bluuebunny/crossref_metadata_2025 huggingface dataset:
Suspected Burn From a 9-Voltage Battery
Authors: Whitelock Courtney , Echternacht Scott , Ahmad Adeel , Habina Matthew , Kia Michael
Published: November 2023

Advancements in technology allow for the utilization of low-voltage battery-powered devices for patients admitted to the hospital. There have been rare cases of burns due to leakage of the internal contents from low-voltage batteries, but to date, there have been no reports of electrical burns caused by low-voltage batteries. We present the case of an 89-year-old female who presented to the general surgery service with a suspected electrical burn from laying on a 9-volt battery. The patient underwent operative debridement with no evidence of a deeper injury. The patient continues to follow up with an outpatient wound clinic and is healing well. This case highlights the importance of teaching and raising awareness of all small devices that may become entangled or lost in patients’ linens, such as 9-volt telemetry batteries, to prevent harm.
Beyond Eosinophilic Esophagitis: Eosinophils in Gastrointestinal Disease—New Insights, “New” Diseases
Authors: Talley Nicholas J , Burns Grace L , Hoedt Emily C , Duncanson Kerith , Keely Simon
Published: November 2023

Functional dyspepsia (FD) is a highly prevalent disorder. Upper endoscopy is normal, and according to the Rome IV criteria, there is no established pathology. Data accumulated over the last 15 years has challenged the notion FD is free of relevant pathology, and in particular, increased duodenal eosinophils have been observed. Intestinal eosinophils play important roles in microbial defence, immune regulation, tissue regeneration and remodelling, and maintaining tissue homeostasis and metabolism; degranulation of eosinophils releases toxic granule products (e.g., major basic protein, eosinophil-derived neurotoxin) which can damage nerves. Normal cut-offs for eosinophil infiltration into the duodenum histologically are less than five eosinophils per high power field (<25 per five high power fields). In clinical practice there is evidence that pathologically increased intestinal eosinophils may often be overlooked. In a meta-analysis duodenal eosinophils were significantly increased in FD although there was substantial heterogeneity; degranulation of duodenal eosinophils was also significantly higher in FD without significant heterogeneity. In addition, increased duodenal permeability, systemic immune activation, and an altered mucosa-associated duodenal microbiome have been identified that may help explain why symptoms arise, often occur after food with exposure to food antigens, and typically fluctuate. Several potentially reversible risk factors for FD have now been identified. We evaluate the current evidence linking duodenal microinflammation and immune activation with FD and disorders of gut–brain interactions that overlap with FD. We propose a two-hit disease model for eosinophilic functional dyspepsia (EoFD) with management implications.
Variation in phoneme inventories: quantifying the problem and improving comparability
Authors: Anderson Cormac , Tresoldi Tiago , Greenhill Simon J , Forkel Robert , Gray Russell , List Johann-Mattis
Published: November 2023

For over a century, the phoneme has played a central role in linguistic research. In recent years, collections of phoneme inventories, originally designed for cross-linguistic purposes, have increasingly been used in comparative studies involving neighbouring disciplines. Despite the extended application of this type of data, there has been no research into its comparability or tests of its reliability. In this study, we carry out a systematic comparison of nine popular phoneme inventory collections. We render them comparable by linking them to standardised formats for the handling of cross-linguistic datasets, develop new measures to test both size and similarity, and release the organised data in supplementary material. We find considerable differences in inventories supposedly representing the same language variety, both in terms of size and transcriptional choices. While some of these differences appear to be predictable, reflecting design decisions in the different collections, much of the observed variation is unsystematic. These results should sound a note of caution for comparative studies based on phoneme inventories, which we suggest need to take the question of comparability more seriously. We make a number of proposals for improving the comparability of phoneme inventories.
D27-like carotenoid isomerases: at the crossroads of strigolactone and abscisic acid biosynthesis
Authors: Tolnai Zoltán , Sharma Himani , Soós Vilmos
Published: November 2023

Strigolactones and abscisic acid (ABA) are apocarotenoid-derived plant hormones. Their biosynthesis starts with the conversion of trans-carotenes into cis forms, which serve as direct precursors. Iron-containing DWARF27 isomerases were shown to catalyse or contribute to the trans/cis conversions of these precursor molecules. D27 converts trans-β-carotene into 9-cis-β-carotene, which is the first committed step in strigolactone biosynthesis. Recent studies found that its paralogue, D27-LIKE1, also catalyses this conversion. A crucial step in ABA biosynthesis is the oxidative cleavage of 9-cis-violaxanthin and/or 9-cis-neoxanthin, which are formed from their trans isomers by unknown isomerases. Several lines of evidence point out that D27-like proteins directly or indirectly contribute to 9-cis-violaxanthin conversion, and eventually ABA biosynthesis. Apparently, the diversity of D27-like enzymatic activity is essential for the optimization of cis/trans ratios, and hence act to maintain apocarotenoid precursor pools. In this review, we discuss the functional divergence and redundancy of D27 paralogues and their potential direct contribution to ABA precursor biosynthesis. We provide updates on their gene expression regulation and alleged Fe–S cluster binding feature. Finally, we conclude that the functional divergence of these paralogues is not fully understood and we provide an outlook on potential directions in research.
Module 8: Confronting Feared and Avoided Situations
Authors: Jaywant Abhishek , Oberlin Lauren E. , Cherestal Stephanie , Bueno Castellano Christina , Wilkins Victoria M. , Kanellopoulos Dora
Published: November 2023

This chapter focuses on how clients can safely confront their fear and situations they have started to avoid. Fear may have developed after contracting COVID-19, and unhelpful avoidance behaviors may be the client’s way of trying to reduce that fear. Due to the fight-or-flight system, the urge to avoid is the brain's way of protecting us from potential harm. However, fear can be disproportionate to the actual level of danger. Avoidance also comes in the form of excessive checking and self-monitoring. The chapter explains the difference between a true alarm and a false alarm, referencing the psychological process of habituation. The importance of home practice is emphasized.
Module 10: Fatigue and Sleep
Authors: Jaywant Abhishek , Oberlin Lauren E. , Cherestal Stephanie , Bueno Castellano Christina , Wilkins Victoria M. , Kanellopoulos Dora
Published: November 2023

This chapter explains strategies that can help clients with persisting symptoms of COVID-19 to handle fatigue and sleep disruption. These strategies primarily focus on developing healthier activity patterns, reframing unhelpful thoughts, and using mindfulness techniques to decrease overfocus on symptoms. People commonly respond to fatigue in a way that helps in the short term but actually makes fatigue a bigger problem in the long term. Strategies are outlined to help clients manage sleep disruption. Managing fatigue and sleep problems can improve clients’ anxiety and depression symptoms over time. Home practice between sessions is crucial for learning and implementing these skills so they will be ready when needed.
Experimental atomic data of spectral lines – I. Cs, Ba, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Hf, Re, and Os in the 370–1000 nm interval
Authors: Ferrara C , Giarrusso M , Leone F
Published: November 2023

Atomic data are fundamental for plasma diagnostics in laboratory and astrophysics through spectroscopy. These data are extensively present in data bases for light elements, however incomplete for high-mass atoms. This paper presents the results of systematic spectroscopy of 17 elements with high Z, expected to be produced in kilonova events generated by neutron star mergers, whose spectral lines are not yet fully identified in stellar spectra and fusion devices. Experimental data are from échelle high-resolution (λ/Δλ = 60 000) spectroscopy of hollow cathode lamps obtained with the Catania Astrophysical Observatory Spectropolarimeter covering the 3700–10 000 Å range in a single exposure. A total of about 7700 spectral lines with energy level classification not previously listed in the NIST, Kurucz, and VALD data bases are here reported for neutral and singly ionized atomic transitions. For the spectral lines of any species, we report the measured wavelengths and their relative intensities. If possible, we also estimate the transition probabilities under the assumptions of optically thin emission and electric-dipole transitions. These are converted into oscillator strengths ready to be inserted in astrophysical data bases for spectral synthesis.
A study of chemical abundances, rotational velocities, and orbital elements in single-lined spectroscopic binary stars in open clusters
Authors: Ramos A A , Holanda N , Drake N A , Rain M J , Maia F F S , Daflon S , Pereira C B
Published: November 2023

Binary interactions play a significant role in stellar evolution. In this study, we present a comprehensive analysis of 17 single-lined spectroscopic binary stars and identify two more as ‘yellow stragglers’, in the context of 15 young open clusters with ages younger than 1.0 Gyr. High-resolution spectroscopy ($R\, \approx \, 48000$) was employed to determine atmospheric parameters and chemical abundances of various elements including Li, C (C2), N (12CN), O, Na, Mg, Al, Ca, Si, Ti, Ni, Cr, Y, Zr, La, Ce, Nd, and Eu, and compared them with the abundances of stars reported in the literature. The projected rotational velocities ($v\, \sin \, \mathrm{ i}$) of 17 stars were determined via the spectral synthesis method. For two stars, we analyse the phenomenon of yellow stragglers based on their spectra and colour–magnitude diagram. Our $v\, \sin \, \mathrm{ i}$ results exhibit excellent agreement with previous studies in the literature for four stars previously analysed. Furthermore, we found a similar set of chemical abundances between thin disc stars and the studied spectroscopic binaries, except for s-process elements, such as La, Ce, and Nd. Also, we confirm that yellow straggler stars are members of binary systems, specifically giant G/K-type stars paired with dwarf A-type stars. Finally, we investigated the relationships between chemical abundances, orbital parameters (obtained from the literature), and $v\, \sin \, \mathrm{ i}$, which can provide insights into the observed anomalies in 7Li abundance in two stars such as NGC 6694-14 and NGC 6709-303. Our findings suggest that the anomalous rotation and lithium enrichment observed in these stars are likely results of interactions within binary companions.
Correlated spectral and recurrence variations of Cygnus X-1
Authors: Broadbent E M , Phillipson R A
Published: November 2023

We present results of recurrence analysis of the black hole X-ray binary Cygnus X-1 using combined observations from the Rossi X-ray Timing Explorer All-sky Monitor and the Japanese Monitor of All-sky X-ray Image aboard the International Space Station. From the time-dependent windowed recurrence plot (RP), we compute 10 recurrence quantities that describe the dynamical behaviour of the source and compare them to the spectral state at each point in time. We identify epochs of state changes corresponding to transitions into highly deterministic or highly stochastic dynamical regimes and their correlation to specific spectral states. We compare k-Nearest Neighbors and Random Forest models for various sizes of the time-dependent RP. The spectral state in Cygnus X-1 can be predicted with greater than 95 per cent accuracy for both types of models explored across a range of RP sizes based solely on the recurrence properties. The primary features from the RP that distinguish between spectral states are the determinism, Shannon entropy, and average line length, all of which are systematically higher in the hard state compared to the soft state. Our results suggest that the hard and soft states of Cygnus X-1 exhibit distinct dynamical variability and the time domain alone can be used for spectral state classification.
Highly collisional regions determined by interplanetary magnetic field structures
Authors: Pan L , Lai H R , Jia Y D , Russell C T , Connors M , Cui J
Published: November 2023

Submicron debris released in interplanetary collisions gets charged in the solar wind and generates disturbances to the magnetic field environment. The unique magnetic field disturbances, named interplanetary field enhancements (IFEs) are recorded by many spacecraft. In this study, we have developed a novel model to trace the IFEs to their origins. By employing this model, we can pinout regions with highly collision frequencies, thereby identifying regions of intense collisional activity. The model can help constrain interplanetary magnetic disturbances and our results can be used to guide part of the interplanetary-object survey.
Subgenomic Stability of Progenitor Genomes During Repeated Allotetraploid Origins of the Same GrassBrachypodium hybridum
Authors: Mu Wenjie , Li Kexin , Yang Yongzhi , Breiman Adina , Yang Jiao , Wu Ying , Zhu Mingjia , Wang Shuai , Catalan Pilar , Nevo Eviatar , Liu Jianquan
Published: November 2023

Both homeologous exchanges and homeologous expression bias are generally found in most allopolyploid species. Whether homeologous exchanges and homeologous expression bias differ between repeated allopolyploid speciation events from the same progenitor species remains unknown. Here, we detected a third independent and recent allotetraploid origin for the model grass Brachypodium hybridum. Our homeologous exchange with replacement analyses indicated the absence of significant homeologous exchanges in any of the three types of wild allotetraploids, supporting the integrity of their progenitor subgenomes and the immediate creation of the amphidiploids. Further homeologous expression bias tests did not uncover significant subgenomic dominance in different tissues and conditions of the allotetraploids. This suggests a balanced expression of homeologs under similar or dissimilar ecological conditions in their natural habitats. We observed that the density of transposons around genes was not associated with the initial establishment of subgenome dominance; rather, this feature is inherited from the progenitor genome. We found that drought response genes were highly induced in the two subgenomes, likely contributing to the local adaptation of this species to arid habitats in the third allotetraploid event. These findings provide evidence for the consistency of subgenomic stability of parental genomes across multiple allopolyploidization events that led to the same species at different periods. Our study emphasizes the importance of selecting closely related progenitor species genomes to accurately assess homeologous exchange with replacement in allopolyploids, thereby avoiding the detection of false homeologous exchanges when using less related progenitor species genomes.
A conserved protein inhibitor brings under check the activity of RNase E in cyanobacteria
Authors: Liu Su-Juan , Lin Gui-Ming , Yuan Yu-Qi , Chen Wenli , Zhang Ju-Yuan , Zhang Cheng-Cai
Published: November 2023

The bacterial ribonuclease RNase E plays a key role in RNA metabolism. Yet, with a large substrate spectrum and poor substrate specificity, its activity must be well controlled under different conditions. Only a few regulators of RNase E are known, limiting our understanding on posttranscriptional regulatory mechanisms in bacteria. Here we show that, RebA, a protein universally present in cyanobacteria, interacts with RNase E in the cyanobacterium Anabaena PCC 7120. Distinct from those known regulators of RNase E, RebA interacts with the catalytic region of RNase E, and suppresses the cleavage activities of RNase E for all tested substrates. Consistent with the inhibitory function of RebA on RNase E, depletion of RNase E and overproduction of RebA caused formation of elongated cells, whereas the absence of RebA and overproduction of RNase E resulted in a shorter-cell phenotype. We further showed that the morphological changes caused by altered levels of RNase E or RebA are dependent on their physical interaction. The action of RebA represents a new mechanism, potentially conserved in cyanobacteria, for RNase E regulation. Our findings provide insights into the regulation and the function of RNase E, and demonstrate the importance of balanced RNA metabolism in bacteria.
Biochemical and cellular insights into the Baz2B protein, a non-catalytic subunit of the chromatin remodeling complex
Authors: Breindl Matthias , Spitzer Dominika , Gerasimaitė Rūta , Kairys Visvaldas , Schubert Thomas , Henfling Ramona , Schwartz Uwe , Lukinavičius Gražvydas , Manelytė Laura
Published: November 2023

Baz2B is a regulatory subunit of the ATP-dependent chromatin remodeling complexes BRF1 and BRF5, which control access to DNA during DNA-templated processes. Baz2B has been implicated in several diseases and also in unhealthy ageing, however limited information is available on the domains and cellular roles of Baz2B. To gain more insight into the Baz2B function, we biochemically characterized the TAM (Tip5/ARBP/MBD) domain with the auxiliary AT-hook motifs and the bromodomain (BRD). We observed alterations in histone code recognition in bromodomains carrying cancer-associated point mutations, suggesting their potential involvement in disease. Furthermore, the depletion of Baz2B in the Hap1 cell line resulted in altered cell morphology, reduced colony formation and perturbed transcriptional profiles. Despite that, super-resolution microscopy images revealed no changes in the overall chromatin structure in the absence of Baz2B. These findings provide insights into the biological function of Baz2B.
DELTEX E3 ligases ubiquitylate ADP-ribosyl modification on nucleic acids
Authors: Zhu Kang , Suskiewicz Marcin J , Chatrin Chatrin , Strømland Øyvind , Dorsey Bryan W , Aucagne Vincent , Ahel Dragana , Ahel Ivan
Published: November 2023

Although ubiquitylation had traditionally been considered limited to proteins, the discovery of non-proteinaceous substrates (e.g. lipopolysaccharides and adenosine diphosphate ribose (ADPr)) challenged this perspective. Our recent study showed that DTX2 E3 ligase efficiently ubiquitylates ADPr. Here, we show that the ADPr ubiquitylation activity is also present in another DELTEX family member, DTX3L, analysed both as an isolated catalytic fragment and the full-length PARP9:DTX3L complex, suggesting that it is a general feature of the DELTEX family. Since structural predictions show that DTX3L possesses single-stranded nucleic acids binding ability and given the fact that nucleic acids have recently emerged as substrates for ADP-ribosylation, we asked whether DELTEX E3s might catalyse ubiquitylation of an ADPr moiety linked to nucleic acids. Indeed, we show that DTX3L and DTX2 are capable of ubiquitylating ADP-ribosylated DNA and RNA synthesized by PARPs, including PARP14. Furthermore, we demonstrate that the Ub-ADPr-nucleic acids conjugate can be reversed by two groups of hydrolases, which remove either the whole adduct (e.g. SARS-CoV-2 Mac1 or PARP14 macrodomain 1) or just the Ub (e.g. SARS-CoV-2 PLpro). Overall, this study reveals ADPr ubiquitylation as a general function of the DELTEX family E3s and presents the evidence of reversible ubiquitylation of ADP-ribosylated nucleic acids.
Amazonian avian biogeography: Broadscale patterns, microevolutionary processes, and habitat-specific models revealed by multidisciplinary approaches
Authors: Capurucho João Marcos Guimarães , Musher Lukas J , Lees Alexander , Rego Marco A , Del-Rio Glaucia , Aleixo Alexandre , Luzuriaga-Aveiga Vanessa E , Ferreira Mateus , Ribas Camila C , Thom Gregory
Published: November 2023

Our understanding of Amazonian biogeography is quickly increasing, catalyzed by the growing use of genomic datasets, improved knowledge of species distributions, and the accumulation of new data on the geological and climatic history of the region. The high number of species in Amazonia and their intricate patterns of geographic distribution triggered the development of many diversification hypotheses that shaped historical biogeography as a discipline. Here, we present a historical overview of avian biogeographic studies in Amazonia, their recent advances, outstanding questions, and future directions. We focus on how new approaches have led to novel understandings of the distribution patterns and diversification processes that underpin avian diversity. We show how genomic tools are being used to establish new hypotheses about the drivers of diversification and highlight the importance of recent studies of birds in previously overlooked environments, such as floodplains and open vegetation enclaves. We emphasize the importance of gene flow, species traits, and habitat affinities in studying diversification processes to fully acknowledge the complexity of Amazonian ecosystems and their history. We then discuss the current gaps in Amazonian taxonomic and biogeographic knowledge, with a focus on the issues that we believe hinder our understanding of the field. Amazonia has been facing increasing levels of forest loss due to agricultural expansion, infrastructure development, mining, climate change, and illegal activities catalyzed by weak governance. To halt biodiversity loss, it is crucial to increase our knowledge of the natural history and biogeography of Amazonian species. We suggest increasing incentives for research and training at institutions based in the region, as well as the establishment of partnerships with governments, local communities, NGOs, and international institutions to bring diverse communities together to address crucial questions.
The positive and negative emotion functions related to loneliness: a systematic review of behavioural and neuroimaging studies
Authors: Luo Qianyi , Shao Robin
Published: November 2023

Loneliness is associated with high prevalences of major psychiatric illnesses such as major depression. However, the underlying emotional mechanisms of loneliness remained unclear. We hypothesized that loneliness originates from both decreases in positive emotional processing and increases in negative emotion processing. To test this, we conducted a systematic review of 29 previous studies (total participants n = 19 560, mean age = 37.16 years, female proportion = 59.7%), including 18 studies that included questionnaire measures of emotions only, and 11 studies that examined the brain correlates of emotions. The main findings were that loneliness was negatively correlated with general positive emotions and positively correlated with general negative emotions. Furthermore, limited evidence indicates loneliness exhibited negative and positive correlations with the brain positive (e.g. the striatum) and negative (e.g. insula) emotion systems, respectively, but the sign of correlation was not entirely consistent. Additionally, loneliness was associated with the structure and function of the brain emotion regulation systems, particularly the prefrontal cortex, but the direction of this relationship remained ambiguous. We concluded that the existing evidence supported a bivalence model of loneliness, but several critical gaps existed that could be addressed by future studies that include adolescent and middle-aged samples, use both questionnaire and task measures of emotions, distinguish between general emotion and social emotion as well as between positive and negative emotion regulation, and adopt a longitudinal design that allows us to ascertain the causal relationships between loneliness and emotion dysfunction. Our findings provide new insights into the underlying emotion mechanisms of loneliness that can inform interventions for lonely individuals.
Pre-existing musculoskeletal pain and its association with mortality in newly diagnosed co-morbid conditions: an electronic health record cohort study
Authors: Marshall Michelle , Mason Kayleigh J , Edwards John J , Mamas Mamas A , Bailey James , Heron Neil , Achana Felix A , Frisher Martin , Huntley Alyson L , Mallen Christian D , Png May Ee , Tatton Stephen , White Simon , Jordan Kelvin P
Published: November 2023

Objective

Musculoskeletal pain is a common risk factor for co-morbid conditions and might increase the risk of poor outcomes. The objective was to determine whether patients with pre-existing musculoskeletal pain have an increased risk for mortality following a new diagnosis of a co-morbid condition.

Methods

Patients aged ≥45 years with a new diagnosis of acute coronary syndrome (ACS), stroke, cancer, dementia or pneumonia recorded in a UK electronic primary care database linked to hospital and mortality records were examined. The association of mortality with musculoskeletal pain (inflammatory conditions, OA and regional pain) was determined.

Results

The sample size varied from 128 649 (stroke) to 406 289 (cancer) by cohort, with 22–31% having pre-existing musculoskeletal conditions. In the ACS cohort, there was a higher rate of mortality for all musculoskeletal types. There were also higher unadjusted mortality rates in patients with inflammatory arthritis compared with those without musculoskeletal pain in the stroke, cancer and dementia cohorts and for patients with OA in the stroke and cancer cohorts. After adjustment for the number of prescribed medications and age, the increased risk of mortality remained only for patients with inflammatory arthritis in the ACS cohort (adjusted hazard ratio = 1.07; 95% CI 1.03, 1.10).

Conclusion

Older adults with inflammatory arthritis and OA have increased risk of mortality when they develop a new condition, which seems to be related to the prescription of multiple medicines. Pre-existing musculoskeletal pain is an indicator of a complex patient who is at risk of poorer outcomes at the onset of new illnesses.
Inaction, Silence, Focus, and Power: Identifying and Assessing Folk Theories of the Racism of Omission
Authors: Warren Evangeline , Valentino Lauren
Published: November 2023

Recent scholarship has advanced a concept of racism operating through omission. Omission captures both inaction and action, highlighting how systems of oppression rely on inertia in addition to discriminatory action to perpetuate inequality. Yet little is known about how laypersons understand the role of omission in propagating racism in the United States. Building on this premise, we employ a mixed-methods approach to document and test folk theories of the racism of omission. We interview diverse individuals (N=40) about their appraisals of racism; we use these findings to design a vignette study which we fielded to a national sample (N=1,174). Interview data reveal that some Americans do understand omission to be a form of racism, highlighting (1) bystander inaction, (2) silencing of experiences of racism, (3) overfocus on White issues, and (4) disparities in positions of power as instances where inaction, exclusion, or inertia constitute a form of racism. Data show that Americans are most likely to consider overfocus and silencing as forms of omission-based racism, and that racism appraisals depend on the victim’s race. We find that political ideology, gender, income, race, and education shape appraisals of racism as omission. These findings have implications for measures of perceived racism and discrimination.
Seroprevalence of SARS-CoV-2 antibodies in pediatric hospital surgical unit: a lower-middle-income country perspective
Authors: Habib Murad , Javed Noshela , Burki Sadia Asmat , Ahmed Mansoor , Chaudhary Muhammad Amjad
Published: November 2023

Background

The objective of our study was to measure and give insight into the seropositivity of anti-SARS-CoV-2 antibodies in the patients in our pediatric hospital surgical unit in Pakistan.

Methods

A prospective cohort study was conducted at a tertiary care pediatric hospital surgical unit in Pakistan between 1 January 2021 and 1 June 2021 on the enrolled neonates and children aged 1 day to 13 years. All patients from three different pediatric strata [neonates (<1 month), infants (1 to 12 months) and children (>1 year)] were enrolled in the study.

Results

Six-hundred patients were enrolled, and 426 patients were included in the study. Among 426 patients, 234 (54.9%) were male, and 192 (45.1%) were female. Overall only 118 (27.7%) patients developed symptoms. The other 308 (72.3%) were asymptomatic of which 28 (9.1%) had fever, 28 (9.1%) had cough, 38 (12.33%) had body aches, 292 (94.8%) had vomiting/diarrhea, and only 28 (9.1%) developed loss of smell and taste. Our results showed seropositivity of 27.7% (n = 118), while 72.3% (n = 308) had negative antibody titers.

Conclusion

A much higher pediatric SARS-CoV-2 burden of 27.7% was found in our pediatric surgical unit than has previously been reported in the literature of 6.8% for children in pediatric hospitals or pediatric surgical units. Contrary to reporting early in the COVID-19 pandemic, this study determined that children experience a significant burden of COVID-19 infection. Thus, children appear very important in SARS-CoV-2 pandemic, from harboring the virus and further studies need to be done to find if they are transmitting the disease silently.
Mitochondrial Dynamics in Auditory Sensory Cells
Authors: Nuttall Alfred L , Foster Sarah , Wilson Teresa
Published: November 2023

Background

The auditory sensory hair cells convert sound vibrations into neuronal impulses. Excessive loud sound exposure can result in the overproduction of oxidative free radicals by the mitochondria in these cells. This can negatively impact hair cell function and viability leading to permanent loss of hearing sensitivity. The mechanisms that initiate this process are thought to include ischemia/reperfusion injury as well as metabolic overstimulation. Despite the importance of auditory hair cells, the basic physiology of the mitochondria in these cells is relatively unknown. Further, whether mitochondrial dynamics and spatial localization are altered to respond to increased energy needs of the cells with loud sound exposure has not been well‐characterized.

Objective

In this study, our goal was to characterize mitochondrial morphology and spatial distribution in auditory cells under normal and loud sound induced stress conditions.

Methods and Results

To examine mitochondria in outer hair cells (OHCs), PhAMfloxed mice were crossed with prestin‐CreERT2 mice to generate mice that express a mitochondrial‐specific version of the Dendra2 fluorescent protein (mito‐Dendra2) in the mitochondria in OHCs. For examination of mitochondria in all organ of Corti cells, immunolabeling for the mitochondrial outer membrane protein Tom20 was performed. These mice were exposed to damaging levels of loud sound and the cochlea harvested at 24 and 48 hours following noise exposure. Airyscan and super resolution imaging of mito‐Dendra2 and Tom20 fluorescence showed primarily fragmented mitochondria in the OHCs and a mixture of punctate and short rod‐shaped mitochondria in the inner hair cells of normal control animals. Following noise exposure, the mitochondria of the organ of Corti cells were examined for alterations in spatial distribution, number, and morphology, and preliminary results demonstrated changes in the distribution of mitochondria in OHCs.

Conclusions

Mitochondria are highly dynamic organelles that are maintained by the conserved actions of mitochondrial division, fusion, motility, and tethering. The presence of excessive cellular stress typically results in attenuated fusion processes and increased mitochondrial fragmentation. The presence of fragmented mitochondria in OHCs suggests that the balance of fission and fusion processes are altered, potentially due to a higher oxidant environment being present in these cells.

Support or Funding Information

Supported by grants 5R01DC000105 (ALN) and P30DC005983.
Stressor‐Enhanced Infectious Colitis is Due to Aberrant Colonic Epithelial Cell Signaling
Authors: Mackos Amy , Bailey Michael T
Published: November 2023

It has been long known that exposure to psychological stressors can exacerbate gastrointestinal disease, however the mechanism by which this occurs has not yet been fully elucidated. One hypothesis is that disruptions in the indigenous microbiota of the intestine by psychological stressors contribute to the exacerbation of disease. Recently, our laboratory has shown that exposing mice to the social stressor, namely, social disruption (SDR) significantly alters the intestinal microbiota community structure, and reduces the levels of beneficial species like Lactobacillus reuteri. These stressor‐induced changes in the microbiota can lead to increased proinflammatory cytokines (e.g., TNF‐α) and chemokines (e.g., CCL2) in the colons of mice challenged with the colonic pathogen Citrobacter rodentium. Exaggerated expression of these pro‐inflammatory cytokines and chemokines can enhance inflammatory monocyte recruitment, leading to enhanced colonic tissue damage. Thus, identifying the cellular source(s) of colonic TNF‐α and CCL2 during stressor exposure has important health implications. Due to close proximity with the colonic microbiota, we hypothesized that colonic epithelial cells (CEC) from stressor‐exposed mice would have increased expression of TNF‐α and CCL2 as compared to CEC from naïve mice. To test this hypothesis mice were exposed to SDR, which involves repeated social defeat, for 2 hours a night for 6 consecutive nights. The morning following the last night of the stressor, mice were euthanized, colons were excised, and both CEC and lamina propria cells were isolated. Results demonstrated that CEC from SDR‐exposed mice had significant increases in both TNF‐α and CCL2 gene expression as compared to CEC isolated from non‐stressed controls. Conversely, TNF‐α and CCL2 gene expression was unchanged in lamina propria cells from stressor exposed mice when compared their control counterparts. Together, these data have led to the proposed model that stressor exposure can lead to aberrant inflammatory gene expression in colonic epithelial cells, which may prime the colon for an overzealous inflammatory response when challenged with an enteric pathogen following stressor exposure.

Support or Funding Information

Supported by NIH grant AT006552‐01A1 (M.T.B).
Dimer Induced Regulation of Protein Kinase Function
Authors: Sicheri Frank
Published: November 2023

Dimerization composes an allosteric switch for the regulation of a growing list of protein kinase families. New insights into normal mechanism of action, pseudo‐kinase evolution, and paradoxical drug interactions gained from our work on RAF, eIF2α, and Ire1/RNase L kinase families will be discussed.
Lactobacillus rhamnosus Isolated from “amabere amaruranu” Cultured Milk Modulated the Production of Inflammatory Cytokines in Caco‐2 Cells
Authors: Ngeny Beverly , Onyango E M
Published: November 2023

Probiotic microorganisms have been shown to confer health benefits on the host when administered in adequate amounts. In the gastrointestinal tract, they promote host immunity, regulate immune signaling pathways and produce anti‐pathogenic factors. The immune effects resulting from interactions between intestinal epithelial cells and commensal bacteria have not yet been fully elucidated. This study examined the effects of a Lactobacillus rhamnosus isolate from “amabere amaruranu” a Kenyan traditional cultured milk, on the production of pro‐inflammatory cytokines (Interleukin 8 and Tumor Necrosis Factor‐α) and anti‐inflammatory cytokines (Interleukin 10 and Transforming Growth Factor‐β) in enterocytes. The L. rhamnosus isolate was cultured in de‐Mann Rogosa Sharpe media overnight, the broth was collected and filtered to obtain filtered spent broth (FSB). Cell pellets resuspended in PBS were sonicated and filtered to obtain cytoplasmic fraction (CF). Differentiated Caco‐2 cell monolayer in transwells, after 21 days post‐confluence were co‐cultured with live L. rhamnosus (MRS6AN) isolate or apically treated with PBS control or CF or FSB. After 6–36 hrs of incubation, cells were collected and lysed and cell supernatants were collected. Enzyme Linked Immunosorbent Assay was used to determine the cytokine content in the cell lysate, apical and basolateral supernatants. Effects of the various treatments (PBS Control, MRS6AN, CF and FSB) on Caco‐2 cell lysate levels of TGF‐β were 14.5, 191.6, 153.3 and 128.8 ng/ml, respectively; of IL10 were 7.1, 44, 33.6 and 31 pg/ml, respectively; of IL8 were 200, 1014, 1489.1 and 1659.6 pg/ml, respectively, and of TNF‐α were 4.1, 27.6, 33.1 and 30.1 pg/ml, respectively. There were very low levels of TGFβ, IL10, IL8 and TNFα cytokines in both the apical and basolateral supernatants. In conclusion, L. rhamnosus isolate and its cytoplasmic fraction or spent media seemed to cause a higher production of anti‐inflammatory TGF‐β and pro‐inflammatory IL8 cytokines by differentiated Caco‐2 cells.

Support or Funding Information

East Tennessee State University
MiR9 is increased in Rheumatoid Arthritis Monocytes and Regulates Monocyte Migration
Authors: Gaudette Joshua , Stinson W Alexander , Fox David A , Amin M Asif , Rabquer Bradley James
Published: November 2023

Purpose

Rheumatoid Arthritis (RA) is characterized by inflammation and joint degradation. Monocytes, a key leukocyte in inflammation, migrate from the blood to damaged tissues where they differentiate into macrophages that serve multiple immune functions. MicroRNA (miRNA), small noncoding regions of RNA, act as regulators of gene expression, bind to and degrade mRNA. We have previously shown that miR9 is up regulated in THP1 monocytes and U937 monocytes with TNFα stimulation. Here we hypothesize that miR9 is up regulated in the inflammatory disease RA, and that mir9 regulates monocyte migration.

Methods and Results

Monocytes were isolated from blood of patients with RA (N=3) and normal subjects (N=6). MiRNA was isolated, cDNA was prepared, and qPCR was performed using primers specific to miR9. miR9 was significantly upregulated in RA monocytes by 2.3 fold compared to normal monocytes (P < 0.05). We searched for miR9 gene targets using miRWALK, MiRanda, and NCBI databases and found 8,778 gene targets. Targets were narrowed to biological pathways specific to human monocytes and inflammation, leaving 39 gene targets. Of these 39 targets, suppressor of cytokine signaling 4 (SOCS 4) was chosen for further study because it showed the highest seed length for miRNA binding. An inhibitor and mimic for miR9 were used to assess its ability in modulating SOCS4 expression. Results showed a 0.2 fold reduction in expression with the miR9 mimic, and a negligible change in expression from the miR9 inhibitor. Chemotaxis assays were performed on THP‐1 monocytes transfected with miR9 mimic or inhibitor to measure the effect of miR9 on monocyte migration. THP‐1 cells treated with the miR9 mimic displayed an increase in migration by 40% (n=10 replicates) compared to control cells, whereas the inhibitor showed no change in migration (n=10 replicates).

Conclusion

Our results suggest miR9 is upregulated in RA monocytes and that miR9 plays a role in monocyte migration by regulating genes such as SOCS4.

Support or Funding Information

Hewlett‐Mellon Fund for Faculty Development at Albion College
Survey on microRNAs Targeting MuRF1 and MuRF2 in Regenerating Skeletal Muscle
Authors: Silva William Jose , Baptista Igor Luchini , Silvestre João Guilherme , Yan Chao Irene , Moriscot Anselmo Sigari
Published: November 2023

Introduction

Skeletal muscle is a very adaptable tissue, mainly due to its regenerative capacity, which is fundamental importance for repairing large lesions and microlesions as well. Recently our research group observed that the E3 ligases MuRF1 and MuRF2, in addition to being implicated the atrophy process is also essential for muscle regeneration (data not published). In view of these results, in this study we investigated the molecular mechanisms involved in the increased expression of MuRFs during regeneration. Our hypothesis contemplates that certain microRNAs (miRNAs or miRs, regulators of gene expression at post‐transcriptional level) can regulate MuRFs expression during the regeneration process.

Objective

Search miRNAs that targets MuRFs, and investigate its impact on the skeletal muscle regeneration.

Materials and Methods

C57/BL6 mice (~8wk. 30±3g) were injected with cardiotoxin (CTX, 10μM) in the Tibialis Anterior (TA) muscle for 1, 3 and 10 days in order to induce muscle injury. After these periods the animals were euthanized and the TA muscles were removed for determination of RNA and protein expression levels. Plasmids pMIR‐3UTRMuRF1 and pMIR‐3UTRMuRF2 were produced out of the amplification of the 3′ UTR of each cDNA and cloned into the vector pMIR‐Report system. Vectors (300ng) were co‐transfected with the specified miRNA (miRNA mimics 40uM or mimic Control#1) in HeLa cells. Then, the luciferase assay was performed. Primary myoblast cultures were transfected with siRNA to MuRFs in pre differentiation and post differentiation phases. Procedures and experimental protocols were approved by the Ethics experimental Committee at University of Sao Paulo ‐ CEUA #118.

Results

The protein expression of MuRF1 rises after 3 days of injury (~100%; p<0.05 vs control), while its gene expression rises as soon as 1 day (~150%; p<0.05 vs control) after injury. MuRF2, gene expression and protein content, rises after 10 days of lesion (~ 50%; p <0.05 vs. control). Transcription factors of MuRFs, FOXO3a and NF‐Kb increase their protein expression after 3 days of injury (>100%; p<0.05 vs. control). The miRs 29c and 101a which target MuRF1 and miRs 133a and 133b which target MuRF2 (TargetScan6.2 analysis) are reduced by 1 and 3 days(~50–80%; p<0.05 vs. control). By using luciferase assays with co‐transfection pMIR‐3UTR‐MuRF1 or pMIR‐3UTR‐MuRF2 and their respective mimics, we showed that miR29c targets MuRF1 and miR133a and 133b target MuRF2. Interestingly, MuRF1 and MuRF2 siRNA knock down do not change the expected modulation of miRs 29c, 133a and 133b. Expression of miRs 133a and 133b are increased after the post differentiation period (~100%; p<0.05 vs pre‐differentiation) in cultured myoblasts.

Conclusion

With these partial results, we identify and validate the miRs 29c and 133a/b target MuRFs.

Support or Funding Information

Grant 2012/22488‐2, Sao Paulo Research Foundation (FAPESP)
Mechanics of cell motility within stratified epithelia
Authors: Czirok Andras , Isai Dona G , Neufeld Zoltan
Published: November 2023

Recently we proposed a three dimensional mechanical model of embryonic tissue dynamics. Mechanically coupled adherent cells are represented as particles interconnected with elastic beams which can exert non‐central forces and torques. Tissue plasticity is modeled by a stochastic process consisting of a connectivity change (addition or removal of a single link) followed by a complete relaxation to mechanical equilibrium. In particular, we assume that (i) two non‐connected, but adjacent particles can form a new link; and (ii) the lifetime of links is reduced by tensile forces. This model yields a realistic macroscopic elasto‐plastic behavior and microscopic parameter values can be inferred from tissue thickness, macroscopic elastic modulus and the magnitude and dynamics of intercellular adhesion forces. In addition to their mechanical role, model particles can also act as simulation agents and actively modulate their connectivity according to specific rules. We demonstrate, that anisotropic link insertion and removal probabilities can give rise to local cell intercalation and large scale convergent extension movements. Cell extrusion from an epithelial layer involves mechanical torques, and can generate bending moments within a stratified (multi‐layered) epithelium ‐‐ a process likely to shape the early embryonic heart field.

Support or Funding Information

R01‐GM102801
Musculoskeletal and Neural Comparison of Normal and Abnormal Development in Humans and Broader Medical Implications
Authors: Alghamdi Malak , Smith Christopher , Ziermann Janine , Diogo Rui
Published: November 2023

Anatomical and medical studies of gross anatomical birth defects tend to focus mainly on external features, or in hard tissues (i.e., bones, cartilages, teeth). As a new, long term project we have been collecting and systematically comparing detailed musculoskeletal and neural information on normal human development and phenotypes seen in human fetuses, neonates and adults with conditions as diverse as anencephaly, trisomy 13, trisomy 18, trisomy 21, and/or cyclopia. This comparison is based on careful dissections and an extensive review of the scarce literature on the subject. Our dissections and comparisons revealed that certain similar anatomical patterns are frequently found in each of these conditions, supporting the “logic of monsters” hypothesis of Pere Alberch, according to which even in extreme cases of birth defects (e.g. anencephaly, cyclopia) there is still a discernable, marked “order”, instead of random, chaotic phenotypes, because of strong internal constraints limiting the amount of possible developmental outcomes. For instance, the absence of muscles that are normally polymorphic in humans (e.g., fibularis tertius, palmaris longus), the absence of tendons to the 5th digit of the hands/feet, and/or the presence of a few ‘atavistic’ muscles, are seen over and over in different cases of abnormal developmental studied by us. We will discuss the broader implications of our results and of the observed patterns by discussing crucial developmental and medical topics such as the links between developmental delay/arrest, ‘atavisms’, variations, anomalies, polymorphisms and the “logic of monsters”.

Support or Funding Information

Grants: This work is funded by start‐up funds to RD from Howard University College of Medicine, and by PhD funds from the Saudi Arabia government to MA.
The ligamentous connection between the anterior belly of the digastric muscle and the mylohyoid
Authors: Swearingen Jordan V , Miller Kyle D , Zdilla Matthew J. , Lambert H. Wayne
Published: November 2023

The anterior belly of the digastric muscle (ABDM) is important in numerous plastic surgeries including superficial musculoaponeurotic system (SMAS) rhytidectomy, alteration of the cervicomental angle via partial resection of the ABDM muscle belly, muscular medialization, the submental artery flap, and the reanimation the mouth after facial nerve palsy. Because the ABDM is important in a variety of plastic surgical procedures, detailed knowledge of its association with nearby anatomy is important. We describe the fascial connection between the ABDM and mylohyoid muscle (MM), which is oftentimes organized into a strong ligamentous connection. An understanding of this connection and its anatomical variability warrants consideration during surgeries performed in the region, particularly during a SMAS rhytidectomy surgical procedure. Likewise, anatomical variation in this connection may cause variation in the propagation of infection between the submental and submandibular fascial spaces among different individuals. Therefore, understanding the connection between the ABDM and MM may help with development of prognoses as well as clinical management of submental and suprahyoid infection in addition to pre‐surgical planning and operative technique.