bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of severe preeclampsia and intrauterine growth restriction based on serum placental exosome miR-520a-5p levels during the first-trimester
Authors: Xu Xin-Ran , Cheng Lan , Wang Yan-Ping 
Published: May 2024

Background:
To assess the predictive capabilities of serum exosomal levels of micro-RNA-520a-5p (miR-520a-5p) concerning the occurrence of severe preeclampsia (sPE) and fetal growth restriction (FGR) during the first trimester of pregnancy.

Methods:
During the period spanning from October 2020 to October 2021, serum samples were procured from the first trimester and subsequently preserved by freezing at −80 ℃. These samples were obtained from 105 pregnant women in a nested case–control study. This cohort consisted of individuals who later developed sPE (sPE group, n = 35) and FGR (FGR group, n = 35) during the third trimester. Additionally, 35 women with normal blood pressure were denoted as normal pregnancy group. Serum samples from the first trimester were retrieved from all groups for further analysis after thawing. Exosomes were extracted from the serum samples collected during the first trimester and examined using transmission electron microscopy, western blot, and nanoparticle tracking analysis. Additionally, the determination of their placental origin was also established during the course of the study. Exosome miR-520a-5p levels were measured using real-time quantitative polymerase chain reaction assays, primarily involving quantitative reverse transcription polymerase chain reactions. Fetal placental tissues from the 3 groups were collected shortly after birth, and miR-520a-5p expression was measured using real-time quantitative polymerase chain reaction. Serum placental exosomes and fetal placental tissues were compared for miR-520a-5p levels. Placental trophoblasts were identified as the source of serum exosomes in all 3 groups.

Results:
It was found that serum placental exosomes exhibited lower levels of miR-520a-5p in both the sPE and FGR groups when compared to the normal pregnancy group. This finding was consistent with observations made in postpartum placental tissues. The predictive accuracy for sPE using miR-520a-5p levels in serum placental exosomes during the first trimester was notably higher (area under the receiver operating characteristic curve = 0.806, P <.05) compared to the prediction of FGR (area under the receiver operating characteristic curve = 0.628, P <.05).

Conclusion:
Placenta-derived exosomes can be extracted from maternal serum during the first trimester of pregnancy and miR-520a-5p detected from the exosomes. The downregulation of miR-520a-5p serves as a more predictive indicator for the subsequent development of sPE compared to predicting FGR.
A Prospective Study of the Diagnostic Performance of Photon-Counting CT Compared With MRI in the Characterization of Renal Masses
Authors: Homayounieh Fatemeh , Gopal Nikhil , Firouzabadi Fatemeh Dehghani , Sahbaee Pooyan , Yazdian Pouria , Nikpanah Moozhan , Do Michael , Wang Muyang , Gautam Rabindra , Ball Mark W. , Pritchard William F. , Jones Elizabeth C. , Wen Han , Linehan W. Marston , Turkbey Evrim B. , Malayeri Ashkan A. 
Published: May 2024

Objectives
The aim of this study was to assess the interreader reliability and per-RCC sensitivity of high-resolution photon-counting computed tomography (PCCT) in the detection and characterization of renal masses in comparison to MRI.

Materials and Methods
This prospective study included 24 adult patients (mean age, 52 ± 14 years; 14 females) who underwent PCCT (using an investigational whole-body CT scanner) and abdominal MRI within a 3-month time interval and underwent surgical resection (partial or radical nephrectomy) with histopathology (n = 70 lesions). Of the 24 patients, 17 had a germline mutation and the remainder were sporadic cases. Two radiologists (R1 and R2) assessed the PCCT and corresponding MRI studies with a 3-week washout period between reviews. Readers recorded the number of lesions in each patient and graded each targeted lesion's characteristic features, dimensions, and location. Data were analyzed using a 2-sample t test, Fisher exact test, and weighted kappa.

Results
In patients with von Hippel–Lindau mutation, R1 identified a similar number of lesions suspicious for neoplasm on both modalities (51 vs 50, P = 0.94), whereas R2 identified more suspicious lesions on PCCT scans as compared with MRI studies (80 vs 56, P = 0.12). R1 and R2 characterized more lesions as predominantly solid in MRIs (R1: 58/70 in MRI vs 52/70 in PCCT, P < 0.001; R2: 60/70 in MRI vs 55/70 in PCCT, P < 0.001). R1 and R2 performed similarly in detecting neoplastic lesions on PCCT and MRI studies (R1: 94% vs 90%, P = 0.5; R2: 73% vs 79%, P = 0.13).

Conclusions
The interreader reliability and per-RCC sensitivity of PCCT scans acquired on an investigational whole-body PCCT were comparable to MRI scans in detecting and characterizing renal masses.

Clinical Relevance Statement
PCCT scans have comparable performance to MRI studies while allowing for improved characterization of the internal composition of lesions due to material decomposition analysis. Future generations of this imaging modality may reveal additional advantages of PCCT over MRI.
Bacterial Colonization on Endoscopic Materials and Surgical Field Without Infections After Transoral Endoscopic Thyroidectomy
Authors: Zhang Daqi , Sun Hui , Kim Hoon Yub , Chai Young Jun , Tufano Ralph P. , Wu Che-Wei , Pino Antonella , Anuwong Angoon , Dionigi Gianlorenzo 
Published: May 2024

Introduction:
Our aim was to determine whether bacteria contamination occurred within the surgical field or on endoscopic equipment during surgery using the transoral endoscopic thyroidectomy vestibular approach (TOETVA).

Materials and Methods:
Participants were recruited from patients planned for TOETVA between May 2017 and December 2019. Bacterial samples were taken before and at the conclusion of the TOETVA procedure. The preoperative and postoperative samples were taken from the endoscopic materials and inferior oral vestibulum using a sterile flocked swab.

Results:
The study resulted in 480 samples (80 TOETVAs). No vestibular, port site, or neck infections occurred in any of the patients. Three (3.7%) out of 80 patients developed postoperative fever. Our results show different microbial communities during TOETVA. The most prevalent species detected were Streptococcus species. Multivariate logistic regression analyses revealed that the degree of contamination depended on the sampling site (inferior vestibulum > equipment) (P=0.03). In addition, the abundance of bacteria was affected by operative time (P=0.013). There were no significant differences observed in isolation frequencies of bacteria in malignancy (P=0.34).

Conclusions:
TOETVA surgery is categorized as a “clean-contaminated” operation. A swab identified the common colonizers of oral microbiota on the endoscopic equipment and within the surgical field.
Cytomegalovirus Matching in Deceased Donor Kidney Allocation: Results From a U.S. National Simulation Model
Authors: Sandikçi Burhaneddin , Ulukuş M. Yasin , Ergün Mehmet Ali , Tanriöver Bekir 
Published: May 2024

Background.Cytomegalovirus (CMV) infects >60% of adults and can pose an independent risk factor for allograft loss and mortality in solid organ transplant recipients. The purpose of this study is to evaluate the impact of a nationwide implementation of CMV seromatching (donor/recipient: D−/R− and D+/R+) in the U.S. deceased donor kidney allocation system (KAS).Methods.Adult candidates on the U.S. kidney-only transplant waiting list and deceased donor kidneys offered to the U.S. transplant centers were considered. A discrete-event simulation model, simulating the pre-COVID-19 period from January 1, 2015, to January 1, 2018, was used to compare the performances of currently employed KAS-250 policy (without CMV matching) to various simulated CMV matching policies parameterized by calculated panel reactive antibody exception threshold. Outcomes included CMV serodistribution, waiting time, access to transplantation among various groups, transplant rate, graft survival, kidney discard rate, and antigen-mismatch distribution, stratified by CMV serostatus.Results.CMV matching policy with a calculated panel reactive antibody exception threshold of 50% (namely, theCMV“>50%”policy) strikes a better balance between benefits and drawbacks of CMV matching. Compared with KAS-250,CMV“>50%”reduced CMV high-risk (D+/R−) transplants (6.1% versus 18.1%) and increased CMV low-risk (D−/R−) transplants (27.2% versus 13.1%); increased transplant rate for CMV R− patients (11.54 versus 12.57) but decreased for R+ patients (10.68 versus 10.48), yielding an increase in aggregate (11.09 versus 10.94); and reduced mean time to transplantation (by 6 wk); and reduced kidney discard rate (25.7% versus 26.2%).Conclusions.Our findings underscore the feasibility and potential advantages of a nationwide CMV seromatching policy in kidney transplantation.
“No-Touch” Left Approach for Recipient Hepatectomy: A Promising Strategy to Minimize Hepatocellular Carcinoma Recurrence in Liver Transplantation
Authors: Yang Shiwei , Rong Guanghua , Tan Haidong , Liu Xiaolei , Si Shuang , Zhou Ruiquan , Wang Haotong , Zhu Jiqiao , Li Xianliang , He Qiang , Han Dongdong 
Published: May 2024

Background.
Managing hepatocellular carcinoma (HCC) presents significant clinical challenges, often necessitating orthotopic liver transplantation (OLT). To mitigate the risk of iatrogenic metastasis during OLT and reduce posttransplantation recurrence (PTR), we introduced the “no-touch” left (NTL) approach for recipient hepatectomy in OLT.

Methods.
In this retrospective cohort study, our aim was to compare the safety and PTR rates in patients undergoing OLT via either the NTL technique or the conventional approach for recipient hepatectomy. We included 106 patients who met the Hangzhou criteria and exhibited a high tumor burden in the right lobe, with 50 patients assigned to the NTL group and 56 to the conventional group. The primary endpoint was the 1-y PTR rate, whereas secondary endpoints encompassed the safety of the NTL approach, PTR rates at 2 and 5 y, and overall survival.

Results.
Baseline demographics and clinical characteristics showed no significant differences between the groups. The NTL approach exhibited major surgical outcomes similar to those of the conventional approach. The cumulative PTR rates at 1, 2, and 5 y were 14.0% in the NTL group, compared with 24.5%, 35.8%, and 35.8% in the conventional group (P = 0.013). Cumulative overall survival rates at 1, 2, and 5 y were 94.0%, 91.9%, and 89.7% in the NTL group and 88.7%, 75.5%, and 72.5% in the conventional group (P = 0.03).

Conclusions.
This innovative surgical technique enhances safety and significantly reduces the risk of PTR, leading to improved long-term survival. Further prospective studies with larger cohorts and longer follow-up periods are needed to validate our findings and establish the NTL approach as a standard practice in OLT.
Identifying Novel Therapeutic Targets for Overcoming TNBC Chemo Resistance Through Comprehensive CRISPR-Cas9 Genome Screening
Authors: Shao Shuai , Li Shangjia , Tang Shan , Fan Kunjie , Li Lang 
Published: May 2024

ABSTRACTTriple-negative breast cancer (TNBC) represents 15-20% of cases but disproportionately contributes to 35% of breast cancer deaths. Chemotherapy resistance remains a significant challenge in TNBC treatment. In this study, we identified the MDA-MB-231 cell line as the most representative model for TNBC chemotherapy-poor responders by comparing genomic profiles from TNBC cell lines and patient samples. We performed a genome-wide CRISPR-Cas9 screen and RNAseq analysis in MDA-MB-231 cells to uncover potential synthetic lethal targets for cisplatin/doxorubicin treatment.Our analysis confirmed the involvement of known essential genes in DNA damage repair and regulation of DNA replication pathways, such as BCL2L1, ATM, CDC25B, and NBN, in sensitizing cells to cisplatin/doxorubicin. Additionally, We identified hundreds of previously unrecognized genes and pathways related to DNA repair, G2/M DNA damage checkpoint, AMPK signaling, and mTOR signaling. The observed differences between transcriptomic responses and essential pathways from the CRISPR screen suggest a complex regulatory system in cellular response to DNA damage drugs. By combining various data analysis methods and biological experimental approaches, we have pinpointed several promising genes, such as MCM9 and NEPPS, which could serve as potential drug targets to overcome chemoresistance.Overall, our approach efficiently identified essential genes with potential synthetic lethal interactions with cisplatin/doxorubicin, offering new possibilities for combination therapies in chemo resistant TNBC patients.
Recombinant inbred line panels inform the genetic architecture and interactions of adaptive traits inDrosophila melanogaster
Authors: Ribeiro Tiago da Silva , Lollar Matthew J. , Sprengelmeyer Quentin D. , Huang Yuheng , Benson Derek M. , Orr Megan S. , Johnson Zachary C. , Corbett-Detig Russell B. , Pool John E. 
Published: May 2024

AbstractThe distribution of allelic effects on traits, along with their gene-by-gene and gene-by-environment interactions, contributes to the phenotypes available for selection and the trajectories of adaptive variants. Nonetheless, uncertainty persists regarding the effect sizes underlying adaptations and the importance of genetic interactions. Herein, we aimed to investigate the genetic architecture and the epistatic and environmental interactions involving loci that contribute to multiple adaptive traits using two new panels ofDrosophila melanogasterrecombinant inbred lines (RILs). To better fit our data, we re-implemented functions from R/qtl (Bromanet al. 2003) using additive genetic models. We found 14 quantitative trait loci (QTL) underlying melanism, wing size, song pattern, and ethanol resistance. By combining our mapping results with population genetic statistics, we identified potential new genes related to these traits. None of the detected QTLs showed clear evidence of epistasis, and our power analysis indicated that we should have seen at least one significant interaction if sign epistasis or strong positive epistasis played a pervasive role in trait evolution. In contrast, we did find roles for gene-by-environment interactions involving pigmentation traits. Overall, our data suggest that the genetic architecture of adaptive traits often involves alleles of detectable effect, that strong epistasis does not always play a role in adaptation, and that environmental interactions can modulate the effect size of adaptive alleles.
The landscape of gene loss and missense variation across the mammalian tree informs on gene essentiality
Authors: Liao Calwing , Ye Robert , Ivankovic Franjo , Fu Jack M. , Walters Raymond , Lowther Chelsea , Walkanas Elise , Churchhouse Claire , Samocha Kaitlin E. , Lindblad-Toh Kerstin , Karlsson Elinor , Hiller Michael , Talkowski Michael E. , Neale Benjamin M. 
Published: May 2024

ABSTRACTBackgroundThe degree of gene and sequence preservation across species provides valuable insights into the relative necessity of genes from the perspective of natural selection. Here, we developed novel interspecies metrics across 462 mammalian species, GISMO (Gene identity score of mammalian orthologs) and GISMO-mis (GISMO-missense), to quantify gene loss traversing millions of years of evolution. GISMO is a measure of gene loss across mammals weighed by evolutionary distance relative to humans, whereas GISMO-mis quantifies the ratio of missense to synonymous variants across mammalian species for a given gene.RationaleDespite large sample sizes, current human constraint metrics are still not well calibrated for short genes. Traversing over 100 million years of evolution across hundreds of mammals can identify the most essential genes and improve gene-disease association. Beyond human genetics, these metrics provide measures of gene constraint to further enable mammalian genetics research.ResultsOur analyses showed that both metrics are strongly correlated with measures of human gene constraint for loss-of-function, missense, and copy number dosage derived from upwards of a million human samples, which highlight the power of interspecies constraint. Importantly, neither GISMO nor GISMO-mis are strongly correlated with coding sequence length. Therefore both metrics can identify novel constrained genes that were too small for existing human constraint metrics to capture. We also found that GISMO scores capture rare variant association signals across a range of phenotypes associated with decreased fecundity, such as schizophrenia, autism, and neurodevelopmental disorders. Moreover, common variant heritability of disease traits are highly enriched in the most constrained deciles of both metrics, further underscoring the biological relevance of these metrics in identifying functionally important genes. We further showed that both scores have the lowest duplication and deletion rate in the most constrained deciles for copy number variants in the UK Biobank, suggesting that it may be an important metric for dosage sensitivity. We additionally demonstrate that GISMO can improve prioritization of recessive disorder genes and captures homozygous selection.ConclusionsOverall, we demonstrate that the most constrained genes for gene loss and missense variation capture the largest fraction of heritability, GISMO can help prioritize recessive disorder genes, and identify the most conserved genes across the mammalian tree.
Crosstalk of growth factor receptors at plasma membrane clathrin-coated sites
Authors: Alfonzo-Méndez Marco A. , Strub Marie-Paule , Taraska Justin W. 
Published: May 2024

AbstractCellular communication is regulated at the plasma membrane by the interactions of receptor, adhesion, signaling, exocytic, and endocytic proteins. Yet, the composition and control of these nanoscale complexes in response to external cues remain unclear. Here, we use high-resolution and high-throughput fluorescence imaging to map the localization of growth factor receptors and related proteins at single clathrin-coated structures across the plasma membrane of human squamous HSC3 cells. We find distinct protein signatures between control cells and cells stimulated with ligands. Clathrin sites at the plasma membrane are preloaded with some receptors but not others. Stimulation with epidermal growth factor induces a capture and concentration of epidermal growth factor-, fibroblast growth factor-, and low-density lipoprotein-receptors (EGFR, FGFR, and LDLR). Regulatory proteins including ubiquitin ligase Cbl, the scaffold Grb2, and the mechanoenzyme dynamin2 are also recruited. Disrupting FGFR or EGFR individually with drugs prevents the recruitment of both EGFR and FGFR. Our data reveals novel crosstalk between multiple unrelated receptors and regulatory factors at clathrin-coated sites in response to stimulation by a single growth factor, EGF. This behavior integrates growth factor signaling and allows for complex responses to extracellular cues and drugs at the plasma membrane of human cells.SignificanceClassically, receptor pathways including epidermal growth factor receptor and fibroblast growth factor receptor were thought of as independent systems. Yet, the plasma membrane is a complex environment where proteins interact, cluster, signal, and associate with organelles. For example, after EGF activation, EGFR is captured at sites on the inner plasma membrane coated with the protein clathrin. This causes clathrin to grow flat across the adherent membrane. Here, we observe co-capture along with EGFR of the related receptor FGFR and unrelated LDLR by clathrin after EGF stimulation. This is specific as other receptors are unaffected. Thus, separate but specific receptor systems co-assemble and signal to each other at nanoscale zones on the plasma membrane organized by clathrin. This provides new avenues for treating diseases like cancer.
Network-based biomarkers in background electroencephalography in childhood epilepsies – A scoping review and narrative synthesis
Authors: Meiklejohn Kay , Junges Leandro , Terry John R. , Whight Alison , Shankar Rohit , Woldman Wessel 
Published: May 2024

AbstractBackgroundBrain network analysis is an emerging field of research that could lead to the development, testing and validation of novel biomarkers for epilepsy. This could shorten the diagnostic uncertainty period, improve treatment, decrease seizure risk and lead to better management. This scoping review summarises the current state of electroencephalogram (EEG)-based network abnormalities for childhood epilepsies. The review assesses the overall robustness, potential generalizability, strengths, and limitations of the methodological frameworks of the identified research studies.MethodsPRISMA guidelines for Scoping Reviews and the PICO framework was used to guide this review. Studies that evaluated candidate network-based features from EEG in children were retrieved from four international indexing databases (Cochrane Central / Embase / Medline / PsycINFO). Each selected study design, intervention characteristics, methodological design, potential limitations, and key findings were analysed.ResultsOf 2,959 studies retrieved nine were included. Studies used a group-level based comparison (e.g. based on a statistical test) or a classification-based method (e.g. based on a statistical model, such as a decision tree). A common limitation was the small sample-sizes (limiting further subgroup or confounder analysis) and the overall heterogeneity in epilepsy syndromes and age groups.ConclusionThe heterogeneity of included studies (e.g. study design, statistical framework, outcome metrics) highlights the need for future studies to adhere to standardized frameworks (e.g. STARD) in order to develop standardized and robust methodologies. This would enable rigorous comparisons between studies, which is critical in assessing the potential of network-based approaches in developing novel biomarkers for childhood epilepsies.
Ecosystem’s Oxygen Deficiency and Selection of Antimicrobial Resistance Genes in a One Health Perspective
Authors: Ortiz-Miravalles Laura , Prieto Amalia , Kieffer Nicolas , Vergara Ester , Cantón Rafael , Millán Álvaro San , Baquero Fernando , Hipólito Alberto , Escudero José Antonio 
Published: May 2024

AbstractBacteria must face and adapt to a variety of physicochemical conditions in the environment and during infection. A key condition is the concentration of dissolved oxygen, proportional to the partial pressure of oxygen (PO2), which is extremely variable among environmental biogeographical areas and also compartments of the human and animal body. Here, we sought to understand if the phenotype of resistance determinants commonly found in Enterobacterales can be influenced by oxygen pressure. To do so, we have compared the MIC in aerobic and anaerobic conditions of isogenicEscherichia colistrains containing 136 different resistance genes against 9 antibiotic families. Our results show a complex landscape of changes in the performance of resistance genes in anaerobiosis. Certain changes are especially relevant for their intensity and the importance of the antibiotic family, like the large decreases in resistance observed against ertapenem and fosfomycin amongblaVIMß-lactamases and certainfosgenes, respectively; however, theblaOXA-48ß-lactamase from the clinically relevant pOXA-48 plasmid conferred 4-fold higher ertapenem resistance in anaerobiosis. Strong changes in resistance patterns in anaerobiosis were also conserved inKlebsiella pneumoniae. Our results suggest that anaerobiosis is a relevant aspect that can affect the action and selective power of antibiotics for specific AMRs in different environments.