Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Varenicline on Cognitive Performance in Heavy Drinkers: Dose-Response Effects and Associations With Drinking Outcomes

Varenicline reduces drinking in people with alcohol use disorder, but little is known about the mechanisms underlying this effect. Varenicline targets &agr;4&bgr;2 and &agr;7 nicotinic acetylcholine receptors, which are associated with several cognitive functions such as working memory. Varenicline may improve drinking outcomes by enhancing cognitive functioning. The current manuscript reports on cognitive outcomes from a placebo-controlled, double-blind human laboratory experiment examining the effects of varenicline on drinking behavior (Verplaetse et al., 2016a). Participants were 55 adult heavy drinkers who met criteria for an alcohol use disorder. They were randomized to receive varenicline (1 mg/day, 2 mg/day) or placebo. They completed a baseline assessment of cognitive functioning (i.e., digits backward task, continuous performance task) before starting medication. After a medication titration period, they attended a laboratory session (post medication Day 8) where they completed the cognitive assessment battery and an alcohol-primed ad libitum drinking task. Blood was collected to measure plasma varenicline levels. Varenicline produced dose-dependent improvements in working memory. Although there was no significant effect of oral varenicline dose on response time on the continuous performance task, participants with higher levels of plasma varenicline showed greater improvement of reaction time (RT). Among participants receiving 2 mg/day varenicline, larger improvements in working memory were associated less drinking, although mediation analyses did not find a significant indirect effect. These findings suggest that varenicline can improve working memory above baseline levels in heavy drinkers. Varenicline may reduce rates of alcohol use by improving working memory.
Iron Oxide Nanoparticles Derived from Mill Scale Waste as Potential Scavenging Agent in Dye Wastewater Treatment for Batik Industry

In this work, iron oxide were derived from millscale has been used as a potential scavenging agent in wastewater treatment due to its high adsorption capacity and its shorter sedimentation time during wastewater treatment. Iron oxide obtained from the magnetic separation technique was subjected to high energy ball milling (HEBM) at different milling time to produce different size of nanoparticles of iron oxide. X-ray diffraction (XRD), Field Emission Scanning Electron Microscope (FESEM) and Scanning Trasmission Electron microscopy (STEM) were performed to study the morphological properties of the iron oxide nanoparticles. After HEBM, iron oxide nanoparticles was modified with Hexadecyltrimethylammonium Bromide (CTAB) to study the adsorption possibility of iron oxide nanoparticle modified with CTAB (Iron oxide– CTAB nanoparticles) in dye wastewater. The variation effect of particle size of derived Iron oxide– CTAB were studied. Permanent magnet was used to separate iron oxide nanoparticles from the solution. The clear part of the solution (treated wastewater) was filtered out and adsorption efficiency of Iron oxide– CTAB nanoparticles was measured using UV – Visible spectroscopy. Efficiency adsorption of iron oxide nanoparticles modified with CTAB greatly achieved above 99 % and the size of iron oxide nanoparticles affected its performance in dye wastewater treatment.
Crowd modeling framework using fast head detection and shape-aware matching

Abstract. A framework for crowd modeling using a combination of multiple kernel learning (MKL)-based fast head detection and shape-aware matching is proposed. First, the MKL technique is used to train a classifier for head detection using a combination of the histogram of oriented gradient and local binary patterns feature sets. Further, the head detection process is accelerated by implementing the classification procedure only at those spatial locations in the image where the gradient points overlap with moving objects. Such moving objects are determined using an adaptive background subtraction technique. Finally, the crowd is modeled as a deformable shape through connected boundary points (head detection) and matched with the subsequent detection from the next frame in a shape-aware manner. Experimental results obtained from crowded videos show that the proposed framework, while being characterized by a low computation load, performs better than other state-of-art techniques and results in reliable crowd modeling.
Psychometric Evaluation of the Electronic Pain Assessment Tool: An Innovative Instrument for Individuals with Moderate-to-Severe Dementia

Background/Aims: Pain is common in aged care residents with dementia; yet it often goes undetected. A novel tool, the electronic Pain Assessment Tool (ePAT), was developed to address this challenging problem. We investigated the psychometric properties of the ePAT. Methods: In a 10-week prospective observational study, the ePAT was evaluated by comparison against the Abbey Pain Scale (APS). Pain assessments were blindly co-performed by the ePAT rater against the nursing staff of two residential aged care facilities. The residents were assessed twice by each rater: at rest and following movement. Results: The study involved 34 residents aged 85.5 ± 6.3 years, predominantly with severe dementia (Psychogeriatric Assessment Scale – Cognitive Impairment score = 19.7 ± 2.5). Four hundred paired assessments (n = 204 during rest; n = 196 following movement) were performed. Concurrent validity (r = 0.911) and all reliability measures (κw = 0.857; intraclass correlation coefficient = 0.904; α = 0.950) were excellent, while discriminant validity and predictive validity were good. Conclusion: The ePAT is a suitable tool for the assessment of pain in this vulnerable population.
A Scaling-Assisted Signed Integer Comparator for the Balanced Five-Moduli Set RNS $\{2^{n}-1, 2^{n}, 2^{n}+ 1, 2^{n+1}- 1, 2^{n-1}- 1\}$

Signed integer comparison occurs prevalently in process control, sorting, address decoding, and conditional branching. Existing algorithms for magnitude comparison in RNS are based either on parity check or partial reverse conversion. With separately designed RNS sign detectors, they can also be used to compare residue representations of signed integers. In this paper, a radically different approach to this problem is proposed for the five-moduli set <inline-formula> <tex-math notation="LaTeX">$\{2^{n}- 1, 2^{n}, 2^{n}+ 1, 2^{n+1}- 1, 2^{n-1}-1\}$ </tex-math></inline-formula>. The signs of the operands in comparison, as well as their difference are detected after scaling by a factor of (<inline-formula> <tex-math notation="LaTeX">$2^{2n}- 1$ </tex-math></inline-formula>)(<inline-formula> <tex-math notation="LaTeX">$2^{n-1}- 1$ </tex-math></inline-formula>). The resulting finite series in the composite modulus channel is further factored into parallel carry-saved additions in the existing mod <inline-formula> <tex-math notation="LaTeX">$2^{n}$ </tex-math></inline-formula> and mod <inline-formula> <tex-math notation="LaTeX">$2^{n+1}- 1$ </tex-math></inline-formula> modulus channels, thus reducing the sizes of modulo adders from <inline-formula> <tex-math notation="LaTeX">$5n$ </tex-math></inline-formula> bits to <inline-formula> <tex-math notation="LaTeX">$n$ </tex-math></inline-formula> and <inline-formula> <tex-math notation="LaTeX">$n + 1$ </tex-math></inline-formula> bits. Upon detecting the signs of the operands and their difference, the relation is inference with a small fraction of logic gates. Our synthesis results in 65-nm CMOS technology show that the proposed design is 36.9% smaller, 7.6% faster, and 45.5% more energy efficient than the best Chinese remainder theorem-II-based magnitude comparator and at least 12.9% smaller, 7.3% faster, and 20.8% more energy efficient than the best reverse-conversion-based implementation of signed integer comparator for the same five-moduli set.
Failure to induce apoptosis via BCL-2 family proteins underlies lack of efficacy of combined MEK and PI3K inhibitors for KRAS-mutant lung cancers.

Although several groups have demonstrated that concomitant use of MEK and phosphoinositide 3-kinase (PI3K) inhibitors (MEKi/PI3Ki) can induce dramatic tumor regressions in mouse models of KRAS-mutant non-small cell lung cancer (NSCLC), ongoing clinical trials investigating this strategy have been underwhelming to date. While efficacy may be hampered by a narrow therapeutic index, the contribution of biologic heterogeneity in the response of KRAS-mutant NSCLCs to MEKi/PI3Ki has been largely unexplored. In this study, we find that most human KRAS-mutant NSCLC cell lines fail to undergo marked apoptosis in response to MEKi/PI3Ki, which is key for tumor responsiveness in vivo. This heterogeneity of apoptotic response occurs despite relatively uniform induction of growth arrest. Using a targeted short hairpin RNA screen of BCL-2 family members, we identify BIM, PUMA, and BCL-XL as key regulators of the apoptotic response induced by MEKi/PI3Ki, with decreased expression of BIM and PUMA relative to BCL-XL in cell lines with intrinsic resistance. In addition, by modeling adaptive resistance to MEKi/PI3Ki both in vitro and in vivo, we find that, upon the development of resistance, tumors have a diminished apoptotic response due to downregulation of BIM and PUMA. These results suggest that the inability to induce apoptosis may limit the effectiveness of MEKi/PI3Ki for KRAS-mutant NSCLCs by contributing to intrinsic and adaptive resistance to this therapy.
Lysines in the tetramerization domain of p53 selectively modulate G1 arrest

ABSTRACT Functional in a tetrameric state, the protein product of the p53 tumor suppressor gene confers its tumor-suppressive activity by transactivating genes which promote cell-cycle arrest, senescence, or programmed cell death. How p53 distinguishes between these divergent outcomes is still a matter of considerable interest. Here we discuss the impact of 2 mutations in the tetramerization domain that confer unique properties onto p53. By changing lysines 351 and 357 to arginine, thereby blocking all post-translational modifications of these residues, DNA binding and transcriptional regulation by p53 remain virtually unchanged. On the other hand, by changing these lysines to glutamine (2KQ-p53), thereby neutralizing their positive charge and potentially mimicking acetylation, p53 is impaired in the induction of cell cycle arrest and yet can still effectively induce cell death. Surprisingly, when 2KQ-p53 is expressed at high levels in H1299 cells, it can bind to and transactivate numerous p53 target genes including p21, but not others such as miR-34a and cyclin G1 to the same extent as wild-type p53. Our findings show that strong induction of p21 is not sufficient to block H1299 cells in G1, and imply that modification of one or both of the lysines within the tetramerization domain may serve as a mechanism to shunt p53 from inducing cell cycle arrest.
A New Natural Product Analog of Blasticidin S Reveals Cellular Uptake Facilitated by the NorA Multidrug Transporter

ABSTRACT The permeation of antibiotics through bacterial membranes to their target site is a crucial determinant of drug activity but in many cases remains poorly understood. During screening efforts to discover new broad-spectrum antibiotic compounds from marine sponge samples, we identified a new analog of the peptidyl nucleoside antibiotic blasticidin S that exhibited up to 16-fold-improved potency against a range of laboratory and clinical bacterial strains which we named P10. Whole-genome sequencing of laboratory-evolved strains of Staphylococcus aureus resistant to blasticidin S and P10, combined with genome-wide assessment of the fitness of barcoded Escherichia coli knockout strains in the presence of the antibiotics, revealed that restriction of cellular access was a key feature in the development of resistance to this class of drug. In particular, the gene encoding the well-characterized multidrug efflux pump NorA was found to be mutated in 69% of all S. aureus isolates resistant to blasticidin S or P10. Unexpectedly, resistance was associated with inactivation of norA, suggesting that the NorA transporter facilitates cellular entry of peptidyl nucleosides in addition to its known role in the efflux of diverse compounds, including fluoroquinolone antibiotics.
Septins: New Microtubule Interacting Partners

Originally characterized as regulators of cytokinesis, septins were later implicated in other cellular processes. Recent studies show that septins have a broader role in microtubule-dependent processes, such as karyokinesis, exocytosis, and maintenance of cell shape. Many members of the septin family have been shown to colocalize or interact with the microtubule cytoskeleton, suggesting that these might be general properties of septins. Septins could play an important role in regulating microtubule dynamics by interacting with microtubule-associated proteins (MAPs) that modulate microtubule stability. Being able to associate with both microtubules and actin, septins can play an important role as adaptors between the two cytoskeletons and as regulators of processes in which both actin and microtubules are involved. As septins are associated with various neurodegenerative diseases and cancer, a better understanding of the biology of septins and their interactions with microtubules is important in order to develop possible therapeutic strategies for these diseases.
Intramuscular Tranexamic Acid in Tactical and Combat Settings.

BACKGROUND Uncontrolled hemorrhage remains a leading cause of preventable death in tactical and combat settings. Alternate routes of delivery of tranexamic acid (TXA), an adjunct in the management of hemorrhagic shock, are being studied. A working group for the Committee for Tactical Emergency Casualty Care reviewed the available evidence on the potential role for intramuscular (IM) administration of TXA in nonhospital settings as soon as possible from the point of injury. METHODS EMBASE and MEDLINE/PubMed databases were sequentially searched by medical librarians for evidence of TXA use in the following contexts and/or using the following keywords: prehospital, trauma, hemorrhagic shock, optimal timing, optimal dose, safe volume, incidence of venous thromboembolism (VTE), IM bioavailability. RESULTS A total of 183 studies were reviewed. The strength of the available data was variable, generally weak in quality, and included laboratory research, case reports, retrospective observational reviews, and few prospective studies. Current volume and concentrations of available formulations of TXA make it, in theory, amenable to IM injection. Current bestpractice guidelines for large-volume injection (i.e., 5mL) support IM administration in four locations in the adult human body. One case series suggests complete bioavailability of IM TXA in healthy patients. Data are lacking on the efficacy and safety of IM TXA in hemorrhagic shock. CONCLUSION There is currently insufficient evidence to support a strong recommendation for or against IM administration of TXA in the combat setting; however, there is an abundance of literature demonstrating efficacy and safety of TXA use in a broad range of patient populations. Balancing the available data and risk- benefit ratio, IM TXA should be considered a viable treatment option for tactical and combat applications. Additional studies should focus on the optimal dose and bioavailability of IM dosing of patients in hemorrhagic shock, with assessment of potential downstream sequelae.
Historical development of vaginal microbicides to prevent sexual transmission of HIV in women: from past failures to future hopes

Infection with human immunodeficiency virus (HIV) remains a global public health concern and is particularly serious in low- and middle-income countries. Widespread sexual violence and poverty, among other factors, increase the risk of infection in women, while currently available prevention methods are outside the control of most. This has driven the study of vaginal microbicides to prevent sexual transmission of HIV from men to women in recent decades. The first microbicides evaluated were formulated as gels for daily use and contained different substances such as surfactants, acidifiers and monoclonal antibodies, which failed to demonstrate efficacy in clinical trials. A gel containing the reverse transcriptase inhibitor tenofovir showed protective efficacy in women. However, the lack of adherence by patients led to the search for dosage forms capable of releasing the active principle for longer periods, and hence to the emergence of the vaginal ring loaded with dapivirine, which requires a monthly application and is able to reduce the sexual transmission of HIV. The future of vaginal microbicides will feature the use of alternative dosage forms, nanosystems for drug release and probiotics, which have emerged as potential microbicides but are still in the early stages of development. Protecting women with vaginal microbicide formulations would, therefore, be a valuable tool for avoiding sexual transmission of HIV.
Development and preliminary evaluation of the resident coordinated-transitional care (RC-TraC) program: A sustainable option for transitional care education

ABSTRACT Older adults often face poor outcomes when transitioning from hospital to home. Although physicians play a key role in overseeing transitions, there is a lack of practice-based educational programs that prepare resident physicians to manage care transitions of older adults. An educational intervention to provide residents with real-life transitional care practice was therefore developed—Resident-coordinated Transitional Care (RC-TraC). RC-TraC adapted the evidence-based Coordinated-Transitional Care (C-TraC) nurse role for residents, providing opportunities to follow patients during the peri-hospital period without additional costs to the residency program. Between July 2010 and June 2013, 31 internal medicine residents participated in RC-TraC, caring for 721 patients. RC-TraC has been a sustainable, low-cost, practice-based education experience that is recognized as transitional care education by residents and continues in operation to this day. RC-TraC is a promising option for geriatric-based transitional care education of resident physicians and could also be adapted for nonphysician learners.
Cortisol in mother’s milk across lactation reflects maternal life history and predicts infant temperament

Lay Summary In monkeys, high cortisol and changes in cortisol levels in mother’s milk are associated with more nervous and less confident infants. Sons are more sensitive than are daughters to changes in cortisol in mother’s milk across lactation. Females that are earlier in their reproductive career tend to have higher cortisol in their milk. Mothers may be “programming” behaviorally cautious offspring that prioritize growth through cortisol signaling.
Presyncopal episodes after implantation of dual-chamber pacemaker programmed in SafeR pacing mode.

On arrival to the emergency department, the patient had no symptoms. Laboratory studies and chest X-ray showed no significant findings, and the electrocardiogram revealed sinus rhythm at 58 bpm and a normal PR interval (160 ms) with left anterior fascicular block and complete right bundle branch block, both previously known. Device interrogation showed how all nine presyncopal episodes coincided with nine checks to detect intrinsic conduction that caused pauses>2.5 s (Figure 1). The pacemaker was adjusted to permanent DDD mode, resolving the symptomatology. Figure 1 Automatic switch to AAI mode after 100 paced ventricular cycles related to presyncopal symptoms. As the atrioventricular block is still present, the third-degree AVB criterion applies and the algorithm makes the switch to DDD mode.
General aspects in the use of graphenes in catalysis

This perspective is aimed at presenting some issues that, in our opinion, have still to be better addressed in the field of graphenes as catalysts. After an introductory section, the article comments on how the number of layers present on the catalyst, termed frequently as graphene, could be in some cases in contradiction with good practices about what should be or not considered as graphene. It will also be commented that some of the characterization tools that are employed in some cases for graphenes as catalysts, like specific surface area measurements based on isothermal gas adsorption on powders or XRD patterns are not well suited to characterizing graphenes. The potential role of impurities and structural defects in graphene catalysis has been highlighted showing the importance of providing exhaustive analysis of the materials. This perspective includes a final section with our view on future progress and wider consensus in the use of graphene in catalysis.
The Corticocortical Structural Connectivity of the Human Insula

Abstract The insula is a complex structure involved in a wide range of functions. Tracing studies on nonhuman primates reveal a wide array of cortical connections in the frontal (orbitofrontal and prefrontal cortices, cingulate areas and supplementary motor area), parietal (primary and secondary somatosensory cortices) and temporal (temporal pole, auditory, prorhinal and entorhinal cortices) lobes. However, recent human tractography studies have not observed connections between the insula and the cingulate cortices, although these structures are thought to be functionally intimately connected. In this work, we try to unravel the structural connectivity between these regions and other known functionally connected structures, benefiting from a higher number of subjects and the latest state‐of‐the‐art high angular resolution diffusion imaging (HARDI) tractography algorithms with anatomical priors. By performing an HARDI tractography analysis on 46 young normal adults, our study reveals a wide array of connections between the insula and the frontal, temporal, parietal and occipital lobes as well as limbic regions, with a rostro‐caudal organization in line with tracing studies in macaques. Notably, we reveal for the first time in humans a clear structural connectivity between the insula and the cingulate, parahippocampal, supramarginal and angular gyri as well as the precuneus and occipital regions.
Intracellular Targeting Mechanisms by Antimicrobial Peptides

ABSTRACT Antimicrobial peptides (AMPs) are expressed in various living organisms as first-line host defenses against potential harmful encounters in their surroundings. AMPs are short polycationic peptides exhibiting various antimicrobial activities. The principal antibacterial activity is attributed to the membrane-lytic mechanism which directly interferes with the integrity of the bacterial cell membrane and cell wall. In addition, a number of AMPs form a transmembrane channel in the membrane by self-aggregation or polymerization, leading to cytoplasm leakage and cell death. However, an increasing body of evidence has demonstrated that AMPs are able to exert intracellular inhibitory activities as the primary or supportive mechanisms to achieve efficient killing. In this review, we focus on the major intracellular targeting activities reported in AMPs, which include nucleic acids and protein biosynthesis and protein-folding, protease, cell division, cell wall biosynthesis, and lipopolysaccharide inhibition. These multifunctional AMPs could serve as the potential lead peptides for the future development of novel antibacterial agents with improved therapeutic profiles.