bluuebunny/crossref_metadata_2025 huggingface dataset:
Connecting With Trauma Patients After Discharge: A Phone Call Follow-Up Study
Authors: Jackson Alicia , Curtin Emma , Giddins Emma , Read-Allsopp Christine , Joseph Anthony
Published: May 2021

Background:

Traumatic injury is sudden and unexpected. It may lead to long-standing physical and physiological consequences. Approximately 10% of the world's disease burden is attributable to traumatic injuries. At the commencement of the study, there was limited information regarding civilian trauma patients' recovery following discharge from the hospital. There are several reasons for this including lack of available resources for follow-up by clinical staff and often trauma patients have multiple injuries, which can result in fragmented care. This limits the ability to assess a patient's recovery following discharge from the hospital.

Objective:

This phone call follow-up study was conducted to assess the number of trauma patients who may be showing symptoms of physical and psychological distress after traumatic injury.

Methods:

The study was carried out in New South Wales (Australia) Metropolitan major (Level 1) trauma center. Consented patients were contacted at 72 hr, 1 month, and 3 months after discharge from the hospital.

Results:

Many patients at all time points had difficulty coping with activities of daily living from pain (183 patients [64%], 121 patients [43%], and 58 patients [23%]), fatigue and sleep disturbance (110 patients [38%], 79 patients [28%], and 49 patients [20%]), as well as anxiety and frustration (38 patients [13%], 79 patients [28%], and 98 patients [39%]) regarding their recovery and returning to their preinjury activities.

Conclusion:

The research indicates that some trauma patients do not recover quickly physically or emotionally. These patients require identification and appropriate management of the consequences of trauma to enable them to return to their preinjury quality of life.
Pediatric Rapid Response Nurse Deployment to Pediatric Trauma Activations: A Process Improvement Initiative
Authors: Moss Lori N. , Cunningham Aaron J. , Tobias Joseph , Hamilton Nick , Jafri Mubeen
Published: May 2021

Background:

Prolonged emergency department length of stay in trauma patients is associated with increased hospital length of stay and inhospital mortality. This problem is compounded in pediatric patients, as injured children have less physiologic reserve and may exhibit only subtle warning signs before decompensation.

Objective:

To determine the impact of deploying pediatric rapid response nurses to full trauma activations for patients transferred to the pediatric intensive care unit on emergency department length of stay.

Methods:

This is a before-and-after analysis of a quality improvement initiative deploying pediatric rapid response nurses to full trauma activations. Trauma registry data collected from January 2016 to August 2020 were statistically analyzed. Demographic and outcome variables were assessed by unpaired t test and χ2 analysis.

Results:

A total of 94 patients met inclusion criteria as full activations admitted to the intensive care unit during the study period. The preimplementation group (n = 60) was 88% (n = 53) male, with a median age of 6.9 years and a median Injury Severity Score of 21. The postimplementation group (n = 34) was 62% (n = 21) male, with a median age of 5.6 years and a median Injury Severity Score of 17. The emergency department length of stay decreased from median (interquartile range) 48.5 (36.0–84.75) min (preimplementation) to 36.5 (27.5–55.5) min (postimplementation; p = .019).

Conclusion:

Deployment of pediatric rapid response nurses to full trauma activations facilitates the assessment and transfer of pediatric trauma to the intensive care unit and decreases emergency department length of stay.
Developing Nursing Leadership Potential Through Education in a Low-Resource Setting
Authors: Street Nancy White , Bermudez Laura , Lawton Alexis , Barry Donna , Mandel Leslie
Published: May 2021

Background

Global partnerships amplify nursing leadership capacity in low-resource countries through targeted education efforts.

Purpose

We examined a nursing faculty partnership between US and Haitian universities, where Haitian faculty completed graduate-level degrees highlighting leadership and education. This marked the first time a Haitian university awarded a master's of nursing degree.

Methods

Longitudinal qualitative research data collection included interviews and observations among 28 participants. Recurrent cross-sectional analysis explored themes and perceived changes in leadership behaviors.

Results

Advanced professional stature, leadership as a nurse educator and in the clinical setting, transformational leadership, and challenges to leadership practice were key themes. Graduate nursing education resulted in an improved vision of nursing, increased perceptions of leadership capacities, and advanced management strategies.

Conclusions

This partnership led to an Office of Nursing Education at the State University of Haiti, a milestone in the advancement of nursing in this low-resource country.
Mangrove sinkholes (
cenotes
) of the Yucatan Peninsula, a global hotspot of carbon sequestration
Authors: Adame M. F. , Santini N. S. , Torres-Talamante O. , Rogers K.
Published: May 2021

Mangroves are among the most carbon-dense ecosystems on the planet. The capacity of mangroves to store and accumulate carbon has been assessed and reported at regional, national and global scales. However, small-scale sampling is still revealing ‘hot spots’ of carbon accumulation. This study reports one of these hotspots, with one of the largest-recorded carbon stocks in mangroves associated with sinkholes (
cenotes
) in the Yucatan Peninsula, Mexico. We assessed soil organic carbon (SOC) stocks, sequestration rates and carbon origin of deep peat soils (1 to 6 m)
.
We found massive amounts of SOC up to 2792 Mg C ha
−1
, the highest value reported in the literature so far. This SOC is primarily derived from highly preserved mangrove roots and has changed little since its deposition, which started over 3220 years ago (±30 BP). Most
cenotes
are owned by Mayan communities and are threatened by increased tourism and the resulting extraction and pollution of groundwater. These hot spots of carbon sequestration, albeit small in area, require adequate protection and could provide valuable financial opportunities through carbon-offsetting mechanisms and other payments for ecosystem services.
Pervasive effects ofWolbachiaon host activity
Authors: Hague Michael T. J. , Woods H. Arthur , Cooper Brandon S.
Published: May 2021

Heritable symbionts have diverse effects on the physiology, reproduction and fitness of their hosts. Maternally transmittedWolbachiaare one of the most common endosymbionts in nature, infecting about half of all insect species. We test the hypothesis thatWolbachiaalter host behaviour by assessing the effects of 14 differentWolbachiastrains on the locomotor activity of nineDrosophilahost species. We find thatWolbachiaalter the activity of six different host genotypes, including all hosts in our assay infected withwRi-likeWolbachiastrains (wRi,wSuz andwAur), which have rapidly spread amongDrosophilaspecies in about the last 14 000 years. WhileWolbachiaeffects on host activity were common, the direction of these effects varied unpredictably and sometimes depended on host sex. We hypothesize that the prominent effects ofwRi-likeWolbachiamay be explained by patterns ofWolbachiatitre and localization within host somatic tissues, particularly in the central nervous system. Our findings support the view thatWolbachiahave wide-ranging effects on host behaviour. The fitness consequences of these behavioural modifications are important for understanding the evolution of host–symbiont interactions, including howWolbachiaspread within host populations.
Submillimetre mechanistic designs of termite-built structures
Authors: Oberst Sebastian , Martin Richard , Halkon Benjamin J. , Lai Joseph C. S. , Evans Theodore A. , Saadatfar Mohammed
Published: May 2021

Termites inhabit complex underground mounds of intricate stigmergic labyrinthine designs with multiple functions as nursery, food storage and refuge, while maintaining a homeostatic microclimate. Past research studied termite building activities rather than the actual material structure. Yet, prior to understanding how multi-functionality shaped termite building, a thorough grasp of submillimetre mechanistic architecture of mounds is required. Here, we identify for
Nasutitermes exitiosus
via granulometry and Fourier transform infrared spectroscopy analysis, preferential particle sizes related to coarse silts and unknown mixtures of organic/inorganic components. High-resolution micro-computed X-ray tomography and microindentation tests reveal wall patterns of filigree laminated layers and sub-millimetre porosity wrapped around a coarse-grained inner scaffold. The scaffold geometry, which is designed of a lignin-based composite and densely biocementitious stercoral mortar, resembles that of trabecula cancellous bones. Fractal dimension estimates indicate multi-scaled porosity, important for enhanced evaporative cooling and structural stability. The indentation moduli increase from the outer to the inner wall parts to values higher than those found in loose clays and which exceed locally the properties of anthropogenic cementitious materials. Termites engineer intricately layered biocementitious composites of high elasticity. The multiple-scales and porosity of the structure indicate a potential to pioneer bio-architected lightweight and high-strength materials.
A homogenized constrained mixture model of restenosis and vascular remodelling after balloon angioplasty
Authors: Maes Lauranne , Cloet An-Sofie , Fourneau Inge , Famaey Nele
Published: May 2021

Restenosis is one of the main adverse effects of the treatment of atherosclerosis through balloon angioplasty or stenting. During the intervention, the arterial wall is overstretched, causing a cascade of cellular events and subsequent neointima formation. This mechanical stimulus and its mechanobiological effects can be reproduced in biomechanical simulations. The aim of these models is to predict the long-term outcome of these procedures, to help increase the understanding of restenosis formation and to allow for
in silico
optimization of the treatment. We propose a predictive finite-element model of restenosis, using the homogenized constrained mixture modelling framework designed to model growth and remodelling in soft tissues. We compare the results with clinical observations in human coronary arteries and experimental findings in non-human primate models. We also explore the model’s clinical relevance by testing its response to different balloon loads and to the use of drug-eluting balloons. The comparison of the results with experimental data shows the relevance of the model. We show its ability to predict both inward and outward remodelling as observed
in vivo
and we show the importance of an improved understanding of restenosis formation from a biomechanical point of view.
In situmeasurements of human cough aerosol hygroscopicity
Authors: Groth Robert , Cravigan Luke T. , Niazi Sadegh , Ristovski Zoran , Johnson Graham R.
Published: May 2021

The airborne dynamics of respiratory droplets, and the transmission routes of pathogens embedded within them, are governed primarily by the diameter of the particles. These particles are composed of the fluid which lines the respiratory tract, and is primarily mucins and salts, which will interact with the atmosphere and evaporate to reach an equilibrium diameter. Measuring organic volume fraction (OVF) of cough aerosol has proved challenging due to large variability and low material volume produced after coughing. Here, the diametric hygroscopic growth factors (GF) of the cough aerosol produced by healthy participants were measuredin situusing a rotating aerosol suspension chamber and a humidification tandem differential mobility analyser. Using hygroscopicity models, it was estimated that the average OVF in the evaporated cough aerosol was 0.88 ± 0.07 and the average GF at 90% relative humidity (RH) was 1.31 ± 0.03. To reach equilibrium in dry air the droplets will reduce in diameter by a factor of approximately 2.8 with an evaporation factor of 0.36 ± 0.05. Hysteresis was observed in cough aerosol at RH = ∼35% and RH = ∼65% for efflorescence and deliquescence, respectively, and may depend on the OVF. The same behaviour and GF were observed in nebulized bovine bronchoalveolar lavage fluid.
Quantifying the cost of decision fatigue: suboptimal risk decisions in finance
Authors: Baer Tobias , Schnall Simone
Published: May 2021

Making decisions over extended periods of time is cognitively taxing and can lead to decision fatigue, which is linked to a preference for the ‘default’ option, namely whatever decision involves relatively little cognitive effort. Such effects have been demonstrated across a number of applied settings, including forensic and clinical contexts. Previous research, however, has not quantified the cost of such suboptimal decisions. We assessed the magnitude of the negative consequences of decision fatigue in the finance sector. Using 26 501 credit loan applications evaluated by credit officers of a major bank, we show that in this real-life financial risk-taking context credit loan approvals across the course of a day decreased during midday compared with early or later in the workday, reflecting a preference for the default option. To quantify the economic loss associated with such decision variability, we then modelled the bank's additional credit collection if all decisions had been made during early morning levels of approval. This would have resulted in $509 023 extra revenue for the bank, for one month. Thus, we provide further evidence that is consistent with a pattern of decision fatigue, and that it can have a substantial negative impact in the finance sector that warrants considerations to counteract it.
Buoys with looming eyes deter seaducks and could potentially reduce seabird bycatch in gillnets
Authors: Rouxel Yann , Crawford Rory , Cleasby Ian R. , Kibel Pete , Owen Ellie , Volke Veljo , Schnell Alexandra K. , Oppel Steffen
Published: May 2021

Bycatch of seabirds in gillnet fisheries is a global conservation issue with an estimated 400 000 seabirds killed each year. To date, no underwater deterrents trialled have consistently reduced seabird bycatch across operational fisheries. Using a combination of insights from land-based strategies, seabirds' diving behaviours and their cognitive abilities, we developed a floating device exploring the effect of large eyespots and looming movement to prevent vulnerable seabirds from diving into gillnets. Here, we tested whether this novel above-water device called ‘Looming eyes buoy' (LEB) would consistently deter vulnerable seaducks from a focal area. We counted the number of birds present in areas with and without LEBs in a controlled experimental setting. We show that long-tailed duck
Clangula hyemalis
abundance declined by approximately 20–30% within a 50 m radius of the LEB and that the presence of LEBs was the most important variable explaining this decline. We found no evidence for a memory effect on long-tailed ducks but found some habituation to the LEB within the time frame of the project (62 days). While further research is needed, our preliminary trials indicate that above-water visual devices could potentially contribute to reduce seabird bycatch if appropriately deployed in coordination with other management measures.
Whole-genome classification of rotavirus C and genetic diversity of porcine strains in the USA
Authors: Wang Yin , Porter Elizabeth P. , Lu Nanyan , Zhu Cong , Noll Lance W. , Hamill Vaughn , Brown Susan J. , Palinski Rachel M. , Bai Jianfa
Published: May 2021

Rotavirus C (RVC) is associated with acute diarrhoea in both children and young animals. Because of its frequent occurrence, additional sequences have recently been generated. In this study, we sequenced 21 complete genomes from porcine diarrhoea samples and analysed them together with all available reference sequences collected from the GenBank database [National Center for Biotechnology Information (NCBI)]. Based on phylogenetic analysis and genetic distance calculation, the number of each segment was identified as 31G, 26P, 13I, 5R, 5C, 5M, 12A, 10 N, 9T, 8E and 4 H for genotypes encoding VP7, VP4, VP6, VP1, VP2, VP3 and NSP1, NSP2, NSP3, NSP4 and NSP5, respectively. From the analysis, genotypes G19–G31, P[22]–P[26], R5, A9–A12, N9–N10, T7–T9 and E6–E8 were defined as newly identified genotypes, and genotype C6 was combined with C5, and M6 was combined with M1, due to their closely related nature. Estimated with the identity frequency ratio between the intergenotype and intragenotype, the nucleotide identity cutoff values for different genotypes were determined as 85, 85, 86, 84, 83, 84, 82, 87, 84, 81 and 79 % for VP7, VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4 and NSP5, respectively. Genotyping of the 49 US strains indicated possible segment reassortment in 9 of the 11 segments, with the exceptions being VP1 and NSP5, and the most prevalent genotypes for each segment genes in the USA were G6/G5/G21/G9-P5/P4-I6/I5-R1-C5-M1-A8-N1/N10-T1-E1-H1. Our study updated the genotypes of RVC strains and provided more evidence of RVC strain diversity that may be relevant to better understand genetic diversity, and the distribution and evolution of RVC strains.
Phenotypic and genomic characterization of a Vibrio parahaemolyticus strain causing disease in Penaeus vannamei provides insights into its niche adaptation and pathogenic mechanism
Authors: Zhang Xue , Sun Jingfeng , Chen Feng , Qi Hongli , Chen Limei , Sung Yeong Yik , Huang Yadong , Lv Aijun , Hu Xiucai
Published: May 2021

The virulence of

Vibrio parahaemolyticus

is variable depending on its virulence determinants. A

V. parahaemolyticus

strain, in which the virulence is governed by the pirA and pirB genes, can cause acute hepatopancreatic necrosis disease (AHPND) in shrimps. Some

V. parahaemolyticus

that are non-AHPND strains also cause shrimp diseases and result in huge economic losses, while their pathogenicity and pathogenesis remain unclear. In this study, a non-AHPND

V. parahaemolyticus

, TJA114, was isolated from diseased Penaeus vannamei associated with a high mortality. To understand its virulence and adaptation to the external environment, whole-genome sequencing of this isolate was conducted, and its phenotypic profiles including pathogenicity, growth characteristics and nutritional requirements were investigated. Shrimps following artificial infection with this isolate presented similar clinical symptoms to the naturally diseased ones and generated obvious pathological lesions. The growth characteristics indicated that the isolate TJA114 could grow well under different salinity (10–55 p.p.t.), temperature (23–37 °C) and pH (6–10) conditions. Phenotype MicroArray results showed that this isolate could utilize a variety of carbon sources, amino acids and a range of substrates to help itself adapt to the high hyperosmotic and alkaline environments. Antimicrobial-susceptibility test showed that it was a multidrug-resistant bacterium. The whole-genomic analysis showed that this

V. parahaemolyticus

possessed many important functional genes associated with multidrug resistance, stress response, adhesions, haemolysis, putative secreted proteases, dedicated protein secretion systems and a variety of nutritional metabolic mechanisms. These annotated functional genes were confirmed by the phenotypic profiles. The results in this study indicated that this

V. parahaemolyticus

isolate possesses a high pathogenicity and strong environmental adaptability.
Characterization of beta-lactam-resistant Escherichia coli from Australian fruit bats indicates anthropogenic origins
Authors: McDougall Fiona K. , Boardman Wayne S. J. , Power Michelle L.
Published: May 2021

Antimicrobial-resistant

Escherichia coli

, particularly those resistant to critically important antimicrobials, are increasingly reported in wildlife. The dissemination of antimicrobial-resistant bacteria to wildlife indicates the far-reaching impact of selective pressures imposed by humans on bacteria through misuse of antimicrobials. The grey-headed flying fox (GHFF; Pteropus poliocephalus), a fruit bat endemic to eastern Australia, commonly inhabits urban environments and encounters human microbial pollution. To determine if GHFF have acquired human-associated bacteria, faecal samples from wild GHFF (n=287) and captive GHFF undergoing rehabilitation following illness or injury (n=31) were cultured to detect beta-lactam-resistant

E. coli

. Antimicrobial susceptibility testing, PCR and whole genome sequencing were used to determine phenotypic and genotypic antimicrobial resistance profiles, strain type and virulence factor profiles. Overall, 3.8 % of GHFF carried amoxicillin-resistant

E. coli

(wild 3.5 % and captive 6.5 %), with 38.5 % of the 13 GHFF

E. coli

isolates exhibiting multidrug resistance. Carbapenem (bla
NDM-5) and fluoroquinolone resistance were detected in one

E. coli

isolate, and two isolates were resistant to third-generation cephalosporins (bla
CTX-M-27 and ampC). Resistance to tetracycline and trimethoprim plus sulfamethoxazole were detected in 69.2% and 30.8 % of isolates respectively. Class 1 integrons, a genetic determinant of resistance, were detected in 38.5 % of isolates. Nine of the GHFF isolates (69.2 %) harboured extraintestinal virulence factors. Phylogenetic analysis placed the 13 GHFF isolates in lineages associated with humans and/or domestic animals. Three isolates were human-associated extraintestinal pathogenic

E. coli

(ST10 O89:H9, ST73 and ST394) and seven isolates belonged to lineages associated with extraintestinal disease in both humans and domestic animals (ST88, ST117, ST131, ST155 complex, ST398 and ST1850). This study provides evidence of anthropogenic multidrug-resistant and pathogenic

E. coli

transmission to wildlife, further demonstrating the necessity for incorporating wildlife surveillance within the One Health approach to managing antimicrobial resistance.
Serological Response in Lung Transplant Recipients after Two Doses of SARS-CoV-2 mRNA Vaccines
Authors: Narasimhan Madhusudhanan , Mahimainathan Lenin , Clark Andrew E. , Usmani Amena , Cao Jing , Araj Ellen , Torres Fernando , Sarode Ravi , Kaza Vaidehi , Lacelle Chantale , Muthukumar Alagarraju
Published: May 2021

The immunological effectiveness of SARS-CoV-2 mRNA vaccines in lung transplant (LT) recipients is largely unknown. Thus, we assessed the effect of Pfizer-BioNTech and Moderna mRNA vaccines’ two-dose (2D) regimen on humoral responses in immunocompromised lung transplant (LT) recipients. About 25% (18/73) of SARS-CoV-2 uninfected-LT patients generated positive spike-IgG response following 2D of vaccines, with 36% (9/25) in the Moderna cohort and only 19% (9/48) in the Pfizer cohort. 2D in LT patients elicited significantly lesser median IgGSP response (1.7 AU/mL, 95% CI: 0.6-7.5 AU/mL) compared to non-transplanted, uninfected naïve subjects (14209 AU/mL, 95% CI: 11261-18836 AU/mL) (p<0.0001). In LT patients, Moderna-evoked seropositivity trend was higher by 23-fold than Pfizer. 2D COVID-19 vaccination elicits a dampened serological response in LT patients. Whether assessing other arms of host immunity combined with higher vaccine dose can better capture and elicit improved immunogenicity in this immunocompromised population warrants investigation.
Phylodynamic modelling of bacterial outbreaks using nanopore sequencing
Authors: Steinig Eike , Duchêne Sebastián , Aglua Izzard , Greenhill Andrew , Ford Rebecca , Yoannes Mition , Jaworski Jan , Drekore Jimmy , Urakoko Bohu , Poka Harry , Wurr Clive , Ebos Eri , Nangen David , Laman Moses , Manning Laurens , Firth Cadhla , Smith Simon , Pomat William , Tong Steven , Coin Lachlan , McBryde Emma , Horwood Paul
Published: May 2021

Nanopore sequencing and phylodynamic modelling have been used to reconstruct the transmission dynamics of viral epidemics, but their application to bacterial pathogens has remained challenging. Here, we implement Random Forest models for single nucleotide polymorphism (SNP) polishing to estimate divergence and effective reproduction numbers (Re) of two community-associated, methicillin-resistant Staphylococcus aureus (MRSA) outbreaks in remote Far North Queensland and Papua New Guinea (n = 159). Successive bar-coded panels of S. aureus isolates (2 × 12 per MinION) sequenced at low-coverage (> 5x - 10x) provided sufficient data to accurately infer assembly genotypes with high recall when compared with Illumina references. De novo SNP calling with Clair was followed by SNP polishing using intra- and inter-species models trained on Snippy reference calls. Models achieved sufficient resolution on ST93 outbreak sequence types (> 70 - 90% accuracy and precision) for phylodynamic modelling from lineage-wide hybrid alignments and birth-death skyline models in BEAST2. Our method reproduced phylogenetic topology, geographical source of the outbreaks, and indications of sustained transmission (Re > 1). We provide Nextflow pipelines that implement SNP polisher training, evaluation, and outbreak alignments, enabling reconstruction of within-lineage transmission dynamics for infection control of bacterial disease outbreaks using nanopore sequencing.
A recurrentSHANK3frameshift variant in Autism Spectrum Disorder
Authors: Loureiro Livia O , Howe Jennifer L , Reuter Miriam , Iaboni Alana , Calli Kristina , Roshandel Delnaz , Pritisanac Iva , Moses Alan , Forman-Kay Julie D. , Trost Brett , Zarrei Mehdi , Rennie Olivia , Lau Lynette , Marshall Christian R , Srivastava Siddharth , Godlewski Brianna , Buttermore Elizabeth , Sahin Mustafa , Hartley Dean , Frazier Thomas , Vorstman Jacob , Georgiades Stelios , Lewis Suzanne ME , Szatmari Peter , Bradley Lisa , Delorme Richard , Bourgeron Thomas , Anagnostou Evdokia , Scherer Stephen W.
Published: May 2021

Autism Spectrum Disorder (ASD) is genetically complex, but specific copy number variants (CNVs; e.g., 1q21.1, 16p11.2) and genes (e.g.,NRXN1, NLGN4) have been identified as penetrant susceptibility factors, and all of these demonstrate pleiotropy. Many ASD-associated CNVs are, in fact, genomic disorder loci where flanking segmental duplications lead to recurrent deletion and duplication events of the same region in unrelated individuals, but these lesions are large and involve multiple genes. To identify opportunities to establish a more specific genotype and phenotype correlation in ASD, we searched genomic data, and the literature, for recurrent predicted damaging sequence-level variants affecting single genes. We identified 17 individuals from 15 unrelated families carrying a heterozygous guanine duplication (rs797044936; NM_033517.1; c.3679dup; p.Ala1227Glyfs*69) occurring within a string of 8 guanines (at genomic location [hg38]g.50,721,512dup) affectingSHANK3, a prototypical ASD gene (6/7,521 or 0.08% of ASD-affected individuals studied by whole genome sequencing carried the p.Ala1227Glyfs*69 variant). This variant, which is predicted to cause a frameshift leading to a premature stop codon truncating the C-terminal region of the corresponding protein, was not reproducibly found in any of the control groups we analyzed. All probands identified carriedde novomutations with the exception of five individuals in three families who inherited it through somatic mosaicism. This same heterozygous variant in published mouse models leads to an ASD-like phenotype. We scrutinized the phenotype of p.Ala1227Glyfs*69 carriers, and while everyone (16/16) formally tested for ASD carried a diagnosis, there was variable expression of core ASD features both within families and between families, underscoring the impact of as yet unknown modifiable factors affecting expressivity in autism.
Cesarean section prevalence at a baby-friendly hospital in southern Brazil: current context in the face of COVID-19
Authors: de Azevedo Bicho Manoela , Fernandes Mayra Pacheco , Vidaletti Luís Paulo , Santos Vaz Juliana dos
Published: May 2021

Objective

To analyze cesarean prevalence at a baby-friendly hospital in Southern Brazil between 2017 and 2020 and possible annual and monthly changes due to the novel coronavirus (COVID-19) pandemic.

Methods

Descriptive cross-sectional study using secondary data retrieved from the electronic information system of a Baby-Friendly Hospital in the municipality of Rio Grande, RS, Brazil. Data was retrieved for all hospitalizations at the obstetric center between January 1st 2017 and December 31st 2020. Data on COVID-19 deaths were obtained from the municipal government website. Annual and monthly cesarean prevalence rates were calculated in comparison to the same periods in 2017, 2018 and 2019. Differences in prevalence rates were tested using a chi-square test, taking a significance level of less than 5%. Prevalence ratios were estimated for 2018/2017, 2019/2018, and 2020/2019.

Results

7,294 childbirths were included. Cesarean prevalence was 42.6% in 2017, 44.3% in 2018, 40.2% in 2019, and 51.0% in 2020. In 2018/2017, there was no statistically significant difference in cesarean prevalence (95%CI: 0.90-1.20). Between 2019/2018, there was a reduction of approximately 20% in prevalence (95%CI: 0.69-0.93). The scenario changes between 2020/2019 with a 40% increase in cesareans (95%CI: 1.20-1.62). The period comprising July to December 2020 was the only period in which over half the deliveries were done by cesarean section, exceeding 60% in July.

Conclusion

Cesarean prevalence rates increased in 2020 in relation to the three preceding years. The data highlight the need to reinforce compliance with childbirth protocols to reduce cesarean sections in baby-friendly hospitals.
Monotreme middle ear is not primitive for Mammalia
Authors: Meng Jin , Mao Fangyuan
Published: May 2021

The study on evolution of the mammalian middle ear has been fueled by continuous discoveries of Mesozoic fossils in the last two decades. Wang et al.1recently reported a specimen ofVilevolodon diplomylos(IMMNH-PV01699)2that adds to the increasing knowledge about the auditory apparatus of ‘haramiyidans’, an extinct Mesozoic group of mammaliaforms. The authors hypothesized that a middle ear with a monotreme-like incus and malleus and incudomallear articulation was primitive for mammals, which challenges the convention that the monotreme middle ear is specialized3or autapomorphic4in mammals. We raise concerns about terminology and identification of the incus presented by Wang et al. and show that their analysis does not support their hypothesis; instead, it supports the one by Mao et al.5,6.
COVID-19 VACCINE PERCEPTIONS AND DIFFERENCES BY SEX, AGE, AND EDUCATION: FINDINGS FROM A CROSS-SECTIONAL ASSESSMENT OF 1367 COMMUNITY ADULTS IN ONTARIO
Authors: Syan Sabrina K. , Gohari Mahmood , Levitt Emily E. , Belisario Kyla , Gillard Jessica , DeJesus Jane , MacKillop James
Published: May 2021

Background

COVID-19 is a global pandemic and vaccination efforts may be impeded by vaccine hesitancy. The present study examined willingness to receive COVID-19 vaccine, the associated reasons for willingness/unwillingness, and vaccine safety perceptions in a cross-sectional assessment of community adults in Ontario.

Methods

1367 individuals (60.3% female, M age = 38.6) completed an online assessment between January 15, 2021 and February 15, 2021. Perceptions were investigated in general and by age, sex and education.

Results

Overall, 82.8% sample reported they were willing to receive a COVID-19 vaccine and 17.2% reported they were unwilling. The three most common reasons for unwillingness were long-term side effects (65.5%), immediate side effects (60.5%), and lack of trust in the vaccine (55.2%). Vaccine willingness significantly differed by sex and education level, with female participants and those with less than a bachelor’s degree being more likely to report unwillingness. Perception of COVID-19 vaccine safety was significantly lower (−10.7%) than vaccines in general and differed by age, sex and education, with females, older adults, and individuals with less than a bachelor’s degree reporting lower perceived COVID-19 vaccine safety.

Conclusion

In this sample of community adults, under one in five individuals was unwilling to receive a COVID-19 vaccine, but with higher rates in population subgroups. Targeting public health messaging to females and individuals with less than Bachelor’s degree, and addressing concerns about long-term and immediate side effects may increase vaccine uptake.
Distinct patterns of blood cytokines beyond a cytokine storm predict mortality in COVID-19
Authors: Herr Christian , Mang Sebastian , Mozafari Bahareh , Günther Katharina , Speer Thimoteus , Seibert Martina , Srikakulam Sanjay Kumar , Beisswenger Christoph , Ritzmann Felix , Keller Andreas , Müller Rolf , Smola Sigrun , Eisinger Dominic , Zemlin Michael , Danziger Guy , Volk Thomas , Hörsch Sabrina , Krawczyk Marcin , Lammert Frank , Adams Thomas , Wagenpfeil Gudrun , Kindermann Michael , Marcu Constantin , Ataya Zuhair Wolf Dietrich , Mittag Marc , Schwarzkopf Konrad , Custodis Florian , Grandt Daniel , Schäfer Harald , Eltges Kai , Lepper Philipp M. , Bals Robert ,   CORSAAR study group
Published: May 2021

Background

COVID-19 comprises several severity stages ranging from oligosymptomatic disease to multi-organ failure and fatal outcomes. The mechanisms why COVID-19 is a mild disease in some patients and progresses to a severe multi-organ and often fatal disease with respiratory failure are not known. Biomarkers that predict the course of disease are urgently needed. The aim of this study was to evaluate a large spectrum of established laboratory measurements.

Patients and methods

Patients from the prospective PULMPOHOM and CORSAAR studies were recruited and comprised 35 patients with COVID-19, 23 with conventional pneumonia, and 28 control patients undergoing elective non-pulmonary surgery. Venous blood was used to measure the serum concentrations of 79 proteins by Luminex multiplex immunoassay technology. Distribution of biomarkers between groups and association with disease severity and outcomes were analyzed.

Findings

The biomarker profiles between the three groups differed significantly with elevation of specific proteins specific for the respective conditions. Several biomarkers correlated significantly with disease severity and death. Uniform manifold approximation and projection (UMAP) analysis revealed a significant separation of the three disease groups and separated between survivors and deceased patients. Different models were developed to predict mortality based on the baseline measurements of several protein markers.

Interpretation

Several newly identified blood markers were increased in patients with severe COVID-19 (AAT, EN-RAGE, ICAM-1, myoglobin, SAP, TIMP-1, vWF, decorin, HGF, MMP7, PECAM-1) or in patients that died (FRTN, SCF, TIMP-1, CA-9, CEA, decorin, HGF). The use of established assay technologies allows for rapid translation into clinical practice.

Funding

No role of the funding source.
Early pre-exposure prophylaxis (PrEP) discontinuation among pregnant and postpartum women: Implications for maternal PrEP roll out in South Africa
Authors: Joseph Davey Dvora Leah , Mvududu Rufaro , Mashele Nyiko , Lesosky Maia , Khadka Nehaa , More Jessica , Bekker Linda-Gail , Gorbach Pamina , Coates Thomas J. , Myer Landon
Published: May 2021

Introduction

Oral pre-exposure prophylaxis (PrEP) is a safe and effective prevention strategy to reduce women’s risk of HIV in pregnancy and postpartum. Effective PrEP requires daily PrEP adherence, but little is known about maternal PrEP continuation and risk factors that influence optimal PrEP use.

Methods

The PrEP in pregnancy and postpartum (PrEP-PP) study is an ongoing cohort study that enrolled consenting pregnant, HIV-uninfected women at first antenatal care (ANC) visit, followed through 12-months postpartum. HIV-uninfected women and girls ≥16-years who were eligible for the study received HIV prevention counseling and were offered PrEP. Interviewers collected socio-demographic, behavioral data from participants at each visit. We analyzed the proportion of women who initiated PrEP and the proportion who continued on PrEP after 3-months with associated correlates, including side effects whilst on PrEP, by estimating the prevalence ratio (95% CI) adjusting for a priori confounders.

Results

Between Aug’19 and Feb’21, we enrolled 891 pregnant women (median gestation=21wks; age=26yrs). Following PrEP counseling, 90% of women initiated PrEP at their first ANC visit (n=801); 60% were married or cohabiting. Three-quarters of women on PrEP returned for a repeat prescription at 1-month; 62% returned at 3-months. One-third of women on PrEP reported a side effect, mostly nausea/vomiting, dizziness, and headache. Women on PrEP in the 1st or 2nd trimester had higher odds of reporting side effects (aOR=2.61; 95%CI=1.17-5.84) vs. postpartum women. Women who reported side effects continued with PrEP less than those who did not report side effects (aPR=0.88; 95% CI=0.78-0.99) adjusting for covariates. Women who had ≥1 previous pregnancy (aPR=0.76;95%CI=0.59-1.00) or were postpartum (aPR=0.86;95%CI=0.75-0.99) continued less than women who were primigravid or pregnant. Women who reported having an HIV+ partner (aPR= 1.70;95% CI=1.55-1.86) or unknown partner serostatus (aPR=1.14;95%CI=1.01-1.29) were more likely to continue on PrEP than those who had HIV-negative partners.

Conclusion

PrEP initiation and early continuation were high in ANC in this setting. Being postpartum and experiencing side effects were associated with lower PrEP continuation, presenting an opportunity for improved clinical management and counseling during pregnancy of nausea/vomiting to address early, transient side effects. Interventions for postpartum women on PrEP are urgently needed.

Clinical Trial Number

NCT03826199
DUX4 induces a homogeneous sequence of molecular changes, culminating in the activation of a stem-cell-like transcriptional network and induction of apoptosis in somatic cells
Authors: Ashoti Ator , Alemany Anna , Sage Fanny , Geijsen Niels
Published: May 2021

Facioscapulohumeral muscular dystrophy (FSHD) is a muscle degenerative disease that disproportionally affects the muscles of the face, shoulder girdle and upper arms. FSHD is caused by the misexpression of Double Homeobox 4 (DUX4), a transcription factor that is normally expressed during early embryonic development. Ectopic expression of DUX4 in somatic cells is cytotoxic and leads to rapid apoptosis. To elucidate the mechanism by which DUX4 induces apoptosis, we determined the temporal transcriptional changes induced by Dux4 at the single-cell level. We observed that induction of DUX4 expression induces a non-random, consecutive sequence of transcriptional changes. DUX4 homogenously induces the activation of a stem cell signature and activates a network of transcription factors that is typically expressed during early embryogenesis and in pluripotent stem cells. Ultimately, these transcriptional changes trigger the induction of apoptosis, suggesting that the induction of this early stemness program is incompatible with a somatic cell program. Our findings shed new light on the timing and dynamic of DUX4-mediated transcriptional reprogramming and may help elucidate why the DUX4 stemness program is required during early embryogenesis, but incompatible with somatic cell viability.
An interpretable connectivity-based decoding model for classification of chronic marijuana use
Authors: Kulkarni Kaustubh R. , Schafer Matthew , Berner Laura , Fiore Vincenzo G. , Heflin Matt , Hutchison Kent , Calhoun Vince , Filbey Francesca , Pandey Gaurav , Schiller Daniela , Gu Xiaosi
Published: May 2021

Background

Psychiatric neuroimaging typically proceeds with one of two approaches: encoding models, which aim to model neural mechanisms, or decoding models, which aim to predict behavioral or clinical characteristics from brain imaging data. In this study, we seek to combine these aims by developing interpretable decoding models that offer both accurate prediction and novel neural insights. We demonstrate the effectiveness of this combined approach in a case study of chronic marijuana use.

Methods

Chronic marijuana (MJ) users (n=195) and non-using healthy controls (n=128) completed a cue-elicited craving task during functional magnetic resonance imaging. Linear machine learning methods were used to classify individuals into chronic MJ users and non-users based on task-evoked, whole-brain functional connectivity. We then used graph theoretic analyses to identify ‘predictive functional connectivities’ among brain regions that contributed most substantially to the classification of chronic marijuana use.

Results

We obtained high (~80% out-of-sample) accuracy across four different classification models, demonstrating that task-evoked, whole-brain functional connectivity can successfully differentiate chronic marijuana users from non-users. Subsequent network analyses revealed key predictive regions (e.g., anterior cingulate cortex, dorsolateral prefrontal cortex, and precuneus) that are often implicated in neuroimaging studies of substance use disorders, as well as some key exceptions. We also identified a core set of networks of brain regions that contributed to successful classification, comprised of many of the same predictive regions.

Conclusions

Our dual aims of accurate prediction and interpretability were successful, producing a predictive model that also provides interpretability at the neural level. This novel approach may complement other predictive-exploratory approaches for a more complete understanding of neural mechanisms in drug use and other neuropsychiatric disorders.
CFTR corrector efficacy is associated with occupancy of distinct binding sites
Authors: Baatallah Nesrine , Elbahnsi Ahmad , Mornon Jean-Paul , Chevalier Benoit , Pranke Iwona , Servel Nathalie , Zelli Renaud , Décout Jean-Luc , Edelman Aleksander , Sermet-Gaudelus Isabelle , Callebaut Isabelle , Hinzpeter Alexandre
Published: May 2021

CFTR misfolding due to cystic fibrosis causing mutations can be corrected with small molecules designated as correctors. VX-809, an investigational corrector compound, is believed to bind CFTR directly to either the first membrane-spanning domain (MSD1) and/or the first nucleotide-binding domain (NBD1). Blind docking onto the 3D structures of these domains, followed by molecular dynamics (MD) simulations, revealed the presence of two potential VX-809 binding sites which, when mutated, abrogated corrector rescue. Mutations altering protein maturation are also shown to be not equally sensitive to the occupancy of the two sites by VX-809, with the most frequent mutation F508del requiring integrity of both sites and allosteric coupling with the F508del region while L206W only requires the integrity of the MSD1 site. A network of charged amino acids in the lasso Lh2 helix and the intracellular loops ICL1 and ICL4 is involved in the allostery between MSD1 and NBD1. Corrector VX-445, which is used in combination in clinics with VX-661, a structurally close analog of VX-809, to fully correct F508del, is also shown to occupy two potential binding sites on MSD1 and NBD1, the latter being shared with VX-809. In conclusion, VX-809 and VX-445 appear to bind different CFTR domains to alleviate specific folding defects. These results provide new insights into therapeutics understanding and may help the development of efficient corrector combinations.
TISON: a next-generation multi-scale modeling theatre forin silicosystems oncology
Authors: Gondal Mahnoor N , Sultan Muhammad U , Arif Ammar , Rehman Abdul , Awan Hira A , Arshad Zainab , Ahmed Waleed , Chaudhary Muhammad FA , Khan Salaar , Tanveer Zain B , Butt Rida Nasir , Hussain Risham , Khawar Huma , Amina Bibi , Akbar Rida , Abbas Fatima , Jami Misha N , Nasir Zainab , Shah Osama S , Hameed Hadia , Butt Muhammad FA , Mustafa Ghulam , Ahmad Muhammad M , Ahmed Sameer , Qazi Romena , Ahmed Fayyaz , Ishaq Omer , Nabi Syed W , Vanderbauwhede Wim , Wajid Bilal , Shehwana Huma , Uddin Emad , Safdar Muhammad , Javed Irfan , Tariq Muhammad , Faisal Amir , Chaudhary Safee U
Published: May 2021

Multi-scale models integrating biomolecular data from genetic, transcriptional, and translational levels, coupled with extracellular microenvironments can assist in decoding the complex mechanisms underlying system-level diseases such as cancer. To investigate the emergent properties and clinical translation of such cancer models, we present Theatre forin silicoSystems Oncology (TISON,https://tison.lums.edu.pk), a next-generation web-based multi-scale modeling and simulation platform forin silicosystems oncology. TISON provides a “zero-code” environment for multi-scale model development by seamlessly coupling scale-specific information from biomolecular networks, microenvironments, cell decision circuits,in silicocell lines, and organoid geometries. To compute the temporal evolution of multi-scale models, a simulation engine and data analysis features are also provided. Furthermore, TISON integrates patient-specific gene expression data to evaluate patient-centric models towards personalized therapeutics. Several literature-based case studies have been developed to exemplify and validate TISON’s modeling and analysis capabilities. TISON provides a cutting-edge multi-scale modeling pipeline for scale-specific as well as integrative systems oncology that can assist in drug target discovery, repositioning, and development of personalized therapeutics.
Capacity to erase gene occlusion is a defining feature distinguishing naive from primed pluripotency
Authors: Foshay Kara M. , Lee Jae Hyun , Zhang Li , Fernandes Croydon J. , Wu Bohou , Gaetz Jedidiah , Baker Samuel W. , Looney Timothy J. , Xiang Andy Peng , Fan Guoping , Lahn Bruce T.
Published: May 2021

Pluripotent stem cells can exist in either the naive state representing a developmental blank slate or the downstream primed state poised for differentiation. Currently, known differences between these two states are mostly phenomenological, and none can adequately explain why the two states should differ in developmental priming. Gene occlusion is a mode of epigenetic inactivation that renders genes unresponsive to their cognate transcriptional activators. It plays a crucial role in lineage restriction. Here, we report that a defining feature distinguishing the two pluripotent states lies in the ability of naive but not primed cells to erase occlusion. This “deocclusion” capacity requires Esrrb, a gene expressed only in the naive but not primed state. Notably, Esrrb silencing in the primed state is itself due to occlusion. Collectively, our data argue that the Esrrb-dependent deocclusion capacity in naive cells is key for sustaining naive pluripotency, and the loss of this capacity in the primed state via the occlusion of Esrrb poises cells for differentiation.