Reticulate evolution: Detection and utility in the phylogenomics era.

Phylogenomics has enriched our understanding that the Tree of Life can have network-like or reticulate structures among some taxa and genes. Two non-vertical modes of evolution - hybridization/introgression and horizontal gene transfer - deviate from a strictly bifurcating tree model, causing non-treelike patterns. However, these reticulate processes can produce similar patterns to incomplete lineage sorting or recombination, potentially leading to ambiguity. Here, we present a brief overview of a phylogenomic workflow for inferring organismal histories and compare methods for distinguishing modes of reticulate evolution. We discuss how the timing of coalescent events can help disentangle introgression from incomplete lineage sorting and how horizontal gene transfer events can help determine the relative timing of speciation events. In doing so, we identify pitfalls of certain methods and discuss how to extend their utility across the Tree of Life. Workflows, methods, and future directions discussed herein underscore the need to embrace reticulate evolutionary patterns for understanding the timing and rates of evolutionary events, providing a clearer view of life's history.

A taxon-rich and genome-scale phylogeny of Opisthokonta.

Ancient divergences within Opisthokonta-a major lineage that includes organisms in the kingdoms Animalia, Fungi, and their unicellular relatives-remain contentious. To assess progress toward a genome-scale Opisthokonta phylogeny, we conducted the most taxon rich phylogenomic analysis using sets of genes inferred with different orthology inference methods and established the geological timeline of Opisthokonta diversification. We also conducted sensitivity analysis by subsampling genes or taxa from the full data matrix based on filtering criteria previously shown to improve phylogenomic inference. We found that approximately 85% of internal branches were congruent across data matrices and the approaches used. Notably, the use of different orthology inference methods was a substantial contributor to the observed incongruence: analyses using the same set of orthologs showed high congruence of 97% to 98%, whereas different sets of orthologs resulted in somewhat lower congruence (87% to 91%). Examination of unicellular Holozoa relationships suggests that the instability observed across varying gene sets may stem from weak phylogenetic signals. Our results provide a comprehensive Opisthokonta phylogenomic framework that will be useful for illuminating ancient evolutionary episodes concerning the origin and diversification of the 2 major eukaryotic kingdoms and emphasize the importance of investigating effects of orthology inference on phylogenetic analyses to resolve ancient divergences.

Training Psychiatrist-Scientists-Excellence on Both Sides of the Hyphen.

This Viewpoint discusses why it is important for psychiatry residency programs to continue to prioritize the training of psychiatrist-scientists.

Role of NEK2 in tumorigenesis and tumor progression.

Never in mitosis A (NIMA)-related kinase 2 (NEK2) is a serine/threonine kinase found in the nucleus and cytoplasm throughout the cell cycle. NEK2 is overexpressed in many cancers and is a biomarker of poor prognosis. Factors contributing to NEK2 elevation in cancer cells include oncogenic transcription factors, decreased ubiquitination, DNA methylation, and the circular RNA (circRNA)/long noncoding RNA (lncRNA)-miRNA axis. NEK2 overexpression produces chromosomal instability and aneuploidy, thereby enhancing cancer progression and suppressing antitumor immunity, which highlights the prominence of NEK2 in tumorigenesis and tumor progression. Small-molecule inhibitors targeting NEK2 have demonstrated promising therapeutic potential in vitro and in vivo across various cancer types. This review outlines the regulatory mechanisms of NEK2 expression, emphasizes its functional roles in cancer initiation and progression, and highlights the anticancer properties of NEK2 inhibitors.

Clock-Line-Mediated Sisyphus Cooling.

We demonstrate subrecoil Sisyphus cooling using the long-lived ^{3}P_{0} clock state in alkaline-earth-like ytterbium. A 1388-nm optical standing wave nearly resonant with the ^{3}P_{0}→^{3}D_{1} transition creates a spatially periodic light shift of the ^{3}P_{0} clock state. Following excitation on the ultranarrow clock transition, we observe Sisyphus cooling in this potential, as the light shift is correlated with excitation to ^{3}D_{1} and subsequent spontaneous decay to the ^{1}S_{0} ground state. We observe that cooling enhances the loading efficiency of atoms into a 759-nm magic-wavelength one-dimensional (1D) optical lattice, as compared to standard Doppler cooling on the ^{1}S_{0}→^{3}P_{1} transition. Sisyphus cooling yields temperatures below 200 nK in the weakly confined, transverse dimensions of the 1D optical lattice. These lower temperatures improve optical lattice clocks by facilitating the use of shallow lattices with reduced light shifts while retaining large atom numbers to reduce the quantum projection noise. This Sisyphus cooling can be pulsed or continuous and is applicable to a range of quantum metrology applications.

Engineering acyclovir-induced RNA nanodevices for reversible and tunable control of aptamer function.

Small molecule-regulated RNA devices have the potential to modulate diverse aspects of cellular function, but the small molecules used to date have potential toxicities limiting their use in cells. Here we describe a method for creating drug-regulated RNA nanodevices (RNs) using acyclovir, a biologically compatible small molecule with minimal toxicity. Our modular approach involves a scaffold comprising a central F30 three-way junction, an integrated acyclovir aptamer on the input arm, and a variable effector-binding aptamer on the output arm. This design allows for the rapid engineering of acyclovir-regulated RNs, facilitating temporal, tunable, and reversible control of intracellular aptamers. We demonstrate the control of the Broccoli aptamer and the iron-responsive element (IRE) by acyclovir. Regulating the IRE with acyclovir enables precise control over iron-regulatory protein (IRP) sequestration, consequently promoting the inhibition of ferroptosis. Overall, the method described here provides a platform for transforming aptamers into acyclovir-controllable antagonists against physiologic target proteins.

3D printed heterogeneous paediatric head and adult thorax phantoms for linear accelerator radiotherapy quality assurance: from fabrication to treatment delivery.

Objective. This study aims to design and fabricate a 3D printed heterogeneous paediatric head phantom and to customize a thorax phantom for radiotherapy dosimetry.Approach. This study designed, fabricated, and tested 3D printed radiotherapy phantoms that can simulate soft tissue, lung, brain, and bone. Various polymers were considered in designing the phantoms. Polylactic acid+, nylon, and plaster were used in simulating different tissue equivalence. Dimensional accuracy, and CT number were investigated. The phantoms were subjected to a complete radiotherapy clinical workflow. Several treatment plans were delivered in both the head and the thorax phantom from a simple single 6 MV beam, parallel opposed beams, and five-field intensity modulated radiotherapy (IMRT) beams. Dose measurements using an ionization chamber and radiochromic films were compared with the calculated doses of the Varian Eclipse treatment planning system (TPS).Main results. The fabricated heterogeneous phantoms represent paediatric human head and adult thorax based on its radiation attenuation and anatomy. The measured CT number ranges are within -786.23 ± 10.55, 0.98 ± 3.86, 129.51 ± 12.83, and 651.14 ± 47.76 HU for lung, water/brain, soft tissue, and bone, respectively. It has a good radiological imaging visual similarity relative to a real human head and thorax depicting soft tissue, lung, bone, and brain. The accumulated dose readings for both conformal radiotherapy and IMRT match with the TPS calculated dose within ±2% and ±4% for head and thorax phantom, respectively. The mean pass rate for all the plans delivered are above 90% for gamma analysis criterion of 3%/3 mm.Significance and conclusion. The fabricated heterogeneous paediatric head and thorax phantoms are useful in Linac end-to-end radiotherapy quality assurance based on its CT image and measured radiation dose. The manufacturing and dosimetry workflow of this study can be utilized by other institutions for dosimetry and trainings.

Viability of shear wave elastography to predict mechanical/ultimate failure in the anterolateral and medial collateral ligaments of the knee.

The purpose of this study was (1) to determine the utility of shear wave elastography as a predictor for the mechanical failure of superficial knee ligaments and (2) to determine the viability of shear wave elastography to assess injury risk potential. Our hypothesis was that shear wave elastography measurements of the anterolateral ligament and medial collateral ligament would directly correlate with the material properties and the mechanical failure of the ligament, serving as a prognostic measurement for injury risk. 8 cadaveric specimens were acquired, and tissue stiffness for the anterolateral ligament and medial collateral ligament were evaluated with shear wave elastography. The anterolateral ligament and medial collateral ligament were dissected and isolated for unilateral mechanical failure testing. Ultimate failure testing was performed at 100 % strain per second after 50 cycles of 3 % strain viscoelastic conditioning. Each specimen was assessed for load, displacement, and surface strain throughout failure testing. Rate of force, rate of strain development, and Young's modulus were calculated from these variables. Shear wave elastography stiffness for the anterolateral ligament correlated with mean longitudinal anterolateral ligament strain at failure (R2 = 0.853; P<0.05). Medial collateral ligament shear wave elastography calculated modulus was significantly greater than the anterolateral ligament shear wave elastography calculated modulus. Shear wave elastography currently offers limited reliability in the prediction of mechanical performance of superficial knee ligaments. The utility of shear wave elastography assessment for injury risk potential remains undetermined.

Environmental impacts of selected metal cations for phosphorus capture in natural waters: A synthesis.

Cultural eutrophication from excessive human-related nutrient (phosphorus, P, and nitrogen, N) inputs is a major concern for water quality. Because P historically was regarded as the critical nutrient in controlling noxious algal/plant growth, P became the focus of "capturing" techniques, with emphasis on removal performance rather than environmental impacts. Here, we synthesize a literature review of known environmental effects linked to use of metal-cation-based P-capturing materials under eutrophic conditions in freshwaters. P-capturing materials with functional cations based on aluminum (Al), calcium (Ca), iron (Fe), lanthanum (La), and magnesium (Mg) were reviewed in terms of their ecotoxicity, persistence, and bioaccumulation-standard criteria used to evaluate environmental risks of chemical substances. We found very few published studies on environmental impacts of metal-cation-based P-capturing materials under eutrophic conditions. Available reports indicated that environmental effects vary depending on the selected material, dose, target organism(s), and experimental conditions. The Al-based materials had the potential to negatively impact various biota; several Fe-based materials caused various levels of toxicity in a limited group of aquatic organisms; La-based materials can bioaccumulate and some were linked to various harmful effects on biota; and Mg-based materials also adversely affected various organisms. The limited number of published studies underscores the need for further research to characterize the environmental impacts of these materials. Results can be used to guide future work and can assist resource managers in sustainable management strategies. Among various research needs, future assessments should assess the impacts of chronic exposures on sensitive species under realistic field conditions in eutrophic waters.

Studies with Direct Industry Affiliation are More Likely to Report Positive Results in Randomized Controlled Trials for Platelet-Rich Plasma Use in Rotator Cuff Pathology: A Systematic Review.

PURPOSE: To perform a systematic review to evaluate the effect of industry affiliation on the outcomes of randomized controlled trials (RCTs) for platelet-rich plasma (PRP) injections in rotator cuff tears. METHODS: PubMed, SPORTdiscus, and Scopus databases were searched from 2010 to the present for terms "rotator cuff" and "platelet-rich plasma." Inclusion criteria were RCTs comparing PRP to controls for treatment of rotator cuff tears and exclusion criteria were systematic reviews, meta-analyses, case reports, cohort studies, basic science studies, other level 3 and below studies, and studies not in English. Degree of industry affiliation was categorized into three groups: direct, indirect, and not affiliated. Direct affiliation required the study or its authors to receive financial support from the company manufacturing the devices used in the study to prepare or administer PRP. Indirect affiliation required financial association with a different company that produces or administers PRP than the one used in the study. Studies were classified as favorable if study outcomes achieved significance (p < 0.05) of PRP over the control, or analogous if there was no statistical significance between PRP and control. Data was analyzed using chi-squared and fisher's exact tests. RESULTS: Of the 47 studies selected for analysis, 8 (17.0%) had no direct industry affiliation, 9 (19.1%) indirect affiliation and 30 (63.8%) no industry affiliation. 22 (46.8%) studies reported favorable results with PRP compared to the control and 25 (53.2%) showed analogous results between PRP and control. Degree of industry affiliation was significantly associated with increased likelihood of reporting favorable study outcomes (p = 0.041). Directly affiliated studies had a significantly increased likelihood of reporting favorable results (p = 0.024) compared to indirectly affiliated. CONCLUSIONS: Studies that used PRP produced by companies that directly fund the study or were financially affiliated with the authors were significantly more likely to report favorable results. LEVEL OF EVIDENCE: Systematic review of Level I and II studies.

Aspergillus fumigatus conidial surface-associated proteome reveals factors for fungal evasion and host immunity modulation.

Aspergillus fumigatus causes aspergillosis and relies on asexual spores (conidia) for initiating host infection. There is scarce information about A. fumigatus proteins involved in fungal evasion and host immunity modulation. Here we analysed the conidial surface proteome of A. fumigatus, two closely related non-pathogenic species, Aspergillus fischeri and Aspergillus oerlinghausenensis, as well as pathogenic Aspergillus lentulus, to identify such proteins. After identifying 62 proteins exclusively detected on the A. fumigatus conidial surface, we assessed null mutants for 42 genes encoding these proteins. Deletion of 33 of these genes altered susceptibility to macrophage, epithelial cells and cytokine production. Notably, a gene that encodes a putative glycosylasparaginase, modulating levels of the host proinflammatory cytokine IL-1ß, is important for infection in an immunocompetent murine model of fungal disease. These results suggest that A. fumigatus conidial surface proteins are important for evasion and modulation of the immune response at the onset of fungal infection.

Assessment of an Artificial Intelligence Tool for Estimating Left Ventricular Ejection Fraction in Echocardiograms from Apical and Parasternal Long-Axis Views.

This work aims to evaluate the performance of a new artificial intelligence tool (ExoAI) to compute the left ventricular ejection fraction (LVEF) in echocardiograms of the apical and parasternal long axis (PLAX) views. We retrospectively gathered echocardiograms from 441 individual patients (70% male, age: 67.3 ± 15.3, weight: 87.7 ± 25.4, BMI: 29.5 ± 7.4) and computed the ejection fraction in each echocardiogram using the ExoAI algorithm. We compared its performance against the ejection fraction from the clinical report. ExoAI achieved a root mean squared error of 7.58% in A2C, 7.45% in A4C, and 7.29% in PLAX, and correlations of 0.79, 0.75, and 0.89, respectively. As for the detection of low EF values (EF < 50%), ExoAI achieved an accuracy of 83% in A2C, 80% in A4C, and 91% in PLAX. Our results suggest that ExoAI effectively estimates the LVEF and it is an effective tool for estimating abnormal ejection fraction values (EF < 50%). Importantly, the PLAX view allows for the estimation of the ejection fraction when it is not feasible to acquire apical views (e.g., in ICU settings where it is not possible to move the patient to obtain an apical scan).

Automated Measurement of Cerebral Hemorrhagic Contusions and Outcomes After Traumatic Brain Injury in the TRACK-TBI Study.

Importance: Because withdrawal of life-sustaining therapy based on perceived poor prognosis is the most common cause of death after moderate or severe traumatic brain injury (TBI), the accuracy of clinical prognoses is directly associated with mortality. Although the location of brain injury is known to be important for determining recovery potential after TBI, the best available prognostic models, such as the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) score, do not currently incorporate brain injury location. Objective: To test whether automated measurement of cerebral hemorrhagic contusion size and location is associated with improved prognostic performance of the IMPACT score. Design, Setting, and Participants: This prognostic cohort study was performed in 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018. Adult participants aged 17 years or older from the US-based Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study with moderate or severe TBI (Glasgow Coma Scale score 3-12) and contusions detected on brain computed tomography (CT) scans were included. The data analysis was performed between January 2023 and February 2024. Exposures: Labeled contusions detected on CT scans using Brain Lesion Analysis and Segmentation Tool for Computed Tomography (BLAST-CT), a validated artificial intelligence algorithm. Main Outcome and Measure: The primary outcome was a Glasgow Outcome Scale-Extended (GOSE) score of 4 or less at 6 months after injury. Whether frontal or temporal lobe contusion volumes improved the performance of the IMPACT score was tested using logistic regression and area under the receiver operating characteristic curve comparisons. Sparse canonical correlation analysis was used to generate a disability heat map to visualize the strongest brainwide associations with outcomes. Results: The cohort included 291 patients with moderate or severe TBI and contusions (mean [SD] age, 42 [18] years; 221 [76%] male; median [IQR] emergency department arrival Glasgow Coma Scale score, 5 [3-10]). Only temporal contusion volumes improved the discrimination of the IMPACT score (area under the receiver operating characteristic curve, 0.86 vs 0.84; P = .03). The data-derived disability heat map of contusion locations showed that the strongest association with unfavorable outcomes was within the bilateral temporal and medial frontal lobes. Conclusions and Relevance: These findings suggest that CT-based automated contusion measurement may be an immediately translatable strategy for improving TBI prognostic models.

The Literature that Commercial Insurance Payers Use to Substantiate Knee Osteochondral Allograft Policies Are of a Low Level of Evidence.

OBJECTIVE: The purpose of this study is to analyze how the largest insurance companies support their medical necessity policies regarding osteochondral allograft transplantation (OCA) and to determine whether the literature they cite in their policies is of a high level of evidence (LOE). DESIGN: The 10 largest national health insurance companies were identified. Each payer was contacted via phone or email to obtain their coverage policy regarding OCA. For each policy, the medical necessity criteria were recorded, and all cited references were screened. For all references applicable to OCA, the LOE was recorded, and each reference was screened to determine whether they mentioned the specific criteria reported in the policies. RESULTS: The medical policies for 6 of the 10 national health insurance companies were identified. These 6 policies cited a collective total of 102 applicable references. Most of these studies were an LOE of IV (n = 58, 56.9%) and an LOE of V (n = 18, 17.6%). There were similarities amongst the medical necessity criteria between different commercial payers; however, most criteria were poorly supported by the cited literature. CONCLUSIONS: Our results demonstrate that commercial insurance companies utilize studies that are of a low LOE when justifying their medical necessity criteria. Moreover, these cited studies infrequently support or mention the commercial payers' criteria. Future studies should continue to explore how well-supported insurance policies are with the goal of potentially increasing access and authorization for well-supported treatment modalities.

Inhomogeneous terminators on the exoplanet WASP-39 b.

Transmission spectroscopy has been a workhorse technique used over the past two decades to constrain the physical and chemical properties of exoplanet atmospheres1-5. One of its classical key assumptions is that the portion of the atmosphere it probes-the terminator region-is homogeneous. Several works from the past decade, however, have put this into question for highly irradiated, hot (Teq ≳ 1,000 K) gas giant exoplanets, both empirically6-10 and through three-dimensional modelling11-17. While models have predicted clear differences between the evening (day-to-night) and morning (night-to-day) terminators, direct morning and evening transmission spectra in a wide wavelength range have not been reported for an exoplanet so far. Under the assumption of precise and accurate orbital parameters for the exoplanet WASP-39 b, here we report the detection of inhomogeneous terminators on WASP-39 b, which has allowed us to retrieve its morning and evening transmission spectra in the near-infrared (2-5 µm) using the James Webb Space Telescope. We have observed larger transit depths in the evening, which are, on average, 405 ± 88 ppm larger than the morning ones, and also have qualitatively larger features than the morning spectrum. The spectra are best explained by models in which the evening terminator is hotter than the morning terminator by 17 7 - 57 + 65 K, with both terminators having C/O ratios consistent with solar. General circulation models predict temperature differences broadly consistent with the above value and point towards a cloudy morning terminator and a clearer evening terminator.

Imaging of Juvenile Idiopathic Arthritis.

MRI, ultrasound, and conventional radiography each play distinct roles in the evaluation of juvenile idiopathic arthritis (JIA), with MRI being the preferred imaging modality of choice for assessing both inflammatory and destructive changes. These various imaging modalities provide valuable insights into JIA in pediatric patients. However, challenges persist in terms of achieving precision, ensuring validity, and distinguishing between pathologic findings and normal anatomic variations. Establishing normal reference values and implementing scoring systems can aid in the precise evaluation of disease activity and provide information to assist treatment decisions for children with JIA. Ongoing advancements in imaging techniques and standardization initiatives aim to bolster the accuracy of JIA diagnosis and assessment, ultimately leading to enhanced patient care and treatment outcomes.

Classification Criteria for Axial Disease in Youth with Juvenile Spondyloarthritis.

OBJECTIVES: To develop and validate classification criteria for axial disease in youth with juvenile spondyloarthritis (SpA; AxJSpA). METHODS: This international initiative consisted of four phases: 1) Item generation; 2) Item reduction; 3) Criteria development; and 4) Validation of the AxJSpA criteria by an independent team of experts in an internationally representative Validation cohort. RESULTS: These criteria are intended to be used on youth with a physician diagnosis of juvenile SpA and for whom axial disease is suspected. Item generation consisted of a systematic literature review and a free-listing exercise using input from international physicians and collectively resulted in 108 items. After the item reduction exercise and expert panel input, 37 items remained for further consideration. The final AxJSpA criteria domains included: imaging: active inflammation, imaging: structural lesions, pain chronicity, pain pattern, pain location, stiffness, and genetics. The most heavily weighted domains were active inflammation and structural lesions on imaging. Imaging typical of sacroiliitis was deemed necessary, but not sufficient, to classify a youth with AxJSpA. The threshold for classification of AxJSpA was a score of ≥55 (out of 100). When tested in the validation data set, the final criteria had a specificity of 97.5% (95% CI: 91.4-99.7), sensitivity of 64.3% (95% CI: 54.9-73.1) and Area Under the Receiver Operating Characteristic (AUROC) curve of 0.81 (95% CI: 0.76-0.86). CONCLUSIONS: The new AxJSpA classification criteria require an entry criterion, physician diagnosis of juvenile SpA, and include seven weighted domains. The AxJSpA classification criteria are validated and designed to identify participants for research studies.

Acute Inpatient Rehabilitation Functional Outcomes and Disposition After Liver Transplant.

Objective: To describe the outcomes (change in functional independence and discharge disposition) of patients who after liver transplantation received acute inpatient rehabilitation in a freestanding rehabilitation hospital. Design: A retrospective chart review was conducted of patients admitted to an acute inpatient rehabilitation hospital within 6 months of undergoing liver transplantation between January 2014 and December 2018. Change in function from rehabilitation admission to discharge was measured using FIM Change and FIM Efficiency. Setting: A freestanding rehabilitation hospital. Participants: 107 patients who underwent acute inpatient rehabilitation at a freestanding rehabilitation hospital within 6 months after liver transplantation who met inclusion criteria (N=107). Most were men (71.96%), and the mean age of the patient population was 62.15 years. Interventions: Acute inpatient rehabilitation consisting of at least 3 hours of therapy 5 days a week split between physical therapy, occupational therapy, and speech language pathology services. Main Outcome Measure: FIM Change, FIM Efficiency, Discharge Disposition. Results: Participants were found to have statistically significant positive FIM Change (P<.00001) and FIM Efficiency (P<.00001). The mean FIM Change and Efficiency were 35.7±11.8 and 2.4±1.0, respectively. 83.2% (n = 89) were ultimately discharged to the community. Conclusion: Acute inpatient rehabilitation provides patients who have received a liver transplant with the opportunity to measurably improve their function and independence, with most patients being able to return home.

Impacts of ocean warming on fish size reductions on the world's hottest coral reefs.

The impact of ocean warming on fish and fisheries is vigorously debated. Leading theories project limited adaptive capacity of tropical fishes and 14-39% size reductions by 2050 due to mass-scaling limitations of oxygen supply in larger individuals. Using the world's hottest coral reefs in the Persian/Arabian Gulf as a natural laboratory for ocean warming - where species have survived >35.0 °C summer temperatures for over 6000 years and are 14-40% smaller at maximum size compared to cooler locations - we identified two adaptive pathways that enhance survival at elevated temperatures across 10 metabolic and swimming performance metrics. Comparing Lutjanus ehrenbergii and Scolopsis ghanam from reefs both inside and outside the Persian/Arabian Gulf across temperatures of 27.0 °C, 31.5 °C and 35.5 °C, we reveal that these species show a lower-than-expected rise in basal metabolic demands and a right-shifted thermal window, which aids in maintaining oxygen supply and aerobic performance to 35.5 °C. Importantly, our findings challenge traditional oxygen-limitation theories, suggesting a mismatch in energy acquisition and demand as the primary driver of size reductions. Our data support a modified resource-acquisition theory to explain how ocean warming leads to species-specific size reductions and why smaller individuals are evolutionarily favored under elevated temperatures.