bluuebunny/crossref_metadata_2025 huggingface dataset:
Uneven Progress in Gender Equality at Plastic Surgery Conferences: Lessons from a Decade of Meetings
Authors: Bregman Dana E. , Ha Grace , Tanna Neil
Published: February 2022

Background:

The demographics of plastic surgeons and plastic surgery trainees are changing, reflecting an increase in the diversity of medical school graduates. The authors investigated the gender diversity of speakers at several plastic surgery conferences and evaluated temporal trends over a 10-year period.

Methods:

The following societies’ conferences and years were included based on the conference agendas available for review: American Society for Aesthetic Plastic Surgery, Plastic Surgery Research Council, American Association of Plastic Surgeons, Northeastern Society of Plastic Surgeons, and American Society for Reconstructive Microsurgery. Differences in the average amount of time spoken were analyzed using an independent one-tailed t test.

Results:

The number of female speakers and the time allotted to speak increased for all conferences. There was not a consistent difference in the amount of time individual men and women were allotted to speak. Across the five conferences, there was no consistent relationship found between years since board certification and female participation in conference. Gender diversity among speakers at plastic surgery conferences has not kept pace with the increase in female plastic surgery trainees because those who are selected to speak are overwhelmingly men. The hypothesis that a paucity of female speakers reflects the relatively shorter duration of career experience of female plastic surgeons was not supported by these findings.

Conclusion:

It is imperative that conferences increase the participation of women and strive toward more accurately reflecting the burgeoning role that female surgeons have in the field at present and will have in the future.
Amino Acid Uptake, Glucose Metabolism, and Neuroinflammation in John Cunningham Virus Associated Progressive Multifocal Leukoencephalopathy
Authors: Unterrainer Marcus , Mahler Christoph , Schumacher Adrian-Minh , Ruf Viktoria , Blum Bernhard , Quach Stefanie , Brendel Matthias , Rupprecht Rainer , Bartenstein Peter , Kerschensteiner Martin , Kümpfel Tania , Albert Nathalie L.
Published: February 2022

A 69-year-old woman presented with progressive dysarthria and cognitive deficits. On MRI, a T2-hyperintense, non–contrast-enhancing lesion was found in the left precentral area. 18F-FET and 18F-FDG PET scans revealed faint amino acid uptake and glucose hypometabolism of the lesion. To assess a neuroinflammatory component, TSPO PET with 18F-GE-180 was performed, where tracer uptake markedly exceeded the T2-hyperintense areas. Histology derived from a stereotactic biopsy findings confirmed John Cunningham virus–associated progressive multifocal leukoencephalopathy. This case underlines that TSPO PET comprises distinct imaging advantages over other established radioligands such as 18F-FET and 18F-FDG in progressive multifocal leukoencephalopathy.
68Ga-DOTANOC PET/CT in Multiple Endocrine Neoplasia 1 With Associated Adrenocortical Carcinoma
Authors: Basheer Shyma , Ratheesan Ramkesh , Sarma Manjit , Palaniswamy Shanmuga Sundaram , Mathews Anitha
Published: February 2022

Multiple endocrine neoplasia 1 (MEN1) syndrome is an autosomal dominant syndrome comprising a triad of pancreatic, pituitary, and parathyroid tumors. Adrenal cortical carcinoma occurs rarely in MEN1 syndrome. Here, we have presented a case of a 62-year-old woman with adrenal mass and elevated serum parathormone levels, who underwent 68Ga-DOTANOC PET/CT. 68Ga-DOTANOC PET/CT showed intense tracer concentration in the left adrenal mass and lesions in the liver, pancreas, and peritoneum. Biopsy of the peritoneal deposit revealed metastatic adrenocortical carcinoma, and further genetic testing showed MEN1 mutation.
The Clinical Significance of Small Vessel Vasculitis on Temporal Artery Biopsies
Authors: Quigley Julian , Sammel Anthony Michael , Laurent Rodger , Brewer Janice , Hsiao Edward , Schembri Geoffrey , Fraser Clare L.
Published: February 2022

Background:

Giant cell arteritis (GCA) is the most common type of systemic vasculitis in the elderly. Untreated, it can lead to irreversible blindness. Its diagnosis relies on a temporal artery biopsy (TAB). However, a proportion of patients have small vessel vasculitis (SVV) on biopsy; the prognosis of which remains unclear. The aim of this study is to compare the clinical presentation and long-term outcomes of those with SVV with negative and positive biopsies to determine whether long-term corticosteroid therapy can be avoided in these patients.

Methods:

Post hoc analysis of patients with suspected GCA who underwent TAB and fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scan as part of a prospective GCA and PET cohort. Patients were divided in to 3 groups based on TAB result: positive (inflammation in the main artery wall), negative (no inflammation), and SVV (isolated vasa vasorum or periadventitial SVV). Clinical, serological, and PET/CT data of patients with SVV were compared with those with positive and those with negative biopsies.

Results:

For the 58 eligible patients recruited between May 2016 and December 2017, 11 had SVV, 12 had positive, and 35 had negative biopsies. Patients with SVV had similar clinical, serological, and PET/CT findings to those with negative biopsies. Compared with those with positive biopsies, patients with SVV had lower erythrocyte sedimentation rate (25 vs 78 mm/hour; P = 0.02), platelet count (296 vs 385 ×109/L; P = 0.03), and a lower median total vascular score on PET/CT scan (1.0 vs 13.5; P = 0.01). Median prednisone dose was lower (4.8 vs 11.7 mg; P = 0.015) and fewer were on steroid-sparing agents (20% vs 67%; P = 0.043) at 6 months. The percentage of patients with a clinical diagnosis of GCA was similar between those with SVV (3/11, 27.3%) and those with negative biopsies (5/35, 14.3%; P = 0.374).

Conclusions:

Patients with SVV on TAB had similar clinical features, PET/CT findings, and 6-month outcomes to those with negative biopsies. Small vessel vasculitis can be treated as equivalent to a negative biopsy when being considered for diagnosis and treatment of GCA.
Social factors and the neurobiology of pathogen avoidance
Authors: Kavaliers Martin , Ossenkopp Klaus-Peter , Tyson Cashmeira-Dove , Bishnoi Indra R. , Choleris Elena
Published: February 2022

Although the evolutionary causes and consequences of pathogen avoidance have been gaining increasing interest, there has been less attention paid to the proximate neurobiological mechanisms. Animals gauge the infection status of conspecifics and the threat they represent on the basis of various sensory and social cues. Here, we consider the neurobiology of pathogen detection and avoidance from a cognitive, motivational and affective state (disgust) perspective, focusing on the mechanisms associated with activating and directing parasite/pathogen avoidance. Drawing upon studies with laboratory rodents, we briefly discuss aspects of (i) olfactory-mediated recognition and avoidance of infected conspecifics; (ii) relationships between pathogen avoidance and various social factors (e.g. social vigilance, social distancing (approach/avoidance), social salience and social reward); (iii) the roles of various brain regions (in particular the amygdala and insular cortex) and neuromodulators (neurotransmitters, neuropeptides, steroidal hormones and immune components) in the regulation of pathogen avoidance. We propose that understanding the proximate neurobiological mechanisms can provide insights into the ecological and evolutionary consequences of the non-consumptive effects of pathogens and how, when and why females and males engage in pathogen avoidance.
Chimpanzees consider freedom of choice in their evaluation of social action
Authors: Engelmann Jan M. , Herrmann Esther , Proft Marina , Keupp Stefanie , Dunham Yarrow , Rakoczy Hannes
Published: February 2022

Judgements of wrongdoing in humans often hinge upon an assessment of whether a perpetrator acted out of free choice: whether they had more than one option. The classic inhibitors of free choice are constraint (e.g. having your hands tied together) and ignorance (e.g. being unaware that an alternative exists). Here, across two studies, we investigate whether chimpanzees consider these factors in their evaluation of social action. Chimpanzees interacted with a human experimenter who handed them a non-preferred item of food, either because they were physically constrained from accessing the preferred item (Experiment 1) or because they were ignorant of the availability of the preferred item (Experiment 2). We found that chimpanzees were more likely to accept the non-preferred food and showed fewer negative emotional responses when the experimenter was physically constrained compared with when they had free choice. We did not, however, find an effect of ignorance on chimpanzee's evaluation. Freedom of choice factors into chimpanzees' evaluation of how they are treated, but it is unclear whether mental state reasoning is involved in this assessment.
Lack of age-related mosaic loss of W chromosome in long-lived birds
Authors: Trujillo Nancy , Martínez-Pacheco Mónica , Soldatini Cecilia , Ancona Sergio , Young Rebecca C. , Albores-Barajas Yuri V. , Orta Alberto H. , Rodríguez Cristina , Székely Tamas , Drummond Hugh , Urrutia Araxi O. , Cortez Diego
Published: February 2022

Females and males often exhibit different survival in nature, and it has been hypothesized that sex chromosomes may play a role in driving differential survival rates. For instance, the Y chromosome in mammals and the W chromosome in birds are often degenerated, with reduced numbers of genes, and loss of the Y chromosome in old men is associated with shorter life expectancy. However, mosaic loss of sex chromosomes has not been investigated in any non-human species. Here, we tested whether mosaic loss of the W chromosome (LOW) occurs with ageing in wild birds as a natural consequence of cellular senescence. Using loci-specific PCR and a target sequencing approach we estimated LOW in both young and adult individuals of two long-lived bird species and showed that the copy number of W chromosomes remains constant across age groups. Our results suggest that LOW is not a consequence of cellular ageing in birds. We concluded that the inheritance of the W chromosome in birds, unlike the Y chromosome in mammals, is more stable.
A taxonomic-based joint species distribution model for presence-only data
Authors: Escamilla Molgora Juan M. , Sedda Luigi , Diggle Peter J. , Atkinson Peter M.
Published: February 2022

Species distribution models (SDMs) are an important class of model for mapping taxa spatially and are a key tool for tackling biodiversity loss. However, most common SDMs depend on presence–absence data and, despite the accumulation and exponential growth of biological occurrence data across the globe, the available data are predominantly presence-only (i.e. they lack real absences). Although presence-only SDMs do exist, they inevitably require assumptions about absences of the considered taxa and they are specified mostly for single species and, thus, do not exploit fully the information in related taxa. This greatly limits the utility of global biodiversity databases such as GBIF. Here, we present a Bayesian-based SDM for multiple species that operates directly on presence-only data by exploiting the joint distribution between the multiple ecological processes and, crucially, identifies the sampling effort per taxa which allows inference on absences. The model was applied to two case studies. One, focusing on taxonomically diverse taxa over central Mexico and another focusing on the monophyletic family Cactacea over continental Mexico. In both cases, the model was able to identify the ecological and sampling effort processes for each taxon using only the presence observations, environmental and anthropological data.
Constrained optimization of divisional load in hierarchically organized tissues during homeostasis
Authors: Ashcroft Peter , Bonhoeffer Sebastian
Published: February 2022

It has been hypothesized that the structure of tissues and the hierarchy of differentiation from stem cell to terminally differentiated cell play a significant role in reducing the incidence of cancer in that tissue. One specific mechanism by which this risk can be reduced is by minimizing the number of divisions—and hence the mutational risk—that cells accumulate as they divide to maintain tissue homeostasis. Here, we investigate a mathematical model of cell division in a hierarchical tissue, calculating and minimizing the divisional load while constraining parameters such that homeostasis is maintained. We show that the minimal divisional load is achieved by binary division trees with progenitor cells incapable of self-renewal. Contrary to the protection hypothesis, we find that an increased stem cell turnover can lead to lower divisional load. Furthermore, we find that the optimal tissue structure depends on the time horizon of the duration of homeostasis, with faster stem cell division favoured in short-lived organisms and more progenitor compartments favoured in longer-lived organisms.
Undefining life's biochemistry: implications for abiogenesis
Authors: Freeland Stephen
Published: February 2022

In the mid-twentieth century, multiple Nobel Prizes rewarded discoveries of a seemingly universal set of molecules and interactions that collectively defined the chemical basis for life. Twenty-first-century science knows that every detail of this Central Dogma of Molecular Biology can vary through either biological evolution, human engineering (synthetic biology) or both. Clearly the material, molecular basis of replicating, evolving entities can be different. There is far less clarity yet for what constitutes this set of possibilities. One approach to better understand the limits and scope of moving beyond life's central dogma comes from those who study life's origins. RNA, proteins and the genetic code that binds them each look like products of natural selection. This raises the question of what step(s) preceded these particular components? Answers here will clarify whether any discrete point in time or biochemical evolution will objectively merit the label of life's origin, or whether life unfolds seamlessly from the non-living universe.
Uncertainty quantification of a three-dimensional in-stent restenosis model with surrogate modelling
Authors: Ye Dongwei , Zun Pavel , Krzhizhanovskaya Valeria , Hoekstra Alfons G.
Published: February 2022

In-stent restenosis is a recurrence of coronary artery narrowing due to vascular injury caused by balloon dilation and stent placement. It may lead to the relapse of angina symptoms or to an acute coronary syndrome. An uncertainty quantification of a model for in-stent restenosis with four uncertain parameters (endothelium regeneration time, the threshold strain for smooth muscle cell bond breaking, blood flow velocity and the percentage of fenestration in the internal elastic lamina) is presented. Two quantities of interest were studied, namely the average cross-sectional area and the maximum relative area loss in a vessel. Owing to the high computational cost required for uncertainty quantification, a surrogate model, based on Gaussian process regression with proper orthogonal decomposition, was developed and subsequently used for model response evaluation in the uncertainty quantification. A detailed analysis of the uncertainty propagation is presented. Around 11% and 16% uncertainty is observed on the two quantities of interest, respectively, and the uncertainty estimates show that a higher fenestration mainly determines the uncertainty in the neointimal growth at the initial stage of the process. The uncertainties in blood flow velocity and endothelium regeneration time mainly determine the uncertainty in the quantities of interest at the later, clinically relevant stages of the restenosis process.
A novel hydrophobically associating water-soluble polymer used as constant rheology agent for cement slurry
Authors: Bu Yuhuan , Xu Mengran , Liu Huajie , Zhou Annan , Du Jiapei , Yang Xin , Guo Shenglai
Published: February 2022

During the process of well cementing in deep water, the cement slurry experiences a wide range of temperature variation from low temperature at seabed to high temperature in downhole. The elevated temperature affects the rheology of cement slurry. The change of rheology of cement slurry could influence the safety of cementing operation. The aim of this paper is to develop a new kind of hydrophobically associating water-soluble polymer (NHAWP) as an additive to prepare a constant rheology oil well cement slurry, which can be used at temperature range from 4°C to 90°C. The acrylamide, 2-acrylamide-2-methylpropionic acid and stearyl methylacrylate were applied to synthesize the NHAWP by the inverse microemulsion polymerization. Test results indicate that the critical association temperature of NHAWP is 45°C. The critical association temperature is independent of NHAWP concentration, salt concentration and alkalinity of solution. When the temperature is below 45°C, NHAWP shows little influence on the viscosity of solution. When the temperature is above 45°C, the NHAWP forms spatial network structure by intermolecular hydrophobic association and thus increases the viscosity of solution significantly. The NHAWP also displays good thermal stability and excellent salt and alkali resistance properties. In addition, the NHAWP shows nearly no negative influence on the basic properties of cement slurry, which indicates that the NHAWP can be used as a constant rheology agent to prepare a cement slurry with constant rheology in the temperature range of 4°C to 90°C.
The puzzling relationship between multi-laboratory replications and meta-analyses of the published literature
Authors: Lewis Molly , Mathur Maya B. , VanderWeele Tyler J. , Frank Michael C.
Published: February 2022

What is the best way to estimate the size of important effects? Should we aggregate across disparate findings using statistical meta-analysis, or instead run large, multi-laboratory replications (MLR)? A recent paper by Kvarven, Strømland and Johannesson (Kvarven
et al.
2020
Nat. Hum. Behav
.
4
, 423–434. (
doi:10.1038/s41562-019-0787-z
)) compared effect size estimates derived from these two different methods for 15 different psychological phenomena. The authors reported that, for the same phenomenon, the meta-analytic estimate tended to be about three times larger than the MLR estimate. These results are a specific example of a broader question: What is the relationship between meta-analysis and MLR estimates? Kvarven
et al.
suggested that their results undermine the value of meta-analysis. By contrast, we argue that both meta-analysis and MLR are informative, and that the discrepancy between the two estimates that they observed is in fact still largely unexplained. Informed by re-analyses of Kvarven
et al.
’s data and by other empirical evidence, we discuss possible sources of this discrepancy and argue that understanding the relationship between estimates obtained from these two methods is an important puzzle for future meta-scientific research.
Inter-community behavioural variation confirmed through indirect methods in four neighbouring chimpanzee communities in Cantanhez NP, Guinea-Bissau
Authors: Bessa Joana , Biro Dora , Hockings Kimberley
Published: February 2022

Culture, while long viewed as exclusively human, has now been demonstrated across diverse taxa and contexts. However, most animal culture data are constrained to well-studied, habituated groups. This is the case for chimpanzees, arguably the most ‘cultural’ non-human species. While much progress has been made charting wild chimpanzees' cultural repertoire, large gaps remain in our knowledge of the majority of the continent's chimpanzees. Furthermore, few studies have compared neighbouring communities, despite such comparisons providing the strongest evidence for culture, and few have studied communities living in anthropogenic habitats although their culture is in imminent danger of disappearing. Here we combine direct, indirect and remote methods, including camera traps, to study, over 2 years, four unhabituated neighbouring chimpanzee communities inhabiting human-impacted habitats in Cantanhez NP, Guinea-Bissau. From traces collected during 1089 km of reconnaissance walks and 4197 videos from 56 camera trap locations, we identified 18 putative cultural traits. These included some noteworthy novel behaviours for these communities, and behaviours possibly new to the species. We created preliminary behavioural profiles for each community, and found inter-community differences spanning tool use, communication, and social behaviour, demonstrating the importance of comparing neighbouring communities and of studying previously neglected communities including those inhabiting anthropogenic landscapes.
High-quality host plant diets partially rescue female fecundity from a poor early start
Authors: Cirino Lauren A. , Moore Patricia J. , Miller Christine W.
Published: February 2022

Nutrition is a dynamic environmental factor and compensatory growth may help animals handle seasonal fluctuations in their diets. Yet, how the dynamic changes in nutrition affect female reproduction is understudied. We took advantage of a specialist insect herbivore,
Narnia femorata
Stål (Hemiptera: Coreidae), that feeds and reproduces on cactus across three seasons. We first examined how cactus quality can affect female reproductive success. Then, we investigated the extent to which reproductive success can be improved by a switch in diet quality at adulthood. We placed
N. femorata
juveniles onto prickly pear cactus pads with early-season (low-quality) or late-season (high-quality) fruit and tracked survivorship and development time. A subset of the females raised on low-quality diets were provided with an improved adult diet to simulate a seasonal change in diet. Adult female survival and egg production were tracked over time. All fitness-related traits were lower for females fed low-quality diets compared with females fed high-quality diets. However, when females had access to an improved adult diet, egg production was partially rescued. These findings show that a seasonal improvement in diet can enhance reproduction, but juvenile nutrition still has lasting effects that females cannot overcome.
Cellular and immunological mechanisms influence host-adapted phenotypes in a vector-borne microparasite
Authors: Lin Yi-Pin , Tufts Danielle M. , Combs Matthew , Dupuis Alan P. , Marcinkiewicz Ashley L. , Hirsbrunner Andrew D. , Diaz Alexander J. , Stout Jessica L. , Blom Anna M. , Strle Klemen , Davis April D. , Kramer Laura D. , Kolokotronis Sergios-Orestis , Diuk-Wasser Maria A.
Published: February 2022

Predicting pathogen emergence and spillover risk requires understanding the determinants of a pathogens' host range and the traits involved in host competence. While host competence is often considered a fixed species-specific trait, it may be variable if pathogens diversify across hosts. Balancing selection can lead to maintenance of pathogen polymorphisms (multiple-niche-polymorphism; MNP). The causative agent of Lyme disease,Borrelia burgdorferi(Bb), provides a model to study the evolution of host adaptation, as someBbstrains defined by their outer surface protein C (ospC) genotype, are widespread in white-footed mice and others are associated with non-rodent vertebrates (e.g. birds). To identify the mechanisms underlying potential strain × host adaptation, we infected American robins and white-footed mice, with threeBbstrains of differentospCgenotypes.Bbburdens varied by strain in a host-dependent fashion, and strain persistence in hosts largely corresponded toBbsurvival at early infection stages and with transmission to larvae (i.e. fitness). Early survival phenotypes are associated with cell adhesion, complement evasion and/or inflammatory and antibody-mediated removal ofBb,suggesting directional selective pressure for host adaptation and the potential role of MNP in maintaining OspC diversity. Our findings will guide future investigations to inform eco-evolutionary models of host adaptation for microparasites.
Comparative genomics of 26 complete circular genomes of 18 different serotypes of Actinobacillus pleuropneumoniae
Authors: Donà Valentina , Ramette Alban , Perreten Vincent
Published: February 2022

Actinobacillus pleuropneumoniae

is a Gram-negative, rod-shaped bacterium of the family

Pasteurellaceae

causing pig pleuropneumonia associated with great economic losses worldwide. Nineteen serotypes with distinctive lipopolysaccharide (LPS) and capsular (CPS) compositions have been described so far, yet complete circular genomes are publicly available only for the reference strains of serotypes 1, 4 and 5b, and for field strains of serotypes 1, 3, 7 and 8. We aimed to complete this picture by sequencing the reference strains of 17 different serotypes with the MinION sequencer (Oxford Nanopore Technologies, ONT) and on an Illumina HiSeq (Illumina) platform. We also included two field isolates of serotypes 2 and 3 that were PacBio- and MinION-sequenced, respectively. Genome assemblies were performed following two different strategies, i.e. PacBio- or ONT-only de novo assemblies polished with Illumina reads or a hybrid assembly by directly combining ONT and Illumina reads. Both methods proved successful in obtaining accurate circular genomes with comparable qualities. blast-based genome comparisons and core-genome phylogeny based on core genes, SNP typing and multi-locus sequence typing (cgMLST) of the 26 circular genomes indicated well-conserved genomes across the 18 different serotypes, differing mainly in phage insertions, and CPS, LPS and RTX-toxin clusters, which, consistently, encode serotype-specific antigens. We also identified small antibiotic resistance plasmids, and complete subtype I-F and subtype II-C CRISPR-Cas systems. Of note, highly similar clusters encoding all those serotype-specific traits were also found in other pathogenic and commensal

Actinobacillus

species. Taken together with the presence of transposable elements surrounding these loci, we speculate a dynamic intra- and interspecies exchange of such virulence-related factors by horizontal gene transfer. In conclusion, our comprehensive genomics analysis provides useful information for diagnostic test and vaccine development, but also for whole-genome-based epidemiological studies, as well as for the surveillance of the evolution of antibiotic resistance and virulence genes in

A. pleuropneumoniae

.
An inactivated SARS-CoV-2 vaccine is safe and induces humoral and cellular immunity against virus variants in healthy children and adolescents in Chile
Authors: Soto Jorge A , Melo-González Felipe , Gutierrez-Vera Cristián , Schultz Bárbara M , Berríos-Rojas Roslye V , Rivera-Pérez Daniela , Piña-Iturbe Alejandro , Hoppe-Elsholz Guillermo , Duarte Luisa F , Vázquez Yaneisi , Moreno-Tapia Daniela , Ríos Mariana , Palacios Pablo A , Garcia-Betancourt Richard , Santibañez Álvaro , Mendez Constanza , Diethelm-Varela Benjamín , Astudillo Patricio , Calvo Mario , Cárdenas Antonio , González Marcela , Goldsack Macarena , Gutiérrez Valentina , Potin Marcela , Schilling Andrea , Tapia Lorena I , Twele Loreto , Villena Rodolfo , Grifoni Alba , Sette Alessandro , Weiskopf Daniela , Fasce Rodrigo A , Fernández Jorge , Mora Judith , Ramírez Eugenio , Gaete-Argel Aracelly , Acevedo Mónica , Valiente-Echeverría Fernando , Soto-Rifo Ricardo , Retamal-Díaz Angello , Muñoz-Jofré Nathalia ,   PedCoronaVac03CL Study Group, Meng Xing , Xin Qianqian , Alarcón-Bustamante Eduardo , González-Aramundiz José V , Corre Nicole Le , Álvarez María Javiera , González Pablo A , Abarca Katia , Perret Cecilia , Carreño Leandro J , Kalergis Alexis M , Bueno Susan M
Published: February 2022

Background

Multiple vaccines against SARS-CoV-2 have been evaluated in clinical trials, but very few include the pediatric population. The inactivated vaccine CoronaVac® has shown to be safe and immunogenic in a phase 1/2 clinical trial in a pediatric cohort in China. This study is an interim safety and immunogenicity report of a phase 3 clinical trial for CoronaVac® in healthy children and adolescents in Chile.

Methods

Participants aged 3 to 17 years old received two doses of CoronaVac® in a four-week interval. Local and systemic adverse reactions were registered in 699 participants that received the first dose and 381 that received the second dose until December 31st, 2021. Whole blood samples were collected from 148 participants for humoral and cellular immunity analyses.

Results

The primary adverse reaction reported after the first and second dose was pain at the injection site. The adverse reactions observed were primarily mild and local, and no severe adverse events were reported. Four weeks after the second dose, a significant increase in the levels of total and neutralizing antibodies was observed. Increased activation of specific CD4+ T cells was also observed four weeks after the second dose. Although antibodies induced by vaccination neutralize variants Delta and Omicron, titers were lower than the D614G variant. Importantly, comparable T cell responses were detected against these variants of concern.

Conclusions

CoronaVac® is safe and immunogenic in subjects aged 3-17 years old and is thus likely to confer protection against infection caused by SARS-CoV-2 variants in this target population.
Childhood Trauma Exposure Increases Long COVID Risk
Authors: Van Den Hurk Alicia W. Villanueva , Ujvari Cady , Greenspan Noah , Malaspina Dolores , Jimenez Xavier F. , Walsh-Messinger Julie
Published: February 2022

Background

A proportion of those who contract COVID-19 will develop long COVID (i.e., symptoms that persist for three months or more). Childhood trauma contributes to a pro-inflammatory state in adulthood evidenced by high morbidity and early mortality, but it has not yet been investigated as a risk factor for long COVID.

Methods

Participants (N=338) completed online measures of premorbid health, COVID-19 positivity, symptoms, recovery, depression, anxiety, and post-traumatic stress disorder (PTSD). Questionnaires about childhood and recent traumatic experiences were completed by half of the sample (N=162).

Results

Fifty-three percent of participants developed long COVID, of whom over 60% endorsed exercise intolerance and protracted myalgias, headaches, brain fog, and shortness of breath. Participants who experienced at least one childhood traumatic event were 3-fold more likely to develop the syndrome (OR=3.11, 95% CI, 1.49 to 6.48), while risk was nearly 6-fold increased for two or more events (OR=5.67, CI, 2.44 to 13.13). Regression models showed childhood trauma (OR=5.32, CI, 1.44 to 19.68), older age (OR=1.11, CI, 1.06 to 1.16), female sex (OR=4.02, CI, 1.34 to 12.12), along with chest pain (OR=8.77, CI, 2.80 to 27.43), brain fog (OR=3.33, CI, 1.16 to 9.57) and phantosmia (OR=5.90, CI, 1.40 to 24.86) during acute illness accurately classified long COVID status in 87% of participants.

Interpretations

Early adversity is a risk-factor for long COVID, likely due to altered immune response, central sensitization, and peripheral dysfunction. Childhood trauma, a crucial social determinant of health, should be routinely assessed in COVID-19 survivors and may aid in determining prognosis.
STability and Shelf-Life of Plasma Bubbling Treated Cow Milk
Authors: Dash Samarpita , Jaganmohan R.
Published: February 2022

The demand of consumers for naturality of food with minimal processing was forced to the scientists for the discovery of non-thermal plasma which is now an emerging technology for the preservation and decontamination of highly perishable food such as milk. In this study, the microbial and physicochemical characteristics of plasma bubbling of raw cow milk were analysed and a comparison of boiled raw cow milk, commercially available pasteurised and UHT milk was observed. Again, shelf-life study was experimented for the plasma bubbling of milk with respect to raw cow milk sample (control). The plasma bubbling was generated at a voltage (200V), the flow rate of air 10 litres/hour (L/h) and applied to fresh cow milk for 5, 10, and 15 minutes (min) of time interval with 100 mL of the sample volume at room temperature. A significant reduction was observed in coliform and yeast at 200V, 10L/h, 15 min time interval of treatment. The pH of the milk was increased significantly to 6.85 after exposure to plasma bubbling. Whereas, a decreasing value was noticed in total soluble solids (TSS) and titratable acid (TA) with respect to time given by the plasma bubbling. Further a nondetrimental effect was observed for the nutrient content of plasma bubbling of milk. The result of the study indicates that plasma bubbling at (200V, 10L/h,100mL,15 min) treatment improves the quality of milk. This study shows that indirect dielectric barrier discharge (DBD) (plasma bubbling) may offer an effective microbial reduction without affecting the quality attributes. The plasma bubbling processing is an initiative for cow raw milk pasteurisation, which could have a future perspective on industrial food applications.
Bayesian Emulation and History Matching of JUNE
Authors: Vernon Ian , Owen Jonathan , Aylett-Bullock Joseph , Cuesta-Lazaro Carolina , Frawley Jonathan , Quera-Bofarull Arnau , Sedgewick Aidan , Shi Difu , Truong Henry , Turner Mark , Walker Joseph , Caulfield Tristan , Fong Kevin , Krauss Frank
Published: February 2022

We analyse June : a detailed model of Covid-19 transmission with high spatial and demographic resolution, developed as part of the RAMP initiative. June requires substantial computational resources to evaluate, making model calibration and general uncertainty analysis extremely challenging. We describe and employ the Uncertainty Quantification approaches of Bayes linear emulation and history matching, to mimic the June model and to perform a global parameter search, hence identifying regions of parameter space that produce acceptable matches to observed data.
Gamma connectivity predicts response to intermittent Theta Burst Stimulation in Alzheimer’s disease: A randomised controlled trial
Authors: Hoy Kate E. , Emonson Melanie R. L. , Bailey Neil W. , Rogers Caitlyn , Coyle Hannah , Stockman Freya , Fitzgerald Paul B.
Published: February 2022

Alzheimer’s disease is characterised by progressive cognitive decline for which there are currently no effective treatments. There is growing evidence that neural network dysfunction is a likely proximate cause of cognitive impairment in Alzheimer’s and, as such, may represent a promising therapeutic target. Here we investigated whether a course of intermittent Theta Burst Stimulation (iTBS) could modulate functional connectivity and cognitive function in mild to moderate Alzheimer’s disease. Fifty-eight participants were randomised to receive a course of either active or sham iTBS. Stimulation was applied to four brain sites sequentially in each treatment session: left DLPFC, right DLPFC, left PPC, and right PPC. Neurobiological (EEG), cognitive (CogState, ADASCog), and functional (QoL-AD, GDS) assessments were undertaken at baseline and end of treatment. Cognitive and functional assessments were also conducted at 3-months (blinded) and 6-months (active group only) following end of treatment. Active iTBS resulted in a significant and large increase in resting state gamma connectivity as well as improved delayed recall on an episodic memory task. Both baseline gamma connectivity, and change in gamma connectivity, were found to be predictive of improved delayed recall following active treatment. These findings support future research into iTBS for the treatment of Alzheimer’s disease focussing on protocol optimisation.
MEDIAL FRONTAL CORTEX GAMMA-AMINOBUTYRIC ACID CONCENTRATIONS IN PSYCHOSIS AND MOOD DISORDERS: A META-ANALYSIS OF PROTON MAGNETIC RESONANCE SPECTROSCOPY STUDIES
Authors: Simmonite Molly , Steeby Clara J. , Taylor Stephan F.
Published: February 2022

Background

Abnormalities of gamma-aminobutyric acid-ergic (GABAegic) systems may play an important role in psychosis spectrum and mood disorders. Proton magnetic resonance spectroscopy allows for non-invasive in vivo quantification of GABA; however, studies of GABA in psychosis have yielded inconsistent findings. This may stem from grouping together disparate voxels from functionally heterogeneous regions.

Methods

We searched the PubMed database for magnetic resonance spectroscopy studies of medial frontal cortex (MFC) GABA in patients with psychosis, bipolar disorder, depression, and individuals meeting ultra-high risk for psychosis criteria. Voxel placements were classified as rostral-, rostral-mid-, mid-, or posterior MFC, and random effects meta-analyses conducted for each group, for each MFC sub-region.

Results

Of 341 screened articles, 23 studies of psychosis (752 patients,856 controls), 6 studies of bipolar disorder (129 patients, 94 controls), 20 studies of depression (463 cases, 449 controls) and 7 studies of ultra-high risk (229 patients, 232 controls) met inclusion criteria. Meta-analysis revealed lower mid-(SMD = -0.28, 95% confidence interval [CI] = -0.48 to -0.07, p < .01) and posterior (SMD = -0.29, 95% CI = -0.49 to -0.09, p <.01) MFC GABA in psychosis, and increased rostral GABA in bipolar disorder (SMD = 0.76, 95% CI = 0.25 to 1.25, p < .01). In depression, reduced rostral MFC GABA (SMD = -0.36, 95% CI = -0.64 to -0.08, p = .01) did not survive correction for multiple comparisons.

Conclusions

These results substantiate the relevance in the ethology of psychosis spectrum and mood disorders and underline the importance of voxel placement.
Breakthrough SARS-CoV-2 infections in immune mediated disease patients undergoing B cell depleting therapy
Authors: Calabrese Cassandra M , Kirchner Elizabeth , Husni Elaine M , Moss Brandon P , Fernandez Anthony J , Jin Yuxuan , Calabrese Leonard H
Published: February 2022

Objectives

Immunocompromised patients with immune mediated inflammatory diseases (IMIDs), undergoing therapy with B cell depleting agents are among the most vulnerable to experience severe COVID-19 disease as well as respond sub-optimally to SARS CoV-2 vaccines yet little is known about the frequency or severity of breakthrough infection in this population. We have analyzed a large cohort of vaccinated IMIDs patients undergoing B cell depleting therapy for the presence of breakthrough infection and assessed their outcomes.

Methods

Utilizing specific ICD codes the pharmacy records and COVID-19 registry at the Cleveland clinic were used to identify all patients with IMIDS treated with B cell depleting monoclonal antibodies who were vaccinated against SARs CoV-2 and experienced breakthrough infections. Each EMR record was hand-reviewed to extract clinical data including vaccine history, demographics, comorbidities, other therapies, details of B cell depleting therapy, and outcomes. Univariate and multivariable logistic/proportional-odds regression models were used to examine the risk factors for severe outcomes.

Results

Of 1696 IMIDS patients on B cell depleting therapies 74 developed breakthrough COVID-19. Outcomes were severe with 24 (35%) hospitalized, 11 (15%) patients requiring critical care and 6 (8 %) deaths. Monoclonal antibodies were used on an outpatient basis to treat 21 with only a single patient requiring hospitalization without oxygen support and no deaths.

Conclusions

In IMIDS patients on B cell depleting therapies breakthrough infections are frequent and associated with severe outcomes. Outpatient use of monoclonal antibody therapy was associated with enhanced clinical outcomes.
Psychological and financial impacts of COVID-19-related travel measures: An international cross-sectional study
Authors: McDermid Pippa , Sooppiyaragath Soumya , Craig Adam , Sheel Meru , Blazek Katrina , Talty Siobhan , Seale Holly
Published: February 2022

Background

The impact of COVID-19 international travel restrictions has to date, not been fully explored, and with the ongoing threat that new variants could potentially restrict movement further, it is important to consider the impacts that travel restrictions have on community members. This study aimed to evaluate the psychological and financial impact of COVID-19 travel restrictions on those separated from their partners or immediate families, as well as temporary visa holders who were unable to migrate.

Methods

Between 4 November 2021 to 1 December 2021, we executed a cross-sectional online survey targeting three specific groups; (1) those stranded from their partners; (2) those stranded from immediate families; and (3) temporary visa holders unable to migrate or cross international borders. We collected data on respondents’ demographic profile; the nature of COVID-19-related travel impacts; depression, anxiety, and stress levels (using the validated DASS-21); and finally, data on respondents financial, employment and accommodation situation.

Results

1363 respondents located globally completed the survey. 71.2% reported financial stress, 76.8% (, SD=5.94) reported moderate-to-extremely severe depression, 51.6% (, SD=5.49) moderate-to-extremely severe anxiety, and 62.6% (, SD=5.55) moderate-to-extremely severe stress levels. Statistically significant factors associated with moderate-to-extremely severe depression, anxiety, and stress included being female, chronic illness, and experiencing financial stress. Employment during COVID-19 – specifically essential services workers or unemployed – was associated with higher levels of anxiety and stress, with only essential workers being a predictor of higher stress severity. Factors that provided psychological protection included being older and having children.

Conclusion

This study is one of the first to explore the impact COVID-19-related international travel restrictions have had on the financial status and psychological health of affected individuals. It highlights the significant human cost associated with the restrictions and identifies psychologically vulnerable populations. These results will help the design of targeted health and social policy responses.
High-dimension to high-dimension screening for detecting genome-wide epigenetic regulators of gene expression
Authors: Ke Hongjie , Ren Zhao , Chen Shuo , Tseng George C , Qi Jianfei , Ma Tianzhou
Published: February 2022

Motivation

The advancement of high-throughput technology characterizes a wide range of epigenetic modifications across the genome involved in disease pathogenesis via regulating gene expression. The high-dimensionality of both epigenetic and gene expression data make it challenging to identify the important epigenetic regulators of genes. Conducting univariate test for each epigenetic-gene pair is subject to serious multiple comparison burden, and direct application of regularization methods to select epigenetic-gene pairs is computationally infeasible. Applying fast screening to reduce dimension first before regularization is more efficient and stable than applying regularization methods alone.

Results

We propose a novel screening method based on robust partial correlation to detect epigenetic regulators of gene expression over the whole genome, a problem that includes both high-dimensional predictors and high-dimensional responses. Compared to existing screening methods, our method is conceptually innovative that it reduces the dimension of both predictor and response, and screens at both node (epigenetic features or genes) and edge (epigenetic-gene pairs) levels. We develop data-driven procedures to determine the conditional sets and the optimal screening threshold, and implement a fast iterative algorithm. Simulations and two applications to long non-coding RNA and DNA methylation regulation in Kidney cancer and Glioblastoma Multiforme illustrate the validity and advantage of our method.

Availability

The R package, related source codes and real data sets used in this paper are provided at https://github.com/kehongjie/rPCor.
Supervised Rank aggregation (SRA): A novel rank aggregation approach for ensemble-based feature selection
Authors: Jain Rahi , Xu Wei
Published: February 2022

Background

Feature selection (FS) is critical for high dimensional data analysis. Ensemble based feature selection (EFS) is a commonly used approach to develop FS techniques. Rank aggregation (RA) is an essential step of EFS where results from multiple models are pooled to estimate feature importance. However, the literature primarily relies on rule-based methods to perform this step which may not always provide an optimal feature set.

Method and Results

This study proposes a novel Supervised Rank Aggregation (SRA) approach to allow RA step to dynamically learn and adapt the model aggregation rules to obtain feature importance. The approach creates a performance matrix containing feature and model performance value from all models and prepares a supervised learning model to get the feature importance. Then, unsupervised learning is performed to select the features using their importance. We evaluate the performance of the algorithm using simulation studies and implement it into real research studies, and compare its performance with various existing RA methods. The proposed SRA method provides better or at par performance in terms of feature selection and predictive performance of the model compared to existing methods.

Conclusion

SRA method provides an alternative to the existing approaches of RA for EFS. While the current study is limited to the continuous cross-sectional outcome, other endpoints such as longitudinal, categorical, and time-to-event medical data could also be used.
Distinct components of cardiovascular health are linked with age-related differences in cognitive abilities
Authors: King Deborah L. O. , Henson Richard N. , Kievit Rogier , Wolpe Noham , Brayne Carol , Tyler Lorraine K. , Rowe James B. ,   Cam-CAN, Tsvetanov Kamen A.
Published: February 2022

Vascular, cardiovascular and neurovascular ageing processes contribute to cognitive impairment. However, the unique and synergistic contributions of cardiovascular factors to cognitive function remain unclear because they are often condensed into a single composite score or examined in isolation of each other. We hypothesized that vascular risk factors, electrocardiographic features and blood pressure indices reveal multiple latent vascular factors, with independent contributions to age differences in cognition. In a population-based deep-phenotyping study of cognition across the lifespan (n=708, age 18-88), path analysis revealed three latent vascular factors dissociating the autonomic nervous system response from two components of blood pressure. These three factors made unique and additive contributions to the variability in crystallized and fluid intelligence. The discrepancy in fluid relative to crystallized intelligence, indicative of cognitive decline, was associated with a latent vascular factor predominantly expressing pulse pressure, suggesting that higher pulse pressure is associated with cognitive decline from expected performance. This association varied with age, such that higher factor scores predicted a greater cognitive discrepancy in older individuals. Controlling pulse pressure may help to preserve cognitive function, particularly in older adults. Our findings highlight the need to better understand the multifactorial nature of vascular aging, its effects on neurocognitive function, and the modifiable risks of cognitive decline.