bluuebunny/crossref_metadata_2025 huggingface dataset:
Delayed sleep wake phase disorder in adolescents: an updated review
Authors: Narala Bhavya , Ahsan Muhammad , Ednick Mathew , Kier Catherine
Published: December 2023

Purpose of review

This review examines the most common circadian rhythm disorder in adolescents, delayed sleep phase disorder. It explores the etiology, prevalence, clinical features, diagnostic tools and criteria, and treatment options to identify sleep disorders early in the course. This is important to help improve youths in terms of education and quality of life.

Recent findings

Recent studies indicate that delayed sleep wake phase disorder has a range of prevalence between 1% and 16%. It is often associated with neurodevelopmental disorders (i.e. attention deficit hyperactivity disorder and autism spectrum disorder) as well as psychopathology (i.e. substance use, anxiety, and depression). It can present with a myriad of symptoms, such as insomnia, restless sleep, and poor daytime cognitive function, often seen in pediatric practice. Important diagnostic measures incorporate history-taking, sleep logs, actigraphy (i.e. Apple watches) and measurement of dim light melatonin onset. Treatments include improved sleep hygiene, chronotherapy, exogenous melatonin administration, and bright light therapy.

There are many environmental and genetic factors that can predispose an individual to circadian rhythm disorders. Delayed sleep phase disorder has detrimental effects on overall health, cognition, and behavior. It is important to screen for this disorder in routine pediatric clinic visits. The goal of early intervention is to prevent health and behavioral complications and treat adolescents using a multimodal approach, especially those with affective/neurodevelopmental conditions, who are prone to having delayed sleep wake phase disorder.
Contemporary Updates on Sex Cord–stromal Tumors of the Testis
Authors: Acosta Andrés M. , Idrees Muhammad T. , Berney Daniel M. , Colecchia Maurizio
Published: December 2023

Testicular sex cord–stromal tumors (TSCSTs) are relatively rare, representing ~5% of testicular neoplasms overall. Historically, TSCSTs have been classified into 3 major entities: Leydig cell tumor, Sertoli cell tumor, and granulosa cell tumor. In recent years, immunophenotypic and molecular analyses have led to a more detailed understanding of the biological and genomic features of these neoplasms, resulting in the description of new entities, some of which have been included in the latest WHO classification. This review summarizes novel histopathologic, clinical, and molecular findings that may lead to a reappraisal of established concepts and help improve the diagnosis and clinical management of TSCSTs in the coming years.
Lymphoglandular Complex-Like Colorectal Carcinoma—A Series of 20 Colorectal Cases, Including Newly Reported Features of Malignant Behavior
Authors: Yilmaz Osman , Westerhoff Maria , Panarelli Nicole , Hart John , Groisman Gabriel , Ruz-Caracuel Ignacio , Loughrey Maurice , Matsukuma Karen , Lee Soo Hyun , Yilmaz Omer , Gonzalez Raul S. , Deshpande Vikram
Published: December 2023

Distinguishing colon carcinoma that is surrounded by well-circumscribed lymphoid tissue from adenomas involving lymphoglandular complexes can be difficult. We assessed a multi-institutional international cohort of 20 colorectal carcinomas with associated prominent lymphoid infiltrates, which we referred to as lymphoglandular complex-like carcinoma (LGCC). We collected clinical and endoscopic features, including lesion size, endoscopic appearance, location, procedure, follow-up, AJCC stage, and mismatch repair status. We recorded the presence of the following histologic features: haphazard gland distribution, gland angulation, gland fusion, solid nest formation, single-cell formation, stromal desmoplasia, presence of lymphovascular invasion and perineural invasion, presence of lamina propria, cytologic atypia as low- or high-grade, presence of goblet cells in the invasive component, and the presence of a surface lesion. Most cases (9 of 13) were described endoscopically as sessile polyps with an average size of 1.56 cm. Most cases (90%) were associated with a surface lesion, of which the majority were tubular adenomas, though a subset was associated with sessile serrated lesions with dysplasia (3 of 18). All cases of LGCC demonstrated haphazard gland distribution and either gland angulation, fusion, or solid nest formation. A portion of cases demonstrated single-cell infiltration (35%) and desmoplasia (50%), and rarely lymphovascular invasion was present (5%). A subset (10%) of cases invaded beyond the submucosa. Deficient mismatch repair was present in 22% (2 of 9) of cases for which it was performed. In cases of colectomy or completion colectomy, nodal metastasis was present in 38% (3 of 8). No cases demonstrated disease recurrence or disease-specific mortality. Overall, LGCC represents an enigmatic subset of carcinomas that is important to distinguish from adenomas involving lymphoglandular complexes due to its varying prognostic outcomes.
DPA714 PET Imaging Shows That Inflammation of the Choroid Plexus Is Active in Chronic-Phase Intracerebral Hemorrhage
Authors: Yao Shaobo , Gao Zhuyu , Fang Wenhua , Fu Ying , Xue Qianqian , Lai Tianmin , Shangguan Huangcheng , Sun Weiwei , Lin Yuanxiang , Lin Fuxin , Kang Dezhi
Published: December 2023

Purpose

Our aims were to investigate the presence of choroid plexus (CP) inflammation in chronic-phase intracerebral hemorrhage (ICH) patients and to characterize any inflammatory cells in the CP.

Patients and Methods

An in vivo 18F-DPA714 PET study was undertaken in 22 chronic-phase ICH patients who were admitted to the First Affiliated Hospital of Fujian Medical University or Tianjin Medical University General Hospital from April 2017 to June 2020. Ten control participants with nonhemorrhagic central nervous system diseases were included. Choroid plexus 18F-DPA714 uptake was calculated as the average SUVR. To aid the interpretation of the 18F-DPA714 uptake results at the CP level, Cy5-DPA714 in vivo imaging and immunofluorescence staining were used to show the presence of CP inflammation in an ICH mouse model during the chronic phase (14 weeks after ICH). Then immunofluorescence staining against translocator protein and other specific biomarkers was used to characterize the cells present in the inflamed CP of ICH mice in the chronic phase.

Results

PET imaging showed that CP DPA714 SUVRs in chronic-phase ICH patients were higher than in controls (mean CP SUVR ± SD; ICH group: 1.05 ± 0.35; control group: 0.81 ± 0.21; P = 0.006). Immunofluorescence staining of the CP in ICH model mice identified a population of CD45+ immune cells, peripheral monocyte-derived CD14+ cells, CD68+ phagocytes, and CD11b+ resident microglia/macrophages expressing translocator protein, possibly contributing to the increased 18F-DPA714 uptake.

Conclusions

Our study shows that CP DPA714 uptake in chronic-phase ICH patients was higher than that of participants with nonhemorrhagic central nervous system diseases, which means that CP inflammation is still active in chronic-phase ICH patients.
Non-typhoidal Salmonella causing urinary tract infection in a young male with renal calculi – a case report and comprehensive review
Authors: Sriramajayam Lavanya , Boopathy Vijayaraghavan Krishna Mohan , Appalaraju Boppe , Jeyaraj Sankarganesh
Published: December 2023

Introduction. Non-typhoidal Salmonella (NTS) causes urinary tract infections infrequently and are usually associated with presence of genitourinary abnormalities.

Case presentation. We report a case of immunocompetent male in his early 20 s with phimosis presented with history of dysuria and burning micturition for 4 months. A renal ultrasonography showed presence of bilateral intrarenal calculi. Urine analysis revealed presence of non-typhoidal Salmonella. Automated identification systems performed poorly in identification of serotype. On serotyping, it was identified as

Salmonella enteritidis

in the referral centre. The patient was managed with oral antibiotics.

Conclusion. This report highlights the issues of inaccurate identification of NTS even with advanced automated systems and early initiation of therapy based on the knowledge of local susceptibility patterns. UTI in immunocompetent individuals by non-typhoidal Salmonella should always be investigated further to rule out genitourinary abnormalities and appropriate antibiotics must be started to avoid chronicity and complications.
β-lactam non-susceptible Group A Streptococcus isolated from clinical samples in Guyana
Authors: Kalladeen Melissa , Cheddie Paul , Akpaka Patrick Eberechi
Published: December 2023

Introduction: Streptococcus pyogenes (or Group A streptococci [GAS]), is the causative agent of pharyngitis and various other syndromes involving cellulitis, streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis. 
 
Methods: In this study, we sought to use Sanger sequencing to identify mutations in PBP genes of Streptococcus pyogenes isolated from hospitalised patients that could confer reduced PBP affinity for penicillin and/or cephalosporin antibiotics. All isolates were screened for susceptibility to penicillin, amoxicillin, and cefazolin using E-test strips. 
 
Results: While there no documented cases of reduced susceptibility to penicillin or amoxicillin. There were 13 isolates were cefazolin non-susceptible. Examination of pbp1a by Sanger sequencing revealed several isolates with single amino acid substitutions, which could potentially reduce the affinity of PBP 1A for cefazolin and possibly other first generation cephalosporins.
 
Conclusion: Penicillin and penicillin-derived antibiotics remain effective treatment options for GAS infections, but active surveillance is needed to monitor for changes to susceptibility patterns against these and other antibiotics and understand the genetic mechanisms contributing to them.
Flavobacterium sedimenticola sp. nov., isolated from sediment
Authors: Wu Ningning , Liu Le , Jiang Xueting , Yuan Ye , Mao Dongmei , Shao Jiahui , He Jian , Shen Qirong
Published: December 2023

A novel yellow-pigmented bacterial strain, designated YZ-48T, was isolated from the sediment of the Yangtze River, PR China. Cells were Gram-stain-negative, non-motile, rod-shaped, strictly aerobic, catalase-positive and oxidase-positive. The strain grew optimally on R2A medium at 37 °C, pH 7.0 and with 1.0 % (w/v) NaCl. Strain YZ-48T showed the closest 16S rRNA gene sequence similarity to

Flavobacterium solisilvae

SE-s27T (96.4 %) and

F. dankookense

DSM 25687T (96.2 %). The phylogenetic trees based on 16S rRNA gene sequences showed that strain YZ-48T belonged to the genus

Flavobacterium

but formed a distinct phylogenetic lineage. The obtained average nucleotide identity and digital DNA–DNA hybridization values between YZ-48T and the two closest strains were 75.0 and 74.5 % and 19.6 and 19.0 %, respectively. The sole respiratory quinone was MK-6. The major polar lipids were phosphatidylethanolamine, two unidentified aminolipids and three unidentified polar lipids. The major cellular fatty acids were iso-C16 : 0, iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3-OH, iso-C15 : 0 3-OH and iso-C16 : 0 3-OH. The DNA G+C content was 40.2 mol%. Based on the phenotypic, chemotaxonomic, phylogenetic and genomic data, strain YZ-48T represents a novel species of the genus

Flavobacterium

, for which the name Flavobacterium sedimenticola sp. nov. is proposed, with strain YZ-48T (=KCTC 82329T=CCTC AB 2023061T=MCCC 1K08804T) as the type strain.
Planting diversity begets multifaceted tree diversity in oil palm landscapes
Authors: Paterno Gustavo Brant , Brambach Fabian , Guerrero-Ramírez Nathaly , Zemp Delphine Clara , Cantillo Aiza Fernanda , Camarretta Nicolò , Moura Carina C. M. , Gailing Oliver , Ballauff Johannes , Polle Andrea , Schlund Michael , Erasmi Stefan , Iddris Najeeb Al-Amin , Khokthong Watit , Sundawati Leti , Irawan Bambang , Hölscher Dirk , Kreft Holger
Published: December 2023

Optimizing restoration outcomes is crucial for enhancing multifaceted diversity, resilience, and ecosystem functioning in monoculture-dominated landscapes globally. Here, we experimentally tested the performance of passive and active restoration strategies to recover taxonomic, phylogenetic, and functional diversity by establishing 52 tree islands in an oil palm landscape. Tree diversity via natural regeneration was shaped by local rather than landscape properties, with the diversity of planted tree species and tree island size driving higher multifaceted diversity. We show that large tree islands with higher initial planted diversity catalyze the recovery of multifaceted diversity at both the local and landscape level, including forest-associated species. Our results demonstrate that planted diversity begets regenerating diversity, overcoming major limitations of natural regeneration in highly modified landscapes. By elucidating the contribution of experimental, local, and landscape drivers to natural regeneration, these findings provide practical insights to make oil palm landscapes more biodiversity-friendly by enhancing functional and phylogenetic diversity within plantations.
Improving generalizability for MHC-I binding peptide predictions through geometric deep learning
Authors: Marzella Dario F. , Crocioni Giulia , Radusinovic Tadija , Lepikhov Daniil , Severin Heleen , Bodor Dani L. , Rademaker Daniel T. , Lin ChiaYu , Georgievska Sonja , Renaud Nicolas , Kessler Amy Lynn , Lopez-Tarifa Pablo , Buschow Sonja , Bekkers Erik , Xue Li C
Published: December 2023

The interaction between peptides and major histocompatibility complex (MHC) molecules is pivotal in autoimmunity, pathogen recognition and tumor immunity. Recent advances in cancer immunotherapies demand for more accurate computational prediction of MHC-bound peptides. We address the generalizability challenge of MHC-bound peptide predictions, revealing limitations in current sequence-based approaches. Our structure-based methods leveraging geometric deep learning (GDL) demonstrated promising improvement in generalizability across unseen MHC alleles. Further, we tackle data efficiency by introducing a self-supervised learning approach on structures (3D-SSL). Without being exposed to any binding affinity data, our 3D-SSL outperforms sequence-based methods trained on ~90 times more datapoints. Finally, we demonstrate the resilience of structure-based GDL methods to biases in binding data on an Hepatitis B virus vaccine immunopeptidomics case study. This proof-of-concept study highlights structure-based methods' potential to enhance generalizability and data efficiency, with important implications for data-intensive fields like T-cell receptor specificity predictions, paving the way for enhanced comprehension and manipulation of immune responses.
Opportunities to improve goat production and food security in Botswana through forage nutrition and the use of supplemental feeds
Authors: Cooke Andrew S. , Machekano Honest , Ventura-Cordero Javier , Louro-Lopez Aranzazu , Joseph Virgil , Gwiriri Lovemore C. , Takahashi Taro , Morgan Eric R. , Lee Michael R. F. , Nyamukondiwa Casper
Published: December 2023

Goats fulfil a central role in food security across Africa with over half of households owning or rearing goats in rural areas. However, goat performance is poor and mortality high. This study assessed the nutritional quality of commonly used feeds and proposes feed-baskets to enhance goat nutrition and health. Feeds were collected from 11 areas within the Central District of Botswana, and macronutrient analyses were conducted, including crude protein, fibre fractions, ash, and metabolizable energy (ME). Forage nutrition was compared across seasons and soil types. Additionally, seasonal supplementation trials were conducted to evaluate consumption rates of various supplements, including crop residues, pellets, Lablab purpureus, and Dichrostachys cinerea. Each supplement was provided ad libitum for a 24-hour period, and consumption rates determined. Findings revealed significant differences in nutrition among various feed sources, across seasons, and in relation to soil types (p < 0.001). Consumption rates of supplements were higher during the dry season, possibly due to reduced forage availability. Supplement consumption rates varied across supplements, with crop residues accounting for approximately 1% of dry matter intake, compared to up to 45% for pellets, 13% for L. purpureus, and 15% for D. cinerea. While wet season feed baskets exhibited higher ME values compared to dry-season feed-baskets, the relative impact of supplementation was more pronounced during the dry season. These results highlight the potential for optimizing goat diets through improved grazing and browsing management, especially during the reduced nutritional availability in the dry season.
A Benchmark of state-of-the-art Deconvolution Methods in Spatial Transcriptomics: Insights from Cardiovascular Disease and Chronic Kidney Disease
Authors: Slabowska Alban Obel , Pyke Charles , Hvid Henning , Jessen Leon Eyrich , Baumgart Simon , Das Vivek
Published: December 2023

A major challenge in sequencing based spatial transcriptomics (ST) is resolution limitations. Tissue sections are divided into hundreds-to thousands of spots, where each spot invariably contains a mixture of cell types. Methods have been developed to deconvolute the mixed transcriptional signal into its constituents. While ST is becoming essential for drug discovery especially in Cardiometabolic diseases, to date no deconvolution benchmark has been performed on these types of tissues and diseases. However, the three methods Cell2location, RCTD and spatialDWLS have previously been shown to perform well in brain tissue and simulated data. Here, we compare these methods to assess best performance when using human data from Cardiovascular Disease (CVD) data and Chronic Kidney Disease (CKD) from patients at different pathological states, evaluated using expert annotation.

In this benchmark, we found that all three methods performed comparably well in deconvoluting verifiable cell types including smooth muscle cells and macrophages in vascular samples and podocytes in kidney samples. RCTD shows the best performance accuracy scores in CVD samples while Cell2location on average achieved the highest performance across test experiments. While all three methods had similar accuracies Cell2location need less reference data to converge at the expense of higher computational intensity. Finally, we also report that RCTD has the fastest computational time and the simplest workflow requiring fewer computational dependencies. In conclusion, we find that each method has particular advantages, and the optimal choice depends on the use case.
Heterogeneous Synaptic Homeostasis: A Novel Mechanism Boosting Information Propagation in the Cortex
Authors: Razi Farhad , Sancristóbal Belén
Published: December 2023

Perceptual awareness of auditory stimuli decreases from wakefulness to sleep, largely due to reduced cortical responsiveness. During wakefulness, neural responses to external stimuli exhibit a broader spatiotemporal propagation pattern compared to deep sleep. A potential mechanism for this phenomenon is the synaptic upscaling of cortical excitatory connections during wakefulness, as posited by the synaptic homeostasis hypothesis. However, we argue that uniform synaptic upscaling alone cannot fully account for this observation. We propose a novel mechanism suggesting that the upscaling of excitatory connections between different cortical areas exceeds that within individual cortical areas during wakefulness. Our computational results demonstrate that the former promotes the transfer of neural responses and information, whereas the latter has diminishing effects. These findings highlight the necessity of heterogeneous synaptic upscaling and suggest the presence of heterogeneity in receptor expression for neuromodulators involved in synaptic modulation along the dendrite.
Macrophage transplantation rescues RNASET2-deficient leukodystrophy by replacing deficient microglia in a zebrafish model
Authors: Rutherford Holly A , Candeias Diogo , Duncan Christopher JA , Renshaw Stephen A , Hamilton Noémie
Published: December 2023

RNaseT2-deficient leukodystrophy is a rare infantile white matter disorder mimicking a viral infection and resulting in severe psychomotor impairments. Despite its severity, there remain no treatments for this disorder, with little understanding of cellular mechanisms of pathogenesis. Recent research using thernaset2mutant zebrafish model has suggested that microglia – brain-resident phagocytes – may be the drivers of neuroinflammation in this disorder, due to their failure to digest apoptotic debris during early development. As such, the current study aimed to develop a strategy for microglial replacement and test the effects of this intervention onrnaset2mutant zebrafish pathology. We developed a strategy for microglial replacement through transplantation of adult whole kidney marrow-derived macrophages into embryonic hosts. Using live imaging, we revealed that transplant-derived macrophages can engraft within host brains and express microglia-specific markers, suggesting adoption of a microglial phenotype. Tissue clearing strategies revealed the persistence of transplanted cells in host brains beyond embryonic stages We demonstrated that transplanted cells clear apoptotic cells within the brain, as well as rescuing overactivation of the antiviral response otherwise seen in mutant larvae. RNA sequencing at the point of peak transplant-derived cell engraftment confirms that transplantation can reduce the brain-wide immune response, and particularly the antiviral response, inrnaset2-deficient brains. Crucially, this reduction in neuroinflammation resulted in behavioural rescue - restoringrnaset2mutant motor activity to wild type levels in embryonic and juvenile stages. Together, these findings demonstrate the role of microglia as the cellular drivers of neuropathology inrnaset2mutants, and that macrophage transplantation is a viable strategy for microglial replacement in the zebrafish. Therefore, microglia-targeted interventions may have therapeutic benefits in RNaseT2-deficient leukodystrophy.
Orientia tsutsugamushiAnk5 directs ubiquitination and proteasomal degradation of NLRC5 to inhibit major histocompatibility complex class I expression
Authors: Adcox Haley E. , Hunt Jason R. , Rodino Kyle G. , Ottens Andrew K. , Carlyon Jason A.
Published: December 2023

How intracellular bacteria subvert the major histocompatibility complex (MHC) class I pathway is poorly understood. Here, we show that the obligate intracellular bacteriumOrientia tsutsugamushiuses its effector protein, Ank5, to orchestrate proteasomal degradation of the MHC class I gene transactivator, NLRC5. Ank5 uses a tyrosine in its fourth ankyrin repeat to bind the NLRC5 N-terminus while its F-box directs host SCF complex ubiquitination of K1194 in the leucine-rich repeat region that dictates NLRC5 susceptibility toOrientia- and Ank5-mediated degradation. The ability ofO. tsutsugamushistrains to degrade NLRC5 correlates withank5genomic carriage. Ectopically expressed Ank5 that can bind but not degrade NLRC5 protects the transactivator duringOrientiainfection. Thus, Ank5 is an immunoevasin that uses its bipartite architecture to rid host cells of NLRC5 and MHC class I molecules. This study offers insight into how intracellular pathogens can impair MHC class I expression to benefit their survival.
Dysregulated Repeat Element Viral-like Immune Response in Hepatocellular Carcinoma
Authors: Coley Avril K. , Lu Chenyue , Pankaj Amaya , Emmett Matthew J. , Lang Evan R. , Song Yuhui , Xu Katherine H. , Xu Nova , Patel Bidish K. , Chougule Abhijit , Nieman Linda T. , Aryee Martin J. , Ferrone Cristina R. , Deshpande Vikram , Franses Joseph W. , Ting David T.
Published: December 2023

Purpose

Dysregulation of viral-like repeat RNAs are a common feature across many malignancies that are linked with immunological response, but the characterization of these in hepatocellular carcinoma (HCC) is understudied. In this study, we performed RNAin situhybridization (RNA-ISH) of different repeat RNAs, immunohistochemistry (IHC) for immune cell subpopulations, and spatial transcriptomics to understand the relationship of HCC repeat expression, immune response, and clinical outcomes.

Experimental Design

RNA-ISH for LINE1, HERV-K, HERV-H, and HSATII repeats and IHC for T-cell, Treg, B-cell, macrophage, and immune checkpoint markers were performed on 43 resected HCC specimens. Spatial transcriptomics on tumor and vessel regions of interest was performed on 28 specimens from the same cohort.

Results

High HERV-K and high LINE1 expression were both associated with worse overall survival. There was a positive correlation between LINE1 expression and FOXP3 T-regulatory cells (r = 0.51 p < 0.001) as well as expression of the TIM3 immune checkpoint (r = 0.34, p = 0.03). Spatial transcriptomic profiling of HERV-K high and LINE-1 high tumors identified elevated expression of multiple genes previously associated with epithelial mesenchymal transition, cellular proliferation, and worse overall prognosis in HCC including SSX1, MAGEC2, and SPINK1.

Conclusion

Repeat RNAs may serve as useful prognostic biomarkers in HCC and may also serve as novel therapeutic targets. Additional study is needed to understand the mechanisms by which repeat RNAs impact HCC tumorigenesis.
Developing Cardiac Digital Twins at Scale: Insights from Personalised Myocardial Conduction Velocity
Authors: Qian Shuang , Ugurlu Devran , Fairweather Elliot , Strocchi Marina , Toso Laura Dal , Deng Yu , Plank Gernot , Vigmond Edward , Razavi Reza , Young Alistair , Lamata Pablo , Bishop Martin , Niederer Steven
Published: December 2023

Large-cohort studies using cardiovascular imaging and diagnostic datasets have assessed cardiac anatomy, function, and outcomes, but typically do not reveal underlying biological mechanisms. Cardiac digital twins (CDTs) provide personalized physics- and physiology-constrainedin-silicorepresentations, enabling inference of multi-scale properties tied to these mechanisms.

We constructed 3464 anatomically-accurate CDTs using cardiac magnetic resonance images from UK biobank and personalised their myocardial conduction velocities (CVs) from electrocardiograms (ECG), through an automated framework.

We found well-known sex-specific differences in QRS duration were fully explained by myocardial anatomy, as CV remained consistent across sexes. Conversely, significant associations of CV with ageing and increased BMI suggest myocardial tissue remodelling. Novel associations were observed with left ventricular ejection fraction and mental-health phenotypes, through a phenome-wide association study, and CV was also linked with adverse clinical outcomes.

Our study highlights the utility of population-based CDTs in assessing intersubject variability and uncovering strong links with mental health.
Healthcare-associated Urinary tract infection and its determinants among Adult Patients Admitted to Intensive Care Units of Addis Ababa Public Governmental Hospitals, Ethiopia; 2020
Authors: Genaneh Wondimagegn , Nega Tigist , Argeta Hindu , Gashaw Silenat , Shimeles Eyouel
Published: December 2023

Back ground

Urinary tract infections are common bacterial infections that affect almost 150 million people internationally each year. A catheter-associated urinary tract infection arises when germs enter the urinary tract via a urinary catheter, leading to infection and have been linked with increased mortality, morbidity, healthcare costs in intensive care units. It is one of the highest prevalent health care-related infections, accounting for nearly 30% of intensive care unit (ICU) reports because of its association to urinary catheterization, but has great preventive potential.

Method

Institutional based cross-sectional study design applied to determine the prevalence and associated factors of Health care-associated urinary tract infections among adult 391 patients admitted to ICU from 2017 to 2019 GC at Addis Ababa Public Governmental Hospital, Addis Ababa, Ethiopia, June-December 2020.Data had manually checked and entered to Epi-data manager version 4.6 and statistical analyses have been performed using SPSS version 23 software program. Strength of association between dependent and independent variables is assessed using crude odds ratio (COR) and adjusted odds ratio (AOR) with confidence Interval (CI) of 95%. Variables that had a value of P < 0.25 on bi-variate analysis were directly forward to be analyzed by multi variable analysis. Goodness of fit test had also computed for logistic regression using Hosmer and Lemeshow test resulted in (sig=0.073), finally having P-values < 0.05 is considered as statistically significant.

Result

the study find that the prevalence of Healthcare Associated Urinary Tract Infection among ICU admitted patients was 91(23.3%) 95%CI ;(19.2-27.4), While length of stay, Having tracheostomy, patients on Mechanical Ventilation and taking Proton pump inhibitor drugs were associated with HAUTI in the study area.

Conclusion

Healthcare-associated Urinary Tract infection is highly emerging clinical condition among ICU admitted patients in the study areas.
Endolysin B as a new archetype inM. tuberculosistreatment
Authors: Griego Anna , Antinori Beatrice , Spitaleri Andrea , Muzzolini Ilaria , Muzzioli Stefano , Calò Luca , Moschetti Giorgia , Genta Marianna , Scarpa Edoardo , Matteis Valeria De , Miggiano Riccardo , Ricagno Stefano , Rizzello Loris
Published: December 2023

So far it is thanks to antibiotics that illnesses, such as Tuberculosis (TB), are treatable. However, antimicrobial misuse combined withMycobacterium tuberculosisphenotypic plasticity are nullifying the effects of the existing therapies. As a result, increasingly people are dying (one person dies of TB every 20 seconds), especially due to the rise of multi-and extensively drug-resistant strains. There is indeed a urgent need for new and more effective therapies, which should match the requirement of avoiding the rise in drug resistance. Among them, the use of bacteriophage – bacteria-restricted viruses – or simply phage lytic enzyme (i.e.,endolysin) represents one of the most promising alternatives. All phages encode for the endolysin A (LysA), which degrades the bacteria cell wall, finally leading to the release of the newly synthesized virions. Nevertheless, mycobacteriophages (bacterial viruses selectively infecting mycobacteria), evolved the additional endolysin B (LysB) to selectively damage the complex mycobacteria cell wall, and to evade from their host. LysB, owing a lipolytic enzyme, can degrade the thick mycolic acid layer, and hence disrupt the integrity of the mycobacterial membrane. Despite its key role in mediating mycobacteria lysis, the molecular mechanism regulating LysB binding to its target remains poorly characterized. Herein, we selected Ms6LysB and created a fluorescent engineered version as a proxy to analyze LysB binding qualitatively and quantitatively to both the fast-growing non-pathogenicMycobacterium smegmatisand the slow-growing pathogenicM. tuberculosis.Additionally, we shed light on LysB antimicrobial activity uponM. tuberculosisinfection, by using alveolar-like mouse macrophages (mAMs) as a cellular model that closely recapitulates the natural niche ofM. tuberculosisinfection. Our study provides the proof-of-principle that Ms6 LysB binding to the outer mycobacterial membrane can impairM. tuberculosisgrowth homeostasis and that LysB retain its lytic properties even when internalized by mAMs. This lays the groundwork for the use of LysB as a new therapeutic strategy to undermineM. tuberculosisinfection.
Sex specific regulation of the cortical transcriptome in response to sleep deprivation
Authors: Shi Tianyi , Shah Ishani , Dang Quang , Taylor Lewis , Jagannath Aarti
Published: December 2023

Multiple studies have documented sex differences in sleep behaviour, however the molecular determinants of such differences remain unknown. Furthermore, most studies addressing molecular mechanisms have been performed only in males, leaving the current state of knowledge biased towards the male sex. To address this, we studied the differences in the transcriptome of the cerebral cortex of male and female C57Bl/6J mice after six hours of sleep deprivation. We found that several genes, including the neurotrophin growth factorBdnf, immediate early genesFosbandFosl2, and the adenylate cyclaseAdcy7are differentially upregulated in males compared to females. We identified the androgen-receptor activating transcription factor EZH2 as the upstream regulatory element specifying sex differences in the sleep deprivation transcriptome. We propose that the pathways downstream of these transcripts, which impact on cellular re-organisation, synaptic signalling and learning may underpin the differential response to sleep deprivation in the two sexes.
Escherichia coliacid phosphatase AphA expression is upregulated under carbon and phosphate starvations and inhibited by CytR
Authors: Kronborg Kristina , Zhang Yong Everett
Published: December 2023

This study investigates the regulation ofE. coli aphAexpression under nutrient starvation. Using transcriptional reporters with truncatedaphApromoter sequences, we found that starvation of carbon and phosphate, but not amino acid, stimulatedaphAexpression through distinct promoter regions. Deletions ofcrporcyaAreducedaphAexpression, confirming their importance inaphAregulation during carbon starvation. Conversely, CytR deletion increasedaphAexpression, suggesting CytR’s role as a repressor ofaphAexpression. Collectively, these data imply a potential connection between CytR,aphAexpression, and the broader context of natural competence evolution and bacterial nutrient absorption.
Non-invasive homogeneous targeted blood-brain barrier disruption using acoustic holography with a clinical focused ultrasound system
Authors: McDannold Nathan , Zhang Yongzhi , Fletcher Stecia-Marie , Livingstone Margaret
Published: December 2023

Holographic methods can be used with phased array transducers to shape an ultrasound field. We tested a simple method to create holograms with a 1024-element phased array transducer. With this method, individual acoustic simulations for each element of the transducer were simultaneously loaded into computer memory. Each element’s phase was systematically modulated until the combined field matched a desired pattern. The method was evaluated with a 220 kHz hemispherical transducer being tested clinically to enhance drug delivery via blood-brain barrier disruption. The holograms were evaluated in a tissue-mimicking phantom andin vivoin experiments disrupting the blood-brain barrier in rats and in a macaque. This approach can enlarge the focal volume in a patient-specific manner and could reduce the number of sonication targets needed to disrupt large volumes, improve the homogeneity of the disruption, and improve our ability to detect microbubble activity in tissues with low vascular density.

Teaser

Holography can shape the focal region of a clinical focused ultrasound system developed for targeted drug delivery in the brain.
Microbial Reduction of Geogenic and Synthetic Goethite and Hematite
Authors: O’Loughlin Edward J.
Published: December 2023

The microbial reduction of Fe(III) is a major component of Fe cycling in terrestrial and aquatic environments and is affected by the Fe(III) mineralogy of the system. The majority of the research examining the bioreduction of Fe(III) oxides by Fe(III)-reducing bacteria (IRB) has focused on the reduction of poorly crystalline Fe(III) phases, primarily ferrihydrite; however, crystalline Fe(III) oxides like goethite (α-FeOOH) and hematite (α-Fe2O3) comprise the majority of Fe(III) oxides in soils. This study examined the bioreduction of goethite and hematite of geogenic and synthetic origin byShewanella putrefaciensCN2, a well-studied model IRB, in laboratory incubations. Overall, the rate and extent of Fe(II) production were greater for goethite than for hematite, and for geogenic Fe(III) oxides relative to their synthetic analogs. Although there was substantial production of Fe(II) (i.e., > 5 mM Fe(II)) in many of the systems, X-ray diffraction analysis of the solids at the end of the incubation did not indicate the formation of any Fe(II)-bearing secondary minerals (e.g., magnetite, siderite, green rust, etc.). The results of this study demonstrate the variability in the extent of bioreduction of geogenic goethite and hematite, and furthermore, that synthetic goethite and hematite may not be good analogs for the biogeochemical behavior of Fe(III) oxides in aquatic and terrestrial environments.
Comprehensive Network and Structural Analysis of Bovine Papillomavirus, Squamous Cell Carcinoma Markers, and Elucidation of Efficacy Mechanisms of Phytochemicals fromThuja Occidentalis
Authors: Rahman Shafiqur , Kumar Arun HS
Published: December 2023

Papillomaviruses infect cutaneous tissue in various species including bovines and from benign warts to malignant squamous cell carcinoma causing severe economic losses to the farmers. The mechanisms by which bovine papillomaviruses interact with host tissue are unclear. Hence in this study using classical network analysis tools, we evaluated interactions of Bovine papilloma (BPV) variants, with markers and receptors implicated in squamous cell carcinoma. Additionally, the thuja phytoconstituents were also evaluated for its potential to target the BPV and squamous cell carcinoma network interactions to understand the mechanism of its clinical benefits. Various protein composition of 14 different virus variants of BPV were assessed against 24 markers of squamous cell carcinoma. Among these interactions EGFR consistently exhibited high-affinity interactions with the E1 protein in all isoforms of BPV. Type 4 BPV displayed the maximum number of binding sites (14) with a binding pocket score ranging from 15.47 to 141.34 and a probability score of 0.75 to 0.99. The comparison of the binding pockets identified that BPV types 2 and 13 had the highest number of common amino acid sequences. Further the alpha helix structure of specific common amino acid sequences, contribute to a more robust and widespread affinity interaction with both E1 of various BPV types and EGFR. Analysis of thuja phytochemicals suggested superior efficacy of Beyerene and Terpinene-4-ol towards all ten BPV targets and bEGFR. In conclusion, our comprehensive study leading to identification of E1 protein of BPV as a major interacting network with bEGFR, their key binding sites, and efficacy of thuja phytoconstituents offer valuable insight into further experimental validation and development of novel therapeutic strategies against BPV-associated diseases.
ADrosophilamodel of mitochondrial disease phenotypic heterogeneity
Authors: Granat Lucy , Knorr Debbra Y. , Ranson Daniel C. , Chakrabarty Ram Prosad , Chandel Navdeep S. , Bateman Joseph M.
Published: December 2023

Mutations in genes that affect mitochondrial function cause primary mitochondrial diseases. Mitochondrial diseases are highly heterogeneous and even patients with the same mitochondrial disease can exhibit broad phenotypic heterogeneity, which is poorly understood. Mutations in subunits of mitochondrial respiratory complex I cause complex I deficiency, which can result in severe neurological symptoms and death in infancy. However, some complex I deficiency patients present with much milder symptoms. The most common nuclear gene mutated in complex I deficiency is the highly conserved core subunit NDUFS1. To model the phenotypic heterogeneity in complex I deficiency we used RNAi lines targeting theDrosophilaNDUFS1 homolog ND-75 with different efficiencies. Strong knockdown of ND-75 inDrosophilaneurons resulted in severe behavioural phenotypes, reduced lifespan, altered mitochondrial morphology, reduced endoplasmic reticulum (ER)-mitochondria contacts and activation of the unfolded protein response (UPR). By contrast, weak ND-75 knockdown caused much milder behavioural phenotypes and changes in mitochondrial morphology. Moreover, weak ND-75 did not alter ER-mitochondria contacts or activate the UPR. Weak and strong ND-75 knockdown resulted in overlapping but distinct transcriptional responses in the brain, with weak knockdown specifically affecting proteosome activity and immune response genes. Metabolism was also differentially affected by weak and strong ND-75 knockdown including gamma-aminobutyric acid (GABA) levels, which may contribute to neuronal dysfunction in ND-75 knockdown flies. Several metabolic processes were only affected by strong ND-75 knockdown including the pentose phosphate pathway and the metabolite 2-hydroxyglutarate (2-HG), suggesting 2-HG as a candidate biomarker of severe neurological mitochondrial disease. Thus, ourDrosophilamodel provides the means to dissect the mechanisms underlying phenotypic heterogeneity in mitochondrial disease.
Quantitative Modeling of the Short-Term Response to Nitrogen Availability that Coordinates Early Events in Lateral Root Initiation
Authors: Gaudinier Allison , Van den Broeck Lisa , Moreno-Risueño Miguel , Rodriguez-Medina Joel , Sozzani Rosangela , Brady Siobhan M.
Published: December 2023

Nitrogen (N) is an essential macronutrient and its bioavailability plays a major role in how plant development is tuned to environmental nutrient status. To find novel factors in early root system architecture responses to N conditions, we performedArabidopsis thalianaroot transcriptome profiling of a short-term time course in limiting and sufficient N conditions. Using this data, we inferred transcriptional regulatory networks in each condition, which revealed the N-condition specific responses of jasmonate regulation; transcriptional factor (TF) ERF107 plays a more generalized role in lateral root development while TF LBD13 is specific to N-limiting conditions. Further, we used a single cell LR cell-type specific transcriptome dataset to model and analyze the roles of TFs LBD13, ERF107, and PDF2 in early stages of LR development. Linking the N time course transcriptomics, LR mutant phenotypes, and cell-type specific single cell profiling, these approaches provide multiple lines of evidence to find and test the roles of TFs that are involved in early root patterning responses to N conditions.
Would an AI chatbot persuade you: an empirical answer from the elaboration likelihood model
Authors: Chen Qian , Yin Changqin , Gong Yeming
Published: December 2023

Purpose

This study investigates how artificial intelligence (AI) chatbots persuade customers to accept their recommendations in the online shopping context.

Design/methodology/approach

Drawing on the elaboration likelihood model, this study establishes a research model to reveal the antecedents and internal mechanisms of customers' adoption of AI chatbot recommendations. The authors tested the model with survey data from 530 AI chatbot users.

Findings

The results show that in the AI chatbot recommendation adoption process, central and peripheral cues significantly affected a customer's intention to adopt an AI chatbot's recommendation, and a customer's cognitive and emotional trust in the AI chatbot mediated the relationships. Moreover, a customer's mind perception of the AI chatbot, including perceived agency and perceived experience, moderated the central and peripheral paths, respectively.

Originality/value

This study has theoretical and practical implications for AI chatbot designers and provides management insights for practitioners to enhance a customer's intention to adopt an AI chatbot's recommendation.

Research highlights

The study investigates customers' adoption of AI chatbots' recommendation.

The authors develop research model based on ELM theory to reveal central and peripheral cues and paths.

The central and peripheral cues are generalized according to cooperative principle theory.

Central cues include recommendation reliability and accuracy, and peripheral cues include human-like empathy and recommendation choice.

Central and peripheral cues affect customers' adoption to recommendation through trust in AI.

Customers' mind perception positively moderates the central and peripheral paths.
Revisiting the impact of consumers' need for touch on webrooming intention: the perspective of maximizing mindset theory
Authors: Hsieh Jung-Kuei , Kumar Sushant
Published: December 2023

Purpose

The purpose of this paper addresses the issue of inconsistent findings regarding the impact of consumers' need for touch (NFT) on webrooming behavior. It investigates the moderator of maximization by drawing on maximizing mindset theory.

Design/methodology/approach

Three studies were carried out to test the hypothesized relationships. The first study investigated the impact of autotelic NFT on webrooming intention. The second study examined the impact of instrumental NFT on webrooming intention. The third study tested all hypotheses by the structural equation modeling approach.

Findings

The results confirm moderation by consumers' maximizing mindset. The moderated mediation analyses show that the interaction effect of autotelic NFT and maximization influences webrooming intention indirectly via anticipated sensory pleasure. Likewise, the interaction effect of instrumental NFT and maximization influences webrooming intention indirectly via product fit uncertainty.

Originality/value

The study draws on maximizing mindset theory to show that consumers' autotelic NFT and instrumental NFT drive their webrooming intentions depending on the activation of their maximizing mindset. The nonsignificant relationship between autotelic NFT and webrooming intention in the context of satisficers explains the conflicting findings reported in the literature. Consumers' affective and cognitive responses were also studied to uncover the underlying mechanisms of their webrooming intention. This research contributes to the literature by enhancing the understanding of webrooming behavior.
Vegetation composition regulates the interaction of warming and nitrogen deposition on net carbon dioxide uptake in a boreal peatland
Authors: Gong Yu , Wu Jianghua , Roulet Nigel , Le Thuong Ba , Ye Chen , Zhang Quanfa
Published: December 2023

Peatlands are carbon sinks and have the potential to mitigate global warming. However, it is unclear whether peatlands will remain carbon sinks or switch to carbon sources under global changes, such as climate warming, elevated nitrogen (N) deposition and vegetation composition change.

In this study, these global changes were mimicked in a boreal peatland for 7 years to explore the interactions of climate warming, elevated N deposition and vegetation composition on the carbon sink function of peatlands.

The results showed that warming has a limited effect on net ecosystem production (NEP), while N addition decreased NEP by 65% owing to the detrimental effect on Sphagnum mosses. The negative impact of N addition on NEP could be mitigated by warming under intact vegetation. Under the treatment of graminoid removal, warming and elevated N addition (WN) decreased NEP by 80%–106%. Under the treatment of shrub removal, 7 years of WN treatment did not affect NEP. These results highlight the importance of vegetation composition in regulating net CO2 flux in peatlands. If peatlands shift to shrub‐dominated ecosystems, the net CO2 uptake in peatlands would be decreased under climate warming and elevated N deposition. If peatlands shift to graminoid‐dominated ecosystems, the net CO2 uptake in peatlands would be unaltered under climate warming and elevated N deposition.

This study sheds new light on the interactions of climate warming, elevated N deposition, and vegetation composition change on the CO2 uptake of peatlands; and could help accurately evaluate the carbon sink function of peatlands under future global change.

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