bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulmonary rehabilitation
Authors: Chapman Stephen J. , Robinson Grace V. , Shrimanker Rahul , Turnbull Chris D. , Wrightson John M.
Published: May 2021

Pulmonary rehabilitation (PR) is a well-established evidence-based multidisciplinary programme of care for patients with symptomatic chronic respiratory impairment, targeting the extrapulmonary manifestations of the disease. The programme is individually tailored and should contain high-intensity progressive aerobic training, strength training, and self-management education. PR is probably the most cost-effective intervention for COPD. It interrupts the vicious cycle of dyspnoea leading to inactivity, subsequent deconditioning, and further worsening dyspnoea on more minimal exertion.
Smoking cessation
Authors: Chapman Stephen J. , Robinson Grace V. , Shrimanker Rahul , Turnbull Chris D. , Wrightson John M.
Published: May 2021

Includes: Aims of smoking cessation interventions, NRT, non-nicotine replacement therapy, drugs, hypnosis, acupuncture/acupressure, electronic cigarettes
Airway management
Authors: Chapman Stephen J. , Robinson Grace V. , Shrimanker Rahul , Turnbull Chris D. , Wrightson John M.
Published: May 2021

Includes: Simple airway adjuncts, oropharyngeal airway (Guedel), nasopharyngeal airway, supra-glottic airway devices (SGAD), intubation, endotracheal tube
Miscellaneous diagnostic tests
Authors: Chapman Stephen J. , Robinson Grace V. , Shrimanker Rahul , Turnbull Chris D. , Wrightson John M.
Published: May 2021

Includes: Skin prick tests, Induced sputum, bronchial provocation testing.
Pleurodesis
Authors: Chapman Stephen J. , Robinson Grace V. , Shrimanker Rahul , Turnbull Chris D. , Wrightson John M.
Published: May 2021

The aim of pleurodesis is to seal visceral to parietal pleura with adhesions to prevent pleural fluid or air accumulating. Pleurodesis is dependent upon lung re-expansion following removal of pleural fluid or air, which allows the apposition of visceral and parietal pleura. This may be encouraged by applying suction to an intercostal drain. Inflammation of the pleural surfaces and local activation of coagulation, required to produce pleural fibrosis and adhesions. May be induced by chemical sclerosing agent or by mechanical pleural abrasion at VATS.
Safe sedation
Authors: Chapman Stephen J. , Robinson Grace V. , Shrimanker Rahul , Turnbull Chris D. , Wrightson John M.
Published: May 2021

Includes: Administration of sedation, drugs used for sedation, sedation in specific circumstances.
Thoracoscopy
Authors: Chapman Stephen J. , Robinson Grace V. , Shrimanker Rahul , Turnbull Chris D. , Wrightson John M.
Published: May 2021

Thoracoscopy is the procedure of examining the parietal pleura, visceral pleura, and diaphragm with a thoracoscope and taking biopsies. Chemical pleurodesis can also be performed. Performed by chest physicians using conscious sedation and local anaesthetic. Occasionally deep sedation is instead delivered by an anaesthetist. Either a rigid or a ‘semi-rigid’ flexible thoracoscope (similar to a bronchoscope) is used, dependent on local availability. Overlap with VATS (equipment similar, but VATS undertaken using general anaesthetic and single lung ventilation).
Off-axis jet scenario for early afterglow emission of low-luminosity gamma-ray burst GRB 190829A
Authors: Sato Yuri , Obayashi Kaori , Yamazaki Ryo , Murase Kohta , Ohira Yutaka
Published: May 2021

Recently, ground-based Imaging Atmospheric Cherenkov Telescopes have reported the detection of very-high-energy (VHE) gamma-rays from some gamma-ray bursts (GRBs). One of them, GRB 190829A, was triggered by the Swift satellite, and about 2 × 104 s after the burst onset the VHE gamma-ray emission was detected by H.E.S.S. with ∼5σ significance. This event had unusual features of having much smaller isotropic equivalent gamma-ray energy than typical long GRBs and achromatic peaks in X-ray and optical afterglow at about 1.4 × 103 s. Here, we propose an off-axis jet scenario that explains these observational results. In this model, the relativistic beaming effect is responsible for the apparently small isotropic gamma-ray energy and spectral peak energy. Using a jetted afterglow model, we find that the narrow jet, which has the initial Lorentz factor of 350 and the initial jet opening half-angle of 0.015 rad, viewed off-axis can describe the observed achromatic behaviour in the X-ray and optical afterglow. Another wide, baryon-loaded jet is necessary for the later-epoch X-ray and radio emissions. According to our model, the VHE gamma rays observed by H.E.S.S. at 2 × 104 s may come from the narrow jet through the synchrotron self-Compton process.
An upper limit for the growth of inner planets?
Authors: Winter Andrew J , Alexander Richard
Published: May 2021

The exotic range of known planetary systems has provoked an equally exotic range of physical explanations for their diverse architectures. However, constraining formation processes requires mapping the observed exoplanet population to that which initially formed in the protoplanetary disc. Numerous results suggest that (internal or external) dynamical perturbation alters the architectures of some exoplanetary systems. Isolating planets that have evolved without any perturbation can help constrain formation processes. We consider the Kepler multiples, which have low mutual inclinations and are unlikely to have been dynamically perturbed. We apply an adaption of previous modelling efforts, accounting for the two-dimensionality of the radius ($R_\mathrm{pl} =0.3\!-\!20\, R_\oplus$) and period (Porb = 0.5–730 d) distribution. We find that an upper limit in planet mass of the form $M_\mathrm{lim} \propto a_\mathrm{pl}^{\beta } \exp (-a_\mathrm{in}/a_\mathrm{pl})$, for semimajor axis apl and a broad range of ain and β, can reproduce a distribution of Porb, Rpl that is indistinguishable from the observed distribution by our comparison metric. The index is consistent with β = 1.5, expected if growth is limited by accretion within the Hill radius. This model is favoured over models assuming a separable PDF in Porb, Rpl. The limit, extrapolated to longer periods, is coincident with the orbits of RV-discovered planets (apl > 0.2 au, $M_\mathrm{pl}\gt 1\, M_\mathrm{J}$) around recently identified low density host stars, hinting at isolation mass limited growth. We discuss the necessary circumstances for a coincidental age-related bias as the origin of this result; such a bias is possible but unlikely. We conclude that, in light of the evidence suggesting that some planetary systems have been dynamically perturbed, simple models for planet growth during the formation stage are worth revisiting.
New archeological marvels of ancient Shu civilization
Authors: Zhao Weijie
Published: May 2021

China Central Television broadcasted live reports on the latest archaeological excavation at the Sanxingdui site over four consecutive days, from 20–23 March 2021. Exquisite large golden mask fragments, as well as numerous bronze, jade, pottery and ivory artefacts, were unearthed in six newly discovered pits at the site. Following the public presentation of these ancient cultural relics, along with the contemporary archaeological excavation technologies, the mysterious Sanxingdui civilization has become a hot topic within the Chinese media and scientific community.
Identification of H3N2 NA and PB1-F2 genetic variants and their association with disease symptoms during the 2014–15 influenza season
Authors: Blumenkrantz Deena R , Mehoke Thomas , Shaw-Saliba Kathryn , Powell Harrison , Wohlgemuth Nicholas , Liu Hsuan , Macias Elizabeth , Evans Jared , Lewis Mitra , Medina Rebecca , Hardick Justin , Sauer Lauren M , Dugas Andrea , DuVal Anna , Lane Andrew P , Gaydos Charlotte , Rothman Richard , Thielen Peter , Pekosz Andrew
Published: May 2021

The 2014–15 influenza season saw the emergence of an H3N2 antigenic drift variant that formed the 3C.2a HA clade. Whole viral genomes were sequenced from nasopharyngeal swabs of ninety-four patients with confirmed influenza A virus infection and primary human nasal epithelial cell cultures used to efficiently isolate H3N2 viruses. The isolates were classified by HA clade and the presence of a new set of co-selected mutations in NA (a glycosylation site, NAg+) and PB1-F2 (H75P). The NA and PB1-F2 mutations were present in a subset of clade 3C.2a viruses (NAg+F2P), which dominated during the subsequent influenza seasons. In human nasal epithelial cell cultures, a virus with the novel NAg+F2P genotype replicated less well compared with a virus with the parental genotype. Retrospective analyses of clinical data showed that NAg+F2P genotype viruses were associated with increased cough and shortness of breath in infected patients.
Cancer Therapeutics–related Cardiac Dysfunction in Patients Treated With Immune Checkpoint Inhibitors: An Understudied Manifestation
Authors: Peleg Hasson Shira , Arnold Joshua , Merdler Ilan , Sivan Ayelet , Shamai Sivan , Geva Ravit , Merimsky Ofer , Shachar Eliya , Waissengrin Barliz , Moshkovits Yonatan , Arbel Yaron , Topilsky Yan , Rozenbaum Zach , Wolf Ido , Laufer-Perl Michal
Published: May 2021

The widespread use of immune checkpoint inhibitors (ICI) has become a mainstay of care for a variety of malignancies. However, these therapies portend a range of adverse effects, including a potentially fatal form of cardiotoxicity which to date has not been elucidated. We aimed to evaluate the baseline characteristics of ICI-mediated cardiotoxicity. We performed a retrospective study evaluating patients treated with ICI who performed at least 2 echocardiography examinations, before and after the initiation of ICI. Cardiotoxicity was defined as Cancer Therapeutics-related Cardiac Dysfunction (CTRCD) development, with an absolute left ventricular ejection fraction reduction of >10%, to a value <53%. Fifty-two patients were included with a male preponderance (65%) and a mean age of 66 (±12) years. Twelve (23%) patients developed CTRCD, of which 2 patients were diagnosed with myocarditis. Among the CTRCD group, patients tended to be older and more likely to have baseline diastolic dysfunction: lower e′ septal (P=0.026), higher E/e′ septal (P=0.035), and a trend of E/e′ average (P=0.076). All-cause and cardiovascular hospitalizations were significantly more common among the CTRCD group (P=0.028 and 0.001, respectively). Higher prevalence of cardiovascular mortality was observed among the CTRCD group (25% vs. 2%, P=0.034). We evaluated the development of CTRCD among patients treated with ICI therapies. Our findings suggest that baseline diastolic parameters may be associated with CTRCD development assisting in the early diagnosis of ICI-induced cardiac injury.
Hemodynamic Adverse Effects of Dexmedetomidine and Propofol in a Critically Ill Trauma and Surgical Population: A Retrospective Cohort
Authors: Nicholson Carli R. , Mullen Chanda , Frazee Lawrence A. , Cucci Michaelia D.
Published: May 2021

Background:

Propofol and dexmedetomidine may cause hemodynamic adverse effects (AEs) and more data are needed in a trauma and surgical population.

Objective:

The objective of this study was to evaluate the rate of hemodynamic AEs requiring an intervention between dexmedetomidine and propofol in a critically ill trauma and surgical population.

Methods:

This was a retrospective cohort study at a Level 1 trauma center. Intensive care unit patients admitted from October 1, 2017, through October 31, 2018, were divided into two groups: dexmedetomidine or propofol. The primary end point was the proportion of patients who required a therapeutic intervention for a hemodynamic AE within the first 24 hr of initiation of dexmedetomidine or propofol.

Results:

A total of 800 charts were reviewed and 85 patients (dexmedetomidine [n = 35] and propofol [n = 50]) were included. The study population consisted of Caucasian (86%) males (61%) with a median age of 61 [interquartile range—IQR 48, 72], and 18% and 24% required antihypertensive and vasopressor agents, respectively. No difference in the primary outcome was observed (17 [49%] vs. 27 [54%], p = .624). There was no difference in the overall incidence of hemodynamic AE (18 [51%] vs. 30 [60%], p = .433). Dexmedetomidine patients had a greater decrease in median heart rate (HR) compared with the propofol (23 [IQR 16, 41] vs. 14 [IQR 5, 24] beats/min, p = .002).

Conclusions:

The rate of hemodynamic AEs requiring therapeutic interventions was similar between dexmedetomidine and propofol in a critically ill trauma and surgical population; however, dexmedetomidine may be associated with a larger decrease in HR.
Matter of Balance Classes Through Physical Therapist Fall Risk Assessment
Authors: Geyer Rebecca L. , Thompson Tara
Published: May 2021

Background:

Falls remain the leading cause of injury-related death for 65 years and older. Matter of Balance is a well-documented community-based program designed to reduce participants' fear of falling. However, Matter of Balance classes' effect on physical measures remains less well studied.

Objective:

The objective of this study was to evaluate the effects of the Matter of Balance program on balance, strength, and fall risk.

Methods:

This is a single-group pretest–posttest evaluation of balance and strength in community participants enrolled in 8-week Matter of Balance classes. Physical therapist assessments of the Functional Reach Test and five times sit-to-stand test at week 1 and week 8 were compared.

Results:

A total of 33 class participants were studied. The average improvement in the Functional Reach Test was M = 1.33 (SD = 1.6) inches and the five times sit-to-stand test was M = −3.24 (SD = 3.42) seconds; p < .05.

Conclusions

Matter of Balance classes resulted in improvement in both balance and strength. This study's findings support Matter of Balance classes' efficacy as a community-based program that can reduce a participant's physical risk for falls.
Natural Disasters Related Traumatic Injuries/Fatalities in the United States and Their Impact on Emergency Preparedness Operations
Authors: Gill Sabrina , Sutherland Mason , Raslan Shahm , McKenney Mark , Elkbuli Adel
Published: May 2021

Introduction:

From 2015 to 2019, the United States experienced a 17% increase in weather-related disasters.

Objectives:

We aimed to study the patterns of natural disaster-related traumatic injuries and fatalities across the United States from 2014 to 2019 and to provide recommendations that can serve to mitigate the impact these natural disasters have on trauma patient morbidity and mortality.

Methods:

A retrospective analysis of the National Safety Council (2014–2019) of natural disaster-related injuries and fatalities was conducted. Descriptive statistics and independent-samples t tests were performed, with significance defined as p < .05.

Results:

Floods produced significantly more mean fatalities per year than tornadoes (118 vs. 33; 95% CI [32.0, 139.0]), wildfires (118 vs. 43, 95% CI [24.8, 155.6]), hurricanes (118 vs. 13, 95% CI [51.5, 159.2]), and tropical storms (118 vs. 15, 95% CI [48.8, 158.2]). Tornadoes produced significantly more mean injuries per year than floods (528 vs. 43, 95% CI [255.9, 715.8]), wildfires (528 vs. 69, 95% CI [227.1, 691.2]), hurricanes (528 vs. 26, 95% CI [270.1, 734.2]), and tropical storms (528 vs. 4, 95% CI [295.9, 753.5]). Southern states experienced greater disaster-related morbidity and mortality over the 6-year study period than other regions with 2,752 injuries and 771 fatalities.

Conclusions:

The incidence of traumatic injuries and fatalities related to certain natural disasters in the United States has significantly increased from 2014 to 2019. Hospital leaders, public health, emergency preparedness personnel, and policy makers must collaborate to implement protocols and guidelines that ensure adequate training, supplies, and personnel to maintain trauma surge capacity, improve emergency preparedness response, and reduce associated morbidity and mortality.
Trauma Prehospital Hypothermia Prevention and Treatment: An Observational Study
Authors: Mota Mauro A. L. , Santos Margarida Reis , Santos Eduardo J. F. , Henriques Carla , Matos Ana , Cunha Madalena
Published: May 2021

Background:

Hypothermia in trauma patients causes increased morbidity and mortality. Swift recognition and treatment are important to prevent any further heat loss. In addition, patient discomfort from cold decreases satisfaction with care. The administration of active and passive rewarming measures is important in the prevention and treatment of hypothermia, but their use in prehospital trauma patients in Portugal has not been previously reported.

Objective:

To assess the prevalence of hypothermia, the impact of rewarming measures, and the management of the discomfort caused by cold.

Methods:

This is a prospective cohort study conducted in Immediate Life Support Ambulances in Portugal between March 1, 2019, and April 30, 2020.

Results:

This study included records of 586 trauma patients; of whom, 66.2% were men. Cranioencephalic trauma was the most common trauma observed, followed by lower limb and thoracic traumas. Mean body temperature increased 0.12 °C between the first and last assessments (p < .05). Most patients experiencing a level of discomfort of 5 or more on a 0–10 scale reported improvement (from 17.2% to 2.4% after nurses' intervention). Warmed intravenous fluids proved to be effective (p < .05) in increasing body temperature, and passive rewarming measures were effective in preventing hypothermia.

Conclusions:

Hypothermia management has to consider the initial temperature, the season, the available rewarming measures, and the objectives to be achieved. The optimization of resources for the monitoring and treatment of hypothermia should be a priority in prehospital assistance. The implementation of rewarming measures improves patients' outcomes and decreases the discomfort caused by cold in prehospital care.
Preparing for an American College of Surgeons Virtual Trauma Reverification Site Visit: One Center's Experience
Authors: McMahon Maria F.
Published: May 2021

Background:

The American College of Surgeons (ACS), Committee on Trauma, trauma center verification process is designed to help hospitals improve trauma care. Due to the COVID-19 pandemic social distancing restrictions, performing virtual site visits was piloted.

Objective:

The purpose of this article is to describe the first pilot ACS pediatric trauma center virtual reverification visit performed in the United States.

Methods:

This is a descriptive review of a 2020 pilot virtual Level I pediatric trauma center reverification visit. In-person site visit checklists were altered to adjust to the virtual format. All documents, prereview questionnaire, patient charts, and resource documents were prepared electronically. Collaboration with the departments of information technology, clinical education and informatics, and the general counsel's office prepared the infrastructure to allow reviewers access to protected health information.

Results:

Multiple hospital departments collaborated to facilitate the transition to an electronic format. Organized virtual meeting room scheduling, communications, and coordination between the ACS staff, the reviewers, and the various hospital departments resulted in a successful virtual visit.

Conclusion:

Lessons learned and opportunities for improvement were identified for this first-ever pilot virtual pediatric trauma center reverification site visit. Once the information technology logistic questions were answered, allowing reviewers protected health information access, the general program and document preparation for a virtual trauma reverification site visit was similar to an in-person site visit. Although the review day agenda was similar, execution challenges were identified.
Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19
Authors: Kory Pierre , Meduri Gianfranco Umberto , Varon Joseph , Iglesias Jose , Marik Paul E.
Published: May 2021

Background:

After COVID-19 emerged on U.S shores, providers began reviewing the emerging basic science, translational, and clinical data to identify potentially effective treatment options. In addition, a multitude of both novel and repurposed therapeutic agents were used empirically and studied within clinical trials.

Areas of Uncertainty:

The majority of trialed agents have failed to provide reproducible, definitive proof of efficacy in reducing the mortality of COVID-19 with the exception of corticosteroids in moderate to severe disease. Recently, evidence has emerged that the oral antiparasitic agent ivermectin exhibits numerous antiviral and anti-inflammatory mechanisms with trial results reporting significant outcome benefits. Given some have not passed peer review, several expert groups including Unitaid/World Health Organization have undertaken a systematic global effort to contact all active trial investigators to rapidly gather the data needed to grade and perform meta-analyses.

Data Sources:

Data were sourced from published peer-reviewed studies, manuscripts posted to preprint servers, expert meta-analyses, and numerous epidemiological analyses of regions with ivermectin distribution campaigns.

Therapeutic Advances:

A large majority of randomized and observational controlled trials of ivermectin are reporting repeated, large magnitude improvements in clinical outcomes. Numerous prophylaxis trials demonstrate that regular ivermectin use leads to large reductions in transmission. Multiple, large “natural experiments” occurred in regions that initiated “ivermectin distribution” campaigns followed by tight, reproducible, temporally associated decreases in case counts and case fatality rates compared with nearby regions without such campaigns.

Conclusions:

Meta-analyses based on 18 randomized controlled treatment trials of ivermectin in COVID-19 have found large, statistically significant reductions in mortality, time to clinical recovery, and time to viral clearance. Furthermore, results from numerous controlled prophylaxis trials report significantly reduced risks of contracting COVID-19 with the regular use of ivermectin. Finally, the many examples of ivermectin distribution campaigns leading to rapid population-wide decreases in morbidity and mortality indicate that an oral agent effective in all phases of COVID-19 has been identified.
The tumour suppressor brain tumour (Brat) regulates linker histone dBigH1 expression in the
Drosophila
female germline and the early embryo
Authors: Climent-Cantó Paula , Carbonell Albert , Tamirisa Srividya , Henn Laszlo , Pérez-Montero Salvador , Boros Imre M. , Azorín Fernando
Published: May 2021

Linker histones H1 are essential chromatin components that exist as multiple developmentally regulated variants. In metazoans, specific H1s are expressed during germline development in a tightly regulated manner. However, the mechanisms governing their stage-dependent expression are poorly understood. Here, we address this question in
Drosophila
, which encodes for a single germline-specific dBigH1 linker histone. We show that during female germline lineage differentiation, dBigH1 is expressed in germ stem cells and cystoblasts, becomes silenced during transit-amplifying (TA) cystocytes divisions to resume expression after proliferation stops and differentiation starts, when it progressively accumulates in the oocyte. We find that dBigH1 silencing during TA divisions is post-transcriptional and depends on the tumour suppressor Brain tumour (Brat), an essential RNA-binding protein that regulates mRNA translation and stability. Like other oocyte-specific variants, dBigH1 is maternally expressed during early embryogenesis until it is replaced by somatic dH1 at the maternal-to-zygotic transition (MZT). Brat also mediates dBigH1 silencing at MZT. Finally, we discuss the situation in testes, where Brat is not expressed, but dBigH1 is translationally silenced too.
Fic and non-Fic AMPylases: protein AMPylation in metazoans
Authors: Chatterjee Bhaskar K. , Truttmann Matthias C.
Published: May 2021

Protein AMPylation refers to the covalent attachment of an AMP moiety to the amino acid side chains of target proteins using ATP as nucleotide donor. This process is catalysed by dedicated AMP transferases, called AMPylases. Since this initial discovery, several research groups have identified AMPylation as a critical post-translational modification relevant to normal and pathological cell signalling in both bacteria and metazoans. Bacterial AMPylases are abundant enzymes that either regulate the function of endogenous bacterial proteins or are translocated into host cells to hijack host cell signalling processes. By contrast, only two classes of metazoan AMPylases have been identified so far: enzymes containing a conserved filamentation induced by cAMP (Fic) domain (Fic AMPylases), which primarily modify the ER-resident chaperone BiP, and SelO, a mitochondrial AMPylase involved in redox signalling. In this review, we compare and contrast bacterial and metazoan Fic and non-Fic AMPylases, and summarize recent technological and conceptual developments in the emerging field of AMPylation.
Iron-sulfur flavoenzymes: the added value of making the most ancient redox cofactors and the versatile flavins work together
Authors: Vanoni Maria Antonietta
Published: May 2021

Iron-sulfur (Fe-S) flavoproteins form a broad and growing class of complex, multi-domain and often multi-subunit proteins coupling the most ancient cofactors (the Fe-S clusters) and the most versatile coenzymes (the flavin coenzymes, FMN and FAD). These enzymes catalyse oxidoreduction reactions usually acting as switches between donors of electron pairs and acceptors of single electrons, and vice versa. Through selected examples, the enzymes' structure−function relationships with respect to rate and directionality of the electron transfer steps, the role of the apoprotein and its dynamics in modulating the electron transfer process will be discussed.
Improving environment drives dynamical change in social game structure
Authors: Chiba Erika , Cuaresma Diane Carmeliza N. , Rabajante Jomar F. , Tubay Jerrold M. , Areja Gavina Maica Krizna , Yamamoto Tatsuki , Yoshimura Jin , Morita Satoru , Ito Hiromu , Okabe Takuya
Published: May 2021

The development of cooperation in human societies is a major unsolved problem in biological and social sciences. Extensive studies in game theory have shown that cooperative behaviour can evolve only under very limited conditions or with additional complexities, such as spatial structure. Non-trivial two-person games are categorized into three types of games, namely, the prisoner's dilemma game, the chicken game and the stag hunt game. Recently, the weight-lifting game has been shown to cover all five games depending on the success probability of weight lifting, which include the above three games and two trivial cases (all cooperation and all defection; conventionally not distinguished as separate classes). Here, we introduce the concept of the environmental value of a society. Cultural development and deterioration are represented by changes in this probability. We discuss cultural evolution in human societies and the biological communities of living systems.
Shortcomings of human-in-the-loop optimization of an ankle-foot prosthesis emulator: a case series
Authors: Welker Cara Gonzalez , Voloshina Alexandra S. , Chiu Vincent L. , Collins Steven H.
Published: May 2021

Human-in-the-loop optimization allows for individualized device control based on measured human performance. This technique has been used to produce large reductions in energy expenditure during walking with exoskeletons but has not yet been applied to prosthetic devices. In this series of case studies, we applied human-in-the-loop optimization to the control of an active ankle-foot prosthesis used by participants with unilateral transtibial amputation. We optimized the parameters of five control architectures that captured aspects of successful exoskeletons and commercial prostheses, but none resulted in significantly lower metabolic rate than generic control. In one control architecture, we increased the exposure time per condition by a factor of five, but the optimized controller still resulted in higher metabolic rate. Finally, we optimized for self-reported comfort instead of metabolic rate, but the resulting controller was not preferred. There are several reasons why human-in-the-loop optimization may have failed for people with amputation. Control architecture is an unlikely cause given the variety of controllers tested. The lack of effect likely relates to changes in motor adaptation, learning, or objectives in people with amputation. Future work should investigate these potential causes to determine whether human-in-the-loop optimization for prostheses could be successful.
Methods for analysing lineage tracing datasets
Authors: Kostiou Vasiliki , Zhang Huairen , Hall Michael W. J. , Jones Philip H. , Hall Benjamin A.
Published: May 2021

A single population of progenitor cells maintains many epithelial tissues. Transgenic mouse cell tracking has frequently been used to study the growth dynamics of competing clones in these tissues. A mathematical model (the ‘single-progenitor model’) has been argued to reproduce the observed progenitor dynamics accurately. This requires three parameters to describe the growth dynamics observed in transgenic mouse cell tracking—a division rate, a stratification rate and the probability of dividing symmetrically. Deriving these parameters is a time intensive and complex process. We compare the alternative strategies for analysing this source of experimental data, identifying an approximate Bayesian computation-based approach as the best in terms of efficiency and appropriate error estimation. We support our findings by explicitly modelling biological variation and consider the impact of different sampling regimes. All tested solutions are made available to allow new datasets to be analysed following our workflows. Based on our findings, we make recommendations for future experimental design.
A new pelomedusoid turtle,Sahonachelys mailakavava, from the Late Cretaceous of Madagascar provides evidence for convergent evolution of specialized suction feeding among pleurodires
Authors: Joyce Walter G. , Rollot Yann , Evers Serjoscha W. , Lyson Tyler R. , Rahantarisoa Lydia J. , Krause David W.
Published: May 2021

The Maevarano Formation in northwestern Madagascar has yielded a series of exceptional fossils over the course of the last three decades that provide important insights into the evolution of insular ecosystems during the latest Cretaceous (Maastrichtian). We here describe a new genus and species of pelomedusoid turtle from this formation,Sahonachelys mailakavava, based on a nearly complete skeleton. A phylogenetic analysis suggests close affinities ofSahonachelys mailakavavawith the coeval MadagascanSokatra antitra. These two taxa are the only known representatives of the newly recognized cladeSahonachelyidae, which is sister to the speciose clade formed byBothremydidaeandPodocnemidoidae. A close relationship with coeval Indian turtles of the cladeKurmademydiniis notably absent. A functional assessment suggests thatSahonachelys mailakavavawas a specialized suction feeder that preyed upon small-bodied invertebrates and vertebrates. This is a unique feeding strategy among crown pelomedusoids that is convergent upon that documented in numerous other clades of turtles and that highlights the distinct evolutionary pathways taken by Madagascan vertebrates.
Cosmetic coloration of cross-fostered eggs affects paternal investment in the hoopoe (Upupa epops)
Authors: Díaz-Lora Silvia , Pérez-Contreras Tomás , Azcárate-García Manuel , Peralta-Sánchez Juan Manuel , Martínez-Bueno Manuel , José Soler Juan , Martín-Vivaldi Manuel
Published: May 2021

The signalling hypothesis suggests that avian eggshell coloration is a sexually selected female signal advertising her quality to its male partner, thereby stimulating his provisioning rate. This hypothesis has been tested for structural eggshell pigments, but not for cosmetic colorations, such as that produced by the uropygial secretion on eggshells. During the breeding season, female hoopoes (Upupa epops) host in their uropygial glands symbiotic bacteria. Females actively smear the eggshells with their secretion, protecting embryos from pathogenic trans-shell infections and changing eggshell coloration. Because the colour of the secretions is related to their antimicrobial potential, cosmetic eggshell coloration may act as a cue or even as a post-mating sexually selected signal if it affects male provisioning rates. To experimentally test this hypothesis, we cross-fostered already-smeared clutches between hoopoe nests, and quantified male feeding behaviour to females before and after the experiment. This approach allows disentanglement of the effects of female quality and of egg coloration on male investment. In accordance with the hypothesis, males adjusted their provisioning rate to the eggshell cosmetic coloration. This is, to our knowledge, the first experimental demonstration that egg colour stained with uropygial secretion could act as a post-mating sexual signal of female quality to males.
A weather surveillance radar view of Alaskan avian migration
Authors: Sivakumar Ashwin H. , Sheldon Daniel , Winner Kevin , Burt Carolyn S. , Horton Kyle G.
Published: May 2021

Monitoring avian migration within subarctic regions of the globe poses logistical challenges. Populations in these regions often encounter the most rapid effects of changing climates, and these seasonally productive areas are especially important in supporting bird populations—emphasizing the need for monitoring tools and strategies. To this end, we leverage the untapped potential of weather surveillance radar data to quantify active migration through the airspaces of Alaska. We use over 400 000 NEXRAD radar scans from seven stations across the state between 1995 and 2018 (86% of samples derived from 2013 to 2018) to measure spring and autumn migration intensity, phenology and directionality. A large bow-shaped terrestrial migratory system spanning the southern two-thirds of the state was identified, with birds generally moving along a northwest–southeast diagonal axis east of the 150th meridian, and along a northeast–southwest axis west of this meridian. Spring peak migration ranged from 3 May to 30 May and between, 18 August and 12 September during the autumn, with timing across stations predicted by longitude, rather than latitude. Across all stations, the intensity of migration was greatest during the autumn as compared to spring, highlighting the opportunity to measure seasonal indices of net breeding productivity for this important system as additional years of radar measurements are amassed.
Nights at the museum: integrated arts and microbiology public engagement events enhance understanding of science whilst increasing community diversity and inclusion
Authors: Duckett Catherine J. , Hargreaves Kate E. , Rawson Kirstie M. , Allen K. Elizabeth , Forbes Sarah , Rawlinson Katherine E. , Shaw Hollie , Lacey Melissa
Published: May 2021

This study uses integrated art and science events to explore a blended approach in improving public understanding of current scientific topics and widening participation within the local community. The events were a Halloween-inspired microbiology-themed series of interactive exhibitions hosted within a national museum as part of an existing series of adult education evenings. A representative sample of 102 mixed methods exit questionnaires, based on determining (i) audience diversity and (ii) understanding of scientific topics, were analysed by qualitative and quantitative approaches, and a post-attendance focus group was carried out to determine longer term impact of the event. Participants were grouped as 'Science', 'Arts', 'Both' or 'Neither', according to their past experience and engagement. These events welcomed more participants from the Arts and Neither subsections hence engaging a group of people who would not usually visit science public engagement events or comparative events hosted in traditional academic settings, highlighting the importance of venue choice in reaching new audiences and widening participation. An increase in perceived understanding of science was observed by all groups of participants with reported enjoyment focused around the science talks, presentations and blended art-science activities. A putative impact in science capital is observed with participants reporting an increased likelihood of attending science events in the future. Furthermore, increased discussion and awareness of science in society is evidenced by participants. Blended art and microbiology exhibitions enhance the accessibly of science public engagement events and is likely to increase science capital; the impact of this on cognitive polyphasia is also discussed.
Comparative genomics reveals an SNP potentially leading to phenotypic diversity of Salmonella enterica serovar Enteritidis
Authors: Ko Duhyun , Choi Sang Ho
Published: May 2021

An SNP is a spontaneous genetic change having a potential to modify the functions of the original genes and to lead to phenotypic diversity of bacteria in nature. In this study, a phylogenetic analysis of

Salmonella enterica

serovar Enteritidis, a major food-borne pathogen, showed that eight strains of S. Enteritidis isolated in South Korea, including FORC_075 and FORC_078, have almost identical genome sequences. Interestingly, however, the abilities of FORC_075 to form biofilms and red, dry and rough (RDAR) colonies were significantly impaired, resulting in phenotypic differences among the eight strains. Comparative genomic analyses revealed that one of the non-synonymous SNPs unique to FORC_075 has occurred in envZ, which encodes a sensor kinase of the EnvZ/OmpR two-component system. The SNP in envZ leads to an amino acid change from Pro248 (CCG) in other strains including FORC_078 to Leu248 (CTG) in FORC_075. Allelic exchange of envZ between FORC_075 and FORC_078 identified that the SNP in envZ is responsible for the impaired biofilm- and RDAR colony-forming abilities of S. Enteritidis. Biochemical analyses demonstrated that the SNP in envZ significantly increases the phosphorylated status of OmpR in S. Enteritidis and alters the expression of the OmpR regulon. Phenotypic analyses further identified that the SNP in envZ decreases motility of S. Enteritidis but increases its adhesion and invasion to both human epithelial cells and murine macrophage cells. In addition to an enhancement of infectivity to the host cells, survival under acid stress was also elevated by the SNP in envZ. Together, these results suggest that the natural occurrence of the SNP in envZ could contribute to phenotypic diversity of S. Enteritidis, possibly improving its fitness and pathogenesis.
Mapping evoked fields in primary motor and sensory areas via magnetoencephalography in tetraplegia
Authors: Foldes Stephen , Chandrasekaran Santosh , Camerone Joseph , Lowe James , Ramdeo Richard , Ebersole John , Bouton Chad E
Published: May 2021

1

Abstract

Devices interfacing with the brain through implantation in cortical or subcortical structures have great potential for restoration and rehabilitation in patients with sensory or motor dysfunction. Typical implantation surgeries are planned based on maps of brain activity generated from intact function. However, mapping brain activity for planning implantation surgeries is challenging in the target population due to abnormal residual function and, increasingly often, existing MRI-incompatible implanted hardware. Here, we present methods and results for mapping impaired somatosensory and motor function in an individual with paralysis and an existing brain-computer interface (BCI) device. Magnetoencephalography (MEG) was used to directly map the neural activity evoked during transcutaneous electrical stimulation and attempted movement of the impaired hand. Evoked fields were found to align with the expected anatomy and somatotopic organization. This approach may be valuable for guiding implants in other applications, such as cortical stimulation for pain and to improve implant targeting to help reduce the craniotomy size.
Adaptive radiation and burst speciation of hillstream cyprinid fishGarrain African river
Authors: Levin Boris , Simonov Evgeniy , Franchini Paolo , Mugue Nikolai , Golubtsov Alexander , Meyer Axel
Published: May 2021

Adaptive radiation of fishes was long thought to be possible only in lacustrine environments. Recently, several studies have shown that also riverine and stream environments provide the ecological opportunity for adaptive radiation. In this study, we report on a riverine adaptive radiation of six ecomorphs of cyprinid hillstream fishes of the genusGarrain a river located in the Ethiopian Highlands in East Africa.Garraare predominantly highly specialized algae-scrapers with a wide distribution ranging from Southeastern Asia to Western Africa. However, adaptive phenotypic diversification in mouth type, sucking disc morphology, gut length and body shape have been found among these new species in a single Ethiopian river. Moreover, we found two novel phenotypes ofGarra(‘thick-lipped’ and ‘predatory’) that were not described before in this species-rich genus (>160 species). Mitochondrial and genome-wide data suggest monophyletic, intra-basin evolution ofGarraphenotypic diversity with signatures of gene flow from other local populations. Although sympatric ecomorphs are genetically distinct and can be considered to being young species as suggested by genome-wide SNP data, mtDNA was unable to identify any genetic structure suggesting a recent and rapid speciation event. Furthermore, we found evidence for a hybrid origin of the novel ‘thick-lipped’ phenotype, as being the result of the hybridization of two other sympatrically occurring species. Here we highlight how, driven by ecological opportunity, an ancestral trophically highly specialized lineage is likely to have rapidly adaptively radiated in a riverine environment, and that this radiation was promoted by the evolution of novel feeding strategies.
Modeling the Pancreatic Cancer Microenvironment in Search of Control Targets
Authors: Plaugher Daniel , Murrugarra David
Published: May 2021

Pancreatic Ductal Adenocarcinoma is among the leading causes of cancer related deaths globally due to its extreme difficulty to detect and treat. Recently, research focus has shifted to analyzing the microenvironment of pancreatic cancer to better understand its key molecular mechanisms. This microenvironment can be represented with a multi-scale model consisting of pancreatic cancer cells (PCCs), pancreatic stellate cells (PSCs), as well as cytokines and growth factors which are responsible for intercellular communication between the PCCs and PSCs. We have built a stochastic Boolean network (BN) model, validated by literature and clinical data, in which we probed for intervention strategies that force this gene regulatory network (GRN) from a diseased state to a healthy state. To do so, we implemented methods from phenotype control theory to determine a procedure for regulating specific genes within the microenvironment. We identify target genes and molecules such that the application of their control drives the GRN to the desired state by suppression (or expression) and disruption of specific signaling pathways that will eventually lead to the eradication of the cancer cells. After applying well studied control methods such as stable motifs, feedback vertex set, and computational algebra, we discovered that each produces a different set of control targets that are not necessarily minimal nor unique. Yet, we were able to gain more insight about the performance of each process and the overlap of targets discovered. Nearly every control set contains cytokines, KRas, and HER2/neu which suggests they are key players in the system’s dynamics. To that end, this model can be used to produce further insight into the complex biological system of pancreatic cancer with hopes of finding new potential targets.
Inactivation of the Hippo Tumor Suppressor Pathway Promotes Melanoma
Authors: Vittoria Marc A. , Kingston Nathan , Xia Eric , Hong Rui , Huang Lee , McDonald Shayna , Tilston-Lunel Andrew , Darp Revati , Campbell Joshua , Lang Deborah , Xu Xiaowei , Ceol Craig , Varelas Xaralabos , Ganem Neil J.
Published: May 2021

Human melanomas are commonly driven by activating mutations inBRAF, which promote melanocyte proliferation through constitutive stimulation of the MAPK pathway. However, oncogenicBRAFalone is insufficient to promote melanoma; instead, its expression merely induces a transient burst of proliferation that ultimately ceases with the development of benign nevi (i.e. moles) comprised of growth-arrested melanocytes. The tumor suppressive mechanisms that induce this melanocytic growth arrest remain poorly understood. Recent modeling studies have suggested that the growth arrest of nevus melanocytes is not solely due to oncogene activation in individual cells, but rather due to cells sensing and responding to their collective overgrowth, similar to what occurs in normal tissues. This cell growth arrest is reminiscent of the arrest induced by activation of the Hippo tumor suppressor pathway, which is an evolutionarily conserved pathway known to regulate organ size. Herein, we demonstrate that oncogenic BRAF signaling activates the Hippo pathwayin vitro, which leads to inhibition of the pro-growth transcriptional co-activators YAP and TAZ, ultimately promoting the growth arrest of melanocytes. We also provide evidence that the Hippo tumor suppressor pathway is activated in growth-arrested nevus melanocytesin vivo, both from single-cell sequencing of mouse models of nevogenesis and human tissue samples. Mechanistically, we observe that oncogenic BRAF promotes both ERK-dependent alterations in the actin cytoskeleton and whole-genome-doubling events, and that these two effects independently promote Hippo pathway activation. Lastly, we demonstrate that abrogation of the Hippo pathway, via melanocyte-specific deletion of the Hippo kinasesLats1/2, enables oncogenicBRAF-expressing melanocytes to bypass nevus formation, thus leading to the rapid onset of melanoma with 100% penetrance. This model is clinically relevant, as co-heterozygous loss ofLATS1/2is observed in ∼15% of human melanomas. Collectively, our data reveal that the Hippo pathway enforces the stable growth arrest of nevus melanocytes and therefore represents a critical and previously unappreciated barrier to melanoma development.