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In this study, the influence of thermomechanical treatments on the microstructure and mechanical properties of a new metastable β-titanium Ti-23.6Nb-5.1Mo-6.7Zr alloy was assessed. The objective was to determine if the alloy is a potential candidate for a future fabrication of orthopedic implants, in particular prosthetic hip stems with a functional gradient of mechanical properties. Two thermomechanical processing routes were investigated: (a) 90% cold-rolled, (b) 90% cold-rolled, followed by annealing at 950 °C for 1 h. After these initial processing steps, samples were aged between 300 °C and 500 °C from 0.5 h to 4 h. Microstructural characterization was conducted by optical microscopy, transmission electron microscopy and x-ray diffraction. Young's modulus and microhardness were measured. Young's modulus of the sample annealed after cold rolling is lower than that after the cold rolled one. Aging was effective at increasing hardness but also increasing Young's modulus. The hardening during aging resulted from fine ωiso and α precipitation. The transmission electron microscopy investigations indicated that an aging treatment at 500 °C leads to a fine (α + β) microstructure, avoiding brittle ωiso precipitation. For these reasons, this alloy is a potential candidate for the manufacture of a hybrid hip prosthetic stem by employing localized aging treatment at 500 °C in the neck region, creating a functional strength gradient and maintaining a low Young's modulus in the distal part, which is needed to mitigate the stress shielding of the bone.

Background: Operative blood loss is associated with postoperative morbidity and mortality in surgery. Hemostatic agents are used as adjuncts for hemostasis during surgery and help to prevent postoperative bleeding. We evaluated the safety and efficacy of an investigational polysaccharide hemostatic (PH) topical product compared to a U.S. Food and Drug Administration (FDA)-approved control in clinical use comprising microporous polysaccharide hemospheres (MPH) to achieve hemostasis of bleeding surfaces during surgery. Study design: This prospective multicenter trial enrolled patients undergoing open elective cardiac, general, or urologic surgery. Patients were stratified by bleeding severity and therapeutic area, then randomized 1:1 to receive PH or MPH. Bleeding assessments occurred intraoperatively using a novel bleeding assessment methodology. Primary endpoint was noninferiority as compared with control via effective hemostasis at 7 min. Patients were monitored and followed daily in the postoperative period until time of discharge and again at 6 weeks. Overall survival was assessed in oncology patients at 24 months. Safety of PH vs. MPH was determined by comparing relative incidence of adverse events. Results: Across 19 centers, 324 (161 PH, 163 MPH) patients were randomized (48 % general surgery, 27 % cardiac surgery, and 25 % urologic surgery). PH was noninferior to MPH and met the primary endpoint of hemostatic success at 7 min at a non-inferiority margin of 10 %. No significant differences were found in adverse event rates. Six deaths were reported within the 6-week follow-up period. No difference in overall survival was observed at 2 years (76 % PH vs. 74 % MPH, P = .66) for patients undergoing cancer operations. Conclusion: Across three therapeutic areas, PH was noninferior to MPH at all hemostasis assessment time points with no safety concerns. PH is an effective alternative to MPH for hemostasis during surgery.ClinicalTrials.gov Identifier: NCT02359994

This work proposes a methodology for designing high-strength precipitation-hardened high entropy alloys (HEAs) with an FCC matrix and L12 precipitates. High-throughput solidification calculations were conducted using the CALPHAD method, evaluating 11,235 alloys in the Cr-Co-Ni-Al-Ti system under specific boundary conditions. The acquired information was used to filter the alloys, focusing on alloys exhibiting an FCC+L12 phase field at 750 °C, a solidification interval narrower than 100 °C, and a solvus temperature under 1100 °C. The filtered alloys were analyzed to estimate their solid solution and precipitation hardening contributions to yield strength, with antiphase boundary energy (APB) assessed using two models. Three alloys were selected for testing the proposed strategy, including one with the highest yield stress and others for comparison. These alloys were produced, processed, and characterized using DSC, synchrotron XRD, SEM, and TEM. The results showed that the desired microstructure was achieved, with the alloys consisting of an FCC matrix and a high-volume fraction of L12 precipitates. Tensile tests at room temperature, 650 °C, 750 °C, and 850 °C demonstrated that the proposed model predicts well the yield strength trends, demonstrating the potential of the proposed approach for accelerating the discovery and development of novel HEAs with tailored properties.

Background: Rumination-focused cognitive behavioral therapy (RF-CBT) is designed to reduce depressive rumination or the habitual tendency to dwell on experiences in a repetitive, negative, passive, and global manner. RF-CBT uses functional analysis, experiential exercises, and repeated practice to identify and change the ruminative habit. This preregistered randomized clinical trial (NCT03859297, R61) is a preregistered replication of initial work. We hypothesized a concurrent reduction of both self-reported rumination and cross-network connectivity between the left posterior cingulate cortex and right inferior frontal and inferior temporal gyri. Methods: Seventy-six youths with a history of depression and elevated rumination were randomized to 10 to 14 sessions of RF-CBT (n = 39; 34 completers) or treatment as usual (n = 37; 28 completers). Intent-to-treat analyses assessed pre-post change in rumination response scale and in functional connectivity assessed using two 5 minute, 12 second runs of resting-state functional magnetic resonance imaging. Results: We replicated previous findings: a significant reduction in rumination response scale and a reduction in left posterior cingulate cortex to right inferior frontal gyrus/inferior temporal gyrus connectivity in participants who received RF-CBT compared with those who received treatment as usual. Reductions were large (z change = 0.84; 0.73, respectively [ps < .05]). Conclusions: This adolescent clinical trial further demonstrates that depressive rumination is a brain-based mechanism that is modifiable via RF-CBT. Here, we replicated that RF-CBT reduces cross-network connectivity, a possible mechanism by which rumination becomes less frequent, intense, and automatic. This National Institute of Mental Health-funded fast-fail study continues to the R33 phase during which treatment-specific effects of RF-CBT will be compared with relaxation therapy.

Lake Kyoga is a shallow, young, flooded basin just north of and about 30m lower than Lake Victoria. The catchment encompasses Lake Kyoga itself, and a constellation of several dozen small satellite lakes following valley contours mostly to its east. The Kyoga basin fish fauna shares many non-cichlid species plus a spectacular, partially endemic radiation of haplochromine cichlids most similar to but still largely distinct from those in Lake Victoria. This fish fauna is of high conservation concern, as it preserves remnants of the regional species flock that have disappeared from Lake Victoria and Lake Kyoga, leaving small remnant populations in some of the satellite lakes. Now, these too are imperiled by limnological dynamics, including fluctuations in the nature and extent of aquatic vegetation. The water bodies in the Kyoga Basin are highly dynamic due both to fluctuation in water level and large amplitude variation in marginal and floating vegetation. This variation has profound evolutionary and conservation implications, since it can create and destroy critical aquatic habitat. It can also alternately anneal and cleave gene flow over time, both between the main lake and its satellites, and among the satellite lakes. The aquatic vegetation cluttering these linkages can create a spatial refugium for many native fish species that are more tolerant of hypoxia than an introduced macropredator, the Nile perch. Anthropogenic impacts to this region have greatly increased in recent years, altering relationships between aquatic vegetation and endangered species, fisheries and other ecosystem services provided by the lake. Understanding these dynamics require a means of mapping aquatic vegetation, connectivity, and habitat through time. Here we develop a new and improved algorithm to map the spatial distribution and dynamics of floating and emergent aquatic vegetation via remote sensing. We utilize a time series of 440 Landsat images dating from 1986 to 2020. A series of water and vegetation indices are designed to reveal change in the aquascape over time. First, two types of water masks are derived using a majority rule - a separate water mask for each image and a composite water mask of the region over the study period. Second, the difference between the two masks is then used to delineate the potential location of macrophytes over the image. Third, an algorithm is developed to separate the floating vegetation from emergent vegetation; this algorithm uses Landsat spectral bands and two additional spatial and temporal metrics that considerably improve classification accuracy. A more extensive analysis of aquascape trajectories using remote sensing can inform fish conservation strategies and fisheries management and illuminate the role of landscape dynamics in macroevolutionary patterns of aquatic taxa.

An integral part of understanding and then designing programs to reduce childhood cancer inequities includes adequate representation of people with cancer in research, including children. A scoping review was carried out to understand how cancer research is oriented toward inequities and to identify who has participated in childhood qualitative cancer research. A systematic search identified 119 qualitative studies that met inclusion criteria, with most studies taking place in high-income countries (n=84). Overall, data were lacking on social determinants of health at multiple levels—structural, household, child, and guardian. Only 29 studies reported on race and/or ethnicity, with the majority of those including predominantly or all white children. Six articles included socioeconomic information, and across most articles, attention was absent to the financial ramifications of cancer care. Limited reporting of sociodemographics highlights a broader issue of neglecting key demographics and social factors that contribute to inequities.

Background: We aimed to assess evidence of long-term effects of exposure to radiofrequency (RF) electromagnetic fields (EMF) on indicators of cognition, including domains of learning and memory, executive function, complex attention, language, perceptual motor ability and social cognition, and of an exposure–response relationship between RF-EMF and cognition. Methods: We searched PubMed, Embase, PsycInfo and the EMF-Portal on September 30, 2022 without limiting by date or language of publication. We included cohort or case-control studies that evaluated the effects of RF exposure on cognitive function in one or more of the cognitive domains. Studies were rated for risk of bias using the OHAT tool and synthesised using fixed effects meta-analysis. We assessed the certainty of the evidence using the GRADE approach and considered modification by OHAT for assessing evidence of exposures. Results: We included 5 studies that reported analyses of data from 4 cohorts with 4639 participants consisting of 2808 adults and 1831 children across three countries (Australia, Singapore and Switzerland) conducted between 2006 and 2017. The main source of RF-EMF exposure was mobile (cell) phone use measured as calls per week or minutes per day.For mobile phone use in children, two studies (615 participants) that compared an increase in mobile phone use to a decrease or no change were included in meta-analyses. Learning and memory. There was little effect on accuracy (mean difference, MD −0.03; 95% CI −0.07 to 0.02) or response time (MD −0.01; 95% CI −0.04 to 0.02) on the one-back memory task; and accuracy (MD −0.02; 95%CI −0.04 to 0.00) or response time (MD −0.01; 95%CI −0.04 to 0.03) on the one card learning task (low certainty evidence for all outcomes). Executive function. There was little to no effect on the Stroop test for the time ratio ((B-A)/A) response (MD 0.02; 95% CI −0.01 to 0.04, very low certainty) or the time ratio ((D-C)/C) response (MD 0.00; 95% CI −0.06 to 0.05, very low certainty), with both tests measuring susceptibility to interference effects. Complex attention. There was little to no effect on detection task accuracy (MD 0.02; 95% CI −0.04 to 0.08), or response time (MD 0.02;95% CI 0.01 to 0.03), and little to no effect on identification task accuracy (MD 0.00; 95% CI −0.04 to 0.05) or response time (MD 0.00;95% CI −0.01 to 0.02) (low certainty evidence for all outcomes). No other cognitive domains were investigated in children.A single study among elderly people provided very low certainty evidence that more frequent mobile phone use may have little to no effect on the odds of a decline in global cognitive function (odds ratio, OR 0.81; 95% CI 0.42 to 1.58, 649 participants) or a decline in executive function (OR 1.07; 95% CI 0.37 to 3.05, 146 participants), and may lead to a small, probably unimportant, reduction in the odds of a decline in complex attention (OR 0.67;95%CI 0.27 to 1.68, 159 participants) and a decline in learning and memory (OR 0.75; 95% CI 0.29 to 1.99, 159 participants). An exposure–response relationship was not identified for any of the cognitive outcomes. Discussion: This systematic review and meta-analysis found only a few studies that provided very low to low certainty evidence of little to no association between RF-EMF exposure and learning and memory, executive function and complex attention. None of the studies among children reported on global cognitive function or other domains of cognition. Only one study reported a lack of an effect for all domains in elderly persons but this was of very low certainty evidence. Further studies are needed to address all types of populations, exposures and cognitive outcomes, particularly studies investigating environmental and occupational exposure in adults. Future studies also need to address uncertainties in the assessment of exposure and standardise testing of specific domains of cognitive function to enable synthesis across studies and increase the certainty of the evidence. Other: This review was partially funded by the WHO radioprotection programme and prospectively registered on PROSPERO CRD42021257548.

Summary: The efficacy of T cell therapies in treating solid tumors is limited by poor in vivo persistence, proliferation, and cytotoxicity, which can be attributed to limited and variable ex vivo activation. Herein, we present a 10-day kinetic profile of T cells subjected to fluid shear stress (FSS) ex vivo, with and without stimulation utilizing bead-conjugated anti-CD3/CD28 antibodies. We demonstrate that mechanical stimulation via FSS combined with bead-bound anti-CD3/CD28 antibodies yields a synergistic effect, resulting in amplified and sustained downstream signaling (NF-κB, c-Fos, and NFAT), expression of activation markers (CD69 and CD25), proliferation and production of pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-2). This study represents the first characterization of the dynamic response of primary T cells to FSS. Collectively, our findings underscore the critical role of mechanosensitive ion channel-mediated mechanobiological signaling in T cell activation and fitness, enabling the development of strategies to address the current challenges associated with poor immunotherapy outcomes.

Transcriptome analysis through next-generation sequencing (NGS) is an invaluable tool for investigating changes in gene expression across diverse organisms. The nematode Caenorhabditis elegans (C. elegans) serves as an excellent model organism for dissecting host responses to bacterial infections. Here, our dataset obtained from bulk RNA-sequencing (RNA-seq) can be used to provide in-depth characterization of the mRNA transcriptome profiles of wild-type N2 animals and null mutants of the cytoskeletal regulatory gene unc-53/Nav2 following exposure to distinct bacterial environments: their natural laboratory food source, Escherichia coli OP50, the human and nematode pathogen Pseudomonas aeruginosa PA14, and the emerging pathogen Elizabethkingia anophelis Ag1. As proof of the dataset quality, downstream differential gene expression analysis reveals significant shifts in gene expression patterns within N2 and unc-53 mutants under varying bacterial conditions that will be useful for our companion studies investigating these pathways. These data provide an effective methodological framework for future investigators to investigate the interplay between cytoskeletal proteins and the innate immune response. The raw FASTQ files generated from our transcriptome experiment is deposited in the publicly available NCBI Sequence Read Archive (SRA) under the BioProject accession number PRJNA1010192, for further exploration and validation by the C. elegans research community.

Background: There is confusion among members of the general public regarding the role of dietitians in healthcare. Little is known about public attitudes towards dietitians among the general public in Israel. Objectives: The present study aims to identify beliefs and attitudes about dietitians in clinical practice held by a representative sample of Israeli adults. Methods: The present cross-sectional survey was conducted online. Results: A total of 402 Israeli adults participated. The majority of respondents indicated that dietitians perform nutrition consultations and weight loss counselling. More than half of respondents knew that dietitians have at least a bachelor’s degree, but more than one third thought the degree was in alternative medicine. The majority of respondents ranked dietitians as the healthcare professionals with the greatest knowledge of human nutrition. Approximately have of respondents had been previously treated by a dietitian, and these people were more likely indicate the importance of nutrition care in treating chronic disease; further, they stated that dietitians utilize biochemical, anthropometric and other data in order to personalize nutrition care. In logistic regression analyses of specific dietitian roles, prior treatment by a dietitian emerged as a robust predictor of the role of the dietitian in healthcare. Discussion: Respondents identified dietitians as the professionals with the most knowledge of nutrition and the clinicians with whom they would most likely consult if they desired to change their eating habits.

BACKGROUND: Perinatal mood and anxiety disorders are common, serious complications of pregnancy. Disparities exist by race and income in the prevalence and treatment of these conditions, and overall treatment rates remain low. Outside of pregnancy, a small body of literature suggests that rural residency may contribute to higher rates of depression for those who identify as women. However, among more diverse populations, evidence suggests urban residency may be associated with higher rates of depression among women of color. It is not known whether these trends hold for mood and anxiety disorders during pregnancy and postpartum. OBJECTIVE: We examined differences in the detection and treatment of perinatal mood and anxiety disorders by rural and urban residents and assessed if the observed differences varied by maternal race or ethnicity. STUDY DESIGN: We conducted a cross-sectional study using linked Medicaid claims and birth certificate records from Oregon and South Carolina from 2016 to 2020. We identified perinatal mood and anxiety disorder diagnoses during the perinatal period (pregnancy and within 60 days postpartum) using International Classification of Disease 10th edition codes and enumerated receipt of pharmacotherapy and psychotherapy treatment using Medicaid claims. We used logistic regression models controlling for relevant clinical and sociodemographic characteristics to estimate associations between rural residence and mood disorder detection and treatment. RESULTS: Among the 185,809 births in our sample, 27% of births (n=50,820) were to people who lived in rural areas and 73% (n=134,989) to those in urban areas. The prevalence of any perinatal mood and anxiety disorders diagnosis was higher for urban residents (19.5%) than for rural residents (18.0%; P

Background: Fine particulate matter (PM2.5) exposure has been associated with liver cancer incidence and mortality in a limited number of studies. We sought to evaluate this relationship for the first time in a U.S. cohort with historical exposure assessment. Methods: We used spatiotemporal prediction models to estimate annual average historical PM2.5 concentrations (1980–2015) at residential addresses of 499,729 participants in the NIH-AARP Diet and Health Study, a cohort in 6 states (California, Florida, Louisiana, New Jersey, North Carolina, and Pennsylvania) and 2 metropolitan areas (Atlanta, Georgia, and Detroit, Michigan) enrolled in 1995–1996 and followed up through 2017. We used a time-varying Cox model to estimate the association for liver cancer and the predominant histologic type, hepatocellular carcinoma (HCC), per 5 µg/m3 increase in estimated outdoor PM2.5 levels, incorporating a 5-year average, lagged 10 years prior to cancer diagnosis and adjusting for age, sex, race/ethnicity, education level and catchment state. We also evaluated PM2.5 interactions with hypothesized effect modifiers. Results: We observed a non-significantly increased risk of liver cancer associated with estimated PM2.5 exposure (Hazard ratio [HR] = 1.05 [0.96–1.14], N = 1,625); associations were slightly stronger for HCC, (84 % of cases; HR = 1.08 [0.98–1.18]). Participants aged 70 or older at enrollment had an increased risk of liver cancer versus other age groups (HR = 1.50 [1.01–2.23]); p-interaction = 0.01) and risk was elevated among participants who did not exercise (HR = 1.81 [1.22–2.70]; p-interaction = 0.01). We found no evidence of effect modification by sex, smoking status, body mass index, diabetes status, or alcohol consumption (p-interaction > 0.05). Conclusions: Our findings in this large cohort suggest that residential ambient PM2.5 levels may be associated with liver cancer risk. Further exploration of the variation in associations by age and physical activity are important areas for future research.

The COVID-19 pandemic and associated need for social isolation left in-person youth mentoring programs scrambling to keep mentees and mentors connected, and many programs turned to e-mentoring. To better understand the transition period and to inform e-mentoring practice in a post-COVID world, this study explored the experience of mentoring programs shifting to e-mentoring during the first year of the pandemic. Seven remote focus group discussions were conducted with twenty-three staff members from twenty U.S. youth mentoring organizations that used the iCouldBe e-mentoring platform during Spring/summer 2020 or Fall/Winter 2020–2021. Thematic content analysis was used to uncover insights from the data. E-mentoring was successful overall for keeping mentees and mentors in touch, especially for matches with a strong connection before the pandemic. Zoom and text messaging were the most used virtual communication methods. Programs faced many challenges but also experienced unexpected positives, including a strong interest in future e-mentoring implementation. Participants recommended that programs interested in e-mentoring start small and with intention; they also requested a central website with e-mentoring support and ways to connect with other programs and mentors. Although the literature on e-mentoring remains limited, this study contributes a picture of e-mentoring success even during a global crisis.

The coastal terrestrial-aquatic interface (TAI) is a highly dynamic system characterized by strong physical, chemical, and biological gradients. In particular, shifting soil redox conditions and consumption of terminal electron acceptors, due in part to dynamic hydrologic conditions, is a strong driver of carbon availability and transformations across TAIs. However, while redox dynamics are well described, our ability to quantitatively forecast rates of oxic to anoxic shifts in soils with different characteristics and inundation regimes is limited. We integrated field measurements, laboratory incubations, and model simulations to improve mechanistic understanding of oxygen consumption dynamics in coastal soils. Continuous in situ monitoring unexpectedly revealed that flooding caused temporary spikes in subsurface dissolved oxygen followed by rapid consumption in the wetlands. To further investigate these mechanisms in a controlled setting, we performed laboratory incubations using surface and subsurface soils from a TAI gradient (defined here as upland forest to transitional forest to wetland) in Western Lake Erie to measure oxygen consumption rates in TAI soils during flood events. In our experiments, wetland soils reached anoxia the fastest, in ∼ 9 h on average, whereas upland soils turned anoxic in ∼ 18 h. Subsurface upland soils did not turn anoxic even after two weeks of saturation in the lab, and their oxygen consumption patterns suggested carbon and/or nutrient limitation. These results are consistent with in-situ groundwater redox and oxygen measurements in the field, where wetland soils exhibited the highest rates of oxygen consumption along the TAI. Model simulations of oxygen consumption suggested that oxygen consumption had stronger abiotic controls in wetland soils but stronger biotic controls in upland soils, providing a useful framework for future incubation experiments. Microbial activity is a strong driver of oxygen consumption in TAI soils, although it is constrained by the availability of dissolved carbon in subsurface soils.

Background: Trait rumination is a habitual response to negative experiences that can emerge during adolescence, increasing risk of depression. Trait rumination is correlated with poor inhibitory control (IC) and altered default mode network (DMN) and cognitive control network (CCN) engagement. Provoking state rumination in high ruminating youth permits investigation of rumination and IC at the neural level, highlighting potential treatment targets. Methods: Fifty-three high-ruminating youth were cued with an unresolved goal that provoked state rumination, then completed a modified Sustained Attention to Response Task (SART) that measures IC (commissions on no-go trials) in a functional MRI study. Thought probes measured state rumination about that unresolved goal and task-focused thoughts during the SART. Results: Greater state rumination during the SART was correlated with more IC failures. CCN engagement increased during rumination (relative to task-focus), including left dorsolateral prefrontal cortex and dorsal-medial prefrontal cortex. Relative to successful response suppression, DMN engagement increased during IC failures amongst individuals with higher state and trait rumination. Exploratory analyzes suggested more bothersome unresolved goals predicted higher left DLPFC activation during rumination. Limitations: The correlational research design did not permit a direct contrast of causal accounts of the relationship between rumination and IC. Conclusions: State rumination was associated with impaired IC and disrupted modulation of DMN and CCN. Increased CCN engagement during rumination suggested effortful suppression of negative thoughts, and this was greater for more bothersome unresolved goals. Relative task disengagement was observed during rumination-related errors. DMN-CCN dysregulation in high-ruminating youth may be an important treatment target.

Objective: To investigate the potential of voice analysis as a prescreening or monitoring tool for type 2 diabetes mellitus (T2DM) by examining the differences in voice recordings between nondiabetic and T2DM individuals. Patients and Methods: Total 267 participants diagnosed as nondiabetic (79 women and 113 men) or T2DM (18 women and 57 men) on the basis of American Diabetes Association guidelines were recruited in India between August 30, 2021 and June 30, 2022. Using a smartphone application, participants recorded a fixed phrase up to 6 times daily for 2 weeks, resulting in 18,465 recordings. Fourteen acoustic features were extracted from each recording to analyze differences between nondiabetic and T2DM individuals and create a prediction methodology for T2DM status. Results: Significant differences were found between voice recordings of nondiabetic and T2DM men and women, both in the entire dataset and in an age-matched and body mass index (BMI [calculated as the weight in kilograms divided by the height in meters squared])-matched sample. The highest predictive accuracy was achieved by pitch (P

Laser powder bed fusion (L-PBF) has emerged as one of the most promising technologies for producing complex geometries that are difficult to achieve with other methods. However, its widespread adoption is hindered by issues such as deleterious microstructure, tensile residual stresses, and porous structure, mainly while working with aluminum alloys. To address these challenges, laser shock peening (LSP) offers a potential solution by mitigating the negative effects associated with aluminum L-PBF. This study investigates the impact of the important LSP parameters, namely energy, spot size, and overlap on L-PBF printed thin AlSi10Mg tubes. A total of 17 specimens were examined by varying the mentioned parameters at three levels each. The outcome of the study was evaluated in terms of residual stresses, porosity, microstructure and surface roughness. The results have shown significant improvements in residual stresses, where a maximum improvement of over 200% was observed and a decrease in porosity by 70%. Furthermore, the microstructure analysis revealed grain refinement and dislocation redistribution as material reactions, aligning with the observed microhardness increase. These findings demonstrate the viability of LSP as a post-processing method for demanding applications, effectively addressing the limitations of the L-PBF process.

Neoadjuvant intratumoral cisplatin has the potential to generate substantial cytotoxicity and immune priming within the tumor environment, while minimizing systemic, off-target, adverse events. We initiated a phase 1A, 3+3 dose-ranging study of neoadjuvant, intratumoral cisplatin, delivered through endobronchial ultrasound bronchoscopy, in the same procedure as the initial diagnosis. There were no dose-limiting toxicity identified at the 20mg level

Human behaviour is at the centre of unsustainable consumption and production. Responsible consumption behaviours must therefore be at the centre of the solution. However, because it is inefficient for policymakers and practitioners, and ineffective for users, to attempt to target all responsible consumption behaviours simultaneously in a given initiative, some form of prioritisation is necessary. Through a combination of collaborative workshops and surveys with key stakeholders, this study applied established methods of prioritisation to identify a ‘long list’ of 84 responsible consumption behaviours across three material streams – fashion, electronics and furniture. The ‘long list’ was then taken to a prioritisation summit with government, academic, business, and community stakeholders. The behaviours were rated against explicit prioritisation criteria related to likelihood of adoption, timing, impact and potential system reach. This yielded a final ‘short list’ of seven prioritised behaviours, including a mixture of achievable consumer behaviours that can be realised in the short-term, as well as larger-scale and longer-term manufacturer- and government-related behaviours supporting fundamental design and policy shifts. By drawing on the collective knowledge and expertise of academic and non-academic experts, the study identified and prioritised behaviours to reduce material resource consumption in Australia that are impactful and transformative, while also being practical and realistic to implement.

Background: Prior research has demonstrated associations between anabolic-androgenic steroid (AAS) use and features from several childhood and adolescent psychosocial domains including body image concerns, antisocial traits, and low levels of parental care. However, prior approaches have been limited by their focus on individual features and lack of consideration of the relevant causal structure. Methods: We re-analyzed data from a previous cross-sectional cohort study of 232 male weightlifters aged 18–40, of whom 101 had used AAS. These men completed retrospective measures of features from their childhood and early adolescence, including body image concerns, eating disorder psychopathology, antisocial traits, substance use, and family relationships. Using an approach informed by principles of causal inference, we applied four machine-learning methods – lasso regression, elastic net regression, random forests, and gradient boosting – to predict AAS use. Results: The four methods yielded similar receiver operating curves, mean area under the curve (range 0.66 to 0.72), and sets of highly important features. Features related to adolescent body image concerns (especially muscle dysmorphia symptoms) were the strongest predictors. Other important features were adolescent rebellious behaviors; adolescent feelings of ineffectiveness and lack of interoceptive awareness; and low levels of paternal care. Conclusions: Applying machine learning within a causally informed approach to re-analyze data from a prior study of weightlifters, we identified six factors (most prominently those related to adolescent body image concerns) as proposed causal factors for the development of AAS use. Compared with the prior analyses, this approach achieved greater methodologic rigor and yielded stronger and broader findings.

We investigated the feasibility of an interactive voice response (IVR) survey in Tanzania and compared its prevalence estimates for tobacco use to the estimates of the 'Global Adult Tobacco Survey (GATS) 2018′. IVR participants were enrolled by random digit dialing. Quota sampling was employed to achieve the required sample sizes of age-sex strata: sex (male/female) and age (18–29-, 30–44-, 45–59-, and ≥60-year-olds). GATS was a nationally representative survey and used a multistage stratified cluster sampling design. The IVR sample’s weights were generated using the inverse proportional weighting (IPW) method with a logit model and the standard age-sex distribution of Tanzania. The IVR and GATS had 2362 and 4555 participants, respectively. Compared to GATS, the unweighted IVR sample had a higher proportion of males (58.7 % vs. 43.2 %), educated people (secondary/above education: 43.3 % vs. 21.1 %), and urban residents (56.5 % vs. 40 %). The weighted prevalence (95 % confidence interval (CI)) of current smoking was 4.99 % (4.11–6.04), 5.22 % (4.36–6.24), and 7.36 % (6.51–8.31) among IVR (IPW), IVR (age-sex standard), and GATS samples, respectively; the weighted prevalence (95 % CI) of smokeless tobacco use was similar: 3.54 % (2.73–4.57), 3.58 % (2.80–4.56), and 2.43 % (1.98–2.98), respectively. Most differences in point estimates for tobacco indicators were small (

Objectives: The assembly and secretion of hepatic very low-density lipoprotein (VLDL) plays pivotal roles in hepatic and plasma lipid homeostasis. Protein disulfide isomerase A1 (PDIA1/P4HB) is a molecular chaperone whose functions are essential for protein folding in the endoplasmic reticulum. Here we investigated the physiological requirement in vivo for PDIA1 in maintaining VLDL assembly and secretion. Methods: Pdia1/P4hb was conditionally deleted in adult mouse hepatocytes and the phenotypes characterized. Mechanistic analyses in primary hepatocytes determined how PDIA1 ablation alters MTTP synthesis and degradation as well as altering synthesis and secretion of Apolipoprotein B (APOB), along with complementary expression of intact PDIA1 vs a catalytically inactivated PDIA1 mutant. Results: Hepatocyte-specific deletion of Pdia1/P4hb inhibited hepatic MTTP expression and dramatically reduced VLDL production, leading to severe hepatic steatosis and hypolipidemia. Pdia1-deletion did not affect mRNA expression or protein stability of MTTP but rather prevented Mttp mRNA translation. We demonstrate an essential role for PDIA1 in MTTP synthesis and function and show that PDIA1 interacts with APOB in an MTTP-independent manner via its molecular chaperone function to support APOB folding and secretion. Conclusions: PDIA1 plays indispensable roles in APOB folding, MTTP synthesis and activity to support VLDL assembly. Thus, like APOB and MTTP, PDIA1 is an obligatory component of hepatic VLDL production.

Scientific research trends and interests evolve over time. The ability to identify and forecast these trends is vital for educational institutions, practitioners, investors, and funding organizations. In this study, we predict future trends in scientific publications using heterogeneous sources, including historical publication time series from PubMed, research and review articles, pre-trained language models, and patents. We demonstrate that scientific topic popularity levels and changes (trends) can be predicted five years in advance across 40 years and 125 diverse topics, including life-science concepts, biomedical, anatomy, and other science, technology, and engineering topics. Preceding publications and future patents are leading indicators for emerging scientific topics. We find the ratio of reviews to original research articles informative for identifying increasing or declining topics, with declining topics having an excess of reviews. We find that language models provide improved insights and predictions into temporal dynamics. In temporal validation, our models substantially outperform the historical baseline. Our findings suggest that similar dynamics apply across other scientific and engineering research topics. We present SciTrends, a user-friendly webtool for predicting future publication trends for any topic covered in PubMed.

Background: While epidemiologic evidence links higher levels of exposure to fine particulate matter (PM2.5) to decreased cognitive function, fewer studies have investigated links with traffic-related air pollution (TRAP), and none have examined ultrafine particles (UFP, ≤100 nm) and late-life dementia incidence. Objective: To evaluate associations between TRAP exposures (UFP, black carbon [BC], and nitrogen dioxide [NO2]) and late-life dementia incidence. Methods: We ascertained dementia incidence in the Seattle-based Adult Changes in Thought (ACT) prospective cohort study (beginning in 1994) and assessed ten-year average TRAP exposures for each participant based on prediction models derived from an extensive mobile monitoring campaign. We applied Cox proportional hazards models to investigate TRAP exposure and dementia incidence using age as the time axis and further adjusting for sex, self-reported race, calendar year, education, socioeconomic status, PM2.5, and APOE genotype. We ran sensitivity analyses where we did not adjust for PM2.5 and other sensitivity and secondary analyses where we adjusted for multiple pollutants, applied alternative exposure models (including total and size-specific UFP), modified the adjustment covariates, used calendar year as the time axis, assessed different exposure periods, dementia subtypes, and others. Results: We identified 1,041 incident all-cause dementia cases in 4,283 participants over 37,102 person-years of follow-up. We did not find evidence of a greater hazard of late-life dementia incidence with elevated levels of long-term TRAP exposures. The estimated hazard ratio of all-cause dementia was 0.98 (95 % CI: 0.92–1.05) for every 2000 pt/cm3 increment in UFP, 0.95 (0.89–1.01) for every 100 ng/m3 increment in BC, and 0.96 (0.91–1.02) for every 2 ppb increment in NO2. These findings were consistent across sensitivity and secondary analyses. Discussion: We did not find evidence of a greater hazard of late-life dementia risk with elevated long-term TRAP exposures in this population-based prospective cohort study.

Summary: The integrated stress response (ISR) is critical for cell survival under stress. In response to diverse environmental cues, eIF2α becomes phosphorylated, engendering a dramatic change in mRNA translation. The activation of ISR plays a pivotal role in the early embryogenesis, but the eIF2-dependent translational landscape in pluripotent embryonic stem cells (ESCs) is largely unexplored. We employ a multi-omics approach consisting of ribosome profiling, proteomics, and metabolomics in wild-type (eIF2α+/+) and phosphorylation-deficient mutant eIF2α (eIF2αA/A) mouse ESCs (mESCs) to investigate phosphorylated (p)-eIF2α-dependent translational control of naive pluripotency. We show a transient increase in p-eIF2α in the naive epiblast layer of E4.5 embryos. Absence of eIF2α phosphorylation engenders an exit from naive pluripotency following 2i (two chemical inhibitors of MEK1/2 and GSK3α/β) withdrawal. p-eIF2α controls translation of mRNAs encoding proteins that govern pluripotency, chromatin organization, and glutathione synthesis. Thus, p-eIF2α acts as a key regulator of the naive pluripotency gene regulatory network.

Endoplasmic reticulum (ER) stress has been linked with various acute and chronic neurodegenerative diseases. We previously found that optic nerve (ON) injury and diseases induce neuronal ER stress in retinal ganglion cells (RGCs). We further demonstrated that germline deletion of CHOP preserves the structure and function of both RGC somata and axons in mouse glaucoma models. Here we report that RGC-specific deletion of CHOP and/or its upstream regulator ATF4 synergistically promotes RGC and ON survival and preserves visual function in mouse ON crush and silicone oil-induced ocular hypertension (SOHU) glaucoma models. Consistently, topical application of the ATF4/CHOP chemical inhibitor ISRIB or RGC-specific CRISPR-mediated knockdown of the ATF4 downstream effector Gadd45a also delivers significant neuroprotection in the SOHU glaucoma model. These studies suggest that blocking the neuronal intrinsic ATF4/CHOP axis of ER stress is a promising neuroprotection strategy for neurodegeneration.

Objective: To investigate the use of a mathematical model of glucose homeostasis, fit to continuous glucose monitor data, as a metric of dysfunctional glycemic control. Patients and Methods: Three hundred eighty four participants recruited from 2 studies between October 2020 and June 2022 were equipped with a continuous glucose monitor, and interstitial glucose data were automatically collected for 2 weeks. The participants were assessed by a physician and diagnosed as being diabetic, prediabetic, or healthy according to the American Diabetes Association guidelines. A mathematical model of glucose homeostasis was fitted to the glucose data, and model parameter values were obtained. The participants were classified into the following 2 groups on the basis of their glucose homeostasis parameters: effective and impaired. Finally, glycemic variability metrics were compared with glucose homeostasis classification. Results: The homeostasis classification resulted in a specificity, sensitivity of individuals with prediabetes, and sensitivity of individuals with type 2 diabetes (T2D) of 0.78, 0.86, and 1.00, respectively, for women and 0.71, 0.86, and 1.00, respectively, for men. This sensitivity was similar to that of glycated hemoglobin A1c measurement (a sensitivity of 0.89 for women and 0.90 for men for prediabetes and a sensitivity of 1.00 for T2D) and superior to that of the oral glucose tolerance test (a sensitivity of 0.18 for women and 0.24 for men for prediabetes and a sensitivity of 0.75 for women and 0.86 for men for T2D). Overall, the individuals classified as impaired had increased glucose variability metrics than the individuals classified as effective (P

Aluminum high pressure castings (HPDC) were successfully produced on two simple but slightly different H13 steel dies that had been coated with AlCrN physical vapor deposition (PVD) coatings and without the use of conventionally-sprayed die lubricants. Over 200 lube-free (no lubricant) castings were produced in both of the dies. Temperature simulations of the dies matched well with thermal camera measurements taken during the trials, and helped explain the positions where small amounts of soldering and aluminum marks developed. Aluminum build-up on the die surfaces was observed as an intermittent phenomenon and did not lead to soldering. Due to the high gate velocities used in these trials, a large fraction of the AlCrN coating was washed out or cracked. No chemical reaction or intermetallic formation was observed on the analyzed surfaces, suggesting that build-up of aluminum on the die surface occurred by mechanical keying rather than by chemical soldering. A mechanistic model was developed to understand the correlation between surface roughness, wetting angle and HPDC pressure, in an attempt to explain why lube-free aluminum HPDC was possible for these simple die geometries, and to shed light on why it is more challenging for more complex die geometries. This study has demonstrated that lube-free aluminum die casting is possible by coating simple geometry dies with duplex AlCrN PVD coatings and suggests that lube-free castings might extend die life.

Background: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. Methods: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. Results: We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for d-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. Conclusion: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.

Secondary plant cell walls are composed of carbohydrate and lignin polymers, and collectively represent a significant renewable resource. Leveraging these resources depends in part on a mechanistic understanding for diffusive processes within plant cell walls. Common wood protection treatments and biomass conversion processes to create biorefinery feedstocks feature ion or solvent diffusion within the cell wall. X-ray fluorescence microscopy experiments have determined that ionic diffusion rates are dependent on cell wall hydration as well as the ionic species through non-linear relationships. In this work, we use classical molecular dynamics simulations to map the diffusion behavior of different plant cell wall components (cellulose, hemicellulose, lignin), ions (Na+, K+, Cu2+, Cl−) and water within a model for an intact plant cell wall at various hydration states (3–30 wt% water). From these simulations, we analyze the contacts between different plant cell wall components with each other and their interaction with the ions. Generally, diffusion increases with increasing hydration, with lignin and hemicellulose components increasing diffusion by an order of magnitude over the tested hydration range. Ion diffusion depends on charge. Positively charged cations preferentially interact with hemicellulose components, which include negatively charged carboxylates. As a result, positive ions diffuse more slowly than negatively charged ions. Measured diffusion coefficients are largely observed to best fit piecewise linear trends, with an inflection point between 10 and 15% hydration. These observations shed light onto the molecular mechanisms for diffusive processes within secondary plant cell walls at atomic resolution.

Background: DNA methylation-based measures of biological aging have been associated with air pollution and may link pollutant exposures to aging-related health outcomes. However, evidence is inconsistent and there is little information for Black women. Objective: We examined associations of ambient particulate matter

Background: Animal and epidemiologic studies indicate that air pollution may adversely affect fertility. However, the level of evidence is limited and specific pollutants driving the association are inconsistent across studies. Methods: We used data from a web-based preconception cohort study of pregnancy planners enrolled during 2013–2019 (Pregnancy Study Online; PRESTO). Eligible participants self-identified as female, were aged 21–45 years, resided in the United States (U.S.) or Canada, and were trying to conceive without fertility treatments. Participants completed a baseline questionnaire and bi-monthly follow-up questionnaires until conception or 12 months. We analyzed data from 8,747 participants (U.S.: 7,304; Canada: 1,443) who had been trying to conceive for

The 4-Poster Tick Control Deer Feeder (4-poster) device applies acaricide to white-tailed deer (Odocoileus virginianus) and can reduce populations of the blacklegged tick (Ixodes scapularis), which transmits the agents of Lyme disease, anaplasmosis, babesiosis, and Powassan virus disease in the Northeastern United States. While 4-poster devices have the potential to provide community-wide management of blacklegged ticks in Lyme disease endemic areas, no recent study has assessed their acceptability among residents. We conducted a survey of residents from 16 counties with high annual average Lyme disease incidence (≥ 10 cases per 100,000 persons between 2013 and 2017) in Connecticut and New York to understand perceptions and experiences related to tickborne diseases, support or concerns for placement of 4-poster devices in their community, and opinions on which entities should be responsible for tick control on private properties. Overall, 37% of 1652 respondents (5.5% response rate) would support placement of a 4-poster device on their own property, 71% would support placement on other private land in their community, and 90% would support placement on public land. Respondents who were male, rented their property, resided on larger properties, or were very or extremely concerned about encountering ticks on their property were each more likely to support placement of 4-poster devices on their own property. The primary reason for not supporting placement of a 4-poster device on one's own property was the need for weekly service visits from pest control professionals, whereas the top reason for not supporting placement on other land (private or public) was safety concerns. Most respondents (61%) felt property owners should be responsible for tick control on private properties. Communities considering 4-poster devices as part of a tick management strategy should consider targeting owners of larger properties and placing devices on public lands.

Background: Studies suggest associations between long-term ambient air pollution exposure and outcomes related to Alzheimer’s disease (AD). Whether a link exists between pollutants and brain amyloid accumulation, a biomarker of AD, is unclear. We assessed whether long-term air pollutant exposures are associated with late-life brain amyloid deposition in Atherosclerosis Risk in Communities (ARIC) study participants. Methods: We used a chemical transport model with data fusion to estimate ambient concentrations of PM2.5 and its components, NO2, NOx, O3 (24-hour and 8-hour), CO, and airborne trace metals. We linked concentrations to geocoded participant addresses and calculated 10-year mean exposures (2002 to 2011). Brain amyloid deposition was measured using florbetapir amyloid positron emission tomography (PET) scans in 346 participants without dementia in 2012–2014, and we defined amyloid positivity as a global cortical standardized uptake value ratio ≥ the sample median of 1.2. We used logistic regression models to quantify the association between amyloid positivity and each air pollutant, adjusting for putative confounders. In sensitivity analyses, we considered whether use of alternate air pollution estimation approaches impacted findings for PM2.5, NO2, NOx, and 24-hour O3. Results: At PET imaging, eligible participants (N = 318) had a mean age of 78 years, 56% were female, 43% were Black, and 27% had mild cognitive impairment. We did not find evidence of associations between long-term exposure to any pollutant and brain amyloid positivity in adjusted models. Findings were materially unchanged in sensitivity analyses using alternate air pollution estimation approaches for PM2.5, NO2, NOx, and 24-hour O3. Conclusions: Air pollution may impact cognition and dementia independent of amyloid accumulation, though whether air pollution influences AD pathogenesis later in the disease course or at higher exposure levels deserves further consideration.