bluuebunny/crossref_metadata_2025 huggingface dataset:
Ecological Characterization of Mosquitoes (Diptera: Culicidae) at the Southern Coast of Mar Chiquita Lake, Argentina
Authors: Visintin Andrés M , Laurito Magdalena , Grech Marta G , Estallo Elizabet L , Grillet María E , Almeida Francisco F Ludueña , Almirón Walter R
Published: December 2021

In the southern coast of Mar Chiquita Lake, central Argentina, mosquitoes affect public health and community livelihood, since they transmit pathogens to human beings causing diseases such as malaria, filariasis, encephalitis, yellow fever, and dengue, among others, and have a negative effect on cattle farming as well. To characterize the structure of the mosquito assemblage of the region, we determined the species composition and diversity, the temporal distribution of different species, and the patterns of species richness, abundance, and diversity across seasons. We collected adult mosquitoes over a two-year period (October 2004–September 2006) by means of CDC light traps baited with CO2 from 18:00 to 08:00 h during the warm season (October–April) and from 12:00 h to 18:00 h in the cold season (May–September). A total of 71,501 individuals from 30 species were collected, with Culex Linnaeus and Aedes Meigen genera representing more than 98% of collected specimens (61.5% and 37.3%, respectively). The higher values of richness and abundance of Culicidae were registered in warm seasons compared to cold seasons. Chao1 estimates suggested that more than 90% of the species were detected in all seasons. Mosquito abundance distribution fit the logarithmic series and log-normal models. Aedes albifasciatus (Macquart), Ae. scapularis (Rondani), Culex interfor Dyar, Cx. saltanensis Dyar, and Cx. dolosus (Lynch Arribálzaga), vectors incriminated in arbovirus transmission, were abundant year-round, with Cx. saltanensis and Cx. dolosus most prevalent in cold seasons. Further studies are needed to assess the role of these species in arbovirus transmission in this region of central Argentina.
Approaching language levels and registers in written Chinese with the Menzerath–Altmann Law
Authors: Chen Heng , Liu Haitao
Published: December 2021

The length of language units, such as word length or sentence length, plays a critical role in register classification studies. However, in this line of work, little attention has been paid to the relationship between the lengths of language units at different levels. The Menzerath–Altmann law (MAL) reflects the functional relationship between the lengths of linguistic units at different levels, and its parameters were shown to be register-sensitive. This article focuses on two interrelated questions based on the MAL: (1) whether there are variations in the hierarchical relationships between language units at different levels and (2) whether such variations will influence register classifications. The results based on written Chinese show that (1) the MAL fittings at the ‘sentence > clause > word’ levels outperform that at the ‘clause > word > character’ levels and (2) the classifications based on two registers, i.e., Press (reportage) and Science (academic prose), demonstrate that the fitting parameters at the ‘sentence > clause > word’ levels also outperform those at the ‘clause > word > character’ levels. These indicate that the variations of hierarchical relationships between language units at different levels should be considered in register analysis. Further interpretations were given from perspectives of the information-theoretic principle and language evolution.
Radiative lifetimes, branching fractions, and oscillator strengths for highly excited levels in singly ionized tantalum (Ta ii)
Authors: Zhang Lijun , Wu Yaxin , Liu Meina , Ma Huiting , Quinet Pascal , Dai Zhenwen
Published: December 2021

Radiative lifetimes of 28 levels of Ta ii in the energy range 29256.907–55128.389 cm−1 were measured by time-resolved laser-induced fluorescence (TR-LIF) spectroscopy in laser-ablation plasma. Among the results, to our knowledge, 24 lifetimes are reported for the first time. These lifetimes, ranging from 2.7 to 111 ns, were combined with theoretical branching fractions obtained from pseudo-relativistic Hartree–Fock calculations including core-polarization effects to deduce semi-empirical transition probabilities and oscillator strengths for 284 Ta ii spectral lines.
New approaches for faint source detection in hard X-ray surveys
Authors: Lepingwell V A , Bird A J , Gunn S R
Published: December 2021

We demonstrate two new approaches that have been developed to aid the production of future hard X-ray catalogues, and specifically to reduce the reliance on human intervention during the detection of faint excesses in maps that also contain systematic noise. A convolutional neural network has been trained on data from the INTEGRAL/ISGRI telescope to create a source detection tool that is more sensitive than previous methods, whilst taking less time to apply to the data and reducing the human subjectivity involved in the process. This new tool also enables searches on smaller observation time-scales than was previously possible. We show that a method based on Bayesian reasoning is better able to combine the detections from multiple observations than previous methods. When applied to data from the first 1000 INTEGRAL revolutions these improved techniques detect 25 sources (about 5 per cent of the total sources) which were previously undetected in the stacked images used to derive the published catalogue made using the same data set.
On Two Different Kinds of Computational Indeterminacy
Authors: Papayannopoulos Philippos , Fresco Nir , Shagrir Oron
Published: December 2021

It is often indeterminate what function a given computational system computes. This phenomenon has been referred to as “computational indeterminacy” or “multiplicity of computations.” In this paper, we argue that what has typically been considered and referred to as the (unique) challenge of computational indeterminacy in fact subsumes two distinct phenomena, which are typically bundled together and should be teased apart. One kind of indeterminacy concerns a functional (or formal) characterization of the system’s relevant behavior (briefly: how its physical states are grouped together and corresponded to abstract states). Another kind concerns the manner in which the abstract (or computational) states are interpreted (briefly: what function the system computes). We discuss the similarities and differences between the two kinds of computational indeterminacy, their implications for certain accounts of “computational individuation” in the literature, and their relevance to different levels of description within the computational system. We also examine the inter-relationships between our proposed accounts of the two kinds of indeterminacy and the main accounts of “computational implementation.”
Sustained HIV Viral Suppression With Dolutegravir, Tenofovir, and Emtricitabine as Initial Therapy Despite High-Level Transmitted Multiclass Resistance
Authors: Nagami Ellen H , Thakarar Kinna , Sax Paul E
Published: December 2021

Multiclass high-level transmitted HIV drug resistance is uncommon, and the selection of the optimal initial antiretroviral drug regimen may be challenging. We report a case of extensive transmitted multiclass resistance successfully treated with dolutegravir, tenofovir, and emtricitabine even though the baseline genotype demonstrated full susceptibility to only 1 drug class, integrase strand transfer inhibitors. Our case highlights both the high resistance barrier of dolutegravir and the residual antiviral activity of nucleoside reverse transcriptase inhibitors despite extensive resistance on genotype.
Contact calls of island Brown-throated Parakeets exhibit both character and variance shifts compared to calls of their mainland relatives
Authors: Eberhard Jessica R , Zager Irene , Ferrer-Paris José R , Rodríguez-Clark Kathryn
Published: December 2021

Learned vocalizations play a key role in parrot social dynamics and vocal dialects have been documented for several mainland species, but to date no studies of geographically structured call variation in parrot species have examined the role of isolation on islands. In a study of the Brown-throated Parakeet (Eupsittula pertinax), which inhabits 5 small Caribbean islands as well as the adjacent mainland, we found that the contact calls of island and mainland parakeets show divergence in vocal characters as well as in call variability. We assessed call variation using 3 approaches: frequency measurements, spectrogram cross-correlation (SPCC) analyses, and call duration measurements. Island parakeets’ calls were longer and had lower mean frequencies, and calls from different islands were distinguishable from each other as well as from mainland calls using measures derived from the SPCCs. In addition, we measured call variability at 2 different levels—within-location and within-individual. We found calls to be more variable for island parakeets for SPCC and duration measures, but less variable for frequency measures. The observed call differentiation among locations may be due to drift, whereas the lower frequency of island calls could either be a response to the windy environment on the islands or a consequence of the island subspecies’ larger body sizes. We also hypothesize that the isolation of parakeet populations on small islands may have resulted in reduced selection for local call convergence, allowing island parakeets to produce more variable calls. We suggest that due to poor signal transmission in the windy island environment, selective pressures may favor variability in more easily perceived call features (like call duration) rather than more subtle features, like frequency shifts. Experimental tests are required to determine whether observed call patterns translate into similarly structured patterns in the responses to vocal variants.
LONG-RANGE ATMOSPHERIC TRANSPORT OF RADON IN EAST ASIA AND DEPOSITION OF ITS PROGENIES IN JAPAN
Authors: Yamazawa Hiromi , Cai Yu , Matsumoto Tatsuya , Moriizumi Jun , Hasegawa Hidenao , Kawano Takafumi
Published: December 2021

A three-dimensional long-range atmospheric transport model for 222Rn and its progenies was applied to simulate 210Pb deposition in Japan and its adjacent waters. Monthly precipitation and 210Pb deposition simulated by the model for winter months were favorably compared with observational data although they were exceptionally underestimated in Aomori. The large monthly deposition along the Japan Sea coast lines during winter was successfully simulated by the model to be nearly 200 Bq m−2, which was contrasted by about 10-fold smaller deposition in other regions. It was also pointed out that the heavy deposition areas formed a narrow band structure along the coastline with width of several tens of kilometers and 210Pb deposition amount positively correlated with the height of mountains located leeward of the heavy deposition areas.
Robust Analysis of Phylogenetic Tree Space
Authors: Smith Martin R
Published: December 2021

Phylogenetic analyses often produce large numbers of trees. Mapping trees’ distribution in “tree space” can illuminate the behavior and performance of search strategies, reveal distinct clusters of optimal trees, and expose differences between different data sources or phylogenetic methods—but the high-dimensional spaces defined by metric distances are necessarily distorted when represented in fewer dimensions. Here, I explore the consequences of this transformation in phylogenetic search results from 128 morphological data sets, using stratigraphic congruence—a complementary aspect of tree similarity—to evaluate the utility of low-dimensional mappings. I find that phylogenetic similarities between cladograms are most accurately depicted in tree spaces derived from information-theoretic tree distances or the quartet distance. Robinson–Foulds tree spaces exhibit prominent distortions and often fail to group trees according to phylogenetic similarity, whereas the strong influence of tree shape on the Kendall–Colijn distance makes its tree space unsuitable for many purposes. Distances mapped into two or even three dimensions often display little correspondence with true distances, which can lead to profound misrepresentation of clustering structure. Without explicit testing, one cannot be confident that a tree space mapping faithfully represents the true distribution of trees, nor that visually evident structure is valid. My recommendations for tree space validation and visualization are implemented in a new graphical user interface in the “TreeDist” R package. [Multidimensional scaling; phylogenetic software; tree distance metrics; treespace projections.]
Recommendations from LGBTQ+ adults for increased inclusion within physical activity: a qualitative content analysis
Authors: Herrick Shannon S C , Baum Tyler , Duncan Lindsay R
Published: December 2021

For decades, physical activity contexts have been inherently exclusionary toward LGBTQ+ participation through their perpetuation of practices and systems that support sexuality- and gender-based discrimination. Progress toward LGBTQ+ inclusivity within physical activity has been severely limited by a lack of actionable and practical suggestions. The purpose of this study was to garner an extensive account of suggestions for inclusivity from LGBTQ+ adults. Using an online cross-sectional survey, LGBTQ+ adults (N = 766) were asked the following open-ended question, “in what ways do you think physical activity could be altered to be more inclusive of LGBTQ+ participation?” The resulting texts were coded using inductive qualitative content analysis. All coding was subject to critical peer review. Participants’ suggestions have been organized and presented under two overarching points of improvement: (a) creation of safe(r) spaces and (b) challenging the gender binary. Participants (n = 558; 72.8%) outlined several components integral to the creation and maintenance of safe(r) spaces such as: (i) LGBTQ+ memberships, (ii) inclusivity training for fitness facility staff, (iii) informative advertisement of LGBTQ+ inclusion, (iv) antidiscrimination policies, and (v) diverse representation. Suggestions for challenging the gender binary (n = 483; 63.1%) called for the creation of single stalls or gender-neutral locker rooms, as well as for the questioning of gender-based stereotypes and binary divisions of gender within physical activity (e.g., using skill level and experience to divide sports teams as opposed to gender). The findings of this study represent a multitude of practical suggestions for LGBTQ+ inclusivity that can be applied to a myriad of physical activity contexts.
Bacteremic and Nonbacteremic Brucellosis in Children in Turkey
Authors: Özdem Suna , Tanır Gönül , Öz Fatma Nur , Yalçınkaya Rumeysa , Cinni Rüveyda Gümüşer , Savaş Şen Zeynep , Aydın Nesibe Nur , Kaman Ayşe , Polat Meltem , Aydın Teke Türkan
Published: December 2021

Introduction

Human brucellosis is one of the most common zoonotic infections in the world. The definitive diagnosis of brucellosis is based on cultured Brucella organisms from blood or other tissue samples. We aimed to compare bacteremic and nonbacteremic brucellosis patients with demographical, epidemiological, clinical and laboratory features and determine the predictive factors affecting blood culture positivity.

Materials and Methods

Children aged 1 month to 18 years who were followed up with the diagnosis of brucellosis between January 2005 and March 2021 were included in this retrospective study. According to the isolation of Brucella melitensis in blood culture, the patients were divided into two groups as bacteremic and nonbacteremic and compared in terms of demographic, clinical and laboratory characteristics.

Results

One hundred eighty-nine (116 male, 61.4%) patients diagnosed with brucellosis were included in the study. There were 76 (40.2%) bacteremic and 113 (59.8%) nonbacteremic patients. Bacteremic patients were younger than nonbacteremic patients. Fever, arthralgia, hepatomegaly and splenomegaly were significantly higher in the culture positive group. High levels of C-reactive protein (CRP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were found to be significant in the bacteremic group.

Conclusion

In our study, history of fever and arthralgia, hepatomegaly and splenomegaly in physical examination and high CRP, ALT and AST levels in the biochemical analysis were important factors determining blood culture positivity.
The (Mis)Use ofSDas Age Diversity Measure: Introducing the MeanSD
Authors: De Meulenaere Kim , Biemann Torsten , Boone Christophe
Published: December 2021

The aging population trend and the associated growing share of older employees lead to high levels of workplace age diversity, which has inspired many researchers to examine the implications. In this article, we show that the prevalent use of the standard deviation (SD) as age diversity measurement may hinder the field in unraveling the effects of age diversity. While SD is known as an operationalization of age diversity as separation—that is, the clustering of work units in distinct age-based subgroups—we argue and show that SD does not fit well with the concept of age separation due to its sensitivity to large age differences. We develop and introduce the mean standard deviation (MSD) as alternative age separation measure. This novel measure is based on SD but is less sensitive to large age differences. We empirically substantiate our concerns and the value of MSD using simple examples of fictitious work units and 2 simulation analyses. We suggest that age diversity scholars use MSD for examining the effects of workplace age diversity as separation. By introducing MSD to the age diversity measurement toolbox, we want to improve the conceptual clarity, measurement, and empirical testing of workplace age diversity.
Diabetes Mellitus Influencing the Bacterial Species in Surgical Site Infections of Orthopedic Trauma Patients
Authors: Angeli Rico , Lippmann Norman , Rodloff Arne C. , Fakler Johannes K. M. , Behrendt Daniel
Published: December 2021

Objective

Diabetes mellitus is a well-known risk factor for delayed wound healing and surgical site infections (SSIs). With the exception of urinary tract infections, information on changes in bacterial etiology and antimicrobial resistance patterns for patients with diabetics is rare. This study compared the prevalence of bacterial species and their antimicrobial resistance in patients with SSI and with or without diabetes mellitus.

Methods

Patients with a postoperative SSI within 6 weeks after orthopedic surgery due to a fracture or joint injury (in a level 1 trauma center in Germany) were analyzed retrospectively for the time period of 2007 to 2012. Microbiological results were assessed by comparing the prevalence of bacterial species and minimal inhibitory concentration of 34 antimicrobial agents for both patient groups.

Results

Three hundred three patients (female = 140, male = 163) were analyzed. Seventy nine (26.1%) of them had diabetes mellitus. Diabetic patients were older (mean age, 70.7 vs 60.1 years, P < 0.001) and more obese (48.1% vs 17.4%; odds ratio [OR], 4.40 [2.51–7.70], P < 0.001). Infection associated mortality was higher in the diabetes group (10.1% vs 2.7%; OR, 4.09 [1.37–12.20], P = 0.012). Most frequent isolates from wound specimen were Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa. Enterococcus faecalis was more frequent in diabetic patients (P = 0.030; OR, 1.89 [1.07–3.34]). There was no difference in resistance against cefuroxime and in the frequency of multidrug-resistant strains in both groups.

Conclusions

Patients with diabetes mellitus and postoperative SSI showed a higher frequency of E. faecalis isolate. However, antibiotic prophylaxis with cephalosporins still seems to be effective in most cases.
Appropriate Antibiotic Prescribing in the Emergency Department
Authors: Oomen Patrick G. A. , Dutilh Jacob C. , Logtenberg Susan J. J. , Sankatsing Sanjay U. C.
Published: December 2021

Background

Data on appropriate antibiotic prescribing in the emergency department (ED) are scarce. The aims of this study were to determine the proportion of ED presentations resulting in antibiotic prescribing and to assess the rate of appropriate antibiotic prescribing in patients receiving antibiotics in the ED over a 4-year period.

Methods

A random sample (10%) of all consecutive patients who visited the ED and received antibiotics between 2013 and 2016 was selected, and 2 independent researchers assessed appropriateness of prescribed antibiotics based on the documented indication. Appropriateness was defined as being in accordance with local antibiotic guidelines at the time. A deviation of antibiotic guidelines with a clearly documented reason was assessed as appropriate. If the indication was surgical prophylaxis, antibiotic appropriateness was not assessed.

Results

Antibiotics were prescribed in 14,461 ED presentations (14.8%), of which 1435 (9.9%) were reviewed. Antibiotic appropriateness was assessed for 1262 indications (excluding surgical prophylaxis). In total, 915 cases (72.5%) were assessed as appropriate, 298 (23.6%) as inappropriate, and 49 (3.9%) were deemed not assessable. The interrater reliability was good (k
= 0.78). Appropriate antibiotic prescribing did not significantly differ between years (P = 0.67). Sepsis was most appropriately treated (93%). Skin and soft tissue infections and upper respiratory infections were treated least appropriately (58.4% and 59.5%). Cultures were obtained in 764 patients (75.4%) receiving antibiotics.

Conclusions

Antibiotics were prescribed in 15% of ED presentations, and 24% of antibiotic prescriptions were assessed as inappropriate, indicating an urgent need to improve awareness and adherence to antibiotic guidelines in the ED.
Prevalence and Predictive Factors of Hypertension Among People Living With HIV in Kebbi State, Nigeria: A Cross-sectional Study
Authors: Badru Oluwaseun , Oduola Taofik , Abdulrazaq Aisha , Peter Chigozie
Published: December 2021

The estimated number of people living with HIV (PLWH) globally in 2018 was 38 million, with sub-Saharan Africa accounting for 70%. Antiretroviral therapy has reduced morbidity among PLWH and has resulted in HIV now being considered a manageable chronic disease rather than a fatal one. The increase in the survival rate of PLWH has led to the emergence of chronic diseases, especially hypertension. The study aimed to assess the prevalence and predictive factors associated with hypertension among PLWH in Kebbi State, Nigeria. A descriptive cross-sectional study was adopted. The blood pressure of 301 PLWH was measured with an automated sphygmomanometer device. The median age of the respondents was 37 years. Females accounted for 61% of the respondents, and the majority were married (55.1%). The prevalence of hypertension was 17%. Older age, lack of exercise, and increasing weight were identified as the predictive factors of hypertension.
Assessment of the Sources of Information by Patients With Rheumatic Diseases
Authors: Izaguirre Germain Maria Pia , Ávila Paola Andrea , Fara Nauan , Pretini Julia , Gaona Maria Elena , Pissani Pia , Saavedra Maira Arias , Aquino Valeria , Espindola Echazu Mariana , Laffont Manuela , Acevedo Magdalena , Garcia Faura Lucrecia , Hassan Romina , Roberts Karen , Brigante Jorge Alejandro , Alvarez Damaris , Micelli Marina Laura , Cosentino Vanesa Laura , Montoya Sandra , Sequeira Gabriel , Kerzberg Eduardo
Published: December 2021

Objective

The aim of this study was to ascertain the frequency of use, search intent (SI), level of accessibility, and degree of reliability of sources of information (SOIs) in rheumatology.

Methods

A survey among adult outpatients with rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and spondyloarthritis was conducted. They were asked if they had procured information from 12 selected SOIs during the past year. Search intent was defined as the source they would like to consult. Accessibility and reliability were assessed through 0-to-10 scales (minimum and maximum, respectively).

Results

Four hundred two patients were surveyed. They had consulted a median of 3 SOIs (interquartile range, 2–6) but described a higher SI: median of 5 SOIs (interquartile range 3–8); p = 0.001.

The most consulted SOIs were the physician (83%), other patients (45%), and Facebook (36%). The main differences between SI and the searches actually performed were observed in community lectures by health care professionals (49%), scientific societies (48%), and associations of patients (27%); p < 0.001. These 3 sources showed low level of accessibility. Facebook, press, radio, and YouTube were the least reliable sources.

Conclusions

Patients consulted a median of 3 SOIs but reported a significantly higher SI. Although patients demand more information, the request is leveled at SOIs with difficult accessibility but high reliability.
Psoriatic Spondylitis: A Disease Manifestation in Debate
Authors: Zeidler Henning K.
Published: December 2021

With the advent of classification criteria for psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), patients with axial manifestations associated with psoriasis, initially described in the l950s as a specific entity termed psoriatic spondylitis (PS), are now categorized within PsA, ankylosing spondylitis (AS), and axSpA. Thus, different terms are used to describe axial disease in patients with PsA including PS, axial psoriatic arthritis (axPsA), and psoriatic spondyloarthritis. Patients with PS may present with inflammatory and/or mechanical back pain, but also may display axial disease on imaging despite not complaining of back pain. Cervical spondylitis has been reported in 35% to 75% of patients with PsA. Axial disease is silent in 20% and 25% of patients with axial PsA and PsA, respectively. The majority of axPsA patients have peripheral arthritis alongside the axial involvement, whereas only 2% to 5% of PsA patients have solely axial arthritis with no peripheral arthritis.

A debate is currently underway as to whether inflammatory axial disease and psoriasis represent axSpA with psoriasis or a subset of PsA named axPsA. Studies have recognized that axial disease in PsA patients seems to be different demographically, genetically, clinically, and radiographically when compared with AS with or without psoriasis. This narrative review summarizes current knowledge regarding axial involvement of PsA in terms of history, terminology, classification, epidemiology, clinical presentation, imaging, diagnosis, and treatment, with the aim of providing advice for management of PS in clinical evidence-based practice. Data-driven studies are needed to develop clear, nonoverlapping classification criteria for spinal involvement in PsA.
ANCA-Associated Vasculitis in Latin America
Authors: Pimentel-Quiroz Victor R. , Sattui Sebastian E. , Ugarte-Gil Manuel F. , Alarcón Graciela S.
Published: December 2021

Most of the existing literature, including epidemiological studies and clinical trials, on antineutrophil cytoplasmic antibodies (ANCA)–associated vasculitis (AAV) include North American (mainly United States and Canada), European, and Asian populations. Few studies have focused on multiethnic populations such as the one from Latin America. Racial and ethnic differences in the incidence of AAV could partially explain the comparatively low number of AAV studies originating in Latin America. However, given the racial/ethnic diversity as well as socioeconomic differences existing in this region, better reporting of AAV presentations and outcomes in Latin America could highlight valuable gaps on the understanding and treatment of these patients. Recently, larger case series and studies have provided better clinical information regarding AAV patients in Latin American countries; however, further information is needed to address gaps such as risk factors, genetic profiles, clinical features, and predictors of clinical outcomes. For these reasons, we have performed a systematic literature review to enhance our understanding of AAV patients in Latin America. We have included 11 articles focused on the epidemiological and clinical features of AAV in Latin America; some similarities and differences with AAV in other regions are shown in these articles. We have identified differences in their prevalence across Latin American countries, which may reflect reporting bias or true ethnic differences among the countries. Our findings should encourage further investigation into AAV in Latin America; such studies will hopefully lead to the optimal management of these patients.
Potential of Donation After Unexpected Circulatory Death Programs Defined by Their Demographic Characteristics
Authors: Brat Aukje , Venema Leonie H. , Bens Bas W.J. , Stieglis Remy , van der Heijden Joris J. , Fondevila Constantino , Reznik Oleg N. , Barrou Benoit , Erasmus Michiel E. , Leuvenink Henri G.D.
Published: December 2021

Background.

Donation after unexpected circulatory death (uDCD) donors are often suggested to increase the number of donor organs. In 2014, a uDCD protocol was implemented in three transplant centers in the Netherlands which unfortunately did not result in additional transplantations. This study was initiated to identify demographic factors influencing the potential success of uDCD programs.

Methods.

Dutch resuscitation databases covering various demographic regions were analyzed for potential donors. The databases were compared with the uDCD implementation project and successful uDCD programs in Spain, France, and Russia.

Results.

The resuscitation databases showed that 61% of all resuscitated patients were transferred to an emergency department. Age selection reduced this uDCD potential to 46% with only patients aged 18–65 years deemed eligible. Of these patients, 27% died in the emergency department. The urban region of Amsterdam showed the largest potential in absolute numbers (52 patients/y). Comparison with the uDCD implementation project showed large similarities in the percentage of potential donors; however, in absolute numbers, it showed a much smaller potential. Calculation of the potential per million persons and the extrapolation of the potential based on the international experience revealed the largest potential in urban regions.

Conclusions.

Implementation of a uDCD program should not only be based on the number of potential donors calculated from resuscitation databases. They show promising potential uDCD percentages for large rural regions and small urban regions; however, actual numbers per hospital are low, leading to insufficient exposure rates. It is, therefore, recommendable to limit uDCD programs to large urban regions.
The Role of Arterial Stiffness in the Estimation of Cardiovascular Risk in Liver Transplant Recipients
Authors: Sastre Lydia , García Raquel , Gándara Julián-Gonzalo , Fernández-Llama Patricia , Amor Antonio J. , Sierra Cristina , Escudé Laia , Ruiz Pablo , Colmenero Jordi , Ortega Emilio , Navasa Miquel , Crespo Gonzalo
Published: December 2021

Background.

Long-term cardiovascular (CV) events are a frequent cause of death and disability after liver transplant (LT). Although a more in-depth, risk-adapted control of CV risk factors may result in improved post-LT CV outcomes, an accurate stratification of the CV risk of LT recipients to better implement preventive strategies is lacking. Aortic pulse wave velocity (aPWV) is a surrogate of arterial stiffness that has been suggested as a biomarker of CV risk; it has never been evaluated in adult LT recipients.

Methods.

In a single-center prospective study, we included 122 LT recipients at 12 (n = 39), 60 (n = 45), or 120 (n = 38) mo after LT. aPWV estimation by oscillometry, clinical assessment of CV risk factors, and CV risk estimation by standard clinical scores (systematic coronary risk evaluation and pooled cohort equation) were performed. The incidence of CV events during prospective follow-up was registered.

Results.

aPWV was independently associated with age and the grade of control of blood pressure. After a median follow-up of 35 mo, 15 patients (12%) presented a CV event. Higher aPWV, diabetes, past or present smoking habit, previous CV events, lower eGFR, being in systematic coronary risk evaluation or pooled cohort equation high-risk groups, and higher levels of total cholesterol, LDL-cholesterol, creatinine, and triglycerides were associated with the incidence of CV events at univariate analysis; aPWV, past or present smoking habit, and triglycerides were independent predictors of CV events.

Conclusions.

According to our results, aPWV mirrors CV risk in LT recipients and thus may be a useful CV risk biomarker in this population. Considering these preliminary results, its accuracy in stratifying risk requires confirmation in further studies.
ICTV Virus Taxonomy Profile: Solemoviridae 2021
Authors: Sõmera Merike , Fargette Denis , Hébrard Eugénie , Sarmiento Cecilia ,   ICTV Report Consortium
Published: December 2021

The family Solemoviridae includes viruses with icosahedral particles (26–34 nm in diameter) assembled on T=3 symmetry with a 4–6 kb positive-sense, monopartite, polycistronic RNA genome. Transmission of members of the genera Sobemovirus and Polemovirus occurs via mechanical wounding, vegetative propagation, insect vectors or abiotically through soil; members of the genera Polerovirus and Enamovirus are transmitted by specific aphids. Most solemoviruses have a narrow host range. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Solemoviridae, which is available at ictv.global/report/solemoviridae.
SARS-CoV-2 Omicron Spike recognition by plasma from individuals receiving BNT162b2 mRNA vaccination with a 16-weeks interval between doses
Authors: Chatterjee Debashree , Tauzin Alexandra , Marchitto Lorie , Yu Gong Shang , Boutin Marianne , Bourassa Catherine , Beaudoin-Bussières Guillaume , Bo Yuxia , Ding Shilei , Laumaea Annemarie , Vézina Dani , Perreault Josée , Gokool Laurie , Morrisseau Chantal , Arlotto Pascale , Fournier Éric , Guilbault Aurélie , Delisle Benjamin , Levade Inès , Goyette Guillaume , Gendron-Lepage Gabrielle , Medjahed Halima , De Serres Gaston , Tremblay Cécile , Martel-Laferrière Valérie , Kaufmann Daniel E. , Bazin Renée , Prévost Jérémie , Moreira Sandrine , Richard Jonathan , Côté Marceline , Finzi Andrés
Published: December 2021

Continuous emergence of SARS-CoV-2 variants of concern (VOC) is fueling the COVID-19 pandemic. Omicron (B.1.1.529), is rapidly spreading worldwide. The large number of mutations in its Spike raised concerns about a major antigenic drift that could significantly decrease vaccine efficacy and infection-induced immunity. A long interval between BNT162b2 mRNA doses was shown to elicit antibodies that efficiently recognize Spikes from different VOCs. Here we evaluated the recognition of Omicron Spike by plasma from a cohort of SARS-CoV-2 naïve and previously-infected individuals that received their BNT162b2 mRNA vaccine 16-weeks apart. Omicron Spike was recognized less efficiently than D614G, Alpha, Beta, Gamma and Delta Spikes. We compared to plasma activity from participants receiving a short (4-weeks) interval regimen. Plasma from individuals of the long interval cohort recognized and neutralized better the Omicron Spike compared to those that received a short interval. Whether this difference confers any clinical benefit against Omicron remains unknown.
Tutorial: Investigating SARS-CoV-2 evolution and phylogeny using MNHN-Tree-Tools
Authors: Haschka Thomas
Published: December 2021

The Covid-19 pandemic has caused at more than 3 million deaths by Mai this year [1]. It had a significant impact on the daily life and the global economy [2]. The virus has since its first recorded outbreak in China [3] mutated into new strains [4]. The Nextstrain [5] project has so far been monitoring the evolution of the virus. At the same time we were developing in our lab the MNHN-Tree-Tools [6] toolkit, primarily for the investigation of DNA repeat sequences. We have further extended MNHN-Tree-Tools [6] to guide phylogenetics. As such the toolkit has evolved into a high performance code, allowing for a fast investigation of millions of sequences. Given the context of the pandemic it became evident that we will use our versatile tool to investigate the evolution of SARS-CoV-2 sequences. Our efforts have cumulated in this tutorial that we share with the scientific community.
Bionized nanoferrite particles alter the course of experimental Cryptococcus neoformans pneumonia
Authors: Liporagi Lopes Livia C. , Korangath Preethi , Dos Santos Junior Samuel R. , Gabrielson Kathleen L. , Ivkov Robert , Casadevall Arturo
Published: December 2021

Cryptococcosis is a devastating fungal disease associated with high morbidity and mortality even when treated with antifungal drugs. Bionized nanoferrite (BNF) nanoparticles are powerful immunomodulators, but their efficacy for infectious diseases has not been investigated. Administration of BNF nanoparticles to mice with experimental cryptococcal pneumonia altered the outcome of infection in a dose response manner as measured by colony forming units and survival. The protective effects were higher at lower doses, with reductions in IL-2, IL-4 and TNF-α, consistent with immune modulation whereby reductions in inflammation translate into reduced host damage, clearance of infection and longer survival.
Combination of Mycobacterium tuberculosis RS ratio and CFU improves the ability of murine efficacy experiments to distinguish between drug treatments
Authors: Dide-Agossou Christian , Bauman Allison A. , Ramey Michelle E. , Rossmassler Karen , Mubarak Reem Al , Pauly Samantha , Voskuil Martin I. , Garcia-Cremades Maria , Savic Rada M. , Nahid Payam , Moore Camille M. , Tasneen Rokeya , Nuermberger Eric L. , Robertson Gregory T. , Walter Nicholas D.
Published: December 2021

Murine tuberculosis drug efficacy studies have historically monitored bacterial burden based on colony forming units of M. tuberculosis in lung homogenate. In an alternative approach, a recently described molecular pharmacodynamic marker called the RS ratio quantifies drug effect on a fundamental cellular process: ongoing ribosomal RNA synthesis. Here we evaluated the ability of different pharmacodynamic markers to distinguish between treatments in three BALB/c mouse experiments at two institutions. We confirmed that different pharmacodynamic markers measure distinct biological responses. We found that a combination of pharmacodynamic markers distinguishes between treatments better than any single marker. The combination of the RS ratio with colony forming units showed the greatest ability to recapitulate the rank order of regimen treatment-shortening activity, providing proof of concept that simultaneous assessment of pharmacodynamic markers measuring different properties will enhance insight gained from animal models and accelerate development of new combination regimens. These results suggest potential for a new era in which antimicrobial therapies are evaluated not only on culture-based measures of bacterial burden but also on molecular assays that indicate how drugs impact the physiological state of the pathogen.
A magnetic bead immunoassay to detect human IgG reactive to SARS-CoV-2 Spike S1 RBD produced in Escherichia coli
Authors: Conzentino Marcelo S. , Gonçalves Ana C. A. , Paula Nigela M. , Rego Fabiane G. M. , Zanette Dalila L. , Aoki Mateus N. , Nardin Jeanine M. , Huergo Luciano F.
Published: December 2021

Immunological assays to detect SARS-CoV-2 Spike receptor binding domain antigen seroconversion in humans are important tools to monitor the levels of protecting antibodies in the population in response to infection and/or immunization. Here we describe a simple, low cost and high throughput Ni2+ magnetic bead immunoassay to detect human IgG reactive to Spike S1 RBD Receptor Binding Domain produced in Escherichia coli. A 6xHis tagged Spike S1 RBD was expressed in E. coli and purified by affinity chromatography. The protein was mobilized on the surface of Ni2+ magnetic beads and used to investigate the presence of reactive IgG in the serum obtained from pre-pandemic and COVID-19 confirmed cases. The method was validated with a cohort of 290 samples and an area under the receiver operating characteristics curve of 0.94 was obtained. The method operated with>82% sensitivity at 98% specificity and was also able to track human IgG raised in response to vaccination with Comirnaty with 85% sensitivity. The IgG signal obtained with the described method was well correlated with the signal obtained when pre fusion Spike produced in HEK cell lines were used as antigen. This novel low-cost and high throughput immunoassay may act as an important tool to investigate protecting IgG antibodies against SARS-CoV-2 in the human population.
Cell Geometry Distinguishes Migration-Associated Heterogeneity in Two-Dimensional Systems
Authors: Varankar Sagar S , Hari Kishore , Bapat Sharmila A , Jolly Mohit Kumar
Published: December 2021

Background

In vitromigration assays are a cornerstone of cell biology and have found extensive utility in research. Over the past decade, several variations of the two-dimensional (2D) migration assay have improved our understanding of this fundamental process. However, the ability of these approaches to capture the functional heterogeneity during migration and their accessibility to inexperienced users has been limited.

Methods

We downloaded published time-lapse 2D cell migration datasets and subjected them to feature extraction with the Fiji software. We used the ‘Analyze Particles’ tool to extract ten cell geometry features (CGFs), which were grouped into ‘shape’, ‘size’ and ‘position’ descriptors. Next, we defined the migratory status of cells using the ‘MTrack2’ plugin. All data obtained from Fiji were further subjected to rigorous statistical analysis with R version 4.0.2.

Results

We observed consistent associative trends between size and shape descriptors and validated the robustness of our observations across four independent datasets. We used these descriptors to resolve the functional heterogeneity during migration by identifying and characterizing ‘non-migrators (NM)’ and ‘migrators (M)’. Statistical analysis allowed us to identify considerable heterogeneity in the NM subset, that has not been previously reported. Interestingly, differences in 2D-packing appeared to affect CGF trends and heterogeneity of the migratory subsets for the datasets under investigation.

Conclusion

We developed an analytical pipeline using open source tools, to identify and morphologically characterize functional migratory subsets from label-free, time-lapse migration data. Our quantitative approach identified a previously unappreciated heterogeneity of non-migratory cells and predicted the influence of 2D-packing on migration.
Accelerating manufacturing to enable large-scale supply of a new adenovirus-vectored vaccine within 100 days
Authors: Joe Carina C D , Segireddy Rameswara R , Oliveira Cathy , Berg Adam , Li Yuanyuan , Doultsinos Dimitrios , Chopra Nitin , Scholze Steffi , Ahmad Asma , Nestola Piergiuseppe , Niemann Julia , Douglas Alexander D
Published: December 2021

The Coalition for Epidemic Preparedness Innovations’ ‘100-day moonshot’ aspires to launch a new vaccine within 100 days of pathogen identification. Here, we describe work to optimize adenovirus vector manufacturing for rapid response, by minimizing time to clinical trial and first large-scale supply, and maximizing the output from the available manufacturing footprint.

We describe a rapid viral seed expansion workflow that allows vaccine release to clinical trials within 60 days of antigen sequence identification, followed by vaccine release from globally distributed sites within a further 40 days. We also describe a new perfusion-based upstream production process, designed to maximize output while retaining simplicity and suitability for existing manufacturing facilities. This improves upstream volumetric productivity of ChAdOx1 nCoV-19 by around four-fold and remains compatible with the existing downstream process, yielding drug substance sufficient for 10000 doses from each liter of bioreactor capacity.

Transition to a new production process across a large manufacturing network is a major task. In the short term, the rapid seed generation workflow could be used with the existing production process. We also use techno-economic modelling to show that, if linear scale-up were achieved, a single cleanroom containing two 2000 L bioreactors running our new perfusion-based process could supply bulk drug substance for around 120 million doses each month, costing <0.20 EUR/dose. We estimate that a manufacturing network with 32000 L of bioreactor capacity could release around 1 billion doses of a new vaccine within 130 days of genomic sequencing of a new pathogen, in a hypothetical ‘surge campaign’ with suitable prior preparation and resources, including adequate fill-and-finish capacity.

This accelerated manufacturing process, along with other advantages such as thermal stability, supports the ongoing value of adenovirus-vectored vaccines as a rapidly adaptable and deployable platform for emergency response.
A spatiotemporal steroidogenic regulatory network in human fetal adrenal glands and gonads
Authors: Wang Yifu , Guo Bingqian , Guo Yajie , Qi Nana , Lv Yufang , Ye Yu , Huang Yan , Long Xinyang , Chen Hongfei , Su Cheng , Zhang Liying , Zhang Qingyun , Li Minxi , Liao Jingling , Yan Yunkun , Mao Xingning , Zeng Yanyu , Jiang Jinghang , Chen Zhongyuan , Guo Yi , Gao Shuai , Cheng Jiwen , Jiang Yonghua , Mo Zengnan
Published: December 2021

Human fetal adrenal glands produce substantial amounts of dehydroepiandrosterone (DHEA), which is one of the most important precursors of sex hormones. However, the underlying biological mechanism remains largely unknown. Herein, we sequenced human fetal adrenal glands and gonads from 7 to 14 GW via the 10× Genomics single-cell transcriptome techniques and reconstructed their location information by Spatial Transcriptome, conducted COOL-seq for the MC2R+ inner zone steroidogenic cells during the time window of sex differentiation (8-12GW). We found that relative to gonads, adrenal glands begin to synthesize steroids early. The coordination among steroidogenic cells and multiple nonsteroidogenic cells promotes adrenal cortex construction and steroid synthesis. Notably, during the time window of sex differentiation (8–12 GW), key enzyme gene expression shifts to accelerate DHEA synthesis in males and cortisol synthesis in females. Furthermore, high SST+ expressions in the adrenal gland and testis amplify androgen synthesis in males. Our research highlights the robustness of the action of fetal adrenal glands on gonads to modify the process of sexual differentiation.