knowledge about skills over skill application, and ad hoc and hard-to-assess field activities over focused and observable skill practice. "Knowledge and skill application laboratories" provide opportunities to experiment with--and receive criteria-based feedback from multiple observers on--new ways of thinking and behaving. They challenge students to integrate course-specific content with universally applicable skills: diagnosis, goal setting, communication, teamwork, and conflict management. We describe the purpose, history, and objectives of this kind of laboratory, sample lab activities, design considerations, and what we learned. (Contains 2 figures and 6 tables.)

This study examines tweets ( N = 1,103,119) sent by 638 US politicians regarding climate change ( N = 10,135). Using data reflecting the risks faced and opinions held by their constituents, the extent to which politicians lead—tweeting about climate change for those most at risk, called trusteeship—or follow—tweeting about climate change for those who are already concerned, called playing to the crowed—is examined. Results reveal that while Democrats generally tweet about climate change more often than Republicans, within each party, tweeting frequency is mostly explained by the level of concern in a politicians’ constituency. Objective risks faced by constituents play no role. Analysis of behavior across different office levels—federal, state, and local—also shows that while federal politicians are more partisan, state and local politicians play to the crowd to a greater degree. Analysis of the tweets shows the politicians’ unequal engagement leads to over-representations of some topics (e.g., “calls for action”) and under-representations of other topics (e.g., criticizing fossil fuels and deniers).

Hyperactivation of signal transducer and activator of transcription 3 (STAT3) has been linked to tumorigenesis in most malignancies, including head and neck squamous cell carcinoma. Intravenous delivery of a chemically modified cyclic STAT3 decoy oligonucleotide with improved serum and thermal stability demonstrated antitumor efficacy in conjunction with downmodulation of STAT3 target gene expression such as cyclin D1 and Bcl-X(L) in a mouse model of head and neck squamous cell carcinoma. The purpose of the present study was to determine the toxicity and dose-dependent antitumor efficacy of the cyclic STAT3 decoy after multiple intravenous doses in Foxn1 nu mice in anticipation of clinical translation. The two doses (5 and 10 mg/kg) of cyclic STAT3 decoy demonstrated a significant decrease in tumor volume compared with the control groups (mutant cyclic STAT3 decoy or saline) in conjunction with downmodulation of STAT3 target gene expression. There was no dose-dependent effect of cyclic STAT3 decoy on tumor volume or STAT3 target gene expression. There were no significant changes in body weights between the groups during the dosing period, after the dosing interval or on the day of euthanasia. No hematology or clinical chemistry parameters suggested toxicity of the cyclic STAT3 decoy compared with saline control. No gross or histological pathological abnormalities were noted at necropsy in any of the animals. These findings suggest a lack of toxicity of intravenous administration of a cyclic STAT3 decoy oligonucleotide. In addition, comparable antitumor effects indicate a lack of dose response at the two dose levels investigated.

Background. COVID-19 may result in multiorgan failure and death. Early detection of patients at risk may allow triage and more intense monitoring. The aim of this study was to develop a simple, objective admission score, based on laboratory tests, that identifies patients who are likely going to deteriorate. Methods. This is a retrospective cohort study of all COVID-19 patients admitted to a tertiary academic medical center in New York City during the COVID-19 crisis in spring 2020. The primary combined endpoint included intubation, stage 3 acute kidney injury (AKI), or death. Laboratory tests available on admission in at least 70% of patients (and age) were included for univariate analysis. Tests that were statistically or clinically significant were then included in a multivariate binary logistic regression model using stepwise exclusion. 70% of all patients were used to train the model, and 30% were used as an internal validation cohort. The aim of this study was to develop and validate a model for COVID-19 severity based on biomarkers. Results. Out of 2545 patients, 833 (32.7%) experienced the primary endpoint. 53 laboratory tests were analyzed, and of these, 47 tests (and age) were significantly different between patients with and without the endpoint. The final multivariate model included age, albumin, creatinine, C-reactive protein, and lactate dehydrogenase. The area under the ROC curve was 0.850 (CI [95%]: 0.813, 0.889), with a sensitivity of 0.800 and specificity of 0.761. The probability of experiencing the primary endpoint can be calculated as p=e−2.4475+0.02492age−0.6503albumin+0.81926creat+0.00388CRP+0.00143LDH/1+e−2.4475+ 0.02492age−0.6503albumin+0.81926creat+0.00388CRP+0.00143LDH. Conclusions. Our study demonstrated that poor outcome in COVID-19 patients can be predicted with good sensitivity and specificity using a few laboratory tests. This is useful for identifying patients at risk during admission.

Stigmella multispicata Rocienė & Stonis, 2014, previously known from the single male holotype from Primorye, Russia, is reported as a new invasive species mining leaves of Siberian elm, Ulmus pumila L., in eastern North America. Both adults and leafmines have been reported from many sites as unidentified Nepticulidae since 2010. Crucial for the identification was a match of the DNA barcode of a single larva collected on Ulmus pumila in Beijing with adults from North America. The single larva constitutes a new record for China. Stigmella multispicata is closely related to the European S. ulmivora (Fologne, 1860), feeding likewise on Ulmus, but differs in details of external morphology and genitalia, particularly in the female, where S. multispicata has a remarkable elongated narrow ovipositor, suitable for oviposition in underside hairy leaf vein axils, where all mines start. In North America S. multispicata is the only Ulmus-feeding nepticulid with green larvae. Currently the species is known from USA: Illinois, Indiana, Iowa, Maryland, Massachusetts, Minnesota, New York, Ohio, Tennessee, Wisconsin, and Canada: Ontario and Québec. In Sagaponack, on Long Island, New York, larvae have been reported to occur en masse on Siberian elms from at least two sites. The current distribution could be reconstructed thanks also to many online photographs from observation websites. The species is redescribed, with the first descriptions of female, larva, and leafmine, and compared with S. ulmivora, which is fully redescribed. The two native North American nepticulid Ulmus leafminers, S. apicialbella (Chambers, 1873) and Ectoedemia ulmella (Braun, 1912), are diagnosed and new provincial and state records are provided. A key to linear mines on Ulmus in North America is provided. We suspect that trade of live plants through nurseries played a role in the sudden spread of this invasive species.

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The physics emphases of the PHENIX collaboration and the design and currentstatus of the PHENIX detector are discussed. The plan of the collaboration formaking the most effective use of the available luminosity in the first years ofRHIC operation is also presented.