bluuebunny/crossref_metadata_2025_split huggingface dataset:
The value of biomarkers in colorectal cancer
Authors: Wang Jun , Liang Wenjia , Wang Xiangwen , Min Guangtao , Chen Wei , Wang Hongpeng , Yao Nan , Wang Jiancheng 
Published: June 2019

Abstract

Background:
Colorectal cancer (CRC) is the third most common cancer in the world, with 694,000 deaths each year. Despite improvements in treatment strategies in recent years, the overall survival rate of CRC is still very low and the survival rate is highly dependent on the stage at the time of diagnosis. Some biomarkers have shown great potential for early screening of CRC and some have been tested in systematic reviews (SRs). However, the quality of these SRs remains unclear and these SRs did not clarify which biomarker is the optimal diagnostic test. This overview will evaluate the methodological quality of available SRs and compare the diagnostic value of different biomarkers in order to find the best biomarker for diagnosing CRC.

Methods:
A comprehensive literature search for SRs published before February 2019 was conducted in the PubMed, Embase.com, Cochrane Library, and Web of Science without any language restrictions. We will use the assessment of multiple systematic reviews-2 instrument to assess the methodological quality of each SR. Bubble plots will be used to summarize the main characteristics and quality of SRs. Standard pairwise meta-analysis and adjusted indirect comparison will be conducted to compare the diagnostic value of different biomarkers.

Results:
The results of this overview will be submitted to a peer-reviewed journal for publication.

Conclusion:
The findings of this project will provide a general overview and evidence of the diagnostic value of biomarkers in detecting CRC.

PROSPERO registration number:
CRD42019125880.
Patient-centered Involvement in Decision-Making
Authors: Perkins Henry S. , Freed Alisa A. , Cortez Josie D. , Hazuda Helen P. 
Published: June 2019

Background/Objectives:
Ideally, doctors ask each patient’s current views about involvement in decision-making, but inquiries prove inconclusive with some inpatients. Doctors may then need indirect indicators of those views. We, therefore, explored ethnic group and sex as cultural indicators of patients’ current preferences and perceptions about such involvement.

Methods:
In open-response interviews, we asked those preferences and perceptions of 26 Mexican American (MA), 18 Euro-American (EA), and 14 African American (AA) adult inpatients. We content-analyzed responses blindly to identify themes and linked those themes to ethnic group and sex.

Results:
Only sex indicated patients’ current preferences. Regardless of ethnic group, most men preferred decision-making by the doctor (with or without the patient); most women, decision-making by the patient (with or without the doctor). But both ethnic group and sex together indicated patients’ current perceptions. Specifically, each ethnic group as a whole most often perceived decision-making by the doctor alone and the patient alone on separate occasions, but the sexes within ethnic groups differed. For MAs roughly equal numbers of men and women perceived such decision making, for EAs more men than women did so, and for AAs more women than men did so. In addition, no EA men but some EA women perceived decision-making by the doctor alone, and some MA men and women—but no EAs or AAs—perceived decision-making by the patient alone. Primarily ethnic group indicated matches between current preferences and perceptions: Most EAs had matches; most MAs and AAs did not.

Conclusions:
Whenever direct inquiries fail, ethnic group and sex may indicate adult inpatients’ current preferences and perceptions about involvement in decision-making. Yet matching those preferences and perceptions, especially for minority patients, remains difficult.
Brief Report: Outcome of Acute Hepatitis B Virus Infection in HIV-1–Infected Patients: Possible Factors Associated With Resolution or Chronicity
Authors: Morsica Giulia , Galli Laura , Bossolasco Simona , Bagaglio Sabrina , Vercesi Riccardo , Salpietro Stefania , Hasson Hamid , Messina Emanuela , Castagna Antonella , Uberti-Foppa Caterina 
Published: June 2019

Background:
HIV-1 infection impairs cellular immunity, causing a detrimental effect on the natural course of hepatitis B virus (HBV) infection. HBV vaccination is less effective in HIV-1–infected patients. This study aimed to gain insight into HIV-1 infection with persistence of hepatitis B surface antigen (HBsAg) defining chronic hepatitis B infection (CBI) after a primary infection and the possible associated factors.

Setting:
Division of Infectious Diseases, San Raffaele Hospital, Italy.

Methods:
This retrospective study analyzed HIV-1–infected patients diagnosed with acute hepatitis B infection (AHB) based on clinical or laboratory records. CBI was defined as a positive HBsAg result recorded >6 months after an AHB diagnosis. Multivariate logistic regression was applied to assess factors (evaluated at AHB diagnosis) that were associated with CBI.

Results:
Of 63 HIV-1–infected patients with AHB, 23 (36.5%) developed CBI. On multivariate analysis, CBI risk was less likely in patients with HIV-RNA of >50 copies/mL (adjusted odds ratio = 0.03, 95% confidence interval: 0.001 to 0.58, P = 0.021). Dually acting antiretroviral treatment, including one or more drugs active against HIV/HBV (lamivudine, emtricitabine, and tenofovir), seemed to be protective in terms of the clinical outcome of CBI (adjusted odds ratio = 0.07, 95% confidence interval: 0.01 to 1.02, P = 0.050). Among the 23 patients with CBI, 15 (65.2%) lost the hepatitis B e-antigen, while 11 (47.8%) had HBsAg seroclearance during follow-up.

Conclusions:
In HIV-1–infected subjects with AHB, the persistence of HBsAg seemed to occur frequently. Factors associated with a lower CBI risk were detectable HIV load and the use of dually acting antiretroviral treatment during AHB.
Demultiplexing overlapping signaling scaffold functions to probe lipid messenger coupling to cytoskeletal dynamics
Authors: Trenton Nicholaus J. , McLaughlin R. Tyler , Bellamkonda Satya K. , Tsao David S. , Mace Emily M. , Orange Jordan S. , Schweikhard Volker , Diehl Michael R. 
Published: June 2019

ABSTRACTThe coordination of lipid messenger signaling with cytoskeletal regulation is central to many organelle-specific signaling and regulatory processes. While central to many aspects of cell physiology, this coupling often depends on the function of multi-domain scaffolds that orchestrate transient interactions and dynamic feedback among a spectrum of signaling intermediates and regulatory proteins on organelles. Understanding scaffold protein functions has remained challenging given this complexity. This work employs live-cell imaging and statistical analyses to deconvolve (demultiplex) how the multi-domain scaffold IQGAP1 coordinates phosphoinositide signaling with organelle-specific actin regulation and membrane processing events. Using actin-ensconced endosomes that localize to the basal cortex of polarized epithelial cells as a model system, we demonstrate abilities to dissect how IQGAP1 transitions between different actin and endosomal-membrane tethered states. We provide evidence IQGAP1 functions as a transient inhibitor of actin growth around the endosomes in at least one of these states. While not easily distilled via standard (static) colocalization analyses or traditional pathway perturbations methods, this negative regulation was revealed via a series of dynamic correlation and multiple regression analyses. These methods also uncovered that the negative actin regulation is linked to GTPase-dependent tethering to the endosomal membrane. Moreover, the scaffold transitions underlying this control are shown to depend on the production of PIP3 lipid messengers by the lipid kinase PI3K. Overall, these methods and results provide new insights in to how IQGAP1 act as a signaling hub by orchestrating time-dependent membrane and cytoskeletal protein interactions and provide new routes to dissect scaffold-mediated pathway regulation in a variety of settings.
scRecover: Discriminating true and false zeros in single-cell RNA-seq data for imputation
Authors: Miao Zhun , Li Jiaqi , Zhang Xuegong 
Published: June 2019

AbstractHigh-throughput single-cell RNA-seq (scRNA-seq) data contains excess zero values, including those of genes not expressed in the cell, and those produced due to dropout events. Existing imputation methods do not distinguish these two types of zeros. We present a modest imputation method scRecover to only impute the dropout zeros. It estimates the zero dropout probability of each gene in each cell, and predicts the number of truly expressed genes in the cell. scRecover is combined with other imputation methods like scImpute, SAVER and MAGIC to fulfil the imputation. Down-sampling experiments show that it recovers dropout zeros with higher accuracy and avoids over-imputing true zero values. Experiments on real data illustrate scRecover improves downstream analysis and visualization.
Modified covariance beamformer for solving MEG inverse problem in the environment with correlated sources
Authors: Kuznetsova Aleksandra , Nurislamova Yulia , Ossadtchi Alexei 
Published: June 2019

AbstractMagnetoencephalography (MEG) is a neuroimaging method ideally suited for non-invasive studies of brain dynamics. MEG’s spatial resolution critically depends on the approach used to solve the ill-posed inverse problem in order to transform sensor signals into cortical activation maps. Over recent years non-globally optimized solutions based on the use of adaptive beamformers (BF) gained popularity.When operating in the environment with a small number of uncorrelated sources the BFs perform optimally and yield spatial super-resolution. However, the BFs are known to fail when dealing with correlated sources acting like poorly tuned spatial filters with low signal-to-noise ratio (SNR) of the output timeseries and often meaningless cortical maps of power distribution.This fact poses a serious limitation on the broader use of this promising technique especially since fundamental mechanisms of brain functioning, its inherent symmetry and task-based experimental paradigms result into a great deal of correlation in the activity of cortical sources. To cope with this problem, we developed a novel beamformer approach that preserves high spatial resolution in the environments with correlated sources.At the core of our method is a projection operation applied to the vectorized sensor-space covariance matrix. This projection does not remove the activity of the correlated sources from the sensor-space covariance matrix but rather selectively handles their contributions to the covariance matrix and creates a sufficiently accurate approximation of an ideal data covariance that could hypothetically be observed should these sources be uncorrelated. Since the projection operation is reciprocal to the PSIICOS method developed by us earlier (Ossadtchi et al. (2018)) we refer to the family of algorithms presented here as ReciPSIICOS.We asses the performance of the novel approach using realistically simulated MEG data and show its superior performance in comparison to the well established MNE and classical BF approaches. We have also applied our approach to the MEG datasets from the two experiments involving two different auditory tasks.The analysis of experimental MEG datasets showed that beamformers from ReciPSIICOS family, but not MNE and the classical BF, discovered the expected bilateral focal sources in the primary auditory cortex and detected motor cortex activity associated with the audio-motor task. Moreover, ReciPSIICOS beamformers yielded cortical activity estimates with amplitude an order of magnitude higher than that obtained with the classical BF, which indicates the severeness of the signal cancellation problem when applying classical beamformers to MEG signals generated by synchronous sources.
SMCHD1 Promotes ATM-dependent DNA Damage Signaling and Repair of Uncapped Telomeres
Authors: Vančevska Aleksandra , Pfeiffer Verena , Feretzaki Marianna , Ahmed Wareed , Lingner Joachim 
Published: June 2019

AbstractSMCHD1 (structural maintenance of chromosomes flexible hinge domain containing protein 1) has been implicated in X-chromosome inactivation, imprinting and DNA damage repair. Mutations inSMCHD1can also cause facioscapulohumoral muscular dystrophy. More recently, SMCHD1 has also been detected as component of telomeric chromatin. Here, we identify requirements of SMCHD1 for DNA damage signaling and non-homologous end joining (NHEJ) at unprotected telomeres. Co-depletion of SMCHD1 with TRF2 reduced the rate of 3’ overhang removal in time course experiments and the number of telomere end fusions. In SMCHD1 deficient cells, the formation of ATM pS1981, γH2AX and 53BP1 containing telomere dysfunction induced foci (TIFs) were diminished indicating defects in checkpoint signaling. Strikingly, removal of TPP1 and subsequent activation of ATR signaling rescued telomere fusion events in TRF2-depletedSMCHD1knockout cells. Together, these data indicate that SMCHD1 depletion reduces telomere fusions in TRF2-depleted cells due to defects in ATM-dependent DNA checkpoint signaling. SMCHD1 mediates DNA damage signaling activation upstream of ATM phosphorylation at uncapped telomeres.
TRIM69 inhibits Vesicular Stomatitis Indiana Virus (VSIV)
Authors: Rihn Suzannah J. , Aziz Muhamad Afiq , Stewart Douglas G. , Hughes Joseph , Turnbull Matthew L. , Varela Mariana , Sugrue Elena , Herd Christie S. , Stanifer Megan , Sinkins Steven P. , Palmarini Massimo , Wilson Sam J. 
Published: June 2019

ABSTRACTVesicular Stomatitis Indiana Virus (VSIV) is a model virus that is exceptionally sensitive to the inhibitory action of interferons. Interferons induce an antiviral state by stimulating the expression of hundreds of interferon stimulated genes (ISGs). These ISGs constrain viral replication, limit tissue tropism, reduce pathogenicity and inhibit viral transmission. Because VSIV is used as a backbone for multiple oncolytic and vaccine strategies, understanding how ISGs restrict VSIV, not only helps in understanding VSIV-pathogenesis, but helps evaluate and understand the safety and efficacy of VSIV-based therapies. Thus there is a need to identify and characterize the ISGs that possess anti-VSIV activity. Using arrayed ISG expression screening, we identified TRIM69 as an ISG that potently inhibits VSIV. This inhibition was highly specific as multiple viruses (including influenza A virus, HIV-1, Rift Valley Fever Virus and dengue virus) were not affected by TRIM69. Indeed, just one amino acid substitution in VSIV can govern sensitivity/resistance to TRIM69. TRIM69 is highly divergent in human populations and exhibits signatures of positive selection that are consistent with this gene playing a key role in antiviral immunity. We propose that TRIM69 is an IFN-induced inhibitor of VSIV and speculate that TRIM69 could be important in limiting VSIV pathogenesis and might influence the specificity and/or efficacy of vesiculovirus-based therapies.IMPORTANCEVesicular Stomatitis Indiana Virus (VSIV) is a veterinary pathogen that is also used as a backbone for many oncolytic and vaccine strategies. In natural and therapeutic settings, VSIV infection is sensed by the host and host-cells make proteins that protect them from viruses. In the case of VSIV, these antiviral proteins constrain viral replication and protect most healthy tissues from virus infection. In order to understand how VSIV causes disease and how healthy tissues are protected from VSIV-based therapies, it is crucial that we identify the proteins that inhibit VSIV. Here we show that TRIM69 is an antiviral defence that can potently and specifically block VSIV infection.
Approximate Bayesian Inference for a Mechanistic Model of Vesicle Release at a Ribbon Synapse
Authors: Schröder Cornelius , James Ben , Lagnado Leon , Berens Philipp 
Published: June 2019

AbstractThe inherent noise of neural systems makes it difficult to construct models which accurately capture experimental measurements of their activity. While much research has been done on how to efficiently model neural activity with descriptive models such as linear-nonlinear-models (LN), Bayesian inference for mechanistic models has received considerably less attention. One reason for this is that these models typically lead to intractable likelihoods and thus make parameter inference difficult. Here, we develop an approximate Bayesian inference scheme for a fully stochastic, biophysically inspired model of glutamate release at the ribbon synapse, a highly specialized synapse found in different sensory systems. The model translates known structural features of the ribbon synapse into a set of stochastically coupled equations. We approximate the posterior distributions by updating a parametric prior distribution via Bayesian updating rules and show that model parameters can be efficiently estimated for synthetic and experimental data from in vivo two-photon experiments in the zebrafish retina. Also, we find that the model captures complex properties of the synaptic release such as the temporal precision and outperforms a standard GLM. Our framework provides a viable path forward for linking mechanistic models of neural activity to measured data.
Neural correlates of perceptual switching while listening to bistable auditory streaming stimuli
Authors: Higgins NC , Little DF , Yerkes BD , Nave KM , Kuruvilla-Mathew A , Elhilali M , Snyder JS 
Published: June 2019

AbstractUnderstanding the neural underpinning of conscious perception remains one of the primary challenges of cognitive neuroscience. Theories based mostly on studies of the visual system differ according to whether the neural activity giving rise to conscious perception occurs in modality-specific sensory cortex or in associative areas, such as the frontal and parietal cortices. Here, we search for modality-specific conscious processing in the auditory cortex using a bistable stream segregation paradigm that presents a constant stimulus without the confounding influence of physical changes to sound properties. ABA_ triplets (i.e., alternating low, A, and high, B, tones, and _ gap) with a 700 ms silent response period after every third triplet were presented repeatedly, and human participants reported nearly equivalent proportions of 1- and 2-stream percepts. The pattern of behavioral responses was consistent with previous studies of visual and auditory bistable perception. The intermittent response paradigm has the benefit of evoking spontaneous perceptual switches that can be attributed to a well-defined stimulus event, enabling precise identification of the timing of perception-related neural events with event-related potentials (ERPs). Significantly more negative ERPs were observed for 2-streams compared to 1-stream, and for switches compared to non-switches during the sustained potential (500-1000 ms post-stimulus onset). Further analyses revealed that the negativity associated with switching was independent of switch direction, suggesting that spontaneous changes in perception have a unique neural signature separate from the observation that 2-streams has more negative ERPs than 1-stream. Source analysis of the sustained potential showed activity associated with these differences originating in anterior superior temporal gyrus, indicating involvement of the ventral auditory pathway that is important for processing auditory objects.Significance StatementWhen presented with ambiguous stimuli, the auditory system takes the available information and attempts to construct a useful percept. When multiple percepts are possible from the same stimuli, however, perception fluctuates back and forth between alternating percepts in a bistable manner. Here, we examine spontaneous switches in perception using a bistable auditory streaming paradigm with a novel intermittent stimulus paradigm, and measure sustained electrical activity in anterior portions of auditory cortex using event-related potentials. Analyses revealed enhanced sustained cortical activity when perceiving 2-streams compared to 1-stream, and when a switch occurred regardless of switch direction. These results indicate that neural responses in auditory cortex reflect both the content of perception and neural dynamics related to switches in perception.
Evolution of satellite plasmids can stabilize the maintenance of newly acquired accessory genes in bacteria
Authors: Zhang Xue , Deatherage Daniel E. , Zheng Hao , Georgoulis Stratton J. , Barrick Jeffrey E. 
Published: June 2019

AbstractPlasmids play a principal role in the spread of antibiotic resistance and other traits by horizontal gene transfer in bacteria. However, newly acquired plasmids generally impose a fitness burden on a cell, and they are lost from a population rapidly if there is not selection to maintain a unique function encoded on the plasmid. Mutations that ameliorate this fitness cost can sometimes eventually stabilize a plasmid in a new host, but they typically do so by inactivating some of its novel accessory genes. In this study, we identified an additional evolutionary pathway that can prolong the maintenance of newly acquired genes encoded on a plasmid. We discovered that propagation of an RSF1010-based IncQ plasmid inEscherichia colioften generated ‘satellite plasmids’ with spontaneous deletions of accessory genes and genes required for plasmid replication. These smaller plasmid variants are nonautonomous genetic parasites. Their presence in a cell drives down the copy number of full-length plasmids, which reduces the burden from the accessory genes without eliminating them entirely. The evolution of satellite plasmids may be favored relative to other plasmid fates because they give a more immediate fitness advantage to a cell’s progeny and because the organization of IncQ plasmids makes them particularly prone to certain deletions during replication. Satellite plasmids also evolved inSnodgrassella alvicolonizing the honey bee gut, suggesting that this mechanism may broadly contribute to the importance of IncQ plasmids as agents of bacterial gene transfer in nature.Significance StatementPlasmids are multicopy DNA elements found in bacteria that replicate independently of a cell’s chromosome. The spread of plasmids carrying antibiotic-resistance genes to new bacterial pathogens is a challenge for treating life-threatening infections. Often plasmids or their accessory genes encoding unique functions are lost soon after transfer into a new cell because they impose a fitness burden. We report that a family of transmissible plasmids can rapidly evolve ‘satellite plasmids’ that replicate as genetic parasites of the original plasmid. Satellite plasmid formation reduces the burden from the newly acquired genes, which may enable them to survive intact for longer after transfer into a new cell and thereby contribute to the spread of antibiotic resistance and other traits within bacterial populations.