bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-reported difficulty initiating sleep and early morning awakenings are associated with nocturnal diastolic non-dipping in older white Swedish men
Authors: Tan Xiao , Lind Lars , Ingelsson Martin , Sundström Johan , Cedernaes Jonathan , Benedict Christian
Published: August 2020

Chronically blunted nocturnal blood pressure (BP) dipping has been shown to increase the future risk of cardiovascular diseases. In the present cross-sectional study, we investigated whether self-reported insomnia symptoms were associated with an altered 24-h BP profile and blunted nocturnal BP dipping (night-to-day BP ratio > 0.90) in older men. For the analysis, we used 24-h ambulatory blood pressure data and reports of insomnia symptoms (difficulty initiating sleep, DIS; and early morning awakenings, EMA) from 995 Swedish men (mean age: 71 years). Compared to men without DIS, those reporting DIS (10% of the cohort) had a higher odds ratio of diastolic non-dipping (1.85 [1.15, 2.98], P = 0.011). Similarly, men who reported EMA (19% of the cohort) had a higher odds ratio of diastolic non-dipping than those without EMA (1.57 [1.09, 2.26], P = 0.015). Despite a slightly higher nocturnal diastolic BP among men with EMA vs. those without EMA (+ 1.4 mmHg, P = 0.042), no other statistically significant differences in BP and heart rate were found between men with and those without insomnia symptoms. Our findings suggest that older men reporting difficulty initiating sleep or early morning awakenings may have a higher risk of nocturnal diastolic non-dipping. Our findings must be replicated in larger cohorts that also include women.
Chemical carving lithography with scanning catalytic probes
Authors: Ki Bugeun , Kim Kyunghwan , Choi Keorock , Oh Jungwoo
Published: August 2020

This study introduces a new chemical carving technique as an alternative to existing lithography and etching techniques. Chemical carving incorporates the concept of scanning probe lithography and metal-assisted chemical etching (MaCE). A catalyst-coated probe mechanically scans a Si substrate in a solution, and the Si is chemically etched into the shape of the probes, forming pre-defined 3D patterns. A metal catalyst is used to oxidize the Si, and the silicon oxide formed is etched in the solution; this local MaCE reaction takes place continuously on the Si substrate in the scanning direction of probes. Polymer resist patterning for subsequent etching is not required; instead, scanning probes pattern the oxidation mask directly and chemical etching of Si occurs concurrently. A prototype that drives the probe with an actuator was used to analyze various aspects of the etching profiles based on the scanning speeds and sizes of the probe used. This technique suggests the possibility of forming arbitrary structures because the carving trajectory is formed according to the scan direction of the probes.
Cerebral tissue pO2 response to treadmill exercise in awake mice
Authors: Moeini Mohammad , Cloutier-Tremblay Christophe , Lu Xuecong , Kakkar Ashok , Lesage Frédéric
Published: August 2020

We exploited two-photon microscopy and Doppler optical coherence tomography to examine the cerebral blood flow and tissue pO2 response to forced treadmill exercise in awake mice. To our knowledge, this is the first study performing both direct measure of brain tissue pO2 during acute forced exercise and underlying microvascular response at capillary and non-capillary levels. We observed that cerebral perfusion and oxygenation are enhanced during running at 5 m/min compared to rest. At faster running speeds (10 and 15 m/min), decreasing trends in arteriolar and capillary flow speed were observed, which could be due to cerebral autoregulation and constriction of arterioles in response to blood pressure increase. However, tissue pO2 was maintained, likely due to an increase in RBC linear density. Higher cerebral oxygenation at exercise levels 5–15 m/min suggests beneficial effects of exercise in situations where oxygen delivery to the brain is compromised, such as in aging, atherosclerosis and Alzheimer Disease.
Quantifying the thermodynamics of protein unfolding using 2D NMR spectroscopy
Authors: Puglisi Rita , Brylski Oliver , Alfano Caterina , Martin Stephen R. , Pastore Annalisa , Temussi Piero A.
Published: August 2020

A topic that has attracted considerable interest in recent years is the possibility to perform thermodynamic studies of proteins directly in-cell or in complex environments which mimic the cellular interior. Nuclear magnetic resonance (NMR) could be an attractive technique for these studies but its applicability has so far been limited by technical issues. Here, we demonstrate that 2D NMR methods can be successfully applied to measure thermodynamic parameters provided that a suitable choice of the residues used for the calculation is made. We propose a new parameter, named RAD, which reflects the level of protection of a specific amide proton in the protein core and can guide through the selection of the resonances. We also suggest a way to calibrate the volumes to become independent of technical limitations. The methodology we propose leads to stability curves comparable to that calculated from CD data and provides a new tool for thermodynamic measurements in complex environments.
High-pressure annealing driven nanocrystal formation in Zr50Cu40Al10 metallic glass and strength increase
Authors: Shibazaki Yuki , Yamada Rui , Saida Junji , Kono Yoshio , Wakeda Masato , Itoh Keiji , Nishijima Masahiko , Kimoto Koji
Published: August 2020

Pressure-induced structural changes in metallic glasses have been of great interest as they are expected to open new ways to synthesize novel materials with unexpected properties. Here, we investigated the effect of simultaneous high-pressure and high-temperature treatment on the structure and properties of a Zr50Cu40Al10 metallic glass by in situ X-ray structure measurement and property analysis of the final material. We found the unusual formation of Cu-rich nanocrystals at high pressure and temperature, accompanied by significant strength and hardness enhancement. Based on reverse Monte Carlo modeling and molecular dynamics simulations, the structure of the metallic glass changed to a densely packed, chemically uniform configuration with high short-range and medium-range ordering at high pressure and temperature. These results show that high-pressure annealing processes provide a new way to improve and control properties without changing their composition.
Nitrogen deficient carbon nitride for efficient visible light driven tetracycline degradation: a combination of experimental and DFT studies
Authors: Wang Mier , Fan Changzheng , Yang Shuaijun , Liu Milan , Luo Jun , Liu Yani , Tang Lin , Gong Zhixuan , Leng Shuwen
Published: August 2020

The narrow visible-light absorption range and a high recombination rate of photo-excited electrons and holes are the main reasons for the confined photocatalytic performance of graphitic carbon nitride (g-C3N4).
Nanopaper-based screen-printed electrodes: a hybrid sensing bioplatform for dual opto-electrochemical sensing applications
Authors: Eynaki Hadi , Kiani Mohammad Ali , Golmohammadi Hamed
Published: August 2020

Herein, we have developed a nanopaper-based screen-printed electrode as a hybrid opto-electrochemical sensing device by taking advantage of the unrivaled physicochemical properties of bacterial cellulose nanopaper in screen printing technology.
Triazole-based osmium(ii) complexes displaying red/near-IR luminescence: antimicrobial activity and super-resolution imaging
Authors: Smitten Kirsty L. , Scattergood Paul A. , Kiker Charlotte , Thomas Jim A. , Elliott Paul I. P.
Published: August 2020

Cellular uptake, luminescence imaging and antimicrobial activity of facial and meridional isomers of Os(ii) triazole-based complexes against methicillin-resistant S. aureus, MRSA.
A modular and divergent approach to spirocyclic pyrrolidines
Authors: Shennan Benjamin D. A. , Smith Peter W. , Ogura Yusuke , Dixon Darren J.
Published: August 2020

A three-step, modular and divergent sequence accessing challenging spirocyclic pyrrolidines has been developed, featuring a novel reductive spirocyclization cascade.
Construction of coacervate-in-coacervate multi-compartment protocells for spatial organization of enzymatic reactions
Authors: Chen Yufeng , Yuan Min , Zhang Yanwen , Liu Songyang , Yang Xiaohai , Wang Kemin , Liu Jianbo
Published: August 2020

A coacervate-in-coacervate micro-architecture is constructed as a multi-compartment protocell model, in which a multi-enzyme cascade is spatially organized for competitive enzymatic reactions.
Yoga as Therapy for People With Aphasia
Authors: Dietz Aimee , Duncan E. Susan , Bislick Lauren , Stegman Sarah , Collins Jenna , Mamlekar Chitrali , Gleason Rachel , McCarthy Michael J.
Published: August 2020

Purpose

This viewpoint offers a perspective on the potential impact of an adapted yoga program for people with stroke-induced aphasia, with a call for additional work in this area.

Conclusion

Aphasia often results in decreased quality of life (QoL) from fewer social interactions, relationship strain between survivors and co-survivors, depression, and a multitude of other factors. We suggest a therapeutic yoga program for survivors and co-survivors could enhance several components of the dyad's lives that are frequently diminished as a result of aphasia, ultimately increasing QoL. In particular, we highlight the role of resilience and coping as essential tools on the rehabilitative journey in aphasia. After exploring yoga and other mind–body practices, we describe documented positive changes—including cognitive function, social integration, and QoL—following use of yoga in other chronic conditions. As people with communication deficits are typically excluded from these studies, further research is needed to establish whether these benefits generalize to people with aphasia.
Carrot production practices.
Authors: Nunez Juan J.
Published: August 2020

This chapter discusses carrot production practices, focusing on climatic and soil requirements, planting, spacing, germination, irrigation, fertilizer (N, P and K) application, harvesting, postharvest handling and storage.
C
*-uniqueness Results for Groupoids
Authors: Austad Are , Ortega Eduard
Published: August 2020

For a 2nd-countable locally compact Hausdorff étale groupoid ${\mathcal{G}}$ with a continuous $2$-cocycle $\sigma $ we find conditions that guarantee that $\ell ^1 ({\mathcal{G}},\sigma )$ has a unique $C^*$-norm.
Postmarketing Analysis of Misuse, Abuse, and Diversion of Xtampza ER
Authors: Geoffrey Severtson Stevan , Kreider Scott E D , Amioka Elise C , Margolin Zachary R , Iwanicki Janetta L , Dart Richard C
Published: August 2020

Objective

To evaluate abuse, misuse, and diversion of Xtampza ER, an extended-release (ER) abuse-deterrent formulation (ADF) of oxycodone.

Methods

Abuse, misuse, and diversion of Xtampza ER were assessed using Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System data sources. Xtampza ER was compared with immediate-release (IR) oxycodone, other ADF ER products combined, and non-ADF ER products combined.

Results

Xtampza ER prescriptions increased 50-fold during the study period. In contrast, cases from poison centers, substance abuse treatment centers, and diversion were infrequent and did not increase. Adjusted for prescriptions dispensed, poison center exposures were greater for IR oxycodone (rate ratio [RR] = 2.3, P = 0.008), other ADF ER opioids (RR = 5.2, P < 0.001), and non-ADF ER opioids (RR = 2.5, P = 0.004) than for Xtampza ER. In Treatment Center Programs Combined, past-month abuse prevalence for other ADF ER opioids (odds ratio [OR] = 7.4, P < 0.001) and non-ADF ER opioids (OR = 2.0, P = 0.002) was greater than Xtampza ER; IR oxycodone was not significantly different (OR = 1.2, P = 0.349). In the Drug Diversion Program, rates for IR oxycodone (RR = 3.7, P = 0.003), other ADF ER opioids (RR = 4.2, P = 0.002), and non-ADF ER opioids (RR = 3.4, P = 0.007) were greater than Xtampza ER. Adjustment using morphine equivalents provided similar results, except that IR oxycodone in Treatment Center Programs Combined became higher than Xtampza ER. Nonoral abuse cases involving Xtampza ER were infrequent; Web monitoring data support findings that Xtampza ER is difficult to abuse nonorally.

Conclusion

Xtampza ER abuse, misuse, and diversion and tampering are low relative to other prescription opioid analgesics. Abuse and diversion did not increase over the study period.
Interventions to improve perioperative neurologic outcomes
Authors: Vandiver Matthew S. , Vacas Susana
Published: August 2020

Purpose of review

Few outcomes in surgery are as important to patients as that of their neurologic status. The purpose of this review is to discuss and categorize the most common perioperative neurologic complications. We will also discuss strategies to help prevent and mitigate these complications for our patients.

Recent findings

There are several strategies the anesthesiologist can undertake to prevent or treat conditions, such as perioperative neurocognitive disorders, spinal cord ischemia, perioperative stroke, and postoperative visual loss.

A thorough understanding of threats to patients’ neurologic well-being is essential to excellent clinical practice.
MULTIFOCAL ELECTRORETINOGRAPHY AND SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY IN MACULA-OFF RHEGMATOGENOUS RETINAL DETACHMENT
Authors: Kosacki Julie , Gallice Mathilde , Palombi Karine , Labarere José , Creuzot-Garcher Catherine , Berthemy-Pellet Sylvie , Aptel Florent , Chiquet Christophe
Published: August 2020

Purpose:

To analyze the temporal trends in structural changes using spectral-domain optical coherence tomography and functional changes using multifocal electroretinogram after rhegmatogenous retinal detachment surgery.

Methods:

This prospective cohort study enrolled 69 patients with macula-off rhegmatogenous retinal detachment who underwent successful surgery. Early Treatment Diabetic Retinopathy Study visual acuity, multifocal electroretinogram evaluation of the central 5°, and spectral–domain optical coherence tomography were recorded at 1, 3, 6, and 12 months (M) after surgery. The fellow eye served as the control group for multifocal electroretinogram parameters.

Results:

Between M1 and M12, visual acuity improved from 64 to 75 letters (P = 0.001) and implicit time of N1 decreased from 27.8 to 25.2 milliseconds (P = 0.001), whereas the other parameters did not vary significantly. Amplitude and implicit time values did not reach normal values at M12. Alterations of the ellipsoid zone and the external limiting membrane decreased over time (P = 0.001). P1 implicit time correlated independently with the alteration of the external limiting membrane (P = 0.007).

Conclusion:

Foveal wave amplitudes remain lower than normal values after successful surgery of rhegmatogenous retinal detachment, whereas anatomical improvement was found for outer retinal abnormalities and subretinal edema fluid. Retinal recovery improves N1 implicit time over time. Disruption of external limiting membrane seems to be predictive of increased P1 implicit time.
Relationships Among Delayed Sleep Phase Disorder, Emotional Dysregulation, and Affective Temperaments in Adults With Attention Deficit Hyperactivity Disorder and Cyclothymia
Authors: Quaranta Giuseppe , Barbuti Margherita , Pallucchini Alessandro , Colombini Paola , Moriconi Martina , Gemmellaro Teresa , Tripodi Beniamino , Palagini Laura , Schiavi Elisa , Perugi Giulio
Published: August 2020

This study aims to explore the relationships between delayed sleep phase disorder (DSPD) and emotional dysregulation in 240 patients (134 with cyclothymia, 81 with attention deficit hyperactivity disorder [ADHD] and 25 with both conditions). DSPD was assessed using the Morningness-Eveningness Questionnaire, followed by a clinical evaluation. Affective temperaments and emotional dysregulation were also investigated through the brief version of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego and the Reactivity, Intensity, Polarity, Stability questionnaires, respectively. Clinical variables were compared in patients with and without DSPD, and a logistic regression model was used to identify the predictive value of the clinical characteristics on the presence of DSPD. DSPD patients (19% of the total sample) were significantly younger than patients without DSPD, showed an about 4 times higher lifetime history of comorbid ADHD and cyclothymia, and reported higher scores in the irritable and cyclothymic temperamental subscales and in the affective instability and impulsivity dimensions. In the multiple logistic regression, we found a negative predictive value of increasing age on the presence of DSPD, whereas comorbid cyclothymia and ADHD and cyclothymic temperament seem to represent risk factors for DSPD.
Anthropometric Parameters of Nasomaxillary Complex in 2, 4, 6, and 12-Month-Old Children as a Reference for Cleft Lip and Palate Reconstructive Surgery
Authors: Jahanbin Arezoo , Emami Ahmad Kafi , Eslami Neda
Published: August 2020

The purpose of this study was to analyze the morphology of the nasomaxillary complex of Iranian healthy infants of 2, 4, 6, and 12-month-old.

In this cross-sectional study, 232 healthy Fars infants of 2, 4, 6, and 12-month-old referred to Mashhad health centers were evaluated. Photographic images were taken from the infants’ frontal view at rest position. Anthropometric landmarks including width of the mouth, nose, columella, width and height of the philtrum, and height of the upper lip were measured by Photoshop software.

The authors did not find any considerable differences in nasolabial morphology of Fars children between boys and girls, except for columellar width and the width of superior philtrum at all intervals. The mean columellar width decreased with increasing age in both sexes. The width of the lower philtrum decreased from 2 to 4 months in both sexes, but increased from 4 to 6 months. In girls, the mean height of the right and left philtrum and height of the upper lip increased by increasing age from 2 to 4 months. But it consistently reduced from 4 months to 6 and 12-month-old. In boys, the mean height of the right and left philtrum and height of the upper lip decreased from 2 to 4 months. It showed a mild increase from 4 to 6 months, and a relatively large reduction from 6 to 12 months.

This study provides useful information for reconstructive surgeries of the nasolabial region in the population studied.
Transcriptome Analysis of Human Induced Excitatory Neurons Supports a Strong Effect of Clozapine on Cholesterol Biosynthesis
Authors: Das Debamitra , Peng Xi , Lam Anh-Thu , Bader Joel S. , Avramopoulos Dimitrios
Published: August 2020

Antipsychotics are known to modulate dopamine and other neurotransmitters which is often thought to be the mechanism underlying their therapeutic effects. Nevertheless, other less studied consequences of antipsychotics on neuronal function may contribute to their efficacy. Revealing the complete picture behind their action is of paramount importance for precision medicine and accurate drug selection. Progress in cell engineering allows the generation of induced pluripotent stem cells (iPSCs) and their differentiation to a variety of neuronal types, providing new tools to study antipsychotics. Here we use excitatory cortical neurons derived from iPSCs to explore their response to therapeutic levels of Clozapine as measured by their transcriptomic output, a proxy for neuronal homeostasis. To our surprise, but in agreement with the results of many investigators studying glial-like cells, Clozapine had a very strong effect on cholesterol metabolism. More than a quarter (12) of all annotated cholesterol genes (46) in the genome were significantly changed at FDR<0.1, all upregulated. This is a 35-fold enrichment with an adjusted p = 8 ×10−11. Notably no other functional category showed evidence of enrichment. Cholesterol is a major component of the neuronal membrane and myelin but it does not cross the blood brain barrier, it is produced locally mostly by glia but also by neurons. By singling out increased expression of cholesterol metabolism genes as the main response of cortical excitatory neurons to antipsychotics, our work supports the hypothesis that cholesterol metabolism may be a contributing mechanism to the beneficial effects of Clozapine and possibly other antipsychotics.
Development and characterization of infectious clones of two strains of Usutu virus
Authors: Bates Tyler , Chuong Christina , Hawks Seth A. , Rai Pallavi , Duggal Nisha K. , Weger-Lucarelli James
Published: August 2020

Usutu virus (USUV; genusFlavivirus; familyFlaviviridae) is a mosquito-borne, positive-sense RNA virus that is currently causing significant die-offs in numerous bird species throughout Europe and has caused infections in humans. Currently, there are no molecular clones for USUV, hence, hindering studies on the pathogenesis and transmission of USUV. In this report, we demonstrate the development and characterization of infectious clones for two modern strains of USUV isolated from Europe and Africa. We show that the infectious clone-derived viruses replicated similarly to the parental strains in both mammalian and insect cells. Additionally, we observed similar levels of replication and pathogenesis in two mouse models. This reverse genetics system will aid the scientific community in studying and developing USUV infection, transmission, diagnostics, and vaccines.
Estimating the Changing Infection Rate of COVID-19 Using Bayesian Models of Mobility
Authors: Liu Luyang , Vikram Sharad , Lao Junpeng , Ben Xue , D’Amour Alexander , O’Banion Shawn , Sandler Mark , Saurous Rif A. , Hoffman Matthew D.
Published: August 2020

In order to prepare for and control the continued spread of the COVID-19 pandemic while minimizing its economic impact, the world needs to be able to estimate and predict COVID-19’s spread. Unfortunately, we cannot directly observe the prevalence or growth rate of COVID-19; these must be inferred using some kind of model. We propose a hierarchical Bayesian extension to the classic susceptible-exposed-infected-removed (SEIR) compartmental model that adds compartments to account for isolation and death and allows the infection rate to vary as a function of both mobility data collected from mobile phones and a latent time-varying factor that accounts for changes in behavior not captured by mobility data. Since confirmed-case data is unreliable, we infer the model’s parameters conditioned on deaths data. We replace the exponential-waiting-time assumption of classic compartmental models with Erlang distributions, which allows for a more realistic model of the long lag between exposure and death. The mobility data gives us a leading indicator that can quickly detect changes in the pandemic’s local growth rate and forecast changes in death rates weeks ahead of time. This is an analysis of observational data, so any causal interpretations of the model’s inferences should be treated as suggestive at best; nonetheless, the model’s inferred relationship between different kinds of trips and the infection rate do suggest some possible hypotheses about what kinds of activities might contribute most to COVID-19’s spread.
CONSERVED INTERACTIONS IN CARDIAC SYNTHETIC THICK FILAMENTS DIFFERENTLY AFFECT MYOSIN SUPER-RELAXED STATE IN HEALTHY, DISEASE AND MAVACAMTEN-TREATED MODELS
Authors: Gollapudi Sampath K. , Nag Suman
Published: August 2020

A hallmark feature of myosin-II is that it can spontaneously self-assemble into bipolar synthetic thick filaments (STFs) in low ionic strength buffers, thereby serving as a reconstituted in vitro model for muscle thick filament. While these STFs have been extensively used for structural characterization, their use for functional studies has been very limited. In this report, we show that the ultra-low ATP-consuming super-relaxed (SRX) state of myosin is electrostatically more stable in STFs as compared with shorter myosin sub-fragments that lack the distal tail required for thick filament assembly. However, this electrostatic stability of the SRX state is weakened by phosphorylation of myosin light chains or the hypertrophic cardiomyopathy-causing myosin R403Q mutation. We also show that ADP binding to myosin depopulates the SRX population in STFs made of wild-type (WT) myosin, but not in S1, HMM, or STFs made of mutant R403Q myosin. Collectively, these findings emphasize that a critical network of inter- and intra-molecular interactions that underlie the SRX state of myosin are mostly preserved in STFs, establishing it as a native-like tool to interrogate myosin regulation. Next, using STFs, we show that a clinical-stage small molecule inhibitor, mavacamten, is more effective in promoting the myosin SRX state in STFs than in S1 or HMM and that it is equally potent in STFs made of atrial-WT, ventricular-WT, and mutant-R403Q myosin. Also, we found that mavacamten-bound heads are not permanently protected in the SRX state but can be recruited in response to physiological perturbations, thus providing new insights into its inhibitory mechanism.
Opposing effects of T cell receptor signal strength on CD4 T cells responding to acute versus chronic viral infection
Authors: Künzli Marco , Reuther Peter , Pinschewer Daniel D. , King Carolyn G.
Published: August 2020

A hallmark of the adaptive immune response is the ability of CD4 T cells to differentiate into a variety of pathogen appropriate and specialized effector subsets. A long-standing question in CD4 T cell biology is whether the strength of TCR signals can instruct one Th cell fate over another. The contribution of TCR signal strength to the development of Th1 and T follicular helper (Tfh) cells has been particularly difficult to resolve, with conflicting results reported in a variety of models. Although cumulative TCR signal strength can be modulated by the infection specific environment, whether or not TCR signal strength plays a dominant role in Th1 versus Tfh cell fate decisions across distinct infectious contexts is not known. Here we characterized the differentiation of CD4 TCR transgenic T cells responding to a panel of recombinant wild type or altered peptide ligand lymphocytic choriomeningitis viruses (LCMV) derived from acute and chronic parental strains. We found that while TCR signal strength positively regulates T cell expansion in both infection settings, it exerts opposite and hierarchical effects on the balance of Th1 and Tfh cells generated in response to acute versus persistent infection. The observation that weakly activated T cells, which comprise up to fifty percent of an endogenous CD4 T cell response, support the development of Th1 effectors highlights the possibility that they may resist functional inactivation during chronic infection. We anticipate that the panel of variant ligands and recombinant viruses described herein will be a valuable tool for immunologists investigating a wide range of CD4 T cell responses.

Graphical abstract

Highlights

Identification of a wide panel of altered peptide ligands for the LCMV-derived GP61 peptide

Generation of LCMV variant strains to examine the impact of TCR signal strength on CD4 T cells responding during acute and chronic viral infection

The relationship between TCR signal strength and Th1 differentiation shifts according to the infection context: TCR signal strength correlates positively with Th1 generation during acute infection but negatively during chronic infection.
Clostridioides difficileexploits toxin-mediated inflammation to alter the host nutritional landscape and exclude competitors from the gut microbiota
Authors: Fletcher Joshua R. , Pike Colleen M. , Parsons Ruth J. , Rivera Alissa J. , Foley Matthew H. , McLaren Michael R. , Montgomery Stephanie A. , Theriot Casey M.
Published: August 2020

Introductory paragraph

Clostridioides difficileis a bacterial pathogen that causes a range of clinical disease from mild to moderate diarrhea, pseudomembranous colitis, and toxic megacolon. Typically,C. difficileinfections (CDIs) occur after antibiotic treatment, which alters the gut microbiota, decreasing colonization resistance againstC. difficile. Disease is mediated by two large toxins and the expression of their genes is induced upon nutrient depletion via the alternative sigma factor TcdR. UsingtcdRmutants in two strains ofC. difficile, we defined how toxin-induced inflammation altersC. difficilemetabolism, tissue gene expression, and the gut microbiota to determine how inflammation by the host may be beneficial toC. difficile. Here we show thatC. difficilemetabolism is significantly different in the face of inflammation, with changes in many carbohydrate and amino acid uptake and utilization pathways. Host gene expression signatures suggest that degradation of collagen and other components of the extracellular matrix by matrix metalloproteinases is a major source of peptides and amino acids that supportsC. difficilegrowthin vivo. Lastly, the inflammation induced byC. difficiletoxin activity alters the gut microbiota, excluding members from the genusBacteroidesthat are able to compete againstC. difficilefor the same essential nutrients released from collagen degradation.
Conscious perception modulates perceptual echoes
Authors: Luo Canhuang , VanRullen Rufin , Alamia Andrea
Published: August 2020

Alpha rhythms (~10Hz) in the human brain are classically associated with idling activities, being predominantly observed during quiet restfulness with closed eyes. However, recent studies demonstrated that alpha (~10Hz) rhythms can directly relate to visual stimulation, resulting in oscillations which can last for as long as one second. This alpha reverberation, dubbed Perceptual Echoes (PE), suggests that the visual system actively samples and processes visual information within the alpha-band frequency. Although PE have been linked to various visual functions, their underlying mechanisms and functional role are not completely understood. In the current study, we investigated whether conscious perception modulates the generation and the amplitude of PE. Specifically, we displayed two colored Gabor patches with different orientations on opposite sides of the screen, and using a set of dichoptic mirrors we induced a binocular rivalry between the two stimuli. We asked participants to continuously report which one of two Gabor patches they consciously perceived, while recording their EEG signals. Importantly, the luminance of each patch fluctuated randomly over time, generating random sequences from which we estimated two impulse-response functions (IRFs) reflecting the perceptual echoes generated by the perceived (dominant) and non-perceived (suppressed) stimulus respectively. We found that the alpha power of the PE generated by the consciously perceived stimulus was comparable with that of the PE generated during monocular vision (control condition), and significantly higher than the PE induced by the suppressed stimulus. Moreover, confirming previous findings, we found that all PEs propagated as a travelling wave from posterior to frontal brain regions, irrespective of conscious perception. All in all our results demonstrate that conscious perception modulates PE, suggesting that the synchronization of neural activity plays an important role in visual sampling and conscious perception.
Predictingin vivoescape dynamics of HIV-1 from a broadly neutralizing antibody
Authors: Meijers Matthijs , Vanshylla Kanika , Gruell Henning , Klein Florian , Lässig Michael
Published: August 2020

Broadly neutralizing antibodies are promising candidates for treatment and prevention of HIV-1 infections. Such antibodies can temporarily suppress viral load in infected individuals; however, the virus often rebounds by escape mutants that have evolved resistance. In this paper, we map anin vivofitness landscape of HIV-1 interacting with broadly neutralizing antibodies, using data from a recent clinical trial. We identify two fitness factors, antibody dosage and viral load, that determine viral reproduction rates reproducibly across different hosts. The model successfully predicts the escape dynamics of HIV-1 in the course of an antibody treatment, including a characteristic frequency turnover between sensitive and resistant strains. This turnover is governed by a dosage-dependent fitness ranking, resulting from an evolutionary tradeoff between antibody resistance and its collateral cost in drug-free growth. Our analysis suggests resistance-cost tradeoff curves as a measure of antibody performance in the presence of resistance evolution.
scREAD: A single-cell RNA-Seq database for Alzheimer’s Disease
Authors: Jiang Jing , Wang Cankun , Qi Ren , Fu Hongjun , Ma Qin
Published: August 2020

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder of the brain and the most common form of dementia among the elderly. The single-cell RNA-sequencing (scRNA-Seq) and single-nucleus RNA-sequencing (snRNA-Seq) techniques are extremely useful for dissecting the function/dysfunction of highly heterogeneous cells in the brain at the single-cell level, and the corresponding data analyses can significantly improve our understanding of why particular cells are vulnerable in AD. We developed an integrated database named scREAD (single-cellRNA-Seq databaseforAlzheimer’sDisease), which is the first database dedicated to the management of all the existing scRNA-Seq and snRNA-Seq datasets from human postmortem brain tissue with AD and mouse models with AD pathology. scREAD provides comprehensive analysis results for 55 datasets from eight brain regions, including control atlas construction, cell type prediction, identification of differentially expressed genes, and identification of cell-type-specific regulons.

Availability and Implementation

scREAD is a one-stop and user-friendly interface and freely available athttps://bmbls.bmi.osumc.edu/scread/. The backend workflow can be downloaded fromhttps://github.com/OSU-BMBL/scread/tree/master/script, to enable more discovery-driven analyses.

Contact

qin.ma@osumc.eduorhongjun.fu@osumc.edu

Supplementary information

Supplementary data are available atBioinformaticsonline.
Besides stem canker severity, oilseed rape host genotype matters for the production ofLeptosphaeria maculansfruiting bodies
Authors: Bousset Lydia , Vallée Patrick , Delourme Régine , Parisey Nicolas , Palerme Marcellino , Leclerc Melen
Published: August 2020

For fungal cyclic epidemics on annual crops, the pathogen carry-over is an important step in designing disease control strategies. However, it remains particularly difficult to estimate and predict. Plant resistance affects the pathogen development within the epidemics but we lack data on the inter-annual transmission of inoculum. We addressed this question by consideringLeptosphaeria maculanson 15 oilseed rape genotypes in field during 4 growing seasons. Stem canker severity of host genotypes was visually scored at harvest while the number of fruiting bodies produced on incubated stubble was quantified using an automated image analysis framework. Our results confirm that higher severity at harvest leads to higher fruiting body production and is significantly affected by host genotype and Nitrogen supply. Most interestingly, we show that the production of fruiting bodies is significantly and substantially affected by host genotype, independently of severity at harvest. Tracking individual stems through incubation, we confirm for the first time that the oilseed rape genotype has a direct effect, not only through disease severity. While the genericity of this finding should be investigated on other fungi, this major effect of genotype on inoculum carry-over should be taken into account in models of varietal deployment strategies.
Gene-based association analysis identified 190 genes with polymorphisms affecting neuroticism
Authors: Belonogova Nadezhda M. , Zorkoltseva Irina V. , Tsepilov Yakov A. , Axenovich Tatiana I.
Published: August 2020

Recent genome-wide studies have reported about 600 genes potentially influencing neuroticism. Little is known about the mechanisms of their action. Here, we aimed to conduct a more detailed analysis of genes whose polymorphisms can regulate the level of neuroticism. Using UK Biobank-based GWAS summary statistics, we performed a gene-based association analysis using four sets of genetic variants within a gene differing in their protein coding properties. To guard against the influence of strong GWAS signals outside the gene, we used the specially designed procedure. As a result, we identified 190 genes associated with neuroticism due to their polymorphisms. Thirty eight of these genes were novel. Within all genes identified, we distinguished two slightly overlapping groups comprising genes that demonstrated association when using protein-coding and non-coding SNPs. Many genes from the first group included potentially pathogenic variants. For some genes from the second group, we found evidence of pleiotropy with gene expression. We demonstrated that the association of almost two hundred known genes could be inflated by the GWAS signals outside the gene. Using bioinformatics analysis, we prioritized the neuroticism genes and showed that the genes influencing the trait by their polymorphisms are the most appropriate candidate genes.
A meta-analysis of the quantitative studies in continuance intention to use an information system
Authors: Franque Frank Bivar , Oliveira Tiago , Tam Carlos , Santini Fernando de Oliveira
Published: August 2020

Purpose

This study aims to describe, synthesise and clarify the findings of published studies on individual continuance intention to use an information system (IS), considering the fact that the number of studies in the continuance intention context are growing exponentially and cover several different subjects.

Design/methodology/approach

The research uses meta- and weight analysis by taking 115 empirical studies from continuance intention to use an IS. The data are presented in different views using significant and non-significant relationships from all the studies. Furthermore, it uses hierarchical linear meta-analysis to analyse potential moderators that can influence continuance intention.

Findings

The results reveal that affective commitment, attitude, satisfaction, hedonic value and flow are the best predictors of continuance intention to use an IS. Sample size, individualism, uncertainty avoidance and long-term orientation moderate the relationship of perceived usefulness on continuance intention. Power distance, masculinity and indulgence moderate relationship satisfaction on continuance intention.

Practical implications

The results reveal that continuance intention to use an IS has been studied in different countries, with different cultures; therefore, IS providers should have diversified managing strategies, to ensure the satisfaction of users and long-term usage of their IS.

Originality/value

The study provides a systematic overview of the most relevant variables used in the literature, including a temporal analysis of the theoretical models, highlighting the evolution of the constructs and presents a moderation analysis.
Financing decisions of firms: the roles of legal systems, shareholder rights and creditor rights
Authors: Özer Gökhan , Çam İlhan
Published: August 2020

We examine how firms finance their investments, dividends, and profit shortfalls in different institutional environments. Using firm‐level data from 71 countries, we employ a dynamic multi‐equation system addressing the interdependence and intertemporal nature of financing decisions. We find that equity and long‐term debt (short‐term debt and cash) play a major role in financing capital expenditures (working asset investment). As the institutional environment strengthens, (i) firms increase (decrease) their reliance on equity (debt) issuance in financing capital expenditures, (ii) firms decrease their leverage, and (iii) they extend their debt maturity. We further report several findings on the effects of financial development.
Lower tumor volume is associated with increased benefit from immune checkpoint inhibitors in patients with advanced non‐small‐cell lung cancer
Authors: Icht Oded , Domachevsky Liran , Groshar David , Dudnik Elizabeth , Rotem Ofer , Allen Aaron M. , Peled Nir , Reinhorn Daniel , Jacobi Oded , Shochat Tzippy , Bernstine Hanna , Zer Alona
Published: August 2020

Aim

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment for advanced non‐small‐cell lung cancer (NSCLC), yet many patients do not benefit from Programmed cell death protein 1 (PD‐1) axis inhibitors, emphasizing the need for additional markers for better patient selection. Our aim was to evaluate the association between tumor volume and response to ICI.

Methods

This retrospective ethically‐approved study included all consecutive patients with advanced NSCLC who were evaluated with a fluorodeoxyglucose‐positron emission tomography scan, prior to the first administration of a single‐agent ICI between 1/2016 and 6/2017. Tumor burden was calculated based on total body metabolic tumor volume and sum of all measurable lesions (SOML).

Results

Median SOML was 88 mm, and was inversely and significantly associated with progression‐free survival (PFS) (hazard ratio [HR] 2, CI 1.28‐3.37, P = .003) and overall survival (OS) (HR 2.36, CI 1.13‐4.94, P = .02). SOML≤80 mm had a significantly longer PFS compared to patients with a SOML≥80 mm (median PFS 9.7 vs 3.7 months, respectively, HR for progression 2.26, CI 1.1‐4.5, P = .02). Patients with a SOML≤80 also had longer median OS compared to patients with SOML≥80 (median OS 12 vs 9.8 months, respectively, HR for death 3.1, CI 1.2‐8, P = .018).

Conclusions

Low tumor burden was associated with higher response rates (RR), and better PFS and OS in advanced NSCLC patients treated with ICI. These results may improve the selection of patients for treatment with single‐agent ICI, as opposed to the combination with chemotherapy, which might be more appropriate for patients with high tumor burden. Prospective analysis is warranted.
Treatment and prognosis of patients with urinary bladder cancer with other primary cancers: a nationwide population‐based study in the Bladder Cancer Data Base Sweden (BladderBaSe)
Authors: Aljabery Firas , Liedberg Fredrik , Häggström Christel , Ströck Viveka , Hosseini Abolfazl , Gårdmark Truls , Sherif Amir , Jerlström Tomas , Malmström Per‐Uno , Hagberg Oskar , Holmberg Lars
Published: August 2020

Objective

To study how patients with urinary bladder cancer (UBC) with previous or concomitant other primary cancers (OPCs) were treated, and to investigate their prognosis.

Patients And Methods

Using nationwide population‐based data in the Bladder Cancer Data Base Sweden (BladderBaSe), we analysed the probability of treatment with curative intent, and UBC‐specific and overall survival (OS) in patients with UBC diagnosed in the period 1997–2014 with or without OPC. The analyses considered the patient’s characteristics, UBC tumour stage at diagnosis, and site of OPC.

Results

There were 38 689 patients, of which 9804 (25%) had OPCs. Those with synchronous OPCs more often had T2 and T3 tumours and clinically distant disease at diagnosis than those with UBC only. Patients with synchronous prostate cancer, female genital cancer and lower gastro‐intestinal cancer were more often treated with curative intent than patients with UBC only. When models of survival were adjusted for age at diagnosis, marital status, education, year of diagnosis, Charlson Comorbidity Index and T‐stage, UBC‐specific survival was similar to patients with UBC only, but OS was lower for patients with synchronous OPC, explained mainly by deaths in OPC primaries with a bad prognosis.

Conclusions

OPC is common in patients with UBC. Treatment for UBC, after or in conjunction with an OPC, should not be neglected and carries just as high a probability of success as treatment in patients with UBC only. The needs of patients with UBC and OPC, and optimisation of their treatment considering their complicated disease trajectory are important areas of research.
Feasibility and rationale of direct current cardioversion immediately after transcatheter percutaneous edge‐to‐edge mitral valve repair
Authors: Lee Ching‐Wei , Frerker Christian , Huang Wei‐Ming , Tsai Yi‐Lin , Huang Chi‐Jung , Yu Wen‐Chung , Hsu Chiao‐Po , Chiang Chern‐En , Chen Chen‐Huan , Sung Shih‐Hsien
Published: August 2020

Aims

Atrial fibrillation (AF) is a frequent comorbidity among patients with severe mitral regurgitation (MR). Direct current (DC) cardioversion is one of the strategies for rhythm control. However, the safety and feasibility of immediate DC cardioversion after MitraClip are not elucidated.

Methods and Results

In this study, patients with symptomatic severe MR who underwent MitraClip were included. After fixing the MR, synchronized DC cardioversion was attempted for those with AF. A total of consecutive 60 patients, 36 subjects (60%), comorbid with AF. DC cardioversion was performed in 30 patients (mean age of 76.0 ± 9.3 years), and the successful conversion was achieved in 15 patients (50%). There was no any adverse event related to the cardioversion. Subjects with sustained conversion to SR experienced significant improvement in 6MWT (failed: 285 ± 110‐308 ± 135 m, P = .278; successful: 269 ± 109 m‐328 ± 78, P = .047) and reduction in NT‐proBNP level (failed: 4411 ± 7401‐3296 ± 4299 ng/mL, P = .217; successful: 4094 ± 2735‐2353 ± 2856 ng/mL, P = .026) at 1 month.

Conclusions

Direct current cardioversion seemed to be safe and feasible immediately after the transcatheter edge‐to‐edge mitral valve repairs. Subjects who maintain SR experienced better functional improvement.
Political vandalism as counter‐speech: A defense of defacing and destroying tainted monuments
Authors: Lai Ten‐Herng
Published: August 2020

Tainted political symbols ought to be confronted, removed, or at least recontextualized. Despite the best efforts to achieve this, however, official actions on tainted symbols often fail to take place. In such cases, I argue that political vandalism—the unauthorized defacement, destruction, or removal of political symbols—may be morally permissible or even obligatory. This is when, and insofar as, political vandalism serves as fitting counter‐speech that undermines the authority of tainted symbols in ways that match their publicity, refuses to let them speak in our name, and challenges the derogatory messages expressed through a mechanism I call derogatory pedestalling: the glorification or honoring of certain individuals or ideologies that can only make sense when members of a targeted group are taken to be inferior.