Miracle-dz/UniFAR-FTUs huggingface dataset:
Spinal block and delirium in oncologic patients after laparoscopic surgery in the Trendelenburg position: A randomized controlled trial

Delirium is the most common postsurgical neurological complication and has a variable incidence rate. Laparoscopic surgery, when associated with the Trendelenburg position, can cause innumerable physiological changes and increase the risk of neurocognitive changes. The association of general anesthesia with a spinal block allows the use of lower doses of anesthetic agents for anesthesia maintenance and facilitates better control over postoperative pain. Our primary outcome was to assess whether a spinal block influences the incidence of delirium in oncologic patients following laparoscopic surgery in the Trendelenburg position. Our secondary outcome was to analyze whether there were other associated factors. A total of 150 oncologic patients who underwent elective laparoscopic surgeries in the Trendelenburg position were included in this randomized controlled trial. The patients were randomized into 2 groups: the general anesthesia group and the general anesthesia plus spinal block group. Patients were immediately evaluated during the postoperative period and monitored until they were discharged, to rule out the presence of delirium. Delirium occurred in 29 patients in total (22.3%) (general anesthesia group: 30.8%; general anesthesia plus spinal block: 13.8% p = 0.035). Patients who received general anesthesia had a higher risk of delirium than patients who received general anesthesia associated with a spinal block (odds ratio = 3.4; 95% confidence interval: 1.2–9.6; p = 0.020). Spinal block was associated with reduced delirium incidence in oncologic patients who underwent elective laparoscopic surgeries in the Trendelenburg position.
Rab11 is required for lysosome exocytosis through the interaction with Rab3a, Sec15 and GRAB.

Lysosomes are dynamic organelles, capable of undergoing exocytosis. This process is crucial for several cellular functions, namely plasma membrane repair. Nevertheless, the molecular machinery involved in this process is poorly understood. Here, we identify Rab11a and Rab11b as regulators of calcium-induced lysosome exocytosis. Interestingly, Rab11-positive vesicles transiently interact with lysosomes at the cell periphery, indicating that this interaction is required for the last steps of lysosome exocytosis. Additionally, we found that the silencing of the exocyst subunit Sec15, a Rab11 effector, impairs lysosome exocytosis, suggesting that Sec15 acts together with Rab11 in the regulation of lysosome exocytosis. Furthermore, we show that Rab11 binds the guanine nucleotide exchange factor for Rab3a (GRAB) and also Rab3a, which we described previously as a regulator of the positioning and exocytosis of lysosomes. Thus, our study identifies new players required for lysosome exocytosis and suggest the existence of a Rab11-Rab3a cascade involved in this process.
Green synthesis of Ni‐Cu‐Zn ferrite nanoparticles using tragacanth gum and their use as an efficient catalyst for the synthesis of polyhydroquinoline derivatives

Ni0.35Cu0. 25Zn0.4Fe2O4 MNPs were synthesized using tragacanth gum as biotemplate and Metals nitrate as the metal source by the sol–gel method. The sample was characterized by powder X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), vibrating sample magnetometer (VSM), scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX). The nanoparticles exhibit ferromagnetic behaviour at room temperature, with a saturation magnetization of 52.76 emu/g and a coercivity of 80.14 Oe. Thereupon, Ni-Cu-Zn ferrite nanoparticles as an efficient catalyst was used for the synthesis of polyhydroquinoline derivatives via multi-component reactions under microwave irradiation. Simple work-up, mild reaction conditions, short reaction times, use of an economically convenient catalyst, and excellent product yields are the advantageous features of this method. The catalyst could easily be recycled and reused few times without noticeable decrease in catalytic activity.
Effects of juvenile hormone in fertility and fertility-signaling in workers of the common wasp Vespula vulgaris

In the highly eusocial wasp, Vespula vulgaris, queens produce honest signals to alert their subordinate workers of their fertility status, and therefore they are reproductively suppressed and help in the colony. The honesty of the queen signals is likely maintained due to hormonal regulation, which affects fertility and fertility cue expression. Here, we tested if hormonal pleiotropy could support the hypothesis that juvenile hormone controls fertility and fertility signaling in workers. In addition, we aimed to check oocyte size as a proxy of fertility. To do that, we treated V. vulgaris workers with synthetic versions of juvenile hormone (JH) analogue and a JH inhibitor, methoprene and precocene, respectively. We dissected the treated females to check ovary activation and analyzed their chemical profile. Our results showed that juvenile hormone has an influence on the abundance of fertility linked compounds produced by workers, and it also showed to increase oocyte size in workers. Our results corroborate the hypothesis that juvenile hormone controls fertility and fertility signaling in workers, whereby workers are unable to reproduce without alerting other colony members of their fertility. This provides supports the hypothesis that hormonal pleiotropy contributes to keeping the queen fertility signals honest.
Moving beyond the constraints of chemistry via crystal structure discovery with isotropic multiwell pair potentials

Significance Which crystal structures are possible if the restrictions of the quantum realm are lifted? Our knowledge of ordered particle geometries was previously restricted to the kinds of structures observable in hard condensed matter—on the atomic scale. Here, we use freely tunable computational models to represent particles with variable properties, and we determine the crystal structures into which they self-assemble. The resulting arrangements often correspond to structures known from atomic-scale materials; however, we discover a comparable number of previously unknown crystal structures with different local coordination motifs, incompatible with the limitations of the chemical bond. Our results can be used to engineer soft condensed matter with unprecedented, ordered geometries, paving the way toward materials with potentially novel properties. The rigid constraints of chemistry—dictated by quantum mechanics and the discrete nature of the atom—limit the set of observable atomic crystal structures. What structures are possible in the absence of these constraints? Here, we systematically crystallize one-component systems of particles interacting with isotropic multiwell pair potentials. We investigate two tunable families of pairwise interaction potentials. Our simulations self-assemble a multitude of crystal structures ranging from basic lattices to complex networks. Sixteen of the structures have natural analogs spanning all coordination numbers found in inorganic chemistry. Fifteen more are hitherto unknown and occupy the space between covalent and metallic coordination environments. The discovered crystal structures constitute targets for self-assembly and expand our understanding of what a crystal structure can look like.
Combined Blockade of MEK and CDK4/6 Pathways Induces Senescence to Improve Survival in Pancreatic Ductal Adenocarcinoma

Activating KRAS mutations, a defining feature of pancreatic ductal adenocarcinoma (PDAC), promote tumor growth in part through the activation of cyclin-dependent kinases (CDK) that induce cell-cycle progression. p16INK4a (p16), encoded by the gene CDKN2A, is a potent inhibitor of CDK4/6 and serves as a critical checkpoint of cell proliferation. Mutations in and subsequent loss of the p16 gene occur in PDAC at a rate higher than that reported in any other tumor type and results in Rb inactivation and unrestricted cellular growth. Therefore, strategies targeting downstream RAS pathway effectors combined with CDK4/6 inhibition (CDK4/6i) may have the potential to improve outcomes in this disease. Herein, we show that expression of p16 is markedly reduced in PDAC tumors compared with normal pancreatic or pre-neoplastic tissues. Combined MEK inhibition (MEKi) and CDK4/6i results in sustained downregulation of both ERK and Rb phosphorylation and a significant reduction in cell proliferation compared with monotherapy in human PDAC cells. MEKi with CDK4/6i reduces tumor cell proliferation by promoting senescence-mediated growth arrest, independent of apoptosis in vitro. We show that combined MEKi and CDK4/6i treatment attenuates tumor growth in xenograft models of PDAC and improves overall survival over 200% compared with treatment with vehicle or individual agents alone in Ptf1acre/+;LSL-KRASG12D/+;Tgfbr2flox/flox (PKT) mice. Histologic analysis of PKT tumor lysates reveal a significant decrease in markers of cell proliferation and an increase in senescence-associated markers without any significant change in apoptosis. These results demonstrate that combined targeting of both MEK and CDK4/6 represents a novel therapeutic strategy to synergistically reduce tumor growth through induction of cellular senescence in PDAC.
Genetic diversity of Francisella tularensis subsp. holarctica in Kazakhstan

Tularemia is a highly dangerous zoonotic infection due to the bacteria Francisella tularensis. Low genetic diversity promoted the use of polymorphic tandem repeats (MLVA) as first-line assay for genetic description. Whole genome sequencing (WGS) is becoming increasingly accessible, opening the perspective of a time when WGS might become the universal genotyping assay. The main goal of this study was to describe F. tularensis strains circulating in Kazakhstan based on WGS data and develop a MLVA assay compatible with in vitro and in silico analysis. In vitro MLVA genotyping and WGS were performed for the vaccine strain and for 38 strains isolated in Kazakhstan from natural water bodies, ticks, rodents, carnivores, and from one migratory bird, an Isabellina wheatear captured in a rodent burrow. The two genotyping approaches were congruent and allowed to attribute all strains to two F. tularensis holarctica lineages, B.4 and B.12. The seven tandem repeats polymorphic in the investigated strain collection could be typed in a single multiplex PCR assay. Identical MLVA genotypes were produced by in vitro and in silico analysis, demonstrating full compatibility between the two approaches. The strains from Kazakhstan were compared to all publicly available WGS data of worldwide origin by whole genome SNP (wgSNP) analysis. Genotypes differing at a single SNP position were collected within a time interval of more than fifty years, from locations separated from each other by more than one thousand kilometers, supporting a role for migratory birds in the worldwide spread of the bacteria.
Association of Lesion Pattern and Dysphagia in Acute Intracerebral Hemorrhage

Supplemental Digital Content is available in the text. Background and Purpose: Dysphagia is a common and severe symptom of acute stroke. Although intracerebral hemorrhages (ICHs) account for 10% to 15% of all strokes, the occurrence of dysphagia in this subtype of stroke has not been widely investigated. The aim of this study was to evaluate the overall frequency and associated lesion locations and clinical predictors of dysphagia in patients with acute ICH. Methods: Our analysis included 132 patients with acute ICH. Clinical swallowing assessment was performed within 48 hours after admission. All patients underwent computed tomography imaging. Voxel-based lesion-symptom mapping was performed to determine lesion sites associated with dysphagia. Results: Eighty-four patients (63.6%) were classified as dysphagic. Higher scores on the National Institutes of Health Stroke Scale, larger ICH volumes, and higher degree of disability were associated with dysphagia. Voxels showing a statistically significant association with dysphagia were mainly located in the right insular cortex, the right central operculum, as well as the basal ganglia, corona radiata, and the left thalamus and left internal capsule. In contrast to lobar regions, in subcortical deep brain areas also small lesion volumes (<10 mL) were associated with a substantial risk of dysphagia. Intraventricular ICH extension and midline shift as imaging findings indicating a space-occupying effect were not associated with dysphagia in multivariate analysis. Conclusions: Dysphagia is a frequent symptom in acute ICH. Distinct cortical and subcortical lesion sites are related to swallowing dysfunction and predictive for the development of dysphagia. Therefore, patients with ICH should be carefully evaluated for dysphagia independently from lesion size, in particular if deep brain regions are affected.
Mechanical basis of shortening functionality

MECHANICAL BASIS OF SHORTENING FUNCTIONALITY Braulio A. Macias Rodriguez Advisor: University of Guelph, 2017 Professor Alejandro G. Marangoni This thesis is an investigation on the functionality of bakery fat shortenings, with major emphasis on the mechanical function of those designed for lamination. Laminating or roll-in shortenings are fats used in the manufacture of layered doughs. Their main role is to separate sheets of dough to allow the formation of a multilayered structure responsible for pastry quality (“puff” and “flakiness”). To achieve this, laminating shortenings must “survive” processing deformations. To date, there is limited understanding on the factors underlying the functionality of these materials. There is also a major shortcoming with their utilization; their typically high content of trans and saturated (inconclusive evidence) fatty acids, implicated in cardiovascular health. These provide strong motivation to understand the structure-function relationships in laminating shortenings. Here, we differentiated physico-chemical and rheological properties of laminating shortenings, from those of shortenings designed for all-purpose, cake and icing applications. We found that laminating shortenings had contents of trisaturated and unsaturated TAGs higher than other shortenings, although their overall “hard” fat content were comparable. Physical properties, believed to be crucial to designate the laminating functionality such as polymorphism, solid fat content and melting, were comparable. Laminating shortenings hosted a range of rheological properties; some common to other fats and some unique to their mechanical functionality. While elastic material properties were comparable to those of other shortenings, their viscous properties were strikingly different. Stress responses to large amplitude oscillatory shear (LAOS) revealed that the laminating shortenings behave as viscoelastic ductile solids, in that they convert the vast majority of the released strain energy into viscous dissipative energy, associated with plastic flow. Structural investigations indicated that laminating shortenings featured smaller and smooth crystal nanoplatelets, three hierarchy levels, and crystal aggregates with layer-like arrangements. It is suggested that the hierarchy and microstructure spatial distribution play a pivotal role on high-energy dissipation (rather than on energy storage) which confers superior load-bearing ability in laminating shortenings. This research provides a good ground for advancing our understanding on the macro functionality of laminating shortenings and guide the selection and design of healthier alternative lipid structuring materials based on the displayed rheological behavior.
Critical slowing down suggests that the western Greenland Ice Sheet is close to a tipping point

Significance It has been suggested that, in response to anthropogenic global warming, the Greenland Ice Sheet may reach a tipping point beyond which its current configuration would become unstable. A crucial nonlinear mechanism for the existence of this tipping point is the positive melt-elevation feedback: Melting reduces ice sheet height, exposing the ice sheet surface to warmer temperatures, which further accelerates melting. We reveal early-warning signals for a forthcoming critical transition from ice-core-derived height reconstructions and infer that the western Greenland Ice Sheet has been losing stability in response to rising temperatures. We show that the melt-elevation feedback is likely to be responsible for the observed destabilization. Our results suggest substantially enhanced melting in the near future. The Greenland Ice Sheet (GrIS) is a potentially unstable component of the Earth system and may exhibit a critical transition under ongoing global warming. Mass reductions of the GrIS have substantial impacts on global sea level and the speed of the Atlantic Meridional Overturning Circulation, due to the additional freshwater caused by increased meltwater runoff into the northern Atlantic. The stability of the GrIS depends crucially on the positive melt-elevation feedback (MEF), by which melt rates increase as the overall ice sheet height decreases under rising temperatures. Melting rates across Greenland have accelerated nonlinearly in recent decades, and models predict a critical temperature threshold beyond which the current ice sheet state is not maintainable. Here, we investigate long-term melt rate and ice sheet height reconstructions from the central-western GrIS in combination with model simulations to quantify the stability of this part of the GrIS. We reveal significant early-warning signals (EWS) indicating that the central-western GrIS is close to a critical transition. By relating the statistical EWS to underlying physical processes, our results suggest that the MEF plays a dominant role in the observed, ongoing destabilization of the central-western GrIS. Our results suggest substantial further GrIS mass loss in the near future and call for urgent, observation-constrained stability assessments of other parts of the GrIS.
Serum lipid and adiponectin/leptin ratio changes after a Mediterranean dietary pattern in non-g-allele carriers of the genetic variant of adiponectin gene rs822393.

OBJECTIVE One common genetic variant rs822393 (-4522C/T) is located in the proximal promoter region of the ADIPOQ gene. The SNP rs822393 regulates adiponectin promoter activity and is associated with hypoadiponectinemia. The aim of our study was to analyze the effects after a hypocaloric diet with Mediterranean diet pattern on serum lipid and adipokine levels taking to account rs822393 of ADIPOQ. PATIENTS AND METHODS A population of 270 obese patients was enrolled. Anthropometric parameter and serum parameters (lipid profile, insulin, homeostasis model assessment (HOMA-IR), glucose, C reactive protein, adiponectin, resistin and leptin levels) were measured, at basal time and after 3 months. All patients were genotyped in the rs822393 polymorphism. RESULTS The genotype distribution was: 160 patients (59.3%) CC, 96 patients CT (35.6%) and 14 patients CT (5.1%). After dietary intervention, BMI, weight, fat mass, waist circumference, systolic blood pressure, insulin levels, HOMA-IR, total cholesterol and LDL- cholesterol improved significantly in both genotypes. After dietary intervention (CC vs. CT+TT), HDL-cholesterol (delta: 5.4±1.4 mg/dl vs. -1.8±0.7 mg/dl; p=0.03), serum adiponectin (delta: 21.2±4.1 ng/dl vs. 3.8±3.3 ng/dl; p=0.02) and adiponectin/leptin ratio (delta: 0.53±0.1 vs. 0.16±0.3 ng/dl; p=0.02) improved only in non-T allele carriers. Basal and post-intervention HDL cholesterol, adiponectin levels and adiponectin/leptin ratio were lower in T-allele carriers than non-T Allele carriers. CONCLUSIONS T allele carriers show lower levels of HDL-cholesterol, adiponectin and adiponectin/leptin ratio than non-T allele carriers. During a hypocaloric diet with Mediterranean partner increases HDL Cholesterol, adiponectin levels and ratio adiponectin/leptin in non-T allele carriers.
Application of beta and gamma carbonic anhydrase sequences as tools for identification of bacterial contamination in the whole genome sequence of inbred Wuzhishan minipig (Sus scrofa) annotated in databases

Abstract Sus scrofa or pig was domesticated thousands of years ago. Through various indigenous breeds, different phenotypes were produced such as Chinese inbred miniature minipig or Wuzhishan pig (WZSP), which is broadly used in the life and medical sciences. The whole genome of WZSP was sequenced in 2012. Through a bioinformatics study of pig carbonic anhydrase (CA) sequences, we detected some β- and γ-class CAs among the WZSP CAs annotated in databases, while β- or γ-CAs had not previously been described in vertebrates. This finding urged us to analyze the quality of whole genome sequence of WZSP for the possible bacterial contamination. In this study, we used bioinformatics methods and web tools such as UniProt, European Bioinformatics Institute, National Center for Biotechnology Information, Ensembl Genome Browser, Ensembl Bacteria, RSCB PDB and Pseudomonas Genome Database. Our analysis defined that pig has 12 classical α-CAs and 3 CA-related proteins. Meanwhile, it was approved that the detected CAs in WZSP are categorized in the β- and γ-CA families, which belong to Pseudomonas spp. and Acinetobacter spp. The protein structure study revealed that the identified β-CA sequence from WZSP belongs to Pseudomonas aeruginosa with PDB ID: 5JJ8, and the identified γ-CA sequence from WZSP belongs to P. aeruginosa with PDB ID: 3PMO. Bioinformatics and computational methods accompanied with bacterial-specific markers, such as 16S rRNA and β- and γ-class CA sequences, can be used to identify bacterial contamination in mammalian DNA samples.
Effects of biofeedback on whole lower limb joint kinematics and external kinetics

ABSTRACT Biofeedback (BFb) is a useful tool to accelerate the skill development process. Limited research has applied BFb to the whole lower-limb in a complex skill therefore the aim of this research was to assess the effectiveness of a biofeedback intervention targeting whole lower limb kinematics. Thirty-two healthy participants were randomized to a BFb (n = 16) and a Control group (n = 16). Participants visited a motion capture laboratory on three occasions during one week, and returned for retention testing at 4–6 weeks. Following introduction to a novel lunge-touch task, visual BFb on lower limb joint kinematic extension angular velocities (ω) and timing were provided following each lunge. BFb was effective in increasing Hipω (F = 3.746, p = 0.03) and Kneeω (F = 10.241, p = 0.01). Peak Ankleω remained unchanged (F = 1.537, p = 0.23, η2 = 0.05), however Peak Ankleθ (F = 10.915, p < 0.001, η2 = 0.27) and AnkleROM (F = 9.543, p < 0.001, η2 = 0.24) significantly increased. Despite kinematic changes, there were no significant changes in any external kinetics. No significant correlations were found between Hipω, Kneeω or Ankleω and horizontal impulse (ImpulseY: r = 0.20, p = 0.26; r = −0.11, p = 0.24; and r = 0.22, p = 0.28, respectively). Findings demonstrate that BFb can be used to alter multiple kinematic variables in a complex skill, but do not necessarily alter associated kinetic variables not directly targeted by BFb.