bluuebunny/crossref_metadata_2025 huggingface dataset:
Single‐cell RNA sequencing in osteoarthritis
Authors: Gu Yuyuan , Hu Yan , Zhang Hao , Wang Sicheng , Xu Ke , Su Jiacan
Published: June 2023

Osteoarthritis is a progressive and heterogeneous joint disease with complex pathogenesis. The various phenotypes associated with each patient suggest that better subgrouping of tissues associated with genotypes in different phases of osteoarthritis may provide new insights into the onset and progression of the disease. Recently, single‐cell RNA sequencing was used to describe osteoarthritis pathogenesis on a high‐resolution view surpassing traditional technologies. Herein, this review summarizes the microstructural changes in articular cartilage, meniscus, synovium and subchondral bone that are mainly due to crosstalk amongst chondrocytes, osteoblasts, fibroblasts and endothelial cells during osteoarthritis progression. Next, we focus on the promising targets discovered by single‐cell RNA sequencing and its potential applications in target drugs and tissue engineering. Additionally, the limited amount of research on the evaluation of bone‐related biomaterials is reviewed. Based on the pre‐clinical findings, we elaborate on the potential clinical values of single‐cell RNA sequencing for the therapeutic strategies of osteoarthritis. Finally, a perspective on the future development of patient‐centred medicine for osteoarthritis therapy combining other single‐cell multi‐omics technologies is discussed. This review will provide new insights into osteoarthritis pathogenesis on a cellular level and the field of applications of single‐cell RNA sequencing in personalized therapeutics for osteoarthritis in the future.
Ecological and biological indicators of the accuracy of species distribution models: lessons from European bryophytes
Authors: Collart Flavien , Broennimann Olivier , Guisan Antoine , Vanderpoorten Alain
Published: June 2023

The predictive power of species distribution models (SDMs) varies substantially among species depending on their ecological and life‐history traits, but which of these traits are the most relevant and how they influence species ‘predictability' remains an area of debate. Here, we address these questions in bryophytes. SDMs employing macroclimatic, topographic and edaphic predictors were calibrated for 411 species in Europe and externally evaluated using an independent dataset. Regression models were implemented to determine whether species characteristics, including life‐history traits, ecological preference and niche breadth, determine the accuracy of SDMs. Variation in SDM accuracy among species was significantly explained by species characteristics, supporting the hypothesis that the strength of species–environment correlations is affected by characteristics of the species themselves. The percent variance of SDM accuracy explained by species traits, however, substantially varied between 9 and 57% depending on the evaluation metrics used. The lower correlation observed between species traits and MaxKappa and the Boyce index than with area under the curve (AUC) and MaxTSS suggests that the former are less suitable than the latter for determining species ‘predictability' based on their traits. SDM accuracy decreased from species restricted to pristine habitats to species thriving in eutrophic habitats with high levels of human disturbance. The widespread distribution of man‐made habitats in fact opens the door for the spread of now ubiquitous species, even in environments that would primarily not be suitable for them. Such species, likely to occur anywhere, reach very high to full occupancy rates, thereby decreasing the accuracy of models aiming at predicting their distributions. The fact that AUC and MaxTSS were higher for species from pristine habitats is important in a conservation context, as ubiquitous species from eutrophic, disturbed environments are precisely the ones of lower conservation relevance.
Long‐term elevated precipitation induces grassland soil carbon loss via microbe‐plant–soil interplay
Authors: Wang Mengmeng , Sun Xin , Cao Baichuan , Chiariello Nona R. , Docherty Kathryn M. , Field Christopher B. , Gao Qun , Gutknecht Jessica L. M. , Guo Xue , He Genhe , Hungate Bruce A. , Lei Jiesi , Niboyet Audrey , Le Roux Xavier , Shi Zhou , Shu Wensheng , Yuan Mengting , Zhou Jizhong , Yang Yunfeng
Published: June 2023

Global climate models predict that the frequency and intensity of precipitation events will increase in many regions across the world. However, the biosphere‐climate feedback to elevated precipitation (eP) remains elusive. Here, we report a study on one of the longest field experiments assessing the effects of eP, alone or in combination with other climate change drivers such as elevated CO2 (eCO2), warming and nitrogen deposition. Soil total carbon (C) decreased after a decade of eP treatment, while plant root production decreased after 2 years. To explain this asynchrony, we found that the relative abundances of fungal genes associated with chitin and protein degradation increased and were positively correlated with bacteriophage genes, suggesting a potential viral shunt in C degradation. In addition, eP increased the relative abundances of microbial stress tolerance genes, which are essential for coping with environmental stressors. Microbial responses to eP were phylogenetically conserved. The effects of eP on soil total C, root production, and microbes were interactively affected by eCO2. Collectively, we demonstrate that long‐term eP induces soil C loss, owing to changes in microbial community composition, functional traits, root production, and soil moisture. Our study unveils an important, previously unknown biosphere‐climate feedback in Mediterranean‐type water‐limited ecosystems, namely how eP induces soil C loss via microbe‐plant–soil interplay.
A claim for a ‘next generation’ of multisite range‐wide forest genetic trials built on the legacy of ecological genetics to anticipate responses to climate
Authors: Sampedro Luis , Alía Ricardo
Published: June 2023

Hacia una nueva generación de ensayos genéticos forestales multisitio para anticipar las respuestas de las especies forestales a la crisis climática

Realizamos un comentario sobre el trabajo de revisión presentado por Leites & Benito‐Garzón (2023) en este número sobre el valor de las redes de ensayos genéticos forestales multi‐sitio para anticipar la distribución y las respuestas de las especies forestales a la actual crisis climática. La persistencia de las masas forestales y de los servicios ecosistémicos que proporcionan necesita de un esfuerzo coordinado sin precedentes de la comunidad científica para comprender, predecir y mitigar los impactos de la crisis climática sobre los bosques templados y boreales. Para ello se necesita información precisa sobre la variación genética, plasticidad fenotípica y la variación genética en plasticidad de las especies forestales. Hacemos una llamada de atención sobre la necesidad urgente de establecer una nueva generación de ensayos genéticos forestales de procedencias replicados multisitio a lo largo del rango de distribución de las especies de interés, y enfocado en la resiliencia al cambio climático. Como científicos debemos facilitar las respuestas evolutivas a los tan rápidos que están viviendo las especies forestales. Debemos ser determinantes en proporcionar información de primera clase a los actores políticos y administradores para desarrollar una gestión forestal basada en la evidencia científica.
Heterogeneity of placebo effects on urinary incontinence in overactive bladder syndrome: A meta‐analysis of Japanese placebo‐controlled clinical trials
Authors: Hara Tomohiko
Published: June 2023

Objectives

The effect sizes, changes over time, and heterogeneity of placebo effects on frequency of urination for voiding disorders in Japanese clinical trials have been published. This study evaluated the characteristics of placebo effects on overall and urge incontinence in overactive bladder patients.

Methods

A meta‐analysis of Japanese placebo‐controlled clinical trials was conducted to determine placebo effects on the daily frequency of overall (n = 16) and urge (n = 11) incontinence and identify factors that should be considered in clinical trials.

Results

The between‐study heterogeneity variance of placebo effects for overall and urge incontinence at 8 weeks was estimated as I2 = 70.3% and 64.2%, and the prediction interval for the ratio of means ranged from g = 0.31–0.91 and 0.32–0.81, respectively. Subgroup analysis using the random‐effects model showed placebo effects in overall incontinence (p = 0.08) and urge incontinence (p < 0.0001). The ratio of means (95% confidence interval) of urge incontinence frequency from baseline to 4 (n = 10), 8 (n = 10), and 12 (n = 7) weeks were 0.65 (0.57, 0.74), 0.51 (0.42, 0.62), and 0.48 (0.36, 0.64), respectively, for the random‐effects model. Regression analysis did not reveal any significant factors that influenced placebo effects.

Conclusions

This meta‐analysis confirmed the characterization of placebo effects on overall and urge incontinence, which demonstrates heterogeneity between trials. The impact of population, follow‐up period, and endpoints on placebo effects should be considered when designing clinical trials for overactive bladder syndrome.
Maintaining a tolerant national identity: Divergent implications for the acceptance of minority groups
Authors: Verkuyten Maykel , Gale Jessica , Adelman Levi , Yogeeswaran Kumar
Published: June 2023

The current research examines the proposition that minority groups can be either accepted or rejected, both in the name of national tolerance. In three studies using national samples in the Netherlands (N = 1572), we focused on three different understandings of what is required to maintain an alleged national identity of tolerance. Data indicated that stronger agreement with the need to live up to the self‐defining tradition of tolerance was associated with higher support for Muslim minority practices. However, stronger agreement with two boundary conditions of what is tolerable in the name of protecting tolerance, upholding a threshold for tolerance, and the need for reciprocity, was found to be associated with lower support for Muslim minority practices. Additionally, perceived identity continuity threat accounted for these associations. The findings demonstrate that a national identity of tolerance can be understood in different ways with differing implications for minority groups.
Competitive actions and supply chain relationships: How suppliers' value‐diminishing actions affect buyers' procurement decisions
Authors: Hofer Christian , D'Oria Laura , Cantor David E. , Ren Xinyi
Published: June 2023

While greater competitive activity is generally associated with competitive advantage, certain competitive actions by a supplier may have spillover effects that adversely impact buying firms, leading them to reduce future purchases from the supplier. We study the effects of competitive actions in the context of vertical buyer–supplier relationships. Specifically, leveraging insights from screening theory, we examine how a supplier firm's value‐diminishing competitive actions—moves that may negatively impact buyer firms—lead to subsequent reductions in the buyer's procurement allocations and how contextual factors moderate such adverse effects. We test the associated hypotheses using a panel dataset comprising 12,690 dyadic buyer–supplier observations. A series of econometric analyses provide consistent evidence that a supplier's value‐diminishing actions are associated with decreases in the buyer's purchases from the supplier, thus highlighting the “dark side” of competitive actions. Furthermore, we find that the supplier's downstream vertical relatedness and the degree to which rival suppliers pursue value‐diminishing actions moderate this effect. Our findings, thus, add to our understanding of factors that shape the success and continuity of supply chain relationships and help supplier firms evaluate the economic viability of their competitive actions.
Measuring self‐regulated learning in a junior high school mathematics classroom: Combining aptitude and event measures in digital learning materials
Authors: Zhidkikh Denis , Saarela Mirka , Kärkkäinen Tommi
Published: June 2023

Background

Measurement of students' self‐regulation skills is an active topic in education research, as effective assessment helps devising support interventions to foster academic achievement. Measures based on event tracing usually require large amounts of data (e.g., MOOCs and large courses), while aptitude measures are often qualitative and need careful interpretation. Precise and interpretable evaluation of self‐regulation skills in a normal K‐12 classroom thus poses a challenge.

Objectives

The present study proposes and explores a learning analytics method of combining aptitude and event measures to evaluate student's self‐regulation skills.

Methods

An explorative learning analytics study was conducted in a junior high school mathematics class ( students), using a three‐lesson intervention with digital learning materials. Students first assessed their self‐regulation skills with a self‐report questionnaire, after which trace logs and observations of student behaviour were collected. Learning sessions were extracted from trace logs, clustered, and linked to learning strategies. Students were clustered by the self‐report results and learning behaviour profiles. Session clusters, student behaviour clusters and assignment grades were also tested for association.

Results and Conclusions

The detected session and student behaviour types were linked to learning tactics and strategies found in prior studies. Additionally, association was found between self‐reported self‐regulation skills and the student behaviour obtained from trace logs.

Implications

The results demonstrate the feasibility of concurrently using aptitude and event measures on a classroom scale, providing teachers with a tool to evaluate and support self‐regulated learning. Combined with further measures like predictive learning analytics, teachers can obtain an early and highly interpretable picture of at‐risk students in their classes.
Reliable and rapid identification of terbinafine resistance in dermatophytic nail and skin infections
Authors: Blanchard Gabriela , Amarov Boyko , Fratti Marina , Salamin Karine , Bontems Olympia , Chang Yun‐Tsan , Sabou Alina Marcela , Künzle Nathalie , Monod Michel , Guenova Emmanuella
Published: June 2023

Background

Fungal infections are the most frequent dermatoses. The gold standard treatment for dermatophytosis is the squalene epoxidase (SQLE) inhibitor terbinafine. Pathogenic dermatophytes resistant to terbinafine are an emerging global threat. Here, we determine the proportion of resistant fungal skin infections, analyse the molecular mechanisms of terbinafine resistance, and validate a method for its reliable rapid identification.

Methods

Between 2013 and 2021, we screened 5634 consecutively isolated Trichophyton for antifungal resistance determined by hyphal growth on Sabouraud dextrose agar medium containing 0.2 μg/mL terbinafine. All Trichophyton isolates with preserved growth capacity in the presence of terbinafine underwent SQLE sequencing. Minimum inhibitory concentrations (MICs) were determined by the broth microdilution method.

Results

Over an 8‐year period, the proportion of fungal skin infections resistant to terbinafine increased from 0.63% in 2013 to 1.3% in 2021. Our routine phenotypic in vitro screening analysis identified 0.83% (n = 47/5634) of Trichophyton strains with in vitro terbinafine resistance. Molecular screening detected a mutation in the SQLE in all cases. Mutations L393F, L393S, F397L, F397I, F397V, Q408K, F415I, F415S, F415V, H440Y, or A398A399G400 deletion were detected in Trichophyton rubrum. Mutations L393F and F397L were the most frequent. In contrast, all mutations detected in T. mentagrophytes/T. interdigitale complex strains were F397L, except for one strain with L393S. All 47 strains featured significantly higher MICs than terbinafine‐sensitive controls. The mutation‐related range of MICs varied between 0.004 and 16.0 μg/mL, with MIC as low as 0.015 μg/mL conferring clinical resistance to standard terbinafine dosing.

Conclusions

Based on our data, we propose MIC of 0.015 μg/mL as a minimum breakpoint for predicting clinically relevant terbinafine treatment failure to standard oral dosing for dermatophyte infections. We further propose growth on Sabouraud dextrose agar medium containing 0.2 μg/mL terbinafine and SQLE sequencing as fungal sporulation‐independent methods for rapid and reliable detection of terbinafine resistance.
The relationships among prior gang involvement, current gang involvement, and victimization among youth in residential placement
Authors: Clark Jim , Gilman Amanda B. , Howell James C. (Buddy) , Harris Meena
Published: June 2023

This study examines patterns of victimization among youth in residential placement facilities using data from the Survey of Youth in Residential Placement. Findings indicate that gang involvement in residential placement is associated with multiple forms of victimization. However, desistance from gang membership resulted in rates of victimization among gang members that were no different from those of youth who had never been involved in gangs. These findings support prior research showing that gang involvement does not appear to serve as a protective function and further specifies the nature and contexts of the relationship between gang association and victimization.
Trauma‐Informed Care for Justice‐Involved Youth: A narrative review and synthesis
Authors: Hill LeRoi , Barnett James E. , Ward James , Morton Allison , Schmidt Adam T.
Published: June 2023

Justice‐involved youth (JIY) experience extremely high prevalence rates of trauma prior to their involvement in the juvenile justice system. Trauma outcomes are heterogeneous, long‐term, and may influence JIY outcomes. Although specific evidence‐based treatments (EBTs) target trauma symptoms, few studies have examined treatment outcomes in relation to adolescent populations, and even fewer have examined treatment outcomes in relation to JIY. This review examines evidence supporting the effectiveness of trauma‐focused treatments with JIY. The existing literature suggests trauma‐focused interventions may be a promising avenue for improving both mental health and juvenile justice outcomes for JIY. Clinical practice and policy implications are discussed.
Confronting the ghost of Elizabeth Gillam: A new look at Ex parte Crouse (1839)
Authors: Robison Erica
Published: June 2023

This article revisits the 1839 Pennsylvania Supreme Court case Ex parte Crouse in light of new historical information. While most legal scholars and historians have analyzed Ex parte Crouse with the assumption that Mary Ann Crouse was sent to the Philadelphia House of Refuge without committing any crime, a search at the Historical Society of Pennsylvania revealed the existence of Crouse's admission record detailing how she had killed a two‐year‐old child. This finding undermines the extensive conclusions that scholars have drawn about the case's significance and highlights the importance of archival work in legal studies.
Effect of the COVID‐19 pandemic on meaningful activity engagement in racially and ethnically diverse older adults
Authors: Oh Anna , Gan Siqi , Boscardin W. John , Neilands Torsten B. , Stewart Anita L. , Nguyen Tung T. , Smith Alexander K.
Published: June 2023

Background

Participation and active engagement in meaningful activities support the emotional and physical well‐being of older adults. In 2020, the onset of the COVID‐19 pandemic altered lives, including the ability to participate in meaningful activities. This study compared meaningful activity engagement before and at the beginning of the COVID‐19 pandemic in a nationally representative, diverse sample >65 years between 2015 and 2020.

Methods

We described the proportions and characteristics of National Health and Aging Trends Study participants and their engagement in four activities: visiting friends or family, attending religious services, participating in clubs/classes/other organized activities, and going out for enjoyment. We used mixed effects logistic regressions to compare probabilities of activity engagement before 2020 and in 2020, adjusting for age, sex, functional status, income, geographic region, anxiety‐depression, and transportation issues.

Results

Of 6815 participants in 2015, the mean age was 77.7 (7.6) years; 57% of participants were female; 22% were Black, 5% Hispanic, 2% were American Indian, and 1% were Asian; 20% had disability; and median income was $33,000. Participation in all four activities remained consistent between 2015 and 2019 and declined in 2020. Significant differences existed in attending religious services (p < 0.01) and going out for enjoyment (p < 0.001) by race and ethnicity, before and after the start of COVID‐19. Black and Hispanic participants experienced the largest decline in attending religious services (−32%, −28%) while Asian and White participants experienced the largest decline in going out for enjoyment (−49%, −56%).

Conclusions

Potential quality of life tradeoffs should be considered to a greater extent in future pandemic emergencies.
C9orf72 poly‐PR helps p53 escape from the ubiquitin‐proteasome system and promotes its stability
Authors: Yang Fumin , Mahaman Yacoubou Abdoul Razak , Zhang Bin , Wang Jian‐Zhi , Liu Rong , Liu Fei , Wang Xiaochuan
Published: June 2023

C9orf72‐derived dipeptide repeats (DPRs) proteins have been regarded as the pathogenic cause of neurodegeneration in amyotrophic lateral sclerosis and frontotemporal dementia (C9‐ALS/FTD). As the most toxic DPRs in C9‐ALS/FTD, poly‐proline‐arginine (poly‐PR) is associated with the stability and accumulation of p53, which consequently induces neurodegeneration. However, the exact molecular mechanism via which C9orf72 poly‐PR stabilizes p53 remains unclear. In this study, we showed that C9orf72 poly‐PR induces not only neuronal damage but also p53 accumulation and p53 downstream gene activation in primary neurons. C9orf72 (PR)50 also slows down p53 protein turnover without affecting the p53 transcription level and thus promotes its stability in N2a cells. Interestingly, the ubiquitin‐proteasome system but not the autophagy function was impaired in (PR)50 transfected N2a cells, resulting in defective p53 degradation. Moreover, we found that (PR)50 induces mdm2 mistranslocation from the nucleus to the cytoplasm and competitively binds to p53, reducing mdm2‐p53 interactions in the nucleus in two different (PR)50 transfected cells. Our data strongly indicate that (PR)50 reduces mdm2‐p53 interactions and causes p53 to escape from the ubiquitin‐proteasome system, promoting its stability and accumulation. Inhibiting or at least downregulating (PR)50 binding with p53 may be therapeutically exploited for the treatment of C9‐ALS/FTD.

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Homeostatic crosstalk among gut microbiome, hypothalamic and hepatic circadian clock oscillations, immunity and metabolism in response to different light–dark cycles: A multiomics study
Authors: Zhen Yongkang , Wang Yifan , He Feiyang , Chen Yifei , Hu Liangyu , Ge Ling , Wang Yusu , Wei Wenjun , Rahmat Ali , Loor Juan J. , Wang Mengzhi
Published: June 2023

The accelerated pace of life at present time has resulted in tremendous alterations in living patterns. Changes in diet and eating patterns, in particular, coupled with irregular light–dark (LD) cycles will further induce circadian misalignment and lead to disease. Emerging data has highlighted the regulatory effects of diet and eating patterns on the host‐microbe interactions with the circadian clock (CC), immunity, and metabolism. Herein, we studied how LD cycles regulate the homeostatic crosstalk among the gut microbiome (GM), hypothalamic and hepatic CC oscillations, and immunity and metabolism using multiomics approaches. Our data demonstrated that central CC oscillations lost rhythmicity under irregular LD cycles, but LD cycles had minimal effects on diurnal expression of peripheral CC genes in the liver including Bmal1. We further demonstrated that the GM could regulate hepatic circadian rhythms under irregular LD cycles, the candidate bacteria including Limosilactobacillus, Actinomyces, Veillonella, Prevotella, Campylobacter, Faecalibacterium, Kingella, and Clostridia vadinBB60 et al. A comparative transcriptomic study of innate immune genes indicated that different LD cycles had varying effects on immune functions, while irregular LD cycles had greater impacts on hepatic innate immune functions than those in the hypothalamus. Extreme LD cycle alterations (LD0/24 and LD24/0) had worse impacts than slight alterations (LD8/16 and LD16/8), and led to gut dysbiosis in mice receiving antibiotics. Metabolome data also demonstrated that hepatic tryptophan metabolism mediated the homeostatic crosstalk among GM‐liver–brain axis in response to different LD cycles. These research findings highlighted that GM could regulate immune and metabolic disorders induced by circadian dysregulation. Further, the data provided potential targets for developing probiotics for individuals with circadian disruption such as shift workers.
Is islet amyloid polypeptide indeed expressed in the human brain?
Authors: Libard Sylwia , Alafuzoff Irina
Published: June 2023

Aims

This study aims to study the association between pancreatic islet amyloid polypeptide (IAPP) and Alzheimer's disease neuropathological change (ADNC) in brain biopsies obtained from subjects with idiopathic normal pressure hydrocephalus (iNPH) and in post‐mortem (PM) brain samples obtained from aged individuals.

Methods

For the immunohistochemical (IHC) analyses, two IAPP antibodies (Abs), monoclonal and polyclonal, and Abs directed towards ADNC were applied.

Results

The iNPH cohort included 113 subjects. Amyloid‐β (Aβ) was detected in 50% and hyperphosphorylated τ (HPτ) in 47% of the cases. Concomitant pathology was seen in 32%. The PM cohort included 77 subjects. Aβ was detected in 69% and HPτ in 91% of the cases. Combined Aβ/HPτ pathology was seen in 62%. Reactivity for the monoclonal IAPP was not detected in the brain tissue in either of the cohorts. Reactivity for the polyclonal IAPP was observed in all 77 PM brain samples.

Conclusions

There was no specific expression of IAPP in human brain tissue; hence, an association between IAPP and ADNC is not assessable. Of note, the observed reactivity of the polyclonal IAPP Ab was not reproduced with a specific monoclonal Ab; thus, we considered the observed staining with the polyclonal Ab to be unreliable. When using IHC, several pitfalls, especially the choice of an Ab, always need to be considered. Polyclonal Abs cross‐react with other epitopes and proteins, thus leading to false‐positive results. This seems to be the case for the polyclonal IAPP Abs in the human brain.
Struggling to return to everyday life—The experiences of quality of life 1 year after delirium in the intensive care unit
Authors: Mortensen Camilla Bekker , Collet Marie Oxenbøll , Samuelson Karin
Published: June 2023

Background

Many critically ill patients report a change in their health‐related quality of life after intensive care unit (ICU) discharge. Patients who experience delirium during their ICU stay are perceived as a fragile group of ICU survivors, and the ‘quality of life’ phenomenon needs to be studied among these patients.

Aim

To explore everyday life experiences of critically ill patients with delirium during the ICU stay, from ICU discharge until 1‐year follow‐up, focusing on their health‐related quality of life and cognitive function.

Study Design

We used a descriptive qualitative research design and interviewed patients 1 year after ICU admission. The participants were recruited from a pre‐planned one‐year follow‐up study of ’Agents Intervening against Delirium for patients in the Intensive Care Unit trial’. Data were analysed using Framework Analysis Method and content analysis.

Results

Nine women and eight men participated and reported a struggle when returning to everyday life or adapting to a new normality from hospital discharge to 1 year later. None of the participants had been aware of the challenges they would face after hospital discharge. They described a need for more information about these challenges to themselves and about primary care to better understand their situation and the struggles they experience during recovery. One overall theme emerged from the analysis ‘From enduring to adapting’ with three subthemes: ‘Struggling to regain a functional life’, ‘Struggling to regain normal cognition’ and ‘Distressing manifestations from the ICU’.

Conclusions

To improve recovery and the quality of rehabilitation for critically ill patients suffering from delirium, it is essential to understand the phenomenon of ICU survivorship and what this fragile group of patients is going through. It is necessary to bridge the gap between secondary and primary care so patients can receive optimal training and support when needed.

Relevance to Clinical Practice

Bridging the gap between primary and secondary healthcare services is urgently needed to improve rehabilitation for ICU survivors after critical illness.
Differentiation of rhizosphere fungal assemblages by host ploidy level in mixed‐ploidy Larrea tridentata populations
Authors: Gerstner Benjamin P. , Mann Michael A. , Laport Robert G. , Whitney Kenneth D.
Published: June 2023

Polyploidy – whole genome duplication – is common in plants. Studies over the last several decades have documented numerous mixed‐ploidy populations. Whether arising via recurrent whole genome duplication events within a population, or from secondary contact, the persistence of mixed populations is possible by niche differentiation. Specifically, one mechanism facilitating ploidy co‐occurrence is microbially‐mediated niche differentiation (MMND), wherein cytotypes occupy different niches via interactions with different sets of microbes. Inherently cryptic, MMND is underexplored in polyploid plant populations. Here, we search for evidence of MMND in creosotebush Larrea tridentata, a dominant desert shrub of the southwestern US and northern Mexico. We sequenced root‐associated fungal taxa in soils of diploid, autotetraploid, and autohexaploid plants growing in two naturally‐occurring mixed‐cytotype populations. Within populations, we found substantial fungal assemblage overlap across host plant cytotypes. However, using indicator species analysis, we identified some fungi that are differentiated by host plant cytotype, satisfying a necessarycondition for MMND. Future study is needed to determine the degree of niche differentiation conferred, if any, and whether the identified fungi play a role in the long‐term persistence of multiple cytotypes within populations.
Genomic and species diversity patterns across multiple trophic levels in riverscapes
Authors: Fargeot Laura , Poesy Camille , Lefort Maxim , Prunier Jérôme G. , Krick Madoka , Veyssière Charlotte , Richard Murielle , Mercier Chiara , Sautreuil Morgan , Huberson Natan , Langford Nadia , Legrand Delphine , Loot Géraldine , Blanchet Simon
Published: June 2023

Testing whether intra‐ and interspecific biodiversity facets co‐vary spatially across trophic levels is of utmost importance to generalize processes driving biodiversity patterns in natural landscapes. Similar processes are expected to act on intra‐ and interspecific diversity, which should lead to positive co‐variation between genetic and species diversity. Although this prediction has been verified within trophic levels, it has rarely been tested across multiple trophic levels. To meet this challenge, we focused on a riverine freshwater ecosystem in which we sampled intra‐ (genomic diversity) and interspecific (species diversity) data across three trophic levels: riparian trees, benthic macroinvertebrates and fishes. For each trophic level, we quantified α‐ and β‐diversity at both the intra‐ (SNP diversity within populations of Alnus glutinosa, Gammarus sp. or Phoxinus dragarum) and interspecific levels (species diversity within communities). We first tested for a global spatial co‐variation of diversity across trophic levels and diversity facets. We then tested whether relevant environmental parameters similarly affected each biodiversity estimate and explained potential spatial co‐variation among biodiversity components. We did not evidence any spatial co‐variation of biodiversity across trophic levels and diversity facets, neither for α‐ nor for β‐diversity. We found that sites situated in the Western part of the sampling area had higher α‐diversities, and that highly connected sites had lower β‐diversities, which holds true for all trophic levels and diversity facets. Nonetheless, the effects of other environmental predictors were specific to each biodiversity component, likely explaining the absence of spatial co‐variation among biodiversity components. Our study demonstrates that global biodiversity patterns in rivers can be hard to generalize and are rather idiosyncratic, even though a few processes might have consistent impacts on biodiversity components across trophic levels.
Choroidal vascularity index as an activity criterion and a treatment response measure in chronic central serous chorioretinopathy
Authors: Sevik Mehmet Orkun , Aykut Aslan , Çam Furkan , Dericioğlu Volkan , Şahin Özlem
Published: June 2023

Purpose

This study aimed to evaluate the choroidal vascularity index (CVI) as an activity criterion in chronic central serous chorioretinopathy (CSC) and as a measure of treatment response after full‐dose‐full‐fluence photodynamic therapy (fd‐ff‐PDT).

Methods

This fellow‐eye‐controlled, retrospective cohort study included 23 patients with unilateral chronic CSC treated with fd‐ff‐PDT (6 mg/m2; 50 μcm2; 83 s). Subfoveal choroidal thickness (SFCT, μm) and CVI (%) of the affected and fellow eyes at baseline as well as at 1, 3 and 6 months after fd‐ff‐PDT were compared.

Results

The patients' mean age was 43.4 ± 7.3 years, and 18 (78.3%) were male. CVI was comparable between the affected and fellow eyes at baseline (66.09 ± 1.56 vs. 65.84 ± 1.57, p = 0.59). However, it became significantly lower in the affected eyes 1 (64.45 ± 1.68 vs. 65.87 ± 1.19, p = 0.002), 3 (64.21 ± 2.08 vs. 65.71 ± 1.59, p = 0.009) and 6 (64.47 ± 2.19 vs. 65.62 ± 1.52, p = 0.045) months after fd‐ff‐PDT. The mean SFCT and the mean CVI were significantly decreased in the affected eyes at all follow‐up visits compared with baseline after fd‐ff‐PDT (p < 0.001).

Conclusion

At baseline, CVI was comparable between affected and fellow eyes. Therefore, its use as an activity criterion in chronic CSC patients is questionable. However, it was significantly decreased in fd‐ff‐PDT‐treated eyes, supporting its role as a measure of treatment response in chronic CSC.
Incidence and predictors of pacemaker implantation at follow‐up after reversible high‐degree sinus node dysfunction or atrioventricular block
Authors: Habbout Ahmed , Sagnard Audrey , Pommier Thibaut , Didier Romain , Garnier Fabien , Fichot Marie , Bertaux Géraldine , Laurent Gabriel , Guenancia Charles
Published: June 2023

Background

A pacemaker implantation is not indicated in cases of reversible high‐degree symptomatic sinus node dysfunction (SND) and atrioventricular block (AVB). However, it remains uncertain whether these reversible automaticity/conduction disorders may recur in some patients at follow‐up, in the absence of reversible cause. This retrospective study aimed to determine the incidence and predictive factors of permanent pacemaker (PPM) implantation at follow‐up and after reversible high‐degree SND/AVB.

Methods

Based on medical electronic files codes, we identified patients who were hospitalized in our cardiac intensive care unit between January 2003 and December 2020 due to reversible high‐degree SND/AVB and who were discharged from the hospital alive and without PPM implantation. Acute myocardial infarction and post‐cardiac surgery patients were excluded. We categorized the patients according to the need for PPM at follow‐up due to non‐reversible high‐degree SND/AVB.

Results

Of the 93 patients included, 26 patients (28%) were readmitted for PPM implantation at follow‐up after hospital discharge. Among baseline characteristics, compared with patients who did not have high‐degree SND/AVB recurrence, those who had subsequent PPM implantation had less frequent previous hypertension (70% vs. 46%, p = .031). Regarding the initial causes of reversible SND/AVB, isolated hyperkalemia was found more often in the patients readmitted for PPM (19% vs. 3% vs. p = .017). Moreover, recurrence of high‐degree SND/AVB was significantly associated with the presence of intraventricular conduction disorders (either bundle branch block or left bundle branch hemiblock) on ECG at discharge (36% in patients without PPM vs. 68% in PPM patients, p = .012).

Conclusion

Almost one third of the patients discharged alive from the hospital after a reversible high‐degree SND/AVB needed a pacemaker implantation at follow‐up. Complete bundle branch block or left bundle branch hemiblock on discharge ECG after recovery of atrioventricular conduction and/or sinus automaticity was associated with a greater risk of recurrence leading to pacemaker implantation.
Virtual interviewing with marginalized young adult mothers: appreciating the New Norm
Authors: Flaherty Serena C. , Sadler Lois S.
Published: June 2023

Background and Objective

Virtual interviewing in qualitative research may promote inclusion, diversify samples, and maximize participation, but there is limited research regarding methodological best practices for marginalized study populations. Emerging adult (ages 18–29) and young adult (through age 40) mothers have ongoing stressors and competing responsibilities that may preclude participation with in‐person interviews. The purpose of this article is to describe the processes and experiences of virtual interviewing among young adult mothers living in under‐resourced communities, based on their responses to specific interview questions.

Design and Sample

As part of an explanatory sequential mixed methods study, qualitative interviews were conducted with a sample of young adult mothers who had previously participated in randomized controlled trials testing an intensive early home visiting intervention. Thirty‐one participants (M = 29.7 years, SD = 2.5) who identified as Black (39%), Hispanic (55%), and White (7%), were interviewed using Zoom.

Results

The overarching theme was Zoom: Appreciating the New Norm. Identified categories were Practical Benefits of Virtual Interviewing, Sharing Stories, and Drawbacks of Virtual Interviewing.

Conclusion

Findings support virtual interviewing as a feasible and potentially ideal method for qualitative studies with emerging/young adults. Further research to examine this approach with other marginalized populations may lead to more inclusive representation in qualitative research.
Biochemical changes after cold acclimation in Nordic red clover (Trifolium pratense L.) accessions with contrasting levels of freezing tolerance
Authors: Zanotto Stefano , Bertrand Annick , Purves Randy W. , Olsen Jorunn E. , Elessawy Fatma M. , Ergon Åshild
Published: June 2023

The ability to tolerate low freezing temperatures is an important component of winter survival and persistence of red clover. Cold acclimation (CA) allows plants to acquire higher levels of freezing tolerance. However, the biochemical responses to cold and the importance of such changes for the plant to acquire adequate freezing tolerance have not been investigated in red clover of Nordic origin, which has a distinct genetic background. To shed light on this, we selected five freezing tolerant (FT) and five freezing susceptible (FS) accessions and studied the effect of CA on the contents of carbohydrates, amino acids, and phenolic compounds in the crowns. Among those compounds which increased during CA, FT accessions had higher contents of raffinose, pinitol, arginine, serine, alanine, valine, phenylalanine, and one phenolic compound (a pinocembrin hexoside derivative) than FS accessions, suggesting a role for these compounds in the freezing tolerance in the selected accessions. These findings, together with a description of the phenolic profile of red clover crowns, significantly add to the current knowledge of the biochemical changes during CA and their role in freezing tolerance in Nordic red clover.
Does the exponential Wells–Riley model provide a good fit for human coronavirus and rhinovirus? A comparison of four dose–response models based on human challenge data
Authors: Aganovic Amar , Kadric Edin
Published: June 2023

The risk assessments during the COVID‐19 pandemic were primarily based on dose–response models derived from the pooled datasets for infection of animals susceptible to SARS‐CoV. Despite similarities, differences in susceptibility between animals and humans exist for respiratory viruses. The two most commonly used dose–response models for calculating the infection risk of respiratory viruses are the exponential and the Stirling approximated β‐Poisson (BP) models. The modified version of the one‐parameter exponential model or the Wells–Riley model was almost solely used for infection risk assessments during the pandemic. Still, the two‐parameter (α and β) Stirling approximated BP model is often recommended compared to the exponential dose–response model due to its flexibility. However, the Stirling approximation restricts this model to the general rules of β ≫ 1 and α ≪ β, and these conditions are very often violated. To refrain from these requirements, we tested a novel BP model by using the Laplace approximation of the Kummer hypergeometric function instead of the conservative Stirling approximation. The datasets of human respiratory airborne viruses available in the literature for human coronavirus (HCoV‐229E) and human rhinovirus (HRV‐16 and HRV‐39) are used to compare the four dose–response models. Based on goodness‐of‐fit criteria, the exponential model was the best fitting model for the HCoV‐229E (k = 0.054) and for HRV‐39 datasets (k = 1.0), whereas the Laplace approximated BP model followed by the exact and Stirling approximated BP models are preferred for both the HRV‐16 (α = 0.152 and β = 0.021 for Laplace BP) and the HRV‐16 and HRV‐39 pooled datasets (α = 0.2247 and β = 0.0215 for Laplace BP).
Aggregation‐prone peptides from within a non‐self‐protein homoaggregate are preferred for MHC association: Historical overview
Authors: Forsdyke Donald R.
Published: June 2023

New technologies assist re‐evaluation of hypotheses on generation of immune cell repertoires and distinctions of self from non‐self. Findings include positive correlations between peptide propensities to aggregate and their binding to major histocompatibility complex (MHC) proteins. This recalls the hypothesis that foreign proteins may homoaggregate in host cytosols prior to releasing their peptides (p) to form pMHC complexes. Clues to this included aggregation‐related phenomena associated with infections (rouleaux formation, pyrexia, certain brain diseases). By virtue of ‘promiscuous’ gene expression by thymic presenting cells – perhaps adapted from earlier evolving gonadal mechanisms – developing T cells monitor surface pMHC clusterings. This evaluates intracellular concentrations of the corresponding proteins, and hence, following Burnet's two signal principle, degrees of self‐reactivity. After positive selection in the thymic cortex for reactivity with ‘near‐self’, high‐level pMHC clustering suffices in the medulla for negatively selection. Following Burnet's principle, in the periphery low‐level clustering suffices for T cell stimulation and high‐level clustering again provokes negative selection (immunological tolerance). For evolving intracellular pathogens, fine‐tuned polymorphisms of their host species have limited to ‘near‐self’ some mimicking adaptations. It is proposed that while entire pathogen proteins may have evolved to minimize their aggregability, the greater aggregability of their peptides remains partially hidden within. Two‐step proofreading mechanisms in prospective hosts select proteins containing aggregable peptide for the generation of pMHC clusters at the surface of presenting cells. Through mutations, some proteins of pathogens and cancer cells tend to converge towards the host ‘near‐self’ that its T cells have auditioned to address.
Including the patient in patient blood management: Development and assessment of an educational animation tool
Authors: Arya Sumedha , Xiang Tracy , Tang Grace H. , Pavenski Katerina
Published: June 2023

Background

Patient blood management (PBM) programs are effective at reducing transfusion‐associated mortality and morbidity; however, patient engagement within the realm of PBM remains relatively unstudied. Our objectives were to develop a novel educational tool utilizing animation to educate preoperative patients about anemia and to evaluate the effectiveness of this intervention.

Study Design and Methods

We created a patient‐facing animation for preoperative surgical patients. The animation addressed characters' health journeys from diagnosis to treatment, addressing the role of PBM. We utilized the concept of patient activation as a means to empower patients, and developed the animation to be as accessible as possible. Post‐viewing, patients provided feedback utilizing an electronic survey.

Results

A final version of the animation can be found here: https://vimeo.com/495857315. A total of 51 participants viewed our animation, the majority of whom were planned to undergo joint replacement or cardiac surgery. Almost all (94%, N = 4) agreed that taking an active role in their health was the most important factor in determining their ability to function. The video was felt to be easy to understand (96%, N = 49), and 92% (N = 47) agreed that they had a better understanding of anemia and its treatment. After watching the animation, patients felt more certain that they could follow through with their PBM plan (98%, N = 50).

Discussion

To the best of our knowledge, there are no other PBM‐specific patient education animations. Patients enjoyed learning about PBM though animation, and patient education may lead to better uptake of PBM interventions. We hope that other hospitals will be inspired to pursue this approach.
Relative regular Riemann–Hilbert correspondence II
Authors: Fiorot Luisa , Monteiro Fernandes Teresa , Sabbah Claude
Published: June 2023

We develop the theory of relative regular holonomic $\mathcal {D}$-modules with a smooth complex manifold $S$ of arbitrary dimension as parameter space, together with their main functorial properties. In particular, we establish in this general setting the relative Riemann–Hilbert correspondence proved in a previous work in the one-dimensional case.