bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut Microbiota–Derived Trimethylamine N-Oxide Contributes to Abdominal Aortic Aneurysm Through Inflammatory and Apoptotic Mechanisms
Authors: Benson Tyler W. , Conrad Kelsey A. , Li Xinmin S. , Wang Zeneng , Helsley Robert N. , Schugar Rebecca C. , Coughlin Taylor M. , Wadding-Lee Caris , Fleifil Salma , Russell Hannah M. , Stone Timothy , Brooks Michael , Buffa Jennifer A. , Mani Kevin , Björck Martin , Wanhainen Anders , Sangwan Naseer , Biddinger Sudha , Bhandari Rohan , Ademoya Akiirayi , Pascual Crystal , Tang W.H. Wilson , Tranter Michael , Cameron Scott J. , Brown J. Mark , Hazen Stanley L. , Owens A. Phillip 
Published: April 2023

Background:
Large-scale human and mechanistic mouse studies indicate a strong relationship between the microbiome-dependent metabolite trimethylamine N-oxide (TMAO) and several cardiometabolic diseases. This study aims to investigate the role of TMAO in the pathogenesis of abdominal aortic aneurysm (AAA) and target its parent microbes as a potential pharmacological intervention.

Methods:

TMAO and choline metabolites were examined in plasma samples, with associated clinical data, from 2 independent patient cohorts (N=2129 total). Mice were fed a high-choline diet and underwent 2 murine AAA models, angiotensin II infusion in low-density lipoprotein receptor–deficient (

Ldlr
−/−

) mice or topical porcine pancreatic elastase in C57BL/6J mice. Gut microbial production of TMAO was inhibited through broad-spectrum antibiotics, targeted inhibition of the gut microbial choline TMA lyase (CutC/D) with fluoromethylcholine, or the use of mice genetically deficient in flavin monooxygenase 3 (

Fmo3
−/−

). Finally, RNA sequencing of in vitro human vascular smooth muscle cells and in vivo mouse aortas was used to investigate how TMAO affects AAA.

Results:

Elevated TMAO was associated with increased AAA incidence and growth in both patient cohorts studied. Dietary choline supplementation augmented plasma TMAO and aortic diameter in both mouse models of AAA, which was suppressed with poorly absorbed oral broad-spectrum antibiotics. Treatment with fluoromethylcholine ablated TMAO production, attenuated choline-augmented aneurysm initiation, and halted progression of an established aneurysm model. In addition,

Fmo3
−/−

mice had reduced plasma TMAO and aortic diameters and were protected from AAA rupture compared with wild-type mice. RNA sequencing and functional analyses revealed choline supplementation in mice or TMAO treatment of human vascular smooth muscle cells–augmented gene pathways associated with the endoplasmic reticulum stress response, specifically the endoplasmic reticulum stress kinase PERK.

Conclusions:
These results define a role for gut microbiota–generated TMAO in AAA formation through upregulation of endoplasmic reticulum stress–related pathways in the aortic wall. In addition, inhibition of microbiome-derived TMAO may serve as a novel therapeutic approach for AAA treatment where none currently exist.
MMR markers correlate with clinical outcome in patients with esophageal squamous cell carcinoma
Authors: Yamauchi Takuro , Fujishima Fumiyoshi , Tsunokake Junichi , Kunimitsu Atsushi , Akaishi Ryujiro , Ozawa Yohei , Fukutomi Toshiaki , Okamoto Hiroshi , Sato Chiaki , Taniyama Yusuke , Kamei Takashi , Ichinohasama Ryo , Sasano Hironobu 
Published: April 2023

Background The DNA mismatch repair system is one of the defense mechanisms in the body, and the inactivation of mismatch repair plays a pivotal role in secondary carcinogenesis and progression. However, the significance of mismatch repair in esophageal squamous cell carcinoma (ESCC) has not been established. In this study, we explored the diagnostic and prognostic significance of mismatch repair markers, mutL homologue 1 (MLH1), post-meiotic segregation increased 2 (PMS2), mutS homologue 2 (MSH2), and mutS homologue 6 (MSH6), in patients with ESCC. Methods We used a notation based on the proportion of immunoreactivity/expression for immunohistochemistry (PRIME notation), which allows the comparison of mismatch repair expression by assigning a score to PRIME notation. MLH1, PMS2, MSH2, and MSH6 were examined immunohistochemically in 189 surgically resected ESCC specimens. Results A total of 100/189 patients with ESCC (53%) received preoperative chemotherapy. The rates of ESCC cases with decreased mismatch repair status were 13.2%, 15.3%, 24.8%, and 12.6% for MLH1, PMS2, MSH2, and MSH6, respectively. The decreased status of individual mismatch repair markers was significantly correlated with worse prognosis in patients with ESCC. Additionally, MSH2, MSH6, and PMS2 were significantly associated with response to preoperative chemotherapy. Multivariate analysis revealed that MLH1, PMS2, and MSH2 are independent prognostic factors. Conclusion Our results suggest that mismatch repair is a prognostic biomarker for ESCC and could contribute to the selection of appropriate adjuvant therapy for patients with ESCC.
Gemcitabine-associated DRESS syndrome: A case report
Authors: Bayram Ertugrul , Toyran Tugba , Paydas Semra 
Published: April 2023

Introduction Gemcitabine is a well-tolerated pyrimidine antimetabolite chemotherapeutic that is increasingly utilized to treat non-small cell lung carcinoma, breast, pancreatic, and urogenital cancers. Myelosuppression is a common side effect and skin rashes can be observed. We discuss a case of the exceedingly rare DRESS syndrome, which appeared following Gemcitabine treatment. Case report A 60-year-old patient with pancreatic cancer and liver metastases received therapy with Gemcitabine as a single agent. Fever, itching, and redness started to be reported on the third day of receiving Gemcitabine treatment. The patient's diffuse maculopapular rash steadily got worse, leading to hospitalization. Management and outcome In the patient's physical examination, a high fever, hepatomegaly, and a diffuse macular papular rash were detected, an increase in eosinophils in the complete blood count and peripheral blood. A skin biopsy was performed. It was determined that the patient had Gemcitabine-associated DRESS syndrome. Antihistamines and local steroids were administered. On the fifth day following treatment, skin lesions and eosinophilia decreased. Discussion The most common cause of DRESS syndrome, a disorder marked by extensive skin eruption, fever, eosinophilia, and systemic symptoms, is medication use. Infections including HHV-6, EBV, and CMV can occasionally be the reason. Gemcitabine is one of the medications that is frequently used in cancer, and a case was provided because the literature review did not mention Gemcitabine-related DRESS syndrome.
Challenges in Use of Practice-based Research Networks for a Medical Device Trial to Detect SARS-CoV-2
Authors: Daly Jeanette M. , O’Connor Laurel , Schmidt Megan E. , Ferrara Laura K. , Parang Kim , Levy Barcey T. 
Published: April 2023

Introduction/Objectives: Primary care practice-based research networks (PBRNs) participated in a point of care (POC) device study funded by by the National Institutes of Health and led by the University of Massachusetts Chan Medical School (UMass) to speed the development, validation, and commercialization of POC tests to detect SARS-CoV-2. The purposes of this study were to describe the characteristics of participating PBRNs and their respective collaborators in this device trial and describe complications challenging its execution. Methods: Semi-structured interviews were conducted with lead personnel from participating PBRNs and UMass. Results: Four PBRNs and UMass were invited to participate and 3 PBRNs and UMass participated. This device trial recruited 321 subjects in 6 months; 65 subjects from PBRNs. Each PBRN and the academic medical center site enrolled and recruited subjects differently. Main challenges identified were having adequate clinic personnel to enroll and aid in consent and questionnaire completion, frequently changing inclusion/exclusion criteria, use of the digital electronic data collection platform, and having access to a −80°C freezer to store supplies. Discussion: This trial involved numerous researchers, primary care clinic leaders and staff, and academic center sponsored program staff and attorneys resulting in a resource-intensive endeavor to enroll 65 subjects in the real-world clinical setting of primary care PBRNs with the academic medical center enrolling the rest. Multiple obstacles to standing up the study were encountered by the PBRNS. Conclusions: Primary care PBRNs rely largely on the goodwill established between academic health centers and participating practices. For future investigations involving device studies, collaborating PBRN leaders should assess whether recruitment criteria may change, obtain detailed lists of equipment needed, and/or know if the study is likely to be halted suddenly to appropriately prepare their member practices.
Cryopreserved placental biopsies maintain mitochondrial activity for high-resolution respirometry
Authors: Giovarelli Matteo , Serati Anais , Zecchini Silvia , Guelfi Fabiola , Clementi Emilio , Mandò Chiara 
Published: April 2023

Abstract
Background
High-resolution respirometry (HRR) of human biopsies can provide useful metabolic, diagnostic, and mechanistic insights for clinical research and comparative medical studies. Fresh tissues analysis offers the potential best condition, the drawback being the need to use them shortly after dissection for mitochondrial respiratory experiments. The development of effective long-term storage protocols for biopsies that allow the assessment of key Electron Transport System (ETS) parameters at later stages is thus a major need.

Methods
We optimised a cryopreservation protocol that preserves mitochondrial membranes intactness, otherwise affected by direct tissue freezing. The protocol is based on a gradual freezing step from on-ice to liquid nitrogen and − 80 °C storage using a specific DMSO-based buffer.

Results
Placenta is a suitable tissue to design and test the effectiveness of long-term storage protocols being metabolically active foetal tissue with mitochondrial dysfunctions contributing to placental disease and gestational disorders. Here we designed and tested the effectiveness of the cryopreservation protocol using human placenta biopsies; we measured the ETS activity by HRR of placenta specimens comparing fresh, cryopreserved, and snap frozen conditions.

Conclusions
By this protocol, Oxygen Consumption Rate (OCR) measurements of fresh and cryopreserved placental specimens are comparable whereas snap frozen procedure impairs mitochondrial activity.

Graphical Abstract
Spatial Expression of Assembly Geometric Errors for Multi-axis Machine Tool Based on Kinematic Jacobian-Torsor Model
Authors: Tian Ang , Liu Shun , Chen Kun , Mo Wei , Jin Sun 
Published: April 2023

AbstractAssembly geometric error as a part of the machine tool system errors has a significant influence on the machining accuracy of the multi-axis machine tool. And it cannot be eliminated due to the error propagation of components in the assembly process, which is generally non-uniformly distributed in the whole working space. A comprehensive expression model for assembly geometric error is greatly helpful for machining quality control of machine tools to meet the demand for machining accuracy in practice. However, the expression ranges based on the standard quasi-static expression model for assembly geometric errors are far less than those needed in the whole working space of the multi-axis machine tool. To address this issue, a modeling methodology based on the Jacobian-Torsor model is proposed to describe the spatially distributed geometric errors. Firstly, an improved kinematic Jacobian-Torsor model is developed to describe the relative movements such as translation and rotation motion between assembly bodies, respectively. Furthermore, based on the proposed kinematic Jacobian-Torsor model, a spatial expression of geometric errors for the multi-axis machine tool is given. And simulation and experimental verification are taken with the investigation of the spatial distribution of geometric errors on five four-axis machine tools. The results validate the effectiveness of the proposed kinematic Jacobian-Torsor model in dealing with the spatial expression of assembly geometric errors.
No difference in extra-axial cerebrospinal fluid volumes across neurodevelopmental and psychiatric conditions in later childhood and adolescence
Authors: Peterson Madeline , Whetten Christopher , Clark Anne M. , Nielsen Jared A. 
Published: April 2023

Abstract
Background
While autism spectrum disorder has been associated with various organizational and developmental aberrations in the brain, an increase in extra-axial cerebrospinal fluid volume has recently garnered attention. A series of studies indicate that an increased volume between the ages of 6 months and 4 years was both predictive of the autism diagnosis and symptom severity regardless of genetic risk for the condition. However, there remains a minimal understanding regarding the specificity of an increased volume of extra-axial cerebrospinal fluid to autism.

Methods
In the present study, we explored extra-axial cerebrospinal fluid volumes in children and adolescents ages 5–21 years with various neurodevelopmental and psychiatric conditions. We hypothesized that an elevated extra-axial cerebrospinal fluid volume would be found in autism compared with typical development and the other diagnostic group. We tested this hypothesis by employing a cross-sectional dataset of 446 individuals (85 autistic, 60 typically developing, and 301 other diagnosis). An analysis of covariance was used to examine differences in extra-axial cerebrospinal fluid volumes between these groups as well as a group by age interaction in extra-axial cerebrospinal fluid volumes.

Results
Inconsistent with our hypothesis, we found no group differences in extra-axial cerebrospinal fluid volume in this cohort. However, in replication of previous work, a doubling of extra-axial cerebrospinal fluid volume across adolescence was found. Further investigation into the relationship between extra-axial cerebrospinal fluid volume and cortical thickness suggested that this increase in extra-axial cerebrospinal fluid volume may be driven by a decrease in cortical thickness. Furthermore, an exploratory analysis found no relationship between extra-axial cerebrospinal fluid volume and sleep disturbances.

Conclusions
These results indicate that an increased volume of extra-axial cerebrospinal fluid may be limited to autistic individuals younger than 5 years. Additionally, extra-axial cerebrospinal fluid volume does not differ between autistic, neurotypical, and other psychiatric conditions after age 4.
Neurophysiological measures of auditory sensory processing are associated with adaptive behavior in children with Autism Spectrum Disorder
Authors: Cotter Mairin , Reisli Seydanur , Francisco Ana Alves , Wakim Kathryn-Mary , Oakes Leona , Crosse Michael J. , Foxe John J. , Molholm Sophie 
Published: April 2023

Abstract
Background
Atypical auditory cortical processing is consistently found in scalp electrophysiological and magnetoencephalographic studies of Autism Spectrum Disorder (ASD), and may provide a marker of neuropathological brain development. However, the relationship between atypical cortical processing of auditory information and adaptive behavior in ASD is not yet well understood.

Methods
We sought to test the hypothesis that early (100-175 ms) auditory processing in ASD is related to everyday adaptive behavior through the examination of auditory event-related potentials (AEPs) in response to simple tones and Vineland Adaptive Behavior Scales in a large cohort of children with ASD (N = 84), aged 6–17, and in age- and IQ- matched neurotypically (NT) developing controls (N = 132).

Results
Statistical analyses revealed significant group differences in early AEPs over temporal scalp regions (150-175 ms), and the expected rightward lateralization of the AEP (100-125 ms and 150-175 ms) to tonal stimuli in both groups. Lateralization of the AEP (150-175 ms) was significantly associated with adaptive functioning in the socialization domain.

Conclusions
These results lend support to the hypothesis that atypical processing of sensory information is related to everyday adaptive behavior in autism.
SCAT8/miR-125b-5p axis triggers malignant progression of nasopharyngeal carcinoma through SCARB1
Authors: Jiang Chunmao , Feng Dandan , Zhang Yu , Yang Kun , Hu Xiaotong , Xie Qian 
Published: April 2023

AbstractNasopharyngeal carcinoma is a tumor with high malignancy and poor prognosis, which severely affects the health of the patients. LncRNAs and microRNAs are crucial for the occurrence and development of nasopharyngeal carcinoma, which regulate the progression of nasopharyngeal carcinoma through the ceRNA network. SCARB1 plays an essential role in nasopharyngeal carcinoma. However, the mechanism underlying the regulation of SCARB1 in nasopharyngeal carcinoma through non-coding RNAs remains unclear. Our findings indicated that the SCAT8/miR-125b-5p axis promoted the malignant progression of nasopharyngeal carcinoma by driving the expression of SCARB1. Mechanistically, the expression of SCARB1 could be regulated by the lncRNA, SCAT8 and the microRNA, miR-125b-5p. Moreover, as a ceRNA of miR-125b-5p, SCAT8 can not only regulate the expression of SCARB1, but also regulate the malignant progression of nasopharyngeal carcinoma. Notably, our results reveal a novel ceRNA regulatory network in nasopharyngeal carcinoma, which could serve as a potential target for the diagnosis and treatment of nasopharyngeal carcinoma.
Genome-wide identification of potential odontogenic genes involved in the dental epithelium-mesenchymal interaction during early odontogenesis
Authors: Chen Jiawen , Sun Tianyu , You Yan , Lin Binbin , Wu Buling , Wu Jingyi 
Published: April 2023

Abstract
Background
Epithelium-mesenchymal interactions are involved in odontogenic processes. Previous studies have focused on the intracellular signalling regulatory network in tooth development, but the functions of extracellular regulatory molecules have remained unclear. This study aims to explore the gene profile of extracellular proteoglycans and their glycosaminoglycan chains potentially involved in dental epithelium-mesenchymal interactions using high-throughput sequencing to provide new understanding of early odontogenesis.

Results
Whole transcriptome profiles of the mouse dental epithelium and mesenchyme were investigated by RNA sequencing (RNA-seq). A total of 1,281 and 1,582 differentially expressed genes were identified between the dental epithelium and mesenchyme at E11.5 and E13.5, respectively. Enrichment analysis showed that extracellular regions and ECM-receptor interactions were significantly enriched at both E11.5 and E13.5. Polymerase chain reaction analysis confirmed that the extracellular proteoglycan family exhibited distinct changes during epithelium-mesenchymal interactions. Most proteoglycans showed higher transcript levels in the dental mesenchyme, whereas only a few were upregulated in the epithelium at both stages. In addition, 9 proteoglycans showed dynamic expression changes between these two tissue compartments. Gpc4, Sdc2, Spock2, Dcn and Lum were expressed at higher levels in the dental epithelium at E11.5, whereas their expression was significantly higher in the dental mesenchyme at E13.5, which coincides with the odontogenic potential shift. Moreover, the glycosaminoglycan biosynthetic enzymes Ext1, Hs3st1/5, Hs6st2/3, Ndst3 and Sulf1 also exhibited early upregulation in the epithelium but showed markedly higher expression in the mesenchyme after the odontogenic potential shift.

Conclusion
This study reveals the dynamic expression profile of extracellular proteoglycans and their biosynthetic enzymes during the dental epithelium–mesenchymal interaction. This study offers new insight into the roles of extracellular proteoglycans and their distinct sulfation underlying early odontogenesis.
Spring irrigation with magnetized water affects soil water-salt distribution, emergence, growth, and photosynthetic characteristics of cotton seedlings in Southern Xinjiang, China
Authors: Yi Guo , Quanjiu Wang , Kang Wang , Jihong Zhang , Kai Wei , Yang Liu 
Published: April 2023

Abstract
Background
Spring irrigation with freshwater is widely used to reduce soil salinity and increase the soil water content in arid areas. However, this approach requires a huge amount of freshwater, which is problematic given limited freshwater resources. Utilizing brackish water for spring irrigation in combination with magnetized water technology may be a promising alternative strategy.

Results
The objective of this study was to evaluate the effects of four spring irrigation methods (freshwater spring irrigation (FS), magnetized freshwater spring irrigation (MFS), brackish water spring irrigation (BS), and magnetized brackish water spring irrigation (MBS)) on soil water and salt distribution, emergence, growth, and photosynthetic characteristics of cotton seedlings. The results showed that for both freshwater and brackish water, magnetized water irrigation can increase the soil water content for improved desalination effect of irrigation water. Additionally, spring irrigation with magnetized water promoted cotton emergence and seedling growth. Compared with FS treatment, cotton finial emergence rate, emergence index, vigor index, plant height, stem diameter, and leaf area index of MFS treatment increased by 6.25, 7.19, 12.98, 15.60, 8.91, and 20.57%, respectively. Compared with BS treatment, cotton finial emergence rate, emergence index, vigor index, plant height, stem diameter, and leaf area index of MBS treatment increased by 27.78, 39.83, 74.79, 26.40, 14.01, and 57.22%, respectively. Interestingly, we found that spring irrigation with magnetized water can increase the chlorophyll content and net photosynthetic rate of cotton seedlings. The rectangular hyperbolic model (RHM), non-rectangular hyperbolic model (NRHM), exponential model (EM), and modified rectangular hyperbolic model (MRHM) were used to fit and compare the cotton light response curve, and MRHM was determined to be the optimal model to fit the data. This model was used to calculate the photosynthetic parameters of cotton. Compared with FS treatment, the net photosynthetic rate (Pnmax), dark respiration rate (Rd), light compensation point (Ic), light saturation point (Isat), and the range of available light intensity (ΔI) of MFS were increased by 5.18, 3.41, 3.18, 2.29 and 2.19%, respectively. Compared with BS treatment, the Pnmax, Rd, Ic, Isat and ΔI of MBS were increased by 26.44, 29.48, 30.05, 5.13, and 2.27%, respectively.

Conclusion
The results show that spring irrigation with magnetized brackish water may be a feasible method to reduce soil salt and increase soil water content when freshwater resources are insufficient.