bluuebunny/crossref_metadata_2025 huggingface dataset:
A Preliminary Study on the Functionality of the Carotid-Vertebral Anastomotic Artery in the Regulation of Blood Flow in the Giraffe (Giraffa camelopardalis) by Duplex Ultrasound Examination
Authors: van der Walt Marna S. , Daffue Willem , Goedhals Jacqueline , Serfontein Corna , Deacon Francois
Published: February 2023

Postural change intermittently between upright and head down in giraffes standing at a height of 4.5 meters is of physiological significance. The length of a giraffe’s neck denotes the flow of blood against the force of gravity, to supply the brain over a 2 m distance. The force of gravity also affects the flow of blood toward the brain, with a posture change from erect to ground level. How do these changes in stance not result in fainting when the head is raised and brain damage when the head is lowered? Giraffe has an advanced interconnection of the common carotid artery and the vertebral artery. The connection is located at the midpoint of the atlas, as indicated by means of computerized tomography and dissection. Duplex ultrasound with Doppler waveform examination showed the unidirectional movement of blood with movement from the vertebral artery into the common carotid artery when the head is erect. The direction of flow allows the provision of blood to the maxillary artery that feeds the rostral epidural rete that supplies to the brain. The flow direction in the carotid-vertebral connection changes when blood moves in the direction of the head along with the force of gravity, when the head is lowered. The rerouting of blood to move from the common carotid into the vertebral artery prevents brain damage. We have confirmed, by utilizing a CT scan, Doppler sonar, and dissection of latex-filled arteries, the existence and blood flow direction within the anastomotic artery associated with variation in posture in the giraffe.
Group Dynamics and Allocation of Advanced Heart Failure Therapies—Heart Transplants and Ventricular Assist Devices—By Gender, Racial, and Ethnic Group
Authors: Breathett Khadijah , Yee Ryan , Pool Natalie , Thomas Hebdon Megan C. , Knapp Shannon M. , Herrera‐Theut Kathryn , de Groot Esther , Yee Erika , Allen Larry A. , Hasan Ayesha , Lindenfeld JoAnn , Calhoun Elizabeth , Carnes Molly , Sweitzer Nancy K.
Published: February 2023

Background

US regulatory framework for advanced heart failure therapies (AHFT), ventricular assist devices, and heart transplants, delegate eligibility decisions to multidisciplinary groups at the center level. The subjective nature of decision‐making is at risk for racial, ethnic, and gender bias. We sought to determine how group dynamics impact allocation decision‐making by patient gender, racial, and ethnic group.

Methods and Results

We performed a mixed‐methods study among 4 AHFT centers. For ≈ 1 month, AHFT meetings were audio recorded. Meeting transcripts were evaluated for group function scores using de Groot Critically Reflective Diagnoses protocol (metrics: challenging groupthink, critical opinion sharing, openness to mistakes, asking/giving feedback, and experimentation; scoring: 1 to 4 [high to low quality]). The relationship between summed group function scores and AHFT allocation was assessed via hierarchical logistic regression with patients nested within meetings nested within centers, and interaction effects of group function score with gender and race, adjusting for patient age and comorbidities. Among 87 patients (24% women, 66% White race) evaluated for AHFT, 57% of women, 38% of men, 44% of White race, and 40% of patients of color were allocated to AHFT. The interaction between group function score and allocation by patient gender was statistically significant (
P
=0.035); as group function scores improved, the probability of AHFT allocation increased for women and decreased for men, a pattern that was similar irrespective of racial and ethnic groups.

Conclusions

Women evaluated for AHFT were more likely to receive AHFT when group decision‐making processes were of higher quality. Further investigation is needed to promote routine high‐quality group decision‐making and reduce known disparities in AHFT allocation.
Sex Differences in Temporal Trends and Risk Factors of Aortic Dissection in Taiwan
Authors: Chang Cherry Yin‐Yi , Wu Ching‐Feng , Muo Chih‐Hsin , Chang Shih‐Sheng , Chen Pei‐Chun
Published: February 2023

Background

Although sex differences in the epidemiological features of aortic dissection (AD) are known, whether there were sex differences in the associations of comorbidities and risk factors with AD is unclear. We evaluated the temporal trends and risk factors of AD by sex.

Methods and Results

Using claims data from a universal health insurance program linked to the National Death Registry in Taiwan, we identified 16 368 men and 7052 women with newly diagnosed AD from 2005 to 2018. In the case‐control analysis, a matched control group without AD was selected for men and women separately. Conditional logistic regression was used to evaluate risk factors of AD and sex differences. Over the 14 years, the annual incidence of diagnosed AD was 12.69 and 5.34 per 100 000 in men and women, respectively. The 30‐day mortality was greater in women than in men (18.1% versus 14.1%; adjusted odds ratio [95% CI], 1.19 [1.10–1.29]), and the sex difference was observed mainly in patients not treated with surgery. The 30‐day mortality declined over time in male patients undergoing surgical treatments, but no significantly temporal change was found in other patient groups stratified by sex and surgery. After multivariable adjustments, atrial fibrillation, chronic kidney disease, and coronary artery bypass graft surgery were associated with a greater increase in the odds of AD occurrence in women than in men.

Conclusions

Greater 30‐day mortality and stronger associations of atrial fibrillation, chronic kidney disease, and coronary artery bypass graft surgery with AD in women than in men require further attention.
Women's Reproductive Milestones and Cardiovascular Disease Risk: A Review of Reports and Opportunities From the CARDIA Study
Authors: Kim Catherine , Catov Janet , Schreiner Pamela J. , Appiah Duke , Wellons Melissa F. , Siscovick David , Calderon‐Margalit Ronit , Huddleston Heather , Ebong Imo Asuquo , Lewis Cora E.
Published: February 2023

In 1985 to 1986, the CARDIA (Coronary Artery Risk Development in Young Adults) study enrolled 5115 Black or White participants, including 2788 women, aged 18 to 30 years. Over the following 35 years, the CARDIA study amassed extensive longitudinal data on women's reproductive milestones, spanning menarche to menopause. Although not initially conceived as a study of women's health, >75 CARDIA study publications address relationships between reproductive factors and events with cardiovascular and metabolic risk factors, subclinical and clinical cardiovascular disease, and social determinants of health. The CARDIA study was one of the earliest population‐based reports to note Black‐White differences in age at menarche and associations with cardiovascular risk factors. Adverse pregnancy outcomes, particularly gestational diabetes and preterm birth, have been assessed along with postpartum behaviors, such as lactation. Existing studies have examined risk factors for adverse pregnancy outcomes and lactation, as well as their relationship to future cardiovascular and metabolic risk factors, diagnoses, and subclinical atherosclerosis. Ancillary studies examining components of polycystic ovary syndrome and ovarian biomarkers, such as anti‐Müllerian hormone, have facilitated examination of reproductive health in a population‐based cohort of young adult women. As the cohort transitioned through menopause, examination of the importance of premenopausal cardiovascular risk factors along with menopause has improved our understanding of shared mechanisms. The cohort is now aged in the 50s to mid‐60s, and women will begin to experience a greater number of cardiovascular events as well as other conditions, such as cognitive impairment. Thus, in the next decade, the CARDIA study will provide a unique resource for understanding how the women's reproductive life course epidemiology informs cardiovascular risk, as well as reproductive and chronological aging.
Differential Impact of Brain Network Efficiency on Poststroke Motor and Attentional Deficits
Authors: Evangelista Giorgia G. , Egger Philip , Brügger Julia , Beanato Elena , Koch Philipp J. , Ceroni Martino , Fleury Lisa , Cadic-Melchior Andéol , Meyer Nathalie H. , Rodríguez Diego de León , Girard Gabriel , Léger Bertrand , Turlan Jean-Luc , Mühl Andreas , Vuadens Philippe , Adolphsen Jan , Jagella Caroline E. , Constantin Christophe , Alvarez Vincent , San Millán Diego , Bonvin Christophe , Morishita Takuya , Wessel Maximilian J. , Van De Ville Dimitri , Hummel Friedhelm C.
Published: February 2023

Background:

Most studies on stroke have been designed to examine one deficit in isolation; yet, survivors often have multiple deficits in different domains. While the mechanisms underlying multiple-domain deficits remain poorly understood, network-theoretical methods may open new avenues of understanding.

Methods:

Fifty subacute stroke patients (7±3days poststroke) underwent diffusion-weighted magnetic resonance imaging and a battery of clinical tests of motor and cognitive functions. We defined indices of impairment in strength, dexterity, and attention. We also computed imaging-based probabilistic tractography and whole-brain connectomes. To efficiently integrate inputs from different sources, brain networks rely on a rich-club of a few hub nodes. Lesions harm efficiency, particularly when they target the rich-club. Overlaying individual lesion masks onto the tractograms enabled us to split the connectomes into their affected and unaffected parts and associate them to impairment.

Results:

We computed efficiency of the unaffected connectome and found it was more strongly correlated to impairment in strength, dexterity, and attention than efficiency of the total connectome. The magnitude of the correlation between efficiency and impairment followed the order attention>dexterity ≈ strength (strength: |
r
|=.03,
P
=0.02, dexterity: |
r
|=.30,
P
=0.05, attention: |
r
|=.55,
P
<0.001). Network weights associated with the rich-club were more strongly correlated to efficiency than non-rich-club weights.

Conclusions:

Attentional impairment is more sensitive to disruption of coordinated networks between brain regions than motor impairment, which is sensitive to disruption of localized networks. Providing more accurate reflections of actually functioning parts of the network enables the incorporation of information about the impact of brain lesions on connectomics contributing to a better understanding of underlying stroke mechanisms.
All (Cautiously) Hail-and Scale-Community!
Authors: Singh Prerna
Published: February 2023

In her essay, Jenna Bednar makes a powerful case and sets out a persuasive framework for refocusing public policy away from the market toward “human flourishing.” In this response, I build on one of the pillars of her framework-community-to showcase its potential to promote human flourishing at scale. I show how communities can promote human flourishing not just locally, but also at the national level. And yet, a focus on the progressive power of nationalism at once also cautions against the dangers inherent in the concept of community itself: that is, that all communities are necessarily bounded and unequal. In laying bare the exclusion and violence that communities can inflict on those beyond their boundaries, and/or down the ladder of “prototypicality,” nationalism is a dark, stark reminder for all communities, including at the local level, to be consistently vigilant to both their boundaries and gradations of belonging. The task that Bednar emphasizes of building mutuality and trust within communities must proceed apace with a commitment to both expanding and building healthy relations with those beyond their boundaries, and ensuring the web of solidarity encompasses all equally within the community.
Identity Group Stratification, Political Economy & Inclusive Economic Rights
Authors: Chelwa Grieve , Hamilton Darrick , Green Avi
Published: February 2023

This essay demonstrates the necessity of formally incorporating identity group stratification as a pillar alongside economic and political understandings of any political economy framework. We make our case by juxtaposing mutual inadequacies and myopic limitations associated with two influential but polar political economy frameworks-Marxian and public choice theory-since neither framework formally incorporates an identity group stratification lens beyond class reductionism. Finally, in addition to presenting an identity group stratification lens to economic thought, we present an Inclusive Economic Rights policy framework as a critical baseline component of human rights, foregrounding political economic tendencies toward identity group stratifications as a pathway forward to achieve a “moral political economy.”
Supplement to the Burmese (Myanmar) amber checklist and bibliography, 2022
Authors: ROSS ANDREW J.
Published: February 2023

This is a supplement to the Burmese (Myanmar) amber checklist and bibliography covering taxa described or recorded during 2022, plus a couple of earlier records that were missed previously. Up to the end of 2022, 2,524 species have been recorded from Kachin amber, of which 350 were named in 2022; ten species have been recorded from older Hkamti amber, of which two were named in 2022 (one species known from both Hkamti and Kachin amber). Another 17 species were named in 2022 though it is uncertain whether they are in Kachin or Hkamti amber. In total 368 species were named from Cretaceous amber from Myanmar in 2022.
Improved modelling of compositional heterogeneity reconciles phylogenomic conflicts among lacewings
Authors: CAI CHEN-YANG , TIHELKA ERIK , LIU XING-YUE , ENGEL MICHAEL S.
Published: February 2023

Exponential growth of large-scale data for Neuropterida, an iconic group of insects used in behavioural, ecological, and evolutionary studies, has greatly changed our understanding of the origin and evolution of lacewings and their allies. Recent phylogenomic studies of Neuropterida based on mitogenomes, anchored hybrid enrichment (AHE) data, and transcriptomes have yielded a well-resolved and largely congruent phylogeny. Some interfamilial relationships of lacewings, however, remain inconsistent among different phylogenomic studies. Here we re-analysed the genome-scale AHE and transcriptomic data for Neuropterida under the better fitting site-heterogeneous CAT-GTR+G model and recovered a strongly supported and congruent tree for the deeper phylogeny of Neuroptera. Integrating the smaller but more broadly sampled AHE and the larger but less-sampled transcriptomic data, we present a holistic phylogeny of Neuropterida from which to explore patterns of evolution across the clade. Our re-analyses of the largest available datasets of Neuropterida highlight the significance of modelling across-site compositional heterogeneity and model comparison in large-scale phylogenomic studies of insects.
The earliest Pupipara (Diptera: Hippoboscoidea): A new genus and species from the lower Eocene of the Green River Formation
Authors: NEL ANDRÉ , GARROUSTE ROMAIN , ENGEL MICHAEL S.
Published: February 2023

Eornithoica grimaldii gen. et sp. nov., the currently earliest Pupipara, is described from the lower Eocene of the Green River Formation. The previously oldest representative of this clade was from the Oligocene. The new fossil has some plesiomorphic character states, suggesting a ‘basal’ position in the clade. Its age, around 52 Ma, suggests that these epizooic ectoparasitic flies originated during the Paleocene or even the latest Cretaceous, prior to the first bats, if the latter. As is the case for several early diverging hippoboscids that feed on birds, E. grimaldii possibly victimized birds or terrestrial mammals. This study is a further example of the quantity of new information that can be obtained by the examination of fossil insects under UV light.
Effects of clay activation and amine chain length on silica–palygorskite heterostructure properties
Authors: Boudriche Lilya , Bergaya Faïza , Boudjemaa Amel
Published: February 2023

Various approaches have been used for the preparation of heterostructured materials based on clay minerals, with numerous potential applications offered by the resulting functional materials. In this study, a fibrous clay mineral (palygorskite) and a tetraethyl orthosilicate reagent were used to obtain silica–palygorskite heterostructures. The aim was to highlight the influence of two factors during the preparation process: the effect of acid activation pre-treatment of the palygorskite with HCl and the effect of varying the length of the amine chains used – dodecylamine and butylamine – on the formation and development of silica nanoparticles on the surface of the palygorskite fibres. The silica–palygorskite heterostructures were obtained after the removal of the organic templates by calcination at 500°C. The textural and structural properties of the silica–palygorskite heterostructured samples were determined using various experimental characterization techniques, such as X-ray diffraction, transmission electron microscopy, gas adsorption and Fourier-transform infrared spectroscopy. The experimental variables targeted in this study appeared to have a significant effect on the textural properties of the silica–palygorskite heterostructure obtained. The great specific surface area and the mesoporous, microporous and ultramicroporous volumes as determined using nitrogen and/or carbon dioxide gas adsorption confirm the benefit of combining the acid activation pre-treatment of the fibrous clay mineral with the use of a long-chain amine co-surfactant (dodecylamine). The resulting silica–palygorskite heterostucture has a great specific surface area (628 m2 g–1) and a well-developed total pore network (VN2 = 0.24 cm3 g–1; Vultra (CO2) = 0.18 cm3 g–1). This material will be tested for the removal of volatile organic compounds at low concentrations.
Developing expert international consensus statements for opioid-sparing analgesia using the Delphi method
Authors: Sng Daniel Da Der , Uitenbosch Giulia , de Boer Hans D. , Carvalho Hugo Nogueira , Cata Juan P. , Erdoes Gabor , Heytens Luc , Lois Fernande Jane , Pelosi Paolo , Rousseau Anne-Françoise , Forget Patrice , Nesvadba David ,   Pain AND Opioids after Surgery (PANDOS) European Society of Anaesthesiology, Intensive Care (ESAIC) Research Group, Abdolmohammadi Sadegh , Asfaw Gebrehiwot , Benhamou Daniel , Blaise Gilbert , Cuvillon Philippe , Tahan Mohamed El , Feldano Emmanuel , Fettes Paul , Finco Gabriele , Fitzpatrick Michael , Kapila Atul , Kaye Callum , Kaura Vikas , May Helen , Meybohm Patrick , Stamer Ulrike , Taylor Daniel , Van De Velde Marc , Van Pee Benoit
Published: February 2023

Introduction

The management of postoperative pain in anaesthesia is evolving with a deeper understanding of associating multiple modalities and analgesic medications. However, the motivations and barriers regarding the adoption of opioid-sparing analgesia are not well known.

Methods

We designed a modified Delphi survey to explore the perspectives and opinions of expert panellists with regard to opioid-sparing multimodal analgesia. 29 anaesthetists underwent an evolving three-round questionnaire to determine the level of agreement on certain aspects of multimodal analgesia, with the last round deciding if each statement was a priority.

Results

The results were aggregated and a consensus, defined as achievement of over 75% on the Likert scale, was reached for five out of eight statements. The panellists agreed there was a strong body of evidence supporting opioid-sparing multimodal analgesia. However, there existed multiple barriers to widespread adoption, foremost the lack of training and education, as well as the reluctance to change existing practices. Practical issues such as cost effectiveness, increased workload, or the lack of supply of anaesthetic agents were not perceived to be as critical in preventing adoption.

Conclusion

Thus, a focus on developing specific guidelines for multimodal analgesia and addressing gaps in education may improve the adoption of opioid-sparing analgesia.
Addressing misclassification bias in vaccine effectiveness studies with an application to Covid-19
Authors: Eusebi Paolo , Speybroeck Niko , Hartnack Sonja , Stærk-Østergaard Jacob , Denwood Matthew J. , Kostoulas Polychronis
Published: February 2023

Safe and effective vaccines are crucial for the control of Covid-19 and to protect individuals at higher risk of severe disease. The test-negative design is a popular option for evaluating the effectiveness of Covid-19 vaccines. However, the findings could be biased by several factors, including imperfect sensitivity and/or specificity of the test used for diagnosing the SARS-Cov-2 infection. We propose a simple Bayesian modeling approach for estimating vaccine effectiveness that is robust even when the diagnostic test is imperfect. We use simulation studies to demonstrate the robustness of our method to misclassification bias and illustrate the utility of our approach using real-world examples.
Recruiting and retaining community-based participants in a COVID-19 longitudinal cohort and social networks study: lessons from Victoria, Australia
Authors: Nguyen Thi , Thomas Alexander J. , Kerr Phoebe , Stewart Ashleigh C. , Wilkinson Anna Lee , Nguyen Long , Altermatt Aimée , Young Kathryn , Heath Katherine , Bowring Anna , Fletcher-Lartey Stephanie , Lusher Dean , Hill Sophie , Pedrana Alisa , Stoové Mark , Gibney Katherine , Hellard Margaret
Published: February 2023

Background

Longitudinal studies are critical to informing evolving responses to COVID-19 but can be hampered by attrition bias, which undermines their reliability for guiding policy and practice. We describe recruitment and retention in the Optimise Study, a longitudinal cohort and social networks study that aimed to inform public health and policy responses to COVID-19.

Methods

Optimise recruited adults residing in Victoria, Australia September 01 2020–September 30 2021. High-frequency follow-up data collection included nominating social networks for study participation and completing a follow-up survey and four follow-up diaries each month, plus additional surveys if they tested positive for COVID-19 or were a close contact. This study compared number recruited to a-priori targets as of September 302,021, retention as of December 31 2021, comparing participants retained and not retained, and follow-up survey and diary completion October 2020–December 2021. Retained participants completed a follow-up survey or diary in each of the final three-months of their follow-up time. Attrition was defined by the number of participants not retained, divided by the number who completed a baseline survey by September 302,021. Survey completion was calculated as the proportion of follow-up surveys or diaries sent to participants that were completed between October 2020–December 2021.

Results

At September 302,021, 663 participants were recruited and at December 312,021, 563 were retained giving an overall attrition of 15% (n = 100/663). Among the 563 retained, survey completion was 90% (n = 19,354/21,524) for follow-up diaries and 89% (n = 4936/5560) for monthly follow-up surveys. Compared to participants not retained, those retained were older (t-test, p <  0.001), and more likely to be female (χ2, p = 0.001), and tertiary educated (χ2, p = 0.018).

Conclusion

High levels of study retention and survey completion demonstrate a willingness to participate in a complex, longitudinal cohort study with high participant burden during a global pandemic. We believe comprehensive follow-up strategies, frequent dissemination of study findings to participants, and unique data collection systems have contributed to high levels of study retention.
Lifesaving skills training in schools – A qualitative study to explore students, teachers, and parent’s perceived opportunities and challenges
Authors: Shaukat Natasha , Ali Daniyal Mansoor , Jaffer Mehtab , Jarrar Zeerak , Ashraf Naela , Hassan Sheza , Daudpota Ali Azim , Qadir Muskaan Abdul , Khowaja Aly Hamza , Razzak Junaid
Published: February 2023

Objective

The objective of this study is to explore the perception of teachers, parents and students’ regarding implementation of a school-based lifesaving skills program and help predict potential barriers and solutions.

Methods

This qualitative exploratory study was conducted in Karachi, Pakistan, from December 2020- to October 2021. We included students, teachers, and parents of secondary (grades VIII, IX, and X) and higher secondary level students (grades XI and XII) in Karachi, Pakistan's public and private schools and colleges. We selected one public, two semi-private, and two private schools. We recruited students, teachers, and parents through convenience sampling. We conducted fifteen focus group discussions (FGDs) with the students, six FGDs with the teachers, and eighteen in-depth interviews (IDIs) with parents. We transcribed the data from audio recordings and translated it into the English language. Finally, we manually analyzed the data using thematic analyses.

Results

This study found that bystanders' main barriers to performing lifesaving skills are lack of knowledge, fear of legal involvement, fear of hurting the patient by incorrect technique, lack of empathy among community stakeholders, and gender bias. However, the participants had a positive and supportive attitude toward implementing lifesaving skills training in schools. They suggested starting student training in the early teenage years, preferred medical staff as trainers, and suggested frequent small sessions in English/Urdu both or Urdu language and training via theory and practical hands-on drills. Furthermore, the training was proposed to be integrated into the school curriculum to make it sustainable. Finally, the government needs to support the program and make the legal environment more conducive for bystanders.

Conclusion

This study identified the significant barriers to performing lifesaving skills in an emergency in a low- and middle-income country (LMIC). The participants supported implementing a national lifesaving skills program in schools and colleges. However, the participants expressed that support is needed by the government for sustainability, integrating lifesaving skills into the school curriculum, providing legal support to the bystanders, and creating awareness among the general public.
Investigating the association between the symptoms of women with Fibromyalgia, Digestive function, and markers of the microbiota of the Gastrointestinal Tract (The FIDGIT Study): study protocol
Authors: Erdrich Sharon , Hawrelak Jason A , Myers Stephen P , Vuyisich Momchilo , Harnett Joanna E
Published: February 2023

Background

Fibromyalgia a common idiopathic condition affecting around 1.4% of adults globally. Its signature symptom is chronic widespread pain, with a constellation of somatic and psychological symptoms. Fibromyalgia is associated with significant reductions in quality of life, yet to date there is no biochemical marker for its diagnosis. Previous studies have indicated a strong association with gastrointestinal dysfunction, and more recently, alterations to the gut microbiome. No studies have examined the inter-relationship between fibromyalgia, gastrointestinal dysfunction, and the microbiome. This prospective observational case-controlled study will gather data on gastrointestinal function, dietary intake, fermentation patterns of ingested carbohydrates, and symptoms commonly associated with fibromyalgia. These will be evaluated alongside human gene expression and metatranscriptomic analysis of the oral and faecal microbiome.

Methods

Adult women aged ≥18 years diagnosed with fibromyalgia and/or meeting ACR 2016 criteria, and healthy family or age-matched controls will be recruited from the community. From consenting participants, we will collect detailed survey information and samples of blood, urine, stool, saliva, and breath.

Discussion

This is the first prospective study examining interactions between digestive function, human gene expression, and the gut microbiome together with general, and fibromyalgia-specific, symptoms experienced by New Zealand women. This exploration will allow an in-depth understanding of clinically relevant factors that are associated with fibromyalgia and will guide further research and contribute to improved management of this poorly understood condition.

Trial Registration

The study was approved by the New Zealand Health and Disability Committee (HDEC) (ref: 20/CEN/197) and registered with the Australia and New Zealand Clinical Trials Registry (ANZCTR), registration number ACTRN12620001337965. Written consent will be obtained after providing participants with detailed information about the procedures. Access to data will be restricted to the immediate research team, and all samples and survey data will be deidentified and coded before analysis.
Inequalities in access to new medication delivery services among non-communicable disease patients during the COVID-19 pandemic: findings from nationally representative surveys in Thailand
Authors: Nontarak Jiraluck , Vichitkunakorn Polathep , Waleewong Orratai
Published: February 2023

Background

This study describes the inequalities in access to a medication delivery service (MDS) during the COVID-19 pandemic and identifies the social determinants of health-related inequalities among non-communicable disease (NCD) patients.

Methods

Data were obtained from a study on the impact of health behaviours and modifications in health behaviours during the COVID-19 pandemic in the Thai population in 2021. The participants were recruited from Bangkok and all four regions of Thailand. The concentration index was used to examine the inequality among income quintiles, which were standardised by age, sex, living area, job type, health insurance scheme, and education level. Logistic regression was used to examine the associations between socio-demographics and access to regular services and new NCD MDSs, adjusted for age, sex, and other covariates.

Results

Among 1,739 NCD patients, greater income inequalities in accessing regular NCD services and collecting medicines at registered pharmacies during the COVID-19 pandemic were observed, for which the concentration index indicated utilisation inequalities in favour of richer households. In contrast, receiving medicine at primary care centres, by postal delivery, and delivered by village health volunteers were the new NCD MDSs, which favoured less wealthy households. NCD patients living in rural areas were more likely to access new NCD MDSs, compared to those in urban areas (adjusted odds ratio = 2.30; 95% confidence interval [CI]: 1.22–4.34). Significant associations with receiving medicine at hospitals were also observed for the income quintiles. Individuals in the lowest and 2nd lowest income quintiles were more likely to access new MDSs than those in the richest quintiles.

Conclusions

This study highlighted a disproportionate concentration of access to new NCD MDSs during the COVID-19 pandemic in Thailand, which was more concentrated in lower-income groups. The government should further study and integrate MDSs with the highest cost benefits into nationwide regular systems, while addressing systematic barriers to access to these services, such as the lack of shared health data across health facilities and tele pharmacy equipment. This will promote access to public services among patients in the less advantaged groups and reduce the health inequality gap.
Myricetin alleviated hydrogen peroxide-induced cellular senescence of nucleus pulposus cell through regulating SERPINE1
Authors: Chen Rongsheng , Zhang Xiaobo , Zhu Xitian , Wang Changsheng , Xu Weihong
Published: February 2023

Background

Myricetin (MYR) is a common plant flavonoid with antioxidant and anticancer properties. However, the anti-aging effect of MYR on nucleus pulposus cells (NPCs) is still unknown. The study aimed to explore the effect of MYR on the senescence of NPCs.

Methods

Methyl-thiazolyl tetrazolium assay was used to detect NPCs viability. Senescence level was evaluated by senescence-associated β-galactosidase (SA-β-Gal) staining and the expression levels of P21, P16, IL-6 and IL-8. RNA-Sequencing (RNA-seq) technology was used to identify differentially expressed genes (DEGs) between hydrogen peroxide + MYR (HO + MYR) group and HO group, and Gene Ontology (GO) functional was performed to analyze DEGs. A Venn diagram was generated to screen overlapping DEGs related to aging and inflammation, and the role of the promising validated DEG was selected for further investigation by gene functional assays.

Results

HO inhibited NPCs viability and stimulated the senescent phenotype of NPCs, whereas MYR treatment significantly reversed SA-β-gal activity in NPCs. MYR also reduced the expression of p21 and p16 and the secretion of IL-6 and IL-8 induced by HO. RNA-seq screened 421 DEGs. The GO enrichment results showed DEGs were mainly enriched in terms such as "sterol biosynthetic process". We also found SERPINE1 has the highest log2FC abs. Silence of SERPINE1 inhibited HO-induced NPCs senescence, and overexpression of SERPINE1 could limit the anti-aging effect of MYR.

Conclusions

MYR alleviated HO-induced senescence of NPCs by regulating SERPINE1 in vitro.
TGF-β is elevated in hyperuricemic individuals and mediates urate-induced hyperinflammatory phenotype in human mononuclear cells
Authors: Klück Viola , Cabău Georgiana , Mies Linda , Bukkems Femke , van Emst Liesbeth , Bakker René , van Caam Arjan ,   HINT consortium, Pop Ioan V. , Popp Radu A. , Rednic Simona , Pamfil Cristina , Farcaş Marius , Marginean Dragoş H. , Gaal Orsolya I. , Badii Medeea O. , Hotea Ioana , Peca Loredana , Mirea Andreea-Manuela , Nica Valentin , Colcear Doina , Pop Mariana S. , Rus Ancuta , Crişan Tania O. , Joosten Leo A. B.
Published: February 2023

Background

Soluble urate leads to a pro-inflammatory phenotype in human monocytes characterized by increased production of IL-1β and downregulation of IL-1 receptor antagonist, the mechanism of which remains to be fully elucidated. Previous transcriptomic data identified differential expression of genes in the transforming growth factor (TGF)-β pathway in monocytes exposed to urate in vitro. In this study, we explore the role of TGF-β in urate-induced hyperinflammation in peripheral blood mononuclear cells (PBMCs).

Methods

TGF-β mRNA in unstimulated PBMCs and protein levels in plasma were measured in individuals with normouricemia, hyperuricemia and gout. For in vitro validation, PBMCs of healthy volunteers were isolated and treated with a dose ranging concentration of urate for assessment of mRNA and pSMAD2. Urate and TGF-β priming experiments were performed with three inhibitors of TGF-β signalling: SB-505124, 5Z-7-oxozeaenol and a blocking antibody against TGF-β receptor II.

Results

TGF-β mRNA levels were elevated in gout patients compared to healthy controls. TGF-β-LAP levels in serum were significantly higher in individuals with hyperuricemia compared to controls. In both cases, TGF-β correlated positively to serum urate levels. In vitro, urate exposure of PBMCs did not directly induce TGF-β but did enhance SMAD2 phosphorylation. The urate-induced pro-inflammatory phenotype of monocytes was partly reversed by blocking TGF-β.

Conclusions

TGF-β is elevated in individuals with hyperuricemia and correlated to serum urate concentrations. In addition, the urate-induced pro-inflammatory phenotype in human monocytes is mediated by TGF-β signalling. Future studies are warranted to explore the intracellular pathways involved and to assess the clinical significance of urate-TGF-β relation.
Phospholipase C delta 1 inhibits WNT/β‐catenin and EGFR-FAK-ERK signaling and is disrupted by promoter CpG methylation in renal cell carcinoma
Authors: Xie Jianlian , Zhou Jun , Xia Jiliang , Zeng Ying , Huang Guo , Zeng Weihong , Fan Tingyu , Li Lili , Zeng Xi , Tao Qian
Published: February 2023

Background

PLCD1, located at 3p22, encodes an enzyme that mediates cellular metabolism and homeostasis, intracellular signal transduction and movement. PLCD1 plays a pivotal role in tumor suppression of several types of cancers; however, its expression and underlying molecular mechanisms in renal cell carcinoma (RCC) pathogenesis remain elusive.

Methods

RT-PCR and Western blot were used to detect PLCD1 expression in RCC cell lines and normal tissues. Bisulfite treatment, MSP and BGS were utilized to explore the CpG methylation status of PLCD1 promoter. Online databases were analyzed for the association between PLCD1 expression/methylation and patient survival. In vitro experiments including CCK8, colony formation, wound-healing, transwell migration and invasion, immunofluorescence and flow cytometry assays were performed to evaluate tumor cell behavior. Luciferase assay and Western blot were used to examine effect of PLCD1 on WNT/β‐catenin and EGFR‐FAK-ERK signaling.

Results

We found that PLCD1 was widely expressed in multiple adult normal tissues including kidney, but frequently downregulated or silenced in RCC due to its promoter CpG methylation. Restoration of PLCD1 expression inhibited the viability, migration and induced G2/M cell cycle arrest and apoptosis in RCC cells. PLCD1 restoration led to the inhibition of signaling activation of WNT/β-catenin and EGFR-FAK-ERK pathways, and the EMT program of RCC cells.

Conclusions

Our results demonstrate that PLCD1 is a potent tumor suppressor frequently inactivated by promoter methylation in RCC and exerts its tumor suppressive functions via suppressing WNT/β‐catenin and EGFR‐FAK-ERK signaling. These findings establish PLCD1 as a promising prognostic biomarker and treatment target for RCC.
Masitinib for mild-to-moderate Alzheimer’s disease: results from a randomized, placebo-controlled, phase 3, clinical trial
Authors: Dubois Bruno , López-Arrieta Jesús , Lipschitz Stanley , Doskas Triantafyllos , Spiru Luiza , Moroz Svitlana , Venger Olena , Vermersch Patrick , Moussy Alain , Mansfield Colin D. , Hermine Olivier , Tsolaki Magda ,   for the AB09004 Study Group Investigators
Published: February 2023

Background

Masitinib is an orally administered tyrosine kinase inhibitor that targets activated cells of the neuroimmune system (mast cells and microglia). Study AB09004 evaluated masitinib as an adjunct to cholinesterase inhibitor and/or memantine in patients with mild-to-moderate dementia due to probable Alzheimer’s disease (AD).

Methods

Study AB09004 was a randomized, double-blind, two parallel-group (four-arm), placebo-controlled trial. Patients aged ≥50 years, with clinical diagnosis of mild-to-moderate probable AD and a Mini-Mental State Examination (MMSE) score of 12–25 were randomized (1:1) to receive masitinib 4.5 mg/kg/day (administered orally as two intakes) or placebo. A second, independent parallel group (distinct for statistical analysis and control arm), randomized patients (2:1) to masitinib at an initial dose of 4.5 mg/kg/day for 12 weeks that was then titrated to 6.0 mg/kg/day, or equivalent placebo. Multiple primary outcomes (each tested at a significance level of 2.5%) were least-squares mean change from baseline to week 24 in the Alzheimer’s Disease Assessment Scale - cognitive subscale (ADAS-cog), or the Alzheimer’s Disease Cooperative Study Activities of Daily Living Inventory scale (ADCS-ADL). Safety for each masitinib dose level was compared against a pooled placebo population.

Results

Masitinib (4.5 mg/kg/day) (n=182) showed significant benefit over placebo (n=176) according to the primary endpoint of ADAS-cog, −1.46 (95% CI [−2.46, −0.45]) (representing an overall improvement in cognition) versus 0.69 (95% CI [−0.36, 1.75]) (representing increased cognitive deterioration), respectively, with a significant between-group difference of −2.15 (97.5% CI [−3.48, −0.81]);p<0.001. For the ADCS-ADL primary endpoint, the between-group difference was 1.82 (97.5% CI [−0.15, 3.79]);p=0.038 (i.e., 1.01 (95% CI [−0.48, 2.50]) (representing an overall functional improvement) versus −0.81 (95% CI [−2.36, 0.74]) (representing increased functional deterioration), respectively). Safety was consistent with masitinib’s known profile (maculo-papular rash, neutropenia, hypoalbuminemia). Efficacy results from the independent parallel group of titrated masitinib 6.0 mg/kg/day versus placebo (n=186 and 91 patients, respectively) were inconclusive and no new safety signal was observed.

Conclusions

Masitinib (4.5 mg/kg/day) may benefit people with mild-to-moderate AD. A confirmatory study has been initiated to substantiate these data.

Trial registration

EudraCT: 2010-021218-50.ClinicalTrials.gov: NCT01872598
Drug-induced interstitial lung disease due to over-the-counter cold medicine taken daily for 25 years: a case report
Authors: Matsumoto Masataka , Ito Isao , Kadowaki Seizo
Published: February 2023

Introduction

We report a rare case of drug-induced interstitial lung disease due to over-the-counter cold medicine taken daily for 25 years to clear the patient’s head.

Case presentation

A 77-year-old Japanese man presented to our hospital with a worsening cough that started 5 years ago. Chest radiographs and computed tomography images showed bilateral opacities, and transbronchial lung biopsy specimens showed an organizing pneumonia pattern. He reported taking the same over-the-counter cold medicine daily for the past 25 years to clear his head. We suspected that the cold medicine caused the lung opacities and asked him to stop taking them. His cough, general fatigue, and chest infiltrate gradually diminished. However, 6 months later, he resumed the same treatment because of a cold. The following month, he presented with severe worsening cough and chest radiographical findings. We diagnosed drug-induced interstitial lung disease. He improved by stopping the cold medicine again and taking prednisolone.

Conclusions

Over-the-counter cold medicines are easily accessible at the drugstore. In cases of diffuse lung disease, we should consider drug-induced interstitial lung disease due to over-the-counter cold medicine, which patients have been taking not only for weeks or months but also years.
Metastatic gastric adenocarcinoma with appendiceal phlegmon: a case report
Authors: Mohammadi Farshid , Razzaghi Mehta , Mousivand Sajad , Amjadinia Ehsan
Published: February 2023

Background

Gastric carcinoma is one of the most frequent malignancies worldwide. Gastric cancer metastasis to the appendix is uncommon in incidence, and has been rarely described in acute-appendicitis-related literature reviews. In this presented case, we have reported a rare case of appendiceal phlegmon, due to a diagnosis of metastatic gastric adenocarcinoma with uncommon symptoms.

Case presentation

A 79-year-old Caucasian male presented to the emergency department with history of weakness, anorexia, lethargy, and mood changes for 2 months. Abdominopelvic computed tomography showed an abscess in right iliac muscle. After percutaneous drainage of the abscess and 6 weeks antibiotic therapy, an appendectomy was done for the patient. Histopathologic findings revealed the involvement of the appendiceal wall by adenocarcinoma, most probably with gastrointestinal origin. Gastric cancer was confirmed later by upper endoscopy and pathologic report.

Conclusions

Although the presence of tumor in appendectomy specimens is rare, and metastasis to appendix is even rarer, it should be considered as a cause of appendicitis, especially in elderly patients.
Impact of lower co-payments on risk-reducing salpingo-oophorectomy and BRCA testing in Japan
Authors: Konnai Katsuyuki , Fujiwara Hiroyuki , Kitagawa Masakazu , Wakabayashi Reina , Yumori Asuna , Notomi Tsuguto , Onose Ryo , Kato Hisamori , Narimatsu Hiroto
Published: February 2023

Background

In April 2020, insurance coverage for risk-reducing salpingo-oophorectomy (RRSO) for breast cancer patients with hereditary breast and ovarian cancer (HBOC) syndrome and BRCA testing were started in Japan. We investigated the impact of insurance coverage on the number of RRSO and BRCA tests performed.

Methods

The subjects were 370 breast cancer patients and 23 of their relatives who received genetic counseling at our institution between April 2014 and December 2021. Finally, 349 patients and 15 relatives were analyzed. We retrospectively compared the number of BRCA tests, RRSO, insurance status, and co-payment of medical expenses before and after insurance coverage based on medical records.

Results

In the 6-year pre-coverage period, 226 patients (mean: 37/year) received genetic counseling and 106 (17/year) received BRCA testing. In the 21-month post-coverage period, 161 patients (92/year) received genetic counseling and 127 (72/year) received BRCA testing. The rate of testing/counseling significantly increased in the post-coverage period (46.9% vs. 78.8%; p < .001). The number of patients who were diagnosed with HBOC were 24 (4/year) and 18 (10/year) and RRSO was performed for 7 (1/year) and 11 (6/year) patients in the pre- and post-coverage periods, respectively. The rate of RRSO/HBOC was significantly increased in the post-coverage period (29.1% vs. 61.1%; p = 0.039). RRSO patients' co-payment rates decreased from 64% to 25% pre- and post-coverage.

Conclusions

Our findings suggest that decreased co-payments were the primary reason for these increases. Insurance coverage is an important factor when promoting preventive medical services such as RRSO.
Associations between sex differences, eating disorder behaviors, physical and mental health, and self-harm among Chinese adolescents
Authors: Wang Yuanyuan , Ma Zhihao , Lu Su , Duan Zhizhou , Wilson Amanda , Jia Yinwei , Yang Yong , Chen Runsen
Published: February 2023

Background and aim

Eating Disorders (ED) result in impaired well-being, but there exist an insufficient number of studies that have focused on the influence of sex and sexual orientation disparities within ED behaviors. Thus, we aimed to investigate ED behaviors among male and female adolescents with different sexual orientations in a school sample to understand prevalence and correlates of different ED behaviors.

Method

Data was analysed from 11,440 Chinese school adolescents with a mean age of 14.74 years (SD = 1.46). Reported data was gathered on sociodemographic information including sexual orientation, ED behaviors, health factors (reported health, cognitive function), mental health factors (depression, anxiety, suicidal ideation, non-suicidal self-injurious behavior), and social functioning (school bully victimization, and school bully perpetration). Logistic regression models were used to estimate the associations with ED behaviors, using the heterosexual orientation as the reference group as they are the majority.

Results

Compared to female adolescents, male adolescents reported lower anxiety symptoms (t = − 12.39, p < 0.001, Cohen’s d = − 0.233), were more likely to be the perpetrator of school bullying (χ2 = 190.61, p < 0.001, φ = 0.129), and reported a lower likelihood of taking dietary restriction (χ2 = 290.08, p < 0.001, φ = 0.160). Overall, the prevalence of dietary restriction presented sex disparities. Adolescents who reported no sexual attraction were less likely to engage in ED behaviors. Using heterosexual orientation as the reference group, the group who reported no sexual attraction was associated with lower risk in dietary restriction and purging in both male and female adolescents. Using the heterosexual orientation as the reference group, female sexual minority groups were at high risk of ED behaviors, with bisexual orientation and gay/lesbian orientation having a higher likelihood of engaging in objective binge eating.

Conclusions

The results revealed significant sex and sexual orientation differences of ED behaviors. The study suggests that adolescents is a period of sexuality development and could be critical for understanding adolescents’ eating behaviors. It is important to guide adolescents to healthy eating during their development and considerations should be made by clinicians when creating interventions for ED behaviors among the different sex and sexual orientation groups.