Miracle-dz/UniFAR-FTUs huggingface dataset:
Pneumonia and Renal Replacement Therapy Are Risk Factors for Ceftazidime-Avibactam Treatment Failures and Resistance among Patients with Carbapenem-Resistant Enterobacteriaceae Infections

ABSTRACT Ceftazidime-avibactam was used to treat 77 patients with carbapenem-resistant Enterobacteriaceae (CRE) infections at our center. Thirty- and 90-day survival rates were 81% and 69%, respectively; these rates were higher than those predicted by SAPS II and SOFA scores at the onset of infection. Clinical success was achieved for 55% of patients but differed by the site of infection. Success rates were lowest for pneumonia (36%) and higher for bacteremia (75%) and urinary tract infections (88%). By multivariate analysis, pneumonia (P = 0.045) and receipt of renal replacement therapy (RRT) (P = 0.046) were associated with clinical failure. Microbiologic failures occurred in 32% of patients and occurred more commonly among patients infected with KPC-3-producing CRE than among those infected with KPC-2-producing CRE (P = 0.002). Pneumonia was an independent predictor of microbiologic failure (P = 0.007). Ceftazidime-avibactam resistance emerged in 10% of patients, including 14% of those infected with Klebsiella pneumoniae and 32% of those with microbiologic failure. RRT was an independent predictor of the development of resistance (P = 0.009). Resistance was identified exclusively among K. pneumoniae bacteria harboring variant KPC-3 enzymes. Upon phylogenetic analysis of whole-genome sequences, resistant isolates from 87.5% (7/8) of patients clustered within a previously defined sequence type 258 (ST258) clade II sublineage; resistant isolates from one patient clustered independently from other ST258 clade II isolates. In conclusion, our report offers new insights into the utility and limitations of ceftazidime-avibactam across CRE infection types. Immediate priorities are to identify ceftazidime-avibactam dosing and therapeutic regimens that improve on the poor outcomes among patients with pneumonia and those receiving RRT.
PLK1 (polo like kinase 1) inhibits MTOR complex 1 and promotes autophagy

ABSTRACT Mechanistic target of rapamycin complex 1 (MTORC1) and polo like kinase 1 (PLK1) are major drivers of cancer cell growth and proliferation, and inhibitors of both protein kinases are currently being investigated in clinical studies. To date, MTORC1′s and PLK1′s functions are mostly studied separately, and reports on their mutual crosstalk are scarce. Here, we identify PLK1 as a physical MTORC1 interactor in human cancer cells. PLK1 inhibition enhances MTORC1 activity under nutrient sufficiency and in starved cells, and PLK1 directly phosphorylates the MTORC1 component RPTOR/RAPTOR in vitro. PLK1 and MTORC1 reside together at lysosomes, the subcellular site where MTORC1 is active. Consistent with an inhibitory role of PLK1 toward MTORC1, PLK1 overexpression inhibits lysosomal association of the PLK1-MTORC1 complex, whereas PLK1 inhibition promotes lysosomal localization of MTOR. PLK1-MTORC1 binding is enhanced by amino acid starvation, a condition known to increase autophagy. MTORC1 inhibition is an important step in autophagy activation. Consistently, PLK1 inhibition mitigates autophagy in cancer cells both under nutrient starvation and sufficiency, and a role of PLK1 in autophagy is also observed in the invertebrate model organism Caenorhabditis elegans. In summary, PLK1 inhibits MTORC1 and thereby positively contributes to autophagy. Since autophagy is increasingly recognized to contribute to tumor cell survival and growth, we propose that cautious monitoring of MTORC1 and autophagy readouts in clinical trials with PLK1 inhibitors is needed to develop strategies for optimized (combinatorial) cancer therapies targeting MTORC1, PLK1, and autophagy.
Distributed Optimization of Media Flows in Peer-to-Peer Overlay Networks

We consider the problem of rate-distortion (RD) optimized media streaming in unstructured peer-to-peer (P2P) overlay networks. We formulate the aforementioned problem as a distributed rate allocation problem, and we solve it by applying classical decomposition techniques so that the network-wide utility of the media distortion is minimized. Information exchange between the peers is employed to ensure updates on the price of the locally calculated rate allocation. Media packets are also piggybacked with RD preambles that contain information regarding their impact on the decoder distortion and their size. The benefit of the aforementioned approach is that peers can convert the calculated optimal rate allocation into simple forwarding or dropping actions allowing thus a lightweight implementation. Our simulation results indicate that significant quality benefits can be achieved when the precise RD characteristics of a media description are taken into account by the streaming algorithm.
Synthesis and Characterization of SiO2-Carbon Nanotube Hybrides Using a Sol-Gel Method

This work is focused on synthesis of SiO2- CNT hybrides via sol-gel method. Homogeneous distribution of carbon nanotubes within silicon matrix was obtained by mixing the functionalized carbon nanotube (CNTCOOH) with active silicic acid followed by titration to the solution of sodium silicate (Na2SiO3) under the average temperature condition of 80? C. Different ratios of multi-walled carbon nanotubes and various concentrations of colloidal silica were used for synthesis of SiO2-CNT. Powder X-Ray Diffraction (XRD) and Scanning Electron Microscopy (SEM) used for studying the structure and morphological characteristics of the synthesized SiO2-CNT hybrids. The results showed that the various morphologies of SiO2-CNTs are obtained with different ratio of precursors. The SEM images indicated the formation of uniform nanoparticles, nanowires and nanotube structures in various samples. In addition, the hydrogen storage capacity and thermal conductivity of SiO2-CNT hybrides were determined and presented in this article. Also total pore volume and BET surface area were calculated for these composites.
Aurora kinase A interacts with H-Ras and potentiates Ras-MAPK signaling

In cancer, upregulated Ras promotes cellular transformation and proliferation in part through activation of oncogenic Ras-MAPK signaling. While directly inhibiting Ras has proven challenging, new insights into Ras regulation through protein-protein interactions may offer unique opportunities for therapeutic intervention. Here we report the identification and validation of Aurora kinase A (Aurora A) as a novel Ras binding protein. We demonstrate that the kinase domain of Aurora A mediates the interaction with the N-terminal domain of H-Ras. Further more, the interaction of Aurora A and H-Ras exists in a protein complex with Raf-1. We show that binding of H-Ras to Raf-1 and subsequent MAPK signaling is enhanced by Aurora A, and requires active H-Ras. Thus, the functional linkage between Aurora A and the H-Ras/Raf-1 protein complex may provide a mechanism for Aurora A's oncogenic activity through direct activation of the Ras/MAPK pathway.
Determination of mild, moderate, and severe pain interference in patients with cancer

Abstract Effective assessment and management of pain in patients with cancer is strengthened by the patient's report of how much pain interferes with daily functioning. This requires a clear delineation of different levels of pain interference. We derived optimal cutpoints for differentiating between mild, moderate, and severe pain interference assessed by the Brief Pain Inventory (BPI) and describe the prevalence and characteristics of pain-induced functional impairment in patients with cancer. Data were pooled across 3 Phase III pivotal trials. Patient-completed questionnaires included the EuroQol 5 dimensions questionnaire (EQ5D), Functional Assessment of Cancer Therapy–General Measure (FACT-G), and BPI. Optimal cutpoints for categorizing pain interference into 3 levels were derived using analysis of variance, with different cutpoint sets for BPI total interference (BPI-PITS, the average score of all 7 items), activity-related interference (BPI-WAW, the average score of work, general activity, and walking), and mood-related interference (BPI-REM, the average score of relations with others, enjoyment of life, and mood) as independent variables and EQ5D–visual analog scale and total FACT-G score as dependent variables. To validate the cutpoints, we assessed whether interference categories were in concordance with Eastern Cooperative Oncology Group performance status (ECOG-PS) levels. The optimal cutpoints were (2,5) for BPI-PITS, (2,6) for BPI-WAW, and (2,5) for BPI-REM. The mild (<2), moderate (2-5 or 2-6), and severe (>5 or >6) pain interference groups were significantly concordant with ECOG-PS levels (P < 0.0001). We empirically derived patient-reported pain interference categories in relation to clinician-rated performance status. These cutpoints may facilitate the conduct and interpretation of clinical evaluation, symptom epidemiology, and clinical trials.
Mating-responsive genes in reproductive tissues of female Drosophila melanogaster

Male-derived accessory gland proteins that are transferred to females during mating have profound effects on female reproductive physiology including increased ovulation, mating inhibition, and effects on sperm utilization and storage. The extreme rates of evolution seen in accessory gland proteins may be driven by sperm competition and sexual conflict, processes that may ultimately drive complex interactions between female- and male-derived molecules and sperm. However, little is known of how gene expression in female reproductive tissues changes in response to the presence of male molecules and sperm. To characterize this response, we conducted parallel genomic and proteomic analyses of gene expression in the reproductive tract of 3-day-old unmated and mated female Drosophila melanogaster. Using DNA microarrays, we identified 539 transcripts that are differentially expressed in unmated vs. mated females and revealed a striking peak in differential expression at 6 h postmating and a marked shift from primarily down-regulated to primarily up-regulated transcripts within 3 h after mating. Combining two-dimensional gel electrophoresis and liquid chromatography mass spectrometry analyses, we identified 84 differentially expressed proteins at 3 h postmating, including proteins that appeared to undergo posttranslational modification. Together, our observations define transcriptional and translational response to mating within the female reproductive tract and suggest a bimodal model of postmating gene expression initially correlated with mating and the final stages of female reproductive tract maturation and later with the declining presence of male reproductive molecules and with sperm maintenance and utilization.
Interleukin-1 Receptor-Associated Kinase M-Deficient Mice Demonstrate an Improved Host Defense during Gram-negative Pneumonia

Pneumonia is a common cause of morbidity and mortality and the most frequent source of sepsis. Bacteria that try to invade normally sterile body sites are recognized by innate immune cells through pattern recognition receptors, among which toll-like receptors (TLRs) feature prominently. Interleukin-1 receptor (IL-1R)-associated kinase (IRAK)-M is a proximal inhibitor of TLR signaling expressed by epithelial cells and macrophages in the lung. To determine the role of IRAK-M in host defense against bacterial pneumonia, RAK-M-deficient (IRAK-M−/−) and normal wild-type (WT) mice were infected intranasally with Klebsiella pneumoniae. IRAK-M mRNA was upregulated in lungs of WT mice with Klebsiella pneumonia, and the absence of IRAK-M resulted in a strongly improved host defense as reflected by reduced bacterial growth in the lungs, diminished dissemination to distant body sites, less peripheral tissue injury and better survival rates. Although IRAK-M−/− alveolar macrophages displayed enhanced responsiveness toward intact K. pneumoniae and Klebsiella lipopolysaccharide (LPS) in vitro, IRAK-M−/− mice did not show increased cytokine or chemokine levels in their lungs after infection in vivo. The extent of lung inflammation was increased in IRAK-M−/− mice shortly after K. pneumoniae infection, as determined by semiquantitative scoring of specific components of the inflammatory response in lung tissue slides. These data indicate that IRAK-M impairs host defense during pneumonia caused by a common gram-negative respiratory pathogen.
Caffeine to optimize cognitive function for military mission-readiness: a systematic review and recommendations for the field

Context In 2001 the Institute of Medicine (IOM) released a report on the use of caffeine during sustained military operations in which recommendations for research and practice were made. Objective This systematic review serves as an update on the current quality of the evidence and addresses gaps in the current literature surrounding the effects of caffeinated foods and beverages on cognitive functioning in healthy adult populations exposed to military-like moderators. Data Sources PubMed, CINAHL, Embase, PsycInfo, and the Cochrane Library were searched. Study Selection Peer-reviewed randomized controlled trials published in the English language since 1998 were eligible. Data Extraction Twenty-five trials were included and assessed for methodological quality, and descriptive data were extracted according to each military-like moderator identified. Data Synthesis Moderators included sleep deprivation (n = 17), physical or mental exertion (n = 4), sleep deprivation combined with a sustained military operation (n = 3), and physical exertion combined with low ambient temperature (n = 1). Conclusions The effects of caffeine supplementation on cognitive functioning in sleep-deprived subjects included improvements in attention and vigilance, complex reaction time, and problem solving and reasoning in the trials reviewed. These findings are consistent with the conclusions reached in the 2001 IOM report. This review contributes to the field by addressing gaps outlined in the IOM report.
Microstructures in Cold-Rolled Ni 3 Al Single Crystals

Microstructure evolution during cold rolling of binary stoichiometric Ni 3 Al single crystals was examined by the optical (OM) and transmission electron microscopy (TEM). In the case of the initial RD, the banded structure is formed. Inside each matrix band, the localized shear deformations occur alternately on two {111} planes. In addition, huge amounts of widely extended superlattice intrinsic stacking faults (SISFs) are observed from relatively early stage of cold rolling. The occurrence of the localized shear deformation is considered to be controlled by the SISFs since they must be strong obstacles for the dislocation motion on the other glide plane. The extensive formation of the SISFs is therefore considered to be one of the most important microstructural features which control the cold rolling behavior of Ni 3 Al.
Predicting First-Grade Reading Performance from Kindergarten Response to Tier 1 Instruction

Many schools are implementing multitier response-to-intervention (RTI) models to reduce reading difficulties. This study was part of our larger ongoing longitudinal RTI investigation within the Florida Learning Disabilities Center grant and was conducted in 7 ethnically and socioeconomically diverse schools. We observed reading instruction in 20 classrooms, examined response rates to kindergarten Tier 1 instruction, and predicted students' first-grade reading performance based on kindergarten growth and end-of-year reading performance (n = 203). Teachers followed an explicit core reading program. Overall, classroom instruction was rated as effective. Results indicate that controlling for students' end-of-kindergarten reading, their growth across kindergarten on a variety of language and literacy measures suppressed predictions of first-grade performance. Specifically, the steeper the students' trajectory to a satisfactory outcome, the less likely they were to demonstrate good performance in first grade. Implications for future research and RTI implementation are discussed.
Effect of a Health Care Professional Communication Training Intervention on Adolescent Human Papillomavirus Vaccination: A Cluster Randomized Clinical Trial

Importance The incidence of human papillomavirus (HPV)–related cancers is more than 35 000 cases in the United States each year. Effective HPV vaccines have been available in the United States for several years but are underused among adolescents, the target population for vaccination. Interventions to increase uptake are needed. Objective To evaluate the effect of a 5-component health care professional HPV vaccine communication intervention on adolescent HPV vaccination. Design, Setting, and Participants A cluster randomized clinical trial using covariate-constrained randomization to assign study arms and an intent-to-treat protocol was conducted in 16 primary care practices in the Denver, Colorado, metropolitan area. Participants included 188 medical professionals and 43 132 adolescents. Interventions The 5 components of the intervention were an HPV fact sheet library to create customized information sheets relevant to each practice’s patient population, a tailored parent education website, a set of HPV-related disease images, an HPV vaccine decision aid, and 2½ hours of communication training on using a presumptive vaccine recommendation, followed by motivational interviewing if parents were resistant to vaccination. Each practice participated in a series of 2 intervention development meetings over a 6-month period (August 1, 2014, to January 31, 2015) before the intervention. Main Outcomes and Measures Differences between control and intervention changes over time (ie, difference in differences between the baseline and intervention period cohorts of patients) in HPV vaccine series initiation (≥1 dose) and completion (≥3 doses) among patients aged 11 to 17 years seen at the practices between February 1, 2015, and January 31, 2016. Vaccination data were obtained from the practices’ records and augmented with state immunization information system data. Results Sixteen practices and 43 132 patients (50.3% female; median age, 12.6 years [interquartile range, 10.8-14.7 years] at the beginning of the study period) participated in this trial. Adolescents in the intervention practices had significantly higher odds of HPV vaccine series initiation (adjusted odds ratio [aOR], 1.46; 95% CI, 1.31-1.62) and completion (aOR, 1.56; 95% CI, 1.27-1.92) than those in the control practices (a 9.5–absolute percentage point increase in HPV vaccine series initiation and a 4.4–absolute percentage point increase in HPV vaccine series completion in intervention practices). The intervention had a greater effect in pediatric practices compared with family medicine practices and in private practices compared with public ones. Health care professionals reported that communication training and the fact sheets were the most used and useful intervention components. Conclusions and Relevance A health care professional communication intervention significantly improved HPV vaccine series initiation and completion among adolescent patients. Trial Registration clinicaltrials.gov Identifier: NCT02456077
Automated Test Case Generation as a Many-Objective Optimisation Problem with Dynamic Selection of the Targets

The test case generation is intrinsically a multi-objective problem, since the goal is covering multiple test targets (e.g., branches). Existing search-based approaches either consider one target at a time or aggregate all targets into a single fitness function (whole-suite approach). Multi and many-objective optimisation algorithms (MOAs) have never been applied to this problem, because existing algorithms do not scale to the number of coverage objectives that are typically found in real-world software. In addition, the final goal for MOAs is to find alternative trade-off solutions in the objective space, while in test generation the interesting solutions are only those test cases covering one or more uncovered targets. In this paper, we present Dynamic Many-Objective Sorting Algorithm (DynaMOSA), a novel many-objective solver specifically designed to address the test case generation problem in the context of coverage testing. DynaMOSA extends our previous many-objective technique Many-Objective Sorting Algorithm (MOSA) with dynamic selection of the coverage targets based on the control dependency hierarchy. Such extension makes the approach more effective and efficient in case of limited search budget. We carried out an empirical study on 346 Java classes using three coverage criteria (i.e., statement, branch, and strong mutation coverage) to assess the performance of DynaMOSA with respect to the whole-suite approach (WS), its archive-based variant (WSA) and MOSA. The results show that DynaMOSA outperforms WSA in 28 percent of the classes for branch coverage (+8 percent more coverage on average) and in 27 percent of the classes for mutation coverage (+11 percent more killed mutants on average). It outperforms WS in 51 percent of the classes for statement coverage, leading to +11 percent more coverage on average. Moreover, DynaMOSA outperforms its predecessor MOSA for all the three coverage criteria in 19 percent of the classes with +8 percent more code coverage on average.
Does a Spontaneous Intracerebral Hemorrhage Predispose to a Secondary, Distant Intracerebral Hemorrhage? A Case Report and Review of the Literature

Cerebrovascular autoregulation may be dysfunctional after acute intracerebral hemorrhage (ICH). This disruption in autoregulation can potentially result in secondary neurological damage that may present as an intracranial hemorrhage at locations distant from the primary site of hemorrhage. We discuss a case of 68-year-old female who presented with acute left hemiparesis from a spontaneous right frontal ICH. Magnetic resonance imaging (MRI) was negative for any other blooming artifact. Her weakness was improving, but after 72 hours from admission, she had an acute change in her mental status and was found to have a new left frontal ICH distant from the primary hemorrhage. Cerebral dysregulation following spontaneous ICH may predispose patients with risk factors, such as chronic hypertension, to a secondary spontaneous ICH distant from initial ICH. Recognizing this phenomenon can guide the management of acute ICH.
Feasibility of a Lifestyle Redesign®-Inspired Intervention for Well Older Adults.

OBJECTIVE We examined the feasibility of Aging Well by Design, a Lifestyle Redesign®-inspired intervention for community-dwelling older adults. The original Lifestyle Redesign program was shortened to 3 mo and implemented as a community outreach program of a major health care system. METHOD Community-dwelling older adults participated in the 12-wk program, which emphasized an occupational approach to healthy aging. Outcomes evaluated were recruitment, attendance, resource use, participant satisfaction, and subjective benefit to participants. RESULTS The 13 participants, ages 66-88 yr, attended an average of 10 of 12 sessions. The intervention was completed as planned, physical resources were suitable, and financial resources were adequate. Participants expressed satisfaction with the program's facilitator, group discussions, and materials. Perceived benefits were social relationships, awareness of community resources, and change in attitude toward aging. CONCLUSION Implementation of a 3-mo Lifestyle Redesign-inspired program within a health care system was feasible.