bluuebunny/crossref_metadata_2025 huggingface dataset:
Colletotrichum caladii sp. nov. Causing Anthracnose Leaf Spot of Caladium × hortulanum (Araceae) in Florida, U.S.A.
Authors: Marin Marcus Vinicius , Wang Nan-Yi , E. Seijo Teresa , Druffel Keri , Deng Zhanao , Peres Natalia A.
Published: June 2024

Caladium (Caladium × hortulanum) is an ornamental plant popular for its variable and colorful foliage. In 2020, plants showing leaf spots and blight, typical of anthracnose, were found in a field trial at the University of Florida’s Gulf Coast Research and Education Center in Wimauma, Florida, U.S.A. Leaf samples consistently yielded a Colletotrichum-like species with curved conidia and abundant setae production in the acervuli. The internal transcribed spacer (ITS), partial sequences of the glyceraldehyde-3-phosphate dehydrogenase gene (gapdh), actin gene (act), chitin synthase 1 gene (chs-1), beta-tubulin gene (tub2), and histone3 gene (his3) were amplified and sequenced. BLASTN searches in the NCBI GenBank database revealed similarities to species of the Colletotrichum truncatum species complex. Phylogenetic analyses using multilocus sequence data supports a distinct species within this complex, with the closest related species being C. curcumae. Based on morphological and phylogenetic analyses, a new species of Colletotrichum, named C. caladii, is reported. Pathogenicity assays and subsequent isolation confirmed that this species was the causal agent of the disease.
Use of Early Ketamine Sedation and Association With Clinical and Cost Outcomes Among Mechanically Ventilated Patients With COVID-19: A Retrospective Cohort Study
Authors: Royce-Nagel Galen , Jarzebowski Mary , Wongsripuemtet Pattrapun , Krishnamoorthy Vijay , Fuller Matthew , Ohnuma Tetsu , Treggiari Miriam , Yaport Miguel , Cobert Julien , Garrigan Ethan , Bartz Raquel , Raghunathan Karthik
Published: June 2024

OBJECTIVES:

To describe the utilization of early ketamine use among patients mechanically ventilated for COVID-19, and examine associations with in-hospital mortality and other clinical outcomes.

DESIGN:

Retrospective cohort study.

SETTING:

Six hundred ten hospitals contributing data to the Premier Healthcare Database between April 2020 and June 2021.

PATIENTS:

Adults with COVID-19 and greater than or equal to 2 consecutive days of mechanical ventilation within 5 days of hospitalization.

INTERVENTION:

The exposures were early ketamine use initiated within 2 days of intubation and continued for greater than 1 day.

MEASUREMENTS:

Primary was hospital mortality. Secondary outcomes included length of stay (LOS) in the hospital and ICUs, ventilator days, vasopressor days, renal replacement therapy (RRT), and total hospital cost. The propensity score matching analysis was used to adjust for confounders.

MAIN RESULTS:

Among 42,954 patients, 1,423 (3.3%) were exposed to early ketamine use. After propensity score matching including 1,390 patients in each group, recipients of ketamine infusions were associated with higher hospital mortality (52.5% vs. 45.9%, risk ratio: 1.14, [1.06–1.23]), longer median ICU stay (13 vs. 12 d, mean ratio [MR]: 1.15 [1.08–1.23]), and longer ventilator days (12 vs. 11 d, MR: 1.19 [1.12–1.27]). There were no associations for hospital LOS (17 [10–27] vs. 17 [9–28], MR: 1.05 [0.99–1.12]), vasopressor days (4 vs. 4, MR: 1.04 [0.95–1.14]), and RRT (22.9% vs. 21.7%, RR: 1.05 [0.92–1.21]). Total hospital cost was higher (median $72,481 vs. $65,584, MR: 1.11 [1.05–1.19]).

CONCLUSIONS:

In a diverse sample of U.S. hospitals, about one in 30 patients mechanically ventilated with COVID-19 received ketamine infusions. Early ketamine may have an association with higher hospital mortality, increased total cost, ICU stay, and ventilator days, but no associations for hospital LOS, vasopressor days, and RRT. However, confounding by the severity of illness might occur due to higher extracorporeal membrane oxygenation and RRT use in the ketamine group. Further randomized trials are needed to better understand the role of ketamine infusions in the management of critically ill patients.
Critically Ill Older Adults’ Representation in Intervention Trials: A Systematic Review
Authors: Forget Marie-France , Wang Han Ting , Carignan Raphaelle , Dessureault Alexandre , Gravel Mathieu , Bienvenue Jeanne , Bouchard Maude , Durivage Camille , Coveney Richard , Munshi Laveena
Published: June 2024

OBJECTIVES:

Older adults may be under-represented in critical care research, and results may not apply to this specific population. Our primary objective was to evaluate the prevalence of inclusion of older adults across critical care trials focused on common ICU conditions or interventions. Our secondary objective was to evaluate whether older age was used as a stratification variable for randomization or outcome analysis.

DESIGN, SETTING AND SUBJECTS:

We performed a systematic review of previously published systematic reviews of randomized controlled trials (RCTs) in critical care. We searched PubMed, Ovid, CENTRAL, and Cochrane from 2009 to 2022. Systematic reviews of any interventions across five topics: acute respiratory distress syndrome (ARDS), sepsis/shock, nutrition, sedation, and mobilization were eligible.

MAIN RESULTS:

We identified 216 systematic reviews and included a total of 253 RCTs and 113,090 patients. We extracted baseline characteristics and the reported proportion of older adults. We assessed whether any upper age limit was an exclusion criterion for trials, whether age was used for stratification during randomization or data analysis, and if age-specific subgroup analysis was present. The most prevalent topic was sepsis (78 trials, 31%), followed by nutrition (62 trials, 25%), ARDS (39 trials, 15%), mobilization (38 trials, 15%), and sedation (36 trials, 14%). Eighteen trials (7%) had exclusion criteria based on older age. Age distribution with information on older adults prevalence was given in six trials (2%). Age was considered in the analysis of ten trials (5%) using analytic methods to evaluate the outcome stratified by age.

Conclusions:

In this systematic review, the proportion of older critically ill patients is undetermined, and it is unclear how age is or is not an effect modifier or to what extent the results are valid for older adult groups. Reporting age is important to guide clinicians in personalizing care. These results highlight the importance of incorporating older critically ill patients in future trials to ensure the results are generalizable to this growing population.
Fibrolipoma of the lower lip: A case report and review of the literature
Authors: Wang Dengshun , Yu Hongwei , Gao Tong , Lu Haibin , Wang Yu’e
Published: June 2024

Background:

Fibrolipoma of the lower lip is an uncommon condition with limited documentation in the literature. This paper provides updated insights into oral and maxillofacial lipomas through a detailed case report and comprehensive literature review, discussing clinical features, pathogenesis, diagnostic approaches, histopathology, and therapeutic strategies.

Case presentation:

A 54-year-old female presented with a painless, enlarging mass on the inner aspect of her right lower lip, first noticed 2 years prior. The mass, now the size of a peanut, interfered with her eating and speech. Physical examination revealed a 2.0 × 2.5 × 1.0 cm mass beneath the mucous membrane of the right lower lip. It was firm, well-demarcated, and mobile. Surgical excision was performed, and histopathological analysis confirmed the diagnosis of a lower lip fibrolipoma. The lesion was successfully removed without recurrence.

Conclusion:

Lipomas in the oral and maxillofacial regions are rare, slow-growing benign tumors, particularly within the lips. Although their diagnosis is straightforward based on clinical presentation, histopathological confirmation is essential. Surgical resection remains the treatment of choice, with excellent prognostic outcomes.
Suboptimally Controlled Diabetes in Pregnancy: A Review to Guide Antepartum and Delivery Management
Authors: Cate Jennifer J. M. , Bloom Elizabeth , Chu Allison , Bauer Samuel T. , Kuller Jeffrey A. , Dotters-Katz Sarah K.
Published: June 2024

Importance

Diabetes mellitus is one of the most common complications in pregnancy with adverse maternal and neonatal risks proportional to the degree of suboptimal glycemic control, which is not well defined. Literature guiding providers in identifying and managing patients at highest risk of complications from diabetes is lacking.

Objective

This article reviews the definition, epidemiology, and pathophysiology of suboptimal control of diabetes in pregnancy, including “diabetic fetopathy”; explores proposed methods of risk stratification for patients with diabetes; outlines existing antepartum management and delivery timing guidelines; and guides direction for future research.

Evidence Acquisition

Original research articles, review articles, and professional society guidelines on diabetes management in pregnancy were reviewed.

Results

The reviewed available studies demonstrate worsening maternal and neonatal outcomes associated with suboptimal control; however, the definition of suboptimal based on parameters followed in pregnancy such as blood glucose, hemoglobin A1c, and fetal growth varied from study to study. Studies demonstrating specific associations of adverse outcomes with defined suboptimal control were reviewed and synthesized. Professional society recommendations were also reviewed to summarize current guidelines on antepartum management and delivery planning with respect to diabetes in pregnancy.

Conclusions

The literature heterogeneously characterizes suboptimal glucose control and complications related to this during pregnancy in individuals with diabetes. Further research into antepartum management and delivery timing for patients with varying levels of glycemic control and at highest risk for diabetic complications is still needed.

Target Audience

Obstetricians and gynecologists, family physicians

Learning Objectives

After completing this activity, the learner will be better able to determine levels of glycemic control associated with adverse outcomes; discuss antepartum management and monitoring of patients with diabetes; and summarize recommendations for delivery timing for pregnancies with suboptimal glycemic control.
Building Knowledge Using a Novel Web-Based Intervention to Promote HPV Vaccination in a Diverse, Low-Income Population
Authors: Webster Emily M. , Ahsan Muhammad Danyal , Kulkarni Amita , Peñate Emilio , Beaumont Shanice , Ma Xiaoyue , Wilson-Taylor Melanie , Chang Jane , Ipp Lisa , Safford Monika M. , Cantillo Evelyn , Frey Melissa , Holcomb Kevin , Chapman-Davis Eloise
Published: June 2024

(Abstracted from Gynecol Oncol 2024;181:102–109)

Significant racial and socioeconomic disparities exist in the incidence, morbidity, and mortality from cervical cancer within the United States and worldwide. Greater than 90% of cervical cancer cases are attributable to human papillomavirus (HPV), and evidence suggests an approximately 90% reduction in cervical cancer incidence among HPV-vaccinated individuals.
Coupled membranes: a mechanism of frequency filtering and transmission in the field cricket ear evidenced by micro-computed tomography, laser Doppler vibrometry and finite element analysis
Authors: Latham Brendan , Reid Andrew , Jackson-Camargo Joseph C. , Williams Jonathan A. , Windmill James F. C.
Published: June 2024

Many animals employ a second frequency filter beyond the initial filtering of the eardrum (or tympanal membrane). In the field cricket ear, both the filtering mechanism and the transmission path from the posterior tympanal membrane (PTM) have remained unclear. A mismatch between PTM vibrations and sensilla tuning has prompted speculations of a second filter. PTM coupling to the tracheal branches is suggested to support a transmission pathway. Here, we present three independent lines of evidence converging on the same conclusion: the existence of a series of linked membranes with distinct resonant frequencies serving both filtering and transmission functions. Micro-computed tomography (µ-CT) highlighted the ‘dividing membrane (DivM)’, separating the tracheal branches and connected to the PTM via the dorsal membrane of the posterior tracheal branch (DM-PTB). Thickness analysis showed the DivM to share significant thinness similarity with the PTM. Laser Doppler vibrometry indicated the first of two PTM vibrational peaks, at 6 and 14 kHz, originates not from the PTM but from the coupled DM-PTB. This result was corroborated by µ-CT-based finite element analysis. These findings clarify further the biophysical source of neuroethological pathways in what is an important model of behavioural neuroscience. Tuned microscale coupled membranes may also hold biomimetic relevance.
Genome sequence data for 61 isolates of Xanthomonas campestris pv. campestris from brassica crops in Serbia
Authors: Popović Milovanović Tatjana , Greer Shannon , Iličić Renata , Jelušić Aleksandra , Brown Daisy , Hussain Mikaeel , Harrison Jamie , Grant Murray , Vicente Joana , Studholme David John
Published: June 2024

This Data Note describes genome sequencing data for 61 isolates of the bacterial pathogen Xanthomonas campestris pv. campestris collected from brassica crops between 2010 and 2021 in Serbia. We present the raw sequencing reads and annotated contig-level genome assemblies. These data can be used to test hypotheses, phylogeographic analyses and inform design of informative molecular markers for population genetics studies. When combined with phenotypic data, they could be used to dissect relationships between genotype and phenotypes such as host range and virulence. Finally, these genome sequences expand our inventory of plasmids known to reside in this pathogen.
Movie reconstruction from mouse visual cortex activity
Authors: Bauer Joel , Margrie Troy W. , Clopath Claudia
Published: June 2024

The ability to reconstruct imagery represented by the brain has the potential to give us an intuitive understanding of what the brain sees. Reconstruction of visual input from human fMRI data has garnered significant attention in recent years. Comparatively less focus has been directed towards vision reconstruction from single-cell recordings, despite its potential to provide a more direct measure of the information represented by the brain. Here, we achieve high-quality reconstructions of videos presented to mice, from the activity of neurons in their visual cortex. Using our method of video optimization via backpropagation through a state-of-the-art dynamic neural encoding model we reliably reconstruct 10-second movies at 30 Hz from two-photon calcium imaging data. We achieve a ≈ 2-fold increase in pixel-by-pixel correlation compared to previous state-of-the-art reconstructions of static images from mouse V1, while also capturing temporal dynamics. We find that critical for high-quality reconstructions are the number of neurons in the dataset and the use of model ensembling. This paves the way for movie reconstruction to be used as a tool to investigate a variety of visual processing phenomena.
The Gene Expression Landscape of Disease Genes
Authors: García-González Judit , Garcia-Gonzalez Saul , Liou Lathan , O’Reilly Paul F.
Published: June 2024

Fine-mapping and gene-prioritisation techniques applied to the latest Genome-Wide Association Study (GWAS) results have prioritised hundreds of genes as causally associated with disease. Here we leverage these recently compiled lists of high-confidence causal genes to interrogate where in the body disease genes operate. Specifically, we combine GWAS summary statistics, gene prioritisation results and gene expression RNA-seq data from 46 tissues and 204 cell types in relation to 16 major diseases (including 8 cancers). In tissues and cell types with well-established relevance to the disease, the prioritised genes typically have higher absolute and relative (i.e. tissue/cell specific) expression compared to non-prioritised ‘control’ genes. Examples include brain tissues in psychiatric disorders (P-value < 1×10−7), microglia cells in Alzheimer’s Disease (P-value = 9.8×10−3) and colon mucosa in colorectal cancer (P-value < 1×10−3). We also observe significantly higher expression for disease genes in multiple tissues and cell types with no established links to the corresponding disease. While some of these results may be explained by cell types that span multiple tissues, such as macrophages in brain, blood, lung and spleen in relation to Alzheimer’s disease (P-values < 1×10−3), the cause for others is unclear and motivates further investigation that may provide novel insights into disease etiology. For example, mammary tissue in Type 2 Diabetes (P-value < 1×10−7); reproductive tissues such as breast, uterus, vagina, and prostate in Coronary Artery Disease (P-value < 1×10−4); and motor neurons in psychiatric disorders (P-value < 3×10−4). In the GTEx dataset, tissue type is the major predictor of gene expression but the contribution of each predictor (tissue, sample, subject, batch) varies widely among disease-associated genes. Finally, we highlight genes with the highest levels of gene expression in relevant tissues to guide functional follow-up studies. Our results could offer novel insights into the tissues and cells involved in disease initiation, inform drug target and delivery strategies, highlighting potential off-target effects, and exemplify the relative performance of different statistical tests for linking disease genes with tissue and cell type gene expression.
Intracranial pressure and pulsatility in different head and body positions
Authors: Bancroft MJ , Moncur EM , Peters AL , D’Antona L , Thorne L , Watkins LD , Day BL , Toma AK
Published: June 2024

Intracranial pressure (ICP) is typically measured with the head in a neutral position whilst the body is in an upright or supine posture. The effect of body position on ICP is well studied, with ICP greater when supine than when upright. In daily life the head is frequently moved away from the neutral position but how this impacts ICP dynamics is unclear. Knowledge of ICP dynamics in different head-on-body positions may improve future treatments that restore normal ICP dynamics such as cerebrospinal fluid (CSF) drainage shunts.

We recruited 57 relatively well, ambulatory patients undergoing clinical ICP monitoring for investigation of possible CSF dynamics disturbances. Forty-one patients were non-shunted, seven had a working shunt and nine had a malfunctioning shunt. We measured ICP and ICP pulsatility (pulse amplitude) over 10 or 20s in different combinations of head and body positions. Positions included right and left head turn and forward tilt in upright (seated, standing) and supine body positions, and right and left lateral tilt and backward tilt in upright body positions.

ICP increased by 3-9 mmHg, on average, when the head moved away from neutral to each head position in upright and supine body positions, except for head forward tilt when supine, where ICP did not change. The increase in ICP with head turn and forward tilt in upright body positions was larger in patients with a malfunctioning shunt than with no shunt or a functioning shunt. Pulsatility also increased by 0.5-2 mmHg on average when the head moved away from neutral to each head position in upright and supine body positions, except for head forward tilt in upright body positions where pulsatility slightly decreased by 0.7 mmHg on average.

ICP and pulsatility generally increase when the head is moved away from the neutral position, but this depends on a combination of head and body position and shunt status. We propose our results can be explained by a combination of changes to neck vasculature and head orientation relative to gravity. Our findings provide potential reason for patient reports that ICP-related symptoms can be induced and/or exacerbated by head movement and could explain behaviours that avoid excess head movement, such as turning the body rather than the head when looking to the side.
Predicting intention to donate blood among secondary school students in Eastern Uganda: An application of the theory of planned behavior
Authors: Akulume Martha , Kisakye Angela N , Nankya Florence R , Kiwanuka Suzanne N
Published: June 2024

Introduction

The availability of donated blood in Uganda rests on the good will of voluntary blood donors. To design interventions aimed at improving the availability of donated blood, there is need to understand the predictors of blood donation. Previous studies have shown that intention to donate blood predicts the practice of blood donation.

Aim

This study aimed at applying the theory of planned behaviour to predict intention to donate blood among secondary school students, the major blood donor group in Uganda.

Methods

We conducted a cross-sectional study among 336 students from four purposively selected secondary schools in Eastern Uganda. Census sampling was used to recruit the students for this study. A self-administered questionnaire was used to collect data on socio-demographic characteristics as well as the theory of planned behavior constructs. Data were analyzed in STATA version 14 using descriptive statistics and regressions.

Results

About 75% (n=252) of the students had intention to donate blood sometime in their life. Students’ perceptions of their ability to donate blood (perceived behavioural control) was the key predictor of intention to donate blood (AOR = 6.35, CI =3.32, 12.15). The influence of subjective norms (AOR = 1.97, CI = 0.92, 4.20) and attitudes towards blood donation (AOR = 1.51, CI = 0.80, 2.87) did not significantly influence blood donation adjusting for other theory of planned behaviour constructs. The theory of planned behaviour constructs explained 15.5% of the students’ intention to donate blood. Regarding the external factors, only location of the school (AOR = 0.50, CI = 0.27, 0.93) and knowing someone who has ever donated (AOR = 0.26, CI = 0.12, 0.56) predicted the intention to donate blood.

Conclusion

Most students intended to donate blood sometime in their life. Efforts should be made to make blood donation sites accessible to students.
Multiomics mapping and characterization of cellular senescence in aging human skeletal muscle uncovers a novel senotherapeutic for sarcopenia
Authors: Li Yang , Li Chuhan , Zhou Qin , Liu Xingyuan , Qiao Yulong , Xie Ting , Sun Hao , Ong Michael Tim-Yun , Wang Huating
Published: June 2024

Cellular senescence is recognized as a hallmark of organismal aging but how it drives aging particularly in human tissues is not fully understood, partly due to the complex heterogeneous nature of senescence. Here in this study, we leverage single-nucleus multiomics to profile senescence in mononucleated cells of human skeletal muscle and provide the first senescence atlas. We demonstrate the intra-and inter-populational transcriptomic and epigenomic heterogeneity and dynamics of senescence in the cells. We also identify commonalities and variations in senescence-associated secretory phenotypes (SASPs) among the cells and elucidate the function of SASPs in mediating cellular interactions and niche deregulation. Furthermore, we identify targetable SASP factors and demonstrate the possibility of using Maraviroc as a pharmacological senotherapeutic for treating age-associated sarcopenia in muscle. Lastly, we define transcription factors that govern senescence state and SASP induction in aging muscle and elucidate the key function and the underlying mechanism of JUNB in regulating SASP activation in senescent cells. Altogether, our findings demonstrate the prevalence and function of cellular senescence in skeletal muscle and identify a novel pharmacological intervention for sarcopenia.
Genome-wide local ancestry and the functional consequences of admixture in African and European cattle populations
Authors: McHugo Gillian P. , Ward James A. , Ng’ang’a Said Ismael , Frantz Laurent A.F. , Salter-Townshend Michael , Hill Emmeline W. , O’Gorman Grace M. , Meade Kieran G. , Hall Thomas J. , MacHugh David E.
Published: June 2024

Bos taurus(taurine) andBos indicus(indicine) cattle diverged at least 150,000 years ago and, since that time, substantial genomic differences have evolved between the two lineages. During the last two millennia, genetic exchange in Africa has resulted in a complex tapestry of taurine-indicine ancestry, with most cattle populations exhibiting varying levels of admixture. Similarly, there are several Southern European cattle populations that also show evidence for historical gene flow from indicine cattle, the highest levels of which are found in the Central Italian White breeds. Here we use two different software tools (MOSAIC and ELAI) for local ancestry inference (LAI) with genome-wide high-and low-density SNP array data sets in hybrid African and Italian cattle populations and obtained broadly similar results despite critical differences in the two LAI methodologies used. Our analyses identified genomic regions with elevated levels of retained or introgressed ancestry from the African taurine, European taurine, Asian indicine lineages. Functional enrichment of genes underlying these ancestry peaks highlighted biological processes relating to immunobiology and olfaction, some of which may relate to differing susceptibilities to infectious diseases, including bovine tuberculosis, East Coast fever, and tropical theileriosis. Notably, for retained African taurine ancestry in admixed trypanotolerant cattle we observed enrichment of genes associated with haemoglobin and oxygen transport. This may reflect positive selection of genomic variants that enhance control of severe anaemia, a debilitating feature of trypanosomiasis disease, which severely constrains cattle agriculture across much of sub-Saharan Africa.
Micro-plaque assays: A high-throughput method to detect, isolate, and characterize bacteriophages
Authors: Nair Gayatri , Chavez-Carbajal Alejandra , Tullio Rachelle Di , French Shawn , Maddiboina Dhanyasri , Harvey Hanjeong , Dizzell Sara , Brown Eric D. , Hosseini-Doust Zeinab , Surette Michael G. , Burrows Lori L. , Hynes Alexander P.
Published: June 2024

The gold standard for the isolation and characterization of bacteriophages (phages), the plaque assay, has remained almost unchanged for over 100 years. The need for improvements to its scalability has been driven home by successes with personalized phage therapy requiring large phage libraries and rapid sensitivity testing. Using a robotic pinning platform, we miniaturized plaque assays from bacterial lawns to micro-colonies from 100 nl of inoculant, increasing throughput by >1000 fold without compromising sensitivity. A comparable manual workflow with one quarter the throughput maintained the same sensitivity. These micro-plaque assays can replace plaque assays as a new gold standard in phage biology. As proof of principle, we used our technique to isolate and de-replicate 21 uniquePseudomonas aeruginosaphages from a single environmental sample. We then demonstrated – using the same assay - that of 17 multi-drug resistant clinicalP. aeruginosastrains, 15 were susceptible to infection by one or more of the 21 phages tested. Our method allows rapid isolation and de-replication of phages, as well as enabling screening of large phage libraries against bacterial isolates of interest.
Resolving human αversusβ cell fate allocation for the generation of stem cell-derived islets
Authors: Akgün Canan Melis , Cozzitorto Corinna , Sterr Michael , Saber Lama , Setyono Eunike S.A. , Wang Xianming , Merl-Pham Juliane , Greisle Tobias , Burtscher Ingo , Lickert Heiko
Published: June 2024

Generating stem cell-derived glucagon-producing α (SC-α cells) and insulin-producing β cells (SC-β cells) allows to engineer anin vitrobiomimetic of the islet of Langerhans, the micro-organ controlling blood glucose, however, there is still a major knowledge gap in the mode and mechanism by which human SC-α and β cells are specified. Mouse studies postulated that Aristaless Related homeobox (Arx) and Paired box 4 (Pax4) transcription factors cross-inhibit each other in endocrine progenitors to promote α or β cell fate allocation, respectively. To test this model in human, we generated anARXCFP/CFP; PAX4mCherry/mCherrydouble knock-in reporter induced pluripotent stem cell (iPSC) line to combine time-resolved cell lineage labeling with high-resolution single cell multiomic analysis. Strikingly, lineage labelling and tracing, proteomic and gene regulatory network (GRN) analysis and potency assays revealed a human specific mode and regulatory logic of αversusβ cell fate allocation. Importantly, pharmacological perturbation using drugs previously proposed to trigger α-to-β cell transdifferentiation or identified via our GRN analysis led to enhanced endocrine induction and directed α vs β cell fate commitment. Thus, shedding light on basic mechanisms of endocrine induction and fate segregation not only paves the way to engineer islets from pluripotent stem cells, but also has broader implications for cell-replacement therapy, disease modelling and drug screening.
Childhood brain morphometry in children with persistent stunting and catch-up growth
Authors: Koshy Beena , Thilagarajan Vedha Viyas , Berkins Samuel , Banerjee Arpan , Srinivasan Manikandan , Livingstone Roshan S , Mohan Venkata Raghava , Scharf Rebecca , Jasper Anitha , Kang Gagandeep
Published: June 2024

Background

Early childhood stunting affects around 150 million young children worldwide and leads to suboptimal human potential in later life. However, there is limited data on the effects of early childhood stunting and catch-up growth on brain morphometry.

Methods

We evaluated childhood brain volumes at nine years of age in a community-based birth-cohort follow-up study in Vellore, south India among four groups based on anthropometric assessments at two, five, and nine years namely ‘Never Stunted’ (NS), ‘Stunted at two years and caught up by five years’ (S2N5), ‘Stunted at two and five years and caught up by nine years’ (S2N9), and ‘Always Stunted’ (AS). T1-weighted magnetic resonance imaging (MRI) images were acquired using a 3T MRI scanner, and brain volumes were quantified using FreeSurfer software.

Findings

Amongst 251 children from the overall cohort, 178 children with a mean age of 9.54 were considered for further analysis. The total brain volume, subcortical volume, bilateral cerebellar white matter, and posterior corpus callosum showed a declining trend from NS to AS. Regional cortical brain analysis showed significant lower bilateral lateral occipital volumes, right pallidum, bilateral caudate, and right thalamus volumes between NS and AS.

Interpretation

To the best of our knowledge, this first neuroimaging analysis to investigate the effects of persistent childhood stunting and catch-up growth on brain volumetry indicates impairment at different brain levels involving total brain and subcortical volumes, networking/connecting centres (thalamus, basal ganglia, callosum, cerebellum) and visual processing area of lateral occipital cortex.
Spatial transcriptomics identifies novelPseudomonas aeruginosavirulence factors
Authors: Zhou Hao , Negrón Oscar , Abbondante Serena , Marshall Michaela , Jones Brandon , Ong Edison , Chumbler Nicole , Tunkey Christopher , Dixon Groves , Lin Haining , Plante Obadiah , Pearlman Eric , Gadjeva Mihaela
Published: June 2024

To holistically unravel the complexity of pathogen-host interactions within infected tissues we leverage a dual spatial transcriptomic approach that, for the first time, simultaneously captures the expression ofPseudomonas aeruginosagenes alongside the entire host transcriptome in a model of ocular infection. This innovative method reveals differential pathogen and host-specific gene expression patterns across specific anatomical regions generating a unified transcriptional map of infection. By integrating these data, we developed a predictive ridge regression model trained on images from infected tissues. The model achieved an R² score of 0.923 in predicting bacterial burden distributions by using host features thereby predicting novel biomarkers associated with disease severity. Our analysis revealed a complex interplay betweenP. aeruginosanutritional requirements and protective host responses and identified novel interactions between bacterial metabolite transport proteins and host autophagy. Among an array of iron acquisition gene transcripts that showed significant enrichment at the host-pathogen interface, we discovered a novel virulence mediator PA2590. This study highlights the power of spatial transcriptomics, particularly in combining bacterial and host transcriptomes, to uncover novel host-pathogen interactions, advance our understanding of bacterial virulence mechanisms, and point to druggable molecules.
The PAZ domain ofAedes aegyptiDicer 2 is critical for accurate and high-fidelity size determination of virus-derived small interfering RNAs
Authors: Reuter Melinda , Parry Rhys H. , McFarlane Melanie , Gestuveo Rommel J. , Arif Rozeena , Khromykh Alexander A. , Brennan Benjamin , Varjak Margus , Castello Alfredo , Redecke Lars , Schnettler Esther , Kohl Alain
Published: June 2024

The exogenous siRNA (exo-siRNA) pathway is a critical RNA interference response involved in controlling arbovirus replication in mosquito cells. It is initiated by the detection of viral long double-stranded RNA (dsRNA) by the RNase III enzyme Dicer 2 (Dcr2), which is processed into predominantly 21 nucleotide (nt) virus-derived small interfering RNAs, or vsiRNAs that are taken up by the Argonaute 2 (Ago2) protein to target viral single-stranded RNAs. The detailed understanding of Dicer structure, function and domains owes much to studies outside the context of viral infection, and how Dcr2 domains contribute to detecting viral dsRNA to mount antiviral responses in infected mosquito cells remains much less understood. Here, we used a Dcr2 reconstitution system inAedes aegyptiderived Dcr2 KO cells to assess the contribution of the PAZ domain to induction of the exo-siRNA pathway following infection with Semliki Forest virus (SFV;Togaviridae,Alphavirus). Amino acids critical for PAZ activity were identified, and loss of PAZ function affected the production of 21 nt vsiRNAs -though not the overall ability of Dcr2 to process viral dsRNA- and silencing activity. This study establishes the importance of correct vsiRNA size in mosquito exo-siRNA antiviral responses, as well as the PAZ domain’s functional contribution to Dcr2 processing of viral dsRNA to 21 nt vsiRNAs.
A flagellar accessory protein links chemotaxis to surface sensing
Authors: Salemi Rachel I. , Cruz Ana K. , Hershey David M.
Published: June 2024

Bacteria find suitable locations for colonization by sensing and responding to surfaces. Complex signaling repertoires control surface colonization, and surface contact sensing by the flagellum plays a central role in activating colonization programs.Caulobacter crescentusadheres to surfaces using a polysaccharide adhesin called the holdfast. InC. crescentus, disruption of the flagellum through interactions with a surface or mutation of flagellar genes increases holdfast production. Our group previously identified severalC. crescentusgenes involved in flagellar surface sensing. One of these, calledfssF, codes for a protein with homology to the flagellar C-ring protein FliN. We show here that a fluorescently tagged FssF protein localizes to the flagellated pole of the cell and requires all components of the flagellar C-ring for proper localization, supporting the model that FssF associates with the C-ring. DeletingfssFresults in a severe motility defect that we show is due to a disruption of chemotaxis. Epistasis experiments demonstrate thatfssFpromotes adhesion through a stator-dependent pathway when late-stage flagellar mutants are disrupted. Separately, we find that disruption of chemotaxis through deletion offssFor other chemotaxis genes results in a hyperadhesion phenotype. Key genes in the surface sensing network (pleD,motB, anddgcB) contribute to both ΔflgH-dependent and ΔfssF-dependent hyperadhesion, but these genes affect adhesion differently in the two hyperadhesive backgrounds. Our results support a model in which the stator subunits of the flagella incorporate both mechanical and chemical signals to regulate adhesion.

Importance

Biofilms pose a threat in clinical and industrial settings. Surface sensing is an early step in biofilm formation. Studying surface sensing can help develop strategies for combating harmful biofilms. Here, we use the freshwater bacteriumCaulobacter crescentusto study surface sensing. We characterize a previously unstudied gene,fssF, and find that it localizes to the cell pole in the presence of three proteins that make up a component of the flagellum called the C-ring. Additionally, we find thatfssFis required for chemotaxis but dispensable for swimming motility. Lastly, our results show that mutatingfssFand other genes required for chemotaxis causes a hyperadhesive phenotype. We propose that surface sensing requires chemotaxis for a robust response to a surface.
Cerebral cortical functional hyperconnectivity in a mouse model of spinocerebellar ataxia type 8 (SCA8)
Authors: Nietz Angela K , Popa Laurentiu S , Carter Russell E , Gerhardt Morgan L , Manikonda Keerthi , Ranum Laura PW , Ebner Timothy J
Published: June 2024

Spinocerebellar Ataxia Type 8 (SCA8) is an inherited neurodegenerative disease caused by a bidirectionally expressed CTG●CAG expansion mutation in the ATXN-8 and ATXN8-OS genes. While primarily a motor disorder, psychiatric and cognitive symptoms have been reported. It is difficult to elucidate how the disease alters brain function in areas with little or no degeneration producing both motor and cognitive symptoms. Using transparent polymer skulls and CNS-wide GCaMP6f expression, we studied neocortical networks throughout SCA8 progression using wide-field Ca2+ imaging in a transgenic mouse model of SCA8. We observed that neocortical networks in SCA8+ mice were hyperconnected globally which led to network configurations with increased global efficiency and centrality. At the regional level, significant network changes occurred in nearly all cortical regions, however mainly involved sensory and association cortices. Changes in functional connectivity in anterior motor regions worsened later in the disease. Near perfect decoding of animal genotype was obtained using a generalized linear model based on canonical correlation strengths between activity in cortical regions. The major contributors to decoding were concentrated in the somatosensory, higher visual and retrosplenial cortices and occasionally extended into the motor regions, demonstrating that the areas with the largest network changes are predictive of disease state.
Oral Hygiene Practices and Their Impact on Oral Health Among the Indigenes of Akpugo Community in Enugu State, Nigeria
Authors: Nnamani Chisom Promise , Yaqub Muneer
Published: June 2024

Objective

This study aims to evaluate the oral hygiene practices and their effectiveness in preventing common oral diseases among the residents of the Akpugo community in Enugu State, Nigeria.

Methods

A cross-sectional survey was conducted among 150 randomly selected participants from the five villages of Akpugo. Data collection involved personal interviews and physical examinations of oral cavities using sterilized instruments. The analysis included percentage calculations, z-tests, and the categorization of participants by socio-economic groups based on age and gender.

Results

The study revealed a high prevalence of oral diseases, with 29.3% of participants having dental caries, 19.3% suffering from halitosis, 18% diagnosed with gingivitis, and 10% with periodontitis. Most participants (90.7%) brushed their teeth once daily, predominantly in the morning, and only 5.3% brushed twice daily. A majority used toothbrushes and toothpaste (58%), while a significant portion still relied on traditional methods such as chewing sticks (26.67%). The presence of dental calculus was observed in 47.3% of participants, with dental plaque noted in 16.7%.

Conclusion

The findings highlight a significant prevalence of poor oral health despite varying levels of awareness regarding preventive practices. The study underscores the need for targeted interventions, including comprehensive oral health education programs, the establishment of dental centers, and community-led initiatives to improve oral hygiene practices. These measures are crucial for reducing the incidence of oral diseases and enhancing the overall health and well-being of the Akpugo community. The study emphasizes the importance of continuous education and intervention to promote optimal oral health in rural areas.
Prevalence and associated factors of psychological distress among patients with oral cancer in Sri Lanka
Authors: Ratnasekera Nadisha , Perera Irosha , Kandapola Arachchige Pushpakumara , Perera Sumeth , Jayasekara Prasanna
Published: June 2024

Introduction Oral cancer is the most common among Sri Lankan males leading to psychological distress due to its impact on the appearance and vital functions. While the negative effects of psychological distress on these patients are well known, its prevalence and associated factors remain largely unknown in Sri Lanka. This study aimed to assess the prevalence and the associated factors of psychological distress among a selected patient cohort with oral cancer in Sri Lanka. Methods A hospital-based cross-sectional study was conducted among 355 patients with oral cancer to assess the prevalence of psychological distress. A nested case-control study among 140 (per arm) patients evaluated the associated factors for psychological distress. The multivariate analysis was carried out to identify significant factors associated with psychological distress. Results The prevalence of psychological distress among patients with oral cancer was 31.0% (95% CI = 27.8%- 35.3%). Being <50 years of age (Adjusted Odds Ratio (AOR)= 1.2, 95% CI= 0.7- 1.7, p= 0.006), having pain (AOR (Adjusted Odds Ratio)= 44.7, 95% CI= 34-53.21, p=0.001 ), late stages of cancer at the diagnosis (AOR= 10.7, 95% CI= 1.07- 28.78, p=0.04), being worried about basic functional disabilities (AOR= 11.4, 95% CI= 10.3- 14.8, p=0.006) and the two psychological factors emerged as significant independent factors that were associated with increased risk of psychological distress among patients with oral cancer. Conclusion One-third of patients with oral cancer in the selected tertiary care hospitals suffered from psychological distress indicating its high prevalence. Our findings on associated factors of psychological distress in patients with oral cancer have contributed to the development of an intervention strategy to reduce psychological distress in this population.
Constructing the equation of state of QCD in a functional QCD based scheme
Authors: Lu Yi , Gao Fei , Fu Baochi , Song Huichao , Liu Yu-xin
Published: June 2024

We construct the equation of state (EOS) of QCD based on the finite chemical potential information from the functional QCD approaches with the results at zero chemical potential being calibrated by lattice QCD simulations. Specifically, the construction is achieved by parametrizing the order parameters from the functional QCD data into the EOS, namely, the dynamical quark mass for the chiral phase transition and the Polyakov loop for the deconfinement phase transition. The obtained EOS is consistent with the up-to-date results of the QCD phase diagram, including a phase transition temperature at zero chemical potential of T=155  MeV, the curvature of the transition line κ=0.016, and also a critical end point at (T,μB)=(118,600)  MeV. We also implement the EOS in hydrodynamic simulations to compute the particle yields and ratios and find that our obtained EOS agrees well with the commonly used one based on the combination of lattice QCD simulation and hadron resonance gas model.

Published by the American Physical Society
2024
Dynamical branes on expanding orbifold and complex projective space
Authors: Nitta Muneto , Uzawa Kunihito
Published: June 2024

We construct some new dynamical p-brane solutions to gravity theories on curved backgrounds. We discuss the relations between dynamical branes, a new time-dependent solution on complex projective space CPn, and the static p-branes on the orbifold Cn/Zn.

Published by the American Physical Society
2024
Battle over trademark: Kirloskar vs Kirloskar
Authors: Gupta Pooja , Sultana Mafruza
Published: June 2024

Learning outcomes

After completion of the case study, students will be able to understand key stakeholders’ current and future role in a family business using techniques like Gersick 3 Axes Model, understand the power dynamics in a family business, understand the power struggles seen in the family business and understand the challenges in the implementation of a deed of family settlement (DFS) with multiple stakeholders.

Case overview/synopsis

Kirloskar group was established in 1888 by Laxmanrao Kirloskar. He started with farm manufacturing equipment and later diversified into various kinds of engine manufacturing units. Kirloskar Group today is an Indian conglomerate multinational company with its headquarters in Pune, Maharashtra; India exports to more than 70 countries, most of which are from Africa, Southeast Asia and Europe. The group was managed as a cohesive unit until Chandrakant Kirloskar was at the helm as the chairman. Each brother’s family was managing a business and companies in the fold in which they started. The Kirloskar Group had first split in 2000 when Bengaluru-based Vijay Kirloskar (Ravindra Kirloskar’s son, fourth son of Laxmanrao Kirloskar) moved out of the group with Kirloskar Electrical while the Pune-based Kirloskar brothers moved out with Kirloskar Oil Engine Engines, Kirloskar Brothers, Kirloskar Pneumatics and related subsidiaries. In 2009, a DFS was signed among the family members, including a noncompete clause against each other regarding the usage of the Kirloskar brand name and the tagline “Kirloskar Enriching Lives.” The current dispute started in 2020 when first Vijay filed a suit against his nephews regarding illegal usage of the Kirloskar brand name for the companies not eligible to use it and second when Sanjay Kirloskar also filed a similar lawsuit against his brothers for illegally using the brand name and violating the noncompete clause. The high court, in its judgment, sent the case for arbitration, but Sanjay approached the Supreme Court of India regarding the stipulated arbitration process. With both sides taking a hard stance, there did not seem to be a quick resolution to this dispute.

Complexity academic level

This case study is suitable for both undergraduate and postgraduate level in entrepreneurship course and family business course.

Subject code

CSS 3: Entrepreneurship

Supplementary materials

Teaching notes are available for educators only.