bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparative study of circulating microRNA expression in blood in patients with coronary artery atherosclerosis and thoracic aortic aneurysm
Authors: Ngo Bilong E. A.V. , Vasiliev S. V. , Rozhkov A. N. , Stonogina D. A. , Shchekochikhin D. Yu. , Filippova Y. I. , Dzhafarova Ch. VK. , Nurutdinov N. P. , Zhelankin A. V. , Generozov E. V. , Akselrod A. S. , Kopylov Ph. Yu. , Syrkin A. L.
Published: July 2024

Aim. To compare the relative expression levels of circulating microRNAs associated with cardiovascular diseases, selected according to the literature review, in the blood plasma samples of patients with two variants of chronic vascular wall injury: coronary artery atherosclerosis (CAA) and thoracic aortic aneurysm (TAA).

Material and methods. Patients admitted to the Clinical Center of the I. M. Sechenov First Moscow State Medical University (University Clinical Hospital No. 1) with CAA (n=45), TAA (n=38), as well as a control group (n=17) were included. Standard clinical and demographic, laboratory and instrumental data were collected in accordance with Russian clinical guidelines, and additional sampling and preparation of blood plasma of patients was carried out with further quantitative determination of the circulating microRNAs level via real-time polymerase chain reaction with reverse transcription. A comprehensive comparative analysis of the profiles of circulating microRNAs in the blood plasma of patients with two different variants of arterial pathology: atherosclerosis and aneurysmal changes, as well as with the control group was carried out. The levels of 12 circulating microRNAs were studied: miR-21-5p, -23a-3p, -29b-3p, -92a-3p, -126-5p, -143-3p, -145-5p, -146a-5p, -150-5p, -181b-5p, 2-23-3p and -451a.

Results. The strongest difference with the control group in patients with CAA and TAA was observed for miR-21-5p, -29b-3p and -126-3p. Most of the circulating microRNAs studied were higher in the TAA group compared with CAA and controls these include miR-21-5p, -23a-3p, -29b-3p, -92a-3p, -126-3p, -126-5p, -146a-5p, -150-5p, -181b-5p. Significant differences between the pathology groups were noted for miR-126-3p and miR-205-5p. Some microRNAs (­miR-143-3p, -92 a3, -195-5 p) can be used to diagnose coronary artery atherosclerosis, other microRNAs (miR-21-5p, -23a-3p, -126-3p, -126-5p, -451a) are TAA-specific.

Conclusion. The present study showed significant differences in the circulating microRNAs in patients with atherosclerotic and aneurysmal lesions of the arteries in comparison with the control group. The most significant difference between norm and pathology was found for miR-21-5p, -29b-5p and -126-3p. The levels of miR-126-3p and -205-5p can be used to differentiate CAA and TAA.
Generalized Joint Hypermobility Is Associated with Type-A Hip Dysplasia in Patients Undergoing Periacetabular Osteotomy
Authors: Ping Hangyu , Kong Xiangpeng , Zhang Hong , Luo Dianzhong , Jiang Qing , Chai Wei
Published: July 2024

Background:

Joint hypermobility may be associated with developmental dysplasia of the hip (DDH), but no definite conclusion has been reached. On the basis of long-term clinical observations, we hypothesized that joint hypermobility was associated with the occurrence, imaging findings, and clinical symptoms of DDH.

Methods:

We conducted a case-control study that included 175 Chinese Han patients between 13 and 45 years of age with Hartofilakidis type-A hip dysplasia. All of these patients underwent periacetabular osteotomy (PAO) between November 2021 and February 2023. An additional 76 individuals of comparable age and sex but without hip dysplasia were selected from the general population to serve as healthy controls. The Beighton 9-point scoring system was used to evaluate joint hypermobility, and a score of ≥4 was defined as generalized joint hypermobility. Standing anteroposterior pelvic radiographs were reviewed. For patients with DDH, the lateral center-edge angle, Tönnis angle, Sharp angle, lateralization of the femoral head, and patient-reported outcomes (iHOT-12, HHS, and WOMAC) were also collected to determine the radiographic severity or clinical symptoms of DDH.

Results:

Patients with DDH had an elevated prevalence of generalized joint hypermobility compared with that in the healthy population (27% versus 12%; p = 0.009). Among patients with DDH, those with concomitant generalized joint hypermobility had lower lateral center-edge angles (3.55° versus 9.36°; p = 0.012), greater lateralization of the femoral head (13.78 versus 12.17 mm; p = 0.020), greater standardized lateralization of the femoral head (0.64 versus 0.54; p = 0.009), and lower iHOT-12 scores (35.22 versus 40.96; p = 0.009) than did those without concomitant generalized joint hypermobility. Further multivariable linear regression analysis revealed that higher Beighton scores and younger age were predictive of more severe hip dysplasia. However, the Beighton score was not found to be independently associated with patient-reported outcomes according to multivariable linear regression analysis.

Conclusions:

The prevalence of generalized joint hypermobility was greater in patients with DDH than in healthy controls. A higher degree of joint hypermobility was also correlated with more severe hip dysplasia. These results suggest that joint laxity, in addition to bone or cartilage factors, is an important factor related to DDH.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
WITHDRAWN: Unleashing the Power of YOLOv8 for Accurate Bengali Mathematical Expression Detection
Authors: Imran Izazul Hoq , Das Tropa , Galib Asadullah Hel , Roy Tanni
Published: July 2024

The full text of this preprint has been withdrawn by the authors as it was submitted and made public without the full consent of all the authors. Therefore, the authors do not wish this work to be cited as a reference. Questions should be directed to the corresponding author.
Analysis of Errors in Medical Certificates of Cause of Death (MCCD) at a Tertiary Care Institute in 2022
Authors: SHARMA NANDITA , Singh Mahendra , Bahurupi Yogesh , Aggarwal Pradeep
Published: July 2024

Medical Certificates of Cause of Death (MCCD) play a pivotal role in shaping national health statistics and public health initiatives. This study investigates the quality of MCCD completion at a Tertiary Care Institute in India, focusing on certification errors made by physicians while issuing death certificates. Methods: Using a retrospective, cross-sectional approach, 1603 MCCDs issued during the study period were analyzed for formal correctness and mistakes. The study employed predefined categories to assess the nature and impact of these errors. While this research did not verify the factual accuracy of the MCCDs against patients' medical records, it categorized errors into major and minor, based on their potential to influence the accurate classification of the underlying cause of death. Results: The study showed the presence of errors in all 1603 death certificates examined, categorizing them as major, minor, or both. Notably, 99.2% of cases lacked the mention of the time interval between death and the morbid condition. Analysis of major errors indicated that in 64.60% of cases, competing causes of death were mentioned, while 77.4% featured multiple causes of death. Furthermore, improper sequencing of the cause of death was identified in 11.2%, whereas 7.9% had poorly defined conditions as the cause of death. Conclusion: To improve the quality of healthcare data and public health management, these findings highlight the necessity for precise MCCD reporting and the significance of comprehending mortality patterns. For informed decision-making and changes to the healthcare system, addressing the found errors and patterns is essential.
The Effect of Replication Protein A Inhibition and Post-Translational Modification on ATR Kinase Signaling
Authors: Jordan Matthew R. , Oakley Greg G. , Mayo Lindsey D. , Balakrishnan Lata , Turchi John J.
Published: July 2024

The ATR kinase responds to elevated levels of single-stranded DNA (ssDNA) to activate the G2/M checkpoint, regulate origin utilization, preserve fork stability, and allow DNA repair towards ensuring genome integrity. The intrinsic replication stress in cancer cells makes this pathway an attractive therapeutic target. The ssDNA that drives ATR signaling is sensed by the ssDNA-binding protein replication protein A (RPA), which acts as a platform for ATRIP recruitment and subsequent ATR activation by TopBP1. We have developed chemical RPA inhibitors (RPAi) that block RPA-ssDNA interactions, termed RPA-DBi, and RPA protein-protein interactions, termed RPA-PPIi; both activities are required for ATR activation. Here, we employ a biochemically reconstituted ATR kinase signaling pathway and demonstrate that both RPA-DBi and RPA-PPIi abrogate ATR-dependent phosphorylation of downstream target proteins. We demonstrate that RPA post-translational modifications (PTMs) impact ATR kinase activation but do not alter sensitivity to RPAi. Specifically, phosphorylation of RPA32 and TopBP1 stimulate, while RPA70 acetylation has no effect on ATR phosphorylation of target proteins. Collectively, this work reveals the RPAi mechanism of action to inhibit ATR signaling that can be regulated by RPA PTMs and offers insight into the anti-cancer activity of ATR pathway targeted cancer therapeutics.
Drug Repurposing: Therapeutic Role of Aripiprazole in the Cartilage Defect
Authors: Lee Jun-Ku , Yeo Hyunjeong , Choi Sujin , Kim Kyeong Mi , Kim Hannah , Lee Sung-Sahn , Lee Hyun Il , Jeong Younghoon , An Hyun-Ju , Lee Soonchul
Published: July 2024

Owing to the limited regenerative capacity of articular cartilage, damaged cartilage does not spontaneously heal over time. Various scientific efforts have been made to improve damaged articular cartilage. Nevertheless, no single approach has achieved a promising outcome for the damaged cartilage. Meanwhile, owing to the increasing cost of drug development, drug repositioning has been actively attempted. We aimed to identify the drug that can improve the cartilage defect, using chondrogenesis related microarray data recruited from the Gene Expression Omnibus (GEO) public database. Furthermore, we attempted to experiment using cellular and animal models to verify the cartilage regeneration potential for the identified drug. To screen for drugs that promote cartilage restoring, chondrogenesis related microarray data were collected from the GEO public database. The GSE69110, GSE107649, GSE111822, and GSE116173 datasets from the GEO were used to identify cartilage differentiation-related genes. Differentially expressed genes were identified using StringTie, and drug data were extracted from the Drug-Gene Interaction database. The effect of aripiprazole on cartilage was evaluated in aripiprazole-treated adipose-derived mesenchymal stem cells (ADMSCs) and chondrocyte using qRT-PCR and 3D pellet culture. The cartilage restoring efficacy was verified in vivo by mixing it with a scaffold and introducing it into the artificially damaged cartilage of Sprague-Dawley rats. Next, mRNA was sequenced for mechanistic analysis. As a result, aripiprazole significantly increased the mRNA expression of COL2A1 and SOX9, two cartilage differentiation-related genes, and chondrogenic condensation in vitro. Moreover, it effectively promoted cartilage regeneration in the cartilage defect rat model. Analysis of mRNA sequencing data from chondrocyte treated with aripiprazole, using KEGG and GOBP, indicated that aripiprazole significantly upregulates genes associated with ribosomes and cytoplasmic translation, thus promoting chondrogenesis. In conclusion, we discovered that aripiprazole can effectively improve damaged cartilage, providing a promising approach for cartilage regeneration.
Construction of an immune-related signature based on single-cell RNA-sequencing and machine learning for optimal prognosis prediction and treatment decisions in hepatocellular carcinoma
Authors: Zhang Huien , Wang Yang , Xu Zihan , Ma Guikai , Wang Xueying , Zhong Shoubin , Wang Bowen , Lun Jia , Li Zhenhua , Zhang Xuede
Published: July 2024

Introduction: Immune cells play a dual role inhepatocellular carcinoma (HCC) – it can both restrain and promote tumor growth, which is the significant component of the tumour immune microenvironment (TIME). This study aimed to develop a immune-related signature model to predict the prognosis and TIME of patients with HCC. Methods: Data for the TCGA-LIHC and GSE14520 cohorts were downloaded from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Single-cell RNA-sequencing data for HCC samples were retrieved from the GSE140228 cohort. The Least Absolute Shrinkage and Selection Operator algorithm was employed to develop a Immune-related signature (IRSig). The predictive value of the IRSig was determined using Kaplan-Meier, Cox regression and Receiver Operating Characteristic curves. Gene set enrichment analysis (GSEA), Gene Set Variation Analysis (GSVA) and gene ontology (GO) analysis were performed to explore the functional enrichment of the IRSig. Finally, the TIMER platform, single sample Gene Set Enrichment Analysis and the Estimation of STromal and Immune cells in MAlignant Tumour tissues using Expression data algorithms were performed to determine the TIME landscape. Results: The immune-related signature demonstrated its superior ability to predict the clinical outcome of patients with HCC. TMB, immune score, stromal score, and ESTIMATE score were higher in the high-risk group compared to the low-risk group. Additionally, most immune checkpoints, including CTLA4, PD1 and PD-L1, were expressed at significantly higher levels in high-risk group. Conclusions: Our study established an immune-related signature based on single-cell RNA-sequencing and machine learning for optimal prognosis prediction and treatment decisions in hepatocellular carcinoma, and verified by TCGA and GEO databases. Besides, we found immune-related cells and pathways were significant differences in high- and low-risk group, which might be helpful for illustrating the application of immunotherapy for HCC patients.
Unraveling the Rapid Progression of Non-Target Lesions: Risk Factors and the Therapeutic Potential of PCSK9 Inhibitors in Post-PCI Patients
Authors: Mei Jiajie , Fu Xiaodan , Liu Zhenzhu , Zhang Lijiao , Geng Zhaohong , Xie Wenli , Yu Ming , Wang Yuxing , Zhao Jinglin , Zhang Xiaodong , Yin Lili , Qu Peng
Published: July 2024

Background
Rapid progression of non-target lesions (NTLs) leads to a high incidence of NTL related cardiac events post-PCI, which accounting half of the recurrent cardiac events. It is important to identify the risk factors for the rapid progression of NTLs post-PCI. Proprotein convertase subtilisin-kexin 9(PCSK9) inhibitors lower low-density lipoprotein cholesterol(LDL-c) levels significantly, also show the anti-inflammation effect, and may have the potential to reduce the rapid progression of NTLs post-PCI.
Methods
This retrospective study included 1250 patients who underwent the first PCI and underwent repeat coronary angiography for recurrence of chest pain within 24 months. Machine learning (LASSO regression) was mainly employed to select the important characteristic risk factors for the rapid progression of NTLs post-PCI, and build prediction models. Finally, mediator analysis was employed to explore the potential mechanisms by which PCSK9 inhibitors reduce the rapid progression of NTLs post-PCI.
Results
There were more diabetes, less beta-blockers and PCSK9 inhibitors application, higher HbA1c, LDL-c, ApoB, TG, TC, uric acid ,higher hs-CRP, TNF-α, IL-6, IL-8, and sIL-2R in NTL progressed group.LDL-c, hs-CRP, IL-8, and sIL-2R were characteristic risk factors for rapid progression of NTLs post-PCI, combining LDL-c, hs-CRP, IL-8, and sIL-2R builds the optimal model for predicting the rapid progression of NTLs post-PCI (AUC = 0.632). LDL-c had a clear and incomplete mediating effect (95% CI, mediating effect: 51.56%) in the reduction of the progression of NTLs by PCSK9 inhibitors, and there was a possible mediating effect of IL-8 (90% CI), and sIL-2R (90% CI).
Conclusions
LDL-c, hs-CRP, IL-8, and sIL-2R may be the key characteristic risk factors for the rapid progression of NTLs post-PCI, and combining these parameters can predict the rapid progression of NTLs post-PCI. The application of PCSK9 inhibitors has a negative correlation with the rapid progression of NTLs. In addition to the significant LDL-c-lowering, PCSK9 inhibitors may reduce the rapid progression of NTLs by reducing local inflammation of plaque.
Registration number:
ChiCTR2200058529; Date of registration: 2022-04-10
Internalized and Externalized Mental Health Symptoms among Latinx Children:A Comparison between Rural Latinx Farmworker and Urban Latinx Low-Income Families Living in North Carolina
Authors: Berenson Lesley , Nugent William , Strand Elizabeth , Zottarelli Lisa , Laurienti Paul
Published: July 2024

This study examined mental health symptoms among 8-11-year-old children of Latinx farmworkers in rural North Carolina (N = 76) and urban children of Latinx parents (N = 65). All had household incomes of 200% below the poverty line. A Spanish version of the Child Behavioral Checklist (CBCL) for children aged 6–18 assessed internalized (anxious/depression) and externalized (aggression) mental health symptoms. CBCL scores obtained at baseline and subsequent follow-up evaluations approximately one year and two years after the first evaluation were analyzed with multi-level regression to determine if the CBCL outcomes changed over time. Children from farmworker families showed lower levels of anxious/depressive symptoms at baseline (mean = 50.59) than urban children (mean = 54.74), but these differences diminished with age. The mean depression score for the urban sample decreased by -1.17 points each year after the initial assessment. Both rural (mean = 44.15) and urban Latinx children (mean = 49.92) developed increased externalized aggressive symptoms over time, and rural children's aggression increased faster than urban children. The rural children showed a statistically significant increase with a mean linear rate of change of + 3.63 over time. This study contributes to the current research on how community settings may affect children's socio-emotional development, and suggests further examination into the impact of social, physical, and economic disadvantages on children's mental health.
Conversion of Naphthenic Hydrocarbons Over Hzm-12 Zeolites - Activity and Selectivity to Light Olefins Depending on Their Acid and Textural Properties and on the Size of the Processed Molecule
Authors: JUNIOR JOSE ROBERTO SILVA
Published: July 2024

The activity and selectivity to light olefins during conversion of naphthenic hydrocarbons over HZSM-12 zeolites depending on the textural and acid properties and the size of the processed molecule were studied. In Two ZSM-12 zeolites were synthesized under hydrothermal conditions with similar Si/Al ratio. To generate intracrystalline mesoporosity, the synthesized ZSM-12 zeolites, identified as HZ12 and MZ12, were subsequently desilicated by alkaline treatment (AT) generating the hierarchical HZ12-AT and MZ12-AT zeolites. After to obtain their protonic form, the samples were characterized by XRD, SEM, EDS, N2 physisorption, 27Al MAS NMR and NH3-TPD. XRD and N2 sorption measurements confirmed, respectively, that the MTW structure of the ZSM-12 zeolite was preserved and that after the AT occurred an increase in the mesoporous volume, consequently increasing the specific external surface area, besides with an increase in the concentration of weak acid sites in the alkaline treated sample under more severe conditions. The catalytic evaluation shows an increase in the conversion of cyclohexane, methylcyclohexane and ethylcyclohexane over the more mesoporous MZ12-AT zeolite with the yield to light olefins increasing with the increase of the length of the substitutive alkyl group in the naphthenic molecule, being this behavior more pronounced over the MZ12-AT sample.
Pharmacokinetic and pharmacodynamic evaluation of various vasopressin doses and routes in a neonatal piglet model
Authors: BSc Ramsie M , Cheung P-Y , M O’Reilly , TF Lee , Schmölzer Georg M.
Published: July 2024

Epinephrine is the only recommended vasopressor during neonatal cardiopulmonary resuscitation. However, there are concerns about the potential adverse effects of epinephrine, which might hamper efficacy during cardiopulmonary resuscitation. An alternative might be vasopressin, which has a preferable adverse effect profile, however, its optimal dose and route of administration is unknown. We aimed to compare the pharmacodynamics and pharmacokinetics of various vasopressin doses administered via intravenous (IV), intraosseous (IO), endotracheal (ETT), and intranasal (IN) routes in healthy neonatal piglets. Forty-four post-transitional piglets (1–3 days of age) were anesthetized, intubated via a tracheostomy, and randomized to receive vasopressin via intravenous (control), IO, ETT, or IN route. Heart rate (HR), arterial blood pressure, carotid blood flow, and cardiac function (e.g., stroke volume, ejection fraction) were continuously recorded throughout the experiment. Blood was collected prior to drug administration and throughout the observation period for pharmacodynamics and pharmacokinetic analysis. Significant changes in hemodynamic parameters were observed following IO administration of vasopressin while pharmacokinetic parameters were not different between IV and IO vasopressin. Administration of vasopressin via ETT or IN did not change hemodynamic parameters and had significantly lower maximum plasma concentrations and systemic absorption compared to piglets administered IV vasopressin (p < 0.05). The IV and IO routes appear the most effective route for vasopressin administration in neonatal piglets, while ETT and IN routes appear not suitable for vasopressin administration.
Bilateral Endobronchial Prostatic Metastases: A Rare Clinical Entity with Diagnostic and Therapeutic Challenges: A Case Report and Literature Review
Authors: Mittal Kriti , Panthi Sagar , VanBacker Justin
Published: July 2024

Background Endobronchial metastases from prostate cancer are uncommon, representing a diagnostic and therapeutic challenge due to their rarity and variable clinical presentation. Here, we present a case of bilateral endobronchial metastases secondary to adenocarcinoma of the prostate in a 73-year-old male with castration-resistant prostate cancer highlighting the importance of recognizing this rare entity for optimal patient management.
Case PresentationThe patient is a 73-year-old male with past medical history of atrial fibrillation on anticoagulation alongside a diagnosis of Gleason 3+4 prostate cancer resistant to castration. He presented with shortness of breath and a hemothorax secondary to a CT-guided lung biopsy several days prior, which prompted a pigtail catheter placement. A minimally invasive chest washout was eventually required due to incomplete drainage leading to an incidental discovery of bilateral endobronchial metastases synchronous with lung parenchymal metastasis. Treatment involved endobronchial tumor ablation given chemotherapy ineffectiveness.
Discussion and Literature ReviewEndobronchial metastases from prostate cancer is rare, but must be considered in patients with respiratory symptoms and a history of prostate cancer with pulmonary metastasis. Our literature review reveals a diverse clinical presentation with cough, dyspnea, and hemoptysis being most common. Diagnostic modalities such as bronchoscopy are crucial for accurate diagnosis, allowing for tailored treatment strategies. Hormonal therapy remains the mainstay of treatment, although other modalities such as chemotherapy and bronchoscopic interventions may be considered based on individual patient factors.
Conclusions Early recognition of endobronchial metastases secondary to prostate cancer with thorough evaluation, including bronchoscopy, is essential for timely diagnosis and appropriate management.
Longitudinal evaluation of circulating tumor cells in operable locally advanced esophageal squamous cell carcinoma
Authors: Wang Jin , Chen Shuang , Zhang Weidi , Li Yang , Han Lu
Published: July 2024

Objective: The detection of circulating tumor cells (CTCs) at a single time point offers restricted insights into prognostic assessment. This study aims to longitudinally investigate alterations in CTCs status throughout the neoadjuvant chemotherapy, surgical, and postoperative chemotherapy phases within a homogeneous cohort. Further more, an assessment of the interrelation between patients' treatment response, survival prognosis, and CTCs status was conducted.
Materials and methods: Thirty-one patients diagnosed with operable locally advanced esophageal squamous cell carcinoma were randomly allocated to either the surgical or neoadjuvant group. CTCs detection was systematically conducted at various time points throughout the treatment on individual patients. Associations between the presence of CTCs/CTM and therapeutic efficacy, as well as clinical outcomes, were subject to rigorous analysis.
Results: We performed a total of 136 CTCs detections at the time points of pre-neoadjuvant chemotherapy, preoperative, postoperative day 2, post-operative 1 week, post-operative 3 months. The CTCs were detected in 6/12(50％), 14/31(45.16％), 22/31(70.97％), 16/31(51.6％) and 5/31(16.1％) of patients before neoadjuvant treatment, prior to surgery, on postoperative day 2, one week after surgery, and three months post-surgery, respectively. The CTC count exhibited an increase before and after surgery, whereas a decrease was observed before and after neoadjuvant chemotherapy. Among patients initially identified with CTCs+, those in the neoadjuvant group experienced extended progression-free survival (PFS) (p=0.05) and overall survival (OS) (p=0.04) compared to those in the surgical group. On postoperative day 2, 17 patients had CTCs＜4, while 14 patients had CTCs≥4. Individuals with CTCs＜4 demonstrated significantly prolonged PFS (p＜0.01, HR=6.26, 95% CI 1.96-19.96) and OS (p＜0.01, HR=6.63, 95% CI 2.08-21.13) compared to those with CTCs≥4. CTM was detected in 45.16% of patients at any given time. Survival analysis indicated that CTM- patients exhibited longer PFS (p=0.029, HR=2.92, 95% CI 1.05-8.07) and OS (p=0.03, HR=2.92, 95% CI 1.06-8.09) than CTM+ patients.
Conclusions: Single-time detection offers limited information for prognostic evaluation, a dynamic fluctuation in the quantity of CTCs/CTM throughout the course of treatment, exhibiting a robust predictive impact on patient prognosis.
High-Fidelity Pose Estimation for Real-Time Extended Reality (XR) Visualization for Cardiac Catheterization
Authors: Mosadegh Bobak , Annabestani Mohsen , Sri Sandhya , Caprio Alexandre , Janghorbani Sepehr , Wong S. Chiu , Sigaras Alexandros
Published: July 2024

Extended reality (XR) technologies are emerging as promising platforms for medical training and procedural guidance, particularly in complex cardiac interventions. This paper presents a high-fidelity methodology to perform real-time 3D catheter tracking and visualization during simulated cardiac interventions. A custom 3D-printed setup with mounted cameras enables biplane video capture of a catheter. A computer vision algorithm processes the biplane images in real-time to reconstruct the 3D catheter trajectory represented by any designated number of points along its length. This method accurately localizes the catheter tip within 1 mm and can reconstruct any arbitrary catheter configuration. The tracked catheter data is integrated into an interactive Unity-based scene rendered on the Meta Quest 3 headset. The visualization seamlessly combines a reconstructed 3D patient-specific heart model with the dynamically tracked catheter, creating an immersive extended reality training environment. Our experimental study, involving six participants, demonstrated that the 3D visualization provided by the proposed XR system significantly outperformed 2D visualization in terms of speed and user experience. This suggests that the XR system has the potential to enhance catheterization training by improving spatial comprehension and procedural skills. The proposed system demonstrates the potential of XR technologies to transform percutaneous cardiac interventions through improved visualization and interactivity.
Kikuchi disease-associated Mollaret meningitis with MEFV gene mutation successfully treated with colchicine
Authors: Handa Hideo , Sugiyama Atsuhiko , Kubosawa Hitoshi , Nakagawa Yuki , Kishida Dai , Uzawa Akiyuki , Aotsuka Akiyo , Kuwabara Satoshi
Published: July 2024

Background: This case report aims to present a case of Mollaret meningitis caused by Kikuchi disease, an uncommon benign inflammatory disorder, thereby highlighting a novel etiology for Mollaret meningitis. Additionally, it discusses colchicine as a new potential treatment option for Kikuchi disease.
Case presentation: A 41-year-old Japanese woman presented with fever and headache. She had nuchal rigidity and bilateral cervical lymphadenopathies. Her past medical history included multiple episodes of aseptic meningitis and cervical lymphadenopathy for more than twenty years. Lumbar puncture showed increased lymphocytes and IL-6 level and pathognomonic Mollaret cells. Excisional lymph node biopsy revealed histiocytic necrotizing lymphadenitis, confirming the diagnosis of Kikuchi disease. Subsequently, her recurrent Kikuchi disease was successfully treated with colchicine. Furthermore, genetic analysis of the MEFV gene revealed heterozygous P369S/R408Q mutation in exon 3.
Conclusion: Mollaret meningitis can be caused by Kikuchi disease, and recurrence of both may be suppressed by colchicine.
Long-term culture of skin biopsies: Maintenance of fibroblast production and competency of reprogramming
Authors: Rathan-Kumar Sudiksha , Ripperger Michael A , Westlake Grant M , Ess Kevin C
Published: July 2024

Primary fibroblasts are a commonly used cell type used in a variety of experimental and therapeutic studies. Patient-derived skin biopsies are an accessible way to generate fibroblasts for use in various assays as well as reprogramming to iPSCs. To understand the potential of long-term skin biopsy culture, we cultured biopsy samples for 6 to 16 months and analyzed subsequent generation of fibroblasts. We found maintenance of morphology and physiology over time. Proliferation assays showed that older generations remained proliferative but at a decreased rate. mRNA analyses revealed transcriptional changes with long-term skin culture. Deep DNA sequencing did not reveal any large deletions or amplifications. Spontaneous DNA mutations seemed to be random and not enriched for any specific signaling pathways. Older fibroblasts generated after 16 months in culture retained competency for reprogramming into iPSCs. Our results support long term culture of skin to generate very large numbers of primary fibroblasts. These cells maintain their identity and integrity enabling the study of human disorders, particularly rare ones.
Endoscopic resection with additional surgery versus primary surgery in T1 colorectal cancer analysis: outcomes and lymph node metastasis risk factors
Authors: Chen Pin-Chun , Kao Yi-Kai , Yang Po-Wen , Chen Chia-Hung , Chen Chih-I
Published: July 2024

Optimal management of T1 colorectal cancer (CRC) remains controversial. This study compared the long-term outcomes of endoscopic resection with additional surgical resection (ER + ASR) versus primary surgical resection (PS) in patients with T1 CRC and identified risk factors for lymph node metastasis (LNM). We conducted a retrospective cohort study involving 373 patients with T1 CRC who underwent ER + ASR or PS between January 2010 and December 2020 at a tertiary center in Taiwan. Surgical and oncological outcomes, including recurrence rates, LNM, 5-year overall survival (OS), and 5-year recurrence-free survival (RFS), were compared. Univariate and multivariate analyses identified risk factors for LNM. No significant differences were observed between the ER + ASR and PS groups in surgical outcomes, recurrence rates, LNM, 5-year OS (93% vs. 89%, P = 0.18), or 5-year RFS (89% vs. 88%, P = 0.47). Patients with ≥ 2 high-risk factors had significantly lower 5-year OS and RFS compared to those with ≤ 1 risk factor (p < 0.01). Poor histology grade and lymphovascular invasion were independent risk factors for LNM. ER + ASR and PS had comparable long-term outcomes in patients with T1 CRC. A multidisciplinary approach and standardized protocols are needed for optimal management of early-stage CRC.
ERα status of invasive ductal breast carcinoma as a result of regulatory interactions between lysine deacetylases KAT6A and KAT6B
Authors: OLBROMSKI MATEUSZ , MROZOWSKA MONIKA , SMOLARZ BEATA , ROMANOWICZ HANNA , RUSAK AGNIESZKA , PIOTROWSKA ALEKSANDRA
Published: July 2024

Background
Breast cancer (BC) is the leading cause of death among cancer patients worldwide. In 2020, almost 12% of all cancers were diagnosed with BC. Therefore, it is important to search for new potential markers of cancer progression that could be helpful in cancer diagnostics and successful anti-cancer therapies. In this study, we investigated the potential role of the lysine acetyltransferases KAT6A and KAT6B in the outcome of patients with invasive breast carcinoma.
Methods
The expression profiles of KAT6A/B in 495 cases of IDC and 38 cases of mastopathy (FBD) were examined by immunohistochemistry. KAT6A/B expression was also determined in the breast cancer cell lines MCF-7, BT-474, SK-BR-3, T47D, MDA-MB-231, and MDA-MB-231/BO2, as well as in the human epithelial mammary gland cell line hTERT-HME1 – ME16C, both at the mRNA and protein level.
Results
Statistical analysis of the results showed that the nuclear expression of KAT6A/B correlates with the estrogen receptor status: KAT6ANUC vs. ER r = 0.2373 and KAT6BNUC vs. ER r = 0.1496. Statistical analysis clearly showed that KAT6A cytoplasmic and nuclear expression levels were significantly higher in IDC samples than in FBD samples (IRS 5.297 ± 2.884 vs. 2.004 ± 1.072, p < 0.0001; IRS 5.133 ± 4.221 vs. 0.1665 ± 0.4024, p < 0.0001, respectively). Moreover, we noticed strong correlations between ER and PR status and the nuclear expression of KAT6A and KAT6B (nucKAT6A vs. ER, p = 0.0048; nucKAT6A vs. PR p = 0.0416; nucKAT6B vs. ER p = 0.0306; nucKAT6B vs. PR p = 0.0213). Significantly higher KAT6A and KAT6B expression was found in the ER-positive cell lines T-47D and BT-474, whereas significantly lower expression was observed in the triple-negative cell lines MDA-MB-231 and MDA-MB-231/BO2.
Conclusions
The outcomes of small interfering RNA (siRNA)-mediated suppression of KAT6A/B genes revealed that within estrogen receptor (ER) positive and negative cell lines, MCF-7 and MDA-MB-231, attenuation of KAT6A led to concurrent attenuation of KAT6A, whereas suppression of KAT6B resulted in simultaneous attenuation of KAT6A. Furthermore, inhibition of KAT6A/B genes resulted in a reduction in estrogen receptor (ER) mRNA and protein expression levels in MCF-7 and MDA-MMB-231 cell lines.
Impact
Based on our findings, the lysine acetyltransferases KAT6A and KAT6B may be involved in the progression of invasive ductal breast cancer. Further research on other types of cancer may show that KAT6A and KAT6B could serve as diagnostic and prognostic markers for these types of malignancies.
Plasmonic semi shells derived from simultaneous in situ gold growth and anisotropic acid etching of ZIF-8 for photothermal ablation of metastatic breast tumor
Authors: Shanavas Asifkhan , Sood Kritika , Mathur Purvi , Rath Sulagna , Yadav Pranjali , Kaur Navneet , Sharma Priyanka , . Mimansa , Chauhan Deepak Singh , Vaidya Sonalika , Srivast Rohit , De Abhijit
Published: July 2024

A rapid colloidal synthetic protocol for PEGylated semi shell (SS) fabrication using nano metal-organic framework, ZIF-8 as a sacrificial template is reported. The mechanism of semi shell formation was found to be simultaneous facet specific anisotropic chemical etching of rhombic dodecahedral ZIF-8 and heterogenous nucleation & growth of gold. The SS possesses a strong localized surface plasmon resonance in the near-infrared region, which is retained after surface passivation with polyethylene glycol and subsequent cryopreservation for extended shelf-life. Freshly reconstituted PEGylated SS was found to be hemocompatible & biocompatible under in vitro conditions as well as safe & non-toxic in healthy C57BL/6 mice post intravenous administration for up to 28 days. The PEGylated SS displayed significant photothermal efficiency of ~ 37% with 808 nm laser irradiation. Preclinical assessment of intra-tumoral photothermal efficacy indicated complete remission of primary breast tumor mass with insignificant metastasis to vital organs in 4T1 FL2 tumor bearing CD1 nude mice. Further, PEGylated SS mediated photothermal therapy also yielded morbidity free survival of 75% in a syngeneic 4T1 breast tumor model for up to 90 days, indicating their potential to significantly improve outcomes in advanced breast tumors.
Human Perception of Bonobo Emotional Expressions: The Role of Expertise and Expression Channel
Authors: Kim Yena , Vogelezang Nick , Karch Julian D. , Kret Mariska
Published: July 2024

Reading emotional states of the interacting partner is fundamental for social communication. This ability of inferring others’ emotions is specialised for within-species communication, but is known to extend to cross-species interactions. Previous studies have suggested both morphological similarity and familiarity with the expressing species play a role in the success in cross-species emotion communication. To investigate the relative contribution of these factors in cross-species emotion perception of closely related species, humans and bonobos, we asked human participants with varying degrees of experience with bonobos to assign emotion labels to images of bonobo emotional expressions, and rate them on valence and intensity. Moreover, we investigated how the channel (face vs. body) and emotional valence (negative vs. positive) of bonobo expressions modulate the perception. The results show that experts agreed more on the labels assigned to positive and neutral faces and bodies than novices or intermediates, while negative bodies were perceived similarly by all three groups. Interestingly, novices showed a higher agreement score than experts and intermediates to label negative facial expressions. The effect of expert superiority for positive and neutral images was attenuated in valence ratings, and the ratings on negative faces remained difficult even for experts. Similar to the results of the emotional labels, novices agreed specifically well on the interpretation of the negative faces. For intensity ratings, expert superiority remained the same for facial expressions with negative facial expressions yielding the highest agreement scores in general. Our results indicate a mixed effect of similarity and familiarity: while novices predominantly use anthropomorphic strategies, experts drew upon their extensive knowledge to evaluate the emotional states from bonobo images. Bodily expressions showed similar effects of expert superiority, though not as strongly as facial expressions. Overall, experience plays a predominant role in cross-species emotion recognition.
Impact of Dietary Macromolecular Quantity and Quality on Host Assimilation of Microbially Derived Essential Amino Acids
Authors: Mertz Conner M. , Mancuso Christy J. , Robinson David M. , James Leigh D. , Fogel Marilyn L. , Takacs-Vesbach Cristina , Newsome Seth D.
Published: July 2024

Background
Protein is the main structural and functional component of cells making it crucial for the survival of all living organisms. Wild mammalian herbivores and omnivores often consume diets deficient in the amount of protein required to grow and maintain homeostasis. To compensate, mammals likely rely on their gut microbiota to synthesize essential amino acids (AAESS) needed for survival. In this study, we investigated whether deer mice (Peromyscus maniculatus) utilized AAESS synthesized by their gut-associated microbiota with a series of controlled feeding experiments with either a synthetic or semi-natural diet that varied in the type (quality) and quantity of protein and carbohydrates mice may encounter in the wild. Our study combines genetic sequencing (16S rRNA gene and shotgun metagenomic) with compound-specific carbon isotope (d13C) analysis to trace the origin of AAESS used by mammals to build their skeletal muscle.
Results
Results show that dietary macromolecular quality, in addition to quantity, plays a substantial role in host assimilation of microbially derived AAESS and drives microbial genomic potential for AAESS biosynthesis. Mice fed diets limited in dietary protein received greater contributions of AAESS of microbial origin, especially branched-chain amino acids (valine, leucine, isoleucine), lysine, and threonine. Gut microbial populations with the genetic potential for AAESS biosynthesis were differentially abundant in mice with substantial contributions of microbially derived AAESS in their skeletal muscle. Significant microbial contributions of AAESS in host muscle were observed in the low (2.5%) protein synthetic diet, while a larger suite of microbial AAESS contributed to tissue synthesis in mice fed the semi-natural diet across all protein treatments (2.5–10%).
Conclusions
Our study highlights the crucial and likely pervasive role the gut microbiome plays in host protein metabolism, especially in wild herbivorous and omnivorous mammals facing dietary protein limitation. Critical interactions between mammals and their associated gut microbiome are often difficult to disentangle. Our work provides a framework for doing so by uniquely combining genetic and isotopic data to advance our understanding of animal physiology and ecology.
Socio-Demographic Determinants of Myelofibrosis Outcomes in an Underserved Center and the SEER National Database
Authors: Yan John , Hammami M Bakri , Wei John , Shah Nishi , Goldfinger Mendel , Mantzaris Ioannis , Kornblum Noah , Gritsman Kira , Sica Alejandro , Cooper Dennis , Feldman Eric , Konopleva Marina , Pradhan Kith , Thakur Rahul , Vegivinti Charan , Qasim Asma , Verma Amit , Goel Swati
Published: July 2024

The influence of demographic characteristics and social determinants on cancer outcomes is widely recognized in various malignancies but remains understudied in myelofibrosis (MF). This study aims to investigate social and demographic variables associated with MF survival. We retrospectively reviewed data of biopsy-proven MF patients from the Surveillance, Epidemiology and End Results (SEER) database (2000–2021) and Montefiore Medical Center (2000–2023), an underserved inner-city hospital. The SEER cohort included 5,403 MF patients and was predominantly Non-Hispanic (NH) White (82%) with a median age of 69 years. The age-adjusted incidence rate of MF was 0.32 cases per 100,000 person-years, increasing annually by 1.3% from 2000 to 2021. Two- and five- year overall survival rates were 69% and 42%, respectively. Worse cause-specific survival was associated with older age, male sex, and diagnosis before 2011 (year of Ruxolitinib approval). NH-Black ethnicity, unmarried status and lower median income were independent predictors of worse overall survival. The single-center analysis included 84 cases, with a median age of 66 years. NH-White patients comprised 37% of the sample, followed by NH-Black (28.5%). Two- and five- year overall survival rates were 90% and 61%, respectively, with NH-Black patients exhibiting the lowest median survival. Age was a significant predictor of worse survival in this cohort. NH-Black and Hispanic patients lived in areas with higher socioeconomic and demographic stress compared to NH-White patients. Overall, this study highlights the association of social and demographic factors with MF survival and emphasizes the need for equitable healthcare and further exploration of social-demographic factors affecting MF survival.
DI George Syndrome in Newborns Conceived From Assisted Reproductive Techniques: Is Preimplantation Screening Necessary? A Discussion of Two Cases
Authors: Rubio-Duarte Andres Felipe , Aristizabal-Perez Laura Cristina , Riaño-Medina Carlos Eduardo
Published: July 2024

Background: Assisted reproductive techniques are increasingly used, and thus the use of tests for the identification of possible genetic errors in the embryo should be optimized, which translate to the occurrence of congenital diseases in newborns. DiGeorge syndrome (DGS) is a severe genetic syndrome that implies a higher risk of complex congenital heart diseases and metabolic and immunological abnormalities. Reports of DGS in newborns conceived via intracytoplasmic sperm injection (ICSI) are limited to only two cases, one of which involved a diagnosis in the implanted embryo, resulting in pregnancy termination. We present two cases of DGS in two pregnancies conceived via ICSI, without prenatal diagnosis and with complex congenital heart disease.
Case presentation: Case 1 involves a full-term female newborn, conceived via ICSI, without prenatal diagnosis of structural anomalies. At birth, the patient presented with hypotonia, hypocalcemia, seizures, and phenotypic characteristics of DGS; she also had congenital heart disease characterized by interruption of the aortic arch. A successful surgical repair of the congenital heart disease was performed, and the patient required oral calcium supplementation and anticonvulsants upon hospital discharge. Case 2 involves a preterm male newborn, conceived via ICSI in a surrogate uterus, born with cyanosis, hypotonia, retrognathia, a short neck, and other minor abnormalities. He was diagnosed with Tetralogy of Fallot and hypocalcemia; surgical correction of the heart disease was performed at 6 months of age, and he required oral calcium supplementation. Both cases had follow-ups at one year of age, without complications, and with a confirmed genetic diagnosis of DGS.
Conclusions: DGS is a genetic syndrome associated with anatomical and immunological abnormalities that can potentially compromise the life of the newborn, including complex congenital heart disease. Its association with assisted reproductive techniques is limited. It is necessary to consider preimplantation screening when there is a suspected increased risk of DGS, especially with a family history of this syndrome. Preimplantation diagnosis should be considered based on the individual characteristics of the gestational carrier, the father, and the findings of congenital anomalies associated with this disease.