bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in total charge on spike protein of SARS-CoV-2 in emerging lineages
Authors: Božič Anže , Podgornik Rudolf
Published: April 2024

Motivation

Charged amino acid residues on the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been shown to influence its binding to different cell surface receptors, its non-specific electrostatic interactions with the environment, and its structural stability and conformation. It is therefore important to obtain a good understanding of amino acid mutations that affect the total charge on the spike protein which have arisen across different SARS-CoV-2 lineages during the course of the virus’ evolution.

Results

We analyse the change in the number of ionizable amino acids and the corresponding total charge on the spike proteins of almost 2200 SARS-CoV-2 lineages that have emerged over the span of the pandemic. Our results show that the previously observed trend toward an increase in the positive charge on the spike protein of SARS-CoV-2 variants of concern has essentially stopped with the emergence of the early omicron variants. Furthermore, recently emerged lineages show a greater diversity in terms of their composition of ionizable amino acids. We also demonstrate that the patterns of change in the number of ionizable amino acids on the spike protein are characteristic of related lineages within the broader clade division of the SARS-CoV-2 phylogenetic tree. Due to the ubiquity of electrostatic interactions in the biological environment, our findings are relevant for a broad range of studies dealing with the structural stability of SARS-CoV-2 and its interactions with the environment.

Availability and implementation

The data underlying the article are available in the Supplementary material.
Postromanticizing the Nigerian Nation in Chinelo Okparanta’s Under the Udala Trees and Ayọ̀bámi Adébáyọ̀’s Stay with Me
Authors: Cruz-Gutiérrez Cristina
Published: April 2024

This essay analyzes representations of (anti)romantic relationships and episodes of “forced intimacy” in Chinelo Okparanta’s Under the Udala Trees (2015) and Ayọ̀bámi Adébáyọ̀’s Stay with Me (2017). I will establish a parallelism between the intimate and romantic relationships described in the novels and the social and political evolution of the Nigerian nation, placing the focus onto the female protagonists and their obligation to conform to preestablished feminine and heterosexual models in agreement with Nigerian traditional practices. Through the analysis of the affective and sociocultural evolution of these women, I aim to prove that there is a direct association between demystified representations of the nation and a disillusionment with the romantic ideals of the couples featured in the novels. I will refer to their evolution as “postromantic” since it transcends the performativity linked to romanticization.
Chronic Kidney Disease in Inflammatory Bowel Disease: a Systematic Review and Meta-analysis
Authors: Zadora Ward , Innocenti Tommaso , Verstockt Bram , Meijers Bjorn
Published: April 2024

Inflammatory bowel disease [IBD] is associated with various immune-mediated disorders including spondylarthritis, pyoderma gangrenosum, primary sclerosing cholangitis, and uveitis. Chronic kidney disease [CKD] is defined by a reduction in kidney function (estimated glomerular filtration rate [eGFR] less than 60 ml/min/1.73m2] and/or damage markers that are present for at least 3 months, regardless of the aetiology. Case reports and cohort studies suggest that IBD is associated with CKD. The extent and magnitude of a potential association is unknown. A comprehensive search was conducted in EMBASE, MEDLINE, Web of Science, the Cochrane database, and SCOPUS. Two separate reviewers were involved in the process of article selection and evaluation. Odds ratios were calculated in those papers with a comparison between an IBD population and a non-IBD control population, the Mantel Haenszel test was employed, using a random effect model. The systematic review was registered in PROSPERO [RD42023381927]. A total of 54 articles was included in the systematic review. Of these, eight articles included data on prevalence of CKD in IBD patients [n = 102 230] vs healthy populations [n = 762 430]. Of these, diagnosis of CKD was based on International Classification of Diseases [ICD] codes in five studies vs on eGFR in three studies. The overall odds ratio of developing CKD in the IBD population is 1.59, [95% CI 1.31-1.93], without any difference between studies using diagnostic coding (odds ratio [OR] 1.70, 95% CI 1.33-2.19] vs diagnosis based on eGFR [OR 1.36, 95% CI 1.33-1.64]. IBD is associated with a clinically meaningful increased CKD prevalence. We provide recommendations on diagnostic evaluation, as well as suggestions for future research.
Introduction: Houses of Worship in Times of War
Authors: Brodie Thomas , Heal Bridget
Published: April 2024

The introduction to the Special Issue ‘Houses of Worship in Times of War’, surveying the relevant historical literature on war and religion and providing an overview of the key themes of the essays.
Fashion and Authors’ Moral Rights
Authors: Härkönen Heidi
Published: April 2024

Due to the judgments Cofemel and Brompton from the Court of Justice of the European Union (CJEU), it is certain that the standard of copyright protection for works of applied art is the same as for any other work categories. However, the harmonising effect of these judgments only extends to the author’s economic rights, and not their moral interests. The moral rights of authors have not been popular topics in legal literature concerning copyright and works of applied art. This raises the question of to what extent moral rights apply to these works, which many national copyright laws used to discriminate against prior to the guidance from the CJEU. This multidisciplinary article delves into the complex relationship between moral rights and works of applied art in the specific context of fashion design. It appears that moral rights are absent from the standard practice in the fashion sector. This is evident, inter alia, in the fact that typically only renowned designers are attributed as authors. The article notes that there is no legally valid reason for fashion houses to overlook designers’ right of attribution. The right of integrity, however, has much less practical significance in the fashion sector. This article suggests the correct approach to moral rights in the fashion sector. The focus is on the European author’s rights tradition. The moral rights tradition of the Nordic states is used as a reference point because it allows for the consideration of the realities in different creative sectors without disrespecting authors’ personal interests.
E-mental health interventions for men: an urgent call for cohesive Australian policy and investment
Authors: Opozda Melissa J , Drummond Murray , Gupta Himanshu , Petersen Jasmine , Smith James A
Published: April 2024

Few men who experience a common mental disorder access any mental healthcare from a health professional. E-mental health (eMH; online) interventions may facilitate men’s access to mental healthcare and reduce inequities in access via assistance in a format that aligns with their preferences and needs. Recent reviews show that men who have used these programmes generally find them useful and satisfactory; however, data on their effectiveness and factors impacting effectiveness in men’s use are limited. Few eMH interventions have been designed specifically to suit men’s preferences and circumstances, and little is known about the eMH-related experiences and needs of men from vulnerable and marginalized backgrounds. Despite their potential, Australian men’s health, digital mental health, preventive health, and Aboriginal and Torres Strait Islander mental health and social and emotional well-being policies—and men’s health policies from Malaysia, Ireland, and South Africa—make no specific mention to progressing the use or evaluation of eMH for men. We present a series of policy recommendations, aiming to improve men’s access to effective and acceptable mental health assistance via eMH and increase health professional confidence to recommend and support these programmes. These include (i) the need for specific, connected health policy actions and targeted funding; (ii) policy priorities for intervention development, dissemination and evaluation; and (iii) for the experiences of men, particularly those from marginalized and vulnerable backgrounds, to be centred in policy. eMH for men should be promoted alongside interventions to reduce systems and social-level determinants of men’s mental health inequities.
Identification of a molecular network regulated by multiple ASD high risk genes
Authors: Wan Lei , Yang Guojun , Yan Zhen
Published: April 2024

Genetic sequencing has identified high-confidence ASD risk genes with loss-of-function mutations. How the haploinsufficiency of distinct ASD risk genes causes ASD remains to be elucidated. In this study, we examined the role of four top-ranking ASD risk genes, ADNP, KDM6B, CHD2, and MED13, in gene expression regulation. ChIP-seq analysis reveals that gene targets with the binding of these ASD risk genes at promoters are enriched in RNA processing and DNA repair. Many of these targets are found in ASD gene database (SFARI), and are involved in transcription regulation and chromatin remodeling. Common gene targets of these ASD risk genes include a network of high confidence ASD genes associated with gene expression regulation, such as CTNNB1 and SMARCA4. We further directly examined the transcriptional impact of the deficiency of these ASD risk genes. Our mRNA profiling with qPCR assays in cells with the knockdown of Adnp, Kdm6b, Chd2 or Med13 has revealed an intricate pattern of their cross-regulation, as well as their influence on the expression of other ASD genes. In addition, some synaptic genes, such as Snap25 and Nrxn1, are strongly regulated by deficiency of the four ASD risk genes, which could be through the direct binding at promoters or indirectly through the targets like Ctnnb1 or Smarca4. The identification of convergent and divergent gene targets that are regulated by multiple ASD risk genes will help to understand the molecular mechanisms underlying common and unique phenotypes associated with haploinsufficiency of ASD-associated genes.
Ustekinumab Offers Long-Term Clinical Remission With Safety in Very Early-Onset Inflammatory Bowel Disease
Authors: Iwama Itaru , Yoshida Masashi , Miyazawa Ayako , Hara Tomoko , Nambu Ryusuke
Published: April 2024

Lay Summary

We observed efficacy and safety of ustekinumab in very early-onset inflammatory bowel disease, which has not been previously reported. Clinical remission at 52% was 75%, often persisting beyond 2 years. Further studies including larger numbers of cases are needed to confirm this observation.
RETRACTED: Associations Between Ticagrelor Use and the Risk of Infections: A Mendelian Randomization Study
Authors: Xia Meng , Wu Qingmeng , Wang Yu , Peng Yongquan , Qian Cheng
Published: April 2024

This article has been retracted. Please see: https://doi.org/10.1093/infdis/jiae356
The Bitemporal Lens Model—toward a holistic approach to chronic disease prevention with digital biomarkers
Authors: Barata Filipe , Shim Jinjoo , Wu Fan , Langer Patrick , Fleisch Elgar
Published: April 2024

Objectives

We introduce the Bitemporal Lens Model, a comprehensive methodology for chronic disease prevention using digital biomarkers.

Materials and Methods

The Bitemporal Lens Model integrates the change-point model, focusing on critical disease-specific parameters, and the recurrent-pattern model, emphasizing lifestyle and behavioral patterns, for early risk identification.

Results

By incorporating both the change-point and recurrent-pattern models, the Bitemporal Lens Model offers a comprehensive approach to preventive healthcare, enabling a more nuanced understanding of individual health trajectories, demonstrated through its application in cardiovascular disease prevention.

Discussion

We explore the benefits of the Bitemporal Lens Model, highlighting its capacity for personalized risk assessment through the integration of two distinct lenses. We also acknowledge challenges associated with handling intricate data across dual temporal dimensions, maintaining data integrity, and addressing ethical concerns pertaining to privacy and data protection.

Conclusion

The Bitemporal Lens Model presents a novel approach to enhancing preventive healthcare effectiveness.
Pharmacological intestinal obstruction because of calcium polystyrene sulfonate administration
Authors: Thorpe Benjamin , Vinagre Salustiano Gonzalez , Santos Daniel , Gomez Javier Caneiro , Bustamante Montalvo Manuel
Published: April 2024

Cation exchange resins are commonly used as treatment for hyperkalaemia in patients with chronic renal disease. There is a relation between cation exchange resins and the development of gastrointestinal adverse effects. A case of an intestinal obstruction at the terminal ileum is presented that underwent an ileocolic resection because of a critical stenosis of the intestine. The pathologist revealed abundant inflammatory cells together with deposits of calcium polystyrene crystals responsible of the intestinal obstruction. A rare cause of intestinal obstruction to bear in mind in chronically medicated patients with cation exchange resins.
Widespread of the Vienna/Hungarian/Brazilian CC8-ST239-SCCmec III MRSA clone in patients hospitalized in the Tunisian Burn and Traumatology Center
Authors: Ben Said Meriam , Thabet Lamia , Cheriet Sarah , Messadi Amen Allah , Gómez Paula , Ruiz-Ripa Laura , Sghaier Senda , Hassen Bilel , Hassen Abdennaceur , Torres Carmen , Abbassi Mohamed Salah
Published: April 2024

The emergence and spread of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals is a major global public health concern. The current study sought to characterize 25 MRSA clinical isolates collected in a Tunisian hospital from December 2015 to September 2016, with the genetic lineages, virulence factors, and antibiotic resistance mechanisms determined for these isolates. Three spa-types were detected: t037 (23 isolates), t932, and t2235 (one isolate each). Isolates were ascribed to agr I (n = 20), agr II (n = 1), with four nontypeable isolates. Depending on sequence type (ST), the 25 MRSA isolates were assigned to two clonal complexes (CC8 and CC5), with a predominance of the lineage ST239-CC8 (n = 24; 96%). All isolates belonging to CC8 had the SCCmec type III, while the unique CC5 isolate had SCCmec type IV. Antimicrobial susceptibility testing revealed high levels of resistance to aminoglycosides, tetracycline, ciprofloxacin and rifampicin for the majority of isolates belonging to the ST239-CC8 lineage. The ST149-CC5 isolate was susceptible to non-β-lactam antibiotics. One isolate harbored the tsst-1 gene (4%); however, lukS/LukF-PV, eta and etb genes were not detected. The MDR ST239-CC8 clone would seem to be widespread in this hospital. Therefore, a rigorous hygienic control system is urgently required.
Management of bacterial wilt caused byCurtobacterium flaccumfacienspv.flaccumfaciensin common bean (Phaseolus vulgaris) using rhizobacterial biocontrol agents
Authors: Munene Lilian , Mugweru Julius , Mwirichia Romano
Published: April 2024

The bacterial wilt of common bean, caused by Curtobacterium flaccumfaciens pv. flaccumfaciens(Cff) is one of the most severe diseases affecting Phaseolus vulgaris production worldwide. This study aimed at evaluating the biocontrol potential of strains of rhizobacteria against bacterial wilt of common bean. Sequence analysis of the 16S rRNA gene was used to identify Cff isolates and also the bacterial antagonists. A soft agar overlay assay was used to select three biocontrol isolates based on their antagonistic activity against Cff. Our findings demonstrate that seed treatment using rhizobacterial P. fluorescens, Bacillus cereus, and Paenibacillus polymyxa species coupled with foliar application significantly reduced Cff disease incidence and disease severity. Therefore, biocontrol methods are potentially a safe, effective, and sustainable alternative to chemicals for controlling bacterial wilt of beans.
Effect of culture method on storage, plasma, and dry heat treatment resistance of Salmonella enterica serovar Typhimurium on black pepper
Authors: Song Won-Jae
Published: April 2024

The purpose of this study was to determine the effect of the culture method on the resistance of Salmonella Typhimurium in low water activity foods to storage, plasma, and dry heat. Whole black peppers were used as the model food. S. Typhimurium cultured in liquid broth (tryptic soy broth) or solid agar (tryptic soy agar) and inoculated on whole black pepper was stored or treated with cold plasma or dry heat. Inactivation of S. Typhimurium cultured in liquid medium was higher in all the treatments. Liquid-cultured S. Typhimurium showed higher DPPP = O (diphenyl-1-pyrenylphosphine oxide) values compared to the solid-cultured S. Typhimurium after plasma or dry heat treatment. Furthermore, the unsaturated fatty acid and saturated fatty acid ratio (USFA/SFA) was significantly (P < 0.05) reduced from 0.41 to 0.29 when S. Typhimurium was cultured on solid agar. These results suggested that the use of food-borne pathogens cultured on solid agar is more suitable for low water activity food pasteurization studies.
Bacillibactin class siderophores produced by the endophyte Bacillus subtilis NPROOT3 as antimycobacterial agents
Authors: Nalli Yedukondalu , Singh Sanju , Gajjar Apexa , Mahizhaveni Balasubramanian , Dusthackeer Vijayan Nynar Azger , Shinde Pramod B
Published: April 2024

The bacterial endophytes isolated from the halophyte Salicornia brachiata were explored for the antimicrobial potential to discover novel microbial inhibitors that combat multidrug resistance. Upon investigation, ethyl acetate extract of the endophyte Bacillus subtilis NPROOT3 displayed significant potency against Mycobacterium smegmatis MTCC6 as well as Mycobacterium tuberculosis H37Rv strain. Further investigation of ethyl acetate crude extract by repeated chromatographic separations followed by characterization using UV, HR-ESI-MS, MALDI-MS, MALDI-MS/MS, CD, and NMR spectroscopy yielded a series of five known siderophores, namely, SVK21 (1), bacillibactin C (2), bacillibactin B (3), tribenglthin A (4), and bacillibactin (5). A total of two out of five compounds, 4 (MIC 38.66 μM) and 5 (MIC 22.15 μM) exhibited significant inhibition against the strain M. smegmatis MTCC6 comparable with positive control rifampicin (MIC 12.15 μM). None of these five bacillibactin molecules are previously reported to exhibit bioactivity against Mycobacterium sp. Herein for the first time, all the compounds were screened for their antibacterial activities against a panel of bacterial pathogens of humans. Furthermore, the probable mechanism of action of bacillibactin compounds for their antimycobacterial activity is also discussed. The findings of this study open up a new chemotype for inhibition of the Mycobacterium sp. and other multidrug-resistant pathogens.
A metagenomic lens into endosphere microbial communities, promises, and discoveries
Authors: Adeleke Bartholomew Saanu , Muller Daniel , Babalola Olubukola Oluranti
Published: April 2024

The word endosphere represents the internal tissues of plants harboring diverse microbes capable of producing active biological products for various biotechnological and agricultural applications. The discreet standalone genes and interdependent association of microbial endophytes with plants can be an underlining factor in predicting their ecological functions. Yet-to-be-cultured endophytic microbes have geared the invention of metagenomics in various environmental studies to determine their structural diversity and functional genes with novel attributes. This review presents an overview of the general concept of metagenomics in microbial endophytic studies. First, the endosphere microbial communities were introduced, followed by metagenomic insights in endosphere biology, a promising technology. Also, the major application of metagenomics and a short brief on DNA stable isotope probing in determining functions and metabolic pathways of microbial metagenome were highlighted. Therefore, the use of metagenomics promises to provide answers to yet-to-be-cultured microbes by unraveling their diversity, functional attributes, and metabolic pathways with prospects in integrated and sustainable agriculture.
Diketopiperazine cyclo(-l-Leu-l-Phe) with plant elicitation activity and anti-oomycete activity against Plasmopara viticola
Authors: Aoki Yoshinao , Kunitomi Motoyasu , Mori Arianna , Watanabe Go , Nojiri Masutoshi , Suzuki Shunji
Published: April 2024

The aim of this study was to contribute to the reduction of synthetic chemical fungicide application in viticulture by using cyclo(-l-Leu-l-Phe) (cLF) produced by Bacillus subtilis KS1, a candidate for biological control agent. cLF is a diketopiperazine and belongs to the family of 2,5-diketopiperazines. KS1 secreted micromolar levels of cLF into culture medium. Micromolar concentrations of cLF structure-dependently decreased by ∼90% both disease severity and lesion density of downy mildew in grapevine cultivated in a growth chamber. Microscopic observation demonstrated that cLF inhibited Plasmopara viticola haustorium formation by 80% but not zoospore germination on leas disks. Interestingly, millimolar concentrations of cLF induced plant defense response, such as expression of genes encoding chitinase and β-1,3-glucanase, in grapevine leaves through the salicylic acid and jasmonate signaling pathways. We demonstrated that cLF was a weapon against P. viticola infection. Further evaluation of cLF in field trials is required to uncover its inherent characteristics.
Frequency distribution of virulence factors and antibiotic resistance genes in uropathogenic Proteus species isolated from clinical samples
Authors: Talebi Alireza , Momtaz Hassan , Tajbakhsh Elahe
Published: April 2024

One of the most common causes of urinary tract infections (UTIs) is Proteus species. Because there is little information on the pathogenicity of Proteus species isolated from Iran, we assessed their virulence characteristics and antibiotic resistance in this study. In Shahrekord, Iran, 260 isolates of Proteus causing UTIs were identified from patients. Polymerase chain reaction for gene amplification was used to determine virulence features and antibiotic resistance gene distribution in uropathogenic Proteus spp. After biochemical and molecular analysis, 72 (27.69%) of the 260 collected samples were recognized as Proteus mirabilis, and 127 (48.84%) specimens were Pr. vulgaris in both male and female forms. A significant interaction effect between Pr. mirabilis and Pr. vulgaris infections and the sex of patients was seen in both the male and female groups. No statistically significant difference was observed between Pr. mirabilis infection and season in different year seasons. However, in different seasons of the year, a statistically significant difference was observed between infection with Pr. vulgaris in autumn and other seasons. There was a considerable difference between Pr. mirabilis and Pr. vulgaris infections at different ages in various age groups. As people aged, infections occurred more frequently. Fim,pap,kspMT, and set1 genes had the highest expression in both Pr. vulgaris and Pr. mirabilis. Also, the highest rate of antibiotic resistance of Pr. vulgaris and Pr. mirabilis is attributed to the high expression of aac(3)-IV,tet(A), and blaSHV genes. In conclusion, identifying these genes as the key controllers of Proteus virulence factors might help with better infection management.
Inactivation of Cronobacter sakazakii biofilms using high voltage atmospheric cold plasma on various food-contact surfaces—a preliminary study
Authors: Phan Ngoc Le Bao , Nguyen Thu , Pedley John , Flint Steve
Published: April 2024

Cronobacter sakazakii is an opportunistic foodborne pathogen in powdered infant formula (PIF) associated with several foodborne outbreaks. Biofilms of C. sakazakii in the PIF manufacturing plant may be a source of contamination, but information on the treatment of these biofilms is limited. This study investigated the inactivation of C. sakazakii biofilms on three food contact surfaces (stainless steel, silicone, and PVC) using high voltage atmospheric cold plasma (HVACP) applied as a dielectric barrier discharge in a 10:90 air: helium modified atmosphere. After the 90 s  of cold plasma exposure at 40 kV, C. sakazakii was reduced by ∼3 log CFU/coupon comparing to without cold plasma treatments. HVACP treatment caused cell shrinkage, fragmentation of the cell membrane, and leakage of cytoplasm. The inactivation of the cells on the surface was confirmed by live/dead staining. These above-mentioned results indicate the antibiofilm efficacy of HVACP on C. sakazakii isolates on various food contact surfaces.
A novel strain of Shigella isolated from the gut of Lepidocephalichthys guntea has in its genome a complete gene package for Type ll secretion system, and elaborate repertoire of genes responsible for multiple antibiotic-resistance and metal resistance via specific efflux channels
Authors: Basak Chandana , Chakraborty Ranadhir
Published: April 2024

The bacterial strain GCP5 was isolated from the gut of a bottom-dwelling fish Lepidocephalichthys guntea, that lives in the Magurmari River near North Bengal University in Siliguri, India. GCP5 was phylogenetically assigned to the Shigella genus using whole genome-based trees, k-mer analysis, the multilocus species tree (MLST), and single nucleotide polymorphism (SNP)-based trees, and the genetic makeup of the isolate was determined following assembly of the genome sequences and genome annotation with several bioinformatics tools. The presence of a complete package of general-secretory-pathway (gsp) genes, grouped in an operon identical to a well-characterized type II secretion system (T2SS), was confirmed by genome mining of Shigella sp. GCP5. The operon’s gsp genes shared the most homology with Escherichia coli gsp genes. A few more high-pathogenicity islands (HPIs) in the GCP5 genome were validated using the pan-genomes analysis pipeline (PGAP) and island viewer. Several antibiotic-resistance genes were found in this genome, as well as the existence of key antibiotic efflux pump families, allowing for the creation of a gene network of several antibiotic efflux transporters. In addition, the genome contained genes specific for nickel transport, the nikABCD system, and the RND family transporter cusCFBA, which confers resistance to copper and silver by effluxing out Cu+ and Ag+ ions.
Assessing the growth-inhibitory activity of postbiotics of Lactobacillus spp. against Staphylococcus aureus under in vitro circumstances and food model
Authors: Khani Nader , Shkouhian Seyed mohamad javad , Kafil Hossein Samadi , Gilani Neda , Abbasi Amin , Rad Aziz Homayouni
Published: April 2024

Postbiotics are soluble metabolites that are liberated from the structure of lysing bacteria or are produced by live bacteria; these byproducts give the host increased biological activity and certain physiological effects. In the current study, the anti-Staphylococcus properties of postbiotics isolated from Lactobacillus acidophilus,L.paracasei,and L.plantarum were investigated in vitro, and pasteurized milk. Potential activity of postbiotics was performed via agar-disk diffusion method. Besides, the effect of heat and pH on the postbiotics antibacterial activity was measured via the agar-well diffusion method. To determine the antioxidant effect and the free radical scavenging potential of the postbiotics, 1,1-Diphenyl-2-picrylhydrazyl (DPPH) method was utilized. The postbiotics chemical composition was identified via gas chromatography-mass spectrometry. The antibacterial activity was mainly associated with lactic acid, laurostearic acid, and isopropylidene-3,3-dimethyl. Also, postbiotics showed strong antioxidant activity. Postbiotics derived from L.plantarum showed the highest antioxidant properties compared to L.paracasei and L.acidophilus. Lower minimum effective concentrations of postbiotic were altered in food model, and substantially, a low minimum effective( MEC) concentrations index (15 mg/mL) was identified for postbiotic of L.plantarum. The Lactobacillus spp. postbiotic, in particular L.plantarum, may have useful functional characteristics (possible antibacterial and antioxidant) in in vitro and food model.
Identifying human pre-mRNA cleavage and polyadenylation factors by genome-wide CRISPR screens using a dual fluorescence readthrough reporter
Authors: Ni Zuyao , Ahmed Nujhat , Nabeel-Shah Syed , Guo Xinghua , Pu Shuye , Song Jingwen , Marcon Edyta , Burke Giovanni L , Tong Amy Hin Yan , Chan Katherine , Ha Kevin C H , Blencowe Benjamin J , Moffat Jason , Greenblatt Jack F
Published: April 2024

Messenger RNA precursors (pre-mRNA) generally undergo 3′ end processing by cleavage and polyadenylation (CPA), which is specified by a polyadenylation site (PAS) and adjacent RNA sequences and regulated by a large variety of core and auxiliary CPA factors. To date, most of the human CPA factors have been discovered through biochemical and proteomic studies. However, genetic identification of the human CPA factors has been hampered by the lack of a reliable genome-wide screening method. We describe here a dual fluorescence readthrough reporter system with a PAS inserted between two fluorescent reporters. This system enables measurement of the efficiency of 3′ end processing in living cells. Using this system in combination with a human genome-wide CRISPR/Cas9 library, we conducted a screen for CPA factors. The screens identified most components of the known core CPA complexes and other known CPA factors. The screens also identified CCNK/CDK12 as a potential core CPA factor, and RPRD1B as a CPA factor that binds RNA and regulates the release of RNA polymerase II at the 3′ ends of genes. Thus, this dual fluorescence reporter coupled with CRISPR/Cas9 screens reliably identifies bona fide CPA factors and provides a platform for investigating the requirements for CPA in various contexts.
Disruption of G-quadruplex dynamicity by BRCA2 abrogation instigates phase separation and break-induced replication at telomeres
Authors: Lee Jennifer J , Kim Hyungmin , Park Haemin , Lee UkJin , Kim Chaelim , Lee Min , Shin Yongdae , Jung Ji-Jung , Lee Han-Byoel , Han Wonshik , Lee Hyunsook
Published: April 2024

Dynamic interaction between BRCA2 and telomeric G-quadruplexes (G4) is crucial for maintaining telomere replication homeostasis. Cells lacking BRCA2 display telomeric damage with a subset of these cells bypassing senescence to initiate break-induced replication (BIR) for telomere synthesis. Here we show that the abnormal stabilization of telomeric G4 following BRCA2 depletion leads to telomeric repeat-containing RNA (TERRA)-R-loop accumulation, triggering liquid–liquid phase separation (LLPS) and the assembly of Alternative Lengthening of Telomeres (ALT)-associated promyelocytic leukemia (PML) bodies (APBs). Disruption of R-loops abolishes LLPS and impairs telomere synthesis. Artificial engineering of telomeric LLPS restores telomere synthesis, underscoring the critical role of LLPS in ALT. TERRA-R-loops also recruit Polycomb Repressive Complex 2 (PRC2), leading to tri-methylation of Lys27 on histone H3 (H3K27me3) at telomeres. Half of paraffin-embedded tissue sections from human breast cancers exhibit APBs and telomere length heterogeneity, suggesting that BRCA2 mutations can predispose individuals to ALT-type tumorigenesis. Overall, BRCA2 abrogation disrupts the dynamicity of telomeric G4, producing TERRA-R-loops, finally leading to the assembly of telomeric liquid condensates crucial for ALT. We propose that modulating the dynamicity of telomeric G4 and targeting TERRA-R-loops in telomeric LLPS maintenance may represent effective therapeutic strategies for treating ALT-like cancers with APBs, including those with BRCA2 disruptions.
The management of very mild and mild asthma in preschoolers, children, and adolescents
Authors: Yang Connie L , Zysman-Colman Zofia , Chétrit Estelle , Hicks Anne , Reisman Joseph , Glicksman Amy
Published: April 2024

This practice point summarizes recommendations from the Canadian Thoracic Society’s 2021 “Guideline update: Diagnosis and management of asthma in preschoolers, children, and adults.” New recommendations include: a decrease in the frequency of daytime symptoms and reliever use to ≤2 per week in the asthma control criteria; assessing for risk of asthma exacerbation; not using as-needed short-acting beta-agonists alone in patients at higher risk for exacerbation; and the option of as-needed budesonide/formoterol (bud/form) in those ≥12 years old if they are unable to take daily inhaled corticosteroids despite extensive asthma education and support. The preference for daily inhaled corticosteroids to manage mild asthma in children, and the recommendation against intermittent short courses of inhaled corticosteroids, are unchanged.
Global dynamics and cytokinin participation of salt gland development trajectory in recretohalophyte Limonium bicolor
Authors: Zhao Boqing , Gao Yaru , Ma Qiuyu , Wang Xi , Zhu Jian-Kang , Li Weiqiang , Wang Baoshan , Yuan Fang
Published: April 2024

Salt gland is an epidermal Na+ secretory structure that enhances salt resistance in the recretohalophyte sea lavender (Limonium bicolor). To elucidate the salt gland development trajectory and related molecular mechanisms, we performed single-cell RNA sequencing of L. bicolor protoplasts from young leaves at salt gland initiation and differentiation stages. Dimensionality reduction analyses defined 19 transcriptionally distinct cell clusters, which were assigned into 4 broad populations—promeristem, epidermis, mesophyll, and vascular tissue—verified by in situ hybridization. Cytokinin was further proposed to participate in salt gland development by the expression patterns of related genes and cytological evidence. By comparison analyses of Single-cell RNA sequencing with exogenous application of 6-benzylaminopurine, we delineated 5 salt gland development-associated subclusters and defined salt gland-specific differentiation trajectories from Subclusters 8, 4, and 6 to Subcluster 3 and 1. Additionally, we validated the participation of TRIPTYCHON and the interacting protein Lb7G34824 in salt gland development, which regulated the expression of cytokinin metabolism and signaling-related genes such as GLABROUS INFLORESCENCE STEMS 2 to maintain cytokinin homeostasis during salt gland development. Our results generated a gene expression map of young leaves at single-cell resolution for the comprehensive investigation of salt gland determinants and cytokinin participation that helps elucidate cell fate determination during epidermis formation and evolution in recretohalophytes.
Age-dependent changes in leaf size in apple are governed by a cytokinin-integrated module
Authors: Jia Xumei , Xu Shuo , Wang Yuting , Jin Lu , Gao Tengteng , Zhang Zhijun , Yang Chao , Qing Yubin , Li Chao , Ma Fengwang
Published: April 2024

Plants undergo various age-dependent changes in leaf morphology during juvenile to adult vegetative stage. However, the precise molecular mechanisms governing these changes in apple (Malus domestica) remain unknown. Here, we showed that CYTOKININ OXIDASE/DEHYDROGENASE5 (MdCKX5), an age-dependent gene, encodes a functional CKX enzyme and serves as the common downstream target of SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factor MdSPL14 and WRKY transcription factor MdWRKY24 to control the degradation of cytokinin (CK). As the target of mdm-microRNA156a, MdSPL14 interacts with MdWRKY24 to coordinately repress the transcription of MdCKX5 by forming the age-mediated mdm-miR156a–MdSPL14–MdWRKY24 module, which regulates age-dependent changes in CK during the juvenile-to-adult phase transition. We further demonstrated that MdARR6, a type-A ARABIDOPSIS RESPONSE REGULATOR (ARR), is a negative feedback regulator in the CK signaling pathway. Silencing of MdARR6 in apple resulted in large leaves with smaller epidermal cells and a greater number of epidermal cells. Biochemical analysis showed that the mdm-miR156a–MdSPL14–MdWRKY24 module acts as a transcriptional repressor to directly regulate MdARR6 expression, thus controlling the age-dependent changes in leaf size by reducing CK responses. These findings established a link between the age pathway and CK signaling and revealed the molecular mechanism underlying age-dependent changes during the juvenile-to-adult phase transition; our results also provide targets for the genetic improvement of the vegetative phase transition in apple.
Daily associations between salivary cortisol and electroencephalographic-assessed sleep: a 15-day intensive longitudinal study
Authors: Yap Yang , Tung Natasha Yan Chi , Shen Lin , Bei Bei , Phillips Andrew , Wiley Joshua F
Published: April 2024

Study Objectives

Current evidence suggests that cortisol levels are bi-directionally associated with sleep. However, the daily, naturalistic cortisol-sleep associations remain unclear, as current evidence is mostly cross-sectional. This study tested whether pre-sleep cortisol predicts sleep duration and quality, and whether these sleep parameters predict the following day’s diurnal cortisol slope using a 15-day intensive longitudinal design with electroencephalographic measures and saliva sampling.

Methods

Ninety-five young adults (Mage = 20.48 ± 1.59 years) provided saliva samples at awakening and pre-sleep over 14 consecutive days, providing 2345 samples (85% viable). The Z-Machine Insight + was used to record over 900 nights of total sleep time (TST) and sleep efficiency (SE). Multilevel models tested these data at the between- and within-person levels.

Results

Higher pre-sleep cortisol predicted shorter TST (p < .001) and lower SE (p < .001) at the within-person level. Individuals with shorter average TST (p = .007) or lower average SE (p < .001) had flatter diurnal cortisol slopes, compared to those with longer average TST or higher average SE. Follow-up analyses showed that individuals with shorter average TST (vs. longer average TST) had higher pre-sleep cortisol levels (p = .01).

Conclusions

Our findings provide evidence that pre-sleep cortisol is associated with sleep duration and quality at the within-individual level. Furthermore, individuals with short or poor sleep had flatter diurnal cortisol slopes. Although the effect sizes are small, these findings show the naturalistic associations between sleep and cortisol in a relatively healthy sample. These findings suggest that sleep maintains the regulation of the stress-response system, which is protective against mental and physical disorders.
A comparison of DNA extraction methods used in the direct molecular detection of Burkholderia pseudomallei from blood
Authors: Mataira Georgia , Francis Fleur , Frazer Jaimie , Norton Robert
Published: April 2024

Background

Melioidosis is caused by Burkholderia pseudomallei. Direct molecular detection from unamplified blood remains insensitive.

Methods

Three different extraction methods—QIAamp UCP Pathogen Mini Kit, High Pure PCR template and MagNA Pure Pathogen Universal—were trialled using spiked human ethylenediaminetetraacetic acid blood. A type III secretion system 1 (TTSS-1) polymerase chain reaction was used for detection.

Results

The QIAamp UCP Pathogen Mini Kit performed best, with a limit of detection of 1.5×102 cfu/ml.

Conclusions

It is planned to use the QIAamp UCP Pathogen Mini Kit to do a larger study on blood collected from patients with melioidosis.
Missing Opportunities in the Screening of Alcohol Use and Problematic Use, and the Provision of Brief Advice and Treatment Information Among Individuals With Alcohol Use Disorder
Authors: Sharma Vinita , Falise Alyssa , Bittencourt Lorna , Zafaranian Amir , Hai Audrey Hang , Lopez-Quintero Catalina
Published: April 2024

Objectives

The aim of this study was to identify sociodemographic and substance-related factors associated with being screened, receiving advice or treatment information from healthcare providers, among individuals who met the criteria for the past 12-month alcohol use disorder (AUD).

Methods

The 2015–2019 National Survey on Drug Use and Health data were analyzed to identify factors associated with being (1) asked about alcohol used among adults with AUD, who visited a healthcare provider within the past 12 months, and were not receiving AUD treatment (sample 1, n = 13,321); (2) asked about problematic use; (3) advised to reduce consumption; and (4) offered alcohol treatment information, among those in sample 1 who were asked about their use (n = 6,905).

Results

About half (52.9%) in sample 1 were asked about their alcohol use. Among them, 21.6% were asked about problematic use, 17.7% were advised to reduce alcohol consumption, and 7.6% were offered information. The odds of being asked about alcohol use among male participants were 0.72 times the odds of female participants; however once asked, male participants showed greater odds of being asked about problematic use (adjusted odds ratio [aOR] = 1.53, 95% confidence interval [CI] = 1.29–1.82), advised to reduce consumption (aOR = 1.64, 95% CI = 1.24–2.16), and offered treatment information (aOR = 1.77, 95% CI = 1.34–2.35). As compared with non-Hispanic White participants, other racial/ethnic groups were less likely to be asked about alcohol use; however, once asked, no differences were observed for other outcomes.

Conclusions

Significant gaps in the screening and provision of advice or treatment information were identified, particularly for racial/ethnic and sex subgroups. Reducing barriers for effective screening could help address AUD-related disparities.
Visualization of Cerebral Pressure Autoregulatory Insults in Traumatic Brain Injury*
Authors: Svedung Wettervik Teodor , Beqiri Erta , Hånell Anders , Bögli Stefan Yu , Placek Michal , Donnelly Joseph , Guilfoyle Mathew R. , Helmy Adel , Lavinio Andrea , Hutchinson Peter J. , Smielewski Peter
Published: April 2024

OBJECTIVES:

The first aim was to investigate the combined effect of insult intensity and duration of the pressure reactivity index (PRx) and deviation from the autoregulatory cerebral perfusion pressure target (∆CPPopt = actual CPP – optimal CPP [CPPopt]) on outcome in traumatic brain injury. The second aim was to determine if PRx influenced the association between intracranial pressure (ICP), CPP, and ∆CPPopt with outcome.

DESIGN:

Observational cohort study.

SETTING:

Neurocritical care unit, Cambridge, United Kingdom.

PATIENTS:

Five hundred fifty-three traumatic brain injury patients with ICP and arterial blood pressure monitoring and 6-month outcome data (Glasgow Outcome Scale [GOS]).

INTERVENTION:

None.

MEASUREMENTS AND MAIN RESULTS:

The insult intensity (mm Hg or PRx coefficient) and duration (minutes) of ICP, PRx, CPP, and ∆CPPopt were correlated with GOS and visualized in heatmaps. In these plots, there was a transition from favorable to unfavorable outcome when PRx remained positive for 30 minutes and this was also the case for shorter durations when the intensity was higher. In a similar plot of ∆CPPopt, there was a gradual transition from favorable to unfavorable outcome when ∆CPPopt went below –5 mm Hg for 30-minute episodes of time and for shorter durations for more negative ∆CPPopt. Furthermore, the percentage of monitoring time with certain combinations of PRx with ICP, CPP, and ∆CPPopt were correlated with GOS and visualized in heatmaps. In the combined PRx/ICP heatmap, ICP above 20 mm Hg together with PRx above 0 correlated with unfavorable outcome. In a PRx/CPP heatmap, CPP below 70 mm Hg together with PRx above 0.2–0.4 correlated with unfavorable outcome. In the PRx-/∆CPPopt heatmap, ∆CPPopt below 0 together with PRx above 0.2–0.4 correlated with unfavorable outcome.

CONCLUSIONS:

Higher intensities for longer durations of positive PRx and negative ∆CPPopt correlated with worse outcome. Elevated ICP, low CPP, and negative ∆CPPopt were particularly associated with worse outcomes when the cerebral pressure autoregulation was concurrently impaired.
The alteration of fecal microbial and metabolic profile of gallstone patients in Taiwan: Single-center study
Authors: Chang Tien-En , Huang Kuo-Hung , Luo Jiing-Chyuan , Huang Yi-Hsiang , Lin Hung-Hsin , Fang Wen-Liang , Hou Ming-Chih
Published: April 2024

Background:

Gallstone disease is a common health problem worldwide. The role of the gut microbiota in gallstone pathogenesis remains obscure. Our aim was to evaluate the association and crosstalk between gut microbiota, gut metabolomic, and metabolic parameters in cholesterol gallstone patients, pigmented gallstone patients, and controls.

Methods:

We collected stool samples from healthy individuals and patients with gallstones in our hospital from March 2019 to February 2021. 16s rRNA sequencing was performed, followed by differential abundance analyses. Measurement of bile acids and short-chain fatty acids was conducted via targeted metabolomics.

Result:

Thirty healthy individuals and 20 gallstone patients were recruited. The intergroup difference of microbial composition was significant between control and gallstone patients. The control group had more abundant Faecalibacterium, Prevotella 9, and Bacteroides plebeius DSM 17135. The cholesterol stones group had higher Desulfovibrionaceae and Bacteroides uniformis than the other two groups, while the pigment stone group had more abundant Escherichia-Shigella. In the analysis of metabolites, only n-butyric acid had a significantly higher concentration in the controls than in the gallstone group (p < 0.01). The level of 3α-hydroxy-12 ketolithocholic acid, deoxycholic acid, and cholic acid showed no intergroup differences but was correlated to the serum cholesterol level and bacterial richness and evenness.

Conclusion:

Our study revealed the key taxa that can discriminate between individuals with or without gallstones. We also identified metabolites that are possibly associated with metabolic parameter and bacterial diversity. However, the correlation of the metabolites to certain clusters of bacteria should be analyzed in a larger cohort.
Hospital Performance on Hospital Consumer Assessment of Healthcare Providers and System Ratings
Authors: Rosenbaum Kathleen E. Fitzpatrick , Lasater Karen B. , McHugh Mathew D. , Lake Eileen T.
Published: April 2024

Objective:

To determine which hospital nursing resources (staffing, skill mix, nurse education, and nurse work environment) are most predictive of hospital Hospital Consumer Assessment of Healthcare Providers and System (HCAHPS) performance.

Background:

HCAHPS surveying is designed to quantify patient experience, a measure of patient-centered care. Hospitals are financially incentivized through the Centers for Medicare and Medicaid Services to achieve high HCAHPS ratings, but little is known about what modifiable hospital factors are associated with higher HCAHPS ratings.

Patients and Methods:

Secondary analysis of multiple linked data sources in 2016 providing information on hospital HCAHPS ratings, hospital nursing resources, and other hospital attributes (eg, size, teaching, and technology status). Five hundred forty non-federal adult acute care hospitals in California, Florida, New Jersey, and Pennsylvania, and 11,786 registered nurses working in those hospitals. Predictor variables included staffing (ie, patient-to-nurse ratio), skill mix (ie, the proportion of registered nurses to all nursing staff), nurse education (ie, percentage of nurses with a bachelor’s degree or higher), and nurse work environment (ie, the quality of the environment in which nurses work). HCAHPS ratings were the outcome variable.

Results:

More favorable staffing, higher proportions of bachelor-educated nurses, and better work environments were associated with higher HCAHPS ratings. The work environment had the largest association with higher HCAHPS ratings, followed by nurse education, and then staffing. Superior staffing and work environments were associated with higher odds of a hospital being a “higher HCAHPS performer” compared with peer hospitals.

Conclusion:

Improving nursing resources is a strategic organizational intervention likely to improve HCAHPS ratings.