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Abstract Since the 19th century, rapid urbanisation coupled with a demographic boom has increased pressures on the global exploitation of natural resources leading to an array of issues at planetary scale. Even though there have been significant ecologically driven human policy efforts, with frameworks addressing ecosystem accounting and management, such are principally constricted at sub-global levels; being regionally focussed, and hence lacking both cohesivity and accountability. Resource management viewed through this lens leads to a number of geopolitical factors as demonstrated recently with the Amazon Forest fires. This incident witnessed calls from numerous countries calling for rapid remediation even though their own policies are harbingers of equally damaging the environments through other means. This disparity in resource accounting and management on a planetary scale is apparent from diverse local and regional groups and needs to be addressed in order to sustain a truly sustainable and liveable ecosystem and their failures in realising a viable ecosystem accounting system. This perspective paper explores this theme and proposes a ‘Global Planetary Ecosystem Accounting’ system based on the principle that ecologically sensitive areas benefiting the global ecosystem need to be economically weighted and its preservation equated to a revenue-generating activity.

Abstract Genetic studies link inherited errors in RNA metabolism to familial neurodegenerative disease. Here, we report such errors and the underlying mechanism in sporadic Alzheimer's disease (AD). AD entorhinal cortices presented globally impaired exon exclusions and selective loss of the hnRNP A/B splicing factors. Supporting functional relevance, hnRNP A/B knockdown induced alternative splicing impairments and dendrite loss in primary neurons, and memory and electrocorticographic impairments in mice. Transgenic mice with disease‐associated mutations in APP or Tau displayed no alterations in hnRNP A/B suggesting that its loss in AD is independent of Aβ and Tau toxicity. However, cholinergic excitation increased hnRNP A/B levels while in vivo neurotoxin‐mediated destruction of cholinergic neurons caused cortical AD‐like decrease in hnRNP A/B and recapitulated the alternative splicing pattern of AD patients. Our findings present cholinergic‐mediated hnRNP A/B loss and impaired RNA metabolism as important mechanisms involved in AD.

Overcoming resistance to therapy is a major challenge in castration-resistant prostate cancer (CRPC). Lineage plasticity towards a neuroendocrine phenotype enables CRPC to adapt and survive targeted therapies. However, the molecular mechanisms of epigenetic reprogramming during this process are still poorly understood. Here we show that the protein kinase PKCλ/ι-mediated phosphorylation of enhancer of zeste homolog 2 (EZH2) regulates its proteasomal degradation and maintains EZH2 as part of the canonical polycomb repressive complex (PRC2). Loss of PKCλ/ι promotes a switch during enzalutamide treatment to a non-canonical EZH2 cistrome that triggers the transcriptional activation of the translational machinery to induce a transforming growth factor β (TGFβ) resistance program. The increased reliance on protein synthesis creates a synthetic vulnerability in PKCλ/ι-deficient CRPC. The transition of androgen receptor-dependent prostate cancer to a therapy resistant cancer with neuroendocrine phenotype is an important process that remains poorly understood. Here, the authors show that PKCλ/ι-loss promotes epigenetic reprogramming resulting in a TGFβ resistance programme via transcriptional upregulation of translational machinery. [ABSTRACT FROM AUTHOR]

The 4CMenB (BexseroR) vaccine contains detergent-extracted outer membrane vesicles (OMVs) from a Neisseria meningitidis (Nm) group B strain NZ98/254 and three recombinant Nm protein antigens: Neisseria adhesin A (NadA), Factor H binding protein (FHbp, as the C-terminal protein in the GNA2091-FHbp fusion), and Neisserial Heparin Binding Antigen (NHBA, as the N-terminal protein in the NHBA-GNA1030 fusion). Previous work has shown that 4CMenB generates serum antibodies to Nm and Neisseria gonorrhoeae (Ng) OMV proteins and lipooligosaccharide (LOS). Mounting evidence indicates 4CMenB can partially protect against mucosal infections with Ng. The immunologic basis for Ng cross protection remains to be fully elucidated. Ten paired human sera obtained pre- and post-immunization with 4CMenB (1 month after a third vaccine dose) were used in ELISAs and in Western blots to determine IgG and IgA serum responses to OMVs from Nm strain NZ98/254 (OMVNm) and two Ng strains, 1291 and CNG20 (OMVNg), and gonococcal recombinant NHBA (rNHBANg) proteins. Post 4CMenB sera, but not pre-sera, showed strong IgG and variable IgA responses to the OMVNm but lower (2–11-fold difference in signal intensity) recognition of OMVNg. All post (not pre) 4CMenB sera showed strong IgG, but variable IgA, recognition of rNHBANg by ELISAs and Western blots. Three post 4CMenB sera at 10% (v/v) concentration had serum bactericidal activity (SBA) against Ng strains 1291 and CNG20 (~30–40% killing), not seen in paired pre-sera. These data confirmed 4CMenB-induced cross-reactive functional antibody responses to Ng. In competitive SBA assays, in which sera were pre-incubated with rNHBA, minimal SBA against Nm strain NZ98/254 was titrated away. However, most of the SBA against Ng strains 1291 and CNG20 required NHBA-specific antibodies, and the Δnhba mutants were resistant to killing by post 4CMenB sera. Removing NHBA-specific and LOS-specific OMV antibodies simultaneously decreased SBA significantly more than the sum of removing individual antibodies alone, suggesting synergy between anti-NHBA and anti-OMV antibodies. Anti- NHBANm antibodies induced by 4CMenB vaccination cross react with NHBANg and substantially contribute to the bactericidal response toward Ng induced by the vaccine. [ABSTRACT FROM AUTHOR]

Psychedelic-assisted therapy (PAT) with substances like psilocybin and MDMA has shown promise for conditions including depression and post-traumatic stress disorder. Psilocybin and MDMA may become approved medicines in the coming decade. This study assessed knowledge and attitudes regarding PAT among 879 U.S. healthcare professionals via anonymous online survey. Multivariable linear regression was used to identify predictors of openness to clinical use. Most participants (71.2%) were female and White (85.8%), with a mean (SD) age of 45.5 (12.7) years. Registered nurses (25.4%) and physicians (17.7%) comprised the largest professional groups. Respondents endorsed strong belief in therapeutic promise, and moderate openness to clinical use and support for legal access to both substances, with higher overall ratings for psilocybin compared to MDMA. Objective knowledge items revealed low knowledge of therapeutic uses, risks, and pharmacology. Primary concerns were lack of trained providers, financial cost, and potential contraindications. Prior psychedelic use, self-rated knowledge, younger age, and professional role predicted openness to clinical use of psilocybin and MDMA, with physicians reporting lower openness. As psychedelics continue to garner popular and scientific interest, results indicate a pressing need for additional formal training to provide balanced, evidence-based information from trusted sources. [ABSTRACT FROM AUTHOR]

Despite the great relevance of the neurosteroid allopregnanolone and related isomers to various health conditions, quantification typically involves immunoassay, which suffers from serious issues with cross-reactivity of closely related molecules. This article describes the development and partial validation of a liquid chromatography coupled with tandem mass spectrometry assay for the simultaneous quantification of allopregnanolone, pregnanolone, isopregnanolone, epi-allopregnanolone, and testosterone in the human serum of healthy males and females aged 5–85 years. 1-amino-4-methylpiperazine (AMP) was used as a derivatisation reagent to enhance the ionisation signal. Linearity was calculated at 0.99 with a lower limit of quantification of 10.08 pg/mL for allopregnanolone, along with a linearity of 0.98 and a lower limit of quantification of 42.32 pg/mL for testosterone. Application of the method showed sex and age effects across the lifespan for both allopregnanolone and testosterone, whereas a comparative immunoassay for allopregnanolone was not able to detect differences in the same samples. Our partial validation of this method should provide a new tool for researchers to discover the role of allopregnanolone and its isomers in human health, and how it compares to testosterone and sex hormones. [ABSTRACT FROM AUTHOR]

Dispersal is an important behavior in many animals, with profound effects on individual fitness and the evolutionary trajectories of populations. This is especially true within taxa with particular life-history strategies, for example those that exploit ephemeral habitat. Further, dispersal is commonly seen to be part of behavioral syndromes - suites of traits that covary across behavioral contexts. The red flour beetle, Tribolium castaneum (Coleoptera, Tenebrionidae), is a major post-harvest crop pest responsible for large losses through the infestation of stored grain. In this system dispersal is known to have a strong genetic basis and differential artificial selection on dispersal traits produces strong phenotypic divergence. However, it is unknown which traits are able to rapidly evolve to produce these results, or which behavioral components underlie differences in dispersal. Using replicate lines of T. castaneum previously selected for divergent dispersal behavior, we test for correlated activity and movement patterns, morphology and substrate surface use. We find robustly repeatable associations between the dispersal phenotype and higher activity, straighter paths, larger body size (but not relative leg length) and increased tendency to remain at the surface of fodder. Together our results suggest that dispersal is part of a syndrome of traits in T. castaneum, and must be treated as such when considering the evolution of dispersal in this system, and in attempting to predict and control its spread. [ABSTRACT FROM AUTHOR]

Purpose: Accurate and rapid needle localization on 3D magnetic resonance imaging (MRI) is critical for MRI-guided percutaneous interventions. The current workflow requires manual needle localization on 3D MRI, which is time-consuming and cumbersome. Automatic methods using 2D deep learning networks for needle segmentation require manual image plane localization, while 3D networks are challenged by the need for sufficient training datasets. This work aimed to develop an automatic deep learning-based pipeline for accurate and rapid 3D needle localization on in vivo intra-procedural 3D MRI using a limited training dataset. Methods: The proposed automatic pipeline adopted Shifted Window (Swin) Transformers and employed a coarse-to-fine segmentation strategy: (1) initial 3D needle feature segmentation with 3D Swin UNEt TRansfomer (UNETR); (2) generation of a 2D reformatted image containing the needle feature; (3) fine 2D needle feature segmentation with 2D Swin Transformer and calculation of 3D needle tip position and axis orientation. Pre-training and data augmentation were performed to improve network training. The pipeline was evaluated via cross-validation with 49 in vivo intra-procedural 3D MR images from preclinical pig experiments. The needle tip and axis localization errors were compared with human intra-reader variation using the Wilcoxon signed rank test, with p < 0.05 considered significant. Results: The average end-to-end computational time for the pipeline was 6 s per 3D volume. The median Dice scores of the 3D Swin UNETR and 2D Swin Transformer in the pipeline were 0.80 and 0.93, respectively. The median 3D needle tip and axis localization errors were 1.48 mm (1.09 pixels) and 0.98°, respectively. Needle tip localization errors were significantly smaller than human intra-reader variation (median 1.70 mm; p < 0.01). Conclusion: The proposed automatic pipeline achieved rapid pixel-level 3D needle localization on intra-procedural 3D MRI without requiring a large 3D training dataset and has the potential to assist MRI-guided percutaneous interventions. [ABSTRACT FROM AUTHOR]

Purpose: To characterize T1 relaxation times of the pancreas, liver, and spleen in children with and without abdominal pathology. Methods: This retrospective study included pediatric patients (< 18-years-old). T1 mapping was performed with a Modified Look-Locker Inversion Recovery sequence. Patients were grouped based on review of imaging reports and electronic medical records. The Kruskal–Wallis test with Dunn's multiple comparison was used to compare groups. Results: 220 participants were included (mean age: 11.4 ± 4.2 years (1.5 T); 10.9 ± 4.5 years (3 T)). Pancreas T1 (msec) was significantly different between subgroups at 1.5 T (p < 0.0001). Significant pairwise differences included: normal (median: 583; IQR: 561–654) vs. acute pancreatitis (731; 632–945; p = 0.0024), normal vs. chronic pancreatitis (700; 643–863; p = 0.0013), and normal vs. acute + chronic pancreatitis (1020; 897–1099; p < 0.0001). Pancreas T1 was also significantly different between subgroups at 3 T (p < 0.0001). Significant pairwise differences included: normal (779; 753–851) vs. acute pancreatitis (1087; 910–1259; p = 0.0012), and normal vs. acute + chronic pancreatitis (1226; 1025–1367; p < 0.0001). Liver T1 was significantly different between subgroups only at 3 T (p = 0.0011) with pairwise differences between normal (818, 788–819) vs. steatotic (959; 848–997; p = 0.0017) and normal vs. other liver disease (882; 831–904; p = 0.0455). Liver T1 was weakly correlated with liver fat fraction at 1.5 T (r = 0.39; 0.24–0.52; p < 0.0001) and moderately correlated at 3 T (r = 0.64; 0.49–0.76; p < 0.0001). There were no significant differences in splenic T1 relaxation times between subgroups. Conclusion: Pancreas T1 relaxation times are higher at 1.5 T and 3 T in children with pancreatitis and liver T1 relaxation times are higher in children with steatotic and non-steatotic chronic liver disease at 3 T. [ABSTRACT FROM AUTHOR]

Context: Widespread ecological degradation has prompted calls for massive global investments in ecological restoration, yet limited resources necessitate efficient application of restoration efforts. In western North America, altered fire regimes are increasing the scale of restoration needed to preserve the sagebrush (Artemisia species) biome but prioritizing and implementing effective restoration is complicated by the vast and heterogeneous sagebrush landscape, which includes gradients in climate, disturbance, and species composition. Objectives: To develop spatially explicit and context-dependent estimates of treatment efficacy and sagebrush recovery rates. Methods: We leveraged a suite of spatio-temporally extensive datasets to evaluate the influence of restoration treatments and environmental conditions on trends in post-disturbance sagebrush cover, with an emphasis on understanding differences between sites recovering naturally and sites receiving restoration treatments. We used estimates from these models to develop spatially explicit projections for sagebrush recovery, conditional on disturbance, restoration practice, and environmental conditions. Results: We found seeding Artemisia spp. increased sagebrush cover over time relative to natural recovery, but this relationship depended on spring soil moisture availability and treatment methods. Natural recovery was positively influenced by soil moisture and sagebrush cover and negatively influenced by cumulative burns and annual herbaceous cover, while the influence of perennial herbaceous cover varied with soil moisture. Conclusions: Our results provide biome-wide insights and spatially explicit tools that can inform economic cost-effectiveness analyses, restoration prioritization tools, and other scientific endeavors to ensure managers have the tools and information needed to effectively steward the sagebrush biome in a rapidly changing world. [ABSTRACT FROM AUTHOR]

Immunosuppression after solid organ transplantation is associated with an increased risk of keratinocyte carcinoma (KC). Despite its established morbidity, KC risk in liver transplant (LT) recipients is understudied, including the contribution of immunosuppression regimen and latitude. A retrospective cohort of 9,966 adult first LT alone recipients alive with their native allograft at 1-year post-LT without prior KC between 2007 and 2016 were identified using linked data from the Organ Procurement and Transplantation Network and Medicare administrative claims. The primary exposures were immunosuppression regimen and latitude of residence. The primary outcome was incident, de novo KC occurring at least 1-year after LT. Adjusted Cox regression analysis stratified by transplant center was used in all analyses. The cohort was 63.4% male, 70.2% White and with median age 61 years (interquartile range, IQR, 54–66) at transplant. Calcineurin inhibitor (CNI) with anti-metabolite combination was independently associated with incident KC when measured as intention-to-treat (adjusted hazard ratio (aHR) 1.21 vs. CNI monotherapy, 95% CI 1.02–1.43, p = 0.026), in a time-updating as-treated analysis (aHR 1.61, 95% CI 1.34–1.93; p < 0.001) and when measured as cumulative exposure (aHR 1.13 per 6-month increase, 95% CI: 1.02–1.33; p = 0.027). More southern latitude of residence was also independently associated with incident KC with an aHR of 1.26 per 5°N decrease towards the Equator (95% CI: 1.08–1.47, p = 0.003). We demonstrate independent effects of CNI with antiM immunosuppression regimen and latitude of residence on the risk of post-LT KC, which will better inform screening practices and immunosuppression management. [ABSTRACT FROM AUTHOR]

Key message: The proteomic analysis of PMeV-complex-infected C. papaya unveiled proteins undergoing modulation during the plant's development. The infection notably impacted processes related to photosynthesis and cell wall dynamics. The development of Papaya Sticky Disease (PSD), caused by the papaya meleira virus complex (PMeV-complex), occurs only after the juvenile/adult transition of Carica papaya plants, indicating the presence of tolerance mechanisms during the juvenile development phase. In this study, we quantified 1609 leaf proteins of C. papaya using a label-free strategy. A total of 345 differentially accumulated proteins were identified—38 at 3 months (juvenile), 130 at 4 months (juvenile/adult transition), 160 at 7 months (fruit development), and 17 at 9 months (fruit harvesting)—indicating modulation of biological processes at each developmental phase, primarily related to photosynthesis and cell wall remodeling. Infected 3- and 4-mpg C. papaya exhibited an accumulation of photosynthetic proteins, and chlorophyll fluorescence results suggested enhanced energy flux efficiency in photosystems II and I in these plants. Additionally, 3 and 4-mpg plants showed a reduction in cell wall-degrading enzymes, followed by an accumulation of proteins involved in the synthesis of wall precursors during the 7 and 9-mpg phases. These findings, along with ultrastructural data on laticifers, indicate that C. papaya struggles to maintain the integrity of laticifer walls, ultimately failing to do so after the 4-mpg phase, leading to latex exudation. This supports initiatives for the genetic improvement of C. papaya to enhance resistance against the PMeV-complex. [ABSTRACT FROM AUTHOR]

Phenotypic plasticity allows a plant cell to alter its structure and function in response to external pressure. This adaptive phenomenon has also been important in the evolution of plants including the emergence of land plants from a streptophyte alga. Penium margaritaceum is a unicellular zygnematophyte (i.e., the group of streptophyte algae that is sister to land plants) that was employed in order to study phenotypic plasticity with a focus on the role of subcellular expansion centers and the cell wall in this process. Live cell fluorescence labeling, immunofluorescence labeling, transmission electron microscopy, and scanning electron microscopy showed significant subcellular changes and alterations to the cell wall. When treated with the actin-perturbing agent, cytochalasin E, cytokinesis is arrested and cells are transformed into pseudo-filaments made of up to eight or more cellular units. When treated with the cyclin-dependent kinase (CDK) inhibitor, roscovitine, cells converted to a unique phenotype with a narrow isthmus zone. [ABSTRACT FROM AUTHOR]

Stony coral tissue loss disease (SCTLD) has swept through Florida reefs and caused mass mortality of numerous coral species. In the wake of these losses, efforts are underway to propagate coral species impacted by SCTLD and promote population recovery. However, numerous knowledge gaps must be addressed to effectively grow, outplant, and restore populations of the slower growing, massive species that were lost. Here, we used sexual recruits of Diploria labyrinthiformis spawned in captivity to understand how conditioning, coral size, and nutritional status at outplanting affect coral survivorship, growth, and susceptibility to predation. We found that ex situ conditioning with supplemental feeding increased coral growth rates, resulting in larger sized corals at the time of outplanting. In turn, these corals had higher growth rates in the field and a lower probability of being removed by predators than outplants that were conditioned in in situ nurseries. Additionally, we found that coral size was an important predictor of survivorship, suggesting that hastening the speed at which young corals grow and outplanting larger juveniles can improve restoration outcomes. Taken together, our results suggest that providing supplemental food to corals at ex situ facilities confers benefits that could help restore populations of massive coral species impacted by SCTLD. [ABSTRACT FROM AUTHOR]

What sort of people like to work from home (WFH)? In this study 1185 adults from different sectors and countries completed a work-related personality test (HPTI) and a self-esteem measure as well as indicating their preference for WFH. Correlations showed that those who were less Adjusted, Conscientious, and Risking Taking showed a preference for WFH. The regression suggested the strongest indicator was sex, degree status, and trait Conscientiousness. We split the sample by sex, age and education and reran the six regressions. Conscientiousness was consistently significant, though other personality factors were important for non-graduates. Explanations and implications of this finding are discussed. The limitations of a cross-sectional study using only self-report data is acknowledged. [ABSTRACT FROM AUTHOR]

Noonan Syndrome (NS) is associated with an increased risk of low-grade central nervous system tumours in children but only very rarely associated with high-grade gliomas. Here we describe the first reported case of a spinal high-grade astrocytoma with piloid features (HGAP) in a child with NS. This case was a diagnostic and treatment dilemma, prior to whole-genome germline and tumour sequencing, tumour transcriptome sequencing and DNA methylation analysis. The methylation profile matched strongly with HGAP and sequencing identified somatic FGFR1 and NF1 variants and a PTPN11 germline pathogenic variant. Therapeutic targets were identified but also alterations novel to HGAP such as differential expression of VEGFA and PD-L1. The germline PTPN11 finding has not been previously described in individuals with HGAP. This case underscores the power of precision medicine from a diagnostic, therapeutic and clinical management perspective, and describes an association between HGAP and NS which has not previously been reported. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact that adjuvant therapies like radiotherapy, chemotherapy, and immunotherapy have on osteobiologic properties and bony regeneration in patients with metastatic spine disease (MSD) undergoing spinal fusion surgery. Methods: PubMed and ClinicalTrials.gov searches were performed. MSD patients undergoing fusion surgery with an osteobiologic and radiotherapy, chemotherapy and/or immunotherapy were included. Demographics, primary tumor, surgery, adjuvant treatments, osteobiologic type, fusion rates with scoring criteria, hardware failure, reoperation rates, follow-up, and survival were extracted. 1487 studies were screened, 20 included. Results: 585 patients (464 with MSD) had fusion rates ranging from 17.9 to 100%. In the setting of radiotherapy, fusion rates of 10 studies using autologous bone graft (autograft), 5 studies using allogenic bone graft (allograft), 5 studies using combination autograft/allograft, 4 studies using biomaterial scaffolds (BMS), 3 studies using demineralized bone matrices (DBM), and 1 study using growth factors (GF), were 50–100%, 17.9–100%, 57.8–100%, 52.9–100%, 20–100%, and 100%, respectively. A higher incidence of fusion in patients with autograft or allograft receiving stereotactic body radiotherapy (SBRT) at lower biologically effective doses (BED) and at least 1-month postoperatively was noted. Chemotherapy had no impact on fusion. No studies evaluated the impact of immunotherapy on fusion. Conclusions: SBRT at lower doses given greater than 1-month postoperatively may enhance bony fusion in patients receiving autograft, allograft, or autograft/allograft. Chemotherapy may delay bony fusion without affecting overall fusion rates. Preclinical studies suggest immunotherapy may prevent osteolysis and promote osteogenesis, but no studies have yet evaluated the clinical impact of these findings on spinal fusion. Further research is needed on osteobiologics in bony regeneration in the MSD population. [ABSTRACT FROM AUTHOR]

Splice site recognition is essential for defining the transcriptome. Drugs like risdiplam and branaplam change how human U1 snRNP recognizes particular 5′ splice sites (5′SS) and promote U1 snRNP binding and splicing at these locations. Despite the therapeutic potential of 5′SS modulators, the complexity of their interactions and snRNP substrates have precluded defining a mechanism for 5′SS modulation. We have determined a sequential binding mechanism for modulation of −1A bulged 5′SS by branaplam using a combination of ensemble kinetic measurements and colocalization single molecule spectroscopy (CoSMoS). Our mechanism establishes that U1-C protein binds reversibly to U1 snRNP, and branaplam binds to the U1 snRNP/U1-C complex only after it has engaged with a −1A bulged 5′SS. Obligate orders of binding and unbinding explain how reversible branaplam interactions cause formation of long-lived U1 snRNP/5′SS complexes. Branaplam targets a ribonucleoprotein, not only an RNA duplex, and its action depends on fundamental properties of 5′SS recognition. Splice sites must be correctly identified for introns to be removed from pre-mRNAs and for expression of the correct mRNA isoforms. Here, the authors elucidate how the human U1 snRNP splicing factor recognizes 5′ splice sites and how a splicing modulating drug can enhance splice site recognition. [ABSTRACT FROM AUTHOR]

Previous research on parent‒child relationships has focused more extensively on younger, school-aged children and adolescents, with mothers receiving more attention than fathers. In addition, there has been a greater focus on problematic parenting (e.g., helicopter parenting) and less research on supportive forms of parenting that can promote positive outcomes during emerging adulthood. The current study utilized the framework of self-determination theory to examine the association between positive parenting and well-being in a sample of emerging adults. Specifically, we examined the associations between positive maternal and paternal parenting approaches and emerging adults' basic psychological needs and well-being, with a focus on emerging adults of diverse ethnicities. Our primary hypotheses were that positive parenting would have significant: (a) direct associations with emerging adults' basic psychological needs and (b) indirect associations with emerging adults' well-being through their basic psychological needs. The participants were 1209 emerging adults aged 18–22 years (M = 19.27; SD = 1.53). The results revealed that parenting had significant positive direct effects on emerging adults' basic psychological needs and indirect associations with their well-being. These findings suggest that positive parenting continues to play an important role in emerging adulthood and highlight the need to work with emerging adults and their parents to establish strategies to support positive parenting that meet psychological needs during this time of life. Highlights: Mothers and fathers make significant and unique contributions to emerging adults' basic psychological needs. Among a diverse sample of emerging adults in North America, the satisfaction of emerging adults' basic psychological needs, including the positive contributions of both mothers and fathers, is important to their well-being and satisfaction with life. [ABSTRACT FROM AUTHOR]

Acinar cell carcinoma (ACC) and pancreatoblastoma (PBL) are rare pancreatic malignancies with acinar differentiation. Proteogenomic profiling of ACC and PBL revealed distinct protein expression patterns compared to pancreatic ductal adenocarcinoma (PDAC) and benign pancreas. ACC and PBL exhibited similarities, with enrichment in proteins related to RNA processing, chromosome organization, and the mitoribosome, while PDACs overexpressed proteins associated with actin-based processes, extracellular matrix, and immune-active stroma. Pathway activity differences in metabolic adaptation, epithelial-to-mesenchymal transition, and DNA repair were characterized between these diseases. PBL showed upregulation of Wnt-CTNNB1 and IGF2 pathways. Seventeen ACC-specific proteins suggested connections to metabolic diseases with mitochondrial dysfunction, while 34 PBL-specific proteins marked this pediatric cancer with an embryonic stem cell phenotype and alterations in chromosomal proteins and the cell cycle. This study provides novel insights into the proteomic landscapes of ACC and PBL, offering potential targets for diagnostic and therapeutic development. [ABSTRACT FROM AUTHOR]

Plants defend themselves chemically against herbivory through secondary metabolites and phytohormones. Few studies have investigated how constitutive variation in secondary metabolites contributes to systemic herbivory response. We hypothesized that plants with lower constitutive defenses would induce a stronger phytohormone response to spatially separated herbivory than plants with high constitutive defense. We used growth chamber bioassays to investigate how aboveground herbivory by Colorado potato beetle (Leptinotarsa decemlineata, CPB) and belowground herbivory by northern root-knot nematode (Meloidogyne hapla, RKN) altered phytohormones and glycoalkaloids in roots and shoots of two lines of wild potato (Solanum chacoense). These lines had different constitutive levels of chemical defense, particularly leptine glycoalkaloids, which are only present in aboveground tissues. We also determined how these differences influenced the preference and performance of CPB. The susceptible wild potato line responded to aboveground damage by CPB through induction of jasmonic acid (JA) and OPDA. However, when challenged by both RKN and CPB, the susceptible line retained high levels of JA, but not OPDA. Beetles gained more mass after feeding on the susceptible line compared to the resistant line, but were not affected by nematode presence. Belowground, JA, JA-Isoleucine, and OPDA were higher in the resistant line compared to the susceptible line, and some compounds demonstrated response to local herbivory. In contrast, the susceptible line did not induce phytohormone defenses belowground. These findings allow us to predict that constitutive level of defense may influence the threshold of herbivory that may lead to plant-mediated effects on spatially separated herbivores. [ABSTRACT FROM AUTHOR]

While dorsal-ventrally compressed chondrichthyans are among the most imperiled fishes in the world, there is still limited knowledge of the biology of many of these species, even in well-studied ocean basins. In the western North Atlantic Ocean, the population structure of the Atlantic angel shark (Squatina dumeril) is not fully understood; therefore, the portioning of genetic variation was assessed among individuals caught along the east coast of the United States (Atlantic) and on the northern Gulf of Mexico (Gulf) using reduced representation genomics and mitochondrial sequencing. Three distinct groups were delineated with nuclear data, the Atlantic, the eastern Gulf, and the western Gulf, along boundaries described by previous research. Mitochondrial data only resolved two groups, with the western Gulf separated from the eastern Gulf and Atlantic combined. Demographic modeling suggested that the Atlantic population separated from a single Gulf population which subsequently split into eastern and western populations. Additionally, there was evidence that adjacent populations experienced gene flow after splitting, which may explain the incongruence between results based on nuclear and mtCR data. Correlations between environmental variables and allele frequencies at 873 loci indicated potential local adaptation. Therefore, the preservation of all three groups is necessary for the conservation of long-term adaptive variation important for species persistence. [ABSTRACT FROM AUTHOR]

The osteon is the primary structural component of bone, contributing significantly to its unique toughness and strength. Despite extensive research on osteonal structure, the properties of osteons have not been fully investigated, particularly within the context of bone fragility diseases like type 2 diabetes mellitus (T2DM). This study aims to isolate osteons from bovine bone, simulate the effects of increased advanced glycation end-products (AGEs) in T2DM through ribosylation, and evaluate the mechanical properties of isolated osteons. Osteons extracted from the posterior section of bovine femur mid-diaphysis were processed to achieve a sub-millimeter scale for microscale imaging. Subsequently, synchrotron radiation micro-computed tomography was employed to precisely localize and isolate the osteon internally. While comparable elastic properties were observed between control and ribosylated osteons, the presence of AGEs led to decreased strain to failure. Young's modulus was quantified (9.9 ± 4.9 GPa and 8.7 ± 3 GPa, respectively), aligning closely with existing literature. This study presents a novel method for the extraction and isolation of osteons from bone and shows the detrimental effect of AGEs at the osteonal level. [ABSTRACT FROM AUTHOR]

Background: Thymoma presents with several autoimmune manifestations and is associated with secondary autoimmune regulator (AIRE) deficiency. Pneumonitis has recently been described as an autoimmune manifestation associated with thymoma presenting with similar clinical, radiographic, histological, and autoantibody features as seen in patients with inherited AIRE deficiency who suffer from Autoimmune PolyEndocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) syndrome. Objectives: To treat two patients with biopsy-proven thymoma-associated pneumonitis with lymphocyte-directed immunomodulation. Methods: Two patients with thymoma were enrolled on IRB-approved protocols at the NIH Clinical Center. We performed history and physical examination; laboratory, radiographic, histologic and pulmonary function evaluations; and measurement of the lung-directed autoantibodies KCNRG and BPIFB1 prior to and at 1- and 6-months following initiation of lymphocyte-directed immunomodulation with azathioprine with or without rituximab. Results: Combination T- and B-lymphocyte-directed immunomodulation resulted in improvement of clinical, functional, and radiographic parameters at 6-month follow-up evaluations in both patients with sustained remission up to 12–36 months following treatment initiation. Conclusion: Lymphocyte-directed immunomodulation remitted autoimmune pneumonitis in two patients with thymoma. [ABSTRACT FROM AUTHOR]

After Fontan operation, decreased venous capacitance and venoconstriction are adaptive mechanisms to maintain venous return and cardiac output. The consequent higher venous pressure may adversely impact end-organ function, exercise capacity and result in worse clinical outcomes. This pilot study evaluated the safety and effect of isosorbide dinitrate (ISDN), a venodilator, on exercise capacity, peripheral venous pressure (PVP), and liver stiffness in patients with Fontan circulation. In this prospective single-arm trial, 15 individuals with Fontan circulation were evaluated at baseline and after 4 weeks of therapeutic treatment with ISDN. Primary aims were to assess the safety of ISDN and the effect on maximal exercise. We also aimed to evaluate the effect of ISDN on ultrasound-assessed liver stiffness, markers of submaximal exercise, and PVP at rest and peak exercise. Repeated measures t-tests were used to assess change in variables of interest in response to ISDN. Mean age was 23.5 ± 9.2 years (range 11.2–39.0 years), and 10/15 (67%) were male. There was no statistically significant change in peak VO2 (1401 ± 428 to 1428 ± 436 mL/min, p = 0.128), but VO2 at the anaerobic threshold increased (1087 ± 313 to 1115 ± 302 mL/min, p = 0.03). ISDN was also associated with a lower peak exercise PVP (22.5 ± 4.5 to 20.6 ± 3.0 mmHg, p = 0.015). Liver stiffness was lower with ISDN, though the difference was not statistically significant (2.3 ± 0.4 to 2.1 ± 0.5 m/s, p = 0.079). Of the patients completing the trial, mild headache was common (67%), but there were no major adverse events. Treatment with ISDN for 4 weeks is well-tolerated in patients with a Fontan circulation. ISDN is associated with an increase in VO2 at anaerobic threshold, lower peak PVP, and a trend toward lower liver stiffness. Larger, longer duration studies will be necessary to define the impact of ISDN on clinical outcomes in the Fontan circulation. Clinical Trial Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT04297241. [ABSTRACT FROM AUTHOR]

Background: A brief, parent-led, transdiagnostic cognitive behavioral therapy (CBT) approach demonstrated utility among youth struggling with emotional problems during the COVID-19 pandemic. Homework completion between sessions is directly associated with psychotherapy treatment outcomes in non-parent-led CBT interventions. The present study sought to examine the relationship between homework completion and treatment response in a parent-led transdiagnostic CBT protocol. Objective: The first aim was to determine if completion of between session CBT homework was associated with change in symptom severity. The second aim was to determine if pre-treatment anxiety severity, social anxiety severity, and depressive symptoms were associated with treatment outcomes. Methods: One-hundred twenty-nine parents of youth (ages 5–13) with significant emotional problems received 6 sessions of telehealth parent-led CBT during the COVID-19 pandemic. Data on children's anxiety symptomology, clinical severity, homework compliance, depression, family relationships, perceptions on the impacts of the pandemic, treatment response, and therapists rating of symptom improvement were collected. Results: Homework completion explained 9% of the variance in symptom improvement at post-treatment. Greater homework completion was associated with a significantly higher odds of treatment response (OR = 1.52, p =.001). Child anxiety severity, depressive symptoms, family relationships, and perceptions on the impacts of the COVID-19 pandemic were not significantly related to treatment outcome. Conclusions: Completion of homework predicted treatment outcomes in parent-led, transdiagnostic CBT for youth with emotional problems during the COVID-19 pandemic, while controlling for parent-rated anxiety, depression, family relationships, and COVID-related distress. Enhancing and targeting homework compliance between CBT sessions should be a central element of parent-led treatment. [ABSTRACT FROM AUTHOR]

Key message: The barley mutant xan-h.chli-1 shows phenotypic features, such as reduced leaf chlorophyll content and daily transpiration rate, typical of wild barley accessions and landraces adapted to arid climatic conditions. The pale green trait, i.e. reduced chlorophyll content, has been shown to increase the efficiency of photosynthesis and biomass accumulation when photosynthetic microorganisms and tobacco plants are cultivated at high densities. Here, we assess the effects of reducing leaf chlorophyll content in barley by altering the chlorophyll biosynthesis pathway (CBP). To this end, we have isolated and characterised the pale green barley mutant xan-h.chli-1, which carries a missense mutation in the Xan-h gene for subunit I of Mg-chelatase (HvCHLI), the first enzyme in the CBP. Intriguingly, xan-h.chli-1 is the only known viable homozygous mutant at the Xan-h locus in barley. The Arg298Lys amino-acid substitution in the ATP-binding cleft causes a slight decrease in HvCHLI protein abundance and a marked reduction in Mg-chelatase activity. Under controlled growth conditions, mutant plants display reduced accumulation of antenna and photosystem core subunits, together with reduced photosystem II yield relative to wild-type under moderate illumination, and consistently higher than wild-type levels at high light intensities. Moreover, the reduced content of leaf chlorophyll is associated with a stable reduction in daily transpiration rate, and slight decreases in total biomass accumulation and water-use efficiency, reminiscent of phenotypic features of wild barley accessions and landraces that thrive under arid climatic conditions. [ABSTRACT FROM AUTHOR]

A key player in energy metabolism is phosphofructokinase-1 (PFK1) whose activity and behavior strongly influence glycolysis and thus have implications in many areas. In this research, PFK1 assays were performed to convert F6P and ATP into F-1,6-P and ADP for varied pH and ATP concentrations. PFK1 activity was assessed by evaluating F-1,6-P generation velocity in two ways: (1) directly calculating the time slope from the first two or more datapoints of measured product concentration (the initial-velocity method), and (2) by fitting all the datapoints with a differential equation explicitly representing the effects of ATP and pH (the modeling method). Similar general trends of inhibition were shown by both methods, but the former gives only a qualitative picture while the modeling method yields the degree of inhibition because the model can separate the two simultaneous roles of ATP as both a substrate of reaction and an inhibitor of PFK1. Analysis based on the model suggests that the ATP affinity is much greater to the PFK1 catalytic site than to the inhibitory site, but the inhibited ATP-PFK1-ATP complex is much slower than the uninhibited PFK1-ATP complex in product generation, leading to reduced overall reaction velocity when ATP concentration increases. The initial-velocity method is simple and useful for general observation of enzyme activity while the modeling method has advantages in quantifying the inhibition effects and providing insights into the process. [ABSTRACT FROM AUTHOR]

Purpose: To report antegrade transvenous obliteration, with or without concurrent portosystemic shunt creation, for the treatment of hemorrhagic rectal varices. Materials and methods: Eight patients, including five (62.5%) females and three (37.5%) males, with mean age of 55.8 ± 13.8 years (range: 30–70 years), underwent transjugular-approach antegrade transvenous obliteration of rectal varices, with or without portosystemic shunt creation. Demographic data, procedural details, technical success of variceal obliteration, clinical success, adverse events, and follow-up outcomes were retrospectively recorded. Clinical success was defined as resolution of rectal hemorrhage. Results: Portal venous access was achieved via a transjugular intrahepatic approach in all patients. The inferior mesenteric vein was selected, and foamy sclerosant (1:2:3 mixture by volume of ethiodized oil: sodium tetradecyl sulfate: air) was injected into the rectal varices with antegrade balloon occlusion in seven (87.5%) and without balloon occlusion in one (12.5%). Five of eight (62.5%) patients underwent concomitant transjugular intrahepatic portosystemic shunt (TIPS) creation (mean diameter 8.4 ± 0.9-mm) immediately following transvenous obliteration. Technical success of variceal obliteration was achieved in all patients. There were no immediate post-procedural adverse events. There were no reported occurrences of rectal ischemia, perforation, or stricture following obliteration. Two (40%) of the patients who underwent concomitant TIPS creation developed hepatic encephalopathy within 30 days of the procedure, which was medically managed. Clinical resolution of hemorrhage was achieved in all patients with no recurrent rectal variceal hemorrhage during mean follow-up of 666 ± 396 days (range: 14 − 1,224 days). Conclusion: Transvenous obliteration, with or without concurrent TIPS creation, is feasible with promising results for the management of rectal variceal hemorrhage. [ABSTRACT FROM AUTHOR]

Research regulations around the world do not impose any limits on the risks to which consenting adults may be exposed. Nonetheless, most review committees regard some risks as too high, even for consenting adults. To justify this practice, commentators have appealed to a range of considerations which are external to informed consent and the risks themselves. Most prominently, some argue that exposing consenting adults to very high risks has the potential to undermine public trust in research. This justification assumes that it is not the magnitude of the risks themselves which raises concern, but the way in which the public might respond to them. This justification thus depends on the possibility that the public will find out about the risks and respond to them in the specified way. Like the other proposed external justifications, it thereby fails to offer a reason to think that exposing consenting adults to very high risks is problematic in itself. In the present paper, we describe and endorse a different justification. Rather than appealing to external factors, we argue that limits on risks for consenting adults trace to internal limits on informed consent, to limits on the things consent can and cannot make ethically permissible. In doing so, we aim to provide a firmer conceptual basis for the view that some research risks are unacceptably high, no matter how the research is conducted. [ABSTRACT FROM AUTHOR]

This research investigates innovative fin-type radiators for automobile engine cooling system. Micro-channel and helical radiators, along with straight type, were analyzed for heat transfer characteristics under various conditions. The uniqueness of this study is evident in the design of microchannel and helical radiators. For helical radiators, the inner rod features 4/8 helical-shaped water galleries, while the outer tube frame with embedded fins remains consistent. In contrast, the microchannel radiators have compact trapezoidal-shaped water galleries with separate fin strips. Furthermore, the novelty of the research is enhanced by the utilization of 3D printing technology in the manufacturing process. In constant fin height analysis at varied water and air flow rate, Microchannel Water Air Radiator with fin height 10.5 mm (MCWAR10.5) depicted a higher heat transfer rate amongst the radiators. In comparison to Straight Water Air Radiator with fin height 9.5 mm (SWAR9.5), the heat transfer rate is 30.3% and 1.3 times higher. However, in constant fin surface area analysis, microchannel radiator (MCWAR3.2) illustrates lower heat dissipation than Helical radiator (HWAR138) but higher than HWAR134 and Straight radiator (SWAR6). The examination of pumping loss indicated that the Micro-channel radiator outperformed helical radiators due to its lower pressure loss. The average pressure loss for Micro-channel radiators was 0.74 kPa, making it 1.2 times higher than that of a straight radiator (0.62 kPa), indicating a better trade-off. [ABSTRACT FROM AUTHOR]

Context: Small carnivores are declining globally due to a complex suite of threats. Conservation of these species requires an understanding of their distributions and potential responses to future land-use and climate change. Objectives: We modelled species-environment relationships of swift fox (Vulpes velox), a species of concern across their range. We developed spatial projections of current and future distribution to aid in conservation planning. Methods: We assembled swift fox occurrence data from managers and community science sources to develop ensemble distribution models. In addition to landscape and climatic predictors, we developed a model of red fox distribution to represent effects of competition. We forecasted spatial predictions into the year 2070 under two climate change scenarios representing high (SSP 5–8.5) and low (SSP 1–2.6) emissions scenarios. Results: Percent cover by grassland, mean annual precipitation, and minimum temperature of the coldest quarter were the three most important variables for swift fox distribution. Current suitable habitat for swift fox extends across 16 North American states and provinces. Future projections of swift fox distribution suggest an overall increase in area of swift fox suitable habitat under both emissions scenarios of > 56.9%, though patterns of gain and loss vary spatially. Conclusions: The expansion of suitable habitat in future scenarios reflects swift fox adaptability to multiple land uses in a period following multi-organizational conservation efforts. Our spatial projections can be used in conservation planning and can serve as a case study of a small carnivore species likely to recover under future change scenarios provided that threats are addressed and landscape-scale conservation efforts continue. [ABSTRACT FROM AUTHOR]

3D reconstruction of biplane cerebral angiograms remains a challenging, unsolved research problem due to the loss of depth information and the unknown pixelwise correlation between input images. The occlusions arising from only two views complicate the reconstruction of fine vessel details and the simultaneous addressing of inherent missing information. In this paper, we take an incremental step toward solving this problem by reconstructing the corresponding 2D slice of the cerebral angiogram using biplane 1D image data. We developed a coordinate-based neural network that encodes the 1D image data along with a deterministic Fourier feature mapping from a given input point, resulting in a slice reconstruction that is more spatially accurate. Using only one 1D row of biplane image data, our Fourier feature network reconstructed the corresponding volume slices with a peak signal-to-noise ratio (PSNR) of 26.32 ± 0.36, a structural similarity index measure (SSIM) of 61.38 ± 1.79, a mean squared error (MSE) of 0.0023 ± 0.0002, and a mean absolute error (MAE) of 0.0364 ± 0.0029. Our research has implications for future work aimed at improving backprojection-based reconstruction by first examining individual slices from 1D information as a prerequisite. [ABSTRACT FROM AUTHOR]

Epidemiological research over the past two decades has highlighted substance use disparities that affect Native Hawaiian and Pacific Islander youth, and the lack of effective approaches to address such disparities (Okamoto et al. in Asian American Journal of Psychology 10(3):239–248, 2019). The Ho'ouna Pono curriculum is a culturally grounded, teacher-implemented, video-enhanced substance use prevention program that has demonstrated efficacy in rural Hawaiʻi in a large-scale trial (Okamoto in Asian American Journal of Psychology 10(3):239–248, 2019). Despite its potential to ameliorate health disparities and address youth substance use, prevention programs such as Ho'ouna Pono have been poorly disseminated and implemented across Hawaiʻi, raising the question: Why are effective prevention programs not used in communities that most need them? The present study used concept mapping to understand previously identified implementation barriers and develop implementation strategies for Ho'ouna Pono. Seven Hawaiʻi Department of Education (HIDOE) educational leaders and administrators sorted Ho'ouna Pono implementation barriers (e.g., "There is a lack of HIDOE funding to support prevention curricula"), named concepts, and rated barriers' perceived impact and difficulty. Multidimensional scaling and cluster analysis yielded a five-cluster solution: (1) Kumu (Hawaiian word for teacher) Controlled, (2) School Level Buy-in, (3) Curriculum, (4) Student Attitudes + Mindsets (Family + Community), and (5) Policy. Participant ratings identified eight high-impact and low-difficulty barriers. Discussion revealed important intersections among barriers indicating the need for coordinated and cross-level implementation strategies to support Ho'ouna Pono sustainment. Brainstormed implementation strategies using participants' own language highlighted a need for participatory methods in school settings to bidirectionally share ways to best sustain substance use prevention programs. [ABSTRACT FROM AUTHOR]

Schools need effective, sustainable implementation strategies to support teachers in using effective Tier 1 (i.e., whole class) and Tier 2 (i.e., targeted) behavioral interventions in the classroom. This paper describes an iterative, community-partnered process of developing implementation resources to support teachers in using Tier 1 and 2 positive behavior management interventions; we call these resources the Positive Behavior Management Toolkit (PBMT). There were two key aspects to the iterative development process: 1) working with a Program Development Team of district—and school-employed partners to identify priorities, interpret data, provide feedback on resources, and plan for sustainment; and 2) conducting a series of tryouts in which teachers used a version of the PBMT in their classrooms and provided quantitative and qualitative feedback on acceptability, appropriateness, feasibility, and recommendations for improvement. In partnership with the Program Development Team, we used data from the tryouts to inform revisions to the PBMT. This paper presents quantitative and qualitative data from the tryouts and describes how these data informed revisions to the PBMT. We also describe the processes by which we engaged the team, considerations related to contextual appropriateness, and lessons learned related to community-engaged intervention development research. [ABSTRACT FROM AUTHOR]

Background: Pectoral nerve (PECs) blocks are established regional anesthesia techniques that can provide analgesia to the anterior chest wall. Although commonly performed preoperatively by anesthesiologists, the feasibility of electrophysiologist-performed PECs blocks from within cardiac implantable electronic device (CIED) pockets at the time of implantation has not been established. The objective of this study is to assess the feasibility of routine PECs blocks performed by the electrophysiologist from within the exposed device pocket at the time of CIED procedures. Methods: Patients undergoing CIED procedures underwent a PECs I block (15 cc of 1% lidocaine/0.25% bupivacaine) injected between the pectoralis major and minor muscles guided by ultrasound placed in the device pocket, or PECs II block, which included a second injection (15 cc) between pectoralis minor and serratus anterior muscles. Postoperatively, pain was assessed on a numeric scale (0–10) at 1, 2, 4, and 24 h, and 2 weeks after the procedure. Results: Among 20 patients (age 65 ± 16 years, 70% male, 55% with history of chronic pain), PECs I (75%) and PECs II (25%) blocks were performed. The procedures were de novo implantation (n = 17) or device revision (n = 3). The average pain score in the first 4 h was 0.4 ± 0.8 and 0.3 ± 0.6 at 24 h after the procedure. During the 24-h postoperative period, 4 patients received opioids. Two patients were discharged with opioids for pain unrelated to the procedure. Conclusions: Intraoperative PECs blocks can be feasibly performed from within an exposed pocket at the time of CIED procedures with minimal postoperative pain. [ABSTRACT FROM AUTHOR]

Affective and psychotic disorders are highly prevalent and severely debilitating mental illnesses that often remain untreated or treatment-resistant. Sulpiride is a common antipsychotic (neuroleptic) drug whose well-established additional (e.g., antidepressant) therapeutic effects call for further studies of a wider spectrum of its CNS effects. Here, we examined effects of acute 20-min exposure to sulpiride (50–200 mg/L) on anxiety- and depression-like behaviors, as well as on brain monoamines, in adult zebrafish (Danio rerio). Overall, sulpiride exerted overt anxiolytic-like effects in the novel tank test and showed tranquilizing-like effects in the zebrafish tail immobilization test, accompanied by lowered whole-brain dopamine and its elevated turnover, without affecting serotonin or norepinephrine levels and their turnover. Taken together, these findings support complex behavioral pharmacology of sulpiride in vivo and reconfirm high sensitivity of zebrafish-based screens to this and, likely, other related clinically active neuroleptics. [ABSTRACT FROM AUTHOR]

Objectives: Examine the effect of a 40-h police sexual assault training and individual-level impulsivity on officers' intention to make an arrest and the importance placed on using procedural justice when interacting with victims. Methods: Training courses were randomly assigned to the treatment and control groups. Vignettes depicting sexual assault reports were randomly assigned to participants (N=318) in each group. Vignette manipulations were randomized by victim-offender relationship (stranger/non-stranger) and rape myth acceptance (present/not present/ambiguous). Results: Training increased officers' intentions to arrest. Training and lower impulsivity increased the importance officers placed on using procedural justice. Vignette manipulations were not significantly correlated with either outcome. Impulsivity did not moderate—or change—training effects. Conclusions: Sexual assault training can increase officers' self-reported intentions to arrest and the perceived importance placed on using procedural justice in interactions with victims. This finding is important as prior research demonstrated that using procedural justice principles can improve victim engagement with investigators. [ABSTRACT FROM AUTHOR]

A critical barrier to transforming separation technology from energy-intensive thermal methods to more efficient material-based adsorption methods is the limited availability of coadsorption data under mixture conditions. While experimentation under realistic conditions seems superior, the difficulty of conducting these experiments is a prevalent limitation to mainstream adoption. Ideal Adsorbed Solution Theory (IAST) and Grand Canonical Monte Carlo (GCMC) simulations offer predictive alternatives to experimental mixture adsorption; however, both have limitations in accuracy and efficiency. Here, we present a systematic study of coadsorption of binary mixtures of carbon dioxide, ethane, and n-butane as examples covering a variety of polarizability and size. Mixture adsorption is investigated in three adsorbents with different motifs: UiO-66 as a baseline material, UiO-66-NH2 as an example with pendant functional amine groups, and HKUST-1 as an example with open metal sites (OMS). Results show near-quantitative matches of fractional loadings between IAST, GCMC, and experiments for n-butane-containing mixtures in UiO-66 and UiO-66-NH2 with significant deviations for other systems. The observed differences can be attributed to insufficient interaction modeling in GCMC, synergetic effects in the adsorbed phase, or diffusion and flow effects under mixture conditions in a fixed bed separation, highlighting where IAST and GCMC are not adequate replacements for experimental measurements. [ABSTRACT FROM AUTHOR]

Aims: To investigate the potential association between gambling disorder and symptoms of sleep problems (including insomnia and excessive daytime sleepiness). It was hypothesised that, compared to controls, individuals with gambling disorder would have significantly greater disturbance of sleep, as indicated by increased scores in: (1) sleep items on the Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Rating Scale for Depression (HAM-D); (2) total score on the HAM-A and HAM-D; and (3) the Epworth Sleepiness Scale (ESS). Methods: Secondary analysis of previously published data from 152 young adults, aged 18–29 years. Individuals were stratified into three groups: controls, those at risk of gambling disorder, and those with gambling disorder. One-way ANOVAs with post-hoc tests were conducted to determine whether groups differed significantly in sleep item scores and total scores of the HAM-A and HAM-D, and the ESS. Results: HAM-D scale insomnia item scores were significantly higher in the disorder group, when compared to controls, this being particularly marked for middle and late insomnia. The HAM-A item score indicated significantly worse sleep quality in the disorder group, compared to at risk and control groups. Total HAM-A and HAM-D scores were significantly higher in the disorder group, but ESS scores did not differ significantly. Conclusion: Measures of disruptions in sleep were significantly higher in gambling disorder than controls. Anxiety and depressive symptom severity was also significantly higher in the gambling disorder group. Further research could have implications for identification and treatment of sleep disorders and psychiatric comorbidities in gambling disorder. [ABSTRACT FROM AUTHOR]

As is true of many complex tasks, the work of discovering, describing, and understanding the diversity of life on Earth (viz., biological systematics and taxonomy) requires many tools. Some of this work can be accomplished as it has been done in the past, but some aspects present us with challenges which traditional knowledge and tools cannot adequately resolve. One such challenge is presented by species complexes in which the morphological similarities among the group members make it difficult to reliably identify known species and detect new ones. We address this challenge by developing new tools using the principles of machine learning to resolve two specific questions related to species complexes. The first question is formulated as a classification problem in statistics and machine learning and the second question is an out-of-distribution (OOD) detection problem. We apply these tools to a species complex comprising Southeast Asian stream frogs (Limnonectes kuhlii complex) and employ a morphological character (hind limb skin texture) traditionally treated qualitatively in a quantitative and objective manner. We demonstrate that deep neural networks can successfully automate the classification of an image into a known species group for which it has been trained. We further demonstrate that the algorithm can successfully classify an image into a new class if the image does not belong to the existing classes. Additionally, we use the larger MNIST dataset to test the performance of our OOD detection algorithm. We finish our paper with some concluding remarks regarding the application of these methods to species complexes and our efforts to document true biodiversity. [ABSTRACT FROM AUTHOR]

DNA crosslinks block DNA replication and are repaired by the Fanconi anaemia pathway. The FANCD2–FANCI (D2–I) protein complex is central to this process as it initiates repair by coordinating DNA incisions around the lesion1. However, D2–I is also known to have a more general role in DNA repair and in protecting stalled replication forks from unscheduled degradation2–4. At present, it is unclear how DNA crosslinks are recognized and how D2–I functions in replication fork protection. Here, using single-molecule imaging, we show that D2–I is a sliding clamp that binds to and diffuses on double-stranded DNA. Notably, sliding D2–I stalls on encountering single-stranded–double-stranded (ss–ds) DNA junctions, structures that are generated when replication forks stall at DNA lesions5. Using cryogenic electron microscopy, we determined structures of D2–I on DNA that show that stalled D2–I makes specific interactions with the ss–dsDNA junction that are distinct from those made by sliding D2–I. Thus, D2–I surveys dsDNA and, when it reaches an ssDNA gap, it specifically clamps onto ss–dsDNA junctions. Because ss–dsDNA junctions are found at stalled replication forks, D2–I can identify sites of DNA damage. Therefore, our data provide a unified molecular mechanism that reconciles the roles of D2–I in the recognition and protection of stalled replication forks in several DNA repair pathways.FANCD2–FANCI is a sliding clamp that diffuses on double-stranded DNA but stalls when it reaches a single-stranded gap, providing a unified molecular mechanism that reconciles the roles of FANCD2–FANCI in the recognition and protection of stalled replication forks. [ABSTRACT FROM AUTHOR]

Heart rate, a measure of the frequency of the cardiac cycle, reflects the health of the cardiovascular system, metabolic rate, and activity of the autonomic nervous system. Whether changes in resting heart rate are related to lifespan has not yet been explored to our best knowledge. In this study, we examined the association between resting heart rate and lifespan using linear regression in the Paris Prospective Study I, the Whitehall I Study, and the Framingham Heart Study. We used Cox proportional hazards regression to relate changes in heart rate over years to mortality risk. We observed a statistically significant association between increases in resting heart rate over a 5-year period and risk of mortality in the Paris Prospective Study I (HR mortality per 10 bpm increase over time: 1.20; 95% CI: 1.13 to 1.27) and over an 8-year period in the Framingham Heart Study (HR: 1.13; 95% CI: 1.07 to 1.19 for men and HR: 1.09; 95% CI: 1.04 to 1.15 for women), after adjusting for classical risk factors and resting heart rate. Our study shows that men and women who increase their resting heart rate over time increase their risk of mortality. [ABSTRACT FROM AUTHOR]

We present a study where predictive mechanistic modeling is combined with deep learning methods to predict individual patient survival probabilities under immune checkpoint inhibitor (ICI) immunotherapy. This hybrid approach enables prediction based on both measures that are calculable from mechanistic models of key mechanisms underlying ICI therapy that may not be directly measurable in the clinic and easily measurable quantities or patient characteristics that are not always readily incorporated into predictive mechanistic models. A deep learning time-to-event predictive model trained on a hybrid mechanistic + clinical data set from 93 patients achieved higher per-patient predictive accuracy based on event-time concordance, Brier score, and negative binomial log-likelihood-based criteria than when trained on only mechanistic model-derived values or only clinical data. Feature importance analysis revealed that both clinical and model-derived parameters play prominent roles in increasing prediction accuracy, further supporting the advantage of our hybrid approach. [ABSTRACT FROM AUTHOR]

Resistance to radiotherapy is a major barrier during cancer treatment. Here using genome-scale CRISPR/Cas9 screening, we identify CD274 gene, which encodes PD-L1, to confer lung cancer cell resistance to ionizing radiation (IR). Depletion of endogenous PD-L1 delays the repair of IR-induced DNA double-strand breaks (DSBs) and PD-L1 loss downregulates non-homologous end joining (NHEJ) while overexpression of PD-L1 upregulates NHEJ. IR induces translocation of PD-L1 from the membrane into nucleus dependent on deglycosylation of PD-L1 at N219 and CMTM6 and leads to PD-L1 recruitment to DSBs foci. PD-L1 interacts with Ku in the nucleus and enhances Ku binding to DSB DNA. The interaction between the IgC domain of PD-L1 and the core domain of Ku is required for PD-L1 to accelerate NHEJ-mediated DSB repair and produce radioresistance. Thus, PD-L1, in addition to its immune inhibitory activity, acts as mechanistic driver for NHEJ-mediated DSB repair in cancer. Resistance to radiotherapy is a major barrier during cancer treatment. Here the authors find that radiation-induced DNA double-strand-breaks (DSBs) facilitate PD-L1 deglycosylation and translocation into the nucleus, leading to promotion of NHEJ-mediated DSB repair and lung cancer radioresistance. [ABSTRACT FROM AUTHOR]