Miracle-dz/UniFAR-FTUs huggingface dataset:
Cytoplasmic Cyclin E Mediates Resistance to Aromatase Inhibitors in Breast Cancer

Purpose: Preoperative aromatase inhibitor (AI) therapy has demonstrated efficacy in hormone receptor (HR)-positive postmenopausal breast cancer. However, many patients have disease that is either intrinsically resistant to AIs or that responds initially but develops resistance after prolonged exposure. We have shown that patients with breast tumors expressing the deregulated forms of cyclin E [low molecular weight forms (LMW-E)] have poor overall survival. Herein, we hypothesize that LMW-E expression can identify HR-positive tumors that are unresponsive to neoadjuvant AI therapy due to the inability of AIs to induce a cytostatic effect. Experimental Design: LMW-E was examined in breast cancer specimens from 58 patients enrolled in the American College of Surgeons Oncology Group Z1031, a neoadjuvant AI clinical trial. The mechanisms of LMW-E–mediated resistance to AI were evaluated in vitro and in vivo using an inducible model system of cyclin E (full-length and LMW-E) in aromatase-overexpressing MCF7 cells. Results: Breast cancer recurrence-free interval was significantly worse in patients with LMW-E–positive tumors who received AI neoadjuvant therapy, compared with those with LMW-E negative tumors. Upon LMW-E induction, MCF7 xenografts were unresponsive to letrozole in vivo, resulting in increased tumor volume after treatment with AIs. LMW-E expression overcame cell-cycle inhibition by AIs in a CDK2/Rb-dependent manner, and inhibition of CDK2 by dinaciclib reversed LMW-E–mediated resistance, whereas treatment with palbociclib, a CDK4/6 inhibitor, did not. Conclusions: Collectively, these findings suggest that cell-cycle deregulation by LMW-E mediates resistance to AIs and a combination of CDK2 inhibitors and AIs may be an effective treatment in patients with HR-positive tumors that express LMW-E. Clin Cancer Res; 23(23); 7288–300. ©2017 AACR.
SURFACE DEFORMATION MONITORING ALONG QINGHAI-TIBET RAILWAY USING SMALL BASELINE SAR INTERFEROMETRY , A CASE STUDY OF BEILUHE SECTION , QINGHAI , CHINA

The project of Qinghai-Tibet Railway (QTR) confronts the challenge of surface displacements resulted from seasonal freezing bulge, thawing subsidence and compression settlement. Therefore the embankment instability monitoring is essential for policy makers as well as emergency managers for its operational safety. In this study, we implemented SAR interferometry for extracting ground deformations along the railway. In total, 38 Envisat ASAR SLC images, spanning from 18 Nov. 2004 to 17 Dec. 2009, were employed to cover the Beiluhe experimental site, Qinghai, China. Based on the small baseline interferometric combination (smaller than 300 m spatially and 175 days temporally), 49 high coherent interferograms were firstly generated to minimize the seasonal decorrelation. Then, the estimated surface deformation rates were compared between stacking and Persistent Scatterers Interferometry (PSI); the result revealed a good agreement with determination coefficient of 0.863 for a linear regression model. Furthermore, the derived deformation rates along the embankment were distinct (-20 to +20 mm/yr) in 5 years, implying the necessity of continued satellite-based surveillance along the QTR.
Effect of diazepam on myocardial blood flow of patients with and without coronary artery disease.

Myocardial blood flow was measured by the 133Xe clearance method in 6 patients with radiologically confirmed disease of the coronary arteries and in 4 patients with normal arteries. The myocardial bloodflow was measured 5 minutes after intravenous diazepam OI mg/kg body weight. There was an increase in myocardial bloodflow in all cases. Patients with normal coronary arteries showed an average increase of 22.5 per cent over control levels while patients with diseased coronary arteries showed a 73 per cent average increase. Both figures were highly significant statistically. Possible mechanisms and implications of these findings are discussed.
Effect of Obesity on Motor Functional Outcome of Rehabilitating Traumatic Brain Injury Patients

ObjectiveThe aim of this study was to determine the association between obesity and functional motor outcome of patients undergoing inpatient rehabilitation after traumatic brain injury. DesignThis retrospective study at an urban acute inpatient rehabilitation center screened data from 761 subjects in the Traumatic Brain Injury Model System who were admitted from January 2010 to September 2013. Inclusion criteria consisted of age of 18 years or older and an abnormal Functional Independence Measure motor score. Body mass index was used to determine obesity in the study population. Patients with a body mass index of 30.0 kg/m2 or greater were considered obese. ResultsA total of 372 subjects met the criteria for inclusion in the study. Of these, 54 (13.2%) were obese. Both obese and nonobese patients showed similar improvement in Functional Independence Measure motor score (mean [SD], 30.4 [12.8] for the obese patients, P = 0.115, and 27.3 [13.1] for the nonobese patients). The mean (SD) Functional Independence Measure motor scores at discharge for the obese and nonobese patients were 63.0 (12.6) and 62.3 (10.1) (P = 0.6548), respectively. ConclusionsObesity had no adverse impact on motor functional outcomes of the traumatic brain injury patients who underwent inpatient rehabilitation. Therefore, obesity should not be considered an obstacle in inpatient rehabilitation after traumatic brain injury, if patients are able to participate in necessary therapy.
Requesting radiological investigations – do junior doctors know their patients? A cross-sectional survey

Objectives To ascertain clinicians' knowledge of their patients when requesting radiological investigations, as required legally by UK government legislation ‘Ionising Radiation (Medical Exposure) Regulations 2000’ (IRMER 2000), following the implementation of European Working Time Directive. Design Cross sectional survey. Participants All doctors requesting radiological requests every Monday, following the weekend on-call, over an 8-week period. There were no exclusion criteria. Main outcome measures Baseline data analysis, including grade and specialty of requesting doctor, types of modality requested, knowledge of their patient, addressograph signature confirming identity and appropriateness of investigation. Results 164 requests were received, the majority (61%) were made by Foundation Programme 1 (FP1) doctors and general medical specialties accounted for the highest proportion of requests (45%). Ultrasound scanning was the most frequently requested investigation (47%), closely followed by computed tomography (CT) scans (42%). Almost a third (30%) of requests were made by doctors who had not seen the patient to be investigated, predominantly by FP1 doctors (p=0.003) and more frequently by general medical specialties (p=0.001). Signatures were absent on 20% of the addressographs and overall, 10% of requests were deemed inappropriate. Conclusions In almost a third of radiological requests, doctors have not seen patients to be investigated, most likely as a result of shift working patterns. This does not fulfil the IRMER 2000 criteria and potentially exposes patients to unnecessary and inappropriate radiation.
Knowledge and beliefs concerning early childhood caries from mothers of children ages zero to 12 months.

PURPOSE This study's purpose was to assess mothers' knowledge and beliefs about early childhood caries (ECC) etiology and prevention. METHODS This cross-sectional study targeted mothers (N=277) of zero- to 12-month-olds visiting 12 public health care centers in Pelotas, Rio Grande do Sul, Brazil. Information on causes of and recommendations to prevent ECC, as well as socioeconomic and demographic variables, was collected. Chi-square, univariate, and multiple logistic regression analyses were performed (P<.05). RESULTS Sugar intake and lack of oral hygiene were the most frequently mentioned causes of caries. Ninety percent of the mothers were aware of the need to begin tooth-brushing during their children's first year. Mothers who had more children and were in lower socioeconomic positions were more likely to not know the correct age for the first dental visit. CONCLUSIONS Our findings showed that mothers do not know all the factors that can influence caries in their children. None reported the role of micro-organisms and lack of fluoride in the caries etiology. These findings highlight the importance of providing preventive orientation to the mothers regarding early childhood caries. Information on age of first dental visit should be emphasized, especially among mothers with more than one child and low-income families.
Safety and Toxicological Evaluation of a Novel, Standardized 3-O-Acetyl-11-keto-β-Boswellic Acid (AKBA)-Enriched Boswellia serrata Extract (5-Loxin®)

The novel anti-inflammatory properties of the gum resin derived from Boswellia serrata, also known as Salai guggal in Ayurvedic medicine, are well recognized and highly recommended for human consumption. The active constituents of the gum resin are boswellic acids (BAs). Among the BAs, AKBA potently inhibits 5-lipoxygenase product formation with an IC50 of 1.5 m μM. We developed a novel Boswellia serrata extract (5-Loxin®) enriched with 30% AKBA (US Patent 2004/0073060A1). The genetic basis of the anti-inflammatory effects of 5-Loxin® was explored in a system of TNFα-induced gene expression in human microvascular endothelial cells. 5-Loxin® significantly prevented the TNFα-induced expression of matrix metalloproteinases and adhesion molecules (ICAM-1 and VCAM-1), and inducible expression of the mediators of apoptosis. With such interesting findings, we planned to determine the broad-spectrum safety of 5-Loxin®. Acute oral, acute dermal, primary skin and eye irritation, and dose-dependent 90-day subchronic toxicity studies were conducted. In safety studies, acute oral LD50 of 5-Loxin® was found to be greater than 5,000 mg/kg in both male and female Sprague-Dawley rats. No changes in body weight or adverse effects were observed following necropsy. Acute dermal LD50 of 5-Loxin® was found to be >2,000 mg/kg. Primary skin irritation test was conducted with 5-Loxin® on New Zealand Albino rabbits and 5-Loxin® was classified as nonirritating. Primary eye irritation test was conducted with 5-Loxin on rabbits and 5-Loxin® was classified as mildly irritating to the eye. A dose-dependent 90-day subchronic toxicity study demonstrated no significant changes in selected organ weights individually and as percentages of body and brain weights. 5-Loxin® supplementation did not cause changes in hepatic DNA fragmentation on 30, 60, or 90 days of treatment. Hematology, clinical chemistry, and histopathological evaluations did not show any adverse effects in all organs tested. Taken together, these results demonstrate the broad spectrum safety of 5-Loxin®.
Classification of Polarimetric SAR Images Using Multilayer Autoencoders and Superpixels

A new polarimetric synthetic aperture radar (PolSAR) images classification method based on multilayer autoencoders and superpixels is proposed in this paper. First, in order to explore the spatial relations between pixels in PolSAR data, the RGB image formed with Pauli decomposition is used to produce superpixels to integrate contextual information of neighborhood. Second, multilayer autoencoders network is used to learning the features used for distinguishing the multiple categories for each pixel, and a softmax regression is applied to produce the predicted probability distributions over all the classes of each pixel. Finally, the probability distributions is regarded as a new probabilistic metric and introduced to k-nearest neighbor to improve the accuracy of classification based on superpixels, which takes spatial relationship between pixels into consideration, and it is robust to speckle noise. The proposed method makes good use of the scattering characteristics in each pixel and spatial information of PolSAR data. Compared with other state-of-the-art methods, the results of proposed method show better agreement with the ground truth and significant improvement in classification accuracy and discriminability of small differences between different categories.
Laughter and Subjective Health Among Community-Dwelling Older People in Japan

Abstract The aim of this study was to evaluate the association of laughter with subjective health independent of socioeconomic status and social participation among older people in Japan. We used the data of 26,368 individuals (men, 12,174; women, 14,194) 65 years or older who participated in the Japan Gerontological Evaluation Study (JAGES) in 2013. Participants provided information on laughter and self-rated health, depression, socioeconomic, and psychosocial factors. We evaluated laughter from three perspectives: frequency, opportunities, and interpersonal interactions. Even after adjustment for depression, sociodemographic factors, and social participation, the prevalence ratio for poor subjective health among women who never or almost never laugh was 1.78 (95% confidence interval, 1.48–2.15) compared with those who reported laughing every day. Similar associations were observed among men. Laughter may be an important factor for the promotion of general and mental health of older adults. The mechanisms linking laughter and health warrant further study.
Arrestin‐dependent but G‐protein coupled receptor kinase‐independent uncoupling of D2‐dopamine receptors

We reconstituted D2 like dopamine receptor (D2R) and the delta opioid receptor (DOR) coupling to G‐protein gated inwardly rectifying potassium channels (Kir3) and directly compared the effects of co‐expression of G‐protein coupled receptor kinase (GRK) and arrestin on agonist‐dependent desensitization of the receptor response. We found, as described previously, that co‐expression of a GRK and an arrestin synergistically increased the rate of agonist‐dependent desensitization of DOR. In contrast, only arrestin expression was required to produce desensitization of D2R responses. Furthermore, arrestin‐dependent GRK‐independent desensitization of D2R‐Kir3 coupling could be transferred to DOR by substituting the third cytoplasmic loop of DOR with that of D2R. The arrestin‐dependent GRK‐independent desensitization of D2R desensitization was inhibited by staurosporine treatment, and blocked by alanine substitution of putative protein kinase C phosphorylation sites in the third cytoplasmic loop of D2R. Finally, the D2R construct in which putative protein kinase C phosphorylation sites were mutated did not undergo significant agonist‐dependent desensitization even after GRK co‐expression, suggesting that GRK phosphorylation of D2R does not play an important role in uncoupling of the receptor.
DNA Methylation and Nonsmall Cell Lung Cancer

Lung cancer is the leading cause of cancer‐related death in men and women worldwide. Owing to the scarcity of effective tools for early detection and therapy strategies, the 5‐year survival rate of lung cancer is very poor. Because the accumulation of multiple genetic and/or epigenetic changes, including DNA methylation, has been suggested to contribute to development and progression of human cancers, improved understanding of the relationship between DNA methylation and lung cancer will provide new insights for identifying promising biomarkers for diagnosis, prognosis, and treatment of lung cancer. Here, we present a relatively comprehensive review of DNA methylation and lung cancer, discuss DNA methylation changes in carcinogenesis and metastasis of lung cancer, and explore the association of microRNA with DNA methylation. Additionally, we outline the applications of DNA methylation in clinical practice, such as diagnosis, prognosis, and therapy of lung cancer. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.
In vivo therapy of malignant melanoma by means of antagonists of alphav integrins.

Integrin alphavbeta3 (vitronectin receptor) has been implicated in human malignant melanoma progression and angiogenesis as a receptor that provides survival signals. However, little is known about the therapeutic potential of antagonists of alphavbeta3. In this report, we characterize the activities of 2 antagonists of alphavbeta3 integrins: a human specific monoclonal antibody (MAb), 17E6, and a cyclic RGD peptide that blocked cell adhesion and induced detachment of previously substrate-attached cells in vitro. In vivo, alphavbeta3 antagonists behaved as anti-tumor drugs in a dose- and time-dependent manner. Moreover, different therapeutic treatments proved to be effective even in the therapy of established macroscopic tumor masses, thus supporting the use of these antagonists in clinical therapy. Using a panel of 6 human melanomas and 5 carcinomas, MAb 17E6 efficiently blocked the in vivo tumor growth of melanomas expressing alphavbeta3 as xenografts but did not affect the alphavbeta3-negative (although alphav integrin-positive) tumors. This demonstrated that alphavbeta3 is a pivotal integrin for the growth of human melanomas. Furthermore, since MAb 17E6 does not recognize murine alphavbeta3, the effect is due only to the direct anti-tumor activity and not to the well-known anti-angiogenic activity of alphav-integrin antagonists. Taken together, our results confirm the essential role of alphavbeta3 integrin in the growth of human malignant melanoma in vivo and provide strong evidence of the therapeutic potential of alphav-integrin antagonists for the treatment of such tumors.
Problems associated with the use of pit latrines in Blantyre, Republic of Malawi

A questionnaire and observational study was conducted to determine the problems associated with construction, design and hygiene methods used to maintain pit latrines in a high-density urban township in Malawi. The survey comprised 100 randomly selected households and the per son responsible for the latrine maintenance was interviewed. Eighty- seven percent of householders used traditional latrines, 67% with earth en and 20% with concrete (i.e. sanitation platform, also known as San- plats) floors. A variety of makeshift squat-hole covers (e.g. iron sheets, rocks, cardboard) are used by those who cannot afford San-plats to reduce fly and odour problems. Most squat-hole covers were fouled with faecal matter and some presented risk of invasive injury due to sharp edges. Five households used ventilated improved latrines whilst the remaining eight per cent made use of their neighbour's latrine. Own ership of property, poverty and theft in the area significantly influenced the type and structural condition of the latrine. Walls, ceilings and doors of the superstructure comprised a mixture of miscellaneous materials (i.e. cardboard, paper, cloth, brick) making the hygienic upkeep of the latrine difficult. Cloth doors were often used for hand drying. Geo graphical location, such as rocky terrain with inadequate soil consolida tion, and environmental conditions, such as heavy rains and floods, exacerbate structural defects. Coupled with the lack of attention afford ed to the disposal of young children's faeces, wash-water and pit sur charging, the potential exists for widespread contamination of the sur rounding environment and transmission of faecal-oral disease. More than half of the respondents stressed that they had not received any information regarding health education and hygienic maintenance of the latrine. As such, there is need for a hygiene education programme to promote awareness of appropriate sanitation and behavioural change. Cultural and religious factors were found not to influence latrine use.
Improvement of the Bone–Screw Interface Strength with Hydroxyapatite-Coated and Titanium-Coated AO/ASIF Cortical Screws

Objective To evaluate whether coating AO/ASIF screws with osteoconductive materials can improve bone–screw fixation. Design Ninety-six AO/ASIF 4.5-millimeter cortical screws were divided into four paired groups and implanted in the femurs and tibiae of six sheep: Group A = standard stainless steel screws; Group B = stainless steel screws coated with highly crystalline hydroxyapatite; Group C = stainless steel screws coated with low crystalline hydroxyapatite; Group D = titanium screws coated with titanium. The screws were implanted according to the standard AO technique to an insertion torque of 2,000 Newton-millimeters. Sheep were killed at one, three, and twelve months after surgery. Main Outcome Measures Extraction torque was measured on six screws from each group selected at random at time of each euthanization. Morphologic analysis of the bone–screw interface was performed on the remaining screws. Results At each euthanization the extraction torque of Group A was lower than that of the other groups (p < 0.0001). At three and twelve months the extraction torque of Group B was higher than that of Group D (p = 0.002). Morphologic results showed extensive bone–screw gap in Group A. Optimal osteointegration was observed in Groups B and C. Osteointegration of Group D was higher than that of Group A and lower than that of Groups B and C. Conclusions It was demonstrated that AO/ASIF screws coated with osteoconductive materials achieve optimal fixation strength, even in the early phase. This fixation strength was significantly higher than that of the standard screws.
Recombinant human interleukin‐4 inhibits the production of granulocyte‐macrophage colony stimulating factor by blood mononuclear cells

Summary. The effect of recombinant human (rh) interleukin‐4 (rIL‐4) on human blood BFU‐E was investigated using two populations of cells: platelet‐depleted low‐density mononuclear cells (FH, Pl− cells), as unpurified cells, and highly purified BFU‐E. When FH, Pl− cells were cultured with rherythropoietin (rEp), rIL‐4 inhibited BFU‐E growth in a dose‐dependent manner. However, the addition of rIL‐4 did not affect rh‐interleukin‐3 (rIL‐3) supported BFU‐E growth. Limiting dilution analysis (LDA) of FH, Pl− cells showed that rIL‐4 suppressed endogenous production of burst‐promoting activity (BPA) by accessory cells. Highly purified BFU‐E were used as target cells to measure BPA in the conditioned medium (CM) that was prepared by FH, Pl− cells. When 100 purified BFU‐E were cultured in 0·5 ml clots with 20% (vol/vol) of the CM, the number of BFU‐E colonies was increased by the CM. The increase was significantly reduced by the addition of the CM prepared in the presence of rIL‐4, but anti‐IL‐4 blocked the effect of rIL‐4. The concentration of IL‐3 and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) in CM was determined by an enzyme‐linked immunoadsorbent assay (ELISA). The spontaneous production of GM‐CSF but not IL‐3 was detected, and this was significantly decreased in the presence of rIL‐4. Anti‐GM‐CSF but not anti‐IL‐3 inhibited CM supported BFU‐E growth, indicating that the main BPA in the CM is GM‐CSF and that rIL‐4 suppresses the spontaneous production of GM‐CSF by accessory cells. From these studies, we conclude that rIL‐4 has a unique mechanism as a negative regulator on erythropoiesis through the inhibition of BPA production by blood mononuclear accessory cells.