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The Human Cell Atlas (HCA) is a global partnership to create comprehensive reference maps of all human cells-the fundamental units of life - as a basis for both understanding human health and diagnosing, monitoring, and treating disease. ( https://www.humancellatlas.org/ ) The atlas shall characterize cells from diverse individuals across the globe to better understand human biology. HCA proactively considers the priorities of, and benefits accrued to, contributing communities. Here, we lay out principles and action items that have been adopted to affirm HCAs commitment to equity so that the atlas is beneficial to all of humanity.

Motor vehicles are among the major sources of pollutants and greenhouse gases in urban areas and a transition to "zero emission vehicles" is underway worldwide. However, emissions associated with brake and tire wear will remain. We show here that previously unrecognized volatile and semi-volatile organic compounds, which have a similarity to biomass burning emissions are emitted during braking. These include greenhouse gases or, these classified as Hazardous Air Pollutants, as well as nitrogen-containing organics, nitrogen oxides and ammonia. The distribution and reactivity of these gaseous emissions are such that they can react in air to form ozone and other secondary pollutants with adverse health and climate consequences. Some of the compounds may prove to be unique markers of brake emissions. At higher temperatures, nucleation and growth of nanoparticles is also observed. Regions with high traffic, which are often disadvantaged communities, as well as commuters can be impacted by these emissions even after combustion-powered vehicles are phased out.

Abstract Background There are no studies that compare the outcomes and complications of single-versus two-stage revision anterior cruciate ligament reconstruction (ACLR) after primary ACLR failure. This purpose of this study is to examine clinical and functional outcomes and complications associated with single and two-stage revision ACLR after primary ACLR failure. Methods All patients who underwent single or two-stage revision ACLR after primary ACLR failure between 2012 and 2021 with a minimum of a 2 year follow-up were included. Patients were excluded if they were not treated at our single academic institution, had inadequate follow-up, or had incomplete medical records. Revision intraoperative data, concomitant injuries, and complications were collected by chart review. Return to sport, numerical pain rating scale (NPRS) score, Knee injury and Osteoarthritis Outcome Score (KOOS), and Veteran Rands 12-item health survey (VR-12 scores) were collected. Results The final analysis included 176 patients. A total of 147 (83.5%) had a single-stage revision ACLR (87 male, 60 female), and 29 (16.5%) had a two-stage revision ACLR (13 male, 16 female). Two-stage revision ACLR was significantly associated with anterior knee pain [odds ratio (OR) 4.36; 95% confidence interval (CI) 1.5 to 12.65; P = 0.007] but with lower failure rates (OR 0.12, 95% CI 0.02 to 0.9; P = 0.04). On multivariate analysis, a two-stage revision ACLR reduced the risk of graft failure by 85% (OR 0.15; 95% CI 0.02 to 1.17; P = 0.07). Two-stage revision ACLR was significantly associated with a lower KOOS pain score (OR −11.7; 95% CI −22.35 to −1.04; P = 0.031), KOOS symptoms score (OR −17.11; 95% CI −28.85 to −5.36; P = 0.004), KOOS Activities of Daily Living (ADL) score (OR −11.15; 95% CI −21.71 to −0.59; P = 0.039) and Veterans RAND 12-Item Health Survey (VR-12) physical component score (OR −9.99; 95% CI −15.77 to −4.22; P = 0.001). Conclusions The clinical outcomes and subjective patient scores significantly differed between the single-stage and two-stage revision ACLR after primary ACLR failure. Patients with a two-stage revision ACLR had a significantly reduced risk of revision graft failure but higher rates of postoperative anterior knee pain, lower pain scores, and lesser knee functional scores than single-stage revision patients. Study design Retrospective cohort study; level of evidence, 3

To what degree does semantic foraging probe semantic network structure? We use a combination of foraging experiments (animals, concrete nouns) and simulations on networks based on nine approaches to semantic similarity to address this question. In data and simulations, we find a significant bias towards naming semantically similar items, and significant correlations between inter-naming time and semantic distance. In previous foraging experiments, a roughly power law distribution with a Lévy range exponent was found in the distribution of inter-naming intervals. We find the value of this exponent is not universal but is sensitive to the search space size in that the exponent decreases (moving further into the Lévy range) as the number of nameable items is exhausted. Moreover, these exponents are not unique to semantic networks but appear in censored random walks on other graphs. Our combined experimental results and simulations provide insights into the topology of semantic memory.

Abstract The Human Cell Atlas (HCA) is a global partnership “to create comprehensive reference maps of all human cells—the fundamental units of life – as a basis for both understanding human health and diagnosing, monitoring, and treating disease.” ( https://www.humancellatlas.org/ ) The atlas shall characterize cells from diverse individuals across the globe to better understand human biology. HCA proactively considers the priorities of, and benefits accrued to, contributing communities. Here, we lay out principles and action items that have been adopted to affirm HCA’s commitment to equity so that the atlas is beneficial to all of humanity.

Abstract The nematode Caenorhabditis elegans is widely employed as a model organism to study basic biological mechanisms. However, transgenic C. elegans are generated by manual injection, which remains low-throughput and labor-intensive, limiting the scope of approaches benefitting from large-scale transgenesis. Here, we report a robotic microinjection system, integrating a microfluidic device capable of reliable worm immobilization, transfer, and rotation, for high-speed injection of C. elegans. The robotic system provides an injection speed 2-3 times faster than that of experts with 7–22 years of experience while maintaining comparable injection quality and only limited trials needed by users to become proficient. We further employ our system in a large-scale reverse genetic screen using multiplexed alternative splicing reporters, and find that the TDP-1 RNA-binding protein regulates alternative splicing of zoo-1 mRNA, which encodes variants of the zonula occludens tight junction proteins. With its high speed, high accuracy, and high efficiency in worm injection, this robotic system shows great potential for high-throughput transgenic studies of C. elegans.

Background: Higher malnutrition risk is associated with mortality among patients with heart failure and heart transplantation (HT). We investigated which malnutrition risk scores – geriatric nutrition risk index (GNRI), prognostic nutritional index (PNI), or controlling nutritional status (CONUT) – have the strongest mortality association for HT candidates, and whether they are prognostic at the time of HT listing or HT operation. Methods: We reviewed adults listed for primary HT at a single center 1987–March 2022, with survival follow-up to November 2022. We constructed Cox proportional hazards models and restricted cubic spline curves for each risk score at both HT listing and HT operation and inputted HT operation as a time-varying covariate for models commencing at listing. Risk scores were assessed as continuous and binary variables. Weight change between listing and HT was evaluated similarly. Results: The 1,024 patients [76% male; median age 55 (46–61) years; HT operation n = 656] had median follow-up of 4.6 (interquartile range 1.6–8.7) years. As a continuous variable, lower GNRI at HT listing (greater malnutrition risk) was independently associated with higher mortality. As binary variables, higher risk GNRI, PNI or CONUT scores at listing were all associated with higher mortality. Conversely, risk scores at time of HT operation were not associated with subsequent mortality. There was a non-significant trend towards higher mortality with greater weight loss between listing and HT operation. Conclusion: Malnutrition risk scores showed prognostic utility only at time of HT listing. As a continuous variable, GNRI at HT listing was independently associated with subsequent mortality.

In many biparental mammalian species, such as California mice (Peromyscus cali- fornicus), new fathers exhibit affiliative behavior toward unfamiliar infants, whereas reproductively naïve males show highly variable behavioral responses to infants. The sources of this variation are unknown. We investigated the effects of acute stress on pup-directed behavior in reproductively naïve male California mice. Each mouse underwent three 10-minute tests with an unfamiliar pup at 48-hour intervals. Males in the stressed group (N=22) were stressed using subcutane- ous oil injections, a common experimental stressor used in rodents, immediate- ly before each of the first two tests. The controls (N=22) were left undisturbed to avoid any experimentally induced stress. Compared to controls, stressed mice spent significantly less time performing paternal behavior in tests 1 and 2, while only marginal differences were seen in test 3. In tests 2 and 3, signifi- cantly fewer stressed mice interacted with the pup than controls. These findings suggest that acute stress experienced by reproductively naïve males might con- tribute to both short-term and long-term differences in pup-directed behavior.

Carbonyl sulfide (COS) is the most abundant sulfur gas in the atmosphere with links to terrestrial and oceanic productivity. We measured COS in ice core air from an intermediate-depth ice core from the South Pole using both dry and wet extraction methods, recovering a 52 500-year record. We find evidence for COS production in the firn, altering the atmospheric signal preserved in the ice core. Mean sea salt aerosol concentrations from the same depth are a good proxy for the COS production, which disproportionately impacts the measurements from glacial period ice with high sea salt aerosol concentrations. The COS measurements are corrected using sea salt sodium (ssNa) as a proxy for the excess COS resulting from the production. The ssNa-corrected COS record displays substantially less COS in the glacial period atmosphere than the Holocene and a 2 to 4-fold COS rise during the deglaciation synchronous with the associated climate signal. The deglacial COS rise was primarily source driven. Oceanic emissions in the form of COS, carbon disulfide (CS2), and dimethylsulfide (DMS) are collectively the largest natural source of atmospheric COS. A large increase in ocean COS emissions during the deglaciation suggests enhancements in emissions of ocean sulfur gases via processes that involve ocean productivity, although we cannot quantify individual contributions from each gas.

BACKGROUND: Although hypospadias outcomes studies typically report a level or type of repair performed, these studies often lack applicability to each surgical practice due to technical variability that is not fully delineated. An example is the tubularized incised plate (TIP) urethroplasty procedure, for which modifications have been associated with significantly decreased complication rates in single center series. However, many studies fail to report specificity in techniques utilized, thereby limiting comparison between series. OBJECTIVE: With the goal of developing a surgical atlas of hypospadias repair techniques, this study examined 1) current techniques used by surgeons in our network for recording operative notes and 2) operative technical details by surgeon for two common procedures, tubularized incised plate (TIP) distal and proximal hypospadias repairs across a multi-institutional surgical network. STUDY DESIGN: A two-part study was completed. First, a survey was distributed to the network to assess surgeon volume and methods of recording hypospadias repair operative notes. Subsequently, an operative template or a representative de-identified operative note describing a TIP and/or proximal repair with urethroplasty was obtained from participating surgeons. Each was analyzed by at least two individuals for natural language that signified specified portions of the procedure. Procedural details from each note were tabulated and confirmed with each surgeon, clarifying that the recorded findings reflected their current practice techniques and instrumentation. RESULTS: Twenty-five surgeons from 12 institutions completed the survey. The number of primary distal hypospadias repairs performed per surgeon in the past year ranged from 1-10 to >50, with 40% performing 1-20. Primary proximal hypospadias repairs performed in the past year ranged from 1-30, with 60% performing 1-10. 96% of surgeons maintain operative notes within an electronic health record. Of these, 66.7% edited a template as their primary method of note entry; 76.5% of these surgeons reported that the template captures their operative techniques very or moderately well. Operative notes or templates from 16 surgeons at 10 institutions were analyzed. In 7 proximal and 14 distal repairs, parameters for chordee correction, urethroplasty suture selection and technique, tissue utilized, and catheter selection varied widely across surgeons. CONCLUSION: Wide variability in technical surgical details of categorically similar hypospadias repairs was demonstrated across a large surgical network. Surgeon-specific modifications of commonly described procedures are common, and further evaluation of short- and long-term outcomes accounting for these technical variations is needed to determine their relative influence.

ObjectiveTo compare secondary patient reported outcomes of perceptions of treatment success and function for patients treated for appendicitis with appendectomy vs. antibiotics at 30 days.Summary background dataThe Comparison of Outcomes of antibiotic Drugs and Appendectomy trial found antibiotics noninferior to appendectomy based on 30-day health status. To address questions about outcomes among participants with lower socioeconomic status, we explored the relationship of sociodemographic and clinical factors and outcomes.MethodsWe focused on 4 patient reported outcomes at 30 days: high decisional regret, dissatisfaction with treatment, problems performing usual activities, and missing >10 days of work. The randomized (RCT) and observational cohorts were pooled for exploration of baseline factors. The RCT cohort alone was used for comparison of treatments. Logistic regression was used to assess associations.ResultsThe pooled cohort contained 2062 participants; 1552 from the RCT. Overall, regret and dissatisfaction were low whereas problems with usual activities and prolonged missed work occurred more frequently. In the RCT, those assigned to antibiotics had more regret (Odd ratios (OR) 2.97, 95% Confidence intervals (CI) 2.05-4.31) and dissatisfaction (OR 1.98, 95%CI 1.25-3.12), and reported less missed work (OR 0.39, 95%CI 0.27-0.56). Factors associated with function outcomes included sociodemographic and clinical variables for both treatment arms. Fewer factors were associated with dissatisfaction and regret.ConclusionsOverall, participants reported high satisfaction, low regret, and were frequently able to resume usual activities and return to work. When comparing treatments for appendicitis, no single measure defines success or failure for all people. The reported data may inform discussions regarding the most appropriate treatment for individuals.Trial registrationClinicaltrials.gov Identifier: NCT02800785.

Introduction: Studies that examine obstetric violence and mistreatment during perinatal care demonstrate that Black women experience higher levels of harm and abuse than other racialized groups. Yet these gender-based concepts do not fully recognize the intersectional gender-and race-based harms that Black women experience within the context of quality, safety, and human rights violations in the U.S. healthcare system. Methods: We performed qualitative secondary analysis from Black women participants in the Giving Voice to Mothers (GVtM) study (n = 304). Primary data collection for the GVtM survey spanned from 2016 to 2017, and our analysis occurred in 2023, focusing on the interpretation of open-ended responses to three categories of inquiry: worst experiences with perinatal care, experiences of being pressured to undergo medical interventions, and desired revisions to birthing experiences. We employed a deductive approach and applied two analytic frameworks – obstetric racism and the Black Birthing Bill of Rights (BBBR)– to categorize Black women's narratives of harm during perinatal care as quality, safety, and human rights violations. Results: Black women described perinatal care experiences with considerable violations of the BBBR, including disrupted time with babies, racially discordant care, and unaffordable care. These experiences illustrated all six domains of obstetric racism. Conclusion: This study contributes to an emerging body of Black feminist approaches to knowledge production in obstetric patient safety, emphasizing the critical intersection of gender and race. Furthermore, this study underscores the value of using Black-women-defined frameworks with typologies to interpret the distinct experiences of Black women instead of the more limited gender-based concepts of obstetric violence, mistreatment, and respectful maternity care that lack historical context and contemporary implications of anti-Black racism and misogynoir.

Abstract Marine turtles are a group of imperiled marine megafauna particularly vulnerable to anthropogenic stressors. Most long‐term studies of marine turtles are based on nesting surveys which focus on numbers of eggs, hatchlings, and nesting females. However, we know less about long‐term abundance trends of immature and adult turtles in the marine environment. To address this data gap, we examined records from 35,000 underwater visual census (UVC) dives (1993–2019) and short‐term in‐water turtle survey data (2009–2014) at Cocos Island, Costa Rica. During UVCs, trained divemasters from UnderSea Hunter recorded observations of two species of marine turtles—green Chelonia mydas and hawksbill Eretmochelys imbricata. Our short‐term in‐water surveys revealed that most turtles at Cocos are greens, but both immature and mature greens occur at Cocos. We analyzed long‐term UVC data using a hierarchical modeling approach and we modeled a 26% decrease in the relative abundance of turtles observed on dives each year. Our model also revealed potential interactions between tiger sharks and turtles, finding that for each additional tiger shark present during a dive, the predicted relative abundance of turtles decreased by 43%. Lastly, our model suggested the influence of environmental variation on marine turtle relative abundance; a 1°C increase in sea surface temperature (SST) decreased the predicted relative abundance of turtles by 7%. Our results suggest that marine turtles are sensitive to long‐term environmental and oceanographic changes, and potentially avoid certain areas to reduce exposure to tiger sharks. Given our study area is already protected, there needs to be more focus on protecting adult turtles during their movements across the Eastern Tropical Pacific. Our work also highlights the importance of long‐term underwater surveys to monitor adult turtles.

Introduction: Currently, there is limited evidence for the relationship of Exosome-based Prostate Intelliscore (EPI) and multiparametric magnetic resonance imaging (mpMRI) in stratifying risk for clinically significant prostate cancer. Using a retrospective cohort study design, we sought to characterize the relationship between these two noninvasive metrics and prostate biopsy outcome. Methods: Data were collected via electronic medical record for all patients who underwent EPI testing from 1 January 2019 to 3 February 2022 and had available medical records at a single mid-western university medical center. Positive test result was defined as >15.6 for EPI, ≥3 PI-RADS score and ≥3 + 4 Gleason Score for biopsy findings. Utility of EPI, mpMRI and combined use was characterized through calculation of sensitivity, specificity, positive predictive value, negative predictive value, and ROC analysis. Results: A total of 226 patients were identified as receiving EPI testing for risk stratification of clinically significant prostate cancer. Sensitivity for EPI was 91%, mpMRI was 90%, and the highest was combined use at 96%. With ROC analysis, AUC for EPI alone was 0.57 (95% CI, 0.47–0.67) and 0.78 (95% CI, 0.70–0.87) for mpMRI alone. With prior positive EPI result, AUC for combined use with mpMRI was 0.80 (95% CI, 0.71–0.89). Further subgroup analysis resulted in increased AUC values of EPI 0.67 (95% CI, 0.48–0.87), mpMRI 0.90 (95% CI, 0.76–1.0), and combined 0.90 (95% CI, 0.75–1.0) in the African American population. Discussion: We observed that the combined use of EPI and mpMRI led to an avoided biopsy in 43% of patients. Using both parameters increased the overall sensitivity and diagnostic accuracy in detecting clinically significant prostate cancer. The best test performance was observed in the African American cohort. Identifying optimal noninvasive tools to assess risk for prostate cancer is crucial to providing accurate and cost-effective care. Future study should utilize a prospective study design to further support the combined use of these metrics.