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Simple Summary: Roughly 25% of non-small cell lung cancer (NSCLC) patients subsequently experience isolated locoregional recurrence following definitive radiation therapy (RT). For these scenarios, thoracic reirradiation (re-RT) has become an increasingly common consideration, with improved feasibility due to technological advancements that have made it safer to deliver high doses of RT in the retreatment setting. Proton beam therapy (PBT) is an attractive choice for re-RT due to its ability to spare radiation to adjacent previously treated normal tissues. Here, we evaluate outcomes with PBT for the definitive re-RT of recurrent NSCLC within the previously irradiated thorax. Background/Objectives: This retrospective study evaluates outcomes of 66 patients who underwent reirradiation (re-RT) with proton beam therapy (PBT) for recurrent non-small cell lung cancer. Methods: Toxicity was scored via the CTCAE v5.0, and outcomes estimated using the Kaplan–Meier method, with associations evaluated via Cox proportional hazards and logistic regression analyses. Results: Patients were treated to a median re-RT prescription of 66 Gy/33 fxs (BED10 = 79 Gy; IQR: 71–84 Gy) at an interval of 1.4 years from prior RT. Half (50%) received concurrent chemotherapy. At 14 months follow-up, the median OS and PFS were 5 months (95%CI: 13–17) and 12.5 months (95%CI: 10–15), respectively. On multivariable analysis, a higher RT dose (BED10 > 70 Gy) [HR0.37; 95%CI: 0.20–0.68, p = 0.001] and concurrent chemotherapy (HR0.48; 95%CI: 0.28–0.81, p = 0.007) were associated with improved PFS, while treatment site overlap was adversely associated (HR1.78; 95%CI: 1.05–3.02, p = 0.031). The median PFS for definitive RT with concurrent chemotherapy (n = 28), definitive RT alone (BED10 > 70 Gy) [n = 22], and lower prescription RT (BED10 < 70 Gy) [n = 16] was 15.5 months (95%CI: 7.3–23.7), 14.1 months (95%CI: 10.9–17.3), and 3.3 months (95%CI: 0–12.3), respectively (log-rank, p = 0.006), with corresponding 2-year estimates of 37% (±9), 18% (±8), and 12.5% (±8), respectively. The incidence of Grade 3+ toxicity was 10.5% (6% pulmonary; 3% esophageal; and 1.5% skin), including one Grade 4 bronchopulmonary hemorrhage but no Grade 5 events. Cases with central site overlap had higher composite Dmax to the esophagus (median 87 Gy [IQR:77–90]), great vessels (median 120 Gy [IQR:110–138]), and proximal bronchial tree (median 120 Gy [IQR:110–138]) as compared to other cases (p ≤ 0.001 for all). However, no significant associations were identified with Grade 3+ events. Conclusions: Thoracic re-RT with PBT is an option for recurrent NSCLC with acceptable outcomes and toxicity for select patients. When feasible, higher prescription doses (BED10 > 70 Gy) should be delivered for definitive intent, and concurrent chemotherapy may benefit individual cases. [ABSTRACT FROM AUTHOR]

Background: Underrepresented minority groups (URMs) in surgery are not significantly increasing despite evidence suggesting that diversity in health care providers leads to excellent patient outcomes and care. Efforts to increase URM representation in surgical residency programs are essential for addressing disparities and improving health care delivery. Methods: This retrospective study outlines a three-phase strategy implemented at a large academic-affiliated hospital to increase URM representation in its general surgery residency program. The strategy encompassed interview selection with a holistic review and implicit bias training for interviewers, modification of the interview scoring rubric, and post-interview recruitment efforts, including a virtual second look event for URM applicants. Results: Following the implementation of these strategies, the URM match rate improved from 0 to 33.3% in the first year and was sustained at 33.3% in the subsequent year. Consequently, the representation of URMs in the residency program rose from 6.7% before our intervention to 13.3% afterwards. Discussion: This structured approach successfully increased URM representation in a surgical residency program, affirming the success of targeted recruitment strategies. By promoting a diverse and inclusive environment, the program better reflects the community it serves, with aims at improved patient care and patient satisfaction. [ABSTRACT FROM AUTHOR]

Background: Regulatory applications for cell therapy face more objections compared to conventional small molecule or biological drugs, leading to delays in market approval and clinical adoption. Increased regulatory objections frequently relate to issues regarding preclinical evidence, such as experimental design of animal studies, selection of animal models, endpoints, and determination of mechanism of action. Synthesis and clarification of the preclinical evidence necessary to demonstrate treatment efficacy and advance into early-phase clinical trials is needed to help researchers avoid regulatory objections. Methods: We conducted a scoping review in which we searched repositories of the International Council for Harmonisation and all national member organizations (N = 38) for documents related to preclinical studies of cell therapies. Active guidance documents related to cell therapy were included, with no restrictions based on the year or language of publication. Data extraction was conducted in duplicate with conflicts resolved through consensus discussion. Results: From 1215 identified documents, a total of 182 were included and analyzed, with 71% originating from ten major regulatory agencies. The most prevalent preclinical item addressed was the mechanism of action (n = 161, 88% of documents), underscoring its importance in bridging preclinical findings to clinical application. Most documents (n = 140, 77%) emphasized the importance of using clinically relevant preclinical models, though specific recommendations on models of disease were less common (n = 81, 45%). Selection of clinically relevant intervention parameters (n = 136, 75%) and outcome measures (n = 121, 66%) were also frequently recommended, but selection of relevant comparator groups appeared less frequently (n = 35, 19%). Furthermore, robust study design elements such as randomization and blinding were less frequently recommended, appearing in 31% of documents (n = 57). Comparison with clinical trial guidance revealed a significant gap in the rigor of study design recommendations for preclinical research. Conclusions: Regulatory guidance for preclinical efficacy studies often recommends a strong emphasis on the clinical relevance of animal models, intervention parameters, outcomes, and mechanism of action. Incorporating these recommendations into early preclinical studies should improve the acceptability of preclinical evidence for approval by the relevant national regulators and can be used as a guide to ensure that all evidence that regulators say they expect is efficiently assembled into new clinical trial applications. [ABSTRACT FROM AUTHOR]

Detailed chemical kinetic mechanisms are necessary for resolving many important chemical processes. As the chemistry of smaller molecules has become better grounded and quantum chemistry calculations have become cheaper, kineticists have become interested in constructing progressively larger kinetic mechanisms to model increasingly complex chemical processes. These large kinetic mechanisms prove incredibly difficult to refine and time‐consuming to interpret. Traditional sensitivity analysis on a large mechanism can range from inconvenient to practically impossible without special techniques to reduce the computational cost. We first present a new time‐local sensitivity analysis we term transitory sensitivity analysis. Transitory sensitivity analysis is demonstrated in an example to accurately identify traditionally sensitive reactions at an 18,000x speed up over traditional sensitivities. By fusing transitory sensitivity analysis with more traditional time‐local branching, pathway, and cluster analyses, we develop an algorithm for efficient automatic mechanism analysis. This automatic mechanism analysis at a time point is able to identify the reactions a target is most sensitive to using transitory sensitivity analysis and then propose hypotheses why the reaction might be sensitive using branching, pathway, and cluster analyses. We implement these algorithms within the reaction mechanism simulator (RMS) package, which enables us to report the automatic mechanism analysis results in highly readable text formats and in molecular flux diagrams. [ABSTRACT FROM AUTHOR]

Background People with HIV (PWH) have lower exercise capacity than peers without HIV, which may be explained by chronotropic incompetence, the inability to increase heart rate during exercise. Methods The Exercise for Healthy Aging Study included adults aged 50 to 75 years with and without HIV. Participants completed 12 weeks of moderate-intensity exercise, before randomization to moderate or high intensity for 12 additional weeks. We compared adjusted heart rate reserve (AHRR; chronotropic incompetence <80%) on cardiopulmonary exercise testing by HIV serostatus and change from baseline to 12 and 24 weeks using mixed effects models. Results Among 32 PWH and 37 controls (median age, 56 years; 7% female), 28% of PWH vs 11% of controls had chronotropic incompetence at baseline (P =.067). AHRR was lower among PWH (91% vs 101%; difference, 10%; 95% CI, 1.9%–18.9%; P =.02). At week 12, AHRR normalized among PWH (+8%; 95% CI, 4%–11%; P <.001) and was sustained at week 24 (+5%; 95% CI, 1%–9%; P =.008) versus no change among controls (95% CI, −4% to 4%; P =.95; interaction P =.004). After 24 weeks of exercise, 15% of PWH and 10% of controls had chronotropic incompetence (P =.70). Conclusions Chronotropic incompetence contributes to reduced exercise capacity among PWH and improves with exercise training. [ABSTRACT FROM AUTHOR]

Background: Carbon dioxide is a potent cerebral vasodilator that may influence outcomes after ischemic stroke. The objective of this study was to investigate the effect of intraprocedural mean end-tidal CO2 (ETCO2) levels on core infarct expansion and neurologic outcome following thrombectomy for anterior circulation ischemic stroke. Methods: A retrospective review was conducted of consecutive patients from March 2020 to June 2021 who underwent mechanical thrombectomy for acute anterior circulation ischemic stroke under general anesthesia and achieved successful recanalization (Thrombolysis in Cerebral Infarction [TICI] ≥ 2b). Only patients with CT perfusion, procedural ETCO2, and postoperative MRI data were included. Segmentation software was used for multi-parametric image analysis. Normocarbia defined as mean ETCO2 of 35 mmHg was used to dichotomize subjects. Univariate and multivariate statistics were applied. Results: Fifty-eight patients met criteria for analysis. Of these, 44 had TICI 3 recanalization, 9 had TICI 2c, and 5 had TICI 2b. Within this combined recanalization group, patients with mean ETCO2 > 35 had significantly higher rates of functional independence at 90 days. Although patients tended to salvage more penumbra and experience smaller final infarcts when ETCO2 exceeded 35 mmHg, this did not reach statistical significance. Conclusions: Stroke patients who underwent successful thrombectomy with general anesthesia achieved higher rates of functional independence when procedural ETCO2 exceeded 35 mmHg. Further studies to confirm this effect and investigate optimal ETCO2 parameters should be considered. [ABSTRACT FROM AUTHOR]

To advance environmentally friendly technologies in the aquaculture of Atractoscion nobilis, and simultaneously to diversify seafood production, a 79-day trial was conducted to assess the performance of Ulva lactuca and Devaleraea mollis cultured in the effluent from A. nobilis in a land-based integrated multi-trophic aquaculture (IMTA) system in southern California, USA. Water quality and performance of macroalgae were measured weekly. The impacted factors on the growth of macroalgae and nutrient uptake rate of macroalgae were assessed. The specific growth rate of juvenile A. nobilis was 0.47–0.52%/d. Total ammonia nitrogen in effluents of A. nobilis tanks ranged from 0.03 to 0.19 mg/L. Ulva lactuca and D. mollis achieved an average productivity of 24.53 and 14.40 g dry weight (DW)/m2/d. The average nitrogen content was 3.48 and 4.89% DW, and accordingly, the average nitrogen uptake rate was 0.88 and 0.71 g/m2/d, respectively. Temperature and nutrient concentration were key factors impacting macroalgae growth, and light intensity also impacted the growth of D. mollis. The high protein content of U. lactuca and D. mollis would make them good for use as human or animal food, or for use in other industries. Research on the interaction effects between seawater exchange rates and aeration rates on the performance and nutrient uptake rates of macroalgae will be conducted in future studies. [ABSTRACT FROM AUTHOR]

The choice between the Schrödinger and Heisenberg pictures can significantly impact the computational resources needed to solve a problem, even though they are equivalent formulations of quantum mechanics. Here, we present a method for analysing Bosonic quantum circuits based on the Heisenberg picture which allows, under certain conditions, a useful factoring of the evolution into signal and noise contributions, similar way to what can be achieved with classical communication systems. We provide examples which suggest that this approach may be particularly useful in analysing quantum computing systems based on the Gottesman–Kitaev–Preskill (GKP) qubits. [ABSTRACT FROM AUTHOR]

The article focuses on the necessity of transdisciplinary collaboration and data sharing to enhance athlete health and human performance in elite sports. Topics include the importance of integrating diverse expertise, the role of data analytics in performance improvement, and strategies for fostering effective teamwork across disciplines.

We are already experiencing the rapid pace of environmental perturbation in the Anthropocene, necessitating the development of new tools and techniques for measuring changes in ecosystem dynamics. Sentinel species, from birds to invertebrates, have been used to provide insights into ecosystem function, as leading indicators of risk to human health and as harbingers of future change, with implications for ecosystem structure and function. Here, we offer an update to previous research identifying marine top predators as indicators of ecosystem shifts and examine terrestrial sentinels and the latest research on sentinels of pollution and human health. Using ecosystem sentinels enables rapid response and adaptation to ecosystem variability and environmental change in part because they may be easier to observe and in part because they may serve as leading indicators of ecosystem disruption. While there may not be a given taxon that is best suited as sentinels, we highlight how to select the most effective sentinels, including examples of when sentinel species have been incorporated into management. Choosing a suite of appropriate sentinels both will give insight into ecosystem processes and can help manage changing ecosystems into the future. [ABSTRACT FROM AUTHOR]

Human APOBEC single-strand (ss) specific DNA and RNA cytidine deaminases change cytosines to uracils (U's) and function in antiviral innate immunity and RNA editing and can cause hypermutation in chromosomes. The resulting U's can be directly replicated, resulting in C to T mutations, or U–DNA glycosylase can convert the U's to abasic (AP) sites which are then fixed as C to T or C to G mutations by translesion DNA polymerases. We noticed that in yeast and in human cancers, contributions of C to T and C to G mutations depend on the origin of ssDNA mutagenized by APOBECs. Since ssDNA in eukaryotic genomes readily binds to replication protein A (RPA) we asked if RPA could affect APOBEC-induced mutation spectrum in yeast. For that purpose, we expressed human APOBECs in the wild-type (WT) yeast and in strains carrying a hypomorph mutation rfa1-t33 in the large RPA subunit. We confirmed that the rfa1-t33 allele can facilitate mutagenesis by APOBECs. We also found that the rfa1-t33 mutation changed the ratio of APOBEC3A-induced T to C and T to G mutations in replicating yeast to resemble a ratio observed in long persistent ssDNA in yeast and in cancers. We present the data suggesting that RPA may shield APOBEC formed U's in ssDNA from Ung1, thereby facilitating C to T mutagenesis through the accurate copying of U's by replicative DNA polymerases. Unexpectedly, we also found that for U's shielded from Ung1 by WT RPA, the mutagenic outcome is reduced in the presence of translesion DNA polymerase zeta. [ABSTRACT FROM AUTHOR]

The article describes three scenarios in the diagnosis of spinal cerebrospinal fluid (CSF) leaks that require advanced clinical reasoning. These include suspected CSF leak but misdiagnosed and seems to be otherwise consistent with spontaneous hypotension and post-dural puncture headache, the presence of CSF leak but with change symptoms such as cerebral venous thrombosis, and treated CSF leak but with retention of symptoms or recurrence.

The neutrino-driven wind cooling phase of proto-neutron stars (PNSs) follows successful supernovae. Wind models without magnetic fields or rotation fail to achieve the necessary conditions for production of the third r -process peak, but robustly produce a weak r- process in neutron-rich winds. Using 2D magnetohydrodynamic simulations with magnetar-strength magnetic fields and rotation, we show that the PNS rotation rate significantly affects the thermodynamic conditions of the wind. We show that high-entropy material is quasiperiodically ejected from the closed zone of the PNS magnetosphere with the required thermodynamic conditions to produce heavy elements. We show that maximum entropy S of the material ejected depends systematically on the magnetar spin period P ⋆ and scales as S ∝ P ⋆ − 5 / 6 for sufficiently rapid rotation. We present results from simulations at a constant neutrino luminosity representative of ∼1–2 s after the onset of cooling for P ⋆ ranging from 5–200 ms and a few simulations with evolving neutrino luminosity where we follow the evolution of the magnetar wind until 10–14 s after the onset of cooling. We estimate at magnetar polar magnetic field strength B 0 = 3 × 1015 G and 1015 G that neutron-rich magnetar winds can, respectively, produce at least ∼1–5 × 10−5 M ⊙ and ∼1–4 × 10−7 M ⊙ of material with the required parameters for synthesis of the third r -process peak, within 1–2 s and 10 s, respectively, in that order after the onset of cooling. We show that proton-rich magnetar winds can have favorable conditions for production of p- nuclei, even at a modest B 0 = 5 × 1014 G. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Spearmint and peppermint teas are widely consumed around the world for their flavor and therapeutic properties. Dynamic headspace sampling (HS) coupled to gas chromatography/mass spectrometry (GC–MS) with principal component analysis (PCA) of ‘fingerprint’ volatile profiles were used to investigate 27 spearmint and peppermint teas. Additionally, comparisons between mint teas were undertaken with an electronic nose (enose).Twenty compounds, all previously known in the literature, were identified using HS–GC–MS. PCA found distinct differences between the fingerprint volatile profiles of spearmint, peppermint and spearmint/peppermint combination teas. HS–GC–MS analysis performed with an achiral column allowed faster processing time and yielded tighter clustering of PCA tea groups than the analysis which used a chiral column. Two spearmint outliers were detected. One showed a high degree of variation in volatile composition and a second wholly overlapped with the peppermint PCA grouping. Enose analysis separated all treatments with no overlaps.Characterizing the volatile fingerprints of mint teas is critical to quality control for this valuable agricultural product. The results of this study show that fingerprint volatile profiles and enose analysis of mint teas are distinctive and could be used to rapidly identify unknown samples. With specific volatile profiles identified for each tea, samples could be tested in the laboratory, or potentially on a farm or along the supply chain, to confirm the provenance and authenticity of mint food or beverage commodities. © 2024 Society of Chemical Industry. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA. [ABSTRACT FROM AUTHOR]

AbstractDiglycolamide (DGA) resin, a product produced by Eichrom Technologies, Inc. employs TODGA (N,N,N′,N′-tetraoctyldiglycolamide) as the active extractant, which will be used by Savannah River National Laboratory to extract trivalent actinides and lanthanides from dissolved irradiated Mark-18A targets. The final form of the extracted material will be an oxide suitable for shipment. A two-step process was developed and validated for the direct recovery of actinides and lanthanides loaded on I-grade DGA resin as nitrates by thermally drying and decomposing resin loaded with Nd(III), a surrogate for trivalent actinides and lanthanides, under inert conditions followed by calcining the resultant residue in air to provide an oxide product. A stepwise heating profile up to 385°C under argon gas flow resulted in 85% to 89% mass loss during the resin drying and decomposition step, and calcination of the resultant Nd-loaded resin residue provided an overall material mass loss of ≥ 98%. Recoveries from resin saturated with Nd(III) from 7 M and 0.35 M nitric acid subjected to this process were 30.7 mg and 27.6 mg Nd/g dry resin, respectively, representing an average of 96.1% of Nd retained in the resin bed. [ABSTRACT FROM AUTHOR]

Communication in the form of nonverbal, social vocalization, or crying is evolutionary conserved in mammals and is impaired early in human infants that are later diagnosed with autism spectrum disorder (ASD). Defects in infant vocalization have been proposed as an early sign of ASD that may exacerbate ASD development. However, the neural mechanisms associated with early communicative deficits in ASD are not known. Here, we expressed a constitutively active mutant of Rheb (RhebS16H), which is known to upregulate two ASD core pathways, mTOR complex 1 (mTORC1) and ERK1/2, in Layer (L) 2/3 pyramidal neurons of the neocortex of mice of either sex. We found that cellular mosaic expression of RhebS16H in L2/3 pyramidal neurons altered the production of isolation calls from neonatal mice. This was accompanied by an expected misplacement of neurons and dendrite overgrowth, along with an unexpected increase in spine density and length, which was associated with increased excitatory synaptic activity. This contrasted with the known decrease in spine density in RhebS16H neurons of 1-month-old mice. Reducing the levels of the actin cross-linking and adaptor protein filamin A (FLNA), known to be increased downstream of ERK1/2, attenuated dendrite overgrowth and fully restored spine properties, synaptic connectivity, and the production of pup isolation calls. These findings suggest that upper-layer cortical pyramidal neurons contribute to communicative deficits in a condition known to affect two core ASD pathways and that these mechanisms are regulated by FLNA. [ABSTRACT FROM AUTHOR]

Many important chemical kinetic systems require detailed chemical kinetic models to resolve. These detailed kinetic models can involve thousands of species and hundreds of thousands of chemical reactions, making them difficult to construct by hand. Modern automatic mechanism generation algorithms can mostly be divided into two classes: rule and rate based. Rule‐based generators choose species based on user defined constraints on species and reaction classes. Rate‐based generators generate a much larger set of potentially important species and reactions and then choose which ones to add based on running simulations of species and reactions deemed important and calculating the flux to potentially important species. In principle, the latter is preferable, as it requires the user to make far fewer assumptions about what is important in the system. However, while the effectiveness of the rate‐based approach has been demonstrated in a wide variety of systems, it has also been demonstrated to have difficulty picking up important low‐flux chemistries. Here we present a discussion of the challenges associated with rate‐based mechanism generation and new algorithms that are able to efficiently mitigate these challenges improving species selection during mechanism generation in a set of case studies. [ABSTRACT FROM AUTHOR]

Improving the degradation performance and enhancing the biocompatibility are the main challenges of Mg-based biodegradable implants. In this study, a nano-hydroxyapatite-enhanced (nHA) Mg matrix composite was fabricated via friction stir processing and characterised, including microstructure, mechanical, in vitro degradation properties, and cytocompatibility. Hydroxyapatite is renowned for its superior bone compatibility, promoting healing responses and tissue growth. Friction stirring created a gradient grain structure in the alloy, with the stir zone exhibiting the highest grain refinement. The stir zone also contained most of the incorporated nHA and exhibited a strong texture with grains preferentially oriented along the [0001] direction. Immersion and polarisation experiments showed an increase in the FSPed WE43-nHA's corrosion resistance due to the refined microstructure. The treatment also caused a shift in the corrosion mode of the alloy from localized to uniform corrosion despite some localized corrosion associated with the nHA. Cytocompatibility tests in human osteoblast (HOB) cell lines indicated good biocompatibility in the Mg-nHA alloy, with cells exhibiting relatively healthy morphology and increased live cell count. Friction stir processing is a viable manufacturing option for creating Mg-based metal matrix composites with improved corrosion resistance and good biocompatibility. [ABSTRACT FROM AUTHOR]

Background: Red cell alloimmunization after exposure to donor red cells is a very common complication of transfusion for patients with sickle cell disease (SCD), resulting frequently in accelerated donor red blood cell destruction. Patients show substantial differences in their predisposition to alloimmunization, and genetic variability is one proposed component. Although several genetic association studies have been conducted for alloimmunization, the results have been inconsistent, and the genetic determinants of alloimmunization remain largely unknown. Study Design and Methods: We performed a genome‐wide association study (GWAS) in 236 African American (AA) SCD patients from the Outcome Modifying Genes in Sickle Cell Disease (OMG‐SCD) cohort, which is part of Trans‐Omics for Precision Medicine (TOPMed), with whole‐genome sequencing data available. We also performed sensitivity analyses adjusting for different sets of covariates and applied different sample grouping strategies based on the number of alloantibodies patients developed. Results: We identified one genome‐wide significant locus on chr12 (p = 3.1e‐9) with no evidence of genomic inflation (lambda = 1.003). Further leveraging QTL evidence from GTEx whole blood and/or Jackson Heart Study PBMC RNA‐Seq data, we identified a number of potential genes, such as ARHGAP9, STAT6, and ATP23, that may be driving the association signal. We also discovered some suggestive loci using different analysis strategies. Discussion: We call for the community to collect additional alloantibody information within SCD cohorts to further the understanding of the genetic basis of alloimmunization in order to improve transfusion outcomes. [ABSTRACT FROM AUTHOR]

The earliest certain witness to an anaphora that bears many obvious similarities to the Roman Canon Missae is found in Book 4 of Ambrose's De Sacramentis. Scholars have characterized the relationship between the two texts however in remarkably contradictory ways. In this article I demonstrate that Ambrose and the Roman Canon contain both earlier and later versions of a shared core text. Through a careful examination of these two texts I demonstrate that in each section of the respective anaphoral texts distinct developments are clearly evident. This can be seen most clearly in the institution narrative where there is a move to make the bread and cup narratives more symmetrical but in ways that show both continuity and discontinuity to each other. We can no longer simply treat the text provided by Ambrose in De sacramentis as the earlier version of what became the Roman Canon. Instead it is evidence of what was likely a wider phenomenon: the parallel development of Latin anaphoral texts that are based on both Greek Alexandrian sources and different biblical manuscripts. The evolution and redaction of the individual sections of each anaphora underwent independent redactions. [ABSTRACT FROM AUTHOR]

We perform a numerical bootstrap study of scalar operators in the critical 3d Gross-Neveu-Yukawa models, a family of conformal field theories containing N Majorana fermions in the fundamental representation of an O(N) global symmetry. We compute rigorous bounds on the scaling dimensions of the next-to-lowest parity-even and parity-odd singlet scalars at N = 2, 4, and 8. All of these dimensions have lower bounds greater than 3, implying that there are only two relevant singlet scalars and placing constraints on the RG flow structure of these theories. [ABSTRACT FROM AUTHOR]

Early identification of knee osteoarthritis (OA) symptoms after anterior cruciate ligament reconstruction (ACLR) could enable timely interventions to improve long-term outcomes. However, little is known about the change in early OA symptoms from 6 to 12 months post-ACLR. To evaluate the change over time in meeting classification criteria for early knee OA symptoms from 6 to 12 months after ACLR. Prospective cohort study. Research laboratory. Eighty-two participants aged 13 to 35 years who underwent unilateral primary ACLR. On average, participants' first and second visits were 6.2 and 12.1 months post-ACLR. Early OA symptoms were classified using generic (Luyten Original) and patient population–specific (Luyten Patient Acceptable Symptom State [PASS]) thresholds on Knee injury and Osteoarthritis Outcome Score (KOOS) subscales. Changes in meeting early OA criteria were compared between an initial and follow-up visit at an average of 6 and 12 months post-ACLR, respectively. Twenty-two percent of participants exhibited persistent early OA symptoms across both visits using both the Luyten Original and PASS criteria. From initial to follow-up visit, 18% to 27% had resolution of early OA symptoms, while 4% to 9% developed incident symptoms. In total, 48% to 51% had no early OA symptoms at either visit. No differences were found for change in early OA status between adults and adolescents. Nearly one-quarter of participants exhibited persistent early knee OA symptoms based on KOOS thresholds from 6 to 12 months post-ACLR. Determining if this symptom persistence predicts worse long-term outcomes could inform the need for timely interventions after ACLR. Future researchers should examine if resolving persistent symptoms in this critical window improves later outcomes. Tracking early OA symptoms over time may identify high-risk patients who could benefit from early treatment. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic led to a proliferation of remote-proctored (or "at-home") assessments. The lack of standardized setting, device, or in-person proctor during at-home testing makes it markedly distinct from testing at a test center. Comparability studies of at-home and test center scores are important in understanding whether these distinctions impact test scores. This study found no significant differences in at-home versus test center test scores on a large-scale admissions test using either a randomized controlled trial or an observational study after adjusting for differences in sample composition along baseline characteristics. [ABSTRACT FROM AUTHOR]

Ewing sarcoma (ES) is a malignant tumor of bone and soft tissue that most often occurs in children, adolescents, and young adults. Debate and controversy remain in the management of relapsed/refractory ES (RR‐ES). The authors leveraged the expertise assembled by the National Ewing Sarcoma Tumor Board, a multidisciplinary virtual tumor board that meets monthly to discuss challenging cases of ES. In this review, they focus on select topics that apply to the management of patients with RR‐ES. The specific topics covered include the initial approach of such patients and discussion of the goals of care, the role of molecular testing, chemotherapy regimens and novel agents to consider, the role of maintenance therapy, and the use of high‐dose chemotherapy with autologous stem cell rescue. The data referenced are often limited to subgroup analyses and/or compiled from multiple sources. Although not intended to replace the clinical judgement of treating physicians, these guidelines are intended to support clinicians and provide some clarity and recommendations for the management of patients with RR‐ES. Plain Language Summary: Ewing sarcoma (ES) is a bone and soft tissue cancer that most often occurs in teenagers and young adults.This article uses the experience of the National Ewing Sarcoma Tumor Board, a multi‐institution, multidisciplinary virtual tumor board that meets monthly to discuss challenging cases of ES and to address questions related to the treatment of patients with relapsed ES.Although not intended to replace the clinical judgement of treating physicians and limited by available data, these consensus recommendations will support clinicians who treat patients with this challenging malignancy, made even more difficult when it recurs. Debates remain in defining the standard of care for treating patients with relapsed Ewing sarcoma. This set of consensus recommendations from the National Ewing Sarcoma Tumor Board are intended to provide some clarity and recommendations for the management of patients with recurrent disease. [ABSTRACT FROM AUTHOR]

We present ReactionMechanismSimulator.jl (RMS), a modern differentiable software for the simulation and analysis of chemical kinetic mechanisms, including multiphase systems. RMS has already been applied to problems in combustion, pyrolysis, polymers, pharmaceuticals, catalysis, and electrocatalysis. RMS is written in Julia, making it easy to develop and allowing it to take advantage of Julia's extensive numerical computing ecosystem. In addition to its extensive library of optimized analytic Jacobians, RMS can generate and use Jacobians computed using automatic differentiation and symbolically generated analytic Jacobians. RMS is demonstrated to be faster than Cantera and Chemkin in several benchmarks. RMS also implements an extensive set of features for analyzing chemical mechanisms, including a library of easy‐to‐call plotting functions, molecular structure resolved flux diagram generation, crash analysis, traditional sensitivity analysis, transitory sensitivity analysis, and an automatic mechanism analysis toolkit. RMS implements efficient adjoint and parallel forward sensitivity analyses. We also demonstrate the ease of adding new features to RMS. [ABSTRACT FROM AUTHOR]

A diagnostic criterion for Major Depressive Disorder (MDD) is difficulty concentrating and increased distractibility. One form of distraction that occurs in everyday life is mind-wandering. The current study aims to test how individuals with MDD and healthy controls differ in their mind-wandering in everyday life. Adults diagnosed with MDD (n = 53) and healthy controls (n = 53) completed a week of experience sampling, with prompts administered up to eight times per day. At each prompt, participants reported the occurrence and characteristics of their mind-wandering. They also reported levels of momentary negative affect (NA), positive affect (PA), and rumination. MDD participants reported mind-wandering almost twice as often as healthy control participants. Compared to healthy participants, MDD participants rated their mind-wandering as more negative, but did not differ in terms of temporal orientation. Higher NA and lower PA predicted mind-wandering in the MDD group but not healthy controls, even after controlling for rumination. Time-lagged analyses revealed that current mind-wandering predicted future levels of PA in MDD participants but not in healthy controls; in contrast, current NA and PA did not predict future mind-wandering. Limitations include our examination of specific forms of mind-wandering (i.e., we did not sample the full spectrum of this construct). Individuals with MDD frequently report engaging in mind-wandering in everyday life, and this appears to be coupled with affect. Mind-wandering may have maladaptive effects in MDD and could serve as a target for intervention. • Individuals with major depressive disorder (MDD) may have difficulties concentrating and may find that their mind wanders. • This study compared rates of mind-wandering in individuals with MDD to healthy controls over a week of experience sampling. • Mind-wandering was higher in MDD and was associated with subsequent changes in affect. • This research highlights that mind-wandering in MDD is common and suggests a potential target for intervention. [ABSTRACT FROM AUTHOR]

Erasmus’s epigrams “On six restored bells” (ca. 1501) draw attention to their material origins in bells remade for the Premonstratensian Abbey of Averbode following a calamitous fire. In doing so, they allow an exploration of the tensions between holy matter speaking with present, embodied, sanctified voices, and a world where resonant matter is marginalized and past material voices speak to the soul through words on the page. By tracing bell cultures in the period, and emphasizing the dense resonances of bronze as a material, this article shows how Erasmus’s approach to sound and matter both resonates with and transforms classical traditions and the local cultures of religious reform in the Low Countries. [ABSTRACT FROM AUTHOR]

The selective synthesis of biomimetic Fe/Mn complexes able to mimic the geometry and catalytic activity of enzymes possessing this cofactor is still a challenge. Herein, we discuss the stepwise synthesis, characterization, and magnetic properties of a Fe(II)/Mn(II) species and related Fe(II)/Fe(II) complexes. [ABSTRACT FROM AUTHOR]

There have been repeated calls for academic institutions to develop policies and procedures to manage institutional conflicts of interest (ICOI) arising from technology transfer activities. While prior research has examined adoption of ICOI policies by medical schools and universities, little is known about how these institutions handle ICOI in practice, hindering the development of evidence-based recommendations to improve ICOI management. To address this gap, we conducted semi-structured interviews with 25 senior administrators responsible for research integrity and conflict of interest issues at academic institutions. Data were analyzed using a descriptive qualitative content analysis approach, combining flexible coding to index the interview data with close examination, interpretation, and synthesis of coded content. Participants identified communication and information sharing between conflict of interest (COI) and technology transfer (TT) offices as a critical factor in the effective management of ICOI and suggested several strategies to strengthen coordination between these offices. These findings suggest that academic research institutions could strengthen COI programs by taking measures to improve communication and information sharing between COI and TT offices. [ABSTRACT FROM AUTHOR]

The ability to prepare and maintain an optimal level of preparedness for action, across some unknown duration, is critical for human behavior. Temporal preparation has historically been analyzed in the context of reaction time (RT) experiments where the interval varies between the start of the trial, or foreperiod (FP), and the required response. Two main findings have come out of such paradigms: the variable FP effect (longer RTs to shorter vs. longer FPs) and the sequential FP effect (longer RTs when shorter FPs follow longer FPs). Several theoretical views of these FP effects have been proposed with some suggesting a dissociation while others argue for an implicit process driven by memory traces. One possible method to test these views of FP effects is to examine how individual differences in working memory capacity (WMC) moderate such effects. To this end, I reanalyzed data from three studies in which participants completed measures of WMC and a simple RT task with a variable FP. Results suggest that individual differences in WMC were related to the magnitude of the variable FP and the sequential FP effect in two of three individual studies. A "mega-analysis" provided supportive evidence for a relationship between WMC and both forms of FP effects. The present combined experimental-individual differences study provides a novel approach to better understand how and why individuals vary in temporal preparation ability. Through leveraging several large-scale databases unseen in FP research, I provide a new way of understanding FP effects and response timing more generally. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Dairy producers are experiencing production and animal welfare pressures from the increasing frequency and severity of heat stress events due to global climate change. Offspring performance during the preweaning and lactating periods is compromised when exposed to heat stress during late gestation (in utero). However, knowledge of the lingering effects of in utero heat stress on yearling dairy heifers is limited. Herein, we investigated the long-term effects of in utero heat stress on heifer growth, feed efficiency, and enteric methane emissions in postpubertal heifers. During the last 56 d of gestation, 38 pregnant cows carrying heifer calves were exposed to either heat stress (IUHT; n = 17) or artificial cooling (IUCL; n = 21). At 18 ± 1 mo of age, the resulting IUCL and IUHT heifers were enrolled in the present 63-d study. Heifers were blocked by weight and randomly assigned to 3 pens with Calan gates. Body weights were recorded on 3 consecutive days at the start and end of the trial and used to calculate ADG. Body condition score, hip width, body length, and chest girth were measured at the start and end of the study. All heifers were fed a TMR comprised of 46.6% oatlage, 44.6% grass/alfalfa haylage, 7.7% male-sterile corn silage, 0.3% urea, and 0.8% mineral/vitamin supplement (on a DM basis). The TMR and refusal samples were obtained daily, composited weekly, and dried to calculate DMI. During the study, each pen had access to a GreenFeed unit for 8 ± 1d to measure CH 4 and CO 2 gas fluxes. During the last 3 d of measuring CH 4 and CO 2 fluxes, fecal samples were collected, composited by animal, dried, and analyzed to calculate NDF, OM, and DM digestibility. On the last day of fecal sampling, blood samples were also collected via coccygeal venipuncture, and GC time-of-flight MS analysis was performed. Residual feed intake (RFI; predicted DMI − observed DMI), and feed conversion efficiency (FCE; DMI/ADG) were calculated to estimate feed efficiency. No differences were found in initial or final BW, hip width, chest girth, or BCS; however, IUCL heifers were longer in body length compared with IUHT heifers. Dry matter intake, ADG, RFI, and FCE were similar between IUHT and IUCL heifers. In utero heat-stressed and IUCL heifers produced similar amounts of CH 4 and CO 2 , and no differences were found in the number of GreenFeed visits or latency to approach the GreenFeed. The concentrations of 6 blood metabolites involved in lipogenic pathways were different between in utero treatments. In conclusion, in utero heat stress does not seem to have long-term effects on feed efficiency or methane emissions during the postpubertal growing phase; however, IUCL heifers maintained a body-length advantage over their IUHT counterparts and differed in concentrations of several candidate metabolites that encourage further exploration of their potential function in key organs, such as the liver and mammary gland. [ABSTRACT FROM AUTHOR]

Background: Histopathological examination is adequate for the diagnosis of most cutaneous melanocytic neoplasms. However, there is a subset that is either difficult to definitively diagnose or would have diagnostic disagreement upon review by multiple dermatopathologists if a more exhaustive review was performed. Methods: Melanocytic lesions underwent an independent, blinded diagnostic histopathological review of hematoxylin and eosin‐stained sections. Each lesion was reviewed by three to six dermatopathologists and categorized as benign, malignant, or unknown malignant potential (UMP). Diagnoses were grouped as concordant (all the same designation); opposing (received benign and malignant designations); majority (single designation with the highest number of diagnoses, no benign/malignant opposing designations); and non‐definitive (equal number of non‐opposing designations [i.e., benign/UMP or malignant/UMP]). Lesions with equivocal designations (concordant or majority UMP, opposing, majority, and non‐definitive) were utilized in a patient treatment model of projected surgical treatment discrepancies. Results: In total, 3317 cases were reviewed, and 23.8% of lesions received equivocal diagnoses. Of these, 7.3% were majority benign, 4.8% were majority malignant, 2.7% were majority UMP, 0.5% were concordant UMP, 6.9% were opposing, and 1.6% were non‐definitive. Patient treatment models of those with equivocal lesions (n = 788) revealed a potential of overall surgical treatment variations ranging from 18% to 72%, with the highest variation amongst lesions with opposing, non‐definitive, or majority UMP (40%–72%) diagnoses. Conclusion: Histopathologic review in this large cohort demonstrated substantial diagnostic variation, with 23.8% of cases receiving equivocal diagnoses. We identified diagnostic ambiguity even in lesions where a definitive diagnosis was previously rendered by a single real‐world dermatopathologist. The combined clinical impact of diagnostic discordance or a final diagnosis of UMP is highlighted by high diagnosis‐dependent treatment variation in the patient treatment model, which could be underreported in a real‐world setting, where review by more than one to two dermatopathologists is relatively rare. [ABSTRACT FROM AUTHOR]

Image-based robotic-assisted total knee arthroplasty (RA-TKA) allows three-dimensional surgical planning informed by osseous anatomy, with intraoperative adjustment based on a dynamic assessment of ligament laxity and gap balance. The aim of this study was to identify ranges of implant alignment and bone resections with RA-TKA. We retrospectively reviewed 484 primary RA-TKA cases, stratified by preoperative coronal alignment. Demographics and intraoperative data were collected and compared using Chi-square and ANOVA tests. Planned limb, femoral, and tibial alignment became increasingly varus in a progressive order from valgus to neutral to the highest in varus knees (p < 0.001). Planned external transverse rotation relative to the TEA was lowest in the valgus cohort; relative to the PCA, whereas the varus cohort was highest (p < 0.001, both). Planned resections of the lateral distal femur and of the medial posterior femur were greater in the varus group compared to neutral and valgus (p < 0.001). There were significant differences between cohorts in planned tibia resections, laterally and medially. Varus knees demonstrated higher variability, while valgus and neutral had more metrics with low variability. This study demonstrated trends in intraoperative planned alignment and resection metrics across various preoperative coronal knee alignments. These findings contribute to the understanding of RA-TKA and may inform surgical decision-making. [ABSTRACT FROM AUTHOR]

The geometric optimization of crystal structures is a procedure widely used in computational chemistry that changes the geometrical placement of the particles inside a structure. It is called structural relaxation and constitutes a local minimization problem with a non‐convex objective function whose domain complexity increases according to the number of particles involved. This work studies the performance of the two most popular gradient methods in structural relaxation, Steepest Descent and Conjugate Gradient. Although frequently employed, there is a lack of their study in this context from an algorithmic point of view. The algorithms are initially benchmarked on the basis of a constant step size. Three concepts for designing dynamic step size rules are then examined in detail and analyzed. Results show that there is a trade‐off between convergence rate and the possibility of an experiment to succeed. In order to address this, a function is proposed as a formal means for assigning utility to each method based on preference. The function is built according to a recently introduced model of preference indication concerning algorithms with deadline and their run time. It introduces the quantification of the optimization algorithms' performance according to convergence speed and success rate, thus enabling the appointment of a specific algorithmic recipe as the best choice for balanced preferences. [ABSTRACT FROM AUTHOR]

Missing visual information, such as a gap between an object or an occluded view, has been shown to disrupt visual search and make amodal completion inefficient. Previous research, using simple black bars as stimuli, failed to show a pop-out effect (flat search slope across increasing visual set sizes) during a feature search when the target was partially occluded, but not in cases where it was fully visible. We wanted to see if this lack of a pop-out effect during feature (orientation) search extended to complex objects (Experiment 1) and identity search (Experiment 2). Participants completed orientation and identity visual search tasks by deciding whether the target was present or not present. Bayesian analyses was conducted to find evidence for observed data to be under the null (pop-out effects) or alternative hypotheses (differences in search slopes). When no occluders or gaps were present, a pop-out effect occurred when searching for a simple objects' orientation or identity. In addition, object complexity affected identity search, with anecdotal evidence suggesting that some complex object may not show a pop-out effect. Furthermore, white occluding bars were more disruptive than having a gap of visual information for feature search but not for identity search. Overall, pop-out effects do occur for simple objects, but when the task is more difficult, search for real-world objects is greatly affected by any type of visual disruption. [ABSTRACT FROM AUTHOR]

There is a wrinkle in the story of common features in West Syrian anaphoras, which John Fenwick called "the Missing Oblation." In this article, I argue that the importance of the "missing oblation" highlighted by Fenwick, Robert Taft, Stefano Parenti and others needs to be balanced against the verbs of oblation that are present. The emphasis on the missing oblation, combined with the tendency to summarize the Antiochene structure with little reference to the importance of these verbs, results in an inaccurate and unbalanced sense of the degree to which the anaphora expresses the belief that the action of offering bread and wine is constitutive of the eucharistic action. This should lead to a caution with the unhelpful heuristic about the spiritualization of sacrifice in contemporary scholarship and the underemphasis of the belief in the materiality of the eucharistic sacrifice in writers such as John Chrysostom and earlier anaphoras. [ABSTRACT FROM AUTHOR]

Objective: This study examined the impact of impairment in two specific cognitive abilities, processing speed and memory, on Dot Counting Test (DCT) classification accuracy by evaluating performance validity classification accuracy across cognitively unimpaired, single-domain impairment, and multidomain impairment subgroups within a mixed clinical sample. Method: Cross-sectional data were analyzed from 348 adult outpatients classified as valid (n = 284) or invalid (n = 64) based on four independent criterion performance validity tests (PVTs). Unimpaired (n = 164), single-domain processing speed impairment (n = 24), single-domain memory impairment (n = 53), and multidomain processing speed and memory impairment (n = 43) clinical subgroups were established among the valid group. Both the traditional DCT E-score and unrounded E-score were examined. Results: Overall, the DCT demonstrated acceptable to excellent classification accuracy across the unimpaired (area under the curve [AUC] traditional E-score=.855; unrounded E-score=.855) and single-domain impairment groups (traditional E-score AUCs =.690–.754; unrounded E-score AUCs =.692–747). However, it did not reliably discriminate the multidomain processing speed and memory impairment group from the invalid performers (traditional and unrounded E-scores AUC =.557). Conclusions: Findings support the DCT as a non-memory-based freestanding PVT for use with single-domain cognitive impairment, with traditional E-score ≥17 (unrounded E-score ≥16.95) recommended for those with memory impairment and traditional E-score ≥19 (unrounded ≥18.08) with processing speed impairment. Moreover, results replicated previously established optimal cutoffs for unimpaired groups using both the traditional (≥14) and unrounded (≥13.84) E-scores. However, the DCT did not reliably discriminate between invalid performance and multidomain cognitive impairment, indicating caution is warranted when using the DCT with patients suspected of greater cognitive impairment. [ABSTRACT FROM AUTHOR]

Development of advanced materials is often time consuming and expensive because of the large number of variables involved and experiments needed. An effective experimentation strategy would accelerate development by reducing the required amount of experiments without sacrificing the obtainable information. In this paper, the development of auxetic polyurethane (PU) foams was discussed as a case study. Auxetic materials are materials with a negative Poisson's ratio and have potential in many structural and functional applications. Auxetic PU foams are the most studied auxetic materials, and their manufacturing and properties are affected by many processing and environmental factors. This paper introduces a sophisticated design of experimental methodology to help reduce the experimental effort while effectively screening these factors. This methodology is then applied in an experiment to illustrate its utility and distinct advantages that greatly facilitate material development. [ABSTRACT FROM AUTHOR]

Age-related differences in mind wandering are robust, with older adults reporting less mind wandering compared to younger adults. While several theories have been put forth to explain this difference, one view has received less attention than others. Specifically, age-related differences in mind wandering might occur because older adults are reluctant to report on their mind wandering. The aim of the current study was to explicitly test this hypothesis. Older and younger adults completed a go/no-go task with intermittent thought probes to assess mind wandering. In one condition, participants were provided with standard instructions about how to respond to questions about their thoughts. In a second condition, participants were provided with a positive framing of mind wandering. Mind wandering was assessed both subjectively (i.e., via thought probes) and objectively (i.e., using different behavioral measures from the go/no-go task). The results of the study suggest that positively framing mind wandering did not impact rates of mind wandering or objective indicators of mind wandering for older or younger adults. Older adults reported less mind wandering, regardless of condition, compared to younger adults. Older adults also had generally better performance on the go/no-go task compared to younger adults. Bayesian analyses suggested that the main effect of framing condition, although not significant in Frequentist terms, did provide moderate evidence of an overall effect on mind wandering rates. We interpret the results as evidence against the reluctance hypothesis, consistent with previous work. [ABSTRACT FROM AUTHOR]

Density functional theory (DFT) calculations were performed to examine the impact of exchange–correlation (XC) functionals and van der Waals corrections (specifically the D3 method) on the structural and vibrational properties of the SrCl2–NaCl and ZrF4–LiF salt systems. Multiple XC functionals, including the local density approximation (LDA), the generalized gradient approximation using the Perdew–Burke–Ernzerhof (PBE) model, and its modified form suitable for solids (PBEsol), the dispersion‐corrected PBE‐D3 and PBEsol‐D3, were considered. Of these functionals, LDA was found to exhibit the highest degree of error, while PBEsol and PBE‐D3 displayed the least error. Underestimated lattice parameters compared with experimental values were observed to result in higher force constants, leading to an overprediction of vibrational frequencies. Conversely, an overestimation of lattice parameters was associated with lower vibrational frequencies. The methodology presented in this study yielded results that are in good agreement with experiment, irrespective of the method (finite differences vs. density functional perturbation theory) employed for calculating infrared and Raman spectra. It was further demonstrated that for alkali halides with weak Raman scattering, utilizing a supercell constructed from primitive cells better predicts Raman features than does the use of conventional cells. [ABSTRACT FROM AUTHOR]

Teacher turnover remains considerably higher at Charter Management Organizations (CMOs), despite initially high perceptions of fit at the time of hire. Grounded in an emerging branch-off of job embeddedness theory—teacher embeddedness—this multi-site case study of one urban CMO used interviews of departed teachers and principals and focus groups of new and veteran teachers to determine the predominating factors of reduced feelings of embeddedness and, ultimately, turnover. Findings indicate that teacher embeddedness is threatened by methods the CMO has proliferated as "best practice" and factors researchers have empirically correlated with turnover. [ABSTRACT FROM AUTHOR]

Recent years have seen a dramatic increase in the number of canine genome assemblies available. Duplications are an important source of evolutionary novelty and are also prone to misassembly. We explored the duplication content of nine canine genome assemblies using both genome self-alignment and read-depth approaches. We find that 8.58% of the genome is duplicated in the canFam4 assembly, derived from the German Shepherd Dog Mischka, including 90.15% of unplaced contigs. Highlighting the continued difficulty in properly assembling duplications, less than half of read-depth and assembly alignment duplications overlap, but the mCanLor1.2 Greenland wolf assembly shows greater concordance. Further study shows the presence of multiple segments that have alignments to four or more duplicate copies. These high-recurrence duplications correspond to gene retrocopies. We identified 3,892 candidate retrocopies from 1,316 parental genes in the canFam4 assembly and find that ∼8.82% of duplicated base pairs involve a retrocopy, confirming this mechanism as a major driver of gene duplication in canines. Similar patterns are found across eight other recent canine genome assemblies, with metrics supporting a greater quality of the PacBio HiFi mCanLor1.2 assembly. Comparison between the wolf and other canine assemblies found that 92% of retrocopy insertions are shared between assemblies. By calculating the number of generations since genome divergence, we estimate that new retrocopy insertions appear, on average, in 1 out of 3,514 births. Our analyses illustrate the impact of retrogene formation on canine genomes and highlight the variable representation of duplicated sequences among recently completed canine assemblies. [ABSTRACT FROM AUTHOR]

Limited research has resulted in conflicting views on the risks versus benefits associated with kratom use. Despite no federal policy in the United States, individual states have implemented diverging policies through kratom bans, and legalization and regulation through Kratom Consumer Protection Acts (KCPAs). The Survey of Non-Medical Use of Prescription Drugs (NMURx) Program employs nationally-representative, repeated cross-sectional surveys on drug use. In 2021, weighted prevalence of past−12 month kratom use was compared across three state legal frameworks: no overarching state policy, KCPAs, and state bans. There was lower estimated prevalence of kratom use in banned states (prevalence: 0.75% (0.44, 1.06) relative to states with a KCPA (1.20% (0.89, 1.51)), and relative to states with no policies (1.04% (0.94, 1.13), though odds of use were not significantly associated with policy type. Kratom use was significantly associated with medicated treatment for opioid use disorder. While there were observed differences in the prevalence of past−12 month kratom use by state policy type, low uptake mitigated meaningful distinctions by limiting statistical precision, and potentially confounding effects, such as accessibility online. Future kratom-related policy decisions should be informed through evidence-based research. [ABSTRACT FROM AUTHOR]

Recent research has suggested that people more readily make genetic attributions for positively valenced or desirable traits than for negatively valenced or undesirable traits—an asymmetry that may be mediated by perceptions that positive characteristics are more 'natural' than negative ones. This research sought to examine whether a similar asymmetry in genetic attributions would emerge between positive and negative health outcomes. Across seven experiments, participants were randomly assigned to read a short vignette describing an individual experiencing a health problem (e.g. hypertension) or a corresponding healthy state (e.g. normal blood pressure). All participants provided ratings of naturalness and genetic attributions for the outcome described in their assigned vignette. For diagnoses other than addictive disorders, participants rated the presence of a diagnosis as less genetically caused than its absence; for addictive disorders, the presence of a diagnosis was rated as more genetically caused than its absence. Participants consistently rated the presence of a health problem as less natural than its absence. Even within a single domain of health, people ascribe differing degrees of 'naturalness' and genetic causation to positive versus negative health outcomes, which could impact their preferences for treatment and prevention strategies. [ABSTRACT FROM AUTHOR]

Qoheleth (Ecclesiastes) and the 2022 film Everything Everywhere All At Once understand the embrace of life's meaninglessness as essential for learning how to live meaningfully. Whereas life's pervasive meaninglessness leads Qoheleth to recommend enjoyment (of food and drink) as the ultimate good, the film insists that the optimal response to life's meaninglessness is to adopt postures of vulnerability and kindness, and to understand how failure can be a virtue. [ABSTRACT FROM AUTHOR]