bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management Considerations for the Surgical Treatment of Colorectal Cancer During the Global Covid-19 Pandemic
Authors: O’Leary Michael P. , Choong Kevin C. , Thornblade Lucas W. , Fakih Marwan G. , Fong Yuman , Kaiser Andreas M. 
Published: May 2020

Objective:
The COVID-19 pandemic requires to conscientiously weigh “timely surgical intervention” for colorectal cancer against efforts to conserve hospital resources and protect patients and health care providers.

Summary Background Data:
Professional societies provided ad-hoc guidance at the outset of the COVID-19 pandemic on deferral of surgical and perioperative interventions, but these lack specific parameters to determine the optimal timing of surgery.

Methods:
Using the GRADE system, published evidence was analyzed to generate weighted statements for stage, site, acuity of presentation, and hospital setting to specify when surgery should be pursued, the time and duration of oncologically acceptable delays, and when to utilize nonsurgical modalities to bridge the waiting period.

Results:
Colorectal cancer surgeries—prioritized as emergency, urgent with imminent emergency or oncologically urgent, or elective—were matched against the phases of the pandemic. Surgery in COVID-19-positive patients must be avoided. Emergent and imminent emergent cases should mostly proceed unless resources are exhausted. Standard practices allow for postponement of elective cases and deferral to nonsurgical modalities of stage II/III rectal and metastatic colorectal cancer. Oncologically urgent cases may be delayed for 6(–12) weeks without jeopardizing oncological outcomes. Outside established principles, administration of nonsurgical modalities is not justified and increases the vulnerability of patients.

Conclusions:
The COVID-19 pandemic has stressed already limited health care resources and forced rationing, triage, and prioritization of care in general, specifically of surgical interventions. Established guidelines allow for modifications of optimal timing and type of surgery for colorectal cancer during an unrelated pandemic.
Oscillatory dynamics in infectivity and death rates of COVID-19
Authors: Pavlíček Tomáš , Rehak Pavel , Král Petr 
Published: May 2020

AbstractThe analysis of systematically collected data for COVID-19 infectivity and death rates has revealed in many countries around the world a typical oscillatory pattern with a 7-days (circaseptan) period. Additionally, in some countries the 3.5-days (hemicircaseptan) and 14-days periodicities have been also observed. Interestingly, the 7-days infectivity and death rates oscillations are almost in phase, showing local maxima on Thursdays/Fridays and local minima on Sundays/Mondays. These observations are in stark contrast with a known pattern, correlating the death rate with the reduced medical staff in hospitals on the weekends. One possible hypothesis addressing these observations is that they reflect a gradually increasing stress with the progressing week, which can trigger the maximal death rates observed on Thursdays/Fridays. Moreover, assuming the weekends provide the likely time for new infections, the maximum number of new cases might fall again on Thursdays/Fridays. These observations deserve further study to provide better understanding of the COVID-19 dynamics.
Calories delivered by nonhuman primate foraging enrichment: Data and methods to inform decisions concerning the dietary consequences of enrichment
Authors: Pierre Peter J. , Torres Nicolette A. , Rosga Michele , Sullivan Jennifer 
Published: May 2020

AbstractForaging opportunities are a key component of enrichment in captive nonhuman primates providing manipulative opportunities in which animals can engage in species-typical behaviors. Recent studies suggest captive NHP populations have increased body weight over time leading to negative health outcomes. Increasing food foraging opportunities provides added calories that can be estimated but often are not directly measured. We assessed 10 commonly used foraging puzzles for the amount of foraging material they held; evaluated the range of caloric content delivered; and determine the labor and usage cost of each. Five preparation areas were sampled. The amount of foraging material contained in each prepared puzzle was calculated by subtracting the average empty puzzle weight from the loaded puzzle weight. A detailed description of food content was used to illustrate caloric content. Larger prepared puzzles held more food (M=104.9 g) as compared to small volumes puzzles (M=59.8 g). Analysis of the weight of food applied and caloric content suggest larger puzzles do have the potential to provide increased caloric load; however, the added food from large foraging puzzles constitutes only 5%-10% of the daily k/cal dietary requirement. The study illustrates the importance of considering puzzle characteristics when selecting foraging toys and discusses the considerations of cost of puzzle deployment, maintenance and interactive benefit. The broad significance of our assessment suggests that calories from foraging opportunities are not excessive and can be managed by adopting standard serving sizes and scheduling intermitted presentation of non-nutritive enrichment options.
Increasing the gradient of energetic cost does not initiate adaptation in human walking
Authors: Simha Surabhi N. , Wong Jeremy D. , Selinger Jessica C. , Abram Sabrina J. , Donelan J. Maxwell 
Published: May 2020

AbstractWhen in a new situation, the nervous system may benefit from adapting its control policy. In determining whether or not to initiate this adaptation, the nervous system may rely on some features of the new situation. Here we tested whether one such feature is salient cost savings. We changed cost saliency by manipulating the gradient of participants’ energetic cost landscape during walking. We hypothesized that steeper gradients would cause participants to spontaneously adapt their step frequency to lower costs. To manipulate the gradient, a mechatronic system applied controlled fore-aft forces to the waist of participants as a function of their step frequency as they walked on a treadmill. These forces increased the energetic cost of walking at high step frequencies and reduced it at low step frequencies. We successfully created three cost landscapes of increasing gradients, where the natural variability in participants’ step frequency provided cost changes of 3.6% (shallow), 7.2% (intermediate) and 10.2% (steep). Participants did not spontaneously initiate adaptation in response to any of the gradients. Using metronome-guided walking— a previously established protocol for eliciting initiation of adaptation—participants next experienced a step frequency with a lower cost. Participants then adapted by −1.41±0.81 (p=0.007) normalized units away from their originally preferred step frequency obtaining cost savings of 4.80±3.12%. That participants would adapt under some conditions, but not in response to steeper cost gradients, suggests that the nervous system does not solely rely on the gradient of energetic cost to initiate adaptation in novel situations.
Influence of Supraphysiologic Biomaterial Stiffness on Ventricular Mechanics and Myocardial Infarct Reinforcement
Authors: Ghanta Ravi K. , Zhao Yunge , Pugazenthi Aarthi , Wall Mathew J. , Russell Lauren N. , Lampe Kyle J. 
Published: May 2020

ABSTRACTInjectable intramyocardial biomaterials have promise to limit adverse ventricular remodeling through mechanical and biologic mechanisms. While some success has been observed by injecting materials to regenerate new tissue, optimal biomaterial stiffness to thicken and stiffen infarcted myocardium to limit adverse remodeling has not been determined. In this work, we present an in-vivo study of the impact of biomaterial stiffness over a wide range of stiffness moduli on ventricular mechanics. We utilized injectable methacrylated polyethylene glycol (PEG) hydrogels fabricated at 3 different mechanical moduli: 5 kPa (low), 25 kPa (medium/myocardium), and 250 kPa (high/supraphysiologic). We demonstrate that the supraphysiological high stiffness favorably alters post-infarct ventricular mechanics and prevents negative tissue remodeling. Lower stiffness materials do not alter mechanics and thus to be effective, must instead target biological reparative mechanisms. These results may influence rationale design criteria for biomaterials developed for infarct reinforcement therapy.
Gwas and Genomic Selection For Increased Anthocyanin Content in Purple Corn
Authors: Chatham Laura A. , Juvik John A. 
Published: May 2020

AbstractPurple corn offers an attractive source of economical natural anthocyanin-based colorant for use in foods and beverages. Yet to maximize the scalability and meet growing demands, both anthocyanin concentrations and agronomic performance must improve in purple corn varieties. We studied flux through the flavonoid biosynthesis pathway using GWAS data derived from a diverse purple corn landrace with anthocyanin-rich pericarp, Apache Red. Trends between flavonoid endpoints suggest that regulators of total flux into the pathway and regulators of partitioning within the pathway may both represent targets for maximizing anthocyanin content. A peak at the end of chromosome 1 nearAat1 (Anthocyanin acyltransferase1) was highly significant in all approaches taken to map anthocyanin flux, suggesting the structural modification of malonylation is required for maximal anthocyanin production. We also identified several candidate MATEs and H+ATPases that could assist in the preferential transport of acylated anthocyanins into the vacuole. These and other candidates identified here suggest there is still much to learn about the regulation of anthocyanin biosynthesis in the pericarp of purple corn. The efficacy of genomic predictions in the population was also studied, yielding an accuracy of 0.71 with cross validation for total anthocyanin content with no improvement found when known anthocyanin regulators were added to the model. These data suggest that genomic selection could be employed effectively in a purple corn breeding program, and especially for a landrace improvement program.
BCG vaccination and socioeconomic variables vs Covid-19 global features: clearing up a controversial issue
Authors: Ventura Luigi , Vitali Matteo , Spica Vincenzo Romano 
Published: May 2020

AbstractBackgroundThe Covid-19 pandemic is characterized by extreme variability in the outcome distribution and mortality rates across different countries. Some recent studies suggested an inverse correlation with BCG vaccination at population level, while others denied this hypothesis. In order to address this controversial issue, we performed a strict epidemiological study collecting data available on a global scale, considering additional variables such as cultural-political factors and adherence to other vaccination coverages.MethodsData on 121 countries, accounting for about 99% of Covid-19 cases and deaths globally, were from John’s Hopkins Coronavirus Resource Center, World Bank, International Monetary Fund, United Nations, Human Freedom Report, and BCG Atlas. Statistical models used were Ordinary Least Squares, Tobit and Fractional Probit, implemented on Stata/MP16 software.ResultsBased on our results, countries where BCG vaccination is or has been mandated in the last decades have seen a drastic reduction in Covid-19 diffusion (−80% on average) and mortality (−50% on average), even controlling for relative wealth of countries and their governmental health expenditure. A significant contribution to this reduction (respectively −50% and −13% on average) was also associated to the outbreak onset during summer, suggesting a possible influence of seasonality. Other variables turned out to be associated, though to a lesser extent.ConclusionsRelying on a very large dataset and a wide array of control variables, our study confirms a strong and robust association between Covid-19 diffusion and mortality with BCG vaccination and a set socio-economic factors, opening new perspectives for clinical speculations and public health policies.
Phase-dependent closed-loop modulation of neural oscillations in vivo
Authors: McNamara Colin G. , Rothwell Max , Sharott Andrew 
Published: May 2020

AbstractNormal brain function is associated with an assortment of oscillations of various frequencies, each reflecting the timing of separate computational processes and levels of synchronization within and between brain areas. Stimulation accurately delivered on a specified phase of a given oscillation provides the opportunity to target individual aspects of brain function. To achieve this, we have developed a highly responsive system to produce a continuous online phase-estimate. In addition to stable oscillations, the system accurately tracks the early cycles of short, transient oscillations and can operate across the frequency range of most established neuronal oscillations (4 to 250 Hz). Here we demonstrate bidirectional modulation of the pathologically elevated parkinsonian beta-band oscillation (around 35 Hz) in 6-OHDA hemi-lesioned rats. Beta phase, monitored using a single channel electrocorticogram above secondary motor cortex, was used to drive electrical stimulation of the globus pallidus on one of eight phases spanning the oscillation cycle. Stimulation of the early ascending phase suppressed the oscillation whereas stimulation of the early descending phase was amplifying. By implementing a rule that prevented stimulation when the phase estimate was unstable, we achieved a system that could adapt stimulation rate and pattern to respond to the changes produced in the target oscillation. This allowed the electronic system to create and maintain a state of equilibrium with the biological system resulting in continuous stable modulation of the target oscillation over time. These results demonstrate the feasibility of phase locked stimulation as a more refined strategy for remediation of pathological beta oscillations in the treatment of the motor symptoms of Parkinson’s disease. Furthermore, they establish the utility of our algorithm and allow for the potential to assess the contribution of rhythmic activity in neuronal computation across a number of brain systems.
Maternal approach behaviors toward neonatal calls are impaired by mother’s experiences of raising pups with a risk gene variant for autism
Authors: Kato Risa , Machida Akihiro , Nomoto Kensaku , Kang Gina , Hiramoto Takeshi , Tanigaki Kenji , Mogi Kazutaka , Hiroi Noboru , Kikusui Takefumi 
Published: May 2020

AbstractHow the intrinsic sequence structure of neonatal mouse pup ultrasonic vocalization (USV) and maternal experiences determine maternal behaviors in mice is poorly understood. Our previous work showed that pups with aTbx1heterozygous (HT) mutation, a genetic risk for autism spectrum disorder (ASD), emit altered call sequences that do not induce maternal approach behaviors in C57BL6/J mothers. Here, we tested how maternal approach behaviors induced by wild-type and HT USVs are influenced by the mother’s experience in raising pups of these two genotypes. The results showed that wild-type USVs were effective in inducing maternal approach behaviors when mothers raised wild-type but not HT pups. The USVs of HT pups were ineffective regardless of whether mothers raised HT or wild-type pups. However, the sequence structure of pup USVs had no effect on the general, non-directional incentive motivation of maternal behaviors. Our data show how the mother’s experience with a pup with a genetic risk for ASD alters the intrinsic incentive values of USV sequences in maternal approach behaviors.
Optogenetic activation of the inhibitory nigro-collicular circuit evokes orienting movements in mice
Authors: Villalobos C.A. , Basso M.A. 
Published: May 2020

ABSTRACTIn contrast to predictions from the current model of basal ganglia (BG) function, we report here that increasing inhibition from the BG to the superior colliculus (SC) through the substantia nigra (nigra) using in vivo optogenetic activation of GABAergic terminals in mice, produces contralateral orienting movements. Orienting movements resulting from activation of inhibitory nigral terminals are unexpected because decreases and not increases, in nigral activity are generally associated with orienting movements. To determine how orienting movements may result from activation of inhibitory terminals, we performed a series of slice experiments and found that the same optogenetic stimulation of nigral terminals used in vivo, evoked post-inhibitory rebound depolarization and spiking in SC output neurons in vitro. Only high frequency (100Hz) stimulation evoked contralateral movements in vivo and triggered rebound spiking in vitro. The latency of orienting movements relative to the stimulation in vivo was similar to the latency of rebound spiking in vitro. Taken together, our results point toward a novel hypothesis that inhibition from the BG may play an active rather than passive role in the generation of orienting movements in mice.
What influences selection of native phosphorelay architectures?
Authors: Alves Rui , Salvado Baldiri , Milo Ron , Vilaprinyo Ester , Sorribas Albert 
Published: May 2020

AbstractPhosphorelays are signal transduction circuits that combine four different phosphorylatable protein domains for sensing environmental changes and use that information to adjust cellular metabolism to the new conditions in the milieu. Five alternative circuit architectures account for more than 99% of all phosphorelay operons annotated in over 9000 fully sequenced genomes, with one of those architectures accounting for more than 72% of all cases.Here we asked if there are biological design principles that explain the selection of preferred phosphorelay architectures in nature and what might those principles be. We created several types of data-driven mathematical models for the alternative phosphorelay architectures, exploring the dynamic behavior of the circuits in concentration and parameter space, both analytically and through over 108numerical simulations. We compared the behavior of architectures with respect to signal amplification, speed and robustness of the response, noise in the response, and transmission of environmental information to the cell.Clustering analysis of massive Monte Carlo simulations suggests that either information transmission or metabolic cost could be important in selecting the architecture of the phosphorelay. A more detailed study using models of kinetically well characterized phosphorelays (Spo0 ofBacillus subtilisand Sln1-Ypd1-Ssk1-Skn7 ofSaccharomyces cerevisiae) shows that information transmission is maximized by the natural architecture of the phosphorelay. In view of this we analyze seventeen additional phosphorelays, for which protein abundance is available but kinetic parameters are not. The architectures of 16 of these are also consistent with maximization of information transmission.Our results highlight the complexity of the genotype (architecture, parameter values, and protein abundance) to phenotype (physiological output of the circuit) mapping in phosphorelays. The results also suggest that maximizing information transmission through the circuit is important in the selection of natural circuit genotypes.
Systemic and mucosal antibody secretion specific to SARS-CoV-2 during mild versus severe COVID-19
Authors: Cervia Carlo , Nilsson Jakob , Zurbuchen Yves , Valaperti Alan , Schreiner Jens , Wolfensberger Aline , Raeber Miro E. , Adamo Sarah , Emmenegger Marc , Hasler Sara , Bosshard Philipp P. , De Cecco Elena , Bächli Esther , Rudiger Alain , Stüssi-Helbling Melina , Huber Lars C. , Zinkernagel Annelies S. , Schaer Dominik J. , Aguzzi Adriano , Held Ulrike , Probst-Müller Elsbeth , Rampini Silvana K. , Boyman Onur 
Published: May 2020

AbstractBackgroundInfection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes an acute illness termed coronavirus disease 2019 (COVID-19). Humoral immune responses likely play an important role in containing SARS-CoV-2, however, the determinants of SARS-CoV-2-specific antibody responses are unclear.MethodsUsing immunoassays specific for the SARS-CoV-2 spike protein, we determined SARS-CoV-2-specific immunoglobulin A (IgA) and immunoglobulin G (IgG) in sera and mucosal fluids of two cohorts, including patients with quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR)-confirmed SARS-CoV-2 infection (n = 56; median age 61 years) with mild versus severe COVID-19, and SARS-CoV-2-exposed healthcare workers (n = 109; median age 36 years) with or without symptoms and tested negative or positive by RT-qPCR.FindingsOn average, SARS-CoV-2-specific serum IgA titers in mild COVID-19 cases became positive eight days after symptom onset and were often transient, whereas serum IgG levels remained negative or reached positive values 9–10 days after symptom onset. Conversely, patients with severe COVID-19 showed a highly significant increase of SARS-CoV-2-specific serum IgA and IgG titers as a function of duration since symptom onset, independent of patient age and comorbidities. Very high levels of SARS-CoV-2-specific serum IgA correlated with severe acute respiratory distress syndrome (ARDS). Interestingly, some of the SARS-CoV-2-exposed healthcare workers with negative SARS-CoV-2-specific IgA and IgG serum titers had detectable SARS-CoV-2-specific IgA antibodies in their nasal fluids and tears. Moreover, SARS-CoV-2-specific IgA levels in nasal fluids of these healthcare workers were inversely correlated with patient age.InterpretationThese data show that systemic IgA and IgG production against SARS-CoV-2 develops mainly in severe COVID-19, with very high IgA levels seen in patients with severe ARDS, whereas mild disease may be associated with transient serum titers of SARS-CoV-2-specific antibodies but stimulate mucosal SARS-CoV-2-specific IgA secretion. The findings suggest four grades of antibody responses dependent on COVID-19 severity.
Confidence Sets for Cohen’sdEffect Size Images
Authors: Bowring Alexander , Telschow Fabian , Schwartzman Armin , Nichols Thomas E. 
Published: May 2020

AbstractCurrent statistical inference methods for task-fMRI suffer from two fundamental limitations. First, the focus is solely on detection of non-zero signal or signal change, a problem that is exasperated for large scale studies (e.g. UK Biobank,N= 40, 000+) where the ‘null hypothesis fallacy’ causes even trivial effects to be determined as significant. Second, for any sample size, widely used cluster inference methods only indicate regions where a null hypothesis can be rejected, without providing any notion of spatial uncertainty about the activation. In this work, we address these issues by developing spatial Confidence Sets (CSs) on clusters found in thresholded Cohen’sdeffect size images. We produce an upper and lower CS to make confidence statements about brain regions where Cohen’sdeffect sizes have exceeded and fallen short of anon-zerothreshold, respectively. The CSs convey information about the magnitude and reliability of effect sizes that is usually given separately in at-statistic and effect estimate map. We expand the theory developed in our previous work on CSs for %BOLD change effect maps (Bowring et al., 2019) using recent results from the bootstrapping literature. By assessing the empirical coverage with 2D and 3D Monte Carlo simulations resembling fMRI data, we find our method is accurate in sample sizes as low asN= 60. We compute Cohen’sdCSs for the Human Connectome Project working memory taskfMRI data, illustrating the brain regions with a reliable Cohen’sdresponse for a given threshold. By comparing the CSs with results obtained from a traditional statistical voxelwise inference, we highlight the improvement in activation localization that can be gained with the Confidence Sets.