bluuebunny/crossref_metadata_2025 huggingface dataset:
Edge resonance: exact results and fresh insights
Authors: Lawrie Jane B.
Published: September 2023

The eigensystem underpinning the classical edge resonance phenomenon in linear elasticity is studied. Several exact results are presented, the most significant being an identically zero sum demonstrating the linear dependence of the stresses. An exact condition for edge resonance is derived. This is cast into a form that is independent of the Lamb modes, robust and highly convergent, enabling the system to be explored by varying Poisson’s ratio (PR) or frequency. An improved estimate of the value of PR for real resonance is determined, as is the non-Lamé frequency corresponding to resonance when PR is zero. Quasi-resonances are explored. It is demonstrated that, for fixed PR, these occur at more than one frequency, and that they occur for negative PR. It is shown that quasi-resonances are associated with one of two distinct families of complex resonances: real PR and complex frequency or real frequency and complex PR. Higher Lamé frequencies are considered. It is demonstrated that a real pure shear resonance exists at the second Lamé frequency when PR is zero. The corresponding edge displacement is simple in form, and it is anticipated that such resonances exist at every Lamé frequency. Finally, point-wise convergence for Lamb-mode eigenfunction expansions is established.
Freshwater connectivity transforms spatially integrated signals of biodiversity
Authors: Littlefair Joanne E. , Hleap José S. , Palace Vince , Rennie Michael D. , Paterson Michael J. , Cristescu Melania E.
Published: September 2023

Aquatic ecosystems offer a continuum of water flow from headwater streams to inland lakes and coastal marine systems. This spatial connectivity influences the structure, function and dynamics of aquatic communities, which are among the most threatened and degraded on the Earth. Here, we determine the spatial resolution of environmental DNA (eDNA) in dendritic freshwater networks, which we use as a model for connected metacommunities. Our intensive sampling campaign comprised over 420 eDNA samples across 21 connected lakes, allowing us to analyse detections at a variety of scales, from different habitats within a lake to entire lake networks. We found strong signals of within-lake variation in eDNA distribution reflective of typical habitat use by both fish and zooplankton. Most importantly, we also found that connecting channels between lakes resulted in an accumulation of downstream eDNA detections in lakes with a higher number of inflows, and as networks increased in length. Environmental DNA achieves biodiversity surveys in these habitats in a high-throughput, spatially integrated way. These findings have profound implications for the interpretation of eDNA detections in aquatic ecosystems in global-scale biodiversity monitoring observations.
Same process, different patterns: pervasive effect of evolutionary time on species richness in freshwater fishes
Authors: García-Andrade Ana Berenice , Tedesco Pablo A. , Carvajal-Quintero Juan D. , Arango Axel , Villalobos Fabricio
Published: September 2023

Tropical lands harbour the highest number of species, resulting in the ubiquitous latitudinal diversity gradient (LDG). However, exceptions to this pattern have been observed in some taxa, explained by the interaction between the evolutionary histories and environmental factors that constrain species' physiological and ecological requirements. Here, we applied a deconstruction approach to map the detailed species richness patterns of Actinopterygian freshwater fishes at the class and order levels and to disentangle their drivers using geographical ranges and a phylogeny, comprising 77% (12 557) of all described species. We jointly evaluated seven evolutionary and ecological hypotheses posited to explain the LDG: diversification rate, time for speciation, species–area relationship, environmental heterogeneity, energy, temperature seasonality and past temperature stability. We found distinct diversity gradients across orders, including expected, bimodal and inverse LDGs. Despite these differences, the positive effect of evolutionary time explained patterns for all orders, where species-rich regions are inhabited by older species compared to species-poor regions. Overall, the LDG of each order has been shaped by a unique combination of factors, highlighting the importance of performing a joint evaluation of evolutionary, historical and ecological factors at different taxonomic levels to reach a comprehensive understanding on the causes driving global species richness patterns.
Generalized mutualisms promote range expansion in both plant and ant partners
Authors: Nathan Pooja , Economo Evan P. , Guénard Benoit , Simonsen Anna K. , Frederickson Megan E.
Published: September 2023

Mutualism improves organismal fitness, but strong dependence on another species can also limit a species' ability to thrive in a new range if its partner is absent. We assembled a large, global dataset on mutualistic traits and species ranges to investigate how multiple plant–animal and plant–microbe mutualisms affect the spread of legumes and ants to novel ranges. We found that generalized mutualisms increase the likelihood that a species establishes and thrives beyond its native range, whereas specialized mutualisms either do not affect or reduce non-native spread. This pattern held in both legumes and ants, indicating that specificity between mutualistic partners is a key determinant of ecological success in a new habitat. Our global analysis shows that mutualism plays an important, if often overlooked, role in plant and insect invasions.
Deforestation strengthens environmental filtering and competitive exclusion in Neotropical streams and rivers
Authors: Cantera Isabel , Jézéquel Céline , Dejean Tony , Murienne Jérôme , Vigouroux Régis , Valentini Alice , Brosse Sébastien
Published: September 2023

Understanding how anthropization impacts the assembly of species onto communities is pivotal to go beyond the observation of biodiversity changes and reveal how disturbances affect the environmental and biotic processes shaping biodiversity. Here, we propose a simple framework to measure the assembly processes underpinning functional convergence/divergence patterns. We applied this framework to northern Amazonian fish communities inventoried using environmental DNA in 35 stream sites and 64 river sites. We found that the harsh and unstable environmental conditions characterizing streams conveyed communities towards functional convergence, by filtering traits related to food acquisition and, to a lower extent, dispersal. Such environmental filtering also strengthened competition by excluding species having less competitive food acquisition traits. Instead, random species assembly was more marked in river communities, which may be explained by the downstream position of rivers facilitating the dispersion of species. Although fish assembly rules differed between streams and river fish communities, anthropogenic disturbances reduced functional divergence in both ecosystems, with a reinforcement of both environmental filtering and weaker competitor exclusion. This may explain the substantial biodiversity alterations observed under slight deforestation levels in Neotropical freshwater ecosystems and underlines their vulnerability to anthropic disturbances that not only affect species persistence but also modify community assembly rules.
Pre-mandibular pharyngeal pouches in early non-teleost fish embryos
Authors: Horackova Agata , Pospisilova Anna , Stundl Jan , Minarik Martin , Jandzik David , Cerny Robert
Published: September 2023

The vertebrate pharynx is a key embryonic structure with crucial importance for the metameric organization of the head and face. The pharynx is primarily built upon progressive formation of paired pharyngeal pouches that typically develop in post-oral (mandibular, hyoid and branchial) domains. However, in the early embryos of non-teleost fishes, we have previously identified pharyngeal pouch-like outpocketings also in the pre-oral domain of the cranial endoderm. This pre-oral gut (POG) forms by early pouching of the primitive gut cavity, followed by the sequential formation of typical (post-oral) pharyngeal pouches. Here, we tested the pharyngeal nature of the POG by analysing expression patterns of selected core pharyngeal regulatory network genes in bichir and sturgeon embryos. Our comparison revealed generally shared expression patterns, including
Shh, Pax9
,
Tbx1, Eya1
,
Six1
,
Ripply3
or
Fgf8,
between early POG and post-oral pharyngeal pouches
.
POG thus shares pharyngeal pouch-like morphogenesis and a gene expression profile with pharyngeal pouches and can be regarded as a pre-mandibular pharyngeal pouch. We further suggest that pre-mandibular pharyngeal pouches represent a plesiomorphic vertebrate trait inherited from our ancestor's pharyngeal metameric organization, which is incorporated in the early formation of the pre-chordal plate of vertebrate embryos.
The first arriving virus shapes within-host viral diversity during natural epidemics
Authors: Jokinen Maija , Sallinen Suvi , Jones Mirkka M. , Sirén Jukka , Guilbault Emy , Susi Hanna , Laine Anna-Liisa
Published: September 2023

Viral diversity has been discovered across scales from host individuals to populations. However, the drivers of viral community assembly are still largely unknown. Within-host viral communities are formed through co-infections, where the interval between the arrival times of viruses may vary. Priority effects describe the timing and order in which species arrive in an environment, and how early colonizers impact subsequent community assembly. To study the effect of the first-arriving virus on subsequent infection patterns of five focal viruses, we set up a field experiment using naïve
Plantago lanceolata
plants as sentinels during a seasonal virus epidemic. Using joint species distribution modelling, we find both positive and negative effects of early season viral infection on late season viral colonization patterns. The direction of the effect depends on both the host genotype and which virus colonized the host early in the season. It is well established that co-occurring viruses may change the virulence and transmission of viral infections. However, our results show that priority effects may also play an important, previously unquantified role in viral community assembly. The assessment of these temporal dynamics within a community ecological framework will improve our ability to understand and predict viral diversity in natural systems.
ENQUIRE RECONSTRUCTS AND EXPANDS CONTEXT-SPECIFIC CO-OCCURRENCE NETWORKS FROM BIOMEDICAL LITERATURE
Authors: Musella Luca , Lai Xin , Widmann Max , Vera Julio
Published: September 2023

The accelerating growth of scientific literature overwhelms our capacity to manually distil complex phenomena like molecular networks linked to diseases. Moreover, biases in biomedical research and database annotation limit our interpretation of facts and generation of hypotheses. ENQUIRE (Expanding Networks by Querying Unexpectedly Inter-Related Entities) offers a time- and resource-efficient alternative to manual literature curation and database mining. ENQUIRE reconstructs and expands co-occurrence networks of genes and biomedical ontologies from user-selected input corpora and network-inferred PubMed queries. The integration of text mining, automatic querying, and network-based statistics mitigating literature biases makes ENQUIRE unique in its broad-scope applications. For example, ENQUIRE can generate co-occurrence gene networks that reflect high-confidence, functional networks. When tested on case studies spanning cancer, cell differentiation and immunity, ENQUIRE identified interlinked genes and enriched pathways unique to each topic, thereby preserving their underlying diversity. ENQUIRE supports biomedical researchers by easing literature annotation, boosting hypothesis formulation, and facilitating the identification of molecular targets for subsequent experimentation.

GRAPHICAL ABSTRACT
Genome-wide patterns of homoeologous gene flow in allotetraploid coffee
Authors: Ortiz Andre J. , Sharbrough Joel
Published: September 2023

Premise

Allopolyploidy – a hybridization-induced whole-genome duplication event – has been a major driver of plant diversification. The extent to which chromosomes pair with their proper homolog vs. with their homoeolog in allopolyploids varies across taxa, and methods to detect homoeologous gene flow (HGF) are needed to understand how HGF has shaped polyploid lineages.

Methods

The ABBA-BABA test represents a classic method for detecting introgression between closely related species, but here we developed a modified use of the ABBA-BABA test to characterize the extent and direction of HGF in allotetraploidCoffea arabica.

Results

We found that HGF is abundant in theC. arabicagenome, with both subgenomes serving as donors and recipients of variation. We also found that HGF is highly maternally biased in plastid-targeted – but not mitochondrial-targeted – genes, as would be expected if plastid-nuclear incompatibilities exist between the two parent species.

Discussion

Together our analyses provide a simple framework for detecting HGF and new evidence consistent with selection favoring overwriting of paternally derived alleles by maternally derived alleles to ameliorate plastid-nuclear incompatibilities. Natural selection therefore appears to shape the direction and intensity of HGF in allopolyploid coffee, indicating that cytoplasmic inheritance has long-term consequences for polyploid lineages.
Neurotransmitter signaling specifies sweat gland stem cell fate through SLN-mediated intracellular calcium regulation
Authors: Remark Juliana , Tong Jie , Lin Meng Ju , Concepcion Axel , Mareedu Satvik , Babu Gopal J , Feske Stefan , Lu Catherine P.
Published: September 2023

Sympathetic nerves co-develop with their target organs and release neurotransmitters to stimulate their functions after maturation. Here, we provide the molecular mechanism that during sweat gland morphogenesis, neurotransmitters released from sympathetic nerves act first to promote sweat duct elongation via norepinephrine and followed by acetylcholine to specify sweat gland stem cell fate, which matches the sequence of neurotransmitter switch. Without neuronal signals during development, the basal cells switch to exhibit suprabasal (luminal) cell features. Sarcolipin (SLN), a key regulator of sarcoendoplasmic reticulum (SR) Ca2+-ATPase (SERCA), expression is significantly down-regulated in the sweat gland myoepithelial cells upon denervation. Loss of SLN in sweat gland myoepithelial cells leads to decreased intracellular Ca2+over time in response to ACh stimulation, as well as upregulation of luminal cell features. In cell culture experiments, we showed that contrary to the paradigm that elevation of Ca2+promote epidermal differentiation, specification of the glandular myoepithelial (basal) cells requires high Ca2+while lowering Ca2+level promotes luminal (suprabasal) cell fate. Our work highlights that neuronal signals not only act transiently for mature sweat glands to function, but also exert long-term impact on glandular stem cell specification through regulating intracellular Ca2+dynamics.
SOX4-SMARCA4 complex promotes glycolysis-dependent TNBC cell growth through transcriptional regulation of Hexokinase 2
Authors: Khanna Pooja , Mehta Rushabh , Mehta Gaurav A. , Bhatt Vrushank , Guo Jessie Y. , Gatza Michael L.
Published: September 2023

Tumor cells rely on increased glycolytic capacity to promote cell growth and progression. While glycolysis is known to be upregulated in the majority of triple negative (TNBC) or basal-like subtype breast cancers, the mechanism remains unclear. Here, we used integrative genomic analyses to identify a subset of basal-like tumors characterized by increased expression of the oncogenic transcription factor SOX4 and its co-factor the SWI/SNF ATPase SMARCA4. These tumors are defined by unique gene expression programs that correspond with increased tumor proliferation and activation of key metabolic pathways, including glycolysis. Mechanistically, we demonstrate that the SOX4-SMARCA4 complex mediates glycolysis through direct transcriptional regulation of Hexokinase 2 (HK2) and that aberrant HK2 expression and altered glycolytic capacity are required to mediate SOX4-SMARCA4-dependent cell growth. Collectively, we have defined the SOX4-SMARCA4-HK2 signaling axis in basal-like breast tumors and established that this axis promotes metabolic reprogramming which is required to maintain tumor cell growth.
Understanding the Impacts and Perceptions of Alcohol Use in Northern Tanzania: A Mixed-Methods Analysis
Authors: Pauley Alena , Metcalf Madeline , Buono Mia , West Kirstin , Rent Sharla , Nkenguye William , Sawe Yvonne , Mikindo Mariana , Kilasara Joseph , Mchome Bariki , Mmbaga Blandina T. , Nickenig Vissoci João Ricardo , Staton Catherine A.
Published: September 2023

Abstract

Background

Worldwide, alcohol is a leading risk factor for death and disability. Tanzania has particularly high rates of consumption and few resources dedicated to minimizing alcohol-related harm. Ongoing policy efforts are hampered by dynamic sociocultural, economic, and regulatory factors contributing to alcohol consumption. Through the voices of Kilimanjaro Christian Medical Center (KCMC) patients and a gender-focused lens, the goal of this project was to investigate community perceptions surrounding alcohol and the impact of its use in this region.

Methods

This was a mixed-methods study conducted at KCMC between October 2021 and May 2022. 678 adult (≥18 years old) Kiswahili-speaking patients who presented to KCMC’s Emergency Department (ED) or Reproductive Health Clinic (RHC) were enrolled through systematic random sampling to participate in quantitative surveys. Nineteen participants were selected for in-depth interviews (IDIs) through purposeful sampling. The impact and perceptions of alcohol use were measured through Drinkers’ Inventory of Consequences (DrInC) scores analyzed in R Studio through descriptive proportions, and IDI responses explored through a grounded theory approach utilizing both inductive and deductive coding methodologies.

Results

ED men were found to have the highest average [SD] DrInC scores (16.4 [19.6]), followed by ED women (9.11 [13.1]), and RHC women (5.47 [9.33]), with higher scores indicating greater perceived consequences. Participants noted alcohol has both perceived advantages and clear harms within their community. Increased conflict, long-term health outcomes, financial instability, stigma, and sexual assault were seen as negative consequences. Benefits were primarily identified for men and included upholding cultural practices, economic growth, and social unity. Physical and financial harm from alcohol impacted both genders, however, alcohol-related stigma and sexual assault were found to disproportionately affect women.

Conclusion

Our findings suggest that perceptions around drinking and alcohol’s social and physical consequences differ significantly by gender. To effectively minimize local alcohol-related harm, future alcohol-focused research and policy efforts should consider the distinct impacts alcohol has between genders.
Expression Level Analysis of ACE2 Receptor Gene in African-American and Non-African-American COVID-19 Patients
Authors: Nyamari Marion N. , Omar Kauthar M. , Fayehun Ayorinde F. , Dachi Oumaima , Bwana Billiah Kemunto , Awe Olaitan I.
Published: September 2023

Background

The COVID-19 pandemic caused by SARS-CoV-2 has spread rapidly across the continents. While the incidence of COVID-19 has been reported to be higher among African-American individuals, the rate of mortality has been lower compared to that of non-African-Americans. ACE2 is involved in COVID-19 as SARS-CoV-2 uses the ACE2 enzyme to enter host cells. Although the difference in COVID-19 incidence can be explained by many factors such as low accessibility of health insurance among the African-American community, little is known about ACE2 expression in African-American COVID-19 patients compared to non-African-American COVID-19 patients. The variable expression of genes can contribute to this observed phenomenon.

Methodology

In this study, transcriptomes from African-American and non-African-American COVID-19 patients were retrieved from the sequence read archive and analyzed for ACE2 gene expression. HISAT2 was used to align the reads to the human reference genome, and HTseq-count was used to get raw gene counts. EdgeR was utilized for differential gene expression analysis, and enrichR was employed for gene enrichment analysis.

Results

The datasets included 14 and 33 transcriptome sequences from COVID-19 patients of African-American and non-African-American descent, respectively. There were 24,092 differentially expressed genes, with 7,718 upregulated (log fold change > 1 and FDR 0.05) and 16,374 downregulated (log fold change −1 and FDR 0.05). The ACE2 mRNA level was found to be considerably downregulated in the African-American cohort (p-value = 0.0242, p-adjusted value = 0.038).

Conclusion

The downregulation of ACE2 in the African-American cohort could indicate a correlation to the low COVID-19 severity observed among the African-American community.
Minimal circuit motifs for second-order conditioning in the insect mushroom body
Authors: Jürgensen Anna-Maria , Schmitt Felix Johannes , Nawrot Martin Paul
Published: September 2023

In well-established first-order conditioning experiments, the concurrence of a sensory cue with reinforcement forms an association, allowing the cue to predict future reinforcement. Once a sensory cue is established as a predictor, it can also serve as indirect reinforcement, a phenomenon referred to as second-order conditioning. In the insect mushroom body, such associations are encoded in the plasticity of the synapses between the intrinsic and output neurons of the mushroom body, a process mediated by the activity of dopaminergic neurons that encode reinforcement signals. In second-order conditioning, a new sensory cue is paired with an already established one that presumably activates dopaminergic neurons due to its predictive power of the reinforcement. We explore minimal circuit motifs in the mushroom body for their ability to support second-order conditioning. We found that dopaminergic neurons can either be activated directly by the mushroom body’s intrinsic neurons or via feedback from the output neurons via several pathways. We demonstrate that the circuit motifs differ in their computational efficiency and robustness and suggest a particular motif that relies on feedforward input of the mushroom body intrinsic neurons to dopaminergic neurons as a promising additional candidate for experimental evaluation. It differentiates well between trained and novel stimuli, demonstrating robust performance across a range of model parameters.
Examining Functional Linkages Between Conformational Dynamics, Protein Stability and Evolution of Cryptic Binding Pockets in the SARS-CoV-2 Omicron Spike Complexes with the ACE2 Host Receptor: Recombinant Omicron Variants Mediate Variability of Conserved Allosteric Sites and Binding Epitopes
Authors: Alshahrani Mohammed , Gupta Grace , Xiao Sian , Tao Peng , Verkhivker Gennady
Published: September 2023

In the current study, we explore coarse-grained simulations and atomistic molecular dynamics together with binding energetics scanning and cryptic pocket detection in a comparative examination of conformational landscapes and systematic characterization of allosteric binding sites in the SARS-CoV-2 Omicron BA.2, BA.2.75 and XBB.1 spike full-length trimer complexes with the host receptor ACE2. Microsecond simulations, Markov state models and mutational scanning of binding energies of the SARS-CoV-2 BA.2 and BA.2.75 receptor binding domain complexes revealed the increased thermodynamic stabilization of the BA.2.75 variant and significant dynamic differences between these Omicron variants. Molecular simulations of the SARS-CoV-2 Omicron spike full length trimer complexes with the ACE2 receptor complemented atomistic studies and enabled an in-depth analysis of mutational and binding effects on conformational dynamic and functional adaptability of the Omicron variants. Despite considerable structural similarities, Omicron variants BA.2, BA.2.75 and XBB.1 can induce unique conformational dynamic signatures and specific distributions of the conformational states. Using conformational ensembles of the SARS-CoV-2 Omicron spike trimer complexes with ACE2, we conducted a comprehensive cryptic pocket screening to examine the role of Omicron mutations and ACE2 binding on the distribution and functional mechanisms of the emerging allosteric binding sites. This analysis captured all experimentally known allosteric sites and discovered networks of inter-connected and functionally relevant allosteric sites that are governed by variant-sensitive conformational adaptability of the SARS-CoV-2 spike structures. The results detailed how ACE2 binding and Omicron mutations in the BA.2, BA.2.75 and XBB.1 spike complexes modulate the distribution of conserved and druggable allosteric pockets harboring functionally important regions. The results of are significant for understanding functional roles of druggable cryptic pockets that can be used for allostery-mediated therapeutic intervention targeting conformational states of the Omicron variants.
Immune Evasion, Infectivity, and Fusogenicity of SARS-CoV-2 Omicron BA.2.86 and FLip Variants
Authors: Qu Panke , Xu Kai , Faraone Julia N. , Goodarzi Negin , Zheng Yi-Min , Carlin Claire , Bednash Joseph S. , Horowitz Jeffrey C. , Mallampalli Rama K. , Saif Linda J. , Oltz Eugene M. , Jones Daniel , Gumina Richard J. , Liu Shan-Lu
Published: September 2023

Evolution of SARS-CoV-2 requires the reassessment of current vaccine measures. Here, we characterized BA.2.86 and the XBB-lineage variant FLip by investigating their neutralization alongside D614G, BA.1, BA.2, BA.4/5, XBB.1.5, and EG.5.1 by sera from 3-dose vaccinated and bivalent vaccinated healthcare workers, XBB.1.5-wave infected first responders, and monoclonal antibody (mAb) S309. We assessed the biology of the variant Spikes by measuring viral infectivity and membrane fusogenicity. BA.2.86 is less immune evasive compared to FLip and other XBB variants, consistent with antigenic distances. Importantly, distinct from XBB variants, mAb S309 was unable to neutralize BA.2.86, likely due to a D339H mutation based on modeling. BA.2.86 had relatively high fusogenicity and infectivity in CaLu-3 cells but low fusion and infectivity in 293T-ACE2 cells compared to some XBB variants, suggesting a potentially differences conformational stability of BA.2.86 Spike. Overall, our study underscores the importance of SARS-CoV-2 variant surveillance and the need for updated COVID-19 vaccines.
MSMEG_0311 is a conserved essential polar protein involved in mycobacterium cell wall metabolism
Authors: Sodani Megha , Misra Chitra S. , Kulkarni Savita , Rath Devashish
Published: September 2023

Cell wall synthesis and cell division are two closely linked pathways in a bacterial cell which distinctly influence the growth and survival of a bacterium. This requires an appreciable coordination between the two processes, more so, in case of mycobacteria with an intricate multi-layered cell wall structure. In this study, we investigated a conserved gene cluster and show that knockdown of most of the genes in this cluster leads to growth defects. We further characterised one of the genes, MSMEG_0311. The repression of this gene not only imparts severe growth defect but also changes colony morphology. We demonstrate that the protein preferentially localises to the polar region and show its influence on the polar growth of the bacillus. A combination of permeability and drug susceptibility assay strongly suggests a cell wall associated function of this gene which is also corroborated by transcriptomic analysis of the knockdown. Considering the gene is highly conserved across mycobacterial species and appears to be essential for growth, it may serve as a potential drug target.
A systematic review on the incidence of influenza viruses in wastewater matrices: Implications for Public Health
Authors: Dlamini Mbasa , Msolo Luyanda , Ebomah Kingsley Ehi , Nontongana Nolonwabo , Okoh Anthony Ifeanyi
Published: September 2023

Influenza has historically been and remains a significant global health concern, causing substantial illness worldwide. Influenza is a serious public health issue in both industrialized and developing nations and it is characterized as an acute respiratory illness resulting from infection with influenza virus. Influenza viruses are RNA viruses with a negative sense and enveloped structure. These viruses possess segmented genomes, with influenza A and B viruses being the prevalent types affecting human populations. These viruses have been associated with disease outbreaks in some regions of the world as a result of excrement being introduced into the environment. Given the global implications of influenza and the limited availability of data for many countries, particularly in the African region where the prevalence and incidence of influenza remain largely unknown, there is a lack of published information regarding the detection of influenza viruses. Therefore, the purpose of this paper is to examine or review the frequency of influenza virus detection in wastewater samples, serving as an initial step toward gaining a better understanding of the burden of influenza. This includes exploring its epidemiology, the consequences of severe influenza infections, and the development of strategies to enhance supportive care and virus-specific therapies in resource-constrained, low-income settings.
Determinants ofde novoB cell responses to drifted epitopes in post-vaccination SARS-CoV-2 infections
Authors: Quirk Grace E. , Schoenle Marta V. , Peyton Kameron L. , Uhrlaub Jennifer L. , Lau Branden , Burgess Jefferey L. , Ellingson Katherine , Beitel Shawn , Romine James , Lutrick Karen , Fowlkes Ashley , Britton Amadea , Tyner Harmony L. , Caban-Martinez Alberto J. , Naleway Allison , Gaglani Manjusha , Yoon Sarang , Edwards Laura , Olsho Lauren , Dake Michael , LaFleur Bonnie J. , Nikolich Janko Ž. , Sprissler Ryan , Worobey Michael , Bhattacharya Deepta
Published: September 2023

Vaccine-induced immunity may impact subsequentde novoresponses to drifted epitopes in SARS-CoV-2 variants, but this has been difficult to quantify due to the challenges in recruiting unvaccinated control groups whose first exposure to SARS-CoV-2 is a primary infection. Through local, statewide, and national SARS-CoV-2 testing programs, we were able to recruit cohorts of individuals who had recovered from either primary or post-vaccination infections by either the Delta or Omicron BA.1 variants. Regardless of variant, we observed greater Spike-specific and neutralizing antibody responses in post-vaccination infections than in those who were infected without prior vaccination. Through analysis of variant-specific memory B cells as markers ofde novoresponses, we observed that Delta and Omicron BA.1 infections led to a marked shift in immunodominance in which some drifted epitopes elicited minimal responses, even in primary infections. Prior immunity through vaccination had a small negative impact on thesede novoresponses, but this did not correlate with cross-reactive memory B cells, arguing against competitive inhibition of naïve B cells. We conclude that dampenedde novoB cell responses against drifted epitopes are mostly a function of altered immunodominance hierarchies that are apparent even in primary infections, with a more modest contribution from pre-existing immunity, perhaps due to accelerated antigen clearance.
Digital markers from smartwatch data relate to non-motor clinical examinations of Parkinson’s disease
Authors: Schalkamp Ann-Kathrin , Harrison Neil A , Peall Kathryn J , Sandor Cynthia
Published: September 2023

Monitoring of Parkinson’s disease (PD) has seen substantial improvement over recent years as digital sensors enable a passive and continuous collection of information in the home environment. However, the primary focus of this work has been motor symptoms, with little focus on the non-motor aspects of the disease. To address this, we combined longitudinal clinical non-motor assessment data and digital multi-sensor data from the Verily Study Watch for 85 participants from the Parkinson’s Progression Monitoring Initiative (PPMI) cohort with a diagnosis of PD. We show that digitally collected physical activity and sleep markers do significantly relate to clinical non-motor assessments of cognitive, autonomic, and daily living impairment. The observed poor predictive performance, however, highlights the need for better targeted digital markers to enable a monitoring of non-motor symptoms.
Prevalence of Long COVID-associated symptoms in adults with and without SARS-CoV-2 infection in Germany: Results of the population-based study “Corona Monitoring Nationwide 2021/22” (RKI-SOEP-2)
Authors: Poethko-Müller Christina , Ordonez-Cruickshank Ana , Nübel Julia , Sarganas Giselle , Gößwald Antje , Schmid Lorenz , Rosario Angelika Schaffrath , Hoebel Jens , Schlaud Martin , Scheidt-Nave Christa
Published: September 2023

Background

Controlled population-based studies on long-term health sequelae of SARS-CoV-2 can help to identify clinical signs specific to “Long COVID” and to evaluate this emerging public health challenge.

Aim

To examine prevalence differences of Long COVID-associated symptoms among adults with and without SARS-CoV-2 infection in Germany.

Methods

This population-based, retrospective study (11/2021-2/2022) included 7,683 working aged adults (18-65 years), a subset of the Corona Monitoring Nationwide study in Germany. Prior SARS-CoV-2 infection was defined based on self-reported PCR-confirmed infections and IgG-antibody dried blood spot testing. Participants answered a questionnaire including 19 common symptoms of Long COVID experienced in the six months preceding the survey. We estimated population-weighted prevalence of (1) individual symptoms, and (2) ≥1 symptom, with and without impact on work ability, by infection status within strata of sex, age group, income and comorbidity. We calculated model-adjusted prevalence differences and the probability that symptoms among infected are attributable to infection.

Results

12 of 19 symptoms showed a significantly higher prevalence in infected than non-infected participants, including fatigue (27.5% versus 18.3%; p<0.001), concentration problems (22.2% vs. 13.1%; p<0.001), shortness of breath (15.6% vs. 7.5%; p<0.001), and smell and taste disorder (10% vs. 1.2%; p<0.001). ≥1 symptom with impact on work ability was more prevalent following infection (16.0% vs. 12.2%; p=0.06) with a model-adjusted prevalence difference of 3.8% (95%-CI -0.5-8.0).

Conclusion

We observed a rather small excess prevalence attributable to SARS-CoV-2 infection. However, the absolute number of persons places great demands on the health care system and may affect economic productivity.
Stress Biomarkers and Child Development in Young Children in Bangladesh
Authors: Butzin-Dozier Zachary , Mertens Andrew N. , Tan Sophia T. , Granger Douglas A. , Pitchik Helen O. , Il’yasova Dora , Tofail Fahmida , Rahman Md. Ziaur , Spasojevic Ivan , Shalev Idan , Ali Shahjahan , Karim Mohammed Rabiul , Shahriar Sunny , Famida Syeda Luthfa , Shuman Gabrielle , Shoab Abul K. , Akther Salma , Hossen Md. Saheen , Mutsuddi Palash , Rahman Mahbubur , Unicomb Leanne , Das Kishor K. , Yan Liying , Meyer Ann , Stewart Christine P. , Hubbard Alan , Naved Ruchira Tabassum , Parvin Kausar , Mamun Md. Mahfuz Al , Luby Stephen P. , Colford John M. , Fernald Lia C. H. , Lin Audrie
Published: September 2023

Background

Hundreds of millions of children in low-and middle-income countries are exposed to chronic stressors, such as poverty, poor sanitation and hygiene, and sub-optimal nutrition. These stressors can have physiological consequences for children and may ultimately have detrimental effects on child development. This study explores associations between biological measures of chronic stress in early life and developmental outcomes in a large cohort of young children living in rural Bangladesh.

Methods

We assessed physiologic measures of stress in the first two years of life using measures of the hypothalamic-pituitary-adrenal (HPA) axis (salivary cortisol and glucocorticoid receptor gene methylation), the sympathetic-adrenal-medullary (SAM) system (salivary alpha-amylase, heart rate, and blood pressure), and oxidative status (F2-isoprostanes). We assessed child development in the first two years of life with the MacArthur-Bates Communicative Development Inventories (CDI), the WHO gross motor milestones, and the Extended Ages and Stages Questionnaire (EASQ). We compared development outcomes of children at the 75th and 25th percentiles of stress biomarker distributions while adjusting for potential confounders (hereafter referred to as contrasts) using generalized additive models, which are statistical models where the outcome is predicted by a potentially non-linear function of predictor variables.

Results

We analyzed data from 684 children (49% female) at both 14 and 28 months of age; we included an additional 765 children at 28 months of age. We observed 135 primary contrasts of the differences in child development outcomes at the 75thand 25thpercentiles of stress biomarkers, where we detected significant relationships in 5 out of 30 contrasts (17%) of HPA axis activity, 1 out of 30 contrasts (3%) of SAM activity, and 3 out of 75 contrasts (4%) of oxidative status. These findings revealed that measures of HPA axis activity were associated with poor development outcomes. We did not find consistent evidence that markers of SAM system activity or oxidative status were associated with developmental status.

Conclusions

Our observations reveal associations between the physiological evidence of stress in the HPA axis with developmental status in early childhood. These findings add to the existing evidence exploring the developmental consequences of early life stress.
Brain-Wide Mendelian Randomization Study of Anxiety Disorders and Symptoms
Authors: Zanoaga Mihaela-Diana , Friligkou Eleni , He Jun , Pathak Gita A. , Koller Dora , Cabrera-Mendoza Brenda , Stein Murray B. , Polimanti Renato
Published: September 2023

Background

To gain insights into the role of brain structure and function on anxiety (ANX), we conducted a genetically informed investigation leveraging information from ANX genome-wide association studies available from UK Biobank (UKB; N=380,379), FinnGen Program (N=290,361), and Million Veteran Program (MVP; N=199,611) together with UKB genome-wide data (N=33,224) related to 3,935 brain imaging-derived phenotypes (IDP).

Methods

A genetic correlation analysis between ANX and brain IDPs was performed using linkage disequilibrium score regression. To investigate ANX–brain associations, a two-sample Mendelian randomization (MR) was performed considering multiple methods and sensitivity analyses. A subsequent multivariable MR (MVMR) was executed to distinguish between direct and indirect effects. Finally, a generalized linear model was used to explore the associations of brain IDPs with ANX symptoms.

Results

After false discovery rate correction (FDR q<0.05), we identified 41 brain IDPs genetically correlated with ANX without heterogeneity among the datasets investigated (i.e., UKB, FinnGen, and MVP). Six of these IDPs showed genetically inferred causal effects on ANX. In the subsequent MVMR analysis, reduced area of the right posterior middle-cingulate gyrus (rpMCG; beta=-0.09, P= 8.01×10-4) and reduced gray-matter volume of the right anterior superior temporal gyrus (raSTG; beta=-0.09, P=1.55×10-3) had direct effects on ANX. In the ANX symptom-level analysis, rpMCG was negatively associated with “tense sore oraching muscles during the worst period of anxiety” (beta=-0.13, P=8.26×10-6).

Conclusions

This study identified genetically inferred effects generalizable across large cohorts, contributing to understand how changes in brain structure and function can lead to ANX.
Development and Standardization of a Classification System for Osteoradionecrosis: Implementation of a Risk-Based Model
Authors: Watson Erin E , Hueniken Katrina , Lee Junhyung , Huang Sophie H , Maghrabi A Amr El , Xu Wei , Moreno Amy C , Tsai C. Jillian , Hahn Ezra , McPartlin Andrew J , Yao Christopher MKL , Goldstein David P , De Almeida John R , Waldon John N , Fuller Clifton David , Hope Andrew J , Ruggiero Salvatore L , Glogauer Michael , Hosni Ali A
Published: September 2023

Purpose

Osteoradionecrosis of the jaw (ORN) can manifest in varying severity. The aim of this study is to identify ORN risk factors and develop a novel classification to depict the severity of ORN.

Methods

Consecutive head-and-neck cancer (HNC) patients treated with curative-intent IMRT (≥45Gy) in 2011-2018 were included. Occurrence of ORN was identified from in-house prospective dental and clinical databases and charts. Multivariable logistic regression model was used to identify risk factors and stratify patients into high-risk and low-risk groups. A novel ORN classification system was developed to depict ORN severity by modifying existing systems and incorporating expert opinion. The performance of the novel system was compared to fifteen existing systems for their ability to identify and predict serious ORN event (jaw fracture or requiring jaw resection).

Results

ORN was identified in 219 out of 2732 (8%) consecutive HNC patients. Factors associated with high-risk of ORN were: oral-cavity or oropharyngeal primaries, received IMRT dose ≥60Gy, current/ex-smokers, and/or stage III-IV periodontal disease. The ORN rate for high-risk vs low-risk patients was 12.7% vs 3.1% (p<0.001) with an area-under-the-receiver-operating-curve (AUC) of 0.71. Existing ORN systems overclassified serious ORN events and failed to recognize maxillary ORN. A novel ORN classification system, RadORN, was proposed based on vertical extent of bone necrosis and presence/absence of exposed bone/fistula. This system detected serious ORN events in 5.7% of patients and statistically outperformed existing systems.

Conclusion

We identified risk factors for ORN, and proposed a novel ORN classification system based on vertical extent of bone necrosis and presence/absence of exposed bone/fistula. It outperformed existing systems in depicting the seriousness of ORN, and may facilitate clinical care and clinical trials.
Challenges in the implementation of preventive treatment for tuberculosis in people living with HIV/Aids: A qualitative study
Authors: Reis Vânia Silva dos , Nascimento Débora Dupas Gonçalves do , Silva Terezinha Alcântara da , Paniago Anamaria Mello Miranda , Negri Adriana Carla Garcia , Ferreira Gabriela , Ferreira Rafaela , Lemos Everton Ferreira , Trajman Anete , Oliveira Sandra Maria do Valle Leone de
Published: September 2023

Treatment of tuberculosis infection (TBI) in people living with HIV/Aids (PLWHA) reduces the risk of tuberculosis disease (TBD), the main cause of death in this population. Recognizing the barriers related to the scale up of tuberculosis preventive treatment (TPT) can contribute to reorganization of health services for achieving TB elimination. This qualitative study aimed to understand the perception of specialized care health professionals of a capital city in Brazil about TPT for PLWHA. Between October 2020 and August 2022 ten physicians and four nurses working for more than six months in reference HIV/Aids services were interviewed. Interviews were guided by a script of previously validated, semi-structured questions. The audios were recorded, transcribed, and categorized based on Grounded Theory, and its analysis was anchored in the theoretical framework of Symbolic Interactionism. Sampling was performed using theoretical saturation. The emerged central phenomenon “Facing challenges in the implementation of TPT in the light of scientific evidence” was supported by four categories:1) Demonstrating theoretical knowledge regarding TBI and its treatment guidelines; 2) Dealing with the complexities of guidelines adherence in the routine service; 3) Building bonds to overcome different challenges in the care of PLWHA; 4) Seeking strategies to facilitate adherence to the TPT guidelines service. Professionals faced challenges in implementing TPT due to structural obstacles in service, hesitation in establishing therapy, and the risk of adverse events when dealing with patients’ vulnerabilities, despite available scientific evidence, theoretical knowledge, and guidelines recommendations. They envisaged ideal conditions to adhere to the TPT guidelines in service, and seeked to mediate confrontations by strengthening their bond with patients through multidisciplinary interaction, teaching, and research.
Prevalence and Risk Factors of Hypertension among Patients with Opioid Use Disorder in Methadone Maintenance Treatment
Authors: Sason Anat , Adelson Miriam , Schreiber Shaul , Peles Einat
Published: September 2023

BACKGROUND

The current prevalence of hypertension (HTN) and risk factors that characterize its occurrence during long-term methadone maintenance treatment (MMT) have not been established.

METHODS

HTN was defined if either systolic blood pressure (BP) ≥140 mmHg or diastolic BP ≥90 mmHg was detected twice (one week apart) among adult MMT patients. Recorded and current body mass index (BMI), BP, methadone dose and serum level, and drugs in urine were analyzed. Data on socioeconomic and addiction history characteristics were also retrieved.

RESULTS

HTN was detected in 103 (35.4%) of the 291 study patients (age range 26-81 years, 62 females). The HTN and non-HTN groups were comparable in sex (P=0.3), age (56.6±9.6 vs. 55.3±9.7 years,P=0.3), and duration in MMT (13.0±9.1 vs. 12.5±8.6 years,P=0.7). Age correlated linearly with duration in MMT (R=0.3,P<0.001) and with systolic BP (R=0.27,P<0.001). Patients with HTN had higher BMI values than those without HTN (28.1±5.4 vs. 25.5±5.2, respectively,P<0.001) and fewer had positive urine test findings to any substance (35.7% vs. 50.5%,P=0.01). Comparison of first methadone serum, BP, and BMI levels 11.9±5.8 years earlier increased more for the HTN group, independent of methadone dose and serum levels that lowered significantly over time. Drug abuse and older age were not associated with increased BMI and BP.

CONCLUSION

Weight gain was associated with BP elevation and characterized patients who succeeded in drug abstinence during MMT.PERSPECTIVESIdentifying HTN and offering treatment for this highly prevalent life-threatening condition among older patients in MMT is recommended.