Miracle-dz/UniFAR-FTUs huggingface dataset:
Cerebrospinal fluid dynamics disorders

Objective To determine the frequency of high-convexity tight sulci (HCTS) in a population-based sample and whether the presence of HCTS and related features influenced participants' cognitive status and classification within the new Alzheimer-biomarker framework. Methods We analyzed 684 participants ≥50 years of age who were enrolled in the prospective population-based Mayo Clinic Study of Aging and underwent structural MRI, amyloid PET imaging, and tau PET imaging. A fully automated machine-learning algorithm that had been developed previously in house was used to detect neuroimaging features of HCTS. On the basis of PET and MRI measures, participants were classified as having normal (A−) or abnormal (A+) amyloid, normal (T−) or abnormal (T+) tau, and normal (N−) or abnormal (N+) neurodegeneration. The neuropsychological battery assessed domain-specific and global cognitive scores. Gait speed also was assessed. Analyses were adjusted for age and sex. Results Of 684 participants, 45 (6.6%) were classified with HCTS according to the automated algorithm. Patients with HCTS were older than patients without HCTS (mean [SD] 78.0 [8.3] vs 71.9 [10.8] years; p < 0.001). More were cognitively impaired after age and sex adjustment (27% vs 9%; p = 0.005). Amyloid PET status was similar with and without HCTS, but tau PET standard uptake value ratio (SUVR) was lower for those with HCTS after age and sex adjustment (p < 0.001). Despite a lower tau SUVR, patients with HCTS had lower Alzheimer disease (AD) signature cortical thickness. With the amyloid-tau-neurodegeneration framework, HCTS was overrepresented in the T−(N)+ group, regardless of amyloid status. Conclusion The HCTS pattern represents a definable subgroup of non-AD pathophysiology (i.e., T−[N]+) that is associated with cognitive impairment. HCTS may confound clinical and biomarker interpretation in AD clinical trials.
PLX3397 inhibits the accumulation of intra‐tumoral macrophages and improves bromodomain and extra‐terminal inhibitor efficacy in melanoma

Bromodomain and extra‐terminal inhibitors (BETi) delay tumor growth, in part, through tumor cell intrinsic alterations and initiation of anti‐tumor CD8+ T‐cell responses. By contrast, BETi effects on pro‐tumoral immune responses remain unclear. Here, we show that the next‐generation BETi, PLX51107, delayed tumor growth to differing degrees in Braf V600E melanoma syngeneic mouse models. These differential responses were associated with the influx of tumor‐associated macrophages during BETi treatment. Tumors that were poorly responsive to PLX51107 showed increased influx of colony‐stimulating factor‐1 receptor (CSF‐1R)‐positive tumor‐associated macrophages. We depleted CSF‐1R+ tumor‐associated macrophages with the CSF‐1R inhibitor, PLX3397, in combination with PLX51107. Treatment with PLX3397 enhanced the efficacy of PLX51107 in poorly responsive Braf V600E syngeneic melanomas in vivo. These findings suggest that tumor‐associated macrophage accumulation limits BETi efficacy and that co‐treatment with PLX3397 can improve response to PLX51107, offering a potential novel combination therapy for metastatic melanoma patients.
The Effect of Aquatic Exercise on Postural Mobility of Healthy Older Adults with Endomorphic Somatotype

The fear of falling (FOF) limits the movements of the older adults, which, in turn, might impair postural mobility. An aquatic environment has a relatively low risk of falling and can improve motor abilities. The aim of this study was to investigate the effect of aquatic exercise on postural mobility of the healthy endomorph elderly somatotype. Therefore, 37 healthy endomorphic older adults with an average age of 64.38 ± 4.12 years participated in this study. Participants were randomly divided into four groups (i.e., Aquatic exercise, Dry-land exercise, Aquatic control, and Dry-land control). The Heath-Carter method was used to estimate the criterion somatotype, and the Tinetti method was used to determine postural mobility. Covariance analysis was used to examine the mean differences at a significance level of p < 0.05. The results showed that there was a significant difference between the aquatic exercise group and the two control groups (p < 0.01), and the dry-land exercise group was significantly different from the aquatic control (p < 0.05) and dry-land control groups (p < 0.01). The results indicate that the design of aquatic exercise programs, especially for endomorphic older adults with inappropriate body shape, for whom dry-land exercises are not appropriate, likely, has a positive effect on the motor control and both the balance and gait and provide appropriate postural mobility without FOF in older adults.
First Evaluation of an Index of Low Vagally-Mediated Heart Rate Variability as a Marker of Health Risks in Human Adults: Proof of Concept

Multiple studies have demonstrated low vagally-mediated heart rate variability (HRV) being associated with a range of risk factors for heart disease and stroke, including inflammation, hyperglycemia, hyperlipidemia, and hypertension. Yet, no cut point exists that indicates elevated risk. In the present study we sought to identify a cut point-value for HRV that is associated with elevated risk across a range of known risk factors. Methods: A total of 9550 working adults from 19 study sites took part in a health assessment that included measures of inflammation, hyperglycemia, hyperlipidemia, and hypertension and vagally-mediated HRV (Root mean square of successive differences between normal heartbeats (RMSSD)). Multiple age and sex adjusted logistic regressions were calculated per risk factor (normal versus clinical range), with RMSSD being entered in binary at different cut points ranging from 15–39 msec with a 2 msec increment. Results: For daytime RMSSD, values below 25 ± 4 indicated elevated risk (odds ratios (OR) 1.5–3.5 across risk factors). For nighttime RMSSD, values below 29 ± 4 indicated elevated risk (OR 1.2–2.0). Conclusion: These results provide the first evidence that a single value of RMSSD may be associated with elevated risk across a range of established cardiovascular risk factors and may present an easy to assess novel marker of cardiovascular risk.
In Utero Exposure to Gestational Diabetes Alters DNA Methylation and Gene Expression of CDKN2A/B in Langerhans Islets of Rat Offspring

Objective DNA methylation, a major epigenetic reprogramming mechanism, contributes to the increased prevalence of type 2 diabetes mellitus (T2DM). Based on genome-wide association studies, polymorphisms in CDKN2A/B are associated with T2DM. Our previous studies showed that gestational diabetes mellitus (GDM) causes apoptosis in β-cells, leading to a reduction in their number in pancreatic tissue of GDM-exposed adult rat offspring. The aim of this study was to examine the impact of intrauterine exposure to GDM on DNA methylation, mRNA transcription, as well as protein expression of these factors in the pancreatic islets of Wistar rat offspring. Our hypothesis was that the morphological changes seen in our previous study might have been caused by aberrant methylation and expression of CDKN2A/B. Materials and Methods In this experimental study, we delineated DNA methylation patterns, mRNA transcription and protein expression level of CDKN2A/B in the pancreatic islets of 15-week-old rat offspring of streptozotocin-induced GDM dams. We performed bisulfite sequencing to determine the DNA methylation patterns of CpGs in candidate promoter regions of CDKN2A/B. Furthermore, we compared the levels of mRNA transcripts as well as the cell cycle inhibitory proteins P15 and P16 in two groups by qPCR and western blotting, respectively. Results Our results demonstrated that hypomethylation of CpG sites in the vicinity of CDKN2A and CDKN2B genes is positively related to increased levels of CDKN2A/B mRNA and protein in islets of Langerhans in the GDM offspring. The average percentage of CDKN2A promoter methylation was significantly lower in GDM group compared to the controls (P<0.01). Conclusion We postulate that GDM is likely to exert its adverse effects on pancreatic β-cells of offspring through hypomethylation of the CDKN2A/B promoter. Abnormal methylation of these genes may have a link with β-cell dysfunction and diabetes. These data potentially lead to a novel approach to the treatment of T2DM.
Does a history of lumbar spine surgery predict radiological cauda equina compression in patients undergoing MRI for suspected cauda equina syndrome?

Abstract Background: The clinical symptoms and signs of Cauda equina syndrome (CES) are non specific and poorly predictive of cauda equina compression on MRI. We aimed to establish whether a history of lumbar spine surgery predicts cauda equina compression on MRI in those presenting with suspected CES. Methods: A retrospective electronic record review was undertaken of 276 patients referred with clinically suspected CES who underwent a lumbosacral spine MRI. Those with a history of prior lumbar surgery were compared to those without. The likelihood of cauda equina compression was compared between the two groups. Results: About 78/276 (28%) patients with suspected CES had radiological compression of the cauda equina and went on to surgical decompression. A total of 54 (20%) patients had undergone prior lumbar surgery. Patients with a history of lumbar surgery were less likely to have cauda equina compression on MRI (χ2 – p = .035). Twenty six (9%) patients presented more than once with suspected CES. Patients with a history of lumbar surgery were more likely to re-present with suspected CES (χ2 – p = .002). Conclusions: Prior lumbar surgery was associated with a higher frequency of re-presentation with clinically suspected CES but a lower frequency of radiological cauda equina compression.
MiR-21, MiR-29a, GATA4, and MEF2c Expression Changes in Endothelin-1 and Angiotensin II Cardiac Hypertrophy Stimulated Isl-1+Sca-1+c-kit+ Porcine Cardiac Progenitor Cells In Vitro

Cost- and time-intensive porcine translational disease models offer great opportunities to test drugs and therapies for pathological cardiac hypertrophy and can be supported by porcine cell culture models that provide further insights into basic disease mechanisms. Cardiac progenitor cells (CPCs) residing in the adult heart have been shown to differentiate in vitro into cardiomyocytes and could contribute to cardiac regeneration. Therefore, it is important to evaluate their changes on the cellular level caused by disease. We successfully isolated Isl1+Sca1+cKit+ porcine CPCs (pCPCs) from pig hearts and stimulated them with endothelin-1 (ET-1) and angiotensin II (Ang II) in vitro. We also performed a cardiac reprogramming transfection and tested the same conditions. Our results show that undifferentiated Isl1+Sca1+cKit+ pCPCs were significantly upregulated in GATA4, MEF2c, and miR-29a gene expressions and in BNP and MCP-1 protein expressions with Ang II stimulation, but they showed no significant changes in miR-29a and MCP-1 when stimulated with ET-1. Differentiated Isl1+Sca1+cKit+ pCPCs exhibited significantly higher levels of MEF2c, GATA4, miR-29a, and miR-21 as well as Cx43 and BNP with Ang II stimulation. pMx-MGT-transfected Isl1+Sca1+cKit+ pCPCs showed significant elevations in MEF2c, GATA4, and BNP expressions when stimulated with ET-1. Our model demonstrates that in vitro stimulation leads to successful Isl1+Sca1+cKit+ pCPC hypertrophy with upregulation of cardiac remodeling associated genes and profibrotic miRNAs and offers great possibilities for further investigations of disease mechanisms and treatment.
Genome-Wide Analysis of Members of the WRKY Gene Family and Their Cold Stress Response in Prunus mume

Prunus mume, which is a rosaceous arbor with very high ornamental, edible and medical values, has a distribution that is mainly restricted by low temperature. WRKY transcription factor genes play crucial roles in the growth, development, and stress responses of plants. However, the WRKY gene family has not been characterised in P. mume. There were 58 PmWRKYs identified from genome of P. mume. They were anchored onto eight link groups and categorised into three broad groups. The gene structure and motif composition were reasonably conservative in each group. Investigation of gene duplication indicated that nine and seven PmWRKYs were arranged in tandem and segmental duplications, respectively. PmWRKYs were discriminately expressed in different tissues (i.e., roots, stems, leaves, flowers and fruits) in P. mume. The 17 cold-related candidate genes were selected based on RNA-seq data. Further, to investigate the function of PmWRKYs in low temperatures, the expression patterns under artificial cold treatments were analysed. The results showed that the expression levels of the 12 PmWRKYs genes significantly and 5 genes slightly changed in stems. In particular, the expression level of PmWRKY18 was up-regulated after ABA treatment. In addition, the spatiotemporal expression patterns of 17 PmWRKYs were analysed in winter. These results indicated that 17 PmWRKYs were potential transcription factors regulating cold resistance in P. mume.
Bacterial Diversity of Diabetic Foot Ulcers: Current Status and Future Prospectives

Diabetic foot ulcers (DFUs) and diabetic foot infections (DFIs) are associated with reduced patient quality of life, lower-extremity amputation, hospitalization, and high morbidity and mortality. Diverse bacterial communities have been identified in DFUs/DFIs, playing a significant role in infection prognosis. However, due to the high heterogeneity of bacterial communities colonized in DFUs/DFIs, culture-based methods may not isolate all of the bacterial population or unexpected microorganisms. Recently, high sensitivity and specificity of DNA (metagenomics) and RNA (metatranscriptomics) technologies have addressed limitations of culture-based methods and have taken a step beyond bacterial identification. As a consequence, new advances obtained from DNA- and RNA-based techniques for bacterial identification can improve therapeutic approaches. This review evaluated the current state of play in aetiology of DFUs/DFIs on culture and molecular approaches, and discussed the impact of metagenomic and metatranscriptomic methods in bacterial identification approaches.
Stability and profiling of urinary microRNAs in healthy cats and cats with pyelonephritis or other urological conditions

Abstract Background Specific biomarkers of pyelonephritis (PN) in cats are lacking. MicroRNAs (miRNAs) have diagnostic potential in human nephropathies. Objectives To investigate the presence/stability of miRNAs in whole urine of cats and the discriminatory potential of selected urinary miRNAs for PN in cats. Animals Twelve healthy cats, 5 cats with PN, and 13 cats with chronic kidney disease (n = 5), subclinical bacteriuria (n = 3), and ureteral obstructions (n = 5) recruited from 2 companion animal hospitals. Methods Prospective case‐control study. Expression profiles of 24 miRNAs were performed by quantitative PCR (qPCR). Effect of storage temperature (4°C [24 hours], −20°C, and −80°C) was determined for a subset of miRNAs in healthy cats. Results Urinary miR‐4286, miR‐30c, miR‐204, miR4454, miR‐21, miR‐16, miR‐191, and miR‐30a were detected. For the majority of miRNAs tested, storage at 4°C and −20°C resulted in significantly lower miRNA yield compared to storage at −80°C (mean log2fold changes across miRNAs from −0.5 ± 0.4 SD to −1.20 ± 0.4 SD (4°C versus −80°C) and from −0.7 ± 0.2 SD to −1.20 ± 0.3 SD (−20°C versus −80°C)). Cats with PN had significantly upregulated miR‐16 with a mean log2fold change of 1.0 ± 0.4 SD, compared with controls (−0.1 ± 0.2, P = .01) and other urological conditions (0.6 ± 0.3, P = .04). Conclusions Upregulation of miR16 might be PN‐specific, pathogen‐specific (Escherichia coli), or both.
Cellular Plasticity in Musculoskeletal Development, Regeneration, and Disease

In this review, we highlight themes from a recent workshop focused on “Plasticity of Cell Fate in Musculoskeletal Tissues” held at the Orthopaedic Research Society's 2019 annual meeting. Experts in the field provided examples of mesenchymal cell plasticity during normal musculoskeletal development, regeneration, and disease. A thorough understanding of the biology underpinning mesenchymal cell plasticity may offer a roadmap for promoting regeneration while attenuating pathologic differentiation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:708‐718, 2020
Microcalcifications Drive Breast Cancer Occurrence and Development by Macrophage-Mediated Epithelial to Mesenchymal Transition

Background: This study aims to investigate: (a) the putative association between the presence of microcalcifications and the expression of both epithelial-to-mesenchymal transition and bone biomarkers, (b) the role of microcalcifications in the breast osteoblast-like cells (BOLCs) formation, and (c) the association between microcalcification composition and breast cancer progression. Methods: We collected 174 biopsies on which we performed immunohistochemical and ultrastructural analysis. In vitro experiments were performed to demonstrate the relationship among microcalcification, BOLCs development, and breast cancer occurrence. Ex vivo investigations demonstrated the significant increase of breast osteoblast-like cells in breast lesions with microcalcifications with respect to those without microcalcifications. Results: In vitro data displayed that in the presence of calcium oxalate and activated monocytes, breast cancer cells undergo epithelial to mesenchymal transition. Also, in this condition, cells acquired an osteoblast phenotype, thus producing hydroxyapatite. To further confirm in vitro data, we studied 15 benign lesions with microcalcification from patients that developed a malignant condition in the same breast quadrant. Immunohistochemical analysis showed macrophages’ polarization in benign lesions with calcium oxalate. Conclusions: Altogether, our data shed new light about the role of microcalcifications in breast cancer occurrence and progression.
Adult moped-related injuries treated in U.S. emergency departments

Abstract Objective: Few studies have investigated U.S. emergency department (ED) moped-related injuries. Our objective was to determine the characteristics of moped crashes among adult riders and to identify associations between key variables. Methods: Data were obtained from the National Electronic Injury Surveillance System (NEISS) for 2002–2014. Descriptive and comparative analyses of the identified cases were performed. Results: Based on a probability sample of 2,453 cases, an estimated 108,229 U.S. adult moped-related ED visits occurred during the study period. Injuries increased 2.7-fold over time. Summer months and weekdays were the most common crash times. Three-fourths of injured riders were male, two-thirds were ages 23–59 years, and 77% were Caucasian. Among cases documented, one-half were helmeted, and almost two-thirds of crashes occurred at ≤20 mph. The predominant mechanism was a non-collision crash (60%). Skin-related and musculoskeletal diagnoses were most common. Almost one-fifth of patients were admitted or transferred. Regression analyses showed that males were less likely than females to be in crashes with multiple riders, and more likely to have used alcohol/drugs and to be in a crash with another motor vehicle (MVC). Older riders (≥40 years) were more likely than those younger to have used alcohol/drugs and to suffer torso injuries, and less likely to be in an MVC. As compared to other crash mechanisms, MVCs were more likely to involve injuries to the head/neck/face and torso. The likelihood of being admitted/transferred was higher for males, with increasing age, and for collision-related crashes. The higher likelihood of being admitted/transferred was also characterized by alcohol/drug use, by lower limb and torso injuries, and almost 8 times more likely for riders with serious head injuries. Conclusions: Moped injuries increased in all adult age groups during the study period. However, there were significant differences in contributing factors, crash mechanism, and outcomes by sex, race, and age. These findings suggest the need for targeted injury prevention interventions.
PRP and BMAC for Musculoskeletal Conditions via Biomaterial Carriers

Platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) are orthobiologic therapies considered as an alternative to the current therapies for muscle, bone and cartilage. Different formulations of biomaterials have been used as carriers for PRP and BMAC in order to increase regenerative processes. The most common biomaterials utilized in conjunction with PRP and BMAC clinical trials are organic scaffolds and natural or synthetic polymers. This review will cover the combinatorial strategies of biomaterial carriers with PRP and BMAC for musculoskeletal conditions (MsCs) repair and regeneration in clinical trials. The main objective is to review the therapeutic use of PRP and BMAC as a treatment option for muscle, bone and cartilage injuries.
Glycerol-Mediated Facile Synthesis of Colored Titania Nanoparticles for Visible Light Photodegradation of Phenolic Compounds

In this study, we developed a glycerol-mediated safe and facile method to synthesize colored titania nanoparticles (NPs) via solution route. Our method is considerably effective and greener than other options currently available. Colored titania NPs were produced by hydrolyzing TiCl4 precursor in aqueous solution containing different concentrations of glycerol (0.0, 1.163, 3.834, and 5.815 mol/L) and subsequent calcination at 300 °C for 1 h. Our results highlight firstly that glycerol-mediated synthesis is unlikely to affect the anatase crystalline structure of TiO2, and secondly, that it would lead to coloration, band gap narrowing, and a remarkable bathochromic redshift of the optical response of titania. More importantly, the synthesized colored titania have Ti3+ ions, which, at least in terms of our samples, is the major factor responsible for its coloration. These Ti3+ species could induce mid gap states in the band gap, which significantly improve the visible light absorption capability and photocatalytic performance of the colored titania. The photocatalytic experiments showed that the colored TiO2 NPs prepared in 1.163 mol/L aqueous glycerol solution displayed the best photocatalytic performance. Almost 48.17% of phenolic compounds and 62.18% of color were removed from treated palm oil mill effluent (POME) within 180 min of visible light irradiation.