bluuebunny/crossref_metadata_2025 huggingface dataset:
The orphan nuclear receptor NR4A3 is dispensable for resident memory CD8+ T cell generation
Authors: Odagiu Livia , Boulet Salix , Maurice-De Sousa Dave , Daudelin Jean-François , Labrecque Nathalie
Published: September 2024

Different memory CD8+ T cell subsets are generated following acute responses: central, effector and resident (Trm). CD8+ Trm cells established residency at the sites of infection and provide an efficient and rapid frontline defense against re-infection. The NR4A family members (NR4A1, NR4A2 and NR4A3) of orphan nuclear receptor are transiently expressed following TCR signaling and NR4As were shown to influence CD8+ T cell response. Interestingly, Nr4a1, Nr4a2 and Nr4a3 have been reported to be transcribed by CD8+ Trm cells. In absence of NR4A1, less CD8+ Trm cells are present in the liver, lungs, small intestine intra-epithelial lymphocytes (IELs) and Peyers patches. NR4A2 was shown to play a role in the generation of small intestine IEL CD8+ Trm cells. However, evidence is still lacking for the contribution of NR4A3 during CD8+ Tm cell differentiation. In this study, we evaluated the role of NR4A3 in the differentiation and maintenance of CD8+ Trm cells. Our data demonstrate that in contrast to the other family members NR4A1 and NR4A2, NR4A3 is dispensable for the generation of CD8+ Trm cells in both epithelial and non-epithelial sites.
Leukemia-derived apelin selects endothelial niche clones to promote tumorigenesis
Authors: Baron Chloe S , Mitchell Olivia , Avagyan Serine , Menard Romain , Yang Song , Robertson Anne L , Potluri Rajiv , Shendure Jay , Madelaine Romain , McKenna Aaron , Zon Leonard I.
Published: September 2024

Hematopoietic stem cells are regulated by endothelial and mesenchymal stromal cells in the marrow niche1-3. Leukemogenesis was long believed to be solely driven by genetic perturbations in hematopoietic cells but introduction of genetic mutations in the microenvironment demonstrated the ability of niche cells to drive disease progression4-8. The mechanisms by which the stem cell niche induces leukemia remain poorly understood. Here, using cellular barcoding in zebrafish, we found that clones of niche endothelial and stromal cells are significantly expanded in leukemic marrows. The pro-angiogenic peptide apelin secreted by leukemic cells induced sinusoidal endothelial cell clonal selection and transcriptional reprogramming towards an angiogenic state to promote leukemogenesis in vivo. Overexpression of apelin in normal hematopoietic stem cells led to clonal amplification of the niche endothelial cells and promotes clonal dominance of blood cells. Knock-out of apelin in leukemic zebrafish resulted in a significant reduction in disease progression. Our results demonstrate that leukemic cells remodel the clonal and transcriptional landscape of the marrow niche to promote leukemogenesis and provide a potential therapeutic opportunity for anti-apelin treatment.
NRF2 translation block by inhibition of cap-dependent initiation sensitizes lymphoma cells to ferroptosis and CAR-T immunotherapy
Authors: Manara Paola , Newsam Austin D , Saralamma Venu VG , Russo Marco V , Martinez Alicia Bilbao , Fattakhov Nikolai , Cunningham Tyler A , Alaoui Abdessamad Y , Chahar Dhanvantri , Carbone Alexandra M , Lightfuss Olivia B , Barroso Alexa M , Hoffman Kyle S , Maura Francesco , Bilbao Daniel , Schatz Jonathan H
Published: September 2024

Cancers coopt stress-response pathways to drive oncogenesis, dodge immune surveillance, and resist cytotoxic therapies. Several of these provide protection from ferroptosis, iron-mediated oxidative cell death. Here, we found dramatic sensitization to ferroptosis upon disruption of cap-dependent translation in diffuse large B-cell lymphoma (DLBCL). Specifically, rocaglate inhibitors of the eIF4A1 RNA helicase synergized with pharmacologic ferroptosis inducers, driven by a collapse of glutathione production that protects polyunsaturated fatty acids from ferroptotic oxidation. These effects occur despite initial up-regulation of specific protective factors. We find lost translation of NRF2, oncogenic master regulator of antioxidant gene-expression, is a key consequence of eIF4A1 inhibition. In vivo, combination of the clinical rocaglate zotatifin with a pharmacologically optimized ferroptosis inducer eradicated DLBCL patient derived xenografts. Moreover, we found zotatifin pre-exposure sensitized DLBCL to CD19-directed chimeric antigen receptor (CAR-19) T cells. Translational disruption therefore provides new opportunities to leverage therapeutic impacts of ferroptosis inducers including cytotoxic immunotherapies.
Three-color single-molecule localization microscopy in chromatin
Authors: Acosta Nicolas , Gong Ruyi , Su Yuanzhe , Frederick Jane , Medina Karla , Li Wing Shun , Mohammadian Kiana , Almassalha Luay , Backman Vadim
Published: September 2024

Super-resolution microscopy has revolutionized our ability to visualize structures below the diffraction limit of conventional optical microscopy and is particularly useful for investigating complex biological targets like chromatin. Chromatin exhibits a hierarchical organization with structural compartments and domains at different length scales, from nanometers to micrometers. Single molecule localization microscopy (SMLM) methods, such as STORM, are essential for studying chromatin at the supra-nucleosome level due to their ability to target epigenetic marks that determine chromatin organization. Multi-label imaging of chromatin is necessary to unpack its structural complexity. However, these efforts are challenged by the high-density nuclear environment, which can affect antibody binding affinities, diffusivity and non-specific interactions. Optimizing buffer conditions, fluorophore stability, and antibody specificity is crucial for achieving effective antibody conjugates. Here, we demonstrate a sequential immunolabeling protocol that reliably enables three-label studies within the dense nuclear environment. This protocol couples multiplexed localization datasets with a robust analysis algorithm, which utilizes localizations from one target as seed points for distance, density and multi-label joint affinity measurements to explore complex organization of all three targets. Applying this multi-plexed algorithm to analyze distance and joint density reveals that heterochromatin and euchromatin are not-distinct territories, but that localization of transcription and euchromatin couple with the periphery of heterochromatic clusters. This work is a crucial step in molecular imaging of the dense nuclear environment as multi-label capacity enables for investigation of complex multi-component systems like chromatin with enhanced accuracy.
SLEEP QUALITY AND CIRCADIAN RHYTHM DISRUPTION IN CRITICALLY ILL PATIENTS IN INTENSIVE CARE UNIT
Authors: Christina-Athanasia Sampani , Georgios Koukoulitsios , Athanasia Liveri , Papageorgiou Dimitrios
Published: September 2024

Aim

The aim of this study was to evaluate the quality of sleep in critically ill patients in the Intensive Care Unit (ICU).

Method and Material

This study investigated the night-time sleep of 135 patients admitted to the general ICU of the General Hospital of Athens “G. Gennimatas” between January 2021 and December 2023. Data were collected using the Richards Campbell Sleep Questionnaire (RCSQ). Sensory stimuli, including noise, light, nursing activities, and invasive procedures, were reduced during the night to improve patients’ sleep. Measures to reduce light included implementing special lighting during nursing tasks and using bedside lamps during care. Noise reduction strategies involved closing doors, minimizing monitor alarms, and discouraging staff from speaking near patient beds. Grouping patient care activities was also promoted to limit sleep disturbances.

Results

Patients in the intervention group showed improved sleep quality compared to the control group, with a significant overall RCSQ score (p<0.05). Gender and age did not significantly affect sleep quality. However, hospital stay duration differed between groups, with the control group experiencing shorter stays. A negative correlation was observed between the duration of hospitalization and sleep quality, with longer stays linked to lower RCSQ scores. Additionally, extended mechanical ventilation was associated with poorer sleep quality.

Conclusion

Patients in the ICU often exhibit abnormal levels of alertness, poor quality of daytime sleep, disrupted nighttime sleep, and sleep patterns that lack both slow-wave and rapid eye movement (REM) sleep. Gaining a deeper understanding of the role circadian rhythms play in managing critical illness could pave the way for future chronotherapeutic strategies, enhancing clinical outcomes and promoting recovery for patients.
Revisiting the cytogenetics ofVelloziaVand.: immunolocalization of KLN1 elucidates the chromosome number for the genus
Authors: Braz Guilherme T. , Riboldi Lucas B. , Pinto Maísa S. , Forni-Martins Eliana R. , Yassitepe Juliana E. C. T. , Dante Ricardo A. , Gerhardt Isabel R.
Published: September 2024

Chromosome number is the most fundamental trait of a karyotype. Accurate chromosome counting is essential for further analyses including cytogenomics, taxonomic, evolutionary, and genomic studies. Despite its importance, miscounting is common, especially in early publications on species with small and morphologically similar chromosomes.VelloziaVand. is a genus mainly distributed throughout South America belonging to the angiosperm family Velloziaceae, a dominant taxon in the Brazilian “campos rupestres”. Cytogenetic studies within the group have been rare and have shown conflicting chromosome counts, even within the same species. These discrepancies are associated with the presence of a few small chromosome-like structures, which were previously classified as possible satellites. Here, to accurately determine the chromosome number of species belonging to the genus, we used different cytogenomics approaches, including the immunostaining of the KNL1 kinetochore protein combined with chromosome spread preparation using tissue culture-derived samples. Our results revealed 2n= 18 chromosomes for all six species studied. This finding suggests that the basic chromosome number forVelloziaisx= 9 and notx= 8, as previously proposed. The immunolocalization of functional centromeres was fundamental for undoubtedly identifying the smaller chromosome pair as real chromosomes and accurately determining the correct chromosome number of these species. This will provide substantial support for further studies, including investigations into karyotype evolution and the generation of reference genomes for the species of the family.
Loss of neuropeptidergic regulation of cholinergic transmission induces CaV1-mediated homeostatic compensation in muscle cells
Authors: Shao Jiajie , Liewald Jana , Costa Wagner , Ruse Christiane , Gruber Jens , Djamshedzad Mohammad , Gebhardt Wulf , Gottschalk Alexander
Published: September 2024

Chemical synaptic transmission at the neuromuscular junction (NMJ) is regulated by electrical activity of the motor circuit, but may also be affected by neuromodulation. Here, we assess the role of neuropeptide signaling in the plasticity of NMJ function in Caenorhabditis elegans. We show that the CAPS (Ca2+-dependent activator protein for secretion) ortholog UNC-31, which regulates the exocytosis of dense core vesicles (DCVs), affects both pre- and post-synaptic functional properties, as well as NMJ-mediated locomotion. Despite reduced evoked acetylcholine transmission, the loss of unc-31 results in a more vigorous response to presynaptic stimulation, i.e., enhanced muscle contraction and Ca2+ transients. Based on expression profiles, we identified neuropeptides involved in both cholinergic (FLP-6, NLP-9, NLP-21 and NLP-38) and GABAergic motor neurons (FLP-15, NLP-15), that mediate normal transmission at the NMJ. In the absence of these peptides, neurons fail to upregulate their transmitter output in response to increased cAMP signaling. We also identified proprotein convertases encoded by aex-5/kpc-3 and egl-3/kpc-2 that act synergistically to generate these neuropeptides. We propose that postsynaptic homeostatic scaling, mediated by increased muscle excitability, could compensate for the reduced cholinergic transmission in mutants affected for neuropeptide signaling, thus maintaining net synaptic strength. We show that in the absence of UNC-31 muscle excitability is modulated by upregulating the expression of the muscular L-type voltage-gated Ca2+ channel EGL-19 (CaV1). Collectively, our results unveil a role for neuropeptidergic regulation in synaptic plasticity, linking changes in presynaptic transmission to compensatory changes in muscle excitability.
Morphology of softening and translucency in the stems of tomato and eggplant seedlings due to infection byRalstonia pseudosolanacearumF1C1
Authors: Bhuyan Shuvam , Boruah Lakhyajit , Jain Monika , Begum Shuhada , Giri Shubhra Jyoti , Dutta Lukapriya , Mandal Manabendra , Ray Suvendra Kumar
Published: September 2024

Ralstonia pseudosolanacearumF1C1 is a soil-borne phytopathogenic bacterium with a broad host range that infects several economically important crops. This study primarily focuses on the infection of this phytopathogen in two such important crop seedlings: tomato and eggplant. The observations of the study reveal a complex set of symptoms that include drooping and blackening of the seedling stem, as well as blackening, chlorosis, and curling of cotyledon leaves. Notably, the symptom of stem softening and translucency is seen primarily in the water-submerged stem regions of the root-inoculated seedlings. Furthermore, the morphology of stem softening and translucency is more frequent in root-inoculated eggplant seedlings, underscoring a difference between tomato and eggplant seedlings regarding the virulence of the bacterium. By investigating these unique pathological phenotypes in the infected seedlings, this study uncovers unique symptoms previously not reported in seedling inoculation experiments. Such findings deepen our understanding of the complex virulence mechanisms of the pathogen. The work also highlights the distinct escape mechanisms exhibited by seedlings, revealing how some of its host plants might resist wilting despite infection, offering new avenues for future research. These findings contribute to the understanding ofR. pseudosolanacearumpathogenesis, shedding light on its virulence and host response mechanisms.
Strategic targeting of Cas9 nickase expands tandem gene arrays
Authors: Takesue Hiroaki , Okada Satoshi , Doi Goro , Sugiyama Yuki , Kusumoto Emiko , Ito Takashi
Published: September 2024

Expanding tandem gene arrays facilitates adaptation through dosage effects and gene family formation via sequence diversification. However, experimental induction of such expansions remains challenging. Here we introduce a method termed break-induced replication (BIR)-mediated tandem repeat expansion (BITREx) to address this challenge. BITREx strategically places Cas9 nickase adjacent to a tandem gene array to break the replication fork that has replicated the array, forming a single-end double-strand break. This break is subsequently end-resected to become single-stranded. Since there is no repeat unit downstream of the break, the single-stranded DNA often invades an upstream unit to initiate ectopic BIR, resulting in array expansion. BITREx has successfully expanded gene arrays in budding yeast, with theCUP1array reaching ∼1 Mb. Furthermore, appropriate splint DNA allows BITREx to generate tandem arrays de novo from single-copy genes. We have also demonstrated BITREx in mammalian cells. Therefore, BITREx will find various unique applications in genome engineering.
G2PDeep-v2: a web-based deep-learning framework for phenotype prediction and biomarker discovery using multi-omics data
Authors: Zeng Shuai , Adusumilli Trinath , Awan Sania Zafar , Immadi Manish Sridhar , Xu Dong , Joshi Trupti
Published: September 2024

The G2PDeep-v2 server is a web-based platform powered by deep learning, for phenotype prediction and markers discovery from multi-omics data in any organisms including humans, plants, animals, and viruses. The server provides multiple services for researchers to create deep-learning models through an interactive interface and train these models using an automated hyperparameter tuning algorithm on high-performance computing resources. Users can visualize the results of phenotype and markers predictions and perform Gene Set Enrichment Analysis for the significant markers to provide insights into the molecular mechanisms underlying complex diseases and other biological processes. The G2PDeep-v2 server is publicly available at https://g2pdeep.org/.
Targeted syndromic next-generation sequencing panel for simultaneous detection of pathogens associated with bovine reproductive failure
Authors: Periyasamy Dhinesh , Huang Yanyun , Hill Janet E.
Published: September 2024

Bovine reproductive failure, which includes infertility, abortion, and stillbirth in cattle, leads to significant economic losses for beef and milk producers. Diagnosing the infectious causes of bovine reproductive failure is challenging as there are multiple pathogens associated with it. The traditional stepwise approach to diagnostic testing is time-consuming and can cause significant delays. In this study, we have developed a syndromic next-generation sequencing panel (BovReproSeq), for the simultaneous detection of 17 pathogens (bacteria, virus and protozoa) associated with bovine reproductive failure. This targeted approach involves amplifying multiple pathogen-specific targets using ultra-multiplex PCR, followed by sequencing with the Oxford Nanopore platform and subsequent analysis of the data using a custom bioinformatic pipeline to determine the presence or absence of pathogens. We tested 116 clinical samples and found that BovReproSeq results matched with current diagnostic methods for 93% of the samples, and most of the disagreements occurring in samples with very low pathogen loads (Ct > 35). At the optimal read-count threshold of 10 reads (minimum number of reads to classify the sample as positive), the clinical sensitivity of the assay was approximately 82%, while clinical specificity was 100%. The overall accuracy of the assay was 98.8%. Matthew’s Correlation Coefficient (correlation coefficient of binary classification) was approximately 0.90 and F1 score (harmonic mean of Precision and Recall) was 0.90, indicating excellent overall performance. Our study presents a significant advancement in detecting the infectious agents associated with bovine reproductive failure and the BovReproSeq panel’s ability to detect 17 pathogens makes it a promising tool for veterinary diagnostics.

Importance

Bovine reproductive failure causes substantial economic losses to beef and milk producers, and infectious disease contributes significantly to this syndrome. Etiologic diagnosis is complicated since multiple pathogens can be involved and infections with some pathogens are asymptomatic or cause similar clinical signs. A stepwise approach to diagnostic testing is time-consuming and increases the risk of missing the correct diagnosis. BovReproSeq is a next-generation sequencing based diagnostic panel that allows detection of 17 reproductive failure pathogens simultaneously.
Development of sensorimotor responses in larval zebrafish: a comparison between wild-type and GCaMP6s transgenic line
Authors: Caperaa Margaux , Roland-Caverivière Mathilde , Herdman Chelsea , Imloul Nesrine , Poulin Sandrine , Lemieux Mado , De Koninck Paul , Bossé Gabriel D
Published: September 2024

During early development, zebrafish larvae exhibit stereotypical behaviors, which rapidly become more complex. Thus, the generation of mutant transgenic lines that maintain transparency throughout their larval stage and that can be used to record brain activity has offered strategic opportunities to investigate the underlying neural correlates of behavior establishment. However, few studies have documented the behavioral profile of these lines during larval development. Here, we set up a behavioral characterization using diverse stimuli (light and vibration) throughout larval development to compare the responses of a transgenic strain expressing a pan-neuronal calcium indicator (GCaMP6s) with that of a wild-type strain. Interestingly, we report a drastic switch in behavioral responses to light transitions at 11 days post-fertilization (dpf) and to vibration stimuli at 14 dpf in both lines. These data highlight a specific time window of behavioral complexification. Meanwhile, we found no major difference in the maturation of sensorimotor responses between GCaMP6s and wild-type strains. Thus, these results support using GCaMP6s strain in investigating the neural mechanisms underlying the developmental maturation of sensorimotor responses. We observed nevertheless some minor differences that suggest careful attention should be taken when using mutant/transgenic lines for behavioral studies.

Highlights

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Longitudinal investigation of sensorimotor responses by zebrafish during their larval development

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During the second week of development, larval zebrafish switch their motor response to light transition

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Pan-neuronal nuclear expression of GCaMP6s has little impact on larval fish response to various stimuli
Impacts of the COVID-19 pandemic on sepsis incidence, etiology and hospitalization costs in France: a retrospective observational study
Authors: Al Rahmoun Marie , Sabaté-Elabbadi Alexandre , Guillemot Didier , Brun-Buisson Christian , Watier Laurence
Published: September 2024

Background

Sepsis is a serious medical condition that causes long-term morbidity and high mortality, annually affecting millions of people worldwide. The COVID-19 pandemic may have impacted its burden.

Objective

To estimate the impact of the COVID-19 pandemic on sepsis incidence, etiology and associated hospitalization costs in metropolitan France.

Methods

This retrospective observational study used data drawn from a cohort of hospitalized sepsis patients in France’s national healthcare database. Sepsis was identified through both explicit ICD-10 codes (E-sepsis) and implicit codes (I-sepsis). Participants included all patients aged 15 years or older hospitalized with E-sepsis or I-sepsis in metropolitan France between January 1, 2018, and December 31, 2022. Patient and hospital stay characteristics were described by sepsis type (E-sepsis, I-sepsis) and overall. The distribution of sepsis etiology was estimated for each year. Annual incidence rates were estimated overall and by sepsis type and etiology. Total and median per-stay hospitalization costs were calculated.

Results

The total age- and sex-standardized sepsis incidence rate per 100,000 increased slightly from 2018 (446, 95% CI 444.2 to 447.7) to 2020 (457, 95% CI 455.1 to 458.6) and then decreased in 2022 (382, 95% CI 380.2-383.7) (p <.0001). Incidence rates decreased for both E-sepsis and bacterial sepsis during the pandemic period, whereas I-sepsis incidence increased in 2020 and 2021, associated with a marked increase in viral sepsis and co-infections (p <.0001 for E- and I-sepsis). Viral sepsis represented about 10% of all sepsis cases during the pandemic, but only about 1% prior to the pandemic. Total sepsis-associated hospitalization costs and extra medication costs increased during the pandemic. Characteristics of patients and their hospital stays were overall stable over the five-year study period.

Conclusions

The COVID-19 pandemic led to a higher burden of sepsis in French hospitals and an increase in hospital stay costs. Critically, our study highlights the need for introducing explicit viral sepsis codes within the ICD-11 classification system and for achieving a consensus on its definition in order to robustly estimate sepsis incidence.
Three-Dimensional virtual reality-based visualization of fetal cardiac anatomy using spatio-temporal image correlation (STIC) ultrasound datasets of normal and abnormal hearts
Authors: Vaidyanathan Balu , Maya Harikrishnan Anil , Xavier Sarin , Kappanayil Mahesh
Published: September 2024

This case report demonstrates the feasibility of creating immersive 3D visualizations (3D Virtual reality and 3D printing) from fetal echocardiographic volume datasets for both normal heart and a heart with transposition of great arteries. Immersive 3D technologies could emerge as powerful tools in future for understanding fetal cardiac anatomy for clinical decision making as well as training and research.
Development and evaluation of codelists for identifying marginalised groups in primary care
Authors: Perchyk Tetyana , de Vere Hunt Isabella , Nicholson Brian D , Mounce Luke , Sykes Kate , Lyratzopoulos Yoryos , Lemanska Agnieszka , Whitaker Katriina L , Kerrison Robert S
Published: September 2024

Background

Primary care electronic health records provide a rich source of information for inequalities research. However, the reliability and validity of the research derived from these records depends on the completeness and resolution of the codelists used to identify marginalised populations.

Aim

The aim of this project was to develop comprehensive codelists for identifying ethnic minorities, people with learning disabilities (LD), people with severe mental illness (SMI) and people who are transgender.

Design and setting

This study was a codelist development project, conducted using primary care data from the United Kingdom.

Method

Groups of interest were defined a priori. Relevant clinical codes were identified by searching Clinical Practice Research Datalink (CPRD) publications, codelist repositories and the CPRD code browser. Relevant codelists were downloaded and merged according to marginalised group. Duplicates were removed and remaining codes reviewed by two general practitioners. Comprehensiveness was assessed in a representative CPRD population of 10,966,759 people, by comparing the frequencies of individuals identified when using the curated codelists, compared to commonly used alternatives.

Results

A total of 52 codelists were identified. 1,420 unique codes were selected after removal of duplicates and GP review. Compared with comparator codelists, an additional 48,017 (76.6%), 52,953 (68.9%) and 508 (36.9%) people with a LD, SMI or transgender code were identified. The frequencies identified for ethnicity were consistent with expectations for the UK population.

Conclusion

The codelists curated through this project will improve inequalities research by improving standards of identifying marginalised groups in primary care data.

HOW THIS FITS IN

The reliability and validity of primary care data for inequalities research depends on the comprehensiveness of the codes used to identify people from marginalised groups.

This study set out to develop comprehensive codelists for the identification of four key groups, known to experience health inequalities.

We developed comprehensive codelists for identifying ethnic minorities, learning disabilities, severe mental illness and people who are transgender, using a systematic approach.

The codelists were validated by two general practitioners, assessed in a representative sample, and can now be used in primary care practice and research, both nationally and internationally.
Tuberculosis Infection Control in MDR-TB designated hospitals, Jiangsu Province of China
Authors: Song Honghuan , Li Guoli , Xu Zhuping , Wang Feixian , Wang Xiaoping , Dai Bing , Zhang Xing , Li Jincheng , Li Yan , Zhu Limei
Published: September 2024

Background

Hospital-acquired TB (Tuberculosis) infection among healthcare workers (HCWs) and patients is a severe problem due to the increased attributable risk of TB infection among these groups.

Methods

A standardized tool was applied. The assessment was conducted by direct observation, document review, and interviews with the facility heads. Baseline evaluation of TBIC (Tuberculosis infection control) in TB outpatient, inpatient departments, and laboratories was completed by January 2019. Based on the results, we implemented a comprehensive package of interventions, including administrative, environmental engineering, and respiratory protection (PPE) three-level hierarchy of controls. Subsequent monitoring was finalized quarterly and improvement measures should be formulated accordingly. More than two years of follow-up data was collected until August 31, 2021, by hospitals, municipality CDCs, and Jiangsu provincial CDC.

Results

At baseline, the implementation rate of administrative, environmental engineering and PPE IC was 57.29%, 59.21%, and 66.63%, respectively. After evaluation and implementation, priority way for cough patients was established, mechanical ventilation and the use of masks were improved, UV and UVGI lights were settled in need. The implementation rate of administrative, environmental and PPE IC were significantly increased to 86.27%, 87.41%, and 98.42%(P<0.05), respectively.

Conclusions

After more than one and a half years of intervention, TBIC in the designated hospitals has significantly improved. However, the availability of separate TB wards remains suboptimal. TB IC measures must be strengthened to reduce TB transmission among HCWs and non-TB patients. This method was practical and suitable to be popularized in countries with high TB burden.
Pharmacist Impact on First-Line Antihypertensives in African American Patients
Authors: Reid Mia Y. , Coates Jamie E. , Yates Naomi Y. , McDonald Bennett
Published: September 2024

Introduction

Current guidelines recommend thiazide/thiazide-type diuretics and dihydropyridine calcium channel blockers as first-line agents in treating African Americans with hypertension. The purpose of this study is to examine the impact that ambulatory care clinical pharmacy specialists (CPSs) had on initiation of first-line antihypertensives in the African American population within an integrated healthcare system.

Methods

This retrospective, matched, observational cohort analysis included African American patients with hypertension not receiving a first-line antihypertensive as of September 1, 2021. Patients followed by CPSs were matched up to 1:4 on age and sex to patients not followed by CPSs. The primary outcome was the percentage of patients started on first-line antihypertensive(s) after working with CPSs. Conditional logistic regression was used to analyze outcomes.

Results

A total of 865 patients followed by CPSs were matched to 3,192 patients not followed by CPSs. Patients followed by CPSs were initiated on first-line antihypertensives at a significantly higher rate (adjusted OR 1.98, 95% CI 1.63-2.41), and a clinically significant improvement in blood pressure was observed with systolic improving an average of 22 points and diastolic 13 points. 283 patients managed by CPSs achieved blood pressure less than 135/85 mmHg.

Conclusion

The initiation of first-line antihypertensives in African American patients by CPSs led to clinically significant reductions in systolic and diastolic blood pressure which supports CPS involvement in hypertension management. The assessment of study outcomes provides guidance to clinical decision-making and contributes to the development of key practice standards across both physician and clinical pharmacy specialist services.
Bullying and Early Brain Development: A Longitudinal Structural Magnetic Resonance Imaging Study from Adolescence to Early Adulthood
Authors: Connaughton Michael , Mitchell Orla , Cullen Emer , O'Connor Michael , Banaschewski Tobias , Barker Gareth , Bokde Arun LW , Bruhl Rudiger , Desrivieres Sylvane , Flor Herta , Garavan Hugh , Gowland Penny Anne , Grigis Antoine Anne , Heinz Andreas , Lemaitre Herve , Martinot Jean-Luc , Martinot Marie-Laure Paillere , Artiges Eric , Nees Frauke , Papadopoulos Orfanos Dimitri , Poustka Luise , Smolka Michael N , Hohmann Sarah , Holz Nathalie E , Vaidya Nilakshi , Walter Henrik , Schumann Gunter , Whelan Robert , Roddy Darren
Published: September 2024

To explore this, we conducted the largest structural MRI analysis to date (n=2094, including 1009 females), across three time points from the IMAGEN study, tracking region-specific brain volume trajectories from adolescence to early adulthood using a data-driven approach. Generally, experienced bullying showed increased subcortical volumes in the putamen (beta=0.12), caudate (beta=0.06), accumbens (beta=0.06), amygdala (beta=0.07), hippocampus (beta=0.06), paired with decreased cerebellar (beta=-0.10), entorhinal, (beta=-0.12), and insula (beta=-0.11) volumes. Females exhibited more volumetric changes in emotional processing areas whereas males had more changes in motor and sensory regions. These findings point to widespread associations between bullying victimization and brain development, offering a potential neurobiological framework to explain the emotional and behavioral difficulties observed. Importantly, this study emphasizes the need for a sex-sensitive approach in future research and interventions related to bullying.
Stress-mediated growth determinesE. colidivision site morphogenesis
Authors: Pelech Petr , Navarro Paula P. , Vettiger Andrea , Chao Luke H. , Allolio Christoph
Published: September 2024

In order to proliferate, bacteria must remodel their cell wall at the division site. The division process is driven by the enzymatic activity of peptidoglycan (PG) synthases and hydrolases around the constricting Z-ring. PG remodelling is reg-ulated by de-and re-crosslinking enzymes, and the directing constrictive force of the Z-ring. We introduce a model that is able to reproduce correctly the shape of the division site during the constriction and septation phase ofE. coli. The model represents mechanochemical coupling within the mathematical framework of morphoelasticity. It contains only two parameters, associated with volumet-ric growth and PG remodelling, that are coupled to the mechanical stress in the bacterial wall. Different morphologies, corresponding either to mutant or wild type cells were recovered as a function of the remodeling parameter. In addition, a plausible range for the cell stiffness and turgor pressure was determined by comparing numerical simulations with bacterial cell lysis data.
Systematic review and meta-analysis ofHyalomma marginatumvertebrate hosts in the EU
Authors: Bah Madiou Thierno , Vial Laurence , Busani Lucas , Souq Léa , Grosbois Vladimir , Bernard Celia , Jori Ferran
Published: September 2024

Host choice is a determining component of tick population and pathogen transmission dynamics. In Europe, ticks of the genusHyalomma, which are involved in the transmission of several pathogens such as the Crimean Congo Haemorrhagic fever (CCHF) virus, are suspected to be spreading into new territories where they were previously unreported. Therefore, we performed a systematic review of the tick-host relationship ofHyalomma sppin Europe with a focus onHyalomma marginatum, combined with a meta-analysis and meta-regression to describe its host preference pattern using three outcome values. Our initial qualitative analysis highlighted an increase in tick-host interaction rate in the last decades mostly in South-eastern and Central Europe.H. marginatumalso appeared as the species holding the highest citation rate in terms of its association with hosts, and for which the largest number of host species were reported. The meta-analysis onHyalomma marginatumhost choice revealed preferential interactions for horses in the adult stage and birds of theEmberizidaeandStrigidaefamilies, in immature stages. Nevertheless, most of the heterogeneity of tick-host interactions remained unexplained suggesting the involvement of multiple drivers such as environmental or climatic conditions. Our results suggest thatH. marginatumis a generalist tick whose distribution depends primarily on environmental conditions such as climate and habitat. Current limitations of our meta-analysis approach to identify hosts preference forH. marginatumand suggestions ways for improvement are further discussed.
Cleavage site heterogeneity at the pre-mRNA 3′-untranslated region regulates gene expression in oxidative stress response
Authors: Shaji Feba , Ali Jamshaid , Laishram Rakesh S.
Published: September 2024

Endonucleolytic cleavage step of the eukaryotic mRNA 3′-end processing is considered imprecise that leads to heterogeneity of cleavage site (CS) with hitherto unknown function. Contrary to the popular belief, we show that this imprecision in cleavage is tightly regulated resulting in CS heterogeneity (CSH) that controls gene expression in antioxidant response. CSH centres at a primary CS followed by a number of subsidiary cleavages that is determined by the position of the CS. Globally and by using reporter antioxidant NQO1 mRNA, we discovered an inverse relationship between the number of CS and the gene expression with the primary CS exhibiting highest cleavage efficiency. Strikingly, reducing CSH and increasing primary CS usage induces gene expression. Under oxidative stress condition (tBHQ, H2O2or NaAsO2), there is a decrease in the CSH and an increase in the primary CS usage to induce antioxidant gene expression. Concomitantly, ectopic NQO1 expression from the primary CS or reduction in CSH imparts cellular oxidative stress tolerance. Genome-wide CS analysis of stress response genes also shows a concomitant result. We show that oxidative stress induces affinity/strength of cleavage complex assembly increasing the fidelity of cleavage at the primary CS thereby reducing CSH inducing antioxidant response.
Inhibition mediated by group III mGluRs regulates habenula activity and defensive behaviors
Authors: Ostenrath Anna Maria , Faturos Nicholas , Çiftci Çobanoğlu Yağnur Işık , Serneels Bram , Jeong Inyoung , Enz Anja , Hinrichsen Francisca , Mutlu Aytac Kadir , Bardenhewer Ricarda , Jetti Suresh Kumar , Neuhauss Stephan C. F. , Jurisch-Yaksi Nathalie , Yaksi Emre
Published: September 2024

Inhibition contributes to various brain computations from sensory motor transformations to cognitive operations. While most studies on inhibition focus on GABA, the main excitatory neurotransmitter of the brain, glutamate, can also elicit inhibition via metabotropic glutamate receptors (mGluRs). The function of mGluR-mediated inhibition remains largely elusive. Here, we investigated the role of group III mGluR-dependent inhibition in the habenula. This primarily glutamatergic and conserved forebrain region acts as a hub between multiple forebrain inputs and neuromodulatory mid- and hindbrain targets that regulate adaptive behaviors. We showed that both zebrafish and mice habenula express group III mGluRs. We identified that group III mGluRs regulate the membrane potential and calcium activity of zebrafish dorsal habenula. Pharmacological and genetic perturbation of group III mGluRs increased sensory-evoked excitation and reduced selectivity of habenular neurons to different sensory modalities. We also observed that inhibition is the main channel of communication between primarily glutamatergic habenula neurons. Blocking group III mGluRs reduced inhibition within habenula and increased correlations during spontaneous activity. In line with such inhibition within habenula, we identified that multi-sensory information is integrated mainly through competition and suppression across habenular neurons, which in part relies on group III mGluRs. Finally, genetic perturbation of a habenula-specific group III mGluR, mGluR6a, amplified neural responses and defensive behaviors evoked by sensory stimulation and environmental changes. Altogether, our results revealed that mGluR driven inhibition is essential in encoding, integration, and communication of information between Hb neurons, ultimately playing a critical role in regulating defensive and adaptive behaviors.
Macrophage-derived RNAseT2 stimulates muscle stem cell fusion via SLK/N-WASP/actin bundling
Authors: Weiss-Gayet Michele , Juban Gaetan , Le Moal Emmeran , Moretta Antonio , Farnetari Camilla , Gobet Christelle , Guillemaud Jules , Le Bihan Marie-Catherine , Shoseyov Oded , Adrait Annie , Ternka Katharina , Boespflug-Tanguy Odile , Kettwig Matthias , Coute Yohann , Mounier Remi , Acquati Francesco , Knight Robert , Chazaud Benedicte
Published: September 2024

Muscle stem cells (MuSCs) fuse to form myofibers to repair skeletal muscle after injury. Within the regenerative MuSC niche, restorative macrophages stimulate MuSC fusion, although the molecular mechanisms involved are largely unknown. Here, we show that restorative macrophages secrete ribonuclease T2 (RNAseT2) to stimulate MuSC fusion. RNAseT2 entered MuSCs via the mannose receptor and induced the formation of actin bundles in MuSCs, enabling cell/cell fusion. Mechanistically, RNAseT2 bound to Ste20-like kinase (SLK), which itself triggered the phosphorylation-mediated activation of N-WASP, through Paxillin phosphorylation, allowing actin bundling necessary for MuSC fusion. In vivo, overexpressing RNAseT2 in regenerating muscle increased fusion in newly formed myofibers in mouse and zebrafish while macrophages deficient for RNAseT2 gene led to fusion defect and smaller myofibers. This study reveals a new function for the highly conserved RNAseT2 and provides a new molecular mechanism by which restorative macrophages support MuSC fusion during muscle repair.
Adrenergic C1 neurons enhance anxiety via projections to PAG
Authors: Fernández-Peña Carlos , Pace Rachel L. , Fernando Lourds M. , Pittman Brittany G. , Schwarz Lindsay A.
Published: September 2024

Anxiety is an emotional state precipitated by the anticipation of real or potential threats. Anxiety disorders are the most prevalent psychiatric illnesses globally and increase the risk of developing comorbid conditions that negatively impact the brain and body. The etiology of anxiety disorders remains unresolved, limiting improvement of therapeutic strategies to alleviate anxiety-related symptoms with increased specificity and efficacy. Here, we applied novel intersectional tools to identify a discrete population of brainstem adrenergic neurons, named C1 cells, that promote aversion and anxiety-related behaviors via projections to the periaqueductal gray matter (PAG). While C1 cells have traditionally been implicated in modulation of autonomic processes, rabies tracing revealed that they receive input from brain areas with diverse functions. Calcium-based in vivo imaging showed that activation of C1 cells enhances excitatory responses in vlPAG, activity that is exacerbated in times of heightened stress. Furthermore, inhibition of C1 cells impedes the development of anxiety-like behaviors in response to stressful situations. Overall, these findings suggest that C1 neurons are positioned to integrate complex information from the brain and periphery for the promotion of anxiety-like behaviors.
Electromagnetic waves destabilize the SARS-CoV-2 Spike protein and reduce SARS-CoV-2 Virus-Like Particle (SC2-VLP) infectivity
Authors: Granatir Skyler , Acosta Francisco M. , Pantoja Christina , Tailor Johann , Fuori Angus , Dower Bill , Marr Henry , Ramirez Peter W.
Published: September 2024

Infection and transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to pose a global public health concern. Using electromagnetic waves represents an alternative strategy to inactivate pathogenic viruses such as SARS-CoV-2 and reduce overall transmission. However, whether electromagnetic waves reduce SARS-CoV-2 infectivity is unclear. Here, we adapted a coplanar waveguide (CPW) to identify electromagnetic waves that could neutralize SARS-CoV-2 virus-like particles (SC2-VLPs). Treatment of SC2-VLPs, particularly at frequencies between 2.5-3.5 GHz at an electric field of 400 V/m for 2 minutes, reduced infectivity. Exposure to a frequency of 3.1 GHz decreased the binding of SC2-VLPs to antibodies directed against the Spike S1 subunit receptor binding domain (RBD). These results suggest that electromagnetic waves alter the conformation of Spike, thereby reducing viral attachment to host cell receptors. Overall, this data provides proof-of-concept in using electromagnetic waves for sanitation and prevention efforts to curb the transmission of SARS-CoV-2 and potentially other pathogenic enveloped viruses.
Demographic responses to climatic changes during the Final Palaeolithic in Europe
Authors: Schmidt Isabell , Gehlen Birgit , Winkler Katja , Arrizabalaga Alvaro , Arts Nico , Bicho Nuno , Crombé Philippe , Eriksen Berit Valentin , Grimm Sonja B. , Kapustka Katarina , Langlais Mathieu , Mevel Ludovic , Naudinot Nicolas , Nerudová Zdeňka , Niekus Marcel , Peresani Marco , Riede Felix , Sauer Florian , Schön Werner , Sobkowiak-Tabaka Iwona , Vandendriessche Hans , Weber Mara-Julia , Zander Annabell , Zimmermann Andreas , Maier Andreas
Published: September 2024

The European Final Palaeolithic witnessed marked changes in almost all societal domains. Despite a rich body of evidence, our knowledge of palaeodemographic processes and regional population dynamics still needs to be improved. In this study, we present regionally differentiated estimates of absolute numbers and population densities for the Greenland Interstadial 1d-a (GI-1d-a; 14-12.7 ka BP) and the Greenland Stadial 1 (GS-1; 12.7-11.6 ka BP) for Southern, Western, Northern and Central Europe. The data were obtained by applying the Cologne Protocol, a geostatistical approach for estimating prehistoric population size and density, to a newly compiled dataset of Final Palaeolithic sites. On a large spatio-temporal scale, we observe a shift of the main areas of human occupation from the Franco-Cantabrian region, which was intensely occupied during most phases of the preceding Upper Palaeolithic, to regions north of the Alps. At smaller scales, we observe divergent regional trends in the Final Palaeolithic meta-population: during GI 1d-a, a decreasing population in southwestern Europe and an increasing population in north-eastern Central Europe. For the first time since the dispersal of anatomically modern humans into Europe, we see that Central Europe becomes the dominant demographic growth area. Subsequently, the climatic cooling of GS-1 coincides with a pronounced population decline in most parts of the study area. An apparent increase in population density occurs only in north-eastern Central Europe and north-eastern Italy. Our estimates suggest that the total population was reduced by half. Similar results, with a relationship between decreasing temperatures and decreasing populations, have already been observed for the late phase of the Gravettian, when populations were reduced to only one third of those estimated for the early phase. Yet, in contrast to the collapse of local populations during the late Gravettian, the increase in population densities in Central Europe during GS-1 indicates population movements eastwards, possibly in response to deteriorating climatic conditions, particularly in western regions during the Younger Dryas.