bluuebunny/crossref_metadata_2025 huggingface dataset:
557 Amniotic Fluid Injections in Chronic Non-Healing Wounds in Pediatric Patients: A Case Series
Authors: Darelli-Anderson Anna M , South Samuel , Lewis Giavonni M
Published: April 2021

Introduction

Amniotic tissues are used to support wound healing in a variety of fields and wound types including chronic stasis ulcers, lower extremity wounds in diabetic patients, poorly healing injuries associated with burns, and surgical wounds associated with intestinal fistulas. To date, the use of amniotic fluid (AF) alone has not been described in the literature. The properties of AF alone would suggest the potential for regenerative and accelerated healing. This descriptive, retrospective review evaluates the effects of AF injected into chronic, poorly healing burn wounds.

Methods

We conducted a retrospective chart review across five years and identified a total of 39 pediatric patients with chronic, poorly healing burn wounds, nine of whom were treated with AF injections. Five of these patients were excluded due to incomplete post-treatment data. All patients were managed in the ambulatory care setting. We evaluated Vancouver Burn Scar Scale (VBSS) and Patient and Observer Scar Assessment Scale (POSAS) scores as well as pre- and post-treatment photos of the wounds.

Results

Four patients aged 1–16 years met inclusion criteria with TBSA ranging from 1% to 57.5%. All patients tolerated the procedure well and none suffered adverse events associated with treatment. The average time from injury to treatment with AF was 14 months. Patient A is a 1-year-old male with bilateral posterior thigh wounds that remained open following skin grafting of a 57.5% TBSA injury who received injection of AF 5 months after injury. One month after treatment with AF injections, both posterior thigh wounds were closed (Figure 1). Patient B is a 9-year-old male with posterior thigh wounds that remained open following grafting of an 8% TBSA injury who received an injection of AF 10 months after injury. Following injections with AF the wounds closed over a period of 6 months (Figure 1). Patient C is a 10-year-old female with extensive contracture scarring across the upper torso, bilateral axilla and neck from a 25% TBSA injury who received an AF injection at 37 months post-injury. Areas of open wound in the axilla closed following a combination of laser treatment to scar areas and AF injections. Patient D is a 16-year-old female with 1% TBSA injury to the posterior thigh treated with split thickness skin grafting that failed to close. Following injection with AF four months after injury, the wound closed over a period of 3 months (Figure 1). VBSS scores and POSAS scores did not significantly correlate with wound healing observed.

Conclusions

Injection of amniotic fluid is a low-risk treatment adjunct that can be used to improve chronic burn wounds.
Finding the Signal in the Noise
Authors: Freeman Lindsay , Vazquez Llorente Raquel
Published: March 2021

The constituent documents of the International Criminal Court (ICC) were formulated in the 1990s, at a time when the internet was still relatively new to most of society. In the four years between the signing of the Rome Statute in 1998 and its entry into force in 2002, there was a surge in technological development. The replacement of dial-up connections by home broadband and wireless internet, the commercial launch of 3G, and the introduction of camera phones all took place during that period, followed only a few years later by the founding of Google, YouTube and Facebook. This trend has only continued. Advanced technologies have changed the way in which societies create information and share it, generating an ever-growing volume of data. The availability and accessibility to new sources of information open up opportunities for international criminal investigators, but the task of using them effectively is not without its challenges. Recent cases before the ICC indicate that digital evidence will play an increasingly central role in investigations and prosecutions. In national jurisdictions, digital evidence is now introduced in the majority of criminal cases, and there have been significant reforms in domestic statutes on evidentiary and procedural rules from admissibility to e-discovery. However, such reforms have not yet materialized at the ICC. This article assesses whether the Rome Statute and Rules of Procedure and Evidence, and their current interpretation, remain effective and appropriate in the face of technological change. The authors examine the emerging challenges related to the use and handling of digital evidence, as well as the unique nature of the internet and other dissemination channels. By drawing attention to the main issues with the existing rules and practices, and raising unresolved questions, the authors highlight the importance of reassessing rules based on obsolete assumptions and expectations as we move towards the future.
Optimization of timing of next-generation emergence inAmaranthus hybridusis determined via modulation of seed dormancy by the maternal environment
Authors: Fernández Farnocchia Rocio Belen , Benech-Arnold Roberto Luis , Mantese Anita , Batlla Diego
Published: March 2021

The timing of emergence of weed species has critical ecological and agronomical implications. In several species, emergence patterns largely depend on the level of dormancy of the seedbank, which is modulated by specific environmental factors. In addition, environmental conditions during seed maturation on the mother plant can have marked effects on the dormancy level at the time of seed dispersal. Hence, the maternal environment has been suggested to affect seedbank dormancy dynamics and subsequent emergence; however, this modulation has not been adequately examined under field conditions, and the mechanisms involved are only partly understood. Combining laboratory and field experiments with population-based models, we investigated how dormancy level and emergence in the field are affected by the sowing date and photoperiod experienced by the mother plant in Amaranthus hybridus, a troublesome weed worldwide. The results showed that an earlier sowing date and a longer photoperiod enhanced the level of dormancy by increasing the dormancy imposed by both the embryo and the seed coat. However, this did not affect the timing and extent of emergence in the field; on the contrary, the variations in dormancy level contributed to synchronizing the emergence of the next generation of plants with the time period that maximized population fitness. Our results largely correspond with effects previously observed in other species such as Polygonum aviculare and Arabidopsis, suggesting a common effect exists within different species.
Detectability of kilonovae in optical surveys: post-mortem examination of the LVC O3 run follow-up
Authors: Sagués Carracedo A , Bulla M , Feindt U , Goobar A
Published: March 2021

The detection of the binary neutron star (BNS) merger GW170817 and the associated electromagnetic (EM) counterpart, the ‘kilonova’ (kN) AT2017gfo, opened a new era in multimessenger astronomy. However, despite many efforts, it has been proven very difficult to find additional kNe, even though LIGO/Virgo has reported at least one BNS event during their latest run, O3. The focus of this work is the exploration of the sensitivity of the adopted optical surveys searching for kNe during O3. We propose ways to optimize the choices of filters and survey depth to boost the detection efficiency for these faint and fast-evolving transients in the future. In particular, we use kN models to explore the dependence on ejecta mass, geometry, viewing angle, wavelength coverage, and source distance. We find that the kN detection efficiency has a strong viewing-angle dependence, especially for filters blueward of i-band. This loss of sensitivity can be mitigated by early, deep, observations. Efficient gri counterpart searches for kNe at ∼200 Mpc would require reaching a limiting magnitude mlim = 23 mag, to ensure good sensitivity over a wide range of the model phase-space. We conclude that kN searches during O3 were generally too shallow to detect BNS optical counterparts, even under optimistic assumptions.
Differences in Switching Away From Smoking Among Adult Smokers Using JUUL Products in Regions With Different Maximum Nicotine Concentrations: North America and the United Kingdom
Authors: Goldenson Nicholas I , Ding Yu , Prakash Shivaani , Hatcher Cameron , Augustson Erik M , Shiffman Saul
Published: April 2021

Introduction

Electronic nicotine delivery systems (ENDS) may improve public health if they facilitate smokers switching away from cigarettes. Conceptually, switching is facilitated when ENDS provide adequate nicotine delivery. Switching rates among smokers who purchased the JUUL System (“JUUL”) were compared in the United Kingdom (UK), where regulations limit nicotine concentration to 20 mg/mL versus North America (N.Am.; United States and Canada), where higher concentrations are available.

Aims and Methods

Adult established smokers (age ≥21, smoked ≥100 cigarettes, smoking some days or every day at baseline) who newly purchased JUUL were recruited into a longitudinal study (UK: N = 1247; N.Am.: N = 8835). Complete switching (no smoking for ≥30 days) was assessed 1, 3, and 6 months after purchase; propensity score matching (PSM) and logistic regression compared switching after adjusting for baseline characteristics.

Results

In both N.Am. and UK, ≥82% of participants reported using the highest JUUL nicotine concentration available (UK: 18 mg/mL; N.Am.: 59 mg/mL). Unadjusted switching rates did not differ at 1 month (17%–18%); unadjusted and adjusted rates were significantly higher in N.Am. (vs. UK) at 3 and 6 months. In the PSM sample, after additional covariate adjustment, rates were significantly higher in N.Am. (vs. UK) at 3 months (31.5% vs. 22.7%; odds ratio [95% confidence interval, CI] = 1.59 [1.25, 2.02]) and 6 months (38.0% vs. 26.0%; odds ratio [95% CI] = 1.79 [1.37, 2.35]).

Conclusions

These results suggest availability of ENDS in nicotine concentrations greater than 20 mg/mL may be associated with increased switching among adult smokers. Differences in smoking and ENDS use characteristics did not explain associations of location and switching; however, between-country differences may be affected by unmeasured factors.

Implications

Switching rates were lower among smokers who purchased the JUUL System (“JUUL”) in the UK, where regulations limit nicotine concentration to 20 mg/mL versus N.Am. (United States and Canada), where higher concentrations are available—before and after controlling for differences in smoking and ENDS use characteristics. These results suggest availability of ENDS in nicotine concentrations greater than 20 mg/mL may be associated with increased switching among adult smokers. Between-country differences may be affected by unmeasured factors; future research should consider these factors and the extent to which regulatory policy environments may explain differences in switching among adult smokers.
A seed coat-specific β-ketoacyl-CoA synthase, KCS12, is critical for preserving seed physical dormancy
Authors: Chai Maofeng , Queralta Castillo Indira , Sonntag Annika , Wang Shixing , Zhao Zhili , Liu Wei , Du Juan , Xie Hongli , Liao Fuqi , Yun Jianfei , Jiang Qingzhen , Sun Juan , Molina Isabel , Wang Zeng-Yu
Published: March 2021

Physical dormancy in seeds exists widely in seed plants and plays a vital role in maintaining natural seed banks. The outermost cuticle of the seed coat forms a water-impermeable layer, which is critical for establishing seed physical dormancy. We previously set up the legume plant Medicago truncatula as an excellent model for studying seed physical dormancy, and our studies revealed that a class II KNOTTED-like homeobox, KNOX4, is a transcription factor critical for controlling hardseededness. Here we report the function of a seed coat β-ketoacyl-CoA synthase, KCS12. The expression level of KCS12 is significantly downregulated in the knox4 mutant. The KCS12 gene is predominantly expressed in the seed coat, and seed development in the M. truncatula kcs12 mutant is altered. Further investigation demonstrated that kcs12 mutant seeds lost physical dormancy and were able to absorb water without scarification treatment. Chemical analysis revealed that concentrations of C24:0 lipid polyester monomers are significantly decreased in mutant seeds, indicating that KCS12 is an enzyme that controls the production of very long chain lipid species in the seed coat. A chromatin immunoprecipitation assay demonstrated that the expression of KCS12 in the seed coat is directly regulated by the KNOX4 transcription factor. These findings define a molecular mechanism by which KNOX4 and KCS12 control formation of the seed coat and seed physical dormancy.
Agency, Power, and Injustice in Metalinguistic Disagreement
Authors: Podosky Paul-Mikhail Catapang
Published: March 2021

In this paper, I explain the kinematics of non-ideal metalinguistic disagreement. This occurs when one speaker has greater control in the joint activity of pairing contents with words in a context. I argue that some forms of non-ideal metalinguistic disagreement are deeply worrying, namely those that involves certain power imbalances. In such cases, a speaker possesses illegitimate control in metalinguistic disagreement owing to the operation of identity prejudice. I call this metalinguistic injustice. The wrong involves restricting a speaker from participating in the processes that determine the epistemic/linguistic resources of a conversation, and/or undermining a speaker's ability to affect metalinguistic outcomes.
Assessing number and quality of urology open access journals: 2011 to 2018
Authors: AlRyalat Saif Aldeen , alessa Zeyad , Mansour Mustafa , Hamidi Mohammed , Obeidat Muhannad , Odtallah Omar
Published: April 2021

Background/Aims:

There is clear evidence that publishing research in an open access (OA) journal or as an OA model is associated with higher impact, in terms of number of reads and citation rates. The development of OA journals and their quality are poorly studied in the field of urology. In this study, we aim to assess the number of OA journals, their quality in terms of CiteScore, percent cited and quartiles, and their scholarly production during the period from 2011 to 2018.

Methods:

We obtained data about journals from www.scopus.com, and we filtered the list for urology journals. We obtained data for all Scopus indexed journals during the period from 2011 to 2018. For each journal, we extracted the following indices: CiteScore, Citations, scholarly output, and SCImago quartiles. We analyzed the difference in quality indices between OA and non-OA urology journals.

Results:

Urology journals have increased from 66 journals in 2011 to 99 journals in 2018. The number of OA urology journals has increased from only 10 (15.2%) journals in 2011 to 33 (33.3%) journals in 2018. The number of quartile 1 (the top 25%) journals has increased from only 1 journal in 2011 to 5 journals in 2018. Non-OA urology journals had significantly higher CiteScore compared with OA journals till the year 2015, after which the mean difference in CiteScore became smaller with insignificant p-value.

Conclusion:

Number and quality of OA journals in the field of urology have increased throughout the last few years. Despite this increase, non-OA urology journals still have higher quality and output.
HLA-B Allele, Genotype, and Haplotype Frequencies in a Group of Healthy Individuals in Colombia
Authors: Romero-Sánchez Consuelo , Hernández Natalia , Chila-Moreno Lorena , Jiménez Karen , Padilla Diana , Bello-Gualtero Juan Manuel , Bautista-Molano Wilson
Published: April 2021

Background

The sequencing of alleles of the HLA-B, a human leukocyte antigen (HLA) class I gene, was established as the most polymorphic of chromosome 6 and of the entire human genome. In this locus, the HLA-B*27 allele is highly polymorphic and has clinical relevance. Literature about the subtypes and singular frequency of these alleles in Colombia’s healthy population is scarce.

Objective

The aim of this study was to establish the HLA-B allele, genotype, and haplotype frequencies in a healthy Colombian population and analyze their association with the sex and geographical distribution of the individuals studied.

Methods

This is a nonexperimental and descriptive study. The data from whole-blood samples whose HLA genes were genotyped by protocol with the Luminex 100/200 xMAP technology were evaluated. HLA-B*27 positivity was confirmed by the new-generation sequencing technology. The associations between the HLA-B alleles and demographic variables were evaluated by χ2 and Fisher exact tests.

Results

Twenty-seven HLA-B genotypes were identified in 255 individuals, with the highest frequencies for HLA-B*35 (44.7%), B*40 (19.6%), and B*44 (16.8%). Additionally, 89 HLA-B alleles were found; the most common were HLA-B*35:01 (6.7%) and B*40:02 (6.5%). Nine individuals tested positive for the HLA-B*27 allele with genotype and allele frequencies of 3.5% and 1.8%, respectively; the HLA-B*27:05:02 subtype predominated.

Conclusions

Here, we report the most common HLA-B allele, genotype, and haplotype frequencies in a healthy Colombian population group and analyzed their association with the sex and geographical distribution of the individuals studied. Results for the HLA-B*27 allele confirm racial mixing in Colombia with a high degree of Caucasian influence, as well as the repopulation of Colombia's central region, attributed to the migration phenomena. Results agree with data published in Colombia that was obtained from cord blood samples.
Dosing Patterns In Treatment of Disabling Spasticity With Intrathecal Baclofen
Authors: Gunnarsson Stina , Lemming Dag , Alehagen Siw , Berntsson Shala , Ertzgaard Per , Samuelsson Kersti
Published: April 2021

Purpose

The aim of this study was to describe and analyze dosing patterns for patients with ITB treatment over time and to identify possible subgroups demonstrating diversity in patterns.

Design

A retrospective design.

Methods

For 81 patients from six different hospitals, baclofen doses from the first 2 years of treatment were identified using medical records. Line graphs of each patient’s doses were analyzed and grouped based on similarities in dosing pattern.

Findings

The analyses of the dosing patterns resulted in four different subgroups classified as stable, slow increase, rapid increase, and fluctuating.

Conclusion

The results highlight the clinical challenge of predicting dose development over time.

Clinical Relevance to Rehabilitation Nursing

This study provides rehabilitation healthcare professionals with a better understanding of intrathecal baclofen dose development. Illustrations of the four subgroups can be used as an educational tool for patients, family, and caregivers.
Visible and real sizes of the COVID-19 pandemic in Ukraine
Authors: Nesteruk Igor
Published: March 2021

To simulate how the number of COVID-19 cases increases versus time, various data sets and different mathematical models can be used. In particular, previous simulations of the COVID-19 epidemic dynamics in Ukraine were based on smoothing of the dependence of the number of cases on time and the generalized SIR (susceptible-infected-removed) model. Since real number of cases is much higher than the official numbers of laboratory confirmed ones, there is a need to assess the degree of data incompleteness and correct the relevant forecasts. We have improved the method of estimating the unknown parameters of the generalized SIR model and calculated the optimal values of the parameters. It turned out that the real number of diseases exceeded the officially registered values by about 4.1 times at the end of 2020 in Ukraine. This fact requires a reassessment of the COVID-19 pandemic dynamics in other countries and clarification of world forecasts.
Degradable endovascular neural interface for minimally invasive neural recording and stimulation
Authors: Fanelli Adele , Ferlauto Laura , Zollinger Elodie Geneviève , Brina Olivier , Reymond Philippe , Machi Paolo , Ghezzi Diego
Published: March 2021

Neural recording and stimulation have been widely used to mitigate traumatic injuries, neurodegenerative diseases or mental disorders. Most neural interfaces commonly require invasive surgery, potentially entailing both transient and permanent complications. A promising strategy designed to overcome these risks involves exploiting the cerebrovascular system as an access route to the neural tissue. Here we present a novel endovascular neural interface for neural recording and stimulation, fully polymeric and degradable. This concept might allow for better integration of the device in the body, reduced inflammatory reaction, the possibility of replacing the implant after degradation, and avoiding removal surgeries. The vasculature’s strategic distribution and the use of soft polymers for the device’s fabrication will permit targeting both the brain vasculature and the peripheral system. Therefore, this novel endovascular neural interface will broaden the range of applications from neurological diseases and mental disorders to bioelectronics medicine.
A unique SARS-CoV-2 spike protein P681H strain detected in Israel
Authors: Zuckerman Neta S. , Fleishon Shay , Bucris Efrat , Bar-Ilan Dana , Linial Michal , Bar-Or Itay , Indenbaum Victoria , Weil Merav ,   Israel National Consortium for SARS-CoV-2 sequencing, Mendelson Ella , Mandelboim Michal , Mor Orna
Published: March 2021

Routine detection, surveillance and reporting of SARS-CoV-2 novel variants is important, as these threaten to hinder vaccination efforts. Herein we report a local novel strain that includes a non-synonymous mutation in the spike (S) protein - P681H and additional synonymous mutations. The P681H Israeli strain has not been associated with higher infection rates and was neutralized by sera from vaccinated individuals in comparable levels to the B.1.1.7 strain and a non-P681H strain from Israel.
Emergence of a SARS-CoV-2 E484K variant of interest in Arizona
Authors: Skidmore Peter T. , Kaelin Emily A. , Holland LaRinda A. , Maqsood Rabia , Wu Lily I. , Mellor Nicholas J. , Blain Joy M. , Harris Valerie , LaBaer Joshua , Murugan Vel , Lim Efrem S.
Published: March 2021

SARS-CoV-2 is locked in a high-stakes arms race between the dynamics of rising population immunity and escape mutations. The E484K mutation in the spike protein reduces neutralization by post-vaccination sera and monoclonal antibody therapeutics. We detected the emergence of an E484K harboring variant B.1.243.1 from a common circulating variant (B.1.243) in the United States. In contrast to other instances when the E484K mutation was acquired independently in the parental lineage, genomic surveillance indicates that the B.1.243.1 variant of interest is in the process of being established in Arizona and beginning to cross state borders to New Mexico and Texas. Genomic, epidemiologic and phylogenetic evidence indicates that the B.1.243.1 variant of interest is poised to emerge. These findings demonstrate the critical need to continue tracking SARS-CoV-2 in real-time to inform public health strategies, diagnostics, medical countermeasures and vaccines.
Machine learning-optimized Combinatorial MRI scale (COMRISv2) correlates highly with cognitive and physical disability scales in Multiple Sclerosis patients
Authors: Kelly Erin , Varosanec Mihael , Kosa Peter , Sandford Mary , Prchkovska Vesna , Moreno-Dominguez David , Bielekova Bibiana
Published: March 2021

Composite MRI scales of central nervous system tissue destruction correlate stronger with clinical outcomes than their individual components in multiple sclerosis (MS) patients. Using machine learning (ML), we previously developed Combinatorial MRI scale (COMRISv1) solely from semi-quantitative (semi-qMRI) biomarkers. Here, we asked how much better COMRISv2 might become with the inclusion of quantitative (qMRI) volumetric features and employment of more powerful ML algorithm.

The prospectively acquired MS patients, divided into training (n=172) and validation (n=83) cohorts underwent brain MRI imaging and clinical evaluation. Neurological examination was transcribed to NeurEx app that automatically computes disability scales. qMRI features were computed by LesionTOADS algorithm. Modified random forest pipeline selected biomarkers for optimal model(s) in the training cohort.

COMRISv2 models validated moderate correlation with cognitive disability (Rho = 0.674; Linh’s concordance coefficient [CCC] = 0.458; p<0.001) and strong correlations with physical disability (Spearman Rho = 0.830-0.852; CCC = 0.789-0.823; p<0.001). The NeurEx led to the strongest COMRISv2 model. Addition of qMRI features enhanced performance only of cognitive disability model, likely because semi-qMRI biomarkers measure infratentorial injury with greater accuracy.

COMRISv2 models predict most granular clinical scales in MS with remarkable criterion validity, expanding scientific utilization of cohorts with missing clinical data.
Joint associations between objectively measured physical activity volume and intensity with body-fatness. The Fenland Study
Authors: Lindsay Tim , Wijndaele Katrien , Westgate Kate , Dempsey Paddy , Strain Tessa , De Lucia Rolfe Emanuella , Forouhi Nita G , Griffin Simon , Wareham Nick J , Brage Søren
Published: March 2021

Background/Objectives

Physical activity energy expenditure (PAEE) represents the total volume of all physical activity. This can be accumulated as different underlying intensity profiles. Although volume and intensity have been studied in isolation, less is known about their joint association with health. We examined this association with body-fatness in a population-based sample of middle-aged British women and men.

Methods

6148 women and 5320 men from the Fenland study with objectively-measured physical activity from individually calibrated combined heart rate and movement sensing and DXA-derived body-fat percentage (BF%) were included in the analyses. We used linear and compositional isocaloric substitution analysis to examine associations of PAEE and its intensity composition with body-fatness. Sex-stratified models were adjusted for socio-economic and dietary covariates.

Results

PAEE was inversely associated with body-fatness in women (beta=-0.16 (95%CI: −0.17; −0.15) BF% per kJ·day-1·kg-1) and men (beta=−0.09 (95%CI: −0.10; −0.08) BF% per kJ·day-1·kg-1). Intensity composition was significantly associated with body-fatness, beyond that of PAEE; the reallocation of energy to vigorous physical activity (>6 METs) from other intensities was associated with less body-fatness, whereas light activity (1.5-3 METs) was positively associated. However, light activity was the main driver of overall PAEE volume, and the relative importance of intensity was marginal compared to that of volume; the difference between PAEE in tertile 1 and 2 in women was associated with 3 percentage-point lower BF%. Higher vigorous physical activity in the same group to the maximum observed value was associated with 1 percentage-point lower BF%.

Conclusions

In this large, population-based cohort study with objective measures, PAEE was inversely associated with body-fatness. Beyond the PAEE association, greater levels of intense activity were also associated with lower body-fatness. This contribution was marginal relative to PAEE. These findings support current guidelines for obesity prevention which emphasise moving more over the specific intensity or duration of that activity.
Mental health in relation to changes in sleep, exercise, alcohol and diet during the COVID-19 pandemic: examination of four UK cohort studies
Authors: Villadsen Aase , Patalay Praveetha , Bann David
Published: March 2021

Background

Responses to the COVID-19 pandemic have included lockdowns and social distancing with considerable disruptions to people’s lives. These changes may have particularly impacted on those with mental health problems, leading to a worsening of inequalities in the behaviours which influence health.

Methods

We used data from four national longitudinal British cohort studies (N=10,666). Respondents reported mental health (psychological distress and anxiety/depression symptoms) and health behaviours (alcohol, diet, physical activity, and sleep) before and during the pandemic. Associations between pre-pandemic mental ill-health and pandemic mental ill-health and health behaviours were examined using logistic regression; pooled effects were estimated using meta-analysis.

Results

Worse mental health was related to adverse health behaviours; effect sizes were largest for sleep, exercise and diet, and weaker for alcohol. The associations between poor mental health and adverse health behaviours were larger during the May lockdown than pre-pandemic. In September, when restrictions had eased, inequalities had largely reverted to pre-pandemic levels. A notable exception was for sleep, where differences by mental health status remained high. Risk differences for adverse sleep for those with the highest level of prior mental ill-health compared to those with the lowest, were 21.2% (95% CI: 16.2, 26.2) before lockdown, 25.5% (20.0, 30.3) in May, and 28.2% (21.2, 35.2) in September.

Conclusions

Taken together, our findings suggest that mental health is an increasingly important factor in health behaviour inequality in the COVID era. The promotion of mental health may thus be an important component of improving post-COVID population health.
Prevalence and associated factors with mental health outcomes among interns and residents physicians during COVID-19 epidemic in Panama: a cross-sectional study
Authors: Espinosa-Guerra Edward A. , Rodríguez-Barría Edgar R. , Donnelly Christl A. , Carrera Jean-Paul
Published: March 2021

Background

A new coronavirus SARS-CoV-2 was associated with a newly identified respiratory syndrome, COVID-19 in Wuhan, China, in early December 2019. SARS-CoV-2 rapidly spread across the globe resulting in 117 million cases and 2.59 million deaths by March 2021. Rapidly increased numbers of COVID-19 cases overwhelmed public health systems across the world, imposing increased working hours and workloads for health care workers. Here, we have evaluated the prevalence of health outcomes and associated factors of interns and resident physicians in Panama.

Methods

A cross-sectional study was undertaken during July 23, 2020, to August 13, 2020, to evaluate the prevalence of health outcomes and associated factors in interns and residents across Panama. Snowball sampling was used to recruit participants. Then an electronic questionnaire with scales to evaluate anxiety disorders (GAD-7), depression (PHQ-9) and post-traumatic stress (IES-R) was evaluated. In addition, socio-demographic variables, clinical history of mental disorders and COVID-19 exposure were evaluated. Independent analyses for each mental health outcome were undertaken using a logistic regression analysis.

Results

A total of 517/1205 (42.9%) interns and residents were nationwide recruited. Of these 274 (53.0%) were interns and 243 (47.0%) residents. The overall prevalence of depression symptoms was 25.3%, 13.7% anxiety and 12.2% post-traumatic stress. At least, 9.3% participants reported having suicidal ideation.

The most parsimonious model showed females had a higher prevalence of mental health disorders, in all results and the married participants were more likely to present depression (OR, 1.73; 95% CI, 1.03-2.91; P = 0.039) or at least one alteration to mental health (OR, 1.66; 95% CI, 1.03-2.68; P = 0.039). Resident physicians in surgical specialties were less likely to have post-traumatic stress (OR, 0.20; 95% CI, 0.06-0.63; P = 0.006) or at least one mental health disturbance (OR, 0.46; 95% CI, 0.26-0.83; P = 0.010). A history of psychological trauma and psychiatric pathology were risk factors for most of the disorders investigated.

Conclusions

A high prevalence of mental health disorders was found, showing the need to mitigate this emotional burden among healthcare workers in the current context of the COVID-19 pandemic.
Kenyan Traditional Medicine: Exploring Old Solutions to the Modern Antibacterial Crises Through Natural Products Chemistry
Authors: Ndegwa Fidensio K. , Kondam Chaitanya , Ghose Debarati , Esan Taiwo E. , Waxali Zohra Sattar , Miller Margaret E. , Meganathan Rangaswamy , Gikonyo Nicholas K. , Mbugua Paul K. , Okemo Paul O. , Hagen Timothy J.
Published: March 2021

Infectious diseases are a major cause of morbidity and mortality around the world, accounting for approximately 50% of all deaths in tropical countries. Despite remarkable progress in the field of microbiology, inability to control or mitigate, epidemics caused by drug-resistant microorganisms pose a serious health hazard to the global population. New therapeutic strategies must be developed as a global initiative for the prevention and control of infectious diseases. This study focuses on Kenyan medicinal plants and their activity against bacteria. Plant extracts obtained from seven Kenyan plants used in traditional medicine, were screened for their antibacterial activity againstEscherichia coli,Pseudomonas aeruginosa, Bacillus cereus, and Mycobacterium smegmatis. Extracts from all these plants showed antibacterial activity against at least one of the tested organisms at a concentration of 2 mg/mL. Chemical screening showed the presence of different classes of phytochemicals such as alkaloids, terpenes, tannins, in some active extracts.
Accessory genomic epidemiology of co-circulating Acinetobacter baumannii clones
Authors: Mateo-Estrada Valeria , Fernández-Vázquez José Luis , Moreno-Manjón Julia , Hernández-González Ismael L. , Rodríguez-Noriega Eduardo , Morfín-Otero Rayo , Alcántar-Curiel María Dolores , Castillo-Ramírez Santiago
Published: March 2021

A. baumannii has become one of the most important multidrug resistant nosocomial pathogens all over the world. Nonetheless, very little is known about the diversity of A. baumannii lineages co-existing in hospital settings. Here, using whole-genome sequencing, epidemiological data and antimicrobial susceptibility tests, we uncover the transmission dynamics of extensive and multidrug resistant A. baumannii in a tertiary hospital for a decade. Our core genome phylogeny of almost 300 genomes suggests that there were several introductions of lineages from international clone 2 into the hospital. The molecular dating analysis shows that these introductions happened between 2004 and 2015. Furthermore, using the accessory genome, we show that these lineages were extensively disseminated across many wards in the hospital. Our results demonstrate that accessory genome variation can be a very powerful tool for conducting genomic epidemiology. We anticipate future studies employing the accessory genome as a phylogenomic marker over very short microevolutionary scales.
Thermoplasmonic nano-rupture of cells reveals Annexin V function in plasma membrane repair
Authors: Moreno-Pescador Guillermo S. , Aswad Dunya S. , Florentsen Christoffer D. , Bahadori Azra , Arastoo Mohammad R. , Danielsen Helena Maria D. , Heitmann Anne Sofie B. , Boye Theresa L. , Nylandsted Jesper , Oddershede Lene B. , Bendix Poul Martin
Published: March 2021

Maintaining the integrity of the cell plasma membrane (PM) is critical for the survival of cells. While an efficient PM repair machinery can aid survival of healthy cells by preventing influx of extracellular calcium, it can also constitute an obstacle in drug delivery and photothermal therapy. We show how nanoscopic holes can be applied to the cell surface thus allowing identification of molecular components with a pivotal role in PM repair. Cells are punctured by locally heating gold nanostructures at the cell surface which causes nano-ruptures in cellular PMs. Recruitment of annexin V near the hole is found to locally reshape the ruptured plasma membrane. Experiments using model membranes, containing recombinant annexin V, provide further biophysical insight into the ability of annexin V to reshape edges surrounding a membrane hole. The thermoplasmonic method provides a general strategy to monitor the response to nanoscopic injuries to the cell surface.
Mass Cytometric and Transcriptomic Profiling of Epithelial-Mesenchymal Transitions in Human Mammary Cell Lines
Authors: Wagner Johanna , Masek Markus , Jacobs Andrea , Soneson Charlotte , Damond Nicolas , de Souza Natalie , Robinson Mark D. , Bodenmiller Bernd
Published: March 2021

Epithelial-mesenchymal transition (EMT) equips breast cancer cells for metastasis and treatment resistance. Inhibition and elimination of EMT-undergoing cells are therefore promising therapy approaches. However, detecting EMT-undergoing cells is challenging due to the intrinsic heterogeneity of cancer cells and the phenotypic diversity of EMT programs. Here, we profiled EMT transition phenotypes in four non-cancerous human mammary epithelial cell lines using a FACS surface marker screen, RNA sequencing, and mass cytometry. EMT was induced in the HMLE and MCF10A cell lines and in the HMLE-Twist-ER and HMLE-Snail-ER cell lines by chronic exposure to TGFβ1 or 4-hydroxytamoxifen, respectively. We observed a spectrum of EMT transition phenotypes in each cell line and the spectrum varied across the time course. Our data provide multiparametric insights at single-cell level into the phenotypic diversity of EMT at different time points and in four human cellular models. These insights are valuable to better understand the complexity of EMT, to compare EMT transitions between the cellular models used herein, and for the design of EMT time course experiments.

Mendeley Data: DOI: 10.17632/pt3gmyk5r2.1

ArrayExpress Data: Accession number E-MTAB-9365
Human herpesvirus 8 molecular mimicry of ephrin ligands facilitates cell entry and triggers EphA2 signaling
Authors: Light Taylor P. , Brun Delphine , Guardado-Calvo Pablo , Pederzoli Riccardo , Haouz Ahmed , Neipel Frank , Rey Felix , Hristova Kalina , Backovic Marija
Published: March 2021

Human herpesvirus 8 (HHV-8) is an oncogenic virus that enters cells by fusion of the viral and endosomal cellular membranes in a process mediated by viral surface glycoproteins. One of the cellular receptors hijacked by HHV-8 to gain access to cells is the EphA2 tyrosine kinase receptor, and the mechanistic basis of EphA2-mediated viral entry remains unclear. Using X-ray structure analysis, targeted mutagenesis and binding studies, we here show that the HHV-8 envelope glycoprotein complex gH/gL binds with sub-nanomolar affinity to EphA2 via molecular mimicry of the receptor’s cellular ligands, ephrins, revealing a pivotal role for the conserved gH residue E52 and the amino-terminal peptide of gL. Using FSI-FRET and cell contraction assays, we further demonstrate that the gH/gL complex also functionally mimics ephrin ligand by inducing EphA2 receptor association via its dimerization interface, thus triggering receptor signaling for cytoskeleton remodeling. These results now provide novel insight into the entry mechanism of HHV-8, opening avenues for the search of therapeutic agents that could interfere with HHV-8 related diseases.
Internalisation and biological activity of nucleic acids delivering cell-penetrating peptide nanoparticles is controlled by the biomolecular corona
Authors: Lorents Annely , Maloverjan Maria , Padari Kärt , Pooga Margus
Published: March 2021

Nucleic acid molecules can be transferred into cells to alter gene expression and, thus, alleviate certain pathological conditions. Cell-penetrating peptides (CPPs) are vectors that can be used for transfecting nucleic acids as well as many other compounds. CPPs associate nucleic acids non-covalently, forming stable nanoparticles and providing efficient transfection of cellsin vitro. However,in vivo, expected efficiency is achieved only in rare cases. One of the reasons for this discrepancy is formation of protein corona around nanoparticles, once they are exposed to a biological environment, e.g. blood stream. In this study, we compared CPP-nucleic acid nanoparticles formed in the presence of bovine, murine and human serum. We used Western blot and mass-spectrometry to identify the major constituents of protein corona forming around nanoparticles, showing that proteins involved in transport, haemostasis and complement system are its major components. We investigated physical features of nanoparticles, and measured their biological efficiency in splice-correction assay. We showed that protein corona constituents might alter the fate of nanoparticlesin vivo, e.g. by subjecting them to phagocytosis. We demonstrated that composition of protein corona of nanoparticles is species-specific that leads to dissimilar transfection efficiency and should be taken into account while developing delivery systems for nucleic acids.
Single-nuclei transcriptomes from human adrenal gland reveals distinct cellular identities of low and high-risk neuroblastoma tumors
Authors: Bedoya-Reina O.C. , Li W. , Arceo M. , Plescher M. , Bullova P , Pui H. , Kaucka M. , Kharchenko P. , Martinsson T. , Holmberg J. , Adameyko I. , Deng Q. , Larsson C. , Juhlin C.C. , Kogner P. , Schlisio S.
Published: March 2021

Childhood neuroblastoma has a remarkable variability in outcome. Age at diagnosis is one of the most important prognostic factors, with children less than 1 year old having favorable outcomes. We studied single-cell and single-nuclei transcriptomes of neuroblastoma with different clinical risk groups and stages, including healthy adrenal gland. We compared tumor cell populations with embryonic mouse sympatho-adrenal derivatives, and post-natal human adrenal gland. We provide evidence that low and high-risk neuroblastoma have different cell identities, representing two disease entities. Low-risk neuroblastoma presents a transcriptome that resembles sympatho- and chromaffin cells, whereas malignant cells enriched in high-risk neuroblastoma resembles an unknown subtype of TRKB+ cholinergic progenitor population identified in human post-natal gland. Analyses of these populations revealed different gene expression programs for worst and better survival in correlation with age at diagnosis. Our findings reveal two cellular identities and a composition of human neuroblastoma tumors reflecting clinical heterogeneity and outcome.
Evaluation of the effect of hydrocortisone in 2D and 3D HEp-2 cell culture
Authors: Fonseca M.O. , Godoi B.H. , Da Silva N.S , Pacheco-Soares C.
Published: March 2021

Cancer is one of the diseases with the highest incidence globally and that associated with the patient’s emotional state, can act positively or negatively in the treatment. Cortisol is a principal primary stress hormone in the human body. The corticoids can increase cell proliferation and reactive oxygen species that contribute to DNA damage. Prolonged exposure to stress can contribute to tissues becoming insensitive to cortisol, the primary human stress hormone. This study explores cortisol’s influence on tumor cell development, particularly in human cells of carcinoma of the human laryngeal (HEp-2). HEp-2 cells were exposed to increasing cortisol (hydrocortisone) concentrations for 24 or 48 hours, and cytotoxicity (MTT assay) proliferation assay (crystal violet assay), and immunolabeled 3D culture for fibronectin and FAK were analyzed. The group treated with hydrocortisone showed a significant increase in mitochondrial activity, as for the evaluation by the violet crystal, the treated group showed similar behavior to the control. The 3D culture showed dispersed cells within 24 hours with reduced FAK labeling; however, no changes were observed within 48 hours. Although some cases favored corticosteroid use in cancer patients, a more detailed analysis is necessary before prescribing them.
Exploring the Plant Aquaporin Solute Transport Network: Functional characterisation ofNicotiana tabacumPIP, TIP and NIP isoforms
Authors: De Rosa Annamaria , Zhang Rose , Byrt Caitlin , Evans John R , Groszmann Michael
Published: March 2021

Aquaporins (AQPs) are multifunctional membrane proteins which have greatly diversified in number and function in the plant Kingdom. In plants, AQPs have evolved to comprise a dynamic solute transport network occurring in all tissues and facilitating transport of water and vital solutes across various cellular membranes. Plant AQPs are involved in a multitude of plant physiological processes, however a better understanding is required of AQP structure-function relationships, multifunctionality and cell membrane localisation in order to begin to describe putative functional roles for the numerous plant AQP gene isoforms. Using an integrated approach, we characterised nine diverseNicotiana tabacum(tobacco) aquaporins, spanning the 3 largest AQP subfamilies (PIP, TIP, and NIP) and with varied gene expression profiles. High-throughput yeast-based functional screens identified novel candidates for water, hydrogen peroxide (H2O2), boric acid (BA) and urea transport across the 3 AQP subfamilies. Using GFP translational fusions, AQPs observedin plantawere localised to the plasma membrane, tonoplast and endoplasmic reticulum. AlphaFold protein models illustrated differences in pore shape and size across subfamilies. Our analysis supports the importance of functional data for deciphering unknown AQP structure-function relationships and uncovering novel candidates forin plantasolute transport.
Tribbles 2 confers enzalutamide resistance in prostate cancer by promoting lineage plasticity
Authors: Monga Jitender , Adrianto Indra , Rogers Craig , Gadgeel Shirish , Chitale Dhananjay , Alumkal Joshi J. , Beltran Himisha , Zoubeidi Amina , Ghosh Jagadananda
Published: March 2021

Second-generation anti-androgen, such as enzalutamide (Xtandi), is commonly prescribed for prostate cancer therapy, but enzalutamide-resistant, lethally incurable disease invariably develops. To understand the molecular basis of enzalutamide resistance, we comprehensively analyzed prostate tumors and clinically relevant models. These studies revealed that enzalutamide resistant prostate cancer cells overexpress Tribbles 2 (Trib2), a pseudokinase. Expression of Trib2 is negatively regulated by androgen receptor signaling. Overexpression of Trib2 makes prostate cancer cells completely resistant to clinically relevant doses of enzalutamide. Trib2 downregulates expression of luminal markers but upregulates the neuronal transcription factor, BRN2, and the stemness factor, SOX2, to induce neuroendocrine differentiation. Our findings indicate that Trib2 confers resistance to enzalutamide therapy via a mechanism involving increased cellular plasticity and lineage switching.
Chromatic bacteria v.2 - A Himar1 transposon based delivery vector to extend the host range of a toolbox to fluorescently tag bacteria
Authors: Stocks Christian , Schlechter Rudolf , Remus-Emsermann Mitja
Published: March 2021

A recent publication described the construction and utility of a comprehensive “Chromatic Bacteria” toolbox containing a set of genetic tools that allows for fluorescently tagging a variety of Proteobacteria. In an effort to expand the range of bacteria taggable with the Chromatic Bacteria toolbox, a Himar1 transposon vector was constructed to mediate insertion of fluorescent protein and abiotic resistant genes. The Himar1 transposon was chosen as it is known to function in a wide range of bacteria. To test the use of the Himar1 derivative of the Chromatic Bacteria plasmid series for fluorescently tagging bacteria, recently isolated non-model organisms were conjugated with the Himar1 transposon plasmids. We were unsuccessful in delivering the plasmids into Gram positive bacterial isolates but were able to successfully integrate the transposon in isolates that we were previously unable to modify such asSphingomonassp. Leaf357 andAcidovoraxsp. Leaf84. This manuscript reports on the currently available plasmids and transposition success in different bacteria. The manuscript will be updated regularly until a full plasmid series is available and a large range of recipient strains was tested.