bluuebunny/crossref_metadata_2025 huggingface dataset:
Stress, Sleep, and Resilience Among Rural BSN Students in a New Nursing Program
Authors: Shapiro April L. , Coddington Heather , Beckman-Sirk Kasey , Raschella Rachel
Published: March 2023

Background:

Nursing students experience stress that may impact their sleep and resilience, especially those attending rural campuses that may have potentially limited access to resources.

Purpose:

The purpose of this study was to examine relationships among perceived stress, sleep quality, resilience, and demographics and predictors of resilience among senior BSN students.

Methods:

In this cross-sectional study, perceived stress, sleep quality, resilience, and demographic data were collected from a senior student cohort attending a new baccalaureate nursing program on a rural Appalachian campus (N = 16). Data were analyzed using descriptive, bivariate, and multiple regression analyses.

Results:

Perceived stress significantly associated with sleep quality, resilience, and gender. Perceived stress, sleep quality, and gender significantly explained 61% of the variance in resilience, with perceived stress as the strongest predictor.

Conclusions:

Early collaborative assessment and intervention focused on mitigating stress may promote improved sleep and resilience. Availability of resources for students attending small rural campuses is essential.
Use of Simulated Telenursing With Standardized Patients to Enhance Prelicensure Nursing Education
Authors: Thomas Rebecca Maeve , Moore Lori Prewitt , Urquhart Brady Baker , Harris Shannon , Davis Sara , Farmer Joseph , Thornton Rebecca , Hawley Nanako
Published: March 2023

Background:

Telenursing is a growing field in health care but remains underutilized as a clinical learning opportunity in the prelicensure nursing curriculum.

Problem:

Prelicensure nursing students need exposure to telenursing as an educational modality, which can serve as an alternative opportunity for clinical hours where facilities and resources are limited.

Approach:

Using standardized patients and a web-based videoconferencing platform, faculty developed an innovative, simulated telenursing encounter to expose nursing students to virtual patient care scenarios. The effectiveness of this learning experience was evaluated through student-teacher satisfaction debriefing and student performance on content-related examinations.

Outcomes:

Students scored higher on targeted examination questions than students from the same cohort who did not participate in the telenursing encounter. In addition, students voiced increased comfort and confidence with conducting patient interviews, providing patient education, and debriefing.

Conclusion:

Using a simulated telenursing encounter is useful in prelicensure nursing education by exposing students to patient interaction outside of traditional clinical settings and reinforcing essential nursing concepts.
Electrodiagnostic findings in COVID-19 patients of an underserved population with neuromuscular complaints: case series
Authors: Chiou-Tan Faye Y. , Mirabi Batool , Forrest Elizabeth
Published: March 2023

Introduction:

Persistent neuromuscular symptoms have occurred in some patients after coronavirus disease 2019 (COVID-19) infection requiring hospitalization.

Objective:

This is a retrospective chart review of an underserved patient population referred to our electrodiagnostic [electromyography (EMG)] laboratory with persistent neuromuscular symptoms after COVID-19 infection hospitalization and recovery.

Methods:

A retrospective review of EMG charts from March 2020 to May 2022 was conducted in an underserved county hospital of a major urban city. History of COVID-19 infection with neuromuscular symptoms that began during hospitalization was included in the study. Demographic, neuromuscular symptoms, EMG data, and diagnosis are reported in this study.

Results:

Fifteen cases are included in this series. All the patients were hospitalized with COVID-19, most required intubation in the intensive care unit. Overall, 86.7% were Hispanic, 6.7% African American, and 6.7% Asian. This compares to 57% Hispanic in this county’s hospital population in general. EMG results diagnoses include sciatic neuropathies, brachial plexopathy, radiculopathy/polyradiculopathy, amyotrophy, and multiple proximal mononeuropathies.

Conclusions:

This case series reports EMG findings in patients post-COVID-19 infection in an underserved county hospital population. Interestingly, many neuropathies were not in the conventional compression sites seen with prolonged immobility in intensive care settings.
Controversies in the Management of Antiphospholipid Syndrome
Authors: Porta Sabrina V. , de Andrade Danieli Castro Oliveira , Erkan Doruk , Gómez-Puerta José A. , Jara Luis J. , Alba Moreyra Paula , Pons-Estel Guillermo J.
Published: March 2023

Strategies to prevent thrombosis in antiphospholipid antibody (aPL)–positive patients are of the utmost importance. The risk of thrombosis in patients with aPLs varies, depending on additional venous thrombosis and cardiovascular risk factors, as well as associated comorbidities. Recurrent thrombosis despite treatment with vitamin K antagonists is relatively common in daily practice. In this context, the effectiveness of the new direct oral anticoagulants in antiphospholipid syndrome is debated, as well as that of low-dose aspirin for primary thromboprophylaxis. There is an urgent unmet need to recognize the subgroup of patients that may benefit from low-dose aspirin use. Here we also discuss different points of view on primary and secondary thrombosis preventions in aPL-positive patients, which were presented as a debate during the 2021 PANLAR Congress (Pan-American League of the Association of Rheumatology) and that was organized by GESAF (Argentine Society of Rheumatology APS Study Group). It is the intention of this article to provide a useful discussion to aid treatment decision-making in daily clinical practice.
A guide to Agrobacterium-mediated transformation of the chytrid fungus Spizellomyces punctatus
Authors: Prostak Sarah M , Medina Edgar M , Kalinka Erik , Fritz-Laylin Lillian K
Published: March 2023

Chytrid fungi play key ecological roles in aquatic ecosystems, and some species cause a devastating skin disease in frogs and salamanders. Despite their importance, little is known about the basic cell biology of chytrids. Additionally, chytrids occupy a unique phylogenetic position– sister to the well-studied Dikarya (the group including yeasts, sac fungi, and mushrooms) and related to animals– making chytrids useful for answering important evolutionary questions. A major barrier to understanding chytrid biology has been a lack of genetic tools with which to test molecular hypotheses. Medina and colleagues recently developed a protocol for Agrobacterium-mediated transformation of Spizellomyces punctatus. In this manuscript, we describe the general procedure including planning steps and expected results. We also provide in-depth, step-by-step protocols and video guides for performing the entirety of this transformation procedure on protocols.io (dx.doi.org/10.17504/protocols.io.x54v9dd1pg3e/v1).
The eEF2 kinase coordinates the DNA damage response to cisplatin by supporting p53 activation
Authors: Lim Jonathan KM , Samiei Arash , Carnie Christopher J , Brinkman Vanessa , Radiloff Daniel , Cran Jordan , Leprivier Gabriel , Sorensen Poul H
Published: March 2023

Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K) is a stress-responsive hub that inhibits the translation elongation factor eEF2, and consequently mRNA translation elongation, in response to hypoxia and nutrient deprivation. EEF2K is also involved in the response to DNA damage but its role in response to DNA crosslinks, as induced by cisplatin, is not known. Here we found that eEF2K is critical to mediate the cellular response to cisplatin. We uncovered that eEF2K deficient cells are more resistant to cisplatin treatment. Mechanistically, eEF2K deficiency blunts the activation of the DNA damage response associated ATM and ATR pathways, in turn preventing p53 activation and therefore compromising induction of cisplatin-induced apoptosis. We also report that loss of eEF2K delays the resolution of DNA damage triggered by cisplatin, suggesting that eEF2K contributes to DNA damage repair in response to cisplatin. In support of this, our data shows that eEF2K promotes the expression of the DNA repair protein ERCC1, critical for the repair of cisplatin-caused DNA damage. Finally, usingCaenorhabditis elegansas an in vivo model, we find that deletion ofefk-1, the wormeEF2Kortholog, mitigates the induction of germ cell death in response to cisplatin. Together, our data highlight that eEF2K represents an evolutionary conserved mediator of the DNA damage response to cisplatin which promotes p53 activation to induce cell death, or alternatively facilitates DNA repair, depending on the extent of DNA damage.
Automated airway quantification associates with mortality in idiopathic pulmonary fibrosis
Authors: Cheung Wing Keung , Pakzad Ashkan , Mogulkoc Nesrin , Needleman Sarah , Rangelov Bojidar , Gudmundsson Eyjolfur , Zhao An , Abbas Mariam , McLaverty Davina , Asimakopoulos Dimitrios , Chapman Robert , Savas Recep , Janes Sam M , Hu Yipeng , Alexander Daniel C. , Hurst John R , Jacob Joseph
Published: March 2023

Objectives

The study was to examine whether the airway metrics associate with mortality in IPF patients.

Methods

We performed an observational cohort study (n=90) of IPF patients identified from Ege University Hospital. An airway analysis tool AirQuant calculated median airway segmental intertapering and segmental tortuosity across 2ndto 6thgenerations of IPF airways. Intertapering measures the difference in median diameter between adjacent airway segments. Tortuosity evaluates the ratio of measured segmental length against direct end- to-end segmental length. Univariable linear regression analyses examined relationships between AirQuant variables, clinical variables and lung function tests. Univariable and Multivariable Cox proportional hazards models estimated mortality risk with the latter adjusted for patient age, gender, smoking status, antifibrotic use, CT usual interstitial pneumonia (UIP) pattern and either forced vital capacity (FVC) or diffusion capacity of carbon monoxide (DLco) if obtained within 3 months of the CT.

Results

No significant collinearity existed between AirQuant variables and clinical or functional variables. On univariable Cox regression analyses, male gender, smoking history, no antifibrotic use, reduced DLco, reduced segmental intertapering and increased segmental tortuosity associated with increased risk of death. On multivariable Cox regression analyses (adjusted using FVC), segmental intertapering (Hazard Ratio (HR)=0.75, 95% CI=0.66-0.85, p<0.001) and segmental tortuosity (HR=1.74, 95% CI=1.22-2.47, p=0.002) independently associated with mortality. Results were maintained with adjustment using DLco.

Conclusions

AirQuant generated measures of segmental intertapering and tortuosity independently associate with mortality in IPF patients. Abnormalities in proximal airway generations, which are not typically considered to be abnormal in IPF, have prognostic value.

Key Points

AirQuant generates measures of segmental intertapering and tortuosity.

Automated airway quantification associates with mortality in IPF independent of established measures of disease severity.

Automated airway analysis could be used to refine patient selection for therapeutic trials in IPF.
Clinical Outcomes of Left Atrial Appendage Occlusion Versus Switch of Direct Oral Anti-coagulant in Atrial Fibrillation
Authors: Ng Andrew Kei-Yan , Ng Pauline Yeung , Ip April , Fung Raymond Chi-Yan , Chui Shing-Fung , Siu Chung-Wah , Yan Bryan P
Published: March 2023

Background

Left atrial appendage occlusion (LAAO) has emerged as an alternative to oral anti-coagulation therapy for stroke prevention in atrial fibrillation (AF), but data comparing LAAO with direct oral anti-coagulant (DOAC) is sparse.

Method

This cohort study compared LAAO (with or without prior anti-coagulation) with a switch of one DOAC to another DOAC. The primary outcome was a composite of all-cause mortality, ischemic stroke and major bleeding.

Results

A total of 2,350 patients (874 in the LAAO group and 1,476 in the DOAC switch group) were generated by 1:2 propensity score matching. After a mean follow up of 1052 ± 694 days, the primary outcome developed in 215 (24.6%) patients in the LAAO group and in 335 (22.7%) patients in the DOAC switch group (hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.80 to 1.12; P=0.516). The LAAO group had a lower all-cause mortality (HR, 0.49; 95% CI, 0.39 to 0.60; P<0.001) and cardiovascular mortality (HR, 0.49; 95% CI, 0.32 to 0.73; P<0.001), but similar risk of ischemic stroke (HR, 0.83; 95% CI, 0.63 to 1.10; P=0.194). The major bleeding risk was similar overall (HR, 1.18; 95% CI, 0.94 to 1.48, P=0.150), but was lower in the LAAO group after 6 months (HR 0.71; 95% CI 0.51 to 0.97; P=0.032).

Conclusions

LAAO conferred a similar risk of composite outcome of all-cause mortality, ischemic stroke and major bleeding, as compared with DOAC switch. The risks of all-cause mortality and cardiovascular mortality were lower with LAAO.

CLINICAL PERSPECTIVE

1)

What Is New?

Data comparing left atrial appendage occlusion (LAAO) with direct oral anti-coagulant (DOAC) in patient with atrial fibrillation (AF) was sparse.

LAAO conferred a similar risk of composite outcome of all-cause mortality, ischemic stroke and major bleeding, as compared with switch of DOAC in patients with AF and intolerant to at least one anti-coagulant.

The risks of all-cause mortality and cardiovascular mortality were halved with LAAO.

2)

What Are the Clinical Implications?

This study highlights the potential role of LAAO as a superior alternative to trying another DOAC for patients with AF and intolerant to at least one DOAC.

Bleeding events after 6 months post LAAO were significantly reduced by 30% in the LAAO group as compared with the DOAC switch group, coinciding with the de-escalation in anti-thrombotic therapy.

Reduction in bleeding during the first 6 months post LAAO represents a potential opportunity to further improve outcomes after LAAO.
Novel glycoside hydrolase family enzymes fromEscherichia coliare associated with osmo-regulated periplasmic glucan synthesis
Authors: Motouchi Sei , Kobayashi Kaito , Nakai Hiroyuki , Nakajima Masahiro
Published: March 2023

Most Gram-negative bacteria synthesize osmo-regulated periplasmic glucans (OPG) in the periplasm or extracellular space. Many pathogens lose their pathogenicity by knocking outopgG, an OPG-related gene indispensable for OPG synthesis. However, the biochemical functions of OpgG and OpgD, a paralog of OpgG, have not been elucidated. In this report, structural and functional analyses of OpgG and OpgD fromEscherichia colirevealed that these proteins are β-1,2-glucanases with remarkably different activity, establishing a new glycoside hydrolase family. Furthermore, a reaction mechanism with an unprecedentedly long proton transfer pathway is proposed for OpgD. The conformation of the region that forms the reaction pathway differs noticeably between OpgG and OpgD, which explains the observed low activity of OpgG. The findings enhance our understanding of OPG biosynthesis and provide insights into functional diversity for this novel enzyme family.
Semiconducting carbon nanotubes decrease neuronal bursting in a network of rat hippocampal neuronsin vitrowhile increasing intrinsic excitability of single neurons
Authors: Kishore Abhinoy , Chakraborty Shagnik , Vasnik Sonali , Ghosh Shinjini , Raees Mohammed , Sikdar Sujit K.
Published: March 2023

The diverse electrical, chemical and structural properties of the functional derivatives of carbon nanotubes (CNTs) have shown biomedical possibilities for neuroprosthesis or neural interfaces. However, the studies have been generally confined to metallic CNTs that affect cell viability unless chemically functionalized for biocompatibility. Here, we explored the effects of semiconducting single-walled carbon nanotubes (ssw-CNT), on the active electrical properties of dissociated hippocampal neuronsin-vitrousing multielectrode array, calcium imaging and whole-cell patch clamp recordings. The findings show that ssw-CNT treatment regulates neural network excitability from burst to tonic firing by changing the calcium dynamics. However, at a single neuronal level, ssw-CNT increases neuronal excitability.
Comammoxand Unknown Candidate AOB Contribute to Nitrite Accumulation in an Integrated A-B stage process that Incorporates Side-stream EBPR (S2EBPR)
Authors: Yan Yuan , Lee Jangho , Han IL , Wang Zijian , Li Guangyu , McCullough Kester , Klaus Stephanie , Kang Da , Wang DongQi , Patel Anand , McQuarrie Jim , Stinson Beverley M. , deBarbadillo Christine , Dombrowski Paul , Bott Charles , Gu April Z.
Published: March 2023

A novel integrated pilot-scale A-stage high rate activated sludge, B-stage short-cut biological nitrogen removal and side-stream enhanced biological phosphorus removal (A/B-shortcut N- S2EBPR) process for treating municipal wastewater was demonstrated with the aim to achieve simultaneous and carbon- and energy-efficient N and P removal. In this studied period, an average of 7.62 ± 2.17 mg-N/L nitrite accumulation was achieved through atypical partial nitrification without canonical known NOB out-selection. Network analysis confirms the central hub of microbial community as Nitrospira, which was one to two orders of magnitude higher than canonical aerobic oxidizing bacteria (AOB) in a B-stage nitrification tank. The contribution of comammox Nitrospira as AOB was evidenced by the increased amoB/nxr ratio and higher ammonia oxidation activity. Furthermore, oligotyping analysis of Nitrospira revealed two dominant sub-clusters (microdiveristy) within the Nitrospira. The relative abundance of oligotype II, which is phylogenetically close to Nitrospira_midas_s_31566, exhibited a positive correlation with nitrite accumulation in the same operational period, suggesting its role as comammox Nitrospira. Additionally, the phylogenetic investigation suggested that heterotrophic organisms from the family Comamonadacea and the order Rhodocyclaceae embedding ammonia monooxygenase and hydroxylamine oxidase may function as heterotrophic nitrifiers. This is the first study that elucidated the impact of integrating the S2EBPR on nitrifying populations with implications on short-cut N removal. The unique conditions in the side-stream reactor, such as low ORP, favorable VFA concentrations and composition, seemed to exert different selective forces on nitrifying populations from those in conventional biological nutrient removal processes. The results provide new insights for integrating EBPR with short-cut N removal process for mainstream wastewater treatment.
Loss ofGrem1-articular cartilage progenitor cells causes osteoarthritis
Authors: Ng Jia Q. , Jafarov Toghrul H. , Little Christopher B. , Wang Tongtong , Ali Abdullah , Ma Yan , Radford Georgette A , Vrbanac Laura , Ichinose Mari , Whittle Samuel , Hunter David , Lannagan Tamsin RM , Suzuki Nobumi , Goyne Jarrad M. , Kobayashi Hiroki , Wang Timothy C. , Haynes David , Menicanin Danijela , Gronthos Stan , Worthley Daniel L. , Woods Susan L. , Mukherjee Siddhartha
Published: March 2023

Osteoarthritis (OA), which carries an enormous disease burden across the world, is characterised by irreversible degeneration of articular cartilage (AC), and subsequently bone. The cellular cause of OA is unknown. Here, using lineage tracing in mice, we show that the BMP-antagonistGremlin 1(Grem1) marks a novel chondrogenic progenitor (CP) cell population in the articular surface that generates joint cartilage and subchondral bone during development and adulthood. Notably, this CP population is depleted in injury-induced OA, and with age. OA is also induced by toxin-mediated ablation ofGrem1CP cells in young mice. Transcriptomic analysis and functional modelling in mice revealed articular surfaceGrem1-lineage cells are dependent onFoxo1; ablation ofFoxo1inGrem1-lineage cells led to early OA. This analysis identified FGFR3 signalling as a therapeutic target, and injection of its activator, FGF18, caused proliferation ofGrem1-lineage CP cells, increased cartilage thickness, and reduced OA pathology. We propose that OA arises from the loss of CP cells at the articular surface secondary to an imbalance in progenitor cell homeostasis and present a new progenitor population as a locus for OA therapy.
Phenotypic drought stress prediction of European beech (Fagus sylvatica) by genomic prediction and remote sensing
Authors: Pfenninger Markus , Langan Liam , Feldmeyer Barbara , Fussi Barbara , Hoffmann Janik , Granado Renan , Hetzer Jessica , Šeho Muhidin , Mellert Karl-Heinz , Hickler Thomas
Published: March 2023

Current climate change species response models usually not include evolution. We integrated remote sensing with population genomics to improve phenotypic response prediction to drought stress in the key forest tree European beech (Fagus sylvaticaL.). We used whole-genome sequencing of pooled DNA from natural stands along an ecological gradient from humid-cold to warm-dry climate. We phenotyped stands for leaf area index (LAI) and moisture stress index (MSI) for the period 2016-2022. We predicted this data with matching meteorological data and a newly developed genomic population prediction score in a Generalised Linear Model. Model selection showed that addition of genomic prediction decisively increased the explanatory power. We then predicted the response of beech to future climate change under evolutionary adaptation scenarios. A moderate climate change scenario would allow persistence of adapted beech forests, but not worst-case scenarios. Our approach can thus guide mitigation measures, such as allowing natural selection or proactive evolutionary management.
Rheological behavior of Pluronic/Pluronic diacrylate hydrogels used for bacteria encapsulation
Authors: Bhusari Shardul , Hoffmann Maxi , Herbeck-Engel Petra , Sankaran Shrikrishnan , Wilhelm Manfred , del Campo Aránzazu
Published: March 2023

Pluronic (Plu) hydrogels containing Pluronic diacrylate (PluDA) have become popular matrices to encapsulate bacteria in engineered living materials. For this purpose, 30 wt% Plu/PluDA hydrogels with variable fraction of covalently crosslinkable PluDA in the hydrogel composition are used. The degree of covalent crosslinking and the consequent different mechanical properties of the hydrogels have been shown to affect bacteria growth, but a systematic investigation of the mechanical response of the hydrogels is still missing. Here we study the rheological response of 30 wt.% Plu/PluDA hydrogels with increasing PluDA fraction between 0 and 1. We quantify the range of viscoelastic properties that can be covered in this system by varying in the PluDA fraction. We present stress relaxation and creep-recovery experiments, and analyze the variation of the critical yield strain/stress, relaxation and recovery parameters of Plu/PluDA hydrogels as function of the covalent crosslinking degree using the Burgers and Weilbull models. We expect this study to help users of Plu/PluDA hydrogels to estimate the mechanical properties of their systems, and eventually to correlate them with the behaviour of bacteria in future Plu/PluDA devices of similar composition.
Efficient PCA denoising of spatially correlated MRI data
Authors: Henriques Rafael Neto , Ianuş Andrada , Novello Lisa , Jovicich Jorge , Jespersen Sune N , Shemesh Noam
Published: March 2023

Marčenko-Pastur (MP) PCA denoising is emerging as an effective means for noise suppression in MRI acquisitions with redundant dimensions. However, MP-PCA performance is severely compromised by spatially correlated noise – an issue typically affecting most modern MRI acquisitions – almost to the point of returning the original images with little or no noise removal. In this study, we develop and apply two new strategies that enable efficient and robust denoising even in the presence of severe spatial correlations. This is achieved by measuring a-priori information about the noise variance and combing these estimates with PCA denoising thresholding concepts. The two denoising strategies developed here are: 1) General PCA (GPCA) denoising that uses a-priori noise variance estimates without assuming specific noise distributions; and 2) Threshold PCA (TPCA) denoising which removes noise components with a threshold computed from a-priori estimated noise variance to determine the upper bound of the MP distribution. These strategies were tested in simulations with known ground truth and applied for denoising diffusion MRI data acquired using pre-clinical (16.4T) and clinical (3T) MRI scanners. In synthetic phantoms, MP-PCA failed to denoise spatially correlated data, while GPCA and TPCA correctly classified all signal/noise components. In cases where the noise variance was not accurately estimated (as can be the case in many practical scenarios), TPCA still provides excellent denoising performance. Our experiments in pre-clinical diffusion data with highly corrupted by spatial correlated noise revealed that both GPCA and TPCA robustly denoised the data while MP-PCA denoising failed. Inin vivodiffusion MRI data acquired on a clinical scanner in healthy subjects, MP-PCA weakly removed noised, while TPCA was found to have the best performance, likely due to misestimations of the noise variance. Thus, our work shows that these novel denoising approaches can strongly benefit future pre-clinical and clinical MRI applications.
The Kinship Formula: inferring the numbers of all kin from any structured population projection model
Authors: Coste Christophe F. D.
Published: March 2023

Structured population projection models are fundamental to many fields of science. They enable abundance forecasting for populations categorized by various traits such as age (for demography), patch (for spatial ecology), genotype (for genetics), infectious stage (for epidemiology) or capital (economics). The demography of a structured population, determined by the transition rates (e.g., survival, fertility) between its various states, also shapes its relatedness – or kinship – structure. This structure (a probabilistic genealogy) is crucial for understanding how individuals are related to the rest of the population and affects effective population size, inclusive fitness, inbreeding, pedigrees, relatedness, familial structures, etc. Despite its significance, the relationship between demography and kinship remains under-explored. By incorporating the generation number as a trait into the population structure, we derive the Kinship Formula, yielding the expected number of any kin for any structured population. This formula is simple to implement and fast to compute, even for complex models. Most importantly, it promises significant theoretical advances. From the Kinship Formula, one can, for instance, assess the impact of embedded processes (e.g., dispersal, inheritance, growth) on kinship, compute mean population relatedness and the eventual number of kin (including kin already dead or not born yet). The Kinship Formula derived here stems from a one-sex constant environment framework. Its simplicity should allow for extensions to include environmental and demographic stochasticity as well as two-sex models.

Data accessibility statement

No new data are used. All data used to illustrate the method are public. The code related to the main text (R and Matlab) can be found in Supplementary Materials (S.M.VIII)
Dynamics of mixed-ploidy populations under demographic and environmental stochasticities
Authors: Gaynor Michelle L. , Kortessis Nicholas , Soltis Douglas E. , Soltis Pamela S. , Ponciano José Miguel
Published: March 2023

The theoretical population dynamics of autopolyploids – organisms with more than two genome copies of a single ancestral species – and their diploid progenitors have been extensively studied. The acquisition of multiple genome copies, being in essence a stochastic process, strongly suggests a probabilistic approach to examine the long-term dynamics of a population with multiple cytotypes. Yet, our current understanding of empirical evidence on the dynamics of autopolyploid populations has not incorporated stochastic population dynamics. To investigate the factors contributing to the probability and stability of coexisting cytotypes, we designed a new population dynamics model with demographic and environmental stochasticities to simulate the formation, establishment, and persistence of diploids, triploids, and autotetraploids over time when gene flow is allowed among cytotypes. Contrary to previous research, increased selfing rates and pronounced reproductive isolation stabilized the long-run coexistence of multiple cyto-types. In stressful environments, these dynamics become much more complex, and our stochastic modeling approach helped reveal the resulting intricacies that give tetraploids competitive advantage over their diploid progenitors. Our work is fundamental to a better understanding of the dynamics of coexistence of multiple cytotypes and is a necessary step for further work modeling the dynamics between an autopolyploid and its diploid progenitor.
High-Dimensional Spectral Cytometry Reveals Therapeutically Relevant Immune Subtypes in Gastric Cancer
Authors: Abate Miseker , Fei Teng , Lin Ya Hui , Shimada Shoji , Drebin Harrison , Chen Eunise , Tang Laura , Strong Vivian E , Vardhana Santosha A.
Published: March 2023

Identification of locally advanced gastric cancer (GC) patients who might potentially benefit from immune-based strategies is limited by both the poor predictive quality of existing biomarkers, including molecular subtypes, tumor mutational burden, and PD-L1 expression, as well as inadequate understanding of the gastric cancer immune microenvironment. Here, we leveraged high-dimensional spectral cytometry to re-classify locally advanced gastric tumors based on immune composition. The gastric cancer microenvironment was comprised of a diverse immune infiltrate including high proportions of plasmablasts, macrophages, and myeloid-derived suppressor cells. Computational cell typing and sample clustering based on tiered broad immune and T-cell focused phenotyping identified three distinct immune subtypes. The most immunogenic subtype exhibited high proportions of activated CD4+ T-cells and plasmablasts and included tumors that would have been classified as non-immunogenic based on prior classifications. Analysis of gastric cancer patients treated with immune checkpoint blockade indicates that patients who responded to immunotherapy had a pre-treatment tumor composition that corresponded to higher immune scores from our analysis. This work establishes a novel immunological classification of gastric cancer including identification of patients and immune networks likely to benefit from immune-based therapies.
HDAC11 inhibition triggers bimodal thermogenic pathways to circumvent adipocyte catecholamine resistance
Authors: Robinson Emma L. , Bagchi Rushita A. , Major Jennifer L. , Bergman Bryan C. , Madsuda Jennifer L. , McKinsey Timothy A.
Published: March 2023

Stimulation of adipocyte β-adrenergic receptors (β-ARs) induces expression of uncoupling protein 1 (UCP1), promoting non-shivering thermogenesis. Association of β-ARs with a lysine myristoylated form of A-kinase anchoring protein 12 (AKAP12)/gravin-α is required for downstream signaling that culminates in UCP1 induction. Conversely, demyristoylation of gravin-α by histone deacetylase 11 (HDAC11) suppresses this pathway. Whether inhibition of HDAC11 in adipocytes is sufficient to drive UCP1 expression independently of β-ARs is not known. Here, we demonstrate that adipocyte-specific deletion of HDAC11 in mice leads to robust induction of UCP1 in adipose tissue (AT), resulting in increased body temperature. These effects are mimicked by treating micein vivoor human ATex vivowith an HDAC11-selective inhibitor, FT895. FT895 triggers biphasic, gravin-α myristoylation-dependent induction of UCP1 protein expression, with a non-canonical acute response that is post-transcriptional and independent of protein kinase A (PKA), and a delayed response requiring PKA activity and newUcp1mRNA synthesis. Remarkably, HDAC11 inhibition promotes UCP1 expression even in models of adipocyte catecholamine resistance where β-AR signaling is blocked. These findings define cell autonomous, multi-modal roles for HDAC11 as a suppressor of thermogenesis, and highlight the potential of inhibiting HDAC11 to therapeutically alter AT phenotype independently of β-AR stimulation.
Trends in serotype distribution and disease severity in adults hospitalised withStreptococcus pneumoniaeinfection in Bristol and Bath: a retrospective cohort study, 2006-2022
Authors: Hyams Catherine , Challen Robert , Hettle David , Amin-Chowdhury Zahin , Grimes Charli , Ruffino Gabriella , Conway Rauri , Heath Robyn , North Paul , Malin Adam , Maskell Nick A , Williams Philip , Martin Williams O. , Ladhani Shamez N , Danon Leon , Finn Adam
Published: March 2023

Ongoing surveillance is essential to inform policy decisions and monitor serotype replacement following pneumococcal conjugate vaccination (PCV) deployment. We report serotype and disease severity trends in this retrospective cohort of hospitalised adults in Bristol-Bath, 2006-22. Of 1686 invasive pneumococcal disease (IPD) cases, 1501 (89.0%) had known serotype. We also identified 2033/3719 cases of non-IPD. IPD declined sharply during the early COVID-19 pandemic. Over 2022 it gradually returned to pre-pandemic levels. Disease severity also changed throughout this period: CURB65 severity and inpatient mortality decreased whilst ICU admissions increased. PCV7 and PCV13-serotype IPD decreased from 2006-09 to 2021-22. However, significant residual PCV13-serotype IPD remains, representing 21.7% [15.5-29.6] of 2021-22 cases, highlighting that significant adult PCV-serotype disease still occurs despite 17-years of paediatric PCV usage in the UK. We found increased proportions of serotype 3 and 8 IPD, whilst 19F and 19A re-emerged. In 2020-22, 68.2% IPD cases were potentially covered by PCV20.

Article Summary

We observed significant serotype shifts but perseverance and re-emergence of some serotypes covered by PCVs over this 17-year retrospective study, which found considerable adult pneumococcal disease attributable to PCV-serotypes despite high uptake of paediatric PCV.
Impact of intestinal dysbiosis on clinical course in severe acute pancreatitis: a multicenter prospective observational study
Authors: Oami Takehiko , Ishida Shigenobu , Oshima Taku , Yamamoto Akinobu , Nakada Taka-aki
Published: March 2023

Background

Dysbiosis, an imbalance of the intestinal microbiota in critically ill patients, reportedly contributes to poor outcomes. Controlling the disruption of intestinal homeostasis could be promising tactics for infectious complications in acute pancreatitis. To improve the mortality rate of severe acute pancreatitis with high frequency of infectious complications, it is warranted to elucidate the pathophysiology for development of new treatment strategies. We hypothesized that patients with severe acute pancreatitis would demonstrate gut dysbiosis, leading to an onset of infectious complications and poor outcomes.

Methods

We will conduct a prospective study to compare the sequential changes in intestinal microbiota using 16s RNA metagenomics and metabolomics between patients with severe acute pancreatitis and mild acute pancreatitis. We will enroll adult patients (18 years of age or older) diagnosed with acute pancreatitis and newly admitted to the hospitals for 48 hours or longer. We will exclude patients with inflammatory bowel disease, patients with diarrhea prior to admission, patients who have received antimicrobial agents for more than 1 week in the 2 months prior to admission. We will collect stool and blood samples on day 1 and 6. The primary outcome is changes in various parameters of the intestinal microbiota, protein concentration in stool, and metabolite concentration. The secondary outcomes include relationship between each parameter and short- and long-term prognosis, correlation of each parameter with treatment details and clinical course during ICU stay, and associations among the amount of diarrhea and alpha-diversity parameters, protein concentration in each stool, and metabolite concentration.
Sociodemographic disparities in the use of GLP-1 receptor agonists and SGLT-2 inhibitors among US adults with type 2 diabetes: NHANES 2005-March 2020
Authors: Mittman Benjamin G. , Le Phuc , Payne Julia Y. , Ayers Gina , Rothberg Michael B.
Published: March 2023

Aim

Type 2 Diabetes (T2D) is a major cause of morbidity and mortality. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are highly effective but underutilized. We assessed racial/ethnic and other sociodemographic disparities in GLP-1/SGLT-2 use among US adults with T2D.

Materials and Methods

We conducted a retrospective analysis using nationally representative data from National Health and Nutrition Examination Survey 2005-March 2020. Participants were adults with T2D taking ≥1 diabetes medication, excluding pregnant women and adults with probable T1D. We performed univariate analyses to examine characteristics of patients using GLP-1/SGLT-2 and multivariable logistic regression to assess disparities in GLP-1/SGLT-2 use after adjusting for other patient factors.

Results

Among 4,585 T2D patients (representing >18 million US adults) taking ≥1 medication, GLP-1/SGLT-2 usage increased from 1.4% in 2005-2006 to 13.3% in 2017-2020. In univariate analyses, patients using GLP-1/SGLT-2 vs. other T2D drugs were more likely to be white than nonwhite (72% vs. 60%, p = .001), but in multivariable analysis there was no significant difference in GLP-1/SGLT-2 use for nonwhite vs. white patients (aOR = 0.84, 95% CI [0.61, 1.16]). GLP-1/SGLT-2 use was higher for patients who completed some college (aOR = 1.83, 95% CI [1.06, 3.15]) or above (aOR = 2.06, 95% CI [1.28, 3.32]) vs. high school or less, and for those with an income-poverty ratio ≥4 vs. <2 (aOR = 2.11, 95% CI [1.30, 3.42]).

Conclusions

Use of GLP-1/SGLT-2 drugs increased over time but remained low in March 2020. Higher education and income, but not race/ethnicity, were associated with GLP-1/SGLT-2 use.
Cognitive Intervention Effects Vary as a Function of Plasma Neurofilament Light Chain Levels: A PICMOR Randomized Controlled Trial
Authors: Otake-Matsuura Mihoko , Sugimoto Hikaru , Sekiguchi Takuya , Abe Masato S. , Miura Kumi W. , Tokunaga Seiki , Akamine Shoshin , Kishimoto Taishiro , Kudo Takashi
Published: March 2023

Background

There is a difference in the neuronal state of individuals. However, this has not been taken into consideration in most intervention studies. Recent advances in analytical technologies in hematological examination enabled us to evaluate neuronal states in a relatively convenient manner.

Objective

Using these advanced technologies, we aimed to investigate whether cognitive intervention effects vary as a function of levels of blood-based biomarkers, such as neurofilament light chain (NfL), since plasma NfL could be a biomarker of neurodegenerative diseases including Alzheimer’s disease.

Methods

In this study, we employed a group conversation-based intervention methodology named Photo-Integrated Conversation Moderated by Robots (PICMOR), which has been shown to improve verbal fluency in older adults. To examine the possibility of varying effects of this intervention method according to the neuronal state of each individual, we conducted a randomized controlled trial (UMIN Clinical Trials Registry number: UMIN000036599) and investigated how longitudinal changes in cognitive performance, such as verbal fluency, vary with the NfL level measured at the baseline.

Results

As the main result, positive intervention effects of PICMOR on verbal fluency were observed in individuals with lower level of NfL, which indicate a relatively intact neuronal state, whereas negative intervention effects were identified in individuals with higher NfL level.

Conclusion

Our findings suggest that cognitive intervention effects vary depending on level of Nfl in the plasma. Thus, future intervention studies should take into account the neuronal status of the participants to examine intervention effects.
Disparities in Mortality Associated with Acute Myocardial Infarction and COVID-19 in the United States: A Nationwide Analysis
Authors: Muhyieddeen Amer , Cheng Susan , Mamas Mamas A , Beasley Dorian , Weins Galen Cook , Gulati Martha
Published: March 2023

Background

The impact of the COVID-19 pandemic on potential racial disparities in acute myocardial infarction (AMI) management and outcomes is unclear. We examined AMI patient management and outcomes during the pandemic’s initial nine months, comparing COVID-19 and non-COVID-19 cases.

Methods

We identified all patients hospitalized for AMI in 2020 using the National Inpatient Sample (NIS), identifying those with or without concurrent COVID-19. Logistic and linear regression was used for analyses of associations, with adjustment for potential confounders.

Results

Patients with both AMI and COVID-19 had higher in-hospital mortality rates (aOR 3.19, 95% CI 2.63-3.88), mechanical ventilation (aOR 1.90, 95% CI 1.54-2.33), and hemodialysis (aOR 1.38, 95% CI 1.05-1.89) compared to those without COVID-19. Black and Asian/Pacific Islander patients had higher in-hospital mortality than White patients, (aOR 2.13, 95% CI 1.35-3.59) and (aOR 3.41, 95% CI 1.5-8.37). Moreover, Black, Hispanic, and Asian/Pacific Islander patients had higher odds of initiating hemodialysis, (aOR 5.48, 95% CI 2.13-14.1), (aOR 2.99, 95% CI 1.13-7.97), and (aOR 7.84, 95% CI 1.55-39.5) and were less likely to receive PCI for AMI, (aOR 0.71, 95% CI 0.67-0.74), (aOR 0.81, 95% CI 0.77-0.86), and (aOR 0.82, 95% CI 0.75-0.90). Additionally, Black patients had a lower likelihood of undergoing CABG surgery for AMI (aOR 0.55, 95% CI 0.49-0.61).

Conclusion

Our study revealed increased mortality and complications in COVID-19 patients with AMI, highlighting significant racial disparities. Urgent measures addressing healthcare disparities, such as enhancing access and promoting culturally sensitive care, are needed to improve health equity.
Delineating the functional role of thePPE50 (Rv3135) - PPE51 (Rv3136)gene cluster in the pathophysiology ofMycobacterium tuberculosis
Authors: Mukku Ravi Prasad , Poornima Kokavalla , Yadav Sangya , Raghunand Tirumalai R.
Published: March 2023

The extraordinary success ofMycobacterium tuberculosis(M. tb) has been attributed to its ability to modulate host immune responses. The genome ofM. tbencodes multiple immunomodulatory factors, including several proteins of the multigenic PE_PPE family, which comprise about 10% of its coding potential. The presence of these proteins in pathogenic mycobacteria strongly suggests that they play a role in disease pathogenesis. To understand its role inM. tbphysiology we have begun to characterise thePPE50 (Rv3135)-PPE51 (Rv3136)gene cluster, one of ninePPE-PPEclusters in theM. tbgenome. We demonstrate that this cluster encodes a co-transcriptional unit and that PPE50 and PPE51 interact bothin vitroandin vivo, the first demonstration of PPE-PPE interaction. THP-1 macrophages infected with recombinantM. smegmatisstrains expressingPPE50andPPE51showed less intracellular viability than the control strain containing the vector alone, the decline in viable counts correlating with an increase in transcript levels of inducible nitric oxide synthase (iNOS2). Macrophages infected with the recombinant strains exhibited an upregulation in levels of the anti-inflammatory cytokineIL-10, indicating an immunomodulatory role for these proteins. Using pull-down assays, we discovered TLR1 to be the cognate receptor for PPE50, with signalling through the receptor being indicated by an increase in IRAK1 phosphorylation. All the phenotypes observed on infection of THP-1 macrophages including the decrease in CFUs, the increase iniNOS2andIL-10levels, as well as signalling through the receptor, were reversed on treatment of macrophages with an anti-TLR1 antibody prior to infection, validating the functional outcome of PPE50-TLR1 interaction. Our data points to a TLR1 dependent role for thePPE50-PPE51cluster in promoting bacillary persistence,viaCFU reduction and a concomitant upregulation of the anti-inflammatory response - a two-pronged strategy to circumvent host immune surveillance.
β-helical protein PerA orchestrates antibiotic uptake across theCaulobacterouter membrane via converging stress signaling systems
Authors: Costafrolaz Jordan , Panis Gaël , Vallet Simon-Ulysse , Gomariz Manuel Velasco , Degeorges Laurence , Fröhlich Kathrin S. , Viollier Patrick H.
Published: March 2023

While large membrane-impermeable antibiotics cannot traverse a lipid barrier, spacious importers such as TonB-dependent receptors (TBDRs) can mistakenly ferry antibiotics across the bacterial outer membrane (OM). We discovered that loss of PerA, an enigmatic β-helix protein in the OM of the oligotrophic α-proteobacteriumCaulobacter crescentus, reprograms the OM TBDR proteome from ChvT that imports the glycopeptide antibiotic vancomycin to an uncharacterized TBDR (BugA) that confers sensitivity to the polypeptide antibiotic bacitracin. Both antibiotics are large zinc-binding molecules that target the peptidoglycan, echoing the zinc stress response induces destabilization of PerA. Inactivation of PerA launches two conserved and interwoven envelope stress programs that remodel the OM with TBDRs, a tripartite multidrug efflux pump and periplasmic proteases. Thus, unanticipated entry routes for antibiotics emerge in stressed diderm bacteria that may be treatable with membrane impermeable antimicrobials owing to an underlying transcriptional stress response pathways coordinated by a novel type of OM regulator.
Respiratory tractMoraxella catarrhalisandKlebsiella pneumoniaecan promote pathogenicity of myelin-reactive Th17 cells
Authors: Mannion Jenny M. , Segal Benjamin M. , McLoughlin Rachel M. , Lalor Stephen J.
Published: March 2023

The respiratory tract is home to a diverse microbial community whose influence on local and systemic immune responses is only beginning to be appreciated. The airways have been linked with trafficking of myelin-specific T cells in the pre-clinical stages of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Th17 cells are important pathogenic effectors in MS and EAE but are innocuous immediately following differentiation. Upregulation of the cytokine GM-CSF appears to be a critical step in their acquisition of pathogenic potential, but little is known about the mechanisms that mediate this process. Here, primed myelin-specific Th17 cells were transferred to congenic recipient mice prior to exposure to various human respiratory tract-associated bacteria and T cell trafficking, phenotype and the severity of resulting EAE monitored. Disease was exacerbated in mice exposed to the ProteobacteriaMoraxella catarrhalisandKlebsiella pneumoniae,but not the FirmicuteVeillonella parvula, and this was associated with a significant increase in GM-CSF+and GM-CSF+IFNγ+ex-Th17-like donor CD4 T cells in the lungs and CNS of these mice. These findings support the concept that respiratory bacteria may contribute to the pathophysiology of CNS autoimmunity by modulating pathogenicity in crucial T cell subsets that orchestrate neuroinflammation.