bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beckwith-Wiedemann syndrome and twinning: case report and brief review of literature
Authors: Elefante Pierandrea , Spedicati Beatrice , Faletra Flavio , Pignata Laura , Cerrato Flavia , Riccio Andrea , Barbi Egidio , Memo Luigi , Travan Laura 
Published: September 2023

Abstract
Background
Beckwith-Wiedemann syndrome (BWS, OMIM #130,650) is a pediatric overgrowth disorder involving a predisposition to tumor development. Although the clinical management of affected patients is well established, it is less clear how to handle with the cases of siblings of affected patients, since the prevalence of the condition in twins (1:1000) is ten times higher than in singletones (1:10000).

Case presentation
We report the case of a premature twin patient who during her follow-up develops a clinical phenotype compatible with BWS, genetically confirmed in blood. However, the methylation alteration characteristic of the condition was also found in the almost phenotypically normal sibling, making it challening her management.

Conclusion
Through our case report we highlight how the diagnosis of BWS can be made without any prenatal suspicion and we propose a review of the literature on how to manage siblings of affected patients in twinning situation.
Predictors and a novel predictive model for intravascular immunoglobulin resistance in Kawasaki disease
Authors: Wang Junjie , Huang Xiaohui , Guo Donghao 
Published: September 2023

Abstract
Background
Early identification of intravenous immunoglobulin (IVIG) resistance contributes to better management of Kawasaki disease (KD). This study aims to establish an effective prediction model for IVIG resistance in the Chinese population.

Methods
A total of 658 eligible patients diagnosed with KD were enrolled in this study, with 461 in the training cohort and 197 in the validation cohort. The demographic characteristics and potential risk factors were compared between IVIG-responsive and resistant groups. Predictors were selected by the Akaike information criterion. The nomogram’s performance was evaluated by calibration curve, decision curve analysis, and operating characteristic curve.

Results
White blood cell counts (WBC), neutrophil-lymphocyte ratio (N/L ratio), hematocrit (HCT), albumin (ALB), total bilirubin (TBIL), lactate dehydrogenase (LDH), and creatinine (Cr) were detected as predictors of IVIG resistance. A predictive nomogram incorporating these predictors was constructed using the training cohort. The calibration curve and decision curve analysis showed good discrimination and calibration of the proposed nomogram in both training and validation sets, and the area under the receiver operating characteristic curve (AUROC) in both sets was 75.8% and 74.2%, respectively.

Conclusion
This study identified WBC, N/L ratio, HCT, ALB, TBIL, LDH, and Cr as predictors for IVIG resistance in patients with KD. The proposed novel nomogram with a high level of accuracy and reliability may benefit clinical decision-making upon treatment initiation.
Elucidating disease-associated mechanisms triggered by pollutants via the epigenetic landscape using large-scale ChIP-Seq data
Authors: Zou Zhaonan , Yoshimura Yuka , Yamanishi Yoshihiro , Oki Shinya 
Published: September 2023

Abstract
Background
Despite well-documented effects on human health, the action modes of environmental pollutants are incompletely understood. Although transcriptome-based approaches are widely used to predict associations between chemicals and disorders, the molecular cues regulating pollutant-derived gene expression changes remain unclear. Therefore, we developed a data-mining approach, termed “DAR-ChIPEA,” to identify transcription factors (TFs) playing pivotal roles in the action modes of pollutants.

Methods
Large-scale public ChIP-Seq data (human, n = 15,155; mouse, n = 13,156) were used to predict TFs that are enriched in the pollutant-induced differentially accessible genomic regions (DARs) obtained from epigenome analyses (ATAC-Seq). The resultant pollutant–TF matrices were then cross-referenced to a repository of TF–disorder associations to account for pollutant modes of action. We subsequently evaluated the performance of the proposed method using a chemical perturbation data set to compare the outputs of the DAR-ChIPEA and our previously developed differentially expressed gene (DEG)-ChIPEA methods using pollutant-induced DEGs as input. We then adopted the proposed method to predict disease-associated mechanisms triggered by pollutants.

Results
The proposed approach outperformed other methods using the area under the receiver operating characteristic curve score. The mean score of the proposed DAR-ChIPEA was significantly higher than that of our previously described DEG-ChIPEA (0.7287 vs. 0.7060; Q = 5.278 × 10–42; two-tailed Wilcoxon rank-sum test). The proposed approach further predicted TF-driven modes of action upon pollutant exposure, indicating that (1) TFs regulating Th1/2 cell homeostasis are integral in the pathophysiology of tributyltin-induced allergic disorders; (2) fine particulates (PM2.5) inhibit the binding of C/EBPs, Rela, and Spi1 to the genome, thereby perturbing normal blood cell differentiation and leading to immune dysfunction; and (3) lead induces fatty liver by disrupting the normal regulation of lipid metabolism by altering hepatic circadian rhythms.

Conclusions
Highlighting genome-wide chromatin change upon pollutant exposure to elucidate the epigenetic landscape of pollutant responses outperformed our previously described method that focuses on gene-adjacent domains only. Our approach has the potential to reveal pivotal TFs that mediate deleterious effects of pollutants, thereby facilitating the development of strategies to mitigate damage from environmental pollution.
MyD88 dimerization inhibitor ST2825 targets the aggressiveness of synovial fibroblasts in rheumatoid arthritis patients
Authors: Ramirez-Perez Sergio , Vekariya Rushi , Gautam Surabhi , Reyes-Perez Itzel Viridiana , Drissi Hicham , Bhattaram Pallavi 
Published: September 2023

Abstract
Background
Dimerization of the myeloid differentiation primary response 88 protein (MyD88) plays a pivotal role in the exacerbated response to innate immunity-dependent signaling in rheumatoid arthritis (RA). ST2825 is a highly specific inhibitor of MyD88 dimerization, previously shown to inhibit the pro-inflammatory gene expression in peripheral blood mononuclear cells from RA patients (RA PBMC). In this study, we elucidated the effect of disrupting MyD88 dimerization by ST2825 on the pathological properties of synovial fibroblasts from RA patients (RA SFs).

Methods
RA SFs were treated with varying concentrations of ST2825 in the presence or absence of bacterial lipopolysaccharides (LPS) to activate innate immunity-dependent TLR signaling. The DNA content of the RA SFs was quantified by imaging cytometry to investigate the effect of ST2825 on different phases of the cell cycle and apoptosis. RNA-seq was used to assess the global response of the RA SF toward ST2825. The invasiveness of RA SFs in Matrigel matrices was measured in organoid cultures. SFs from osteoarthritis (OA SFs) patients and healthy dermal fibroblasts were used as controls.

Results
ST2825 reduced the proliferation of SFs by arresting the cells in the G0/G1 phase of the cell cycle. In support of this finding, transcriptomic analysis by RNA-seq showed that ST2825 may have induced cell cycle arrest by primarily inhibiting the expression of critical cell cycle regulators Cyclin E2 and members of the E2F family transcription factors. Concurrently, ST2825 also downregulated the genes encoding for pain, inflammation, and joint catabolism mediators while upregulating the genes required for the translocation of nuclear proteins into the mitochondria and members of the mitochondrial respiratory complex 1. Finally, we demonstrated that ST2825 inhibited the invasiveness of RA SFs, by showing decreased migration of LPS-treated RA SFs in spheroid cultures.

Conclusions
The pathological properties of the RA SFs, in terms of their aberrant proliferation, increased invasiveness, upregulation of pain and inflammation mediators, and disruption of mitochondrial homeostasis, were attenuated by ST2825 treatment. Taken together with the previously reported anti-inflammatory effects of ST2825 in RA PBMC, this study strongly suggests that targeting MyD88 dimerization could mitigate both systemic and synovial pathologies in a variety of inflammatory arthritic diseases.
Plasma aryl hydrocarbon receptor associated with epicardial adipose tissue in men: a cross-sectional study
Authors: Cheng Yu-Cheng , Ma Wei-Chun , Li Yu-Hsuan , Wu Junyi , Liang Kae-Woei , Lee Wen-Jane , Liu Hsiu-Chen , Sheu Wayne Huey-Herng , Lee I-Te 
Published: September 2023

AbstractBackgroundEpicardial adipose tissue (EAT) is a type of ectopic fat with endocrine and paracrine functions. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that responds to environmental stimuli. AhR expression is associated with obesity. In this cross-sectional study, we aimed to determine the relationship between circulating AhR concentrations and EAT.MethodsA total of 30 men with obesity and 23 age-matched men as healthy controls were enrolled. Plasma AhR concentrations were determined at fasting. The EAT thickness was measured on the free wall of the right ventricle from the basal short-axis plane by magnetic resonance imaging.ResultsThe participants with obesity had a higher plasma AhR level than the controls (81.0 ± 24.5 vs. 65.1 ± 16.4 pg/mL, P = 0.010). The plasma AhR level was positively correlated with EAT thickness (correlation coefficient = 0.380, P = 0.005). After adjusting for fasting glucose levels, plasma AhR levels were still significantly associated with EAT thickness (95% CI 0.458‒5.357, P = 0.021) but not with body mass index (P = 0.168).ConclusionPlasma AhR concentrations were positively correlated with EAT thickness on the free wall of the right ventricle in men. Further investigations are needed to evaluate the causal effects and underlying mechanisms between AhR and EAT.
Utility of contrast enhanced ultrasound (CEUS) in penile trauma
Authors: Gómez-Bermejo Miguel A. , Huang Dean Y. , Bertolotto Michele , Sidhu Paul S. 
Published: September 2023

AbstractPenile traumatic injuries are rare with potentially severe consequences, with clinical assessment challenging due to pain and swelling. Ultrasound is the primary imaging modality for assessing the penis. It has a high spatial resolution and rapid availability and is portable. Contrast enhanced ultrasound is an advanced ultrasound technique that adds real-time dynamic vascular imaging safely, increasing diagnostic precision and confidence, allowing for better therapeutic management of traumatic penile injuries. Contrast enhanced ultrasound helps to delineate the extent of a haematoma, distinguishing this from the herniated corpus cavernosum, detecting the point of rupture of the tunica albuginea, showing vascular abnormalities, localising a dislocated penis and determining penile viability. The integrity of the urethra may be assessed with intracavitary contrast enhanced ultrasound. Additionally, contrast enhanced ultrasound allows monitoring of the response to endovascular and surgical treatment. This review aims to detail the anatomy and pathogenesis of penile trauma, to give guidance on optimising the contrast enhanced ultrasound technique and to obtain diagnostic examinations. Illustration of the spectrum of aspects of penile trauma will be complemented with a literature review.Critical relevance statement Contrast enhanced ultrasound is a safe and efficient imaging modality that allows for highly accurate diagnoses, helping achieve more successful and conservative treatments of penile trauma complications.Key points• Ultrasound is an accurate and safe imaging test for penile trauma.• CEUS adds dynamic vascular imaging in real-time increasing diagnostic confidence.• CEUS can delineate penile haematomas, locate fractures and demonstrate vessel integrity.• CEUS potentially allows for more conservative treatment of penile trauma complications.
Graphical Abstract
Early chest CT abnormalities to predict the subsequent occurrence of chronic lung allograft dysfunction
Authors: Habert Paul , Chetrit Elsa , Coiffard Benjamin , Bregeon Fabienne , Thomas Pascal , Loundou Anderson , Bermudez Julien , Reynaud-Gaubert Martine , Gaubert Jean-Yves 
Published: September 2023

Abstract
Introduction
Chronic lung allograft dysfunction (CLAD) can take two forms: bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS). The aim was to determine if chest-CT abnormalities after lung transplantation (LTx) could predict CLAD before respiratory functional deterioration.

Materials and methods
This monocentric retrospective study analyzed consecutive patients who underwent LTx from January 2015 to December 2018. Initial CT post-LTx (CTi) and a follow-up CT at least 9 months post-LTx (CTf) were reviewed. CLAD was defined as a persistent respiratory functional decline (> 20% of basal FEV1) outside acute episode. A Cox regression was performed in univariate, then in multivariate analysis (including features with p < 0.01 in univariate or of clinical importance) to determine risk factors for CLAD. Subgroup analyses were made for BOS, RAS, and death.

Results
Among 118 LTx patients (median (min–max) 47 (18–68) years), 25 developed CLAD during follow-up (19 BOS). The median time to CLAD since LTx was 570 days [150–1770]. Moderate pulmonary artery stenosis (30–50%) was associated with the occurrence of CLAD on CTi (hazard ratio HR = 4.6, CI [1.6–13.2]) and consolidations and pleural effusion on CTf (HR = 2.6, CI [1.3–4.9] and HR = 4.5, CI [1.5–13.6] respectively). The presence of mosaic attenuation (HR = 4.1, CI [1.4–12.5]), consolidations (HR = 2.6, CI [1.3–5.4]), and pleural effusions (p = 0.01, HR = 5.7, CI [1.4–22.3]) were risk factors for BOS on CTf. The consolidations (p = 0.029) and pleural effusions (p = 0.001) were risk factors for death on CTf.

Conclusions
CTi and CTf in the monitoring of LTx patients could predict CLAD. Moderate pulmonary artery stenosis, mosaic pattern, parenchyma condensations, and pleural effusions were risk factors for CLAD.

Critical relevance statement
There is a potential predictive role of chest CT in the follow-up of LTx patients for chronic lung allograft dysfunction (CLAD). Early chest CT should focus on pulmonary artery stenosis (risk factor for CLAD in this study). During the follow-up (at least 9 months post-LTx), parenchymal consolidations and pleural effusions were shown to be risk factors for CLAD, and death in subgroup analyses.

Key points
• Pulmonary artery stenosis (30–50%) on initial chest-CT following lung transplantation predicts CLAD HR = 4.5; CI [1.6–13.2].
• Pleural effusion and consolidations 1 year after lung transplantation predict CLAD and death.
• Early evaluation of lung transplanted patients should evaluate pulmonary artery anastomosis.

Graphical Abstract
Predictive modeling based on tumor spectral CT parameters and clinical features for postoperative complications in patients undergoing colon resection for cancer
Authors: Tan Xiaoying , Yang Xiao , Hu Shudong , Chen Xingbiao , Sun Zongqiong 
Published: September 2023

Abstract
Background
Colon cancer is a particularly prevalent malignancy that produces postoperative complications (POCs). However, limited imaging modality exists on the accurate diagnosis of POCs. The purpose of this study was therefore to construct a model combining tumor spectral CT parameters and clinical features to predict POCs before surgery in colon cancer.

Methods
This retrospective study included 85 patients who had preoperative abdominal spectral CT scans and underwent radical colon cancer resection at our institution. The patients were divided into two groups based on the absence (no complication/grade I) or presence (grades II–V) of POCs according to the Clavien-Dindo grading system. The visceral fat areas (VFA) of patients were semi-automatically outlined and calculated on L3-level CT images using ImageJ software. Clinical features and tumor spectral CT parameters were statistically compared between the two groups. A combined model of spectral CT parameters and clinical features was established by stepwise regression to predict POCs in colon cancer. The diagnostic performance of the model was evaluated using the receiver operating characteristic (ROC) curve, including area under the curve (AUC), sensitivity, and specificity.

Results
Twenty-seven patients with POCs and 58 patients without POCs were included in this study. MonoE40keV-VP and VFA were independent predictors of POCs. The combined model based on predictors yielded an AUC of 0.84 (95% CI: 0.74–0.91), with a sensitivity of 77.8% and specificity of 87.9%.

Conclusions
The model combining MonoE40keV-VP and VFA can predict POCs before surgery in colon cancer and provide a basis for individualized management plans.

Critical relevance statement
The model combining MonoE40keV-VP and visceral fat area can predict postoperative complications before surgery in colon cancer and provide a basis for individualized management plans.

Key points
• Visceral fat area and MonoE40keV-VP were independent predictors of postoperative complications in colon cancer.
• The combined model yielded a high AUC, sensitivity, and specificity in predicting postoperative complications.
• The combined model was superior to the single visceral fat area or MonoE40keV-VP in predicting postoperative complications.

Graphical Abstract
Metastatic lung adenocarcinoma with BRCA2 mutation and longstanding disease control on olaparib, developing triple negative breast adenocarcinoma with additional BRCA2 reversion mutation: a case report
Authors: del Giglio Auro , da Costa Aguiar Alves Beatriz , Murad André Márcio , Fonseca Fernando Luiz Affonso 
Published: September 2023

AbstractBackgroundTheBRCA2gene is a well-known tumor suppressor gene implicated in breast and ovarian cancers.BRCA1/2mutations can be sensitive to poly ADP-ribose polymerase (PARP) inhibitors such as olaparib. However, some of these patients develop resistance to this treatment and an essential factor contributing to acquired insensitivity is the occurrence of reversion mutations in theBRCA1/2genes.Case presentationWe report the case of a 65-year-old Brazilian female patient who had previously been diagnosed with metastatic lung carcinoma carrying aBRCA2mutation that had extended to the central nervous system. Following disease progression, olaparib was administered, resulting in a stabilizing effect on her condition for ~ 30 months. During a routine follow-up, a new triple-negative breast tumor was found. Genetic testing revealed the presence of two distinctBRCA2gene mutations in the breast tumor. The original mutation (p.Val220Ilefs4) led to a frameshift, culminating in the production of a truncated and non-functional BRCA2 protein; the second mutation, K437fs22, rectified the reading frame of exon 11. Consequently, Rad51 could properly bind to BRCA2—an essential protein crucial for DNA repair. This restoration resulted in a functional BRCA2 protein, effectively elucidating the clinical resistance observed in the new breast tumor in this case.ConclusionsThis case report highlights the clinical significance of comprehensive next-generation sequencing analyses for lung adenocarcinomas, both at diagnosis and upon progression. Such analyses enable informed decisions regarding targeted therapies and facilitate a deeper comprehension of resistance mechanisms.
Efficacy of fractional CO2 laser in combination with stromal vascular fraction (SVF) compared with fractional CO2 laser alone in the treatment of burn scars: a randomized controlled clinical trial
Authors: Roohaninasab Masoumeh , Khodadad Fariba , Sadeghzadeh-Bazargan Afsaneh , Atefi Najmolsadat , Zare Sona , Jafarzadeh Alireza , Rahimi Seyyedeh Tahereh , Nouri Maryam , Nilforoushzadeh Mohammad Ali , Behrangi Elham , Goodarzi Azadeh 
Published: September 2023

Abstract
Background
The appearance of skin scars is known as one of the main side effects of skin burns. Stromal vascular fraction (SVF), as a rich source of cell populations with tissue regeneration properties, plays an important role in the healing of skin lesions. Fractional CO2 lasers have occupied a special place in treating skin lesions, particularly skin scars, since their introduction. Our study aimed to compare the combination of SVF and fractional CO2 laser with fractional CO2 laser alone in the treatment of burn scars.

Method
This double-blind clinical trial study was conducted on ten patients with burn scars that were treated three times with a fractional CO2 laser at site of burn lesions, and one of the two areas studied was randomly injected with SVF. Two months after completion of the procedure, patients' scars were assessed using the Vancouver scar scale (VSS), biometric criteria, and physician and patient satisfaction ratings.

Results
The results confirmed a significant improvement in VSS, cutometry, R7 criteria, complete density sonography, and skin density sonography in the fractional CO2 laser-treated group. The VSS criteria, epidermal thickness sonography, complete density sonography, and skin density sonography in the group treated with the combination of fractional CO2 laser and SVF also showed significant improvement. The VSS criteria and melanin index of Mexameter in the group treated with SVF in combination with fractional CO2 laser were significantly better than the group treated with fractional CO2 laser alone. Also, physician and patient satisfaction in the group treated with SVF injection in combination with fractional CO2 laser was significantly higher than the other group.

Conclusion
The results confirm the efficacy of SVF injection in combination with fractional CO2 laser in the treatment of burn scars and can be considered as a treatment option for better management of these lesions.
Trial registration: The study protocol was retrospectively registered at Iranian Registry of Clinical Trials with code: IRCT20210515051307N1, Registration date: 2021-11-14, URL: https://www.irct.ir/trial/56337.