bluuebunny/crossref_metadata_2025 huggingface dataset:
IQ domain-containing protein ZmIQD27 modulates water transport in maize
Authors: Li Haiyan , Xie Jun , Gao Yongmeng , Wang Xuemei , Qin Li , Ju Wei , Roberts Jeremy A , Cheng Beijiu , Zhang Xuebin , Lu Xiaoduo
Published: July 2023

Plant metaxylem vessels provide physical support to promote upright growth and the transport of water and nutrients. A detailed characterization of the molecular network controlling metaxylem development is lacking. However, knowledge of the events that regulate metaxylem development could contribute to the development of germplasm with improved yield. In this paper, we screened an EMS-induced B73 mutant library, which covers 92% of maize (Zea mays) genes, to identify drought-sensitive phenotypes. Three mutants were identified, named iqd27-1, iqd27-2, and iqd27-3, and genetic crosses showed that they were allelic to each other. The causal gene in these 3 mutants encodes the IQ domain-containing protein ZmIQD27. Our study showed that defective metaxylem vessel development likely causes the drought sensitivity and abnormal water transport phenotypes in the iqd27 mutants. ZmIQD27 was expressed in the root meristematic zone where secondary cell wall deposition is initiated, and loss-of-function iqd27 mutants exhibited a microtubular arrangement disorder. We propose that association of functional ZmIQD27 with microtubules is essential for correct targeted deposition of the building blocks for secondary cell wall development in maize.
Photosystem II monomeric antenna CP26 plays a key role in nonphotochemical quenching in Chlamydomonas
Authors: Cazzaniga Stefano , Kim Minjae , Pivato Matteo , Perozeni Federico , Sardar Samim , D’Andrea Cosimo , Jin EonSeon , Ballottari Matteo
Published: July 2023

Thermal dissipation of excess excitation energy, called nonphotochemical quenching (NPQ), is 1 of the main photoprotective mechanisms in oxygenic photosynthetic organisms. Here, we investigated the function of the monomeric photosystem II (PSII) antenna protein CP26 in photoprotection and light harvesting in Chlamydomonas reinhardtii, a model organism for green algae. We used CRISPR/Cas9 genome editing and complementation to generate cp26 knockout mutants (named k6#) that did not negatively affect CP29 accumulation, which differed from previous cp26 mutants, allowing us to compare mutants specifically deprived of CP26, CP29, or both. The absence of CP26 partially affected PSII activity, causing reduced growth at low or medium light but not at high irradiances. However, the main phenotype observed in k6# mutants was a more than 70% reduction of NPQ compared to the wild type (Wt). This phenotype was fully rescued by genetic complementation and complemented strains accumulating different levels of CP26, demonstrating that ∼50% of CP26 content, compared to the Wt, was sufficient to restore the NPQ capacity. Our findings demonstrate a pivotal role for CP26 in NPQ induction, while CP29 is crucial for PSII activity. The genetic engineering of these 2 proteins could be a promising strategy to regulate the photosynthetic efficiency of microalgae under different light regimes.
DNA methylation role in subgenome expression dominance of Juglans regia and its wild relative J. mandshurica
Authors: Li Mengdi , Ou Mengwei , He Xiaozhou , Ye Hang , Ma Jiayu , Liu Hengzhao , Yang Huijuan , Zhao Peng
Published: July 2023

Subgenome expression dominance plays a crucial role in the environmental adaptation of polyploids. However, the epigenetic molecular mechanism underlying this process has not been thoroughly investigated, particularly in perennial woody plants. Persian walnut (Juglans regia) and its wild relative, Manchurian walnut (Juglans mandshurica), are woody plants of great economic importance and are both paleopolyploids that have undergone whole-genome duplication events. In this study, we explored the characteristics of subgenome expression dominance in these 2 Juglans species and examined its epigenetic basis. We divided their genomes into dominant subgenome (DS) and submissive subgenome (SS) and found that the DS-specific genes might play critical roles in biotic stress response or pathogen defense. We comprehensively elucidated the characteristics of biased gene expression, asymmetric DNA methylation, transposable elements (TEs), and alternative splicing (AS) events of homoeologous gene pairs between subgenomes. The results showed that biased expression genes (BEGs) in 2 Juglans species were mainly related to external stimuli response, while non-BEGs were related to complexes that might be involved in signal transduction. DS genes had higher expression and more AS events while having less DNA methylation and TEs than homoeologous genes from the SS in the 2 Juglans species. Further studies showed that DNA methylation might contribute to the biased expression of gene pairs by modifying LTR/TIR/nonTIR TEs and improving the AS efficiency of corresponding precursor mRNAs in a particular context. Our study contributes to understanding the epigenetic basis of subgenome expression dominance and the environmental adaptation of perennial woody plants.
How membership in the North Atlantic Treaty Organization transforms public support for war
Authors: Tomz Michael , Weeks Jessica L P , Bansak Kirk
Published: July 2023

How do military alliances affect public support for defending targets of aggression? We studied this question by fielding an experiment on 14,000 voters in 13 member countries of the North Atlantic Treaty Organization (NATO). Our experiment involved a hypothetical scenario in which Russia attacked a target country. We randomly varied the identity of the target (Bosnia, Finland, Georgia, or Sweden), and whether the target was a member of NATO at the time of the attack. We found that voters in every member country were far more willing to use military force to defend each target when the target was in NATO, than when the target was outside the alliance. The expansion of NATO could, therefore, transform European security by altering the likelihood and scale of future wars. We also uncovered important heterogeneity across targets: the benefits of joining NATO were considerably larger for Bosnia and Georgia than for Finland and Sweden, since most voters in NATO countries would defend Finland and Sweden even if they remained outside the alliance. Finally, the effect of NATO was much stronger among voters who perceived NATO as valuable for their own country. Rhetorical attacks on NATO could, therefore, undermine the alliance by eroding the public's willingness to defend other members, whereas rhetoric highlighting the benefits of NATO could bolster defense and deterrence. These findings advance knowledge about the effects of alliances, while also informing policy debates about the value and size of NATO.
Nudging enforcers: how norm perceptions and motives for lying shape sanctions
Authors: Dimant Eugen , Gesche Tobias
Published: July 2023

We conduct three studies, employing diverse methodologies (a behavioral experiment, a vignette experiment, and a norm elicitation experiment), to investigate when and how norm enforcement patterns can be modified using norm interventions in the context of dishonesty. Our preregistered, three-part data collection effort explores the extent to which norm violations are sanctioned, the impact of norm-nudges on punishment behavior, and the connection to norm perception. Using a representative sample of US participants in Study 1, we present robust evidence that norm enforcement is sensitive not only to the magnitude of the observed transgression (i.e. the size of the lie) but also to its consequences (whether the lie addresses or creates payoff inequalities). We also find that norm enforcers respond to norm-nudges conveying social information about actual lying behavior or its social disapproval. The results of a separate vignette experiment in Study 2 are consistent with the results in our behavioral experiment, thus hinting at the generalizability of our findings. To understand the interplay of norms, information about them, and punishment, we examine norm perceptions across different transgressions in Study 3. We find that norm perceptions are malleable and norm-nudges are most effective when preexisting norms are ambiguous. In sum, we show how norm enforcement can be nudged and which factors matter for doing so across various contexts and discuss their policy implications.
The effects of an active breaks intervention on physical and cognitive performance: results from the I-MOVE study
Authors: Masini Alice , Marini Sofia , Ceciliani Andrea , Barone Giuseppe , Lanari Marcello , Gori Davide , Bragonzoni Laura , Toselli Stefania , Stagni Rita , Bisi Maria Cristina , Sansavini Alessandra , Tessari Alessia , Dallolio Laura
Published: July 2023

Background

The present quasi-experimental study aimed to evaluate the effects of active breaks intervention (ABs) to promote physical and cognitive improvement in primary school.

Methods

The active breaks group (ABsG) performed 10 min of ABs three times per school day and the control group (CG) did normal lessons. The baseline and follow-up evaluation was conducted respectively in October 2019 and in May 2021. Cognitive performance was assessed using working memory test, physical performance was analyzed with ActiGraph accelerometers and physical fitness tests, quality of life was monitored using the Paediatric Quality of Life questionnaire (PedsQL) and classroom behavior was collected with an ad hoc questionnaire.

Results

We enrolled 153 children (age: 7.61 ± 1.41, 54.2% males). Working memory significantly increased in the ABsG (ΔWM: 1.30 ± 1.17) than in CG (ΔWM: 0.96 ± 1.20). The 6 min Cooper test increased in the ABsG (Δ: 1.77 ± 136.03) but not in CG (Δ: −156.42 ± 187.53), P < 0.05. The weekly physical activity levels increased in both groups; however, the sedentary behavior significantly increased both in ABsG and CG. Children reported improvements in their quality of school life including feeling better in class and in school when using ABs; moreover, children improved their time on task behaviors in ABsG.

Conclusion

The present study has proven to be effective on children’s physical and cognitive performance.
Predicting and Preventing Gun Violence: An Experimental Evaluation of READI Chicago
Authors: Bhatt Monica P , Heller Sara B , Kapustin Max , Bertrand Marianne , Blattman Christopher
Published: July 2023

Gun violence is the most pressing public safety problem in U.S. cities. We report results from a randomized controlled trial (N = 2,456) of a community-researcher partnership called the Rapid Employment and Development Initiative (READI) Chicago. The program offered an 18-month job alongside cognitive behavioral therapy and other social support. Both algorithmic and human referral methods identified men with strikingly high scope for gun violence reduction: for every 100 people in the control group, there were 11 shooting and homicide victimizations during the 20-month outcome period. Fifty-five percent of the treatment group started programming, comparable to take-up rates in programs for people facing far lower mortality risk. After 20 months, there is no statistically significant change in an index combining three measures of serious violence, the study’s primary outcome. Yet there are signs that this program model has promise. One of the three measures, shooting and homicide arrests, declined 65% (p = .13 after multiple-testing adjustment). Because shootings are so costly, READI generated estimated social savings between ${\$}$182,000 and ${\$}$916,000 per participant (p = .03), implying a benefit-cost ratio between 4:1 and 18:1. Moreover, participants referred by outreach workers—a prespecified subgroup—saw enormous declines in arrests and victimizations for shootings and homicides (79% and 43%, respectively) which remain statistically significant even after multiple-testing adjustments. These declines are concentrated among outreach referrals with higher predicted risk, suggesting that human and algorithmic targeting may work better together.
Psychological stress, the central nervous system and arrhythmias
Authors: Lambiase P D , Garfinkel S N , Taggart P
Published: July 2023

This review highlights the links between psychological stress and the neurocircuitry of cardiac–brain interactions leading to arrhythmias. The role of efferent and afferent connections in the heart–brain axis is considered, with the mechanisms by which emotional responses promote arrhythmias illustrated by inherited cardiac conditions. Novel therapeutic targets for intervention in the autonomic nervous system are considered.
Gut microbiota alterations are associated with phenotype and genotype in familial Mediterranean fever
Authors: Delplanque Marion , Benech Nicolas , Rolhion Nathalie , Oeuvray Cyriane , Straube Marjolène , Galbert Chloé , Brot Loic , Henry Thomas , Jamilloux Yvan , Savey Léa , Grateau Gilles , Sokol Harry , Georgin-Lavialle Sophie
Published: July 2023

Objective

FMF is the most common monogenic autoinflammatory disease associated with MEFV mutations. Disease phenotype and response to treatment vary from one patient to another, despite similar genotype, suggesting the role of environmental factors. The objective of this study was to analyse the gut microbiota of a large cohort of FMF patients in relation to disease characteristics.

Methods

The gut microbiotas of 119 FMF patients and 61 healthy controls were analysed using 16 s rRNA gene sequencing. Associations between bacterial taxa, clinical characteristics, and genotypes were evaluated using multivariable association with linear models (MaAslin2), adjusting on age, sex, genotype, presence of AA amyloidosis (n = 17), hepatopathy (n = 5), colchicine intake, colchicine resistance (n = 27), use of biotherapy (n = 10), CRP levels, and number of daily faeces. Bacterial network structures were also analysed.

Results

The gut microbiotas of FMF patients differ from those of controls in having increased pro-inflammatory bacteria, such as the Enterobacter, Klebsiella and Ruminococcus gnavus group. Disease characteristics and resistance to colchicine correlated with homozygous mutations and were associated with specific microbiota alteration. Colchicine treatment was associated with the expansion of anti-inflammatory taxa such as Faecalibacterium and Roseburia, while FMF severity was associated with expansion of the Ruminococcus gnavus group and Paracoccus. Colchicine-resistant patients exhibited an alteration of the bacterial network structure, with decreased intertaxa connectivity.

Conclusion

The gut microbiota of FMF patients correlates with disease characteristics and severity, with an increase in pro-inflammatory taxa in the most severe patients. This suggests a specific role for the gut microbiota in shaping FMF outcomes and response to treatment.
Asymmetric Information and Corporate Lending: Evidence from SME Bond Markets
Authors: Iannamorelli Alessandra , Nobili Stefano , Scalia Antonio , Zaccaria Luana
Published: July 2023

Using a comprehensive dataset of Italian small and medium-sized enterprises, we find that differences between private and public information on firm creditworthiness affect the decision to issue bonds. Our evidence supports favorable (rather than adverse) selection in corporate bond markets. Specifically, holding public information constant, firms with better private fundamentals are more likely to access bond markets. These effects are weaker for opaque firms and stronger for firms with worse publicly observable risk. Additionally, credit conditions improve for issuers following the bond placement, compared with a matched sample of non-issuers. This is consistent with a model where banks offer more flexibility than markets during financial distress and firms use market lending to signal credit quality to outside stakeholders.
Heritable epigenetic modification of BpPIN1 is associated with leaf shapes in Betula pendula
Authors: Gu Chenrui , Han Rui , Liu Chaoyi , Fang Gonggui , Yuan Qihang , Zheng Zhimin , Yu Qibin , Jiang Jing , Liu Sanzhen , Xie Linan , Wei Hairong , Zhang Qingzhu , Liu Guifeng
Published: July 2023

The new variety Betula pendula ‘Dalecarlica’, selected from Betula pendula, shows high ornamental value owing to its lobed leaf shape. In this study, to identify the genetic components of leaf shape formation, we performed bulked segregant analysis and molecular marker-based fine mapping to identify the causal gene responsible for lobed leaves in B. pendula ‘Dalecarlica’. The most significant variations associated with leaf shape were identified within the gene BpPIN1 encoding a member of the PIN-FORMED family, responsible for the auxin efflux carrier. We further confirmed the hypomethylation at the promoter region promoting the expression level of BpPIN1, which causes stronger and longer veins and lobed leaf shape in B. pendula ‘Dalecarlica’. These results indicated that DNA methylation at the BpPIN1 promoter region is associated with leaf shapes in B. pendula. Our findings revealed an epigenetic mechanism of BpPIN1 in the regulation of leaf shape in Betula  Linn. (birch), which could help in the molecular breeding of ornamental traits.
Do Working and Parenting Trajectories Influence Retirement Timing? Evidence From Spain, Using a Sequence Analysis Approach and Focusing on Women
Authors: Tambellini Elisa , Danielsbacka Mirkka , Rotkirch Anna
Published: July 2023

This paper investigates the association between accumulated experiences in the working and parenting spheres and retirement timing among Spanish women, utilizing data from the Survey of Health, Ageing and Retirement in Europe (SHARE). The study examines whether labor market attachment or cumulative disadvantage characterizes women’s retirement and how these factors relate with the number of children. Firstly, multichannel sequence analysis and cluster analysis were employed to identify distinct work–family life courses from ages 20 to 50. Seven clusters were identified: “Full-time work with 2+ children,” “Out of the labour force and 2+ children,” “Mid-life discontinuity and 2+ children,” “Full-time work and 1 child,” “Full-time work and childless,” “Part-time work and 2+ children,” and “Part-time work or out of the labor force and 1 child.” Secondly, the study examines the association between these identified groups and retirement timing. The results indicate that Spanish women who have experienced more unstable careers characterized by extended periods of inactivity or part-time work, particularly in combination with having 2 or more children, are more likely to retire at a later age compared with women with continuous careers, with or without children. These findings underscore the ongoing challenges of balancing unpaid care work and wage work in Spain, while also revealing notable variations among women.
Osmotic stress tolerance and transcriptomic response of Ramazzottius varieornatus (Eutardigrada: Ramazzottiidae) following tun formation
Authors: Emdee Napat , Møbjerg Ask , Grollmann Milena M , Møbjerg Nadja
Published: July 2023

To thrive in harsh environments, tardigrades have evolved the ability to enter the quiescent state of cryptobiosis, often characterized by transition into a so-called ‘tun’. Here, we investigate osmobiosis, a substate of cryptobiosis induced by rising osmolyte concentrations. We follow the behaviour and morphology of Ramazzottius varieornatus during transfer from freshwater conditions into 3 Osmol/kg sucrose solution. The tardigrades easily survive the extreme change in external osmolality. During gradual exposure, they initiate tun formation at 0.2 Osmol/kg, with most specimens fully contracted into a tun at 0.5 Osmol/kg. The first transcriptomic profiling of osmobiotic tuns in comparison to active tardigrades reveals a modest shift, with 16% of the 3322 differentially expressed transcripts having a |log2 fold change| > 1. A gene ontology enrichment analysis shows enrichment within protein homeostasis and neurohormonal signalling, with a ubiquitin-conjugating enzyme and neurotransmitter receptor transcripts being down- and upregulated, respectively. A putative Hsp70 is upregulated, whereas transcripts related to eutardigrade-specific proteins, antioxidant defence and DNA repair show minor fold changes. Among putative membrane transporters, a monocarboxylate and two amino acid transporters are downregulated. Our findings are in agreement with previous studies in Ramazzottius indicating that cryptobiosis and tun formation involve no change or modest change in transcription.
Clinical Evaluation of Competence in Nursing Education: What Do We Know?
Authors: Van Horn Elizabeth , Lewallen Lynne P.
Published: July 2023

AIM

The purpose of this article was to examine the research literature to identify objective, replicable measurement of clinical competence in undergraduate nursing education.

BACKGROUND

Although a standardized licensure examination is used to determine minimal competence to practice, no consensus on the definition or components of competence exists in the research literature.

METHOD

A comprehensive search was conducted to locate studies that evaluated nursing students’ general competence in the clinical setting. Twelve reports published from 2010 to 2021 were examined.

RESULTS

Measures to evaluate competence were varied and contained multiple concepts including attributes of knowledge, attitudes and behaviors, ethics and values, personal attributes, and cognitive or psychomotor skills. Most studies used researcher-created instruments.

CONCLUSION

Although essential to nursing education, competence in the clinical setting is not commonly defined or evaluated. The lack of standardized instruments has contributed to the use of varied methods and measures for evaluating competence in nursing education and research.
Improving Graduate Medical Education by Aggregating Data Across the Medical Education Continuum
Authors: Thelen Angela E. , George Brian C. , Burkhardt John C. , Khamees Deena , Haas Mary R.C. , Weinstein Debra
Published: July 2023

Meaningful improvements to graduate medical education (GME) have been achieved in recent decades, yet many GME improvement pilots have been small trials without rigorous outcome measures and with limited generalizability. Thus, lack of access to large-scale data is a key barrier to generating empiric evidence to improve GME. In this article, the authors examine the potential of a national GME data infrastructure to improve GME, review the output of 2 national workshops on this topic, and propose a path toward achieving this goal.

The authors envision a future where medical education is shaped by evidence from rigorous research powered by comprehensive, multi-institutional data. To achieve this goal, premedical education, undergraduate medical education, GME, and practicing physician data must be collected using a common data dictionary and standards and longitudinally linked using unique individual identifiers. The envisioned data infrastructure could provide a foundation for evidence-based decisions across all aspects of GME and help optimize the education of individual residents.

Two workshops hosted by the National Academies of Sciences, Engineering, and Medicine Board on Health Care Services explored the prospect of better using GME data to improve education and its outcomes. There was broad consensus about the potential value of a longitudinal data infrastructure to improve GME. Significant obstacles were also noted.

Suggested next steps outlined by the authors include producing a more complete inventory of data already being collected and managed by key medical education leadership organizations, pursuing a grass-roots data sharing pilot among GME-sponsoring institutions, and formulating the technical and governance frameworks needed to aggregate data across organizations.

The power and potential of big data is evident across many disciplines, and the authors believe that harnessing the power of big data in GME is the best next step toward advancing evidence-based physician education.
Association between “Balance Billing” Legislation and Anesthesia Payments in California: A Retrospective Analysis
Authors: Dixit Anjali A. , Heavner D. Lee , Baker Laurence C. , Sun Eric C.
Published: July 2023

Background

Insured patients who receive out-of-network care may receive a “balance bill” for the difference between the practitioner’s charge and their insurer’s contracted rate. In 2017, California banned balance billing for anesthesia care. This study examined the association between California’s law and subsequent payments for anesthesia care. The authors hypothesized that, after the law’s implementation, there would be no change in in-network payment amounts, and that out-of-network payment amounts and the portion of claims occurring out-of-network would decline.

Methods

The study used average, quarterly, California county-level payment data (2013 to 2020) derived from a claims database of commercially insured patients. Using a difference-in-differences approach, the change was estimated in payment amounts for intraoperative or intrapartum anesthesia care, along with the portion of claims occurring out-of-network, after the law’s implementation. The comparison group was office visit payments, expected to be unaffected by the law. The authors prespecified that they would refer to differences of 10% or greater as policy significant.

Results

The sample consisted of 43,728 procedure code-county-quarter-network combinations aggregated from 4,599,936 claims. The law’s implementation was associated with a significant 13.6% decline in payments for out-of-network anesthesia care (95% CI, –16.5 to –10.6%; P < 0.001), translating to an average $108 decrease across all procedures (95% CI, –$149 to –$64). There was a statistically significant 3.0% increase in payments for in-network anesthesia care (95% CI, 0.9 to 5.1%; P = 0.007), translating to an average $87 increase (95% CI, $64 to $110), which may be notable in some circumstances but did not meet the study threshold for identifying a change as policy significant. There was a nonstatistically significant increase in the portion of claims occurring out-of-network (10.0%, 95% CI, –4.1 to 24.2%; P = 0.155).

Conclusions

California’s balance billing law was associated with significant declines in out-of-network anesthesia payments in the first 3 yr after implementation. There were mixed statistical and policy significant results for in-network payments and the proportion of out-of-network claims.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Vaspin alleviates pathological cardiac hypertrophy by regulating autophagy-dependent myocardial senescence
Authors: Rui Haiying , Yu Huaxiang , Zou Dan , Chi Kai , Xu Ping , Song Xiaoshuai , Liu Lulu , Wu Xuting , Wang Jinxin , Xue Li
Published: July 2023

Background

Visceral adipose tissue–derived serine protease inhibitor (vaspin), a secretory adipokine, protects against insulin resistance. Recent studies have demonstrated that serum vaspin levels are decreased in patients with coronary artery disease and that vaspin protects against myocardial ischemia-reperfusion injury and atherosclerosis. However, it remains unclear whether vaspin exerts specific effects on pathological cardiac hypertrophy.

Methods

An in vivo study was conducted using a cardiac hypertrophy model established by subcutaneous injection of isoproterenol (ISO) in C57BL/6 and vaspin-ko mice. Rapamycin was administered intraperitoneally to mice, for further study. H9c2 cells and neonatal rat ventricular myocytes (NRVMs) were treated with ISO to induce hypertrophy. Human vaspin fusion protein, the proteasome inhibitor MG132, and chloroquine diphosphate were used for further mechanistic studies.

Results

Here, we provide the first evidence that vaspin knockdown results in markedly exaggerated cardiac hypertrophy, fibrosis, and cardiomyocyte senescence in mice treated with ISO. Conversely, the administration of exogenous recombinant human vaspin protected NRVMs in vitro against ISO-induced hypertrophy and senescence. Furthermore, vaspin significantly potentiated the ISO-induced decrease in autophagy. Both rapamycin and chloroquine diphosphate regulated autophagy in vivo and in vitro, respectively, and participated in vaspin-mediated cardioprotection. Moreover, the PI3K-AKT-mTOR pathway plays a critical role in vaspin-mediated autophagy in cardiac tissues and NRVMs. Our data showed that vaspin downregulated the p85 and p110 subunits of PI3K by linking p85 and p110 to NEDD4L-mediated ubiquitination degradation.

Conclusion

Our results show, for the first time, that vaspin functions as a critical regulator that alleviates pathological cardiac hypertrophy by regulating autophagy-dependent myocardial senescence, providing potential preventive and therapeutic targets for pathological cardiac hypertrophy.
The M1-muscarinic acetylcholine receptor subtype may play a role in learning and memory performance in the hippocampus of neonatal monosodium glutamate-obese rats
Authors: Silva Marcelo Florencio Passos , Rafael Christian Pereira , Mamona Silva Jeferson Rubens , e Silva Tiago Guardia de Souza , Alponti Rafaela Fadoni , Alves Patricia Lucio , Sandoval Maria Regina Lopes , Abdalla Fernando Maurício Francis
Published: July 2023

Here, we investigate the effects of obesity induced by monosodium glutamate (MSG) on cognitive impairment and whether this model induces any alteration in the affinity, density, and subtypes of muscarinic acetylcholine receptors (mAChRs) in rat hippocampus. Healthy rats were used as controls, and MSG-obese rats were selected via the Lee index > 0.300. The effects of MSG-induced obesity on hippocampal spatial learning and memory processes were evaluated by using the working memory versions of the Morris’ water maze task and the evaluation of mAChRs by binding assay and their subtypes by immunoprecipitation assays. [3H]Quinuclidinyl benzilate specific binding analysis showed that the equilibrium dissociation constant (KD) did not differ between control and MSG, indicating that affinity is not affected by obesity induced by MSG. The maximum number of binding sites (Bmax) obtained in MSG subjects was lower than that obtained from control rats, indicating a decrease in the expression of total mAChRs. Immunoprecipitation assays reveal a decrease in the expression of M1 subtype of MSG when compared with control rats (M2 to M5 subtypes did not differ between control and MSG). We also observed that MSG promotes a disruption of the spatial working memory which was accompanied by a decrease in the M1 mAChR subtype in rat hippocampus, thus suggesting deleterious long-term effects besides the obesity. In conclusion, these findings provide new insights into how obesity can influence spatial learning and memory that is hippocampal-dependent. The data suggest that the M1 mAChR subtype protein expression is a potential therapeutic target.
Radiation and Dose-densification of R-CHOP in Primary Mediastinal B-cell Lymphoma: Subgroup Analysis of the UNFOLDER Trial
Authors: Held Gerhard , Thurner Lorenz , Poeschel Viola , Ott German , Schmidt Christian , Christofyllakis Konstantinos , Viardot Andreas , Borchmann Peter , Engel-Riedel Walburga , Frickhofen Norbert , Nickelsen Maike , Shpilberg Ofer , Witzens-Harig Mathias , Griesinger Frank , Krammer-Steiner Beate , Neubauer Andreas , de Nully Brown Peter , Federico Massimo , Glass Bertram , Schmitz Norbert , Wulf Gerald , Truemper Lorenz , Bewarder Moritz , Murawski Niels , Stilgenbauer Stephan , Rosenwald Andreas , Altmann Bettina , Engelhard Marianne , Schmidberger Heinz , Fleckenstein Jochen , Berdel Christian , Loeffler Markus , Ziepert Marita ,   on behalf of the German Lymphoma Alliance (GLA)
Published: July 2023

UNFOLDER (NCT00278408, EUDRACT 2005-005218-19) is a phase-3 trial in patients with aggressive B-cell lymphoma and intermediate prognosis, including primary mediastinal B-cell lymphoma (PMBCL). In a 2 × 2 factorial design, patients were randomized to 6× R-CHOP-14 or R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prediso(lo)ne) and to consolidation radiotherapy to extralymphatic/bulky disease or observation. Response was assessed according to the standardized criteria from 1999, which did not include F-18 fluordesoxyglucose positron emission tomography/computed tomography (FDG-PET) scans. Primary end point was event-free survival (EFS). A subgroup of 131 patients with PMBCLs was included (median age, 34 y; 54% female, 79% elevated lactate dehydrogenase (LDH), 20% LDH >2× upper limit of normal [ULN], and 24% extralymphatic involvement). Eighty-two (R-CHOP-21: 43 and R-CHOP-14: 39) patients were assigned to radiotherapy and 49 (R-CHOP-21: 27, R-CHOP-14: 22) to observation. The 3-year EFS was superior in radiotherapy arm (94% [95% confidence interval (CI), 89-99] versus 78% [95% CI, 66-89]; P = 0.0069), due to a lower rate of partial responses (PRs) (2% versus 10%). PR triggered additional treatment, mostly radiotherapy (n = 5; PR: 4; complete response/unconfirmed complete response: 1). No significant differences were observed in progression-free survival (PFS) (95% [95% CI, 90-100] versus 90% [95% CI, 81-98]; P = 0.25) nor in overall survival (OS) (98% [95% CI, 94-100] versus 96% [95% CI, 90-100]; P = 0.64). Comparing R-CHOP-14 and R-CHOP-21, EFS, PFS, and OS were not different. A prognostic marker for adverse outcome was elevated LDH >2× ULN (EFS: P = 0.016; PFS: P = 0.0049; OS: P = 0.0014). With the limitation of a pre-PET-era trial, the results suggest a benefit of radiotherapy only for patients responding to R-CHOP with PR. PMBCL treated with R-CHOP have a favorable prognosis with a 3-year OS of 97%.
Ocular Surface Disease in Patients With Atopic Dermatitis Treated With Dupilumab: A Prospective Case–Control Study
Authors: Marolo Paola , Ribero Simone , Caselgrandi Paolo , Ghilardi Andrea , de Sanctis Ugo , Parisi Guglielmo , Fallico Matteo , Borrelli Enrico , Ortoncelli Michela , Gelato Federica , Mastorino Luca , Tibaldi Tommaso , Roccuzzo Gabriele , Quaglino Pietro , Reibaldi Michele
Published: July 2023

Purpose:

The aim of this study was to evaluate the variation of dry eye disease (DED) prevalence in patients with atopic dermatitis (AD) treated with dupilumab.

Methods:

This prospective case–control study included consecutive patients with moderate-to-severe AD scheduled for dupilumab between May and December 2021 and healthy subjects. DED prevalence, the Ocular Surface Disease Index, tear film breakup time test, osmolarity, Oxford staining score, and Schirmer test results were collected at baseline, 1 month, and 6 months after dupilumab therapy. The Eczema Area and Severity Index was assessed at baseline. Ocular side effects and discontinuation of dupilumab were also recorded.

Results:

Seventy-two eyes from 36 patients with AD treated with dupilumab and 36 healthy controls were included. Prevalence of DED increased from 16.7% at baseline to 33.3% at 6 months in the dupilumab group (P = 0.001), whereas it remained unchanged in the control group (P = 0.110). At 6 months, the Ocular Surface Disease Index and Oxford score increased (from 8.5 ± 9.8 to 11.0 ± 13.0, P = 0.068, and from 0.1 ± 0.5 to 0.3 ± 0.6, P = 0.050, respectively), the tear film breakup time test and Schirmer test results decreased (from 7.8 ± 2.6 s to 7.1 ± 2.7 s, P < 0.001, and from 15.4 ± 9.6 mm to 13.2 ± 7.9 mm, P = 0.036, respectively) in the dupilumab group, whereas they remained stable in the control group (P > 0.05). Osmolarity was unchanged (dupilumab P = 0.987 and controls P = 0.073). At 6 months after dupilumab therapy, 42% of patients had conjunctivitis, 36% blepharitis, and 2.8% keratitis. No severe side effects were reported, and none of the patients discontinued dupilumab. No association between Eczema Area and Severity Index and DED prevalence was shown.

Conclusions:

DED prevalence increased in patients with AD treated with dupilumab at 6 months. However, no severe ocular side effects were found and no patient discontinued therapy.
A Systematic Review of Glaucoma Diagnosis in Prevalence Studies and Quality of Reporting
Authors: Al-Timimi Zayn , Huang-Lung Jessie , Keay Lisa , Healey Paul , Yang Eleanor , Dunn Hamish
Published: July 2023

Précis:

This systematic review has revealed that variable definitions of glaucoma continue to be used in prevalence studies, despite the introduction of the International Society of Geographic and Epidemiologic Ophthalmology (ISGEO) criteria.

Purpose:

To systematically review diagnostic criteria and examinations performed in glaucoma prevalence studies over time and determine the quality of reporting. Accurate estimates of glaucoma prevalence are crucial to inform resource allocation. However, diagnosis of glaucoma comprises inherently subjective examinations and the cross-sectional nature of prevalence studies precludes monitoring for progression.

Methods:

A systematic review of PubMed, Embase, Web of Science, and Scopus was performed to examine diagnostic protocols used by glaucoma prevalence studies and evaluate uptake of the ISGEO criteria, introduced in 2002 to standardize glaucoma diagnosis in prevalence studies. Detection bias and compliance with the Strengthening Reporting of Observational Studies in Epidemiology (STROBE) guidelines were evaluated.

Results:

Ten thousand five hundred forty-four articles were identified. After deduplication, 5589 articles were screened, yielding 136 articles pertaining to 123 studies. An absence of data in many countries was identified. Ninety-two percent of studies stated diagnostic criteria, and 62% used the ISGEO criteria since their publication. Weaknesses of the ISGEO criteria were identified. Temporal variations in the performance of various examinations were observed, including heterogeneity in angle assessment. Mean STROBE compliance was 82% (range 59–100%); 72 articles had a low risk of detection bias, 4 had a high risk, and 60 had some concerns.

Conclusion:

Heterogeneous diagnostic definitions persist in glaucoma prevalence studies, despite introduction of the ISGEO criteria. Standardization of criteria remains imperative and the development of new criteria represent a valuable opportunity to achieve this goal. In addition, methods of determining diagnoses are poorly reported, suggesting a need for improvement in study conduct and reporting. Accordingly, we propose the Reporting of quality Of GlaUcoma Epidemiological Studies (ROGUES) Checklist. We have also identified a need for further prevalence studies in regions with limited data and to update Australian angle closure glaucoma prevalence. Design and reporting of future studies can be informed by this review’s insights into diagnostic protocols previously used.
Effectiveness of Tick-borne Encephalitis Vaccines in Children, Latvia, 2018–2020
Authors: Zavadska Dace , Freimane Zane , Karelis Guntis , Ermina Ineta , Harper Lisa R. , Bender Cody , Zhang Pingping , Angulo Frederick J. , Erber Wilhelm , Bormane Antra , Griskevica Aija , Moïsi Jennifer C. , Jodar Luis
Published: July 2023

Background:

Tick-borne encephalitis (TBE) is an infection by the tick-borne encephalitis virus (TBEV) with symptoms of central nervous system inflammation. TBE is endemic in Latvia and other parts of Europe. TBE vaccination is recommended for children in Latvia. TBE vaccine effectiveness (VE) was estimated in Latvia, a country with high TBE incidence, providing the first VE estimates against a range of TBEV infection outcomes in children 1–15 years-of-age.

Methods:

Rīga Stradinš University conducted nationwide surveillance for suspected TBE cases. Serum and cerebrospinal fluid were ELISA tested for TBEV-specific IgG and IgM antibodies. A fully vaccinated child was an individual who had received the 3-dose primary series and appropriately timed boosters. The proportion of laboratory-confirmed TBE cases fully vaccinated (PCV) was determined from interviews and medical records. The proportion of the general population fully vaccinated (PPV) was determined from national surveys conducted in 2019 and 2020. TBE VE in children 1–15 years-of-age was estimated using the screening method: VE = 1 − [PCV/(1 − PCV)/PPV/(1 − PPV)].

Results:

From 2018 to 2020, surveillance identified 36 TBE cases in children 1–15 years-of-age; all were hospitalized, 5 (13.9%) for >12 days. Of the TBE cases, 94.4% (34/36) were unvaccinated compared with 43.8% of children in the general population. VE against TBE hospitalization in children 1–15 years-of-age was 94.9% (95% confidence interval 63.1–99.3). In 2018–2020, vaccination in children 1–15 years-of-age averted 39 hospitalized TBE cases.

Conclusion:

Pediatric TBE vaccines were highly effective in preventing TBE in children. Increasing TBE vaccine uptake in children is essential to maximize the public health impact of TBE vaccination.
Reconstruction of Large Full-Thickness Lower Eyelid Defects With Remnant Eyelid Rotation, Semicircular Skin and Muscle Flap, and Lateral Tarsoconjunctival Flap
Authors: Camacho Maria Belen , Han Michael M. , Dermarkarian Christopher R. , Tao Jeremiah P.
Published: July 2023

Purpose:

To describe and assess the results of reconstruction of large, full-thickness defects of the central or medial lower eyelid using a semicircular skin flap, rotation of the remnant lateral eyelid, and a lateral tarsoconjunctival flap.

Methods:

The surgical approach is described, and the authors performed a retrospective chart review of consecutive patients between 2017 and 2023 reconstructed with this technique. Outcomes were assessed for size of eyelid defect, vision, subjective symptoms, facial and palpebral aperture symmetry, eyelid position and closure, corneal examination, surgical complications, and need for subsequent surgical intervention. Postoperative appearance was graded on malposition, distortion, asymmetry, contour deformity, and scarring (MDACS).

Results:

Charts of 45 patients were identified. The average size of the lower eyelid defect was 18 mm (ranging from 12 to 26 mm). Facial and palpebral aperture symmetry were acceptable and all patients had preserved visual acuity and eyelid position and closure. The MDACS cosmetic score was perfect (0) in 15.6% (7/45) of eyelids, good (1–4) in 80.0% (36/45) of eyelids, and mediocre (5–14) in 4.4% (2/45) of eyelids. Second stage reconstruction was not necessary in 32 (71.1%) cases. There were no serious surgical complications, but minor complications included redness of the eyelid margin and pyogenic granulomas.

Conclusions:

Medial rotation of the remnant lower eyelid with a lateral semicircular skin and muscle flap over a lateral tarsoconjunctival flap was very effective in this series. Benefits include scarring within the facial skin tension lines, maintained vision throughout the recovery period, no eyelid retraction, and often single stage reconstruction.
Comparative Different Interventions to Improve Medication Adherence in Patients with Hypertension
Authors: Yuan Wei , Zhang Yu , MA LiHua
Published: July 2023

Background

Hypertension has become a major public problem. One of every 4 adults has hypertension. Medications are critical in controlling blood pressure, but patient medication adherence is low. Therefore, it is very crucial to promote medication adherence. However, the complexity and variety of interventions cause clinical decision-making difficulties for health managers and patients.

Objective

The aim of this study was to compare the effectiveness of different interventions to improve medication adherence in patients with hypertension.

Methods

We searched PubMed, Cochrane Library, Web of Science, EMBASE, Wan Fang, China National Knowledge Infrastructure, China Science and Technology Journal Database, and China Biology Medicine disc databases for eligible studies. Medication adherence rate and medication adherence difference were assessed as outcomes. Sensitivity analysis and inconsistency detection were performed to evaluate whether the exclusion of high-risk studies affected the validity. The risk of bias was assessed using the risk of bias table in Review Manager 5.4. The surface under the cumulative ranking curve was used to estimate the rankings among different interventions.

Results

Twenty-seven randomized controlled trials were included, and the interventions involved were categorized into 8 different categories. The network meta-analysis showed that the health intervention was the best to promote medication compliance in patients with hypertension.

Conclusions

Health intervention is recommended to improve medication adherence in patients with hypertension.

Clinical Implications

Health managers are recommended to provide health intervention to patients with hypertension to improve their medication adherence. This approach reduces morbidity, mortality, and healthcare costs for patients with cardiovascular disease.
Inflammatory Milieu Related to Dysbiotic Gut Microbiota Promotes Tumorigenesis of Hepatocellular Carcinoma
Authors: Huang Caizhi , Mei Si , Zhang Xue , Tian Xuefei
Published: July 2023

Hepatocellular carcinoma (HCC) is an invasive primary liver cancer caused by multiple pathogenic factors and is a significant global health concern. With few effective therapeutic options, HCC is a heterogeneous carcinoma that typically arises in an inflammatory environment. Recent studies have suggested that dysbiotic gut microbiota is involved in hepatocarcinogenesis via multiple mechanisms. In this review, we discuss the effects of gut microbiota, microbial components, and microbiota-derived metabolites on the promotion and progression of HCC by feeding a persistent inflammatory milieu. In addition, we discuss the potential therapeutic modalities for HCC targeting the inflammatory status induced by gut microbiota. A better understanding of the correlation between the inflammatory milieu and gut microbiota in HCC may be beneficial for developing new therapeutic strategies and managing the disease.
Effectiveness of Meaning-Centered Coaching on the Job of Oncology Nurses on Spiritual Care Competences
Authors: Modderkolk Linda , van Meurs Jacqueline , de Klein Veronique , Engels Yvonne , Wichmann Anne B.
Published: July 2023

Background

Nurses’ competences in providing spiritual care can increase quality of care for and quality of life of patients with cancer and job satisfaction but are often suboptimal. Training to improve this mostly takes place off-site, although implementation in daily care practice is key.

Objectives

The aims of this study were to implement a meaning-centered coaching on the job intervention and to measure its effects on oncology nurses’ spiritual care competences and job satisfaction, and factors influencing this.

Methods

A participatory action research approach was adopted. Mixed methods were used to assess intervention effects in which nurses of an oncology ward in a Dutch academic hospital participated. Spiritual care competences and job satisfaction were quantitatively measured and complemented with content analysis of qualitative data.

Results

Thirty nurses participated. A significant increase in spiritual care competences was found, particularly regarding communication, personal support, and professionalization. More self-reported awareness of personal experiences in caring for patients, and an increase in mutual communication and involvement around meaning-centered care provision as a team were found. Mediating factors were related to nurses’ attitudes, support structures, and professional relations. No significant impact was found on job satisfaction.

Conclusion

Meaning-centered coaching on the job increased oncology nurses’ spiritual care competences. Nurses developed a more exploratory attitude in their communication with patients—instead of acting based on their own assumptions about what is of meaning.

Implications for Practice

Attention to and improving spiritual care competences should be integrated into existing work structures, and terminology used should match existing understandings and sentiments.