bluuebunny/crossref_metadata_2025_split huggingface dataset:
Schizophrenia and Criminal Responsibility
Authors: Tsimploulis Georgios , Niveau Gérard , Eytan Ariel , Giannakopoulos Panteleimon , Sentissi Othman 
Published: April 2018

Abstract
The significant progress of psychiatry in the 20th century provided a sophisticated theoretical framework to analyze the complex relationships between crime and mental illness. Schizophrenia has been traditionally associated with severe cognitive and affective deficits that heavily influence empathy, judgment capacities, but also control of impulsiveness. Although there is an association between psychotic disorders and absence or decrease of legal responsibility, their relationship is also determined by sociodemographic, developmental, and clinical factors. These disorders are associated not only with abolished criminal responsibility but also with diminished responsibility. We conduct a systematic literature review to examine the relation between schizophrenia and criminal responsibility. We have found that this clinical entity is often associated with diminished or abolished criminal liability. We discuss these findings, focusing on the specific deficits found in patients with schizophrenia and examining how this problem affects their behavior and eventually their accountability for their crimes.
Forearm-Based Turnover Muscle Flaps for Elbow Soft-Tissue Reconstruction: A Comparison of Regional Coverage Based on Distal Flap Perfusion
Authors: Avashia Yash J. , Shammas Ronnie L. , Poveromo Luke P. , Dekker Travis J. , Brubacher Jacob W. , Richard Marc J. , Ruch David S. , Mithani Suhail K. 
Published: April 2018

Background:
Elbow wounds pose a reconstructive challenge. Prior studies have described the vascular anatomy of both the brachioradialis and flexor carpi ulnaris muscle flaps. The goal of this study was to describe the distal flap perfusion of the flexor carpi radialis, with a direct comparison of the brachioradialis, flexor carpi ulnaris, and flexor carpi radialis muscle flaps for coverage around the elbow.

Methods:
Six fresh-frozen upper extremity specimens were dissected for brachioradialis, flexor carpi radialis, and flexor carpi ulnaris flaps. Vascular data from prior studies were combined with our anatomical measurements to determine the area of perfused coverage around the elbow for the brachioradialis and flexor carpi ulnaris. The flexor carpi radialis flap distal vascular perfusion was examined separately with transverse sections at 1-cm intervals after India ink injections to determine distal flap perfusion and elbow coverage. Perfusion data were plotted on x and y axes over the posterior elbow.

Results:
The brachioradialis muscle covered an average of 56 percent of the x axis and 7.4 percent of the y axis. The flexor carpi ulnaris muscle covered an average of 90 percent of the elbow along the x axis and 23.3 percent of elbow along the y axis. The flexor carpi radialis covered an average of 34 percent of the x axis and 4.8 percent of the y axis.

Conclusion:
The flexor carpi ulnaris muscle provides the most versatile and robust coverage over the posterior elbow, followed by the brachioradialis muscle, which consistently provides coverage over the lateral epicondyle.
Effect of One-Stage versus Two-Stage Palatoplasty on Hypernasality and Fistula Formation in Children with Complete Unilateral Cleft Lip and Palate: A Randomized Controlled Trial
Authors: Reddy Rajgopal R. , Gosla Reddy Srinivas , Chilakalapudi Anusha , Kokali Swapnika , Bronkhorst Ewald M. , Kummer Ann W. , Bergé Stefaan J. , Kuijpers-Jagtman Anne Marie 
Published: April 2018

Background:
Is one-stage or two-stage palatoplasty more effective for preventing fistula formation and hypernasality in patients with complete unilateral cleft lip and palate?

Methods:
This parallel blocked randomized controlled trial included 100 patients with nonsyndromic complete unilateral cleft lip and palate with a repaired cleft lip, divided into two equal groups. Group A had one-stage palatoplasty patients at age 12 to 13 months while group B had two-stage palatoplasty patients with soft palatoplasty at age 12 to 13 months and hard palatoplasty at age 24 to 25 months. Presence of a fistula was tested clinically at 3 years and speech was tested using nasometry and perceptual analyses at 6 years. Group C consisted of noncleft controls (n = 20, age 6 years) for speech using nasometry. Fistula rates, hypernasality ratings, and nasalance scores were compared between groups A and B. Nasometry recordings of groups A and B were compared with control group C.

Results:
There was no difference in fistula rates between groups A and B (p = 0.409; 95 percent CI, 0.365 to 11.9). Mean nasalance scores of group A showed higher nasalance than group B (p = 0.006; 95 percent CI, 1.16 to 6.53). Perceptual analysis showed no difference between groups A and B (p = 0.837 and p = 1.000). Group A showed higher mean nasalance than group C (p = 0.837 and p = 1.000), whereas group B showed no difference (p = 0.088; 95 percent CI, −0.14 to 2.02).

Conclusions:
There was no difference in fistula rates between groups. Nasalance was slightly higher in patients in the one-stage palatoplasty group than two-stage palatoplasty group, but the difference was not clinically significant.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, II.
Impact of the Glymphatic System on the Kinetic and Distribution of Gadodiamide in the Rat Brain
Authors: Taoka Toshiaki , Jost Gregor , Frenzel Thomas , Naganawa Shinji , Pietsch Hubertus 
Published: April 2018

Objectives
The glymphatic system is a recently hypothesized waste clearance system of the brain in which perivascular space constitutes a pathway similar to the lymphatic system in other body regions. Sleep and anesthesia are reported to influence the activity of the glymphatic system. Because rats are nocturnal animals, the glymphatic system is expected to be more active during the day. We attempted to elucidate the influence of the glymphatic system for intravenously injected gadodiamide in the rat brain by 2 experiments. One was a magnetic resonance imaging (MRI) experiment to evaluate the short-term dynamics of signal intensity changes after gadodiamide administration. The other was a quantification experiment to evaluate the concentration of retained gadolinium within the rat brain after repeated intravenous administration of gadodiamide at different times of day and levels of anesthesia.

Materials and Methods
The imaging experiment was performed on 6 rats that received an intravenous injection of gadodiamide (1 mmol/kg) and dynamic MRI for 3 hours at 2.4-minute intervals. The time course of the signal intensity changes was evaluated for different brain structures. The tissue quantification experiment was performed on 24 rats divided into 4 groups by injection time (morning, late afternoon) and anesthesia (none, short, long) during administration. All animals received gadodiamide (1.8 mmol/kg, 8 times over 2 weeks). Gadolinium concentration of dissected brain tissues was quantified 5 weeks after the last administration by inductively coupled plasma mass spectrometry.

Results
In the imaging experiment, muscle and the fourth ventricle showed an instantaneous signal intensity increase immediately after gadodiamide injection. The signal curve of the cerebral cortex and deep cerebellar nuclei reached the peak signal intensity later than the fourth ventricle but earlier than that of the prepontine cistern. In the gadolinium quantification experiment, the concentration in the group with the morning injection showed a significantly lower concentration than the late afternoon injection group. The lowest tissue gadolinium concentrations were found in the groups injected in the morning during long anesthesia.

Conclusions
Instantaneous transition of gadodiamide from blood to cerebrospinal fluid was indicated by dynamic MRI. The gadodiamide distribution to the cerebral cortex and deep cerebellar nuclei seemed to depend on both blood flow and cerebrospinal fluid. This confirms previous studies indicating that the cerebrospinal fluid is one potential pathway of gadolinium-based contrast agent entry into the brain. For the distribution and clearance of the gadodiamide from brain tissue, involvement of the glymphatic system seemed to be indicated in terms of the influence of sleep and anesthesia.
Influence of hyaluronic acid transitions in tumor microenvironment on glioblastoma malignancy and invasive behavior
Authors: Chen Jee-Wei E , Pedron Sara , Shyu Peter , Hu Yuhang , Sarkaria Jann N , Harley Brendan A C 
Published: April 2018

AbstractThe extracellular matrix (ECM) is critical in tumor growth and invasive potential of cancer cells. In glioblastoma tumors, some components of the native brain ECM such as hyaluronic acid (HA) have been suggested as key regulators of processes associated with poor patient outlook such as invasion and therapeutic resistance. Given the importance of cell-mediated remodeling during invasion, it is likely that the molecular weight of available HA polymer may strongly influence GBM progression. Biomaterial platforms therefore provide a unique opportunity to systematically examine the influence of the molecular weight distribution of HA on GBM cell activity. Here we report the relationship between the molecular weight of matrix-bound HA within a methacrylamide-functionalized gelatin (GelMA) hydrogel, the invasive phenotype of a patient-derived xenograft GBM population that exhibits significant in vivo invasivity, and the local production of soluble HA during GBM cell invasion. Hyaluronic acid of different molecular weights spanning a range associated with cell-mediated remodeling (10, 60, and 500 kDa) was photopolymerized into GelMA hydrogels, with cell activity compared to GelMA only conditions (-HA). Polymerization conditions were tuned to create a homologous series of GelMA hydrogels with conserved poroelastic properties (i.e. shear modulus, Poisson’s ratio, and diffusivity). GBM migration was strongly influenced by HA molecular weight. While markers associated with active remodeling of the HA content, hyaluronan synthase and hyaluronidase, were found to be insensitive to matrix immobilized HA content. These results provide new information regarding the importance of local hyaluronic acid content on the invasive phenotype of GBM.
WDFY2 restrains matrix metalloprotease secretion and cell invasion by retention of VAMP3 in endosomal tubules
Authors: Sneeggen Marte , Pedersen Nina Marie , Campsteijn Coen , Haugsten Ellen Margrethe , Stenmark Harald , Schink Kay Oliver 
Published: April 2018

AbstractThe endosomal FYVE- and WD40-domain-containing protein WDFY2 has been assigned a function as tumour suppressor, but its functional mechanism has remained elusive. Here we have used confocal, widefield and super-resolution fluorescence microscopy to show that WDFY2 localizes to the base of retromer-containing endosomal tubules by a mechanism that involves recognition of a specific pool of phosphatidylinositol 3-phosphate (PtdIns3P) by the WDFY2 FYVE domain. Affinity purification and mass spectrometry identified the v-SNARE VAMP3 as an interaction partner of WDFY2, and cellular knockout of WDFY2 caused a strong redistribution of VAMP3 into small vesicles near the plasma membrane. This was accompanied by increased secretion of the matrix metalloprotease MT1-MMP, enhanced degradation of extracellular matrix, and increased cell invasion. WDFY2 is frequently lost in metastatic cancers, most predominantly in ovarian and prostate cancer. We propose that WDFY2 acts as a tumor suppressor by serving as a gatekeeper for VAMP3 recycling.
Spatial Mark-Resight for Categorically Marked Populations with an Application to Genetic Capture-Recapture
Authors: Augustine Ben C. , Stewart Frances E. C. , Royle J. Andrew , Fisher Jason T. , Kelly Marcella J. 
Published: April 2018

AbstractThe estimation of animal population density is a fundamental goal in wildlife ecology and management, commonly met using mark recapture or spatial mark recapture (SCR) study designs and statistical methods. Mark-recapture methods require the identification of individuals; however, for many species and sampling methods, particularly noninvasive methods, no individuals or only a subset of individuals are individually identifiable. The unmarked SCR model, theoretically, can estimate the density of unmarked populations; however, it produces biased and imprecise density estimates in many sampling scenarios typically encountered. Spatial mark-resight (SMR) models extend the unmarked SCR model in three ways: 1) by introducing a subset of individuals that are marked and individually identifiable, 2) introducing the possibility of individual-linked telemetry data, and 3) introducing the possibility that the capture-recapture data from the survey used to deploy the marks can be used in a joint model, all improving the reliability of density estimates. The categorical spatial partial identity model (SPIM) improves the reliability of density estimates over unmarked SCR along another dimension, by adding categorical identity covariates that improve the probabilistic association of the latent identity samples. Here, we combine these two models into a “categorical SMR” model to exploit the benefits of both models simultaneously. We demonstrate using simulations that SMR alone can produce biased and imprecise density estimates with sparse data and/or when few individuals are marked. Then, using a fisher (Pekania pennanti) genetic capture-recapture data set, we show how categorical identity covariates, marked individuals, telemetry data, and jointly modeling the capture survey used to deploy marks with the resighting survey all combine to improve inference over the unmarked SCR model. As previously seen in an application of the categorical SPIM to a real-world data set, the fisher data set demonstrates that individual heterogeneity in detection function parameters, especially the spatial scale parameter σ, introduces positive bias into latent identity SCR models (e.g., unmarked SCR, SMR), but the categorical SMR model provides more tools to reduce this positive bias than SMR or the categorical SPIM alone. We introduce the possibility of detection functions that vary by identity category level, which will remove individual heterogeneity in detection function parameters than is explained by categorical covariates, such as individual sex. Finally, we provide efficient SMR algorithms that accommodate all SMR sample types, interspersed marking and sighting periods, and any number of identity covariates using the 2-dimensional individual by trap data in conjunction with precomputed constraint matrices, rather than the 3-dimensional individual by trap by occasion data used in SMR algorithms to date.
Dilution and titration of cell-cycle regulators may control cell size in budding yeast
Authors: Heldt Frank S. , Lunstone Reece , Tyson John J. , Novák Béla 
Published: April 2018

AbstractThe size of a cell sets the scale for all biochemical processes within it, thereby affecting cellular fitness and survival. Hence, cell size needs to be kept within certain limits and relatively constant over multiple generations. However, how cells measure their size and use this information to regulate growth and division remains controversial. Here, we present two mechanistic mathematical models of the budding yeast (S. cerevisiae) cell cycle to investigate competing hypotheses on size control: inhibitor dilution and titration of nuclear sites. Our results suggest that an inhibitor-dilution mechanism, in which cell growth dilutes the transcriptional inhibitor Whi5 against the constant activator Cln3, can facilitate size homeostasis. This is achieved by utilising a positive feedback loop to establish a fixed size threshold for the STARTtransition, which efficiently couples cell growth to cell cycle progression. Yet, we show that inhibitor dilution cannot reproduce the size of mutants that alter the cell’s overall ploidy andWHI5gene copy number. By contrast, size control through titration of Cln3 against a constant number of genomic binding sites for the transcription factor SBF recapitulates both size homeostasis and the size of these mutant strains. Moreover, this model produces an imperfect ‘sizer’ behaviour in G1 and a ‘timer’ in S/G2/M, which combine to yield an ‘adder’ over the whole cell cycle; an observation recently made in experiments. Hence, our model connects these phenomenological data with the molecular details of the cell cycle, providing a systems-level perspective of budding yeast size control.
Modified Pearson Correlation Coefficient for Two-color Imaging in Spherocylindrical Cells
Authors: Mohapatra Sonisilpa , Weisshaar James C. 
Published: April 2018

AbstractThe revolution in fluorescence microscopy enables sub-diffraction-limit (“superresolution”) localization of hundreds or thousands of copies of two differently labeled proteins in the same live cell. In typical experiments, fluorescence from the entire three-dimensional (3D) cell body is projected along thez-axis of the microscope to form a 2D image at the camera plane. For imaging of two different species, here denoted “red” and “green”, a significant biological question is the extent to which the red and green spatial distributions are positively correlated, anti-correlated, or uncorrelated. A commonly used statistic for assessing the degree of linear correlation between two image matricesRandGis the Pearson Correlation Coefficient (PCC). PCC should vary from –1 (perfect anti-correlation) to 0 (no linear correlation) to +1 (perfect positive correlation). However, in the special case of spherocylindrical bacterial cells such asE.coliorB.subtilis, we show that the PCC fails both qualitatively and quantitatively. PCC returns the same +1 value for 2D projections of distributions that are either perfectly correlated in 3D or completely uncorrelated in 3D. The PCC also systematically underestimates the degree of anti-correlation between the projections of two perfectly anti-correlated 3D distributions. The problem is that the projection of a random spatial distribution within the 3D spherocylinder is non-random in 2D, whereas PCC compares every matrix element ofRorGwith the constant mean valueRorG. We propose a modified Pearson Correlation Coefficient (MPCC) that corrects this problem for spherocylindrical cell geometry by using the proper reference matrix for comparison withRandG. Correct behavior of MPCC is confirmed for a variety of numerical simulations and on experimental distributions of HU and RNA polymerase in liveE.colicells. The MPCC concept should be generalizable to other cell shapes.
Mono-homologous linear DNA recombination by the non-homologous end-joining pathway as a novel and simple gene inactivation method: a proof of concept study inDietziasp. DQ12-45-1b
Authors: Lu Shelian , Nie Yong , Wang Meng , Xu Hong-Xiu , Ma Dong-Ling , Liang Jie-Liang , Wu Xiao-Lei 
Published: April 2018

ABSTRACTNon-homologous end-joining (NHEJ) is critical for genome stability because of its roles in double-strand break repair. Ku and ligase D (LigD) are the crucial proteins in this process, and strains expressing Ku and LigD can cyclize linear DNAin vivo.Herein, we established a proof-of-concept mono-homologous linear DNA recombination for gene inactivation or genome editing by which cyclization of linear DNAin vivoby NHEJ could be used to generate non-replicable circular DNA and could allow allelic exchanges between the circular DNA and the chromosome. We achieved this approach inDietziasp. DQ12-45-1b, which expresses Ku and LigD homologs and presents NHEJ activity. By transforming the strain with a linear DNA mono homolog to the sequence in chromosome, we mutated the genome. This method did not require the screening of suitable plasmids and was easy and time-effective. Bioinformatic analysis showed that more than 20% prokaryotic organisms contain Ku and LigD, suggesting the wide distribution of NHEJ activities. Moreover, theEscherichia colistrain also showed NHEJ activity when the Ku and LigD ofDietziasp. DQ12-45-1b were introduced and expressed in it. Therefore, this method may be a widely applicable genome editing tool for diverse prokaryotic organisms, especially for non-model microorganisms.IMPORTANCEThe non-model gram-positive bacteria lack efficient genetic manipulation systems, but they express genes encoding Ku and LigD. The NHEJ pathway inDietziasp. DQ12-45-1b was evaluated and was used to successfully knockout eleven genes in the genome. Since bioinformatic studies revealed that the putative genes encoding Ku and LigD ubiquitously exist in phylogenetically diverse bacteria and archaea, the mono-homologous linear DNA recombination by the NHEJ pathway could be a potentially applicable genetic manipulation method for diverse non-model prokaryotic organisms.
Preferred hexoses influence long-term memory and induction of lactose catabolism byStreptococcus mutans
Authors: Zeng Lin , Burne Robert A. 
Published: April 2018

ABSTRACTBacteria prioritize sugar metabolism via carbohydrate catabolite repression, which regulates global gene expression to optimize the catabolism of preferred substrates. Here, we report an unusual long-term memory effect in certainStreptococcus mutansstrains that alters adaptation to growth on lactose after prior exposure to glucose or fructose. In strain GS-5, cells that were first cultured on fructose then transferred to lactose displayed an exceptionally long lag (>11 h) and slower growth, compared to cells first cultured on glucose or cellobiose, which displayed a reduction in lag phase by as much as 10 h. Mutants lacking the cellobiose-PTS or phospho-β-glucosidase lost the accelerated growth on lactose associated with prior culturing on glucose. The memory effects of glucose or fructose on lactose catabolism were not as profound in strain UA159, but the lag phase was considerably shorter in mutants lacking the glucose-PTS EIIMan. Interestingly, whenS.mutanswas cultivated on lactose, significant quantities of free glucose accumulated in the medium, with higher levels found in the cultures of strains lacking EIIMan, glucokinase, or both. Free glucose was also detected in cultures that were utilizing cellobiose or trehalose, albeit at lower levels. Such release of hexoses byS.mutansis likely of biological significance as it was found that cells required small amounts of glucose or other preferred carbohydrates to initiate efficient growth on lactose. These findings suggest thatS.mutansmodulates the induction of lactose utilization based on its prior exposure to glucose or fructose, which can be liberated from common disaccharides.IMPORTANCEUnderstanding the molecular mechanisms employed by oral bacteria to control sugar metabolism is key to developing novel therapies for management of dental caries and other oral diseases. Lactose is a naturally occurring disaccharide that is abundant in dairy products and commonly ingested by humans. However, for the dental caries pathogenStreptococcus mutans, relatively little is known about the molecular mechanisms that regulate expression of genes required for lactose uptake and catabolism. Two peculiarities of lactose utilization byS.mutansare explored here: a)S.mutansexcretes glucose that it cleaves from lactose and b) prior exposure to certain carbohydrates can result in a long-term inability to use lactose. The study begins to shed light on howS.mutansmay bet-hedge to optimize its persistence and virulence in the human oral cavity.