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Abstract Recent research in patients with functionally univentricular hearts (UVH) is focusing on pathologies of the lymphatic vessels. Morphology of the abdominal lymphatic vessels was analyzed by MRI in patients with UVH following total cavopulmonary connection (TCPC) and it was examined, if clinical and laboratory parameters correlate with changes after TCPC. We prospectively examined 33 patients at the age of 19.8 (14.6;30.2) years [median (Q1;Q3)] after TCPC (follow-up 14.3 years (9.7;24.9) with a heavily T2-weighted MRI sequence on a 3.0 T scanner. Examinations in coronal orientation were performed with respiratory gating, slice thickness 0.6 mm, TR 2400 ms, TE 692 ms, FoV 460 mm (covering thoracic and abdominal regions), scan time 14:41 min (13:18;16:30) after a solid meal and a cup of pineapple juice. The findings were classified according to delineation of abdominal lymphatic vessels. Type 1: 6 av and/or oedematous changes or ascites. The results were correlated with parameters obtained at the annual routine check-up. Statistical analysis was performed using U-test and Chi-square test. Fifteen patients (group 1) showed type 3 lymphatic morphologies, two of which had ascites. Eighteen patients (group 2) showed lower grade morphologies (type 1–2). Image quality was rated considering the delineation of the common hepatic duct and did not differ between groups (p = 0.134). “Lymphatic burden” was automatically examined and was indexed to the number of delineated abdominal vessels and showed quantification according to the chosen categories type 1–3. Patients in group 1 were younger at MRI examination (17.4;14.3/18.9 vs. 26.2;18.2/32.3 years, p = 0.03). Superior cavopulmonary connection (SCPC) had been performed earlier in group 1 (9.9;7.9/25.5 vs. 29.2;13.7/66.6 months, p = 0.018). Laboratory examinations in group 1 showed lower levels for Immunoglobulin G (IgG), Lipase, α-Antitrypsin, Cystatin C and TSH. There were no significant differences for total protein, NTproBNP, lymphocytes or platelets. A history of chylothorax was present in 7/15 versus 2/18 p = 0.022. Protein-losing enteropathy (PLE) occurred in 4/15 versus 1/18 (p = 0.092). T2 weighted MRI is feasible for noninvasive delineation of abdominal lymphatic vessel in patients following TCPC. In the long-term follow-up, patients with more pronounced changes of the abdominal lymphatic vessels were younger at SCPC and were more likely to show a history of chylothorax and lower IgG values.

Abstract Isomalto/malto-polysaccharides (IMMPs) are a novel type of soluble dietary fibres with a prebiotic potential promoting growth of beneficial microbes in the gut. However, the mode of action of IMMPs remains unknown. Previous studies on IMMPs showed an increase in total bacteria, especially lactobacilli, and higher production of short chain fatty acids (SCFA) when IMMPs were fed to rats or used during in vitro fermentation. Here we used metatranscriptomics to investigate how IMMPs with different amounts of α − (1 → 6) glycosidic linkages affected microbial function during incubation with human fecal inoculum. We showed that active microbial community dynamics during fermentation varied depending on the type of IMMP used and that the observed changes were reflected in the community gene expression profiles. Based on metatranscriptome analysis, members of Bacteroides, Lactobacillus and Bifidobacterium were the predominant degraders of IMMPs, and the increased gene expression in these bacteria correlated with high amounts of α − (1 → 6) glycosidic linkages. We also noted an increase in relative abundance of these bacteria and an activation of pathways involved in SCFA synthesis. Our findings could provide a baseline for more targeted approaches in designing prebiotics for specific bacteria and to achieve more controlled modulation of microbial activity towards desired health outcomes.

Abstract Generative machine learning is poised to revolutionise a range of domains where rational design has long been the de facto approach: where design is practically a time consuming and frustrating process guided by heuristics and intuition. In this article we focus on the domain of flow chemistry, which is an ideal candidate for generative design approaches. We demonstrate a generative machine learning framework that optimises diverse, bespoke reactor elements for flow chemistry applications, combining evolutionary algorithms and a scalable fluid dynamics solver for in silico performance assessment. Experimental verification confirms the discovery of never-before-seen bespoke mixers whose performance exceeds the state of the art by 45%. These findings highlight the power of autonomous generative design to improve the operational performance of complex functional structures, with potential wide-ranging industrial applications.

Abstract A fast and reliable range monitoring method is required to take full advantage of the high linear energy transfer provided by therapeutic ion beams like carbon and oxygen while minimizing damage to healthy tissue due to range uncertainties. Quasi-real-time range monitoring using in-beam positron emission tomography (PET) with therapeutic beams of positron-emitters of carbon and oxygen is a promising approach. The number of implanted ions and the time required for an unambiguous range verification are decisive factors for choosing a candidate isotope. An experimental study was performed at the FRS fragment-separator of GSI Helmholtzzentrum für Schwerionenforschung GmbH, Germany, to investigate the evolution of positron annihilation activity profiles during the implantation of $$^{14}$$ 14 O and $$^{15}$$ 15 O ion beams in a PMMA phantom. The positron activity profile was imaged by a dual-panel version of a Siemens Biograph mCT PET scanner. Results from a similar experiment using ion beams of carbon positron-emitters $$^{11}$$ 11 C and $$^{10}$$ 10 C performed at the same experimental setup were used for comparison. Owing to their shorter half-lives, the number of implanted ions required for a precise positron annihilation activity peak determination is lower for $$^{10}$$ 10 C compared to $$^{11}$$ 11 C and likewise for $$^{14}$$ 14 O compared to $$^{15}$$ 15 O, but their lower production cross-sections make it difficult to produce them at therapeutically relevant intensities. With a similar production cross-section and a 10 times shorter half-life than $$^{11}$$ 11 C, $$^{15}$$ 15 O provides a faster conclusive positron annihilation activity peak position determination for a lower number of implanted ions compared to $$^{11}$$ 11 C. A figure of merit formulation was developed for the quantitative comparison of therapy-relevant positron-emitting beams in the context of quasi-real-time beam monitoring. In conclusion, this study demonstrates that among the positron emitters of carbon and oxygen, $$^{15}$$ 15 O is the most feasible candidate for quasi-real-time range monitoring by in-beam PET that can be produced at therapeutically relevant intensities. Additionally, this study demonstrated that the in-flight production and separation method can produce beams of therapeutic quality, in terms of purity, energy, and energy spread.

Abstract The contextual non-invasive monitoring and tracking of multiple human targets for health and surveillance purposes is an increasingly investigated application. Radars are good candidates, since they are able to remotely monitor people without raising privacy concerns. However, radar systems are typically based on complex architectures involving multiple channels and antennas, such as multiple-input and multiple-output (MIMO) or electronic beam scanning, resulting also in a high power consumption. In contrast with existing technologies, this paper proposes a single-input and single-output (SISO) frequency-modulated continuous wave (FMCW) radar in combination with frequency scanning antennas for tracking multiple subjects in indoor environments. A data processing method is also presented for angular separation and clutter removal. The system was successfully tested in five realistic indoor scenarios involving paired subjects, which were either static or moving along predefined paths varying their range and angular position. In all scenarios, the radar was able to track the targets, reporting a maximum mean absolute error (MAE) of 20 cm and 5.64 $$^\circ$$ ∘ in range and angle, respectively. Practical applications arise for ambient assisted living, telemedicine, smart building applications and surveillance.

Abstract Extended cut-off filtration by medium cut-off membranes (MCO) has been shown to be safe in maintenance hemodialysis (HD). The notion of using them for the control of chronic low-grade inflammation and positively influencing cellular immune aberrations seems tempting. We conducted an open label, multicenter, randomized, 90 day 2-phase cross over clinical trial (MCO- vs. high flux-HD). 46 patients underwent randomization of which 34 completed the study. Dialysate- or pre- and post-dialysis serum inflammatory mediators were assayed for each study visit. Ex vivo T cell activation was assessed from cryopreserved leucocytes by flow cytometry. Linear mixed models were used to compare treatment modalities, with difference in pre-dialysis serum MCP-1 levels after 3 months as the predefined primary endpoint. Filtration/dialysate concentrations of most mediators, including MCP-1 (mean ± SD: 10.5 ± 5.9 vs. 5.1 ± 3.8 pg/ml, P

Abstract Actinic keratosis (AK) are precancerous lesions of the skin which may progress to invasive squamous cell carcinoma. However, single lesions may also persist or even regress and heal spontaneously. Until now, evidence on the natural course of AK including spontaneous regression is limited. We aimed to synthesize regression rates of AK. We performed a systematic literature research in Medline, Embase, and CENTRAL for eligible trials until 3rd March 2020. Spontaneous regression rates were pooled using a random-effects model to calculate pooled proportions of participant-specific and lesion-specific complete clearance rates reported for the placebo arms of randomized controlled trials. Subgroup analyses were performed to dissect differences according to the type of placebo, immunocompetence of the participants, and localization of the lesions. Data from 38 records was included. The pooled participant-specific clearance rate was 8% (95% CI 6–10%, I2 = 71%) while the lesion-specific clearance rate was 23% (95% CI 16–31%, I2 = 97%). The highest participant- and lesion-specific clearance rates were achieved 12 weeks after the end of treatment (12% and 33%, respectively). Subgroup analysis revealed participant- as well as lesion-specific clearance rates of 0% for organ transplant recipients (OTR). We conclude that only a few participants achieve complete regression of their AK without any active treatment. Besides, the results underline that lesion clearance without active treatment is unlikely in OTR. Thus, early and consequent treatment of AK is recommended. Special attention should be paid when treating AK of OTR.

Abstract Synergistic effects of fibrinolytic and additional antithrombotic treatment during cardiopulmonary resuscitation in out-of-hospital cardiac arrest of assumed cardiac origin were evaluated retrospectively. Data were drawn from electronic files of the physician-staffed Emergency Medical Services Tyrol. During a 22-month observation period 53 adult patients were treated with tenecteplase (mean 7641 IU), 19 (32.1%) of whom received additional antithrombotic treatment with heparin (4000–5000 IU) and acetylsalicylic acid (250–500 mg). Lasting return of spontaneous circulation occurred in four of 34 patients who received fibrinolytic treatment only and in seven of 19 patients with additional antithrombotic treatment (p = 0.037). Four of five patients who were discharged from hospital had received additional antithrombotic treatment during CPR and were in appropriate neurological status (CPC 1). Considering the small sample size in this retrospective study, the argument may be still be made that fibrinolytic and adjunctive antithrombotic treatment during cardiopulmonary resuscitation in out-of-hospital cardiac arrest of assumed cardiac origin may increase the chances for survival.

Abstract Register-based studies indicate a possible association of monoclonal gammopathy of undetermined significance (MGUS) and prostate cancer (PCa). Aim of the present study was to investigate the relationship between MGUS and PCa considering potentially shared risk factors. Data from the prospective population-based Heinz Nixdorf Recall cohort study of 2.385 men (age 45–85) were analyzed. MGUS was determined at three points in time; cases of cancer were assessed annually. Potentially shared risk factors were assessed at baseline. Hazard ratios (HR), adjusted for age and educational attainment, and corresponding 95%-confidence intervals (95%-CI) were calculated. 157 cases of MGUS and 143 incident cases of PCa were detected. Of 19 participants diagnosed with both, MGUS and incident PCa, only in one case MGUS did not clearly occur before PCa. MGUS was associated with PCa presenting a HR of 2.00 (95%-CI: 1.23–3.25). Stratified by isotype, IgM-MGUS showed the strongest association with PCa. There was no relevant change of the effect estimate when adjusting for potentially shared risk factors. We were able to give supporting evidence for an association between MGUS and PCa and pointed out its temporality. There was no indication that the observed association is due to shared risk factors. The present study indicated that different isotypes of MGUS differ in the strength of the effect on PCa-risk. Based on these findings, future studies investigating the pathophysiological background of the association will be needed.

Recent research in patients with functionally univentricular hearts (UVH) is focusing on pathologies of the lymphatic vessels. Morphology of the abdominal lymphatic vessels was analyzed by MRI in patients with UVH following total cavopulmonary connection (TCPC) and it was examined, if clinical and laboratory parameters correlate with changes after TCPC. We prospectively examined 33 patients at the age of 19.8 (14.6;30.2) years [median (Q1;Q3)] after TCPC (follow-up 14.3 years (9.7;24.9) with a heavily T2-weighted MRI sequence on a 3.0 T scanner. Examinations in coronal orientation were performed with respiratory gating, slice thickness 0.6 mm, TR 2400 ms, TE 692 ms, FoV 460 mm (covering thoracic and abdominal regions), scan time 14:41 min (13:18;16:30) after a solid meal and a cup of pineapple juice. The findings were classified according to delineation of abdominal lymphatic vessels. Type 1: <3 abdominal vessels (av) definable; type 2: 4-6 av definable; type 3: >6 av and/or oedematous changes or ascites. The results were correlated with parameters obtained at the annual routine check-up. Statistical analysis was performed using U-test and Chi-square test. Fifteen patients (group 1) showed type 3 lymphatic morphologies, two of which had ascites. Eighteen patients (group 2) showed lower grade morphologies (type 1-2). Image quality was rated considering the delineation of the common hepatic duct and did not differ between groups (p = 0.134). "Lymphatic burden" was automatically examined and was indexed to the number of delineated abdominal vessels and showed quantification according to the chosen categories type 1-3. Patients in group 1 were younger at MRI examination (17.4;14.3/18.9 vs. 26.2;18.2/32.3 years, p = 0.03). Superior cavopulmonary connection (SCPC) had been performed earlier in group 1 (9.9;7.9/25.5 vs. 29.2;13.7/66.6 months, p = 0.018). Laboratory examinations in group 1 showed lower levels for Immunoglobulin G (IgG), Lipase, α-Antitrypsin, Cystatin C and TSH. There were no significant differences for total protein, NTproBNP, lymphocytes or platelets. A history of chylothorax was present in 7/15 versus 2/18 p = 0.022. Protein-losing enteropathy (PLE) occurred in 4/15 versus 1/18 (p = 0.092). T2 weighted MRI is feasible for noninvasive delineation of abdominal lymphatic vessel in patients following TCPC. In the long-term follow-up, patients with more pronounced changes of the abdominal lymphatic vessels were younger at SCPC and were more likely to show a history of chylothorax and lower IgG values., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Consent for publication: Written informed consent was obtained from the patient for publication and any accompanying pictures. A copy of the written consent is available for review by the Editor of this journal., (© 2024. The Author(s).)

Abstract Given that a substantial proportion of the subgroup of COVID-19 patients that face a severe disease course are younger than 60 years, it is critical to understand the disease-specific characteristics of young COVID-19 patients. Risk factors for a severe disease course for young COVID-19 patients and possible non-linear influences remain unknown. Data were analyzed from COVID-19 patients with clinical outcome in a single hospital in Wuhan, China, collected retrospectively from Jan 24th to Mar 27th. Clinical, demographic, treatment and laboratory data were collected from patients' medical records. Uni- and multivariable analysis using logistic regression and random forest, with the latter allowing the study of non-linear influences, were performed to investigate the clinical characteristics of a severe disease course. A total of 762 young patients (median age 47 years, interquartile range [IQR] 38–55, range 18–60; 55.9% female) were included, as well as 714 elderly patients as a comparison group. Among the young patients, 362 (47.5%) had a severe/critical disease course and the mean age was statistically significantly higher in the severe subgroup than in the mild subgroup (59.3 vs. 56.0, Student's t-test: p

A fast and reliable range monitoring method is required to take full advantage of the high linear energy transfer provided by therapeutic ion beams like carbon and oxygen while minimizing damage to healthy tissue due to range uncertainties. Quasi-real-time range monitoring using in-beam positron emission tomography (PET) with therapeutic beams of positron-emitters of carbon and oxygen is a promising approach. The number of implanted ions and the time required for an unambiguous range verification are decisive factors for choosing a candidate isotope. An experimental study was performed at the FRS fragment-separator of GSI Helmholtzzentrum für Schwerionenforschung GmbH, Germany, to investigate the evolution of positron annihilation activity profiles during the implantation of 14 O and 15 O ion beams in a PMMA phantom. The positron activity profile was imaged by a dual-panel version of a Siemens Biograph mCT PET scanner. Results from a similar experiment using ion beams of carbon positron-emitters 11 C and 10 C performed at the same experimental setup were used for comparison. Owing to their shorter half-lives, the number of implanted ions required for a precise positron annihilation activity peak determination is lower for 10 C compared to 11 C and likewise for 14 O compared to 15 O, but their lower production cross-sections make it difficult to produce them at therapeutically relevant intensities. With a similar production cross-section and a 10 times shorter half-life than 11 C, 15 O provides a faster conclusive positron annihilation activity peak position determination for a lower number of implanted ions compared to 11 C. A figure of merit formulation was developed for the quantitative comparison of therapy-relevant positron-emitting beams in the context of quasi-real-time beam monitoring. In conclusion, this study demonstrates that among the positron emitters of carbon and oxygen, 15 O is the most feasible candidate for quasi-real-time range monitoring by in-beam PET that can be produced at therapeutically relevant intensities. Additionally, this study demonstrated that the in-flight production and separation method can produce beams of therapeutic quality, in terms of purity, energy, and energy spread. [ABSTRACT FROM AUTHOR]

Clustered regularly interspaced short palindromic repeats (CRISPR) in conjunction with CRISPRassociated proteins (Cas) can be employed to introduce double stand breaks into mammalian genomes at user-defined loci. The endonuclease activity of the Cas complex can be targeted to a specific genomic region using a single guide RNA (sgRNA). We developed a ligation-independent cloning (LIC) assembly method for efficient and bias-free generation of large sgRNA libraries. Using this system, we performed an iterative shotgun cloning approach to generate an arrayed sgRNA library that targets one critical exon of almost every protein-coding human gene. An orthogonal mixing and deconvolution approach was used to obtain 19,506 unique sequence-validated sgRNAs (91.4% coverage). As tested in HEK 293T cells, constructs of this library have a median genome editing activity of 54.6% and employing sgRNAs of this library to generate knockout cells was successful for 19 out of 19 genes tested. [ABSTRACT FROM AUTHOR]

The vertebral foramen, lamina, and vertebral body are three critical components of the spine structure, essential for maintaining spinal connectivity and stability. Accurately segmenting lumbar structures such as the vertebral body, vertebral foramen, and lamina in MRI cross-sections helps doctors better understand and diagnose the pathological causes of spine-related diseases. This study presents a multi-structure semantic segmentation method for vertebral transverse section MRI slices using WGAN with a residual U-Net and clustered Transformer. The generator network was replaced with a combination of a residual U-Net and a clustered Transformer-based segmentation network. The enhanced U-Net encoder, utilizing dilated convolutions and residual structures, improved multi-scale feature extraction capabilities. Meanwhile, the clustered Transformer structure, with reduced progressive linear complexity, ensured the extraction of global positional information. The results of multiple experiments show that the Dice coefficient for vertebral body segmentation increased by 3.1%, the Hausdorff distance decreased by 0.6 mm, mIOU improved by 4.1–96.2%, and PPV increased by 2.0–98.8% compared to mainstream segmentation models. These improvements are statistically significant (p < 0.05).Ablation experiments further validated the effectiveness of the proposed enhanced modules in improving segmentation accuracy for the three target structures. [ABSTRACT FROM AUTHOR]

Assessing the risk of postoperative cardiovascular events before performing non-cardiac surgery is clinically important. The current risk score systems for preoperative evaluation may not adequately represent a small subset of high-risk populations. Accordingly, this study aimed at applying iterative random forest to analyze combinations of factors that could potentially be clinically valuable in identifying these high-risk populations. To this end, we used the Japan Medical Data Center database, which includes claims data from Japan between January 2005 and April 2021, and employed iterative random forests to extract factor combinations that influence outcomes. The analysis demonstrated that a combination of a prior history of stroke and extremely low LDL-C levels was associated with a high non-cardiac postoperative risk. The incidence of major adverse cardiovascular events in the population characterized by the incidence of previous stroke and extremely low LDL-C levels was 15.43 events per 100 person-30 days [95% confidence interval, 6.66–30.41] in the test data. At this stage, the results only show correlation rather than causation; however, these findings may offer valuable insights for preoperative risk assessment in non-cardiac surgery. [ABSTRACT FROM AUTHOR]

While numerous studies have underscored the implication of immune cells and metabolites in temporomandibular disorders (TMD), conclusive evidence for causality remains elusive. Consequently, our aim is to explore the causal connections between immunophenotypes and plasma metabolites in relation to TMD employing a bidirectional Mendelian randomization (MR) approach. Summary statistics data on 731 immunophenotypes (n = 3757) and 1091 plasma metabolites (n = 8299) were obtained from comprehensive genome-wide association studies (GWAS), while TMD data (5668 cases and 205,355 controls) were acquired from the FinnGen Consortium. Bidirectional MR analyses and a two-step MR approach assessed causal relationships and potential intermediaries. Various corrections and sensitivity analyses were utilized to assess the robustness of the findings. Two immunophenotypes and seven metabolites were significantly associated with TMD risk. Specifically, Alpha-hydroxyisovalerate mediated the link between CD33 on CD33dim HLA DR + CD11b + and TMD (β = 0.034, P = 5.95 × 10–5), while CD8 on NKT cells mediated the causal relationship between 5-acetylamino-6-formylamino-3-methyluracil levels and TMD (β = 0.069, P = 5.11 × 10–5). Our findings revealed the causal relationships between immunophenotypes and plasma metabolites on TMD from a genetic perspective, potentially aiding in TMD prevention. [ABSTRACT FROM AUTHOR]

The turtle shell is a remarkable structure that has intrigued not only evolutionary biologists but also engineering and material scientists because of its multi-scale complexity and various functions. Although protection is its most apparent role, the carapace and plastron are also related to many physiological functions and their shape influences hydrodynamics and self-righting ability. As such, analysing the functional morphology of the shell could help understanding the ecology of Triassic stem-turtles, which will contribute to the century-long debate on the evolutionary origins of turtles. Here, we used 3D imaging techniques to digitize the shells of two of the earliest stem-turtle taxa, Proganochelys and Proterochersis, and submitted their models to biomechanical and shape analyses. We analysed the strength performance under five predation scenarios and tested the function of two morphological traits found in stem-turtles, the epiplastral processes and an attached pelvic girdle. The latter, also present in the crown-lineage of side-necked turtles, has been suggested to increase load-bearing capacity of the shell or to improve swimming in pleurodires. Our results do not confirm the shell-strengthening hypothesis and, together with the results of our shape analyses, suggest that at least one of the first stem-turtles (Proterochersis) was an aquatic animal. [ABSTRACT FROM AUTHOR]

Erectile dysfunction (ED) is closely related to oxidative stress, and antioxidant is a treatment and prevention method for erectile dysfunction. The Compound Dietary Antioxidant Index (CDAI) represents the overall dietary antioxidant intake of the human body. However, the link between CDAI and ED is unclear. The objective of this research was to examine the linkage between CDAI and ED. The research utilized information collected from the National Health and Nutrition Examination Survey (NHANES) spanning the years 2001 to 2004. To assess the association between CDAI and ED, the analysis employed weighted multivariate logistic regression along with weighted restricted cubic splines (RCS). Additionally, subgroup interaction analysis was conducted to confirm the findings. In this investigation, 3184 adults from the U.S., all above the age of 20, were part of the study cohort, with 863 of them identified as having ED. Adjustments for potential confounding variables revealed that the odds ratio (95% confidence interval) of CDAI associating with ED was 0.95 (0.92–0.99; P = 0.01). Besides, compared to the lowest tertile, the highest tertile of CDAI was associated with a lower risk of ED (0.63 [0.46–0.88]; P = 0.01). The application of weighted restricted cubic splines (RCS) analysis delineated a nonlinear inverse relationship between CDAI levels and the probability of ED. Subgroup analysis further demonstrated that the association between CDAI and ED remained consistent across subgroups. This cross-sectional analysis revealed a significant correlation, indicating that elevated levels of CDAI are closely linked with a lower likelihood of ED. [ABSTRACT FROM AUTHOR]

Initial research indicates a possible connection between exposure to phthalates and the development of anemia. To fill the gap in epidemiological data, our study utilized data from across the United States, representative on a national scale, to evaluate the association between the concentration of phthalate metabolites in urine and both anemia and iron levels. We gathered data on 11,406 individuals from the National Health and Nutrition Examination Survey (NHANES) database, spanning 2003–2018. We conducted logistic and linear regression analyses, adjusted for potential confounding factors, to evaluate the correlations between different phthalate metabolites and anemia, as well as serum iron levels, including gender-stratified analysis. Most urinary phthalate metabolites were positively correlated with an increased risk of anemia, and the majority were negatively correlated with serum iron levels. The study revealed that for every unit increase in ln-transformed metabolite concentrations, the odds ratios (ORs) for anemia increased to varying degrees, depending on the phthalate: Monobutyl phthalate (MBP) at 1.08 (95% CI 1.01–1.17, P = 0.0314), mono(3-carboxypropyl) phthalate (MCPP) at 1.17 (95% CI 1.10–1.24, P < 0.0001), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) at 1.08 (95% CI 1.02–1.15, P = 0.0153), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) at 1.14 (95% CI 1.07–1.21, P < 0.0001), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) at 1.11 (95% CI 1.03–1.18, P = 0.0030), monocarboxynonyl phthalate (MCNP) at 1.11 (95% CI 1.03–1.19, p = 0.0050), and monocarboxyoctyl phthalate (MCOP) at 1.13 (95% CI 1.07–1.19, P < 0.0001). Increased levels of MBP, MEHP, MBzP, MCPP, MEHHP, MEOHP, MIBP, MECPP, MCNP, and MCOP were linked with changes in serum iron levels, ranging from − 0.99 µg/dL (95% CI − 1.69 to − 0.29) to − 3.72 µg/dL (95% CI − 4.32 to − 3.11). Mixed-exposure analysis shows consistency with single-exposure model. Further mediation analysis showed that the association between single urinary phthalates and the risk of anemia was mediated by serum iron with a mediation ratio of 24.34–95.48% (P < 0.05). The presence of phthalate metabolites in urine shows a positive correlation with the prevalence of anemia, which was possibly and partly mediated by iron metabolism. Nonetheless, to confirm a definitive causal link and comprehend the underlying mechanisms of how phthalate exposure influences anemia, additional longitudinal and experimental research is required. [ABSTRACT FROM AUTHOR]

Permanent artificial lighting systems in tourist underground environments promote the proliferation of photoautotrophic biofilms, commonly referred to as lampenflora, on damp rock and sediment surfaces. These green-colored biofilms play a key role in the alteration of native community biodiversity and the irreversible deterioration of colonized substrates. Comprehensive chemical or physical treatments to sustainably remove and control lampenflora are still lacking. This study employs an integrated approach to explore the biodiversity, eco-physiology and molecular composition of lampenflora from the Pertosa-Auletta Cave, in Italy. Reflectance analysis showed that photoautotrophic biofilms are able to absorb the totality of the visible spectrum, reflecting only the near-infrared light. This phenomenon results from the production of secondary pigments and the adaptability of these organisms to different metabolic regimes. The biofilm structure mainly comprises filamentous organisms intertwined with the underlying mineral layer, which promote structural alterations of the rock layer due to the biochemical attack of both prokaryotes (mostly represented by Brasilonema angustatum) and eukaryotes (Ephemerum spinulosum and Pseudostichococcus monallantoides), composing the community. Regardless of the corrosion processes, secondary CaCO3 minerals are also found in the biological matrix, which are probably biologically mediated. These findings provide valuable information for the sustainable control of lampenflora. [ABSTRACT FROM AUTHOR]

The Permian Fengcheng Formation (P1f.) in the Hashan area, situated on the southwestern margin of the Junggar Basin, has witnessed a remarkable breakthrough in shale oil exploration in recent years with nearly 789 million tons of shale oil resources. As a unique set of mixed sedimentary shales, the Fengcheng Formation in the Hashan area is characterized by mixed sedimentation of terrigenous siliciclastic sediments, authigenic minerals, and tuffaceous materials. However, the understanding of pore characteristics in the mixed sedimentary reservoir still remains limited, prohibiting accurate estimation of the oil content and insights into oil mobility. Scanning electron microscopy (SEM), X-ray diffraction (XRD), mercury injection capillary pressure (MICP), nuclear magnetic resonance (NMR), X-Ray Computer Tomography (X-CT), and geochemical analysis were performed to investigate the pore size distribution and main controlling factors of the mixed sedimentary reservoir. Results showed that the main pore types in the mixed sedimentary reservoir are intergranular pores and dissolution pores. The pores of the P1f. mixed shales in the Hashan area were classified into II-micropores (< 25 nm), I-micropores (25–100 nm), mesopores (100–1000 nm) and macropores (> 1000 nm). In general, the mixed sedimentary rocks of P1f. formation feature few macropores but a large number of micropores and mesopores. The CS exhibits the most favourable physical properties among all lithofacies. It is concluded that the abundance and maturity of organic matter, mineral composition, sedimentary structure, and diagenesis of reservoir together impact the pore structure in the mixed sedimentary reservoirs. The maturity of organic matter and the content of tuffaceous minerals are the most significant in influencing the pore structure of P1f. shales. Overall, the pore structure of complex lithologic reservoir formed by mixed deposition and its influence on physical properties are studied, and the characteristics of the microscopic pore-throat system of the dominant lithofacies in the Hashan area are clarified, which is of great significance as a guide for the exploration and development of mixed sedimentary reservoirs in continental shale oil in China. [ABSTRACT FROM AUTHOR]

Stegosaur tracks were unknown until the identification of Deltapodus more than 20 years ago. Currently, the Iberian Peninsula, especially Teruel Province, is one of the areas globally with the most occurrences of these tracks. However, their identification, based on the global record, is problematic due to their similarities with sauropod tracks. A review of the largest number of analyzed Deltapodus tracks globally, including the holotype of D. ibericus and a description of new occurrences, has been carried out. Our research shows substantial morphological variations, but all the studied tracks can be considered D. ibericus based on the manus morphology and the morphometric data. These variations are related to substrate differences and/or different dynamic foot postures (possibly ontogenetically related) during locomotion, as evidenced by changes within the same trackway. We provide detailed comparisons via 3D modeling with sauropod tracks, and our data show that they generally have proportionally longer manus and wider pes because of the differences in the metapodial bones. The scarcity of stegosaur trackways in the fossil record has prevented the identification of gregarious behavior in this group of herbivorous dinosaurs. Two of the studied tracksites show evidence of this behavior, being the only examples among stegosaurs described thus far in the fossil record. [ABSTRACT FROM AUTHOR]

Natural polymers have found increased use in a wider range of applications due to their less harmful effects. Notably, bacterial cellulose has gained significant consideration due to its exceptional physical and chemical properties and its substantial biocompatibility, which makes it an attractive candidate for several biomedical applications. This study attempts to thoroughly unravel the microstructure of bacterial cellulose precursors, known as bioflocculants, which to date have been poorly characterised, by employing both electron and optical microscopy techniques. Here, starting from bioflocculants from Symbiotic Culture of Bacteria and Yeast (SCOBY), we proved that their microstructural features, such as porosity percentage, cellulose assembly degree, fibres' density and fraction, change in a spatio-temporal manner during their rising toward the liquid–air interface. Furthermore, our research identified a correlation between electron and optical microscopy parameters, enabling the assessment of bioflocculants' microstructure without necessitating offline sample preparation procedures. The ultimate goal was to determine their potential suitability as a novel cellulose-based building block material with tuneable structural properties. Our investigations substantiate the capability of SCOBY bioflocculants, characterized by distinct microstructures, to successfully assemble within a microfluidic device, thereby generating a cellulose sheet endowed with specific and purposefully designed structural features. [ABSTRACT FROM AUTHOR]

We present a multi-proxy investigation of a lower Carnian basinal succession from Polzberg in the Northern Calcareous Alps (Lower Austria). A section comprising a unique Konservat-Lagerstätte was studied based on bio- and chemostratigraphy along with geophysical methods, yielding a detailed and robust stratigraphic calibration of the Polzberg succession. The Polzberg section revealed the paleoceanographic history and helped to identify a global climatic reversal, the Carnian Pluvial Episode. The age of the Upper Triassic Reingraben formation in the Northern Calcareous Alps is refined as the Austrotrachyceras austriacum Zone within the lower Carnian (Julian 2). Ammonoids and conodonts provide a detailed biostratigraphic subdivision that serves as a basis for analyses of the faunal distribution and the paleoenvironmental evolution of the Upper Triassic Reifling Basin. The succession includes lithological and facies changes similar to those of coeval units in the Tethys. The Carnian was characterized by a weak (~ 1‰) positive δ13C trend, punctuated by a negative shift during the lower Carnian corresponding to the initiation of the Carnian Pluvial Episode, a period representing the onset of early/late Carnian transitional global greenhouse conditions. Organic maturity parameters and the conodont alteration index (CAI) show that the thermal overprint of the Polzberg section is low. Biomarker proxies suggest that the organic matter of the uppermost Göstling formation is a mixture of marine and terrestrial material deposited in a dysoxic environment. Within the overlaying Reingraben formation, the amount of marine biomass decreased gradually upwards. Oxygen-depleted conditions, probably due to water-column stratification, continued during deposition of the Reingraben formation. Bacterial sulfate reduction played a major role in organic matter degradation. [ABSTRACT FROM AUTHOR]

The inflammatory corpuscle recombinant absents in melanoma 2 (AIM2) and cholesterol efflux protein ATP binding cassette transporter A1(ABCA1) have been reported to play opposing roles in atherosclerosis (AS) plaques. However, the relationship between AIM2 and ABCA1 remains unclear. In this study, we explored the potential connection between AIM2 and ABCA1 in the modulation of AS by bioinformatic analysis combined with in vitro experiments. The GEO database was used to obtain AS transcriptional profiling data; screen differentially expressed genes (DEGs) and construct a weighted gene co-expression network analysis (WGCNA) to obtain AS-related modules. Phorbol myristate acetate (PMA) was used to induce macrophage modelling in THP-1 cells, and ox-LDL was used to induce macrophage foam cell formation. The experiment was divided into Negative Control (NC) group, Model Control (MC) group, AIM2 overexpression + ox-LDL (OE AIM2 + ox-LDL) group, and AIM2 short hairpin RNA + ox-LDL (sh AIM2 + ox-LDL) group. The intracellular cholesterol efflux rate was detected by scintillation counting; high-performance liquid chromatography (HPLC) was used to detect intracellular cholesterol levels; apoptosis levels were detected by TUNEL kit; levels of inflammatory markers (IL-1β, IL-18, ROS, and GSH) were detected by ELISA kits; and levels of AIM2 and ABCA1 proteins were detected by Western blot. Bioinformatic analysis revealed that the turquoise module correlated most strongly with AS, and AIM2 and ABCA1 were co-expressed in the turquoise module with a trend towards negative correlation. In vitro experiments demonstrated that AIM2 inhibited macrophage cholesterol efflux, resulting in increased intracellular cholesterol levels and foam cell formation. Moreover, AIM2 had a synergistic effect with ox-LDL, exacerbating macrophage oxidative stress and inflammatory response. Silencing AIM2 ameliorated the above conditions. Furthermore, the protein expression levels of AIM2 and ABCA1 were consistent with the bioinformatic analysis, showing a negative correlation. AIM2 inhibits ABCA1 expression, causing abnormal cholesterol metabolism in macrophages and ultimately leading to foam cell formation. Inhibiting AIM2 may reverse this process. Overall, our study suggests that AIM2 is a reliable anti-inflammatory therapeutic target for AS. Inhibiting AIM2 expression may reduce foam cell formation and, consequently, inhibit the progression of AS plaques. [ABSTRACT FROM AUTHOR]

During the middle Permian through the Triassic, Tasmania moved from paleo-latitudes of 78° to 69°S, wedged between Antarctica and Australia, within the paleo-South polar circle. During this time, significant global carbon cycle disturbances triggered major environmental and climatic changes and mass extinction events globally. The Bicheno-5 core from Eastern Tasmania, Australia, provides the opportunity to examine middle Permian and Upper Triassic sediments from the paleo-Antarctic, using high-resolution organic carbon isotope (δ13CTOC) chemostratigraphy, pXRF, and sedimentology, combined with new palynological data integrated with the existing radiometric age model. While there is a significant unconformity in the Upper Permian to the middle Triassic associated with eustatic sea-level fall as a result of regional uplift in eastern Australia, three distinct carbon isotope excursions (CIEs), characterized by negative shifts of up to − 6 ‰ were identified; the middle Permian Guadalupian Carbon Isotope Excursions (G-CIE), the Carnian Pluvial Episode (CPE), and the mid-Norian Event (MNE). These three events highlight a significant climate shift through glacial and interglacial cycles to warmer non-glacial intervals in the Late Triassic, with evidence of the polar record of the Carnian Pluvial Episode and the mid-Norian Event, which are poorly studied in the Southern Hemisphere, specifically within the Paleo-Antarctic circle. [ABSTRACT FROM AUTHOR]