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Abstract Microbial biochemistry is central to the pathophysiology of inflammatory bowel diseases (IBD). Improved knowledge of microbial metabolites and their immunomodulatory roles is thus necessary for diagnosis and management. Here, we systematically analyzed the chemical, ecological, and epidemiological properties of ~82k metabolic features in 546 Integrative Human Microbiome Project (iHMP/HMP2) metabolomes, using a newly developed methodology for bioactive compound prioritization from microbial communities. This suggested >1000 metabolic features as potentially bioactive in IBD and associated ~43% of prevalent, unannotated features with at least one well-characterized metabolite, thereby providing initial information for further characterization of a significant portion of the fecal metabolome. Prioritized features included known IBD-linked chemical families such as bile acids and short-chain fatty acids, and less-explored bilirubin, polyamine, and vitamin derivatives, and other microbial products. One of these, nicotinamide riboside, reduced colitis scores in DSS-treated mice. The method, MACARRoN, is generalizable with the potential to improve microbial community characterization and provide therapeutic candidates.

Abstract Authors used an andragogy framework to help undergraduate allied health students better understand social determinants of health (SDOH) using a photo essay assignment. The study examined students’ perceptions of SDOH in various communities, description of health outcomes associated with their chosen SDOH, and lessons learned and suggestions to improve the assignment for future cohorts. Data were extracted from photo essays from 2019–2021 and entered in Microsoft Excel and Word for data analysis after course completion. Conventional qualitative content analysis was used to analyze student evaluation data from open-ended questions. Data were extracted from 53 student essays from 2019 to 2021. Most photo essays described communities in South Carolina (n = 42, 79.2%), urban areas (n = 37, 69.8%), or intermediary SDOH (75.5%). Several themes emerged concerning lessons learned (awareness and empathy are key to addressing SDOH), health equity (collaboration is necessary to provide resources, especially for underserved populations), and constructive feedback for the instructor (more time to discuss SDOH and assignment with peers and instructor). Faculty must work with students to think about more upstream factors like policy and cultural and societal values. Collecting evaluation data, specifically lessons learned and constructive feedback for faculty, can help faculty continuously improve course topics and assignments. Following a transparency framework can support student success and help faculty become effective leaders in the classroom while teaching subjects like SDOH and social justice.

Condoms continue to be used by many gay, bisexual, and other men who have sex with men (GBM) to reduce the risk of HIV transmission. However this is impacted by condom failure events, defined here as condom breakage and slippage. In a prospective, observational cohort study of 343 HIV serodiscordant male couples recruited through high HIV caseload clinics and hospitals between 2012 and 2016 in Australia, Brazil, and Thailand, condom failure rates and associated factors were analysed, including with the study partner versus other sexual partners. There were 717 reported instances of condom failure from an estimated total of 25,831 sex acts with condoms, from over 588.4 participant years of follow up. Of the HIV-negative partners (n = 343) in the study, more than a third (n = 117, 36.7%) reported at least one instance of condom failure with any partner type during study follow-up. Condom failure with their study partner was reported by 91/343 (26.5%) HIV-negative partners, compared with 43/343 (12.5%) who reported condom failure with other partners. In total, there were 86 events where the HIV-negative partner experienced ano-receptive condom failure with ejaculation, representing 12.0% of all failure events. In multivariable analysis, compared to Australia, HIV-negative men in Brazil reported a higher incidence risk rate of condom failure (IRR = 1.64, 95%CI 1.01–2.68, p = 0.046) and HIV-negative men who reported anal sex with other partners reported an increased risk of condom failure compared with men who only had sex with their study partner (IRR = 1.89, 95%CI 1.08–3.33, p = 0.025). Although at least one event of condom failure was reported by a significant proportion of participants, overall condom failure events represented a small proportion of the total condom protected sex acts. [ABSTRACT FROM AUTHOR]

There is considerable research evaluating the effects of family members implementing shared book reading interventions, especially during early childhood. However, less is known about the effects of family members providing instruction to help their school-aged children develop literacy skills, including both code-focused and meaning-focused skills that facilitate reading comprehension. The purpose of this meta-analysis was to describe and evaluate recent research examining the effects of at-home, family-implemented literacy interventions for school-aged children. A total of 25 interventions across 22 studies (12 with group designs and 10 with single-case experimental designs) were analyzed. The average effect on combined literacy outcomes was estimated as g = 0.36 (p <.01; Q = 191.83; I2 = 36.17) for group design studies and g = 1.50 (p <.01; Q = 114.58; I2 = 38.58) for single-case experimental design studies. Notably, for group design studies, effects varied by literacy outcome type. The mean effect for code-focused outcomes (i.e., PA, decoding/word reading, spelling, text reading) was g = 0.28 (p <.01) and the mean effect for meaning-focused outcomes (i.e., vocabulary, listening comprehension, reading comprehension) was g = 0.41 (p <.01). Overall, these findings support the implementation of family-delivered literacy interventions to improve literacy outcomes for school-aged children. At the same time, this meta-analysis revealed the paucity of research examining the effects of family-implemented literacy interventions, especially for older children, indicating a need for more research on this topic. [ABSTRACT FROM AUTHOR]

The Grignard reaction represents one of the most powerful carbon-carbon bond forming reactions and is the subject of continual study. Investigations of alkyl magnesium halide additions to β-hydroxy ketones identified a unique effect of the magnesium halide on diastereoselectivity, with alkylmagnesium iodide reagents demonstrating high levels of selectivity for the formation of 1,3-syn diols. Density functional theory (DFT) calculations and mechanistic studies suggest that the Lewis acidity of a chelated magnesium alkoxide can be tuned by the choice of halide, with the highest levels of diasteroselectivity achieved using alkyl magnesium iodide reagents. Exploiting this finding, we demonstrate that the diastereoselective addition of alkyl magnesium iodide reagents to ketofluorohydrins enables rapid access to naturally configured C4'-modified nucleosides. This work provides a platform to support antiviral and anticancer drug discovery and development efforts. The Grignard reaction represents one of the most powerful carbon-carbon bond forming reactions and is the subject of continual study. Here, the authors report a halide effect on the diastereoselectivity of 1,2-addition reactions to β-hydroxy ketones involving Grignard reagents, serving as a foundation for the rapid production of C4'-modified nucleosides with diversifiable positions at the nucleobase and C4'. [ABSTRACT FROM AUTHOR]

Machine learning offers great promise for fast and accurate binding affinity predictions. However, current models lack robust evaluation and fail on tasks encountered in (hit-to-) lead optimisation, such as ranking the binding affinity of a congeneric series of ligands, thereby limiting their application in drug discovery. Here, we address these issues by first introducing a novel attention-based graph neural network model called AEV-PLIG (atomic environment vector–protein ligand interaction graph). Second, we introduce a new and more realistic out-of-distribution test set called the OOD Test. We benchmark our model on this set, CASF-2016, and a test set used for free energy perturbation (FEP) calculations, that not only highlights the competitive performance of AEV-PLIG, but provides a realistic assessment of machine learning models with rigorous physics-based approaches. Moreover, we demonstrate how leveraging augmented data (generated using template-based modelling or molecular docking) can significantly improve binding affinity prediction correlation and ranking on the FEP benchmark (weighted mean PCC and Kendall's τ increases from 0.41 and 0.26 to 0.59 and 0.42). These strategies together are closing the performance gap with FEP calculations (FEP+ achieves weighted mean PCC and Kendall's τ of 0.68 and 0.49 on the FEP benchmark) while being ~400,000 times faster. Machine learning offers great promise for fast and accurate binding affinity predictions, however, current models lack robust evaluation and fail on tasks encountered in drug discovery. Here, the authors introduce an attention-based graph neural network model, AEV-PLIG, and demonstrate that augmenting the training data with semi-synthetic data significantly improves AEV-PLIG's performance on benchmarks used for free energy perturbation calculations, narrowing the performance gap to simulation-based methods. [ABSTRACT FROM AUTHOR]

Climate change is a fundamentally a call for human change. What is being asked of us as pastoral practitioners in this new situation? This article reflects on this question through the lens of listening. Traditionally, we have listened primarily to other humans and/or the voice of the transcendent mediated through human channels. But these are not the only voices. Other-than-human voices—wind, water, fire, atmosphere, and non-human creatures—are now making their presences urgently felt. Earth herself is crying out. In response to this challenge, we attempted to re-imagine a traditional program of pastoral formation known as clinical pastoral education (CPE). To begin to listen to Earth's voice involves a radical turning, a change of worldview and practices of attention. Reflection on a classic text (or theological reflection), a core component of the CPE process, played a critical role. In this article we listen to the classic wisdom text of the book of Job, particularly the astonishing speech of YHWH in chapters 38–39; provide an overview of the structural changes developed in CPE programs in eco-ministry; and trace the journey of one intern within one of these programs. This example shows the transformative outcomes that can occur when the core of pastoral care, empathic listening, is extended to the more-than-human world. [ABSTRACT FROM AUTHOR]

The Journal of Mathematics Teacher Education explores theoretical and methodological eclecticism in its 28th volume, emphasizing diverse perspectives and approaches from authors worldwide. The articles in this issue delve into topics such as teacher cognition, student thinking, and research-practice partnerships, showcasing a range of studies on mathematics education. The journal aims to increase representation from underrepresented regions, shorten review times, and engage the editorial board in new ways, reflecting a commitment to advancing the field of mathematics teacher learning. [Extracted from the article]

Purpose: The purpose of this systematic review and meta-analysis was to examine the clinical outcomes and complication rates for fusion procedures of adult spinal deformity (ASD) performed via an anterior-posterior approach as compared to a posterior-only approach to guide surgical decision-making. Numerous surgical techniques exist for operative management of ASD; however, no systematic review and meta-analysis exists comparing combined anterior-posterior approaches to posterior-only approach, despite significant interest in the current literature. Methods: Four databases were used to collect articles from database inception until September 9th, 2023. Inclusion criteria was articles that examined both anterior-posterior or posterior only surgical approach, adult patients, comparative studies, and articles in English. Results: Seven comparative articles met the inclusion criteria. Included patients had a frequency weighted (FW) mean age of 60.2 ± 5.1 years and a FW mean follow-up of 40.4 ± 12.5 months. Qualitative data did not favor either group in terms of length of stay, radiographic outcomes, or functional outcomes. There was a total of 306 complications in the Anterior-Posterior group with a complication rate per patient of 1.0 ± 0.9 complications whereas there was a total of 380 complications in the Posterior Only group with a complication rate per patient of 1.0 ± 1.2 complications. Meta-analysis of specific complications found no significant difference in revision rate, dural tear rate, neurological complication rate, infection rate, or pseudoarthrosis rate. Conclusion: Surgical management for ASD may provide comparable results in terms of surgical parameters, radiographic outcomes, functional outcomes, and complication rates, irrespective of surgical approach. [ABSTRACT FROM AUTHOR]

Background: Surgical site infections (SSIs) are a major driver of morbidity after combined liver and colorectal surgery for metastatic colorectal cancer. Available literature is inadequate to characterize risk factors and benchmarks for quality improvement. Methods: Consecutive cases of simultaneous liver and colorectal surgery for colorectal adenocarcinoma from November 2013 through September 2022 were reviewed for SSIs per National Surgical Quality Improvement Program (NSQIP) and National Healthcare Safety Network (NHSN) criteria. Univariable and multivariable logistic regression evaluated associations with NSQIP 30-day organ-space SSIs. Results: In 580 procedures, the rate of 30-day organ-space SSIs was 16% (n = 94) using NSQIP criteria and 11% (n = 64) using NHSN criteria; 4% (n = 24) had incisional SSIs by both criteria. Most organ-space SSIs were perihepatic, and a minority were associated with bile (26%) or anastomotic (15%) leak. Independent risk factors for organ-space SSIs included major liver resection, upper abdominal (compared with lower abdominal/pelvic) colorectal procedure, and ostomy reversal. Organ-space SSI rates increased over time by approximately 16% per calendar year (p = 0.02) despite a declining rate of major liver resection; incisional SSI rates remained low. Overall, major morbidity was 22%, with 7-day median length of stay (interquartile range 6–9) and 0.3% 90-day mortality. Conclusion: Organ-space SSIs are a significant driver of postoperative morbidity in simultaneous liver and colorectal resections for metastatic colorectal adenocarcinoma. Our findings confirm simultaneous resection remains safe and interventions to mitigate the risk of perihepatic organ-space SSIs in high-risk patients are warranted. [ABSTRACT FROM AUTHOR]

Background: Appendiceal epithelial tumors are rare and encompass a broad set of adenocarcinoma histologies, including mucinous (mAC), colonic-type (cAC), and goblet cell (GCA) adenocarcinomas. It has previously been reported that nodal disease predicted recurrence in patients with nonmetastatic appendiceal adenocarcinomas, supporting diagnostic laparoscopy with right hemicolectomy for staging and assessment for risk of recurrence. In this update, we sought to identify predictors of nodal disease on initial diagnostic pathology in nonmetastatic adenocarcinomas. Methods: Patients with nonmetastatic appendiceal adenocarcinoma at a single institution from 1994 to 2020 were included. Clinicopathologic characteristics that predict recurrence and lymph node metastasis were analyzed. Workup included staging laparoscopy with right hemicolectomy, seriel imaging and biochemical monitoring. Results: A total of 147 patients with mAC (18%), cAC (22%), and GCAs (59%) were included. After median follow-up of 53 months, 23 (16%) patients recurred, most commonly in the peritoneal cavity (17/23, 74%). Recurrence rates were higher among node-positive patients (59% vs. 5%, P < 0.001). Nodal disease was more common in mAC (27%) and cAC (37%) than in GCA (11%); however, adenocarcinoma grade was not associated with nodal involvement. Conclusions: Nodal metastasis was more common in mAC and cAC compared with GCA and was the only significant predictor of recurrence in appendix cancer. [ABSTRACT FROM AUTHOR]

The heavy chain of an antibody is crucial for mediating antigen binding. IGHV genes, which partially encode the heavy chain of antibodies, exhibit vast genetic diversity largely through polymorphism and copy number variation (CNV). These genetic variations impact population-level expression levels. In this study, we analyzed expressed antibody transcriptomes and matched germline IGHV genes from donors from KwaZulu-Natal, South Africa. Amplicon NGS targeting germline IGHV sequences was performed on genomic DNA from 70 participants, eight of whom had matched datasets of expressed antibody transcriptomes. Germline IGHV sequencing identified 161 unique IGHV alleles, of which 32 were novel. A further 21 novel IGHV alleles were detected in the expressed transcriptomes of these donors. We also examined the datasets for CNV, uncovering gene duplications of 10 IGHV genes from germline sequencing and 33 genes in the expressed transcriptomes. Many of the IGHV gene duplications have not been described in other populations. This study expands our understanding of genetic differences in distinct populations and suggests the potential impact of genetic diversity on immune responses. [ABSTRACT FROM AUTHOR]

Tumoroids, sometimes referred to as cancer organoids, are patient-derived cancer cells grown as 3D, self-organized multicellular structures that maintain key characteristics (e.g., genotype, gene expression levels) of the tumor from which they originated. These models have emerged as valuable tools for studying tumor biology, cytotoxicity, and response of patient-derived cells to cancer therapies. However, the establishment and maintenance of tumoroids has historically been challenging, labor intensive, and highly variable from lab to lab, hindering their widespread use. Here, we characterize the establishment and/or expansion of colorectal, lung, head and neck, breast, pancreas, and endometrial tumoroids using the standardized, serum-free Gibco OncoPro Tumoroid Culture Medium. Newly derived tumoroid lines (n = 20) were analyzed by targeted genomic profiling and RNA sequencing and were representative of tumor tissue samples. Tumoroid lines were stable for over 250 days in culture and freeze-thaw competent. Previously established tumoroid lines were also transitioned to OncoPro medium and exhibited, on average, similar growth rates and conserved donor-specific characteristics when compared to original media systems. Additionally, OncoPro medium was compatible with both embedded culture in extracellular matrix and growth in a suspension format for facile culture and scale up. An example application of these models for assessing the cytotoxicity of a natural killer cell line and primary natural killer cells over time and at various doses demonstrated the compatibility of these models with assays used in compound and cell therapy development. We anticipate that the standardization and versatility of this approach will have important benefits for basic cancer research, drug discovery, and personalized medicine and help make tumoroid models more accessible to the cancer research community. [ABSTRACT FROM AUTHOR]

Anesthetic gases contribute to global warming. We described a two-year performance improvement project to examine the association of individualized provider dashboard feedback of anesthetic gas carbon dioxide equivalent (CDE20) production and median perioperative fresh gas flows (FGF) during general anesthetics during perioperative management. Using a custom structured query language (SQL) query, hourly CDE20 for each anesthetic gas and median FGF were determined. During the first year, practitioners were not given any feedback on their use of anesthetic gases. During the second year of the study protocol, a commercially available business intelligence platform was used to deliver individualized monthly dashboard of these parameters to each practitioner. Continuous values are expressed as median [first quartile, third quartile]. During the study period, 53,294 patients managed by 79 anesthesiologists were available for analysis. Bivariate analysis revealed an overall decrease in median FGF from 2.0 [1.9, 3.0] liters/minute (l/min) to 1.9 [1.7, 2.0] l/min (p < 0.001). There was a significant decrease in the overall total CDE20 from 5.10 [0,12.3] to 3.59 [0,8.78] kg/hr (p < 0.001). Multivariate analysis demonstrated an initial decrease in monthly practitioner total CDE20 production with the intervention (odds ratio (OR) 0.875 95% confidence interval (CI) 0.809–0.996, p < 0.001) and a faster decrease rate in monthly total CDE20 (OR 0.986, 95% CI 0.976—0,996, p < 0.001). Dashboard distribution initially decreased isoflurane (intervention OR 0.97 95% CI 0.96–0.99, p = 0.001) and N2O (OR 0.82 95% CI 0.73–0.94, p = 0.003) CDE20 production and was associated with a steeper declining rate of isoflurane (OR 0.87, CI 0.79–0.94, p < 0.001) and desflurane (OR 0.9, 0.84—0.97, p = 0.005) CDE20 production. The intervention did not have a significant effect on the monthly rate of decline of sevoflurane or N2O CDE20. The average practitioner FGF decreased by 0.3 l/m (95% confidence interval (CI): -0,011, -0.5, p = 0.002) with dashboard distributions. Dashboard distribution may be an effective tool to decrease FGF as well as components of anesthetic greenhouse gas emissions. [ABSTRACT FROM AUTHOR]

Purpose: While treatment modalities for Maisonneuve fractures involving the proximal third of the fibula are established, no studies to date have reported outcomes associated with syndesmotic-only fixation of middle third fibular shaft fractures. The purpose of this study was to evaluate outcomes associated with syndesmotic-only fixation in the treatment of Maisonneuve fractures involving the middle third of the fibula. Methods: A retrospective review was conducted on 257 cases of syndesmotic ankle instability with associated fibular fractures at a level 1 trauma center between 2013 and 2023. Patients were divided into cohorts based on fibular fracture location in the proximal, middle, or distal third of the fibula. The Chi-square test of independence, two-sample t-test, and analysis of variance were used to compare outcome measures between cohorts. Results: Sixty-six patients were identified including 48% (n = 32) with proximal third fibular fractures, 20% (n = 13) with middle third fibular fractures, and 32% (n = 21) with distal third fibular fractures. Rates of infection, loss of reduction, wound healing complications, and reoperation did not vary significantly between cohorts. Functional outcome measures including range of motion, time to weight-bearing, and tibiofibular/medial clear space measurements at final follow-up were similar across cohorts. Conclusion: Patients with Maisonneuve fractures involving the middle third of the fibula demonstrated positive outcomes with syndesmotic fixation alone, with no documented cases of infection, loss of reduction, or wound healing issues. By demonstrating maintenance of anatomic reduction and low rates of complications, our results support the use of syndesmotic-only fixation in the treatment of middle third Maisonneuve fractures. [ABSTRACT FROM AUTHOR]

As we assess the habitability of other worlds, we are limited by being able to only study terrestrial life adapted to terrestrial conditions. The environments found on Earth, though tremendously diverse, do not approach the multitude of potentially habitable environments beyond Earth, and so limited terrestrial adaptive capabilities tell us little about the fundamental biochemical boundaries of life. One approach to this problem is to use experimental laboratory evolution to adapt microbes to these novel environmental conditions. This approach can be dramatically improved through functional metagenomics, large-scale introduction of foreign genetic material to screen for phenotypes in a new host organism. This takes advantage of Earth's immense biological diversity with high-throughput screening for genetic tools that can facilitate adaptation. We address a key gap in functional metagenomics work by exploring the impact of the experimental parameters chosen for functional metagenomics libraries. Experimental design dictates both fragment size and copy number, and we show that both can have outsized effects on the resultant phenotypes in non-intuitive ways. These results highlight the potential of functional metagenomics for adapting life rapidly to challenging new environments, with important implications in both astrobiology and bioindustry, while also emphasizing the impacts of decisions in experimental design. [ABSTRACT FROM AUTHOR]

Neurons encode information in the highly variable spiking activity of neuronal populations, so that different repetitions of the same stimulus can generate action potentials that vary significantly in terms of the count and timing. How does spiking variability originate, and does it have a functional purpose? Leveraging large-scale intracellular electrophysiological data, we relate the spiking reliability of cortical neurons in-vitro during the intracellular injection of current resembling synaptic inputs to their morphologic, electrophysiologic, and transcriptomic classes. Our findings demonstrate that parvalbumin+ (PV) interneurons, a subclass of inhibitory neurons, show high reliability compared to other neuronal subclasses, particularly excitatory neurons. Through computational modeling, we predict that the high reliability of PV interneurons allows for strong and precise inhibition in downstream neurons, while the lower reliability of excitatory neurons allows for integrating multiple synaptic inputs leading to a spiking rate code. These findings illuminate how spiking variability in different neuronal classes affect information propagation in the brain, leading to precise inhibition and spiking rate codes. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the utility of CT-based abdominal fat measures for predicting the risk of death and cardiometabolic disease in an asymptomatic adult screening population. Methods: Fully automated AI tools quantifying abdominal adipose tissue (L3 level visceral [VAT] and subcutaneous [SAT] fat area, visceral-to-subcutaneous fat ratio [VSR], VAT attenuation), muscle attenuation (L3 level), and liver attenuation were applied to non-contrast CT scans in asymptomatic adults undergoing CT colonography (CTC). Longitudinal follow-up documented subsequent deaths, cardiovascular events, and diabetes. ROC and time-to-event analyses were performed to generate AUCs and hazard ratios (HR) binned by octile. Results: A total of 9223 adults (mean age, 57 years; 4071:5152 M:F) underwent screening CTC from April 2004 to December 2016. 549 patients died on follow-up (median, nine years). Fat measures outperformed BMI for predicting mortality risk—5-year AUCs for muscle attenuation, VSR, and BMI were 0.721, 0.661, and 0.499, respectively. Higher visceral, muscle, and liver fat were associated with increased mortality risk—VSR > 1.53, HR = 3.1; muscle attenuation < 15 HU, HR = 5.4; liver attenuation < 45 HU, HR = 2.3. Higher VAT area and VSR were associated with increased cardiovascular event and diabetes risk—VSR > 1.59, HR = 2.6 for cardiovascular event; VAT area > 291 cm2, HR = 6.3 for diabetes (p < 0.001). A U-shaped association was observed for SAT with a higher risk of death for very low and very high SAT. Conclusion: Fully automated CT-based measures of abdominal fat are predictive of mortality and cardiometabolic disease risk in asymptomatic adults and uncover trends that are not reflected in anthropomorphic measures. Clinical relevance statement: Fully automated CT-based measures of abdominal fat soundly outperform anthropometric measures for mortality and cardiometabolic risk prediction in asymptomatic patients. Key Points: Abdominal fat depots associated with metabolic dysregulation and cardiovascular disease can be derived from abdominal CT. Fully automated AI body composition tools can measure factors associated with increased mortality and cardiometabolic risk. CT-based abdominal fat measures uncover trends in mortality and cardiometabolic risk not captured by BMI in asymptomatic outpatients. [ABSTRACT FROM AUTHOR]

The Artemis program and lunar gateway present an opportunity to advance NASA’s presence away from Earth’s orbit and back to the Moon. Astronauts will be faced with many dermatological challenges unique to the lunar environment, such as the surface material on the Moon. We used PubMed and Google Scholar to perform a literature review with articles related to the effects of lunar dust on skin collated and analyzed to assess the dermatological implications of these missions. The effects of lunar dust on wound generation and healing were reviewed, while also analyzing passive and active measures used to minimize astronaut exposure to lunar dust. A myriad of methods involving advances in medicine and engineering (e.g. bioinspired texturing of materials, staged decontamination, emollients) will need to be employed to best protect astronauts from the effects of lunar surface materials and other insults to best protect the Artemis astronauts. These advances will help with future NASA missions to Mars and beyond as other terrestrial space bodies will likely present astronauts with similar dermatological insults from surface materials and regolith. Dermatologists can serve a role in helping researchers develop techniques to protect skin health and understand the pathophysiology involved with lunar dust exposure. [ABSTRACT FROM AUTHOR]

During memory formation, the hippocampus is presumed to represent the content of stimuli, but how it does so is unknown. Using computational modelling and human single-neuron recordings, we show that the more precisely hippocampal spiking variability tracks the composite features of each individual stimulus, the better those stimuli are later remembered. We propose that moment-to-moment spiking variability may provide a new window into how the hippocampus constructs memories from the building blocks of our sensory world. The hippocampus is thought to encode the content of stimuli, but how it does so is unknown. The authors show that when hippocampal spiking variability tracks the abstract building blocks of individual stimuli, memories are formed successfully. [ABSTRACT FROM AUTHOR]

Abstract With the COVID‐19 pandemic caused by SARS‐CoV‐2 now in its second year, there remains an urgent need for diagnostic testing that can identify infected individuals, particularly those who harbor infectious virus. Various RT–PCR strategies have been proposed to identify specific viral RNA species that may predict the presence of infectious virus, including detection of transcriptional intermediates (e.g., subgenomic RNA [sgRNA]) and replicative intermediates (e.g., negative‐strand RNA species). Using a novel primer/probe set for detection of subgenomic (sg)E transcripts, we successfully identified 100% of specimens containing culturable SARS‐CoV‐2 from a set of 126 clinical samples (total sgE CT values ranging from 12.3 to 37.5). This assay showed superior performance compared to a previously published sgRNA assay and to a negative‐strand RNA assay, both of which failed to detect target RNA in a subset of samples from which we isolated live virus. In addition, total levels of viral RNA (genome, negative‐strand, and sgE) detected with the WHO/Charité primer‐probe set correlated closely with levels of infectious virus. Specifically, infectious virus was not detected in samples with a CT above 31.0. Clinical samples with higher levels of viral RNA also displayed cytopathic effect (CPE) more quickly than those with lower levels of viral RNA. Finally, we found that the infectivity of SARS‐CoV‐2 samples is significantly dependent on the cell type used for viral isolation, as Vero E6 cells expressing TMRPSS2 extended the analytical sensitivity of isolation by more than 3 CT compared to parental Vero E6 cells and resulted in faster isolation. Our work shows that using a total viral RNA Ct cutoff of > 31 or specifically testing for sgRNA can serve as an effective rule‐out test for the presence of culturable virus.

Abstract Mitochondrial disorders are clinically and genetically diverse, with isolated complex III (CIII) deficiency being relatively rare. Here, we describe two affected cousins, presenting with recurrent episodes of severe lactic acidosis, hyperammonaemia, hypoglycaemia and encephalopathy. Genetic investigations in both cases identified a homozygous deletion of exons 2 and 3 of UQCRH, which encodes a structural complex III (CIII) subunit. We generated a mouse model with the equivalent homozygous Uqcrh deletion (Uqcrh−/−), which also presented with lactic acidosis and hyperammonaemia, but had a more severe, non‐episodic phenotype, resulting in failure to thrive and early death. The biochemical phenotypes observed in patient and Uqcrh−/− mouse tissues were remarkably similar, displaying impaired CIII activity, decreased molecular weight of fully assembled holoenzyme and an increase of an unexpected large supercomplex (SXL), comprising mostly of one complex I (CI) dimer and one CIII dimer. This phenotypic similarity along with lentiviral rescue experiments in patient fibroblasts verifies the pathogenicity of the shared genetic defect, demonstrating that the Uqcrh−/− mouse is a valuable model for future studies of human CIII deficiency.

Ascochyta blight, caused by the necrotrophic fungus Ascochyta rabiei, is a major threat to chickpea production worldwide. Resistance genes with broad-spectrum protection against virulent A. rabiei strains are required to secure chickpea yield in the US Northern Great Plains. Here, we performed a genome-wide association (GWA) study to discover novel sources of genetic variation for Ascochyta blight resistance using a worldwide germplasm collection of 219 chickpea lines. Ascochyta blight resistance was evaluated at 3, 9, 11, 13, and 14 days post-inoculation. Multiple GWA models revealed eight quantitative trait nucleotides (QTNs) across timepoints mapped to chromosomes 1, 3, 4, 6, and 7. Of these eight QTNs, only CM001767.1_28299946 on Chr 4 had previously been reported. QTN CM001766.1_36967269 on Chr 3 explained up to 33% of the variation in disease severity and was mapped to an exonic region of the pentatricopeptide repeat-containing protein At4g02750-like gene (LOC101506608). This QTN was confirmed across all models and timepoints. A total of 153 candidate genes, including genes with roles in pathogen recognition and signaling, cell wall biosynthesis, oxidative burst, and regulation of DNA transcription, were observed surrounding QTN-targeted regions. Further gene expression analysis on the QTNs identified in this study will provide insights into defense-related genes that can be further incorporated into breeding of new chickpea cultivars to minimize fungicide applications required for successful chickpea production in the US Northern Great Plains. [ABSTRACT FROM AUTHOR]

The ability to prioritize among input features according to relevance enables adaptive behaviors across the human lifespan. However, relevance often remains ambiguous, and such uncertainty increases demands for dynamic control. While both cognitive stability and flexibility decline during healthy ageing, it is unknown whether aging alters how uncertainty impacts perception and decision-making, and if so, via which neural mechanisms. Here, we assess uncertainty adjustment across the adult lifespan (N = 100; cross-sectional) via behavioral modeling and a theoretically informed set of EEG-, fMRI-, and pupil-based signatures. On the group level, older adults show a broad dampening of uncertainty adjustment relative to younger adults. At the individual level, older individuals whose modulation more closely resembled that of younger adults also exhibit better maintenance of cognitive control. Our results highlight neural mechanisms whose maintenance plausibly enables flexible task-set, perception, and decision computations across the adult lifespan. Reduced flexibility is a hallmark of cognitive ageing. Here, the authors examine EEG, fMRI and pupillometry signatures to show that older adults adapt less to variable uncertainty and identify neural mechanisms that support uncertainty adjustment in aging populations. [ABSTRACT FROM AUTHOR]

This systematic review and synthesis summarizes intervention research for Grade K-12 students with a reading difficulty and co-occurring inattention to identify (a) the relevant intervention literature base, (b) the student, study, and intervention characteristics of these studies, (c) the effects of these interventions on reading and behavior outcomes, and (d) the collateral impact of reading interventions and behavior interventions on behavior outcomes and reading outcomes, respectively. Our search process yielded 14 eligible studies. Findings suggest that word reading instruction is associated with improved word reading outcomes and self-monitoring and function-based interventions are associated with improved student behavior. No study measured a collateral effect for reading or behavior interventions. Future reading intervention research is needed to better understand how to improve the reading and behavior outcomes for Grade K-12 students with a reading difficulty and co-occurring inattention. A PRISMA-compliant abstract can be found at https://osf.io/5v8ke/?view_only=d78b4cdc7eb946ae997df91e08fe2809. [ABSTRACT FROM AUTHOR]

The article discusses the use of digital tools in analyzing and integrating data to enhance collaboration between mouse and human brain research, particularly in the context of rare diseases and neurodevelopmental disorders. By comparing gene expression in mice and humans, researchers identified potential candidate genes related to schizophrenia and other brain disorders. The study highlights the importance of detailed brain region analysis and cross-species comparisons to advance our understanding of brain health and disease mechanisms. The research was supported by funding from various sources, including the European Union's Horizon Europe Programme. [Extracted from the article]

Extended-connectivity fingerprints (ECFPs) are a ubiquitous tool in current cheminformatics and molecular machine learning, and one of the most prevalent molecular feature extraction techniques used for chemical prediction. Atom features learned by graph neural networks can be aggregated to compound-level representations using a large spectrum of graph pooling methods. In contrast, sets of detected ECFP substructures are by default transformed into bit vectors using only a simple hash-based folding procedure. We introduce a general mathematical framework for the vectorisation of structural fingerprints via a formal operation called substructure pooling that encompasses hash-based folding, algorithmic substructure selection, and a wide variety of other potential techniques. We go on to describe Sort & Slice, an easy-to-implement and bit-collision-free alternative to hash-based folding for the pooling of ECFP substructures. Sort & Slice first sorts ECFP substructures according to their relative prevalence in a given set of training compounds and then slices away all but the L most frequent substructures which are subsequently used to generate a binary fingerprint of desired length, L. We computationally compare the performance of hash-based folding, Sort & Slice, and two advanced supervised substructure-selection schemes (filtering and mutual-information maximisation) for ECFP-based molecular property prediction. Our results indicate that, despite its technical simplicity, Sort & Slice robustly (and at times substantially) outperforms traditional hash-based folding as well as the other investigated substructure-pooling methods across distinct prediction tasks, data splitting techniques, machine-learning models and ECFP hyperparameters. We thus recommend that Sort & Slice canonically replace hash-based folding as the default substructure-pooling technique to vectorise ECFPs for supervised molecular machine learning. Scientific contribution A general mathematical framework for the vectorisation of structural fingerprints called substructure pooling; and the technical description and computational evaluation of Sort & Slice, a conceptually simple and bit-collision-free method for the pooling of ECFP substructures that robustly and markedly outperforms classical hash-based folding at molecular property prediction. [ABSTRACT FROM AUTHOR]

Electrochemical technologies add a unique dimension for ore refinement, representing tunable methods that can integrate with renewable energy sources and existing downstream process flows. However, the development of electrochemical extraction technologies has been impeded by the technological maturity of hydro- and pyro-metallurgy, as well as the electrical insulating properties of many metal oxide ores. The fabrication and use of carbon/insulating material composite electrodes has been a longstanding method to enable electrochemical activation. Here, using real hectorite ore, we employ this technical approach to fabricate hectorite-carbon black composite electrodes (HCCEs) and achieve electrochemical activation of hectorite. Anodic polarization results in lithium-ion release through a multi-step chemical and electrochemical mechanism that results in 50.7 ± 4.4% removal of lithium from HCCE, alongside other alkaline ions. This technical proof-of-concept study underscores that electrochemical activation of ores can facilitate lattice deterioration and ion removal from ores. Electrochemical technologies for ore refinement provide a unique opportunity to integrate with renewable energy sources but are impeded by the insulating properties of many ores. Here, the authors take inspiration from the lithium-ion battery field and fabricate hectorite–carbon black composite electrodes to enhance electron percolation into hectorite enabling lithium-ion release through a multi-step (electro)chemical mechanism. [ABSTRACT FROM AUTHOR]

The lncRNA Crossfirre was identified as an imprinted X-linked gene, and is transcribed antisense to the trans-acting lncRNA Firre. The Firre locus forms an inactive-X-specific interaction with Dxz4, both loci providing the platform for the largest conserved chromatin structures. Here, we characterize the epigenetic profile of these loci, revealing them as the most female-specific accessible regions genome-wide. To address their in vivo role, we perform one of the largest X-linked knockout studies by deleting Crossfirre, Firre, and Dxz4 individually and in combination. Despite their distinct epigenetic features observed on the X chromosome, our allele-specific analysis uncovers these loci as dispensable for imprinted and random X chromosome inactivation. However, we provide evidence that Crossfirre affects autosomal gene regulation but only in combination with Firre. To shed light on the functional role of these sex-specific loci, we perform an extensive standardized phenotyping pipeline and uncover diverse knockout and sex-specific phenotypes. Collectively, our study provides the foundation for exploring the intricate interplay of conserved X-linked loci in vivo. The authors present a characterization of complex X-linked lncRNA loci with sex- and allele-specific epigenetic signatures that serve as a platform for the largest chromatin structures in mammals, thereby elucidating diverse phenotypes and combinatorial effects on autosomes. [ABSTRACT FROM AUTHOR]

To explore the frequency and predictive factors of erectile dysfunction diagnosis after colorectal cancer surgery. The Surveillance, Epidemiology, and End Results—Medicare database was used to identify a national sample of men undergoing surgery for colorectal cancer from 2004 to 2015. Men aged > 65 years with any index surgery within 1 year of diagnosis of colorectal cancer were included. Men with a history of prior erectile dysfunction, metastatic cancer, or genitourinary cancer prior to their index procedure were excluded. The primary outcome was a new diagnosis of erectile dysfunction within 2 years of the index procedure. A total of 28,248 men aged > 65 years who underwent colorectal cancer surgery were identified. The rates of erectile dysfunction diagnosis 2 years after surgery were 3.6% for hemicolectomy, 5.3% for low anterior resection, and 6.4% for abdominoperineal resection. On multivariable analysis, low anterior resection (HR: 1.27, 95%CI 1.08 to 1.51, p < 0.01) and abdominoperineal resection (HR: 1.49, 95%CI 1.14 − 1.93, p < 0.01) were independently associated with increased risk of erectile dysfunction compared to hemicolectomy. Minimally invasive surgery was independently associated with an increased risk of erectile dysfunction compared to open surgery (HR: 1.44, 95% CI 1.25–1.65, p < 0.001). Compared to hemicolectomy, men treated with low anterior resection and abdominoperineal resection have a higher risk of being diagnosed with erectile dysfunction within 2 years of treatment. The absolute rate of erectile dysfunction diagnosis was low compared to rates reported in prior controlled trials, suggesting that patients are underdiagnosed in real-world settings. [ABSTRACT FROM AUTHOR]

Drastic declines observed in coral reefs in response to changes in climate and other anthropogenic stressors have hinged the survival of these ecosystems largely on the overall health and reproductive success of stony corals. One specific threat, Karenia brevis blooms, has drawn increased public attention in recent decades and has been documented to reach the Florida Keys, a vulnerable coral ecosystem. The purpose of this study was to investigate the sublethal impact of K. brevis exposure on three South Florida "restoration" coral species. Fragments of Porites astreoides, Acropora cervicornis, and Siderastrea radians were exposed to three environmentally relevant concentrations of K. brevis for 2 weeks in a controlled aquaria setting. At the end of exposure, ultra-high-performance liquid chromatography coupled to high-resolution tandem mass spectrometry (UHPLC-HRMS/MS) was used to perform nontargeted lipidomics and metabolomics analyses to assess physiological changes in the corals in response to red tide exposure, as well as highlight possible biological processes and pathways altered. Significant changes to the lipidome and metabolome were observed in all three species following exposure. Furthermore, the multi-omics analysis highlighted important pathways for further study including impacts on oxidative stress, energy metabolism, the immune system, and nitrogen fixation/photosynthesis of symbionts. Due to the use of environmentally relevant exposure levels and duration, these results are invaluable to understand possible future impacts of red tide on coral reef areas as well as to inform future coral reef restoration and management decisions. [ABSTRACT FROM AUTHOR]

Copyright of International Journal of Early Childhood is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: Financial toxicity, cancer-treatment-related financial harm, is associated with expensive treatments like immunotherapy. The purpose of this study was to explore financial toxicity among advanced cancer patients receiving immunotherapies and their caregivers and, secondarily, to study how recent inflation and the COVID-19 pandemic impacted these experiences. Methods: Advanced cancer patients receiving immunotherapies and their caregivers were recruited to participate in semi-structured interviews about supportive care needs from 2022 to 2023. The Comprehensive Score for Financial Toxicity was collected. Guided by Jones et al.’s cancer financial toxicity model, the content analysis was conducted by two trained coders using NVIVO R1. Results: Sixteen patients and 10 caregivers (including 7 dyads) across 5 states participated in interviews in 2022–2023. Participants averaged 63.43 years (SD = 12.75), and patients received an average of 14.6 months of immunotherapy (SD = 9.415). The majority lived in non-metropolitan areas (67%) and were white (95%). Three theory-driven themes were developed: (1) Sources of Financial Toxicity, (2) Buffers of Financial Toxicity, and (3) Consequences of Financial Toxicity. Inflation was added to financial toxicity for non-metropolitan dwelling participants due to increased prices of gas and accommodation. Social support systems buffered the impact of financial toxicity. Material and psychological impacts of financial toxicity disproportionately affected younger and privately insured participants. Conclusion: While immunotherapy patients face high medical costs of treatment, the burdens of accessing treatment for people living at a distance from the cancer center can exacerbate financial toxicity. Clinicians and researchers should also consider external financial pressures such as national economic impacts that compound the financial toxicity of treatment. [ABSTRACT FROM AUTHOR]

Introduction: The costs associated with proper disposal, management, and regulatory compliance of controlled substances in healthcare systems are substantial. In the context of the current opioid crisis, and given the high abuse potential of controlled substances, it is imperative that waste is minimized and waste procedures are followed to ensure safe disposal of controlled substances. This study aims to quantify the costs associated with fentanyl, hydromorphone, morphine, midazolam, and ketamine waste in intraoperative areas through a multi-site observational analysis. Methods: The study used an observational design across various hospital procedural and post-procedural units in the Southwest Florida region of the United States. Automated and non-automated workflows for wasting controlled substances were compared. As with a previous study conducted by Hertig et al., waste was evaluated as (1) the quantity (mg/μg) of medication disposed defined as 'pharmaceutical waste' or 'product waste' (PW); and (2) workforce time associated with the waste disposal process defined as 'workforce time waste' (WTW). Secondary measures include workforce costs associated with the waste disposal process. The product waste analysis was conducted between October and December 2023. The workforce time waste analysis was examined over a 10-day period in January and February 2024. A yearly extrapolation model was applied to cost data. Results: The findings revealed substantial costs linked to both PW and WTW, emphasizing the financial burden of controlled substance waste. Study data validated previous literature describing the extent of fentanyl, hydromorphone, and morphine waste while documenting significant amounts of midazolam and ketamine waste. The combined annual waste cost for the two study hospitals was estimated at US$56,557, with workforce time accounting for 36%–50% of this total cost. Conclusion: This study provides vital insights into the financial and operational impact of medication waste in procedural and post-procedural areas, supporting ongoing efforts to minimize waste, ensuring the safe and effective use of controlled substances. Future research should explore the impact of medication waste across diverse healthcare settings and the cost implications associated with pharmacy professionals in the waste compliance process. [ABSTRACT FROM AUTHOR]

Earthquakes and tsunamis are natural phenomena that have strongly affected communities located along the Chilean active plate margin. Large-magnitude megathrust earthquakes produced at the plate interface of the subduction zone and their associated tsunamis have repeatedly impacted the Chilean coast, leaving a sedimentary record at particular sites from historic and prehistoric times. Here we assess paleoseismic sites related to late Holocene (< 1.5 ka) earthquakes and tsunamis that occurred along the Pacific coastline of south-central Chile (38°-42°S), which record critical information for the study of megathrust earthquakes. We focus on sites along the Valdivia segment that were affected by the great earthquake and tsunami of 1960 (Mw = 9.5; the largest recorded by modern seismology), which host geologic evidence of coseismic land-level changes found in tidal marshes and wetlands. We present an inventory of seven paleoseismic geosites composed mainly of different layers of buried soils and sand deposits, and a quantitative assessment of their scientific value, their potential touristic and educational value, and their degradation risk. These sites are considered part of the paleoseismic heritage of Chile and are relevant globally. Our inventory contributes to the establishment of management strategies for geoconservation of the coastal area of south-central Chile, and the mitigation of the effects of seismological hazards through the promotion of educational, touristic and outreach activities. [ABSTRACT FROM AUTHOR]

Digital twins (DTs) are an emerging capability in additive manufacturing (AM), set to revolutionize design optimization, inspection, in situ monitoring, and root cause analysis. AM DTs typically incorporate multimodal data streams, ranging from machine toolpaths and in-process imaging to X-ray CT scans and performance metrics. Despite the evolution of DT platforms, challenges remain in effectively inspecting them for actionable insights, either individually or in a multidisciplinary, geographically distributed team setting. Quality assurance, manufacturing departments, pilot labs, and plant operations must collaborate closely to reliably produce parts at scale. This is particularly crucial in AM where complex structures require a collaborative and multidisciplinary approach. Additionally, the large-scale data originating from different modalities and their inherent 3D nature pose significant hurdles for traditional 2D desktop-based inspection methods. To address these challenges and increase the value proposition of DTs, we introduce a novel virtual reality (VR) framework to facilitate collaborative and real-time inspection of DTs in AM. This framework includes advanced features for intuitive alignment and visualization of multimodal data, visual occlusion management, streaming large-scale volumetric data, and collaborative tools, substantially improving the inspection of AM components and processes to fully exploit the potential of DTs in AM. [ABSTRACT FROM AUTHOR]

We used natural language processing (NLP) in convergent mixed methods to evaluate young adults' experiences with Call it a Night (CIAN), a digital personalized feedback and coaching sleep-alcohol intervention. Young adults with heavy drinking (N = 120) were randomized to CIAN or controls (A + SM: web-based advice + self-monitoring or A: advice; clinicaltrials.gov, 8/31/18, #NCT03658954). Most CIAN participants (72.0%) preferred coaching to control interventions. Control participants found advice more helpful than CIAN participants (X2 = 27.34, p < 0.001). Most participants were interested in sleep factors besides alcohol and appreciated increased awareness through monitoring. NLP corroborated generally positive sentiments (M = 15.07(10.54)) and added critical insight that sleep (40%), not alcohol use (12%), was a main participant motivator. All groups had high adherence, satisfaction, and feasibility. CIAN (Δ = 0.48, p = 0.008) and A + SM (Δ = 0.55, p < 0.001) had higher reported effectiveness than A (F(2, 115) = 8.45, p < 0.001). Digital sleep-alcohol interventions are acceptable, and improving sleep and wellness may be important motivations for young adults. [ABSTRACT FROM AUTHOR]

Extremely high-Q microresonators provide an attractive platform for a plethora of photonic applications including optical frequency combs, high-precision metrology, telecommunication, microwave generation, narrow linewidth lasers, and stable frequency references. Moreover, the desire for compactness and a low power threshold for nonlinear phenomena have spurred investigation into integrated and scalable solutions. Historically, crystalline microresonators with Q 109 were one of the first material platforms providing unprecedented optical performance in a small form factor. A key challenge, though, with these devices is in finding alternatives to fragile, bulky, and free-space couplers, such as tapered fibers, prisms, and cleaved fibers. Here, we present for the first time, the evanescent coupling of a photonic wire bond (PWB) to a MgF2-based microresonator to generate solitons and a pure, low-noise microwave signal based on Kerr-microcombs. These results open a path towards scalable integration of crystalline microresonators with integrated photonics. Moreover, because PWBs possess advantages over traditional coupling elements in terms of ease of fabrication, size, and flexibility, they constitute a more advanced optical interface for linear and nonlinear photonics. [ABSTRACT FROM AUTHOR]

The ability to lubricate and resist wear at temperatures above 600 °C in an oxidative environment remains a significant challenge for metals due to their high-temperature softening, oxidation, and rapid degradation of traditional solid lubricants. Herein, we demonstrate that high-temperature lubricity can be achieved with coefficients of friction (COF) as low as 0.10-0.32 at 600-900 °C by tailoring surface oxidation in additively-manufactured Inconel superalloy. By integrating high-temperature tribological testing, advanced materials characterization, and computations, we show that the formation of spinel-based oxide layers on superalloy promotes sustained self-lubrication due to their lower shear strength and more negative formation and cohesive energy compared to other surface oxides. A reversible phase transformation between the cubic and tetragonal/monoclinic spinel was driven by stress and temperature during high temperature wear. To span Ni- and Cr-based ternary oxide compositional spaces for which little high-temperature COF data exist, we develop a computational design method to predict the lubricity of oxides, incorporating thermodynamics and density functional theory computations. Our finding demonstrates that spinel oxide can exhibit low COF values at temperatures much higher than conventional solid lubricants with 2D layered or Magnéli structures, suggesting a promising design strategy for self-lubricating high-temperature alloys. The authors develop an approach for enhancing the wear resistance and lubricity of metals at elevated temperatures of in oxidative environments, where traditional solid lubricants fail. By engineering surface oxidation in additively manufactured Inconel, they achieve low friction coefficients, between 0.10 and 0.32 at 600-900 °C, through the formation of a spinel-based oxide layer. [ABSTRACT FROM AUTHOR]

Purpose: The study aim was to assess the impact of clinically significant weight loss (CSWL; ≥5% weight reduction) on postoperative complications following abdominal wall reconstruction with the component separation technique (CST). Methods: A retrospective review of patients who underwent open ventral hernia repair (VHR) with CST from November 2008 to January 2022 was performed. Cohorts were stratified by presence of CSWL from baseline weight at preoperative consultation. Results: Of 180 total patients, 40 (22.2%) achieved CSWL prior to VHR. Mean age was 59.6 ± 11.2 years. Patients in the CSWL cohort represented a higher average body mass index (BMI) (33.6 vs. 31.7 kg/m2, p = 0.076), and were obese more frequently (80.0% vs. 56.4%, p = 0.007). The CSWL cohort had a higher proportion of patients in Ventral Hernia Working Group (VHWG) classification II (82.5% vs. 63.6%) while the non-CSWL cohort had more VHWG classification III/IV (20.0% vs. 10.0%, p = 0.078). Mean follow-up duration was 6.1 ± 13.4 months. Complications, including 30- and 90-day surgical site occurrence (SSO), return to operating room, readmission, and hernia recurrence (CSWL: 5.0% vs. non-CWL 1.4%, p = 0.179), were comparable between cohorts. BMI was an independent predictor of any complication (OR 1.07, p = 0.044) and 90-day SSO (OR 1.10, p = 0.043). Conclusion: Achievement of CSWL prior to open VHR utilizing CST results in similar post-reconstruction outcomes to patients who maintained a comparable BMI at baseline. Higher day-of-surgery BMI was more consequential to postoperative complications than percent weight loss. [ABSTRACT FROM AUTHOR]

Background: Genetic testing to identify germline high-risk pathogenic variants in breast cancer susceptibility genes is increasingly part of the breast cancer diagnostic pathway. Novel patient-centred pathways may offer opportunity to expand capacity and reduce turnaround time. Methods: We recruited 1140 women with unselected breast cancer to undergo germline genetic testing through the BRCA-DIRECT pathway (which includes a digital platform, postal saliva sampling and a genetic counsellor telephone helpline). Ahead of consenting to the test, participants were randomised to receive information about genetic testing digitally (569/1140, 49.9%) or via a pre-test genetic counselling consultation (571/1140, 50.1%). Results: 1001 (87.8%) participants progressed to receive their pre-test information and consented to testing. The primary outcome, uptake of genetic testing, was higher amongst participants randomised to receive digital information compared with those randomised to a pre-test genetic counselling consultation (90.8% (95% CI: 88.5% to 93.1%) vs 84.7% (95% CI: 81.8% to 87.6%), p = 0.002, adjusted for participant age and site). Non-inferiority was observed in relation to patient knowledge, anxiety, and satisfaction. Conclusions: Findings demonstrate that standardised, digital information offers a non-inferior alternative to conventional genetic counselling, and an end-to-end patient-centred, digital pathway (supported by genetic counselling hotline) could feasibly be implemented into breast oncology settings. Clinical trial registration: The study is registered with, and protocol available on, ClinicalTrials.gov (NCT04842799). [ABSTRACT FROM AUTHOR]

We study the prevalence of SARS-CoV-2 antibodies in a diverse population in Milwaukee County, Wisconsin from May 2021 to June 2022. We find that 99.4% (523/526) of the participants had positive results for antibodies to the SARS CoV2 spike protein over April-June 2022, soon after the early-2022 Omicron surge. Positive tests for spike protein antibodies were very high (86%; 19/22) even among unvaccinated persons who reported no knowledge of prior infection. Thus, by mid-2022, almost all persons were no longer COVID-naïve, defined as vaccination, infection (often without symptoms), or both. Nucleocapsid antibody tests, especially the Abbott test, were far less sensitive than spike protein tests, and Abbott test sensitivity faded with time since infection. Thus, studies which rely on nucleocapsid tests will understate prior infection rates. We also report large sample evidence on the performance of the Abbott and Roche spike and nucleocapsid protein tests in capturing prior vaccination, infection, or both. The Roche spike protein test outperforms the Abbott spike test, and the Roche nucleocapsid test greatly outperforms the Abbott nucleocapsid test. [ABSTRACT FROM AUTHOR]

Two-dimensional (2D) van der Waals (vdW) materials have been an exciting area of research ever since scientists first isolated a single layer of graphene. Single layer magnetic materials can provide a pathway for vdW heterostructures with magnetic properties. While most of the magnetic vdW materials exhibit ordering transitions in the bulk, here we report a successful exfoliation of a triangular lattice S = 1 antiferromagnet NiGa S , which already demonstrates exotic magnetism in the bulk material. We establish the number of layers of the material by atomic force microscopy (AFM) and detail a careful characterization using Raman and optical spectroscopy to demonstrate how the optical, electronic, and structural properties of NiGa S change as a function of sample thickness. Optical measurements and electronic structure calculations of bulk versus monolayer NiGa S confirm the material to be a Mott insulator with an electronic gap of about 1.5 eV, which slightly increases for layers below 10 L. We conclude with a theoretical analysis of the possibility of doping monolayer NiGa S by proximity to a metal. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause human respiratory diseases and are major targets for vaccine development. In this study, we design uncleaved prefusion-closed (UFC) trimers for the fusion protein (F) of both viruses by examining mutations critical to F metastability. For RSV, we assess four previous prefusion F designs, including the first and second generations of DS-Cav1, SC-TM, and 847A. We then identify key mutations that can maintain prefusion F in a native-like, closed trimeric form (up to 76%) without introducing any interprotomer disulfide bond. For hMPV, we develop a stable UFC trimer with a truncated F2-F1 linkage and an interprotomer disulfide bond. Dozens of UFC constructs are characterized by negative-stain electron microscopy (nsEM), x-ray crystallography (11 RSV-F structures and one hMPV-F structure), and antigenic profiling. Using an optimized RSV-F UFC trimer as bait, we identify three potent RSV neutralizing antibodies (NAbs) from a phage-displayed human antibody library, with a public NAb lineage targeting sites Ø and V and two cross-pneumovirus NAbs recognizing site III. In mouse immunization, rationally designed RSV-F and hMPV-F UFC trimers induce robust antibody responses with high neutralizing titers. Our study provides a foundation for future prefusion F-based RSV and hMPV vaccine development. RSV and hMPV infections pose significant health risks in vulnerable populations. Here, the authors used a systematic approach to identify mutations critical for fusion protein metastability and rationally design uncleaved prefusion-closed trimers for RSV and hMPV F proteins that induce robust antibody responses in vivo. [ABSTRACT FROM AUTHOR]

Electron beam melting is a powder bed fusion process capable of manufacturing parts from a variety of high-temperature alloys. Given that the process relies on feedstock recycling for process economics, understanding process-part quality relationships is critical. This work investigates process-part quality relationships in terms of the internal and external defects and component microstructure relative to a feedstock subjected to 33 build cycles without replacement. To accomplish this, a volume of fluid mesoscale model consisting of three different powder distributions were considered: (1) Monomodal; (2) As-measured; and (3) Irregular. Particle morphology was characterized using shape factors examined via optical microscopy. To approximate the particle shapes in three-dimensions, a method is presented that utilizes a binarized domain to define low frequency, macroscale particle "base" shapes implicitly and is thus not restricted to starlike particles. The discrete element method was also used to investigate velocity distributions and packing densities of the as-measured and irregular particles with respect to deviations in the nominal layer thickness of 50 μm. In general, beam power and scan speed were found to have an appreciable effect on microstructure formation and surface roughness. Finally, correlations were found between specific classifications of irregular particles and lack of fusion defect formation. [ABSTRACT FROM AUTHOR]

Acute kidney injury is a serious public health problem worldwide, being ischemia and reperfusion (I/R) the main lesion-aggravating factor that contributes to the evolution towards chronic kidney disease. Nonetheless, intervention approaches currently available are just considered palliative options. In order to offer an alternative treatment, it is important to understand key factors involved in the development of the disease including the rescue of the affected cells and/or the release of paracrine factors that are crucial for tissue repair. Bioactive lipids such as sphingosine 1-phosphate (S1P) have significant effects on the modulation of signaling pathways involved in tissue regeneration, such as cell survival, proliferation, differentiation, and migration. The main objective of this work was to explore the protective effect of S1P using human kidney proximal tubule cells submitted to a mimetic I/R lesion, via ATP depletion. We observed that the S1P pre-treatment increases cell survival by 50% and preserves the cell proliferation capacity of injured cells. We showed the presence of different bioactive lipids notably related to tissue repair but, more importantly, we noted that the pre-treatment with S1P attenuated the ischemia-induced effects in response to the injury, resulting in higher endogenous S1P production. All receptors but S1PR3 are present in these cells and the protective and proliferative effect of S1P/S1P receptors axis occur, at least in part, through the activation of the SAFE pathway. To our knowledge, this is the first time that S1PR4 and S1PR5 are referred in these cells and also the first indication of JAK2/STAT3 pathway involvement in S1P-mediated protection in an I/R renal model. [ABSTRACT FROM AUTHOR]

Purpose: Well-differentiated papillary peritoneal mesothelial tumors (WDPMTs) are understudied and discrete from peritoneal mesotheliomas (PMs). We report clinicopathologic characteristics and outcomes of a large prospective WDPMT cohort. Methods: Patients with WDPMT identified between August 2007 and December 2020 were followed through January 2023. Clinical characteristics and outcomes were annotated. Overall survival (OS) was assessed from pathologic diagnosis. Germline variants were analyzed, and targeted next-generation sequencing (NGS; MSK-IMPACT) data were compared to PMs and diffuse pleural mesotheliomas (DPMs). Results: Among 54 patients, median age at diagnosis was 55 (range 20–76), 50% were female (n = 27), and 46% were smokers (n = 25; median 8 pack/years). Most (94%, n = 51) WDPMTs were found during surgical explorations for other indications, primarily other malignancies. Two patients underwent surgical resection for WDPMT; none received systemic therapy for WDPMT. Median OS was not reached (19/54; median follow up 4.5 years). Somatic NGS was available for 35% (19/54) of patients. TRAF7 alterations were enriched in WDPMT (89%; 17/19) compared with PM (0%; 0/50; p < 0.0001) and DPM (0%; 0/74; p < 0.0001). In WDPMT compared with PM and DPM, there were less BAP1 (0% [0/0] vs. 4% [8/50] vs. 46% [34/74]; p = 0.001 and p < 0.0001, respectively) and NF2 (0% [0/0] vs. 24% [12/50] vs. 31% [23/74]; p = 0.03 and p = 0.001 respectively) alterations. Pathogenic germline variants were present in 23% (4/17) of WDPMTs. Conclusions: Well-differentiated papillary peritoneal mesothelial tumors were primarily incidental findings. There was no WDPMT-related mortality, so there was no distinct role for routine cytoreductive surgery or systemic therapy. Genomic profiles can help to differentiate WDPMT from DPM and PM. [ABSTRACT FROM AUTHOR]

Introduction: Numerous studies demonstrate that modifiable lifestyle risk factors can influence patient outcomes including survivability, quality of life, and postoperative complications following orthopaedic surgery. The purpose of this study was to determine the impact of modifiable lifestyle risk factors on postoperative medical and surgical complications following a total joint arthroplasty (TJA) in a large national healthcare system. Methods: A retrospective chart review of a large national health system database was performed to identify patients who underwent TJA between 2017 and 2021. TJA included total knee arthroplasty, total hip arthroplasty, and total shoulder arthroplasty. Modifiable lifestyle risk factors were defined as tobacco use, narcotic drug abuse, hypertension, and diabetes mellitus. Postoperative medical complications and postoperative surgical complications were collected. Logistic regression and odds ratio point estimate analysis were conducted to assess for associations between postoperative complications and modifiable lifestyle risk factors. Results: Of the 16,940 patients identified, the mean age was 71 years, mean BMI was 29.7 kg/m2, and 62% were women. We found that 3.5% had used narcotics, 8.7% were past or current smokers, 24% had diabetes, and 61% had hypertension; in addition, 5.4% experienced postoperative medical complications and 6.4% experienced postoperative surgical complications. Patients who used narcotics were 90% more likely to have postoperative complications (p < 0.0001) and 105% more likely to experience prosthetic complications (p < 0.0001). Similarly, patients with tobacco use were 65% more likely to have postoperative complications (p < 0.0001) and 27% more likely to experience prosthetic complications. Conclusions: Our results demonstrate critical rates of increased postoperative medical and surgical complications after TJA for patients with narcotic abuse, tobacco use, or diabetes mellitus. Furthermore, adopting preoperative interventions and optimization programs informed by our findings on specific modifiable risk factors could aid orthopaedic surgeons in optimizing patient health. Level of evidence: III; Retrospective study. [ABSTRACT FROM AUTHOR]

Objective: To assess the diagnostic performance of post-contrast CT for predicting moderate hepatic steatosis in an older adult cohort undergoing a uniform CT protocol, utilizing hepatic and splenic attenuation values. Materials and methods: A total of 1676 adults (mean age, 68.4 ± 10.2 years; 1045M/631F) underwent a CT urothelial protocol that included unenhanced, portal venous, and 10-min delayed phases through the liver and spleen. Automated hepatosplenic segmentation for attenuation values (in HU) was performed using a validated deep-learning tool. Unenhanced liver attenuation < 40.0 HU, corresponding to > 15% MRI-based proton density fat, served as the reference standard for moderate steatosis. Results: The prevalence of moderate or severe steatosis was 12.9% (216/1676). The diagnostic performance of portal venous liver HU in predicting moderate hepatic steatosis (AUROC = 0.943) was significantly better than the liver–spleen HU difference (AUROC = 0.814) (p < 0.001). Portal venous phase liver thresholds of 80 and 90 HU had a sensitivity/specificity for moderate steatosis of 85.6%/89.6%, and 94.9%/74.7%, respectively, whereas a liver–spleen difference of −40 HU and −10 HU had a sensitivity/specificity of 43.5%/90.0% and 92.1%/52.5%, respectively. Furthermore, livers with moderate–severe steatosis demonstrated significantly less post-contrast enhancement (mean, 35.7 HU vs 47.3 HU; p < 0.001). Conclusion: Moderate steatosis can be reliably diagnosed on standard portal venous phase CT using liver attenuation values alone. Consideration of splenic attenuation appears to add little value. Moderate steatosis not only has intrinsically lower pre-contrast liver attenuation values (< 40 HU), but also enhances less, typically resulting in post-contrast liver attenuation values of 80 HU or less. Clinical relevance statement: Moderate steatosis can be reliably diagnosed on post-contrast CT using liver attenuation values alone. Livers with at least moderate steatosis enhance less than those with mild or no steatosis, which combines with the lower intrinsic attenuation to improve detection. Key Points: The liver–spleen attenuation difference is frequently utilized in routine practice but appears to have performance limitations. The liver–spleen attenuation difference is less effective than liver attenuation for moderate steatosis. Moderate and severe steatosis can be identified on standard portal venous phase CT using liver attenuation alone. [ABSTRACT FROM AUTHOR]