bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-volume Hydrodissection for the Treatment of Chronic Achilles Tendinopathy
Authors: Dosal Gerardo Capo , Schroeder Jeremy D , Oh Robert C
Published: December 2022

Chronic Achilles tendinopathy (AT) is a common ailment for many active duty service members that adversely affects readiness. Patients present with pain, swelling, and limited functional ability. Kager’s fat pad is a mass of adipose tissue that protects the blood vessels supplying the Achilles tendon and preserves its function. A popular hypothesis is that scarring, tethering, and neovascularization play a significant role in the pathogenesis of AT. Current literature supports the effectiveness of high-volume (40–50 mL) hydrodissection, a procedure in which fluid is injected under ultrasound guidance into the tissues surrounding the Achilles tendon to mechanically separate the paratenon from the underlying Kager’s fat pad. There may also be a beneficial effect of scar tissue and neoneurovascular breakdown. However, high-volume injections result in short-term discomfort and decreased mobility. Lowering injection volume (2–10 mL) may reduce this morbidity and facilitate use in limited-resource environments. This case report presents a 29-year-old active duty male with recalcitrant post-traumatic AT who achieved significant pain reduction and faster return to full service using low-volume hydrodissection. The use of 10 mL volume has not been described previously and provides additional support for using lower volumes in chronic AT. This technique is a direct adjunctive treatment option with rehabilitation at a military treatment facility or in the operational environment.
3D PIC Simulations for relativistic jets with a toroidal magnetic field
Authors: Meli Athina , Nishikawa Kenichi , Köhn Christoph , Duţan Ioana , Mizuno Yosuke , Kobzar Oleh , MacDonald Nicholas , Gómez José L , Hirotani Kouichi
Published: December 2022

We have investigated how kinetic instabilities such as the Weibel instability (WI), the mushroom instability (MI), and the kinetic Kelvin–Helmholtz instability (kKHI) are excited in jets without and with a toroidal magnetic field, and how such instabilities contribute to particle acceleration. In this work, we use a new jet injection scheme, where an electric current is self-consistently generated at the jet orifice by the jet particles, which produce the toroidal magnetic field. We perform five different simulations for a sufficiently long time to examine the non-linear effects of the jet evolution. We inject unmagnetized e± and e−– p+ (mp/me = 1836), as well as magnetized e± and e−– i+ (mi/me = 4) jets with a top-hat jet density profile into an unmagnetized ambient plasmas of the same species. We show that WI, MI, and kKHI excited at the linear stage, generate a non-oscillatory x-component of the electric field accelerating, and decelerating electrons. We find that the two different jet compositions (e± and e−– i+) display different instability modes, respectively. Moreover, the magnetic field in the non-linear stage generated by different instabilities is dissipated and reorganized into new topologies. A 3D magnetic field topology depiction indicates possible reconnection sites in the non-linear stage, where the particles are significantly accelerated by the dissipation of the magnetic field associated to a possible reconnection event.
The cosmic UV background and the beginning and end of star formation in simulated field dwarf galaxies
Authors: Pereira-Wilson Matthew , Navarro Julio F , Benítez-Llambay Alejandro , Santos-Santos Isabel
Published: December 2022

We use the APOSTLE cosmological simulations to examine the role of the cosmic UV background in regulating star formation (SF) in low-mass Lambda cold dark matter (ΛCDM) haloes. In agreement with earlier work, we find that after reionization SF proceeds mainly in haloes whose mass exceeds a redshift-dependent ‘critical’ mass, Mcrit, set by the structure of the haloes and by the thermal pressure of UV-heated gas. Mcrit increases from $\sim 10^{8}\, \mathrm{M}_\odot$ at z ∼ 10 to $M_{\rm crit}\sim 10^{9.7}\, \mathrm{M}_\odot$ at z = 0, roughly following the average mass growth of haloes in that mass range. This implies that haloes well above or below critical at present have remained so since early times. Haloes of luminous dwarfs today were already above-critical and star forming at high redshift, explaining naturally the ubiquitous presence of ancient stellar populations in dwarfs, regardless of luminosity. The SF history of systems close to the critical boundary is more complex. SF may cease or reignite in dwarfs whose host halo falls below or climbs above the critical boundary, suggesting an attractive explanation for the episodic nature of SF in some dwarfs. Also, some subcritical haloes today may have been above critical in the past; these systems should at present make up a sizable population of faint field dwarfs lacking ongoing star formation. Although few such galaxies are currently known, the discovery of this population would provide strong support for our results. Our work indicates that, rather than stellar feedback, it is the ionizing UV background and mass accretion history what regulates SF in the faintest dwarfs.
Unravelling the interplay between SIDM and baryons in MW haloes: defining where baryons dictate heat transfer
Authors: Rose Jonah C , Torrey Paul , Vogelsberger Mark , O’Neil Stephanie
Published: December 2022

We present a new set of cosmological zoom-in simulations of a Milky Way (MW)-like galaxy that for the first time include elastic velocity-dependent self-interacting dark matter (SIDM) and IllustrisTNG physics. With these simulations, we investigate the interaction between SIDM and baryons and its effects on the galaxy evolution process. We also introduce a novel set of modified dark matter-only simulations that can reasonably replicate the effects of fully realized hydrodynamics on the DM halo while simplifying the analysis and lowering the computational cost. We find that baryons change the thermal structure of the central region of the halo to a greater extent than the SIDM scatterings for MW-like galaxies. Additionally, we find that the new thermal structure of the MW-like halo causes SIDM to create cuspier central densities rather than cores because the SIDM scatterings remove the thermal support by transferring heat away from the centre of the galaxy. We find that this effect, caused by baryon contraction, begins to affect galaxies with a stellar mass of 108 M⊙ and increases in strength to the MW-mass scale.
The evolution of phase space densities in star-forming regions
Authors: Blaylock-Squibbs George A , Parker Richard J
Published: December 2022

The multidimensional phase space density (both position and velocity) of star-forming regions may encode information on the initial conditions of star and planet formation. Recently, a new metric based on the Mahalanobis distance has been used to show that hot Jupiters are more likely to be found around exoplanet host stars in high six-dimensional phase space density, suggesting a more dynamic formation environment for these planets. However, later work showed that this initial result may be due to a bias in the age of hot Jupiters and the kinematics of their host stars. We test the ability of the Mahalanobis distance and density to differentiate more generally between star-forming regions with different morphologies by applying it to static regions that are either substructured or smooth and centrally concentrated. We find that the Mahalanobis distance is unable to distinguish between different morphologies, and that the initial conditions of the N-body simulations cannot be constrained using only the Mahalanobis distance or density. Furthermore, we find that the more dimensions in the phase space, the less effective the Mahalanobis density is at distinguishing between different initial conditions. We show that a combination of the mean three-dimensional (x, y, z) Mahalanobis density and the Q-parameter for a region can constrain its initial virial state. However, this is due to the discriminatory power of the Q-parameter and not from any extra information imprinted in the Mahalanobis density. We therefore recommend continued use of multiple diagnostics for determining the initial conditions of star-forming regions, rather than relying on a single multidimensional metric.
Imposters and Tricksters
Authors: Frost-Arnold Karen
Published: December 2022

Chapter 3 examines internet hoaxes. It argues for a crucial distinction between internet imposters who cause epistemic damage by violating norms of authenticity and internet tricksters who violate these norms in acts of resistance that encourage trust in the oppressed. This chapter shows that objectivity and truth acquisition depend on inclusive networks of trust. Next, it demonstrates that imposture can undermine trust, and that trustworthiness is a core epistemic virtue. However, trickery is an epistemically important resistance strategy. So we need a virtue epistemology that recognizes when violating norms of authenticity is veritistically valuable. The chapter presents some guidelines for virtuous online self-presentation that help us determine how to avoid the vices of imposters and decide whether and how to be tricksters.
Selfless Receptivity
Authors: Bommarito Nicolas , Ganeri Jonardon
Published: December 2022

A natural way to think of epistemic virtue is by analogy with an archer. Just as a skilled archer is able to take aim and hit a target, a skilled epistemic agent will aim at truth and, if things go well, get things right. Here we highlight aspects of epistemic virtue that do not fit this model, particularly ways in which epistemic virtues can be non-voluntary and not goal-directed. In doing so, we draw on two important figures in the history of philosophy: the 6th-century Indian Buddhist Buddhaghosa and the 20th-century French philosopher Simone Weil. Despite many differences, both thinkers emphasize the importance of attention in moral and epistemic virtue. Their work highlights ways in which attention that is neither voluntary nor goal-directed can nevertheless play an important role in moral and epistemic life.
Knowledge and Independent Checks in Mīmāṃsā
Authors: Das Nilanjan
Published: December 2022

This chapter is about a classical Indian debate about the Independent Check Thesis, the thesis that, if an agent is to rationally believe (or judge) that she knows that p, she must rely on some source of information that provides her independent evidence about the truth or reliability of her belief (or judgement) that p. While some Buddhists and Nyāya philosophers defended this thesis, the Bhāṭṭa Mīmāṃsakas rejected it. Here, I reconstruct the Bhāṭṭa Mīmāṃsakas’ arguments against the Independent Check Thesis. I show that these arguments reveal a tension between this thesis and a plausible principle that connects knowledge and action.
Living Toward Virtue
Authors: Woodruff Paul
Published: December 2022

Virtue ethics can be practical if we give it a new start, working from Socrates’ approach to ethics as represented in Plato. This approach is more promising than that of most recent virtue ethicists, who begin from Aristotle. It is also more practical than modern ethical theories. Socrates asks us to nurture the moral health of our souls all our lives, whereas Aristotle teaches us to acquire virtues as traits. Traits are not reliable, however, and false confidence in one’s virtue is a major cause of moral error and the moral injury that results from error. I must never think with any certainty that I have a virtue. It is especially dangerous for me to think that I have the wisdom or moral knowledge that would keep me on the right path. Socrates sets an example by recognizing his ignorance through self-examination and by making that recognition a cornerstone of human wisdom. But Socrates does not explain how we can seek virtue when we do not know for sure what it is. This book goes beyond what we know of Socrates in order to show how we can seek virtue without having knowledge. Using real-life examples, some of them from warfare, the book shows how we can nurture our souls and avoid moral injury so far as possible. The outcome of a life on this Socratic model is beauty of soul and a special kind of happiness.
Resources
Authors: Woodruff Paul
Published: December 2022

We have limited knowledge for making ethical judgments, but we still have a wide range of resources for doing so. Socrates has little to say on this score, but there is much to be said. Two main resources are our communities and our human nature (nurture and nature). Both must be used with care and critical judgment. Friends are important, as they can tell us truths about ourselves that we are loath to recognize. The experience of love can be transformative, and here we are back on Socratic ground, which I will explore more thoroughly in the final chapter. Experts, emotions, and intuitions are not in themselves valuable resources on the neo-Socratic model. By contrast, our orientation to the good, which questioning may bring to our attention, is our fundamental resource for exercising good judgment. Appendices treat the Jewish-Christian ethics of love and the success of Socratic questioning.
Is it possible to prepare for a pandemic?
Authors: Omberg Robert Tucker , Tabarrok Alex
Published: December 2022

How effective were investments in pandemic preparation? We use a comprehensive and detailed measure of pandemic preparedness, the Global Health Security (GHS) Index produced by the Johns Hopkins Center for Health Security (JHU), to measure which investments in pandemic preparedness reduced infections, deaths, excess deaths, or otherwise ameliorated or shortened the pandemic. We also look at whether values or attitudinal factors such as individualism, willingness to sacrifice, or trust in government—which might be considered a form of cultural pandemic preparedness—influenced the course of the pandemic. Our primary finding is that almost no form of pandemic preparedness helped to ameliorate or shorten the pandemic. Compared to other countries, the United States did not perform poorly because of cultural values such as individualism, collectivism, selfishness, or lack of trust. General state capacity, as opposed to specific pandemic investments, is one of the few factors which appears to improve pandemic performance. Understanding the most effective forms of pandemic preparedness can help guide future investments. Our results may also suggest that either we aren’t measuring what is important or that pandemic preparedness is a global public good.
The Afterlife of Daniel Defoe’s Captain Singleton in the Seven Years’ War
Authors: Seager Nicholas
Published: December 2022

Daniel Defoe’s pirate novel Captain Singleton (1720) was republished in 1757, during the political and military crises of the early stages of the Seven Years’ War. The fact that Singleton at this time was extensively rewritten has gone entirely unnoticed by scholars. The present article explains how this version of Defoe’s maritime picaresque fiction responded to national anxieties about naval performance, aristocratic leadership, and martial masculinity following the loss of Minorca, seeking to galvanize its readers during the privateering rush of this period and the more general appetite for a ‘blue-water’, colonial war strategy. In 1757, Bob Singleton is transformed from the stateless sea rover of Defoe’s original into a patriotic privateer who serves the British nation in an unofficial capacity, both as an African explorer in the first half and a maritime adventurer in the second. The 1757 novel shows the ways in which the rising taste for sentimental fiction, moving away from individualistic adventure stories, coalesced with imperialist and nationalist agendas in the mid-eighteenth century. This example of literary appropriation rewards the investigation of the afterlives of eighteenth-century fiction, aiding recognition of how novels endured and were revived, often in revised or remediated states, to reach different readerships and speak to new sociocultural contexts.
Deposit Insurance and Depositor Behavior: Evidence from Colombia
Authors: de Roux Nicolás , Limodio Nicola
Published: December 2022

This paper studies the effect of deposit insurance on depositor behavior. Our theoretical framework integrates insights from public and financial economics and predicts that (1) deposit insurance induces bunching at the threshold in the deposit distribution and (2) an increase in the insurance threshold promotes deposit growth, particularly higher for individuals bunching at the initial limit. We exploit a large and unexpected increase in the Colombian insurance together with monthly depositor-level records from a major bank to test these predictions. We validate the existence of bunching in deposits and quantify the heterogeneous effect of deposit insurance on individual deposit growth.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
How to conduct an acupuncture dose–effect relationship study? A discussion based on study methodology
Authors: Li Boxuan , Zhang Menglong , Ngaenklangdon Sakhorn , Jiang Hailun , Zhu Weiming , Zhuo Bifang , Qin Chenyang , Lyu Yuanhao , Du Yuzheng , Deng Shizhe , Meng Zhihong
Published: December 2022

Acupuncture therapy is widely used in the clinic, and its therapeutic effects have been proven by numerous studies. The dose–effect relationship of acupuncture is a fundamental aspect of the acupuncture research system. Recent studies found that different acupuncture dosages altered study results directly, indicating the importance of screening the optimal stimulation dosage. However, the system for studying the acupuncture dose–effect relationship is still in its infancy, and the methodology of the system needs to be improved. This review aimed to define the factors impacting acupuncture “dosage” and “effect,” and to improve the methodological system for research on the dose–effect relationship of acupuncture. By summarizing the current findings of acupuncture dose–effect studies, we discussed the vital acupuncture parameters and methodological problems that influence the relationship between acupuncture dosage and its effects. These factors consist of specific influencing factors (acupoint selection, acupuncture manipulation parameters, de qi response) and nonspecific influencing factors (comparison selection, blinding procedure, patient expectancy). Our perspectives offer suggestions for the design of acupuncture dosage–effect trials. Further studies need to be conducted to establish the methodological system and provide systematic evidence of the acupuncture dose–effect relationship.

Graphical abstract:

http://links.lww.com/AHM/A37
Tirzepatide: A Dual Glucose-dependent Insulinotropic Polypeptide and Glucagon-Like Peptide-1 Agonist for the Management of Type 2 Diabetes Mellitus
Authors: Wong Elaine , Cope Rebecca , Dima Lorena , Nguyen Timothy
Published: December 2022

Background:

Diabetes is a chronic disease that can lead to many complications, and controlling glucose balance is essential. Incretin hormones are produced in the gut and are essential to maintaining glucose homeostasis. Their effects range from increasing insulin synthesis, insulin secretion, and glucose sensing and decreasing glucagon secretion to promote satiety and suppressing appetite. Tirzepatide is a first in class dual glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide (GIP) analog approved for the management of adult patients with type 2 diabetes mellitus as an adjunct to diet and exercise.

Pharmacodynamics and Pharmacokinetics:

Tirzepatide is a synthetic chemical structure based on the GIP sequence and consists of 39 amino acid peptides. Tirzepatide increases insulin secretion, reduces glucagon release in a glucose-dependent manner, decreases fasting and postprandial glucose levels, promotes satiety, decreases body weight, and delays gastric emptying. Pharmacodynamics and pharmacokinetics properties of tirzepatide were similar in patients with kidney and hepatic impairment, and its metabolites are excreting through urine and feces.

Clinical Trials:

The SURPASS trials are pivotal phase 3 trials assessing the efficacy and safety of tirzepatide as monotherapy and as an add-on to different antihyperglycemic drugs for the management of T2DM. Tirzepatide consistently showed reductions in HbA1c, as well as benefits with weight loss, with common adverse events reported related to gastrointestinal issues.

Therapeutic Advance:

Tirzepatide is a novel first in class dual GIP and glucagon-like peptide-1 agonist that improves overall glycemic control as an adjunct to diet and exercise. It has the potential benefits in other therapeutic areas such as obesity.
The emotional impact of COVID-19 on Australian cancer patients, their caregivers, and oncology health professionals over time: a longitudinal qualitative study
Authors: Shaw Joanne , Havard Polly E. , Dhillon Haryana M. , Kelly Brian , Beatty Lisa , Juraskova Ilona , Sharpe Louise , Cigolini Maria , Chan Raymond J. , Kirsten Laura , Best Megan , Butow Phyllis
Published: December 2022

Background:

Cross-sectional research has highlighted the emotional impacts of coronavirus disease 2019 (COVID-19) in cancer communities. The aim of this study was to extend findings and to provide a longitudinal perspective of emotional effects of COVID-19 on a range of participants, including patients with cancer, their family members, and oncology health professionals (HPs) in Australia.

Methods:

This mixed-methods, longitudinal study incorporated semistructured interviews and psychological well-being survey data collected at three time points between June 2020 and October 2021.

Results:

Seventy-seven participants volunteered at time point 1 (T1; 32 patients, 16 caregivers, 29 HPs), 52 at timepoint 2 (23 patients, 10 caregivers, 19 HPs), and 43 at timepoint 3 (19 patients, 8 caregivers, 16 HPs). Overall, participants were psychologically well; however, elevated depressive symptoms were detected in HPs by timepoint 3. Qualitative results highlighted the emotional toll of COVID-19 for all participant groups over time. Three shared themes emerged: (1) balancing fear and safety, (2) uncertainty in an ever-changing situation, and (3) fatigue due to lack of support and sense of isolation. An additional theme unique to HPs was also identified: (4) a sense of dread for what is to come in an already exhausted workforce.

Conclusion:

Despite Australia's relatively low COVID-19 case numbers, an emotional toll on the cancer community was apparent. Longitudinal results indicate consistency of themes over time with the burden for HPs adding a theme by the third interview. Participants were challenged to balance needs of personal safety against cancer priorities in an environment of uncertainty and isolation. Over time, a sense of fatigue emerged, and for HPs, increased workloads left many feeling overwhelmed and unsupported with a sense of dread around future outcomes.
Competition and co-association, but not phosphorous availability, shape the benefits of phosphate solubilising root bacteria for maize (Zea mays).
Authors: Williamson Joseph , Matthews Andrew Charles , Raymond Ben
Published: December 2022

Predicting the conditions under which rhizobacteria benefit plant growth remains challenging. Here we tested the hypothesis that benefits from inoculation with phosphate-solubilising rhizobacteria will depend upon two environmental conditions: phosphate availability and competition between bacteria. Maize-associated rhizobacteria with varying phosphate solubilisation ability were used in experiments in soil, sterilised soil and gnotobiotic microcosms under conditions of varying orthophosphate availability, while we manipulated intensity of competition by varying the number of isolates in plant inocula. Growth promotion by microbes did not depend on phosphate availability but was affected by interactions between inoculants: beneficial effects of one Serratia isolate were detectable only when plants were inoculated with a single strain and beneficial effects of a competition sensitive Rhizobium was only detectable in sterilised soil or in microcosms inoculated with single strains. Moreover, microcosm experiments suggested that facilitation of a parasitic isolate, not competitive interactions between bacteria, prevented plants from gaining benefits from a potential mutualist. Competition and facilitation affected colonization of plants in microcosms but growth promotion by Serratia was more affected by inoculation treatment than culturable densities on roots. Experimental manipulation of seed inocula can reveal whether plant growth stimulation is robust with respect to competition, as well as the ecological strategies of different rhizobacteria. From an applied perspective, phosphate solubilisation may not provide the mechanism for bacterial growth promotion but may indicate mutualistic potential due to phylogenetic associations. Importantly, benefits to plants are vulnerable to interactions between rhizobacteria and may not persist in mixed inoculations.
Relationship between Blood Group (ABO) and Risk of COVID-19 Infection
Authors: Fatollahi Asal , bashizadeh fakhar haniyeh , Shaghaghi Babak
Published: December 2022

Background and purpose: Coronavirus (COVID-19) is a contagious disease causing severe acute respiratory syndrome which had a catastrophic effect on the world population and resulted in more than 2.9 million deaths worldwide. Epidemiological investigations have recently announced blood type has an association with the incidence of COVID-19 infection. Consequently, research in this regard can be effective in determining a person's susceptibility to a viral infection. Therefore, we investigated the relationship between blood types and the risk of COVID-19 in patients admitted to Khorshid laboratory, Tehran, Iran.
Materials and methods: From January to March 2020, around 50 nasal and throat swap samples of patients’ secretions were obtained from patients who were admitted to Khorshid laboratory. They were confirmed to have COVID-19 virus RNA and real-time polymerase chain reaction (PCR)-ABI, and their blood type was determined simultaneously. After collecting data to determine the relationship between COVID-19 infection and blood type, a confidence interval of 12% was considered using SPSS 16.
Results: The mean age of the patients was measured at 38.4±6.3 years. According to PCR results, 100% of the subjects with COVID-19 showed blood type A. In addition, the ratio of blood type A to the percentage of reference type O was higher (P:0.009).
Conclusion: There was a significant relationship between ABO blood type and susceptibility to COVID-19. As the current study suggests, those with blood type A are at a higher COVID-19 infection risk than those with blood type O.
Bdellovibrio reynosensis sp. nov., from a Mexico soil sample
Authors: Ajao Yewande Olajumoke , Rodríguez-Luna Isabel Cristina , Elufisan Temidayo Oluyomi , Sánchez-Varela Alejandro , Cortés-Espinosa Diana Verónica , Camilli Andrew , Guo Xianwu
Published: December 2022

A novel predatory bacterium, strain LBG001T, has been isolated from Reynosa, Mexico. The 16S rRNA shares approximately 97 % sequence identity with many reported strains in the genus

Bdellovibrio

including the type strain

Bdellovibrio bacteriovorus

HD100T. Phylogenetic trees based on the 16S rRNA gene and on 30 concatenated housekeeping genes or core genes showed that LBG001T is on a separate branch from the

B. bacteriovorus

group. LBG0001T has a genome size of 3 582 323 bp with a G+C content of 43.1 mol %. The average nucleotide identity, average amino acid identity and digital DNA–DNA hybridization values with other members of the genus

Bdellovibrio

(<79, <72 and <17 %, respectively) qualifies the strain to represent a new species in the genus. Strain LBG001T formed visible plaques on all 10 tested Gram-negative bacterial species. The phenotypic characteristics, phylogenetic analysis and genomic taxonomic studies support the classification of the strain as representing a new species for which the name Bdellovibrio reynosensis sp. nov. is proposed. The type strain is LBG001T(=ATCC TSD-288T
=CM-CNRG 0932T).
A systematic evaluation revealed that detecting translated non-canonical ORFs from ribosome profiling data remains challenging
Authors: Lei Tianyu , Chang Yue , Yao Chao , Zhang Hong
Published: December 2022

Non-canonical open reading frames (ORFs), which are ORFs that are not included in reference genome annotations, are gaining more and more research interest in recent years. While vast numbers of non-canonical ORFs have been identified with ribosome profiling (Ribo-Seq) by various state-of-the-art computational methods, the performance of these methods has not been assessed systematically. To this end, we evaluated the four most popular methods for translated non-canonical ORF prediction using various public datasets. We found that non-canonical ORFs predicted by different methods differ substantially and are not saturated at typical sequence depths. Furthermore, the precision and accuracy of all four methods are not satisfactory, especially for ORFs with near-cognate start codons. Based on these results, we suggest that improved sequence depth, biological repetitions, and translation initiation site profiling should be considered to obtain a high-quality catalog of translated non-canonical ORFs in future studies.
THE STATE OF CURRENT MANAGEMENT OF THE HEIGHTENED RISK FOR ATHEROSCLEROTIC CARDIOVASCULAR EVENTS IN AN ESTABLISHED COHORT OF PATIENTS WITH LUPUS ERYTHEMATOSUS
Authors: Zhao Megan , Feng Rui , Werth Victoria P. , Williams Kevin Jon
Published: December 2022

Background

Patients with lupus erythematosus (LE) are at a heightened risk for clinical events, chiefly heart attacks and strokes, caused by atherosclerotic cardiovascular disease (ASCVD). We recently proposed new guidelines to categorize levels of risk for future ASCVD events specifically in LE patients, with recommendations for management. Here, we assessed the state of current management of ASCVD event risk in light of these new recommendations.

Methods

We studied our entire UPenn Longitudinal Lupus Cohort of patients with cutaneous LE, without or with concurrent systemic LE, for whom we had full access to medical records (n=370, LE-ASCVD Study Cohort, years 2007-2021).

Results

Of our LE-ASCVD Study Cohort, 336/370 (90.8%) had a designated primary-care physician. By the new guidelines, the most recent plasma LDL cholesterol levels were above goal for 252/370 (68.1%) of the Cohort. Two hundred sixty-six (71.9%) had hypertension, which was under- or un-treated in 198/266 (74.4%). Of current smokers, 51/63 (81.0%) had no documented smoking cessation counseling or referrals. Diabetes was generally well-managed, and hypertriglyceridemia was uncommon. Of the Cohort, 254 patients qualified for two widely used online calculators in primary prevention that estimate the risk of an ASCVD event in the next 10 years: the ACC-ASCVD Risk Estimator Plus and QRisk3. We also stratified these 254 patients into the categories of ASCVD event risk we recently defined specifically for LE. Surprisingly, these three methods for estimating ASCVD event risk showed clinically meaningful agreement for only 100/254 (39.4%), i.e., discordance for over 60% that could affect clinical management. The documented rate of ASCVD events in the first 10 years after enrollment was 22.3% (95% CI 16.9%, 27.4%), indicating a high-risk population despite a preponderance of women and a median age at enrollment of only 47 years.

Conclusion

Cutaneous LE patients are under-treated compared with the new guidelines and, accordingly, they experience a substantial burden of ASCVD events. Moreover, it is unclear how to accurately assess future ASCVD event risk in these patients – except that it is high – and this uncertainty may complicate clinical management. Efforts are underway to improve ASCVD event risk estimation and guideline implementation in lupus patients.
A subnational family planning estimation tool (SFPET) for estimating contraceptive use and unmet need by subnational areas and demographic subgroups
Authors: Kong David , Claps Emily , Kirkman Clark , Enriquez Minerva , Ressler Bryan , Mercer Laina D. , Buxton Sam , Izzo Mandy , Proctor Joshua L.
Published: December 2022

Background

Access to safe, effective, and voluntary family planning (FP) is a fundamental human right and is an important step toward achieving gender equality and economic autonomy. Global organizations have set ambitious goals to create universal access to FP services but assessing progress can be challenging, especially at the local geographic scale. Here, we present a quantitative visualization tool called the subnational family planning estimation tool (SFPET) that can be used by policy makers to monitor programmatic success at subnational levels and gain insight into trends within demographic subgroups.

Methods

The visualization tool builds on the statistical methods and analyses presented in earlier research to generate model-based estimates of FP indicators for 25 sub-Saharan countries at administrative units one and two. Here, we have extended this modeling approach to more demographic and geographic subgroups, integrated recently released survey data, and constructed a web-based dashboard to navigate survey and model-based estimates.

Findings

Significant heterogeneity in the levels and trends of FP indicators exist at subnational levels and across demographic subgroups. This tool provides the ability to efficiently navigate these model-based estimates across local regions within countries and across demographic subgroups. The tool also helps highlight regions and groups that may be falling behind the national trends as well as identify exemplars that exceed the national average.

Interpretation

SFPET1is an interactive dashboard created to aid policymakers in assessing progress towards family planning goals by visualizing both model-based and direct survey estimates of family planning indicators at the subnational level. This framework provides insight into locations and population segments experiencing the greatest unmet need, enabling targeting and allocation of resources to achieve family planning goals.
A unifying theory explains seemingly contradicting biases in perceptual estimation
Authors: Hahn Michael , Wei Xue-Xin
Published: December 2022

Perceptual biases are widely regarded as a window into the computational principles underlying human perception. To understand these biases, previous work has proposed a number of conceptually different and even seemingly contradicting ingredients, including attraction to a Bayesian prior, repulsion from the prior due to efficient coding, and central tendency effects on a bounded range. We present a unifying Bayesian theory of biases in perceptual estimation. We theoretically demonstrate an additive decomposition of perceptual biases into attraction to a prior, repulsion away from regions with high encoding precision, and regression away from the boundary. The results reveal a simple and universal rule for predicting the direction of perceptual biases. Our theory accounts for, and leads to new understandings of biases in the perception of a variety of stimulus attributes, including orientation, color, and magnitude.
Infer global, predict local: quantity-quality trade-off in protein fitness predictions from sequence data
Authors: Posani Lorenzo , Rizzato Francesca , Monasson Rémi , Cocco Simona
Published: December 2022

Predicting the effects of mutations on protein function is an important issue in evolutionary biology and biomedical applications. Computational approaches, ranging from graphical models to deep-learning architectures, can capture the statistical properties of sequence data and predict the outcome of high-throughput mutagenesis experiments probing the fitness landscape around some wild-type protein. However, how the complexity of the models and the characteristics of the data combine to determine the predictive performance remains unclear. Here, based on a theoretical analysis of the prediction error, we propose descriptors of the sequence data, characterizing their quantity and quality relative to the model. Our theoretical framework identifies a trade-off between these two quantities, and determines the optimal subset of data for the prediction task, showing that simple models can outperform complex ones when inferred from adequately-selected sequences. We also show how repeated subsampling of the sequence data allows for assessing how much epistasis in the fitness landscape is not captured by the computational model. Our approach is illustrated on several protein families, as well as on in silico solvable protein models.

Significance Statement

Is more data always better? Or should one prefer fewer data, but of higher quality? Here, we investigate this question in the context of the prediction of fitness effects resulting from mutations to a wild-type protein. We show, based on theory and data analysis, that simple models trained on a small subset of carefully chosen sequence data can perform better than complex ones trained on all available data. Furthermore, we explain how comparing the simple local models obtained with different subsets of training data reveals how much of the epistatic interactions shaping the fitness landscape are left unmodeled.
Modelling Spontaneous Firing Activity of the Motor Cortex in a Spiking Neural Network with Random and Local Connectivity
Authors: Haggie Lysea , Besier Thor , McMorland Angus
Published: December 2022

Computational models of cortical activity can provide in-sight into the mechanisms of higher-order processing in the human brain including planning, perception and the control of movement. Activity in the cortex is ongoing even in the absence of sensory input or discernible movements and is thought to be linked to the topology of the underlying cortical circuitry [1]. However, the connectivity and its functional role in the generation of spatio-temporal firing patterns and cortical computations are still unknown.

Movement of the body is a key function of the brain, with the motor cortex the main cortical area implicated in the generation of movement. We built a spiking neural network model of the motor cortex which incorporates a laminar structure and circuitry based on a previous cortical model by Potjans and Diesmann [2]. A local connectivity scheme was implemented to introduce more physiological plausibility to the cortex model, and the effect on the rates, distributions and irregularity of neuronal firing was compared to the original random connectivity method and experimental data. Local connectivity increased the distribution of and overall rate of neuronal firing. It also resulted in the irregularity of firing being more similar to those observed in experimental measurements, and a reduction in the variability in power spectrum measures.

The larger variability in dynamical behaviour of the local connectivity model suggests that the topological structure of the connections in neuronal population plays a significant role in firing patterns during spontaneous activity. This model took steps towards replicating the macroscopic network of the motor cortex, replicating realistic spatiotemporal firing to shed light on information coding in the cortex. Large scale computational models such as this one can capture how structure and function relate to observable neuronal firing behaviour, and investigates the underlying computational mechanisms of the brain.
Biomechanical influence of plate configurations on mandible subcondylar fracture fixation: a finite element study
Authors: Gupta Anoushka , Dutta Abir , Dutta Kaushik , Mukherjee Kaushik
Published: December 2022

Mandible subcondylar fractures have very high complication rate, yet there is no consensus in a suitable plate design for optimal patient outcomes. The present study is aimed at understanding the subcondylar fracture fixation by comparing load transfer in intact and reconstructed fractured mandibles with five different plates: single mini, trapezoid, lambda, strut, and double-mini plates under the complete mastication cycle. Under contralateral molar occlusion (LMOL), the single mini plate resulted in the highest strains. On the contrary, during ipsilateral molar clenching (RMOL), the tensile and compressive strain distributions were found to be reversed, with the tensile strains at the posterior border resulting in lesser strain in reconstructed mandible with single mini plate. Owing to the reduced strains in the reconstructed mandibles, the contralateral molar clenching task is preferred during the immediate post-surgery period for patients. Under this contralateral molar clenching, the peak von Mises stresses in the plate decreased with increase in the number of screws. Furthermore, the presence of two arms seems beneficial to neutralise the tensile and compressive strains across load cases. Consequently, double mini and trapezoid plates were found to perform better as compared to single mini plate during the entire mastication cycle for subcondylar fracture fixation.
Evaluating hippocampal replay without a ground truth
Authors: Takigawa M. , Huelin Gorriz M. , Tirole M. , Bendor D.
Published: December 2022

During rest and sleep, memory traces replay in the brain. The dialogue between brain regions during replay is thought to stabilize labile memory traces for long-term storage. However, because replay is an internally-driven, spontaneous phenomenon, it does not have a ground truth - an external reference that can validate whether a memory has truly been replayed. Instead, replay detection is based on the similarity between the sequential neural activity comprising the replay event and the corresponding template of neural activity generated during active locomotion. If the statistical likelihood of observing such a match by chance is sufficiently low, the candidate replay event is inferred to be replaying that specific memory. However, without the ability to evaluate whether replay detection methods are successfully detecting true events and correctly rejecting non-events, the evaluation and comparison of different replay methods is challenging. To circumvent this problem, we present a new framework for evaluating replay, tested using hippocampal neural recordings from rats exploring two novel linear tracks. Using this two-track paradigm, our framework selects replay events based on their temporal fidelity (sequence-based detection), and applies a cross-validation using each event’s trajectory discriminability, where sequenceless decoding across both tracks is used to quantify whether the track replaying is also the most likely track being reactivated.
A multifunctional Wnt regulator underlies the evolution of coat pattern in African striped mice
Authors: Johnson Matthew R. , Li Sha , Guerrero-Juarez Christian F. , Miller Pearson , Brack Benjamin J. , Mereby Sarah A. , Feigin Charles , Gaska Jenna , Nie Qing , Rivera-Perez Jaime A. , Ploss Alexander , Shvartsman Stanislav Y. , Mallarino Ricardo
Published: December 2022

Animal pigment patterns are excellent models to elucidate mechanisms of biological organization. Although theoretical simulations, such as Turing reaction-diffusion systems, recapitulate many animal patterns, they are insufficient to account for those showing a high degree of spatial organization and reproducibility. Here, we compare the coats of the African striped mouse (Rhabdomys pumilio) and the laboratory mouse (Mus musculus) to study the molecular mechanisms controlling stripe pattern formation. By combining transcriptomics, mathematical modeling, and mouse transgenics, we show thatSfrp2regulates the distribution of hair follicles and establishes an embryonic prepattern that foreshadows pigment stripes. Moreover, by developing and employingin vivogene editing experiments in striped mice, we find thatSfrp2knockout is sufficient to alter the stripe pattern. Strikingly, mutants also exhibit changes in coat color, revealing an additional function ofSfrp2in regulating hair color. Thus, a single factor controls coat pattern formation by acting both as an orienting signaling mechanism and a modulator of pigmentation. By uncovering a multifunctional regulator of stripe formation, our work provides insights into the mechanisms by which spatial patterns are established in developing embryos and the molecular basis of phenotypic novelty.
Longevity and rejuvenation effects of cell reprogramming are decoupled from loss of somatic identity
Authors: Kriukov Dmitrii , Khrameeva Ekaterina E. , Gladyshev Vadim N. , Dmitriev Sergey E. , Tyshkovskiy Alexander
Published: December 2022

Partial somatic cell reprogramming has been touted as a promising rejuvenation strategy. However, its association with mechanisms of aging and longevity at the molecular level remains unclear. We identified a robust transcriptomic signature of reprogramming in mouse and human cells that revealed co-regulation of genes associated with reprogramming and response to lifespan-extending interventions, including those related to DNA repair and inflammation. We found that age-related gene expression changes were reversed during reprogramming, as confirmed by transcriptomic aging clocks. The longevity and rejuvenation effects induced by reprogramming in the transcriptome were mainly independent of pluripotency gain. Decoupling of these processes allowed predicting interventions mimicking reprogramming-induced rejuvenation (RIR) without affecting somatic cell identity, including an anti-inflammatory compound osthol,ATG5overexpression, andC6ORF223knockout. Overall, we revealed specific molecular mechanisms associated with RIR at the gene expression level and developed tools for discovering interventions that support the rejuvenation effect of reprogramming without posing the risk of neoplasia.
Extending eco-evolutionary theory with oligomorphic dynamics
Authors: Lion Sébastien , Sasaki Akira , Boots Mike
Published: December 2022

Understanding the interplay between ecological processes and the evolutionary dynamics of quantitative traits in natural systems remains a major challenge. Two main theoretical frameworks are used to address this question, adaptive dynamics and quantitative genetics, both of which have strengths and limitations and are often used by distinct research communities to address different questions. In order to make progress, new theoretical developments are needed that integrate these approaches and strengthen the link to empirical data. Here, we discuss a novel theoretical framework that bridges the gap between quantitative genetics and adaptive dynamics approaches. “Oligomorphic dynamics” can be used to analyse eco-evolutionary dynamics across different time scales and extends quantitative genetics theory to account for multimodal trait distributions, the dynamical nature of genetic variance, the potential for disruptive selection due to ecological feed-backs, and the non-normal or skewed trait distributions encountered in nature. Oligomorphic dynamics explicitly takes into account the effect of environmental feedback, such as frequency- and density-dependent selection, on the dynamics of multi-modal trait distributions and we argue it has the potential to facilitate a much tighter integration between eco-evolutionary theory and empirical data.