bluuebunny/crossref_metadata_2025 huggingface dataset:
Barley HOMOCYSTEINE METHYLTRANSFERASE 2 confers drought tolerance by improving polyamine metabolism
Authors: Qiu Cheng-Wei , Ma Yue , Wang Qing-Qing , Fu Man-Man , Li Chengdao , Wang Yizhou , Wu Feibo
Published: June 2023

Drought stress poses a serious threat to crop production worldwide. Genes encoding homocysteine methyltransferase (HMT) have been identified in some plant species in response to abiotic stress, but its molecular mechanism in plant drought tolerance remains unclear. Here, transcriptional profiling, evolutionary bioinformatics, and population genetics were conducted to obtain insight into the involvement of HvHMT2 from Tibetan wild barley (Hordeum vulgare ssp. agriocrithon) in drought tolerance. We then performed genetic transformation coupled with physio-biochemical dissection and comparative multiomics approaches to determine the function of this protein and the underlying mechanism of HvHMT2-mediated drought tolerance. HvHMT2 expression was strongly induced by drought stress in tolerant genotypes in a natural Tibetan wild barley population and contributed to drought tolerance through S-adenosylmethionine (SAM) metabolism. Overexpression of HvHMT2 promoted HMT synthesis and efficiency of the SAM cycle, leading to enhanced drought tolerance in barley through increased endogenous spermine and less oxidative damage and growth inhibition, thus improving water status and final yield. Disruption of HvHMT2 expression led to hypersensitivity under drought treatment. Application of exogenous spermine reduced accumulation of reactive oxygen species (ROS), which was increased by exogenous mitoguazone (inhibitor of spermine biosynthesis), consistent with the association of HvHMT2-mediated spermine metabolism and ROS scavenging in drought adaptation. Our findings reveal the positive role and key molecular mechanism of HvHMT2 in drought tolerance in plants, providing a valuable gene not only for breeding drought-tolerant barley cultivars but also for facilitating breeding schemes in other crops in a changing global climate.
CURLY LEAF modulates apoplast liquid water status in Arabidopsis leaves
Authors: Wu Jingni , Mei Xiao , Zhang Jinyu , Ye Luhuan , Hu Yezhou , Chen Tao , Wang Yiping , Liu Menghui , Zhang Yijing , Xin Xiu-Fang
Published: June 2023

The apoplast of plant leaves, the intercellular space between mesophyll cells, is normally largely filled with air with a minimal amount of liquid water in it, which is essential for key physiological processes such as gas exchange to occur. Phytopathogens exploit virulence factors to induce a water-rich environment, or “water-soaked” area, in the apoplast of the infected leaf tissue to promote disease. We propose that plants evolved a “water soaking” pathway, which normally keeps a nonflooded leaf apoplast for plant growth but is disturbed by microbial pathogens to facilitate infection. Investigation of the “water soaking” pathway and leaf water control mechanisms is a fundamental, yet previously overlooked, aspect of plant physiology. To identify key components in the “water soaking” pathway, we performed a genetic screen to isolate Arabidopsis (Arabidopsis thaliana) severe water soaking (sws) mutants that show liquid water overaccumulation in the leaf under high air humidity, a condition required for visible water soaking. Here, we report the sws1 mutant, which displays rapid water soaking upon high humidity treatment due to a loss-of-function mutation in CURLY LEAF (CLF), encoding a histone methyltransferase in the POLYCOMB REPRESSIVE COMPLEX 2 (PRC2). We found that the sws1 (clf) mutant exhibits enhanced abscisic acid (ABA) levels and stomatal closure, which are indispensable for its water soaking phenotype and mediated by CLF's epigenetic regulation of a group of ABA-associated NAM, ATAF, and CUC (NAC) transcription factor genes, NAC019/055/072. The clf mutant showed weakened immunity, which likely also contributes to the water soaking phenotype. In addition, the clf plant supports a substantially higher level of Pseudomonas syringae pathogen-induced water soaking and bacterial multiplication, in an ABA pathway and NAC019/055/072-dependent manner. Collectively, our study sheds light on an important question in plant biology and demonstrates CLF as a key modulator of leaf liquid water status via epigenetic regulation of the ABA pathway and stomatal movement.
Exploring the potential of intranasal drug delivery systems in the management of hypertension
Authors: Hassan Rinada H , Gad Heba A , Shaker Dalia S , Ishak Rania A H
Published: June 2023

Objectives

The current review gives an overview of the anatomical and cellular structure of the nasal cavity. It presents some possibilities and different techniques to enhance the drug penetration through the nasal barrier. It comprehensively details the intranasal drug delivery system and the treatment modalities of hypertension, with an emphasis on nanotechnology-based products.

Methods

Gather published works about the research progression in the systemic delivery of antihypertensive drugs through the nasal epithelium, the formulation tactics and their related in vitro, ex vivo and in vivo assessment technologies in this field.

Key findings

Intranasal drug delivery is one of the potential routes for avoiding the first pass effect, lowering drug doses, reducing systemic side effects of most antihypertensive drugs and enhancing drug bioavailability.

Conclusions

Compared to oral medications, nasal medications often have better bioavailability and fewer adverse effects at the same dosage, which encourages pharmaceutical companies to manufacture additional medications in the form of nasal formulations intended for systemic treatment.
Severe strongyloidiasis: a systematic review and meta-analysis of 339 cases
Authors: Rojas Olga C , Montoya Alexandra M , Villanueva-Lozano Hiram , Carrion-Alvarez Diego
Published: June 2023

Strongyloidiasis is a parasitosis representing a significant public health problem in tropical countries. It is often asymptomatic in immunocompetent individuals but its mortality rate increases to approximately 87% in severe forms of the disease. We conducted a systematic review, including case reports and case series, of Strongyloides hyperinfection and dissemination from 1998 to 2020 searching PubMed, EBSCO and SciELO. Cases that met the inclusion criteria of the Preferred Reported Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist were analysed. Statistical analysis was performed using Fisher’s exact test and Student's t-test and a Bonferroni correction for all the significant values. A total of 339 cases were included in this review. The mortality rate was 44.83%. The presence of infectious complications, septic shock and a lack of treatment were risk factors for a fatal outcome. Eosinophilia and ivermectin treatment were associated with an improved outcome.
Vasodilators activate TMEM16A channels in endothelial cells to reduce blood pressure
Authors: Mata-Daboin Alejandro , Garrud Tessa A. C. , Fernandez-Pena Carlos , Peixoto-Neves Dieniffer , Leo M. Dennis , Bernardelli Angelica K. , Singh Purnima , Malik Kafait U. , Jaggar Jonathan H.
Published: June 2023

Endothelial cells (ECs) regulate vascular contractility to control regional organ blood flow and systemic blood pressure. Several cation channels are expressed in ECs which regulate arterial contractility. In contrast, the molecular identity and physiological functions of anion channels in ECs is unclear. Here, we generated tamoxifen-inducible, EC-specificTMEM16Aknockout (TMEM16AecKO) mice to investigate the functional significance of this chloride (Cl-) channel in the resistance vasculature. Our data demonstrate that TMEM16A channels generate calcium-activated Cl-currents in ECs of control (TMEM16Afl/fl) mice that are absent in ECs ofTMEM16AecKO mice. Acetylcholine (ACh), a muscarinic receptor agonist, and GSK101, a TRPV4 agonist, activate TMEM16A currents in ECs. Single molecule localization microscopy data indicate that surface TMEM16A and TRPV4 clusters locate in very close nanoscale proximity, with ∼18% exhibiting overlap in ECs. ACh stimulates TMEM16A currents by activating Ca2+influx through surface TRPV4 channels without altering the size or density of TMEM16A or TRPV4 surface clusters, their spatial proximity or colocalization. ACh-induced activation of TMEM16A channels in ECs produces hyperpolarization in pressurized arteries. ACh, GSK101 and intraluminal ATP, another vasodilator, all dilate pressurized arteries through TMEM16A channel activation in ECs. Furthermore, EC-specific knockout of TMEM16A channels elevates systemic blood pressure in conscious mice. In summary, these data indicate that vasodilators stimulate TRPV4 channels, leading to Ca2+-dependent activation of nearby TMEM16A channels in ECs to produce arterial hyperpolarization, vasodilation and a reduction in blood pressure. We identify TMEM16A as an anion channel present in ECs that regulates arterial contractility and blood pressure.

One sentence summary

Vasodilators stimulate TRPV4 channels, leading to calcium-dependent activation of nearby TMEM16A channels in ECs to produce arterial hyperpolarization, vasodilation and a reduction in blood pressure.
Multiple introductions and country-wide spread of DENV-2 genotype II (Cosmopolitan) in Brazil
Authors: Gräf Tiago , Ferreira Caroline do Nascimento , de Lima Gustavo Barbosa , de Lima Raul Emídio , Machado Lais Ceschini , Campos Tulio de Lima , Schemberger Michelle Orane , Faoro Helisson , Paiva Marcelo Henrique Santos , Bezerra Matheus Filgueira , Nascimento Valdinete , Souza Victor , Nascimento Fernanda , Mejía Matilde , Silva Dejanane , de Oliveira Yasmin Silva , Gonçalves Luciana , Ramos Tatyana Costa Amorim , de Castro Daniel Barros , Arcanjo Ana Ruth ,   LACEN-AM team, Dantas Herton Augusto Pinheiro ,   LAFRON-AM team, Presibella Mayra Marinho ,   LACEN-PR team, Fernandes Sandra Bianchini ,   LACEN-SC team, Gregianini Tatiana Schaffer ,   CEVS-RS team, e Silva Keilla Maria Paz ,   LACEN-PE team, Sacchi Claudio Tavares ,   IAL team, Ribeiro Cruz Ana Cecília ,   IEC team, dos Santos Claudia Nunes Duarte , de Filippis Ana Maria Bispo , Salvato Richard Steiner , Bello Gonzalo , Wallau Gabriel Luz , Naveca Felipe
Published: June 2023

Dengue virus serotype 2, genotype Cosmopolitan (DENV-2-GII), is one of the most widespread DENV strains globally. In the Americas, DENV-2 epidemics has been dominated by DENV-2 genotype Asian-American (DENV-2-GIII) and the first cases of DENV-2-GII were only described in 2019, in Peru, and in 2021 in Brazil. To gain new information about the circulation of DENV-2-GII in Brazil, we sequenced 237 DENV-2 confirmed cases sampled between March 2021 and March 2023 and revealed that DENV-2-GII is already present in all geographic regions of Brazil. Phylogeographic analysis inferred that DENV-2-GII was introduced at least four times in Brazil, between May 2020 and August 2022, generating multiple clades that spread throughout the country with different success. Despite multiple introductions of DENV-2-GII, analysis of the country-wide laboratory surveillance data showed that the Brazilian dengue epidemic in 2022 was dominated by DENV-1 in most states. We suggest that massive circulation of DENV-2-GIII in previous years in Brazil might have created a population immune barrier for widespread transmission of DENV-2-GII, leading to sustained cryptic circulation and localized outbreaks of this new genotype. In summary, our study stresses the importance of arboviral genomic surveillance to close monitoring and better understand the potential impact of DENV-2-GII in the coming years.
Reliability, validity and dimensionality of the GHQ-12 in South African populations: Structural equation modelling (SEM)
Authors: Kufe Clement Nyuyki , Bernstein Colleen , Wilson Kerry
Published: June 2023

Introduction

Health Care Workers (HCWs) were among the high-risk groups for SARS-CoV-2 infection and suffer a high burden of poor mental health including depression, anxiety, traumatic stress, avoidance and burnout. The 12-Item General Health Questionnaire (GHQ-12) has showed best fit in both a one-factor structure and a multidimensional structure for the screening of common mental disorders and psychiatric well-being. The aim was to test for the reliability and validity and ascertain the factor structure of the GHQ-12 in a South African HCW population.

Methods

Data was collected from 832 public hospital and clinic staff during the COVID-19 pandemic in Gauteng, South Africa. The factor structure of the GHQ12 in this professional population was examined by exploratory factor analysis (EFA) to identify factors, confirmatory factor analysis (CFA) for construct validity and structural equation modelling (SEM).

Results

The GHQ-12 median score was higher (25) in women than in men (24), p=0.044. The determinant for the correlation matrix was=0.047, the Barlett test of sphericity was p<0.001, Chi square=2086.9 and Kaiser-Meyer-Olkin (KMO) of sampling adequacy was 0.86. The four factors identified were labelled as Social-Dysfunction (37.8%), Anxiety-Depression (35.4%) Capable (24.9%) and Self-Efficacy (22.7%). The entire sample had a Cronbach’s alpha of 0.85, with 0.69 for Social-Dysfunction, 0.74 for Anxiety-Depression, 0.64 for Capable and 0.52 for Self-Efficacy in orthogonal (varimax) factor loadings.

Conclusions

The GHQ-12 tool displayed adequate reliability and validity in measuring psychological distress in a professional group with a four-factor model suggesting multidimensionality in this group rather than a unidimensional construct.
Low-Field Combined Diffusion-Relaxation MRI for Mapping Placenta Structure and Function
Authors: Slator Paddy J. , Aviles Verdera Jordina , Tomi-Tricot Raphael , Hajnal Joseph V. , Alexander Daniel C. , Hutter Jana
Published: June 2023

Purpose

Demonstrating quantitative multi-parametric mapping in the placenta with combined T2*-diffusion MRI at low-field (0.55T).

Methods

We present 57 placental MRI scans performed on a commercially available 0.55T scanner. We acquired the images using a combined T2*-diffusion technique scan that simultaneously acquires multiple diffusion preparations and echo times. We processed the data to produce quantitative T2* and diffusivity maps using a combined T2*-ADC model. We compared the derived quantitative parameters across gestation in healthy controls and a cohort of clinical cases.

Results

Quantitative parameter maps closely resemble those from previous experiments at higher field strength, with similar trends in T2* and ADC against gestational age observed.

Conclusion

Combined T2*-diffusion placental MRI is reliably achievable at 0.55T. The advantages of lower field strength - such as cost, ease of deployment, increased accessibility and patient comfort due to the wider bore, and increased T2* for larger dynamic ranges - can support the widespread roll out of placental MRI as an adjunct to ultrasound during pregnancy.
Acute Ischemic Stroke in Tsutsugamushi: Understanding the Underlying Mechanisms and Risk Factors
Authors: Kim Dain , Cho Yeon Hee , Chung Ji Yeon , Kim Young Seo , Shin Byoung-Soo , Kang Hyun Goo
Published: June 2023

Background

Tsutsugamushi, also known as scrub typhus, is an acute infectious febrile disease common in the Asia–Pacific region. Its common symptoms include lymphadenopathy, fever, and myalgia. Tsutsugamushi rarely causes acute ischemic stroke (AIS); however, it has been reported to increase the likelihood of AIS development. Here, we aimed to test the hypothesis that tsutsugamushi infection could trigger AIS.

Method

We retrospectively examined patients diagnosed with AIS within 2 weeks of tsutsugamushi diagnosis at three hospitals over 15 years. We categorized patients who developed AIS while being treated for tsutsugamushi as the case group; patients who did not develop AIS while being treated for tsutsugamushi at the same hospital and were of similar age and sex with the case group were categorized as the control group. The case and control groups had 22 and 66 participants, respectively. When a scattered pattern was observed or lesions were found in two or more vascular territories on diffusion-weighted imaging, the pattern was defined as embolic. Other patterns were defined as non-embolic.

Results

Among the 19 patients, excluding three with transient ischemic attack, 15 (78.9%) showed an embolic pattern. Fever was common at the time of the visit in the control group; however, it was less common in the case group (93.8% vs. 27.3%, respectively; p<0.001). Multivariate analysis revealed that higher D-dimer levels at the time of hospitalization were associated with AIS development in patients with tsutsugamushi (adjusted odds ratio, 1.58; 95% confidence interval, 1.06–2.34; p=0.023).

Discussion

AIS in patients with tsutsugamushi showed an embolic rather than a non-embolic pattern on brain magnetic resonance imaging. This embolic pattern was more likely to occur in patients with stroke risk factors. These patients were unlikely to have a fever or high D-dimer levels. We speculated that D-dimers played a vital role in the pathophysiology, as tsutsugamushi infection increased the likelihood of AIS.
THE DISTRIBUTION OF KERATOMETRY READINGS, CORNEAL POWER AND CORNEAL ASTIGMATISM AMONG MALAWIAN YOUNG ADULTS
Authors: Gondwe Kenneth , Mzumara Thokozani , Afonne Joseph
Published: June 2023

Background/objectives

keratometry and corneal measurements differ among populations. The aim of the study was to assess the distribution of keratometric values and corneal astigmatism and examine the association with age and gender among normal Malawian adults.

Methods

This was a cross-sectional study conducted among Mzuzu university students in Malawi. Participants were selected using systematic sampling techniques. K readings were measured using a manual keratometer. Data was entered in SPSS v 26. Chi-square was used to assess association, spearman to assess correction, and an independent t-test to compare the mean.

Results

We recruited 98 participants, of whom 59 (60.2%) were male and 39 (39.8%) were female. The Mean age of participants was 27.13 years (SD=5.616). Based on gender, it was 27.97 (SD=5.860) among males and 25.87 (SD=5.038) among females. But an independent t-test showed no significant difference in age according to gender(t(96)= 1.8, p=0.71). On average, the flat and steep K reading was 44.93D (SD=1.49) and 45.40D (SD=1.53) respectively. The mean K was 45.17D (SD=1.47). With regards to gender, the mean K was 45.17D (SD=1.38) and 45.18D (SD=1.62) among males and females respectively, but it was not statistically significant. (t(96)=-0.045, p=0.96). Spearman test showed that the correlation between mean K and age was statistically non-significant mean

Conclusion

Corneal astigmatism is relatively tiny among this population group hence surgeons can use techniques to correct and other techniques to achieve greater visual rehabilitation. This study confirms that Environment and genetics play a major role in corneal changes.
Status of Compassionate Health Care Practice and Associated Factors in Public Hospitals of Addis Ababa from patient’s perspective: cross sectional study
Authors: Tadesse Elias Teshome , Soboka Dawit Regasa , Debelew Gurmesa Tura
Published: June 2023

Background

Compassionate health care is lauded as a cornerstone of quality healthcare by patients, families, clinicians, and policy makers. Compassionate Care’ within the healthcare setting has received much attention globally, following concerns that healthcare often fails at a fundamental level.

Objective

To assess Status of compassionate health care practice and associated factors in public hospitals of Addis Ababa.

Methods

Institution based cross-sectional study design was conducted. A structured and prtested interviewer administered questionnaire was used to collect the data from 605 study participants. Study participant was selected using a systematic sampling technique by allocating a proportion sample to each hospitals. The data was entered with Epi data version 3.1 and exported to Statistical Package for Social Sciences version 25.0 for further analysis. Both bivariate and multivariate logistic regression analysis were performed to identify associated factors. P values < 0.05 with 95% confidence level were used to declare statistical significance.

Result

The status of compassioante health care practice was found to be 42.6% [(95% CI: 39.0%-47.0%)]. Covariates such as: relatively higher education [AOR = 0.534 (95% CI 0.305-0.934)], Not married [AOR=0.561 (95% CI 0.330-0.955)], government employee [AOR=2.178 (95% CI 1.071-4.430)], Room accommodation comfortability [AOR=0.309 (95% CI 0.178-0.535)], and Cleanness of toilet [AOR=2.158 (95% CI 1.326-3.513)] had statistically significant association with compassionate health care practice.

Conclusion

The status of compassionate health care practice was found to be low compared to similar study conducted with in and out of Ethiopia. Compassionate health care practice was significantly associated with educational s, occupation, marital status, cleanness of toilet, and room accommodation comfortability. Therefore, health workers, Hospitals and Addis Ababa health bureau should understand these weak areas and plan for a better service delivery to compassionate care.
The Role of Vaccine Status Homophily in the COVID-19 Pandemic: A Cross-Sectional Survey with Modeling
Authors: Are Elisha B. , Card Kiffer G. , Colijn Caroline
Published: June 2023

Background

Vaccine homophily describes non-heterogeneous vaccine uptake within contact networks. This study was performed to determine observable patterns of vaccine homophily, associations between vaccine homophily, self-reported vaccination, COVID-19 prevention behaviours, contact network size, and self-reported COVID-19, as well as the impact of vaccine homophily on disease transmission within and between vaccination groups under conditions of high and low vaccine efficacy.

Methods

Residents of British Columbia, Canada, aged ≥16 years, were recruited via online advertisements between February and March 2022, and provided information about vaccination status, perceived vaccination status of household and non-household contacts, compliance with COVID-19 prevention guidelines, and history of COVID-19. A deterministic mathematical model was used to assess transmission dynamics between vaccine status groups under conditions of high and low vaccine efficacy.

Results

Vaccine homophily was observed among the 1304 respondents, but was lower among those with fewer doses (p<0.0001). Unvaccinated individuals had larger contact networks (p<0.0001), were more likely to report prior COVID-19 (p<0.0001), and reported lower compliance with COVID-19 prevention guidelines (p<0.0001). Mathematical modelling showed that vaccine homophily plays a considerable role in epidemic growth under conditions of high and low vaccine efficacy. Further, vaccine homophily contributes to a high force of infection among unvaccinated individuals under conditions of high vaccine efficacy, as well as elevated force of infection from unvaccinated to vaccinated individuals under conditions of low vaccine efficacy.

Interpretation

The uneven uptake of COVID-19 vaccines and the nature of the contact network in the population play important roles in shaping COVID-19 transmission dynamics.
The Mediating Role of Body Mass Index in the Association between Dietary Inflammatory Index and 10-year risk of CVD: a counterfactual mediation analysis
Authors: Xie Zechun , Wang Ling , Sun Mengzi , Wang Rui , Liu Yan , Li Jing , Wang Xuhan , Guo Ruirui , Wang Yuxiang , Li Bo
Published: June 2023

Abstract

Introduction

Dietary with higher inflammatory potential are associated with cardiovascular disease (CVD) risk over the next decade, while studies have shown body mass index (BMI) to be one of the mediators between dietary inflammatory index (DII) and multiple diseases such as depression and diabetes. However, the role of BMI in the association between DII and 10-year risk of CVD is unclear.

Methods

Study based on 14,355 adults from the National Health and Nutrition Examination Survey (NHANES). Participants’ diet, obesity level and CVD risk were assessed using the DII, BMI and Framingham Risk Score (FRS). Linear regression and counterfactual model were used to analyze this relationship.

Results

Participants on a pro-inflammatory diet had a higher risk of CVD over the next ten years compared to participants on an anti-inflammatory diet. Counterfactual models showed a 34.0% partial mediating role of BMI in this relationship, most particularly in males (17.3%) and non-elderly (28.6%-100%).

Conclusion

Inflammatory diet adversely affects cardiovascular risk, a large part of which operates through BMI, especially in males and non-elderly populations. These findings are beneficial in facilitating research on the mechanisms of diet-related inflammation on CVD.
Comparison of Rupture Risk Between Saccular and Fusiform Abdominal Aortic Aneurysms Using a National Clinical Database in Japan
Authors: Ozawa Hirotsugu , Takahashi Arata , Bessho Ryuzo , Hoshina Katsuyuki , Shukuzawa Kota , Ohki Takao
Published: June 2023

Background

Saccular AAAs are thought to pose an elevated risk of rupture, but not much is known about the extent of this risk. Therefore, we aimed to conduct a survey of saccular abdominal aortic aneurysms (AAAs) and to compare the risk of rupture between fusiform and saccular AAAs.

Methods

We performed a retrospective cohort study on patients who underwent primary endovascular repair for a degenerative AAA between 2016 and 2019, and who were registered in the National Clinical Database in Japan.

Results

A total of 27,290 patients were included in the study. Of these, 7.8 % (n=2142) had saccular AAAs and the remaining 92.2% (n = 25,148) were fusiform. In addition, 4.3% (n = 92) of saccular AAAs and 5.4% (n = 1351) of fusiform AAAs were ruptured. Saccular AAAs ruptured at smaller dimeters than fusiform AAAs (median, 55.6 mm vs 68.0 mm, p < 0.001), and were operated on at smaller diameters than fusiform AAAs in non-ruptured cases (median, 44.0 mm vs 51.0 mm, p < 0.001). The rupture rate was significantly higher in saccular AAAs than in fusiform AAAs in the 40-54 mm diameter range, in which saccular morphology was found to be an independent risk factor for rupture by adjusting for gender and aneurysm diameter (odds ratio, 2.54, 95% confidence interval, 1.75-3.69). In addition, receiver-operating characteristic analysis revealed that the cut-off diameter to predict rupture was smaller in saccular AAAs than in fusiform AAAs (50.5 mm and 59.5 mm, respectively).

Conclusion

Saccular AAAs are more prone to rupture than fusiform AAAs in the 40-54 mm diameter range, which supports the idea that saccular AAAs should be treated at smaller diameters. The 9.0 mm difference in the predicted diameters for the rupture between fusiform and saccular AAAs suggests that the threshold diameter for intervention of saccular AAAs can be set approximately 1 cm smaller than that of fusiform AAAs.

Clinical Perspective

What Is New?

Saccular abdominal aortic aneurysms (AAAs) ruptured at smaller dimeters than fusiform AAAs (median, 55.6 mm vs 68.0 mm, p < 0.001), and receiver-operating characteristic analysis revealed that the cut-off diameter to predict rupture was smaller in saccular AAAs than in fusiform AAAs (50.5 mm and 59.5 mm, respectively).

In AAAs with a dimeter of 40-54 mm, saccular morphology turned out to be an independent risk factor for rupture by adjusting for gender and aneurysm diameter (odds ratio, 2.54, 95% confidence interval, 1.75-3.69).

What Are the Clinical Implications?

Saccular AAAs are more prone to rupture than fusiform AAAs in the 40-54 mm diameter range, which supports the current idea that saccular AAAs should be treated at smaller diameters.

The 9.0 mm difference in the predicted diameters for the rupture between fusiform and saccular AAAs suggests that the threshold diameter for intervention of saccular AAAs can be set approximately 1 cm smaller than that of fusiform AAAs.
“One more tool in the tool belt”: A qualitative interview study investigating patient and clinician opinions on the integration of psychometrics into routine testing for disorders of gut-brain interaction
Authors: Law Mikaela , Bartlett Esme , Sebaratnam Gabrielle , Pickering Isabella , Simpson Katie , Keane Celia , Daker Charlotte , Gharibans Armen , O’Grady Greg , Andrews Christopher N. , Calder Stefan
Published: June 2023

Background

Psychological comorbidities are common in patients with disorders of gut-brain interaction (DGBIs) and are often linked with poorer patient outcomes. Likewise, extensive research has shown a bidirectional association between psychological factors and gastrointestinal symptoms, termed the gut-brain axis. Consequently, assessing and managing mental wellbeing, in an integrated care pathway, may lead to improvements in symptoms and quality of life for some patients. This study aimed to explore patients’ and gastroenterology clinicians’ opinions on integrating psychometrics into routine DGBI testing.

Methods

Semi-structured interviews were conducted with 16 patients with a gastroduodenal DGBI and 19 clinicians who see and treat these patients. Interviews were transcribed verbatim and analysed using inductive, reflexive thematic analysis.

Results

Three key clinician themes were developed: (1) psychology as part of holistic care, emphasising the importance of a multidisciplinary approach; (2) the value of psychometrics in clinical practice, highlighting their potential for screening and expanding management plans; and (3) navigating barriers to utilising psychometrics, addressing the need for standardisation and external handling to maintain the therapeutic relationship. Four key patient themes were also developed: (1) the utility of psychometrics in clinical care, reflecting the perceived benefits; (2) openness to psychological management, indicating patients’ willingness to explore psychological treatment options; (3) concerns with psychological integration, addressing potential stigma and fear of labelling; and (4) the significance of clinician factors, emphasising the importance of clinician bedside manner, knowledge, and collaboration.

Conclusions

The themes generated from the interviews indicated that patients and clinicians see value in integrating psychometrics into routine DGBI testing. Despite potential barriers, psychometrics would advance the understanding of a patient’s condition and facilitate holistic and multidisciplinary management. Recommendations for navigating challenges were provided, and considering these, patients and clinicians supported the use of psychometrics as mental health screening tools for patients with gastroduodenal DGBIs.
Private Practice Infectious Disease: Metro Infectious Disease Consultants
Authors: Petrak Russell , Fliegelman Robert , Van Hise Nicholas , Chundi Vishnu , Didwania Vishal , Han Alice , Harting Brian
Published: June 2023

Despite the stimulating nature of infectious diseases (ID), fellowship programs have failed, on a yearly basis, to fill multiple positions. In addition, numerous entities have published information showing that infectious disease physicians are poorly reimbursed compared to their colleagues in other specialties and likely to feel overwhelmed. To assess the status of our ID group and define opportunities for improvement, Metro Infectious Disease Consultants (MIDC) conducted an internal audit. Eighty-nine percent of employees and 94% of partners were satisfied or very satisfied with MIDC. In addition, based on a Medscape survey, MIDC employees received financial compensation that was 18% greater and partners 235% greater than the average for all ID physicians. A private practice model of infectious diseases is a viable, lucrative, and professionally stimulating option to other ID models. This allows for enhanced lifestyle flexibility and should be viewed by potential ID applicants as a realistic and widely available option to practice this dynamic specialty.
The Impact of Sleep on Breast Cancer-Specific Mortality: A Mendelian Randomisation Study
Authors: Hayes Bryony L , Fleming Leanne , Mahmoud Osama , Martin Richard M , Lawlor Deborah A , Robinson Timothy , Richmond Rebecca C
Published: June 2023

The relationship between sleep traits and survival in breast cancer is uncertain and complex. There are multiple biological, psychological and treatment-related factors that could link sleep and cancer outcomes. Previous studies could be biased due to methodological limitations such as reverse causation and confounding. Here, we used two-sample mendelian randomisation (MR) to investigate the causal relationship between sleep and breast cancer mortality.

Publicly available genetic summary data from females of European ancestry from UK Biobank and 23andme and the Breast Cancer Association Consortium were used to generate instrumental variables for sleep traits (chronotype, insomnia symptoms, sleep duration, napping, daytime-sleepiness, and ease of getting up (N= 446,118-1,409,137)) and breast cancer outcomes (15 years post-diagnosis, stratified by tumour subtype and treatment (N=91,686 and Ndeaths=7,531 over a median follow-up of 8.1 years)). Sensitivity analyses were used to assess the robustness of analyses to MR assumptions.

Initial results found some evidence for a per category increase in daytime-sleepiness reducing overall breast cancer mortality (HR=0.34, 95% CI=0.14, 0.80), and for insomnia symptoms reducing odds of mortality in oestrogen receptor positive breast cancers not receiving chemotherapy (HR=0.18, 95% CI=0.05, 0.68) and in patients receiving aromatase inhibitors (HR=0.23, 95% CI=0.07, 0.78). Importantly, these relationships were not robust following sensitivity analyses meaning we could not demonstrate any causal relationships.

This study did not provide evidence that sleep traits have a causal role in breast cancer mortality. Further work characterising disruption to normal sleep behaviours and its effects on tumour biology, treatment compliance and quality of life are needed.
Association of Clonal Hematopoiesis of Indeterminate Potential with Incident Heart Failure with Preserved Ejection Fraction
Authors: Reiner Alex P. , Roberts Mary B. , Honigberg Michael C. , Kooperberg Charles , Desai Pinkal , Bick Alexander G. , Natarajan Pradeep , Manson JoAnn E. , Whitsel Eric A. , Eaton Charles B.
Published: June 2023

Background

Clonal hematopoiesis of indeterminate potential (CHIP) was recently identified as a risk factor for incident heart failure (HF). Whether CHIP is associated selectively with risk of heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF) subtypes is unknown

Objectives

To evaluate whether CHIP is associated with incident HF subtypes, HFrEF versus HFpEF.

Methods

We obtained CHIP status from whole genome sequencing of blood DNA in participants without prevalent HF from a multi-ethnic sample of post-menopausal women without prevalent HF (N=5,214) from the Women’s Health Initiative (WHI). Cox proportional hazards models were performed, adjusting for demographic and clinical risk factors.

Results

CHIP was significantly associated with a 42% (95%CI 6%, 91%) increased risk of HFpEF (P=0.02). In contrast, there was no evidence of association between CHIP and risk of incident HFrEF. When the three most common CHIP subtypes were assessed individually, the risk of HFpEF was more strongly associated with TET2 (HR=2.5; 95%CI 1.54, 4.06; P<0.001), than DNMT3A or ASXL1.

Conclusion

CHIP, particularly mutations inTET2, represents a potential new risk factor for incident HFpEF.
BrainRBPedia: a resource for RNA-binding proteins relevant to neurodevelopmental disorders
Authors: Han Kara , Wainberg Michael , Calarco John A. , Smibert Craig A. , Lipshitz Howard D. , Lee Hyun O. , Tripathy Shreejoy J
Published: June 2023

RNA-binding proteins (RBPs) are crucial players in the post-transcriptional regulation of mRNA and play major roles in ensuring proper neuronal development and function. Deficits in RBP function have been implicated in a number of neurodevelopmental disorders including autism spectrum disorder (ASD) and intellectual disability (ID), yet we lack resources that integrate current knowledge of RBP function, tissue expression, and disease association in one place to aid in their experimental characterization. Here we introduce BrainRBPedia – a database of 1072 RBPs with both disease annotations for neurodevelopmental disorders and functional annotations relevant to these disorders, including loss-of-function intolerance and expression specificity to the brain, neurons, and neuronal development. Using these functional annotations, we develop a machine learning model to prioritize RBPs likely to be involved in ASD and ID. Our model indicates that RBPs with high loss-of-function intolerance and those upregulated during neuronal differentiation are disproportionately likely to contribute to ASD and ID etiology. In summary, BrainRBPedia comprises a unique resource for researchers interested in the experimental characterization of RBPs in relation to neurodevelopmental disorders and suggests functional signatures of RBPs likely to play a role in neurodevelopment.
Transcription dosage compensation does not occur in Down syndrome
Authors: Hunter Samuel , Dowell Robin D. , Hendrix Josephina , Freeman Justin , Allen Mary A.
Published: June 2023

Background:

Trisomy 21, also known as Down syndrome, describes the genetic condition of having an extra copy of chromosome 21. The increase in DNA copy number has led to the "DNA dosage hypothesis", which claims that the level of gene transcription is proportional to the gene’s DNA copy number. Yet many reports have suggested that a proportion of chromosome 21 genes are dosage compensated back towards typical expression levels (1.0x). In contrast, other reports suggest that dosage compensation is not a common mechanism of gene regulation in Trisomy 21, providing support to the DNA dosage hypothesis.

Results

In our work, we use both simulated and real data to dissect the elements of differential expression analysis that can lead to the appearance of dosage compensation even when compensation is demonstrably absent. Using lymphoblastoid cell lines derived from a family of an individual with Down syndrome, we demonstrate that dosage compensation is nearly absent at both nascent transcription (GRO-seq) and steady-state RNA (RNA-seq) levels.

Conclusions

Transcriptional dosage compensation does not occur in Down syndrome. Simulated data containing no dosage compensation can appear to have dosage compensation when analyzed via standard methods. Moreover, some chromosome 21 genes that appear to be dosage compensated are consistent with allele specific expression.
Daily Activity Profiles over the Lifespan of Female Medflies as Biomarkers of Aging and Longevity
Authors: Chen Han , Müller Hans-Georg , Rodovitis Vasilis G. , Papadopoulos Nikos T. , Carey James R.
Published: June 2023

The relationship between the early age activity of Mediterranean fruit flies or other fruit flies and their lifespan has not been much studied, in contrast to the connections between lifespan and diet, sexual signaling and reproduction. The objective of this study is to assess intraday and day-to-day activity profiles of female Mediterranean fruit flies and their role as biomarker of longevity as well as to explore the relationships between these activity profiles, diet and age-at-death throughout the lifespan. Three distinct patterns of activity variations in early age activity profiles can be distinguished. A low-caloric diet is associated with a delayed activity peak, while a high-caloric diet is linked with an earlier activity peak. We find that age-at-death of individual medflies is connected to their activity profiles in early life. An increased risk of mortality is associated with increased activity in early age, as well as with a higher contrast between daytime and nighttime activity. Conversely, medflies are more likely to have a longer lifespan when they are fed a medium caloric diet and when their daily activity is more evenly distributed across the early age span and between daytime and nighttime. The before-death activity profile of medflies displays two characteristic before-death patterns, where one pattern is characterized by slowly declining daily activity and the other by a sudden decline in activity that is followed by death.
Inhibition of CPEB3 ribozyme elevates CPEB3 protein expression and polyadenylation of its target mRNAs, and enhances object location memory
Authors: Chen Claire C. , Han Joseph , Chinn Carlene A. , Rounds Jacob S. , Li Xiang , Nikan Mehran , Myszka Marie , Tong Liqi , Passalacqua Luiz F. M. , Bredy Timothy W. , Wood Marcelo A. , Lupták Andrej
Published: June 2023

A self-cleaving ribozyme that maps to an intron of the cytoplasmic polyadenylation element binding protein 3 (CPEB3) gene is thought to play a role in human episodic memory, but the underlying mechanisms mediating this effect are not known. We tested the activity of the murine sequence and found that the ribozyme’s self-scission half-life matches the time it takes an RNA polymerase to reach the immediate downstream exon, suggesting that the ribozyme-dependent intron cleavage is tuned to co-transcriptional splicing of theCPEB3mRNA. Our studies also reveal that the murine ribozyme modulates maturation of its harboring mRNA in both cultured cortical neurons and the hippocampus: inhibition of the ribozyme using an antisense oligonucleotide leads to increased CPEB3 protein expression, which enhances polyadenylation and translation of localized plasticity-related target mRNAs, and subsequently strengthens hippocampal-dependent long-term memory. These findings reveal a previously unknown role for self-cleaving ribozyme activity in regulating experience-induced co-transcriptional and local translational processes required for learning and memory.

Significance Statement

Cytoplasmic polyadenylation-induced translation is one of the key steps for regulating protein synthesis and neuroplasticity in the hippocampus. The CPEB3 ribozyme is a highly conserved mammalian self-cleaving catalytic RNA with unknown biological roles. In this study, we investigated how the intronic ribozyme affects theCPEB3mRNA maturation and translation, and its subsequent effect on memory formation. Our findings show that the ribozyme activity is anti-correlated withCPEB3mRNA splicing: inhibition of the ribozyme results in higher mRNA and protein levels, which contribute to long-term memory. Our studies offer new insights into the role of the CPEB3 ribozyme in neuronal translational control for the activity-dependent synaptic functions that underlie long-term memory and demonstrate a novel biological role for self-cleaving ribozymes.
The chromatin landscape of healthy and injured cell types in the human kidney
Authors: Gisch Debora L. , Brennan Michelle , Lake Blue B. , Basta Jeannine , Keller Mark , Ferreira Ricardo Melo , Akilesh Shreeram , Ghag Reetika , Lu Charles , Cheng Ying-Hua , Collins Kimberly S. , Parikh Samir V. , Rovin Brad H. , Robbins Lynn , Conklin Kimberly Y. , Diep Dinh , Zhang Bo , Knoten Amanda , Barwinska Daria , Asghari Mahla , Sabo Angela R. , Ferkowicz Michael J. , Sutton Timothy A , Kelly Katherine J , Boer Ian H. De , Rosas Sylvia E. , Kiryluk Krzysztof , Hodgin Jeffrey B. , Alakwaa Fadhl , Jefferson Nichole , Gaut Joseph P. , Gehlenborg Nils , Phillips Carrie L. , El-Achkar Tarek M. , Dagher Pierre C. , Hato Takashi , Zhang Kun , Himmelfarb Jonathan , Kretzler Matthias , Mollah Shamim ,   Kidney Precision Medicine Project (KPMP), Jain Sanjay , Rauchman Michael , Eadon Michael T.
Published: June 2023

There is a need to define regions of gene activation or repression that control human kidney cells in states of health, injury, and repair to understand the molecular pathogenesis of kidney disease and design therapeutic strategies. However, comprehensive integration of gene expression with epigenetic features that define regulatory elements remains a significant challenge. We measured dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and H3K27ac, H3K4me1, H3K4me3, and H3K27me3 histone modifications to decipher the chromatin landscape and gene regulation of the kidney in reference and adaptive injury states. We established a comprehensive and spatially-anchored epigenomic atlas to define the kidney’s active, silent, and regulatory accessible chromatin regions across the genome. Using this atlas, we noted distinct control of adaptive injury in different epithelial cell types. A proximal tubule cell transcription factor network ofELF3,KLF6, andKLF10regulated the transition between health and injury, while in thick ascending limb cells this transition was regulated byNR2F1. Further, combined perturbation ofELF3,KLF6, andKLF10distinguished two adaptive proximal tubular cell subtypes, one of which manifested a repair trajectory after knockout. This atlas will serve as a foundation to facilitate targeted cell-specific therapeutics by reprogramming gene regulatory networks.
A trigger may not be necessary to cause senescence in deciduous broadleaf forests
Authors: Wheeler Kathryn I. , Dietze Michael C.
Published: June 2023

Plant phenological changes drive many ecosystem processes and are a key ecological indicator of climate change. Traditional models represent the onset of autumn leaf senescence, or color change, as a threshold response triggered by the accumulation of cold temperatures and declining day lengths, but the physiological mechanisms behind plant thermal memory and chilling thresholds remain elusive. Here we show that we can predict senescence in forest canopies by dynamically modeling daily greenness as the “memoryless” balance between chlorophyll synthesis, linearly-related to daily temperatures and day lengths, and breakdown. Indeed, summer-only data can be used to estimate breakdown and synthesis rates that in many cases successfully predict senescence at both calibration and validation sites. This mechanistic model shows that neither a trigger nor a physiological memory of coldness is necessary for senescence to start. These findings suggest that the start of senescence is not an irreversible transition, but a continuum of decreasing greenness where concurrent environmental conditions determine the rate of initial senescence. Furthermore, this emphasizes that in order to predict how senescence will shift in response to global change we likely need to focus on understanding the impacts on chlorophyll synthesis.

Significance statement

Plant phenology is a leading ecological indicator of climate change and has wide-ranging ecological and climatological impacts. Our findings here contradict the key assumption that senescence in deciduous broadleaf trees is actively triggered only when a threshold of cumulative cooling in combination of other stressors is reached. Instead we show that canopy greenness can be modeled as a passive process – balancing chlorophyll breakdown and temperature- and photoperiod-controlled synthesis – and still predict a rapid decline in greenness during senescence. This work is particularly important because it emphasizes that in order to understand climate change induced shifts in senescence, we need to focus on impacts on chlorophyll synthesis.