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Studies have demonstrated the importance of the gut microbiota during pregnancy, and there is emerging literature on the postpartum maternal gut microbiota. The primary objective of this paper was to synthesize the literature on the postpartum gut microbiome composition and diversity measured in stool samples from healthy mothers of predominantly term infants. The secondary objectives were (1) to identify biological and environmental factors that influence postpartum maternal gut microbiota and (2) to assess health conditions and clinical intermediate measures associated with postpartum gut microbiota changes in all mothers. Electronic searches were conducted November 9, 2020 and updated July 25, 2021 without publication time limits on PubMed, Embase, CINHAL, Scopus, Cochrane Library, BioArchives, and OpenGrey.eu. Primary research on maternal gut microbiota in the postpartum (up to one year after childbirth) were eligible. Postpartum gut microbiota comparisons to pregnancy or non-pregnancy gut microbiota were of interest, therefore, studies examining these in addition to the postpartum were included. Studies were excluded if they were only conducted in animals, infants, pregnancy, or microbiome of other body locations (e.g., vaginal). Data extraction of microbial composition and diversity were completed and synthesized narratively. Studies were assessed for risk of bias. A total of 2512 articles were screened after deduplication and 27 were included in this review. Of the 27 included studies, 22 addressed the primary objective. Firmicutes was the predominant phylum in the early (

Plastic pollution (including microplastics) has been reported in a variety of biotic and abiotic compartments across the circumpolar Arctic. Due to their environmental ubiquity, there is a need to understand not only the fate and transport of physical plastic particles, but also the fate and transport of additive chemicals associated with plastic pollution. Further, there is a fundamental research gap in understanding long-range transport of chemical additives to the Arctic via plastics as well as their behavior under environmentally relevant Arctic conditions. Here, we comment on the state of the science of plastic as carriers of chemical additives to the Arctic, and highlight research priorities going forward. We suggest further research on the transport pathways of chemical additives via plastics from both distant and local sources and laboratory experiments to investigate chemical behavior of plastic additives under Arctic conditions, including leaching, uptake, and bioaccumulation. Ultimately, chemical additives need to be included in strategic monitoring efforts to fully understand the contaminant burden of plastic pollution in Arctic ecosystems.

We studied the floral reproductive biology and nectar chemistry of Jaltomata grandiflora (Solanaceae), an apparently rare perennial of Michoacán, Mexico. During day 1, flowers are pistillate (stigma receptive, anthers not yet presenting pollen); flowers close for the night. Early in the morning of day 2, the corolla re-opens, stamens elongate to five times their earlier length, and anthers dehisce; the dehisced anthers remain about 2 mm from the stigma for much of day 2. In the afternoon of day 2, the corolla again closes, the corolla–androecium abscises, and only then can pollen be seen on the stigma. Protogyny and herkogamy likely promote outcrossing during days 1 and 2, respectively. Autonomous self-pollination takes place at the end of the corolla's life and allows fruit and seed production in the absence of pollinators but results in fruits that are lighter and contain fewer seeds than fruits resulting from manual self-pollinations. Carbohydrates from floral nectar samples were separated and quantified using hydrophilic interaction liquid chromatography coupled with corona charged aerosol detection. In nectar, mean sucrose concentration (0.482 mg/mg nectar), is about 10 and five times higher than glucose (0.043 mg/mg nectar) and fructose (0.095 mg/mg nectar) concentrations.

This article traces the course of the Elbe River from Czechoslovakia through the German Democratic Republic (GDR) into the Federal Republic, where it flows into the North Sea. As the GDR's main water artery, the Elbe's border crossings became a site of security concern for the GDR. Traversing the GDR's border with fellow communist state Czechoslovakia as well as its rival West German state, the river linked the GDR to a larger ecological system as well as transnational sociopolitical dynamics. These connections illuminated the GDR's crucial position in central Europe and beyond. Yet the Elbe also presented challenges for the GDR in terms of controlling information, people, and pollution that streamed into—and out of—the country. The river thus was a precious and contested resource that revealed the communist dictatorship's limited ability to control nature, humans, or interactions between the two. Ultimately, the Elbe's border crossings were a site of transnational and global connection that called into question the GDR's domestic legitimacy and international standing.

Wild meat is associated with an increased risk of zoonotic diseases. In some West African countries wild meat consumption declined as the result of official restrictions following Ebola outbreaks during 2013–2016, and was also affected by the current Covid-19 pandemic. In Sierra Leone, a country affected by these diseases, we documented wild meat use in four markets in the capital, Freetown. From a total of 197 interviews, we analysed the influence of age and gender on the types of wild meat eaten and the reasons for their consumption. We found that more men than women consumed wild meat, and for both genders taste was the main reason for eating wild meat. Age did not affect wild meat consumption amongst women. Evidence for changes in consumer behaviour in response to zoonotic disease risk was mixed. Although some consumers avoided wild meat because of disease risk, none stated this was the primary reason for not eating wild meat, and monkeys (presumed to carry a high zoonotic disease risk) were amongst the species cited as being consumed often. More work is needed to identify the best pathway towards safe and sustainable consumption of wild meat in urban Sierra Leone.

The Australian continent contributes substantially to the year-to-year variability of the global terrestrial carbon dioxide (CO2) sink. However, the scarcity of in-situ observations in remote areas prevents deciphering the processes that force the CO2 flux variability. Here, examining atmospheric CO2 measurements from satellites in the period 2009-2018, we find recurrent end-of-dry-season CO2 pulses over the Australian continent. These pulses largely control the year-to-year variability of Australia's CO2 balance, due to 2-3 times higher seasonal variations compared to previous top-down inversions and bottom-up estimates. The CO2 pulses occur shortly after the onset of rainfall and are driven by enhanced soil respiration preceding photosynthetic uptake in Australia's semi-arid regions. The suggested continental-scale relevance of soil rewetting processes has large implications for our understanding and modelling of global climate-carbon cycle feedbacks., Comment: 28 pages (including supplementary materials), 3 main figures, 7 supplementary figures; v2 changes: Last name of first author changed

Microplastics contaminate environments worldwide and are ingested by numerous species, whose health is affected in multiple ways. A key dimension of health that may be affected is the gut microbiome, but these effects are relatively unexplored. Here, we investigated if microplastics are associated with changes in proventricular and cloacal microbiomes in two seabird species that chronically ingest microplastics: northern fulmars and Cory’s shearwaters. The amount of microplastics in the gut was significantly correlated with gut microbial diversity and composition: microplastics were associated with decreases in commensal microbiota and increases in (zoonotic) pathogens and antibiotic-resistant and plastic-degrading microbes. These results illustrate that environmentally relevant microplastic concentrations and mixtures are associated with changes in gut microbiomes in wild seabirds.

Background: Targeting constitutively active mutant kinases with selective small molecule inhibitors is a key therapeutic pillar of precision oncology. Phosphatidylinositol-4,5bisphosphate-3 kinase, catalytic subunit alpha (PIK3CA) mutations leading to oncogenic activation of PI3Kα represent the largest opportunity for this approach in solid tumors. However, there is no selective inhibitor that targets mutant PI3Kα in the clinic. Toxicity related to non-selective inhibition of WT PI3Kα (hyperglycemia) and other PI3K isoforms limits the tolerability, dosing and efficacy of the orthosteric inhibitor, alpelisib, the only approved solid tumor PI3K inhibitor. RLY-2608, a novel oral allosteric PI3Kα inhibitor, is uniquely designed to overcome these limitations via mutant- and isoform-selective PI3Kα inhibition for greater target coverage, improved tolerability and antitumor activity. We initiated a first-in-human (FIH), study to evaluate the clinical activity of RLY-2608 as a single agent in advanced solid tumor patients (pts) with PI3KCA mutations and in combination with fulvestrant in pts with PIK3CA mutant, HR+, HER2- metastatic breast cancer (MBC). Methods: This is a global, multi-center, dose escalation/expansion study (NCT05216432) of RLY2608 as a single agent in adults who have advanced solid tumors and are refractory, intolerant, or declined standard therapy and RLY-2608 in combination with fulvestrant in previously treated pts with HR+/HER2- MBC. Eligibility criteria include presence of PI3KCA mutation (blood or tumor) per local assessment, ECOG performance status 0-1, measurable or evaluable disease per RECIST 1.1 and no prior PI3K inhibitor (except combination group 2). RLY-2608 is administered on a continuous schedule with 4-week cycles. Adverse events (AEs) per CTCAE v5, PK, biomarkers (mutant ctDNAs and insulin pathway markers) and anti-tumor activity are assessed serially. Dose escalation employs a Bayesian Optimal Interval design to identify MTD and RP2D. Following dose escalation, pts will be treated with RLY-2608 at the MTD/RP2D in a monotherapy dose expansion with 5 groups (N=75, 15 each): 1. Clear cell ovarian carcinoma 2. Head and neck squamous cell carcinoma 3. Cervical cancer 4. Other solid tumors 5. PI3KCA double mutations. In addition, two expansion cohorts will enroll patients with HR+/HER2- MBC treated with RLY-2608 and fulvestrant combination (N = 30, 15 each): 1. No prior PI3K therapy 2. Intolerant to PI3K inhibitors. The primary endpoints are MTD/RP2D and AE profile for single agent and combination; key secondary endpoints are PI3KCA genotype in blood and tumor, PK, biomarkers, and overall response rate. US enrollment began December 2021 and ex-USA startup is under way. Citation Format: Andreas Varkaris, Erika Hamilton, Jason Henry, Alexander I. Spira, Alison M. Schram, Julia E. McGuinness, Gege Tan, Xiaoyan Li, Tamieka Hunter, Ramin Samadani, Alison Timm, Djuro Karanovic, Vivek Subbiah, Cesar A. Perez. First-in-human global multi-center study of RLY-2608, a pan mutant and isoform selective PI3Kα inhibitor, as a single agent in advanced solid tumor patients and in combination with fulvestrant in patients with advanced breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-22-01.

Frontline health care workers who perform potentially aerosol-generating procedures, such as endotracheal intubations, in patients with coronavirus disease 2019 may be at an increased risk of exposure to severe acute respiratory syndrome coronavirus 2. To continue to care for patients with coronavirus disease 2019, minimizing exposure is paramount. Using simulation, we devised a testing method to evaluate devices that may mitigate the spread of aerosol and droplet-sized particles.In this prospective single-center study, participants intubated a manikin 3 times using standard personal protective equipment, once with no barrier device, once with an acrylic box, and once with a modified horizontal drape. The micrometer-sized particle count, generated by a nebulization model, was recorded before and after each intubation. The first-pass intubation rate and time to intubation were recorded. Each operator completed a postsimulation survey about their experience using the barrier devices.Thirty airway proceduralists completed the simulation and survey. There was no significant difference in particle counts (aerosols or droplets) or first-pass intubation, but the horizontal drape was found to significantly increase intubation time (P = 0.01). Most participants preferred the drape over the acrylic box or no barrier device.The acrylic box and plastic drape did not mitigate particle spread. However, our testing method can be used to test barrier designs using negative pressure or other mitigation strategies for particle spread.

ImportanceThyroid cancer is the most common pediatric endocrine malignant neoplasm. Disparities in the workup of thyroid nodules may be significantly associated with thyroid cancer outcomes.ObjectiveTo determine the association of sociodemographic factors with the odds of receiving a biopsy, timeliness of the procedure, and risk of nodule malignancy.Design, Setting, and ParticipantsThis was a retrospective cross-sectional study using insurance claims data from the Optum Clinformatics Data Mart database. The study cohort comprised pediatric patients diagnosed with single thyroid nodules between 2003 and 2020. Data analysis was performed from January 1, 2003, to June 30, 2020.Main Outcomes and MeasuresMultivariable logistic regression models were used to identify demographic variables associated with biopsy and nodule malignant neoplasm. A multivariable linear regression model was used to assess the time between thyroid nodule diagnosis and biopsy.ResultsOf 11 643 children (median [IQR] age at diagnosis or procedure, 15 [12-17] years; 8549 [73.2%] were female and 3126 [26.8%] were male) diagnosed with single thyroid nodules, 2117 (18.2%) received a biopsy. Among the patients who received a biopsy, 304 (14.4%) were found to have a malignant nodule. Greater parental education was associated with a shorter diagnosis-to-biopsy interval (mean difference, −7.24 days; 95% CI, −13.75 to −0.73). Older age at nodule diagnosis (odds ratio [OR], 1.11; 95% CI, 1.09-1.13) and female gender (OR, 1.25; 95% CI, 1.11-1.40) were associated with increased odds of receiving a biopsy, while Black/African American (OR, 0.80; 95% CI, 0.65-0.99) and Hispanic (OR, 0.84; 95% CI, 0.72-0.99) patients had lower odds of receiving a biopsy compared with White patients. Finally, female gender (OR, 1.08; 95% CI, 0.80-1.47) was not associated with lower odds of nodule malignant neoplasm.Conclusions and RelevanceFindings of this cross-sectional study highlight disparities in the diagnostic management of pediatric thyroid nodules. These results call for future work to ensure equitable access to thyroid care for all children.

Background. The role of recently discovered neurospecific peptides in the pathogenesis of acute and progressive neurologic disorders, their neuroprotective features, and possibilities to use them as markers for the course and prognosis of certain diseases have been actively studied in recent decades. However, neurospecific peptides are almost not studied in chronic residual diseases. In our study we measured the levels of neurospecific peptides and some other markers to achieve understanding of general neurophysiological trends in congenital and acquired chronic non-progressive brain pathology with reference to the selection of relevant groups — study objects. Objective. The aim of the study is to study patterns of neurospecific peptides, neurotransmitters and neuroreceptor markers distribution in the serum of children with various pathogenetic variants of chronic neuropathology. Methods. The study included children from 3 to 16 years old with different pathologies. The sample was divided into groups by pathology type: no sensory and neurological disorders, congenital sensory deficit due to mutation of genes expressed and not expressed in the brain, early acquired sensory deficit of multifactorial nature, congenital mild and severe organic disorders of central nervous system (CNS) in residual stage without baseline sensory deficit, acquired functional CNS disorders without baseline organic defect and sensory deficit. The following laboratory data (neurophysiological components) was studied: nerve growth factor, brain-derived neurotropic factor, neurotrophin-3, neurotrophin-4, neuregulin-1-beta-1, beta-secretase, sirtuin-1, synaptophysin, neuronal nitric oxide synthase, and anti-NR2 glutamate receptor antibodies. The parameters of cognitive activity, sense of vision, sense of smell, and acoustic sense were also evaluated. Results. The study included 274 participants. Neuropeptides and markers have shown a variable degree and range in the group spectrum of differences from normal levels. The most variable in the examined sample was NO-synthase, as well as levels of both neurotrophins, beta-secretase, and glutamate receptor marker. All visual deficits were associated with increased NO-synthase levels (p < 0.001). Neuroplasticity peptides (beta-secretase, neurotrophin-3 and 4) have been activated in all pathological conditions. Nerve growth factor and brain-derived neurotropic factor were specifically activated in mild organic CNS lesions (mild cognitive impairments), while neuregulin — in congenital genetically determined visual deficits. There was no specific activation of neuropeptides and NO-synthase level tended to decrease in cases of severe CNS lesions. Conclusion. The study results suggest that all types of early visual impairment are associated with increased physiological neuronal activity, and non-organic neurological functional disorders — mainly with increased physiological synaptic activity. General neuroplasticity processes were activated in all cases of visual deficits but more specific. However, more specific and well-studied processes were activated in mild organic CNS lesions, and neuroplasticity processes did not activate adequately in severe organic CNS lesions probably due to the limited neuronal and synaptic resources.

A new multi-target, multi-effect glycopeptide antibiotic that compromises membrane integrity, delocalizes cell division proteins and inhibits cell division besides inhibiting cell wall biosynthesis in both Gram-positive and Gram-negative bacteria.

An indium-111-labelled peptide binds to myeloma cells, enabling SPECT imaging of myeloma cell accumulation in lungs after intravenous administration. This is the first report of a radiolabelled cell-membrane binding peptide for cell tracking.

Controversy persists regarding the ideal surgical approach for repair of esophageal atresia with tracheoesophageal fistula (EA/TEF). We examined complications and outcomes of infants undergoing thoracoscopy and thoracotomy for repair of Type C EA/TEF using propensity score-based overlap weights to minimize the effects of selection bias.Secondary analysis of two databases from multicenter retrospective and prospective studies examining outcomes of infants with proximal EA and distal TEF who underwent repair at 11 institutions was performed based on surgical approach. Regression analysis using propensity score-based overlap weights was utilized to evaluate outcomes of patients undergoing thoracotomy or thoracoscopy for Type C EA/TEF repair.Of 504 patients included, 448 (89%) underwent thoracotomy and 56 (11%) thoracoscopy. Patients undergoing thoracoscopy were more likely to be full term (37.9 vs. 36.3 weeks estimated gestational age, p 0.001), have a higher weight at operative repair (2.9 vs. 2.6 kg, p 0.001), and less likely to have congenital heart disease (16% vs. 39%, p 0.001). Postoperative stricture rate did not differ by approach, 29 (52%) thoracoscopy and 198 (44%) thoracotomy (p = 0.42). Similarly, there was no significant difference in time from surgery to stricture formation (p 0.26). Regression analysis using propensity score-based overlap weighting found no significant difference in the odds of vocal cord paresis or paralysis (OR 1.087 p = 0.885), odds of anastomotic leak (OR 1.683 p = 0.123), the hazard of time to anastomotic stricture (HR 1.204 p = 0.378), or the number of dilations (IRR 1.182 p = 0.519) between thoracoscopy and thoracotomy.Infants undergoing thoracoscopic repair of Type C EA/TEF are more commonly full term, with higher weight at repair, and without congenital heart disease as compared to infants repaired via thoracotomy. Utilizing propensity score-based overlap weighting to minimize the effects of selection bias, we found no significant difference in complications based on surgical approach. However, our study may be underpowered to detect such outcome differences owing to the small number of infants undergoing thoracoscopic repair.Level III.

In 2009, the U.S. Preventive Services Task Force updated recommended mammography screening frequency from annual to biennial for average-risk women aged 50-74 years. The association between estimated breast cancer risk and mammography screening frequency was evaluated.A single-center retrospective cohort study was conducted among racially/ethnically diverse women, aged 50-74 years, who underwent screening mammography from 2014 to 2018. Data on age, race/ethnicity, first-degree family history of breast cancer, previous benign breast biopsies, and mammographic density were extracted from the electronic health record to calculate Breast Cancer Surveillance Consortium 5-year risk of invasive breast cancer, with a 5-year risk ≥1.67% defined as high risk. Multivariable analyses were conducted to determine the association between breast cancer risk factors and mammography screening frequency (annual versus biennial). Data were analyzed from 2020 to 2022.Among 12,929 women with a mean age of 61±6.9 years, 82.7% underwent annual screening mammography, and 30.7% met high-risk criteria for breast cancer. Hispanic women were more likely to screen annually than non-Hispanic Whites (85.0% vs 79.8%, respectively), despite fewer meeting high-risk criteria. In multivariable analyses adjusting for breast cancer risk factors, high- versus low/average-risk women (OR=1.17; 95% CI=1.04, 1.32) and Hispanic versus non-Hispanic White women (OR=1.46; 95% CI=1.29, 1.65) were more likely to undergo annual mammography.A majority of women continue to undergo annual screening mammography despite only a minority meeting high-risk criteria, and Hispanic women were more likely to screen annually despite lower overall breast cancer risk. Future studies should focus on the implementation of risk-stratified breast cancer screening strategies.

The computational description of correlated electronic structure, and particularly of excited states of many-electron systems, is an anticipated application for quantum devices. An important ramification is to determine the dominant molecular fragmentation pathways in photo-dissociation experiments of light-sensitive compounds, like sulfonium-based photo-acid generators used in photolithography. Here we simulate the static and dynamical electronic structure of the H$_3$S$^+$ molecule, taken as a minimal model of a triply-bonded sulfur cation, on a superconducting quantum processor of the IBM Falcon architecture. To this end, we generalize a qubit reduction technique termed entanglement forging or EF [A. Eddins et al., Phys. Rev. X Quantum, 2022, 3, 010309], currently restricted to the evaluation of ground-state energies, to the treatment of molecular properties. While in a conventional quantum simulation a qubit represents a spin-orbital, within EF a qubit represents a spatial orbital, reducing the number of required qubits by half. We combine the generalized EF with quantum subspace expansion [W. Colless et al, Phys. Rev. X, 2018, 8, 011021], a technique used to project the time-independent Schrodinger equation for ground and excited states in a subspace. To enable experimental demonstration of this algorithmic workflow, we deploy a sequence of error-mitigation techniques. We compute dipole structure factors and partial atomic charges along the ground- and excited-state potential energy curves, revealing the occurrence of homo- and heterolytic fragmentation. This study is an important step towards the computational description of photo-dissociation on near-term quantum devices, as it can be generalized to other photodissociation processes and naturally extended in different ways to achieve more realistic simulations., 13 pages, 7 figures

The aim of this study was to evaluate de immunoexpression of ezrin in gastric cells of domestic cats infected with Helicobacter spp. and with chronic gastritis. Twenty paraffin-embedded gastric samples were selected based on previous positive results for Helicobacter spp. in the Rapid Urease Test, Warthin-Starry staining and cytology. Haematoxylin-eosin stained sections was done to evaluate inflammatory cell infiltrates. Immunohistochemical analysis was done using anti-Helicobacter pylori and anti-Ezrin antibodies. The analysis of inflammatory infiltrates revealed 8/20 (40%) in score 0, 11/20 (55%) in score 1 and 1/20 (5%) in score 2. The labelling observed in the immunohistochemical analysis using anti-Helicobacter spp. antibody showed no samples with score 0; 4/20 (20%) with score 1; 7/20 35% with score 2 and 9/20 (45%) with score 3. Ezrin overexpression on the cytoplasm of parietal cells was revealed in 18 out of 20 samples (90%). Of these, 10 cases (45%) achieved the score 1; 6 cases (30%) the score 2 and 2 cases (10%) the score 3. On the surface and pit cells there was an increase in Ezrin immnoexpression in 12 out of the 20 samples (60%), of which 8 samples (40%) achieved the score 1 and 4 samples (20%) the score 2. No sample were classified in score 3. Statistically significant differences (p = 0.026) were observed between the inflammatory infiltrate in the gastric mucosa and the immunoexpression of Ezrin in the cytoplasm of parietal cells. It was concluded that ezrin had an increased immunoexpression in the gastric mucosa of cats with chronic gastritis.

Background. Speech development impairment is urgent and common problem in pediatric neurology. Transcranial magnetic stimulation (TMS) is one of the promising treatment variants for children with speech disorders. Objective. The aim of the study is to evaluate efficacy and safety of the developed approaches to TMS usage in the management of children with speech disorders. Methods. It was non-randomized controlled study. It included 46 children with speech disorders aged from 3 to 6.5 years. All children were divided into two groups comparable by gender and age: 26 children of the treatment group received TMS course, 20 children of the control group received treatment with hopantenic acid. All patients with speech disorders underwent psychological and pedagogical evaluation of speech and cognitive development, electroencephalography (EEG) before and after treatment. Moreover, comparative analysis of TMS and nootropic therapy efficacy was carried out. Specialized examination of speech and cognitive development was also performed via E.A. Strebeleva method for psychological and pedagogical diagnosis of children development. Furthermore, we carried out side reactions / adverse events registration according to patients and/or their parents complaints confirmed by physical examination, patient’s behavior observation, data from specially developed questionnaire for assessing child’s behavior and well-being (filled up by parents). Finally, we evaluated brain bioelectric activity recorded by EEG. Results. The study results have shown that it is possible to achieve significant positive dynamics in cognitive and speech development in preschool children with speech disorders in both groups (TMS course and medical treatment). But hereby, TMS treatment has demonstrated significantly higher positive dynamics in two out of the three evaluated parameters. There were no cases of adverse events in TMS group leading to early course discontinuation. Conclusion. TMS is non-invasive and safe method for treatment of children with speech disorders. This study has demonstrated the efficacy of the method in the field of personalized management of children with impaired speech and cognitive development.

Mutations in the gene Additional Sex-Combs Like 1 (ASXL1) are recurrent in myeloid malignancies as well as the pre-malignant condition clonal hematopoiesis, where they are universally associated with poor prognosis. However, the role of ASXL1 in myeloid lineage maturation is incompletely described. To define the role of ASXL1 in myelopoiesis, we employed single cell RNA sequencing and a murine model of hematopoietic-specific Asxl1 deletion. In granulocyte progenitors, Asxl1 deletion leads to hyperactivation of MYC and a quantitative decrease in neutrophil production. This loss of granulocyte production was not accompanied by significant changes in the landscape of covalent histone modifications. However, Asxl1 deletion results in a decrease in RNAPII promoter-proximal pausing in granulocyte progenitors, indicative of a global increase in productive transcription. These results suggest that ASXL1 inhibits productive transcription in granulocyte progenitors, identifying a new role for this epigenetic regulator in myeloid development.

As the demand for lifelong learning increases, many working adults have turned to online graduate education in order to update their skillsets and pursue advanced credentials. Simultaneously, the volume of data available to educators and scholars interested in online learning continues to rise. This study seeks to extend learning analytics applications typically oriented toward understanding student interaction with course content, instructors, and peers to the program level in order to gain insight into the ways in which adult learners manage their learning progress over multiple courses and multiple semesters. Using optimal matching analysis, we identify four distinct profiles of course enrollment behaviour among 1,801 successful graduates of an online master’s program that differ with respect to course load, semesters off, and graduation speed. We found that profiles differed significantly as a function of age and knowledge background, but not with respect to gender, ethnicity, or previous academic performance. Findings indicate the utility of expanding learning analytics focused on the micro-level of analysis to the macro-level of analysis and the utility of grounding learning analytics applications geared toward adult learners in a lifespan development perspective. Implications for program design and educational interventions are discussed.

El estallido de una epidemia o una pandemia es siempre un momento de amenaza, emergencia e incertidumbre. Cuando la salud y la vida de las personas se pone en peligro se requieren respuestas urgentes y coordinadas por parte de los agentes estatales a nivel nacional, regional y global que tengan el potencial de contener la pandemia y evitar su propagación. De esta situación de emergencia y de continuos cambios en las normas que imponen nuevas restricciones, obligaciones y responsabilidades a los ciudadanos, se deriva dilema sobre el equilibrio entre la protección del derecho a la salud y otros derechos económicos, sociales y culturales.

We evaluate the incidence, outcomes, and management of peri‑umbilical hernias after sutured or sutureless gastroschisis closure.A retrospective, longitudinal follow-up of neonates with gastroschisis who underwent closure at 11 children's hospitals from 2013 to 2016 was performed. Patient encounters were reviewed through 2019 to identify the presence of a peri‑umbilical hernia, time to spontaneous closure or repair, and associated complications.Of 397 patients, 375 had follow-up data. Sutured closure was performed in 305 (81.3%). A total of 310 (82.7%) infants had uncomplicated gastroschisis. Peri-umbilical hernia incidence after gastroschisis closure was 22.7% overall within a median follow-up of 2.5 years [IQR 1.3,3.9], and higher in those with uncomplicated gastroschisis who underwent primary vs. silo assisted closure (53.0% vs. 17.2%, p0.001). At follow-up, 50.0% of sutureless closures had a persistent hernia, while 16.4% of sutured closures had a postoperative hernia of the fascial defect (50.0% vs. 16.4%, p0.001). Spontaneous closure was observed in 38.8% of patients within a median of 17 months [9,26] and most frequently observed in those who underwent a sutureless primary closure (52.2%). Twenty-seven patients (31.8%) underwent operative repair within a median of 13 months [7,23.5]. Rate and interval of spontaneous closure or repair were similar between the sutured and sutureless closure groups, with no difference between those who underwent primary vs. silo assisted closure.Peri-umbilical hernias after sutured or sutureless gastroschisis closure may be safely observed similar to congenital umbilical hernias as spontaneous closure occurs, with minimal complications and no additional risk with either closure approach.Level II.

To determine whether individuals from a historically underrepresented racial group have a higher cardiometabolic risk than historically represented individuals with type 1 diabetes (T1D) considering socioeconomic deprivation.We used the multivariable logistic and linear regression models to examine socioeconomic deprivation (upper 10th percentile) by race/ethnicity interaction for each cardiometabolic risk factor and cardiometabolic risk burden score, respectively, across 6320 zip code tabulation areas. We also determined the age-adjusted prevalence of low, moderate, and high cardiometabolic risks defined as 0, 1 to 2, and 3 or more risk factors for hypertension, obesity, dyslipidemia, and off-target glycemia for non-Hispanic White (n = 15 746), non-Hispanic Black (n = 1019), Hispanic (n = 1115), and other (n = 887), respectively.The sample comprised 18 767 adolescents and adults with T1D. Those identifying as non-Hispanic Black were more likely to have a high cardiometabolic risk profile, including a 4.5-fold increase in the odds of off-target glycemia, a twofold increase in the odds of systolic hypertension, and 0.29 (unadjusted) and 0.46 (adjusted) increases in a higher cardiometabolic risk burden compared with non-Hispanic White individuals (P.01). Those identifying as Hispanic had a 3.4-fold increase in the odds of off-target glycemia but were less likely to be overweight/obese or have systolic hypertension compared with non-Hispanic White. However, the lower likelihood of overweight/obesity and hypertension did not persist after considering covariates.There is a need to investigate additional determinants of racially/ethnically underrepresented cardiometabolic health, including structural racism and implicit bias in cardiometabolic care for individuals with T1D.

Objectives: To (1) determine the weight-reducing effect of the Koa Family Program (KFP), a community-based, telewellness obesity intervention and (2) examine the impact of the KFP on improving weight-related health indicators. Design: Randomised controlled trial. Setting: Community-based in Sacramento, California, USA. Methods: Seventy women with overweight or obesity (25 ⩽ BMI Results: The overall treatment effect of the KFP was weight loss at both Week 18 (–7.69 pounds [ p Conclusions: The KFP resulted in weight loss significant at individual and population levels.

We assess the land surface model JSBACHv4 (Jena Scheme for Biosphere Atmosphere Coupling in Hamburg version 4), which was recently developed at the Max Planck Institute for Meteorology as part of the effort to build the new Icosahedral Nonhydrostatic (ICON) Earth system model (ESM), ICON-ESM. We assess JSBACHv4 in simulations coupled with ICON-A, the atmosphere model of ICON-ESM, hosting JSBACHv4 as land component to provide the surface boundary conditions. The assessment is based on a comparison of simulated albedo, land surface temperature (LST), leaf area index (LAI), terrestrial water storage (TWS), fraction of absorbed photosynthetic active radiation (FAPAR), net primary production (NPP), and water use efficiency (WUE) with corresponding observational data. JSBACHv4 is the successor of JSBACHv3; therefore, another purpose of this study is to document how this step in model development has changed model biases. This is achieved by also assessing, in parallel, the results of coupled land–atmosphere simulations with the preceding model ECHAM6 hosting JSBACHv3. Large albedo biases appear in both models over ice sheets and in central Asia. The temperate to boreal warm bias observed in simulations with JSBACHv3 largely remained in JSBACHv4, despite the very good agreement with observed LST in the global mean. For the assessment of changes in land water storage, a novel procedure is suggested to compare the gravitational data from the Gravity Recovery And Climate Experiment (GRACE) satellites to simulated TWS. It turns out that the agreement of the changes in the seasonal cycle of TWS is sensitive to the representation of precipitation in the atmosphere model. The LAI is generally too high, which is partly caused by too high soil moisture and also by the parameterization of the phenology itself. The pattern of WUE is, for both models, largely as observed. In India, WUE is too high, probably because JSBACH does not incorporate irrigation in our simulations. WUE differences between the two models can be traced back to differences in precipitation patterns in the two coupled land–atmosphere simulations. For both models, most NPP biases can be associated with biases in water stress, LAI, and FAPAR. In particular, the NPP bias of the Eurasian steppes has switched from positive in JSBACHv3 to negative in JSBACHv4. This difference is mainly caused by weaker precipitation and lower FAPAR of ICON-A–JSBACHv4 in July, which is most probably caused by a feedback loop between too little soil moisture, evaporation, and clouds. While the size and patterns of biases in albedo and LST are largely similar between the two model versions, they are less well correlated for precipitation- and vegetation-related variables like FAPAR. Overall, the biases found in the different assessment variables are either already known from the previous implementation in the Max Planck Institute Earth System Model (MPI-ESM) or have changed because of the coupling with the new atmospheric component ICON-A. Accordingly, this study demonstrates the technically successful completion of the re-implementation of JSBACH into ICON-ESM-V1. As discussed, there is a good perspective on mitigating the biases by an improved representation of the processes.

This paper explores whether the psychological construct of flow plays an important role in shaping motorcycle tourism behavior and examines the relative success of methodologies previously used to model flow, in general. The systematic quantitative literature review (SQLR) method was applied. It is concluded that flow, the mental state, is likely a meaningful intrinsic motivator of motorcycle tourism. Limitations related to previous efforts to model this phenomenon are identified. Suggestions for future research on the role of flow in the motorcycle tourism context are provided with domain-specific methodological strategies outlined.

The prevalence of wildfires continues to grow globally with exposures resulting in increased disease risk. Characterizing these health risks remains difficult due to the wide landscape of exposures that can result from different burn conditions and fuel types. This study tested the hypothesis that biomass smoke exposures from variable fuels and combustion conditions group together based on similar transcriptional response profiles, informing which wildfire-relevant exposures may be considered as a group for health risk evaluations. Mice (female CD-1) were exposed via oropharyngeal aspiration to equal mass biomass smoke condensates produced from flaming or smoldering burns of eucalyptus, peat, pine, pine needles, or red oak species. Lung transcriptomic signatures were used to calculate transcriptomic similarity scores across exposures, which informed exposure groupings. Exposures from flaming peat, flaming eucalyptus, and smoldering eucalyptus induced the greatest responses, with flaming peat grouping with the pro-inflammatory agent lipopolysaccharide. Smoldering red oak and smoldering peat induced the least transcriptomic response. Groupings paralleled pulmonary toxicity markers, though they were better substantiated by higher data dimensionality and resolution provided through -omic-based evaluation. Interestingly, groupings based on smoke chemistry signatures differed from transcriptomic/toxicity-based groupings. Wildfire-relevant exposure groupings yield insights into risk assessment strategies to ultimately protect public health.

A weighted chemical coexpression network analysis (WCCNA) was utilized to identify chemicals co-modulated to variable burning of anthropogenic materials and to link chemicals to biological responses (lung toxicity and mutagenicity). Polyaromatic hydrocarbons (PAHs) were co-modulated with increased concentrations in flaming smoke particulate matter (PM) from the burning of plastic-containing materials and showed significant association with increased neutrophil influx, cytokine levels, and mutagenicity. Inorganic elements were co-modulated with increased concentrations in flaming plywood and cardboard smoke PM and showed significant association with increased protein and albumin levels. This study shows the potential for using a computational network analysis to identify and prioritize hazardous chemical components within complex environmental mixtures and provides guidance on key chemical tracers required for intervention research to protect public health from the exposure.

If left unrepaired, the major oxidative DNA lesion 7,8-dihydro-8-oxoguanine (oxoG) promotes G-to-T transversions by favorably adopting a syn conformation and base pairing with dATP during replication. The human oxoG DNA glycosylase hOGG1 senses and removes oxoG amid millions-fold excess of guanine, thereby counteracting the genotoxic effects of the major oxidative damage. Crystal structures of hOGG1 in complex with oxoG-containing DNA have provided key insights into the lesion recognition and catalysis mechanisms of the enzyme. These lesion-recognition complex (LRC) structures typically involve a catalytically inactive hOGG1 mutant, where one of the catalytic-site amino acid residues is mutated to prevent the cleavage of oxoG. The use of a catalytically incompetent hOGG1 mutant has thus precluded understanding of unscathed interactions between oxoG and hOGG1 catalytic site as well as interactions among catalytic-site amino acid residues. As an orthogonal approach to visualize such interactions, we have co-crystallized a catalytically competent hOGG1 bound to 2′-fluoro-oxodG-containing DNA, a transition state destabilizing inhibitor that binds hOGG1 but is not processed by the enzyme. In this fluorinated lesion-recognition complex (FLRC), the 8-oxo moiety of oxoG is recognized by Gly42 and the Watson–Crick edge of oxoG is contacted by Gln315 and Pro266. The previously observed salt bridge between Lys249 and Cys253 is lacking in the FLRC, suggesting Lys249 is primed by Cys253 and poised for nucleophilic attack on C1′ of oxodG. Overall, hOGG1 FLRC marks the first structure of oxoG presented into an intact catalytic site of hOGG1 and provides complementary insights into the glycosylase mechanisms of the enzyme.