Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic value of tumoral thymidylate synthase and p53 in metastatic colorectal cancer patients receiving fluorouracil-based chemotherapy: phenotypic and genotypic analyses.

PURPOSE The aim of this multicenter prospective study was to evaluate the role of intratumoral parameters related to fluorouracil (FU) sensitivity in 103 metastatic colorectal cancer patients receiving FU-folinic acid. PATIENTS AND METHODS Liver metastatic biopsy specimens were obtained for all patients and primary tumor biopsy specimens for 54 patients. Thymidylate synthase (TS), folylpolyglutamate synthetase, and dihydropyrimidine dehydrogenase were measured by radioenzymatic assays; TS promoter polymorphism (2R/2R v 2R/3R v 3R/3R) was determined by polymerase chain reaction; and p53 protein and mutations were analyzed by immunoluminometric assay and denaturing gradient gel electrophoresis, respectively. RESULTS p53 mutations were observed in 56.7% of metastases. TS activity was significantly higher in 2R/3R tumors as compared with 2R/2R or 3R/3R. TS activity in metastasis was the only parameter linked to clinical responsiveness (responders exhibited the lower TS, P =.047). Univariate Cox analyses demonstrated that TS activity in primary tumor (the greater the TS, the poorer the survival; P =.040), TS promoter polymorphism in primary tumor (risk of death of 2R/3R v 2R/2R, 2.68; P =.035), and p53 stop mutation in metastasis (risk of death of stop mutations v wild type, 3.14; P =.018) were the only significant biologic predictors of specific survival. Stepwise analysis did not discriminate between TS activity and TS polymorphism. CONCLUSION Present results confirm the value of tumoral TS activity for predicting FU responsiveness, point out the importance of detailed p53 mutation analysis for predicting survival, and suggest that TS genotype in primary tumor carries a prognostic value similar to that of TS activity.
Immunodiagnosis of aspergillosis

Aspergillus species are ubiquitous fungi and have been implicated as the causative agents of a variety of lung disorders in humans. These disorders include allergic, saprophytic, and systemic manifestations. The allergic disorders mainly affect atopic persons, and invasive or systemic diseases affect immunosuppressed individuals. Immunodiagnosis can help the practitioner diagnose these diseases. Demonstration of circulating antibodies is a useful criterion, but the lack of dependable and standardized antigens is a limiting factor in the diagnosis of most Aspergillus-induced diseases. Despite this limitation, however, immunodiffusion and enzyme-linked immunosorbent assays have been widely used for the detection of antibodies in the sera of patients with aspergillosis. Similarly, crude and semipurified antigens are being used to demonstrate skin hypersensitivity in patients, and several methods have been useful in the detection of antigenemia in patients with invasive aspergillosis. With a growing number of reports on the incidence of aspergillosis and an increase in the number of immunosuppressed individuals in the population, more rapid methods and more reliable reagents for immunodiagnosis are needed. With recent attempts at obtaining reliable reagents for through hybridoma technology and molecular biological techniques, substantial progress toward efficient immunodiagnosis may be achieved.
PET/MR imaging: technical aspects and potential clinical applications.

UNLABELLED Instruments that combine positron emission tomography (PET) and magnetic resonance (MR) imaging have recently been assembled for use in humans, and may have diagnostic performance superior to that of PET/computed tomography (CT) for particular clinical and research applications. MR imaging has major strengths compared with CT, including superior soft-tissue contrast resolution, multiplanar image acquisition, and functional imaging capability through specialized techniques such as diffusion-tensor imaging, diffusion-weighted (DW) imaging, functional MR imaging, MR elastography, MR spectroscopy, perfusion-weighted imaging, MR imaging with very short echo times, and the availability of some targeted MR imaging contrast agents. Furthermore, the lack of ionizing radiation from MR imaging is highly appealing, particularly when pediatric, young adult, or pregnant patients are to be imaged, and the safety profile of MR imaging contrast agents compares very favorably with iodinated CT contrast agents. MR imaging also can be used to guide PET image reconstruction, partial volume correction, and motion compensation for more accurate disease quantification and can improve anatomic localization of sites of radiotracer uptake, improve diagnostic performance, and provide for comprehensive regional and global structural, functional, and molecular assessment of various clinical disorders. In this review, we discuss the historical development, software-based registration, instrumentation and design, quantification issues, potential clinical applications, potential clinical roles of image segmentation and global disease assessment, and challenges related to PET/MR imaging. SUPPLEMENTAL MATERIAL http://radiology.rsna. org/lookup/suppl/doi:10.1148/radiol.13121038/-/DC1.
Treatment of the Dysplastic Acetabulum with Wagner Spherical Osteotomy: A Study of Patients Followed for a Minimum of Twenty Years

Background: The purpose of this study was to evaluate the long-term clinical and radiographic results of spherical acetabular osteotomy, performed with the surgical technique described by Wagner, in patients with hip dysplasia. Methods: The results of the first twenty-two spherical osteotomies performed by one surgeon at one institution were reviewed at a minimum of twenty years (median, 23.9 years; maximum, 29.3 years) postoperatively. Preoperative and follow-up radiographic measurements included the lateral and anterior center-edge angles, acetabular index angle, and acetabulum-head index of Heyman and Herndon. Anteroposterior radiographs of the pelvis were evaluated for the presence of joint congruency, joint-space narrowing, increased sclerosis of the subchondral bone, and bone cysts. Clinical evaluation was performed with use of the Harris hip score. Results: Osteotomy improved the mean lateral center-edge angle from -2° to +13° and the mean acetabulum-head index from 52% to 72%. The mean postoperative anterior center-edge angle was 23° (range, -1° to 62°). Seven (32%) of the twenty-two hips were converted to a total hip replacement. At the latest follow-up examination, the average Harris hip score of the remaining fifteen patients was 86 points (range, 50 to 100 points). The clinical result was rated good or excellent for eleven of the fifteen patients. At the latest follow-up examination, the severity grade of the osteoarthritis was unchanged in thirteen hips. Only three of the nine hips that subsequently required a total hip replacement or that showed progressive osteoarthritis had been congruent after the index operation, whereas ten of the thirteen hips that did not require total hip replacement or show progressive osteoarthritis had been congruent after the index operation. The twenty-year Kaplan-Meier survival estimate, with conversion to total hip replacement as the end point, was 86.4% (95% confidence interval, 63.4% to 95.4%). The twenty-five-year survival estimate was 65.1% (95% confidence interval, 35.6% to 83.7%). Conclusions: The Wagner spherical osteotomy prevented progression of osteoarthritis both clinically and radiographically in a high proportion of patients with residual hip dysplasia who were followed for a minimum of twenty years. Operative restoration of joint congruency is associated with a satisfactory long-term outcome in a very high proportion of cases. Level of Evidence: Therapeutic study, Level IV (case series [no, or historical, control group]). See Instructions to Authors for a complete description of levels of evidence.
Patients with polycythemia vera have worst impairment of quality of life among patients with newly diagnosed myeloproliferative neoplasms

Abstract The quality of life (QoL) at the time of diagnosis of myeloproliferative neoplasm (MPN) has, to date, not been studied. One hundred and seventy-nine patients with MPN: 80 with essential thrombocythemia (ET), 73 with polycythemia vera (PV), 22 with primary myelofibrosis (PMF) and four with MPN undifferentiated, were included in this study. European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQC30) and the MPN-Symptom Assessment Form (MPN-SAF) were used to evaluate QoL. Fatigue was the most reported symptom in these patients. Patients with PV reported significantly higher mean scores for inactivity, dizziness, cough, itching, depression and lower total QoL compared to patients with ET. Patients with PV had significantly more headache and itching compared to patients with PMF. When the newly diagnosed patients with MPN were compared with a cohort of patients with MPN with mean disease duration of 7.8 years, the differences were most striking for patients with PMF, with significantly more fatigue, abdominal discomfort, concentration problems, insomnia, fever, weight loss and lower overall QoL developed over time.
Surgical accessibility of the distal internal carotid artery on carotid endarterectomy evaluated using magnetic resonance angiography.

BACKGROUND Magnetic resonance angiography (MRA) is helpful for preoperatively evaluating the degree of carotid stenosis, although it is not always useful for assessing surgical accessibility to the distal internal carotid artery (ICA) due to the lack of osteological information. OBJECTIVE To demonstrate a method for evaluating the accessible distal portion of the ICA for carotid endarterectomy (CEA) using MRA. METHODS As an indicator of the upper limit of the operating field, a line drawn from the C1 transverse process to the hyoid bone (C1-H line) was defined. The cross-point between the C1-H line and distal ICA was delineated on 3-dimensional (3-D) MRA and 3-D tomography angiography (CTA). The distance between the carotid bifurcation and C1-H line was measured in 11 patients. The exposed distal ICA was compared with the extent of intraoperative ICA exposure. RESULTS The mean vertical distance (27.5 mm) from the carotid bifurcation to the C1-H line measured using 3-D MRA was almost the same as the distance (28 mm) evaluated on 3-D CTA. The discrepancy in distance between the 2 modalities was 1.9 ± 1.7 mm. Furthermore, the point of the ICA across the C1-H line created on 3-D MRA was in accordance with the intraoperative measurement (28.7 mm) of the exposed ICA. CONCLUSION The C1-H line measured on 3-D MRA is a simple and useful indicator of the distal point of the accessible ICA during CEA, especially in patients with renal dysfunction and allergies to contrast medium.
Microsatellite Instability in Keratoacanthoma

Background. Tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC) and from a subset of patients with the related Muir‐Torre syndrome (MTS) exhibit a novel type of genomic instability known as microsatellite instability (MIN). In general, this form of genomic instability results from mutations that inactivate DNA mismatch repair genes. The detection of MIN in a keratoacanthoma (KA) from a patient with MTS suggested that defective mismatch repair may play a role in the pathogenesis of these neoplasms.
Perceptions of “futile care” among caregivers in intensive care units

Background: Many caregivers in intensive care units (ICUs) feel that they sometimes provide inappropriate or excessive care, but little is known about their definition of “futile care” or how they attempt to limit its impact. We sought to explore how ICU staff define medically futile care, why they provide it and what strategies might promote a more effective use of ICU resources. Methods: Using semi-structured interviews, we surveyed 14 physician directors, 16 nurse managers and 14 respiratory therapists from 16 ICUs across Ontario. We analyzed the transcripts using a modified grounded-theory approach. Results: From the interviews, we generated a working definition of medically futile care to mean the use of considerable resources without a reasonable hope that the patient would recover to a state of relative independence or be interactive with his or her environment. Respondents felt that futile care was provided because of family demands, a lack of timely or skilled communication, or a lack of consensus among the treating team. Respondents said they were able to resolve cases of futile care most effectively by improving communication and by allowing time for families to accept the reality of the situation. Respondents felt that further efforts to limit futile care should focus on educating the public and health care professionals about the role of the ICU and about alternatives such as palliative care; mandating early and skilled discussion of resuscitation status; establishing guidelines for admission to the ICU; and providing legal and ethical support for physicians who encounter difficulties. There was a broad consistency in responses among all disciplines. Interpretation: ICU physicians, nurses and respiratory therapists have similar and well-formed opinions about how to define and resolve medically futile care and where to focus future efforts to limit the impact of futile care in the ICU.
Measurement of surface acoustic waves in high-frequency ultrasound: Preliminary results

Skin lesions change elastic properties near the surface. In the last decades, several non-invasive elastography techniques have been developed for detecting the mechanical properties of tissue. In particular, harmonic elastography is characterized for inducing shear wave propagation by an external vibrator in order to estimate shear modulus. However, near the boundary region, propagation is governed by surface acoustic waves (SAW). This paper combines crawling waves elastography with a high-frequency ultrasound (HFUS) system for the estimation of the SAW-to-shear compensation factor when ultrasound (US) gel is used as coupling interface. Experiments explore the SAWspeed in a homogeneous phantom with a solid-water interface in order to corroborate theoretical findings. Subsequently, experiments in a solid-US gel interface are conducted in order to find the correct compensation factor. Preliminary results suggest that SAW propagation can be detected using HFUS, and shear velocity maps can be generated by applying the estimated empirical correction factor. This study will potentially avoid the underestimation of shear modulus when using SAW-based HFUS elastography which is promising for the better diagnosis of skin diseases.
Inflammatory responses of RAW 264.7 macrophages upon exposure to nanoparticles: Role of ROS-NFκB signaling pathway

Abstract Recent advances in particle-forming chemistries used for developing nanotechnology has not only widened novel applications for nanoscale materials but also has provided significant concern regarding their biological effects. The present study investigates the inflammatory responses of RAW 264.7 mouse macrophages exposed to nanoparticles (NPs, 5 μg/ml) of varied sizes including silver (Ag), aluminum (Al), carbon black (CB), carbon-coated silver (CAg) and gold (Au). A significant increase in IL-6, reactive oxygen species (ROS) generation, nuclear translocation of nuclear factor-kappa B (NF-κB), induction of cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-α) expression was observed in macrophages with maximum response found in cells exposed to Ag NPs followed by Al, CB and CAg. These pro-inflammatory effects of NPs were dependent on size and duration of exposure and comparable to those induced by lipopolysaccharide (LPS), a known inflammatory mediator. Au NPs, on the other hand, induced small but significant inflammatory responses in macrophages upon prolonged exposure. These studies reveal that Ag NPs exhibit higher propensity in inducing inflammation, mediated by ROS and NF-κB signaling pathways and leading to the induction of COX-2, TNF-α and IL-6. However, no such prominent pro-inflammatory responses were observed with Au NPs, suggesting their bio-compatibility.
Effects of supine rest duration on ultrasound measures of the vastus lateralis

Due to the potential for intramuscular fluid shifts from changing body position, researchers often utilize a 10‐ to 15‐min period of supine rest as a standardizing procedure prior to ultrasound assessment of the lower limbs. However, no previous research has observed the changes in muscle morphological characteristics via ultrasonography of the lower limbs depending on the length of time of supine rest to determine whether 10–15 min of supine rest is necessary. The aim of this study was to examine changes in muscle morphology of the vastus lateralis (VL) at various time‐points over the course of 15 min of supine rest.
In vitro fertilization failure: identification of gamete defects by investigation of sperm‐zona pellucida binding capacity of unfertilized oocytes

Summary. The objective of the study was to determine whether fertilization failure was due to spermatozoal or oocyte factors. Twenty‐five unfertilized oocytes from 12 IVF/GIFT couples showing total or partial fertilization failure were evaluated for sperm zona binding potential under hemizona assay (HZA) conditions. Hemizonae were separately incubated with a sperm sample from the husband and that of a fertile control. Tight sperm binding to hemizonae was assessed. First, among the 12 patients, results showed a possible zona defect thought to be the cause of fertilization failure in five cases. Second, in two cases, fertilization failure was possibly caused by poor sperm binding potential of spermatozoa. Third, in two cases, fertilization failure was possibly caused by an oocyte defect, and fourth, three cases showed a mixture of possible causes. The results stress the need to develop a sequential analytic programme for those couples with repeated total or partial fertilization failure.
Increased BRAF Heterodimerization Is the Common Pathogenic Mechanism for Noonan Syndrome-Associated RAF1 Mutants

ABSTRACT Noonan syndrome (NS) is a relatively common autosomal dominant disorder characterized by congenital heart defects, short stature, and facial dysmorphia. NS is caused by germ line mutations in several components of the RAS–RAF–MEK–extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway, including both kinase-activating and kinase-impaired alleles of RAF1 (∼3 to 5%), which encodes a serine-threonine kinase for MEK1/2. To investigate how kinase-impaired RAF1 mutants cause NS, we generated knock-in mice expressing Raf1D486N. Raf1D486N/+ (here D486N/+) female mice exhibited a mild growth defect. Male and female D486N/D486N mice developed concentric cardiac hypertrophy and incompletely penetrant, but severe, growth defects. Remarkably, Mek/Erk activation was enhanced in Raf1D486N-expressing cells compared with controls. RAF1D486N, as well as other kinase-impaired RAF1 mutants, showed increased heterodimerization with BRAF, which was necessary and sufficient to promote increased MEK/ERK activation. Furthermore, kinase-activating RAF1 mutants also required heterodimerization to enhance MEK/ERK activation. Our results suggest that an increased heterodimerization ability is the common pathogenic mechanism for NS-associated RAF1 mutations.
Transconjunctival versus Transcutaneous Lower Eyelid Blepharoplasty: A Prospective Study

Debate continues over the relative merits of transconjunctival and the more customary subciliary transcutaneous approaches for lower lid blepharoplasty. Ten consecutive patients presented for blepharoplasty, and in all patients the transcutaneous subciliary musculocutaneous flap approach was used on the left lower eyelid and the transconjunctival preseptal approach was used on the right. Patients served as their own controls. Follow-up was evaluated clinically by patient questionnaire and by standardized photographs preoperatively and at 5 days, 1 month, 3 months, and 6 months postoperatively. Photographs were graded independently by four blinded examiners. No statistical difference was identified in measured for-nix depth between preoperative patients and postoperatively on each side. Average fat removed from each side was the same, and no patient had an identified “missed fat compartment. ” Three patients had mild bilateral scleral show postoperatively, and a fourth developed it on the left (transcutaneous) side. However, overall grading on both sides was universally very good with no significant difference on the two sides—0.68 on the right and 0.60 on the left (maximum worst grade could be 5.0 and best grade 0). The potential for external scarring was never a perceived problem in the transcutaneous technique.
Disturbed Cholesterol Homeostasis in a Peroxisome-Deficient PEX2 Knockout Mouse Model

ABSTRACT We evaluated the major pathways of cholesterol regulation in the peroxisome-deficient PEX2−/− mouse, a model for Zellweger syndrome. Zellweger syndrome is a lethal inherited disorder characterized by severe defects in peroxisome biogenesis and peroxisomal protein import. Compared with wild-type mice, PEX2 −/− mice have decreased total and high-density lipoprotein cholesterol levels in plasma. Hepatic expression of the SREBP-2 gene is increased 2.5-fold in PEX2 −/− mice and is associated with increased activities and increased protein and expression levels of SREBP-2-regulated cholesterol biosynthetic enzymes. However, the upregulated cholesterogenic enzymes appear to function with altered efficiency, associated with the loss of peroxisomal compartmentalization. The rate of cholesterol biosynthesis in 7- to 9-day-old PEX2 −/− mice is markedly increased in most tissues, except in the brain and kidneys, where it is reduced. While the cholesterol content of most tissues is normal in PEX2 −/− mice, in the knockout mouse liver it is decreased by 40% relative to that in control mice. The classic pathway of bile acid biosynthesis is downregulated in PEX2 −/− mice. However, expression of CYP27A1, the rate-determining enzyme in the alternate pathway of bile acid synthesis, is upregulated threefold in the PEX2 −/− mouse liver. The expression of hepatic ATP-binding cassette (ABC) transporters (ABCA1 and ABCG1) involved in cholesterol efflux is not affected in PEX2 −/− mice. These data illustrate the diversity in cholesterol regulatory responses among different organs in postnatal peroxisome-deficient mice and demonstrate that peroxisomes are critical for maintaining cholesterol homeostasis in the neonatal mouse.