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The association of cocaine use disorder (CUD) and comorbid major depressive disorder (MDD; CUD/MDD) is characterized by high prevalence and poor treatment outcomes. CUD/MDD may be primary (primary MDD) or cocaine-induced (CUD-induced MDD). Specific biomarkers are needed to improve diagnoses and therapeutic approaches in this dual pathology. Platelet biomarkers [5-HT2A receptor and imidazoline receptor antisera selected (IRAS)/nischarin] were assessed by Western blot in subjects with CUD and primary MDD (n = 16) or CUD-induced MDD (n = 9; antidepressant free, AD−; antidepressant treated, AD+) and controls (n = 10) at basal level and/or after acute tryptophan depletion (ATD). Basal platelet 5-HT2A receptor (monomer) was reduced in comorbid CUD/MDD subjects (all patients: 43%) compared to healthy controls, and this down-regulation was independent of AD medication (decreases in AD−: 47%, and in AD+: 40%). No basal differences were found for IRAS/nischarin contents in AD+ and AD− comorbid CUD/MDD subjects. The comparison of IRAS/nischarin in the different subject groups during/after ATD showed opposite modulations (i.e., increases and decreases) in response to low plasma tryptophan levels with significant differences discriminating between the subgroups of CUD with primary MDD and CUD-induced MDD. These specific alterations suggested that platelet IRAS/nischarin might be useful as a biomarker to discriminate between primary and CUD-induced MDD in this dual pathology.

We applied a site evaluation approach combining Lagrangian Stochastic footprint modeling with a quality assessment approach for eddy-covariance data to 25 forested sites of the CarboEurope-IP network. The analysis addresses the spatial representativeness of the flux measurements, instrumental effects on data quality, spatial patterns in the data quality, and the performance of the coordinate rotation method. Our findings demonstrate that application of a footprint filter could strengthen the CarboEurope-IP flux database, since only one third of the sites is situated in truly homogeneous terrain. Almost half of the sites experience a significant reduction in eddy-covariance data quality under certain conditions, though these effects are mostly constricted to a small portion of the dataset. Reductions in data quality of the sensible heat flux are mostly induced by characteristics of the surrounding terrain, while the latent heat flux is subject to instrumentation-related problems. The Planar-Fit coordinate rotation proved to be a reliable tool for the majority of the sites using only a single set of rotation angles. Overall, we found a high average data quality for the CarboEurope-IP network, with good representativeness of the measurement data for the specified target land cover types.

Production of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and lower-middle-income countries is needed. NDV-HXP-S is an inactivated egg-based recombinant Newcastle disease virus vaccine expressing the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A public sector manufacturer in Vietnam assessed the immunogenicity of NDV-HXP-S (COVIVAC) relative to an authorized vaccine. This phase 2 stage of a randomised, observer-blind, controlled, phase 1/2 trial was conducted at three community health centers in Thai Binh Province, Vietnam. Healthy males and non-pregnant females, 18 years of age and older, were eligible. Participants were randomised by age (18-59, ≥60 years) to receive one of three treatments by intramuscular injection twice, 28 days apart: COVIVAC at 3 μg or 6 μg, or AstraZeneca COVID-19 vaccine VAXZEVRIA™. Participants and personnel assessing outcomes were masked to treatment. The vaccine dose was selected based on Phase 1 results. A 6 μg dose was chosen to explore the immunogenicity gain over the 3-μg dose. The study's aim is to evaluate the safety and immunogenicity of COVIVAC at two dose levels compared to VAXZEVRIA, the most commonly used COVID-19 vaccine in Vietnam. The main outcome was the induction of 50% neutralising antibody titers against vaccine-homologous pseudotyped virus 14 days (day 43) and 6 months (day 197) after the second vaccination by age group. The primary immunogenicity and safety analyses included all participants who received one dose of the vaccine. ClinicalTrials.govNCT05940194. During August 10-23, 2021, 737 individuals were screened, and 374 were randomised (124-125 per group); all subjects received vaccine dose one and all but three received doses two four weeks later. Subjects 18-59 years of age achieved the following geometric mean titers of PNA 14 days after vaccine dose two: 153⋅28 (95 % CI 124·2-189⋅15) for COVIVAC 3 μg, 176⋅2 (95 % CI 141⋅45-220.27) for COVIVAC 6 μg, and 99⋅92(95 % CI 80.80-123⋅56) for VAXZEVRIA. Subjects ≥60 years of age also achieved potent geometric mean titers of PNA at the same timepoint: 183⋅57 (95 % CI 133.4-252⋅61) for COVIVAC 3 μg, 257⋅87 (95 % CI 181⋅6-367⋅18) for COVIVAC 6 μg, and 79⋅49(95 % CI 55⋅68-113⋅4) for VAXZEVRIA. On day 43, the geometric mean fold rise of 50 % neutralising antibody titers for subjects age 18-59 years was 31·20 (COVIVAC 3 μg N = 82, 95 % CI 25·14-38·74), 35·80 (COVIVAC 6 μg; N = 83, 95 % CI 29·03-44·15), 18·85 (VAXZEVRIA; N = 82, 95 % CI 15·10-23·54), and for subjects age ≥ 60 years was 37·27 (COVIVAC 3 μg; N = 42, 95 % CI 27·43-50·63), 50·10 (COVIVAC 6 μg; N = 40, 95 % CI 35·46-70·76), 16·11 (VAXZEVRIA; N = 40, 95 % CI 11·73-22·13). Among subjects seronegative for anti-S IgG at baseline, the day 43 geometric mean titer ratio of neutralising antibody (COVIVC 6 μg/VAXZEVRIA) was 1·77 (95 % CI 1·30-2·40) for subjects age 18-59 years and 3·24 (95 % CI 1·98-5·32) for subjects age ≥ 60 years. On day 197, the age-specific ratios were 1·11 (95 % CI 0·51-2·43) and 2·32 (0·69-7·85). Vaccines were well tolerated; reactogenicity was predominantly mild and transient. The percentage of subjects with unsolicited adverse events (AEs) during 28 days after vaccinations was similar among treatments (COVIVAC 3 μg 29·0 %, COVIVAC 6 μg 23·2 %, VAXZEVRIA 31·2 %); no vaccine-related AE was reported. Considering that induction of neutralising antibodies against SARS-CoV-2 has been correlated with the efficacy of COVID-19 vaccines, including VAXZEVRIA, our results suggest that vaccination with COVIVAC may afford clinical benefit matching or exceeding that of the VAXZEVRIA vaccine. ClinicalTrials.govNCT05940194., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alessandro Sette reports financial support was provided by National Institutes of Health. Daniela Weiskopf reports a relationship with Moderna Inc. that includes: consulting or advisory. Daniela Weiskopf is an associate editor for Vaccine. La Jolla Institute has patents issued for various aspects of T cell epitope and vaccine design work. Juan Manuel Carreno reports funding was provided by Icahn School of Medicine at Mount Sinai Department of Microbiology. Florian Krammer reports a relationship with Avimex Laboratories that includes: royalties or licenses and consulting. Florian Krammer reports a relationship with Kantaro Biosciences that includes: royalties or licenses. Florian Krammer reports a past relationship with Pfizer that includes: consulting or advisory. Florian Krammer reports a past relationship with Seqirus Inc. that includes: consulting or advisory. Florian Krammer reports a past relationship with GSK that includes: consulting or advisory. Florian Krammer reports a relationship with Gritstone bio Inc. that includes: consulting or advisory. Florian Krammer reports a relationship with CastleVax that includes: equity or stocks, royalties or licenses, and consulting. Florian Krammer has patents regarding SARS-CoV-2 vaccines and serological assays issued to Icahn School of Medicine at Mount Sinai. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective:  This study aimed to examine associations of fetal biometric and amniotic fluid measures with intrapartum primary cesarean delivery (PCD) and develop prediction models for PCD based on ultrasound parameters and maternal factors., Study Design:  Secondary analysis of the National Institute of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-singleton cohort (2009-2013) including patients with uncomplicated pregnancies and intent to deliver vaginally at ≥37 0/7 weeks. The estimated fetal weight, individual biometric parameters, fetal asymmetry measurements, and amniotic fluid single deepest vertical pocket assessed at the final scan (mean 37.5 ± 1.9 weeks) were categorized as <10th, 10th to 90th (reference), and >90th percentiles. Logistic regression analyses examined the association between the ultrasound measures and PCD. Fetal and maternal SuperLearner prediction algorithms were constructed for the full and nulliparous cohorts., Results:  Of the 1,668 patients analyzed, 249 (14.9%) had PCD. The fetal head circumference, occipital-frontal diameter, and transverse abdominal diameter >90th percentile (adjusted odds ratio [aOR] = 2.50, 95% confidence interval [95% CI]: 1.39, 4.51; aOR = 1.86, 95% CI: 1.02, 3.40; and aOR = 2.13, 95% CI: 1.16, 3.89, respectively) were associated with PCD. The fetal model demonstrated poor ability to predict PCD in the full cohort and in nulliparous patients (area under the receiver-operating characteristic curve [AUC] = 0.56, 95% CI: 0.52, 0.61; and AUC = 0.54, 95% CI: 0.49, 0.60, respectively). Conversely, the maternal model had better predictive capability overall (AUC = 0.79, 95% CI: 0.75, 0.82) and in the nulliparous subgroup (AUC = 0.72, 95% CI: 0.67, 0.77). Models combining maternal/fetal factors performed similarly to the maternal model (AUC = 0.78, 95% CI: 0.75, 0.82 in full cohort, and AUC = 0.71, 95% CI: 0.66, 0.76 in nulliparas)., Conclusion:  Although a few fetal biometric parameters were associated with PCD, the fetal prediction model had low performance. In contrast, the maternal model had a fair-to-good ability to predict PCD., Key Points: · Fetal HC >90th percentile was associated with cesarean delivery.. · Fetal parameters did not effectively predict PCD.. · Maternal factors were more predictive of PCD.. · Maternal/fetal and maternal models performed similarly.. · Prediction models had lower performance in nulliparas.., Competing Interests: D.A.W. has been a consultant for Parsagen, for which she received no compensation. The other authors did not report any potential conflict of interest., (Thieme. All rights reserved.)

Ovarian cancer is resistant to immunotherapy, and this is influenced by the immunosuppressed tumor microenvironment (TME) dominated by macrophages. Resistance is also affected by intratumoral heterogeneity, whose development is poorly understood. To identify regulators of ovarian cancer immunity, we employed a spatial functional genomics screen (Perturb-map), focused on receptor/ligands hypothesized to be involved in tumor-macrophage communication. Perturb-map recapitulated tumor heterogeneity and revealed that interleukin-4 (IL-4) promotes resistance to anti-PD-1. We find ovarian cancer cells are the key source of IL-4, which directs the formation of an immunosuppressive TME via macrophage control. IL-4 loss was not compensated by nearby IL-4-expressing clones, revealing short-range regulation of TME composition dictating tumor evolution. Our studies show heterogeneous TMEs can emerge from localized altered expression of cancer-derived cytokines/chemokines that establish immune-rich and immune-excluded neighborhoods, which drive clone selection and immunotherapy resistance. They also demonstrate the potential of targeting IL-4 signaling to enhance ovarian cancer response to immunotherapy., Competing Interests: Declaration of interests B.D.B. has a patent application on the Pro-Codes, which have been licensed to Immunai and Noetik. P.K.S. is co-founder of Glencoe Software and member of the SAB for RareCyte, NanoString, and Montai Health; he holds equity in Glencoe and RareCyte. N.R. is the founder of R&A Data., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: We examined trends in prepregnancy obesity and gestational weight gain, with a focus on racial and ethnic differences, before and during the COVID-19 pandemic in South Carolina., Methods: Hospital and emergency department discharge codes were linked to birth certificates. Prepregnancy obesity was defined as a body mass index (kg/m 2 ) of 30 or higher. Gestational weight gain was defined as inadequate, adequate, or excessive based on the 2009 Institute of Medicine guidelines. A generalized linear model with a multinomial distribution and glogit link estimated the risk of inadequate weight gain and excessive weight gain with adequate weight gain as the reference group. The generalized linear model with a modified Poisson distribution and log link estimated prepregnancy obesity risk with nonobese as the reference group., Results: Our study included 306,344 full-term, singleton live births among 239,597 mothers from 2015 through 2021. The prevalence of inadequate weight gain increased across all racial and ethnic groups prepandemic (relative risk [RR] = 1.02; 95% CI, 1.01-1.02) and attenuated during the pandemic (RR = 0.99; 95% CI, 0.96-1.01). The prevalence of excessive weight gain was high and remained stable across all races and ethnicities before and during the pandemic. The prevalence of prepregnancy obesity increased across all racial and ethnic groups prepandemic; the prevalence after the start of the pandemic increased only among women of "other" races and ethnicities (RR = 1.12; 95% CI, 1.05-1.19) while attenuating among Hispanic, non-Hispanic Black, and non-Hispanic White women., Conclusion: The COVID-19 pandemic did not alter trends of gestational weight gain; however, it did have a small effect on trends in prepregnancy obesity, with differential effects across racial and ethnic groups. The prevalence of prepregnancy obesity, inadequate weight gain, and excessive weight gain remains high among pregnant women in South Carolina. Obesity and weight gain are risk factors for many adverse maternal and infant pregnancy outcomes. Their high prevalence indicates the importance of developing effective weight management programs for women of childbearing age and pregnant women.

Aquatic habitats provide a bridge for influenza transmission among wild and domestic species. However, water sources pose highly variable physicochemical and ecological characteristics that affect avian influenza virus (AIV) stability. Therefore, the risk of survival or transmissibility of AIV in the environment is quite variable and has been understudied. In this study, we determine the risk of waterborne transmission and environmental persistence of AIV in a wild/domestic bird interface in the Central Mexico plateau (North America) during the winter season using a multi-criteria decision analysis (MCDA). A total of 13 eco-epidemiological factors were selected from public-access databases to develop the risk assessment. The MCDA showed that the Atarasquillo wetland presents a higher persistence risk in January. Likewise, most of the backyard poultry farms at this wild-domestic interface present a high persistence risk (50%). Our results suggest that drinking water may represent a more enabling environment for AIV persistence in contrast with wastewater. Moreover, almost all backyard poultry farms evidence a moderate or high risk of waterborne transmission especially farms close to water bodies. The wildlife/domestic bird interface on the Atarasquillo wetland holds eco-epidemiological factors such as the presence of farms in flood-prone areas, the poultry access to outdoor water, and the use of drinking-water troughs among multiple animal species that may enhance waterborne transmission of AIV. These findings highlight the relevance of understanding the influence of multiple factors on AIV ecology for early intervention and long-term control strategies., (© 2024. The Author(s).)

Objective: To examine trends with a focus on racial and ethnic disparities in reported gestational diabetes mellitus (GDM) and related outcomes (macrosomia, large for gestational age infants) before and during the COVID-19 pandemic in South Carolina (SC). Methods: A retrospective cohort study of pregnancies resulting in livebirths from 2015 through 2021 was conducted in SC. Statewide maternal hospital and emergency department discharge codes were linked to birth certificate data. GDM was defined by ICD-9-CM (i.e., 648.01-648.02, 648.81-648.82) or ICD-10-CM codes (i.e., O24.4, O24.1, O24.9), or indication of GDM on the birth certificate without evidence of diabetes outside pregnancy (ICD-9-CM: 250.xx; ICD-10-CM: E10, E11, O24.0, O24.1, O24.3). Results: Our study included 194,777 non-Hispanic White (White), 108,165 non-Hispanic Black (Black), 25,556 Hispanic, and 16,344 other race-ethnic group pregnancies. The relative risk for GDM associated with a 1-year increase was 1.01 (95% confidence interval [CI]: 1.01-1.02) before the pandemic and 1.12 (1.09-1.14) during the pandemic. While there were race-ethnic differences in the prevalence of GDM, increasing trends were similar across all race-ethnic groups before and during the pandemic. From quarter 1, 2020, to quarter 4, 2021, the prevalence of reported GDM increased from 8.92% to 10.85% in White, from 8.04% to 9.78% in Black, from 11.2% to 13.65% in Hispanic, and from 13.3% to 16.16% in other race-ethnic women. Conclusion: An increasing prevalence of diagnosed GDM was reported during the COVID-19 pandemic. Future studies are needed to understand the mechanisms underlying increasing trends, to develop interventions, and to determine whether the increasing trend continues in subsequent years.

An increasing adoption of electric vehicles (EVs) is expected in the coming decades mainly due to the need to achieve carbon neutrality until 2050. However, predicting electric mobility's future is challenging due to three main factors: technological advancements, regulatory policies, and consumer behaviour. The projections presented in this study are based on several scenarios driven mainly from reports published by public entities and consultants. It considers the evolution of electric road mobility by defined targets in the electrification of the transport sector. Therefore, the gathered data addresses different horizon times regarding EV penetration in the World, Europe, Portugal, Denmark, Greece, and Slovenia. Thus, an extensive literature review and estimating approach for EV forecast was conducted concerning EV markets, charging infrastructure, and electricity demand. Also, the dataset aims to provide a demand projection by 2050 and serving as a critical input to further work on EV mass deployment in the context of the project Electric Vehicles Management for carbon neutrality in Europe (EV4EU) and other works related to this field., (© 2024. The Author(s).)

The recent acceleration of commercial, private and multi-national spaceflight has created an unprecedented level of activity in low Earth orbit, concomitant with the largest-ever number of crewed missions entering space and preparations for exploration-class (lasting longer than one year) missions. Such rapid advancement into space from many new companies, countries and space-related entities has enabled a 'second space age'. This era is also poised to leverage, for the first time, modern tools and methods of molecular biology and precision medicine, thus enabling precision aerospace medicine for the crews. The applications of these biomedical technologies and algorithms are diverse, and encompass multi-omic, single-cell and spatial biology tools to investigate human and microbial responses to spaceflight. Additionally, they extend to the development of new imaging techniques, real-time cognitive assessments, physiological monitoring and personalized risk profiles tailored for astronauts. Furthermore, these technologies enable advancements in pharmacogenomics, as well as the identification of novel spaceflight biomarkers and the development of corresponding countermeasures. In this Perspective, we highlight some of the recent biomedical research from the National Aeronautics and Space Administration, Japan Aerospace Exploration Agency, European Space Agency and other space agencies, and detail the entrance of the commercial spaceflight sector (including SpaceX, Blue Origin, Axiom and Sierra Space) into aerospace medicine and space biology, the first aerospace medicine biobank, and various upcoming missions that will utilize these tools to ensure a permanent human presence beyond low Earth orbit, venturing out to other planets and moons., (© 2024. Springer Nature Limited.)

Spaceflight induces molecular, cellular and physiological shifts in astronauts and poses myriad biomedical challenges to the human body, which are becoming increasingly relevant as more humans venture into space 1-6 . Yet current frameworks for aerospace medicine are nascent and lag far behind advancements in precision medicine on Earth, underscoring the need for rapid development of space medicine databases, tools and protocols. Here we present the Space Omics and Medical Atlas (SOMA), an integrated data and sample repository for clinical, cellular and multi-omic research profiles from a diverse range of missions, including the NASA Twins Study 7 , JAXA CFE study 8,9 , SpaceX Inspiration4 crew 10-12 , Axiom and Polaris. The SOMA resource represents a more than tenfold increase in publicly available human space omics data, with matched samples available from the Cornell Aerospace Medicine Biobank. The Atlas includes extensive molecular and physiological profiles encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics and microbiome datasets, which reveal some consistent features across missions, including cytokine shifts, telomere elongation and gene expression changes, as well as mission-specific molecular responses and links to orthologous, tissue-specific mouse datasets. Leveraging the datasets, tools and resources in SOMA can help to accelerate precision aerospace medicine, bringing needed health monitoring, risk mitigation and countermeasure data for upcoming lunar, Mars and exploration-class missions., (© 2024. The Author(s).)

Human spaceflight has historically been managed by government agencies, such as in the NASA Twins Study 1 , but new commercial spaceflight opportunities have opened spaceflight to a broader population. In 2021, the SpaceX Inspiration4 mission launched the first all-civilian crew to low Earth orbit, which included the youngest American astronaut (aged 29), new in-flight experimental technologies (handheld ultrasound imaging, smartwatch wearables and immune profiling), ocular alignment measurements and new protocols for in-depth, multi-omic molecular and cellular profiling. Here we report the primary findings from the 3-day spaceflight mission, which induced a broad range of physiological and stress responses, neurovestibular changes indexed by ocular misalignment, and altered neurocognitive functioning, some of which match those of long-term spaceflight 2 , but almost all of which did not differ from baseline (pre-flight) after return to Earth. Overall, these preliminary civilian spaceflight data suggest that short-duration missions do not pose a significant health risk, and moreover present a rich opportunity to measure the earliest phases of adaptation to spaceflight in the human body at anatomical, cellular, physiological and cognitive levels. Finally, these methods and results lay the foundation for an open, rapidly expanding biomedical database for astronauts 3 , which can inform countermeasure development for both private and government-sponsored space missions., (© 2024. The Author(s).)

Background: Both progestogens and cerclage are individually effective in preterm birth prevention in high risk pregnancies. However, national and international guidelines cite a lack of data available to comment on the potential benefit of concurrent progestogen therapy after cerclage has been placed. Studies to date have been small with mixed results regarding benefit of concurrent progestogen with cerclage leaving uncertainty regarding best clinical practice., Objective: This study aimed to evaluate whether cerclage with progestogen therapy was superior to cerclage alone in the prevention of spontaneous preterm birth in singleton pregnancies., Methods: This is an international retrospective cohort study of singleton pregnancies, without major anomaly or aneuploidy, and with cerclage placed at 10 different institutions in the United States and Colombia from June 2016 to June 2020. Exclusion criteria were lack of documentation regarding whether progestogen was prescribed, unavailable delivery outcome, and pregnancy termination (spontaneous or induced) before 16 weeks' gestation. The exposure of interest was progestogen use with cerclage placement, which included those who continued to use progestogen or who started progestogen after cerclage. The comparison group consisted of those without progestogen use after cerclage placement, which included those who had no progestogen use during the entire pregnancy or who initiated progestogen and then stopped it after cerclage placement. Progestogen type, cerclage indication, maternal baseline characteristics, and maternal/neonatal outcomes were collected. The primary outcome was spontaneous preterm birth at <37 weeks. The secondary outcomes were spontaneous preterm birth at <34 weeks, gestational age at delivery, and a composite neonatal outcome including ≥1 of the following: perinatal mortality, confirmed sepsis, grade III or IV intraventricular hemorrhage, retinopathy of prematurity, respiratory distress syndrome, and bronchopulmonary dysplasia. There were planned subgroup analyses by cerclage indication, progestogen type (vaginal progesterone vs 17-hydroxyprogesterone caproate), preterm birth history, and site. Continuous variables were compared in adjusted analyses with analysis of covariance, and categorical variables were compared with multivariable logistic regression, adjusting for potential confounders with adjusted odds ratio. A Cox regression survival curve was generated to compare latency to spontaneous delivery, censored after 37 weeks., Results: During the study period, a total of 699 singletons met the inclusion criteria: 561 in the progestogen with cerclage group and 138 with cerclage alone. Baseline characteristics were similar, except the higher likelihood of previous spontaneous preterm birth in the progestogen group (61% vs 41%; P<.001). Within the progestogen group, 52% were on 17-hydroxyprogesterone caproate weekly, 44% on vaginal progesterone daily, and 3% on oral progesterone daily. Progestogen with cerclage was associated with a significantly lower frequency of spontaneous preterm birth <37 weeks (31% vs 39%; adjusted odds ratio, 0.59 [0.39-0.89]; P=.01) and <34 weeks (19% vs 27%; adjusted odds ratio, 0.55 [0.35-0.87]; P=.01), increased latency to spontaneous delivery (hazard ratio for spontaneous preterm birth <37 weeks, 0.66 [0.49-0.90]; P=.009), and lower frequency of perinatal death (7% vs 16%; adjusted odds ratio, 0.37 [0.20-0.67]; P=.001). In planned subgroup analyses, association with reduced odds of preterm birth <37 weeks persisted in those on vaginal progesterone, those without a previous preterm birth, those with ultrasound- or examination-indicated cerclage, those who started progestogen therapy before cerclage, and in sites restricted to the United States., Conclusion: Use of progestogen with cerclage was associated with reduced rates of spontaneous preterm birth and early spontaneous preterm birth compared with cerclage alone. Although this study was not sufficiently powered for subgroup analysis, the strength of evidence for benefit appeared greatest for those with ultrasound- or examination-indicated cerclage, and with vaginal progesterone. El resumen está disponible en Español al final del artículo., (Copyright © 2024 Elsevier Inc. All rights reserved.)

As spaceflight becomes more common with commercial crews, blood-based measures of crew health can guide both astronaut biomedicine and countermeasures. By profiling plasma proteins, metabolites, and extracellular vesicles/particles (EVPs) from the SpaceX Inspiration4 crew, we generated "spaceflight secretome profiles," which showed significant differences in coagulation, oxidative stress, and brain-enriched proteins. While >93% of differentially abundant proteins (DAPs) in vesicles and metabolites recovered within six months, the majority (73%) of plasma DAPs were still perturbed post-flight. Moreover, these proteomic alterations correlated better with peripheral blood mononuclear cells than whole blood, suggesting that immune cells contribute more DAPs than erythrocytes. Finally, to discern possible mechanisms leading to brain-enriched protein detection and blood-brain barrier (BBB) disruption, we examined protein changes in dissected brains of spaceflight mice, which showed increases in PECAM-1, a marker of BBB integrity. These data highlight how even short-duration spaceflight can disrupt human and murine physiology and identify spaceflight biomarkers that can guide countermeasure development., (© 2024. The Author(s).)

The SpaceX Inspiration4 mission provided a unique opportunity to study the impact of spaceflight on the human body. Biospecimen samples were collected from four crew members longitudinally before (Launch: L-92, L-44, L-3 days), during (Flight Day: FD1, FD2, FD3), and after (Return: R + 1, R + 45, R + 82, R + 194 days) spaceflight, spanning a total of 289 days across 2021-2022. The collection process included venous whole blood, capillary dried blood spot cards, saliva, urine, stool, body swabs, capsule swabs, SpaceX Dragon capsule HEPA filter, and skin biopsies. Venous whole blood was further processed to obtain aliquots of serum, plasma, extracellular vesicles and particles, and peripheral blood mononuclear cells. In total, 2,911 sample aliquots were shipped to our central lab at Weill Cornell Medicine for downstream assays and biobanking. This paper provides an overview of the extensive biospecimen collection and highlights their processing procedures and long-term biobanking techniques, facilitating future molecular tests and evaluations.As such, this study details a robust framework for obtaining and preserving high-quality human, microbial, and environmental samples for aerospace medicine in the Space Omics and Medical Atlas (SOMA) initiative, which can aid future human spaceflight and space biology experiments., (© 2024. The Author(s).)

Spaceflight can change metabolic, immunological, and biological homeostasis and cause skin rashes and irritation, yet the molecular basis remains unclear. To investigate the impact of short-duration spaceflight on the skin, we conducted skin biopsies on the Inspiration4 crew members before (L-44) and after (R + 1) flight. Leveraging multi-omics assays including GeoMx™ Digital Spatial Profiler, single-cell RNA/ATAC-seq, and metagenomics/metatranscriptomics, we assessed spatial gene expressions and associated microbial and immune changes across 95 skin regions in four compartments: outer epidermis, inner epidermis, outer dermis, and vasculature. Post-flight samples showed significant up-regulation of genes related to inflammation and KRAS signaling across all skin regions. These spaceflight-associated changes mapped to specific cellular responses, including altered interferon responses, DNA damage, epithelial barrier disruptions, T-cell migration, and hindered regeneration were located primarily in outer tissue compartments. We also linked epithelial disruption to microbial shifts in skin swab and immune cell activity to PBMC single-cell data from the same crew and timepoints. Our findings present the inaugural collection and examination of astronaut skin, offering insights for future space missions and response countermeasures., (© 2024. The Author(s).)

Spaceflight induces an immune response in astronauts. To better characterize this effect, we generated single-cell, multi-ome, cell-free RNA (cfRNA), biochemical, and hematology data for the SpaceX Inspiration4 (I4) mission crew. We found that 18 cytokines/chemokines related to inflammation, aging, and muscle homeostasis changed after spaceflight. In I4 single-cell multi-omics data, we identified a "spaceflight signature" of gene expression characterized by enrichment in oxidative phosphorylation, UV response, immune function, and TCF21 pathways. We confirmed the presence of this signature in independent datasets, including the NASA Twins Study, the I4 skin spatial transcriptomics, and 817 NASA GeneLab mouse transcriptomes. Finally, we observed that (1) T cells showed an up-regulation of FOXP3, (2) MHC class I genes exhibited long-term suppression, and (3) infection-related immune pathways were associated with microbiome shifts. In summary, this study reveals conserved and distinct immune disruptions occurring and details a roadmap for potential countermeasures to preserve astronaut health., (© 2024. The Author(s).)

The advent of civilian spaceflight challenges scientists to precisely describe the effects of spaceflight on human physiology, particularly at the molecular and cellular level. Newer, nanopore-based sequencing technologies can quantitatively map changes in chemical structure and expression at single molecule resolution across entire isoforms. We perform long-read, direct RNA nanopore sequencing, as well as Ultima high-coverage RNA-sequencing, of whole blood sampled longitudinally from four SpaceX Inspiration4 astronauts at seven timepoints, spanning pre-flight, day of return, and post-flight recovery. We report key genetic pathways, including changes in erythrocyte regulation, stress induction, and immune changes affected by spaceflight. We also present the first m 6 A methylation profiles for a human space mission, suggesting a significant spike in m 6 A levels immediately post-flight. These data and results represent the first longitudinal long-read RNA profiles and RNA modification maps for each gene for astronauts, improving our understanding of the human transcriptome's dynamic response to spaceflight., (© 2024. The Author(s).)

Preterm delivery (PTD) complications are a major cause of childhood morbidity and mortality. We aimed to assess trends in PTD and small for gestational age (SGA) and whether trends varied between race-ethnic groups in South Carolina (SC). We utilized 2015-2021 SC vital records linked to hospitalization and emergency department records. PTD was defined as clinically estimated gestation less than (<) 37 weeks (wks.) with subgroup analyses of PTD < 34 wks. and < 28 wks. SGA was defined as infants weighing below the 10th percentile for gestational age. This retrospective study included 338,532 (243,010 before the COVID-19 pandemic and 95,522 during the pandemic) live singleton births of gestational age ≥ 20 wks. born to 260,276 mothers in SC. Generalized estimating equations and a change-point during the first quarter of 2020 helped to assess trends. In unadjusted analyses, pre-pandemic PTD showed an increasing trend that continued during the pandemic (relative risk (RR) = 1.04, 95% CI: 1.02-1.06). PTD < 34 wks. rose during the pandemic (RR = 1.07, 95% CI: 1.02-1.12) with a significant change in the slope. Trends in SGA varied by race and ethnicity, increasing only in Hispanics (RR = 1.02, 95% CI: 1.00-1.04) before the pandemic. Our study reveals an increasing prevalence of PTD and a rise in PTD < 34 wks. during the pandemic, as well as an increasing prevalence of SGA in Hispanics during the study period.

Background: The Inspiration4 (I4) mission, the first all-civilian orbital flight mission, investigated the physiological effects of short-duration spaceflight through a multi-omic approach. Despite advances, there remains much to learn about human adaptation to spaceflight's unique challenges, including microgravity, immune system perturbations, and radiation exposure., Methods: To provide a detailed genetics analysis of the mission, we collected dried blood spots pre-, during, and post-flight for DNA extraction. Telomere length was measured by quantitative PCR, while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations. A robust bioinformatic pipeline was used for data analysis, including variant calling to assess mutational burden., Result: Telomere elongation occurred during spaceflight and shortened after return to Earth. Cell-free DNA analysis revealed increased immune cell signatures post-flight. No significant clonal hematopoiesis of indeterminate potential (CHIP) or whole-genome instability was observed. The long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months post-flight., Conclusion: Our findings provide valuable insights into the physiological consequences of short-duration spaceflight, with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to Earth. CHIP sequencing data will serve as a reference point for studying the early development of CHIP in astronauts, an understudied phenomenon as previous studies have focused on career astronauts. This study will serve as a reference point for future commercial and non-commercial spaceflight, low Earth orbit (LEO) missions, and deep-space exploration., Competing Interests: Christopher E. Mason is a co-Founder of Cosmica Biosciences. Braden Tierney is compensated for consulting with Seed Health and Enzymetrics Biosciences on microbiome study design and holds an ownership stake in the former. Kelly Bolton receives research funding from Servier and Bristol Myers Squibb and serves on the medical advisory board of GoodCell. Kelly Blease, Juan Moreno, Andrew Boddicker, Junhua Zhao, Bryan Lajoie, Andrew Altomare, Semyon Kruglyak, and Shawn Levy are employees of and have a financial interest in Element Biosciences. Irina Matei is a Co-Principal Investigator for research projects funded by Atossa Therapeutics. Caleb M. Schmidt, Julian C. Schmidt, and Michael A. Schmidt hold shares in Sovaris Holdings, LLC. Min Yu is the founder and president of CanTraCer Biosciences Inc. Authors not listed here do not have competing interests. Besides, as an Editorial Board Member of Precision Clinical Medicine, the corresponding author Christopher E. Mason was blinded from reviewing and making decision on this manuscript., (© The Author(s) 2024. Published by Oxford University Press on behalf of the West China School of Medicine & West China Hospital of Sichuan University.)

Gestational hypertension, preeclampsia, eclampsia, and chronic hypertension (CHTN) are associated with adverse infant outcomes and disproportionately affect minoritized race/ethnicity groups. We evaluated the relationships between hypertensive disorders of pregnancy (HDP) and/or CHTN with infant mortality, preterm delivery (PTD), and small for gestational age (SGA) in a statewide cohort with a diverse racial/ethnic population. All live, singleton deliveries in South Carolina (2004-2016) to mothers aged 12-49 were evaluated for adverse outcomes: infant mortality, PTD (20 to less than <37 weeks) and SGA (<10th birthweight-for-gestational-age percentile). Logistic regression models adjusted for sociodemographic, behavioral, and clinical characteristics. In 666,905 deliveries, mothers had superimposed preeclampsia (HDP + CHTN; 1.0%), HDP alone (8.0%), CHTN alone (1.8%), or no hypertension (89.1%). Infant mortality risk was significantly higher in deliveries to women with superimposed preeclampsia, HDP, and CHTN compared with no hypertension (relative risk [RR] = 1.79, 1.39, and 1.48, respectively). After accounting for differing risk by race/ethnicity, deliveries to women with HDP and/or CHTN were more likely to result in PTD (RRs ranged from 3.14 to 5.25) or SGA (RRs ranged from 1.67 to 3.64). As CHTN, HDP and superimposed preeclampsia confer higher risk of adverse outcomes, prevention efforts should involve encouraging and supporting mothers in mitigating modifiable cardiovascular risk factors.

Cholesterol 24-hydroxylase (CYP46A1) is an exclusively neuronal cytochrome P450 enzyme responsible for converting cholesterol into 24S-hydroxycholesterol, which serves as the primary pathway for eliminating cholesterol in the brain. We and others have shown that increased activity of CYP46A1 leads to reduced levels of cholesterol and has a positive effect on cognition. Therefore, we hypothesized that CYP46A1 could be a potential therapeutic target in Niemann-Pick type C (NPC) disease, a rare and fatal neurodegenerative disorder, characterized by cholesterol accumulation in endolysosomal compartments. Herein, we show that CYP46A1 ectopic expression, in cellular models of NPC and in Npc1 tm(I1061T) mice by adeno-associated virus-mediated gene therapy improved NPC disease phenotype. Amelioration in functional, biochemical, molecular and neuropathological hallmarks of NPC disease were characterized. In vivo, CYP46A1 expression partially prevented weight loss and hepatomegaly, corrected the expression levels of genes involved in cholesterol homeostasis, and promoted a redistribution of brain cholesterol accumulated in late endosomes/lysosomes. Moreover, concomitant with the amelioration of cholesterol metabolism dysregulation, CYP46A1 attenuated microgliosis and lysosomal dysfunction in mouse cerebellum, favoring a pro-resolving phenotype. In vivo CYP46A1 ectopic expression improves important features of NPC disease and may represent a valid therapeutic approach to be used concomitantly with other drugs. However, promoting cholesterol redistribution does not appear to be enough to prevent Purkinje neuronal death in the cerebellum. This indicates that cholesterol buildup in neurons might not be the main cause of neurodegeneration in this human lipidosis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nathalie Cartier is a founder of BrainVectis. All other authors declare not to disclose any financial interest from the present research work., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Hypertensive disorders of pregnancy (HDP) and pre-pregnancy hypertension contribute to maternal morbidity and mortality. We examined the association of HDP and pre-pregnancy hypertension with subsequent venous thromboembolic (VTE) events. The retrospective cohort study included 444,859 women with ≥1 live, singleton birth in South Carolina (2004-2016). Hospital and emergency department visit and death certificate data defined incident VTE, HDP, and pre-pregnancy hypertension. Birth certificate data also defined the exposures. Adjusted Cox proportional hazards methods modeled VTE events risk. Of the cohort, 2.6% of women had pre-pregnancy hypertension, 5.8% had HDP, 2.8% had both pre-pregnancy hypertension and HDP (both conditions), and 88.8% had neither condition. The risk of incident VTE events within one year of delivery was higher in women with HDP (hazard ratio [HR] = 1.62, 95% confidence interval [CI]: 1.15-2.29) and both conditions (HR = 2.32, 95% CI: 1.60-3.35) compared to those with neither condition as was the risk within five years for women with HDP (HR = 1.35, 95% CI: 1.13-1.60) and for women with both conditions (HR = 1.82, 95% CI: 1.50-2.20). One- and five-year risks did not differ in women with pre-pregnancy hypertension compared to women with neither condition. Compared to non-Hispanic White (NHW) women with neither condition, the incident VTE event risk was elevated within five years of delivery for NHW (HR = 1.29, 95% CI: 1.02-1.63; HR = 1.59, 95% CI: 1.16-2.17) and non-Hispanic Black (NHB; HR = 1.51, 95% CI: 1.16-2.96; HR = 2.08, 95% CI: 1.62-2.66) women with HDP and with both conditions, respectively, and for NHB women with pre-pregnancy hypertension (HR = 1.50, 95% CI: 1.09-2.07). VTE event risk was highest in women with HDP, and the event rates were higher in NHB women than in NHW women in the same exposure group., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.