Miracle-dz/UniFAR-FTUs huggingface dataset:
The structures of penicillin-binding protein 4 (PBP4) and PBP5 from Enterococci provide structural insights into β-lactam resistance

The final steps of cell-wall biosynthesis in bacteria are carried out by penicillin-binding proteins (PBPs), whose transpeptidase domains form the cross-links in peptidoglycan chains that define the bacterial cell wall. These enzymes are the targets of β-lactam antibiotics, as their inhibition reduces the structural integrity of the cell wall. Bacterial resistance to antibiotics is a rapidly growing concern; however, the structural underpinnings of PBP-derived antibiotic resistance are poorly understood. PBP4 and PBP5 are low-affinity, class B transpeptidases that confer antibiotic resistance to Enterococcus faecalis and Enterococcus faecium, respectively. Here, we report the crystal structures of PBP4 (1.8 Å) and PBP5 (2.7 Å) in their apo and acyl-enzyme complexes with the β-lactams benzylpenicillin, imipenem, and ceftaroline. We found that, although these three β-lactams adopt geometries similar to those observed in other class B PBP structures, there are small, but significant, differences that likely decrease antibiotic efficacy. Further, we also discovered that the N-terminal domain extensions in this class of PBPs undergo large rigid-body rotations without impacting the structure of the catalytic transpeptidase domain. Together, our findings are defining the subtle functional and structural differences in the Enterococcus PBPs that allow them to support transpeptidase activity while also conferring bacterial resistance to antibiotics that function as substrate mimics.
Effects of the Namaste Care Family programme on quality of life of nursing home residents with advanced dementia and on family caregiving experiences: study protocol of a cluster-randomised controlled trial

Introduction Quality of life of people with advanced dementia living in nursing homes is often suboptimal. Family caregivers can feel frustrated with limited contact with their relatives, which results in visits that are perceived as stressful and not very meaningful. Few psychosocial interventions are specifically developed for people with advanced dementia, and actively involve family caregivers or volunteers. Also, interventions usually stop when it becomes difficult for people to participate. The Namaste Care Family programme aims to increase the quality of life of people with advanced dementia, and improve family caregiving experiences through connecting to people and making them comfortable. Methods and analysis Our study will evaluate the effects of the Namaste Care Family programme on quality of life of people with advanced dementia living in nursing homes and family caregiving experiences using a cluster-randomised controlled trial. Longitudinal analyses will be performed taking into account clustering at the nursing home level. Both a cost-effectiveness and a cost-utility analysis from a societal perspective will be performed. We will modify the Namaste Care Family programme to increase family and volunteer involvement in ongoing and end-of-life care. Data collection involves assessments by family caregivers, nursing staff and elderly care physicians using questionnaires, and observations by the researchers at baseline and multiple times over 12 months. The last questionnaire will be sent up to month 24 after the death of the person with dementia. During semistructured interviews, the feasibility, accessibility and sustainability of the Namaste Care Family programme will be assessed. Ethics and dissemination The study protocol is approved by the Medical Ethics Review Committee of the VU University Medical Center in Amsterdam (protocol no. 2016.399) and registered with the Nederlands Trial Register (NTR5692). The findings will be disseminated via publications in peer-reviewed journals, conference presentations and presentations for healthcare professionals where appropriate. Trial registration number NTR5692.
Chromatin Remodeling Factors Isw2 and Ino80 Regulate Chromatin, Replication, and Copy Number of the Saccharomyces cerevisiae Ribosomal DNA Locus

In the budding yeast Saccharomyces cerevisiae, ribosomal RNA genes are encoded in a highly repetitive tandem array referred to as the ribosomal DNA (rDNA) locus. The yeast rDNA is the site of a diverse set of DNA-dependent processes, including transcription of ribosomal RNAs by RNA polymerases I and III, transcription of noncoding RNAs by RNA polymerase II, DNA replication initiation, replication fork blocking, and recombination-mediated regulation of rDNA repeat copy number. All of this takes place in the context of chromatin, but little is known about the roles played by ATP-dependent chromatin remodeling factors at the yeast rDNA. In this work, we report that the Isw2 and Ino80 chromatin remodeling factors are targeted to this highly repetitive locus. We characterize for the first time their function in modifying local chromatin structure, finding that loss of these factors decreases the fraction of actively transcribed 35S ribosomal RNA genes and the positioning of nucleosomes flanking the ribosomal origin of replication. In addition, we report that Isw2 and Ino80 promote efficient firing of the ribosomal origin of replication and facilitate the regulated increase of rDNA repeat copy number. This work significantly expands our understanding of the importance of ATP-dependent chromatin remodeling for rDNA biology.
Symptom Expression in Patients with Advanced Cancer Admitted to an Acute Supportive/Palliative Care Unit With and Without Delirium.

AIM The aim of this study was to investigate the relationship between delirium and symptom expression in patients with advanced cancer admitted to an acute supportive/palliative care unit (ASPCU). METHODS A consecutive sample of patients with advanced cancer who were admitted to an ASPCU was prospectively assessed for a period of 10 months. The Edmonton Symptom Assessment Scale (ESAS) and the MDAS (Memorial Delirium Assessment Scale) were measured at admission (T0) and after 7 days of palliative care (T7). RESULTS Two hundred forty-six patients had complete data regarding MDAS measurements, at either T0 and T7. Of these, 75 (30.5%) and 63 patients (25.6%) had delirium at T0 and after a week of palliative care (T7), with a decrease in the frequency of delirium of 4.9% (from 30.5% to 25.6%); that means that 16% of patients with delirium improved their cognitive status after initiation of palliative care. Intensities of pain, depression, poor well-being, and global ESAS were significantly higher in patients with delirium. Patients who did not have delirium at T0 but developed delirium during admission after 1 week of palliative care had a higher level of symptom expression for pain, weakness, nausea, anxiety, dyspnea, appetite, and consequently global ESAS. Patients who did not develop delirium at any time had a relevant decrease in intensity of all ESAS items after 1 week of palliative care. The decrease of symptom intensity was significant for pain, insomnia, appetite, poor well-being, and global ESAS in patients with delirium either at T0 and T7, although these differences were less relevant than those observed in patients without delirium. In patients with delirium at T0 who improved their cognitive function at T7 (no delirium), significant changes were found in most ESAS items. CONCLUSION Symptom expression is amplified in patients with delirium, whereas patients without delirium may be more responsive to palliative treatments with a significant decrease in intensity of ESAS items. IMPLICATIONS FOR PRACTICE Symptom expression is amplified in patients with cancer who have delirium, whereas patients without delirium may be more responsive to palliative treatments with a significant decrease in symptom intensity.
Fusion of LiDAR and Camera by Scanning in LiDAR Imagery and Image-Guided Diffusion for Urban Road Detection

This paper proposes a new method for road detection based on a 3D LiDAR and a camera. First, the original LiDAR point cloud is re-organized in an ordered way to generate a LiDAR imagery. Then the flat region is extracted from the LiDAR imagery as the candidate road region. Next, a strategy of row- and column- scanning is given in the LiDAR imagery to detect a finer road region from the candidate region. To fuse the point cloud with image information, we transform the point cloud that corresponds to the above detected road region to the image space according to the calibration parameters between the LiDAR and camera. Then we give two image-guided diffusion schemes to conduct image segmentation of road area, respectively. Our experiments demonstrate that this training free approach detects the road region fast, accurately and robustly, and compares favorably with the state-of-the-art on the KITTI benchmark.
Properties of novel surfactin‐derived biosurfactants obtained through solid‐phase synthesis

Eight molecules, four peptides (SPs) and four lipopeptides (LPs) derived by rational design from surfactin, a well‐known secreted biosurfactant from Bacillus subtilis, were produced employing Fmoc‐based solid‐phase synthesis. These new peptides were tested to evaluate their potential biosurfactant and biological activities, aiming at possible applications in industrial, biological, pharmaceutical, and medical use. Five molecules (SP1, SP2, SP4, LP5, and LP8) presented potential for medical uses, mainly due to their drug delivery properties as suggested by their synergistic activity with the antibiotic vancomycin against Staphylococcus aureus. All synthetic peptides showed low toxicity against Vero cell cultures, in assays of hemolysis, and in different cytotoxicity assays. In addition, we found that three peptides (SP1, LP6, and LP7) had potential technological and industrial use because of their emulsifying capacity, low toxicity, and ability to physically stabilize solutions. These novel molecules retained some properties of the parental molecule (surfactin, which was originally obtained through nonribosomal synthesis in Bacillus subtilis) but have the advantage of being linear peptides, which can be produced at large scales through the use of conventional heterologous protein expression protocols.
Development of human electrophysiological brain networks

Functional activity in the human brain is intrinsically organized into independently active, connected brain regions. These networks include sensorimotor systems, as well as higher-order cognitive networks such as the default mode network (DMN), which dominates activity when the brain is at rest, and the frontoparietal (FPN) and salience (SN) networks, which are often engaged during demanding tasks. Evidence from functional magnetic resonance imaging (fMRI) suggests that although sensory systems are mature by the end of childhood, the integrity of the FPN and SN develops throughout adolescence. There has been little work to corroborate these findings with electrophysiology. Using magnetoencephalography (MEG) recordings of 48 participants (aged 9–25 yr) at rest, we find that beta-band functional connectivity within the FPN, SN, and DMN continues to increase through adolescence, whereas connectivity in the visual system is mature by late childhood. In contrast to fMRI results, but replicating the MEG findings of Schäfer et al. (Schäfer CB, Morgan BR, Ye AX, Taylor MJ, Doesburg SM. Hum Brain Mapp 35: 5249–5261, 2014), we also see that connectivity between networks increases rather than decreases with age. This suggests that the development of coordinated beta-band oscillations within and between higher-order cognitive networks through adolescence might contribute to the developing abilities of adolescents to focus their attention and coordinate diverse aspects of mental activity. NEW & NOTEWORTHY Using magnetoencephalography to assess beta frequency oscillations, we show that functional connectivity within higher-order cognitive networks increases from childhood, reaching adult values by age 20 yr. In contrast, connectivity within a primary sensory (visual) network reaches adult values by age 14 yr. In contrast to functional MRI findings, connectivity between cognitive networks matures at a rate similar to within-network connectivity, suggesting that coordination of beta oscillations both within and between networks is associated with maturation of cognitive skills.
Vantage perspective in analogue trauma memories: an experimental study

ABSTRACT Vantage perspective during recall is thought to affect the emotionality and accessibility of distressing memories. This study aimed to test the effects of vantage perspective during recall on memory associated distress and intrusion development. An adapted version of the trauma film paradigm was used in an experimental design with three conditions. Participants were asked to listen to eyewitness reports of car accidents (e.g. Trauma Analogue Induction) and imagine the scenes vividly using mental imagery. Afterwards, they were asked to recall the most distressing scene from field perspective, observer perspective, or to recall a neutral image from observer perspective (control condition) (e.g. Trauma Analogue Recall). Recall from field perspective resulted in higher negative mood, state-anxiety, and a higher number of short-term intrusions compared to the observer perspective condition and control condition. Negative mood and state-anxiety were mediators in the relationship between vantage perspective and intrusions. In comparison to observer perspective, field perspective increased the amount of short-term intrusions as a result of higher levels of negative mood and state-anxiety after memory retrieval. Future research on the interaction between vantage perspective at recall and negative mood and anxiety effects is warranted.
High-Salt Diet Causes Expansion of the Lymphatic Network and Increased Lymph Flow in Skin and Muscle of Rats

Objective— A commonly accepted pivotal mechanism in fluid volume and blood pressure regulation is the parallel relationship between body Na+ and extracellular fluid content. Several recent studies have, however, shown that a considerable amount of Na+ can be retained in skin without commensurate water retention. Here, we asked whether a salt accumulation shown to result in VEGF (vascular endothelial growth factor)-C secretion and lymphangiogenesis had any influence on lymphatic function. Approach and Results— By optical imaging of macromolecular tracer washout in skin, we found that salt accumulation resulted in an increase in lymph flow of 26% that was noticeable only after including an overnight recording period. Surprisingly, lymph flow in skeletal muscle recorded with a new positron emission tomography/computed tomography method was also increased after salt exposure. The transcapillary filtration was unaffected by the high-salt diet and deoxycorticosterone-salt treatment, suggesting that the capillary barrier was not influenced by the salt accumulation. A significant reduction in lymph flow after depletion of macrophages/monocytes by clodronate suggests these cells are involved in the observed lymph flow response, together with collecting vessels shown here to enhance their contraction frequency as a response to extracellular Na+. Conclusions— The observed changes in lymph flow suggest that the lymphatics may influence long-term regulation of tissue fluid balance during salt accumulation by contributing to fluid homeostasis in skin and muscle. Our studies identify lymph clearance as a potential disease-modifying factor that might be targeted in conditions characterized by salt accumulation like chronic kidney disease and salt-sensitive hypertension.
Analysis on Biosignal Characteristics to Evaluate Road Rage of Younger Drivers: A Driving Simulator Study*

This paper focused on biosignal characteristics to analyze road rage of young drivers in a driving simulator experiment. A total of 12 subjects were enrolled during the experimental study. At first, an unfair incident video is utilized to induce the anger emotion of drivers, and then the anger state is recorded based on the Likert anger scale; meanwhile, a physiological recorder is used to acquire electroencephalogram (EEG) and electrocardiogram (ECG) signals of the subjects. In biosignal processing stage, four typical rhythm bands of α,β,δ, and θ are extracted from the original EEG using a digital filter and wavelet packet decomposition, and power spectrums of the four typical rhythm bands are obtained with a fast Fourier transform analysis. In addition, the average heart rate and R-R standard deviation are calculated through a temporal domain analysis from the original ECG signals. Furthermore, the relationships are analyzed between the sex calculated indicators and four angry levels. It indicates that there is a mainly statistical effect of the angry state for typical rhythm bands of α,β,δ, average heart rate and R-R standard deviation, indicating that these features were significantly different for the normal state, light anger, moderate anger, and heavy anger. The research results provide a theoretical basis and data support for driving emotion detection and aggressive driving behavior analyzing.
Real-time Semantic Segmentation-based Depth Upsampling using Deep Learning

We propose a new real-time depth upsampling method based on convolutional neural networks (CNNs) that uses the local context provided by semantic information. Two solutions based on convolutional networks are introduced, modeled according to the level of sparsity given by the depth sensor. While first CNN upsamples data from a partial-dense input, the second one uses dilated convolutions as means to cope with sparse inputs from cost-effective depth sensors. Experiments over data extracted from Kitti dataset highlight the performance of our methods while running in real-time (11 ms for the first case and 17 ms for the second) on a regular GPU.
Code Cleaning for Software Defect Prediction: A Cautionary Tale

In this paper, we describe our experience of developing a new technique to improve defect prediction (code cleaning) which performed very encouragingly on the first two systems on which we evaluated it (both systems had their origins in one company). Code cleaning also worked well on an additional open source system (Eclipse). But our code cleaning technique then performed disappointingly on all 69 subsequent open source systems on which we evaluated it. Without our round two evaluations on these 69 open source systems we would have published misleading prediction results. We discuss the need for performance evaluations to be performed on carefully selected samples of systems if reliable conclusions are to be drawn.
Screening for Intimate Partner Violence, Elder Abuse, and Abuse of Vulnerable Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force

Importance Intimate partner violence (IPV), elder abuse, and abuse of vulnerable adults are common and result in adverse health outcomes. Objective To review the evidence on screening and interventions for IPV, elder abuse, and abuse of vulnerable adults to inform the US Preventive Services Task Force. Data Sources MEDLINE, Cochrane Library, EMBASE, and trial registries through October 4, 2017; references; experts; literature surveillance through August 1, 2018. Study Selection English-language randomized clinical trials (RCTs), studies evaluating test accuracy, and cohort studies with a concurrent control group assessing harms. Data Extraction and Synthesis Dual review of titles and abstracts, full-text articles, and study quality; qualitative synthesis of findings. Data were not pooled, primarily because of heterogeneity of populations, interventions, and outcomes. Main Outcomes and Measures Abuse or neglect, morbidity caused by abuse, test accuracy, and harms. Results Thirty studies were included (N = 14 959). Three RCTs (n = 3759) compared IPV screening with no screening; none found significant improvements in outcomes (eg, IPV or quality of life) over 3 to 18 months and 2 (n = 935) reported no harms of screening. Nine studies assessed tools to detect any past-year or current IPV in women; for past-year IPV (5 studies [n = 6331]), sensitivity of 5 tools ranged from 65% to 87% and specificity ranged from 80% to 95%. The accuracy of 5 tools (4 studies [n = 1795]) for detecting current abuse varied widely; sensitivity ranged from 46% to 94% and specificity ranged from 38% to 95%. Eleven RCTs (n = 6740) evaluated interventions for women with screen-detected IPV. Two enrolling pregnant women (n = 575) found significantly less IPV among women in the intervention group: 1 home visiting intervention (standardized mean difference [SMD], −0.34 [95% CI, −0.59 to −0.08]) and 1 behavioral counseling intervention for multiple risks (IPV, smoking, depression, tobacco exposure) (SMD, −0.40 [95% CI, −0.68 to −0.12]). No studies evaluated screening or interventions for elder abuse or abuse of vulnerable adults. One study assessing a screening tool for elder abuse had poor accuracy (sensitivity, 46% and specificity, 73% for detecting physical or verbal abuse). Conclusions and Relevance Although available screening tools may reasonably identify women experiencing IPV, trials of IPV screening in adult women did not show a reduction in IPV or improvement in quality of life over 3 to 18 months. Limited evidence suggested that home visiting and behavioral counseling interventions that address multiple risk factors may lead to reduced IPV among pregnant or postpartum women. No studies assessed screening or treatment for elder abuse and abuse of vulnerable adults.
Effect of Intracoronary Metformin on Myocardial Infarct Size in Swine

Rationale: Metformin has been demonstrated to decrease infarct size (IS) and prevent postinfarction left ventricular (LV) remodeling in rodents when given intravenously at the time of reperfusion. It remains unclear whether similar cardioprotection can be achieved in a large animal model. Objective: The objective of this study was to determine whether intravascular infusion of metformin at the time of reperfusion reduces myocardial IS in a porcine model of acute myocardial infarction. Methods and Results: In a blinded and randomized preclinical study, closed-chest swine (n=20) were subjected to a 60-minute left anterior descending coronary artery occlusion to produce myocardial infarction. Contrast-enhanced computed tomography was performed during left anterior descending coronary artery occlusion to assess the ischemic area-at-risk. Animals were randomized to receive either metformin or vehicle as an initial intravenous bolus (5 mg/kg) 8 minutes before reperfusion, followed by a 15-minute left coronary artery infusion (1 mg/kg per minute) commencing with the onset of reperfusion. Echocardiography and computed tomographic imaging of LV function were performed 1 week later, at which time the heart was removed for postmortem pathological analysis of area-at-risk and IS (triphenyltetrazolium chloride). Baseline variables including hemodynamics and LV function were similar between groups. Peak circulating metformin concentrations of 374±35 µmol/L were achieved 15 minutes after reperfusion. There was no difference between the area-at-risk as a percent of LV mass by computed tomography (vehicle: 20.7%±1.1% versus metformin: 19.7%±1.3%; P=0.59) or postmortem pathology (22.4%±1.2% versus 20.2%±1.2%; P=0.21). IS relative to area-at-risk averaged 44.5%±5.0% in vehicle-treated versus 38.2%±6.8% in metformin-treated animals (P=0.46). There was no difference in global function 7 days after myocardial infarction as assessed by echocardiography or computed tomographic ejection fraction (56.2%±2.6% versus 56.3%±2.4%; P=0.98). Conclusions: In contrast to rodent hearts, postconditioning with high-dose metformin administered immediately before reperfusion does not reduce IS or improve LV function 7 days after myocardial infarction in swine. These results reinforce the importance of rigorously testing therapies in large animal models to facilitate clinical translation of novel cardioprotective therapies.