bluuebunny/crossref_metadata_2025 huggingface dataset:
Moral Constraints on Belief?
Authors: Begby Endre
Published: March 2021

The assumption that moral normativity and epistemic normativity run on separate tracks has recently come under pressure from developments such as “moral encroachment” and “doxastic morality.” Motivating these developments is the idea that in morally charged scenarios—for instance where we stand to impart unwarranted harms on others by forming certain beliefs about them—our epistemic requirements change: beliefs that would be justified by the evidence in a morally inert scenario may no longer be justified once the “moral stakes” are taken into account. In this sense, morality can act as a constraint on rational belief formation. This chapter argues that none of these approaches can carry out the task set for them. Specifically, both founder on the fact that moral and non-moral reasoning are often deeply entangled: even if we agreed about the moral principles, our assessment of who falls under the principles would depend on our further, non-moral beliefs.
Glucocorticoids in spondyloarthritis—systematic review and real-world analysis
Authors: Dhir Varun , Mishra Debasish , Samanta Joydeep
Published: March 2021

Objective

The objective of this study was to identify and summarize the efficacy and safety of systemic glucocorticoids (GCs) and local injections of GC in SpA.

Methods

PubMed (Medline) and EMBASE were searched with pre-defined keywords for relevant articles in English reporting randomized controlled trials (RCTs), non-randomized interventional studies and non-randomized observational studies of the efficacy of GC in SpA, with five or more patients, for inclusion in a systematic literature review. Local injections of GC included IA and entheseal injections, but excluded SI joint injections.

Results

Out of 9657 records identified, there were 14 studies on the use of systemic GCs in SpA (364 patients), including two RCTs of oral prednisolone. On pooling data from two placebo-controlled RCTs (≤24 weeks), BASDAI 50 was 4.2 times more likely (95% CI: 1.5, 11.5) and Ankylosing Spondylitis Assessment Group (ASAS) 20 was twice more likely (95% CI: 1.1, 3.64) to occur in patients on high-dose oral prednisolone (± taper). Pulsed GCs led to dramatic improvements that lasted a few weeks to a few months. There were no deaths or major adverse events. There were 10 studies (560 patients) on local GCs in SpA. IA injection was effective in achieving a sustained response in 51.5–90% of joints at 6 months. Entheseal injections led to reduced pain and improved US parameters.

Conclusion

There were limited studies on either systemic or local injections of GCs in SpA. However, there was good evidence of efficacy with the use of high-dose systemic GCs in the short term (≤6 months) in SpA. Both IA and entheseal injections seemed safe and effective.
Determination of in vitro dry matter, protein, and fiber digestibility and fermentability of novel corn coproducts for swine and ruminants
Authors: Palowski A , Yang Z , Jang J , Dado T , Urriola P E , Shurson G C
Published: March 2021

New processes are being used in some dry-grind ethanol plants in the United States and Brazil to improve ethanol yield and efficiency of production while also providing nutritionally enhanced corn coproducts compared with conventional corn distillers dried grains with solubles (DDGS). The objectives of this study were to determine the chemical composition and in vitro digestibility of 5 conventional corn DDGS sources and 10 emerging novel corn coproducts for swine and ruminants, and compare coproducts produced using similar processes in the United States and Brazil. Chemical composition, on a dry matter (DM) basis, among the 15 coproducts ranged from 18.5% to 54.7% for crude protein (CP), 12.3% to 51.4% for neutral detergent fiber (NDF), 1.6% to 8.6% for acid detergent fiber, 4.7% to 12.3% for ether extract, and 1.6% to 8.6% for ash. For swine, in vitro hydrolysis of DM and CP were greater (P < 0.01) for the three U.S. corn DDGS sources compared with the two Brazilian corn DDGS sources, but in vitro fermentability of DM was comparable (P > 0.05) among all sources except one U.S. DDGS source that had less fermentable DM. High-protein and yeast dried distillers grains (Ultramax, UM; StillPro, SP) coproducts also had comparable (P > 0.05) DM fermentability for swine, but UM coproducts had greater (P < 0.01) DM and CP hydrolysis compared with SP. High-protein distillers dried grains (HP-DDG) from Brazil had greater (P < 0.01) DM and CP hydrolysis, but less (P < 0.01) DM fermentability for swine than HP-DDG produced in the United States, using the same process. For ruminants, total DM digestibility was greater (P < 0.01) in conventional DDGS sources from the United States compared with the two DDGS sources from Brazil. Total protein digestibility for ruminants was comparable and above 81% for all coproducts except for a DDGS source from Brazil, a HP-DDG source from the United States, and a UM sample. Interestingly, the corn fiber + solubles coproduct had not only relatively high digestibility of NDF (67.9%), DM (91.6%), and total CP (81.9%) for ruminants, but it also had relatively high total tract digestibility of DM (86.2%) and CP (69.9%) for swine. These results suggest that nutrient digestibility of conventional DDGS sources produced in the United States appear to be greater than corn Brazilian DDGS sources, but new process technologies being implemented in ethanol and coproduct production in both countries can enhance the nutritional value of corn coproducts for both swine and ruminants.
Discrepancies Between Clinician and Participant Intervention Adherence Ratings Predict Percent Weight Change During a Six-Month Behavioral Weight Loss Intervention
Authors: Berry Michael P , Seburg Elisabeth M , Butryn Meghan L , Jeffery Robert W , Crane Melissa M , Levy Rona L , Forman Evan M , Sherwood Nancy E
Published: March 2021

Background

Individuals receiving behavioral weight loss treatment frequently fail to adhere to prescribed dietary and self-monitoring instructions, resulting in weight loss clinicians often needing to assess and intervene in these important weight control behaviors. A significant obstacle to improving adherence is that clinicians and clients sometimes disagree on the degree to which clients are actually adherent. However, prior research has not examined how clinicians and clients differ in their perceptions of client adherence to weight control behaviors, nor the implications for treatment outcomes.

Purpose

In the context of a 6-month weight-loss treatment, we examined differences between participants and clinicians when rating adherence to weight control behaviors (dietary self-monitoring; limiting calorie intake) and evaluated the hypothesis that rating one’s own adherence more highly than one’s clinician would predict less weight loss during treatment.

Methods

Using clinician and participant-reported measures of self-monitoring and calorie intake adherence, each assessed using a single item with a 7- or 8-point scale, we characterized discrepancies between participant and clinician adherence and examined associations with percent weight change over 6 months using linear mixed-effects models.

Results

Results indicated that ratings of adherence were higher when reported by participants and supported the hypothesis that participants who provided higher adherence ratings relative to their clinicians lost less weight during treatment (p < 0.001).

Conclusions

These findings suggest that participants in weight loss treatment frequently appraise their own adherence more highly than their clinicians and that participants who do so to a greater degree tend to lose less weight.
Dengue and leptospirosis infection during the coronavirus 2019 outbreak in Sri Lanka
Authors: Niriella M A , Ediriweera D S , De Silva A P , Premarathna B H R , Jayasinghe S , de Silva H J
Published: March 2021

A significant decrease in dengue fever cases and a contrasting increase in leptospirosis cases were reported for the second quarter of 2020 compared with 2019 in Sri Lanka. In the absence of significant environmental and weather-related differences to account for these changes in incidence, we investigated the possibility that the effects of the COVID-19 pandemic on public health, social behaviour and the restrictions imposed during the lockdown influenced the fluctuations in dengue and leptospirosis infections.
The history of foot-and-mouth disease virus serotype C: the first known extinct serotype?
Authors: Paton David J , Di Nardo Antonello , Knowles Nick J , Wadsworth Jemma , Pituco Edviges M , Cosivi Ottorino , Rivera Alejandro M , Kassimi Labib Bakkali , Brocchi Emiliana , de Clercq Kris , Carrillo Consuelo , Maree Francois F , Singh Raj K , Vosloo Wilna , Park Min-Kyung , Sumption Keith J , Ludi Anna B , King Donald P
Published: March 2021

Foot-and-mouth disease (FMD) is a highly contagious animal disease caused by an RNA virus subdivided into seven serotypes that are unevenly distributed in Asia, Africa, and South America. Despite the challenges of controlling FMD, since 1996 there have been only two outbreaks attributed to serotype C, in Brazil and in Kenya, in 2004. This article describes the historical distribution and origins of serotype C and its disappearance. The serotype was first described in Europe in the 1920s, where it mainly affected pigs and cattle but as a less common cause of outbreaks than serotypes O and A. No serotype C outbreaks have been reported in Europe since vaccination stopped in 1990. FMD virus is presumed to have been introduced into South America from Europe in the nineteenth century, although whether serotype C evolved there or in Europe is not known. As in Europe, this serotype was less widely distributed and caused fewer outbreaks than serotypes O and A. Since 1994, serotype C had not been reported from South America until four small outbreaks were detected in the Amazon region in 2004. Elsewhere, serotype C was introduced to Asia, in the 1950s to the 1970s, persisting and evolving for several decades in the Indian subcontinent and for eighteen years in the Philippines. Serotype C virus also circulated in East Africa between 1957 and 2004. Many serotype C viruses from European and Kenyan outbreaks were closely related to vaccine strains, including the most recently recovered Kenyan isolate from 2004. International surveillance has not confirmed any serotype C cases, worldwide, for over 15 years, despite more than 2,000 clinical submissions per year to reference laboratories. Serology provides limited evidence for absence of this serotype, as unequivocal interpretation is hampered by incomplete intra-serotype specificity of immunoassays and the continued use of this serotype in vaccines. It is recommended to continue strengthening surveillance in regions of FMD endemicity, to stop vaccination against serotype C and to reduce working with the virus in laboratories, since inadvertent escape of virus during such activities is now the biggest risk for its reappearance in the field.
Quantifying the dynamics of viral recombination during free virus and cell-to-cell transmission in HIV-1 infection
Authors: Kreger Jesse , Garcia Josephine , Zhang Hongtao , Komarova Natalia L , Wodarz Dominik , Levy David N
Published: March 2021

Recombination has been shown to contribute to human immunodeficiency virus-1 (HIV-1) evolution in vivo, but the underlying dynamics are extremely complex, depending on the nature of the fitness landscapes and of epistatic interactions. A less well-studied determinant of recombinant evolution is the mode of virus transmission in the cell population. HIV-1 can spread by free virus transmission, resulting largely in singly infected cells, and also by direct cell-to-cell transmission, resulting in the simultaneous infection of cells with multiple viruses. We investigate the contribution of these two transmission pathways to recombinant evolution, by applying mathematical models to in vitro experimental data on the growth of fluorescent reporter viruses under static conditions (where both transmission pathways operate), and under gentle shaking conditions, where cell-to-cell transmission is largely inhibited. The parameterized mathematical models are then used to extrapolate the viral evolutionary dynamics beyond the experimental settings. Assuming a fixed basic reproductive ratio of the virus (independent of transmission pathway), we find that recombinant evolution is fastest if virus spread is driven only by cell-to-cell transmission and slows down if both transmission pathways operate. Recombinant evolution is slowest if all virus spread occurs through free virus transmission. This is due to cell-to-cell transmission 1, increasing infection multiplicity; 2, promoting the co-transmission of different virus strains from cell to cell; and 3, increasing the rate at which point mutations are generated as a result of more reverse transcription events. This study further resulted in the estimation of various parameters that characterize these evolutionary processes. For example, we estimate that during cell-to-cell transmission, an average of three viruses successfully integrated into the target cell, which can significantly raise the infection multiplicity compared to free virus transmission. In general, our study points towards the importance of infection multiplicity and cell-to-cell transmission for HIV evolution.
Jurisdiction, Civilization, and the Ends of Native American Citizenship: The View from 1866
Authors: Kantrowitz Stephen
Published: March 2021

Most nineteenth-century political debates over U.S. citizenship revolved around the claims of people, often African Americans or immigrants, who aspired to that status. But Native American citizenship’s genealogy began instead with the United States assertion of the right to purchase or conquer the territory of its Indigenous neighbors, to replace them as its sole or primary inhabitants, and to make policy for the people thereby dispossessed. These very different histories of citizenship collided in 1866, when the U.S. Senate considered how to codify that status in the Civil Rights Act and Fourteenth Amendment. This article interprets these debates as the collision of an array of distinct and divergent settler colonial processes and experiences. It argues that the ultimate resolution—a half-articulated commitment to let local settler communities decide—both contradicted the ostensible purposes of the Civil Rights Act and accurately reflected how the era’s settler colonial society understood the purposes and functions of Native citizenship.
Perioperative Methadone and Ketamine for Postoperative Pain Control in Spinal Surgical Patients: A Randomized, Double-blind, Placebo-controlled Trial
Authors: Murphy Glenn S. , Avram Michael J. , Greenberg Steven B. , Benson Jessica , Bilimoria Sara , Maher Colleen E. , Teister Kevin , Szokol Joseph W.
Published: March 2021

Background

Despite application of multimodal pain management strategies, patients undergoing spinal fusion surgery frequently report severe postoperative pain. Methadone and ketamine, which are N-methyl-d-aspartate receptor antagonists, have been documented to facilitate postoperative pain control. This study therefore tested the primary hypothesis that patients recovering from spinal fusion surgery who are given ketamine and methadone use less hydromorphone on the first postoperative day than those give methadone alone.

Methods

In this randomized, double-blind, placebo-controlled trial, 130 spinal surgery patients were randomized to receive either methadone at 0.2 mg/kg (ideal body weight) intraoperatively and a 5% dextrose in water infusion for 48 h postoperatively (methadone group) or 0.2 mg/kg methadone intraoperatively and a ketamine infusion (0.3 mg · kg−1 · h−1 infusion [no bolus] intraoperatively and then 0.1 mg · kg−1 · h−1 for next 48 h [both medications dosed at ideal body weight]; methadone/ketamine group). Anesthetic care was standardized in all patients. Intravenous hydromorphone use on postoperative day 1 was the primary outcome. Pain scores, intravenous and oral opioid requirements, and patient satisfaction with pain management were assessed for the first 3 postoperative days.

Results

Median (interquartile range) intravenous hydromorphone requirements were lower in the methadone/ketamine group on postoperative day 1 (2.0 [1.0 to 3.0] vs. 4.6 [3.2 to 6.6] mg in the methadone group, median difference [95% CI] 2.5 [1.8 to 3.3] mg; P < 0.0001) and postoperative day 2. In addition, fewer oral opioid tablets were needed in the methadone/ketamine group on postoperative day 1 (2 [0 to 3] vs. 4 [0 to 8] in the methadone group; P = 0.001) and postoperative day 3. Pain scores at rest, with coughing, and with movement were lower in the methadone/ketamine group at 23 of the 24 assessment times. Patient-reported satisfaction scores were high in both study groups.

Conclusions

Postoperative analgesia was enhanced by the combination of methadone and ketamine, which act on both N-methyl-d-aspartate and μ-opioid receptors. The combination could be considered in patients having spine surgery.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Factors Associated With Failure of Superior Pubic Ramus Screws
Authors: Comadoll Shea M. , Matuszewski Paul E. , Liu Boshen , Scott Alesha , Cooper Colin , Scott Brandon , Wright Raymond D.
Published: March 2021

Objective:

Examine factors associated with fixation failure in patients treated with superior intramedullary ramus screws.

Design:

Retrospective.

Setting:

Single, Level 1 trauma center.

Patients:

Unstable pelvic ring fractures amenable fixation that included superior intramedullary ramus screws.

Intervention:

Percutaneously inserted intramedullary superior ramus screw fixation of superior pubic ramus (SPR) fractures.

Main Outcome Measurements:

Loss of reduction (LOR) of the SPR fracture defined as >2 mm displacement on pelvic radiographs at any time point in follow-up.

Results:

Two hundred eighty-five fractures in 211 patients (age 44, 95% confidence interval 40.8%–46.4%, 59.3% women, 55.1% retrograde screws) were included in the analysis. 14 (4.9%) of fractures had LOR. Patients were significantly more likely to have LOR as age increased (P = 0.01), body mass index (BMI) increased (P = 0.01), and if they were women (P < 0.01). There was a significantly decreased LOR (P < 0.01) as fractures moved further from the pubis symphysis. Retrograde screws were significantly (P < 0.01) more likely to have LOR. In SPR fractures treated with retrograde screws, failure was significantly associated with increasing BMI (P = 0.02), the presence of an inferior ramus fracture (P = 0.02), and trended toward significance with increasing age (P = 0.06), and decreased distance from the symphysis (P = 0.07).

Conclusions:

Superior ramus screws are associated with a low failure rate (4.9%), which is lower than previously reported. Retrograde screw insertion, distance from the symphysis, increasing age, increasing BMI, decreased distance from the symphysis, and ipsilateral inferior ramus fractures were predictors of failure. In these patients, alternative modalities should be considered, although low rates of failure can still be expected.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Genitourinary syndrome of menopause: a systematic review on prevalence and treatment
Authors: Mili Nikoletta , Paschou Stavroula A. , Armeni Anastasia , Georgopoulos Neoklis , Goulis Dimitrios G. , Lambrinoudaki Irene
Published: March 2021

Importance:

Genitourinary syndrome of menopause (GSM) consists of genitourinary tract symptoms that occur due to physical changes caused by estrogen concentrations decline after menopause. Unlike menopausal symptoms, which subside with time, GSM symptoms persist throughout a woman's life.

Objective:

This article aimed to systematically review the literature to investigate the prevalence of GSM and its treatment.

Evidence Review:

The search was conducted in the electronic databases PubMed, CENTRAL, and EMBASE until October 2020. Eligible for the systematic review were studies and surveys conducted via questionnaires or medical interviews evaluating the existence of GSM symptoms with or without gynecological examination in postmenopausal women or women >40 years of age.

Findings:

After the application of predefined inclusion/exclusion criteria, 27 studies were included in the systematic review. The prevalence of GSM-related symptoms, such as vaginal dryness, irritation, itching, and dyspareunia, ranged from 13% to 87%. The use of GSM-specific treatment varied from 13% to 78%. Over-the-counter lubricants and moisturizers were the most popular therapeutic options (24.0%-85.5%), followed by low-dose vaginal estrogens (4.8%-35.0%). Vaginal health is not frequently discussed during doctor visits and awareness about the condition and the number of treatment options is low. Women are concerned about the long-term safety and side effects of hormonal treatment. The majority of women who suffer from genitourinary symptoms are dissatisfied by the treatment they have used.

Conclusions and Relevance:

GSM is a highly prevalent condition among women. Nevertheless, women are frequently not aware of its cause and its treatment options. The findings of this review underline the need for education of patients and healthcare professionals regarding GSM diagnosis and treatment options.

Video Summary:

http://links.lww.com/MENO/A720.
Experiences of menopause during incarceration
Authors: Jaffe Elana F. , Palmquist Aunchalee E.L. , Knittel Andrea K.
Published: March 2021

Objective:

Despite increasing representation of older women in US jail and prison facilities, their menopause experiences and access to related care remain uncharacterized. Our objective is to explore the menopause experiences of women incarcerated in jail and prison facilities.

Methods:

We conducted a pilot study of four semi-structured in-depth interviews with women in the community who experienced menopause symptoms while incarcerated in either a prison or jail facility.

Results:

Preliminary findings suggest critical gaps in access to menopause-related resources and medical care. Participants described that lifestyle and medical interventions for menopause in prison were inaccessible, and that untreated symptoms contributed to significant distress. Participants reported feeling as though medical staff did not believe their concerns and were dismissive of their complaints. In some cases, menopause symptoms and symptom management exacerbated the ways in which institutional barriers reproduce criminalization within the carceral system.

Conclusions:

Individuals going through the menopause transition while experiencing incarceration have significant unmet needs and poor access to relieving lifestyle changes or medical interventions. Policy and practice changes should address menopause-related needs of individuals experiencing incarceration.

Video Summary:

http://links.lww.com/MENO/A730.
International Association for the Study of Pain Presidential Task Force on Cannabis and Cannabinoid Analgesia: research agenda on the use of cannabinoids, cannabis, and cannabis-based medicines for pain management
Authors: Haroutounian Simon , Arendt-Nielsen Lars , Belton Joletta , Blyth Fiona M. , Degenhardt Louisa , Di Forti Marta , Eccleston Christopher , Finn David P. , Finnerup Nanna B. , Fisher Emma , Fogarty Alexandra E. , Gilron Ian , Hohmann Andrea G. , Kalso Eija , Krane Elliot , Mohiuddin Mohammed , Moore R. Andrew , Rowbotham Michael , Soliman Nadia , Wallace Mark , Zinboonyahgoon Nantthasorn , Rice Andrew S.C.
Published: March 2021

The President of the International Association for the Study of Pain established a task force on cannabis and cannabinoid analgesia to systematically examine the evidence on (1) analgesic pharmacology of cannabinoids and preclinical evidence on their efficacy in animal models of injury-related or pathological persistent pain; (2) the clinical efficacy of cannabis, cannabinoids, and cannabis-based medicines for pain; (3) harms related to long-term use of cannabinoids; as well as (4) societal issues and policy implications related to the use of these compounds for pain management. Here, we summarize key knowledge gaps identified in the task force outputs and propose a research agenda for generating high-quality evidence on the topic. The systematic assessment of preclinical and clinical literature identified gaps in rigor of study design and reporting across the translational spectrum. We provide recommendations to improve the quality, rigor, transparency, and reproducibility of preclinical and clinical research on cannabis and cannabinoids for pain, as well as for the conduct of systematic reviews on the topic. Gaps related to comprehensive understanding of the endocannabinoid system and cannabinoid pharmacology, including pharmacokinetics and drug formulation aspects, are discussed. We outline key areas where high-quality clinical trials with cannabinoids are needed. Remaining important questions about long-term and short-term safety of cannabis and cannabinoids are emphasized. Finally, regulatory, societal, and policy challenges associated with medicinal and nonmedicinal use of cannabis are highlighted, with recommendations for improving patient safety and reducing societal harms in the context of pain management.
Willingness to Pay for Select Tick-Borne Disease Prevention Measures in Endemic Areas
Authors: Niesobecki Sara , Rutz Heather , Niccolai Linda , Hook Sarah , Feldman Katherine , Hinckley Alison
Published: March 2021

Tick-borne diseases (TBDs) are increasing despite prevention recommendations. We explored whether cost is a barrier to prevention use in Connecticut and Maryland, using a cross-sectional survey. Respondents were queried regarding their willingness to pay for chemical, natural, and rodent-targeted yard pesticide treatments and permethrin-treated clothing. We evaluated associations between demographics, TBD knowledge and attitudes, and willingness to pay for prevention methods.

Most respondents would pay for yard treatments (85%); 95% preferring natural pesticide, and 82% would pay for permethrin-treated clothing. Most did not want to pay more than $99 for any of the yard treatments. Having a household income of $100 000 was associated with willingness to pay $100 or more for chemical, natural, or rodent-targeted treatments and $25 or more for permethrin self-treated and pretreated clothing. Yard treatments, especially natural pesticides, were acceptable for TBD prevention; however, current pricing may be cost-prohibitive. Permethrin-treated clothing may be an affordable and acceptable prevention method.
Behavioural plasticity in a native species may be related to foraging resilience in the presence of an aggressive invader
Authors: Keiller Melinda L. , Lopez Laura K. , Paijmans Kai C. , Wong Marian Y. L.
Published: March 2021

Competition between invasive and native species can result in the exploitation of resources by the invader, reducing foraging rates of natives. However, it is increasingly recognized that multiple factors can enhance the resilience of native species competing for limiting resources with invaders. Although extensively studied in terrestrial species, little research has focused on behavioural plasticity in aquatic ecosystems and how this influences native species resilience. Here, we examined the role of behavioural plasticity in interactions between a native Australian fish,
Pseudomugil signifer,
and a widespread invasive fish,
Gambusia holbrooki
. To determine whether
P. signifer
displays behavioural plasticity that may mitigate competition with
G. holbrooki
, we first quantified social behaviours (aggression, submission and affiliation) and shoal cohesion for each species in single- and mixed-species groups. Second, we compared the feeding rates of both species in these groups to ascertain if any modulation of social behaviours and cohesion related to foraging success. We found that aggressive and submissive behaviours of
G. holbrooki
and
P. signifer
showed plasticity in the presence of heterospecifics, but social affiliation, shoaling and, most importantly, foraging, remained inflexible. This variation in the degree of plasticity highlights the complexity of the behavioural response of a native species and suggests that both behavioural modulation and consistency may be related to sustaining foraging efficiency in the presence of an invader.
Learning differential equation models from stochastic agent-based model simulations
Authors: Nardini John T. , Baker Ruth E. , Simpson Matthew J. , Flores Kevin B.
Published: March 2021

Agent-based models provide a flexible framework that is frequently used for modelling many biological systems, including cell migration, molecular dynamics, ecology and epidemiology. Analysis of the model dynamics can be challenging due to their inherent stochasticity and heavy computational requirements. Common approaches to the analysis of agent-based models include extensive Monte Carlo simulation of the model or the derivation of coarse-grained differential equation models to predict the expected or averaged output from the agent-based model. Both of these approaches have limitations, however, as extensive computation of complex agent-based models may be infeasible, and coarse-grained differential equation models can fail to accurately describe model dynamics in certain parameter regimes. We propose that methods from the equation learning field provide a promising, novel and unifying approach for agent-based model analysis. Equation learning is a recent field of research from data science that aims to infer differential equation models directly from data. We use this tutorial to review how methods from equation learning can be used to learn differential equation models from agent-based model simulations. We demonstrate that this framework is easy to use, requires few model simulations, and accurately predicts model dynamics in parameter regions where coarse-grained differential equation models fail to do so. We highlight these advantages through several case studies involving two agent-based models that are broadly applicable to biological phenomena: a birth–death–migration model commonly used to explore cell biology experiments and a susceptible–infected–recovered model of infectious disease spread.
Non-local interactions in collective motion
Authors: King Arthur E. B. T. , Turner Matthew S.
Published: March 2021

The collective motion of animal groups often exhibits velocity–velocity correlations between nearest neighbours, with the strongest velocity correlations observed at the shortest inter-animal spacings. This may have been a motivational factor in the development of models based primarily on short-ranged interactions. Here we ask whether such observations necessarily mean that the interactions are short-ranged. We develop a minimal model of collective motion capable of supporting interactions of arbitrary range and show that it represents a counterexample: the strongest velocity correlations emerge at the shortest distances, even when the interactions are explicitly non-local.
Estimating COVID-19 cases and outbreaks on-stream through phone calls
Authors: Alvarez Ezequiel , Obando Daniela , Crespo Sebastian , Garcia Enio , Kreplak Nicolas , Marsico Franco
Published: March 2021

One of the main problems in controlling COVID-19 epidemic spread is the delay in confirming cases. Having information on changes in the epidemic evolution or outbreaks rise before laboratory-confirmation is crucial in decision making for Public Health policies. We present an algorithm to estimate on-stream the number of COVID-19 cases using the data from telephone calls to a COVID-line. By modelling the calls as background (proportional to population) plus signal (proportional to infected), we fit the calls in Province of Buenos Aires (Argentina) with coefficient of determinationR2> 0.85. This result allows us to estimate the number of cases given the number of calls from a specific district, days before the laboratory results are available. We validate the algorithm with real data. We show how to use the algorithm to track on-stream the epidemic, and present the Early Outbreak Alarm to detect outbreaks in advance of laboratory results. One key point in the developed algorithm is a detailed track of the uncertainties in the estimations, since the alarm uses the significance of the observables as a main indicator to detect an anomaly. We present the details of the explicit example in Villa Azul (Quilmes) where this tool resulted crucial to control an outbreak on time. The presented tools have been designed in urgency with the available data at the time of the development, and therefore have their limitations which we describe and discuss. We consider possible improvements on the tools, many of which are currently under development.
Object manipulation without hands
Authors: Sugasawa Shoko , Webb Barbara , Healy Susan D.
Published: March 2021

Our current understanding of manipulation is based on primate hands, resulting in a detailed but narrow perspective of ways to handle objects. Although most other animals lack hands, they are still capable of flexible manipulation of diverse objects, including food and nest materials, and depend on dexterity in object handling to survive and reproduce. Birds, for instance, use their bills and feet to forage and build nests, while insects carry food and construct nests with their mandibles and legs. Bird bills and insect mandibles are much simpler than a primate hand, resembling simple robotic grippers. A better understanding of manipulation in these and other species would provide a broader comparative perspective on the origins of dexterity. Here we contrast data from primates, birds and insects, describing how they sense and grasp objects, and the neural architectures that control manipulation. Finally, we outline techniques for collecting comparable manipulation data from animals with diverse morphologies and describe the practical applications of studying manipulation in a wide range of species, including providing inspiration for novel designs of robotic manipulators.
Comparative analysis of helminth infectivity: growth in intermediate hosts increases establishment rates in the next host
Authors: Froelick Spencer , Gramolini Laura , Benesh Daniel P.
Published: March 2021

Parasitic worms (i.e. helminths) commonly infect multiple hosts in succession before reproducing. At each life cycle step, worms may fail to infect the next host, and this risk accumulates as life cycles include more successive hosts. Risk accumulation can be minimized by having high establishment success in the next host, but comparisons of establishment probabilities across parasite life stages are lacking. We compiled recovery rates (i.e. the proportion of parasites recovered from an administered dose) from experimental infections with acanthocephalans, cestodes and nematodes. Our data covered 127 helminth species and 16 913 exposed hosts. Recovery rates increased with life cycle progression (11%, 29% and 46% in first, second and third hosts, respectively), because larger worm larvae had higher recovery, both within and across life stages. Recovery declined in bigger hosts but less than it increased with worm size. Higher doses were used in systems with lower recovery, suggesting that high doses are chosen when few worms are expected to establish infection. Our results indicate that growing in the small and short-lived hosts at the start of a complex life cycle, though dangerous, may substantially improve parasites' chances of completing their life cycles.
Changes in CD163+, CD11b+, and CCR2+ peripheral monocytes relate to Parkinson’s disease and cognition
Authors: Nissen Sara Konstantin , Farmen Kristine , Carstensen Mikkel , Schulte Claudia , Goldeck David , Brockmann Kathrin , Romero-Ramos Marina
Published: March 2021

1.

Alpha-synuclein pathology is associated with immune activation and neurodegeneration in Parkinson’s disease. The immune activation involves not only microglia but also peripheral immune cells, such as mononuclear phagocytes found in blood and infiltrated in the brain. Understanding peripheral immune involvement is essential for developing immunomodulatory treatment. Therefore, we aimed to study circulating mononuclear phagocytes in early- and late-stage Parkinson’s disease, defined by disease duration of less or more than five years, respectively, and analyze their association with clinical phenotypes. We performed a cross-sectional multi-color flow cytometry study on 78 sex-balanced individuals with sporadic Parkinson’s disease, 28 controls, and longitudinal samples from seven patients and one control. Cell frequencies and surface marker expressions on natural killer cells, monocyte subtypes, and dendritic cells were compared between groups and correlated with standardized clinical scores. We found elevated frequencies and surface levels of migration-(CCR2, CD11b) and phagocytic-(CD163) markers, particularly on classical and intermediate monocytes in early Parkinson’s disease. HLA-DR expression was increased in advanced stages of the disease, whereas TLR4 expression was decreased in women with Parkinson’s Disease. The disease-associated immune changes on CCR2 and CD11b correlated with worse cognition. Increased TLR2 expression was related to worse motor symptoms. In conclusion, our data highlights the TLR2 relevance in the symptomatic motor presentation of the disease and a role for peripheral CD163+ and migration-competent monocytes in Parkinson’s disease cognitive defects. Our study suggests that the peripheral immune system is dynamically altered in Parkinson’s disease stages and directly related to both symptoms and the sex bias of the disease.

Highlights

TLR2 expression increased in patients with worse motor symptoms.

Increased CD163 and HLA-DR monocytic expression in patients with long PD duration.

Sexual-dimorphism for CCR2, CD11b, and TLR4 expression on PD monocytes.

CCR2 and CD11b expression are associated with cognitive impairment in PD.
Rapid base-specific calling of SARS-CoV-2 variants of concern using combined RT-PCR melting curve screening and SIRPH technology
Authors: Sascha Tierling , Kathrin Kattler , Markus Vogelgesang , Thorsten Pfuhl , Stefan Lohse , Christina Lo Porto , Beate Schmitt , Abdulrahman Salhab , Sigrun Smola , Jörn Walter
Published: March 2021

The emergence of novel variants of concern of SARS-CoV-2 demands a fast and reliable detection of such variants in local populations. Here we present a cost-efficient and fast workflow combining a pre-screening of SARS-CoV-2 positive samples using RT-PCR melting curve analysis with multiplexed IP-RP-HPLC-based single nucleotide primer extensions (SIRPH). The entire workflow from positive SARS-CoV-2 testing to base-specific identification of variants requires about 24 h. We applied the sensitive method to monitor the local VOC outbreaks in a few hundred positive samples collected in a confined region of Germany.
JAX-CNV: A whole genome sequencing-based algorithm for copy number detection at clinical grade level
Authors: Lee Wan-Ping , Zhu Qihui , Yang Xiaofei , Liu Silvia , Cerveira Eliza , Ryan Mallory , Mil-Homens Adam , Bellfy Lauren , Ye Kai , Zhang Chengsheng , Lee Charles
Published: March 2021

We aimed to develop a whole genome sequencing (WGS)-based copy number variant (CNV) calling algorithm with the potential of replacing chromosomal microarray assay (CMA) for clinical diagnosis. JAX-CNV is thus developed for CNV detection from WGS. The performance of this CNV calling algorithm was evaluated in a blinded manner on 31 samples and compared to the results of clinically-validated CMAs. Comparing to 112 CNVs reported by clinically-validated CMAs of the 31 samples, JAX-CNV is 100% recalling them. Besides, JAX-CNV identified an average of 30 CNVs per individual that is an approximately seven-fold increase compared to calls of clinically-validated CMAs. Experimental validation of 24 randomly selected CNVs, showed one false positive (i.e., a false discovery rate of 4.17%). A robustness test on lower-coverage data revealed a 100% sensitivity for CNVs greater than 300 kb (the current threshold for College of American Pathologists) down to 10x coverage. For CNVs greater than 50 kb, sensitivities were 100% for coverages deeper than 20x, 97% for 15x, and 95% for 10x. We developed a WGS-based CNV pipeline, including this newly developed CNV caller JAX-CNV, and found it capable of detecting CMA reported CNVs at 100% sensitivity with about 4% false discovery rate. We propose that JAX-CNV could be further examined in a multi-institutional study to justify the transition of first-tier genetic testing from CMAs to WGS. JAX-CNV is available on https://github.com/TheJacksonLaboratory/JAX-CNV.
Post-stroke fatigue is linked to resting state posterior hypoactivity and prefrontal hyperactivity
Authors: Cotter Georgia , Khlif Mohamed Salah , Bird Laura , Howard Mark E , Brodtmann Amy , Egorova Natalia
Published: March 2021

Background and Purpose

Fatigue is associated with poor functional outcomes and increased mortality following stroke. Survivors identify fatigue as one of their key unmet needs. Despite the growing body of research into post-stroke fatigue, the specific neural mechanisms remain largely unknown.

Methods

This observational study included 63 stroke survivors (22 women; age 30-89 years; mean 67.5±13.4 years) from the Cognition And Neocortical Volume After Stroke (CANVAS) study, a cohort study examining cognition, mood, and brain volume in stroke survivors following ischaemic stroke. Participants underwent brain imaging 3 months post-stroke, including a 7-minute resting state fMRI echoplanar sequence. We calculated the fractional amplitude of low-frequency fluctuations, a measure of resting state brain activity at the whole-brain level.

Results

Forty-five participants reported experiencing post-stroke fatigue as measured by an item on the Patient Health Questionnaire-9. A generalised linear regression model analysis with age, sex, and stroke severity covariates was conducted to compare resting state brain activity in the 0.01-0.08 Hz range, as well as its subcomponents - slow-5 (0.01-0.027 Hz), and slow-4 (0.027-0.073 Hz) frequency bands between fatigued and non-fatigued participants. We found no significant associations between post-stroke fatigue and ischaemic stroke lesion location or stroke volume. However, in the overall 0.01-0.08 Hz band, participants with post-stroke fatigue demonstrated significantly lower resting-state activity in the calcarine cortex (p<0.001, cluster-corrected pFDR=0.009, k=63) and lingual gyrus (p<0.001, cluster-corrected pFDR=0.025, k=42) and significantly higher activity in the medial prefrontal cortex (p<0.001, cluster-corrected pFDR=0.03, k=45), attributed to slow-4 and slow-5 oscillations, respectively.

Conclusions

Post-stroke fatigue is associated with posterior hypoactivity and prefrontal hyperactivity, reflecting dysfunction within large-scale brain systems such as fronto-striatal-thalamic and frontal-occipital networks. These systems in turn might reflect a relationship between post-stroke fatigue and abnormalities in executive and visual functioning. This first whole-brain resting-state study provides new targets for further investigation of post-stroke fatigue beyond the lesion approach.
Fast and accurate genome-wide predictions and structural modeling of protein-protein interactions using Galaxy
Authors: Guerler Aysam , Baker Dannon , van den Beek Marius , Gruening Bjoern , Bouvier Dave , Coraor Nate , Shank Stephen D. , Zehr Jordan D. , Schatz Michael C. , Nekrutenko Anton
Published: March 2021

Protein-protein interactions play a crucial role in almost all cellular processes. Identifying interacting proteins reveals insight into living organisms and yields novel drug targets for disease treatment. Here, we present a publicly available, automated pipeline to predict genome-wide protein-protein interactions and produce high-quality multimeric structural models.

Application of our method to the Human and Yeast genomes yield protein-protein interaction networks similar in quality to common experimental methods. We identified and modeled Human proteins likely to interact with the papain-like protease of SARS-CoV2’s non-structural protein 3 (Nsp3). We also produced models of SARS-CoV2’s spike protein (S) interacting with myelin-oligodendrocyte glycoprotein receptor (MOG) and dipeptidyl peptidase-4 (DPP4). The presented method is capable of confidently identifying interactions while providing high-quality multimeric structural models for experimental validation.

The interactome modeling pipeline is available at usegalaxy.org and usegalaxy.eu.
Predicting continuous ground reaction forces from accelerometers during uphill and downhill running: A recurrent neural network solution
Authors: Alcantara Ryan S. , Edwards W. Brent , Millet Guillaume Y. , Grabowski Alena M.
Published: March 2021

Ground reaction forces (GRFs) are important for understanding human movement, but their measurement is generally limited to a laboratory. Previous studies used neural networks to predict GRF waveforms during running from wearable device data, but these predictions are limited to the stance phase of level-ground running. We sought to develop a recurrent neural network capable of predicting continuous normal (perpendicular to surface) GRFs across a range of running speeds and slopes from accelerometer data.

19 subjects ran on a force-measuring treadmill at five slopes (0°, ±5°, ±10°) and three speeds (2.5, 3.33, 4.17 m/s) per slope with sacral- and shoe-mounted accelerometers. We then trained a recurrent neural network to predict normal GRF waveforms frame-by-frame. The predicted versus measured GRF waveforms had an average ± SD RMSE of 0.16 ± 0.04 BW and relative RMSE of 6.4 ± 1.5% across all conditions and subjects.

The recurrent neural network predicted continuous normal GRF waveforms across a range of running speeds and slopes with greater accuracy than neural networks implemented in previous studies. This approach may facilitate predictions of biomechanical variables outside the laboratory in near real-time and improves the accurately of quantifying and monitoring external loads experienced by the body when running.