Miracle-dz/UniFAR-FTUs huggingface dataset:
GE11 peptide-conjugated nanoliposomes to enhance the combinational therapeutic efficacy of docetaxel and siRNA in laryngeal cancers

In this study, dual therapeutic-loaded GE11 peptide-conjugated liposomes were developed and applied to enhance therapeutic efficacies of standard-of-care regimens for the treatment of laryngeal cancer. The therapeutic strategy used here was a combination treatment with the chemotherapeutic docetaxel (DTX) and siRNA against the ABCG2 gene that regulates multidrug resistance in many tumor types. Liposome-encapsulated DTX/ABCG2–siRNA molecules were targeted to recognize tumor cells of squamous morphology by conjugation to the EGFR-targeting ligand, GE11. Targeted, drug-infused liposomes were nanosized and exhibited controlled release of DTX. Presence of GE11 peptides on liposomal surfaces enhanced the quantities of liposomal constructs taken up by Hep-2 laryngeal cancer cells. GE11 peptide-conjugated liposomes also enhanced cytotoxic effects against Hep-2 laryngeal cancer cells when compared to treatment with free DTX, thereby reducing IC50 values. Additionally, GE11 peptide-conjugated liposomes had significantly increased anti-tumor and apoptotic effects. Treatments with the GDSL nanoparticle formulation inhibited tumor growth in Hep-2 xenograft-bearing nude mouse models when compared to treatments with non-targeted NP constructs. Treatment of the mouse models with GE11 peptide-conjugated liposomes mitigated toxicities observed after treatment with free DTX. Taken together, liposomal encapsulation of DTX and ABCG2–siRNA improved the anti-tumor effects of treatment with free DTX in Hep-2 cell lines, and conjugation of GE11 peptides to liposomal constructs enhanced anti-tumor efficacies and specificities in laryngeal cancer cells.
Towards False Alarm Reduction Using Fuzzy If-Then Rules for Medical Cyber Physical Systems

Cyber-Physical Systems (CPS) are integrations of computation, networking, and physical processes. Its process control is often referred to as embedded systems. Generally, CPS and Internet of Things have the same basic architecture, whereas the former shows a higher combination and coordination between physical and computational elements, i.e., wireless sensor networks can be a vital part of CPS applications. With the rapid development, CPS has been applied to healthcare industry, where a wide range of medical sensors are used within a healthcare organization. However, these sensors may generate a large number of false alarms in practice, which could significantly reduce the system effectiveness. Targeting on this issue, in this work, we attempt to design a Medical Fuzzy Alarm Filter (named MFAFilter) for healthcare environments by means of fuzzy logic, especially fuzzy if-then rules, which could handle the vague and imprecise among data. In the evaluation, we conducted two major experiments to explore the performance of our approach in a simulated and a real network environment, respectively. Experimental results demonstrate that the use of fuzzy if-then rules could achieve a better accuracy as compared to the traditional supervised algorithms, and that our designed filter is effective in the practical environment.
Parity and Risk of Thyroid Autoimmunity Based on the NHANES (2001‐2002, 2007‐2008, 2009‐2010, and 2011‐2012)

Context: Autoimmune thyroid disease is more common in women than in men. Fetal microchimerism has been implicated as a potential explanation for this disparity. Objective: The objective of this study was to evaluate the relationship between parity and thyroid autoimmunity in the US population. Design, Setting, Patients: The National Health and Nutrition Examination Survey was used to identify females with antithyroperoxidase (TPOAb) and antithyroglobulin antibody (TgAb) measurements and parity data. Subjects (n = 4864) were categorized as never pregnant (n = 909) or previously pregnant (n = 3955). The association of parity with thyroid autoantibodies was examined both qualitatively and quantitatively. Thyroid autoimmunity was defined as TPOAb and/or TgAb titers above the reference limits. Results: Previous pregnancy carried an odds ratio (OR) of 1.55 [95% confidence interval (CI): 1.26 to 1.91] for thyroid autoimmunity compared with never pregnant. Number of pregnancies was associated with thyroid autoimmunity: OR = 1.37 (95% CI: 1.02 to 1.84); 1.4 (95% CI: 1.08 to 1.81); 1.52 (95% CI: 1.18 to 1.96); and 1.73 (95% CI: 1.38 to 2.18) for 1, 2, 3, and ≥4 pregnancies, respectively. Because ever‐pregnant women differed in several variables—age, race, smoking status, history of thyroid disease, and urinary iodine level—from never‐pregnant women (P < 0.001), a multivariate regression analysis was performed, which showed no association of pregnancy with thyroid autoimmunity. The association was further examined utilizing an age‐matched analysis, which confirmed the absence of an association between thyroid autoimmunity and parity. Conclusion: Although we initially observed a strong association between parity and thyroid autoimmunity, after controlling for age and other variables, we were unable to identify an association.
Characterisation and outcomes of adult patients with paracetamol overdose presenting to a tertiary hospital in Singapore.

INTRODUCTION Paracetamol is the most common pharmaceutical agent implicated in toxic exposure in Singapore. This study aimed to describe the characteristics of paracetamol overdose in the adult population managed at a tertiary healthcare facility in Singapore. METHODS Medical records of adult patients hospitalised with a diagnosis of paracetamol overdose at National University Hospital, Singapore, over a three-year period from January 2011 to December 2013 were retrospectively reviewed. RESULTS A total of 177 patients had paracetamol overdose. The median age was 25 years, with a significant female predominance (71.2%). Intentional ingestion accounted for the majority (76.8%) of cases. The median dose of paracetamol ingested was 10 (interquartile range 8-15) g. Among patients who reported ingesting more than 10 g, 46.5% perceived the overdose as non-lethal. N-acetylcysteine was administered in 76.3% of patients, among whom 24.4% experienced an anaphylactoid reaction. Of the 10 (5.6%) patients who had severe hepatotoxicity, 2 (1.1%) developed acute liver failure. Most patients had resolving transaminases at discharge and none required liver transplantation. The median length of hospitalisation was three days. There were no fatalities. CONCLUSION Paracetamol overdose occurred predominantly in young adults with intentional ingestion, suggesting that preventive measures targeted at promoting public awareness may not suffice. However, the perceived lack of lethality by many patients who ingested potentially toxic amounts of paracetamol reflects a certain knowledge gap. Healthcare providers should proactively educate consumers on the proper use of paracetamol and the consequences of its overdose.
mTORC1 is necessary but mTORC2 and GSK3β are inhibitory for AKT3-induced axon regeneration in the central nervous system

Injured mature CNS axons do not regenerate in mammals. Deletion of PTEN, the negative regulator of PI3K, induces CNS axon regeneration through the activation of PI3K-mTOR signaling. We have conducted an extensive molecular dissection of the cross-regulating mechanisms in axon regeneration that involve the downstream effectors of PI3K, AKT and the two mTOR complexes (mTORC1 and mTORC2). We found that the predominant AKT isoform in CNS, AKT3, induces much more robust axon regeneration than AKT1 and that activation of mTORC1 and inhibition of GSK3β are two critical parallel pathways for AKT-induced axon regeneration. Surprisingly, phosphorylation of T308 and S473 of AKT play opposite roles in GSK3β phosphorylation and inhibition, by which mTORC2 and pAKT-S473 negatively regulate axon regeneration. Thus, our study revealed a complex neuron-intrinsic balancing mechanism involving AKT as the nodal point of PI3K, mTORC1/2 and GSK3β that coordinates both positive and negative cues to regulate adult CNS axon regeneration. DOI: http://dx.doi. org/10.7554/eLife.14908. 001
New cardiac expression of two adenosine-2A receptor isoforms in dysfunctioning minipigs

Abstract Purpose: Eight A2AR variants are reported in humans while no A2AR isoforms in pigs. The aim of this study was to evaluate potential isoforms presence in cardiac pig tissue to better define possible involvement of A2AR in the cardiovascular pathophysiology. Materials and methods: In adult male minipigs (n = 4) left ventricular dysfunction (LVD) was induced by pacing at 200 bpm in the right ventricular (RV) apex. In these animals and in sham operated pigs (C-SHAM, n = 4) cardiac tissue was collected from LV-septal wall (LV-SW)-close to pacing site-and from lateral (opposite) site (LV-OSW). A2AR specific primers, derived from Sus scrofa AY772412 sequence, were used for Real-Time PCR. The DNA was sequenced using the Sanger method. Histological analysis was also performed. Results: In LV-SW of LVD minipigs the A2AR melting curves were characterized by a sharp peak between 87 and 91 °C (short isoform, 1–94 bp) on the right of the principal peak corresponding to a long A2AR isoform (GenBank: JQ229674.1) 1–213 bp. As for C-SHAM only one peak was observed in LV-OSW region of LVD animals. The short isoform had an alternative promoter region and a specific translated protein. Histology showed in LVD-LV-SW prominent Purkinje cells compared to LV-OSW and C-SHAM. No difference in A2AR expression was observed between LVD animals and C-SHAM although a slight decrease was observed in LVD-LV-OSW. Conclusions: The presence of two different isoforms in the myocardium close to the insertion of pacing is suggestive of a differential state-specific expression of A2AR in cardiac tissue.
Discovering and Comparing Topic Hierarchies

Hierarchies have been used for organization, summarization, and access to information, yet a lingering issue is how best to construct them. In this paper, our goal is to automatically create domain specific hierarchies that can be used for browsing a document set and locating relevant documents. We examine methods of automatically generating hierarchies and evaluating them. To this end, we compare and contrast two methods of generating topic hierarchies from the text of documents: one, subsumption hierarchies, uses subsumption relations found within document sets, and the other, lexical hierarchies, utilizes frequently used words within phrases. Our evaluation shows that subsumption hierarchies divide documents into smaller groups, allowing one to find all relevant documents without looking at as many non-relevant documents. However, such hierarchies are more likely to contain no path to a relevant document.
Phase 2 studies of oral hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 for treatment of anemia in China

Abstract Background FG-4592 (roxadustat) is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (HIF-PHI) promoting coordinated erythropoiesis through the transcription factor HIF. Two Phase 2 studies were conducted in China to explore the safety and efficacy of FG-4592 (USAN name: roxadustat, CDAN name: ), a HIF-PHI, in patients with anemia of chronic kidney disease (CKD), both patients who were dialysis-dependent (DD) and patients who were not dialysis-dependent (NDD). Methods In the NDD study, 91 participants were randomized to low (1.1–1.75 mg/kg) or high (1.50–2.25 mg/kg) FG-4592 starting doses or to placebo. In the DD study, 87 were enrolled to low (1.1–1.8 mg/kg), medium (1.5–2.3 mg/kg) and high (1.7–2.3 mg/kg) starting FG-4592 doses or to continuation of epoetin alfa. In both studies, only oral iron supplementation was allowed. Results In the NDD study, hemoglobin (Hb) increase ≥1 g/dL from baseline was achieved in 80.0% of subjects in the low-dose cohort and 87.1% in the high-dose cohort, versus 23.3% in the placebo arm (P < 0.0001, both). In the DD study, 59.1%, 88.9% (P = 0.008) and 100% (P = 0.0003) of the low-, medium- and high-dose subjects maintained their Hb levels after 5- and 6-weeks versus 50% of the epoetin alfa-treated subjects. In both studies, significant reductions in cholesterol were noted in FG-4592-treated subjects, with stability or increases in serum iron, total iron-binding capacity (TIBC) and transferrin (without intravenous iron administration). In the NDD study, hepcidin levels were significantly reduced across all FG-4592-treated arms as compared with no change in the placebo arm. In the DD study, hepcidin levels were also reduced in a statistically significant dose-dependent manner in the highest dose group as compared with the epoetin alfa-treated group. Adverse events were similar for FG-4592-treated and control subjects. Conclusions FG-4592 may prove an effective alternative for managing anemia of CKD. It is currently being investigated in a pivotal global Phase 3 program.
A long-term evaluation of the stage of change approach and compensable injury outcomes – a cluster-randomised trial

Abstract This study investigated the long-term injury outcomes for workers in companies from a range of industries which had been randomly allocated to receive ergonomics interventions tailored according to the stage of change (SOC) approach or standard ergonomics advice. Differences in compensable injury outcomes between the groups were analysed using logistic regression models. Questionnaire results from face-to-face interviews to assess musculoskeletal pain and discomfort (MSPD), job satisfaction and other factors were also analysed. Although not significant at the 0.05 level, after adjusting for workgroup clustering, workers in receipt of tailored advice were 55% (OR = 0.45, 95% CI = 0.19–1.08) less likely to report a compensable injury than those in receipt of standard ergonomics advice. Workload, job satisfaction and MSPD were significantly correlated with injury outcomes. The observed outcomes support the potential value of the SOC approach, as well as highlighting the need to consider workload, job satisfaction and MSPD when planning injury prevention programmes. Practitioner Summary: This study investigated compensable injury outcomes for workers who had received ergonomics advice tailored according to the stage of change (SOC) approach compared with standard ergonomics advice. The results support the potential value of the SOC approach and highlight the need to consider workload, job satisfaction and musculoskeletal pain and discomfort when planning injury prevention interventions.
Upper bounds on the min-entropy of RO Sum, Arbiter, Feed-Forward Arbiter, and S-ArbRO PUFs

The focus and novelty of this work is the derivation of tight upper bounds on the min-entropy of several physically unclonable funcions (PUFs), i.e., Ring Oscillator Sum, Arbiter, Feed-Forward Arbiter, and S-ArbRO PUFs. This constrains their usability for the fuzzy extraction of a secret key, as an alternative to storing keys in non-volatile memory. For example, it is shown that an ideal Arbiter PUF with 64 stages cannot provide more than 197 bits of min-entropy. At Financial Cryptography 2012, Van Herrewege et al. assume that 1785 bits of min-entropy can be extracted, which renders their 128-bit key generator instantly insecure. We also derive upper bounds that comply with non-ideal PUFs, attributed to, e.g., manufacturing in silicon. As a side contribution hereby, we refute the claim that S-ArbRO PUFs are highly resistant against machine learning.
Challenging the 48-Hour Rule-Out for Central Line-Associated Bloodstream Infections in the Pediatric Intestinal Failure Population: A Retrospective Pilot Study.

INTRODUCTION While parenteral nutrition (PN) has revolutionized the management of patients with intestinal failure (IF), central line-associated bloodstream infections (CLABSIs) remain a leading cause of mortality and morbidity in this population. The objective of this study is to characterize the presentation of CLABSIs in pediatric IF and to determine the time to positivity of blood cultures. METHODS A retrospective cohort study of children with IF who presented to our institution for evaluation of a possible CLABSI from January 1, 2012, to December 31, 2012, was performed. RESULTS Sixty patients with IF were identified. There were 33 cases of CLABSI in 16 patients, with a rate of 1.5 infections per 1000 catheter days. There were no significant differences in age, growth parameters, or catheter days between patients with or without CLABSI. Fever was documented in 85% of patients with CLABSI. These patients demonstrated an increased percentage of neutrophils and higher C-reactive protein levels compared with patients without CLABSI. The mean time to culture positivity was 13.2 hours, and 97% of cultures were positive within 24 hours. CONCLUSION Our data suggest that most pediatric patients with IF who have CLABSI develop positive cultures within 24 hours, and the absence of fever and leukocytosis does not necessarily indicate the absence of infection. These findings may support clinical practice guidelines in favor of shorter hospital stay when CLABSI is suspected; however, a prospective analysis of CLABSI in this population is recommended to determine the safety and appropriate setting prior to any practice change.
Using community-based reporting of vital events to monitor child mortality: Lessons from rural Ghana

Background Reducing neonatal and child mortality is a key component of the health-related sustainable development goal (SDG), but most low and middle income countries lack data to monitor child mortality on an annual basis. We tested a mortality monitoring system based on the continuous recording of pregnancies, births and deaths by trained community-based volunteers (CBV). Methods and findings This project was implemented in 96 clusters located in three districts of the Northern Region of Ghana. Community-based volunteers (CBVs) were selected from these clusters and were trained in recording all pregnancies, births, and deaths among children under 5 in their catchment areas. Data collection lasted from January 2012 through September 2013. All CBVs transmitted tallies of recorded births and deaths to the Ghana Birth and deaths registry each month, except in one of the study districts (approximately 80% reporting). Some events were reported only several months after they had occurred. We assessed the completeness and accuracy of CBV data by comparing them to retrospective full pregnancy histories (FPH) collected during a census of the same clusters conducted in October-December 2013. We conducted all analyses separately by district, as well as for the combined sample of all districts. During the 21-month implementation period, the CBVs reported a total of 2,819 births and 137 under-five deaths. Among the latter, there were 84 infant deaths (55 neonatal deaths and 29 post-neonatal deaths). Comparison of the CBV data with FPH data suggested that CBVs significantly under-estimated child mortality: the estimated under-5 mortality rate according to CBV data was only 2/3 of the rate estimated from FPH data (95% Confidence Interval for the ratio of the two rates = 51.7 to 81.4). The discrepancies between the CBV and FPH estimates of infant and neonatal mortality were more limited, but varied significantly across districts. Conclusions In northern Ghana, a community-based data collection systems relying on volunteers did not yield accurate estimates of child mortality rates. Additional implementation research is needed to improve the timeliness, completeness and accuracy of such systems. Enhancing pregnancy monitoring, in particular, may be an essential step to improve the measurement of neonatal mortality.
Effects of CTGF Blockade on Attenuation and Reversal of Radiation-Induced Pulmonary Fibrosis

Background: Radiotherapy is a mainstay for the treatment of lung cancer that can induce pneumonitis or pulmonary fibrosis. The matricellular protein connective tissue growth factor (CTGF) is a central mediator of tissue remodeling. Methods: A radiation-induced mouse model of pulmonary fibrosis was used to determine if transient administration of a human antibody to CTGF (FG-3019) started at different times before or after 20 Gy thoracic irradiation reduced acute and chronic radiation toxicity. Mice (25 mice/group; 10 mice/group in a confirmation study) were examined by computed tomography, histology, gene expression changes, and for survival. In vitro experiments were performed to directly study the interaction of CTGF blockade and radiation. All statistical tests were two-sided. Results: Administration of FG-3019 prevented (∼50%–80%) or reversed (∼50%) lung remodeling, improved lung function, improved mouse health, and rescued mice from lethal irradiation (P < .01). Importantly, when antibody treatment was initiated at 16 weeks after thoracic irradiation, FG-3019 reversed established lung remodeling and restored lung function. CTGF blockade abrogated M2 polarized macrophage influx, normalized radiation-induced gene expression changes, and reduced myofibroblast abundance and Osteopontin expression. Conclusion: These results indicate that blocking CTGF attenuates radiation-induced pulmonary remodeling and can reverse the process after initiation. CTGF has a central role in radiation-induced fibrogenesis, and FG-3019 may benefit patients with radiation-induced pulmonary fibrosis or patients with other forms or origin of chronic fibrotic diseases.
Funduscopy in Adult Zebrafish and Its Application to Isolate Mutant Strains with Ocular Defects

Funduscopy is one of the most commonly used diagnostic tools in the ophthalmic practice, allowing for a ready assessment of pathological changes in the retinal vasculature and the outer retina. This non-invasive technique has so far been rarely used in animal model for ophthalmic diseases, albeit its potential as a screening assay in genetic screens. The zebrafish (Danio rerio) is well suited for such genetic screens for ocular alterations. Therefore we developed funduscopy in adult zebrafish and employed it as a screening tool to find alterations in the anterior segment and the fundus of the eye of genetically modified adult animals. A stereomicroscope with coaxial reflected light illumination was used to obtain fundus color images of the zebrafish. In order to find lens and retinal alterations, a pilot screen of 299 families of the F3 generation of ENU-treated adult zebrafish was carried out. Images of the fundus of the eye and the anterior segment can be rapidly obtained and be used to identify alterations in genetically modified animals. A number of putative mutants with cataracts, defects in the cornea, eye pigmentation, ocular vessels and retina were identified. This easily implemented method can also be used to obtain fundus images from rodent retinas. In summary, we present funduscopy as a valuable tool to analyse ocular abnormalities in adult zebrafish and other small animal models. A proof of principle screen identified a number of putative mutants, making funduscopy based screens in zebrafish feasible.