bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of 18F-DCFPyL PET/MRI in Selecting Men With Low-/Intermediate-Risk Prostate Cancer for Focal Ablative Therapies
Authors: Basso Dias Adriano , Ghai Sangeet , Ortega Claudia , Mirshahvalad Seyed Ali , Perlis Nathan , Berlin Alejandro , Avery Lisa , Veit-Haibach Patrick , van der Kwast Theodorus , Metser Ur 
Published: September 2023

Purpose
To compare the diagnostic performance of multiparametric (mp) MRI to 18F-DCFPyL PET/MRI for detecting clinically significant (cs) prostate cancer (PCa) in men with low-/intermediate-risk PCa being considered for focal ablative therapy (FT), using 2 interpretation schemes, and to assess the rate of exclusion from FT for each modality.

Methods
This prospective study evaluated men with low- or intermediate-risk PCa, potential candidates for FT based on initial biopsy as per institutional protocol, who underwent 18F-DCFPyL PET/MRI. Each modality (mpMRI, PET/MRI using PROMISE classification [PET/MRI PROMISE], and PET/MRI considering any focal lesion on PET as positive [PETFL/MRI]) was assessed independently. All suspicious lesions underwent PET/MRI-ultrasound fusion biopsies. Diagnostic performances were calculated and compared using the exact binomial test on paired proportions.

Results
Thirty-four men (median age, 64 years; interquartile range, 60–70 years) were included. Overall, 40 of 67 lesions (60%) identified on mpMRI and/or PET/MRI were malignant, and 34 of 40 lesions (85%) were csPCa (≥6 mm ISUP [International Society of Urological Pathology Grade Group] GG1 or ISUP-GG ≥2). On lesion-level analysis, for detecting csPCa, sensitivity appeared higher for PETFL/MRI than mpMRI and PET/MRI PROMISE (97% vs 76% and 79%, respectively [P = 0.02 and 0.03]), whereas specificity was lower (30% vs 85% and 88%, respectively [P < 0.001]). The calculated overall accuracy rates for PETFL/MRI, mpMRI, and PET/MRI PROMISE were 64%, 81%, and 84%, respectively. PETFL/MRI, mpMRI, and PET/MRI PROMISE excluded 10 of 34 (29%), 7 of 34 (21%), and 6 of 34 (18%) men from FT, respectively.

Conclusions

18F-DCFPyL PET/MRI excluded nearly 30% of patients with low-/intermediate-risk PCa from FT, with a potential role in decreasing selection failure. Compared with mpMRI, PET/MRI had a higher sensitivity for detecting csPCa in men who were candidates for FT.
ClinicalTrials.gov identifier NCT03149861.
The Morphological and Functional Effects of the Endoscope-Assisted One-Stage Approach for Crooked Nose
Authors: Sun Yi-Dan , Xie Li-Feng , Zhen Yong-Huan , Li Dong , Zhao Zhen-Min , An Yang 
Published: September 2023

Background:
A crooked nose is an external nose deformity predominantly caused by congenital aplasia or acquired secondary to trauma or surgery, often accompanied by a deviated nasal septum. Patients with crooked nose have dual needs to improve both esthetic and functional problems.

Methods:
The clinical and photographic information of 48 patients diagnosed with a crooked nose and nasal septum deviation treated from January 2018 to January 2022 was acquired. The morphology and functional effects were investigated by evaluating the general condition of the operation, measuring the esthetic indexes of the nose, and subjectively scoring.

Results:
For both morphology and function, endoscopy-assisted one-stage correction showed positive results in this study. The external nose deviation distance postoperatively measured 1.28 (0.85, 1.97) mm, which significantly decreased from the preoperative value of 3.96 (3.31, 5.29) mm. The scores of doctors and irrelevant medical students on nose morphology increased significantly from 4.75±1.88 and 3.84±0.76 to 6.48±1.21 and 7.21±0.67, respectively. The rhinoplasty outcome evaluation score and the “nasal obstruction symptom evaluation “score of patients were both significantly improved (t = −7.508 and t=6.310, respectively, P < 0.001).

Conclusion:
Endoscope-assisted one-stage correction of the crooked nose can restore nasal morphology, improve the symptoms of nasal obstruction, and achieve patient satisfaction. It is a minimally invasive, safe, effective, and fast recovery approach for patients who need to solve both esthetic and functional problems.
Magnetic Resonance Imaging Findings in Patients With Duane Retraction Syndrome
Authors: Guo Yatu , Zhang Quan , Zhang Tingting , Guo Lingzhi , Liu Shichang , Zhao Kanxing , Zhang Wei 
Published: September 2023

Background:
Duane retraction syndrome (DRS) is known to relate to the absence of the abducens nucleus, with abnormal innervation of the lateral rectus (LR) muscle by branches
of the oculomotor nerve (CN III). The purposes of this study were to investigate the morphological characteristics of the oculomotor nerve (CN III), the abducens nerve (CN VI), and the extraocular muscles in patients with clinically diagnosed Duane retraction syndrome (DRS) using MRI. In addition, we assessed the association between ocular motility, horizontal rectus muscle volumes, and CN III/VI in patients with Duane retraction syndrome (DRS).

Methods:
The study comprised 20 orthotropic control subjects (40 eyes) and 42 patients with Duane syndrome (48 eyes), including 20 patients with DRS Type I (24 eyes), 5 patients with DRS Type II (6 eyes), and 17 patients with DRS Type III (18 eyes). Three-dimensional (3D) T1/2 images of the brainstem and orbit were obtained to visualize the cranial nerves, especially the abducens (VI) and oculomotor (III) nerves, as well as extraocular muscles.

Results:
Based on the clinical classification, among 42 patients, MRI showed that the abducens nerves (CN VI) on the affected side were absent in 24 of 24 eyes (100%; 20 patients) with Type I DRS and in 16 of 18 eyes (88%; 16 patients) with Type III DRS. However, CN VI was observed in 6 of 6 eyes (100%; 5 patients) with Type II DRS and in 2 of 18 eyes (11%) with Type III DRS. CN III was observed in all patients. The oculomotor nerves on the affected side were thicker than those on the nonaffected contralateral side in DRS Type I (P < 0.05) and Type III (P < 0.05), but not in DRS Type II. Smaller LR and larger MR volumes were shown in the affected eye than that in the nonaffected eye in DRS Types I and III. Based on the presence or absence of CN VI, there was a tendency for thicker oculomotor nerves in the affected eye than in the nonaffected eye in the absence groups (P < 0.05). However, no significant difference was found in the present group. In the CN VI absence groups, similar results were found in the affected eyes than in the nonaffected eyes as in DRS Types I and III. In addition, the presence of CN VI was correlated with better abduction (P = 0.008). The LR and MR volumes have positive correlations with the oculomotor nerve diameter in the affected eye. However, there was no correlation between the range of adduction/abduction and the LR/MR ratio in patients with or without an abducens nerve.

Conclusions:
Different types of DRS have different characteristic appearances of CN VI and CN III on MRI. Horizontal rectus muscles have morphological changes to adapt to dysinnervation of CN VI and aberrant innervation of CN III. Thus, these neuroimaging findings may provide a new diagnostic criterion for the classification of DRS, improving the comprehension of the physiopathogenics of this disease.
Using a polygenic score to account for genomic risk factors in a model to detect individuals with dilated ascending thoracic aortas
Authors: DePaolo John , Biagetti Gina , Judy Renae , Wang Grace J. , Kelly John , Iyengar Amit , Goel Nicholas J. , Desai Nimesh , Szeto Wilson Y. , Bavaria Joseph E. , Levin Michael G. , Damrauer Scott M. 
Published: September 2023

AbstractBackgroundAscending thoracic aortic dilation is a complex trait that involves modifiable and non-modifiable risk factors and can lead to thoracic aortic aneurysm and dissection. Clinical risk factors have been shown to predict ascending thoracic aortic diameter. Polygenic scores (PGS) are increasingly used to assess clinical risk for multifactorial diseases. The degree to which a PGS can improve aortic diameter prediction is not known. In this study we tested the extent to which the addition of a PGS to clinical prediction algorithms improves the prediction of aortic diameter.MethodsThe patient cohort comprised 6,790 Penn Medicine Biobank (PMBB) participants with available echocardiography and clinical data linked to genome-wide genotype data. Linear regression models were used to integrate PGS weights derived from a large genome wide association study of thoracic aortic diameter in the UK biobank and were compared to the performance of the standard and a reweighted variation of the recently published AORTA Score.ResultsCohort participants were 56% male, had a median age of 61 years (IQR 52-70) with a mean ascending aortic diameter of 3.4 cm (SD 0.5). Compared to the AORTA Score which explained 28.4% (95% CI 28.1% to 29.2%) of the variance in aortic diameter, AORTA Score + PGS explained 28.8%, (95% CI 28.1% to 29.6%), the reweighted AORTA score explained 30.4% (95% CI 29.6% to 31.2%), and the reweighted AORTA Score + PGS explained 31.0% (95% CI 30.2% to 31.8%). The addition of a PGS to either the AORTA Score or the reweighted AORTA Score improved model sensitivity for the identifying individuals with a thoracic aortic diameter ≥ 4 cm. The respective areas under the receiver operator characteristic curve for the AORTA Score + PGS (0.771, 95% CI 0.756 to 0.787) and reweighted AORTA Score + PGS (0.785, 95% CI 0.770 to 0.800) were greater than the standard AORTA Score (0.767, 95% CI 0.751 to 0.783) and reweighted AORTA Score (0.780 95% CI 0.765 to 0.795).ConclusionsWe demonstrated that inclusion of a PGS to the AORTA Score results in a small but clinically meaningful performance enhancement. Further investigation is necessary to determine if combining genetic and clinical risk prediction improves outcomes for thoracic aortic disease.
Unraveling the role of rise in temperature on the emergence of antimicrobial resistance
Authors: Goswami Anuradha , Morris J. Jeffrey 
Published: September 2023

ABSTRACTThe ability of bacteria to resist the effects of antibiotics, or antimicrobial resistance (AMR), is a growing risk to world health, making it more challenging to combat infectious health problems. The growth rate of bacteria is significantly influenced by temperature, particularly temperatures between 35 and 37°C, often considered the most suitable for the spread of human illnesses. Knowing that a rise in temperature influences bacterial growth rate, contributing to a higher infection rate, it is imperative to unravel and comprehend the association between climate change and the emergence of AMR. We hypothesized that rising temperatures could exacerbate the emergence of AMR in opportunistic and pathogenic bacteria. To test our hypothesis, we investigated the global distribution of AMR and the correlation between AMR and socioeconomic factors, climate change, and air quality in the United States. The study found high resistance rates to common infections such as Methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-resistant enterococcus (VRE) infections are prevalent in many countries. In the United States, MRSA-AMR was more common in low-income states with increased poverty rates and poor air quality. The study also found a positive correlation between the rise in temperature over the past 10 years and AMR bacterial infections. The investigation concluded that socioeconomic factors, climate change, and race collectively impact the prevalence of AMR infections. The probability of AMR infection upsurging in the next decade was highest within states with more frequent rises in temperature over the last 10 years. The model predicted that states with at least 1 °C rise in temperature over the previous 10 years are expected to experience a surge in AMR bacterial infections in coming years. Though the statistical details might vary depending on the data collected in future, the correlation between climate change and the emergence of AMR in bacterial infection is alarming. The study indicates that climate change has an essential, largely unrecognized influence on AMR bacterial infections that warrants additional research. It implies that comprehensive and integrated strategies are needed to address the AMR and climate change challenges.
An emerging Ferroptosis-Correlated Genes Character for Renal Cell Carcinoma
Authors: Zhang Lin , Zhou Ying , Zhou Jiashun 
Published: September 2023

AbstractRenal Cell Carcinoma (RCC), composed of various subtypes, faces a prognostic prediction challenge. Ferroptosis, an emerging cell death form, has been considered as a vital factor for the development of cancer. However, it remains a further exploration of the predictive value for ferroptosis-correlated genes in RCC. In our work, we paid attention to the gene expression data related to clinical profiles of RCC patients which derived from public databases, TCGA and ICGC. The least absolute shrinkage and selection operator (LASSO) Cox regression performed to establish an optimally predictive model based on the TCGA data. The RCC patients derived from ICGC applied to the validation of the predictive model above. Under expectation, our observation indicated that major ferroptosis-correlated genes (75%) expressed significantly between tumorous and adjacently normal cells in the TCGA cohort. Combined with the differentially expressed genes (DEGs) (P< 0.05) and overall survival (OS), there were twenty-seven genes eventually approached the subsequent analyses. With the optimal 12-genes model screened by LASSO analysis, we aimed to classify RCC patients into the high-risk or low-risk groups based on the median scores. And we created a novel predictive model based on the 12-genes’ risk score. Compared with the two groups, our work discovered that patients in the high-risk group presented more observably shrunken OS than the low (P < 0.05). Through the multivariate cox regression, the predictive model became an independent risk factor in OS (HR =2.053, P<0.001). Moreover, the receiver operating characteristic (ROC) curve proved the significantly predictive value for our predictive model. Functional research unexpectedly showed the immune cells and immune function pathways enriched differently, which emphasized the immune role for the progress of RCC. In a word, an emerging ferroptosis-correlated signature might be popular for medical prediction in RCC. The targeted treatment on ferroptosis may be a potential schedule for RCC.
Development and Characterization of Proteomic Aging Clocks in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Wang Authors: Shuo , Rao Zexi , Cao Rui , Blaes Anne H. , Coresh Josef , Joshu Corinne E. , Lehallier Benoit , Lutsey Pamela L. , Pankow James S. , Sedaghat Sanaz , Tang Weihong , Thyagarajan Bharat , Walker Keenan A. , Ganz Peter , Platz Elizabeth A. , Guan Weihua , Prizment Anna 
Published: September 2023

AbstractBiological age may be estimated by proteomic aging clocks (PACs). Previous published PACs were constructed either in smaller studies or mainly in White individuals, and they used proteomic measures from only one-time point. In the Atherosclerosis Risk in Communities (ARIC) study of about 12,000 persons followed for 30 years (around 75% White, 25% Black), we created de novo PACs and compared their performance to published PACs at two different time points. We measured 4,712 plasma proteins by SomaScan in 11,761 midlife participants, aged 46-70 years (1990-92), and 5,183 late-life pariticpants, aged 66-90 years (2011-13). All proteins were log2-transformed to correct for skewness. We created de novo PACs by training them against chronological age using elastic net regression in two-thirds of healthy participants in midlife and late life and compared their performance to three published PACs. We estimated age acceleration (by regressing each PAC on chronological age) and its change from midlife to late life. We examined their associations with mortality from all-cause, cardiovascular disease (CVD), cancer, and lower respiratory disease (LRD) using Cox proportional hazards regression in all remaining participants irrespective of health. The model was adjusted for chronological age, smoking, body mass index (BMI), and other confounders. The ARIC PACs had a slightly stronger correlation with chronological age than published PACs in healthy participants at each time point. Associations with mortality were similar for the ARIC and published PACs. For late-life and midlife age acceleration for the ARIC PACs, respectively, hazard ratios (HRs) per one standard deviation were 1.65 and 1.38 (both p<0.001) for all-cause mortality, 1.37 and 1.20 (both p<0.001) for CVD mortality, 1.21 (p=0.03) and 1.04 (p=0.19) for cancer mortality, and 1.46 and 1.68 (both p<0.001) for LRD mortality. For the change in age acceleration, HRs for all-cause, CVD, and LRD mortality were comparable to those observed for late-life age acceleration. The association between the change in age acceleration and cancer mortality was insignificant. In this prospective study, the ARIC and published PACs were similarly associated with an increased risk of mortality and advanced testing in relation to various age-related conditions in future studies is suggested.
Enhancer-driven regulatory network of forebrain human development provides insights into autism
Authors: Jourdon Alexandre , Mariani Jessica , Wu Feinan , Capauto Davide , Norton Scott , Tomasini Livia , Amiri Anahita , Schreiner Jeremy , Nguyen Cindy Khanh , Nolan Neal , Szekely Anna , McPartland James C. , Pelphrey Kevin , Chawarska Katarzyna , Ventola Pamela , Abyzov Alexej , Vaccarino Flora M. 
Published: September 2023

AbstractCell differentiation involves shifts in chromatin organization allowing transcription factors (TFs) to bind enhancer elements and modulate gene expression. The TF-enhancer-gene regulatory interactions that control the formation of neuronal lineages have yet to be charted in humans. Here, we mapped enhancer elements and conducted an integrative analysis of epigenomic and transcriptomic profiles across 60 days of differentiation of human forebrain organoids derived from 10 individuals with autism spectrum disorder (ASD) and their neurotypical fathers. This multi-omics profiling allowed us to build an enhancer-driven gene regulatory network (GRN) of early neural development. We validated the GRN by performing a loss-of-function experiment with FOXG1 – one of the master TFs in the development of the mammalian brain. Analysis of the constructed GRN identified regulatory hierarchies driving the specification of neuronal cell types. By analyzing differential gene expression in ASD through the GRN hierarchy, we associated the ASD transcriptomic signatures to altered activity of key TFs. We found that macrocephalic ASD was principally driven by an increased activity of BHLHE22, FOXG1, EOMES, and NEUROD2, which are major regulators of excitatory neuron fate. Normocephalic ASD, on the contrary, was driven by decreased activity of those same TFs and by an increased activity of LMX1B and FOXB1 – two upstream TF repressors of FOXG1. These findings suggest that ASD is characterized by an altered early gene regulatory program that specifies neuronal cell lineages in the fetal brain. Thus, constructing a GRN of early brain development modeled in organoids provides insights into the etiology of ASD and can guide future experimental approaches to establish its genetic causes and treatment strategies.
Serum levels of adipokines and insulin are associated with markers of brain atrophy and cognitive decline in the spectrum of Alzheimer’s Disease
Authors: Garcia-Garcia Isabel , Kamal Farooq , Donica Olga , Dadar Mahsa ,   Alzheimer’s Disease Neuroimaging Initiative
Published: September 2023

ABSTRACTThe discovery that metabolic alterations often coexist with neurodegenerative conditions has sparked interest in the examination of gastrointestinal factors as potential modulators of brain health. Here, we examined the role of adipokines (leptin, adiponectin, resistin, and IL6) and insulin on different markers of brain atrophy in participants on the spectrum of Alzheimer’s Disease. We included 566 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset with 1063 follow-up time points (average follow-up: one year); and examined the association between gastrointestinal factors and volumetric MRI values, white matter hyperintensities, and measures of cognitive impairment. Higher leptin, resistin, IL6, and insulin were associated with markers of cerebral atrophy, such as lower total brain volume, or higher ventricular volume. Higher leptin and resistin were also associated with greater impairment in daily life activities. Higher adiponectin was associated with lower ventricle volume. There was no association between adipokines or insulin with white matter hyperintensities. Our findings indicate a co-occurrence between alterations in gastrointestinal factors and in brain volume along the preclinical to clinical spectrum of Alzheimer’s Disease. These results suggest that strategies aimed at promoting metabolic health may positively impact brain health.
Neurovascular Mechanisms of Cognitive Aging: Sex-Related Differences in the Average Progression of Arteriosclerosis, White Matter Atrophy, and Cognitive Decline
Authors: Bowie Daniel C. , Low Kathy A. , Rubenstein Samantha L. , Islam Samia S. , Zimmerman Benjamin , Camacho Paul B. , Sutton Bradley P. , Gratton Gabriele , Fabiani Monica 
Published: September 2023

AbstractArterial stiffness (arteriosclerosis) has been linked to heightened risks for cognitive decline, and ultimately for Alzheimer’s disease and other forms of dementia. Importantly, neurovascular outcomes generally vary according to one’s biological sex. Here, capitalizing on a large sample of participants with neuroimaging and behavioral data (N= 203, age range = 18-87 years), we aimed to provide support for a hierarchical model of neurocognitive aging, which links age-related declines in cerebrovascular health to the rate of cognitive decline via a series of intervening variables, such as white matter integrity. By applying a novel piecewise regression approach to our cross-sectional sample to support Granger-like causality inferences, we show that, on average, a precipitous decline in cerebral arterial elasticity (measured with diffuse optical imaging of the cerebral arterial pulse; pulse-DOT)temporally precedesan acceleration in the development of white matter lesions by nearly a decade, with women protected from these deleterious effects until approximately age 50, the average onset of menopause. By employing multiple-mediator path analyses while controlling for sex, we show that age may impair cognition via the sequential indirect effects of arteriosclerosis and white matter atrophy on fluid, but not crystallized, abilities. Importantly, we replicate these results using pulse pressure, an independent index of arterial health, thereby providing converging evidence for the central role of arteriosclerosis as an accelerating factor in normal and pathological aging and identifying robust sex-related differences in the progression of cerebral arteriosclerosis and white matter degradation.