Miracle-dz/UniFAR-FTUs huggingface dataset:
Infusion of donor-derived CD8+ memory T cells for relapse following allogeneic hematopoietic cell transplantation.

Murine models showed that CD8+CD44hi memory T (TM) cells could eradicate malignant cells without inducing graft-versus-host disease (GVHD). We evaluated the feasibility and safety of infusing freshly isolated and purified donor-derived phenotypic CD8+ TM cells into adults with disease relapse after allogeneic hematopoietic cell transplantation (HCT). Phenotypic CD8 TM cells were isolated after unmobilized donor apheresis using a tandem immunomagnetic selection strategy of CD45RA depletion followed by CD8+ enrichment. Fifteen patients received CD8+ TM cells at escalating doses (1 × 106, 5 × 106, or 10 × 106 cells per kg). Thirteen received cytoreduction before CD8+ TM cell infusion, and 9 had active disease at the time of infusion. Mean yield and purity of the CD8+ TM infusion were 38.1% and 92.8%, respectively; >90% had CD8+ T effector memory phenotype, cytokine expression, and secretion profile. No adverse infusional events or dose-limiting toxicities occurred; GVHD developed in 1 patient (grade 2 liver). Ten patients (67%) maintained or achieved response (7 complete response, 1 partial response, 2 stable disease) for at least 3 months after infusion; 4 of the responders had active disease at the time of infusion. With a median follow-up from infusion of 328 days (range, 118-1328 days), median event-free survival and overall survival were 4.9 months (95% confidence interval [CI], 1-19.3 months) and 19.6 months (95% CI, 5.6 months to not reached), respectively. Collection and enrichment of phenotypic CD8+ TM cells is feasible, well tolerated, and associated with a low incidence of GVHD when administered as a manipulated infusion of donor lymphocytes in patients who have relapsed after HCT. This trial was registered at www.clinicaltrials. gov as #NCT01523223.
Whole-Genome Sequencing and Variant Analysis of Human Papillomavirus 16 Infections

ABSTRACT Human papillomavirus (HPV) is a strongly conserved DNA virus, high-risk types of which can cause cervical cancer in persistent infections. The most common type found in HPV-attributable cancer is HPV16, which can be subdivided into four lineages (A to D) with different carcinogenic properties. Studies have shown HPV16 sequence diversity in different geographical areas, but only limited information is available regarding HPV16 diversity within a population, especially at the whole-genome level. We analyzed HPV16 major variant diversity and conservation in persistent infections and performed a single nucleotide polymorphism (SNP) comparison between persistent and clearing infections. Materials were obtained in the Netherlands from a cohort study with longitudinal follow-up for up to 3 years. Our analysis shows a remarkably large variant diversity in the population. Whole-genome sequences were obtained for 57 persistent and 59 clearing HPV16 infections, resulting in 109 unique variants. Interestingly, persistent infections were completely conserved through time. One reinfection event was identified where the initial and follow-up samples clustered differently. Non-A1/A2 variants seemed to clear preferentially (P = 0.02). Our analysis shows that population-wide HPV16 sequence diversity is very large. In persistent infections, the HPV16 sequence was fully conserved. Sequencing can identify HPV16 reinfections, although occurrence is rare. SNP comparison identified no strongly acting effect of the viral genome affecting HPV16 infection clearance or persistence in up to 3 years of follow-up. These findings suggest the progression of an early HPV16 infection could be host related. IMPORTANCE Human papillomavirus 16 (HPV16) is the predominant type found in cervical cancer. Progression of initial infection to cervical cancer has been linked to sequence properties; however, knowledge of variants circulating in European populations, especially with longitudinal follow-up, is limited. By sequencing a number of infections with known follow-up for up to 3 years, we gained initial insights into the genetic diversity of HPV16 and the effects of the viral genome on the persistence of infections. A SNP comparison between sequences obtained from clearing and persistent infections did not identify strongly acting DNA variations responsible for these infection outcomes. In addition, we identified an HPV16 reinfection event where sequencing of initial and follow-up samples showed different HPV16 variants. Based on conventional genotyping, this infection would incorrectly be considered a persistent HPV16 infection. In the context of vaccine efficacy and monitoring studies, such infections could potentially cause reduced reported efficacy or efficiency.
Epigenetically induced ectopic expression of UNCX impairs the proliferation and differentiation of myeloid cells

We here describe a leukemogenic role of the homeobox gene UNCX, activated by epigenetic modifications in acute myeloid leukemia (AML). We found the ectopic activation of UNCX in a leukemia patient harboring a t(7;10)(p22;p14) translocation, in 22 of 61 of additional cases [a total of 23 positive patients out of 62 (37.1%)], and in 6 of 75 (8%) of AML cell lines. UNCX is embedded within a low-methylation region (canyon) and encodes for a transcription factor involved in somitogenesis and neurogenesis, with specific expression in the eye, brain, and kidney. UNCX expression turned out to be associated, and significantly correlated, with DNA methylation increase at its canyon borders based on data in our patients and in archived data of patients from The Cancer Genome Atlas. UNCX-positive and -negative patients displayed significant differences in their gene expression profiles. An enrichment of genes involved in cell proliferation and differentiation, such as MAP2K1 and CCNA1, was revealed. Similar results were obtained in UNCX-transduced CD34+ cells, associated with low proliferation and differentiation arrest. Accordingly, we showed that UNCX expression characterizes leukemia cells at their early stage of differentiation, mainly M2 and M3 subtypes carrying wild-type NPM1. We also observed that UNCX expression significantly associates with an increased frequency of acute promyelocytic leukemia with PML-RARA and AML with t(8;21)(q22;q22.1); RUNX1-RUNX1T1 classes, according to the World Health Organization disease classification. In summary, our findings suggest a novel leukemogenic role of UNCX, associated with epigenetic modifications and with impaired cell proliferation and differentiation in AML.
Assessment of Virus Interference in a Test-negative Study of Influenza Vaccine Effectiveness

Background: The observational test-negative study design is used to estimate vaccine effectiveness against influenza virus infection. An important assumption of the test-negative design is that vaccination does not affect the risk of infection with another virus. If such virus interference occurred, detection of other respiratory viruses would be more common among influenza vaccine recipients and vaccine effectiveness estimates could differ. We evaluated the potential for virus interference using data from the Influenza Incidence Surveillance Project. Methods: From 2010 to 2013, outpatients presenting to clinics in 13 US jurisdictions with acute respiratory infections were tested for influenza and other respiratory viruses. We investigated whether virus interference might affect vaccine effectiveness estimates by first evaluating the sensitivity of estimates using alternative control groups that include or exclude patients with other respiratory virus detections by age group and early/middle/late stage of influenza seasons. Second, we evaluated the association between influenza vaccination receipt and other respiratory virus detection among influenza test-negative patients. Results: Influenza was detected in 3,743/10,650 patients (35%), and overall vaccine effectiveness was 47% (95% CI: 42%, 52%). Estimates using each control group were consistent overall or when stratified by age groups, and there were no differences among early, middle, or late phase during influenza season. We found no associations between detection of other respiratory viruses and receipt of influenza vaccination. Conclusions: In this 3-year test-negative design study in an outpatient setting in the United States, we found no evidence of virus interference or impact on influenza vaccine effectiveness estimation.
Stress Relaxation Behavior of Short Pineapple Fiber Reinforced Polyethylene Composites

Stress relaxation behavior of short pineapple fiber reinforced polyethylene composites in tension has been studied with special reference to the effect of fiber loading, fiber length, chemical treatment and fiber orientation. Chemical treatments of fiber with reagents such as isocyanate, silane, alkali and peroxide were carried out to improve the interface adhesion between fiber and matrix. The effects of strain level, chemical treatments, pre-straining, and aging on the rate of relaxation have been investigated. It was found that the stress relaxation rate decreases with strain level. It was found that incorporation of fiber results in two relaxation processes. The rate of relaxation is decreased with fiber content. It is observed that chemical treatment has significant influence on the relaxation behavior. Composites containing fibers oriented longitudinally have higher relaxation rate than transversely oriented composites. Aging of samples improved the relaxation modulus due to improved interfacial adhesion at higher temperature. It has been demonstrated that the stress relaxation modulus values measured at different strains can be superimposed by a shift along the logarithmic time axis to yield master curves of modulus over an extended time period.
Spinal cord multi‐parametric magnetic resonance imaging for survival prediction in amyotrophic lateral sclerosis

Assessing survival is a critical issue in patients with amyotrophic lateral sclerosis (ALS). Neuroimaging seems to be promising in the assessment of disease severity and several studies also suggest a strong relationship between spinal cord (SC) atrophy described by magnetic resonance imaging (MRI) and disease progression. The aim of the study was to determine the predictive added value of multimodal SC MRI on survival.
Investigation of photoplethysmography and arterial blood oxygen saturation from the ear-canal and the finger under conditions of artificially induced hypothermia

Pulse oximeters relay on the technique of photoplethysmography (PPG) to estimate arterial oxygen saturation (SpO2). In conditions of poor peripheral perfusion such as hypotension, hypothermia, and vasoconstriction, pulse oximeters become inaccurate or provide no reading. This is due to the poor quality of the PPG signals detected at that instance. In order to overcome this problem, the ear canal has been proposed as a alternative measurement site for measuring reliable SpO2. Hence, an ear canal PPG sensor was developed along with a PPG processing system. The performance of the sensor was evaluated by measuring the red and infrared PPGs and SpO2 from 10 healthy volunteers undergoing artificially induced hypothermia. The results from the ear canal sensor were compared with simultaneously acquired results from the finger. Hypothermia was induced by exposing the volunteers to cold temperatures of 10 ± 1°C. The results acquired suggest that the ear canal pulse oximeter endures more in estimating SpO2 values accurately when compared with the more common finger pulse oximeter.
Comparison of Corneal Endothelial Cell Loss Between Two Femtosecond Laser Platforms and Standard Phacoemulsification.

PURPOSE To analyze and compare the changes in endothelial cell density (ECD) and cumulative dissipated energy (CDE) in patients having cataract surgery with two different femtosecond laser platforms and standard phacoemulsification. METHODS This prospective non-randomized comparative study included patients scheduled to undergo cataract extraction using femtosecond laser-assisted cataract surgery (FLACS) (60 eyes) or standard phacoemulsification (60 eyes) between September 2013 and March 2016. The main outcome measures were CDE and percentage of endothelial cell loss. Comparative analysis of CDE and percentage of endothelial cell loss between the two phacoemulsification platforms with respect to conventional and FLACS techniques was performed. RESULTS The CDE and the 1-month mean percentage of endothelial cell loss was 6.11 ± 3.52 and 9.06% ± 8.77% in the standard phacoemulsification group and 4.65 ± 3.61 and 6.00% ± 8.02% in the FLACS group, respectively (P = .039). In the subgroup analysis based on cataract grading, the CDE was significantly less in the FLACS group compared to the standard phacoemulsification group in both the early and advanced cataract group (P = .002). The percent decrease in endothelial cell loss was statistically lower in the FLACS group when compared to the standard phacoemulsification group in the advanced cataract subgroup (P = .02). CONCLUSIONS FLACS pretreatment resulted in a decrease in CDE and less endothelial cell loss when compared to standard phacoemulsification. The decrease in endothelial cell loss was more prominent in the denser cataract group; thus, FLACS may be most beneficial in those cases. There was no significant difference in results between the two laser platforms. [J Refract Surg. 2017;33(10):708-712. ].
Differential Interaction Kinetics of a Bipolar Structure-Specific Endonuclease with DNA Flaps Revealed by Single-Molecule Imaging

As DNA repair enzymes are essential for preserving genome integrity, understanding their substrate interaction dynamics and the regulation of their catalytic mechanisms is crucial. Using single-molecule imaging, we investigated the association and dissociation kinetics of the bipolar endonuclease NucS from Pyrococcus abyssi (Pab) on 5′ and 3′-flap structures under various experimental conditions. We show that association of the PabNucS with ssDNA flaps is largely controlled by diffusion in the NucS-DNA energy landscape and does not require a free 5′ or 3′ extremity. On the other hand, NucS dissociation is independent of the flap length and thus independent of sliding on the single-stranded portion of the flapped DNA substrates. Our kinetic measurements have revealed previously unnoticed asymmetry in dissociation kinetics from these substrates that is markedly modulated by the replication clamp PCNA. We propose that the replication clamp PCNA enhances the cleavage specificity of NucS proteins by accelerating NucS loading at the ssDNA/dsDNA junctions and by minimizing the nuclease interaction time with its DNA substrate. Our data are also consistent with marked reorganization of ssDNA and nuclease domains occurring during NucS catalysis, and indicate that NucS binds its substrate directly at the ssDNA-dsDNA junction and then threads the ssDNA extremity into the catalytic site. The powerful techniques used here for probing the dynamics of DNA-enzyme binding at the single-molecule have provided new insight regarding substrate specificity of NucS nucleases.
Determinants of poor cognitive function using A-IQCODE among Lebanese older adults: a cross-sectional study

ABSTRACT Introduction: Dementia characterized by gradual cognitive decline is an increasing public health problem due to population ageing. This study aims at assessing the prevalence and determinants of cognitive decline among Lebanese older adults. Methods: Secondary analysis of data from a cross-sectional sample of 502 elders from two Lebanese governorates was conducted. Cognitive decline was assessed using the Arabic Version of 16-item Informant Questionnaire on Cognitive Decline for the older adults (A-IQCODE 16). A multivariable logistic regression model assessed the associations of socio-demographic, clinical and behavioral factors with the presence of cognitive decline. Results: Almost one of six Lebanese older adults (14.8%) scored below 3.34. Higher odds of cognitive decline were associated with higher age, being female, having heart disease and suffering from depression. Pack-years of cigarette smoking showed a protective effect and this relationship seems to be only statistically significant among older adults aged more than 75 years. Conclusions: Screening programs of cardiovascular risk factors and early detection of depression are ‘best buy’ public health interventions that could prevent cognitive decline among Lebanese older adults. Differential survival bias seems the reasonable explanation for the protective effect of smoking that is not the common finding from the literature.
Structure of human IFIT1 with capped RNA reveals adaptable mRNA binding and mechanisms for sensing N1 and N2 ribose 2′-O methylations

Significance IFIT1 is an antiviral effector of host innate-immunity that selectively recognizes the 5′-end of viral mRNAs, which are often capped to mimic host mRNA, and blocks their translation. Our X-ray structural analysis reveals that the cap and four additional nucleotides are encircled by IFIT1 through a central tunnel in an adaptable manner, which gives it the flexibility required to defend against many different viruses, and to deter their ability to rapidly evolve. Host mRNA, normally ribose methylated at the first and second nucleotides following the cap, avoids IFIT1 recognition through tight complementary interfaces at these positions. This study uncovers the molecular basis for how IFIT1 selectively recognizes viral mRNAs and will help guide development of viral vaccines and mRNA therapeutics. IFIT1 (IFN-induced protein with tetratricopeptide repeats-1) is an effector of the host innate immune antiviral response that prevents propagation of virus infection by selectively inhibiting translation of viral mRNA. It relies on its ability to compete with the translation initiation factor eIF4F to specifically recognize foreign capped mRNAs, while remaining inactive against host mRNAs marked by ribose 2′-O methylation at the first cap-proximal nucleotide (N1). We report here several crystal structures of RNA-bound human IFIT1, including a 1.6-Å complex with capped RNA. IFIT1 forms a water-filled, positively charged RNA-binding tunnel with a separate hydrophobic extension that unexpectedly engages the cap in multiple conformations (syn and anti) giving rise to a relatively plastic and nonspecific mode of binding, in stark contrast to eIF4E. Cap-proximal nucleotides encircled by the tunnel provide affinity to compete with eIF4F while allowing IFIT1 to select against N1 methylated mRNA. Gel-shift binding assays confirm that N1 methylation interferes with IFIT1 binding, but in an RNA-dependent manner, whereas translation assays reveal that N1 methylation alone is not sufficient to prevent mRNA recognition at high IFIT1 concentrations. Structural and functional analysis show that 2′-O methylation at N2, another abundant mRNA modification, is also detrimental for RNA binding, thus revealing a potentially synergistic role for it in self- versus nonself-mRNA discernment. Finally, structure-guided mutational analysis confirms the importance of RNA binding for IFIT1 restriction of a human coronavirus mutant lacking viral N1 methylation. Our structural and biochemical analysis sheds new light on the molecular basis for IFIT1 translational inhibition of capped viral RNA.
Outage performance of multiuser cooperative wireless networks with cochannel interferers

The outage behavior of a dual-hop multi-source multi-relay cooperative communication network is investigated. With the presence of multiple cochannel interferers at both the relays and destination, we propose a signal-to-interference-plus-noise ratio based scheme for the combined use of cooperative diversity and multiuser diversity. Firstly, the best source node with the highest direct-link signal-to-interference-plus-noise ratio is selected to transmit. Then, according to proactive decode-and-forward relaying protocol, the selected best relay forwards the source messages. In this context, exact outage probability is derived for selection combining over Rayleigh fading channels. Particularly, we consider the dependence among the received signal-to-interference-plus-noise ratios at the destination caused by multiple cochannel interferers. Finally, simulated results are provide to verify the theoretical analysis. It is shown that the diversity gain cannot be obtained for multiuser cooperative wireless networks with cochannel interferers.
T2 Mapping for Noninvasive Assessment of Interstitial Edema in Acute Cardiac Allograft Rejection in a Mouse Model of Heterotopic Heart Transplantation

Objectives Heart transplantation (HTX) in mice is used to characterize gene-deficient mice and to test new treatment strategies. The purpose was to establish noninvasive magnetic resonance imaging techniques in mice to monitor pathophysiological changes of the allograft during rejection. Materials and Methods Magnetic resonance imaging was performed at baseline and days 1 and 6 after isogenic (n = 10, C57BL/6) and allogenic (n = 12, C57BL/6 to BALB/c) heterotopic HTX on a 7 T small animal scanner. Respiratory- and electrocardiogram-gated multislice multi-echo spin echo sequences were acquired, and parameter maps of T2 relaxation time were generated. T2 times in septal, anterior, lateral, and posterior myocardial segments as well as global T2 times were calculated and compared between groups. At day 7 animals were sacrificed and graft pathology was assessed by semiquantitative regional analysis and correlated with magnetic resonance imaging results. Results Myocardial T2 relaxation time was significantly increased in allogenic (33.4 ± 0.1 ms) and isogenic cardiac grafts (31.8 ± 1.8 ms) on day 1 after HTX compared with healthy donor hearts at baseline (23.1 ± 0.3 ms, P < 0.001). Until day 6 after HTX, myocardial T2 further increased markedly in allografts but not in isografts (43.4 ± 1.9 vs 31.2 ± 1.1 ms, P < 0.001). Mean segmental T2 values as well as mean global T2 values in allogenic compared with isogenic cardiac grafts on day 6 were significantly higher (P < 0.01). Histologically, isogenic grafts were almost normal besides small focal leukocyte infiltrates and signs of interstitial edema, most likely due to ischemia reperfusion injury (histological sum score, 0.9 ± 0.4). In allogenic HTX, histology revealed severe inflammation and tissue edema representing allograft rejection with increased histological scores (5.3 ± 0.7, P < 0.001). Higher histological scores of rejection were significantly associated with increased T2 times on a segmental and a global level. Conclusions We could show that T2 mapping is a suitable noninvasive imaging method to monitor global and regional HTX pathologies in experimental heart transplantation in mice. Progressive prolongation of T2 time was significantly associated with pathological signs of rejection.
Filterbank-energy estimation using mixture and Markov models for recognition of noisy speech

An estimation algorithm for noise robust speech recognition, the minimum mean log spectral distance (MMLSD), is presented. The estimation is matched to the recognizer by seeking to minimize the average distortion as measured by a Euclidean distance between filterbank log-energy vectors, approximating the weighted-cepstral distance used by the recognizer. The estimation is computed using a clean speech spectral probability distribution, estimated from a database, and a stationary, ARMA model for the noise. When trained on clean speech and tested with additive white noise at 10-dB SNR, the recognition accuracy with the MMLSD algorithm is comparable to that achieved with training the recognizer at the same constant 10-dB SNR. The algorithm is also highly efficient with a quasi-stationary environmental noise, recorded with a desktop microphone, and requires almost no tuning to differences between this noise and the computer-generated white noise. >