bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterisation of patients referred to a tertiary-level inherited cardiac condition clinic with suspected arrhythmogenic right ventricular cardiomyopathy (ARVC)
Authors: Aljehani A. , Kew T. , Baig S. , Cox H. , Sommerfeld L. C. , Ensam B. , Kalla M. , Steeds R. P. , Fabritz L.
Published: January 2023

Background

Arrhythmogenic right ventricular cardiomyopathy (ARVC) or arrhythmogenic cardiomyopathy is a rare inherited disease with incomplete penetrance and an environmental component. Although a rare disease, ARVC is a common cause of sudden cardiac death in young adults. Data on the different stages of ARVC remains scarce. The purpose of this study is to describe the initial presentation and cardiac phenotype of definite and non-definite ARVC for patients seen at a tertiary service.

Methods

This is a single centre, observational cohort study of patients with definite and non-definite ARVC seen at the Inherited Cardiac Conditions services at University Hospital Birmingham (UHB) in the period 2010–2021. Patients were identified by interrogation of digital health records, medical history, imaging and by examining 12-lead electrocardiograms (ECG).

Result

The records of 1451 patients were reviewed; of those, 165 patients were at risk of ARVC (mean age 41 ± 17 years, 56% male). 60 patients fulfilled task force criteria for definite ARVC diagnosis (n = 40, 67% males), and 38 (72%) of them carried a known pathogenic variant. The remaining 105 patients (50% males) were non-definite, and of these 45 (62%) carried a known pathogenic variant. Patients in the definite group were more symptomatic, with palpitations (57% vs. 17%), syncope (35% vs. 6%) and shortness of breath (28% vs. 5%, p < 0.001). T-wave inversion in V1-V3 and epsilon waves were observed only in the definite group. Both PR interval and QRS duration were longer in the definite (170 ± 34 ms and 100 ± 19 ms, p < 0.001) compared to (149 ± 25 and 91 ± 14 ms, p = 0.005). Patients with definite ARVC had significantly larger RV end diastolic areas and significantly reduced biventricular function (RVEDA = 27 ± 10 cm2, RVFAC = 37 ± 11% and EF = 56 ± 12%) compared to the non-definite group (RVEDA = 18 ± 4 cm2, RVFAC 49 ± 6% and LVEF 64 ± 7%, p < 0.001). Sustained ventricular tachycardia (VT) occurred more frequently in the definite group compared to the non-definite group (27% vs. 2%, p < 0.001). Ventricular fibrillation was observed in the definite group only (8 of 60 patients, 13%).

Conclusion

Our study showed differences between definite and non-definite ARVC patients in terms of clinical, electrophysiological and imaging features. Major adverse cardiac events occurred more commonly in the definite group, but also were observed in non-definite ARVC. This single centre observational cohort study forms a basis for further prospective multicentre interventional studies.
Temporary atrial septal defect balloon occlusion test as a must in the elderly
Authors: Alexandre André , Luz André , de Frias André Dias , Santos Raquel Baggen , Brochado Bruno , Oliveira Filomena , Silveira João , Torres Severo
Published: January 2023

Background

Atrial septal defect (ASD) can often remain asymptomatic until adulthood. It still remains unclear whether large ASD closure in senior people should be performed or not. Temporary ASD balloon occlusion test has been suggested as a tool to assess the risk of acute left ventricular heart failure post-ASD closure, and it allows to better distinguish responders from non-responders.

Case presentation

An 83-year-old man with a long-standing uncorrected secundum ASD was admitted for recently decompensated right-sided heart failure. During hospitalization, this patient was studied with trans-esophageal echocardiography, cardiac magnetic resonance imaging, and right heart catheterization, showing high Qp:Qs ratio and favorable anatomical conditions for percutaneous closure. Because of patient’s increasing need for intravenous diuretics and worsening renal function, it was considered that transcatheter ASD closure could improve symptoms, hence it was performed an attempt of percutaneous closure of the ASD with a fenestrated device. Unfortunately, irrespective of ASD being hemodynamically significant, it was found a very significant increase in pulmonary capillary wedge pressure during the temporary balloon occlusion test, supporting the existence of concealed left ventricular diastolic dysfunction. As a result, it was decided to abandon the procedure and not to close the ASD.

Conclusion

This clinical case illustrates the value of temporary balloon occlusion test before permanent percutaneous closure of ASD in elderly patients, regardless of left ventricular (systolic or diastolic) dysfunction.
Power and sample size analysis for longitudinal mixed models of health in populations exposed to environmental contaminants: a tutorial
Authors: Harrall Kylie K. , Muller Keith E. , Starling Anne P. , Dabelea Dana , Barton Kelsey E. , Adgate John L. , Glueck Deborah H.
Published: January 2023

Background

When evaluating the impact of environmental exposures on human health, study designs often include a series of repeated measurements. The goal is to determine whether populations have different trajectories of the environmental exposure over time. Power analyses for longitudinal mixed models require multiple inputs, including clinically significant differences, standard deviations, and correlations of measurements. Further, methods for power analyses of longitudinal mixed models are complex and often challenging for the non-statistician. We discuss methods for extracting clinically relevant inputs from literature, and explain how to conduct a power analysis that appropriately accounts for longitudinal repeated measures. Finally, we provide careful recommendations for describing complex power analyses in a concise and clear manner.

Methods

For longitudinal studies of health outcomes from environmental exposures, we show how to [1] conduct a power analysis that aligns with the planned mixed model data analysis, [2] gather the inputs required for the power analysis, and [3] conduct repeated measures power analysis with a highly-cited, validated, free, point-and-click, web-based, open source software platform which was developed specifically for scientists.

Results

As an example, we describe the power analysis for a proposed study of repeated measures of per- and polyfluoroalkyl substances (PFAS) in human blood. We show how to align data analysis and power analysis plan to account for within-participant correlation across repeated measures. We illustrate how to perform a literature review to find inputs for the power analysis. We emphasize the need to examine the sensitivity of the power values by considering standard deviations and differences in means that are smaller and larger than the speculated, literature-based values. Finally, we provide an example power calculation and a summary checklist for describing power and sample size analysis.

Conclusions

This paper provides a detailed roadmap for conducting and describing power analyses for longitudinal studies of environmental exposures. It provides a template and checklist for those seeking to write power analyses for grant applications.
The reporting of prognostic prediction models for obstetric care was poor: a cross-sectional survey of 10-year publications
Authors: Liu Chunrong , Qi Yana , Liu Xinghui , Chen Meng , Xiong Yiquan , Huang Shiyao , Zou Kang , Tan Jing , Sun Xin
Published: January 2023

Background

To investigate the reporting of prognostic prediction model studies in obstetric care through a cross-sectional survey design.

Methods

PubMed was searched to identify prognostic prediction model studies in obstetric care published from January 2011 to December 2020. The quality of reporting was assessed by the TRIPOD checklist. The overall adherence by study and the adherence by item were calculated separately, and linear regression analysis was conducted to explore the association between overall adherence and prespecified study characteristics.

Results

A total of 121 studies were included, while no study completely adhered to the TRIPOD. The results showed that the overall adherence was poor (median 46.4%), and no significant improvement was observed after the release of the TRIPOD (43.9 to 46.7%). Studies including both model development and external validation had higher reporting quality versus those including model development only (68.1% vs. 44.8%). Among the 37 items required by the TRIPOD, 10 items were reported adequately with an adherence rate over of 80%, and the remaining 27 items had an adherence rate ranging from 2.5 to 79.3%. In addition, 11 items had a report rate lower than 25.0% and even covered key methodological aspects, including blinding assessment of predictors (2.5%), methods for model-building procedures (4.5%) and predictor handling (13.5%), how to use the model (13.5%), and presentation of model performance (14.4%).

Conclusions

In a 10-year span, prognostic prediction studies in obstetric care continued to be poorly reported and did not improve even after the release of the TRIPOD checklist. Substantial efforts are warranted to improve the reporting of obstetric prognostic prediction models, particularly those that adhere to the TRIPOD checklist are highly desirable.
A digital divide in the COVID-19 pandemic: information exchange among older Medicare beneficiaries and stakeholders during the COVID-19 pandemic
Authors: Castillo Aaron , Rivera-Hernandez Maricruz , Moody Kyle A.
Published: January 2023

Background

The COVID-19 pandemic resulted in unprecedented challenges for older adults. Medicare enrollment was already an overwhelming process for a high fraction of older adults pre-pandemic. Therefore, the purpose of this qualitative study was to gain understanding from community organizations and stakeholders about their pre-pandemic and during-pandemic experiences while adapting to continue offering insurance advice to seniors, what resources are available to seniors, and what needs to be done to help seniors make higher quality insurance choices in the Medicare program. In addition, we wanted to explore how the COVID-19 pandemic may have changed the ways that these stakeholders interacted with Medicare beneficiaries.

Methods

We employed a qualitative strategy to gain a deep understanding of the challenges that these organizations may have faced while offering advice/counseling to older adults. We accomplished this by interviewing a group of 30 stakeholders from different states.

Results

Every stakeholder mentioned that some older adults have difficulty making Medicare decisions, and 16 stakeholders mentioned that their system is complex and/or overwhelming for older adults. Twenty-three stakeholders mentioned that Medicare beneficiaries are often confused about Medicare, and this is more noticeable among new enrollees. With the onset of the pandemic, 22 of these organizations mentioned that they had to move to a virtual model in order to assist beneficiaries, especially at the beginning of the pandemic. However, older adults seeking advice/meetings have a strong preference for in-person meetings even during the pandemic. Given that the majority of the beneficiaries that these stakeholders serve may not have access to technology, it was difficult for some of them to smoothly transition to a virtual environment. With Medicare counseling moving to virtual or telephone methods, stakeholders discussed that many beneficiaries had difficulty utilizing these options in a variety of ways.

Conclusions

Findings from our interviews with stakeholders provided information regarding experiences providing Medicare counseling pre- and during-COVID-19 pandemic. Some of the barriers faced by older adults included a complex and overwhelming system, a strong preference for in-person meetings among beneficiaries, challenges with technology, and an increased risk of information overload and misinformation. While bias may exist within the study and sample, given that technology-savvy beneficiaries may not seek help from organizations our study participants work in, they show how the current Medicare system may impact vulnerable older adults who may need support with access to high-speed internet and digital literacy.
UK prescribing practice of anticoagulants in patients with chronic kidney disease: a nephrology and haematology-based survey
Authors: Parker Kathrine , Choudhuri Satarupa , Lewis Penny , Thachil Jecko , Mitra Sandip
Published: January 2023

A survey to gain insight into anticoagulant prescribing practice in the setting of chronic kidney disease (CKD) across the UK was disseminated via renal and haematology networks. Areas of anticoagulant use included patients with venous thromboembolism (VTE), requiring thromboprophylaxis for VTE, Atrial Fibrillation (AF) and nephrotic syndrome.

An online-survey was disseminated via British Haematology Society, UK Kidney Association, and Renal Pharmacy Group over a five month period. All responses were voluntary and anonymous.

Among 117 responses there were 49 nephrology doctors, 47 renal pharmacists and 20 haematology clinicians. A specialist multidisciplinary team to discuss the specific anticoagulant management of these patients was only available to 3% (4/117) respondents. Renal function estimate used for anticoagulant dosing was mainly Cockcroft-Gault for pharmacists and haematology but lab-based estimates were used by nephrology doctors. Therapeutic dose of Low Molecular Weight Heparin was mostly likely to be reduced by one-third when used for VTE treatment, with the majority of units undertaking anti-Xa monitoring in CKD stage 5 and dialysis. Direct-acting Oral Anticoagulants are being used in patients with nephrotic syndrome, those with CKD stage 5 and on dialysis for VTE and AF in the absence of license in these indications.

This survey highlighted the significant differences between anticoagulant prescribing in CKD between two professional specialties and marked variation between centres in anticoagulant management strategies employed for these patients. With gaps still existing in the evidence base and answers to these not expected within the next few years, development of a best-practice guideline would be warranted to support clinicians in this field.
Study protocol of the Berlin Research Initiative for Diagnostics, Genetics and Environmental Factors in Schizophrenia (BRIDGE-S)
Authors: Braun Alice , Kraft Julia , Ripke Stephan
Published: January 2023

Background

Large-scale collaborative efforts in the field of psychiatric genetics have made substantial progress in unraveling the biological architecture of schizophrenia (SCZ). Although both genetic and environmental factors are known to play a role in schizophrenia etiology our mechanistic understanding of how they shape risk, resilience and disease trajectories remains limited.

Methods

Here, we present the study protocol of the Berlin Research Initiative for Diagnostics, Genetic and Environmental Factors of Schizophrenia (BRIDGE-S), which aims to collect a densely phenotyped genetic cohort of 1,000 schizophrenia cases and 1,000 controls. The study’s main objectives are to build a resource for i) promoting genetic discoveries and ii) genotype–phenotype associations to infer specific disease subtypes, and iii) exploring gene-environment interactions using polyrisk models. All subjects provide a biological sample for genotyping and complete a core questionnaire capturing a variety of environmental exposures, demographic, psychological and health data. Approximately 50% of individuals in the sample will further undergo a comprehensive clinical and neurocognitive assessment.

Discussion

With BRIDGE-S we created a valuable database to study genomic and environmental contributions to schizophrenia risk, onset, and outcomes. Results of the BRIDGE-S study could yield insights into the etiological mechanisms of schizophrenia that could ultimately inform risk prediction, and early intervention and treatment strategies.
Gender differences in risk exposures for acute hepatitis C infection in Taiwan: a nationwide case–control study
Authors: Huang Hsin-I , Su Chia-Ping , Huang Wan-Ting , Chen Wan-Chin
Published: January 2023

Background

In Taiwan, medical providers are required to report all acute hepatitis C (AHC) patients to National Notifiable Disease Surveillance System (NNDSS). Identifying factors associated with AHC may inform the strategies to prevent the spread of hepatitis C virus (HCV). We used the national surveillance data to assess gender difference in risk factors associated with AHC in Taiwan and propose control measures in at-risk groups.

Methods

We conducted a nationwide case–control study using data from NNDSS and AHC case investigation questionnaires, for the period of March 6, 2014–December 31, 2016. Cases were AHC confirmed in NNDSS; controls were reported AHC with negative HCV nucleic acid test and negative serum anti-HCV antibody. We used bivariate analysis to identify characteristics and risk exposures for AHC and conducted gender stratified analyses.

Results

We identified 602 AHC cases (66.9% males, median age 48 years) and 90 controls. Older age, male gender (OR: 1.85, 95% CI: 1.18–2.90), history of viral hepatitis (OR: 7.93, 95% CI:1.91–32.88), history of sexually transmitted infections (OR: 21.02, 95% CI: 2.90–152.43), and having healthcare-associated risk exposures (OR: 2.02, 95% CI: 1.25–3.25) were associated with AHC. Stratified analyses showed receiving intravenous infusion, history of hepatitis B, syphilis, and human immunodeficiency virus infection were risk factors for male AHC; receiving hemodialysis was risk factor for females.

Conclusions

Our study demonstrates risk factors for AHC in Taiwan with gender difference. Proper infection control practices in healthcare settings and interventions targeting male patients with HIV and other STIs, remain crucial to prevent individuals from AHC.
A multi-country survey on access to healthcare and treatment services among individuals with critical medical care needs during the first wave of the pandemic
Authors: Folayan Morenike Oluwatoyin , Abeldaño Zuñiga Roberto Ariel , Virtanen Jorma I. , Ezechi Oliver C. , Yousaf Muhammad Abrar , Al-Tammemi Ala’a B. , Jafer Mohammed , Ellakany Passent , Ara Eshrat , Ayanore Martin Amogre , Ishabiyi Anthonia Omotola , Gaffar Balgis , Aly Nourhan M. , Lusher Joanne , El Tantawi Maha , Nguyen Annie L.
Published: January 2023

Background

Healthcare services were significantly interrupted during the early phase of the COVID-19 pandemic. The aim of the present study was to determine the associations between sociodemographic factors and healthcare access during the first wave of the COVID-19 pandemic among individuals with critical care needs.

Methods

This was a secondary analysis of the data of 5,156 participants recruited from 152 countries during the first wave of the COVID-19 pandemic. The dependent variables were self-reported difficulty of access to health care, challenges with obtaining medication, and the use of alternative medical services. The independent variables were age at last birthday; sex at birth, level of education, employment status and the macro-social vulnerability status. The confounding variable was the country income level. Three multivariable logistic regression analyses were conducted to determine the associations between the dependent variables and the independent variables after adjusting for the confounder.

Results

Difficulty accessing health care services and obtaining medications was experienced by 1922 (37.3%) and 3746 (72.7%) participants respectively. Also, 1433 (27.8%) used alternative medical care. Retirees (AOR:1.59), unemployed (AOR:1.198), people living with HIV (AOR:2.36) and at increased risk of COVID-19 (AOR:2.10), people who used drugs (AOR:1.83) and transacted sex (AOR:1.971) had significantly higher odds for reporting difficulty with access to health care. Males (AOR:1.23), respondents with secondary level of education (AOR:1.39), retirees (AOR:2.19), unemployed (AOR:1.47), people living with HIV (AOR:2.46), people who used drugs (AOR:1.79), transacted sex (AOR:2.71) and those who might be (AOR: 1.66) and were at (AOR: 2.3) increased risk of severe COVID-19 had significantly higher odds for reporting difficulty with access to medications. People who used drugs (AOR:2.093) transacted sex (AOR:1.639), who might be (AOR: 1.211) and were at (AOR: 1.511) increased risk of severe COVID-19, and who had difficulty accessing usual healthcare (AOR: 9.047) and obtaining medications (AOR:2.16) had significantly higher odds of reporting alternative medical care use. People living with HIV (AOR:0.562) had significantly lower odds of using alternative medical care.

Conclusion

We identified populations who had challenges with access to healthcare and obtaining medications used alternative medical care except for people living with HIV. Priority attention should be given to alternative medical care use during future health pandemics.
The effect of Er, Cr:YSGG laser debonding on the bond strength of two ceramic materials to dentin
Authors: Abdel Sadek Hoda M. , Abdel Khalek Ahmed M. , Wahsh Marwa M.
Published: January 2023

Objectives

Evaluating the bond strength of two ceramic materials to dentin after Er,Cr:YSGG laser debonding. Would laser debonding affect the bond strength of ceramic to dentin?

Materials and methods

Recently extracted human molars were ground to expose dentin. Forty square shaped samples were prepared from CAD/CAM ceramic blocks. Samples were divided into two groups according to the type of ceramic material; group E: Lithium disilicate and group T: Ultra-translucent Zirconia (n = 20) Each group was divided into two subgroups (n = 10) according to the laser debonding effect (subgroup B: bonded samples, subgroup R: re-bonded samples after laser debonding). Ceramic samples were bonded to dentin using dual cure self-adhesive resin cement. Laser debonding of ceramic samples of subgroups R using Er, Cr:YSGG laser, were then re-bonded again to dentin surface with same resin cement. The Shear bond strength test using Universal testing machine was done. The failure mode was analyzed. Two-way analysis of variance was used to compare the mean bond strength and re-bond strength of two materials. The significance level was set at P ≤ 0.05.

Results

Two-Way ANOVA showed that ceramic type had a significant effect on the re-bond strength to dentin. The predominant failure mode was adhesive.

Conclusions

Laser debonding of Lithium disilicate and Ultra translucent Zirconia decreased the re-bond strength to dentin. Deterioration in re-bond strength for Lithium disilicate ceramics was more pronounced than for Ultra translucent Zirconia. Clinical Relevance Deterioration in the bond strength between ceramics & dentin after laser debonding still needs improvement to allow its clinical use.
Estimation of the demand for palliative care in non-oncologic patients in Chile
Authors: Armijo Nicolás , Abbot Tomás , Espinoza Manuel , Neculhueque Ximena , Balmaceda Carlos
Published: January 2023

Background

Access to palliative care is an emerging global public health challenge. In Chile, a palliative care law was recently enacted to extend palliative care coverage to the non-oncologic population. Thus, a reliable and legitimate estimate of the demand for palliative care is needed for proper health policy planning.

Objective

To estimate the demand for Palliative Care in Chile.

Methodology

Diseases likely to require palliative care were identified according to literature and expert judgement. Annual deaths of diseases identified were estimated for the periods 2018–2020. Demand estimation corresponds to the identification of the proportion of deceased patients requiring palliative care based on the burden of severe health-related suffering. Finally, patient-years were estimated based on the expected survival adjustment.

Results

The estimated demand for palliative care varies between 25,650 and 21,679 patients depending on the approximation used. In terms of annual demand, this varies between 1,442 and 10,964 patient-years. The estimated need has a minor variation between 2018 and 2019 of 0.85% on average, while 2020 shows a slightly higher decrease (7.26%).

Conclusion

This is a replicable method for estimating the demand of palliative care in other jurisdictions. Future studies could approach the demand based on the decedent population and living one for a more precise estimation and better-informed health planning. It is hoped that our methodological approach will serve as an input for implementing the palliative care law in Chile, and as an example of estimating the demand for palliative care in other jurisdictions.
CD4+ and CD8+ regulatory T cell characterization in the rat using a unique transgenic Foxp3-EGFP model
Authors: Ménoret Séverine , Tesson Laurent , Remy Séverine , Gourain Victor , Sérazin Céline , Usal Claire , Guiffes Aude , Chenouard Vanessa , Ouisse Laure-Hélène , Gantier Malika , Heslan Jean-Marie , Fourgeux Cynthia , Poschmann Jeremie , Guillonneau Carole , Anegon Ignacio
Published: January 2023

Background

Regulatory T cells (Treg) in diverse species include CD4+ and CD8+ T cells. In all species, CD8+ Treg have been only partially characterized and there is no rat model in which CD4+ and CD8+ FOXP3+ Treg are genetically tagged.

Results

We generated a Foxp3-EGFP rat transgenic line in which FOXP3 gene was expressed and controlled EGFP. CD4+ and CD8+ T cells were the only cells that expressed EGFP, in similar proportion as observed with anti-FOXP3 antibodies and co-labeled in the same cells. CD4+EGFP+ Treg were 5–10 times more frequent than CD8+EGFP+ Treg. The suppressive activity of CD4+ and CD8+ Treg was largely confined to EGFP+ cells. RNAseq analyses showed similarities but also differences among CD4+ and CD8+ EGFP+ cells and provided the first description of the natural FOXP3+CD8+ Treg transcriptome. In vitro culture of CD4+ and CD8+ EGFP− cells with TGFbeta and IL-2 generated induced EGFP+ Treg. CD4+ and CD8+ EGFP+ Treg were expanded upon in vivo administration of a low dose of IL-2.

Conclusions

This new and unique rat line constitutes a useful model to identify and isolate viable CD4+ and CD8+ FOXP3+ Treg. Additionally, it allows to identify molecules expressed in CD8+ Treg that may allow to better define their phenotype and function not only in rats but also in other species.
Pulmonary sequestration in adult patients: a single-center retrospective study
Authors: Ren Siying , Yang Lulu , Xiao Ying , Tong Zhongyi , Wang Li , Hu Yan
Published: January 2023

Background

Pulmonary sequestration (PS) is a rare congenital lower airway malformation. This study presents the clinical and imaging features and surgical outcomes of PS in adults, and compare the safety and feasibility of minimally invasive surgery versus open thoracotomy for PS.

Methods

Adult patients with PS treated at our center from July 2011 to September 2021 were included. Information regarding the patient demographics, clinical and CT features, arterial supply and venous drainage, and surgical outcomes were collected.

Results

Ninety seven patients were included. The most common CT findings were mass lesions (50.5%) and cystic lesions (20.6%). The vast majority of the lesions (96 out of 97) were located close to the spine in the lower lobes (left vs. right: 3.6 vs. 1). Arterial supply was mainly provided by the thoracic aorta (87.4%) and abdominal aorta (10.5%). Intralobar and extralobar PS accounted for 90.7% and 9.3% of the patients, respectively. Three (4.5%) patients who underwent minimally invasive surgery were converted to open thoracotomy due to dense adhesions. Though no significant differences regarding operative time (P = 0.133), the minimally invasive surgery group was significantly better than the open thoracotomy group regarding intraoperative blood loss (P = 0.001), drainage volume (P = 0.004), postoperative hospital days (P = 0.017) and duration of chest drainage (P = 0.001). There were no cases of perioperative mortality. Only four (4.1%) patients developed postoperative complications, and no significant difference existed between the two groups.

Conclusion

Our study revealed PS can present with a variety of different clinical and radiologic manifestations. Clinicians should consider the possibility of PS when diagnosing a lesion in the lower lobes close to the spine. Moreover, minimally invasive surgery is a safe and effective treatment modality for the treatment of PS in an experienced center.
Sexual dimorphism in selenium deficiency is associated with metabolic syndrome and prevalence of heart disease
Authors: Weening Eerde H. , Al-Mubarak Ali A. , Dokter Martin M. , Dickstein Kenneth , Lang Chim C. , Ng Leong L. , Metra Marco , van Veldhuisen Dirk J. , Touw Daan J. , de Boer Rudolf A. , Gansevoort Ron T. , Voors Adriaan A. , Bakker Stephan J. L. , van der Meer Peter , Bomer Nils
Published: January 2023

Background

Serum selenium levels have been associated with the incidence of heart failure (HF) and signs of the metabolic syndrome. In addition, notable differences have been reported between males and females in food intake and micronutrient metabolism, possibly explaining different health outcomes.

Objective

Our objective was to elucidate sex-specific, cross-sectional phenotypic differences in the association of serum selenium concentrations with parameters of metabolic syndrome and HF.

Methods

We investigated data from individuals from a community-based cohort (PREVEND; N = 4288) and heart failure cohort (BIOSTAT-CHF; N = 1994). In both populations, cross-sectional analyses were performed for potential interaction (p < 0.1) between sex and serum selenium with overlapping signs and clinical parameters of the metabolic syndrome and HF.

Results

Baseline selenium levels of the total cohort were similar between PREVEND (85.7 μg/L) and BIOSTAT-CHF (89.1 μg/L). Females with lower selenium levels had a higher BMI and increased prevalence of diabetes than females with higher selenium, in both PREVEND (pinteraction < 0.001; pinteraction = 0.040, resp.) and BIOSTAT-CHF (pinteraction = 0.021; pinteraction = 0.024, resp.), while opposite associations were observed for males. Additionally, in females, but not in males, lower selenium was associated with a higher prevalence of myocardial infarction (MI) in PREVEND (pinteraction = 0.021) and BIOSTAT-CHF (pinteraction = 0.084).

Conclusion

Lower selenium was associated with a higher BMI and increased prevalence of diabetes in females, opposite to males, and was also associated with more MI in females. Interventional studies are needed to validate this observation.
Bidirectional hybrid erythritol-inducible promoter for synthetic biology in Yarrowia lipolytica
Authors: Vidal Lea , Lebrun Esteban , Park Young-Kyoung , Mottet Guillaume , Nicaud Jean-Marc
Published: January 2023

Background

The oleaginous yeast Yarrowia lipolytica is increasingly used as a chassis strain for generating bioproducts. Several hybrid promoters with different strengths have been developed by combining multiple copies of an upstream activating sequence (UAS) associated with a TATA box and a core promoter. These promoters display either constitutive, phase-dependent, or inducible strong expression. However, there remains a lack of bidirectional inducible promoters for co-expressing genes in Y. lipolytica.

Results

This study built on our previous work isolating and characterizing the UAS of the erythritol-induced genes EYK1 and EYD1 (UAS-eyk1). We found an erythritol-inducible bidirectional promoter (BDP) located in the EYK1-EYL1 intergenic region. We used the BDP to co-produce YFP and RedStarII fluorescent proteins and demonstrated that the promoter’s strength was 2.7 to 3.5-fold stronger in the EYL1 orientation compared to the EYK1 orientation. We developed a hybrid erythritol-inducible bidirectional promoter (HBDP) containing five copies of UAS-eyk1 in both orientations. It led to expression levels 8.6 to 19.2-fold higher than the native bidirectional promoter. While the BDP had a twofold-lower expression level than the strong constitutive TEF promoter, the HBDP had a 5.0-fold higher expression level when oriented toward EYL1 and a 2.4-fold higher expression level when oriented toward EYK1. We identified the optimal media for BDP usage by exploring yeast growth under microbioreactor conditions. Additionally, we constructed novel Golden Gate biobricks and a destination vector for general use.

Conclusions

In this research, we developed novel bidirectional and hybrid bidirectional promoters of which expression can be fine-tuned, responding to the need for versatile promoters in the yeast Y. lipolytica. This study provides effective tools that can be employed to smoothly adjust the erythritol-inducible co-expression of two target genes in biotechnology applications. BDPs developed in this study have potential applications in the fields of heterologous protein production, metabolic engineering, and synthetic biology.
Current practice and recommendations for advancing how human variability and susceptibility are considered in chemical risk assessment
Authors: Varshavsky Julia R. , Rayasam Swati D. G. , Sass Jennifer B. , Axelrad Daniel A. , Cranor Carl F. , Hattis Dale , Hauser Russ , Koman Patricia D. , Marquez Emily C. , Morello-Frosch Rachel , Oksas Catherine , Patton Sharyle , Robinson Joshua F. , Sathyanarayana Sheela , Shepard Peggy M. , Woodruff Tracey J.
Published: January 2023

A key element of risk assessment is accounting for the full range of variability in response to environmental exposures. Default dose-response methods typically assume a 10-fold difference in response to chemical exposures between average (healthy) and susceptible humans, despite evidence of wider variability. Experts and authoritative bodies support using advanced techniques to better account for human variability due to factors such as in utero or early life exposure and exposure to multiple environmental, social, and economic stressors.

This review describes: 1) sources of human variability and susceptibility in dose-response assessment, 2) existing US frameworks for addressing response variability in risk assessment; 3) key scientific inadequacies necessitating updated methods; 4) improved approaches and opportunities for better use of science; and 5) specific and quantitative recommendations to address evidence and policy needs.

Current default adjustment factors do not sufficiently capture human variability in dose-response and thus are inadequate to protect the entire population. Susceptible groups are not appropriately protected under current regulatory guidelines. Emerging tools and data sources that better account for human variability and susceptibility include probabilistic methods, genetically diverse in vivo and in vitro models, and the use of human data to capture underlying risk and/or assess combined effects from chemical and non-chemical stressors.

We recommend using updated methods and data to improve consideration of human variability and susceptibility in risk assessment, including the use of increased default human variability factors and separate adjustment factors for capturing age/life stage of development and exposure to multiple chemical and non-chemical stressors. Updated methods would result in greater transparency and protection for susceptible groups, including children, infants, people who are pregnant or nursing, people with disabilities, and those burdened by additional environmental exposures and/or social factors such as poverty and racism.
The alteration of intrauterine microbiota in chronic endometritis patients based on 16S rRNA sequencing analysis
Authors: Chen Qing , Zhang Xiaowei , Hu Qicai , Zhang Wei , Xie Yi , Wei Weixia
Published: January 2023

Background

Chronic endometritis (CE) is a disease of continuous and subtle inflammation occurring in the endometrial stromal area, which is often asymptomatic or present with non-specific clinical symptoms.

Methods

This study investigated the composition and distribution of the intrauterine microbiota of 71 patients who underwent hysteroscopy during the routine clinical inspection of infertility. Among them, patients who were diagnosed with chronic endometritis (CE) were allocated into CE group (n = 29) and others into non-CE group (n = 42). There was no significant difference in average age between the two groups (P = 0.19). Uterine flushing fluid was collected by the self-developed cervical trocar uterine cavity sampler and 16S rRNA sequencing was performed.

Results

The alpha diversity in the CE group was significantly higher than that in the non-CE group (P < 0.05). Firmicutes (newly named Bacillota) were the dominant phylum in the non-CE group (72.23%), while their abundance was much lower in the CE group (49.92%), but there was no statistically significant difference between the two groups. The abundances of Actinobacteriota and Cyanobacteria in the CE group were significantly higher than those in the non-CE group (P < 0.05). At the genus level, the abundance of Lactobacillus dominated in all samples, which presented a significantly lower abundance in the CE group (40.88%) than that in the non-CE group (64.22%) (P < 0.05). Correspondingly, the abundance of non-Lactobacillus was higher in the CE group, among which Pseudomonas and Cutibacterium increased significantly (P < 0.01). Moreover, compared with the non-CE group, the pathways involved in arginine and proline metabolism and retinol metabolism were significantly enriched in the CE group (P < 0.05), while the metabolism of lipid and prenyltransferases were significantly decreased in the CE group (P < 0.05).

Conclusions

A certain microbial community was colonized in the uterine cavity, which was dominated by Lactobacillus. The structure and distribution of intrauterine microbiota in the CE group were different from those in the non-CE group by showing a lower abundance of Lactobacillus, and a significantly higher abundance of Pseudomonas and Cutibacterium. Additionally, the microbial metabolism was altered in the CE group. This study elaborated the alteration of intrauterine microbiota in CE patients, which may contribute to the diagnosis of CE and provide a reference for antibiotic treatment of CE.
Advancements in nanoparticle-based treatment approaches for skin cancer therapy
Authors: Zeng Leli , Gowda B. H. Jaswanth , Ahmed Mohammed Gulzar , Abourehab Mohammed A. S. , Chen Zhe-Sheng , Zhang Changhua , Li Jia , Kesharwani Prashant
Published: January 2023

Skin cancer has emerged as the fifth most commonly reported cancer in the world, causing a burden on global health and the economy. The enormously rising environmental changes, industrialization, and genetic modification have further exacerbated skin cancer statistics. Current treatment modalities such as surgery, radiotherapy, conventional chemotherapy, targeted therapy, and immunotherapy are facing several issues related to cost, toxicity, and bioavailability thereby leading to declined anti-skin cancer therapeutic efficacy and poor patient compliance. In the context of overcoming this limitation, several nanotechnological advancements have been witnessed so far. Among various nanomaterials, nanoparticles have endowed exorbitant advantages by acting as both therapeutic agents and drug carriers for the remarkable treatment of skin cancer. The small size and large surface area to volume ratio of nanoparticles escalate the skin tumor uptake through their leaky vasculature resulting in enhanced therapeutic efficacy. In this context, the present review provides up to date information about different types and pathology of skin cancer, followed by their current treatment modalities and associated drawbacks. Furthermore, it meticulously discusses the role of numerous inorganic, polymer, and lipid-based nanoparticles in skin cancer therapy with subsequent descriptions of their patents and clinical trials.

Graphical Abstract
CircNDC80 promotes glioblastoma multiforme tumorigenesis via the miR-139-5p/ECE1 pathway
Authors: Wang Yuhang , Wang Binbin , Zhou Fengqi , Lv Kun , Xu Xiupeng , Cao Wenping
Published: January 2023

Background

Circular RNAs (circRNAs) have been shown to be essential for the emergence and growth of different cancers. However, further research is required to validate the function of circRNA in glioblastoma (GBM).

Methods

CircNDC80 expression in both normal brain tissues (NBTs) and glioma tissues was determined using real-time PCR. The impact of circNDC80 on GBM cell proliferation, migration, and invasion was then confirmed by CCK-8, colony formation, EdU incorporation, Transwell, and wound healing assays. To determine how circNDC80 affects the capacity of glioma stem cells (GSCs) to maintain their stemness and self-renewal, a CellTiter-Glo assay, clonogenic assay and extreme limiting dilution assay were utilized. To ascertain the impact of circNDC80 in vivo, intracranial xenograft models were established.

Results

When compared to NBT, glioblastoma tissue had a higher level of circNDC80 expression. In functional assays, circNDC80 promoted glioblastoma cell proliferation, migration, and invasion, while sustaining the stemness and fostering the self-renewal of glioma stem cells. In addition, a dual luciferase reporter assay and circRIP were used to verify that circNDC80 simultaneously affects the expression of ECE1 mRNA by sponging miR-139-5p, and a rescue experiment was used to verify the above results further.

Conclusions

According to our research, circNDC80 is an oncogenic factor that promotes glioblastoma through the miR-139-5p/ECE1 pathway. This implies that circNDC80 may be employed as a novel therapeutic target and a possible predictive biomarker.
A machine learning framework develops a DNA replication stress model for predicting clinical outcomes and therapeutic vulnerability in primary prostate cancer
Authors: Huang Rong-Hua , Hong Ying-Kai , Du Heng , Ke Wei-Qi , Lin Bing-Biao , Li Ya-Lan
Published: January 2023

Recent studies have identified DNA replication stress as an important feature of advanced prostate cancer (PCa). The identification of biomarkers for DNA replication stress could therefore facilitate risk stratification and help inform treatment options for PCa. Here, we designed a robust machine learning-based framework to comprehensively explore the impact of DNA replication stress on prognosis and treatment in 5 PCa bulk transcriptomic cohorts with a total of 905 patients. Bootstrap resampling-based univariate Cox regression and Boruta algorithm were applied to select a subset of DNA replication stress genes that were more clinically relevant. Next, we benchmarked 7 survival-related machine-learning algorithms for PCa recurrence using nested cross-validation. Multi-omic and drug sensitivity data were also utilized to characterize PCa with various DNA replication stress. We found that the hyperparameter-tuned eXtreme Gradient Boosting model outperformed other tuned models and was therefore used to establish a robust replication stress signature (RSS). RSS demonstrated superior performance over most clinical features and other PCa signatures in predicting PCa recurrence across cohorts. Lower RSS was characterized by enriched metabolism pathways, high androgen activity, and a favorable prognosis. In contrast, higher RSS was significantly associated with TP53, RB1, and PTEN deletion, exhibited increased proliferation and DNA replication stress, and was more immune-suppressive with a higher chance of immunotherapy response. In silico screening identified 13 potential targets (e.g. TOP2A, CDK9, and RRM2) from 2249 druggable targets, and 2 therapeutic agents (irinotecan and topotecan) for RSS-high patients. Additionally, RSS-high patients were more responsive to taxane-based chemotherapy and Poly (ADP-ribose) polymerase inhibitors, whereas RSS-low patients were more sensitive to androgen deprivation therapy. In conclusion, a robust machine-learning framework was used to reveal the great potential of RSS for personalized risk stratification and therapeutic implications in PCa.
The uptake of key elements of sexual and reproductive health services and its predictors among rural adolescents in Southern Ethiopia, 2020: application of a Poisson regression analysis
Authors: Habte Aklilu , Dessu Samuel
Published: January 2023

Background

Although 25% of the Ethiopian population is young, Sexual and Reproductive Health (SRH) Services have not been adequately researched and intervened, leaving adolescents with many reproductive health challenges. Assessment of the uptake of each element of SRH service and its determinants among those age groups is essential to improving service uptake and reducing the burden of illness and disability in adolescents. Thus, this study aimed at assessing the uptake of key elements of SRH services and its determinants among adolescents residing in rural districts of Guraghe zone, Southern Ethiopia.

Methods

A community-based cross-sectional study was carried out from May 1 to 30, 2020, and a multi-stage sampling technique was employed to randomly select 1028 adolescents. The data were collected by using a pre-tested interviewer-administered questionnaire. The data were coded and entered into Epi-Data version 3.1 and exported into SPSS version 23 for analysis. Independent t-tests and analysis of variance (ANOVA) were run to determine whether there were statistically significant differences in the mean number of SRH services used across each categorical variable. A multivariable generalized linear regression (GLM) model with a Poisson link was used to determine the effect of each variable on the mean number of SRH services used. Adjusted odds ratios with their corresponding 95% confidence interval were used to declare the statistical significance of the independent variables.

Results

The study included 1,009 adolescents, yielding a response rate of 98.1%. The use of the SRH service was assessed using eight elements, and the mean (± SD) score of service uptake was 4.05 (± 1.94), with only 6.8% of adolescents receiving all key elements. Comprehensive sexuality education (55.1%) and voluntary HIV/AIDS counseling and testing (51.0%) were the commonest service items used by adolescents, while the provision of contraceptives was the lowest service item received (25.9%). Educational level (AOR: 1.28, 95% CI: 1.03–1.56), having a parental discussion (AOR: 1.31, 95% CI: 1.13–1.51), lack of youth clubs (AOR: 0.71, 95% CI: 0.66–0.87), and knowledge on SRH issues (AOR: 0.79, 95% CI: 0.73–0.85) were identified as significant predictors of the uptake of key elements of SRH services.

Conclusion

The overall uptake of SRH services was found to be low in the study area. Schools should be an excellent means of educating adolescents to increase their knowledge of key elements of SRH services. Furthermore, stakeholders must work together to improve the culture of parental discussion with adolescents and establish and strengthen youth clubs, as measures for encouraging the use of SRH services.