bluuebunny/crossref_metadata_2025 huggingface dataset:
INSP-17. Augmented Drug Delivery for Pediatric Diffuse Midline Glioma using Convection Enhanced Delivery
Authors: Souweidane Mark M
Published: June 2022

Convection enhanced delivery (CED), an alternative to systemic chemotherapy, spans nearly two decades of clinical experience. The application of CED in pediatric neuro-oncology has been mainly used in children with DMG. This exploratory period is highlighted by widely variable features including procedural technique, disease extent, device interface, infusion parameters, and therapeutic agent. This presentation is meant to critically assess if CED for DMG is a logical therapeutic strategy. Most convincing to the perpetuation of this platform is the reproducible demonstration of augmented drug delivery. Post-treatment ratios of intralesional to systemic drug concentrations consistently exceed 1000. CED in the brain stem satisfies a desirable goal of CNS drug delivery: achieving high target tissue drug concentrations while avoiding systemic exposure. Surgical targeting of the brain stem and cannula deployment are solidly established as safe and accurate. Catheter insertion complications such as clinically relevant hemorrhage, CNS infection, and neurological injury are exceptional. Likewise, targeting error is on a millimeter scale with infrequent need for catheter repositioning. The use of intrinsic MRI signals, direct drug labeling, and surrogate tracers have all been used for measuring distribution of the infusion. The experience using a radio-labelled theragnostic agent has provided detailed distribution and dosimetry information. Based on estimates of tumor and hence target volumes, a rationale goal is to reach volumes of distribution in the range of 15-25 cm3. Optimizing this goal has focused on surgical targeting, infusion duration, and multiple treatment plans. Computational predictive modeling is being employed as a preoperative adjunct for maximizing distribution. Experience in DMG thus far has been limited to feasibility and safety studies. There is a paucity of Phase 2 studies and hence outcome has not yet been rigorously tested. Anecdotal increase in survival and long-term survival has been reproducibly reported. Of particular interest are the occasional cases of children exhibiting late out-of-treatment field and even extra-CNS recurrence. Available data is convincing that CED should serve be further explored in future clinical trials designs for children with DMG. Important features of any Phase 2 study design however should include monitoring of drug distribution, measures of tumor coverage, early response monitoring techniques, and possibly combination with whole CNS axis treatment.
Management of neurofibromatosis type 1-associated plexiform neurofibromas
Authors: Fisher Michael J , Blakeley Jaishri O , Weiss Brian D , Dombi Eva , Ahlawat Shivani , Akshintala Srivandana , Belzberg Allan J , Bornhorst Miriam , Bredella Miriam A , Cai Wenli , Ferner Rosalie E , Gross Andrea M , Harris Gordon J , Listernick Robert , Ly Ina , Martin Staci , Mautner Victor F , Salamon Johannes M , Salerno Kilian E , Spinner Robert J , Staedtke Verena , Ullrich Nicole J , Upadhyaya Meena , Wolters Pamela L , Yohay Kaleb , Widemann Brigitte C
Published: June 2022

Plexiform Neurofibromas (PN) are a common manifestation of the genetic disorder neurofibromatosis type 1 (NF1). These benign nerve sheath tumors often cause significant morbidity, with treatment options limited historically to surgery. There have been tremendous advances over the past two decades in our understanding of PN, and the recent regulatory approvals of the MEK inhibitor selumetinib are reshaping the landscape for PN management. At present, there is no agreed upon PN definition, diagnostic evaluation, surveillance strategy, or clear indications for when to initiate treatment and selection of treatment modality. In this review, we address these questions via consensus recommendations from a panel of multidisciplinary NF1 experts.
Isotopic constraints confirm the significant role of microbial nitrogen oxides emissions from the land and ocean environment
Authors: Song Wei , Liu Xue-Yan , Houlton Benjamin Z , Liu Cong-Qiang
Published: June 2022

Nitrogen oxides (NOx, the sum of nitric oxide (NO) and N dioxide (NO2)) emissions and deposition have increased markedly over the past several decades, resulting in many adverse outcomes in both terrestrial and oceanic environments. However, because the microbial NOx emissions have been substantially underestimated on the land and unconstrained in the ocean, the global microbial NOx emissions and their importance relative to the known fossil-fuel NOx emissions remain unclear. Here we complied data on stable N isotopes of nitrate in atmospheric particulates over the land and ocean to ground-truth estimates of NOx emissions worldwide. By considering the N isotope effect of NOx transformations to particulate nitrate combined with dominant NOx emissions in the land (coal combustion, oil combustion, biomass burning and microbial N cycle) and ocean (oil combustion, microbial N cycle), we demonstrated that microbial NOx emissions account for 24 ± 4%, 58 ± 3% and 31 ± 12% in the land, ocean and global environment, respectively. Corresponding amounts of microbial NOx emissions in the land (13.6 ± 4.7 Tg N yr−1), ocean (8.8 ± 1.5 Tg N yr−1) and globe (22.5 ± 4.7 Tg N yr−1) are about 0.5, 1.4 and 0.6 times on average those of fossil-fuel NOx emissions in these sectors. Our findings provide empirical constraints on model predictions, revealing significant contributions of the microbial N cycle to regional NOx emissions into the atmospheric system, which is critical information for mitigating strategies, budgeting N deposition and evaluating the effects of atmospheric NOx loading on the world.
Cryptococcal and Histoplasma Antigen Screening Among People With Human Immunodeficiency Virus in Ghana and Comparative Analysis of OIDx Histoplasma Lateral Flow Assay and IMMY Histoplasma Enzyme Immunoassay
Authors: Ocansey Bright K , Otoo Benjamin , Asamoah Isabella , Ganu Vincent , Berko Kofi P , Oladele Oluwakemi , Amankwa Emmanuella A , Opoku-Asare Bismark , Agyei Martin , George Lawrence , Kotey Fleischer C N , Kosmidis Chris , Puplampu Peter , Opintan Japheth A , Denning David W
Published: June 2022

Background

Cryptococcal meningitis (CM) and disseminated histoplasmosis (DH) are common in people with human immunodeficiency virus (PWH) and diagnosed by detecting cryptococcal antigen (CrAg) and Histoplasma antigen (HistoAg), respectively. In Ghana, CM and DH are rarely suspected by clinicians due to limited epidemiological data.

Methods

This study was conducted among PWH in Ghana who are unwell. Sociodemographic and clinical data were collected by questionnaire. Serum and/or urine were screened for CrAg and HistoAg, using IMMY CrAg lateral flow assay (LFA) and IMMY Histoplasma enzyme immunoassay (EIA) kits, respectively, regardless of symptoms. Samples run with IMMY Histoplasma EIA were simultaneously run with Optimum Imaging Diagnostics (OIDx) Histoplasma LFA. Laboratory investigations were conducted by the research team, and diagnosis incorporating clinical assessment, screening, and confirmatory testing results and treatment decisions were made by the clinical team. Treatment and outcome information on CM and DH patients were evaluated.

Results

Overall, 150 participants were recruited. There were 73% (n = 109) females, and the age range was 18–62 years. The prevalence rates of CrAg and HistoAg were 2.7% (4 of 150) and 4.7% (5 of 107), respectively. The OIDx Histoplasma LFA showed a high concordance (98.4%) with the IMMY Histoplasma EIA. All antigen-positive cases by standard tests were diagnosed with CM and DH. Antifungal treatment was given in 5 patients and follow-up revealed 2 deaths and 3 recoveries.

Conclusions

Histoplasmosis among PWH may be more common than previously anticipated and may be more frequent than cryptococcosis in Ghana. The performance of the OIDx Histoplasma LFA should be further explored.
The relationship of the neutron skin thickness to the symmetry energy and its slope
Authors: Suzuki Toshio
Published: June 2022

The neutron skin thickness of asymmetric semi-infinite nuclear matter (δRM) is shown to be a function of the Coulomb energy (Vc), the asymmetry energy coefficient (J), the slope (L) of the asymmetry energy, and the incompressibility coefficient (K), in addition to the Fermi momentum (kF) and the asymmetry parameter (I = (N − Z)/A). The relational formula is derived on the basis of the Hugenholtz–Van Hove theorem in the mean-field (MF) approximation for nuclear matter. Using the formula as a guide, the neutron skin thickness (δR) in 208Pb is examined in the MF models. The apparently spurious linear correlation between L and δR appears through the model-dependent correlation of L with J that is included in the main components of the formula.
Global bifurcation of capillary-gravity dark solitary waves on the surface of a conducting fluid under normal electric fields
Authors: Doak A , Gao T , Vanden-Broeck J -M
Published: June 2022

This article is concerned with capillary-gravity waves travelling on the interface of a dielectric gas and a conducting fluid under the effect of a vertical electric field. A boundary integral equation method is employed to compute fully nonlinear steady travelling wave solutions. The global bifurcation diagram of periodic waves, solitary waves, generalised solitary waves and dark solitary waves is presented and discussed in detail.
Dry matter and crude protein degradability of Napier grass (Pennisetum purpureum) silage is affected by fertilization with cow-dung bio-digester slurry and fermentable carbohydrate additives at ensiling
Authors: Rambau Mashudu D , Fushai Felix , Callaway Todd R , Baloyi Joseph J
Published: June 2022

Dry seasons pose a major nutritional constraint on ruminant livestock production in tropical regions, which justifies forage conservation to meet the dry season feed requirement. Napier grass is a tropical forage that is used for silage in South Africa. The present objective was to determine the effects of Napier grass fertilization with bio-digester slurry (BDS) and the inclusion of fermentable carbohydrate additives at ensiling on the chemical composition and ruminal degradability of Napier grass silage. Napier grass was established in 5 × 4 m plots, replicated three times in a completely randomized design, and irrigated weekly with either BDS or water. After 12 weeks, the Napier was cut and ensiled for 90 days in 1-liter glass jars in a 2 (BDS, water) × 4 (no-additive, molasses, brown sugar, and maize meal) factorial arrangement replicated three times. The nutrient composition was determined using standard protocols. The ruminal degradability of dry matter (DM) and crude protein (CP) was determined using the nylon bag technique. Fertilization with BDS increased (P < 0.05) pH and CP and reduced (P < 0.05) fat content of fresh-cut Napier. Additives increased (P < 0.01) silage DM content and reduced (P < 0.01) acid detergent fiber, neutral detergent fiber content. The BDS fertilization with molasses inclusion increased (P < 0.05) silage DM relative to the no-additive and maize meal inclusion, and decreased (P < 0.05) fat content compared to the no-fertilizer, added maize meal silage. Molasses increased silage water-soluble carbohydrate and decreased the NH3-N content (P < 0.05) compared to the no-additive and maize meal treatments. For DM, the BDS fertilized, no additive silage had the least “a” fraction (P < 0.01), while the no BDS, no-additive silage had the least “b” fraction (P < 0.01), with least (P < 0.01) potential degradability (PD) observed for the no BDS, no-additive treatment. Fertilization increased (P < 0.01) effective degradability of DM at outflow rates k = 0.02, 0.05, 0.08, with same effect for molasses and maize meal inclusion. Relative to the control, molasses inclusion increased (P < 0.01) PD of silage CP. In conclusion, our results suggested BDS fertilization of Napier grass ensiling with added readily fermentable carbohydrate substrate, particularly from molasses, induced changes in silage chemical and fermentation characteristics likely to promote better forage preservation and ruminal microbial function.
Water uptake patterns of tropical canopy trees in Borneo: species-specific and temporal variation and relationships with aboveground traits
Authors: Hiiragi Katsuura , Matsuo Naoko , Sakai Shoko , Kawahara Kazuma , Ichie Tomoaki , Kenzo Tanaka , Aurelia Dulce Chung , Kume Tomonori , Nakagawa Michiko
Published: June 2022

Root water uptake depth and its temporal variation are important determinants of tree mortality, resource partitioning and drought resistance; however, their effects on tropical trees remain poorly understood. In this study, we investigated interspecific differences in water uptake depth and its temporal variation using stable isotope analysis and examined the relationships between water uptake depth and aboveground traits in a humid aseasonal tropical rainforest in Borneo. Species-specific differences in water uptake depth were examined for six dominant dipterocarp species. Temporal variation in water uptake depth for various canopy trees was assessed in three periods with different soil moisture conditions. We then examined the relationships between water uptake depth and aboveground traits including wood density, maximum tree height, flowering frequency and growth rate. Dipterocarpus globosus appeared to be more reliant on deep water resources than the other dipterocarp species. Water uptake from the soil layers varied among the three sampling periods. Trees generally utilized deeper soil water during the second driest sampling period, when temperatures were lowest. During the driest and wettest sampling periods, species with higher flowering frequencies tended to preferentially uptake deep soil water. These results suggest that low temperature and soil moisture promote increased deep soil water uptake in the study region. Dynamic relationships between water uptake patterns and aboveground tree traits may be related to resource partitioning among co-existing species.
Diagnostic Utility of Cerebrospinal Fluid Procalcitonin in Neonatal Meningitis
Authors: Nagaraj Meghana , Bandiya Prathik , Jagannatha Bhavana , Shivanna Niranjan , Benakappa Naveen , Bandyopadhyay Tapas
Published: June 2022

We aimed to study the diagnostic utility of cerebrospinal fluid (CSF) procalcitonin (PCT) in neonates with meningitis. All the neonates with sepsis who qualified for lumbar puncture were prospectively evaluated. The neonates were classified into Meningitis and No meningitis group based on predefined criteria. CSF PCT was estimated in these neonates along with cytological and biochemical parameters. A total of 113 neonates were included in the study with 29 in the meningitis group and 84 in the no meningitis group. The median PCT levels were higher in babies with meningitis as compared to those without meningitis [0.194 (0.034–0.534) in meningitis group vs. 0.012 (0.012–0.012) ng/ml in no meningitis group, p < 0.001]. The area under curve for CSF PCT was 0.867 (0.77–0.95) and at a cut-off level of 0.120 ng/ml CSF PCT had a sensitivity of 83%, specificity of 84% and positive and negative predictive likelihood ratios of 5.35 and 0.20, respectively for the diagnosis of meningitis. CSF PCT has a good diagnostic accuracy similar to other parameters in the diagnosis of neonatal meningitis and can be considered as an additional diagnostic marker particularly when CSF culture is negative and cytochemical analysis is inconclusive.
Epidemiological inference from pathogen genomes: A review of phylodynamic models and applications
Authors: Featherstone Leo A , Zhang Joshua M , Vaughan Timothy G , Duchene Sebastian
Published: June 2022

Phylodynamics requires an interdisciplinary understanding of phylogenetics, epidemiology, and statistical inference. It has also experienced more intense application than ever before amid the SARS-CoV-2 pandemic. In light of this, we present a review of phylodynamic models beginning with foundational models and assumptions. Our target audience is public health researchers, epidemiologists, and biologists seeking a working knowledge of the links between epidemiology, evolutionary models, and resulting epidemiological inference. We discuss the assumptions linking evolutionary models of pathogen population size to epidemiological models of the infected population size. We then describe statistical inference for phylodynamic models and list how output parameters can be rearranged for epidemiological interpretation. We go on to cover more sophisticated models and finish by highlighting future directions.
Phenotypic and Genetic Characterization of the Lentil Single Plant-Derived Core Collection for Resistance to Root Rot Caused by Fusarium avenaceum
Authors: Heineck Garett C. , Altendorf Kayla R. , Coyne Clarice J. , Ma Yu , McGee Rebecca , Porter Lyndon D.
Published: June 2022

Lentil (Lens culinaris) is a pulse crop grown for its amino acid profile, moderate drought tolerance, and ability to fix nitrogen. As the global demand for lentils expands and new production regions emerge so too have the complement of diseases that reduce yield, including the root rot complex. Although the predominant causal pathogen varies based on growing region, Fusarium avenaceum is often found to be an important contributor to disease. This study screened part of the lentil single plant-derived core collection for resistance to F. avenaceum in a greenhouse. Plants were phenotyped for disease severity using three scoring scales and the differences in biomass traits due to pathogen presence were measured. Lentil accessions varied in disease severity and differences in biomass traits were found to be correlated with each visual severity estimate (r = −0.37 to −0.63, P < 0.001), however, heritability estimates were low to moderate among traits (H2 = 0.12 to 0.43). Results of a genome-wide association study (GWAS) using single nucleotide polymorphism (SNP) markers derived from genotyping-by-sequencing revealed 11 quantitative trait loci (QTL) across four chromosomes. Two pairs of QTL colocated for two traits and were found near putative orthologs that have been previously associated with plant disease resistance. The identification of lentil accessions that did not exhibit a difference in biomass traits may serve as parental material in breeding or in the development of biparental mapping populations to further validate and dissect the genetic control of resistance to root rot caused by F. avenaceum.
Recombinant Human Nerve Growth Factor for Pediatric Neurotrophic Keratopathy
Authors: Niruthisard Duangratn , Fung Simon S. M.
Published: June 2022

A 4-year-old boy presented with right neurotrophic corneal ulcer, lagophthalmos, and facial palsy 8 months after neurosurgery for synchronous brain tumors. Initial treatment with topical antibiotics, topical corticosteroids, lubrication, and lateral tarsorrhaphy successfully treated the corneal epithelial defect; however, the cornea continued to demonstrate diffuse epitheliopathy and a dense stromal opacity and remained insensate on Cochet–Bonnet esthesiometry. After a course of topical cenegermin, central corneal sensation normalized, and the corneal epitheliopathy was markedly improved. Two years after the completion of cenegermin, corneal sensation was maintained; there were no recurrences of epithelial defects, and the stromal opacity had markedly improved. In vivo confocal microscopy (IVCM) demonstrated the presence of subbasal corneal innervation. This report highlights the safety and prolonged effects of cenegermin for the treatment of pediatric iatrogenic neurotrophic keratopathy, as evidenced by the clinical course and IVCM.
Novel Surgical Techniques to Control Flow with PreserFlo® MicroShunt for Late Hypotony After Baerveldt Drainage Device Implantation
Authors: Fritsche Raphael , Müller Luzia , Bochmann Frank
Published: June 2022

We report a new surgical technique for controlling flow with a PreserFlo® MicroShunt, in patients with late postoperative hypotony, following a Baerveldt glaucoma drainage device implantation. We present two cases with late postoperative hypotony after Baerveldt-shunt implantations. In both cases, the outflow resistance of the Baerveldt tube was modulated by the insertion of a PreserFlo® MicroShunt into the lumen of the Baerveldt tube. In the first case, the Microshunt was inserted through the distal opening of the tube in the anterior chamber. In the second case, an end plate, sided approach was chosen after opening the conjunctiva. In both cases, the hypotony was successfully treated. The intraocular pressure rose immediately after the procedure, and it remained well controlled within the targeted range during the first postoperative months without additional pressure-lowering medication. This novel surgical technique provided predictable flow reductions, according to the Hagen-Poiseuille equation. This approach offers a valuable alternative to permanent tube ligation.
Preferences for Risks and Benefits of Islet Cell Transplantation for Persons With Type 1 Diabetes With History of Episodes of Severe Hypoglycemia: A Discrete-Choice Experiment to Inform Regulatory Decisions
Authors: Wilson Leslie , Kwok Tiffany , Ma Yanlei , Wong Jenise , Ho Martin , Ionova Yelena , McGrath Maureen , Mueller Monica M. , Gitelman Stephen E. , Irony Telba
Published: June 2022

Background.

The advisory panel for US Food and Drug Administration (FDA) recently endorsed pancreatic islet cell transplantation (ICT) therapy for suboptimally controlled type 1 diabetes (T1D), and FDA approval is under consideration. An important part of regulatory approval includes the patient perspective, through discrete choice. We developed a discrete-choice instrument and used it to determine how 90 people with T1D weigh the risks and benefits of ICT to inform regulatory decisions.

Methods.

Sawtooth software created a random, full-profile, balanced-overlap experimental design for a measure with 8 attributes of ICT risks/benefits, each with 3 to 5 levels. We asked 18 random task pairs, sociodemographics, diabetes management, and hypoglycemia questions. Analysis was performed using random parameters logistic regression technique.

Results.

The strongest preference was for avoiding the highest chance (15%) of serious procedure-related complications (β = −2.03, P < 0.001). The strongest positive preference was for gaining 5-y insulin independence (β = 1.75, P < 0.001). The desire for 5-y HbA1C-defined clinical treatment success was also strong (β = 1.39, P < 0.001). Subgroup analysis suggested strong gender differences with women showing much higher preferences for all benefits (68% higher for 5-y insulin independence), and men were generally more risk averse than women. Those with high versus low diabetes distress showed 3 times stronger preference for 5-y insulin independence but also twice preference to avoid risks of serious complications.

Conclusions.

Despite showing the most preference for avoiding serious ICT complications, people with T1D had a strong preference for achieving ICT benefits, especially insulin independence. We identified important attributes of ICT and demonstrated that patients are willing to make these trade-offs, showing support for the introduction of ICT.
Metabolic profiling of rheumatoid arthritis neutrophils reveals altered energy metabolism that is not affected by JAK inhibition
Authors: Chokesuwattanaskul Susama , Alarcon Michele Fresneda , Mangalakumaran Sangeetha , Grosman Rudi , Cross Andrew L , Chapman Elinor A , Mason David , Moots Robert J , Phelan Marie M , Wright Helen L
Published: June 2022

Neutrophils play a key role in the pathophysiology of rheumatoid arthritis (RA) where release of ROS and proteases directly causes damage to joints and tissues. Neutrophil function can be modulated by Janus Kinase (JAK) inhibitor drugs, including tofacitinib and baricitinib, which are clinically effective treatments for RA. However clinical trials have reported increased infection rates and transient neutropenia during therapy. The subtle differences in the mode of action, efficacy and safety of JAK inhibitors has been the primary research topic of many clinical trials and systematic reviews, to provide a more precise and targeted treatment to patients. The aim of this study was to determine both the differences in the metabolome of neutrophils from healthy controls and people with RA, and the effect of different JAK inhibitors on the metabolome of healthy and RA neutrophils. Isolated neutrophils from healthy controls (HC) (n=6) and people with RA (n=7) were incubated with baricitinib, tofacitinib or a pan-JAK inhibitor (all 200ng/mL) for 2h. Metabolites were extracted and 1H nuclear magnetic resonance (NMR) was applied to study the metabolic changes. Multivariate analyses and machine learning models showed a divergent metabolic pattern in RA neutrophils compared to HC at 0h (F1 score = 86.7%) driven by energy metabolites (ATP, ADP, GTP and glucose). No difference was observed in the neutrophil metabolome when treated with JAK inhibitors. However, JAK inhibitors significantly inhibited ROS production and baricitinib decreased NET production (p<0.05). Bacterial killing was not impaired by JAK inhibitors, indicating the effect of JAK inhibitors on neutrophils can inhibit joint damage in RA without impairing host defence. This study highlights altered energy metabolism in RA neutrophils which may explain the cause of their dysregulation in inflammatory disease.
One to host them all: genomics of the diverse bacterial endosymbionts of the spiderOedothorax gibbosus
Authors: Halter Tamara , Köstlbacher Stephan , Rattei Thomas , Hendrickx Frederik , Manzano-Marín Alejandro , Horn Matthias
Published: June 2022

Bacterial endosymbionts of the groupsWolbachia, CardiniumandRickettsiaceaeare well-known for their diverse effects on their arthropod hosts, ranging from mutualistic relationships to reproductive phenotypes. Here, we analyzed a unique system in which the dwarf spiderOedothorax gibbosusis co-infected with up to five different endosymbionts affiliated withWolbachia, ‘CandidatusTisiphia’ (formerly Torix groupRickettsia), Cardinium,andRhabdochlamydia.Using short-read genome sequencing data, we show that the endosymbionts are heterogeneously distributed amongO. gibbosuspopulations and are frequently found co-infecting spider individuals. To study this intricate host-endosymbiont system on a genome resolved level, we used long-read sequencing to reconstruct closed genomes of theWolbachia, ‘Ca.Tisiphia’ andCardiniumendosymbionts. We provide insights in the ecology and evolution of the endosymbionts and shed light on the interactions with their spider host. We detected high quantities of transposable elements in all endosymbiont genomes and provide evidence that ancestors of theCardinium, ‘Ca.Tisiphia’ andWolbachiaendosymbionts have co-infected the same hosts in the past. Our findings contribute to broadening our knowledge about endosymbionts infecting one of the largest animal phyla on earth and show the usefulness of transposable elements as an evolutionary “contact-tracing” tool.

Data summary

All supporting data, code and protocols have been provided within the article or through supplementary data files. Seven supplementary figures and seven supplementary tables are available with the online version of this article. Sequencing data used in this study was generated and previously published by Hendrickxet al.,2021. Genome assemblies generated in this study have been deposited under the project PRJEB52003 at DDBJ/ENA/GenBank. The MAG ofR. oedothoracisOV001 was deposited at DDBJ/ENA/GenBank under the sample SAMN28026840. The genome of‘CandidatusRhabdochlamydia oedothoracis W744×776’ was previously published by Halteret al.,2022 and is available at DDBJ/ENA/GenBank (accession:CP075587-CP075588). The collection of genomes and proteomes, all files for phylogenetic analyses including gene alignments, concatenated alignments, and tree files, and original output files of the HGT and SNP predictions used in this study are available at zenodo (https://doi.org/10.5281/zenodo.6362846).
A comparison of sleep-wake patterns among school-age children and adolescents in Hong Kong before and during the COVID-19 pandemic
Authors: Chau Steven WH , Hussain Samara , Chan Sandra SM , Wong Oscar WH , Zhang Jihui , Feng Hongliang , Lai Kelly YC , Ma Suk Ling , So Suzanne HW , Tsoi Kelvin KF , Wing Yun Kwok , Hung Se Fong , Leung Patrick WL
Published: June 2022

Background

Lifestyle of children and adolescents have changed extensively during the COVID-19 pandemic due to school suspension and social distancing measures, which can affect their sleep health. Existing studies in the area used convenient samples and focused on the initial months of the pandemic.

Method

As part of a territory-wide epidemiological study in Hong Kong, this cross-sectional study recruited primary and secondary school students by stratified random sampling. We investigated the pandemic’s effects on sleep parameters using multivariate regression, adjusting for age, sex, household income, seasonality and presence of mental disorders, and the effects’ moderators and mediators.

Findings

Between September 1, 2019 and June 2, 2021, 791 primary and 442 school students were recruited and analysed. After correcting for multiple testing, being assessed during COVID predicted a longer sleep latency in primary and secondary school students in school days (95% CI = 1.0–5.2 minutes, adjusted p-value = 0.010; and 95% CI= 3.9–13.0 minutes, adjusted p-value =0.004, respectively) and non-school days (95% CI = 1.7–7.2 minutes, adjusted p-value = 0.005; 95% CI = 3.4–13.7 minutes, adjusted p-value = 0.014, respectively). Low household income was a moderator for later bedtime (adjusted p-value = 0.032) and later sleep onset (adjusted p-value = 0.043) during non-school days among secondary school students. Sex and digital leisure time were not moderator and mediator of the pandemic’s effect on sleep parameters, respectively.

Interpretation

Changes associated with the COVID-19 pandemic have a widespread and enduring effect on sleep health of school-aged students in Hong Kong. Household income play a role in adolescents’ sleep health’s resilience against these changes, and anti-epidemic measures effects on the health gap of the youth should be considered.

Funding

Government of the Hong Kong Special Administrative Region, Food and Health Bureau, Health and Medical Research Fund (Ref. No.: MHS-P1(Part 1)-CUHK).
LIVER-RELATED AND OTHER-CAUSE MORTALITY RISK IN EXCESSIVE DRINKERS: ANALYSIS OF DATA FROM THE UK BIOBANK
Authors: Whitfield John B , Seth Devanshi , Morgan Timothy R ,   GenomALC Consortium
Published: June 2022

Background and Aims

High alcohol intake is associated with increased mortality. We aimed to identify factors affecting mortality in people drinking extreme amounts.

Approach and Results

Information was obtained from the UK Biobank on approximately 500,000 participants aged 40-70 years at baseline assessment in 2006-2010. Habitual alcohol intake, lifestyle and physiological data, laboratory test results, and hospital diagnoses and death certificate data (to June 2020) for 5136 men (2.20% of male participants) and 1504 women (0.60%) who reported taking ≥80 g/day or ≥50g/day, respectively, were used in survival analysis. Compared to all other participants, their mortality HRs were 9.40 (95% CI 7.00-12.64) for any liver disease (ICD-10 K70-K76), 2.02 (1.89-2.17) for all causes, 1.89 (1.69-2.12) for any cancer (C00-C99), and 1.87 (1.61-2.17) for any circulatory disease (I00-I99). Liver disease diagnosis or abnormal liver function tests predicted not only deaths attributed to liver disease but also those from cancers or circulatory diseases. Mortality among excessive drinkers was also associated with quantitative alcohol intake, diagnosed alcohol dependence (ICD-10 F10.2), and current smoking at assessment.

Conclusions

People with chronic excessive alcohol intake experience decreased average survival but there is substantial variation in their mortality, with liver abnormality and alcohol dependence each associated with worse prognosis. Clinically, patients with these risk factors as well as high alcohol intake should be considered for early or intensive management. Research can usefully focus on the factors predisposing to dependence or liver abnormality.
Intrapersonal predictors of internalized stigma among school going adolescents living with HIV in southwestern Uganda
Authors: Kirabira Joseph , Ashaba Scholastic , Favina Allain , Maling Samuel , Nansera Denis , Zanoni Brian C.
Published: June 2022

Background

HIV is one of the most stigmatized conditions globally significantly affecting the quality of life of people living with HIV. Stigma particularly affects adolescents living with HIV (ALHIV) due to challenges associated with developmental stage including physical and psychological changes and the need to build peer relationships. The effect of intrapersonal factors including resilience, health locus of control, self-efficacy, and empowerment on HV stigma among ALHIV in Uganda has not been studied. This study aimed at assessing the association between internalized HIV stigma and resilience, health locus of control, coping self-efficacy and empowerment among ALHIV.

Methods

We conducted a cross-sectional study between August and October 2020 among 173 adolescents who were attending the HIV clinic at Mbarara Regional Referral Hospital. We measured HIV stigma (the internalized AIDS Related Stigma scale), health locus of control (the 18-item Form C version of the Multi-Dimensional Health Locus of Control measure), resilience (25-item Resilience Scale), self-efficacy (the coping self-efficacy scale), and empowerment (the 28-item empowerment scale). Linear regression models were run to determine the association between HIV stigma and intrapersonal factors and adjusted for sociodemographic characteristics.

Results

The median age of participants was 16 (IQR 15-18) years and the median HIV stigma score was 3 (IQR 2-4). There was a negative correlation between HIV stigma and internal health locus of control (b= -0.08, p<0.001), resilience (b= -0.03p<0.001) and coping self-efficacy (b= -0.02, p<0.001) while empowerment score was positively correlated (b= 0.05, p=0.003). However, after mutually adjusting for the intrapersonal factors (resilience, internal locus of control, empowerment and coping self-efficacy), and sociodemographic characteristics, only internal health locus of control (p=0.008) and coping self-efficacy (p<0.001) remained significantly associated with HIV stigma.

Conclusion

Internal health locus of control, resilience, coping self-efficacy and empowerment are strong intrapersonal predictors of internalized stigma among ALHIV. Designing interventions focusing on strengthening these factors among the adolescents may be a significant step in the fight against internalized HIV stigma.
Effective conservation decisions require models designed for purpose: a case study for boreal caribou in Ontario’s Ring of Fire
Authors: Dyson Matt , Endicott Sarah , Simpkins Craig , Turner Julie W. , Avery-Gomm Stephanie , Johnson Cheryl A. , Leblond Mathieu , Neilson Eric W. , Rempel Rob , Wiebe Philip A. , Baltzer Jennifer L. , Hughes Josie , Stewart Frances E.C.
Published: June 2022

Decision making in conservation science often relies on the best available information. This may include using models that were not designed for purpose and are not accompanied by an assessment of limitations. To begin addressing these issues, we sought to reproduce, and evaluate the suitability of, the best available models for predicting impacts of proposed mining on boreal woodland caribou (Rangifer tarandus caribou)resource selection and demography in northern Ontario. We then evaluated their suitability for projecting the impacts of development in the Ring of Fire region. To aid in accessibility, we developed an R package for data preparation, analyses of resource selection, and demographic parameters. We found existing models were either ill suited, or lacking, for ongoing regional planning. The specificity of the regional resource selection model limited its usefulness for predicting impacts of development, and the high variability across caribou ranges limited the usefulness of a national aspatial demographic model for predicting range-specific impacts. Variability in model coefficients across caribou ranges suggests selection responses vary with habitat availability (i.e. a functional response) while demographic responses continue to decline with increasing disturbance. Models designed for forecasting that are continuously updated by range-specific demographic and habitat information, are required to better inform conservation decisions and ongoing policy and planning practices in the Ring of Fire region.
Motor unit dysregulation following 15 days of unilateral lower limb immobilisation
Authors: Inns Thomas B. , Bass Joseph J. , Hardy Edward J.O. , Wilkinson Daniel J. , Stashuk Daniel W. , Atherton Philip J. , Phillips Bethan E. , Piasecki Mathew
Published: June 2022

Disuse atrophy, caused by situations of unloading such as limb immobilisation, causes a rapid yet diverging reduction in skeletal muscle function compared to muscle mass. While mechanistic insight into the loss of mass is well studied, deterioration of muscle function with a focus towards the neural input to muscle remains underexplored. This study aimed to determine the role of motor unit adaptation in disuse-induced neuromuscular deficits. Ten young, healthy male volunteers underwent 15 days of unilateral lower limb immobilisation with intramuscular EMG (iEMG) recorded from the vastus lateralis during knee extensor contractions normalised to maximal voluntary contraction (MVC) pre and post disuse. Muscle cross-sectional area was determined by ultrasound. Individual MUs were sampled and analysed for changes in MU discharge and MU potential (MUP) characteristics. Vastus lateralis (VL) CSA was reduced by approximately 15% which was exceeded by a two-fold decrease of 31% in muscle strength in the immobilised limb, with no change in either parameter in the non-immobilised VL. Parameters of MUP size were largely reduced with immobilisation, while neuromuscular junction (NMJ) transmission instability increased, and MU firing rate decreased at several contraction levels. All adaptations were observed in the immobilised limb only. These findings highlight impaired neural input following immobilisation reflected by suppressed MU discharge rate and instability of transmission at the NMJ which may underpin the disproportionate reductions of strength relative to muscle size.

Key points

Muscle mass and function decline rapidly in situations of disuse such as bed rest and limb immobilisation.

The reduction in muscle function commonly exceeds that of muscle mass, which may be associated with the dysregulation of neural input to the muscle.

We have used intramuscular electromyography to sample individual motor unit and near fibre potentials from the vastus lateralis following 15 days of unilateral limb immobilisation. Following disuse, the disproportionate loss of muscle strength when compared to size was associated with suppressed motor unit firing rate and increased markers of neuromuscular junction transmission instability.

These central and peripheral motor unit adaptations were observed at multiple contraction levels and in the immobilised limb only. Our findings demonstrate neural dysregulation as a key component of functional loss following muscle disuse in humans.
Complex chromosomal rearrangements induced by transposons in maize
Authors: Sharma Sharu Paul , Peterson Thomas
Published: June 2022

Eukaryotic genomes are large and complex, and gene expression can be affected by multiple regulatory elements and their positions within the dynamic chromatin architecture. Transposable Elements (TEs) are known to play important roles in genome evolution, yet questions remain as to how TEs alter genome structure and affect gene expression. Previous studies have shown that genome rearrangements can be induced by Reversed Ends Transposition (RET) involving termini of Activator (Ac) and related TEs in maize and other plants. Here, we show that complex alleles can be formed by the rapid and progressive accumulation of Ac-induced duplications and rearrangements. The p1 gene enhancer in maize can induce ectopic expression of the nearby p2 gene in pericarp tissue when placed near it via different structural rearrangements. By screening for p2 expression, we identified and studied five cases in which multiple sequential transposition events occurred and increased the p1 enhancer copy number. We see active p2 expression due to multiple copies of the p1 enhancer present near p2 in all five cases. The p1 enhancer effects are confirmed by the observation that loss of p2 expression is correlated with transposition-induced excision of the p1 enhancers. We also performed a targeted Chromosome Conformation Capture (3C) experiment to test the physical interaction between the p1 enhancer and p2 promoter region. Together, our results show that transposon-induced rearrangements can accumulate rapidly, and progressively increase genetic variation important for genomic evolution.
Composition and Functional Properties of Hemp Seed Protein Isolates from Various Hemp Cultivars
Authors: Liu Martin , Toth Jacob A. , Childs Mackenzie , Smart Lawrence B. , Abbaspourrad Alireza
Published: June 2022

Hemp seed protein isolates (HPI) were extracted from the seeds of seven commercial hemp cultivars, a Cornell breeding line, and a commercial hemp heart product. The composition and functional properties of the resulting HPI were investigated. HPI were of high protein purity >96% and contained various ratios of the major protein classes edestin, vicilin, and albumin, depending on the source. Protein solubility varied across HPI, and there was a positive correlation between greater levels of vicilin and albumin and improved solubility. The isoelectric points of HPI ranged from 5.50 to 5.94 but did not show significant effects associated with major protein class ratio. Significant differences in HPI foam capacity (52.9–84.9%), foam stability (68.1–89.4%), water holding capacity (0.83–1.05 g water/g protein isolate), and oil holding capacity (1.28–1.81 g oil/g protein isolate) were observed. In general, the emulsions generated from HPI performed poorly in terms of emulsifying activity, stability, and emulsion particle size. The ratio of edestin, vicilin, and albumin was found to play a major role in HPI functionality, suggesting that certain hemp cultivars may be better suited for generating protein ingredients that can functionalize plant-based foods.
Multi-task learning from single-cell multimodal omics with Matilda
Authors: Liu Chunlei , Huang Hao , Yang Pengyi
Published: June 2022

Single-cell multimodal omics technologies enable multiple molecular programs to be simultaneously profiled at a global scale in individual cells, creating opportunities to study biological systems at a resolution that was previously inaccessible. However, the analysis of single-cell multimodal omics data is challenging due to the lack of methods that can integrate across multiple data modalities generated from such technologies. Here, we present Matilda, a multi-task learning method for integrative analysis of single-cell multimodal omics data. By leveraging the interrelationship among tasks, Matilda learns to perform data simulation, dimension reduction, cell type classification, and feature selection in a single unified framework. We compare Matilda with other state-of-the-art methods on datasets generated from some of the most popular single-cell multimodal omics technologies. Our results demonstrate the utility of Matilda for addressing multiple key tasks on integrative single-cell multimodal omics data analysis.
A metagenomic approach to the molecular analysis of bacterial communities in tailings of a gold mine
Authors: Parsania Somayeh , Mohammadi Parisa , Soudi Mohammad Reza , Gharavi Sara
Published: June 2022

Gold mine operations release arsenic pollutants in environment. The present study investigated the diversity of bacterial communities in the arsenic-contaminated tailings dam effluent (TDE) of Zarshuran gold mine, Takab, northwest of Iran. The bacterial communities were examined using the next-generation sequencing method (Illumina) targeting the V3-V4 region of 16S rRNA genes. Bacteroidetes (50.3%), Proteobacteria (45.49%), Actinobacteria (1.14%) and Firmicutes (1.08%) constituted dominant phyla in the TDE. Its diversity was analyzed, and compared with that of three previously-studied arsenic-contaminated groundwater (GW) microbiomes. The raw sequencing data were analyzed in QIIME2. The prevalent taxonomic groups observed in all of the samples belonged to Proteobacteria (8.06-45.49%), Bacteroidetes (1.85-50.32%), Firmicutes (1.00-6.2%), Actinobacteria (0.86-5.09%), Planctomycetes (0.05-9.37%) and Cyanobacteria (0.6-2.71%). According to Principal Coordinates Analysis (PCoA), the TDE and GW samples were divided into high and low groups, based on their arsenic content, respectively. The average numbers of observed alpha diversity indices, i.e. Pielou’s evenness and Faith’s phylogenetic diversity, were not significantly different (P=0.18, Kruskal-Wallis test). According to the beta diversity analysis (unweighted), the observed operational taxonomic units (OTUs) and the diversity of the bacterial populations were not significantly different in the TDE, compared to the GW samples (PERMANOVA, P=0.276, 999 Permutations).
Trends in SARS-CoV-2 infection prevalence during England’s roadmap out of lockdown, January to July 2021
Authors: Eales Oliver , Wang Haowei , Haw David , Ainslie Kylie E. C. , Walters Caroline E. , Atchison Christina , Cooke Graham , Barclay Wendy , Ward Helen , Darzi Ara , Ashby Deborah , Donnelly Christl A. , Elliott Paul , Riley Steven
Published: June 2022

Background

Following rapidly rising COVID-19 case numbers, England entered a national lockdown on 6 January 2021, with staged relaxations of restrictions from 8 March 2021 onwards.

Aim

We characterise how the lockdown and subsequent easing of restrictions affected trends in SARS-CoV-2 infection prevalence.

Methods

On average, risk of infection is proportional to infection prevalence. The REal-time Assessment of Community Transmission-1 (REACT-1) study is a repeat cross-sectional study of over 98,000 people every round (rounds approximately monthly) that estimates infection prevalence in England. We used Bayesian P-splines to estimate prevalence and the time-varying reproduction number (Rt) nationally, regionally and by age group from round 8 (beginning 6 January 2021) to round 13 (ending 12 July 2021) of REACT-1. As a comparator, a separate segmented-exponential model was used to quantify the impact on Rt of each relaxation of restrictions.

Results

Following an initial plateau of 1.54% until mid-January, infection prevalence decreased until 13 May when it reached a minimum of 0.09%, before increasing until the end of the study to 0.76%. Following the first easing of restrictions, which included schools reopening, the reproduction number Rt increased by 82% (55%, 108%), but then decreased by 61% (82%, 53%) at the second easing of restrictions, which was timed to match the Easter school holidays. Following further relaxations of restrictions, the observed Rt increased steadily, though the increase due to these restrictions being relaxed was masked by the effects of vaccination and the rapid rise of Delta. There was a high degree of synchrony in the temporal patterns of prevalence between regions and age groups.

Conclusion

High-resolution prevalence data fitted to P-splines allowed us to show that the lockdown was highly effective at reducing risk of infection with school holidays/closures playing a significant part.