Conscience, Caricatures, and Catholic Identities.

Catholic health care is often viewed as antithetical to secular conceptions of autonomy. This view can engender calls to protect "choice" in Catholic facilities. However, this view is built on a fundamental misunderstanding of the Ethical and Religious Directives for Catholic Health Care Services (ERDs). This commentary, which responds to "Principled Conscientious Provision: Referral Symmetry and Its Implications for Protecting Secular Conscience," by Abram Brummett et al., seeks to demonstrate the nuance of the ERDs as well as to address some of the challenges various Catholic identities have when interpreting and living out the ERDs so that all patients receive high-quality, compassionate care. By highlighting the Church's desire to protect all people at every stage, I hope to dispel the caricatures that often result from misunderstandings by Catholics and non-Catholics alike.

Phylotranscriptomic relationships of the Oophila clade of green algae associated to amphibian egg masses.

Green algae usually assigned to the genus Oophila are known to colonize egg capsules of amphibian egg masses across the Nearctic and Palearctic regions. We study the phylogenetic relationships of these algae using a phylotranscriptomic data set of 76 protein-coding single-copy nuclear genes. Our data set includes novel RNAseq data for six amphibian-associated and five free-living green algae, and draft genomes of two of the latter. Within the Oophila clade (nested within Moewusinia), we find samples from two European frogs (Rana dalmatina and R. temporaria) closely related to those of the North American frog R. aurora (Oophila subclade III). An isolate from the North American R. sylvatica (subclade IV) appears to be sister to the Japanese isolate from the salamander Hynobius nigrescens (subclade J1), and subclade I algae from Ambystoma maculatum are sister to all other lineages in the Oophila clade. Two free-living algae (Chlamydomonas nasuta and Cd. pseudogloeogama) are nested within the Oophila clade, and a strain of the type species of Chlorococcum (Cc. infusionum) is related to this assemblage. Our phylotranscriptomic tree suggests that recognition of different species within the Oophila clade ("clade B" of earlier studies) is warranted, and calls for a comprehensive taxonomic revision of Moewusinia.

Three-Dimensional Computed Tomography Reconstructions May Detect Pincer Lesions With Higher Sensitivity Than Radiographs in Patients With Femoroacetabular Impingement Syndrome.

Purpose: To assess the diagnostic capability of radiographs (XRs) to detect pincer lesions compared with 3-dimensional (3D) computed tomography scans in patients undergoing hip arthroscopy for femoroacetabular impingement syndrome (FAIS). Methods: We performed a retrospective review of all patients who underwent hip arthroscopy for FAIS between September 1, 2020, and October 2, 2022. Preoperative imaging was reviewed. Pincer lesions were defined as a lateral center-edge angle greater than 40°; a Tönnis angle greater than 0°; the presence of the ischial spine, crossover, or posterior wall sign; and the presence of overcoverage greater than 80%. Under "select criteria," patients were classified as having a pincer lesion on XRs and 3D computed tomography reconstructions (CTRs) based on the lateral center-edge angle or Tönnis angle alone, whereas "all criteria" added the presence of the crossover sign and coverage percentage. Statistical analysis was performed to determine the diagnostic accuracy of XRs compared with 3D CTRs. Results: A total of 69 patients met the inclusion criteria. There were 21 male patients (30.4%) and 48 female patients (69.6%). The mean age was 33 ± 13.5 years. χ2 Analysis for select criteria found that 3D CTR was more likely than XRs to detect a pincer lesion. χ2 Analysis for all criteria found that 3D CTR was more likely than XRs to detect a pincer lesion. χ2 Analysis further showed that when using XRs, a pincer lesion was more likely to be detected under all criteria than under select criteria. Likewise, when using 3D CTR, a pincer lesion was more likely to be detected under all criteria than under select criteria. Conclusions: In this study, we found that 3D CTR detected pincer lesions in patients undergoing hip arthroscopy for FAIS with significantly higher sensitivity than XRs alone. Level of Evidence: Level III, retrospective cohort study.

Do Surgical Smoke Evacuators Increase the Risk of Hearing Loss for Operative Personnel During Routine Adenotonsillectomy Surgery?

INTRODUCTION: Aerosol mitigation equipment implemented due to COVID-19 has increased noise levels in the operating room (OR) during otolaryngological procedures. Intraoperative sound levels may potentially place personnel at risk for occupational hearing loss. This study hypothesized that cumulative intraoperative noise exposures with aerosol mitigation equipment exceed recommended occupational noise exposure levels. METHODS: Sound levels generated by the surgical smoke evacuator (SSE) during adenotonsillectomy were measured using a sound level meter and compared to surgery without SSE. RESULTS: Thirteen adenotonsillectomy surgeries were recorded. Mean sound levels with the SSE were greater than the control (72 ± 3 A-weighted decibels (dBA) vs. 68 ± 2 dBA; p=0.015). Maximum noise levels during surgery with SSE reached 82 ± 3 dBA. CONCLUSION: Surgeons performing adenotonsillectomy with aerosol mitigation equipment are exposed to significant noise levels. Intraoperative sound levels exceeded international standards for work requiring concentration. Innovation is needed to reduce cumulative OR noise exposures.

Differing physiological performance of coexisting cool- and warmwater fish species under heatwaves in the Midwestern United States.

Heatwaves are becoming more frequent and intensified with climate change. Freshwater ecosystems are among the most threatened, within which, differing responses between cool- and warmwater species to heatwaves can lead to fundamental changes in communities. Physiological experiments can identify potential mechanisms underlying the impacts of such heatwaves on fish communities. In the current study, we quantified the oxygen consumption rate, aerobic scope and swimming performance of cool- and warmwater fish species following the simulation of short-term heatwaves currently occurring in streams in the Midwestern United States. The coolwater predator walleye (Sander vitreus) showed clear thermal disadvantages relative to the warmwater predator largemouth bass (Micropterus salmoides), based on a high metabolic cost during the heatwave, low metabolic activity when encountering prey, and reduced swimming performance following the heatwave. Largemouth bass also showed a thermal advantage relative to the warmwater prey fathead minnow (Pimephales promelas) related to swimming performance and energetic costs, highlighting differing thermal responses between predators and prey. This study demonstrates the importance of considering short-term extreme thermal events in the response of aquatic communities to climate stressors.

Probing the dynamic landscape of peptides in molecular assemblies by synergized NMR experiments and MD simulations.

Peptides or proteins containing small biomolecular aggregates, such as micelles, bicelles, droplets and nanodiscs, are pivotal in many fields ranging from structural biology to pharmaceutics. Monitoring dynamics of such systems has been limited by the lack of experimental methods that could directly detect their fast (picosecond to nanosecond) timescale dynamics. Spin relaxation times from NMR experiments are sensitive to such motions, but their interpretation for biomolecular aggregates is not straightforward. Here we show that the dynamic landscape of peptide-containing molecular assemblies can be determined by a synergistic combination of solution state NMR experiments and molecular dynamics (MD) simulations. Solution state NMR experiments are straightforward to implement without an excessive amount of sample, while direct combination of spin relaxation data to MD simulations enables interpretation of dynamic landscapes of peptides and other aggregated molecules. To demonstrate this, we interpret NMR data from transmembrane, peripheral, and tail anchored peptides embedded in micelles. Our results indicate that peptides and detergent molecules do not rotate together as a rigid body, but peptides rotate in a viscous medium composed of detergent micelle. Spin relaxation times also provide indirect information on peptide conformational ensembles. This work gives new perspectives on peptide dynamics in complex biomolecular assemblies.

Measuring the visual angle of polarization-related entoptic phenomena using structured light.

The ability to perceive polarization-related entoptic phenomena arises from the dichroism of macular pigments held in Henle's fiber layer of the retina and can be inhibited by retinal diseases, such as age-related macular degeneration, which alters the structure of the macula. Structured light tools enable the direct probing of macular pigment density and retinal structure through the perception of polarization-dependent entoptic patterns. Here, we directly measure the visual angle of an entoptic pattern created through the illumination of the retina with a structured state of light and a perception task that is insensitive to corneal birefringence. The central region of the structured light stimuli was obstructed, with the size of the obstruction varying according to a psychophysical staircase. Two stimuli, one producing 11 azimuthal fringes and the other three azimuthal fringes, were presented to 24 healthy participants. The pattern with 11 azimuthal fringes produced an average visual angle threshold of 10° ± 1° and a 95% confidence interval (C.I.) of [6°, 14°]. For the pattern with three azimuthal fringes, a threshold extent of 3.6° ± 0.3° C.I. = [1.3°, 5.8°] was measured, a value similar to the published extent of Haidinger's brush (4°). The increase in apparent size and clarity of entoptic phenomena produced by the presented structured light stimuli offers the potential to detect the early signs of macular disease over perception tasks using uniform polarization stimuli.

Taxonomy and nomenclature of Oophila amblystomatis (Chlorophyceae, Chlamydomonadales).

The unicellular green alga Oophila amblystomatis was named by Lambert in 1905 based upon its association with egg masses of the spotted salamander Ambystoma maculatum. We collected algal cells from Lambert's original egg capsule preparations that were contributed to Phycotheca Boreali-Americana (PBA) in 1905 and subjected them to DNA extraction and PCR with O. amblystomatis-specific 18S rRNA gene primers. DNA amplified from these preparations was cloned and nine clones were sequenced. Along with representative sequences from the Oophila clade and Chlorophyceae, a phylogenetic tree was inferred. Seven sequences clustered within the Oophila clade and two clustered with Chlamydomonas moewusii, which is included in a sister clade to Oophila. By sequencing algal material from the egg capsules of representative type material we can unambiguously characterize O. amblystomatis and define a monophyletic clade centered on this type material. Accordingly, we reject a recent proposal that this species be transferred to Chlorococcum.

Phosphate starvation signaling increases mitochondrial membrane potential through respiration-independent mechanisms.

Mitochondrial membrane potential directly powers many critical functions of mitochondria, including ATP production, mitochondrial protein import, and metabolite transport. Its loss is a cardinal feature of aging and mitochondrial diseases, and cells closely monitor membrane potential as an indicator of mitochondrial health. Given its central importance, it is logical that cells would modulate mitochondrial membrane potential in response to demand and environmental cues, but there has been little exploration of this question. We report that loss of the Sit4 protein phosphatase in yeast increases mitochondrial membrane potential, both by inducing the electron transport chain and the phosphate starvation response. Indeed, a similarly elevated mitochondrial membrane potential is also elicited simply by phosphate starvation or by abrogation of the Pho85-dependent phosphate sensing pathway. This enhanced membrane potential is primarily driven by an unexpected activity of the ADP/ATP carrier. We also demonstrate that this connection between phosphate limitation and enhancement of mitochondrial membrane potential is observed in primary and immortalized mammalian cells as well as in Drosophila. These data suggest that mitochondrial membrane potential is subject to environmental stimuli and intracellular signaling regulation and raise the possibility for therapeutic enhancement of mitochondrial function even in defective mitochondria.

Effects of spatial frequency cross-adaptation on the visual number sense.

When observing a simple visual scene such as an array of dots, observers can easily and automatically extract their number. How does our visual system accomplish this? We investigate the role of specific spatial frequencies to the encoding of number through cross-adaptation. In two experiments, observers were peripherally adapted to six randomly generated sinusoidal gratings varying from relatively low-spatial frequency (M = 0.44 c/deg) to relatively high-spatial frequency (M = 5.88 c/deg). Subsequently, observers judged which side of the screen had a higher number of dots. We found a strong number-adaptation effect to low-spatial frequency gratings (i.e., participants significantly underestimated the number of dots on the adapted side) but a significantly reduced adaptation effect for high-spatial frequency gratings. Various control conditions demonstrate that these effects are not due to a generic response bias for the adapted side, nor moderated by dot size or spacing effects. In a third experiment, we observed no cross-adaptation for centrally presented gratings. Our results show that observers' peripheral number perception can be adapted even with stimuli lacking any numeric or segmented object information and that low spatial frequencies adapt peripheral number perception more than high ones. Together, our results are consistent with recent number perception models that suggest a key role for spatial frequency in the extraction of number from the visual signal (e.g., Paul, Ackooij, Ten Cate, & Harvey, 2022), but additionally suggest that some spatial frequencies - especially in the low range and in the periphery - may be weighted more by the visual system when estimating number. We argue that the cross-adaptation paradigm is also a useful methodology for discovering the primitives of visual number encoding.

Hexagonal Boron Nitride Slab Waveguides for Enhanced Spectroscopy of Encapsulated 2D Materials.

The layered insulator hexagonal boron nitride (hBN) is a critical substrate that brings out the exceptional intrinsic properties of two-dimensional (2D) materials such as graphene and transition metal dichalcogenides (TMDs). In this work, the authors demonstrate how hBN slabs tuned to the correct thickness act as optical waveguides, enabling direct optical coupling of light emission from encapsulated layers into waveguide modes. Molybdenum selenide (MoSe2 ) and tungsten selenide (WSe2 ) are integrated within hBN-based waveguides and demonstrate direct coupling of photoluminescence emitted by in-plane and out-of-plane transition dipoles (bright and dark excitons) to slab waveguide modes. Fourier plane imaging of waveguided photoluminescence from MoSe2 demonstrates that dry etched hBN edges are an effective out-coupler of waveguided light without the need for oil-immersion optics. Gated photoluminescence of WSe2 demonstrates the ability of hBN waveguides to collect light emitted by out-of-plane dark excitons.Numerical simulations explore the parameters of dipole placement and slab thickness, elucidating the critical design parameters and serving as a guide for novel devices implementing hBN slab waveguides. The results provide a direct route for waveguide-based interrogation of layered materials, as well as a way to integrate layered materials into future photonic devices at arbitrary positions whilst maintaining their intrinsic properties.

Using Participatory Implementation Science to Advance Health Equity.

Participatory approaches to implementation science (IS) offer an inclusive, collaborative, and iterative perspective on implementing and sustaining evidence-based interventions (EBIs) to advance health equity. This review provides guidance on the principles and practice of participatory IS, which enables academic researchers, community members, implementers, and other actors to collaboratively integrate practice-, community-, and research-based evidence into public health and health care services. With a foundational focus on supporting academics in coproducing knowledge and action, participatory IS seeks to improve health, reduce inequity, and create transformational change. The three main sections of this review provide (a) a rationale for participatory approaches to research in implementation science, (b) a framework for integrating participatory approaches in research utilizing IS theory and methods, and (c) critical considerations for optimizing the practice and impact of participatory IS. Ultimately, participatory approaches can move IS activities beyond efforts to make EBIs work within harmful systems toward transformative solutions that reshape these systems to center equity.

Evaluation of the Closure of Patent Ductus Arteriosus With Ibuprofen Compared to Indomethacin.

OBJECTIVE: Limited data exist comparing indomethacin and ibuprofen for the treatment of patent ductus arteriosus (PDA). The objective was to compare the safety and efficacy of indomethacin and ibuprofen for treatment of PDA closure. METHODS: This single-center, pre-test/post-test quasi-experiment included preterm infants admitted to the neonatal intensive care unit who received indomethacin (July 1, 2013-September 30, 2015) or ibuprofen (December 1, 2015-July 31, 2019) for PDA. Patients were excluded if they were thrombocytopenic, had existing kidney injury, unresolved intraventricular hemorrhage (IVH) or necrotizing enterocolitis (NEC) at treatment initiation. Data were obtained from the electronic health record. Study outcomes were complete PDA closure, degree of PDA closure, resolution of symptoms, and new-onset acute kidney injury (AKI), IVH, or NEC. RESULTS: A total of 114 patients were included: 44 (39%) received indomethacin and 70 (61%) received -ibuprofen. Twenty-one (21%) patients experienced successful PDA closure within 1 week: 13 (32%) indomethacin patients and 8 (13%) ibuprofen patients (p = 0.023). PDA size reduction occurred in 43 (46%) patients with 29 (25%) experiencing complete symptom resolution. Significantly more indomethacin patients compared with ibuprofen patients experienced new-onset AKI (48% vs 17%; p < 0.001) and received concomitant nephrotoxins (68% vs 39%; p = 0.002). There were no significant differences in new-onset IVH or NEC. CONCLUSIONS: Indomethacin administration successfully closed the PDA in more neonates than ibuprofen but resulted in higher rates of AKI. However, this was confounded by more frequent administration of concomitant nephrotoxins. Larger trials are needed to help elucidate the optimal drug for closure of the PDA in neonates.

Movement and behavioral states of common carp (Cyprinus carpio) in response to a behavioral deterrent in a navigational lock.

BACKGROUND: Freshwater ecosystems are some of the most affected by biological invasions due, in part, to the introduction of invasive carp worldwide. Where carp have become established, management programs often seek to limit further range expansion into new areas by reducing their movement through interconnected rivers and waterways. Lock and dams are important locations for non-physical deterrents, such as carbon dioxide (CO2), to reduce unwanted fish passage without disrupting human use. The purpose of this study was to evaluate the behavioral responses of common carp (Cyprinus carpio) to non-physical deterrents within a navigation structure on the Fox River, Wisconsin. Acoustic telemetry combined with hidden Markov models (HMMs) was used to analyze variation in carp responses to treatments. Outcomes may inform CO2 effectiveness at preventing invasive carp movement through movement pinch-points. METHODS: Carbon dioxide (CO2) was recently registered as a pesticide in the United States for use as a deterrent to invasive carp movement. As a part of a multi-component study to test a large-scale CO2 delivery system within a navigation lock, we characterized the influence of elevated CO2 and forced water circulation in the lock chamber on carp movements and behavior. Through time-to-event analyses, we described the responses of acoustic-tagged carp to experimental treatments including (1) CO2 injection in water with forced water circulation, (2) forced water circulation without CO2 and (3) no forced water circulation or CO2. We then used hidden Markov models (HMMs) to define fine-scale carp movement and evaluate the relationships between carp behavioral states and CO2 concentration, forced water circulation, and temperature. RESULTS: Forced water circulation with and without CO2 injection were effective at expelling carp from the lock chamber relative to null treatments where no stimulus was applied. A portion of carp exposed to forced water circulation with CO2 transitioned from an exploratory to an encamped behavioral state with shorter step-lengths and a unimodal distribution in turning angles, resulting in some carp remaining in the lock chamber. Whereas carp exposed to forced water circulation only remained primarily in an exploratory behavioral state, resulting in all carp exiting the lock chamber. CONCLUSION: Our findings illustrate the potential of forced water circulation, alone, as a non-physical deterrent and the efficacy of CO2 injection with forced water circulation in expelling carp from a navigation lock. Results demonstrate how acoustic telemetry and HMMs in an experimental context can describe fish behavior and inform management strategies.

Aerobic response to thermal stress across ontogeny and habitats in a teleost fish.

Near-future climate change projections predict an increase in sea surface temperature that is expected to have significant and rapid effects on marine ectotherms, potentially affecting a number of critical life processes. Some habitats also undergo more thermal variability than others, and the inhabitants therefore must be more tolerant to acute periods of extreme temperatures. Mitigation of these outcomes may occur through acclimation, plasticity or adaptation, although the rate and extent of a species' ability to adjust to warmer temperatures is largely unknown, specifically as it pertains to effects on various performance metrics in fishes that inhabit multiple habitats throughout ontogenetic stages. Here, the thermal tolerance and aerobic performance of schoolmaster snapper (Lutjanus apodus Walbaum, 1792) collected from two different habitats were experimentally assessed under different warming scenarios (temperature treatments = 30, 33, 35, 36°C) to assess vulnerability to an imminently changing thermal habitat. Larger subadult and adult fish collected from a 12 m deep coral reef exhibited a lower critical thermal maximum (CTmax ) compared to smaller juvenile fish collected from a 1 m deep mangrove creek. However, the CTmax of the creek-sampled fish was only 2°C above the maximum water temperature measured in the habitat from which they were collected, compared to a CTmax that was 8°C higher in the reef-sampled fish, resulting in a wider thermal safety margin at the reef site. A generalized linear model showed a marginally significant effect of temperature treatment on resting metabolic rate (RMR), but there were no effects of any of the tested factors on maximum metabolic rate or absolute aerobic scope. Post hoc tests revealed that RMR was significantly higher for creek-collected fish at the 36°C treatment and significantly higher for reef-collected fish at 35°C. Swimming performance [measured by critical swimming speed] was significantly lower at the highest temperature treatment for creek-collected fish and trended down with each successive increase in temperature treatment for reef-collected fish. These results show that metabolic rate and swimming performance responses to thermal challenges are somewhat consistent across collection habitats, and this species may be susceptible to unique types of thermal risk depending on its habitat. We show the importance of intraspecific studies that couple habitat profiles and performance metrics to better understand possible outcomes under thermal stress.

Protocol for a scoping review of health equity frameworks and models applied in empirical studies of chronic disease prevention and control.

BACKGROUND: Chronic diseases, such as cancers and cardiovascular diseases, present the greatest burden of morbidity and mortality worldwide. This burden disproportionately affects historically marginalized populations. Health equity is rapidly gaining increased attention in public health, health services, and implementation research, though many health inequities persist. Health equity frameworks and models (FM) have been called upon to guide equity-focused chronic disease and implementation research. However, there is no clear synthesis of the health equity FM used in chronic disease research or how these are applied in empirical studies. This scoping review seeks to fill this gap by identifying and characterizing health equity FM applied in empirical studies along the chronic disease prevention and control continuum, describing how these FM are used, and exploring potential applications to the field of implementation science. METHODS: We follow established guidance for conducting scoping reviews, which includes six stages: (1) identify the research question; (2) identify relevant studies; (3) select studies for inclusion; (4) data extraction; (5) collating, summarizing, and reporting the results; and (6) consultation. This protocol presents the iterative, collaborative approach taken to conceptualize this study and develop the search strategy. We describe the criteria for inclusion in this review, methods for conducting two phases of screening (title and abstract, full text), data extraction procedures, and quality assurance approaches taken throughout the project. DISCUSSION: The findings from this review will inform health-equity focused chronic disease prevention and control research. FM identified through this review will be added to an existing website summarizing dissemination and implementation science frameworks, and we will offer case examples and recommendations for utilizing a health equity FM in empirical studies. Our search strategy and review methodology may serve as an example for scholars seeking to conduct reviews of health equity FM in other health disciplines. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework Registration https://doi.org/10.17605/OSF.IO/SFVE6.

Bacterial Diversity in Egg Capsular Fluid of the Spotted Salamander Ambystoma maculatum Decreases with Embryonic Development.

Egg capsules within egg masses of the spotted salamander Ambystoma maculatum host a symbiosis with the unicellular green alga Oophila amblystomatis. However, this alga is not the only microbe to inhabit those capsules, and the significance of these additional taxa for the symbiosis is unknown. Spatial and temporal patterns of bacterial diversity in egg capsules of A. maculatum have recently begun to be characterized, but patterns of bacterial diversity as a function of embryonic development are unknown. We sampled fluid from individual capsules in egg masses over a large range of host embryonic development in 2019 and 2020. We used 16S rRNA gene amplicon sequencing to examine how diversity and relative abundance of bacteria changed with embryonic development. In general, bacterial diversity decreased as embryos developed; significant differences were observed (depending on the metric) by embryonic development, pond, and year, and there were interaction effects. The function of bacteria in what is thought of as a bipartite symbiosis calls for further research.

High-throughput screens identify a lipid nanoparticle that preferentially delivers mRNA to human tumors in vivo.

Lipid nanoparticles (LNPs) are a clinically relevant way to deliver therapeutic mRNA to hepatocytes in patients. However, LNP-mRNA delivery to end-stage solid tumors such as head and neck squamous cell carcinoma (HNSCC) remains more challenging. While scientists have used in vitro assays to evaluate potential nanoparticles for HNSCC delivery, high-throughput delivery assays performed directly in vivo have not been reported. Here we use a high-throughput LNP assay to evaluate how 94 chemically distinct nanoparticles delivered nucleic acids to HNSCC solid tumors in vivo. DNA barcodes were used to identify LNPHNSCC, a novel LNP for systemic delivery to HNSCC solid tumors. Importantly, LNPHNSCC retains tropism to HNSCC solid tumors while minimizing off-target delivery to the liver.

CDK4/6 Inhibition Induces Senescence and Enhances Radiation Response by Disabling DNA Damage Repair in Oral Cavity Squamous Cell Carcinoma.

PURPOSE: HPV(-) OCSCC resists radiation treatment. The CDKN2A gene, encoding p16INK4A, is commonly disrupted in OCSCC. p16 inhibits CDK4/CDK6, leading to cell cycle arrest, but the biological sequelae of CDK4/6 inhibition in OCSCC remains understudied. This study examines whether inhibition of CDK4/6 enhances radiation response in OCSCC. METHODS: MTT assays were performed in OCSCC cell lines HN5 and CAL27 following treatment with palbociclib. Clonogenic survival and synergy were analyzed after radiation (RT-2 or 4Gy), palbociclib (P) (0.5 µM or 1 µM), or concurrent combination treatment (P+RT). DNA damage/repair and senescence were examined. CDK4/6 were targeted via siRNA to corroborate P+RT effects. Three-dimensional immortalized spheroids and organoids derived from patient tumors (conditionally reprogrammed OCSCC CR-06 and CR-18) were established to further examine and validate responses to P+RT. RESULTS: P+RT demonstrated reduced viability and synergy, increased ß-gal expression (~95%), and ~two-fold higher γH2AX. Rad51 and Ku80 were reduced after P+RT, indicating impairment of both HR and NHEJ. siCDK4/6 increased senescence with radiation. Spheroids showed reduced proliferation and size with P+RT. CR-06 and CR-18 further demonstrated three-fold reduced proliferation and organoids size with P+RT. CONCLUSION: Targeting CDK4/6 can lead to improved efficacy when combined with radiation in OCSCC by inducing senescence and inhibiting DNA damage repair.

Agricultural conservation may not help Midwestern US freshwater biodiversity in a changing climate.

Global climate change and agricultural disturbance often drive freshwater biodiversity changes at the regional level, particularly in the Midwestern US. Agricultural conservation practices have been implemented to reduce sediment and nutrient loading (e.g., crop rotation, cover crops, reduced tillage, and modified fertilizer application) for long-term economic sustainability and environmental resilience. However, the effectiveness of these efforts on freshwater biodiversity is not conclusive. In this study, we used the Kaskaskia River Watershed, Illinois as an example to evaluate how agricultural conservation practices affects both taxonomic and functional diversity under climate changes. The measures of trait-based functional diversity provide mechanistic explanations of biological changes. In specific, we model and predict 1) species richness (SR), 2) functional dispersion (FDis), and 3) functional evenness (FEve). FDis and FEve were based on ecology (life history, habitat preference, and trophic level) and physiology (thermal preference, swimming preference, etc.). The best random-forest regression models showed that flow, temperature, nitrate, and the watershed area were among the top predictors of the three biodiversity measures. We then used the models to predict the changes of SR and FDis under RCP8.5 climate change scenarios. SR and FDis were predicted to decrease in most sites, up to 20 % and 4 % by 2099, respectively. When agricultural conservation practices were considered together with climate changes, the decreasing trends of SR and FDis remained, suggesting climate change outweighed potential agriculture conservation efforts. Thus, climate-change effects on temperature and flow regimes need to be incorporated into the design of agricultural practices for freshwater biodiversity conservation.