bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinants of Maternal Health Service Utilization and Continuum of Care in Nepal: An Analysis from Demographic and Health Survey 2022
Authors: Pandey Achyut Raj , Adhikari Bikram , Sangroula Raj Kumar , Regmi Shophika , Sharma Shreeman , Dulal Bishnu , Lamichhane Bipul , KC Saugat Pratap , Dhakal Pratistha , Baral Sushil Chandra 
Published: August 2023

AbstractBackgroundContinuum of care for maternal health services is essential in minimizing preventable fatalities linked to pregnancy and childbirth. The study focuses on assessing determinants of maternal health service utilization i.e., four or more antenatal care (ANC) visits, institutional delivery, and postnatal care (PNC) visit within the first 2 days of delivery and the continuum of care.MethodsWe performed weighted analysis of Nepal Demographic and Health Survey 2022 accounting for complex survey design. Categorical variables are presented using frequency, percentage, and 95% confidence intervals (CI), while numerical variables were represented as mean and a 95% CI. We performed bivariable and multivariable binary logistic regression and the results are odds ratios presented with 95%.ResultsAmong total participants, 80.5% (95% CI: 77.9, 82.8) had four or more antenatal care (ANC) visits, 79.4% (95% CI: 76.8, 81.9) had institutional delivery and 70.2% (95% CI:67.5, 72.9 postnatal care (PNC) visit within 2 days of delivery. The proportion of participants having both four or more ANC visits and institutional delivery was 67.6% (95% CI: 64.7, 70.4) those completing all three components of care (4 or more ANC visits, delivering in health facility and having PNC visit for mother within 2 days of delivery) was 51.2% (95% CI: 48.3, 54.0).Compared to participants in poorest wealth quintile, participants in wealthiest quintile had 12 folds higher odds (AOR: 11.96, 95% CI: 14.36, 32.79) of having both four or more ANC visits and institutional delivery. Residents of the Madhesh had lower odds (AOR: 0.47, 95% CI: 0.23, 0.99), Sudurpaschim had higher odds (AOR: 2.37, 95% CI: 1.17, 4.82) of having 4 or more ANC visits and institutional delivery compared to Koshi Province. Residents of Bagmati Province had lower odds (AOR:0.49, 95% CI: 0.28, 0.87) of having all three components of care: 4 or more ANC visits, institutional delivery and PNC visit within 2 days of delivery for mother.ConclusionThere are notable differences in coverage of maternal health services based on education, wealth quintile, province and place of residence. Addressing economic inequalities and provincial differences and harnessing technology to provide and equitable access to vital maternal and newborn health initiatives.
Machine Learning Reveals Synovial Fibroblast Genes Associated with Pain Affect Sensory Nerve Growth in Rheumatoid Arthritis
Authors: Bai Zilong , Bartelo Nicholas , Aslam Maryam , Hale Caryn , Blachere Nathalie E. , Parveen Salina , Spolaore Edoardo , DiCarlo Edward , Gravallese Ellen , Smith Melanie H. ,   Accelerating Medicines Partnership Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Network, Frank Mayu O. , Jiang Caroline S. , Zhang Haotan , Lewis Myles J. , Sikandar Shafaq , Pitzalis Costantino , Malfait Anne-Marie , Miller Rachel E. , Zhang Fan , Goodman Susan , Darnell Robert , Wang Fei , Orange Dana E. 
Published: August 2023

AbstractIt has been presumed that rheumatoid arthritis (RA) joint pain is related to inflammation in the synovium; however, recent studies reveal that pain scores in patients do not correlate with synovial inflammation. We identified a module of 815 genes associated with pain, using a novel machine learning approach, Graph-based Gene expression Module Identification (GbGMI), in samples from patients with longstanding RA, but limited synovial inflammation at arthroplasty, and validated this finding in an independent cohort of synovial biopsy samples from early, untreated RA patients. Single-cell RNA-seq analyses indicated these genes were most robustly expressed by lining layer fibroblasts and receptor-ligand interaction analysis predicted robust lining layer fibroblast crosstalk with pain sensitive CGRP+ dorsal root ganglion sensory neurons. Netrin-4, which is abundantly expressed by lining fibroblasts and associated with pain, significantly increased the branching of pain-sensitive CGRP+ neuronsin vitro. We conclude GbGMI is a useful method for identifying a module of genes that associate with a clinical feature of interest. Using this approach, we find that Netrin-4 is produced by synovial fibroblasts in the absence of inflammation and can enhance the outgrowth of CGRP+ pain sensitive nerve fibers.One Sentence SummaryMachine Learning reveals synovial fibroblast genes related to pain affect sensory nerve growth in Rheumatoid Arthritis addresses unmet clinical need.
Analytic optimization ofPlasmodium falciparummarker gene haplotype recovery from amplicon deep sequencing of complex mixtures
Authors: Lapp Zena , Freedman Elizabeth , Huang Kathie , Markwalter Christine F , Obala Andrew A , Prudhomme-O’Meara Wendy , Taylor Steve M 
Published: August 2023

AbstractMolecular epidemiologic studies of malaria parasites commonly employ amplicon deep sequencing (AmpSeq) of marker genes derived from dried blood spots (DBS) to answer public health questions related to topics such as transmission and drug resistance. As these methods are increasingly employed to inform direct public health action, it is important to rigorously evaluate the risk of false positive and false negative haplotypes derived from clinically-relevant sample types. We performed a control experiment evaluating haplotype recovery from AmpSeq of 5 marker genes (ama1,csp,msp7,sera2, andtrap) from DBS containing mixtures of DNA from 1 to 10 knownP. falciparumreference strains across 3 parasite densities in triplicate (n=270 samples). While false positive haplotypes were present across all parasite densities and mixtures, we optimized censoring criteria to remove 83% (148/179) of false positives while removing only 8% (67/859) of true positives. Post-censoring, the median pairwise Jaccard distance between replicates was 0.83. We failed to recover 35% (477/1365) of haplotypes expected to be present in the sample. Haplotypes were more likely to be missed in low-density samples with <1.5 genomes/µL (OR: 3.88, CI: 1.82-8.27, vs. high-density samples with ≥75 genomes/µL) and in samples with lower read depth (OR per 10,000 reads: 0.61, CI: 0.54-0.69). Furthermore, minority haplotypes within a sample were more likely to be missed than dominant haplotypes (OR per 0.01 increase in proportion: 0.96, CI: 0.96-0.97). Finally, in clinical samples the percent concordance across markers for multiplicity of infection ranged from 40%-80%. Taken together, our observations indicate that, with sufficient read depth, haplotypes can be successfully recovered from DBS while limiting the false positive rate.
FGF23 is a potential prognostic biomarker in uterine sarcoma
Authors: Yang Ling , Cai Ying , Wang Yunjia , Huang Yue , Zhang Chi , Ma Hu , Zhou Jian-Guo 
Published: August 2023

AbstractBackgroundUterine sarcoma (US) is a highly malignant cancer with poor prognosis and high mortality in women. In this study, we evaluated the expression of human fibroblast growth factor 23 (FGF23) in different US subtypes and the relationship between survival and clinicopathological characteristics.MethodsWe conducted a comparative analysis of FGF23 gene expression in different pathological types of US. Utilizing a cohort from The Cancer Genome Atlas (TCGA) of 57 patients, a 50-patient microarray dataset (GSE119043) from the Gene Expression Omnibus (GEO) and a clinical cohort of 44 patients, we analyzed gene expression profiles and corresponding clinicopathological information. Immunohistochemistry (IHC) was used to examine the expression level of FGF23 in four US subtypes. Survival analysis was used to assess the relationship between FGF23 expression and prognosis in US patients.ResultsCompared with uterine normal smooth muscle (UNSM) and uterine leiomyoma (ULM), FGF23 expression was significantly upregulated in US and was differentially expressed in four US subtypes. Uterine carcinosarcoma (UCS) exhibited the highest expression of FGF23 among the subtypes. Survival analysis indicated that FGF23 expression was unrelated to overall survival and progression-free survival in US (P>0.05). Similar results were obtained from the validation cohorts. Univariate and multivariate analyses showed no significant correlation between FGF23 expression and the US prognosis. Tumor stage, CA125 and tumor recurrence were independent prognostic factors for survival of US patients.ConclusionFGF23 was highly expressed in uterine sarcoma and was promising as a novel potential biomarker for the diagnosis and prognosis of uterine sarcoma.
Back to the Basics: An Alternative Approach to ABG Interpretation
Authors: Nguyen Emily , Turpin Chase , deLuna Andres 
Published: August 2023

AbstractMedical education has promoted the rapid interpretation of the arterial blood gas (ABG) as a crucial skill in the management of critically ill patients. The first step of many algorithms focuses on using log-linear estimates to determine the internal consistency of ABG values. However, because of modern computing advances, these estimates are no longer necessary. We demonstrate an alternative method for ascertaining internal consistency of ABG values based on direct calculation derived directly from Henderson-Hasselbach and demonstrate its efficiency and accuracy.Deidentified ABG values were collected from electronic medical records for the month of September 2022. Estimated hydrogen concentration was calculated by log linear estimation and by the proposed method of direct calculation. Time of computation, a measure of efficiency, was also recorded.Of the 1008 ABGs used for analysis, 185 (18.4%) had estimated hydrogen concentrations that were greater than a 5% threshold according to the guidelines method, suggesting potential internal inconsistency. However, only 13 (1.3%) had estimated hydrogen concentrations greater than 5% by direct calculation. Analysis was also performed at a 10% threshold. On further analysis, 4 ABGs that were identified by the guidelines method as being internally inconsistent, but not identified by the direct calculation method, were found to have pH <7.0, outside the range provided for the current guidelines for log-linear estimation, and were thus incorrectly identified by the guidelines method as being internally inconsistent. The time of computation for direct calculation was approximately 8-fold faster, although the total time of calculation for this dataset was minimal.This study demonstrates a direct calculation method as an alternative approach to traditional guidelines to assess internal ABG value consistency, the first step of ABG interpretation. We demonstrate that direct calculation is more accurate, identifying less potentially internally inconsistent values, notably at extremes in pH. In addition, the direct calculation algorithm is 8-fold more efficient than guidelines-based algorithm, although actual processing times were miniscule for the data set regardless of the method used. Furthermore, with modern calculators and computers, the direct calculation method is easier to understand and implement than the guideline based approach. Therefore, based on the results of this study, we propose the use of direct calculation as an alternative to log-linear based estimation for the assessment of internal consistency of ABGs.
DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response
Authors: Yulyaningsih Ernie , Suh Jung H. , Fanok Melania H. , Chau Roni , Solanoy Hilda , Takahashi Ryan , Bakardjiev Anna I. , Becerra Isabel , Benitez N. Butch , Chiu Chi-Lu , Davis Sonnet S , Dowdle William E. , Earr Timothy , Estrada Anthony A. , Gill Audrey , Ha Connie , Haddick Patrick C. G. , Henne Kirk R. , Larhammar Martin , Leung Amy Wing-Sze , Maciuca Romeo , Memarzadeh Bahram , Nguyen Hoang N. , Nugent Alicia , Osipov Maksim , Ran Yingqing , Rebadulla Kevin , Roche Elysia , Sandmann Thomas , Wang Jing , Lewcock Joseph W. , Scearce-Levie Kimberly , Kane Lesley A. , Sanchez Pascal E. 
Published: August 2023

ABSTRACTThe integrated stress response (ISR) is a conserved pathway in eukaryotic cells that is activated in response to multiple sources of cellular stress. Although acute activation of this pathway restores cellular homeostasis, intense or prolonged ISR activation perturbs cell function and may contribute to neurodegeneration. DNL343 is an investigational CNS-penetrant small molecule ISR inhibitor designed to activate the eukaryotic initiation factor 2B (eIF2B) and suppress aberrant ISR activation. DNL343 reduced CNS ISR activity and neurodegeneration in a dose-dependent manner in two establishedin vivomodels – the optic nerve crush injury and an eIF2B loss of function (LOF) mutant – demonstrating neuroprotection in both and preventing motor dysfunction in the LOF mutant mouse. Treatment with DNL343 at a late stage of disease in the LOF model reversed elevation in plasma biomarkers of neuroinflammation and neurodegeneration and prevented premature mortality. Several proteins and metabolites that are dysregulated in the LOF mouse brains were normalized by DNL343 treatment, and this response is detectable in human biofluids. Several of these biomarkers show differential levels in CSF and plasma from patients with vanishing white matter disease (VWMD), a neurodegenerative disease that is driven by eIF2B LOF and chronic ISR activation, supporting their potential translational relevance. This study demonstrates that DNL343 is a brain penetrant ISR inhibitor capable of attenuating neurodegeneration in mouse models and identifies several biomarker candidates that may be used to assess treatment responses in the clinic.
The odor of a nontoxic tetrodotoxin analog, 5,6,11-trideoxytetrodotoxin, is detected by specific olfactory sensory neurons of the green spotted puffers
Authors: Suzuki Takehisa , Nakahigashi Ryota , Adachi Masaatsu , Nishikawa Toshio , Abe Hideki 
Published: August 2023

AbstractToxic puffers accumulate tetrodotoxin (TTX), a well-known neurotoxin, by feeding on TTX-bearing organisms and using it to defend themselves from predators. Our previous studies have demonstrated that toxic puffers are attracted to 5,6,11-trideoxytetrodotoxin (TDT), a nontoxic TTX analog that is simultaneously accumulated with TTX in toxic puffers and their prey. In addition, activity labeling using immunohistochemistry targeting neuronal activity marker suggests that TDT activates crypt olfactory sensory neurons (OSN) of the green spotted puffer. However, it remains to be determined whether individual crypt OSNs can physiologically respond to TDT. By employing electroporation to express GCaMP6s in OSNs, we successfully identified a distinct group of oval OSNs that exhibited a specific calcium response when exposed to TDT in green spotted puffers. These oval OSNs showed no response to amino acids (AAs), which serve as food odor cues for teleosts. Furthermore, oval morphology and surface positioning of TDT-sensitive OSNs in the olfactory epithelium closely resemble that of crypt OSNs. These findings further substantiate that TDT is specifically detected by crypt OSNs in green spotted puffer. The TDT odor may act as a chemoattractant for finding conspecific toxic puffers and for feeding TTX-bearing organisms for effective toxification.
“Role of a Pdlim5:PalmD complex in directing dendrite morphology”
Authors: Srivastava Yogesh , Donta Maxsam , Mireles Lydia L. , Paulucci-Holthauzen Adriana , Waxham M. Neal , McCrea Pierre D. 
Published: August 2023

SUMMARYNeuronal connectivity is regulated during normal brain development with the arrangement of spines and synapses being dependent on the morphology of dendrites. Further, in multiple neurodevelopmental and aging disorders, disruptions of dendrite formation or shaping is associated with atypical neuronal connectivity. We showed previously that Pdlim5 binds delta-catenin and promotes dendrite branching (Baumert et al.,J Cell Biol2020). We report here that Pdlim5 interacts with PalmD, a protein previously suggested by others to interact with the cytoskeleton (e.g.,viaadducin/spectrin) and to regulate membrane shaping. Functionally, the knockdown of PalmD or Pdlim5 in rat primary hippocampal neurons dramatically reduces branching and conversely, PalmD exogenous expression promotes dendrite branching as does Pdlim5. Further, we show that each proteins’ effects are dependent on the presence of the other. In summary, using primary rat hippocampal neurons we reveal the contributions of a novel Pdlim5:PalmD protein complex, composed of functionally inter-dependent components responsible for shaping neuronal dendrites.
A phylogenetic approach to explore theAspergillus fumigatusconidial surface-associated proteome and its role in pathogenesis
Authors: Valero Clara , Pinzan Camila Figueiredo , de Castro Patrícia Alves , van Rhijn Norman , Earle Kayleigh , Liu Hong , Horta Maria Augusta Crivelente , Kniemeyer Olaf , Krüger Thomas , Pschibul Annica , Coemert Derya Nur , Heinekamp Thorsten , Brakhage Axel A. , Steenwyk Jacob L. , Mead Matthew E. , Rokas Antonis , Filler Scott G. , da Rosa-Garzon Nathalia Gonsales , Cabral Hamilton , Deljabe Endrews , Bromley Michael J. , Angeli Claudia B. , Palmisano Giuseppe , Ibrahim Ashraf S , Gago Sara , dos Reis Thaila F. , Goldman Gustavo H. 
Published: August 2023

ABSTRACTAspergillus fumigatus, an important pulmonary fungal pathogen causing several diseases collectively called aspergillosis, relies on asexual spores or conidia for initiating host infection. Here, we used a phylogenomic approach to compare proteins in the conidial surface ofA. fumigatus, two closely related non-pathogenic species,Aspergillus fischeriandAspergillus oerlinghausenensis, and the cryptic pathogenAspergillus lentulus. After identifying 62 proteins uniquely expressed on theA. fumigatusconidial surface, we deleted 42 genes encoding conidial proteins. We found deletion of 33 of these genes altered susceptibility to macrophage killing, penetration and damage to epithelial cells, and cytokine production. Notably, a gene that encodes glycosylasparaginase, which modulates levels of the host pro-inflammatory cytokine IL-1β, is important for infection in an immunocompetent murine model of fungal disease. These results suggest thatA. fumigatusconidial surface proteins and effectors are important for evasion and modulation of the immune response at the onset of fungal infection.
Critical factors for precise and efficient RNA cleavage by RNase Y inStaphylococcus aureus
Authors: Le Scornet Alexandre , Jousselin Ambre , Baumas Kamila , Kostova Gergana , Durand Sylvain , Poljak Leonora , Barriot Roland , Coutant Eve , Pigearias Romain , Tejero Gabriel , Lootvoet Jonas , Péllisier Céline , Munoz Gladys , Condon Ciarán , Redder Peter 
Published: August 2023

AbstractCellular processes require precise and specific gene regulation, in which continuous mRNA degradation is a major element. The mRNA degradation mechanisms should be able to degrade a wide range of different RNA substrates with high efficiency, but should at the same time be limited, to avoid killing the cell by elimination of all cellular RNA. RNase Y is a major endoribonuclease found in most Firmicutes, includingBacillus subtilisandStaphylococcus aureus. However, the molecular interactions that direct RNase Y to cleave the correct RNA molecules at the correct position remain unknown. In this work we have identified transcripts that are homologs inS. aureusandB. subtilis, and are RNase Y targets in both bacteria. Two such transcript pairs were used as models to show a functional overlap between theS. aureusand theB. subtilisRNase Y, which highlighted the importance of the nucleotide sequence of the RNA molecule itself in the RNase Y targeting process. Cleavage efficiency is driven by the primary nucleotide sequence immediately downstream of the cleavage site and base-pairing in a secondary structure a few nucleotides downstream. Cleavage positioning is roughly localised by the downstream secondary structure and fine-tuned by the nucleotide immediately upstream of the cleavage. The identified elements were sufficient for RNase Y-dependent cleavage, since the sequence elements from one of the model transcripts were able to convert an exogenous non-target transcript into a target for RNase Y.Author summaryIn order to correctly regulate the level of RNAs, bacteria require their RNA to be continuously synthesised and degraded. However, even related bacterial species can have different sets of ribonucleases, each with their own target criteria. Here we explore which sequence elements of an RNA are important for being targeted by the endoribonuclese RNase Y in the two bacteria,Staphylococcus aureusandBacillus subtilis. We specifically examine the RNase Y dependent cleavage of two transcripts that have homologs in both bacteria. We identify a short single-stranded regions immediately downstream of the cleavage position can be modified to change the cleavage efficiency up to 20-fold. We furthermore discover that a secondary structure a few nucleotides downstream of the cleavage is required for cleavage and that the positioning of the cleavage can be modulated by moving this structure.
PRO-LDM: Protein Sequence Generation with a Conditional Latent Diffusion Model
Authors: Zhang Sitao , Jiang Zixuan , Huang Rundong , Mo Shaoxun , Zhu Letao , Li Peiheng , Zhang Ziyi , Pan Emily , Chen Xi , Long Yunfei , Liang Qi , Tang Jin , Xu Renjing , Qing Rui 
Published: August 2023

AbstractsDeep learning-driven protein design holds enormous potential despite the complexities in sequences and structures. Recent developments in diffusion models yielded success in structure design, but awaits progress in sequence design and are computationally demanding. Here we present PRO-LDM: an efficient framework combining design fidelity and computational efficiency, utilizing the diffusion model in latent space to design proteins with property tuning. The model employs a joint autoencoder to capture latent variable distributions and generate meaningful embeddings from sequences. PRO-LDM (1) learns representations from biological features in natural proteins at both amino-acid and sequence level; (2) generates native-like new sequences with enhanced diversity; and (3) conditionally designs new proteins with tailored properties or functions. The out-of-distribution design enables sampling notably different sequences by adjusting classifier guidance strength. Our model presents a feasible pathway and an integratable tool to extract physicochemical and evolutionary information embedded within primary sequences, for protein design and optimization.