bluuebunny/crossref_metadata_2025_split huggingface dataset:
A landscape of gene expression regulation for synovium in arthritis
Authors: Jiang Feng , Hu Shou-Ye , Tian Wen , Wang Nai-Ning , Yang Ning , Dong Shan-Shan , Song Hui-Miao , Zhang Da-Jin , Gao Hui-Wu , Wang Chen , Wu Hao , He Chang-Yi , Zhu Dong-Li , Chen Xiao-Feng , Guo Yan , Yang Zhi , Yang Tie-Lin 
Published: February 2024

AbstractThe synovium is an important component of any synovial joint and is the major target tissue of inflammatory arthritis. However, the multi-omics landscape of synovium required for functional inference is absent from large-scale resources. Here we integrate genomics with transcriptomics and chromatin accessibility features of human synovium in up to 245 arthritic patients, to characterize the landscape of genetic regulation on gene expression and the regulatory mechanisms mediating arthritic diseases predisposition. We identify 4765 independent primary and 616 secondary cis-expression quantitative trait loci (cis-eQTLs) in the synovium and find that the eQTLs with multiple independent signals have stronger effects and heritability than single independent eQTLs. Integration of genome-wide association studies (GWASs) and eQTLs identifies 84 arthritis related genes, revealing 38 novel genes which have not been reported by previous studies using eQTL data from the GTEx project or immune cells. We further develop a method called eQTac to identify variants that could affect gene expression by affecting chromatin accessibility and identify 1517 regions with potential regulatory function of chromatin accessibility. Altogether, our study provides a comprehensive synovium multi-omics resource for arthritic diseases and gains new insights into the regulation of gene expression.
TFvelo: gene regulation inspired RNA velocity estimation
Authors: Li Jiachen , Pan Xiaoyong , Yuan Ye , Shen Hong-Bin 
Published: February 2024

AbstractRNA velocity is closely related with cell fate and is an important indicator for the prediction of cell states with elegant physical explanation derived from single-cell RNA-seq data. Most existing RNA velocity models aim to extract dynamics from the phase delay between unspliced and spliced mRNA for each individual gene. However, unspliced/spliced mRNA abundance may not provide sufficient signal for dynamic modeling, leading to poor fit in phase portraits. Motivated by the idea that RNA velocity could be driven by the transcriptional regulation, we propose TFvelo, which expands RNA velocity concept to various single-cell datasets without relying on splicing information, by introducing gene regulatory information. Our experiments on synthetic data and multiple scRNA-Seq datasets show that TFvelo can accurately fit genes dynamics on phase portraits, and effectively infer cell pseudo-time and trajectory from RNA abundance data. TFvelo opens a robust and accurate avenue for modeling RNA velocity for single cell data.
Ca-dimers, solvent layering, and dominant electrochemically active species in Ca(BH4)2 in THF
Authors: Sanz Matias Ana , Roncoroni Fabrice , Sundararaman Siddharth , Prendergast David 
Published: February 2024

AbstractDivalent ions (Mg, Ca, and Zn) are being considered as competitive, safe, and earth-abundant alternatives to Li-ion electrochemistry, but present challenges for stable cycling due to undesirable interfacial phenomena. We explore the formation of electroactive species in the electrolyte Ca(BH4)2∣THF using molecular dynamics coupled with a continuum model of bulk and interfacial speciation. Free-energy analysis and unsupervised learning indicate a majority population of neutral Ca dimers and monomers with diverse molecular conformations and an order of magnitude lower concentration of the primary electroactive charged species – the monocation, $${\rm{CaBH}}_{4}^{+}$$

CaBH

4

+

– produced via disproportionation of neutral complexes. Dense layering of THF molecules within ~1 nm of the electrode surface strongly modulates local electrolyte species populations. A dramatic increase in monocation population in this interfacial zone is induced at negative bias. We see no evidence for electrochemical activity of fully-solvated Ca2+. The consequences for performance are discussed in light of this molecular-scale insight.
Flexible and cost-effective genomic surveillance of P. falciparum malaria with targeted nanopore sequencing
Authors: de Cesare Mariateresa , Mwenda Mulenga , Jeffreys Anna E. , Chirwa Jacob , Drakeley Chris , Schneider Kammerle , Mambwe Brenda , Glanz Karolina , Ntalla Christina , Carrasquilla Manuela , Portugal Silvia , Verity Robert J. , Bailey Jeffrey A. , Ghinai Isaac , Busby George B. , Hamainza Busiku , Hawela Moonga , Bridges Daniel J. , Hendry Jason A. 
Published: February 2024

AbstractGenomic surveillance of Plasmodium falciparum malaria can provide policy-relevant information about antimalarial drug resistance, diagnostic test failure, and the evolution of vaccine targets. Yet the large and low complexity genome of P. falciparum complicates the development of genomic methods, while resource constraints in malaria endemic regions can limit their deployment. Here, we demonstrate an approach for targeted nanopore sequencing of P. falciparum from dried blood spots (DBS) that enables cost-effective genomic surveillance of malaria in low-resource settings. We release software that facilitates flexible design of amplicon sequencing panels and use this software to design two target panels for P. falciparum. The panels generate 3–4 kbp reads for eight and sixteen targets respectively, covering key drug-resistance associated genes, diagnostic test antigens, polymorphic markers and the vaccine target csp. We validate our approach on mock and field samples, demonstrating robust sequencing coverage, accurate variant calls within coding sequences, the ability to explore P. falciparum within-sample diversity and to detect deletions underlying rapid diagnostic test failure.
Integrated microcavity electric field sensors using Pound-Drever-Hall detection
Authors: Ma Xinyu , Cai Zhaoyu , Zhuang Chijie , Liu Xiangdong , Zhang Zhecheng , Liu Kewei , Cao Bo , He Jinliang , Yang Changxi , Bao Chengying , Zeng Rong 
Published: February 2024

AbstractDiscerning weak electric fields has important implications for cosmology, quantum technology, and identifying power system failures. Photonic integration of electric field sensors is highly desired for practical considerations and offers opportunities to improve performance by enhancing microwave and lightwave interactions. Here, we demonstrate a high-Q microcavity electric field sensor (MEFS) by leveraging the silicon chip-based thin film lithium niobate photonic integrated circuits. Using the Pound-Drever-Hall detection scheme, our MEFS achieves a detection sensitivity of 5.2 μV/(m$$\sqrt{{{{{{{{\rm{Hz}}}}}}}}}$$

Hz

), which surpasses previous lithium niobate electro-optical electric field sensors by nearly two orders of magnitude, and is comparable to atom-based quantum sensing approaches. Furthermore, our MEFS has a bandwidth that can be up to three orders of magnitude broader than quantum sensing approaches and measures fast electric field amplitude and phase variations in real-time. The ultra-sensitive MEFSs represent a significant step towards building electric field sensing networks and broaden the application spectrum of integrated microcavities.
Assessing the impact of mRNA vaccination in chronic inflammatory murine model
Authors: Lee Seonghyun , Lee Jisun , Cho Sun-Hee , Roh Gahyun , Park Hyo-Jung , Lee You-Jeung , Jeon Ha-Eun , Lee Yu-Sun , Bae Seo-Hyeon , Youn Sue Bean , Cho Youngran , Oh Ayoung , Ha Dahyeon , Lee Soo-Yeon , Choi Eun-Jin , Cho Seongje , Lee Sowon , Kim Do-Hyung , Kang Min-Ho , Yoon Mee-Sup , Lim Byung-Kwan , Nam Jae-Hwan 
Published: February 2024

AbstractThe implications of administration of mRNA vaccines to individuals with chronic inflammatory diseases, including myocarditis, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD), are unclear. We investigated mRNA vaccine effects in a chronic inflammation mouse model implanted with an LPS pump, focusing on toxicity and immunogenicity. Under chronic inflammation, mRNA vaccines exacerbated cardiac damage and myocarditis, inducing mild heart inflammation with heightened pro-inflammatory cytokine production and inflammatory cell infiltration in the heart. Concurrently, significant muscle damage occurred, with disturbances in mitochondrial fusion and fission factors signaling impaired muscle repair. However, chronic inflammation did not adversely affect muscles at the vaccination site or humoral immune responses; nevertheless, it partially reduced the cell-mediated immune response, particularly T-cell activation. These findings underscore the importance of addressing mRNA vaccine toxicity and immunogenicity in the context of chronic inflammation, ensuring their safe and effective utilization, particularly among vulnerable populations with immune-mediated inflammatory diseases.
Effectiveness and safety of telehealth medication abortion in the USA
Authors: Upadhyay Ushma D. , Koenig Leah R. , Meckstroth Karen , Ko Jennifer , Valladares Ena Suseth , Biggs M. Antonia 
Published: February 2024

AbstractTelehealth abortion has become critical to addressing surges in demand in states where abortion remains legal but evidence on its effectiveness and safety is limited. California Home Abortion by Telehealth (CHAT) is a prospective study that follows pregnant people who obtained medication abortion via telehealth from three virtual clinics operating in 20 states and Washington, DC between April 2021 and January 2022. Individuals were screened using a standardized no-test protocol, primarily relying on their medical history to assess medical eligibility. We assessed effectiveness, defined as complete abortion after 200 mg mifepristone and 1,600 μg misoprostol (or lower) without additional intervention; safety was measured by the absence of serious adverse events. We estimated rates using multivariable logistic regression and multiple imputation to account for missing data. Among 6,034 abortions, 97.7% (95% confidence interval (CI) = 97.2–98.1%) were complete without subsequent known intervention or ongoing pregnancy after the initial treatment. Overall, 99.8% (99.6–99.9%) of abortions were not followed by serious adverse events. In total, 0.25% of patients experienced a serious abortion-related adverse event, 0.16% were treated for an ectopic pregnancy and 1.3% abortions were followed by emergency department visits. There were no differences in effectiveness or safety between synchronous and asynchronous models of care. Telehealth medication abortion is effective, safe and comparable to published rates of in-person medication abortion care.
A neuron–glia lipid metabolic cycle couples daily sleep to mitochondrial homeostasis
Authors: Haynes Paula R. , Pyfrom Elana S. , Li Yongjun , Stein Carly , Cuddapah Vishnu Anand , Jacobs Jack A. , Yue Zhifeng , Sehgal Amita 
Published: February 2024

AbstractSleep is thought to be restorative to brain energy homeostasis, but it is not clear how this is achieved. We show here that Drosophila glia exhibit a daily cycle of glial mitochondrial oxidation and lipid accumulation that is dependent on prior wake and requires the Drosophila APOE orthologs NLaz and GLaz, which mediate neuron–glia lipid transfer. In turn, a full night of sleep is required for glial lipid clearance, mitochondrial oxidative recovery and maximal neuronal mitophagy. Knockdown of neuronal NLaz causes oxidative stress to accumulate in neurons, and the neuronal mitochondrial integrity protein, Drp1, is required for daily glial lipid accumulation. These data suggest that neurons avoid accumulation of oxidative mitochondrial damage during wake by using mitophagy and passing damage to glia in the form of lipids. We propose that a mitochondrial lipid metabolic cycle between neurons and glia reflects a fundamental function of sleep relevant for brain energy homeostasis.
Long term outcomes of hyperbaric oxygen therapy in post covid condition: longitudinal follow-up of a randomized controlled trial
Authors: Hadanny Amir , Zilberman-Itskovich Shani , Catalogna Merav , Elman-Shina Karin , Lang Erez , Finci Shachar , Polak Nir , Shorer Ran , Parag Yoav , Efrati Shai 
Published: February 2024

AbstractIn our previous randomized controlled trial, we documented significant improvements in cognitive, psychiatric, fatigue, sleep, and pain symptoms among long Coronavirus disease 2019 (COVID) patients who underwent hyperbaric oxygen therapy (HBOT). The primary objective of the present study was to evaluate the enduring 1 year long term effects of HBOT on long COVID syndrome. This longitudinal long-term follow-up included 31 patients with reported post COVID-19 cognitive symptoms, who underwent 40 daily sessions of HBOT. Participants were recruited more than one year (486 ± 73) after completion of the last HBOT session. Quality of life, assessed using the short form-36 (SF-36) questionnaire revealed, that the long-term results exhibited a similar magnitude of improvement as the short-term outcomes following HBOT across most domains. Regarding sleep quality, improvements were observed in global score and across five sleep domains with effect sizes of moderate magnitude during the short-term evaluation, and these improvements persisted in the long-term assessment (effect size (ES1) = 0.47–0.79). In the realm of neuropsychiatric symptoms, as evaluated by the brief symptom inventory-18 (BSI-18), the short-term assessment following HBOT demonstrated a large effect size, and this effect persisted at the long-term evaluation. Both pain severity (ES1 = 0.69) and pain interference (ES1 = 0.83), had significant improvements during the short-term assessment post HBOT, which persisted at long term. The results indicate HBOT can improve the quality of life, quality of sleep, psychiatric and pain symptoms of patients suffering from long COVID. The clinical improvements gained by HBOT are persistent even 1 year after the last HBOT session.
The effect of minimizing central line days for very low birth weight infants through quality improvement
Authors: Shin Jeongmin , Kang Hyun Mi , Kim Sae Yun , Youn Young-Ah , Choi Chang Won , Chang Yun Sil 
Published: February 2024

AbstractBlood culture proven sepsis is associated with increased mortality and morbidity. Given the extended hospitalization of very preterm infants, catheter-related blood stream infections (CRBSIs) play a substantial role in sepsis. The reported incidence of CRBSIs in neonates varies from 3.2 to 21.8 CRBSIs per 1000 catheter line days. Moreover, discrepancies in neonatal practices and potential neglect may lead to the unwarranted prolongation of central lines. This study aims to compare two distinct periods (Pre-QI vs. Post-QI) in relation to the central line insertion rate and duration, as well as blood culture proven sepsis, duration of total parenteral nutrition (TPN), and the progression of feeding. These factors are known to be associated with prolonged hospitalization and increased morbidities. A total of 210 very low birth weight infants (VLBWIs), defined as either less than 32 weeks of gestational age (GA) or weighing less than 1500 g, were admitted to the Neonatal Intensive Care Unit (NICU) at Seoul St. Mary’s Hospital, The Catholic University of Korea, between January 2020 and June 2023. Fourteen infants were excluded from the study as they did not survive beyond 1 month of life, and one was excluded due to a congenital anomaly. Consequently, the analysis included 195 VLBWIs. The Quality Improvement (QI) initiative began in January 2022, marking the division into two distinct epochs: the Pre-QI period, encompassing the years 2020 to 2021, and the Post-QI period, spanning from 2022 to 2023. The primary outcome measures included PICC insertion rates, duration, and feeding advancement or feeding-related complications. The hospital outcome measures were also compared between the two periods. A total of 195 VLBWI were included in the analysis. The birth weight was significantly lower in the pre-QI period, with an average of 1023 g compared to 1218 g (P < 0.001). Severe BPD ≥ moderate was significantly lower in the post-QI period (36.2% vs. 53.9%) (P < 0.001) along with shorter mechanical ventilation days (12 ± 29 vs. 22 ± 27) (P = 0.046). The PICC insertion rate was significantly decreased from 95.6% in pre-QI period compared to 55.2% in post-QI period (P < 0.001) along with a notable reduction in blood culture-proven sepsis (25.6% vs. 10.5%, P = 0.008). CRBSI rate was reduced from 1.3 to 1.1 per 1000 catheter days in the post-QI period. Moreover, the time required to achieve full enteral feeding of 100 mL/kg/day was significantly shorter in the post-QI (24 ± 23 vs. 33 ± 25) (P = 0.006). Multivariable logistic regression analysis for sepsis revealed that both birth weight and pre/post QI consistently demonstrated an association with lower sepsis rates in the Post-QI period. QI has the potential to reduce the burden of unnecessary interventions and blood culture proven sepsis rate along with CRBSI rate, thereby, optimizing the better care of very preterm babies.
Neonatal lupus erythematosus as a rare trigger of gastrointestinal involvement in neonates
Authors: Fu Changchang , Sun Wenqiang , Peng Hanghang , Zhu Xueping 
Published: February 2024

AbstractCutaneous and cardiac involvement in neonatal lupus erythematosus (NLE) has been extensively studied; however, gastrointestinal system involvement (GSI) remains unexplored. This study aimed to investigate the clinical features of GSI in patients with NLE with a particular focus on feeding intolerance (FI) and diarrhea. We conducted a retrospective analysis of the clinical data of patients diagnosed with NLE at the Children’s Hospital of Soochow University between 2011 and 2022. In this study, of 39 patients diagnosed with NLE, 27 presented with GSI. 9 patients who presented with FI or diarrhea as the primary manifestation were positive for anti-SSA antibody, and 5 were dual positive for anti-SSA and anti-SSB antibodies. Among the mothers of the NLE patients with GSI, 18 had systemic lupus erythematosus, 3 had Sjogren’s syndrome, 2 had mixed connective tissue disease, and one each had autoantibody abnormalities and photosensitivity symptoms; 4 mothers denied having any autoimmune disease. In this study, 69.23% of patients with NLE exhibited GSI, which was linked to hypocomplementemia and anti-SSA antibodies. Thus, clinicians should remain vigilant for NLE in neonates, particularly when accompanied with rash and other organ dysfunction and when the high-risk factors of FI and diarrhea have been excluded.
The use of blackcurrant pomace and erythritol to optimise the functional properties of shortbread cookies
Authors: Raczkowska Ewa , Wojdyło Aneta , Nowicka Paulina 
Published: February 2024

AbstractAs a result of the production of blackcurrant juice, pomace is produced, which is a cheap, easy to further process raw material with high health benefits. The aim of the research was to develop a recipe for shortbread cookies based on blackcurrant pomace (0, 10, 30, 50%) and erythritol, and to assess their nutritional value (content of proteins, fats, sugars, dietary fibre, selected minerals and energy value), pro-health properties (antioxidant and anti-diabetic capacity) and sensory evaluation. The energy value of products with 50% of pomace sweetened with erythritol was nearly 30% lower compared to traditional cookies, while the content of dietary fibre was 10 times higher in products with the highest percentage of pomace. The antioxidant capacity and the total content of polyphenolic compounds increased with the increase in pomace content. The ability to inhibit α-amylase by shortbread cookies without pomace was about 400 times lower than those with 50% pomace. The results of the sensory evaluation showed that erythritol-sweetened cookies have more desirable characteristics compared to sucrose-sweetened cookies. Finally, it was proved that the proposed products are an excellent proposal for people struggling with food-dependent diseases, as well as being an opportunity to manage waste from the fruit industry.
Analysis and identification of oxidative stress-ferroptosis related biomarkers in ischemic stroke
Authors: Zhang Lin-Ming , Liang Xing-ling , Xiong Gui-fei , Xing xuan-lin , Zhang Qiu-juan , Zhang Bing-ran , Liu Ming-wei 
Published: February 2024

AbstractStudies have shown that a series of molecular events caused by oxidative stress is associated with ferroptosis and oxidation after ischemic stroke (IS). Differential analysis was performed to identify differentially expressed mRNA (DEmRNAs) between IS and control groups. Critical module genes were identified using weighted gene co-expression network analysis (WGCNA). DEmRNAs, critical module genes, oxidative stress-related genes (ORGs), and ferroptosis-related genes (FRGs) were crossed to screen for intersection mRNAs. Candidate mRNAs were screened based on the protein–protein interaction (PPI) network and the MCODE plug-in. Biomarkers were identified based on two types of machine learning algorithms, and the intersection was obtained. Functional items and related pathways of the biomarkers were identified using gene set enrichment analysis (GSEA). Finally, single-sample GSEA (ssGSEA) and Wilcoxon tests were used to identify differential immune cells. An miRNA-mRNA-TF network was created. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the expression levels of biomarkers in the IS and control groups. There were 8287 DE mRNAs between the IS and control groups. The genes in the turquoise module were selected as critical module genes for IS. Thirty intersecting mRNAs were screened for overlaps. Seventeen candidate mRNAs were also identified. Four biomarkers (CDKN1A, GPX4, PRDX1, and PRDX6) were identified using two types of machine-learning algorithms. GSEA results indicated that the biomarkers were associated with steroid biosynthesis. Nine types of immune cells (activated B cells and neutrophils) were markedly different between the IS and control groups. We identified 3747 miRNA-mRNA-TF regulatory pairs in the miRNA-mRNA-TF regulatory network, including hsa-miR-4469-CDKN1A-BACH2 and hsa-miR-188-3p-GPX4-ATF2. CDKN1A, PRDX1, and PRDX6 were upregulated in IS samples compared with control samples. This study suggests that four biomarkers (CDKN1A, GPX4, PRDX1, and PRDX6) are significantly associated with IS. This study provides a new reference for the diagnosis and treatment of IS.
Structural insights into the ubiquitylation strategy of the oligomeric CRL2FEM1B E3 ubiquitin ligase
Authors: Dai Zonglin , Liang Ling , Wang Weize , Zuo Peng , Yu Shang , Liu Yaqi , Zhao Xuyang , Lu Yishuo , Jin Yan , Zhang Fangting , Ding Dian , Deng Weiwei , Yin Yuxin 
Published: February 2024

AbstractCullin-RING E3 ubiquitin ligase (CRL) family members play critical roles in numerous biological processes and diseases including cancer and Alzheimer’s disease. Oligomerization of CRLs has been reported to be crucial for the regulation of their activities. However, the structural basis for its regulation and mechanism of its oligomerization are not fully known. Here, we present cryo-EM structures of oligomeric CRL2FEM1B in its unneddylated state, neddylated state in complex with BEX2 as well as neddylated state in complex with FNIP1/FLCN. These structures reveal that asymmetric dimerization of N8-CRL2FEM1B is critical for the ubiquitylation of BEX2 while FNIP1/FLCN is ubiquitylated by monomeric CRL2FEM1B. Our data present an example of the asymmetric homo-dimerization of CRL. Taken together, this study sheds light on the ubiquitylation strategy of oligomeric CRL2FEM1B according to substrates with different scales.