bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delayed-onset eptifibatide-induced thrombocytopenia
Authors: Huffman Travis , Gleaves Evan , Lenoir Glee , Rafeedheen Rahil 
Published: October 2023

Abstract

Purpose
We present a unique case of delayed-onset, profound eptifibatide-induced thrombocytopenia that occurred 5 days after initiation of the drug.

Summary
Eptifibatide is a platelet glycoprotein IIb/IIIa receptor inhibitor with indications for use in patients with acute coronary syndromes. Eptifibatide-induced thrombocytopenia is uncommon but well studied and typically occurs within 24 hours of initiation of the drug. In the case described here, a 62-year-old male with a past history of coronary artery disease (including percutaneous coronary intervention within the past 12 months) was started on eptifibatide at a dosage of 2 µg/kg per minute for management of significant thrombus burden prior to a planned cardiac revascularization procedure; heparin for anticoagulation was also initiated. About 5 days after initiation of eptifibatide, the patient developed severe thrombocytopenia, with the platelet count dropping precipitously from 249 × 103/µL on admission to less than 1 × 103/µL. After eptifibatide and heparin therapy were discontinued and the patient was switched to argatroban, the platelet count recovered to 38 × 103/µL over the next 2 days. An eptifibatide platelet antibody assay was positive for IgG-mediated reactions consistent with eptifibatide-induced thrombocytopenia. Scoring of this case with the Naranjo scale yielded a score of 4, suggesting a possible adverse reaction to eptifibatide.

Conclusion
This is the first published case report of profound eptifibatide-induced thrombocytopenia occurring more than 24 hours after eptifibatide initiation and serves to bring awareness that a delayed reaction can occur.
Salmon nasal cartilage proteoglycan stimulates hair growth
Authors: Nakane Akio , Hirose Shouhei , Kawai Noriaki , Fujimoto Naoki , Kondo Eriko , Asano Krisana 
Published: October 2023

ABSTRACT
Hair loss is a commonly encountered problem. In this study, hair growth was enhanced by daily oral ingestion of salmon nasal cartilage proteoglycan (PG) in mice. Proteoglycan stimulated vesicular endothelial growth factor production in human follicle dermal papilla cells through insulin growth factor-1 receptor signaling, suggesting the possibility of hair loss improvement by PG ingestion.
Elevated 4R tau contributes to endolysosomal dysfunction and neurodegeneration in VCP-related frontotemporal dementia
Authors: Hung Christy , Patani Rickie 
Published: October 2023

Abstract
Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are two incurable neurodegenerative diseases that exist on a clinical, genetic and pathological spectrum. The VCP gene is highly relevant, being directly implicated in both FTD and ALS. Here, we investigate the effects of VCP mutations on the cellular homoeostasis of human induced pluripotent stem cell-derived cortical neurons, focusing on endolysosomal biology and tau pathology. We found that VCP mutations cause abnormal accumulation of enlarged endolysosomes accompanied by impaired interaction between two nuclear RNA binding proteins: fused in sarcoma (FUS) and splicing factor, proline- and glutamine-rich (SFPQ) in human cortical neurons. The spatial dissociation of intranuclear FUS and SFPQ correlates with alternative splicing of the MAPT pre-mRNA and increased tau phosphorylation. Importantly, we show that inducing 4R tau expression using antisense oligonucleotide technology is sufficient to drive neurodegeneration in control human neurons, which phenocopies VCP-mutant neurons.
In summary, our findings demonstrate that tau hyperphosphorylation, endolysosomal dysfunction, lysosomal membrane rupture, endoplasmic reticulum stress and apoptosis are driven by a pathogenic increase in 4R tau.
The Current Mismatch Between COVID-19 Clinical Trial Design and the Evolving Profile of Hospitalized Patients: A Retrospective Cohort Analysis
Authors: Montejano Rocio , Soler-Carracedo Alfredo , Borobia Alberto M , Martin-Quiros Alejandro , Grandioso David , Cañada Carlos , Roman Alicia , Arribas Jose R 
Published: October 2023

Abstract
Evaluating 100 adult coronavirus disease 2019 (COVID-19) patients at a Madrid hospital, we identified a mismatch between current clinical trial designs and the evolving profile of hospitalized patients. Most patients were ineligible due to design constraints, suggesting a need to rethink trial criteria for a more accurate representation of the hospitalized COVID-19 cohort.
Canonical Wnt pathway and the LDL receptor superfamily in neuronal cholesterol homeostasis and function
Authors: Borrell-Pages Maria , Luquero Aureli , Vilahur Gemma , Padró Teresa , Badimon Lina 
Published: October 2023

Abstract

Aims
There is little information on the regulation of cholesterol homeostasis in the brain. Whether cholesterol crosses the blood–brain barrier is under investigation, but the present understanding is that cholesterol metabolism in the brain is independent from that in peripheral tissues. Lipoprotein receptors from the LDL receptor family (LRPs) have key roles in lipid particle accumulation in cells involved in vascular and cardiac pathophysiology; however, their function on neural cells is unknown.

Methods and results
The expression of LRP5 and the components and targets of its downstream signalling pathway, the canonical Wnt pathway, including β-catenin, LEF1, VEGF, OPN, MMP7, and ADAM10, is analysed in the brains of Wt and Lrp5−/− mice and in a neuroblastoma cell line. LRP5 expression is increased in a time- and dose-dependent manner after lipid loading in neuronal cells; however, it does not participate in cholesterol homeostasis as shown by intracellular lipid accumulation analyses. Neurons challenged with staurosporin and H2O2 display an anti-apoptotic protective role for LRP5.

Conclusions
For the first time, it has been shown that neurons can accumulate intracellular lipids and lipid uptake is performed mainly by the LDLR, while CD36, LRP1, and LRP5 do not play a major role. In addition, it has been shown that LRP5 triggers the canonical Wnt pathway in neuronal cells to generate pro-survival signals. Finally, Lrp5−/− mice have maintained expression of LRP5 only in the brain supporting the biological plausible concept of the need of brain LRP5 to elicit pro-survival processes and embryonic viability.
Outcomes of catheter ablation in high-risk patients with Brugada syndrome refusing an implantable cardioverter defibrillator implantation
Authors: Li Le , Ding Ligang , Zhou Likun , Wu Lingmin , Zheng Lihui , Zhang Zhenhao , Xiong Yulong , Zhang Zhuxin , Yao Yan 
Published: October 2023

Abstract

Aims
The aim of this study was to investigate the outcomes of catheter ablation (CA) in preventing arrhythmic events among patients with symptomatic Brugada syndrome (BrS) who declined implantable cardioverter defibrillator (ICD) implantation.

Methods and results
A total of 40 patients with symptomatic BrS were included in the study, of which 18 refused ICD implantation and underwent CA, while 22 patients received ICD implantation. The study employed substrate modification (including endocardial and epicardial approaches) and ventricular fibrillation (VF)-triggering pre-mature ventricular contraction (PVC) ablation strategies. The primary outcomes were a composite endpoint consisting of episodes of VF and sudden cardiac death during the follow-up period. The study population had a mean age of 43.8 ± 9.6 years, with 36 (90.0%) of them being male. All patients exhibited the typical Type 1 BrS electrocardiogram pattern, and 16 (40.0%) were carriers of an SCN5A mutation. The Shanghai risk scores were comparable between the CA and the ICD groups (7.05 ± 0.80 vs. 6.71 ± 0.86, P = 0.351). Ventricular fibrillation–triggering PVCs were ablated in 3 patients (16.7%), while VF substrates were ablated in 15 patients (83.3%). Epicardial ablation was performed in 12 patients (66.7%). During a median follow-up of 46.2 (17.5–73.7) months, the primary outcomes occurred more frequently in the ICD group than in the CA group (5.6 vs. 54.5%, Log-rank P = 0.012).

Conclusion
Catheter ablation is an effective alternative therapy for improving arrhythmic outcomes in patients with symptomatic BrS who decline ICD implantation. Our findings support the consideration of CA as an alternative treatment option in this population.
Dysbiosis of the oral microbiota composition is associated with oral squamous cell carcinoma and the impact of radiotherapy: a pilot study
Authors: Anjali Kanadan , Manzoor Muhammed , Suryavanshi Mangesh Vasant , Rudrapathy Parthiban , Rekha Punchappady Devasya , Das Ranajit , Hameed Asif , Arun Ananthapadmanabha Bhagwath 
Published: October 2023

Abstract
Radiotherapy can potentially influence the diversity and composition of the oral microbiome. We performed a study comparing the composition of oral microbiota in patients with oral squamous cell carcinoma (OSCC) before radiotherapy (n = 6), at three months (n = 6), and six months (n = 6) post-radiotherapy, and controls (n = 6). We profiled the oral microbiome by 16S rRNA gene sequencing using Illumina MiSeq. Alpha diversity (Chao1 index) showed significant differences in species richness between healthy controls and OSCC patients (P = 0.014). Conversely, no noteworthy distinctions were observed in the Chao1 index when comparing the pre-and post-radiation periods at both three and six months. The beta diversity of the oral microbiota differed significantly between the controls and OSCC patients (P = 0.014). However, no significant differences were observed in beta diversity between pre- and post-radiation at three months, whereas a significant difference was observed at six months (P = 0.038). Linear Discriminant Analysis Effect Size (LEfSe) demonstrated lower abundance of Corynebacterium, Actinomyces, Veillonella, and Haemophilus, and higher abundance of Selenomonas and Mycoplasma in OSCC patients than in healthy controls. The oral microbiome composition varied among healthy controls, patients with OSCC, and post-radiation therapy patients with OSCC. The observed recovery in the numerical dominance of specific beneficial oral taxa and the reduction in pathogenic bacteria after radiation therapy highlights the need for further investigations into their clinical implications.
Characterization of a novel ArsR regulates divergent ars operon in Ensifer adhaerens strain ST2
Authors: Zhang Jun , Li Yan-Ning , Shen Jie , Nadar Venkadesh Sarkarai , Chen Jian 
Published: October 2023

Abstract
Microbes evolved resistance determinates for coping with arsenic toxicity are commonly regulated by a variety of transcriptional repressors (ArsRs). Ensifer adhaerens strain ST2 was previously shown tolerance to environmental organoarsenical methylarsenite (MAs(III)), which has been proposed to be a primordial antibiotic. In E. adhaerens strain ST2 chromosomal ars operon, two MAs(III) resistance genes, arsZ, encoding MAs(III) oxidase, and arsK, encoding MAs(III) efflux transporter, are controlled by a novel ArsR transcriptional repressor, EaArsR. It has two conserved cysteine pairs, Cys91-92 and Cys108-109. Electrophoretic mobility shift assays (EMSAs) demonstrate that EaArsR binds to two inverted-repeat sequences within the ars promoter between arsR and arsZ to repress ars operon transcription and that DNA binding is relieved upon binding of As(III) and MAs(III). Mutation of either Cys91 or Cys92 to serine (or both) abolished these mutants binding to the ars promoter. In contrast, both C108S and C109S mutants kept responsiveness to As(III) and MAs(III). These results suggest that cysteine pair Cys91-Cys92 and either Cys108 or Cys109 contribute to form arsenic binding site. Homology modeling of EaArsR indicates the binding site consisted of Cys91-Cys92 pair from one monomer and Cys108-Cys109 pair from the other monomer, which displays the diverse evolution of arsenic binding site in the ArsR metalloregulators.
ABC superfamily transporter Rv1273c of Mycobacterium tuberculosis acts as a multidrug efflux pump
Authors: Adhikary Anwesha , Chatterjee Debasmita , Ghosh Anindya Sundar 
Published: October 2023

Abstract
Efflux pump-mediated drug resistance in bacteria is a common occurrence effective for the general survival of the organism. The Mycobacterium tuberculosis genome has an abundance of adenosine triphosphate (ATP) dependent cassette transporter genes but only a handful of them are documented for their contribution to drug resistance. In this study, we inspected the potential of an ABC transporter Rv1273c from M. tuberculosis as a multidrug efflux pump and a contributor to intrinsic drug resistance. Expression of Rv1273c in Escherichia coli and M. smegmatis conferred tolerance to various structurally unrelated antibiotics. Lower accumulation of fluoroquinolones in intact E. coli and M. smegmatis cells expressing the transporter implied its active efflux activity. Energy-dependent efflux by Rv1273c was observed in real time using the lipophilic dye Nile Red. Expression of Rv1273c also resulted in an increase in biofilm formation by E. coli and M. smegmatis cells. Overall, the results indicate the possibility that Rv1273c might be a multidrug transporter with a wide substrate range and a probable contributor to biofilm formation.
Titanium dioxide E171 consumption exacerbates Listeria monocytogenes infection in mice
Authors: Teng Yue , Wang Ailin , Zhao Dongyun , Li Guopeng , Liu Longze , Zou Yue , Xia Xiaodong 
Published: October 2023

Abstract
The food additive titanium dioxide is commonly utilized to enhance the appearance and flavor of food products. However, this substance has been linked to gastrointestinal disorders. The aim of this study was to investigate the impact of dietary exposure of titanium dioxide E171 on Listeria monocytogenes infection in mice. Mice were mainly divided into the control, LM group (L. monocytogenes infection), and E171+LM groups (E171 supplementation before L. monocytogenes infection). Pre-exposure to E171 resulted in increased bacterial counts in the liver, spleen, ileum, colon, mesenteric lymph nodes, and feces of mice after L. monocytogenes infection. Moreover, E171 exposure increased the levels of pro-inflammatory cytokines while attenuating the levels of anti-inflammatory cytokines in mice infected with L. monocytogenes. Meanwhile, mice in the E171+LM group exhibited considerably more severe colonic inflammation and worse intestinal barrier function than mice in the LM group. The 16S rRNA gene sequencing revealed a shift in the composition of the gut microbiota of mice in the E171+LM group, characterized by a decrease in the relative abundance of Firmicutes and a decrease in the Firmicutes-to-Bacteroidetes ratio. The levels of acetate, butyrate, and isobutyrate were markedly decreased within the cecum of mice in the E171+LM group in comparison to mice in the LM group. In conclusion, these results suggest that E171 exposure could exacerbate L. monocytogenes infection in mice, which may provide useful information for future risk assessment of this commonly used food additive.
Seismic imaging of the Northern Andean subduction zone from teleseismic tomography: a torn and fragmented Nazca slab
Authors: Rodríguez E E , Beck S L , Ruiz M , Meltzer A , Portner D E , Hernández S , Segovia M , Agurto-Detzel H , Charvis P 
Published: October 2023

SUMMARY
The Nazca-South America subduction zone in Ecuador is characterized by a complicated along-strike geometry as the slab transitions from flat slab subduction in the south, with the Peruvian flat slab, to what has been characterized as ‘normal’ dipping subduction beneath central Ecuador. Plate convergence additionally changes south to north as the trench takes on a convex shape. Highly heterogeneous bathymetry at the trench, including the aseismic oceanic Carnegie Ridge (CR), and sparse intermediate-depth seismicity has led many to speculate about the behaviour of the downgoing plate at depth. In this study, we present a finite-frequency teleseismic P-wave tomography model of the northern Andes beneath Ecuador and Colombia from 90 to 1200 km depth. Our model builds on prior tomography models in South America by adding relative traveltime residuals recorded at stations in Ecuador. The complete data set is comprised of 114 096 relative traveltime residuals from 1133 stations across South America, with the added data serving to refine the morphology of the Nazca slab in the mantle beneath the northern Andes. Our tomography model shows a Nazca slab with a fragmented along-strike geometry and the first teleseismic images of several proposed slab tears in this region. At the northern edge of the Peruvian flat slab in southern Ecuador, we image a shallow tear at 95–200 km depth that appears to connect mantle flow from beneath the flat slab to the Ecuadorian Arc. Beneath central Ecuador at the latitudes of the CR, the Nazca slab is continuous into the lower mantle. Beneath southern Colombia, the Malpelo Tear breaks the Nazca slab below ∼200 km depth.
Identification of conserved skeletal enhancers associated with craniosynostosis risk genes
Authors: He(何璇) Xuan Anita , Berenson Anna , Bernard Michelle , Weber Chris , Cook Laura E , Visel Axel , Fuxman Bass Juan I , Fisher Shannon 
Published: October 2023

Abstract
Craniosynostosis, defined by premature fusion of one or multiple cranial sutures, is a common congenital defect affecting more than 1/2000 infants and results in restricted brain expansion. Single gene mutations account for 15%–20% of cases, largely as part of a syndrome, but the majority are nonsyndromic with complex underlying genetics. We hypothesized that the two noncoding genomic regions identified by a GWAS for craniosynostosis contain distal regulatory elements for the risk genes BMPER and BMP2. To identify such regulatory elements, we surveyed conserved noncoding sequences from both risk loci for enhancer activity in transgenic Danio rerio. We identified enhancers from both regions that direct expression to skeletal tissues, consistent with the endogenous expression of bmper and bmp2. For each locus, we also found a skeletal enhancer that also contains a sequence variant associated with craniosynostosis risk. We examined the activity of each enhancer during craniofacial development and found that the BMPER-associated enhancer is active in the restricted region of cartilage closely associated with frontal bone initiation. The same enhancer is active in mouse skeletal tissues, demonstrating evolutionarily conserved activity. Using enhanced yeast one-hybrid assays, we identified transcription factors that bind each enhancer and observed differential binding between alleles, implicating multiple signaling pathways. Our findings help unveil the genetic mechanism of the two craniosynostosis risk loci. More broadly, our combined in vivo approach is applicable to many complex genetic diseases to build a link between association studies and specific genetic mechanisms.
Morphological and functional alterations of neuromuscular synapses in a mouse model of ACTA1 congenital myopathy
Authors: Liu Yun , Lin Weichun 
Published: October 2023

Abstract
Mutations in skeletal muscle α-actin (Acta1) cause myopathies. In a mouse model of congenital myopathy, heterozygous Acta1 (H40Y) knock-in (Acta1+/Ki) mice exhibit features of human nemaline myopathy, including premature lethality, severe muscle weakness, reduced mobility, and the presence of nemaline rods in muscle fibers. In this study, we investigated the impact of Acta1 (H40Y) mutation on the neuromuscular junction (NMJ). We found that the NMJs were markedly fragmented in Acta1+/Ki mice. Electrophysiological analysis revealed a decrease in amplitude but increase in frequency of miniature end-plate potential (mEPP) at the NMJs in Acta1+/Ki mice, compared with those in wild type (Acta1+/+) mice. Evoked end-plate potential (EPP) remained similar at the NMJs in Acta1+/Ki and Acta1+/+ mice, but quantal content was increased at the NMJs in Acta1+/Ki, compared with Acta1+/+ mice, suggesting a homeostatic compensation at the NMJs in Acta1+/Ki mice to maintain normal levels of neurotransmitter release. Furthermore, short-term synaptic plasticity of the NMJs was compromised in Acta1+/Ki mice. Together, these results demonstrate that skeletal Acta1 H40Y mutation, albeit muscle-origin, leads to both morphological and functional defects at the NMJ.
Performance of Metagenomic Next-Generation Sequencing of Cell-Free DNA From Vitreous and Aqueous Humor for Diagnoses of Intraocular Infections
Authors: Qian Zhuyun , Xia Han , Zhou Jiemin , Wang Ruifeng , Zhu Dan , Chen Li , Kang Hao , Feng Jing , Hu Xiaofeng , Wang Lu , Xu Songtao , Lou Zheng , Tao Yong 
Published: October 2023

Abstract

Background
Delayed diagnosis and improper therapy for intraocular infections usually result in poor prognosis. Due to limitations of conventional culture and polymerase chain reaction methods, most causative pathogens cannot be identified from vitreous humor (VH) or aqueous humor (AH) samples with limited volume.

Methods
Patients with suspected intraocular infections were enrolled from January 2019 to August 2021. Metagenomic next-generation sequencing (mNGS) was used to detected causative pathogens.

Results
This multicenter prospective study enrolled 488 patients, from whom VH (152) and AH (336) samples were respectively collected and analyzed using mNGS of cell-free DNA (cfDNA). Taking final comprehensive clinical diagnosis as the gold standard, there were 39 patients with indefinite final diagnoses, whereas 288 and 161 patients were diagnosed as definite infectious and noninfectious diseases, respectively. Based on clinical adjudication, the sensitivity (92.2%) and total coincidence rate (81.3%) of mNGS using VH samples were slightly higher than those of mNGS using AH samples (85.4% and 75.4%, respectively).

Conclusions
Using mNGS of cfDNA, an era with clinical experience for more rapid, independent, and impartial diagnosis of bacterial and other intraocular infections can be expected.
RTS,S/AS02A Malaria Vaccine-Induced IgG Responses Equally Recognize Native-Like Fucosylated and Nonfucosylated Plasmodium falciparum Circumsporozoite Proteins
Authors: Jairoce Chenjerai , Macià Dídac , Torres-Yaguana Jorge P , Mayer Leonie , Vidal Marta , Santano Rebeca , Hurtado-Guerrero Ramón , Reiter Karine , Narum David L , Lopez-Gutierrez Borja , Hamerly Timothy , Sacarlal Jahit , Aguilar Ruth , Dinglasan Rhoel R , Moncunill Gemma , Izquierdo Luis , Dobaño Carlota 
Published: October 2023

Abstract
The RTS,S/AS02A malaria vaccine is based on the Plasmodium falciparum circumsporozoite protein (PfCSP), which is O-fucosylated on the sporozoite surface. We determined whether RTS,S/AS02A-induced immunoglobulin G (IgG) antibodies recognize vaccine-like nonfucosylated PfCSP better than native-like fucosylated PfCSP. Similar to previous vaccine trials, RTS,S/AS02A vaccination induced high anti-PfCSP IgG levels associated with malaria protection. IgG recognition of nonfucosylated and fucosylated PfCSP was equivalent, suggesting that PfCSP fucosylation does not affect antibody recognition.
Clinical Trials Registration. NCT00197041.