bluuebunny/crossref_metadata_2025 huggingface dataset:
57 A review of the utilisation of the SHARE frailty instruments (SHARE-FI and SHARE-Fi75+) in the literature
Authors: Doherty H , Jennings A H , Kocka M , Neichel A , Scauso J , Lionetti E , Chen C , Romero-Ortuno R
Published: September 2023

Background

The Survey of Health, Ageing and Retirement in Europe (SHARE) frailty instruments SHARE-FI and SHARE-FI75+ were developed as non-commercial, open access frailty phenotype-based identification tools for rapid use in the primary care setting. This literature review examined their utilisation since their publication.

Methods

We used the Google Scholar ‘cited by’ function (accessed on February 20th, 2023) to identify all citations of the original SHARE-FI and SHARE-FI75+ studies. Included articles were categorised into four themes: epidemiological studies (prevalence and associated factors); associations with geriatric syndromes, diseases and health outcomes; randomised clinical trials (RCTs); and expert consensus and practice guidelines.

Results

Of 529 articles screened (446 citing SHARE-FI and 83 citing SHARE-FI75+), 64 (12.1%) were included in the narrative review. Sixteen (25.0%) were epidemiological; 35 (54.7%) described associations; 10 (15.6%) were RCTs; and 3 (4.7%) were expert consensus or practice guidelines. Frailty was associated with older age; female sex; higher morbidity; lower education; social isolation; worse nutrition and mobility; rheumatological, cardiovascular, and endocrine diseases; and greater healthcare utilisation and mortality. SHARE-FI was used in RCTs as entry criterion, controlling variable and intervention outcome. The most commonly studied interventions were exercise, nutrition and social support. SHARE-FI and SHARE-FI75+ have been recommended to aid the management of atrial fibrillation anticoagulation (2015 European Heart Rhythm Association (EHRA) Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation) and hypertension (2016 Expert Opinion From the European Society of Hypertension-European Union Geriatric Medicine Society Working Group on the Management of Hypertension in Very Old, Frail Subjects), respectively.

Conclusion

SHARE-FI and SHARE-FI75+, two open access phenotypical frailty measurement tools, have been utilised for diverse purposes, and mostly in epidemiological/associational studies. The relative paucity of RCTs and guidelines vis-à-vis epidemiological and associational studies highlights scope for their future utilisation in studies that will be able to generate higher-level evidence.
97 Attending a memory clinic for assessment and diagnosis of dementia: a qualitative systematic review
Authors: Lafferty R , Daly L
Published: September 2023

Background

Memory clinics have gained recognition for assessment, diagnosis and treatment of a range of memory and cognitive conditions and are often the single point of access for people with suspected dementia. Few studies have focused on the experiences of those who attend a memory clinic for assessment and who receive a dementia diagnosis. The aim of the systematic review reported herein was to explore the experiences of attending a memory clinic from the perspectives of those who receive a dementia diagnosis.

Methods

A meta-synthesis systematic review was undertaken using six databases including CINAHL Complete, Medline, EMBASE, PsychINFO, ASSIA and Web of Science. An extensive grey literature search was also undertaken. The search yielded 10,490 studies, and following screening by two reviewers, those studies that met the inclusion criteria were then quality assessed using the Brunton et al. (2011) Quality Assessment Criteria and Scoring Tool. Thematic analysis was used to analyse the included studies.

Results

Ten studies met the inclusion criteria. The resultant meta-synthesis of the evidence identified three analytical themes: (1) ‘Assessment and diagnosis: an emotional journey’ demonstrated that attending a memory clinic can involve a broad range of emotions; (2) ‘Assessment: a relational experience’ highlighted the significance of the nature and quality of the clinician-person relationship; (3) ‘Information: a variable experience’ identified the importance of information and its timeliness.

Conclusion

Findings highlighted the need to raise awareness of dementia and the role of memory clinics and to keep those who attend, informed about the assessment process at each stage. This may help to alleviate some of the challenging emotions associated with attending a memory clinic. Findings further suggest the potential importance of additional communication training for clinicians, especially where difficult and complex disclosures of dementia need to be made.
216 The relationship between anxiety and physical functional decline in older Irish adults: analysis of the Irish Longitudinal Study on Ageing
Authors: Fitzgerald M
Published: September 2023

Background

Research has shown the prevalence of anxiety in the older adult population and its significant impact on physical health. The Irish population is ageing and will have an increasing proportion of the population experiencing physical functional decline. Both anxiety and physical functional decline are associated with reduced quality of life and increased healthcare costs. The aim of this study was to explore if there is an association between anxiety and physical functional decline in older Irish adults.

Methods

This study used data from the Irish Longitudinal Study on Ageing (TILDA). The sample cohort were derived from those who had completed the Hospital Anxiety and Depression Scale (HADS-A) and who reported having difficulty with Activities of Daily Living (ADL) at Wave 1. This cohort were analysed at Wave 2 for a possible association between anxiety, as measured by the HADS-A and physical functional decline, as measured by an ADL self-reporting questionnaire and a Timed Up and Go (TUG).

Results

The sample cohort consisted of 535 participants. The result of the logistic regression found that the odds of continuing to report an ADL difficulty at Wave 2 are 1.78 (95% Confidence Interval [CI]: 1.15, 2.76) times higher for those with anxiety compared to those without and is statistically significant at p = 0.029. The result of the logistic regression analysis found that those with anxiety are more likely to have a longer TUG time (12.4 sec) than those without (11.19 sec) and the result is statistically significant (p = 0.023).

Conclusion

Anxiety is a mental health condition that has a significant impact on physical health. This study has established that there is an association between anxiety and physical functional decline in the older adult population in Ireland. Further research is needed to establish the nature and directionality of the relationship.
Demographic and Geographic Characterization of Excess Mortality During the COVID-19 Pandemic in Baltimore City, Maryland, March 2020 to March 2021
Authors: Aune Kyle T , Grantz Kyra H , Menezes Neia Prata , Robsky Katherine O , Gurley Emily S , Marx Melissa A , Phelan-Emrick Darcy F
Published: September 2023

Estimates of excess mortality can provide insight into direct and indirect impacts of the coronavirus disease 2019 (COVID-19) pandemic beyond deaths specifically attributed to COVID-19. We analyzed death certificate data from Baltimore City, Maryland, from March 1, 2020, to March 31, 2021, and found that 1,725 individuals (95% confidence interval: 1,495, 1,954) died in excess of what was expected from all-cause mortality trends in 2016–2019; 1,050 (61%) excess deaths were attributed to COVID-19. Observed mortality was 23%–32% higher than expected among individuals aged 50 years and older. Non-White residents of Baltimore City also experienced 2 to 3 times higher rates of excess mortality than White residents (e.g., 37.4 vs. 10.7 excess deaths per 10,000 population among Black residents vs. White residents). There was little to no observed excess mortality among residents of hospice, long-term care, and nursing home facilities, despite accounting for nearly 30% (312/1,050) of recorded COVID-19 deaths. There was significant geographic variation in excess mortality within the city, largely following racial population distributions. These results demonstrate the substantial and unequal impact of the COVID-19 pandemic on Baltimore City residents and the importance of building robust, timely surveillance systems to track disparities and inform targeted strategies to remediate the impact of future epidemics.
Alcohol outlet density and marketing in Abeokuta, Nigeria
Authors: Odeigah Ogochukwu W , Patton Robert , Trangenstein Pamela
Published: September 2023

Aim: The physical availability of alcohol is a modifiable determinant of alcohol consumption and related harm. However, Nigeria currently does not have national regulations restricting the physical availability of alcohol. The study measured alcohol outlet density and marketing in Abeokuta, Nigeria. Methods: A descriptive community design was employed. Seven wards in Abeokuta South local government were surveyed street by street for functional alcohol outlets and nearby public institutions (schools and worship centres). Outlet characteristics were documented, and the location of outlets and public institutions was geocoded using a global positioning system app. The density and proximity of outlets and public institutions were analysed using QGIS 3.22. Results: Four hundred and seventy-six alcohol outlets and 194 public institutions (82 schools, 87 churches, and 25 mosques) were sampled across the 7 wards. The most common type of alcohol premises and outlets was on/off-premises and liquor/non-alcoholic drinks stores. Alcohol banners on liquor store lintels were the most prevalent marketing item. Alcohol outlet density ranged from 8.06 to 200 per km2. The smallest average distance between alcohol outlets was 28 m in Sodeke, while Ago Egun/Ijesa had the highest number of outlets and on/off premises. The shortest distance from an outlet to a school was 18.77 m in Ijaiye and 44 (14.7%) schools were located within ≤100 m of an outlet. Conclusions: Findings indicate high alcohol density, resulting in short distances between alcohol outlets and public institutions in Abeokuta South local government area. These results underscore the importance of implementing evidence-based alcohol availability policies in Nigeria.
Accurate Plane Fat Grafting in Gluteal Augmentation: An Anatomic Study
Authors: Kelishadi S Sean , Chiemi Julia A , Chowdhry Saeed , Colorado Avery , Herring Nicole R , Kinney Brian , Wilhelmi Bradon J
Published: September 2023

Background

The safety of gluteal fat grafting is a global concern in plastic surgery.

Objective

The goal of this study was to test whether fat grafting to the buttocks with Auto Stop Reach (ASR) technology prevents penetration from the subcutaneous space into the fascia and muscle layers of the buttocks.

Methods

Fat transfer simulation was performed with blue dye on 8 fresh tissue cadaver buttocks by 3 board-certified plastic surgeons (S.S.K., S.C., B.W.). An open control was utilized to visualize the process in the different anatomic layers, and all of the other procedures were performed blindly, akin to live surgery. After blue dye transfer reached maximum capacity (ranging from 400-800 mL per buttock), dissection of the anatomical layers of the buttocks was performed to determine the plane(s) of injection.

Results

Blue dye fat transfer injection to the buttocks did not penetrate the gluteal fascia or muscle layers from the subcutaneous space while using ASR.

Conclusions

Auto Stop Reach technology supports the safety of gluteal fat transfer in the subcutaneous space by board-certified plastic surgeons.

Level of Evidence: 4
Interleukin-21 knockout reduces bone loss in ovariectomized mice by inhibiting osteoclastogenesis
Authors: Hou Junlong , Xu Ping , Zhong Yanheng , Zhou Zhigang , Zhang Wencai
Published: September 2023

Estrogen deficiency accelerates osteoporosis in elderly women. However, the role of IL-21 in postmenopausal osteoporosis remains unclear. Female wild-type (WT) C57BL/6 and IL-21 knockout (KO) mice were used for ovariectomy (OVX). Here, IL-21 levels were significantly increased in the serum and bone tissues of WT-OVX mice. The trabecular bone space of the femur was significantly increased, and the bone mass was reduced in OVX mice, accompanied by a significant decrease in the maximum load, energy absorption, and elastic modulus indices. In contrast, IL-21 knockout effectively alleviated the effects of OVX on bone mass. Serum TRACP-5b and receptor activator of nuclear factor kappa B ligand (RANKL) levels and osteoclastogenesis were significantly higher in OVX mice than in sham mice, while serum TRACP-5b and RANKL levels and osteoclastogenesis were significantly decreased in IL-21 KO + OVX mice compared to WT + OVX mice. IL-21 knockdown reduces TRACP-5b, RANKL, and osteoclastogenesis, effectively preventing bone resorption and alleviating the progression of OVX-induced osteoporosis.
Enhanced intestinal barrier function as the mechanism of antibiotic growth promoters in feed additives
Authors: Uehara Akinori , Maekawa Mayumi , Nakagawa Kazuki
Published: September 2023

Antibiotic growth promoters (AGPs) are a cost-effective tool for improving livestock productivity. However, antimicrobial-resistant bacteria have emerged, and the search for alternatives to AGPs has consequently intensified. To identify these alternatives without the risk of the emergence of antimicrobial resistance, it is important to determine the mechanism of action of AGPs and, subsequently, search for compounds with similar properties. We investigated the antimicrobial and anti-inflammatory activities and intestinal barrier function of several AGPs using epithelial and immune cells. At the minimum administered dose of antibiotics, which effectively function as a growth promoter, the mechanism of action is to enhance the intestinal barrier function, but not the antimicrobial activity as determined using Dunnett's test (n = 3, P < .05). Inflammatory response was dependent on the combination of antibiotics (100 µmol/L) and immune cells. The results suggest that future studies should screen for nonantibiotic compounds that ameliorate intestinal barrier function.
Detecting biased validation of predictive models in the positive-unlabeled setting: disease gene prioritization case study
Authors: Molotkov Ivan , Artomov Mykyta
Published: September 2023

Motivation

Positive-unlabeled data consists of points with either positive or unknown labels. It is widespread in medical, genetic, and biological settings, creating a high demand for predictive positive-unlabeled models. The performance of such models is usually estimated using validation sets, assumed to be selected completely at random (SCAR) from known positive examples. For certain metrics, this assumption enables unbiased performance estimation when treating positive-unlabeled data as positive/negative. However, the SCAR assumption is often adopted without proper justifications, simply for the sake of convenience.

Results

We provide an algorithm that under the weak assumptions of a lower bound on the number of positive examples can test for the violation of the SCAR assumption. Applying it to the problem of gene prioritization for complex genetic traits, we illustrate that the SCAR assumption is often violated there, causing the inflation of performance estimates, which we refer to as validation bias. We estimate the potential impact of validation bias on performance estimation. Our analysis reveals that validation bias is widespread in gene prioritization data and can significantly overestimate the performance of models. This finding elucidates the discrepancy between the reported good performance of models and their limited practical applications.

Availability and implementation

Python code with examples of application of the validation bias detection algorithm is available at github.com/ArtomovLab/ValidationBias.
mbQTL: an R/Bioconductor package for microbial quantitative trait loci (QTL) estimation
Authors: Movassagh Mercedeh , Schiff Steven J , Paulson Joseph N
Published: September 2023

Motivation

In recent years, significant strides have been made in the field of genomics, with the commencement of large-scale studies aimed at collecting host mutational profiles and microbiome data. The amalgamation of host gene mutational profiles in both healthy and diseased subjects with microbial abundance data holds immense promise in providing insights into several crucial research questions, including the development and progression of diseases, as well as individual responses to therapeutic interventions. With the advent of sequencing methods such as 16s ribosomal RNA (rRNA) sequencing and whole genome sequencing, there is increasing evidence of interplay of human genetics and microbial communities. Quantitative trait loci associated with microbial abundance (mbQTLs), are genetic variants that influence the abundance of microbial populations within the host.

Results

Here, we introduce mbQTL, the first R package integrating 16S ribosomal RNA (rRNA) sequencing and single-nucleotide variation (SNV) and single-nucleotide polymorphism (SNP) data. We describe various statistical methods implemented for the identification of microbe–SNV pairs, relevant statistical measures, and plot functionality for interpretation.

Availability and implementation

mbQTL is available on bioconductor at https://bioconductor.org/packages/mbQTL/.
BioThings Explorer: a query engine for a federated knowledge graph of biomedical APIs
Authors: Callaghan Jackson , Xu Colleen H , Xin Jiwen , Cano Marco Alvarado , Riutta Anders , Zhou Eric , Juneja Rohan , Yao Yao , Narayan Madhumita , Hanspers Kristina , Agrawal Ayushi , Pico Alexander R , Wu Chunlei , Su Andrew I
Published: September 2023

Knowledge graphs are an increasingly common data structure for representing biomedical information. These knowledge graphs can easily represent heterogeneous types of information, and many algorithms and tools exist for querying and analyzing graphs. Biomedical knowledge graphs have been used in a variety of applications, including drug repurposing, identification of drug targets, prediction of drug side effects, and clinical decision support. Typically, knowledge graphs are constructed by centralization and integration of data from multiple disparate sources. Here, we describe BioThings Explorer, an application that can query a virtual, federated knowledge graph derived from the aggregated information in a network of biomedical web services. BioThings Explorer leverages semantically precise annotations of the inputs and outputs for each resource, and automates the chaining of web service calls to execute multi-step graph queries. Because there is no large, centralized knowledge graph to maintain, BioThings Explorer is distributed as a lightweight application that dynamically retrieves information at query time.

Availability and implementation

More information can be found at https://explorer.biothings.io and code is available at https://github.com/biothings/biothings_explorer.
SCORPIO: a utility for defining and classifying mutation constellations of virus genomes
Authors: Colquhoun Rachel , Jackson Ben , O’Toole Áine , Rambaut Andrew
Published: September 2023

Scorpio provides a set of command line utilities for classifying, haplotyping, and defining constellations of mutations for an aligned set of genome sequences. It was developed to enable exploration and classification of variants of concern within the SARS-CoV-2 pandemic, but can be applied more generally to other species.

Availability and implementation

Scorpio is an open-source project distributed under the GNU GPL version 3 license. Source code and binaries are available at https://github.com/cov-lineages/scorpio, and binaries are also available from Bioconda. SARS-CoV-2 specific definitions can be installed as a separate dependency from https://github.com/cov-lineages/constellations.
A machine learning-based quantitative model (LogBB_Pred) to predict the blood–brain barrier permeability (logBB value) of drug compounds
Authors: Shaker Bilal , Lee Jingyu , Lee Yunhyeok , Yu Myeong-Sang , Lee Hyang-Mi , Lee Eunee , Kang Hoon-Chul , Oh Kwang-Seok , Kim Hyung Wook , Na Dokyun
Published: September 2023

Motivation

Efficient assessment of the blood–brain barrier (BBB) penetration ability of a drug compound is one of the major hurdles in central nervous system drug discovery since experimental methods are costly and time-consuming. To advance and elevate the success rate of neurotherapeutic drug discovery, it is essential to develop an accurate computational quantitative model to determine the absolute logBB value (a logarithmic ratio of the concentration of a drug in the brain to its concentration in the blood) of a drug candidate.

Results

Here, we developed a quantitative model (LogBB_Pred) capable of predicting a logBB value of a query compound. The model achieved an R2 of 0.61 on an independent test dataset and outperformed other publicly available quantitative models. When compared with the available qualitative (classification) models that only classified whether a compound is BBB-permeable or not, our model achieved the same accuracy (0.85) with the best qualitative model and far-outperformed other qualitative models (accuracies between 0.64 and 0.70). For further evaluation, our model, quantitative models, and the qualitative models were evaluated on a real-world central nervous system drug screening library. Our model showed an accuracy of 0.97 while the other models showed an accuracy in the range of 0.29–0.83. Consequently, our model can accurately classify BBB-permeable compounds as well as predict the absolute logBB values of drug candidates.

Availability and implementation

Web server is freely available on the web at http://ssbio.cau.ac.kr/software/logbb_pred/. The data used in this study are available to download at http://ssbio.cau.ac.kr/software/logbb_pred/dataset.zip.
Association between new plasma inflammatory markers and risk of colorectal neoplasms in individuals over 50 years old
Authors: Su Jia-Yi , Wang Yun , Wu Shang-Shang , Li Wen-Kun , Wang Cheng-Yao , Ma Jiu-Yue , Qiu Yu-Ting , Zhou Min-Si , Wang Zhan , Li Peng , Liu Chun-Tao , Wu Jing
Published: September 2023

Objective(s)

The prognostic value of systemic cytokine profiles and inflammatory markers in colorectal cancer were explored by several studies. We want to know more about inflammatory biomarkers in colorectal adenoma and early cancer.

Method

The level of 38 inflammatory markers in the plasma of 112 adenoma patients, 72 Tis-T1 staging of colorectal carcinoma patients, 34 T2–T4 staging of colorectal carcinoma patients and 53 normal subjects were detected and compared.

Result(s)

Eight inflammatory biomarkers (Eotaxin, GCSF, IL-4, IL-5, IL-17E, MCP-1, TNF-α and VEGF-A) have higher plasma concentrations in colorectal adenoma and cancer patients compared with normal participants over 50 years old.

Conclusion(s)

Inflammatory markers may have the prognostic value for colorectal adenoma and early-stage carcinoma.
Rapid response to spesolimab in a patient with severe refractory pyoderma gangrenosum
Authors: Ma Li , Chen Xiaohong , Guo Qing , Qiao Zhuhui , Wang Nansong , Pai Pearl , Liu Xiaoming
Published: September 2023

We report on a patient with severe ulcerative pyoderma gangrenosum that was recalcitrant to systemic corticosteroid, tumour necrosis factor antagonist and ciclosporin treatment and finally controlled when spesolimab was added to the treatment regimen.
Advancing dermatology: artificial intelligence-based solutions to reducing the risk of misdiagnosis
Authors: Klabukov Ilya , Baranovskii Denis
Published: September 2023

Artificial intelligence has potential applications in dermatology in reducing rates of misdiagnosis. Despite evidence-based recommendations, misdiagnosis still occurs due to the complexity of the problem. Multispectral imaging, such as near- and far-infrared imaging, has the potential to aid in the identification of skin malignancies.
Switching to biosimilars in dermatology: a patients’ perspective
Authors: Goh Alicia , Griffin Laoise , Sadlier Muriel
Published: September 2023

Biosimilars are legitimate copies of a biopharmaceuticals (originator biologics) that are no longer protected by patent and have undergone rigorous analytical and clinical assessment compared with their reference product, demonstrating efficacy and safety with significant cost savings when prescribed. This qualitative study was conducted to better understand the patient experience around the transition to biosimilars. Three main themes that influenced patient decisions were identified: the impact of disease, the information around biosimilars and patient autonomy. This study highlights the importance of counselling patients appropriately regarding transitioning to biosimilars and reinforces the importance of good communication to ensure patient empowerment and satisfaction.
Air pollution and out-of-hospital cardiac arrest risk: a 7-year study from a highly polluted area
Authors: Moderato Luca , Aschieri Daniela , Lazzeroni Davide , Rossi Luca , Biagi Andrea , Binno Simone Maurizio , Monello Alberto , Pelizzoni Valentina , Sticozzi Concetta , Zanni Alessia , Capucci Alessandro , Nani Stefano , Ardissino Diego , Nicolini Francesco , Niccoli Giampaolo
Published: September 2023

Aims

Globally, nearly 20% of cardiovascular disease deaths were attributable to air pollution. Out-of-hospital cardiac arrest (OHCA) represents a major public health problem; therefore, the identification of novel OHCA triggers is of crucial relevance. The aim of the study was to evaluate the association between air pollution (short-, mid-, and long-term exposures) and OHCA risk, during a 7-year period in a highly polluted urban area in northern Italy, with a high density of automated external defibrillators (AEDs).

Methods and results

Out-of-hospital cardiac arrests were prospectively collected from the ‘Progetto Vita Database’ between 1 January 2010 and 31 December 2017; day-by-day air pollution levels were extracted from the Environmental Protection Agency stations. Electrocardiograms of OHCA interventions were collected from the AED data cards. Day-by-day particulate matter (PM) 2.5 and 10, ozone (O3), carbon monoxide (CO), and nitrogen dioxide (NO2) levels were measured. A total of 880 OHCAs occurred in 748 days. A significant increase in OHCA risk with a progressive increase in PM2.5, PM10, CO, and NO2 levels was found. After adjustment for temperature and seasons, a 9% and 12% increase in OHCA risk for each 10 μg/m3 increase in PM10 (P < 0.0001) and PM2.5 (P < 0.0001) levels was found. Air pollutant levels were associated with both asystole and shockable rhythm risk, while no correlation was found with pulseless electrical activity.

Conclusion

Short- and mid-term exposures to PM2.5 and PM10 are independently associated with the risk of OHCA due to asystole or shockable rhythm.
Case report—right atrial mass: a very rare presentation of endometrial cancer metastasis
Authors: Erturk Emre , Soyler Onur , Pehlivan Fatma Seher , Arslan Cagatay
Published: September 2023

Background

We report a case of a 47-year-old woman with right atrial metastasis of endometrioid adenocarcinoma, which is an uncommon clinical presentation for patients with endometrial cancer (EC). The principal aim of this case is to demonstrate the possibility of distant metastasis, something rarely encountered among this group of patients.

Case summary

Our patient, diagnosed with EC and receiving chemotherapy and radiotherapy after surgery, was found to have enhanced 18-fluorodeoxyglucose uptake inside the right atrium on the repeat positron emission tomography–computed tomography scan at the ninth month after initial diagnosis. Following trans-oesophageal echocardiography, cardiac magnetic resonance imaging showed a hyper-vascular mass with right atrial lateral wall involvement likely to be malignant in nature. A right atrial tumour was successfully removed by cardiovascular surgeons, and a pericardial patch was placed at the site of the excised atrium. The pathological examination showed EC metastasis. Following surgery, systemic treatment was planned for recurrent EC. The patient had an uneventful recovery after the surgery.

Discussion

Endometrial cancer is the most common gynaecologic malignancy and the fourth most common cancer in women. The lymphatic pathway is the main metastatic behaviour of EC; however, haematogenous metastases are not uncommon, especially in patients with higher stages of the disease. Our patient did not show any signs and symptoms of cardiac involvement. Nevertheless, clinicians should be alert for symptoms of cardiac involvement like new-onset murmur, embolism, or dyspnoea. Having known the behavioural pattern of the primary tumour, timely utilization of diagnostic imaging methods in accordance with clinical suspicions in patients with rapidly growing tumours can be lifesaving.
Mid- and long-term outcomes after surgical correction of subaortic stenosis: a 27-year experience
Authors: Bandara Dushan , Salve Gananjay G , Marathe Supreet P , Betts Kim S , Cole Andrew D , Ayer Julian G , Nicholson Ian A , Orr Yishay
Published: September 2023

OBJECTIVES

We reviewed the mid- and long-term surgical outcomes of patients with subaortic stenosis (SAS).

METHODS

Patients operated for SAS from April 1990 to August 2016 were reviewed retrospectively. Patients with major associations such as aortic arch obstruction were excluded. Time to reintervention and predictors of recurrence were assessed using Kaplan–Meier analysis, log-rank test and uni/multivariable Cox regression.

RESULTS

120 patients at a median age of 4.7 years (interquartile range 2.9, 8.1) underwent primary operation (median peak preoperative left ventricular outflow tract gradient 52.5 mmHg, interquartile range 40, 70) involving fibrous tissue excision (n = 120) with septal myectomy (93%; n = 112) as the procedure of choice.

At median follow-up of 13 years (interquartile range 7, 18), freedom from reintervention at 1, 3, 5 and 10 years was 99% (95% confidence interval 94%, 99%), 94% (87%, 97%), 93% (86%, 96%) and 90% (82%, 94%), respectively. Recurrence occurred in 18% (n = 20) with 15 patients undergoing reinterventions, 13 of whom required radical reoperation. Multivariable analysis revealed higher preoperative peak left ventricular outflow tract gradient (hazard risk 1.06, confidence interval 1.03, 1.09, P < 0.001), and presence of bicuspid aortic valve (hazard risk 14.13, confidence interval 3.32, 60.1, P < 0.001) as predictors for reintervention. Mild/moderate aortic regurgitation occurred in 49% (n = 55) of patients at the most recent follow-up.

CONCLUSIONS

Reintervention for recurrent SAS is common, predicted by higher preoperative peak left ventricular outflow tract gradient, and presence of bicuspid aortic valve, and frequently involves a radical procedure. Aortic regurgitation is a major consequence of SAS, but its severity usually remains low.

Clinical Registration Number

SCHN HREC reference number 2019/ETH02729, approved on 09 July 2019.
Mechanical atrioventricular valve replacement in patients with single ventricle palliation
Authors: Morgan Conall T , Chetan Devin , Varenbut Jaymie , Haller Christoph , Seed Mike , Mertens Luc L , Honjo Osami
Published: September 2023

OBJECTIVES

Atrioventricular valve (AVV) replacements in patients with single-ventricle circulations pose significant surgical risks and are associated with high morbidity and mortality.

METHODS

From 1997 to 2021, 16 consecutive patients with functionally single-ventricle physiology underwent mechanical AVV replacement. Primary outcome was transplant-free survival. Secondary outcomes included major postoperative morbidity.

RESULTS

The median age of AVV replacement was 2 years old (interquartile range 0.6–3.8 years). All AVV replacements were performed with a St. Jude Medical mechanical valve, median 24 mm (range, 19–31mm). Extracorporeal membrane oxygenation (ECMO) was required in 4 patients. Operative mortality was 38% (6/16). There were 2 late deaths and 3 transplants. Transplant-free survival was 50% at 1 year, 37.5% at 5 years, and 22% at 10 years. Transplant-free survival was higher for patients with preserved ventricular function (P = 0.01). Difference in transplant-free survival at 1 year was 75% vs 25%, at 5 years was 62.5% vs 12.5% and at 10 years was 57% vs 0%. Three (19%) patients had complete heart block requiring permanent pacemaker insertion. 6 of 13 patients (46%) patients reached Fontan completion (3 patients operated at/after Fontan). Significant bleeding events occurred in 8 patients (50%) with 3 patients suffering major cerebrovascular accidents. There were 6 events of valve thrombosis in 5 patients, resulting in 2 deaths and 2 heart transplants.

CONCLUSIONS

Mechanical valve replacement carries significant morbidity and mortality risk. While it successfully salvages about half of patients with preserved ventricular function, careful consideration of alternative options should be made before embarking upon mechanical valve replacement.
Asymptomatic atrial fibrillation among hospitalized patients: clinical correlates and in-hospital outcomes in Improving Care for Cardiovascular Disease in China-Atrial Fibrillation
Authors: Lin Jing , Wu Xue-Ying , Long De-Yong , Jiang Chen-Xi , Sang Cai-Hua , Tang Ri-Bo , Li Song-Nan , Wang Wei , Guo Xue-Yuan , Ning Man , Sun Zhao-Qing , Yang Na , Hao Yong-Chen , Liu Jun , Liu Jing , Du Xin , Fonarow Gregg C , Smith Sidney C , Lip Gregory Y H , Zhao Dong , Dong Jian-Zeng , Ma Chang-Sheng
Published: September 2023

Aims

The clinical correlates and outcomes of asymptomatic atrial fibrillation (AF) in hospitalized patients are largely unknown. We aimed to investigate the clinical correlates and in-hospital outcomes of asymptomatic AF in hospitalized Chinese patients.

Methods and results

We conducted a cross-sectional registry study of inpatients with AF enrolled in the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation Project between February 2015 and December 2019. We investigated the clinical characteristics of asymptomatic AF and the association between the clinical correlates and the in-hospital outcomes of asymptomatic AF. Asymptomatic and symptomatic AF were defined according to the European Heart Rhythm Association score. Asymptomatic patients were more commonly males (56.3%) and had more comorbidities such as hypertension (57.4%), diabetes mellitus (18.6%), peripheral artery disease (PAD; 2.3%), coronary artery disease (55.5%), previous history of stroke/transient ischaemic attack (TIA; 17.9%), and myocardial infarction (MI; 5.4%); however, they had less prevalent heart failure (9.6%) or left ventricular ejection fractions ≤40% (7.3%). Asymptomatic patients were more often hospitalized with a non-AF diagnosis as the main diagnosis and were more commonly first diagnosed with AF (23.9%) and long-standing persistent/permanent AF (17.0%). The independent determinants of asymptomatic presentation were male sex, long-standing persistent AF/permanent AF, previous history of stroke/TIA, MI, PAD, and previous treatment with anti-platelet drugs. The incidence of in-hospital clinical events such as all-cause death, ischaemic stroke/TIA, and acute coronary syndrome (ACS) was higher in asymptomatic patients than in symptomatic patients, and asymptomatic clinical status was an independent risk factor for in-hospital all-cause death, ischaemic stroke/TIA, and ACS.

Conclusion

Asymptomatic AF is common among hospitalized patients with AF. Asymptomatic clinical status is associated with male sex, comorbidities, and a higher risk of in-hospital outcomes. The adoption of effective management strategies for patients with AF should not be solely based on clinical symptoms.
Assessing the Presence of Recent Adaptation in the Human Genome With Mixture Density Regression
Authors: Salazar-Tortosa Diego F , Huang Yi-Fei , Enard David
Published: September 2023

How much genome differences between species reflect neutral or adaptive evolution is a central question in evolutionary genomics. In humans and other mammals, the presence of adaptive versus neutral genomic evolution has proven particularly difficult to quantify. The difficulty notably stems from the highly heterogeneous organization of mammalian genomes at multiple levels (functional sequence density, recombination, etc.) which complicates the interpretation and distinction of adaptive versus neutral evolution signals. In this study, we introduce mixture density regressions (MDRs) for the study of the determinants of recent adaptation in the human genome. MDRs provide a flexible regression model based on multiple Gaussian distributions. We use MDRs to model the association between recent selection signals and multiple genomic factors likely to affect the occurrence/detection of positive selection, if the latter was present in the first place to generate these associations. We find that an MDR model with two Gaussian distributions provides an excellent fit to the genome-wide distribution of a common sweep summary statistic (integrated haplotype score), with one of the two distributions likely enriched in positive selection. We further find several factors associated with signals of recent adaptation, including the recombination rate, the density of regulatory elements in immune cells, GC content, gene expression in immune cells, the density of mammal-wide conserved elements, and the distance to the nearest virus-interacting gene. These results support the presence of strong positive selection in recent human evolution and highlight MDRs as a powerful tool to make sense of signals of recent genomic adaptation.
Fluoxetine Promotes Longevity via Reactive Oxygen Species in Caenorhabditis elegans
Authors: Zhou Can , Zhou Yiming , Liang Yu , Chen Lijuan , Liu Li , Wei Fang , Li Guolin
Published: September 2023

Although several antidepressants have been identified as potential geroprotectors, the effect and mechanism of fluoxetine, a representative selective serotonin reuptake inhibitor, on longevity have not been fully elucidated. Here, we found that fluoxetine promoted longevity in Caenorhabditis elegans with a concomitant extension of a healthy life span as indicated by increasing mobility, reducing fertility and lipofuscin accumulation, and enhanced resistance to different abiotic stresses. Fluoxetine increased the level of reactive oxygen species (ROS), and antioxidant N-acetylcysteine abolished ROS elevation and the pro-longevity effect of fluoxetine. Additionally, fluoxetine extended life span through the daf-2-sod-3 pathway in daf-16-dependent and -independent manners, and fluoxetine-induced life-span extension was abolished in C. elegans sod-3, daf-2, and daf-16 mutants. In conclusion, these findings suggest that fluoxetine can promote health and longevity in C. elegans via the interaction of ROS and insulin signaling.
Establishment of Baseline Urinary Antimicrobial Peptide Levels by Age: A Prospective Observational Study
Authors: Caterino Jeffrey M , Stephens Julie A , Wexler Randell , Camargo Carlos A , Hunold Katherine M , Wei Lai , Hains David , Southerland Lauren T , Bischof Jason J , Schwaderer Andrew
Published: September 2023

Background

Antimicrobial peptides (AMPs) are key effectors of urinary tract innate immunity. Identifying differences in urinary AMP levels between younger and older adults is important in understanding older adults’ susceptibility and response to urinary tract infections (UTI) and AMP use as diagnostic biomarkers. We hypothesized that uninfected older adults have higher urinary human neutrophil peptides 1-3 (HNP 1-3), human alpha-defensin-5 (HD-5), and human beta-defensin-2 (hBD-2), but lower urinary cathelicidin (LL-37) than younger adults.

Methods

We conducted a cross-sectional study of patients aged ≥18 years completing a family medicine clinic nonacute visit. Enzyme-linked immunosorbent assays were performed for AMPs. We identified associations between age and AMPs using unadjusted and multivariable linear regression models.

Results

Of the 308 subjects, 144 (46.8%) were ≥65 years of age. Comparing age ≥65 versus < 65 years, there were no significant differences in HNP 1-3 (p = .371), HD5 (p = .834), or LL-37 (p = .348) levels. Values for hBD-2 were lower in older adults versus younger (p < .001). In multivariable analyses, older males and females had significantly lower hBD-2 levels (p < .001 and p = .004). Models also showed urine leukocyte esterase was associated with increased levels of HNP 1-3 and HD5; hematuria with increased hBD-2; and urine cultures with contamination with increased HNP 1-3 and hBD-2.

Conclusions

Baseline urinary HNP 1-3, HD-5, and LL-37 did not vary with age. Older adults had lower baseline hBD-2. This finding has implications for the potential use of urinary AMPs as diagnostic markers and will facilitate further investigation into the role of innate immunity in UTI susceptibility in older adults.
The Effectiveness of Home-Based Exergames Training on Cognition and Balance in Older Adults: A Comparative Quasi-Randomized Study of Two Exergame Interventions
Authors: Begde Ahmet , Alqurafi Alaa , Pain Matthew T G , Blenkinsop Glen , Wilcockson Thomas D W , Hogervorst Eef
Published: September 2023

Background and Objectives

The effectiveness of exergames on fall risk and related physical and cognitive function in older adults is still unclear, with conflicting findings. The discrepancy in these results could be due to the different components and task-specific demands of individual exergame interventions. This open-label quasi-randomized study aimed to compare the efficacy of 2 different home-based dual-task exergame treatments on cognition, mobility, and balance in older people.

Research Design and Methods

Fifty older adults (65–85 years of age) were allocated to one of two 8-week exergame interventions: Cognitive-Intensive Exergame Training (CIT) or Physical-Intensive Exergame Training (PIT). Cognitive functions, balance, and mobility were assessed at baseline and after 8 weeks. Group × time interaction was measured by repeated-measure ANOVA, and both intention-to-treat (ITT) and per-protocol (PP) analyses were performed to assess the effectiveness of exergame interventions.

Results

ITT analyses showed that improvement in visual processing speed and visuospatial working memory was greater in the CIT group, with a medium effect size (p = .04; η2 = 0.09 and p = .01; η2 = 0.12). The improvement in verbal memory and attention was significant within both groups (p < .05), but this improvement was not different between the groups (p > .05). A significant improvement in balance was also observed in the PIT group, with a medium effect size (p = .04; η2 = 0.09). Although mobility improved significantly in both groups (p < .01), there was no significant difference between groups (p = .08). These results were largely supported by the PP analysis.

Discussion and Implications

Dual-task exergame training can improve mobility and cognition in older adults. However, the different cognitive and physical demands of these interventions may have varying impacts on fall risk and related physical or cognitive functions. Therefore, a training program that includes both cognitive and physical domains with appropriate intensity is essential for the development of tailored exergame interventions to reduce fall risk in older adults.
A daisy chain method to quickly determine lithosphere, asthenosphere and mantle properties from the loading history of an area
Authors: Cathles Lawrence M , Fjeldskaar Willy , Amantov Aleksey
Published: September 2023

The lithosphere and asthenosphere are fundamental to plate tectonics and many other earth processes. Vertical motions can be measured quickly and accurately by the satellite Global Positioning System, GPS and other methods. This paper describes a new analytic method for inferring the elastic and viscous properties of the lithosphere and upper mantle from the uplift rate and history of an area that has been subjected to past surface load changes. The viscous response time of the centre of loading is determined from the dimensions of the load, a loading history comprised of linear segments, an estimate of the flexural rigidity of the lithosphere and a single constraint such as the current central uplift rate. The response time is then interpreted in terms of the elastic properties of the lithosphere, and the elastic and viscous depth profiles of the underlying mantle. The method is described mathematically and then illustrated through analysis of the isostatic adjustment observed in nine areas affected by Little Ice Age glaciation. The method replicates published conclusions, extracts insights from an extensive literature, provides new ways to separate the impacts of the lithosphere and asthenosphere on uplift rates and emergence, and indicates the widespread geographic distribution of a thin asthenosphere.
Spherical-wave elastic inversion in transversely isotropic media with a vertical symmetry axis
Authors: Cheng Guangsen , He Chuanlin , Liang Zhanyuan , Yin Xingyao , Zhang Xiaoyu , Zheng Yi
Published: September 2023

Although subsurface media are usually assumed to be isotropic, anisotropy is ubiquitous in crustal rocks and leads to the variation of seismic response with direction. Transversely isotropic media with a vertical symmetry axis (VTI media) are widely found in the real world, such as in textured shale reservoirs. Plane-wave reflection coefficients (PRCs) in VTI media have been widely exploited in amplitude variation with offset (AVO) inversion to estimate the elastic and anisotropy parameters of subsurface media. However, the PRCs in VTI media meet some fundamental problems, especially at near-critical or post-critical incidence angles where the spherical-wave effect is significant. To consider the wave front curvature, a complex spherical-wave reflection coefficient (SRC) in VTI media is derived. To better understand the spherical-wave seismic response in VTI media, we investigate the dependence of the complex SRC on frequency, reflector depth and Thomsen anisotropy parameters ($\varepsilon $ and $\delta $). Based on a complex convolution model, a spherical-wave AVO inversion approach in VTI media is proposed to estimate the vertical (symmetry-axis) compressional and shear wave velocities (P and S waves), density and Thomsen anisotropy parameters from observed seismic data with different incidence angle and frequency components. Synthetic data with Gaussian random noise are used to verify the robustness of the spherical-wave AVO inversion approach in VTI media. Field data examples show that the proposed approach can produce reasonable inversion results that match well with the well-logging data.
Earnings, job satisfaction, and turnover of nurse practitioners across employment settings
Authors: Hnath Joseph G P , Rambur Betty , Grabowski David C
Published: September 2023

Nurse practitioners (NPs) are an important part of the health care workforce. However, little information is available on NP earnings, job satisfaction, or turnover. National survey data from 2018 offer a pre–COVID-19 baseline for ongoing NP workforce monitoring. We found evidence that NPs earned approximately $92 500 annually, ranging from $82 800 in long-term care to $95 600 in hospital settings. Wages increased with tenure in the workforce and varied considerably by geography. Approximately 1 in 5 NPs switched jobs annually, with some net in-flow to ambulatory settings. Both NPs who left their position or considered leaving reported better pay and benefits, burnout, management role, stressful work environment, career advancement, and inadequate staffing as the primary explanations. These findings were augmented by analysis of 2012–2022 Bureau of Labor Statistics data that illustrated substantial growth in the NP workforce. Improving NP job satisfaction has the direct benefit of supporting a critical and growing segment of the health workforce; it has the additional benefit of reducing job turnover and the associated costs, potentially increasing earnings for NPs. Policies that improve working conditions for NPs in different employment settings will not just increase immediate job satisfaction but also ideally strengthen the longer-term labor market to improve patient outcomes.