bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sustained aviremia despite anti-retroviral therapy non-adherence in male children after in utero HIV transmission
Authors: Bengu Nomonde , Cromhout Gabriela , Adland Emily , Govender Katya , Herbert Nicholas , Lim Nicholas , Fillis Rowena , Sprenger Kenneth , Vieira Vinicius , Kannie Samantha , van Lobenstein Jeroen , Chinniah Kogielambal , Kapongo Constant , Bhoola Roopesh , Krishna Malini , Mchunu Noxolo , Pascucci Giuseppe Rubens , Cotugno Nicola , Palma Paolo , Tagarro Alfredo , Rojo Pablo , Roider Julia , Garcia-Guerrero Maria C. , Ochsenbauer Christina , Groll Andreas , Reddy Kavidha , Giaquinto Carlo , Rossi Paolo , Hong Seohyun , Dong Krista , Ansari M. Azim , Puertas Maria C. , Ndung’u Thumbi , Capparelli Edmund , Lichterfeld Mathias , Martinez-Picado Javier , Kappes John C. , Archary Moherndran , Goulder Philip 
Published: June 2024

Abstract
After sporadic reports of post-treatment control of HIV in children who initiated combination anti-retroviral therapy (cART) early, we prospectively studied 284 very-early-cART-treated children from KwaZulu-Natal, South Africa, after vertical HIV transmission to assess control of viremia. Eighty-four percent of the children achieved aviremia on cART, but aviremia persisting to 36 or more months was observed in only 32%. We observed that male infants have lower baseline plasma viral loads (P = 0.01). Unexpectedly, a subset (n = 5) of males maintained aviremia despite unscheduled complete discontinuation of cART lasting 3–10 months (n = 4) or intermittent cART adherence during 17-month loss to follow-up (n = 1). We further observed, in vertically transmitted viruses, a negative correlation between type I interferon (IFN-I) resistance and viral replication capacity (VRC) (P < 0.0001) that was markedly stronger for males than for females (r = −0.51 versus r = −0.07 for IFN-α). Although viruses transmitted to male fetuses were more IFN-I sensitive and of higher VRC than those transmitted to females in the full cohort (P < 0.0001 and P = 0.0003, respectively), the viruses transmitted to the five males maintaining cART-free aviremia had significantly lower replication capacity (P < 0.0001). These data suggest that viremic control can occur in some infants with in utero–acquired HIV infection after early cART initiation and may be associated with innate immune sex differences.
Deconwolf enables high-performance deconvolution of widefield fluorescence microscopy images
Authors: Wernersson Erik , Gelali Eleni , Girelli Gabriele , Wang Su , Castillo David , Mattsson Langseth Christoffer , Verron Quentin , Nguyen Huy Q. , Chattoraj Shyamtanu , Martinez Casals Anna , Blom Hans , Lundberg Emma , Nilsson Mats , Marti-Renom Marc A. , Wu Chao-ting , Crosetto Nicola , Bienko Magda 
Published: June 2024

AbstractMicroscopy-based spatially resolved omic methods are transforming the life sciences. However, these methods rely on high numerical aperture objectives and cannot resolve crowded molecular targets, limiting the amount of extractable biological information. To overcome these limitations, here we develop Deconwolf, an open-source, user-friendly software for high-performance deconvolution of widefield fluorescence microscopy images, which efficiently runs on laptop computers. Deconwolf enables accurate quantification of crowded diffraction limited fluorescence dots in DNA and RNA fluorescence in situ hybridization images and allows robust detection of individual transcripts in tissue sections imaged with ×20 air objectives. Deconvolution of in situ spatial transcriptomics images with Deconwolf increased the number of transcripts identified more than threefold, while the application of Deconwolf to images obtained by fluorescence in situ sequencing of barcoded Oligopaint probes drastically improved chromosome tracing. Deconwolf greatly facilitates the use of deconvolution in many bioimaging applications.
Profiling expression strategies for a type III polyketide synthase in a lysate-based, cell-free system
Authors: Sword Tien T. , Dinglasan Jaime Lorenzo N. , Abbas Ghaeath S. K. , Barker J. William , Spradley Madeline E. , Greene Elijah R. , Gooden Damian S. , Emrich Scott J. , Gilchrist Michael A. , Doktycz Mitchel J. , Bailey Constance B. 
Published: June 2024

AbstractSome of the most metabolically diverse species of bacteria (e.g., Actinobacteria) have higher GC content in their DNA, differ substantially in codon usage, and have distinct protein folding environments compared to tractable expression hosts like Escherichia coli. Consequentially, expressing biosynthetic gene clusters (BGCs) from these bacteria in E. coli often results in a myriad of unpredictable issues with regard to protein expression and folding, delaying the biochemical characterization of new natural products. Current strategies to achieve soluble, active expression of these enzymes in tractable hosts can be a lengthy trial-and-error process. Cell-free expression (CFE) has emerged as a valuable expression platform as a testbed for rapid prototyping expression parameters. Here, we use a type III polyketide synthase from Streptomyces griseus, RppA, which catalyzes the formation of the red pigment flaviolin, as a reporter to investigate BGC refactoring techniques. We applied a library of constructs with different combinations of promoters and rppA coding sequences to investigate the synergies between promoter and codon usage. Subsequently, we assess the utility of cell-free systems for prototyping these refactoring tactics prior to their implementation in cells. Overall, codon harmonization improves natural product synthesis more than traditional codon optimization across cell-free and cellular environments. More importantly, the choice of coding sequences and promoters impact protein expression synergistically, which should be considered for future efforts to use CFE for high-yield protein expression. The promoter strategy when applied to RppA was not completely correlated with that observed with GFP, indicating that different promoter strategies should be applied for different proteins. In vivo experiments suggest that there is correlation, but not complete alignment between expressing in cell free and in vivo. Refactoring promoters and/or coding sequences via CFE can be a valuable strategy to rapidly screen for catalytically functional production of enzymes from BCGs, which advances CFE as a tool for natural product research.
Impact of vitamin D deficiency on iron status in children with type I diabetes
Authors: Moslhy Eman A. M. , Tadros May M. M. , Thabet Rasha A. , Hemida Eman H. A. , Noureldeen Amani F. H. 
Published: June 2024

AbstractVitamin D deficiency (VDD) and anemia are both public health nutrition concerns. An association between VDD and anemia has been suggested in various healthy and diseased populations. The current study aimed to elucidate the effect of VDD on iron status in children with type I diabetes mellitus (T1DM). The study recruited two groups of children with T1DM: control group comprised of 38 T1DM children with sufficient vitamin D (> 30 ng/ml) and a case group, consisted of 52 T1DM children with VDD (< 20 ng/ml). Both groups had comparable gender, age, BMI, and disease duration. The laboratory measurements included analysis of blood indices, markers of iron metabolism, hepcidin and inflammatory markers included interleukin 6 (IL-6) and C-reactive protein (CRP). Compared to control group, T1DM children with VDD differs specifically in terms of some markers of blood indices, such as decreased hemoglobin and increased red blood cell distribution width. Moreover, decreased serum iron, ferritin, total iron-binding capacity and transferrin along with elevated inflammatory markers were observed in case group. Results of the study indicated that VDD had increased the risk of iron deficiency anemia in children with T1DM as well as inflammatory related anemia. Furthermore, in T1DM children, VDD had raised the incidence of both absolute and functional iron deficiency, with greater incidence of the former. This study may indicate that VDD may be a risk factor that may worsen iron deficiency anemia in T1DM.
New sulfonamide-based glycosides incorporated 1,2,3-triazole as cytotoxic agents through VEGFR-2 and carbonic anhydrase inhibitory activity
Authors: Abbas Hebat-Allah S. , Nossier Eman S. , El-Manawaty May A. , El-Bayaa Mohamed N. 
Published: June 2024

AbstractNew sulfonamide-triazole-glycoside hybrids derivatives were designed, synthesised, and investigated for anticancer efficacy. The target glycosides’ cytotoxic activity was studied with a panel of human cancer cell lines. Sulfonamide-based derivatives, 4, 7 and 9 exhibited promising activity against HepG-2 and MCF-7 (IC50 = 8.39–16.90 μM against HepG-2 and 19.57–21.15 μM against MCF-7) comparing with doxorubicin (IC50 = 13.76 ± 0.45, 17.44 ± 0.46 μM against HepG-2 and MCF-7, rescpectively). To detect the probable action mechanism, the inhibitory activity of these targets was studied against VEGFR-2, carbonic anhydrase isoforms hCA IX and hCA XII. Compoumds 7 and 9 gave favorable potency (IC50 = 1.33, 0.38 μM against VEGFR-2, 66, 40 nM against hCA IX and 7.6, 3.2 nM against hCA XII, respectively), comparing with sorafenib and SLC-0111 (IC50 = 0.43 μM, 53 and 4.8 nM, respectively). Moreover, the docking simulation was assessed to supply better rationalization and gain insight into the binding affinity between the promising derivatives and their targeted enzymes that was used for further modification in the anticancer field.
Maternal diet quality with child allergic and respiratory multimorbidity in the Elfe birth cohort
Authors: Delvert Rosalie , Charles Marie-Aline , Leynaert Bénédicte , Kadawathagedara Manik , Adel-Patient Karine , Divaret-Chauveau Amandine , Dufourg Marie-Noëlle , Raherison Chantal , Varraso Raphaëlle , de Lauzon-Guillain Blandine , Bédard Annabelle 
Published: June 2024

AbstractEvidence linking maternal diet during pregnancy to allergic or respiratory diseases in children remains sparse, and outcomes were mainly studied separately. We aim to investigate these associations by considering clusters of allergic and respiratory multimorbidity among 9679 mother–child pairs from the Elfe birth cohort. Maternal diet quality was evaluated using a food-based score (Diet Quality score), a nutrient-based score (PANDiet score) and food group intakes. Adjusted multinomial logistic regressions on allergic and respiratory multimorbidity clusters up to 5.5 years were performed. Child allergic and respiratory diseases were described through five clusters: “asymptomatic” (43%, reference), “early wheeze without asthma” (34%), “asthma only” (7%), “allergies without asthma” (7%), “multi-allergic” (9%). A higher PANDiet score and an increased legume consumption were associated with a reduced risk of belonging to the “early wheeze without asthma” cluster. A U-shaped relationship was observed between maternal fish consumption and the “allergies without asthma” cluster. To conclude, adequate nutrient intake during pregnancy was weakly associated with a lower risk of “early wheeze without asthma” in children. No association was found with food groups, considered jointly or separately, except for legumes and fish, suggesting that maternal adherence to nutritional guidelines might be beneficial for allergic and respiratory diseases prevention.
Characterization of heavy metal contamination in groundwater of typical mining area in Hunan Province
Authors: Hao Wenjie , Liu Huan , Hao Shuli , Mao Kuanzhen 
Published: June 2024

AbstractHeavy metal pollution in mining areas is a major cause of groundwater contamination, characterized by high toxicity, difficult degradability, and easy accumulation, and the source of pollution is not easily identified. Relying on the results of groundwater quality analysis tests in a typical mining area, this paper uses the SPSS 18.0 statistical analysis model to analyze the statistical characteristics of different indicator factors in the antimony mining area. The conclusions play a crucial role in implementing health and safety measures for the mining area and its surrounding residents. The statistical study results show that Mn, Se, As, and Sb are closely related to human mining activities and are polluted to varying degrees; the principal component analysis model indicates that the upstream monitoring points 26#, 22#, and 25# in the mining area groundwater are less polluted. The five monitoring points with a comprehensive principal component F > 1 are all located within the range of the metal mine cluster, indicating that the groundwater in the mining area is particularly sensitive to the impact of anthropogenic mineral extraction. This research summarizes the hydrogeological and geochemical statistical characteristics of the groundwater in the mining area, providing a reference for groundwater pollution risk diagnosis, ecological restoration, and heavy metal pollution prevention and control in this and similar mining areas.
Deterioration in cognitive control related mPFC function underlying development of treatment resistance in early psychosis
Authors: Crisp Charlotte M. , Sahni Angad , Pang Sze W. , Vanes Lucy D. , Szentgyorgyi Timea , Averbeck Bruno , Moran Rosalyn J. , Shergill Sukhwinder S. 
Published: June 2024

AbstractOne third of people with psychosis become antipsychotic treatment-resistant and the underlying mechanisms remain unclear. We investigated whether altered cognitive control function is a factor underlying development of treatment resistance. We studied 50 people with early psychosis at a baseline visit (mean < 2 years illness duration) and follow-up visit (1 year later), when 35 were categorized at treatment-responsive and 15 as treatment-resistant. Participants completed an emotion-yoked reward learning task that requires cognitive control whilst undergoing fMRI and MR spectroscopy to measure glutamate levels from Anterior Cingulate Cortex (ACC). Changes in cognitive control related activity (in prefrontal cortex and ACC) over time were compared between treatment-resistant and treatment-responsive groups and related to glutamate. Compared to treatment-responsive, treatment-resistant participants showed blunted activity in right amygdala (decision phase) and left pallidum (feedback phase) at baseline which increased over time and was accompanied by a decrease in medial Prefrontal Cortex (mPFC) activity (feedback phase) over time. Treatment-responsive participants showed a negative relationship between mPFC activity and glutamate levels at follow-up, no such relationship existed in treatment-resistant participants. Reduced activity in right amygdala and left pallidum at baseline was predictive of treatment resistance at follow-up (67% sensitivity, 94% specificity). The findings suggest that deterioration in mPFC function over time, a key cognitive control region needed to compensate for an initial dysfunction within a social-emotional network, is a factor underlying development of treatment resistance in early psychosis. An uncoupling between glutamate and cognitive control related mPFC function requires further investigation that may present a future target for interventions.
Advanced environmental scanning electron microscopy reveals natural surface nano-morphology of condensed mitotic chromosomes in their native state
Authors: Neděla Vilém , Tihlaříková Eva , Cápal Petr , Doležel Jaroslav 
Published: June 2024

AbstractThe challenge of in-situ handling and high-resolution low-dose imaging of intact, sensitive and wet samples in their native state at nanometer scale, including live samples is met by Advanced Environmental Scanning Electron Microscopy (A-ESEM). This new generation of ESEM utilises machine learning-based optimization of thermodynamic conditions with respect to sample specifics to employ a low temperature method and an ionization secondary electron detector with an electrostatic separator. A modified electron microscope was used, equipped with temperature, humidity and gas pressure sensors for in-situ and real-time monitoring of the sample. A transparent ultra-thin film of ionic liquid is used to increase thermal and electrical conductivity of the samples and to minimize sample damage by free radicals. To validate the power of the new method, we analyze condensed mitotic metaphase chromosomes to reveal new structural features of their perichromosomal layer, and the organization of chromatin fibers, not observed before by any microscopic technique. The ability to resolve nano-structural details of chromosomes using A-ESEM is validated by measuring gold nanoparticles with achievable resolution in the lower nanometre units.
Multinational proficiency tests for EGFR exon 20 insertions reveal that the assay design matters
Authors: Ihle Michaela A. , Heydt Carina , Schultheis Anne Maria , Stöhr Robert , Haller Florian , Herold Sylvia , Aust Daniela , Dietmaier Wolfgang , Evert Matthias , Eszlinger Markus , Haak Anja , Laßmann Silke , Vorholt Daniela , Breitenbücher Frank , Werner Martin , Streubel Anna , Mairinger Thomas , Grassow-Narlik Maja , Merkelbach-Bruse Sabine 
Published: June 2024

AbstractInsertion mutations in exon 20 of the epidermal growth factor receptor gene (EGFR exon20ins) are rare, heterogeneous alterations observed in non-small cell lung cancer (NSCLC). With a few exceptions, they are associated with primary resistance to established EGFR tyrosine kinase inhibitors (TKIs). As patients carrying EGFR exon20ins may be eligible for treatment with novel therapeutics—the bispecific antibody amivantamab, the TKI mobocertinib, or potential future innovations—they need to be identified reliably in clinical practice for which quality-based routine genetic testing is crucial. Spearheaded by the German Quality Assurance Initiative Pathology two international proficiency tests were run, assessing the performance of 104 participating institutes detecting EGFR exon20ins in tissue and/or plasma samples. EGFR exon20ins were most reliably identified using next-generation sequencing (NGS). Interestingly, success rates of institutes using commercially available mutation-/allele-specific quantitative (q)PCR were below 30% for tissue samples and 0% for plasma samples. Most of these mutation-/allele-specific (q)PCR assays are not designed to detect the whole spectrum of EGFR exon20ins mutations leading to false negative results. These data suggest that NGS is a suitable method to detect EGFR exon20ins in various types of patient samples and is superior to the detection spectrum of commercially available assays.
Pediatric health service utilization at tertiary hospitals in Denmark 2000–2018
Authors: Madsen Pi Vejsig , Jensen Andreas , Eriksson Frank , Stensballe Lone Graff 
Published: June 2024

AbstractPediatric health service differs between and within countries. To prioritize limited resources, data-driven studies on pediatric tertiary hospital contacts are warranted. This population-based register study identified all contacts with four Danish tertiary hospitals 2000–2018 by 0–17-year-old patients. During 2000–2018, 2,496,001 individuals resided in Denmark while 0–17 years old, and the study described 829,562 inpatient and 3,932,744 outpatient contacts at tertiary hospitals by hospital, sex, age, diagnosis, department, and residence. Male patients accounted for more contacts overall (inpatient 55.51%, outpatient 52.40%) and more contacts with severe chronic disease (inpatient 56.24%, outpatient 54.41%). Median (interquartile range) patient age was 3.09 (0.26–9.96) and 8.48 (2.78–13.70) years for in- and outpatient contacts. Overall, 28.23% and 21.02% of in- and outpatient contacts included a diagnosis of a severe chronic disease, but the proportions differed across hospitals. A pattern of pediatric healthcare directed towards less severe diseases was observed: While the total number of outpatient visits at tertiary hospitals increased from 2000 to 2018, the proportion of these contacts which had a diagnosis of a severe chronic disease decreased. Future comparisons between hospitals regarding pediatric outcomes should consider potential differences in terms of uptake and diagnosis severity. Such findings may have implications for future pediatric organization, nationally and internationally.
Exploring the relationship between heavy metals and diabetic retinopathy: a machine learning modeling approach
Authors: Gui Yanchao , Gui Siyu , Wang Xinchen , Li Yiran , Xu Yueyang , Zhang Jinsong 
Published: June 2024

AbstractDiabetic retinopathy (DR) is one of the leading causes of adult blindness in the United States. Although studies applying traditional statistical methods have revealed that heavy metals may be essential environmental risk factors for diabetic retinopathy, there is a lack of analyses based on machine learning (ML) methods to adequately explain the complex relationship between heavy metals and DR and the interactions between variables. Based on characteristic variables of participants with and without DR and heavy metal exposure data obtained from the NHANES database (2003–2010), a ML model was developed for effective prediction of DR. The best predictive model for DR was selected from 11 models by receiver operating characteristic curve (ROC) analysis. Further permutation feature importance (PFI) analysis, partial dependence plots (PDP) analysis, and SHapley Additive exPlanations (SHAP) analysis were used to assess the model capability and key influencing factors. A total of 1042 eligible individuals were randomly assigned to two groups for training and testing set of the prediction model. ROC analysis showed that the k-nearest neighbour (KNN) model had the highest prediction performance, achieving close to 100% accuracy in the testing set. Urinary Sb level was identified as the critical heavy metal affecting the predicted risk of DR, with a contribution weight of 1.730632 ± 1.791722, which was much higher than that of other heavy metals and baseline variables. The results of the PDP analysis and the SHAP analysis also indicated that antimony (Sb) had a more significant effect on DR. The interaction between age and Sb was more significant compared to other variables and metal pairs. We found that Sb could serve as a potential predictor of DR and that Sb may influence the development of DR by mediating cellular and systemic senescence. The study revealed that monitoring urinary Sb levels can be useful for early non-invasive screening and intervention in DR development, and also highlighted the important role of constructed ML models in explaining the effects of heavy metal exposure on DR.
Unraveling the relationship between serum parathyroid hormone levels and trabecular bone score: a cross-sectional study
Authors: Zhao Tingxiao , Li Yanlei , Tian Jinlong , Kang Yao , Xu Jiongnan , Shao Haiyu , Zhou Jinlei , Xia Chen , Wang Yongguang , Zhang Jun 
Published: June 2024

AbstractThe TBS is a new method for clinicians to assess the bone quality. It is directly related to the mechanical strength of bone and helps predict fracture risk. The present analysis aimed to investigate the associations between serum PTH levels and TBS by analyzing data from the National Health and Nutrition Examination Survey (NHANES). A total of 3516 participants from the NHANES 2005–2006 were included in this cross-sectional study. The independent variable was serum PTH, and the outcome variable was TBS. The associations of serum PTH levels with TBS were examined using multivariable linear regression models. After adjusting for covariates, there was a negative association between serum PTH level and TBS (β = − 0.0034; 95% confidence interval, − 0.0050 to − 0.0017). However, in the subgroup analysis stratified by gender, race, and age, this association became negative only in Non-Hispanic White (β =  − 0.0047, 95% CI:  −  0.0071 to  −  0.0048) and young people (age < 60) (β = − 0.0036, 95% CI: − 0.0057, − 0.0016), regardless of gender. In addition, the association of serum PTH with TBS was an U-shaped curve, with a point of inflection at 6.71 pmol/L. This study showed that serum PTH level was negatively associated with TBS. Maintaining PTH levels in a lower reasonable clinical range may be beneficial to bone health, especially for young non-Hispanic white.