bluuebunny/crossref_metadata_2025 huggingface dataset:
An Image Processing Tool for Automated Quantification of Bacterial Burdens in Zebrafish Larvae
Authors: Yamaguchi Naoya , Otsuna Hideo , Eisenberg-Bord Michal , Ramakrishnan Lalita
Published: August 2024

Zebrafish larvae are used to model the pathogenesis of multiple bacteria. This transparent model offers the unique advantage of allowing quantification of fluorescent bacterial burdens (fluorescent pixel counts: FPC) in vivo by facile microscopical methods, replacing enumeration of bacteria using time-intensive plating of lysates on bacteriological media. Accurate FPC measurements require laborious manual image processing to mark the outside borders of the animals so as to delineate the bacteria inside the animals from those in the culture medium that they are in. Here, we have developed an automated ImageJ/Fiji-based macro that accurately detect the outside borders of Mycobacterium marinum-infected larvae.
FindingNemo: A Toolkit for DNA Extraction, Library Preparation and Purification for Ultra Long Nanopore Sequencing
Authors: Cahyani Inswasti , Tyson John , Holmes Nadine , Quick Josh , Moore Chris , Loman Nick , Loose Matthew
Published: August 2024

Since the advent of long read sequencing, achieving longer read lengths has been a key goal for many users. Ultra-long read sets (N50 ≥ 100 kb) produced from Oxford Nanopore sequencers have improved genome assemblies in recent years. However, despite progress in extraction protocols and library preparation methods, ultra-long sequencing remains challenging for many sample types. Here we compare various methods and introduce theFindingNemoprotocol that: (1) optimises ultra-high molecular weight (UHMW) DNA extraction and library clean-up by using glass beads and Hexamminecobalt(III) chloride (CoHex), (2) can deliver high ultra-long sequencing yield of >20 Gb of reads from a single MinION flow cell or >100 Gb from PromethION devices (R9.4 to R10.4 pore variants), and (3) is scalable to using fewer input cells or lower DNA amounts, with extraction to sequencing possible in a single working day. By comparison, we show this protocol is superior to previous ones due to precise determination of input DNA quantity and quality by cell count, sample dilution and homogenization approaches.
Direction and modality of transcription changes caused by TAD boundary disruption inSlc29a3/Unc5blocus depends on tissue-specific epigenetic context
Authors: Salnikov Paul , Belokopytova Polina , Yan Alexandra , Viesná Emil , Korablev Alexey , Serova Irina , Lukyanchikova Varvara , Stepanchuk Yana , Torgunakov Nikita , Tikhomirov Savelii , Fishman Veniamin
Published: August 2024

Topologically associated domains (TADs) are believed to be involved in the regulation of gene expression. While the impact of TAD perturbations is usually studied in developmental genes with highly cell-type-specific expression patterns, this study examines genes with broad expression profiles divided by a strong insulatory boundary. We focused on mouseSlc29a3/Unc5blocus, which encompasses two distinct TADs. Our analysis demonstrates that deletions of CTCF binding sites within this locus lead to alterations in local chromatin architecture, disrupting existing loops and forming novel long-range interactions. We evaluated the transcription changes ofUnc5b, Slc29a3, Psap, Vsir, Cdh23, andSgpl1genes across various organs, finding that TAD boundary disruption results in variable transcriptional responses, where not only magnitude, but also direction of gene expression changes are tissue-specific. Current models of genome architecture, including enhancer competition and hijacking, only partially account for these transcriptional changes, indicating the need for further investigation into the mechanisms underlying TAD function and gene regulation.
Xylazine Exacerbates Fentanyl-Induced Respiratory Depression and Bradycardia
Authors: Demery-Poulos Catherine , Moore Sierra C. , Levitt Erica S. , Anand Jessica P. , Traynor John R.
Published: August 2024

Fatal opioid overdoses in the United States have nearly tripled during the past decade, with greater than 92% involving a synthetic opioid like fentanyl. Fentanyl potently activates the μ-opioid receptor to induce both analgesia and respiratory depression. The danger of illicit fentanyl has recently been exacerbated by adulteration with xylazine, an α2-adrenergic receptor agonist typically used as a veterinary anesthetic. In 2023, over a 1,000% increase in xylazine-positive overdoses was reported in some regions of the U.S. Xylazine has been shown to potentiate the lethality of fentanyl in mice, yet a mechanistic underpinning for this effect has not been defined. Herein, we evaluate fentanyl, xylazine, and their combination in whole-body plethysmography (to measure respiration) and pulse oximetry (to measure blood oxygen saturation and heart rate) in male and female CD-1 mice. We show that xylazine decreases breathing rate more than fentanyl by increasing the expiration time. In contrast, fentanyl primarily reduces breathing by inhibiting inspiration, and xylazine exacerbates these effects. Fentanyl but not xylazine decreased blood oxygen saturation, and when combined, xylazine did not change the maximum level of fentanyl-induced hypoxia. Xylazine also reduced heart rate more than fentanyl. Finally, loss in blood oxygen saturation correlated with the frequency of fentanyl-induced apneas, but not breathing rate. Together, these findings provide insight into how the addition of xylazine to illicit fentanyl may increase the risk of overdose.

Graphical Abstract
Classifying epithelial-mesenchymal transition states in single cell cancer data using large language models
Authors: Pan Shi , Withnell Eloise , Secrier Maria
Published: August 2024

Epithelial–mesenchymal plasticity plays a significant role in various biological processes including tumour progression and chemoresistance. However, the expression programmes underlying the epithelial–mesenchymal transition (EMT) in cancer are diverse, and accurately defining the EMT status of tumour cells remains a challenging task. In this study, we employed a pre-trained single-cell large language model (LLM) to develop an EMT-language model (EMT-LM) that allows us to capture discrete states within the EMT continuum in single cell cancer data. In capturing EMT states, we achieved an average Area Under the Receiver Operating Characteristic curve (AUROC) of 90% across multiple cancer types. We propose a new metric, ADESI, to aid the biological interpretability of our model, and derive EMT signatures liked with energy metabolism and motility reprogramming underlying these state switches. We further employ our model to explore the emergence of EMT states in spatial transcriptomics data, uncovering hybrid EMT niches with contrasting potential for antitumour immunity or immune evasion. Our study provides a proof of concept that LLMs can be applied to characterise cell states in single cell data, and proposes a generalisable framework to predict EMT in single cell RNA-seq that can be adapted and expanded to characterise other cellular states.
Rapid in situ forming PEG hydrogels for mucosal drug delivery
Authors: Yeruva Taj , Morris Robert J , Zhao Luke , Kofinas Peter , Duncan Gregg A
Published: August 2024

In situ gelling polymeric biomaterials have proven useful as drug delivery vehicles to enable sustained release at sites of disease or injury. However, if delivered to mucosal tissues, such as the eyes, nose, gastrointestinal, and cervicovaginal tract, these gels must also possess the ability to adhere to an epithelium coated in mucus. Towards this end, we report a new rapid in situ gelling polyethylene glycol-based hydrogel. Unlike other chemistries that enable rapid gel formation which form via irreversible covalent bonds, we use a bio-reducible linker allowing the gels to be naturally degraded over several days once administered. We identified a set of 6 lead formulations, which rapidly form into disulfide-linked PEG hydrogels in 30 seconds or less. These rapidly forming PEG hydrogels were also able to conform and adhere to mucosal tissues via PEG-mucin entanglements and hydrogen bonding. Controlled release of protein-based cargoes from the PEG gels was achieved over several hours whereas 40 nm nanoparticle-based cargos were retained over 24 hours. We also found these rapid in situ forming PEG gels were well-tolerated by mammalian cells. These studies support further testing and development of rapid in situ forming PEG gels for drug delivery to improve therapeutic retention and efficacy at mucosal sites.
MiniXL: An open-source, large field-of-view epifluorescence miniature microscope for mice capable of single-cell resolution and multi-brain region imaging
Authors: Zhao Pingping , Guo Changliang , Xie Mian , Chen Liangyi , Golshani Peyman , Aharoni Daniel
Published: August 2024

Capturing the intricate dynamics of neural activity in freely behaving animals is essential for understanding the neural mechanisms underpinning specific behaviors. Miniaturized microscopy enables investigators to track population activity at cellular level, but the field of view (FOV) of these microscopes have been limited and does not allow multiple-brain region imaging. To fill this technological gap, we have developed the eXtra Large field-of-view Miniscope (MiniXL), a 3.5g lightweight miniaturized microscope with an FOV measuring 3.5 mm in diameter and an electrically adjustable working distance of 1.9 mm ± 200 μm. We demonstrated the capability of MiniXL recording the activity of large neuronal population in both subcortical area (hippocampal dorsal CA1) and deep brain regions (medial prefrontal cortex, mPFC and nucleus accumbens, NAc). The large FOV allows simultaneous imaging of multiple brain regions such as bilateral mPFCs or mPFC and NAc during complex social behavior and tracking cells across multiple sessions. As with all microscopes in the UCLA Miniscope ecosystem, the MiniXL is fully open-source and will be shared with the neuroscience community to lower the barriers for adoption of this technology.
The GenPPI tool enhanced Protein Interaction Network Generation with Machine Learning-Based Protein Similarity Inference
Authors: William Alisson , Godoy Iury , Marquez Carlos , Silva Lucas , Prado Matheus , Avila Natanael , Santos Anderson Rodrigues dos
Published: August 2024

The study of protein interaction is still promising for a better understanding of diseases. At first glance, the term interaction among proteins could allude to, for instance, the interaction between the protein of a host and a pathogen. Such an interaction is being pursued mainly via machine learning algorithms since it is difficult to discriminate direct rules for it. However, the interaction among proteins on the same genome is also critical, for instance, to understand how a pathogen survives, starts, or maintains an infection. We can analyze interactions within a genome deterministically at the price of significant hardware employment. Our software GenPPI, in its first edition, allows us to explore interaction networks in genomes using mainly the known rules for neighborhood and phylogenetic profiles conserved. However, despite the speed, it suffered from underrepresentation from the core pangenome due to a simplistic algorithm to raise that, losing a pair of proteins possessing less than 90% of amino acid identity. The present work describes the new GenPPI software enhancements on determining homology between protein pairs, which is one of the principal bottlenecks in creating ab initio interaction networks from genomes and the primary step inferring neighborhood and phylogenetic profiles conserved for all genomes under analysis. This improvement was achieved using the Random Forest algorithm, working on biophysical features derived from ten amino acid propensity indexes used to calculate sixty features for each genome's proteins. We crafted a training data set of homolog and non-homolog proteins using nine full proteomes from critical bacteria. A significant number of expressive genomes as the training dataset allowed us to classify similar proteins with more than 65% amino acid identity via a machine learning test, an average result obtained from dozens of validations. Such a strategy resulted in more comprehensive and accurate protein interaction networks capable of analyzing genomes of different organisms. Our testing of the new GenPPI improvement using the bacterium Buchenera aphidicola yielded impressive results. We achieved an overlap of 62% with the interactions documented in the STRING, surpassing the previous GenPPI version, which was limited to less than 50% compared to STRING. More notably, we were able to achieve a full overlap using alternative GenPPI parameters, albeit at the cost of interactions absent on the STRING database. This significant achievement underscores the software's potential as a flexible tool for advancing research in various areas of biomedicine and other scientific fields, balancing precision, completeness, and a lower density of interaction networks. GenPPI is available for access at \url{https://genppi.facom.ufu.br/
Connectivity of the neuronal network for contextual fear memory is disrupted in a mouse model of third-trimester binge-like ethanol exposure
Authors: Morningstar Mitchell D , Lopez Katalina M , Mayfield Stefanie S , Almeida-Mancero Roberto N , Marquez Joshua , Flores Andres M , Hafer Brooke R , Estrada Edilberto , Holtzman Gwen A , Goranson Emerald V , Reid Natalie M , Aldrich Abigale R , Ghatalia Desna V , Patel Juhee R , Padilla Christopher M , Chavez Glenna J , Roman Javier Kelly , Bhakta Pooja A , Valenzuela C. Fernando , Linsenbardt David D
Published: August 2024

Background: In rodents, third-trimester equivalent alcohol exposure (TTAE) produces significant deficits in hippocampal-dependent memory processes such as contextual fear conditioning (CFC). The present study sought to characterize changes in both behavior and Fos+ neurons following CFC in ethanol (EtOH)-treated versus saline-treated mice using TRAP2:Ai14 mice that permanently label Fos+ neurons following a tamoxifen injection. We hypothesized that TTAE would produce long-lasting disruptions to the networks engaged following CFC with a particular emphasis on the limbic memory system. Methods: On postnatal day 7, mice received either two injections of saline or 2.5 g/kg EtOH spaced 2 hours apart. The mice were left undisturbed until they reached adulthood, at which point they underwent CFC. After context exposure on day 2, mice received a tamoxifen injection. Brain tissue was harvested. Slides were automatically imaged using a Zeiss AxioScanner. Manual counts on a priori regions of interest were conducted. Automated counts were performed on the whole brain using the QUINT 2D stitching pipeline. Last, novel network analyses were applied to identify future regions of interest. Results: TTAE reduced context recall on day 2 of CFC. Fos+ neural density increased in the CA1 and CA3. Fos+ counts were reduced in the anteroventral (AV) and anterodorsal thalamus. The limbic memory system showed significant hyperconnectivity in male TTAE mice and the AV shifted affinity towards hippocampal subregions. Last, novel regions such as a subparafascicular area and basomedial amygdalar nucleus were implicated as important mediators. Discussion: These results suggest that CFC is mediated by the limbic memory system and is disrupted following TTAE. Given the increase in CA1 and CA3 activity, a potential hypothesis is that TTAE causes disruptions to memory encoding following day 1 conditioning. Future studies will aim to determine whether this disruption specifically affects the encoding or retrieval of fear memories.
A Continuous, Low-Flow, and Multiplexing Pumping System for Microfluidics Applications
Authors: Walp Kara A. , Patel Yash H. , Alsadoun Woud , Gordon Hailey Lenn , Rastaghi Hamed , M. D. Oliveira Samuel
Published: August 2024

Microfluidics optimize experimental procedures but often require external pumps for precise, steady, and low flow rates. These procedures typically require extended, continuous operation for long-duration experiments. We introduce the Dual-Syringe Continuous Pumping Mechanism (DSCPM), a low-cost, precise, and continuous pump for microfluidic applications with input multiplexing capability. With a 3D-printed housing and standard components, the DSCPM is easy to fabricate and accessible. Operating at a microliter per minute flow rates, the DSCPM uses fluidic bridge rectification to combine syringe pump precision with continuous infusion. We validated laminar flow in microfluidic "cell traps" without disrupting microbial growth. COMSOL simulations confirmed safe shear stress levels. We also developed and tested fluidic multiplexers for greater modularity and automation. Addressing current pump limitations, such as discontinuity and high costs, the DSCPM can enhance experimental capabilities and promote efficiency and precision while increasing accessibility of hardware automation in many fields.
Computational model of the human cochlea with motion of the layered osseous spiral lamina
Authors: Tubelli Andrew , Secchia Paul , Nakajima Hideko Heidi , Puria Sunil
Published: August 2024

Purpose: In the base of the human cochlea, the partition anatomy is distinct from the commonly recognized anatomy of laboratory animals. The human features a radially wide, osseous spiral lamina (OSL) and a soft-tissue bridge region that connects the OSL to the basilar membrane proper. In addition to the basilar membrane, the human OSL and bridge move considerably. We investigated the complex cochlear partition in human emphasizing the layered structure of the OSL with a finite element model. Model results were calibrated with experimental measurements of motion from optical coherence tomography. Methods: The box model contained two fluid chambers separated by a cochlear partition and a helicotrema. Model geometrical and material properties either came from literature, measurements, or were tuned to produce a frequency-place map for the passive human cochlea as well as motion results similar to experimental measurements. Results: The model motion results of the cochlear partition were similar to experimental results mostly within 5 dB but with differences at the high frequencies in both magnitude and phase beyond the best frequency. Around the best frequency location, the radial profile of cochlear partition motion was generally similar in both shape and magnitude. Sensitivity analysis, changing material-property parameters of the middle layer where the cochlear nerve fibers run between the layers of OSL plates, produced small changes in the model response and also showed negligible stress compared to the outer OSL plates. Conclusion: These results suggest that the layered OSL anatomy is favorable as a conduit and protection for the nerve fibers while simultaneously functioning as a mechanical lever.
Enhanced Piezoelectric Performance of PVDF-TrFE Nanofibers through Annealing for Tissue Engineering Applications
Authors: Krutko Maksym , Poling Holly M. , Bryan Andrew E. , Sharma Manju , Singh Akaljot , Reza Hasan A. , Wikenheiser-Brokamp Kathryn A. , Takebe Takanori , Helmrath Michael A. , Harris Greg M. , Esfandiari Leyla
Published: August 2024

This study investigates bioelectric stimulation’s role in tissue regeneration by enhancing the piezoelectric properties of tissue-engineered grafts using annealed poly(vinylidene fluoride-trifluoroethylene) (PVDF-TrFE) scaffolds. Annealing at temperatures of 80°C, 100°C, 120°C, and 140°C was assessed for its impact on material properties and physiological utility. Analytical techniques such as Differential Scanning Calorimetry (DSC), Fourier-Transform Infrared Spectroscopy (FTIR), and X-ray Diffraction (XRD) revealed increased crystallinity with higher annealing temperatures, peaking in β-phase content and crystallinity at 140°C. Scanning Electron Microscopy (SEM) showed that 140°C annealed scaffolds had enhanced lamellar structures, increased porosity, and maximum piezoelectric response. Mechanical tests indicated that 140°C annealing improved elastic modulus, tensile strength, and substrate stiffness, aligning these properties with physiological soft tissues. In vitro assessments in Schwann cells demonstrated favorable responses, with increased cell proliferation, contraction, and extracellular matrix attachment. Additionally, genes linked to extracellular matrix production, vascularization, and calcium signaling were upregulated. The foreign body response in C57BL/6 mice, evaluated through Hematoxylin and Eosin (H&E) and Picrosirius Red staining, showed no differences between scaffold groups, supporting the potential for future functional evaluation of the annealed group in tissue repair.
Conservation of imprinted expression across genotypes is correlated with consistency of imprinting across endosperm development in maize
Authors: Higgins Kaitlin , Nyabashi Vital , Anderson Sarah
Published: August 2024

Imprinted expression is an essential process for seed viability affecting hundreds of genes in Zea mays endosperm, however most studies have examined just one time point for analysis. The focus on single time points can limit our ability to identify imprinted genes, and our ability to draw conclusions for the role of imprinting in endosperm. In this study we examine imprinted expression across four time points ranging from the transition to endoreduplication from mitotic division through the beginning of programmed cell death. Additionally, we assessed imprinting variation across eight diverse maize lines, six of which have never before been assessed for imprinting. Through this analysis we identify over 700 imprinted genes with varying consistency across time points including 258 genes imprinted at every time point and 104 genes displaying transient imprinting. We find a correlation between high consistency of imprinting across time and high conservation of parental bias across eight diverse maize lines reciprocally crossed with B73. Additionally, we identify evidence of imprinting for three zein genes that are critical for nutrient accumulation in the endosperm, suggesting that imprinting may play a more important role in seed composition than previously thought. Taken together, this study provides a more holistic view of imprinting variation across time and across genotypes in maize and enables us to more thoroughly investigate the complex imprinting landscape.

Though genomic imprinting is essential for seed development, changes in imprinted expression through endosperm development remain unclear. Here, the authors present a time series analysis of genomic imprinting in maize endosperm identifying over 1000 imprinted genes displaying consistent and transient imprinting. Additionally, the authors utilize imprinting data from B73 reciprocally crossed with eight diverse genotypes, and identify a correlation between consistency and conservation of imprinted expression. Together these results offer a more holistic view of imprinted expression in maize endosperm.
BundleAGE: Predicting White Matter Age using Along-Tract Microstructural Profiles from Diffusion MRI
Authors: Feng Yixue , Villalon-Reina Julio E , Nir Talia M , Chandio Bramsh Q , Jahanshad Neda , Thompson Paul M
Published: August 2024

Brain Age Gap Estimation (BrainAGE) is an estimate of the gap between a person's chronological age (CA) and a measure of their brain's 'biological age' (BA). This metric is often used as a marker of accelerated aging, albeit with some caveats. Age prediction models trained on brain structural and functional MRI have been employed to derive BrainAGE biomarkers, for predicting the risk of neurodegeneration. While voxel-based and along-tract microstructural maps from diffusion MRI have been used to study brain aging, no studies have evaluated along-tract microstructure for computing BrainAGE. In this study, we train machine learning models to predict a person's age using along-tract microstructural profiles from diffusion tensor imaging. We were able to demonstrate differential aging patterns across different white matter bundles and microstructural measures. The novel Bundle Age Gap Estimation (BundleAGE) biomarker shows potential in quantifying risk factors for neurodegenerative diseases and aging, while incorporating finer scale information throughout white matter bundles.
Leveraging Machine Learning and AlphaFold2 Steering to Discover State-Specific Inhibitors Across the Kinome
Authors: Trozzi Francesco , Tran Oanh , Al Masri Carmen , Lin Shu-Hang , Ravikumar Balaguru , Rahman Rayees
Published: August 2024

Protein kinases are structurally dynamic proteins that control downstream signaling cascades by phosphorylating their substrates. Protein kinases regulate their function by adopting several conformational states in their active site determined by the movements of several motifs such as the αC-Helix, DFG residues and the activation loop. Each conformational state represents a distinct physicochemical environment that accepts or precludes ligand binding. However, most of the kinome have not been crystalized across these possible conformational states. It has been shown that shallow Multiple Sequence Alignments (MSA) can enable AlphaFold2 (AF2) to model kinases in alternative conformations. However, it is unclear if these models can be leveraged for structure-based drug discovery. Additionally, there are several machine learning tools to predict protein-ligand interactions based on ligand chemotype and binding pocket properties, but these models cannot be used to identify ligands with clear state specificity. Here, we first present an approach called AlphaFold2 Steering (AF2-Steering), a systematic methodology to direct AF2 to sample kinases in the active and inactive conformations. We use our approach to model the protein kinome in precise conformational states. We demonstrate the utility of these AF2-steered kinase models by employing them in a prospective virtual screening study that integrates machine learning with docking to find state specific inhibitors for well-studied and dark kinases that lack structures in the active conformational state. We then experimentally validate the hits, an essential step often overlooked, and later experimentally confirm the conformation-specificity of the ligands identified for FLT3, a protein kinase that currently lacks an active state crystal structure. Against a strict binding criterion of at least 1μM Kd, our modelled structures achieved an overall hit rate of 53%. We also confirm the conformation-specificity of 4/7 FLT3 ligands, thus demonstrating the value of MSA-steered AF2 modelled kinase structures combined with machine learning and docking to guide conformation-specific kinase drug discovery.
Socioeconomic Factors and Human Knowledge and Behaviours Associated with Aedes aegypti abundance in Ouagadougou, Burkina Faso.
Authors: Ouedraogo Wendegoudi Mathias , Sombie Aboubacar , Guglielmo Federica , Serme Mamadou , Toe Hyacinthe Kobie , Facchinelli Luca , Bationo Fernand , Pare Lea , Ouedraogo Hamed S. , Viana Mafalda , Sanon Antoine , Weetman David , McCall Philip J. , Badolo Athanase
Published: August 2024

Background Since 2013, Burkina Faso has experienced regular dengue outbreaks, especially in Ouagadougou, the capital city, and Bobo-Dioulasso. Insufficient knowledge of the disease and some daily practices and attitudes of the human population may contribute to the proliferation of the vector and subsequently to dengue transmission. The objective of this study was to assess the levels of population knowledge of dengue and its primary vector, Aedes aegypti, and to elucidate the behavioural and environmental factors associated with the proliferation of this species. Methods A cross-sectional Knowledge, Attitude, and Practice (KAP) survey was conducted among 514 individuals, in 514 houses concurrently with a survey on Ae. aegypti larval sites, between September and October 2021 in three health districts (HDs) of Ouagadougou. Compound characteristics, including building materials, annual income, presence of waste, and water storage practices, were also documented. Results A proportion of 94.36% of the respondents demonstrated knowledge of dengue, with 50% recognizing primary symptoms like fever and headaches, and 70.52% knowing about its transmission mode. Only 53.51% could identify Aedes larval containers, while 14.04% were familiar with mosquito immature stages. Certain practices were linked to increased dengue vector proliferation or biting, including water storage, open water containers, water-holding waste, and the absence of mosquito screens. The study noted a high number and diversity of potential Aedes larval sites with elevated Stegomyia indices (Container Index >47%, House Index >86%, and Breteau Index >230) across all HDs. Moreover, compound infestation by immature mosquitoes was correlated with tap water presence, resident count, and construction type. Conclusion Despite the dengue outbreaks in the city of Ouagadougou over the past decade and the resulting awareness campaigns, population knowledge of dengue and its vector remains limited. Therefore, there is a critical need to enhance awareness activities through campaigns aimed at changing practices and attitudes, and improving the population's knowledge regarding the disease and its vector.
A prospective pilot study demonstrating non-invasive calibration-free glucose measurement
Authors: Rothenbühler Martina , Lizoain Aritz , Rebeaud Fabien , Perotte Adler , Stoffel Marc , DeVries J. Hans
Published: August 2024

Glucose is an essential molecule in energy metabolism. Dysregulated glucose metabolism, the defining feature of diabetes, requires active monitoring to prevent significant morbidity and mortality. Current technologies for intermittent and continuous glucose measurement are invasive. Non-invasive glucose measurement would eliminate this barrier towards making glucose monitoring more accessible, extending the benefits from people living with diabetes to prediabetes and the healthy. We developed and investigated a spectroscopy-based system for measuring glucose non-invasively and without per-person calibration. Using data from a study including adults with insulin-treated diabetes, we constructed a computational model from a development cohort of 15 subjects and found a mean absolute relative difference of 14.5% in an independent validation cohort of five subjects. The correlation between the average model sensitivity by wavelength and the spectrum of glucose was 0.45 (p<0.001). Our findings suggest that spectroscopy-based non-invasive measurement of glucose without invasive calibration is possible.
Inpatient Burden of Respiratory Syncytial Virus Infection and Influenza in Children Younger than 5 years in Japan, 2011-2022: A database study
Authors: Arashiro Takeshi , Kramer Rolf , Jin Jing , Kano Munehide , Wang Fangyuan , Miyairi Isao
Published: August 2024

Background Respiratory syncytial virus (RSV) and influenza virus are major viral etiologies of pediatric lower respiratory tract infection, but comparative data on inpatient burden are lacking. Methods Using a large-scale health claims database in Japan, we identified patients under 5 years of age with a confirmed RSV or influenza diagnosis as an outpatient or inpatient between 2011-2022. Hospitalization rate, inpatient characteristics, various in-hospital outcomes/complications, and healthcare resource utilization were described. Results A total of 176,911 RSV-confirmed outpatients, 153,383 influenza-confirmed outpatients, 90,413 RSV-confirmed hospitalizations, and 11,186 influenza-confirmed hospitalizations were identified. Among outpatients, 24.7% of RSV infection and 2.8% of influenza cases required hospitalization within one week. There was no comorbidities/prematurity for 95.0% of RSV hospitalizations and 96.5% of influenza hospitalizations. Proportions of in-hospital outcomes/complications were (RSV infection vs influenza): oxygen use 47.6% vs 14.8%, mechanical ventilation 2.1% vs 0.7%, pneumonia 33.6% vs 12.8%, otitis media 7.7% vs 2.3%, febrile seizure 1.5% vs 34.4%, encephalitis/encephalopathy 0.1% vs 0.5%, myocarditis <0.1% vs 0.6%, antibiotics prescription 48.0% vs 24.4%. The mean inpatient stay was 6.1 vs 4.3 days at direct medical costs of 435,744 vs 315,809 JPY/patient. These trends held true in age-stratified data. In-hospital death occurred in 31 RSV infection and 6 influenza cases. Conclusions Although both infections resulted in substantial burden, RSV infection led to more frequent hospitalizations, worse in-hospital outcomes, longer inpatient stays, higher medical costs, and more frequent antibiotics prescription compared to influenza. Most RSV hospitalizations occurred among healthy term children, emphasizing the need for prevention measures in all children.
Three-dimension transcriptomics maps of whole mouse embryo during organogenesis
Authors: Cheng Mengnan , Zheng Huiwen , Fang Qi , Bai Yinqi , Liu Chao , Pan Hailin , Zhang Zhewei , Lu Qin , Shi Chang , Xia Tianyi , Jing Zehua , Liu Huanlin , Feng Ning , Fu Guojun , Li Yumei , Feng Jing , Li Zepeng , Wang Jingjing , Chen Yuanyuan , Wang Lianying , Deng Zhonghan , Li Mei , Liu Longqi , Chen Ao , Xu Xun
Published: August 2024

Understanding mammalian development heavily relies on classical animal models like the house mouse (Mus musculus). Advanced spatial transcriptomics has enabled biologists to break new ground in studies of molecular dynamics and cellular patterning during embryonic development with spatiotemporal resolution. To construct a comprehensive developmental trajectory, current three-dimensional (3D) spatial transcriptomic profiling leverages mouse embryos from gastrulation (E5.5) to organogenesis (E13.5) in continuity. However, a crucial phase for early organogenesis between E9.5 and E11.5 was deficient. To unveil the mystery of this stage, we present the 3D transcriptomics of mouse embryos at E9.5 and E11.5, with a widely applicable reconstruction workflow that bypasses sophisticated bioinformatic calculations. As our 3D atlas is generated at single-cell resolution, we demonstrate how organogenetic processes can be interpreted at different levels of granularity, from local cellular interactions to whole embryonic regionalization. We release the open-access database MOSTA3D (Mouse Organogenesis Spatiotemporal Transcriptomic Atlas in Three-dimensional) and hope a broader community will contribute to extending this framework from conception to senility in the near future.
Natural alleles ofLEAFYandWAPO1interact to regulate spikelet number per spike in wheat
Authors: Zhang Junli , Burguener German F. , Paraiso Francine , Dubcovsky Jorge
Published: August 2024

Spikelet number per spike (SNS) is an important yield component in wheat that determines the maximum number of grains that can be formed in a wheat spike. In wheat, loss-of-function mutations in LEAFY (LFY) or its interacting protein WHEAT ORTHOLOG OF APO1 (WAPO1) significantly reduce SNS by reducing the rate of formation of spikelet meristems. In previous studies, we identified a natural amino acid change in WAPO1 (C47F) that significantly increases SNS in hexaploid wheat. In this study, we searched for natural variants in LFY that were associated with differences in SNS, and detected significant effects in theLFY-Bregion in a nested association mapping population. We generated a large mapping population and confirmed that the LFY-B polymorphism R80S is linked with the differences in SNS, suggesting thatLFY-Bis the likely causal gene. A haplotype analysis revealed two amino acid changes P34L and R80S, which were both enriched during wheat domestication and breeding suggesting positive selection. We also explored the interactions between the LFY and WAPO1 natural variants using biparental populations and identified significant interaction, in which the positive effect of the 80S and 34L alleles from LFY-B was only detected in the WAPO-A1 47F background but not in the 47C background. Based on these results we propose that the allele combination WAPO-A1-47F / LFY-B 34L 80S can be used in wheat breeding programs to maximize SNS and increase grain yield potential in wheat.

Key message

Specific combinations ofLFYandWAPO1natural alleles maximize spikelet number per spike in wheat.
Circadian clock in the lateral habenula affects motor function in mice through the regulation of daily rhythms in the nigrostriatal pathway
Authors: Goldfarb Cassandra , Baharav Nadav , Jiang Heng , Szubinski Amanda , Amir Shimon , Schöttner Konrad
Published: August 2024

Alterations to the dopaminergic system can have several consequences on behaviour such as the development of disorders like addiction, schizophrenia, and Parkinsons. The lateral habenula (LHb) is uniquely positioned to act on a large group of dopaminergic (DA) neurons, sending inhibitory signals both directly and indirectly to the ventral tegmental area (VTA) and the substantia nigra (SN). Additionally, the LHb houses a circadian clock that appears to function independently from the central circadian pacemaker. We investigated the role of the LHb as a pacemaker for the production and release of DA along the nigrostriatal pathway. Using male and femaleBmal1floxed mice, we injected AAV-2/9 Cre-eGFP virus into the LHb to selectively knockoutBmal1, a clock gene essential for clock functioning. We found a significant impact on motor functioning in both male and female knockout mice. Analysis of daily rhythms of expression of circadian clock genes and genes involved in DA synthesis, and liquid chromatography coupled mass spectrometry for striatal DA measurements revealed blunting of rhythms in the dorsal striatum (DS) and (SN) of knockout animals, that may contribute to the observed behavioural phenotype. As proper functioning of the striatum is likely maintained by a mutual interaction of the circadian clock and DAergic system, these findings support that disrupting the LHb clock can impact functioning of the nigrostriatal DA pathway.
Viral suppression among patients in HIV/AIDS care at healthcare facilities in Ethiopia: Same-day antiretroviral initiation
Authors: Chachu Kidanu Hurisa , Maboe Kefiloe Adolphina
Published: August 2024

To achieve the 2030 goal of eradicating the HIV epidemic, the Joint United Nations Programme on HIV/AIDS has set 95-95-95 targets: 95% of HIV-infected individuals should know their status, 95% should initiate antiretroviral therapy (ART), and 95% should achieve virologic suppression. In Ethiopia, progress has been made, but challenges remain. This study evaluates same-day ART initiation and its effect viral suppression for patients in HIV/AIDS care in Ethiopia. A cross-sectional study design was used to analyze 332 clinical records of patients who initiated same-day ART between October 1, 2017, and October 30, 2019. A probability simple random sampling technique was used in the selection of the clinical records of patients started on ART. Data were analyzed using Statistical Package for Social Science (SPSS) version 28.0, employing both descriptive and inferential statistical analyses. The results showed that viral suppression rates at 6, 12, and 24 months were 93%, 95%, and 86%, respectively, indicating progress towards the global target of 95% by 2030. This supports the effectiveness of same-day ART initiation in achieving viral suppression. Chi-square test results indicated no significant relationship between gender and suppression status (p=1.00), age and suppression status (p=0.876), or WHO stage and suppression status (p=0.404). However, significant associations were found between resident type and suppression status (p<0.05), as well as retention in care and suppression status (p<0.05). No significant association was observed between HIV disclosure status and suppression status (p=0.072). The results suggest an urgent need for follow-up and monitoring of viral suppression as months on ART increase. Additionally, enhancing viral load testing coverage at 6, 12, and 24 months is crucial to ensure sustained viral suppression.
The Role of PITPNC1 in Lung Adenocarcinoma: Differential Expression, Immune Infiltration, and Prognostic Significance
Authors: Li Chao , Chen Junsong , Zhang Ganggang , Guo Fang , Zhang Xin
Published: August 2024

Lung adenocarcinoma (LUAD) is one of the most prevalent and deadly forms of lung cancer, necessitating the identification of novel biomarkers for diagnosis and prognosis. This study aims to explore the differential expression, diagnostic potential, underlying mechanisms, and clinical significance of PITPNC1 (phosphatidylinositol transfer protein, cytoplasmic 1) in LUAD.We utilized data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, comprising 530 LUAD samples and 59 control samples from TCGA-LUAD, as well as GSE10072 and GSE75037 datasets with a total of 224 samples. Data preprocessing included normalization to Fragments Per Kilobase of transcript per Million mapped reads (FPKM) format and batch effect correction using the R package sva. Differential gene expression analysis was performed using DESeq2 for TCGA-LUAD and limma for GEO datasets. Receiver Operating Characteristic (ROC) curve analysis was conducted to assess the diagnostic efficacy of PITPNC1.Our results revealed that PITPNC1 is significantly overexpressed in LUAD samples compared to controls (p < 0.001 in TCGA-LUAD; p < 0.01 in GEO). However, ROC curve analysis indicated moderate diagnostic accuracy with Area Under Curve (AUC) values between 0.5 and 0.7. Differential expression analysis identified 3838 genes associated with PITPNC1 expression, which were further subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. These genes were enriched in pathways related to external stimulus response, hormone level regulation, nitrogen metabolism, and neuroactive ligand-receptor interaction.Gene Set Enrichment Analysis (GSEA) highlighted significant enrichment in IL12 signaling pathway, Notch signaling pathway, MAPK6/MAPK4 signaling pathway, and Hedgehog On State pathway. Immune infiltration analysis using single-sample Gene Set Enrichment Analysis (ssGSEA) showed significant differences in five immune cell types between high and low PITPNC1 expression groups. Cox regression analysis indicated that PITPNC1 expression along with clinical stages are significant predictors of overall survival in LUAD patients.In conclusion, our comprehensive bioinformatics analysis underscores the potential role of PITPNC1 as a biomarker for LUAD diagnosis and prognosis.
The Effectiveness and Cost-Effectiveness of Community Health Workers in Delivering Antenatal Care and Immunization Services to Pregnant Mothers and Children Under 5 in Rural Africa: A Study Protocol for a Systematic Review and Meta-Analysis
Authors: Zumani Kebby , Irumba Henry , Afolabi Adebukunola Olajumoke , Dube Semkelokuhle , Byaruhanga Vincent , George Olaotuyombo , Nortey Mark Anum , Ofori Emmanuel Owusu , Valentine Birungi Bk , Peru Patience , Kamwengo Chikosa , Mensima Amoah Roberta
Published: August 2024

Background

Maternal and child health care, particularly antenatal care (ANC) and immunization services, are essential to improving health outcomes in rural Africa. Despite global efforts, access to high-quality health care services remains limited in rural areas, contributing to high maternal and childhood mortality rates. Community Health Workers (CHWs) have been recognized as a promising solution for bridging this gap by providing essential services directly to underserved populations. This systematic review and meta-analysis aims to evaluate the effectiveness and cost-effectiveness of CHWs in delivering antenatal care and immunization services to pregnant mothers and children under 5 in rural Africa.

Methods

This review will include randomized controlled trials (RCTs), cohort studies, case-control studies, and observational studies published from 2014 onward. The search strategy will be implemented across multiple databases, including Google Scholar, Academic Info, Cochrane, Refseek, PubMed, and MEDLINE. The primary outcomes will focus on clinical and economic measures, including maternal and child health outcomes and cost-effectiveness of CHW interventions. Data extraction and quality assessment will be conducted independently by two reviewers, with discrepancies resolved through discussion or the involvement of a third reviewer.

Discussion

The findings from this review will contribute to the understanding of the role CHWs play in improving maternal and child health outcomes in rural Africa. The results will provide valuable insights for policymakers, health care providers, and stakeholders to inform future interventions and resource allocation strategies.

Registration

This protocol is registered in PROSPERO Registration number CRD42024529963.
Exploring the bidirectional relationship between localized musculoskeletal pain and gait abnormalities: a Mendelian randomization study
Authors: Xie Xiaoming , Zhang Kuayue , Li Xinyi , Lin Yi , Huang Liangqing , Tian Guihua
Published: August 2024

Background  Abnormal gait will alter lower extremity joint mechanics load-bearing patterns, accelerate the osteoarticular disease process, trigger new oste-oarticular complications, and bring about multiple mobility impairments; scientific pain management strategies can help with walking training and rehabilitation exercises. However, studies to date on the relationship between localized musculoskeletal pain and gait abnormalities have not reached definitive conclusions. Purpose  To investigate the bidirectional causal relationship between localized musculoskeletal pain and gait abnormalities. Methods  The independent single nucleotide polymorphism (SNP) loci strongly associated with pain were extracted as instrumental variables (IVs) from Genome-wide association study (GWAS) data of localized musculoskeletal pain according to preset thresholds, and Inverse-variance weighted (IVW) method was used to assess the association between pain-related phenotypes and gait abnormalities; the Cochran Q test was used to assess the heterogeneity of the SNPs.  Results Low back pain (OR=1.53, 95%CI=1.058~2.219, P=0.023) and hip pain (OR=1.55, 95%CI=1.067~2.252, P=0.021) were significantly genetically predisposed to gait abnormalities, but knee pain (OR=2.15, 95%CI=0.234~19.789, P=0.498) was not significantly genetically susceptible to gait abnormalities. None of the results of the reverse MR analysis supported reverse causality. The Cochran Q test showed no heterogeneity among the SNPs. Conclusion This study suggests a robust correlation, gait abnormalities are related to low back pain and hip pain. Our findings contribute to a deeper comprehension of the intricate interplay between localized musculoskeletal pain and gait abnormalities, emphasizing the importance of employing tailored strategies to alleviate localized musculoskeletal pain.