Miracle-dz/UniFAR-FTUs huggingface dataset:
Individual magnetic resonance imaging and radiographic features of knee osteoarthritis in subjects with unilateral knee pain: the health, aging, and body composition study.

OBJECTIVE Strong associations between radiographic features of knee osteoarthritis (OA) and pain have been demonstrated in persons with unilateral knee symptoms. This study was undertaken to compare radiographic and magnetic resonance imaging (MRI) features of knee OA and assess their ability to discriminate between painful and nonpainful knees in persons with unilateral symptoms. METHODS The study population included 283 individuals ages 70-79 years with unilateral knee pain who were enrolled in the Health, Aging, and Body Composition Study, a study of weight-related diseases and mobility. Radiographs of both knees were read for Kellgren/Lawrence (K/L) grade and individual radiographic features, and 1.5T MRIs were assessed using the Whole-Organ Magnetic Resonance Imaging Score. The association between structural features and pain was assessed using a within-person case-control design and conditional logistic regression. Receiver operating characteristic (ROC) analysis was then used to test the discriminatory performance of structural features. RESULTS In conditional logistic analyses, knee pain was significantly associated with both radiographic features (any joint space narrowing grade ≥ 1) (odds ratio 3.20 [95% confidence interval 1.79-5.71]) and MRI features (any cartilage defect scored ≥ 2) (odds ratio 3.67 [95% confidence interval 1.49-9.04]). However, in most subjects, MRI revealed osteophytes and cartilage and bone marrow lesions in both knees, and using ROC analysis, no individual structural feature discriminated well between painful and nonpainful knees. The best-performing MRI feature (synovitis/effusion) was not significantly more informative than K/L grade ≥ 2 (P = 0.42). CONCLUSION In persons with unilateral knee pain, MRI and radiographic features were associated with knee pain, confirming that structural abnormalities in the knee have an important role in the etiology of pain. However, no single MRI or radiographic finding performed well in discriminating between painful and nonpainful knees. Further work is needed to examine how structural and nonstructural factors influence knee pain.
Preparative Separation of Axifolin-3-Glucoside, Hyperoside and Amygdalin from Plant Extracts by High Speed Countercurrent Chromatography

Abstract High speed countercurrent chromatography (HSCCC) was successfully used to isolate three bioactive compounds, i.e., amygdalin from bitter almond and taxifolin-3-glucoside and quercetin-3-galactoside (hyperoside) from water extract of A. pilosa Ledeb, respectively. From 1 g of the crude extract 65 mg of amygdalin was isolated at 97% purity using a two phase solvent system composed of ethyl acetate-n-butanol-water (5:2:5, v/v) by preparative HSCCC. From a 400 mg amount of crude extract of A. pilosa Ledeb, 11 mg of taxifolin-3-glucoside and 8 mg of hyperoside were isolated at 96% purity, using a two phase solvent system composed of ethyl acetate-methanol-water (25:1:25, v/v) similarly by preparative HSCCC. The final structural identification was performed by MS, 1H-NMR, and 13C-NMR spectra.
New encouraging developments in contact prediction: Assessment of the CASP11 results

This article provides a report on the state‐of‐the‐art in the prediction of intra‐molecular residue‐residue contacts in proteins based on the assessment of the predictions submitted to the CASP11 experiment. The assessment emphasis is placed on the accuracy in predicting long‐range contacts. Twenty‐nine groups participated in contact prediction in CASP11. At least eight of them used the recently developed evolutionary coupling techniques, with the top group (CONSIP2) reaching precision of 27% on target proteins that could not be modeled by homology. This result indicates a breakthrough in the development of methods based on the correlated mutation approach. Successful prediction of contacts was shown to be practically helpful in modeling three‐dimensional structures; in particular target T0806 was modeled exceedingly well with accuracy not yet seen for ab initio targets of this size (>250 residues). Proteins 2016; 84(Suppl 1):131–144. © 2015 Wiley Periodicals, Inc.
Screening for Atypical Femur Fractures Using Extended Femur Scans by DXA

Atypical femur fractures (AFFs) are a rare but serious complication associated with the use of antiresorptive drugs such as bisphosphonates. Assessment of incomplete AFFs on extended femur scans by dual‐energy X‐ray absorptiometry (DXA) may prevent the development of complete fractures. The aim of this study was to evaluate the potential of extended femur scans by DXA as a screening tool for incomplete AFFs. From June 2014 until September 2016, extended femur scans were routinely performed in all consecutive patients undergoing DXA scanning who had used bisphosphonates or denosumab at any given moment in the previous year. When “beaking” was found, defined as a localized periosteal or endosteal thickening of the lateral cortex, a radiograph of the femur was performed to confirm incomplete AFF. Beaking was detected in 12 of 282 patients (4.3%) with extended scans of both femora. In 9 patients (3.2%), beaking corresponded with the radiological presence of incomplete AFFs, of whom 4 already had an X‐ray made because of a previous complete AFF of the other leg. Five patients (1.8%) were newly diagnosed with 6 yet unknown incomplete AFFs. No additional X‐ray was performed in 2 patients because of loss of follow‐up. Beaking was explained by known soft tissue calcifications in 1 patient. The positive predictive value of beaking on extended femur scan was 83.3% in our study. Three cases in whom the new diagnosis of incomplete AFF has affected medical and surgical treatment are further discussed to illustrate the relevance of early detection. We conclude that extended femur scans by DXA can detect incomplete AFFs in patients on antiresorptive treatment and should therefore be considered a clinically relevant screening tool because early identification of AFFs has therapeutic consequences. © 2017 American Society for Bone and Mineral Research.
Parent and Patient Perceptions of Functional Impairment Due to Tourette Syndrome: Development of a Shortened Version of the Child Tourette Syndrome Impairment Scale

The Child Tourette Syndrome Impairment Scale (CTIM) rates 37 problems in school, social, and home domains separately for tics and for comorbid diagnoses. However, a shorter version would be easier to implement in busy clinics. Using published data from 85 children with Tourette syndrome, 92 controls, and parents, factor analysis was used to generate a “mini-CTIM” composed of 12 items applied to tic and comorbid diagnoses. Child- and parent-rated mini-CTIM scores were compared and correlated across raters and accounting for clinician-rated tic severity and presence of attention-deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). The mini-CTIM achieved domain Cronbach alphas ranging from 0.71 to 0.94 and intra-item correlation coefficients ranging from 0.84 to 0.96. The resulting scale correlated with clinician-rated tic severity and reflected the presence of ADHD and OCD. The mini-CTIM appears promising as a practical assessment tool for tic- and non–tic-related impairment in children with Tourette syndrome.
Radiotherapy for patients with the human immunodeficiency virus: Are special precautions necessary?

Shortly after the onset of the acquired immunodeficiency syndrome (AIDS) epidemic in the 1980s, reports of radiation‐associated toxicity in patients with the human immunodeficiency virus (HIV) and AIDS began to appear in the medical literature. Although the majority of reports have focused on AIDS‐defining malignancies such as Kaposi sarcoma, greater‐than‐expected toxicity after a course of radiotherapy or chemoradiotherapy has also been documented in cancers not generally classified as being related to HIV. With improved antiretroviral therapies, HIV patients are living longer and have the potential to develop a variety of HIV‐associated and nonassociated malignancies that require treatment, including radiotherapy. This review reports the published data regarding the interactions of HIV, AIDS, and antiretroviral therapy with radiotherapy and implications for the management of malignancies in patients with HIV. Cancer 2010. Published 2009 by the American Cancer Society.
mRECIST response combined with sorafenib‐related adverse events is superior to either criterion alone in predicting survival in HCC patients treated with TACE plus sorafenib

The mRECIST and dermatologic adverse events (AEs) can be used to assess the patient response to transarterial chemoembolization (TACE) and/or sorafenib for hepatocellular carcinoma (HCC). Here, we aimed to combine the two criteria to stratify the prognosis in patients with unresectable HCC receiving TACE plus sorafenib (TACE‐S). In total, 176 consecutive HCC patients treated with TACE‐S were enrolled. CT scans and laboratory tests were conducted pretreatment (at baseline, 5–7 days before the TACE‐S) and post‐treatment (at 1, 2 and 3 months). The radiological response was assessed according to mRECIST. Sorafenib‐related AEs were recorded every 2 weeks after oral administration, and patients with dermatologic AEs of Grade 2 or more were defined as dermatologic responders. The earliest time at which mRECIST and dermatologic responses correlated with survival was 2 months after therapy. The mRECIST‐dermatologic AE combination assessment stratified patients into three different prognoses; responders on both assessments exhibited the longest median overall survival (OS), followed by responders on one assessment and non‐responders on both assessments (30.5, 17.4 and 8.3 months, respectively; p < 0.001). Achieving the highest C‐index, the mRECIST‐dermatologic AE combination showed better performance in predicting survival than either mRECIST or dermatologic AEs alone. Furthermore, the mRECIST‐dermatologic AE combination remained a significant predictor of OS, even when the patients were stratified according to the BCLC stage, ECOG score or alpha‐fetoprotein (AFP) value. This study showed that the combination of mRECIST response and dermatologic AEs is superior to either criterion used alone for predicting the survival of HCC patients treated with TACE‐S.
Coping with death and dying.

The death of a loved one is a ubiquitous human experience, one that is widely regarded as a serious threat to health and well-being. Consequently, it is important to understand how people cope with death and dying and whether some ways of coping are more adaptive than others. This voluminous research work can be divided into two broad categories: (a) how people cope with their own impending death or that of a loved one and (b) the grieving process that typically ensues after a loved one’s death. Among those studying how people cope with their own impending death or that of a loved one, variables such as the place of death, or the quality of care received by the dying, are of paramount importance. These variables play virtually no role in the study of the grieving process. Instead, grief researchers are more likely to examine such factors as how the person died, the mourner’s attachment style, or the nature of the bereaved person’s relationship with the deceased. Because of these differences in the focus of research, a review of studies in both of these areas is beyond the scope of this chapter. Consequently, I have chosen to examine how people cope with their own or a family member’s imminent death. In particular, this chapter focuses on elderly individuals who are diagnosed with an incurable illness, their family members, and the health care professionals who attempt to meet their physical and psychological needs. The vast majority of terminal illnesses occur among adults who are age 65 years or older. According to U.S. Census data, the United States is likely to experience a marked increase in the number of elderly Americans and, consequently, in the total number of deaths. By 2050, the number of older Americans is expected to increase by 72% to nearly 90 million. Approximately three million baby boomers are expected to reach retirement age every year for the next 20 years, which will place enormous strain on an already-stressed health care system. Experts agree that this demographic shift is the most powerful force operating in the U.S. health care system today (Barr, 2014). Most late-life deaths occur after a prolonged period of chronic illness such as coronary vascular disease, cancer, or Parkinson’s disease (Carr, 2012). In many cases, the diseases that take the lives of older Americans are painful and debilitating, and they are often associated with cognitive impairments as well as physical decline. It is becoming increasingly apparent that dying is a process, not an event. In most cases, this process begins with the diagnosis of an incurable illness and ends with the patient’s death. As a result of biomedical advances, the interval between diagnosis and death is becoming longer. Consequently, elderly people may spend many months living with dying (GolijaniMoghaddam, 2014). When people receive a diagnosis of terminal illness, what can they and their family members expect from the health care system? Despite a growing number of research studies and calls for change,
Low-Dose Radiation Exposure and Atherosclerosis in ApoE−/− Mice

Abstract The hypothesis that single low-dose exposures (0.025–0.5 Gy) to low-LET radiation given at either high (about 150 mGy/min) or low (1 mGy/min) dose rate would promote aortic atherosclerosis was tested in female C57BL/6J mice genetically predisposed to this disease (ApoE−/−). Mice were exposed either at an early stage of disease (2 months of age) and examined 3 or 6 months later or at a late stage of disease (8 months of age) and examined 2 or 4 months later. Changes in aortic lesion frequency, size and severity as well as total serum cholesterol levels and the uptake of lesion lipids by lesion-associated macrophages were assessed. Statistically significant changes in each of these measures were observed, depending on dose, dose rate and disease stage. In all cases, the results were distinctly non-linear with dose, with maximum effects tending to occur at 25 or 50 mGy. In general, low doses given at low dose rate during either early- or late-stage disease were protective, slowing the progression of the disease by one or more of these measures. Most effects appeared and persisted for months after the single exposures, but some were ultimately transitory. In contrast to exposure at low dose rate, high-dose-rate exposure during early-stage disease produced both protective and detrimental effects, suggesting that low doses may influence this disease by more than one mechanism and that dose rate is an important parameter. These results contrast with the known, generally detrimental effects of high doses on the progression of this disease in the same mice and in humans, suggesting that a linear extrapolation of the known increased risk from high doses to low doses is not appropriate.
Cell tracking, survival, and differentiation capacity of adipose‐derived stem cells after engraftment in rat tissue

Adipose tissue is an important source of adipose derived stem cells (ADSCs). These cells have the potential of being used for certain therapies, in which the main objective is to recover the function of a tissue/organ affected by a disease. In order to contribute to repair of the tissue, these cells should be able to survive and carry out their functions in unfavorable conditions after being transplanted. This process requires a better understanding of the biology involved: such as the time cells remain in the implant site, how long they stay there, and whether or not they differentiate into host tissue cells. This report focuses on these questions. ADSC were injected into three different tissues (substantia nigra, ventricle, liver) and they were tracked in vivo with a dual GFP‐Luc reporter system. The results show that ADSCs were able to survive up to 4 months after the engraftment and some of them started showing resident cell tissue phenotype. These results demonstrate their long‐term capacity of survival and differentiation when injected in vivo.
Effect of lapatinib on the outgrowth of metastatic breast cancer cells to the brain.

BACKGROUND The brain is increasingly being recognized as a sanctuary site for metastatic tumor cells in women with HER2-overexpressing breast cancer who receive trastuzumab therapy. There are no approved or widely accepted treatments for brain metastases other than steroids, cranial radiotherapy, and surgical resection. We examined the efficacy of lapatinib, an inhibitor of the epidermal growth factor receptor (EGFR) and HER2 kinases, for preventing the outgrowth of breast cancer cells in the brain in a mouse xenograft model of brain metastasis. METHODS EGFR-overexpressing MDA-MB-231-BR (231-BR) brain-seeking breast cancer cells were transfected with an expression vector that contained or lacked the HER2 cDNA and used to examine the effect of lapatinib on the activation (ie, phosphorylation) of cell signaling proteins by immunoblotting, on cell growth by the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and on cell migration using a Boyden chamber assay. The outgrowth of large (ie, >50 microm(2)) and micrometastases was counted in brain sections from nude mice that had been injected into the left cardiac ventricle with 231-BR cells and, beginning 5 days later, treated by oral gavage with lapatinib or vehicle (n = 22-26 mice per treatment group). All statistical tests were two-sided. RESULTS In vitro, lapatinib inhibited the phosphorylation of EGFR, HER2, and downstream signaling proteins; cell proliferation; and migration in 231-BR cells (both with and without HER2). Among mice injected with 231-BR-vector cells, those treated with 100 mg lapatinib/kg body weight had 54% fewer large metastases 24 days after starting treatment than those treated with vehicle (mean number of large metastases per brain section: 1.56 vs 3.36, difference = 1.80, 95% confidence interval [CI] = 0.92 to 2.68, P < .001), whereas treatment with 30 mg lapatinib/kg body weight had no effect. Among mice injected with 231-BR-HER2 cells, those treated with either dose of lapatinib had 50%-53% fewer large metastases than those treated with vehicle (mean number of large metastases per brain section, 30 mg/kg vs vehicle: 3.21 vs 6.83, difference = 3.62, 95% CI = 2.30 to 4.94, P < .001; 100 mg/kg vs vehicle: 3.44 vs 6.83, difference = 3.39, 95% CI = 2.08 to 4.70, P < .001). Immunohistochemical analysis revealed reduced phosphorylation of HER2 in 231-BR-HER2 cell-derived brain metastases from mice treated with the higher dose of lapatinib compared with 231-BR-HER2 cell-derived brain metastases from vehicle-treated mice (P < .001). CONCLUSIONS Lapatinib is the first HER2-directed drug to be validated in a preclinical model for activity against brain metastases of breast cancer.
The detection and significance of EGFR and BRAF in cell-free DNA of peripheral blood in NSCLC

Objective Although driver mutation status is crucial to targeted therapy decision-making in non-small cell lung cancer (NSCLC), due to unavailable or inadequate biopsies, there are still many patients with unknown mutation status. A promising way to solve this problem is liquid biopsy, such as cell-free DNA (cfDNA) in peripheral blood. Additionally, due to the little amount of cfDNA, detecting methods with high sensitivity, specificity and economy are required in clinical practice. Here, we explored the feasibility of Competitive Allele-Specific TaqMan® PCR (CastPCR) detecting driver mutations in cfDNA from plasma in lung adenocarcinoma patients. Results Sensitivity, specificity, concordance, PPV and NPV of CastPCR detecting EGFR mutations in cfDNA was 56.4% (31/55), 94.2% (49/52), 74.8% (80/107), 91.2% (31/34) and 67.1% (49/73), respectively. Notably, specificity and PPV for p.T790M both reached 100.0%. For BRAF detection, it was 28.6% (2/7), 93.0% (93/100), 88.8% (95/107), 22.2% (2/9) and 94.9% (93/98), respectively. Materials and Methods Plasma specimens of 107 lung adenocarcinoma patients and their matched tumor formalin fixed paraffin embedded (FFPE) samples were analyzed. CastPCR was used to detect EGFR (c.2235_2249del, c.2236_2250del, c.2369C>T p.T790M, c.2573T>G p.L858R) and BRAF (c.1406G>C p.G469A, c.1799T>A p.V600E, c.1781A>G p.D594G) mutations. Mutation results of tumor tissue was set as gold standard, and the sensitivity, specificity, concordance, positive predictive value (PPV) and negative predictive value (NPV) were calculated for each mutation. Conclusions For patients whose tumor tissue is unavailable or inadequate, EGFR mutation detection in cfDNA with CastPCR could be first choice. Mutation positive results may provide reference for further clinical medication. While negative results indicate that detection in tissue should be considered as the following step. In this way, tumor tissue could be economized to the maximum extent and the risk of repeated percutaneous transthoracic lung biopsy could also be lowered to the maximum extent. For BRAF detection in cfDNA, CastPCR is a specific method while the sensitivity needs further exploration.
The Avian Hippocampal Formation and the Stress Response

Though widely studied for its function in memory and navigation, the hippocampal formation (HF) in mammals also plays an important role in regulating the stress response. If this is an ancestral feature of the hippocampus, then it is likely that the avian HF plays a similar role. Indeed, the avian HF strongly expresses both mineralocorticoid and glucocorticoid receptors, and has indirect projections to the paraventricular nucleus of the hypothalamus, which controls the hypothalamic-pituitary-adrenal (HPA) axis. Hippocampal lesions increase HPA activity, while electrical stimulation suppresses it. In addition, adult hippocampal neurogenesis in birds is reduced in response to different acute and chronic stressors, as it is in mammals. Because the mammalian hippocampus is functionally specialized along its septotemporal axis, with the temporal pole playing a more important role in the stress response, the hypothesis is put forward that a similar functional specialization exists in birds along the rostrocaudal hippocampal axis. Some, though not all, of the evidence supports a rostrocaudal functional gradient. The evidence for whether this is equivalent to the mammalian septotemporal organization is currently ambiguous at best and needs to be more extensively investigated.