Miracle-dz/UniFAR-FTUs huggingface dataset:
Early Detection of Pancreatic Cancer

Abstract A diagnosis of pancreatic cancer is devastating owing to its poor prognosis, with a 5-year survival rate of only 9%. Currently, most individuals are diagnosed at a late stage when treatment options are limited. Early detection of pancreatic cancer provides the greatest hope for making substantial improvements in survival. The Kenner Family Research Fund in partnership with the American Pancreatic Association has sponsored a series of fora to stimulate discussion and collaboration on early detection of pancreatic cancer. At the first forum in 2014, “Early Detection of Sporadic Pancreatic Cancer Summit Conference,” a strategic plan was set forth by an international group of interdisciplinary scientific representatives and subsequently The Strategic Map for Innovation was generated. The current conference report is the third forum in the series, “Early Detection of Pancreatic Cancer: The Role of Industry in the Development of Biomarkers,” which was held in Boston, Massachusetts, on October 27, 2016. This report provides an overview of examples of innovative initiatives by industry and confirms the critical need for collaboration among industry, government, research institutions, and advocacy groups in order to make pancreatic cancer more easily detectable in its earlier stages, when it is more treatable.
Comparison of Mode Switched Controllers for a Pseudo Continuous Current Mode Boost Converter

The pseudo continuous current mode (PCCM) operation of a boost converter can be treated as an intermediate between the continuous current mode (CCM) and discontinuous current mode (DCM) operation. The advantages in DCM operation and CCM operation can be effectively compromised to get this intermediate operation. In addition, the control flexibility and stability in DCM operation of a boost converter can be attributed to the PCCM operation as far as the control design is concerned. In this paper, three types of mode switched control designs based on the hybrid automaton model, namely, system theoretical design, circuit theoretical design and energy based design for a PCCM boost converter are analyzed and compared. Analysis, control design and simulation results are presented.
An alternative way – tyrosine kinase inhibitor (TKI) de-escalation – to discontinue TKIs in order to achieve treatment-free remission

Since the introduction of imatinib ‘the first tyrosine kinase inhibitor (TKI)’ that targets BCR-ABL1, chronic myeloid leukemia (CML) has become a controlled malignancy at which patients with optimal responses would expect similar life expectancies of normal population [1]. Second-generation TKIs (2GTKIs; dasatinib, nilotinib, and bosutinib) and thirdgeneration TKI (ponatinib) were introduced as a salvage treatment option in patients with imatinib resistance or inadequate tolerability as well as a frontline alternative to imatinib [2,3]. Following a long-term TKI therapy, substantial portion of CML patients will achieve major molecular response (MMR); defined as a BCR-ABL1/ABL1 transcript ratio of ≤0.1%, also called MR [molecular response of three logs below an arbitrary standard baseline] expressed on international scale. A deep molecular response (DMR) is also defined as either MR (BCR-ABL1/ABL1 transcript ratio ≤0.01%) or MR (BCR-ABL1/ABL1 transcript ratio ≤0.0032%) [4]. Final update of the DASISION trial showed higher MR rates within 5 years among patients treated with dasatinib (43%) in comparison to imatinib-treated group (33%), determining the favorable outcomes of dasatinib as first-line treatment for CML [5]. Similarly, patients treated with nilotinib in ENESTnd trial had significant higher MR rates (300 mg twice daily, 54%; 400 mg twice daily, 52%) in comparison to imatinib group (31%) at 5 years of follow-up [6]. Although with a shorter follow-up period, BFORE trial indicated significantly higher rates of MR with bosutinib versus imatinib (8.1% vs. 3.3%) at 12 months [7].
Newcastle Disease Virus Isolation and Its Prevalence in Uganda Poultry Farms

The present research work was carried out to isolate and identify Newcastle disease virus (NDV) by using haemagglutination inhibition (HI) test and HA-HI virus isolation, embryonated eggs (EE) and chicken embryo fibroblasts (CEF). A total of 95 clinical (blood, tracheal and cloacal swabs) and post-mortem (brain, lung, colon and spleen) samples were collected from chickens of field outbreaks of suspected Newcastle disease virus (NDV). The HI and HA-HI were employed to detect NDV in tissue homogenates of all the clinical and post-mortem samples as well as laboratory samples (AF and ICF). Among the four different types of post-mortem samples, virus isolation rate was found to be low in body organs. In CEF cell culture system, the rate of virus isolation from all the aforesaid samples was found to be at 100% with the exception of serum samples; while in tracheal and cloacal swabs, it was at 90%; while in serum, it was at 10%, in all clinical cases. The isolation rate of NDV was higher in CEF culture system (66.7%) compared to that of avian embryos (33.3%). Samples were inoculated and the allantoic fluid (AF) of the dead embryos and the infected culture fluid (ICF) of the CEF were harvested at 24 to 96 hours of the post-infection, respectively, which revealed that the virulent strain of NDV is highly prevalent in the region. The prevalence of NDV was established at 1.1%, 2.1% and 4.2% using HA-HI, EE, and CEF methods. Rapid detection and identification of the virus are crucial for the effective control of the disease as conventional diagnostic methods such as virus isolation on embryonated eggs followed by serological identification in haemagglutination-inhibition test are laborious and time-consuming. The speed of the diagnosis can be considerably increased by using methods based on molecular biology, e.g. reverse transcription—polymerase chain reaction. However, the genetic variability of APMV-1 isolates should be considered carefully as the potential cause for false negative results of genetic-based laboratory tests.
Impact of non-invasive brain stimulation on transcallosal modulation in mild traumatic brain injury: a multimodal pilot investigation

ABSTRACT Background: We combined performance on working memory (WM) tasks with diffusion (dMRI) and functional (fMRI) magnetic resonance imaging in young adults who had suffered a concussion to better understand the inter-hemispheric effects of unilateral repetitive transcranial magnetic stimulation (rTMS). Methods: The article is presenting pilot data on 8 symptomatic patients with persistent post-concussion symptoms for over 6 months. They received 20 sessions of rTMS over the left dorsolateral prefrontal cortex. Fractional anisotropy and mean diffusivity of the corpus callosum (CC) and fMRI measurement of blood-oxygen-level dependent signal changes during WM tasks were carried out before and after rTMS stimulation. Results: After participants had completed the rTMS sessions, we observed three main results: (1) bilateralization of activation within the WM network; (2) shift from transcallosal inhibition to transcallosal activation of the right-sided WM network via the anterior callosal fibres; and (3) shift from transcallosal activation to transcallosal inhibition of the right-sided WM network via the posterior parts of the CC. More nuanced patterns of transcallosal mediation in the region of the right-sided WM network were observed via the medial part of the CC. Conclusion: Our preliminary results encourage trends of further research supporting the use of rTMS to restore inter-hemispheric balance within the bilateral WM network in young adults with a history of concussion.
Early metabolic response assessment of breast cancer liver metastases: 4-week posttreatment FDG PET predicts survival after 90Y microsphere radioembolization

Abstract Aim To evaluate the feasibility of early metabolic response assessment with 18F-FDG PET/CT in patients with breast cancer liver metastases 4 weeks after radioembolization with Yttrium-90 labeled microspheres. Methods 25 patients (mean age 58y, range 40–74) with advanced stage liver metastases of breast cancer were treated with 1.9 ± 0.4 GBq of 90Y-microspheres in the salvage setting and underwent 18F-FDG PET/CT at baseline and 4 weeks post-radioembolization. 14 patients (56 %) had an excessive hepatic tumor burden (> 50 % of total liver volume), 21 patients (84 %) had extrahepatic disease. Liver lesions with the highest SUVmax were selected as target lesions and a cut-off was set at 50 % reduction to separate responders from non-responders. The predictive impact of metabolic response on overall survival (OS) was investigated along with other prognostic factors. Results The median OS in this highly advanced metastatic cohort was 7 months (95 % CI, 5–9). All patients had a reduction in SUVmax (mean ΔSUVmax: –49 ± 26 %) at 4 weeks post-treatment. Patients with > 50 % SUVmax reduction survived longer (median OS 13 mo, 95 % CI 8–18) than the remaining patients (median OS 4 mo, 95 % CI 2–6; p = 0.001). From all investigated baseline factors including age, performance status, and presence of extra-hepatic disease, only the hepatic tumor burden had a significant impact on OS (p = 0.02). Conclusions This is the first preliminary evidence in breast cancer that early post-radioembolization molecular response assessment of treated liver metastases – as early as 4 weeks posttreatment – may predict survival. If confirmed by larger series, FDG PET/CT could be considered for early response-adapted treatment modifications.
Stochastic imputation for integrated transcriptome association analysis of a longitudinally measured trait

The mechanistic pathways linking genetic polymorphisms and complex disease traits remain largely uncharacterized. At the same time, expansive new transcriptome data resources offer unprecedented opportunity to unravel the mechanistic underpinnings of complex disease associations. Two-stage strategies involving conditioning on a single, penalized regression imputation for transcriptome association analysis have been described for cross-sectional traits. In this manuscript, we propose an alternative two-stage approach based on stochastic regression imputation that additionally incorporates error in the predictive model. Application of a bootstrap procedure offers flexibility when a closed form predictive distribution is not available. The two-stage strategy is also generalized to longitudinally measured traits, using a linear mixed effects modeling framework and a composite test statistic to evaluate whether the genetic component of gene-level expression modifies the biomarker trajectory over time. Simulations studies are performed to evaluate relative performance with respect to type-1 error rates, coverage, estimation error, and power under a range of conditions. A case study is presented to investigate the association between whole blood expression for each of five inflammasome genes with inflammatory response over time after endotoxin challenge.
Protein contact prediction using metagenome sequence data and residual neural networks

MOTIVATION Almost all protein residue contact prediction methods rely on the availability of deep multiple sequence alignments (MSAs). However, many proteins from the poorly populated families do not have sufficient number of homologs in the conventional UniProt database. Here we aim to solve this issue by exploring the rich sequence data from the metagenome sequencing projects. RESULTS Based on the improved MSA constructed from the metagenome sequence data, we developed MapPred, a new deep learning-based contact prediction method. MapPred consists of two component methods, DeepMSA and DeepMeta, both trained with the residual neural networks. DeepMSA was inspired by the recent method DeepCov, which was trained on 441 matrices of covariance features. By considering the symmetry of contact map, we reduced the number of matrices to 231, which makes the training more efficient in DeepMSA. Experiments show that DeepMSA outperforms DeepCov by 10-13% in precision. DeepMeta works by combining predicted contacts and other sequence profile features. Experiments on three benchmark datasets suggest that the contribution from the metagenome sequence data is significant with P-values less than 4.04E-17. MapPred is shown to be complementary and comparable the state-of-the-art methods. The success of MapPred is attributed to three factors: the deeper MSA from the metagenome sequence data, improved feature design in DeepMSA, and optimized training by the residual neural networks. AVAILABILITY AND IMPLEMENTATION http://yanglab.nankai. edu.cn/mappred/. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Zostavax vaccine effectiveness among US elderly using real‐world evidence: Addressing unmeasured confounders by using multiple imputation after linking beneficiary surveys with Medicare claims

Medicare claims can provide real‐world evidence (RWE) to support the Food and Drug Administration's ability to conduct postapproval studies to validate products' safety and effectiveness. However, Medicare claims do not contain comprehensive information on some important sources of bias. Thus, we piloted an approach using the Medicare Current Beneficiary Survey (MCBS), a nationally representative survey of the Medicare population, to (a) assess cohort balance with respect to unmeasured confounders in a herpes zoster vaccine (HZV) effectiveness claims‐based study and (b) augment Medicare claims with MCBS data to include unmeasured covariates.
Using High-Fidelity Simulation to Evaluate Clinical Skills in Prelicensure Nursing Students

Abstract A prelicensure associate degree nursing program identified the need to formally validate clinical skills and decision-making within nursing students across the program and implemented a process using high-fidelity simulation. The simulated experiences provided an opportunity for both formative and summative evaluation while also affording an opportunity to level student performance across the program. Faculty reported improved consistency in their expectations of student performance within each nursing course, and students reported improved confidence in their clinical practice skills.
Temperature and precipitation extremes in century‐long gridded observations, reanalyses, and atmospheric model simulations

Knowledge about long‐term changes in climate extremes is vital to better understand multidecadal climate variability and long‐term changes and to place today's extreme events in a historical context. While global changes in temperature and precipitation extremes since the midtwentieth century are well studied, knowledge about century‐scale changes is limited. This paper analyses a range of largely independent observations‐based data sets covering 1901–2010 for long‐term changes and interannual variability in daily scale temperature and precipitation extremes. We compare across data sets for consistency to ascertain our confidence in century‐scale changes in extremes. We find consistent warming trends in temperature extremes globally and in most land areas over the past century. For precipitation extremes we find global tendencies toward more intense rainfall throughout much of the twentieth century; however, local changes are spatially more variable. While global time series of the different data sets agree well after about 1950, they often show different changes during the first half of the twentieth century. In regions with good observational coverage, gridded observations and reanalyses agree well throughout the entire past century. Simulations with an atmospheric model suggest that ocean temperatures and sea ice may explain up to about 50% of interannual variability in the global average of temperature extremes, and about 15% in the global average of moderate precipitation extremes, but local correlations are mostly significant only in low latitudes.
Draft Genome Sequence of Haemophilus haemolyticus Strain 16/010 O, Isolated from a Sputum Sample from a Cystic Fibrosis Patient

Haemophilus haemolyticus is considered a commensal of the respiratory tract that can cause opportunistic infections. It is closely related to Haemophilus influenzae. ABSTRACT Haemophilus haemolyticus is considered a commensal of the respiratory tract that can cause opportunistic infections. It is closely related to Haemophilus influenzae. Here, we report the genome sequence of H. haemolyticus 16/010 O, which was isolated from sputum from a cystic fibrosis patient.
Critical evaluation of the DNA-methylation markers ABCG1 and SREBF1 for Type 2 diabetes stratification.

Aim: Validation of epigenome-wide association studies is sparse. Therefore, we evaluated the methylation markers cg06500161 (ABCG1) and cg11024682 (SREBF1) as classifiers for diabetes stratification. Patients & methods: DNA methylation was measured in blood (n = 167), liver (n = 99) and visceral adipose tissue (n = 99) of nondiabetic or Type 2 diabetic subjects by bisulfite pyrosequencing. Results: DNA methylation at cg11024682 in blood and liver correlated with BMI. Methylation at cg06500161 was influenced by the adjacent SNP rs9982016. Insulin-resistant and sensitive subjects could be stratified by DNA methylation status in blood or visceral adipose tissue. Conclusion: DNA methylation at both loci in blood presents a promising approach for risk group stratification and could be valuable for personalized Type 2 diabetes risk prediction in the future.
Effects of concurrent exercise training on muscle dysfunction and systemic oxidative stress in older people with COPD

Oxidative stress is associated with disease severity and limb muscle dysfunction in COPD. Our main goal was to assess the effects of exercise training on systemic oxidative stress and limb muscle dysfunction in older people with COPD. Twenty‐nine outpatients with COPD (66‐90 years) were randomly assigned to a 12‐week exercise training (ET; high‐intensity interval training (HIIT) plus power training) or a control (CT; usual care) group. We evaluated mid‐thigh muscle cross‐sectional area (CSA; computed tomography); vastus lateralis (VL) muscle thickness, pennation angle, and fascicle length (ultrasonography); peak VO2 uptake (VO2peak) and work rate (Wpeak) (incremental cardiopulmonary exercise test); rate of force development (RFD); maximal muscle power (Pmax; force‐velocity testing); systemic oxidative stress (plasma protein carbonylation); and physical performance and quality of life. ET subjects experienced changes in mid‐thigh muscle CSA (+4%), VL muscle thickness (+11%) and pennation angle (+19%), VO2peak (+14%), Wpeak (+37%), RFD (+32% to 65%), Pmax (+38% to 51%), sit‐to‐stand time (−24%), and self‐reported health status (+20%) (all P < 0.05). No changes were noted in the CT group (P > 0.05). Protein carbonylation decreased among ET subjects (−27%; P < 0.05), but not in the CT group (P > 0.05). Changes in protein carbonylation were associated with changes in muscle size and pennation angle (r = −0.44 to −0.57), exercise capacity (r = −0.46), muscle strength (r = −0.45), and sit‐to‐stand performance (r = 0.60) (all P < 0.05). The combination of HIIT and power training improved systemic oxidative stress and limb muscle dysfunction in older people with COPD. Changes in oxidative stress were associated with exercise‐induced structural and functional adaptations.
miR-27a suppresses TLR4-induced renal ischemia-reperfusion injury

Ischemia reperfusion injury (IRI) is one of the primary causes of acute renal injury and even acute renal failure. An increasing body of evidence has indicated that the aberrant expression of microRNAs (miRNA/miR) is closely associated with the progression of IRI. In the process of renal IRI, inflammatory reactions, cell adhesion and the death of renal tubular epithelial cells serve important roles. The present study investigated the expression of renal miRNAs following renal IRI in an attempt to identify the miRNAs that exert pivotal functions in renal IRI. The present study revealed that miR-27a, which was downregulated in IRI, and the 3′-untranslated region (UTR) of Toll-like receptor 4 (TLR4) have associated binding sites. The levels of TLR4, miR-27a and specific associated proteins in the renal tissues of gestational rats were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, immunohistochemistry and western blotting. The associations between miR-27a and TLR4 were analyzed, and the regulatory effect of miR-27a on TLR4 was detected via a luciferase reporter gene assay, western blotting and RT-qPCR in vivo and in vitro. In addition, the present study demonstrated that miR-27a suppressed the expression of TLR4 by binding to the 3′UTR of TLR4. The overexpression of miR-27a downregulated the expression of TLR4, which in turn inhibited the inflammation, cell adhesion and cell death in IRI. Therefore, miR-27a inhibited inflammation in IRI by decreasing the expression of TLR4.
Systemic Interferon-γ Increases MHC Class I Expression and T-cell Infiltration in Cold Tumors: Results of a Phase 0 Clinical Trial

Interferon-γ, an FDA approved drug, can drive inflammation of non-inflamed cancers, potentially facilitating immunotherapy with PD-1 inhibitors. A multicenter trial sponsored by the Cancer Immunotherapy Trials Network is based on these results. Interferon-γ (IFNγ) has been studied as a cancer treatment with limited evidence of clinical benefit. However, it could play a role in cancer immunotherapy combination treatments. Despite high expression of immunogenic cancer–testis antigens, synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCL) have a cold tumor microenvironment (TME), with few infiltrating T cells and low expression of major histocompatibility complex class I (MHC-I). We hypothesized that IFNγ treatment could drive inflammation in a cold TME, facilitating further immunotherapy. We conducted a phase 0 clinical trial treating 8 SS or MRCL patients with weekly systemic IFNγ. We performed pre- and posttreatment biopsies. IFNγ changed the SS and MRCL TME, inducing tumor-surface MHC-I expression and significant T-cell infiltration (P < 0.05). Gene-expression analysis suggested increased tumor antigen presentation and less exhausted phenotypes of the tumor-infiltrating T cells. Newly emergent antigen-specific humoral and/or T-cell responses were found in 3 of 7 evaluable patients. However, increased expression of PD-L1 was observed on tumor-infiltrating myeloid cells and in some cases tumor cells. These findings suggest that systemic IFNγ used to convert SS and MRCL into “hot” tumors will work in concert with anti–PD-1 therapy to provide patient benefit.