Miracle-dz/UniFAR-FTUs huggingface dataset:
Osteogenic effect of bone marrow mesenchymal stem cell-derived exosomes on steroid-induced osteonecrosis of the femoral head

Background Animal studies have demonstrated the therapeutic effect of mesenchymal stem cells (MSCs) on osteogenesis, but little is known about the functions of exosomes (Exos) released by bone MSCs (BMSCs). Here, we investigated the effect of BMSC Exos on steroid-induced femoral head necrosis (SFHN) and explored the vital genes involved in this process. Materials and methods BMSCs were isolated from healthy and SFHN rats. BMSC Exos were isolated using the Exosome Precipitation Kit and characterized by transmission electron microscopy and Western blotting. SFHN BMSCs were incubated with Exos from healthy BMSCs. Osteogenic ability was assessed by oil red O staining and alizarine red staining. Differentially expressed genes (DEGs) induced by Exos were screened using the Osteogenesis RT2 Profiler PCR Array. The effect of upregulated Sox9 was examined using lentivirus-mediated siRNA. Results The results revealed that BMSC Exos were 100-150 nm in size and expressed CD63. Moreover, BMSC Exo-treated SFHN cells exhibited suppressed adipogenesis compared to model cells. PCR array showed that eleven and nine genes were upregulated and downregulated, respectively, in the BMSC Exo-treated SFHN cells compared to the model group. Among the DEGs, osteogenesis-related genes, including Bmp2, Bmp6, Bmpr1b, Mmp9, and Sox9, may play important roles in SFHN. Furthermore, the DEGs were mainly involved in immune response, osteoblast differentiation, and in the transforming growth factor-β/bone morphogenetic protein signaling pathway. The level of the SOX9 protein was upregulated by Exos, and Sox9 silencing significantly decreased the osteogenic effect of BMSC Exos. Conclusion Our data suggest that Exos derived from BMSCs mainly affect SFHN osteogenesis, and this finding can be further investigated to develop a novel therapeutic agent for SFHN.
Body Mass Index is Negatively Associated with Endometrial Cancer Stage, Regardless of Subtype and Menopausal Status

Objective: Obesity is one of the common risk factors for developing of endometrial cancer and is negatively associated with its survival, although this result is controversial. Endometrial cancer stages range from stage I, which has better clinical outcomes to stage IV, which has poorer clinical outcomes. Endometrial cancer traditionally divides into type 1 and type 2 dependent on histology which has different clinical outcomes. In this study we investigated whether obesity is associated with the stages of endometrial cancer taking into account subtypes of cancer and menopausal status. Methods: Data on 1,104 women with endometrial cancer were retrospectively collected from the largest women's hospital in China and analysed. Data included age at diagnosis, body mass index (BMI), histology of cancer and menopausal status. Results: The BMI in patients with stage I endometrial cancer was significantly higher than that in patients with stage II or III or IV (p=0.0001). However, there was no statistical difference in BMI between patients with stage II, and stage III endometrial cancer. This negative association was persisted with type 1 and type 2 endometrial cancer (p=0.1989) and premenopausal and post-menopausal status (p=0.4342). In addition, the proportion of over-weight or obese women in type1 endometrial cancer with stage I was not different to type 2 endometrial cancer with stage I. Conclusion: Our data demonstrate that BMI is negatively associated with endometrial cancer in early stage regardless of subtypes of cancer, menopausal status and obesity may be also a potential risk factor for developing type 2 endometrial cancer.
Testing the paradigm of an ideal glass transition: Dynamics of an ultrastable polymeric glass

Measurements on nanogram samples of ultrastable polymer Teflon films challenge paradigms of the glass transition event. A major challenge to understanding glass-forming materials is obtaining equilibrium data far below the laboratory glass transition temperature Tg. The challenge arises because it takes geologic aging times to achieve the equilibrium glassy state when temperatures are well below Tg. Here, we finesse this problem through measurements on an ultrastable amorphous Teflon with fictive temperature Tf near to its Kauzmann temperature TK. In the window between Tf and Tg, the material has a lower molecular mobility than the equilibrium state because of its low specific volume and enthalpy. Our measurements show that the determined scaled relaxation times deviate strongly from the classical expectation of divergence of time scales at a finite temperature. The results challenge the view of an ideal glass transition at or near to TK.
Sex differences in clinical characteristics and 1-year outcomes of young ischemic stroke patients in East China

Background Data concerning sex differences in clinical characteristics and outcomes of young ischemic stroke (IS) patients in Eastern China are scarce. Understanding sex differences in clinical characteristics and long-term outcomes of young IS patients might provide valuable evidence for designing preventative measures and therapeutic interventions. Methods The study included 228 acute IS patients aged up to 50 years recruited in the prospective Nanjing First Hospital Stroke Registry over a 5-year period. Univariable and multivariable logistic regression analyses were performed to determine whether there were sex differences in clinical characteristics and outcomes of young IS patients. Results Admission systolic blood pressure (130.12±24.3 vs 137.96±24.3 mmHg, P=0.005) of women was significantly lower than that of men. Logistic regression showed that young women had poorer outcomes defined as having modified Rankin Scale score of 3-6 at 12 months after the adjustment for history of prior stroke, NIHSS score, and complication of pneumonia (adjusted OR: 3.45; 95% CI: 1.43-8.32). Conclusion Our study indicates that there may be significant differences in clinical characteristics between young women and men with acute IS in East China. Young women were more likely to be dead or dependent at 12 months after stroke onset. More attention should be paid to young women's IS prevention and management in East China.
Prevalence of Hypertension in Children

In 2017, the American Academy of Pediatrics issued a new clinical practice guideline for defining hypertension in children as an update to the previous Fourth Report guidelines issued in 2004. Prevalence of confirmed pediatric hypertension in children has ranged from 2% to 4% based on previous guidelines yet it is unknown what the prevalence is under the new guideline. We estimated the prevalence of elevated blood pressure, stage 1, and stage 2 hypertension by the new American Academy of Pediatrics guideline in our school-based blood pressure screening program. New prevalence estimates were compared with Fourth Report prevalence estimates in the same population by sex, age, and height factors. In 22 224 students aged 10 to 17 years screened in school as part of the Houston Pediatric and Hypertension Program at the University of Texas McGovern Medical School, the prevalence of elevated blood pressure (previously called prehypertension) increased from 14.8% by Fourth Report to 16.3% by the new American Academy of Pediatrics guideline. This increase in elevated blood pressure resulted from differential classification changes in younger and older children. Prevalence of confirmed hypertension remains at 2% to 4% in this population, however shorter children <13 years old and taller, older children 13+ years old are systematically more likely to be diagnosed with hypertension by new guidelines.
Organizing palliative care in the rural areas of Iran: are family physician-based approaches suitable?

Introduction The provision of palliative end-of-life care (P/EOLc) for patients, wherever they live, is an increasingly important service, particularly given the increasing rates of cancer and other life-threatening diseases in Iran. However, unfortunately, those living in the rural areas of Iran are greatly disadvantaged with respect to this type of care. Therefore, the present study explored the feasibility of organizing P/EOLc in the rural areas of Iran. Methods In this qualitative study, two focus group (FG) discussions were held in Tabriz (Iran) with rural family physicians (FPs, n=23) and key P/EOLc stakeholders (n=13). The FG sessions were recorded, transcribed, and the transcriptions checked by participants before the data were subjected to content analysis. Results While most FPs indicated that they did not have sufficient involvement in providing P/EOLc, they emphasized the necessity of providing P/EOLc through four main themes and 25 subthemes. The four main themes were labeled as "structures and procedures," "health care provider teams," "obstacles," and "strategies or solutions. " Furthermore, according to the main themes and subthemes identified here, the key stakeholders believed that the Iranian health system and the FPs' team have the potential to provide P/EOLc services in rural areas. Conclusion The most feasible strategy for providing P/EOLc in Iranian rural areas would be to use the current health care framework and base the process around the FP.
The comorbidities of dysmenorrhea: a clinical survey comparing symptom profile in women with and without endometriosis

Purpose Dysmenorrhea is a common disorder that substantially disrupts the lives of young women. The frequency of 14 associated symptoms both within and outside the pelvis was determined. Patients and methods Symptom questionnaires were completed by 168 women with dysmenorrhea, allocated to three groups based on their diagnostic status for endometriosis confirmed (Endo+), endometriosis excluded (Endo−), or endometriosis diagnosis unknown (No Lap). Those with endometriosis confirmed were further divided into current users (Endo+ Hx+) and non-users of hormonal treatments (Endo+ Hx−). Users of hormonal treatments were further divided into users (Endo+ Hx+ LIUCD+) and non-users (Endo+ Hx+ LIUCD−) of a levonorgestrel-releasing intra-uterine contraceptive device (LIUCD). The frequency and number of symptoms within groups and the effect of previous distressing sexual events were sought. Results Women with and without endometriosis lesions had similar symptom profiles, with a mean of 8.5 symptoms per woman. Only 0.6% of women reported dysmenorrhea alone. The presence of stabbing pelvic pains was associated with more severe dysmenorrhea (P=0.006), more days per month of dysmenorrhea (P=0.003), more days per month of pelvic pain (P=0.016), and a diagnosis of migraine (P=0.054). The symptom profiles of the Endo+ Hx+ and Endo+ Hx− groups were similar. A history of distressing sexual events was associated with an increased number of pain symptoms (P=0.003). Conclusion Additional symptoms are common in women with dysmenorrhea, and do not correlate with the presence or absence of endometriosis lesions. Our study supports the role of central sensitization in the pain of dysmenorrhea. The presence of stabbing pelvic pains was associated with increased severity of dysmenorrhea, days per month of dysmenorrhea, days per month of pelvic pain, and a diagnosis of migraine headache. A past history of distressing sexual events is associated with an increased number of pain symptoms.
Improving safety and efficiency in care: multi-stakeholders’ perceptions associated with a peritoneal dialysis virtual care solution

Background Although there is a growing body of literature on the outcomes and impacts of remote home management with peritoneal dialysis (PD) patients, less is understood how this virtual care solution impacts the quality and efficiency of the healthcare system care. In this context, a study was undertaken to understand the perceptions of patients and their caregivers, healthcare providers, health system decision makers, and vendors associated with a remote monitoring and tracking solution aimed at enhancing the outcomes and experiences of chronic kidney disease (CKD) patients receiving PD at home. Methods A qualitative design using semi-structured interviews with 25 stakeholders was used in this study. Narrative data were analyzed by a thematic analysis approach. Results The following two themes emerged from the data: (1) leveraging data to monitor and intervene to keep patients safe and (2) increasing efficiencies and having control over supplies. Discussion Our study findings elucidated the ability of patients (and in some cases, caregivers) to monitor and trend their data and order and track directly on-line their dialysis supplies were key to their active participation in managing their CKD and keeping them safe at home. Their active participation and functionality of the virtual care solution also led to enhanced efficiencies (eg, process faster, easier, convenient, time savings) for both patients and healthcare providers. Conclusion The virtual care solution showed promising signs of a patient-centric approach and may serve as a blueprint for other virtual care solutions for chronic disease management.
Influenced but not determined by historical events: genetic, demographic and morphological differentiation in Heleobia ascotanensis from the Chilean Altiplano

In the present study, we focus on the phylogeographic pattern, demographic history and morphological differentiation of Heleobia ascotanensis, a freshwater gastropod restricted to the Ascotán saltpan in the Chilean Altiplano. The current distribution of the species is limited to twelve isolated or partially isolated springs that were affected by transitions between humid and arid periods during last glaciations. The genetic analysis of 322 specimens showed that H. ascotanensis is subdivided into three genetically divergent populations, with low and moderate degrees of historical gene flow among them and incipient morphological differentiation as a consequence of genetic and geographical isolation. Molecular analyses revealed different demographic histories among populations which seem to respond independently to climatic events, probably due to an environmental imposition and idiosyncratic strategies developed to cope with water availability. The results of this study and co-distributed taxa support the hypothesis that contemporary and historical events have influenced microevolutionary differentiation of these snails, although there is a need to complement further information to predict genetic or morphological divergence at microgeographic scale.
Tocilizumab in the treatment of rheumatoid arthritis: an evidence-based review and patient selection

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by articular and systemic manifestations, such as anemia, fatigue, osteoporosis, and increased risk for cardiovascular diseases. The pathogenesis of RA is driven by a complex network of proinflammatory cytokines, with a pivotal role of IL-6 and tumor necrosis factor (TNF). The management of RA has been dramatically changed during the last years by the introduction of a treat-to-target approach aiming to achieve an acceptable disease control. Nowadays, TNF inhibitors (TNFis) are the most frequently prescribed class of biologic therapies, but the significant proportion of patients experiencing the failure of a TNFi led to the development of alternative therapeutic options targeted on different pathways. Considering the increasing number of targeted therapeutic options for RA, there is a growing interest in the identification of potential predictors of clinical response to each available mechanism of action, with the aim to drive the management of the disease toward a personalized approach according to the concept of precision medicine. Tocilizumab (TCZ) is the first humanized anti-IL-6 receptor subunit alpha (anti-IL-6R) monoclonal antibody approved for the treatment of RA refractory to methotrexate or TNFis. TCZ inhibits both the cis- and trans-signaling cascades involving the Janus kinase-signal transducer and the activator of transcription pathway, playing a crucial role in modulating not only joint inflammation but also the previously mentioned extra-articular manifestations and comorbidities of RA, such as fatigue, anemia, bone loss, depression, type 2 diabetes, and increased cardiovascular risk. In this review, moving from pathogenetic insights and evidence-based clinical data from randomized controlled trials and real-life observational studies, we will discuss the drivers for the selection of patient candidates to receive TCZ, in order to clarify the current positioning of this drug in the treatment algorithm of RA.
Extending fragment‐based free energy calculations with library monte carlo simulation: Annealing in interaction space

Pre‐calculated libraries of molecular fragment configurations have previously been used as a basis for both equilibrium sampling (via library‐based Monte Carlo) and for obtaining absolute free energies using a polymer‐growth formalism. Here, we combine the two approaches to extend the size of systems for which free energies can be calculated. We study a series of all‐atom poly‐alanine systems in a simple dielectric solvent and find that precise free energies can be obtained rapidly. For instance, for 12 residues, less than an hour of single‐processor time is required. The combined approach is formally equivalent to the annealed importance sampling algorithm; instead of annealing by decreasing temperature, however, interactions among fragments are gradually added as the molecule is grown. We discuss implications for future binding affinity calculations in which a ligand is grown into a binding site. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2011
Exploiting non‐orthogonal multiple access in downlink coordinated multipoint transmission with the presence of imperfect channel state information

In this paper, the impact of imperfect channel state information (CSI) on a downlink coordinated multipoint (CoMP) transmission system with non‐orthogonal multiple access (NOMA) is investigated since perfect knowledge of a channel cannot be guaranteed in practice. Furthermore, the channel estimation error is applied to estimate the channel information wherein its a priori of variance is assumed to be known. The impact of the number of coordinated base stations (BSs) on downlink CoMP NOMA is investigated. Users are classified into one of two groups according to their position within the cell, namely, cell‐center user (CCU) and cell‐edge user (CEU). In this paper, ergodic capacity and sum capacity for both CCU and CEU are derived as closed forms. In addition, various experiments are conducted with different parameters such as SNR, error variance, and power allocation to show their impact on the CoMP method. The results show that CoMP NOMA outperforms the CoMP orthogonal multiple access (OMA) wherein the condition of the channel impacts the performance of CoMP NOMA less. It is worth noting that a higher number of coordinated BSs enhances the total capacity of CoMP NOMA. Finally, the performance analysis is validated due to the close accordance between the analytical and simulation results.
Integrity Constraints Revisited: From Exact to Approximate Implication

Integrity constraints such as functional dependencies (FD) and multi-valued dependencies (MVD) are fundamental in database schema design. Likewise, probabilistic conditional independences (CI) are crucial for reasoning about multivariate probability distributions. The implication problem studies whether a set of constraints (antecedents) implies another constraint (consequent), and has been investigated in both the database and the AI literature, under the assumption that all constraints hold exactly. However, many applications today consider constraints that hold only approximately. In this paper we define an approximate implication as a linear inequality between the degree of satisfaction of the antecedents and consequent, and we study the relaxation problem: when does an exact implication relax to an approximate implication? We use information theory to define the degree of satisfaction, and prove several results. First, we show that any implication from a set of data dependencies (MVDs+FDs) can be relaxed to a simple linear inequality with a factor at most quadratic in the number of variables; when the consequent is an FD, the factor can be reduced to 1. Second, we prove that there exists an implication between CIs that does not admit any relaxation; however, we prove that every implication between CIs relaxes "in the limit". Then, we show that the implication problem for differential constraints in market basket analysis also admits a relaxation with a factor equal to 1. Finally, we show how some of the results in the paper can be derived using the I-measure theory, which relates between information theoretic measures and set theory. Our results recover, and sometimes extend, previously known results about the implication problem: the implication of MVDs and FDs can be checked by considering only 2-tuple relations.
Image-To-Image Translation via Group-Wise Deep Whitening-And-Coloring Transformation

Recently, unsupervised exemplar-based image-to-image translation, conditioned on a given exemplar without the paired data, has accomplished substantial advancements. In order to transfer the information from an exemplar to an input image, existing methods often use a normalization technique, e.g., adaptive instance normalization, that controls the channel-wise statistics of an input activation map at a particular layer, such as the mean and the variance. Meanwhile, style transfer approaches similar task to image translation by nature, demonstrated superior performance by using the higher-order statistics such as covariance among channels in representing a style. In detail, it works via whitening (given a zero-mean input feature, transforming its covariance matrix into the identity). followed by coloring (changing the covariance matrix of the whitened feature to those of the style feature). However, applying this approach in image translation is computationally intensive and error-prone due to the expensive time complexity and its non-trivial backpropagation. In response, this paper proposes an end-to-end approach tailored for image translation that efficiently approximates this transformation with our novel regularization methods. We further extend our approach to a group-wise form for memory and time efficiency as well as image quality. Extensive qualitative and quantitative experiments demonstrate that our proposed method is fast, both in training and inference, and highly effective in reflecting the style of an exemplar.
Deep neural networks are biased towards simple functions

We prove that the binary classifiers of bit strings generated by random wide deep neural networks are biased towards simple functions. The simplicity is captured by the following two properties. For any given input bit string, the average Hamming distance of the closest input bit string with a different classification is at least $\sqrt{n\left/\left(2\pi\ln n\right)\right. }$, where $n$ is the length of the string. Moreover, if the bits of the initial string are flipped randomly, the average number of flips required to change the classification grows linearly with $n$. On the contrary, for a uniformly random binary classifier, the average Hamming distance of the closest input bit string with a different classification is one, and the average number of random flips required to change the classification is two. These results are confirmed by numerical experiments on deep neural networks with two hidden layers, and settle the conjecture stating that random deep neural networks are biased towards simple functions. The conjecture that random deep neural networks are biased towards simple functions was proposed and numerically explored in [Valle P\'erez et al., arXiv:1805.08522] to explain the unreasonably good generalization properties of deep learning algorithms. By providing a precise characterization of the form of this bias towards simplicity, our results open the way to a rigorous proof of the generalization properties of deep learning algorithms in real-world scenarios.