bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 688: PTEN Protects Against Vascular Smooth Muscle Cell Pro-inflammatory Dedifferentiation Through Metabolic Rewiring
Authors: Lu Sizhao , Jolly Austin , Dubner Allison , Noble Tysen , Nemenoff Raphael , Moulton Karen , Weiser-Evans Mary C
Published: October 2023

Vascular smooth muscle cells (SMCs) play a critical role in intimal hyperplasia in atherosclerosis and restenosis. SMCs in diseased arteries exhibit a modulated phenotype with reduced contractile gene expression, elevated proliferation, and a proinflammatory/profibrotic phenotype. Metabolic reprogramming accompanies and is essential for SMC phenotypic modulation. Our group previously demonstrated that the tumor suppressor gene, PTEN, contributes to the maintenance of the SMC contractile phenotype. Analysis of GTEx project data established a negative correlation between expression of PTEN and inflammatory genes in human artery tissues. As a metabolic regulator, the function of PTEN in SMC metabolism has not been examined. We subjected SMC lineage tracing mice with systemic (sPTEN) and inducible, SMC-specific (iPTEN) PTEN overexpression to disease models of atherosclerosis and carotid artery (CA) injury. Compared to control mice, sPTEN and iPTEN mice are protected from atherosclerotic lesion formation and ligation-induced neointima formation. The observed vascular protection effect of PTEN was associated with reduced inflammation and expression of key regulators of glycolysis, including GLUT1, HIF1a and PKM2, which were up-regulated in dedifferentiated SMCs. Consistently, unbiased metabolomics analysis confirmed that CA injury induced SMC metabolic phenotype, including accumulation of pyruvate, reduction of OXPHOS and increase of fatty acid synthesis, were rescued in iPTEN mice. Through high throughput screening, we previously identified and validated 5-azacytidine (5-aza) as potent transcriptional activator of PTEN expression. scRNA-seq data support that 5-aza reversed injury-induced SMC metabolic reprogramming and dedifferentiation trajectory. Altogether, the data support that PTEN antagonizes the metabolic changes in SMC dedifferentiation and can be therapeutically targeted to maintain the SMC metabolism and phenotype.
Abstract 693: Endothelial-specific Nck1 Deletion Reduces Proinflammatory Endothelial Activation And Atherosclerosis Without Affecting Ischemic Angiogenesis
Authors: Ben Dhaou Cyrine , Alfaidi Mabruka , Cockerham Elizabeth D , Scott Matthew L , Shen Xinggui , Yurdagul Arif , Rashdan Nabil , Pattillo Christopher B , Orr Wayne W
Published: October 2023

The Nck family of signaling adaptors, including both Nck1 and Nck2, classically regulate cell motility during vascular development and postnatal angiogenesis. While Nck1 and Nck2 play redundant roles in this regard with deletion of both isoforms required to affect tissue remodeling, we demonstrated that global Nck1 deletion was sufficient to reduce atherosclerotic plaque formation and selective Nck1 inhibition reduces proinflammatory endothelial activation in response to oscillatory shear stress. Therefore, we sought to determine the role of endothelial Nck1 in atherosclerosis and ischemic angiogenesis using novel endothelial-specific Nck1 knockout mice. Endothelial-specific Nck1 inhibition significantly reduced Western dietinduced atherosclerotic plaque formation at multiple sites compared to mice expressing endothelial-specific Cre alone or to endothelial-specific Nck2 knockout mice. This reduced plaque formation was characterized by diminished macrophage and smooth muscle incorporation despite enhanced weight gain in endothelial Nck1 knockout mice. RNA Sequencing analysis of endothelial cells in culture showed that Nck1 depletion reduces the expression of a variety of proinflammatory pathways but enhances the expression of genes involved in central carbon metabolism and proliferation. In addition, mass spectrometry analysis of Nck1 interacting proteins showed overrepresentation in binding partners involved in cell metabolism, consistent with published GWAS associations between Nck1 and body mass index and circulating plasma lipids. In contrast, Nck1 inhibition did not affect angiogenesis or limb perfusion in the femoral artery ligation model of hind limb ischemia. Taken together, endothelial Nck1 inhibition reduces atherosclerotic plaque formation associated with diminished proinflammatory responses without limiting ischemic angiogenesis, suggesting that Nck1 inhibition could be utilized to reduce atherosclerosis without preventing ischemic angiogenesis in the affected tissue.
Abstract 699: Blockade Of IL-6 Signaling Alleviates Atherosclerosis In Tet2 Deficient Clonal Hematopoiesis
Authors: Liu Wenli , Wang Nan , Tall Alan
Published: October 2023

Clonal hematopoiesis (CH) increases the risk of atherosclerotic cardiovascular disease (CVD) possibly due to increased plaque inflammation. Human studies suggest that limitation of interleukin 6 (IL-6) signaling could be beneficial in people with large CH clones, particularly in TET2 CH. Here we show that IL-6 receptor antibody treatment completely reverses atherosclerosis promoted by Tet2 CH, with reduction of monocytosis and lesional macrophage burden, and reversal of increased colony stimulating factor 1 receptor (CSF1R) expression in lesional macrophages. IL-6 induces expression of Csf1r in Tet2 deficient macrophages through decreased methylation of its promoter and enhanced STAT3 binding. In mouse and human embryonic stem cell-derived Tet2-deficient macrophages, increased CSF1R expression and signaling via CSF1R/PI3K/AKT enhances macrophage survival. Moreover, treatment with the CSF1R inhibitor PLX3397 reduced accelerated atherosclerosis in Tet2CH mice to the same level as controls. Our data demonstrate the causality of IL-6 signaling in Tet2 CH accelerated atherosclerosis, identify IL-6 regulated CSF1R expression as a critical mechanism, and support blockade of IL-6 signaling as a potential therapy of CH-driven CVD.
Abstract 704: Autophagy Activation Promotes Atherosclerosis Regression
Authors: Robichaud Sabrina , Rochon Valérie , Emerton Chrissy , Ouimet Mireille I
Published: October 2023

Atherosclerosis is characterized by the deposition of cholesterol-rich plaques within the artery wall that are primarily comprised of macrophage and vascular smooth muscle cell (VSMC) foam cells. Atherogenesis is associated with a progressive defect in autophagy, a cell process that promotes cellular cholesterol homeostasis by degrading excess lipids and promoting cholesterol efflux. We recently showed that during atherosclerosis
progression,
autophagy and cholesterol efflux to HDL was particularly defective in VSMC foam cells as compared to macrophage foam cells. While previous studies have shown that autophagy activation of transcription factor EB by trehalose protects against atherosclerosis, the ability of this therapeutic compound to shrink pre-existing atherosclerotic plaque (atherosclerosis
regression
) is unknown.

We hypothesized that activating autophagy with trehalose would promote atherosclerosis regression in mice by enhancing macrophage and VSMC reverse cholesterol transport.

Mice were injected with a gain of function PCSK9 adeno-associated virus and fed a Western Diet for 16 weeks to promote atherosclerotic plaque progression, followed by a switch to chow diet for 6 weeks to induce plaque regression. During the regression phase, mice received sub-cutaneous injections of saline or trehalose biweekly. Aortic sinuses were evaluated for changes in plaque size and lipid content. Circulating immune cells were quantified by flow cytometry.

A switch to chow diet decreased circulating inflammatory and patrolling monocytes as compared to baseline, although no changes between the trehalose and saline treatment groups were observed. Oil Red O staining revealed a decrease in plaque lipid content in trehalose-treated mice as compared to the saline group, suggesting that autophagy activation in mice during atherosclerosis regression promotes favorable plaque remodeling.

Our data demonstrates the therapeutic potential of autophagy activation in reducing atherosclerotic plaque burden. Further analysis of autophagy and inflammatory markers to characterize the mechanisms by which trehalose improves atherosclerosis regression is ongoing.
Abstract 711: Plasma Carotenoids Are Not Independent Determinants Of Subclinical Atherosclerosis In Coronary And Carotid Arteries
Authors: Neelissen Jan , Jonasson Lena , Leanderson Per , Chung Rosanna W
Published: October 2023

The association between dietary intake and/or plasma carotenoids and increased risk of cardiovascular events is well-established. Carotenoids have been proposed to protect against atherosclerosis by regulating inflammation and oxidative stress, however, the association between carotenoids and subclinical atherosclerosis is sparsely documented. Here, we hypothesized that plasma carotenoids were independently associated with subclinical atherosclerosis in coronary and carotid arteries in a Swedish population-based cohort (50-64 years), thus supporting the therapeutic potential of high carotenoid intake. In total, 986 subjects (mean age 57, 50% females) without known cardiovascular disease received CT calcium scoring (CACS), CT coronary angiography and carotid ultrasonography. Major carotenoids (lutein + zeaxanthin, β-cryptoxanthin, lycopene, α- and β-carotene) were measured in plasma. Intake of β-carotene was calculated based on a food frequency questionnaire. Data on sedentary behavior was derived from tri-axial accelerometers. Multinominal logistic regression was used to compare lower and upper tertiles of carotenoids with regard to CACS and atherosclerosis. Of all 986 subjects, 103 (10.4%) had CACS > 100, 197 (20.0%) had significant carotid atherosclerosis (> 1 plaque in carotid arteries), 295 (29.9%) had any coronary atherosclerosis and 37 (3.8%) had significant coronary atherosclerosis (≥ 50% stenosis in any coronary artery). In unadjusted models, low levels of total carotenoids, α- and β-carotene were significantly correlated with CAC > 100, coronary and carotid atherosclerosis. Low lutein correlated with carotid plaques and low intake of β-carotene with coronary and carotid plaques only. However, all associations lost significance after adjustment for age, sex, smoking status, abdominal obesity, BMI, sedentary behavior, hypertension, diabetes, total cholesterol, HDL cholesterol, triglycerides and C-reactive protein. To conclude, major carotenoids were not independent determinants of subclinical atherosclerosis. Data indicate that low levels of carotenoids depend on several other risk factors, such as male sex, obesity and sedentarism, and highlight the need of multifactorial lifestyle interventions.
Abstract 719: Impact Of Healthcare Coverage On Ischemic Heart Disease Mortality
Authors: Ibrahim Ramzi , Habib Adam , Terrani Kristina , Ravi Soumiya , Takamatsu Chelsea , Salih Mohammed , Lee Justin Z
Published: October 2023

Introduction:
Ischemic heart disease (IHD) is a leading cause of morbidity and mortality in the United States (U.S.). Health insurance influences outcomes associated with cardiovascular disease. Therefore, we explore the impact of the lack of health insurance on IHD mortality rates in the U.S.

Hypothesis:
Populations with a high prevalence of adults without health insurance have greater IHD mortality rates.

Methods:
Cross-sectional analyses were conducted to obtain IHD mortality and healthcare coverage data from the CDC Wide-Ranging Online Data for Epidemiologic Research and PLACES databases, respectively. Age-adjusted mortality rates (AAMR) related to IHD (ICD10: I20-I25) were obtained for 2018 and 2019. The age-adjusted prevalence of current lack of health insurance among individuals aged 18 to 64 years were obtained and placed into four quartiles. First quartile (Q1) included the least age-adjusted prevalence of adults without health insurance and fourth quartile (Q4) included the greatest age-adjusted prevalence of adults without health insurance. IHD-related AAMR were compared among quartiles.

Results:
Overall AAMR was higher in Q4 (92.79 [95% CI, 92.35 - 93.23]) compared to Q1 (83.14 [95% CI, 82.74 - 83.54]), accounting for 9.65 excess deaths per 100,000 person-years. Mortality rates in Q4 for males (126.20 [95% CI, 125.42 - 126.98] and females (65.57 [95% CI, 65.08 - 66.05]) were higher compared to Q1 (115.72 [95% CI, 114.99 - 116.44] and 57.48 [95% CI, 57.04 - 57.91], respectively), accounting for 10.48 and 8.09 excess deaths per 100,000 person-years for males and females, respectively. Similar trends were seen among Hispanic and non-Hispanic populations. Compared to Q1, a higher age-adjusted prevalence of adults without insurance in Q4 accounted for 27.13 and 13.64 excess deaths for Hispanic and non-Hispanic populations, respectively. Lastly, geographic analyses revealed similar trends for Northeastern, Southern, and Western regions, with Q4 accounting for 49.2, 8.15, and 29.04 excess deaths per 100,000 person-years, respectively, compared to Q1. No increase in mortality within Q4 compared to Q1 was observed for Midwestern regions.

Conclusion:
A lack of healthcare coverage is associated with increased IHD mortality rates.
Abstract 722: Smooth Muscle Cell Estrogen Receptor Alpha Deletion Protects Against Aging-associated Arterial Stiffness In Females
Authors: DuPont Jennifer J , Turner Casey , Martin Gregory , Sun Zhe , Hill Michael
Published: October 2023

Background:
Aging is associated with increasing arterial stiffness (AS), an independent risk factor for cardiovascular disease. While estrogen and estrogen receptor alpha (ERα) are protective in premenopausal females, the role of estrogen/ERα in aging-associated AS has not been defined and the mechanisms of the sexually-dimorphic development of aging-associated AS are unknown. We hypothesize that ERα contributes to sex differences in aging-associated AS.

Methods/Results:
We created novel smooth muscle cell-specific (SMC) ERα knockout mice (SMC-ERα-KO) and measured aortic pulse wave velocity (PWV), an index of AS, in 3, 12, and 18 mo old male and female intact and KO mice. Male mice develop AS at 12 mths compared to 18 mths in females (p<0.05, n=5-7/group). Deletion of SMC-ERα- protected females from the aging-associated increase in AS (p<0.05, n=5-7/group). Circulating estrogens declined in 18 mth old females vs. 3 mth. (p<0.05, n=6/group), suggesting a role for unliganded SMC-ERα in aging-associated AS. We also measured aortic gene expression of the vasoprotective angiotensin II type 2 receptor (AT2R) and found SMC-ERα-KO females were protected from the aging-associated decline in aortic AT2R expression observed in intact females (p<0.05, n=3-5/group), suggesting SMC-ERα regulates AT2R expression. To investigate the in vivo role of unliganded SMC-ERα in AS, we performed ovariectomy (OVX) or sham surgeries in young female intact and KO mice. We observed an OVX-driven increase in AS that was prevented by SMC-ERα-KO (p<0.05, n=5/group). This was also associated with an OVX-mediated decrease in aortic expression of AT2R, which was prevented by SMC-ERα-KO (p<0.05, n=5/group). In vitro studies also demonstrated that estrogen upregulates AT2R mRNA and protein expression in female mouse aortic SMC (p<0.05, n=5/group), supporting an estrogen-mediated mechanism of AT2R driven vascular protection in females that appears to be lost with age.

Conclusion:
These data indicate that with age, as circulating estrogens decline, SMC-ERα becomes detrimental and contributes to the development of aging-associated AS via reductions in AT2R in females. Further, these results suggest that AT2R agonist therapy may improve cardiovascular outcomes in aging women.
Standardized Definitions for Cardiogenic Shock Research and Mechanical Circulatory Support Devices: Scientific Expert Panel From the Shock Academic Research Consortium (SHARC)
Authors: Waksman Ron , Pahuja Mohit , van Diepen Sean , Proudfoot Alastair G. , Morrow David , Spitzer Ernest , Nichol Graham , Weisfeldt Myron L. , Moscucci Mauro , Lawler Patrick R. , Mebazaa Alexandre , Fan Eddy , Dickert Neal W. , Samsky Marc , Kormos Robert , Piña Ileana L. , Zuckerman Bram , Farb Andrew , Sapirstein John S. , Simonton Charles , West Nick E.J. , Damluji Abdulla A. , Gilchrist Ian C. , Zeymer Uwe , Thiele Holger , Cutlip Donald E. , Krucoff Mitchell , Abraham William T.
Published: October 2023

The Shock Academic Research Consortium is a multi-stakeholder group, including representatives from the US Food and Drug Administration and other government agencies, industry, and payers, convened to develop pragmatic consensus definitions useful for the evaluation of clinical trials enrolling patients with cardiogenic shock, including trials evaluating mechanical circulatory support devices. Several in-person and virtual meetings were convened between 2020 and 2022 to discuss the need for developing the standardized definitions required for evaluation of mechanical circulatory support devices in clinical trials for cardiogenic shock patients. The expert panel identified key concepts and topics by performing literature reviews, including previous clinical trials, while recognizing current challenges and the need to advance evidence-based practice and statistical analysis to support future clinical trials. For each category, a lead (primary) author was assigned to perform a literature search and draft a proposed definition, which was presented to the subgroup. These definitions were further modified after feedback from the expert panel meetings until a consensus was reached. This manuscript summarizes the expert panel recommendations focused on outcome definitions, including efficacy and safety.
A novel exidioides fungi, Myxarium boreale (Auriculariales, Basidiomycota) discovered from Northern China
Authors: WANG XIA , BAU TOLGOR
Published: October 2023

Myxarium boreale sp. nov., a new species of Myxarium in China, was identified based on ITS and nrLSU sequences along with morphological and molecular phylogenetic analyses. It is characterized by basidiomata gelatinous, cerebriform, hyaline with yellowish-white, with grooves when fresh; they appear as a thin layer that is raw-umber and contains mineral particles on the hymenial surface when dry; when covered with water, they absorb water and expand, slightly transparent, milk-white, and light yellowish is almost invisible; basidia 4(2)-celled, globose to subglobose; basidiospores allantoid to narrow cylindrical; hyphae clamped.
A new species of Psychotria (Rubiaceae) from Bidoup - Nui Ba National Park, Vietnam
Authors: NGUYEN QUOC BAO , QUACH VAN TOAN EM , HUYNH HUU DUC , PHAM QUOC TRONG , TRUONG BA VUONG , YAHARA TETSUKAZU , TAGANE SHUICHIRO , DANG VAN-SON
Published: October 2023

A new species, Psychotria ngotphamii (sect. Psychotrieae), is described and illustrated from Bidoup - Nui Ba National Park, Lam Dong Province, Vietnam. Psychotria ngotphamii is most similar to P. bonii Pit. but distinguished by its smaller leaf blades, shorter petioles, longer calyx and corolla lobes, and larger fruits. Photographs, vernacular name, preliminary conservation assessment, and a table comparing P. ngotphamii with its closest allies are provided.
Taxonomic notes on the group of Mischocyttarus heliconius Richards 1941, with description of four new species (Hymenoptera: Vespidae, Polistinae)
Authors: PINHEIRO MILEUDIANE O. , SILVEIRA ORLANDO T.
Published: October 2023

Mischocyttarus heliconius was described by Richards (1941), being initially assigned to subgenus Kappa, and later to Clypeopolybia. That author subsequently described other similar species, and Silveira (2008) conceived the group as also including M. iperuae Richards, M. sericeus Richards, M. chanchamayoensis Richards, and M. piger Richards. However, the latter species is not a member of this group, which otherwise can be easily recognized by morphological characters. Three of these species were retrieved as forming a monophyletic group by Silveira (2008), but relations with other groups in Mischocyttarus are uncertain. Types and new material of the M. heliconius group are here revised, with addition of four new species (M. gorotire sp. nov., M. ipixuna sp. nov., M. luciliae sp. nov., M. ticuna sp. nov.), and a new identification key is presented. Mischocyttarus piger Richards is reassigned to the group of M. iheringi Zikán in the subgenus Haplometrobius Richards.
Linking Instantaneous and Climatological Perspectives on Eddy-Driven and Subtropical Jets
Authors: Spensberger Clemens , Li Camille , Spengler Thomas
Published: October 2023

The distinction between eddy-driven and subtropical jets is conceptually important and well-founded based on different driving mechanisms and dominant types of variability. This climatological perspective may be augmented by considering instantaneous maxima in the wind field and linking these to the time-mean jets. Inspired by EOF and cluster analyses to explore the variability in jet occurrences, we propose a straightforward framework that naturally distinguishes subtropical from eddy-driven jets in instantaneous data. We document that for most ocean basins, there is a clear bimodality in instantaneous jet occurrences in potential temperature–wind speed space. The two types of jets in this phase space align well with the conceptual expectations for subtropical and eddy-driven jets regarding their vertical structure as well as their regional occurrence. Interestingly, the bimodality in phase space is most pronounced in the western North Pacific during winter. The climatological jet in this region is typically regarded as “merged,” resulting from a mixture of thermal driving and eddy driving. Our results clarify that the strongest instantaneous jets in this region are classified as subtropical, with eddy-driven jets occurring in close proximity to the climatological mean jet, though weaker and slightly more poleward. We also show that the regions of climatological transition from predominantly subtropical to predominantly eddy-driven jets are just downstream of the strongest climatological jets.
How Have Hydrological Extremes Changed over the Past 20 Years?
Authors: Li Bailing , Rodell Matthew
Published: October 2023

Severe floods and droughts, including their back-to-back occurrences (weather whiplash), have been increasing in frequency and severity around the world. Improved understanding of systematic changes in hydrological extremes is essential for preparation and adaptation. In this study, we identified and quantified extreme wet and dry events globally by applying a clustering algorithm to terrestrial water storage (TWS) data from the Gravity Recovery and Climate Experiment (GRACE) and GRACE Follow-On (FO). The most intense events, ranked using an intensity metric, often reflect impacts of large-scale oceanic oscillations such as El Niño–Southern Oscillation and consequences of climate change. The severity of both wet and dry events, represented by standardized TWS anomalies, increased significantly in most cases, likely associated with intensification of wet and dry weather regimes in a warmer world, and consequently, exhibited strongest correlation with global temperature. In the Dry climate, the number of wet events decreased while the number of dry events increased significantly, suggesting a drying trend that may be attributed to climate variability and possible increases in irrigation and reliance on groundwater. In the Continental climate where temperature has risen faster than global average, dry events increased significantly. Characteristics of extreme events often showed strong correlations with global temperature, especially when averaged over all climates. These results suggest changes in hydrological extremes and underscore the importance of quantifying total water storage changes when studying hydrological extremes. Extending the GRACE/FO record, which spans 2002 to the present, is essential to continuously tracking changes in TWS and hydrological extremes.
Type Synthesis of Fully Decoupled Three Translational Parallel Mechanism with Closed-Loop Units and High Stiffness
Authors: Li Shihua , Wang Sen , Li Haoran , Wang Yongjie , Chen Shuang
Published: October 2023

In order to solve the problem of weak stiffness of the existing fully decoupled parallel mechanism, a new synthesis method of fully decoupled three translational (3T) parallel mechanisms (PMs) with closed-loop units and high stiffness is proposed based on screw theory. Firstly, a new criterion for the full decoupled of PMs is presented that the reciprocal product of the transmission wrench screw matrix and the output twist screw matrix of PMs is a diagonal matrix, and all elements on the main diagonal are nonzero constants. The forms of the transmission wrench screws are determined by the criterion. Secondly, the forms of the actuated and unactuated screws can be obtained according to their relationships with the transmission wrench screws. The basic decoupled limbs are generated by combination of the above actuated and unactuated screws. Finally, a closed-loop units construction method is investigated to apply the decoupled mechanisms in a better way on the high stiffness occasion. The closed-loop units are constructed in the basic decoupled limbs to generate a high-stiffness fully decoupled 3T PM. Kinematic and stiffness analyses show that the Jacobian matrix is a diagonal matrix, and the stiffness is obviously higher than that of the coupling mechanisms, which verifies the correctness of the proposed synthesis method. The mechanism synthesized by this method has a good application prospect in vehicle durability test platform.
An unusual case of thrombotic storm in an amateur cricketer—a case report
Authors: Shankar Takshak , Vempalli Nagasubramanyam , Bairwa Archana
Published: October 2023

Background

Thrombotic storm is a series of acute to subacute thrombotic events that evolve over a few days to weeks and result in progressive thromboses at multiple sites. There is often a predisposing event to thromboses, such as trauma or infections. Prompt initiation of anti-coagulation can prove life-saving in such patients.

Case report

We describe a previously healthy young male who developed thromboses of the right axillary, brachial, radial, and ulnar arteries while bowling in a cricket match. A few hours later, he developed a stroke involving the right anterior and middle cerebral arteries. His thrombophilia workup was significant for elevated homocysteine levels. Although he had a delayed presentation to our hospital, he was treated with anticoagulation and given a trial of thromboembolectomy, which failed and he had to ultimately undergo a right below-elbow guillotine amputation.

Conclusion

Thrombotic storm should be recognized promptly in the Emergency Department and timely anticoagulation should be initiated.
Implementation of web-based respondent driven sampling in epidemiological studies
Authors: Ferrer-Rosende Pedro , Feijoo-Cid María , Fernández-Cano María Isabel , Salas-Nicás Sergio , Stuardo-Ávila Valeria , Navarro-Giné Albert
Published: October 2023

Background

Respondent-driven sampling (RDS) is a peer chain-recruitment method for populations without a sampling frame or that are hard-to-reach. Although RDS is usually done face-to-face, the online version (WebRDS) has drawn a lot of attention as it has many potential benefits, despite this, to date there is no clear framework for its implementation. This article aims to provide guidance for researchers who want to recruit through a WebRDS.

Methods

Description of the development phase: guidance is provided addressing aspects related to the formative research, the design of the questionnaire, the implementation of the coupon system using a free software and the diffusion plan, using as an example a web-based cross-sectional study conducted in Spain between April and June 2022 describing the working conditions and health status of homecare workers for dependent people.

Results

The application of the survey: we discuss about the monitoring strategies throughout the recruitment process and potential problems along with proposed solutions.

Conclusions

Under certain conditions, it is possible to obtain a sample with recruitment performance similar to that of other RDS without the need for monetary incentives and using a free access software, considerably reducing costs and allowing its use to be extended to other research groups.
Unusual herpetic reactivation in a young female following botox injection: a case report study
Authors: Amini-Salehi Ehsan , Eslami Narges , Tamimi Amirhossein , Sedighi Nasrin , Moghdam Saman Soltani , Yaghubi-Kalurazi Tofigh , Hassanipour Soheil , Joukar Farahnaz , Mansour-Ghanaei Fariborz , Eftekhari Hojat
Published: October 2023

Background

Botox injections are commonly used for cosmetic and therapeutic purposes because they temporarily paralyze muscles, reduce wrinkles, and alleviate certain medical conditions. Although generally considered safe and effective, Botox injections may cause potential complications. While herpes reactivation is more commonly associated with immunosuppressive therapies, such as chemotherapy or corticosteroid use, its association with Botox injection is poorly documented.

Case Presentation

A 33-year-old woman presented with progressive painful rashes and vesicles on her forehead, scalp, and right upper eyelid, accompanied by fever and malaise following a Botox injection to treat wrinkles. A positive Tzanck smear test result confirmed the diagnosis of herpes infection. The patient was treated with antiviral medication, and her symptoms gradually regressed over several days.

Conclusions

Although herpes reactivation is more commonly associated with immunosuppressive therapies, few cases of herpes zoster and herpes simplex following Botox injection have been reported. The pathogenesis of herpes reactivation following Botox injection is unclear; however, it has been hypothesized that the Botox protein is a potent antigen that may activate the cellular immune system, making it easier for the virus to reactivate. Healthcare providers should be aware of this potential complication and consider it when evaluating patients who present with painful rashes following Botox injections. In addition, individuals who want to receive Botox injections should be informed of this complication. The diagnosis of herpetic infection should be made promptly, and antiviral therapy should be initiated to minimize the risk of complications. Further research is needed to better understand the pathogenesis and risk factors for herpes following Botox injection and to develop strategies for preventing and managing this complication.
Effect of nausea and vomiting during pregnancy on mother-to-infant bonding and the mediation effect of postpartum depression: the Japan Environment and Children’s Study
Authors: Yang Gui , Hisada Aya , Yamamoto Midori , Kawanami Akiko , Mori Chisato , Sakurai Kenichi ,   The Japan Environment, Children’s Study (JECS) Group, Kamijima Michihiro , Yamazaki Shin , Ohya Yukihiro , Kishi Reiko , Yaegashi Nobuo , Hashimoto Koichi , Ito Shuichi , Yamagata Zentaro , Inadera Hidekuni , Nakayama Takeo , Sobue Tomotaka , Shima Masayuki , Kageyama Seiji , Suganuma Narufumi , Ohga Shoichi , Katoh Takahiko
Published: October 2023

Background

Mother-to-infant bonding (MIB) is critical for the health and well-being of the mother and child. Furthermore, MIB has been shown to boost the social-emotional development of infants, while also giving mothers a sense of happiness in raising their children. Nausea and vomiting during pregnancy (NVP) is a normal complication of pregnancy, occurring in approximately 50–90% of pregnant women in the early stages of pregnancy. Despite widespread knowledge of MIB and postpartum depression, little research attention has been given to the effects of NVP on MIB. This study aimed to investigate the relationship between NVP and MIB and the mediating effects of postpartum depression.

Methods

We analyzed the data of 88,424 infants and 87,658 mothers from the Japan Environment and Children’s Study (JECS), which is a government-funded nationwide birth prospective cohort study. The Japanese version of the Mother-to-Infant Bonding Scale (MIBS-J) was used to assess MIB, and the Edinburgh Postpartum Depression Scale (EPDS) was utilized to assess postpartum depression. We divided participants into four groups according to a self-reported questionnaire assessing NVP (No NVP, Mild NVP, Moderate NVP, and Severe NVP). MIB disorder was defined as a MIBS-J score ≥ 5. Logistic analysis was performed to evaluate the effect of NVP on MIB disorder at one year after delivery. A mediation analysis was conducted to examine whether postpartum depression mediated the association between NVP and MIBS-J scores.

Results

The logistic regression analysis results revealed reduced risks of MIB disorder among mothers with Moderate NVP (adjusted OR 0.93; 95% confidence interval, 0.86–0.99) and Severe NVP (adjusted OR 0.81; 95% confidence interval, 0.74–0.89), compared to those with No NVP. The mediation analysis revealed that NVP positively correlated with MIBS-J score in the indirect effect via postpartum depression, while NVP (Mild NVP, Moderate NVP, and Severe NVP) negatively correlated with MIBS-J score in the direct effect.

Conclusion

The risks of MIB disorder were reduced in the Moderate NVP and Severe NVP mothers, although NVP inhibited the development of MIB via postpartum depression. The development of effective interventions for postpartum depression is important to improve MIB among mothers with NVP.
Exosomes-mediated transfer of LINC00691 regulates the formation of CAFs and promotes the progression of gastric cancer
Authors: Xia Bin , Gu Xiuyu , Xu Tingting , Yan Meina , Huang Lan , Jiang Chun , Li Meifen , Zhai Guanghua , Zhang Guoping , Wu Jian , Zhou Yu , Sun Chunrong , Liang Wei
Published: October 2023

Objective

Gastric cancer (GC) is one of the malignant tumors with the highest mortality worldwide. Our previous studies have revealed that LINC00691 is up-regulated in serum of GC patients as a novel potential biomarker for GC diagnosis and prognosis. However, the roles of serum exosomal LINC00691 in GC has not been clarified. This study aimed to find the expression pattern of serum exosomal LINC00691 in GC patients and the correlation between the level of serum exosomal LINC00691 and the pathology of gastric cancer patients.

Methods

We collected the serum of 94 GC patients before surgery and extracted exosomes to detect the expression level of exosomal LINC00691, with 21 healthy volunteers and 17 patients with benign gastric diseases as controls. Surgical GC tissues and paired healthy tissues were collected to culture primary cancer-associated fibroblasts (CAFs) and normal fibroblasts (NFs). We then treated NFs with LINC00691-rich GC cell culture supernatant or exosomes and detected the activation markers and biological functions of the fibroblasts.

Results

The results of real-time qPCR indicated that the serum exosomal LINC00691 of GC patients was significantly higher than that of healthy subjects and patients with benign gastric diseases, and was associated with the clinicopathology of GC patients. More interestingly, when the NFs were treated with GC exosomes, the level of LINC00691 was significantly increased, the cell proliferation and migration were noticeably enhanced, and the ability to accelerate GC cell proliferation and invasion was promoted, which means that the induced fibroblasts gained the properties of CAFs. In addition, we found that knockdown of LINC00691 and the use of the JAK2/STAT3 signaling pathway inhibitor ruxolitinib effectively deprived exosome-containing GC cell supernatants of the effects on NFs.

Conclusion

Our study suggested that exosomal LINC00691 promoted NFs to gained the properties of CAFs depending on JAK2/STAT3 signaling pathway as a potential diagnostic biomarker for GC.
Early echocardiographic pulmonary artery measurements as prognostic indicators in left congenital diaphragmatic hernia
Authors: Park Sung Hyeon , Kim Mi Jin , Lee Ha Na , Lee Jeong Min , Kim Soo Hyun , Jeong Jiyoon , Lee Byong Sop , Jung Euiseok
Published: October 2023

Background

To predict whether the left pulmonary artery (LPA) to the main pulmonary artery (MPA) ratio measured by echocardiography in left congenital diaphragmatic hernia (CDH) was related to death or need for extracorporeal membrane oxygenation (ECMO).

Methods

This retrospective study analyzed neonates with left CDH born between 2018 and 2022 in a single tertiary medical institution. Echocardiography was performed immediately after birth. The diameter of the LPA was measured at the bifurcation, and the diameter of the MPA was measured at the maximal dimension during the systolic phase. The Nakata index, McGoon ratio, and ejection fraction (EF) were analyzed and compared with the LPA: MPA ratio as predictive values.

Results

Seventy-two neonates with left CDH were included, 19 (26.4%) died or needed ECMO, and 53 (73.6%) survived without ECMO. The lower observed/expected lung-to-head ratio, lower EF, lower LPA: MPA ratio, lower RPA: MPA ratio, lower Nakata index, and lower McGoon ratio were associated with death or need for ECMO. By multivariate analysis, lower LPA: MPA ratio, RPA: MPA ratio, and Nakata index were independent postnatal risk factors for death or need for ECMO. Among the measurements, the LPA: MPA ratio had the highest area under the curve (0.957) with a sensitivity of 84.2% and specificity of 96.3% at a cut-off value of 31.2%.

Conclusion

In patients with left CDH, the LPA: MPA ratio measured by echocardiography could be used as an independent postnatal predictor of death or need for ECMO.
Using systems thinking to understand the scale-up and sustainability of health innovation: a case study of seasonal malaria chemoprevention processes in Burkina Faso
Authors: Niang Marietou , Gagnon Marie-Pierre , Dupéré Sophie
Published: October 2023

Background

Scale-up and sustainability are often studied separately, with few studies examining the interdependencies between these two processes and the implementation contexts of innovations towards malaria prevention and control. Researchers and implementers offer much more attention to the content of innovations, as they focus on the technological dimensions and the conditions for expansion. Researchers have often considered innovation a linear sequence in which scaling up and sustainability represented the last stages. Using systems thinking in this manuscript, we analyze complex scaling and sustainability processes through adopting and implementing seasonal malaria chemoprevention (SMC) in Burkina Faso from 2014 to 2018.

Methods

We conducted a qualitative case study involving 141 retrospective secondary data (administrative, press, scientific, tools and registries, and verbatim) spanning from 2012 to 2018. We complemented these data with primary data collected between February and March 2018 in the form of 15 personal semi-structured interviews with SMC stakeholders and non-participant observations. Processual analysis permitted us to conceptualize scale-up and sustainability processes over time according to different vertical and horizontal levels of analysis and their interconnections.

Results

Our results indicated six internal and external determinants of SMC that may negatively or positively influence its scale-up and sustainability. These determinants are effectiveness, monitoring and evaluation systems, resources (financial, material, and human), leadership and governance, adaptation to the local context, and other external elements. Our results revealed that donors and implementing actors prioritized financial resources over other determinants. In contrast, our study clearly showed that the sustainability of the innovation, as well as its scaling up, depends significantly on the consideration of the interconnectedness of the determinants. Each determinant can concurrently constitute an opportunity and a challenge for the success of the innovation.

Conclusion

Our findings highlight the usefulness of the systemic perspective to consider all contexts (international, national, subnational, and local) to achieve large-scale improvements in the quality, equity, and effectiveness of global health interventions. Thus, complex and systems thinking have made it possible to observe emergent and dynamic innovation behaviors and the dynamics particular to sustainability and scaling up processes.
Screening and identifying of biomarkers in early colorectal cancer and adenoma based on genome-wide methylation profiles
Authors: He Chungang , Huang Qinyuan , Zhong Shibiao , Chen Li Sheng , Xiao Hewei , Li Lei
Published: October 2023

Background

Colorectal cancer is one of the most common malignant tumors worldwide with high morbidity and mortality. This study aimed to identify different methylation sites as new methylation markers in CRC and colorectal adenoma through tissue detection.

Methods

DNA extraction and bisulfite modification as well as Infinium 450K methylation microarray detection were performed in 46 samples of sporadic colorectal cancer tissue, nine samples of colorectal adenoma, and 20 normal samples, and bioinformatic analysis was conducted involving genes enrichments of GO and KEGG. Pyrosequencing methylation detection was further performed in 68 sporadic colorectal cancer tissues, 31 samples of colorectal adenoma, and 49 normal colorectal mucosae adjacent to carcinoma to investigate the differentially methylated genes obtained from methylation microarray.

Results

There were 65,535 differential methylation marker probes, among which 25,464 were hypermethylated markers and 40,071 were hypomethylated markers in the adenoma compared with the normal group, and 395,571 were differentially methylated markers in patients with sporadic colorectal cancer compared with the normal group, including 21,710 hypermethylated markers and 17,861 hypomethylated markers. Five hypermethylated genes including ZNF471, SND1, SPOCK1, FBLIM1, and OTX1 were detected and confirmed in 68 cases of colorectal cancer, 31 cases of adenoma, and 49 cases of normal control group.

Conclusions

Hypermethylated genes of ZNF471, SND1, SPOCK1, FBLIM1, and OTX1 were obtained from methylation chip detection and further confirm analysis in colorectal cancer and adenoma compared with normal tissue, which may be promising diagnostic markers of colorectal cancer and colorectal adenoma.
Exploring the dynamic interplay between cancer stem cells and the tumor microenvironment: implications for novel therapeutic strategies
Authors: Li Yan-Ruide , Fang Ying , Lyu Zibai , Zhu Yichen , Yang Lili
Published: October 2023

Cancer stem cells (CSCs) have emerged as key contributors to tumor initiation, growth, and metastasis. In addition, CSCs play a significant role in inducing immune evasion, thereby compromising the effectiveness of cancer treatments. The reciprocal communication between CSCs and the tumor microenvironment (TME) is observed, with the TME providing a supportive niche for CSC survival and self-renewal, while CSCs, in turn, influence the polarization and persistence of the TME, promoting an immunosuppressive state. Consequently, these interactions hinder the efficacy of current cancer therapies, necessitating the exploration of novel therapeutic approaches to modulate the TME and target CSCs. In this review, we highlight the intricate strategies employed by CSCs to evade immune surveillance and develop resistance to therapies. Furthermore, we examine the dynamic interplay between CSCs and the TME, shedding light on how this interaction impacts cancer progression. Moreover, we provide an overview of advanced therapeutic strategies that specifically target CSCs and the TME, which hold promise for future clinical and translational studies in cancer treatment.
Causal associations between sleep traits and brain structure: a bidirectional Mendelian randomization study
Authors: Wang Qiao , Hu Shimin , Qi Lei , Wang Xiaopeng , Jin Guangyuan , Wu Di , Wang Yuke , Ren Liankun
Published: October 2023

Background

Emerging evidence suggests bidirectional causal relationships between sleep disturbance and psychiatric disorders, but the underlying mechanisms remain unclear. Understanding the bidirectional causality between sleep traits and brain imaging-derived phenotypes (IDPs) will help elucidate the mechanisms. Although previous studies have identified a range of structural differences in the brains of individuals with sleep disorders, it is still uncertain whether grey matter (GM) volume alterations precede or rather follow from the development of sleep disorders.

Results

After Bonferroni correction, the forward MR analysis showed that insomnia complaint remained positively associated with the surface area (SA) of medial orbitofrontal cortex (β, 0.26; 95% CI, 0.15–0.37; P = 5.27 × 10–6). In the inverse MR analysis, higher global cortical SA predisposed individuals less prone to suffering insomnia complaint (OR, 0.89; 95%CI, 0.85–0.94; P = 1.51 × 10–5) and short sleep (≤ 6 h; OR, 0.98; 95%CI, 0.97–0.99; P = 1.51 × 10–5), while higher SA in posterior cingulate cortex resulted in a vulnerability to shorter sleep durations (β, − 0.09; 95%CI, − 0.13 to − 0.05; P = 1.21 × 10–5).

Conclusions

Sleep habits not only result from but also contribute to alterations in brain structure, which may shed light on the possible mechanisms linking sleep behaviours with neuropsychiatric disorders, and offer new strategies for prevention and intervention in psychiatric disorders and sleep disturbance.
May we routinely spare hippocampal region in primary central nervous system lymphoma during whole brain radiotherapy?
Authors: Mazzarella Ciro , Chiesa Silvia , Toppi Lucrezia , Hohaus Stefan , Gaudino Simona , D’Alo Francesco , Dinapoli Nicola , Davide Resta , Zinicola Tiziano , Bracci Serena , Martino Antonella , Beghella Bartoli Francesco , Lepre Elisabetta , Bertolini Roberta , Mariani Silvia , Colosimo Cesare , Frascino Vincenzo , Mattiucci Gian Carlo , Gambacorta Maria Antonietta , Valentini Vincenzo , Balducci Mario
Published: October 2023

Purpose

One of the main limiting factors of whole-brain radiation therapy (WBRT) for primary central nervous system lymphoma (PCNSL) is the impairment of neurocognitive functions (NCFs), which is mainly caused by radiation-induced injury to the hippocampus. With a view to preventing NCF impairment and personalizing treatment, we explored the feasibility of sparing the hippocampus during WBRT by correlating the sites of PCNSL lesions with the hippocampus.

Methods and materials

Pre-treatment MR images from patients who underwent WBRT between 2010 and January 2020—and post-radiotherapy images in cases of relapse—were imported into the Varian Eclipse treatment-planning system and registered with the simulation CT. We constructed three 3-dimensional envelopes around the hippocampus at distances of 5, 10 and 15 mm and also contoured primary lesions and recurrences.

Results

We analyzed 43 patients with 66 primary lesions: 9/66 (13.6%) involved the hippocampus and 11/66 (16.7%) were located within 5 mm of it. Thirty-six lesions (54.5%) were situated more than 15 mm from the hippocampus, while 10/66 (15.2%) were between 5 and 15 mm from it. The most common location was in deep brain structures (31%). Thirty-five of the 66 lesions relapsed: in field in 14/35 (40%) and outfield in 21/35 (60%) in different sites. Globally, 16/35 recurrences (45.7%) were located in the hippocampus or within 5 mm of it.

Conclusion

These data show that routinely sparing the hippocampus is not feasible. This approach could be considered in selected patients, when the lesion is more than 15 mm from the hippocampus.