Miracle-dz/UniFAR-FTUs huggingface dataset:
Lactoferrin- and RGD-comodified, temozolomide and vincristine-coloaded nanostructured lipid carriers for gliomatosis cerebri combination therapy

Purpose Glioblastoma multiforme (GBM) is the most common malignant brain tumor originating in the central nervous system in adults. Based on nanotechnology such as liposomes, polymeric nanoparticles, and lipid nanoparticles, recent research efforts have been aimed to target drugs to the brain. Methods In this study, lactoferrin- and arginine–glycine–aspartic acid (RGD) dual- ligand-comodified, temozolomide and vincristine-coloaded nanostructured lipid carriers (L/RT/V-NLCs) were introduced for GBM combination therapy. The physicochemical properties of L/R-T/V-NLCs such as particle size, zeta potential, and encapsulated efficiency are measured. The drug release profile, cellular uptake, cytotoxicity, tissue distribution, and antitumor activity of L/R-T/V-NLCs are further investigated in vitro and in vivo. Results L/R-T/V-NLCs were stable with nanosize and high drug encapsulation efficiency. L/R-T/V-NLCs exhibited sustained-release behavior, high cellular uptake, high cytotoxicity and synergy effects, increased drug accumulation in the tumor tissue, and obvious tumor inhibition efficiency with low systemic toxicity. Conclusion L/R-T/V-NLCs could be a promising drug delivery system for glioblastoma chemotherapy.
Healthy Sisters: A Feasibility study of a health behavior intervention for women of color breast cancer survivors

ABSTRACT There is strong evidence for the need to educate and empower women of color breast cancer survivors (WCBCS) to adopt healthy lifestyle behaviors. The purpose of this study was to explore feasibility and preliminary efficacy of a culturally grounded lifestyle intervention on functional ability, quality of life, and health behaviors. A community-based sample of WCBCS was recruited from two inner cities, with encouragement to invite a partner. There were 30 WCBCS and 10 partners who participated in the 6-week interactive intervention. Data were collected at baseline, end of intervention and 3 and 6 months. There was significant improvement in healthy lifestyle behaviors (p = 0.041), physical activity (p = 0.003), nutrition (p = 0.007), and stress management (p = 0.010) for WCBCS and, for partners, improvements in healthy lifestyle behaviors (p = 0.041), nutrition (p = 0.007), and health responsibility (p = 0.034).
Structural and Molecular Characterization of the Hemagglutinin from the Fifth-Epidemic-Wave A(H7N9) Influenza Viruses

The A(H7N9) viruses circulating in China are of great public health concern. Here, we report a molecular and structural study of the major surface proteins from several recent A(H7N9) influenza viruses. Our results improve the understanding of these evolving viruses and provide important information on their receptor preference that is central to ongoing pandemic risk assessment. ABSTRACT The avian influenza A(H7N9) virus continues to cause human infections in China and is a major ongoing public health concern. Five epidemic waves of A(H7N9) infection have occurred since 2013, and the recent fifth epidemic wave saw the emergence of two distinct lineages with elevated numbers of human infection cases and broader geographic distribution of viral diseases compared to the first four epidemic waves. Moreover, highly pathogenic avian influenza (HPAI) A(H7N9) viruses were also isolated during the fifth epidemic wave. Here, we present a detailed structural and biochemical analysis of the surface hemagglutinin (HA) antigen from viruses isolated during this recent epidemic wave. Results highlight that, compared to the 2013 virus HAs, the fifth-wave virus HAs remained a weak binder to human glycan receptor analogs. We also studied three mutations, V177K-K184T-G219S, that were recently reported to switch a 2013 A(H7N9) HA to human-type receptor specificity. Our results indicate that these mutations could also switch the H7 HA receptor preference to a predominantly human binding specificity for both fifth-wave H7 HAs analyzed in this study. IMPORTANCE The A(H7N9) viruses circulating in China are of great public health concern. Here, we report a molecular and structural study of the major surface proteins from several recent A(H7N9) influenza viruses. Our results improve the understanding of these evolving viruses and provide important information on their receptor preference that is central to ongoing pandemic risk assessment.
Characterization of HBV integration patterns and timing in liver cancer and HBV-infected livers

Integration of Hepatitis B virus (HBV) into the human genome can cause genetic instability, leading to selective advantages for HBV-induced liver cancer. Despite the large number of studies for HBV integration into liver cancer, little is known about the mechanism of initial HBV integration events owing to the limitations of materials and detection methods. We conducted an HBV sequence capture, followed by ultra-deep sequencing, to screen for HBV integrations in 111 liver samples from human-hepatocyte chimeric mice with HBV infection and human clinical samples containing 42 paired samples from non-tumorous and tumorous liver tissues. The HBV infection model using chimeric mice verified the efficiency of our HBV-capture analysis and demonstrated that HBV integration could occur 23 to 49 days after HBV infection via microhomology-mediated end joining and predominantly in mitochondrial DNA. Overall HBV integration sites in clinical samples were significantly enriched in regions annotated as exhibiting open chromatin, a high level of gene expression, and early replication timing in liver cells. These data indicate that HBV integration in liver tissue was biased according to chromatin accessibility, with additional selection pressures in the gene promoters of tumor samples. Moreover, an integrative analysis using paired non-tumorous and tumorous samples and HBV-related transcriptional change revealed the involvement of TERT and MLL4 in clonal selection. We also found frequent and non-tumorous liver-specific HBV integrations in FN1 and HBV-FN1 fusion transcript. Extensive survey of HBV integrations facilitates and improves the understanding of the timing and biology of HBV integration during infection and HBV-related hepatocarcinogenesis.
Broad-band spectral analysis of the accreting millisecond X-ray pulsar SAX J1748.9−2021

We analyzed a 115 ks XMM-Newton observation and the stacking of 8 days of INTEGRAL observations, taken during the raise of the 2015 outburst of the accreting millisecond X-ray pulsar SAX J1748.9-2021. The source showed numerous type-I burst episodes during the XMM-Newton observation, and for this reason we studied separately the persistent and burst epochs. We described the persistent emission with a combination of two soft thermal components, a cold thermal Comptonization component (~2 keV) and an additional hard X-ray emission described by a power-law (photon index ~2.3). The continuum components can be associated with an accretion disc, the neutron star (NS) surface and a thermal Comptonization emission coming out of an optically thick plasma region, while the origin of the high energy tail is still under debate. In addition, a number of broad (~0.1-0.4 keV) emission features likely associated to reflection processes have been observed in the XMM-Newton data. The estimated 1.0-50 keV unabsorbed luminosity of the source is ~5x10^37 erg/s, about 25% of the Eddington limit assuming a 1.4 solar mass NS. We suggest that the spectral properties of SAX J1748.9-2021 are consistent with a soft state, differently from many other accreting X-ray millisecond pulsars which are usually found in the hard state. Moreover, none of the observed type-I burst reached the Eddington luminosity. Assuming that the burst ignition and emission are produced above the whole NS surface, we estimate a neutron star radius of ~7-8 km, consistent with previous results.
Precision medicine based on surgical oncology in the era of genome‐scale analysis and genome editing technology

Accumulated evidence suggests that multiple molecular and cellular interactions promote cancer evolution in vivo. Surgical oncology is of growing significance to a comprehensive understanding of the malignant diseases for therapeutic application. We have analyzed more than 1000 clinical samples from surgically resected tissue to identify molecular biomarkers and therapeutic targets for advanced malignancies. Cancer stemness and mitotic instability were then determined as the essential predictors of aggressive phenotype with poor prognosis. Recently, whole genome/exome sequencing showed a mutational landscape underlying phenotype heterogeneity in caners. In addition, integrated genomic, epigenomic, transcriptomic, metabolic, proteomic and phenomic analyses elucidated several molecular subtypes that cluster in liver, pancreatic, biliary, esophageal and gastroenterological cancers. Identification of each molecular subtype is expected to realize the precise medicine targeting subtype‐specific molecules; however, there are obstacle limitations to determine matching druggable targets or synthetic lethal interactions. Current breakthroughs in genome editing technology can provide us with unprecedented opportunity to recapitulate subtype‐specific pathophysiology in vitro and in vivo. Given a great potential, on‐demand editing system can design actionable strategy and revolutionize precision cancer medicine based on surgical oncology.
Assessment of Esophageal High-Resolution Impedance Manometry in Patients with Nonobstructive Dysphagia

Background High-resolution impedance manometry (HRIM) can calculate the bolus motion parameters and the ratio of complete esophageal transit besides the conventional esophageal dynamic parameters; therefore, we could better manage the patients with nonobstructive dysphagia (NOD) clinically. Aim To analyze the HRIM parameter results of NOD patients and evaluate the characteristics of their esophageal motility and transit function. Methods In total, 58 NOD patients were assessed and the clinical diagnoses were determined. HRIM was performed, and both conventional high-resolution manometry and esophageal transit parameters were analyzed. Results In 58 NOD patients, 28 patients had achalasia, 3 esophagogastric junction outflow obstruction, and 20 nonspecific esophageal motility disorders, and 7 were normal. Impedance results demonstrated that all the patients with achalasia exhibited incomplete esophageal transit (ICET), three patients with esophagogastric junction outflow obstruction showed ICET, and the average bolus transit time (BTT) was 6.6 ± 1.2 sec. In 20 nonspecific esophageal motility disorders, 13 patients with gastroenterologly reflux disease (GERD) presented ineffective esophageal motility and fragmented peristalsis, and 65.0% swallows had exhibited ICET. However, 49.1% swallows of 7 nonspecific esophageal motility disorder patients with non-GERD had exhibited ICET. The average BTT in 13 GERD patients was longer than that in the non-GERD patients (8.1 ± 1.1 sec versus 5.5 ± 0.3 sec, P < 0.05). And in the seven patients with normal esophagus function, 3.5% swallows showed ICET and BTT was 5.6 ± 0.3 sec. Conclusion Achalasia was the most common esophageal dysmotility in NOD patients, followed by nonspecific esophageal motility disorders. The clinical diagnoses of NOD were mostly achalasia and GERD. Impedance assessments showed that all achalasia cases exhibited ICET, and other esophageal motility abnormalities that represented ICET were associated with contraction break and ineffective swallow. Compared to non-GERD patients, BTT was significantly prolonged in patients with GERD.
NBER WORKING PAPER SERIES ASSET PRICING WITH FADING MEMORY

Building on evidence that lifetime experiences shape individuals' macroeconomic expectations, we study asset prices in an economy in which a representative agent learns with fading memory about unconditional mean endowment growth. With IID fundamentals, constant risk aversion, and memory decay calibrated to microdata, the model generates a high and strongly countercyclical objective equity premium, while the subjective equity premium is virtually constant. Consistent with this theory, experienced payout growth (a weighted average of past growth rates) is negatively related to future stock market excess returns and subjective expectations errors in surveys, and positively to analyst forecasts of long-run earnings growth. Stefan Nagel University of Chicago Booth School of Business 5807 South Woodlawn Avenue Chicago, IL 60637 and NBER stefan.nagel@chicagobooth.edu Zhengyang Xu Ross School of Business University of Michigan Ann Arbor, MI 48109 zhengyxu@umich.edu
An integrated groupwork methodology for working with sex offenders

Abstract There is now a considerable literature on the assessment and treatment of sexual offenders. There exists another substantial literature on therapeutic groupwork and its relevance to a range of clinical populations. These bodies of work have made reference to the other in terms of their mutual relevance. However, there has been no comprehensive attempt to apply groupwork theory and principles systematically to work with sex offenders. While this work is generally carried out using a group format and the application of groupwork principles is promoted enthusiastically in the field, the application is underdeveloped both empirically and even more so conceptually. As a result, practices vary greatly. We argue here that a systematic and integrated consideration of the application of groupwork methodology to the treatment of sex offenders has the potential to enhance treatment effectiveness significantly. We conclude with implications for training and clinical practice.
Auxin production in diploid microsporocytes is necessary and sufficient for early stages of pollen development

Gametophytic development in Arabidopsis depends on nutrients and cell wall materials from sporophytic cells. However, it is not clear whether hormones and signaling molecules from sporophytic tissues are also required for gametophytic development. Herein, we show that auxin produced by the flavin monooxygenases YUC2 and YUC6 in the sporophytic microsporocytes is essential for early stages of pollen development. The first asymmetric mitotic division (PMI) of haploid microspores is the earliest event in male gametophyte development. Microspore development in yuc2yuc6 double mutants arrests before PMI and consequently yuc2yuc6 fail to produce viable pollens. Our genetic analyses reveal that YUC2 and YUC6 act as sporophytic genes for pollen formation. We further show that ectopic production of auxin in tapetum, which provides nutrients for pollen development, fails to rescue the sterile phenotypes of yuc2yuc6. In contrast, production of auxin in either microsporocytes or microspores rescued the defects of pollen development in yuc2yuc6 double mutants. Our results demonstrate that local auxin biosynthesis in sporophytic microsporocytic cells and microspore controls male gametophyte development during the generation transition from sporophyte to male gametophyte.
Using Paraphrasing and Memory-Augmented Models to Combat Data Sparsity in Question Interpretation with a Virtual Patient Dialogue System

When interpreting questions in a virtual patient dialogue system one must inevitably tackle the challenge of a long tail of relatively infrequently asked questions. To make progress on this challenge, we investigate the use of paraphrasing for data augmentation and neural memory-based classification, finding that the two methods work best in combination. In particular, we find that the neural memory-based approach not only outperforms a straight CNN classifier on low frequency questions, but also takes better advantage of the augmented data created by paraphrasing, together yielding a nearly 10% absolute improvement in accuracy on the least frequently asked questions.
Canine Diabetes Mellitus Associated Ocular Disease

&NA; Diabetes mellitus (DM) is a commonly encountered disease in companion animal veterinary practice. Ocular complications in dogs with DM are thought to be common but there are no reports of the overall incidence of DM‐associated ocular disease. Some complications, such as cataracts and ocular surface disease, can lead to vision loss and significant morbidity among DM patients, therefore early recognition and intervention are essential for successful outcomes. The purpose of this article is to provide a review of several currently known or suspected ocular diseases associated with DM.
Term Definitions Help Hypernymy Detection

Existing methods of hypernymy detection mainly rely on statistics over a big corpus, either mining some co-occurring patterns like “animals such as cats” or embedding words of interest into context-aware vectors. These approaches are therefore limited by the availability of a large enough corpus that can cover all terms of interest and provide sufficient contextual information to represent their meaning. In this work, we propose a new paradigm, HyperDef, for hypernymy detection – expressing word meaning by encoding word definitions, along with context driven representation. This has two main benefits: (i) Definitional sentences express (sense-specific) corpus-independent meanings of words, hence definition-driven approaches enable strong generalization – once trained, the model is expected to work well in open-domain testbeds; (ii) Global context from a large corpus and definitions provide complementary information for words. Consequently, our model, HyperDef, once trained on task-agnostic data, gets state-of-the-art results in multiple benchmarks
The Correlation between Cell Phone Use and Sleep Quality in Medical Students

Introduction The negative health effects of electromagnetic radiation and psychological dependence are among the major consequences of widespread cell phone use in the general population, especially among adolescents. In this study, the relationship between cell phone use and sleep quality parameters was evaluated. Materials and Methods The study sample consisted of 820 students (305 males and 515 females), recruited from Arak University of Medical Sciences, Arak, Iran. The participants completed Pittsburgh Sleep Quality Index (PSQI) and Cell-phone Overuse Scale (COS); the validity of these questionnaires had been previously confirmed in the Iranian population. Information on demographic characteristics and variables associated with cell phone exposure, such as the frequency and duration of phone calls and number of messages was collected in a separate questionnaire. Results Data analysis showed that cell phone overuse was significantly correlated with sleep quality and its components. Moreover, the results indicated that the global PSQI score and some sleep components were significantly correlated with several variables related to cell phone use. Based on the findings, the mean PSQI score was significantly different among heavy and light cell phone users (P<0.01). Moreover, among heavy cell phone users, females had a higher global PSQI score, compared to males (P<0.01). Conclusion According to the literature and the present study, services provided by modern cell phones, along with the extensive use of these devices, could be considered as potential threats to public health, especially adolescents’ sleep quality. In order to reach a definitive conclusion, further systematic and laboratory studies are required.
Pattern of HIV-1 drug resistance among adults on ART in Nigeria.

Background: The development of anitiretroviral drug resistance may limit the benefit of antiretroviral therapy. Therefore the need to closely monitor these mutations, especially the use of ART is increasing. This study was therefore designed to determine the ARV drug resistance pattern among ART naive and expose individuals attending a PEPFAR supported by antiretroviral clinic in Nigeria. Methodology: The study participants included patients attending the PEPFAR supported by University College Hospital (UCH), Ibadan ART clinic who have been on HIV treatment for at least one year with consecutive viral load of over 2000 copies/ml as well some ART Naive individuals with high (>50,000 copies/ml) baseline viral level attending the hospital for pre-ART assessment. Blood sample was collected from each individual for CD4 enumeration, viral load level determination and DNA sequencing for genotypic typing. Antiretroviral drug resistance mutations (DRM) were determined by using the Viroseq software and drug mutations generated by using a combination of Viroseq and Stanford algorithm. DRM were classified as major or minor mutations based on the June 2013 Stanford DR database. Results: The most common major NRTI, NNRTI and PI mutation were D67N (33.3%), Y181C (16.7%) and M46L/I (55.6%) respectively. Lamivudine (3TC) and emtricitabine (FTC); nevirapine (NVP) and nelfinavir (NFV) were the most common NRTI, NNRTI, and PI drugs to which the virus in the infected individuals developed resistance. Isolates from 4 patients were resistant to triple drug class, including at least one NRTI, NNRTI and a PI. Only one (4.8%) of the isolates from drug Naive individuals had major DRM that conferred resistance to any drug. Conclusion: Demonstration of high rates of antiretroviral DRM among patients on 1 st and 2 nd line ART and the presence of DRM in drug Naive individuals in this study show the importance of surveillance for resistance to ARV in line with the magnitude of scaling up of treatment program in the country.
Long‐term survival after childhood acute lymphoblastic leukaemia: population‐based trends in cure and relapse by clinical characteristics

‘Cure models’ offer additional information to traditional epidemiological approaches to assess survival for cancer patients by simultaneously estimating the proportion cured and the survival of those ‘uncured’. The proportion cured is a summary of long‐term survival while the median survival time of the uncured provides important information on those who are not long‐term survivors. Population‐based trends in the cure proportion and survival of the uncured for childhood acute lymphoblastic leukaemia (ALL) by clinical prognostic risk factors were estimated using flexible parametric cure models, based on overall survival and event‐free survival. Children aged 1–17 years diagnosed between 1990 and 2011 in Yorkshire, UK, were included (n = 492). The percentage cured increased from 77% (95% confidence interval 70–84%) in 1990–1997 to 89% (84–93%) in 2003–2011, while the median survival time of the uncured decreased from 3·2 years (2·2–4·1 years) to 0·7 years (0–1·5 years). Models based on event‐free survival showed a similar trend. The 5‐year cumulative incidence of relapse substantially decreased from 35% in 1990–97 to 9% in 2003–2011. These results show selective improvement in survival between 1990 and 2011 with a significant reduction in the risk of relapse alongside a reduced absolute duration of survival for those destined to be uncured.
A performability model for the BRT system

Large cities have increasing mobility problems due to the large number of vehicles on the streets, which results in traffic jams and thus a waste of time and money. An alternative to improve traffic is to prioritize the public transportation system. Several metropolises around the world are adopting Bus Rapid Transit (BRT) systems since they present compelling results considering the cost-benefit perspective. Evaluating metrics such as performance, dependability, and performability, aids in planning, monitoring, and optimizing BRT systems. This paper presents hierarchical models, using CTMC modeling techniques, to assess metrics such as performance and performability. Results show that these models pointed to the peak intervals that are more likely to arrive at the destination in a shorter time, in addition to showing the probability of the vehicle being affected by the failure at each interval. It was also possible to establish bases for the replication of the model in different scenarios to enable new comparative studies.