bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of Inflammatory Response by Tissue Microenvironment
Authors: Wu Zhongyang , Pope Scott D. , Ahmed Nasiha S. , Leung Diana L. , Hajjar Stephanie , Yue Qiuyu , Anand Diya M. , Kopp Elizabeth B. , Okin Daniel , Ma Weiyi , Kagan Jonathan C. , Hargreaves Diana C. , Medzhitov Ruslan , Zhou Xu
Published: May 2024

Inflammation is an essential defense response but operates at the cost of normal functions. Whether and how the negative impact of inflammation is monitored remains largely unknown. Acidification of the tissue microenvironment is associated with inflammation. Here we investigated whether macrophages sense tissue acidification to adjust inflammatory responses. We found that acidic pH restructured the inflammatory response of macrophages in a gene-specific manner. We identified mammalian BRD4 as a novel intracellular pH sensor. Acidic pH disrupts the transcription condensates containing BRD4 and MED1, via histidine-enriched intrinsically disordered regions. Crucially, decrease in macrophage intracellular pH is necessary and sufficient to regulate transcriptional condensatesin vitroandin vivo, acting as negative feedback to regulate the inflammatory response. Collectively, these findings uncovered a pH-dependent switch in transcriptional condensates that enables environmental sensing to directly control inflammation, with a broader implication for calibrating the magnitude and quality of inflammation by the inflammatory cost.

Highlights

Acidic pH regulates a switch-like gene-specific inflammatory response in macrophages

Acidic pH impacts chromatin remodeling and transcription circuits to control inflammatory programs

BRD4 transcriptional condensates are regulated by intracellular pH via pH-sensitive motifs located within the intrinsically disordered region

Tissue inflammation decreases intracellular pH and disrupts BRD4 condensates as a negative feedback
Giraffe: a tool for comprehensive processing and visualization of multiple long-read sequencing data
Authors: Liu Xudong , Shao Yanwen , Guo Zhihao , Ni Ying , Sun Xuan , Leung Anskar Yu Hung , Li Runsheng
Published: May 2024

Third-generation sequencing techniques have become increasingly popular due to their ability to generate long, high-quality reads. Utilizing datasets from various samples and multiple sequencing platforms for comparative and comprehensive analysis is essential for exploring biological mechanisms and establishing benchmark baselines. However, current tools for long reads primarily focus on quality control (QC) and read processing for individual samples, complicating the profiling and comparison of multiple datasets. The lack of tools for data comparison and visualization presents challenges for researchers with limited bioinformatics experience. Furthermore, developing a comprehensive long-read QC method that facilitates comparative analysis and visualization across multiple samples and platforms is necessary to establish benchmark baselines for selecting appropriate sequencing platforms. We introduce Giraffe, a Python3-based command line tool designed for comparative analysis and visualization across multiple samples and platforms. Giraffe enables the assessment of read quality, sequencing bias, and genomic regional methylation proportions for both DNA and direct RNA sequencing reads. Its usability has been demonstrated in various scenarios, including comparisons of different biological processing methods (whole genome amplification vs. shotgun), sequencing platforms (Oxford Nanopore Technology vs. Pacific Biosciences), tissues (kidney marrow with and without blood), and biological replicates (kidney marrows). Additionally, our findings indicate that Oxford Nanopore duplex reads outperform PacBio HiFi reads in homopolymer identification and GC evenness while maintaining comparable overall read quality.
Keys to the cabinet: unlocking biodiversity data in public entomology collections
Authors: Gibson Joel F. , Howse Mackenzie , Paillard Claire , Penfold Cassandra , Penno Alannah , van der Voort Genevieve E. , Huber Dezene P.W.
Published: May 2024

Canadian entomology collections contain valuable biodiversity and ecological data, but they must be digitized in order to be usable by those working outside of the collections. Multiple analyses of the digital database of the Odonata collection at the Royal British Columbia Museum were conducted. These analyses reveal that complete digital datasets can be used to explore questions of historical and current geographical distribution and species composition differences based on ecoprovince and elevation. The results of these analyses can be used directly in conservation and climate change impact mitigation decisions. These analyses are only possible because the Odonata collection has received concerted effort to digitize all specimen records. The full value of long-term historical insect biodiversity data can only be accessed once collections are digitized. Additional training and employment of collection management and curatorial staff is essential to optimize the use of abundant, but underutilized, Canadian biodiversity data.
Elucidating immune-related gene transcriptional programs via factorization of large-scale RNA-profiles
Authors: He Shan , Gubin Matthew M. , Rafei Hind , Basar Rafet , Dede Merve , Jiang Xianli , Liang Qingnan , Tan Yukun , Kim Kunhee , Gillison Maura L. , Rezvani Katayoun , Peng Weiyi , Haymaker Cara , Hernandez Sharia , Solis Luisa M. , Mohanty Vakul , Chen Ken
Published: May 2024

Recent developments in immunotherapy, including immune checkpoint blockade (ICB) and adoptive cell therapy, have encountered challenges such as immune-related adverse events and resistance, especially in solid tumors. To advance the field, a deeper understanding of the molecular mechanisms behind treatment responses and resistance is essential. However, the lack of functionally characterized immune-related gene sets has limited data-driven immunological research. To address this gap, we adopted non-negative matrix factorization on 83 human bulk RNA-seq datasets and constructed 28 immune-specific gene sets. After rigorous immunologist-led manual annotations and orthogonal validations across immunological contexts and functional omics data, we demonstrated that these gene sets can be applied to refine pan-cancer immune subtypes, improve ICB response prediction and functionally annotate spatial transcriptomic data. These functional gene sets, informing diverse immune states, will advance our understanding of immunology and cancer research.
Varroa mites escape the evolutionary trap of haplodiploidy
Authors: Eliash Nurit , Tetsuya Endo , Johnston Spencer J. , Techer Maeva A. , Holmes Valerie R. , Rangel Juliana , Economo Evan P. , Mikheyev Alexander S.
Published: May 2024

Genetic diversity is essential for populations adapting to environmental changes. Due to genetic bottlenecks invasive species have reduced genetic diversity. However, they must quickly adapt to changes in new environments, potentially including anthropogenic countermeasures. This paradox raises a fundamental question: how do species adapt to changes while having low genetic diversity? The invasion paradox is more pronounced for some species. Parasites go through additional bottlenecks between hosts. Haplodiploid species have a lower effective population size as males can inherit and transmit only half of their mother’s genome. Trying to solve this paradox, we investigated inheritance in the Varroa mite (Varroa destructor), a well-studied invasive parasite of honey bees fitting all of the above criteria. By following the flow of alleles across three-generation pedigrees we found that Varroa, so far believed to be haplodiploid, is actually not. Rather, it has a unique reproductive system in which females clonally produce functionally diploid sons. While males lose somatic DNA during development, they can transmit either copy of the maternal genome to their daughters. This enhances female fitness, particularly under sib-mating typical of Varroa. We suggest this allows a greater effective population size relative to haplodiploidy and, thus, an increased evolutionary potential. This reversion to diploidy is a singular example of escaping the ‘evolutionary trap’ of haplodiploidy, which is believed to be an evolutionary stable end state. Plasticity in reproductive systems could be more common than assumed, and may potentially explain the remarkable resilience and high adaptivity of Varroa and other invasive parasites.

Significance

Varroa mites have driven the collapse of honey bee populations since their worldwide spread in the middle of the 20th century. Despite repeated genetic bottlenecks, Varroa has adapted to diverse environments and has overcome many pesticides. Using pedigree analysis, we found that Varroa re-evolved diplodiploid reproduction from an evolutionary history of haplodiploidy. Diplodiploidy permits a higher effective population size and evolutionary potential, likely facilitating Varroa’s ongoing success. Females produce males clonally, passing on their entire genomes. Varroa is a singular exception to the theoretically and empirically observed rule that, one evolved, haplodiploidy is an evolutionarily stable end state (an ‘evolutionary trap’). Novel mechanistic studies of even well-known organisms can lead to surprising insights into the evolutionary plasticity of reproductive systems.
BIMSA: Accelerating Long Sequence Alignment Using Processing-In-Memory
Authors: Alonso-Marín Alejandro , Fernandez Ivan , Aguado-Puig Quim , Gómez-Luna Juan , Marco-Sola Santiago , Mutlu Onur , Moreto Miquel
Published: May 2024

Motivation

Recent advances in sequencing technologies have stressed the critical role of sequence analysis algorithms and tools in genomics and healthcare research. In particular, sequence alignment is a fundamental building block in many sequence analysis pipelines and is frequently a performance bottleneck both in terms of execution time and memory usage. Classical sequence alignment algorithms are based on dynamic programming and often require quadratic time and memory with respect to the sequence length. As a result, classical sequence alignment algorithms fail to scale with increasing sequence lengths and quickly become memory-bound due to data-movement penalties.

Results

Processing-In-Memory (PIM) is an emerging architectural paradigm that seeks to accelerate memory-bound algorithms by bringing computation closer to the data to mitigate data-movement penalties. This work presents BIMSA (Bidirectional In-MemorySequenceAlignment), a PIM design and implementation for the state-of-the-art sequence alignment algorithm BiWFA (Bidirectional Wavefront Alignment), incorporating new hardware-aware optimizations for a production-ready PIM architecture (UPMEM). BIMSA supports aligning sequences up to 100K bases, exceeding the limitations of state-of-the-art PIM implementations. First, BIMSA achieves speedups up to 22.24×(11.95×on average) compared to state-of-the-art PIM-enabled implementations of sequence alignment algorithms. Second, achieves speedups up to 5.84×(2.83×on average) compared to the highest-performance multicore CPU implementation of BiWFA. Third, BIMSA exhibits linear scalability with the number of compute units in memory, enabling further performance improvements with upcoming PIM architectures equipped with more compute units and achieving speedups up to 9.56×(4.7×on average).

Availability

Code and documentation are publicly available athttps://github.com/AlejandroAMarin/BIMSA.

Contact

alejandro.alonso1@bsc.es
WITHDRAWN: Elucidating the molecular mechanism of phytochemicals against Parkinson’s disease through an integrated systems biology and molecular modeling approach
Authors: Bhowmik Ratul , Kumar Sunil , Manaithiya Ajay , Mohan C. Gopi , Mathew Bijo , Parkkila Seppo , Aspatwar Ashok
Published: May 2024

Withdrawal Statement

The authors have withdrawn their manuscript owing to the inability to complete the revisions or follow up on the manuscript at this time, due to personal circumstances. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
A novel expectation-maximization approach to infer general diploid selection from time-series genetic data
Authors: Fine Adam G. , Steinrücken Matthias
Published: May 2024

Detecting and quantifying the strength of selection is a main objective in population genetics. Since selection acts over multiple generations, many approaches have been developed to detect and quantify selection using genetic data sampled at multiple points in time. Such time series genetic data is commonly analyzed using Hidden Markov Models, but in most cases, under the assumption of additive selection. However, many examples of genetic variation exhibiting non-additive mechanisms exist, making it critical to develop methods that can characterize selection in more general scenarios. Thus, we extend a previously introduced expectation-maximization algorithm for the inference of additive selection coefficients to the case of general diploid selection, in which the heterozygote and homozygote fitness are parameterized independently. We furthermore introduce a framework to identify bespoke modes of diploid selection from given data, as well as a procedure for aggregating data across linked loci to increase power and robustness. Using extensive simulation studies, we find that our method accurately and efficiently estimates selection coefficients for different modes of diploid selection across a wide range of scenarios; however, power to classify the mode of selection is low unless selection is very strong. We apply our method to ancient DNA samples from Great Britain in the last 4,450 years, and detect evidence for selection in six genomic regions, including the well-characterized LCT locus. Our work is the first genome-wide scan characterizing signals of general diploid selection.

Author Summary

Natural selection increases the likelihood that beneficial genetic variants are passed from parent to offspring and thus forms the basis of genetic adaptation to novel environments. Genomic data sampled at multiple timepoints, such as genetic material extracted from ancient remains (ancient DNA) or data from evolve and resequence experiments, can enable more precise identification of genetic variants subject to selective pressure than contemporary samples alone. However, most methods for identifying genetic variation under selection focus on additive selection, where the fitness of the heterozygote is exactly intermediate between the homozygotes. Leveraging genetic data at multiple timepoints, we develop a method to detect additive and non-additive selection as well as to infer the most likely dominance mechanism. We apply our methods to a dataset of ancient DNA from Great Britain dated less than 4,450 years before present and identify six regions with signals of recent selection, including one at the TFR2 locus that has not been previously reported as a target of selection. Our work enables more accurate quantification of non-additive selection dynamics and can be used to test more complex models of selection.
Screening the human miRNA interactome reveals coordinated upregulation in melanoma, adding bidirectional regulation to miRNA networks
Authors: Jame-Chenarboo Faezeh , Reyes Joseph N. , Twells Nicholas M. , Ng Hoi-Hei , Macdonald Dawn , Hernando Eva , Mahal Lara K.
Published: May 2024

Cellular protein expression is coordinated post-transcriptionally by an intricate regulatory network. The current presumption is that miRNA work by repression of functionally related targets within a system. In recent work, upregulation of protein expression via direct interactions of mRNA with miRNA has been found in dividing cells, providing an additional mechanism of regulation. Herein, we demonstrate coordinated upregulation of functionally-coupled proteins by miRNA. We focused on CD98hc, the heavy chain of the amino acid transporter LAT1, and α-2,3-sialyltransferases ST3GAL1 and ST3GAL2, which are critical for CD98hc stability in melanoma. Profiling miRNA regulation using our high-throughput miRFluR assay, we identified miRNA that upregulated expression of both CD98hc and either ST3GAL1 or ST3GAL2. These co-upregulating miRNAs were enriched in melanoma datasets associated with transformation and progression. Our findings add co-upregulation by miRNA into miRNA regulatory networks and adds a new bidirectional twist to the impact miRNA have on protein regulation and glycosylation.
Green microwave-assisted extraction ofEuphorbia guyoniana:Optimization, metabolite profile andin vivoanti-inflammatory potential
Authors: Issaadi Halima Meriem , Bachir Yacine Nait , Naama Alaaeddine Ben , Aiter Imad , Szőri Kornél , Hunyadi Attila
Published: May 2024

This study aimed to optimize microwave-assisted extraction of phenolic compounds from undervalued traditional plantEuphorbia guyoniana(Boiss. & Reut.) using central composite design of response surface methodology. The independent variables were extraction time (x1: 5 – 25 min), ethanol concentration in the extractive solvent (x2: 30 – 70%), microwave power (x3: 180 – 800 Watt) and feed-to-solvent ratio (x4: 1:7.5 – 1:17.5) while dependent variables were total phenolic content (TPC) and total flavonoid content (TFC). Extract obtained by using the optimal extraction parameters was evaluated for itsin vivoanti-inflammatory activity by the carrageenan-induced paw edema model and was subjected to RP-HPLC-PDA-ESI-MS analysis to investigate the presence of phenolic compounds. The optimal conditions for highest TPC (377.22 ± 5.42 mg GAE/100g) and TFC (184.40 ± 1.18 mg QE/100g) were obtained at extraction time of 25 min, ethanol concentration of 40.57%, microwave power of 450 Watt and feed-to-solvent ratio of 1:17.5. The quadratic models significantly (p < 0.0001) fitted the experimental data with R2values of 0.984 and 0.970 for TPC and TFC, respectively. Optimal extract ofEuphorbia guyonianasignificantly higher inhibited carrageenan induced inflammation with a concentration of 50 mg/kg (75,98%) when compared with reference anti-inflammatory drug ibuprofen (43,77%). Finally, above the previously reported phenolic constituents, i.e, quercetin and kaempferol derivatives, hydroxycinnamates have been identified for the first time inEuphorbia guyonianaplant extract.
Exploring variations in the implementation of a health system level policy intervention to improve maternal and child health outcomes in resource limited settings: A qualitative multiple case study from Uganda
Authors: Walugembe David Roger , Plamondon Katrina , Kaharuza Frank , Waiswa Peter , Wylie Lloy , Wathen Nadine , Kothari Anita
Published: May 2024

Background

Despite growing literature, few studies have explored the implementation of policy interventions to reduce maternal and perinatal mortality in low- and middle-income countries (LMICs). Even fewer studies explicitly articulate the theoretical approaches used to understand contextual influences on policy implementation. This under-use of theory may account for the limited understanding of the variations in implementation processes and outcomes. We share findings from a study exploring how a health system-level policy intervention was implemented to improve maternal and child health outcomes in a resource limited LMIC.

Methods

Our qualitative multiple case study was informed by the Normalization Process Theory (NPT). It was conducted across eight districts and among ten health facilities in Uganda, with 48 purposively selected participants. These included health care workers located at each of the case sites, policy makers from the Ministry of Health, and from agencies and professional associations. Data were collected using semi-structured, in-depth interviews to understand uptake and use of Uganda’s maternal and perinatal death surveillance and response (MPDSR) policy and were inductively and deductively analyzed using NPT constructs and subconstructs.

Results

We identified six broad themes that may explain the observed variations in the implementation of the MPDSR policy. These include: 1) perception of the implementation of the policy, 2) leadership of the implementation process, 3) structural arrangements and coordination, 4) extent of management support and adequacy of resources, 5) variations in appraisal and reconfiguration efforts and 6) variations in barriers to implementation of the policy.

Conclusion and recommendations

The variations in sense making and relational efforts, especially perceptions of the implementation process and leadership capacity, had ripple effects across operational and appraisal efforts. Adopting theoretically informed approaches to assessing the implementation of policy interventions is crucial, especially within resource limited settings.
The retrotransposon-derived capsid genesPNMA1andPNMA4maintain reproductive capacity
Authors: Wood Thomas W.P. , Henriques William S. , Cullen Harrison B. , Romero Mayra , Blengini Cecilia S. , Sarathy Shreya , Sorkin Julia , Bekele Hilina , Jin Chen , Kim Seungsoo , Chemiakine Alexei , Khondker Rishad C. , Isola José V.V. , Stout Michael B. , Gennarino Vincenzo A. , Mogessie Binyam , Jain Devanshi , Schindler Karen , Suh Yousin , Wiedenheft Blake , Berchowitz Luke E.
Published: May 2024

The human genome contains 24gag-like capsid genes derived from deactivated retrotransposons conserved among eutherians. Although some of their encoded proteins retain the ability to form capsids and even transfer cargo, their fitness benefit has remained elusive. Here we show that thegag-like genesPNMA1andPNMA4support reproductive capacity. Six-week-old mice lacking eitherPnma1orPnma4are indistinguishable from wild-type littermates, but by six months the mutant mice become prematurely subfertile, with precipitous drops in sex hormone levels, gonadal atrophy, and abdominal obesity; overall they produce markedly fewer offspring than controls. Analysis of donated human ovaries shows that expression of both genes declines normally with aging, while severalPNMA1andPNMA4variants identified in genome-wide association studies are causally associated with low testosterone, altered puberty onset, or obesity. These findings expand our understanding of factors that maintain human reproductive health and lend insight into the domestication of retrotransposon-derived genes.
3D chromatin maps of a brown alga reveal U/V sex chromosome spatial organization
Authors: Liu Pengfei , Vigneau Jeromine , Craig Rory , Barrera-Redondo Josue , Avdievich Elena , Martinho Claudia , Borg Michael , Haas Fabian B. , Liu Chang , Coelho Susana M
Published: May 2024

Sex chromosomes are unique genomic regions displaying structural and evolutionary features that distinguish them markedly from autosomes. Although nuclear three dimensional (3D) folding of chromatin structure is im-portant for gene expression regulation and correct developmental programs, very little is known about the 3D architecture of sex chromosomes within the nucleus, and how that impacts their function in sex determination. Here, we determine the sex-specific 3D organization of the model brown algaEctocarpuschromosomes at 2 kb resolution, by comprehensively mapping long-range chromosomal interactions using Hi-C coupled with Oxford Nanopore long reads. We report thatEctocarpusinterphase chromatin exhibits a non-Rabl conformation, with strong contacts among telomeres and among centromeres, which feature centromere-specific LTR retrotranspos-ons. TheEctocarpuschromosomes do not contain large local interactive domains that resemble TADs described in animals, but their 3D genome organization is largely shaped by post-translational modifications of histone pro-teins that regulate chromatin compaction and mediate transcriptional regulation. We describe the spatial confor-mation and sub-nuclear positioning of the sex determining region (SDR) within the U and V chromosomes and show that these regions are very insulated and span the centromeres. Moreover, we link sex-specific chromatin dynamics and gene expression levels to the 3D chromatin structure of U and V chromosomes. Finally, we uncover the unique conformation of a large genomic region on chromosome 6 harboring an endogenous viral element (EVE), providing insights regarding the functional significance of the chromatin organisation of latent giant dsDNA virus.
Phenotype and function of IL-10 producing NK cells in individuals with malaria experience
Authors: McNitt Sarah A. , Dick Jenna K. , Hernandez Castaneda Maria , Sangala Jules A. , Pierson Mark , Macchietto Marissa , Burrack Kristina S. , Crompton Peter D. , Seydel Karl B. , Hamilton Sara E. , Hart Geoffrey T.
Published: May 2024

Plasmodium falciparuminfection can trigger high levels of inflammation that lead to fever and sometimes severe disease. People living in malaria-endemic areas gradually develop resistance to symptomatic malaria and control both parasite numbers and the inflammatory response. We previously found that adaptive natural killer (NK) cells correlate with reduced parasite load and protection from symptoms. We also previously found that murine NK cell production of IL-10 can protect mice from experimental cerebral malaria. Human NK cells can also secrete IL-10, but it was unknown what NK cell subsets produce IL-10 and if this is affected by malaria experience. We hypothesize that NK cell immunoregulation may lower inflammation and reduce fever induction. Here, we show that NK cells from subjects with malaria experience make significantly more IL-10 than subjects with no malaria experience. We then determined the proportions of NK cells that are cytotoxic and produce interferon gamma and/or IL-10 and identified a signature of adaptive and checkpoint molecules on IL-10-producing NK cells. Lastly, we find that co-culture with primary monocytes,Plasmodium-infected RBCs, and antibody induces IL-10 production by NK cells. These data suggest that NK cells may contribute to protection from malaria symptoms via IL-10 production.
Quantifying Normal Diaphragmatic Motion and Shape and their Developmental Changes via Dynamic MRI
Authors: Hao You , Udupa Jayaram K. , Tong Yubing , Wu Caiyun , McDonough Joseph M. , Gogel Samantha , Mayer Oscar H. , Alnoury Mostafa , Cahill Patrick J. , Anari Jason B. , Torigian Drew A.
Published: May 2024

Background

The diaphragm is a critical structure in respiratory function, yet in-vivo quantitative description of its motion available in the literature is limited.

Research Question

How to quantitatively describe regional hemi-diaphragmatic motion and curvature via free-breathing dynamic magnetic resonance imaging (dMRI)?

Study Design and Methods

In this prospective cohort study we gathered dMRI images of 177 normal children and segmented hemi-diaphragm domes in end-inspiration and end-expiration phases of the constructed 4D image. We selected 25 points uniformly located on each 3D hemi-diaphragm surface. Based on the motion and local shape of hemi-diaphragm at these points, we computed the velocities and sagittal and coronal curvatures in 13 regions on each hemi-diaphragm surface and analyzed the change in these properties with age and gender.

Results

Our cohort consisted of 94 Females, 6-20 years (12.09+3.73), and 83 Males, 6-20 years (11.88+3.57). We observed velocity range: ∼2mm/s to ∼13mm/s; Curvature range –Sagittal: ∼3m-1to ∼27m-1; Coronal: ∼6m-1to ∼20m-1. There was no significant difference in velocity between genders, although the pattern of change in velocity with age was different for the two groups. Strong correlations in velocity were observed between homologous regions of right and left hemi-diaphragms. There was no significant difference in curvatures between genders or change in curvatures with age.

Interpretation

Regional motion/curvature of the 3D diaphragmatic surface can be estimated using free-breathing dynamic MRI. Our analysis sheds light on here-to-fore unknown matters such as how the pediatric 3D hemi-diaphragm motion/shape varies regionally, between right and left hemi-diaphragms, between genders, and with age.
Estimating lung volumetric parameters via rapid, limited-slice, free-breathing thoracic dynamic MRI
Authors: Hao You , Udupa Jayaram K. , Tong Yubing , Wu Caiyun , McDonough Joseph M. , Gogel Samantha , Biko David M. , Anari Jason B. , Torigian Drew A. , Cahill Patrick J.
Published: May 2024

Purpose

We present an observational study involving free-breathing short-scan-time dynamic MRI (dMRI) method that can be routinely used for computing dynamic lung volumes accurately.

Materials and Methods

(i) Full-resolution free-breathing sagittally-acquired 2D dMRI scans are gathered from 45 normal children via True-FISP sequence. Sparse dMRI (s-dMRI) scans are simulated from these datasets by subsampling in the spatio-temporal domains via a limited numberNSSof selected sagittal locations andTSSof time instances (respectively,NFSandTFSfor full scan). (ii) A 4D image is constructed from both full and sparse scans. Lungs are segmented from 4D image, and their volumes from full (VF) and sparse dMRI (VS) scans are computed. (iii) A regression model is fit forVFas a function ofVSon a training set, and the full-resolution volumeVPpredicted by the model is estimated fromVS. (iv) The deviation ofVPfromVFis analyzed on both synthesized sparse dMRI scans from a separate full-resolution test set and actual s-dMRI scans prospectively acquired from 10 normal children.

Results

WithNSS=5 (per lung) andTSS=40, the deviation ofVPfromVFwas ∼2% with a total scan-time of ∼9 min (45-60 min for the full scan withNFS=15-22 (per lung) andTFS=80). These metrics become 0.4%, and <20 min for s-dMRI withNSS=15-22 (per lung) andTSS=40.

Conclusion

s-dMRI is a practical approach for computing dynamic lung volumes that can be used routinely with no radiation concern, especially on patients who cannot tolerate long scan times.
Assessment of knowledge, Attitudes and Practices regarding Hepatitis B virus among Nurses in Bangladesh: a cross-sectional study
Authors: Rahman Salekur , Das Sadhan Kumar , Farhana Zaki , Bakkar Siddik Md Abu , Roy Anjan Kumar , Dey Piue , Kundu Shuvojit Kumar , Hossain Md Anwar , Islam S M Shahinul , Kamil Anton Abdulbasah , Khanam Jahan Ara , Rahman Mohammad Meshbahur
Published: May 2024

Background

Hepatitis B virus (HBV) infection is a worldwide issue. Nurses are particularly at risk of occupational HBV contamination. In Bangladesh, there is little understanding of the knowledge, attitude, and practices (KAP) of nurses regaarding HBV. Therefore, the study aimed to assess the KAP of nurses regarding HBV.

Methods

This cross-sectional study was conducted among 120 nurses through face-to-face interviews through a semi-structured questionnaire using a convenient sample technique. Different statistical tools including frequency distribution, Pearson Chi-square test, and t-tests were used in data analysis.

Results

The average age of the participants was 34.5 years where majority of them were 31-40 years old (50.0%) and female (83%). This study revealed that 25.0% had good knowledge, 43.3% exhibited a good (positive) attitude, and 56.7% of nurses demonstrated good practices regarding HBV. Conversely, nurses exhibit a poor knowledge rate of 30.0%, a poor attitude rate of 30.8%, and a poor practice rate of 29.2% regarding HBV. The independent sample t-test and one-way ANOVA demonstrated that nurses’ from rural residences had a significantly higher knowledge [0.80 (0.79-0.82) versus 0.78 (0.77-0.79)]; p=0.001] regarding HBV. Similarly, female [mean attitude score: 0.88 (0.85-0.91) versus 0.77 (0.86-0.69); p=0.009] and nurses from Muslim [0.79(0.61-0.97) versus 0.79(0.76-0.83); p=0.035] faiths has significantly higher positive attitude and good practice behaviors compared to their counterparts.

Conclusions

Increasing the vaccination coverage rate of all nurses, as well as implementing additional techniques for preventing exposure in the workplace, training programs on HBV infection, including PEP, comes highly recommended.
ILC2s navigate tissue redistribution during infection using stage-specific S1P receptors
Authors: Ito Takamasa , Ishida Yoshihiro , Zhang Yingyu , Guichard Vincent , Zhang Wanwei , Han Richard , Guckian Kevin , Chun Jerold , Que Jianwen , Smith Allen , Urban Joseph F. , Huang Yuefeng
Published: May 2024

Lymphocytes can circulate as well as take residence within tissues. While the mechanisms by which circulating populations are recruited to infection sites have been extensively characterized, the molecular basis for the recirculation of tissue-resident cells is less understood. Here, we show that helminth infection- or IL-25-induced redistribution of intestinal group 2 innate lymphoid cells (ILC2s) requires access to the lymphatic vessel network. Although the secondary lymphoid structure is an essential signal hub for adaptive lymphocyte differentiation and dispatch, it is redundant for ILC2 migration and effector function. Upon IL-25 stimulation, a dramatic change in epigenetic landscape occurs in intestinal ILC2s, leading to the expression of sphingosine-1-phosphate receptors (S1PRs). Among the various S1PRs, we found that S1PR5 is critical for ILC2 exit from intestinal tissue to lymph. By contrast, S1PR1 plays a dominant role in ILC2 egress from mesenteric lymph nodes to blood circulation and then to distal tissues including the lung where the redistributed ILC2s contribute to tissue repair. The requirement of two S1PRs for ILC2 migration is largely due to the dynamic expression of the tissue-retention marker CD69, which mediates S1PR1 internalization. Thus, our study demonstrates a stage-specific requirement of different S1P receptors for ILC2 redistribution during infection. We therefore propose a fundamental paradigm that innate and adaptive lymphocytes utilize a shared vascular network frame and specialized navigation cues for migration.
Acceleration of genome rearrangement in clitellate annelids
Authors: Schultz Darrin T. , Heath-Heckman Elizabeth A.C. , Winchell Christopher J. , Kuo Dian-Han , Yu Yun-sang , Oberauer Fabian , Kocot Kevin M. , Cho Sung-Jin , Simakov Oleg , Weisblat David A.
Published: May 2024

Comparisons of multiple metazoan genomes have revealed the existence of ancestral linkage groups (ALGs), genomic scaffolds sharing sets of orthologous genes that have been inherited from ancestral animals for hundreds of millions of years (Simakov et al. 2022; Schultz et al. 2023) These ALGs have persisted across major animal taxa including Cnidaria, Deuterostomia, Ecdysozoa and Spiralia. Notwithstanding this general trend of chromosome-scale conservation, ALGs have been obliterated by extensive genome rearrangements in certain groups, most notably including Clitellata (oligochaetes and leeches), a group of easily overlooked invertebrates that is of tremendous ecological, agricultural and economic importance (Charles 2019; Barrett 2016). To further investigate these rearrangements, we have undertaken a comparison of 12 clitellate genomes (including four newly sequenced species) and 11 outgroup representatives. We show that these rearrangements began at the base of the Clitellata (rather than progressing gradually throughout polychaete annelids), that the inter-chromosomal rearrangements continue in several clitellate lineages and that these events have substantially shaped the evolution of the otherwise highly conserved Hox cluster.
Analysis of differential expression of matrix metalloproteins and defensins in the nasopharyngeal milieu of mild and severe COVID-19 cases
Authors: Imtiaz Khekashan , Farooqui Nida , Ahmed Khalid , Zhamalbekova Alnara , Anwar Muhammad Faraz , Gul Khitab , Hussain Azhar , Sarría-Santamera Antonio , Abidi Syed Hani
Published: May 2024

Introduction

A subset of COVID-19 disease patients suffers a severe form of the illness, however, underlying early pathophysiological mechanisms associated with the severe form of COVID-19 disease remain to be fully understood. Several studies showed the association of COVID-19 disease severity with the changes in the expression profile of various matrix metalloproteinases (MMPs) and defensins. However, the link between the changes in the expression of matrix metalloproteinase (MMPs) and defensins (DA) in the nasopharyngeal milieu, during early phases of infection, and disease severity remains poorly understood. Therefore, we performed differential gene expression analysis of matrix metalloproteinases (MMPs) and defensins in the nasopharyngeal swab samples collected from mild and severe COVID-19 cases within three days of infection and examined the association between MMP and DA expression and disease severity.

Material and Method

A total of 118 previously collected nasopharyngeal samples from mild and severe COVID-19 patients (as per the WHO criteria) were used in this study. To determine the viral loads and assess the mRNA expression of matrix metalloproteinase (MMPs) and defensins, a real-time qPCR assay was used. To assess statistically significant differences in the mean expression of viral loads and the cytokines in between the severe and mild groups, an unpaired T-test was applied. The Pearson correlation test was used to assess the correlation between cytokine expressions. In addition, a multivariable logistic regression analysis was carried out with all the variables from the data set using ‘severity’ as the outcome variable.

Results

Our results showed that the expression of DA3 and MMP2 to be considerably lower in the severe group than in the mild group. Furthermore, there was a significant association between MMP1 and DA4 and DA6 (r=0.5, p=0.0001); as well as between MMP7 and DA1 and DA6 (r=0.5, p=0.00). Additionally, the regression analysis shows a significant correlation (p 0.05) between MMP2 and the severity of COVID-19 disease.

Conclusion

The early detection of changes in the expression of MMPs and defensins may act as a useful biomarker/predictor for possible severe COVID-19 disease, which may be useful in the clinical management of patients to reduce COVID-19-associated morbidity and mortality.
Enhancing Variant of Uncertain Significance (VUS) Interpretation in Neurogenetics: Collaborative Experiences from a Tertiary Care Centre
Authors: Horowitz Kayla , Fotopoulos Nellie H. , Mistry Alana J. , Simo Justin , Medeiros Miranda , Bucco Isabela D. , Ginsberg Mia , Dwosh Emily , La Piana Roberta , Rouleau Guy A. , Dilliott Allison A. , Farhan Sali M.K.
Published: May 2024

Background:The findings of variants of uncertain significance (VUS) on a clinical genetic testing report pose a challenge for attending healthcare professionals (HCPs) in patient care. Here, we describe the outcomes of multidisciplinary VUS Rounds, implemented at a neurological disease tertiary care centre, which aid in interpreting and communicating VUS identified in our neurogenetics patient population.Methods:VUS Rounds brought together genetic counsellors, molecular geneticists, and scientists to evaluate VUS against genomic and phenotypic evidence and assign an internal temperature classification "VUS Hot", "True VUS", or "VUS Cold", corresponding to potential pathogenicity. Biweekly meetings were held among the committee to deliberate variant classifications, determine additional clinical management actions, and discuss nuances of VUS result communication.Results:In total, 143 VUS identified in 72 individuals with neurological disease were curated between October 2022 and December 2023. Of these, 12.6% were classified as VUS Hot, carried by 22.2% of the individuals, allowing for prioritization of additional evaluation to determine potential pathogenicity of the variants, such as clinical follow-up or segregation analysis. In contrast, 45.4% of VUS were Cold and could be eliminated from further consideration in the carrier's care. Herein, we thoroughly evaluated the various evidence that contributed to our VUS classifications and resulting clinical actions.Conclusions:The assessment of VUS leveraging multidisciplinary collaboration allowed us to delineate required follow-up analyses for our neurology patient population. Integration of VUS Rounds into healthcare practices, ensures equitable knowledge dissemination amongst HCPs and effective incorporation of uncertain genetic results into patient care.
Enhancing data integrity in Electronic Health Records: Review of methods for handling missing data
Authors: Vahdati Amin , Cotterill Sarah , Marsden Antonia , Kontopantelis Evangelos
Published: May 2024

Introduction

Electronic Health Records (EHRs) are vital repositories of patient information for medical research, but the prevalence of missing data presents an obstacle to the validity and reliability of research. This study aimed to review and category ise methods for handling missing data in EHRs, to help researchers better understand and address the challenges related to missing data in EHRs.

Materials and Methods

This study employed scoping review methodology. Through systematic searches on EMBASE up to October 2023, including review articles and original studies, relevant literature was identified. After removing duplicates, titles and abstracts were screened against inclusion criteria, followed by full-text assessment. Additional manual searches and reference list screenings were conducted. Data extraction focused on imputation techniques, dataset characteristics, assumptions about missing data, and article types. Additionally, we explored the availability of code within widely used software applications.

Results

We reviewed 101 articles, with two exclusions as duplicates. Of the 99 remaining documents, 21 underwent full-text screening, with nine deemed eligible for data extraction. These articles introduced 31 imputation approaches classified into ten distinct methods, ranging from simple techniques like Complete Case Analysis to more complex methods like Multiple Imputation, Maximum Likelihood, and Expectation-Maximization algorithm. Additionally, machine learning methods were explored. The different imputation methods, present varying reliability. We identified a total of 32 packages across the four software platforms (R, Python, SAS, and Stata) for imputation methods. However, it’s significant that machine learning methods for imputation were not found in specific packages for SAS and Stata. Out of the 9 imputation methods we investigated, package implementations were available for 7 methods in all four software platforms.

Conclusions

Several methods to handle missing data in EHRs are available. These methods range in complexity and make different assumptions about the missing data mechanisms. Knowledge gaps remain, notably in handling non-monotone missing data patterns and implementing imputation methods in real-world healthcare settings under the Missing Not at Random assumption. Future research should prioritize refining and directly comparing existing methods.
Early Life Domains as Predictors of Obesity and Hypertension Comorbidity: Findings from the 1970 British Cohort Study (BCS70)
Authors: Stannard S , Owen RK , Berrington A , Ziauddeen N , Fraser SDS , Paranjothy S , Hoyle RB , Alwan N A
Published: May 2024

Background

Obesity and hypertension are major public health problems and are associated with adverse health outcomes. To model realistic prevention scenarios and inform policy, it may be helpful to conceptualise early lifecourse domains of risk and incorporate such information when predicting comorbidity outcomes. We identify exposures across five pre-hypothesised childhood domains and explore them as predictors of obesity and hypertension comorbidity in adulthood.

Methods

The analytical sample included 7858 participants in the 1970 British Cohort Study. The outcome was obesity (BMI of ≥30) and hypertension (blood pressure>140/90mm Hg or self-reported doctor’s diagnosis) comorbidity at age 46. Early life domains included: ‘prenatal, antenatal, neonatal and birth’, ‘developmental attributes and behaviour’, ‘child education and academic ability’, ‘socioeconomic factors’ and ‘parental and family environment’. We conducted prediction analysis of the outcome in three stages:(1) stepwise backward elimination to select variables for inclusion for each domain (2) calculation of predicted risk scores of obesity-hypertension for each cohort member within each domain (3) multivariable logistic regression analysis including domain-specific risk scores, sex and ethnicity to assess how well the outcome could be predicted. We additionally included potential adult predictors of obesity-hypertension comorbidity as sensitivity analysis.

Results

Including all domain-specific risk scores in the same model, all five domains were significant predictors of obesity-hypertension comorbidity. The predictive power of the model, measured by the area under the curve (AUC), was 0.63 (95%CI 0.61-0.65). Including adult predictors increase the AUC to 0.68 (95%CI 0.66-0.70), and three early life domains - the parental and family environment domain (OR 1.11 95%CI 1.05-1.17) the socioeconomic factors domain (OR 1.09 95%CI 1.04-1.16), and the education and academic ability domain (OR 1.07 95%CI 1.02-1.13) remained predictors of obesity-hypertension comorbidity.

Conclusions

We found three robust domains for predicting obesity-hypertension comorbidity. Interventions that address these early life factors could reduce the burden of comorbidity.
Retention in care and antiretroviral therapy adherence among Medicaid beneficiaries with HIV, 2001-2015
Authors: Rudolph Jacqueline E. , Calkins Keri L. , Zhang Xueer , Zhou Yiyi , Xu Xiaoqiang , Wentz Eryka L. , Joshu Corinne E. , Lau Bryan
Published: May 2024

Disparities in HIV care by socioeconomic status, place of residence, and race/ethnicity prevent progress toward epidemic control. No study has comprehensively characterized the HIV care cascade among people with HIV enrolled in Medicaid – an insurance source for low-income individuals in the US. We analyzed data from 246,127 people with HIV enrolled in Medicaid 2001-2015, aged 18-64, living in 14 US states. We estimated monthly prevalence of four steps of the care cascade: retained in care/adherent to ART; retained/not adherent; not retained/adherent; not retained/not adherent. Beneficiaries were retained in care if they had an outpatient care encounter every six months. Adherence was based on medication possession ratio. We estimated prevalence using a non-parametric multi-state approach, accounting for death as a competing event and for Medicaid disenrollment using inverse probability of censoring weights. Across 2001-2015, the proportion of beneficiaries with HIV who were retained/ART adherent increased, overall and in all subgroups. By 2015, approximately half of beneficiaries were retained in care, and 42% of beneficiaries were ART adherent. We saw meaningful differences by race/ethnicity and region. Our work highlights an important disparity in the HIV care cascade by insurance status during this time period.