bluuebunny/crossref_metadata_2025 huggingface dataset:
Mindfulness Coaching with Digital Lifestyle Monitoring Enhances Selective Attention in Medical Scientists
Authors: Jaiswal Satish , Nan Jason , Purpura Suzanna R. , Manchanda James K. , Garcia-pak Iris , Ramanathan Dhakshin S. , Chuss Dawna , Rana Deborah T. , Beck Ellen , Insel Paul A. , Chi Neil , Roth David M. , Patel Hemal H. , Mishra Jyoti
Published: January 2024

Medical scientists have dual commitments to clinical care and research efforts. Such commitments can create hectic and stressful work schedules, which may impact on well-being and cognition. In this study, we tested the hypothesis that mindfulness coaching plus wearable-based lifestyle monitoring can benefit such individuals. We conducted a waitlist-controlled intervention study (n=43) with M.D./Ph.D. preclinical or graduate students and post M.D./Ph.D. trainees/faculty. Assessments of quantitative outcomes included subjective measures of burnout, mindfulness, self-compassion, and well-being, as well as objective cognitive assessments. The results showed no impacts on subjective measures. However, amongst objective cognitive measures, selective attention performance was significantly improved following the intervention (bias corrected effect size, Hedges’ g = 1.13, p=0.005). Extent of improvement in selective attention correlated with suppression of visual alpha oscillations – a neural marker for distractibility - measured using electroencephalography (EEG) (r=-0.32, p<0.05). Qualitative feedback showed that after receiving the intervention, participants in both groups equally rated the overall experience as “very good” (3.70 ±0.98 out 5). They also appreciated that the intervention emphasized healthy lifestyle behaviors, and contributed to mindfulness, compassion, and a sense of community. A majority (57%) of the participants reported that they expect to change their well-being related behaviors because of the intervention. Overall, this study suggests the utility of mindfulness coaching to improve selective attention skills in medical scientists and that more needs to be done to enhance subjective well-being in such individuals.
Assessing Causal Relationships Between Diabetes Mellitus and Idiopathic Pulmonary Fibrosis
Authors: Moss Samuel , Minelli Cosetta , Leavy Olivia , Allen Richard , Oliver Nick , Wain Louise , Jenkins Gisli , Stewart Iain
Published: January 2024

Rationale

Idiopathic Pulmonary Fibrosis (IPF) is a disease of progressive lung scarring. There is a known association between IPF and diabetes mellitus (DM), but it is unclear whether this association is due to causal relationships between these traits.

Objectives

To examine causal relationships between DM, diabetes-associated traits, and IPF using a Mendelian randomisation approach.

Methods

Following a two-sample Mendelian randomisation (MR) approach, we used genetic variants identified from genome wide association studies (GWAS) for type 1 diabetes (T1D), type 2 diabetes (T2D), glycated haemoglobin level (HbA1c), fasting insulin level, and body mass index (BMI) to assess for evidence of causal effects of these traits on IPF risk. Further analyses using pleiotropy-robust and multivariable MR methods were performed to account for the inherent complexity of the traits being investigated.

Results

Results did not suggest that either T1D (OR = 1.00, 95% CI: 0.93-1.07, p = 0.902) or T2D (OR = 1.02, 95% CI: 0.93-1.11, p = 0.692) are in the causal pathway of IPF. No significant effects were suggested of HbA1c (OR = 1.19, 95% CI: 0.63-2.22, p = 0.592) or fasting insulin level (OR = 0.60, 95% CI: 0.31-1.15, p = 0.124) on IPF risk, but effects of BMI on IPF risk were indicated (OR = 1.44, 95% CI: 1.12-1.85, p = 0.004).

Conclusion

This study suggests that DM and IPF are unlikely to be causally linked. This comorbid relationship may instead be driven by shared risk factors or treatment effects.

Key messages

What is already known on this topic:Idiopathic pulmonary fibrosis is associated with diabetes mellitus epidemiologically, but it is unclear if these traits are linked by causal effects.

What this study adds:Idiopathic pulmonary fibrosis and diabetes mellitus are unlikely to be causally linked, suggesting that shared environmental risk factors or treatment effects may drive this comorbid relationship.

How this study might affect research, practice, or policy:Further research investigating the relationship between diabetes mellitus and idiopathic pulmonary fibrosis should focus on potential shared risk factors such as smoking, and treatment effects including corticosteroid use.
Automated Classification of At-home SARS-CoV-2 Lateral Flow Assay Test Results using Image Matching and Transfer Learning: multiple-pipeline study
Authors: Safarzadeh Meysam , Herbert Carly , Wong Steven Koon , Stamegna Pamela , Guilarte-Walker Yurima , Wright Colton , Suvarna Thejas , Nowak Chris , Kheterpal Vik , Pandey Shishir , Wang Biqi , Lin Honghuang , O’Connor Laurel , Hafer Nathaniel , Luzuriaga Katherine , Manabe Yuka , Broach John , Zai Adrian H , McManus David D , Du Xian , Soni Apurv
Published: January 2024

Introduction

Rapid antigen testing for SARS-CoV-2 is an important tool for the timely diagnosis of COVID-19, especially in at-home settings. However, the interpretation of test results can be subjective and prone to error. We describe an automated image analysis pipeline to accurately classify test types and results without human intervention using a dataset of 51,274 rapid antigen test images across three distinct test card brands.

Methods

The proposed method classifies participant-submitted images into four categories: positive for SARS-CoV-2, negative for SARS-CoV-2, invalid/uncertain, and unclassifiable. The model includes four stages: test card classification and region of interest detection using image-matching algorithms, elimination of invalid results using a developed Siamese neural network, and test result classification using transfer learning.

Results

The model accuracy was very good for test-card classification (100%), region of interest detection (83.5%), and identification of invalid results ranging from 95.6% to 100% for different test types. Performance of the model for test result classification varied by tests; the model’s sensitivity, specificity, and precision for Abbott BinaxNOW™ was 0.761, 0.989, and 0.946, BD Veritor™ At-Home COVID-19 Test was 0.955, 0.993, and 0.877, and for QuickVue® At-Home OTC COVID-19 Test was 0.816, 0.988, and 0.930.

Conclusion

The proposed method improved the interpretation of rapid antigen tests, particularly in invalid result detection compared to human-read, and offers a great opportunity for standardization of rapid antigen test interpretation and for providing feedback to participants with invalid tests.
Endometriosis risk is associated with shorter anogenital distance by meta-analysis
Authors: Crespi Bernard J.
Published: January 2024

Background

Anogenital distance is a well-validated marker of prenatal testosterone, with shorter distances indicating lower levels during early gestation. A suite of studies has linked anogenital distance with risk of endometriosis, but the findings are variable, leading to uncertainty in interpretation. The relationship of anogenital distance with endometriosis is especially important because lower testosterone has been associated with endometriosis in recent Mendelian Randomization studies, which implies causality in the association, with direct implications for future research and treatment.

Methods

A systematic review and meta-analysis was conducted on the association of endometriosis with anogenital distance. Three databases were queried in the identification phase, and a random-effects meta-analysis was applied to the data in studies that met the inclusion criteria.

Results

Shorter anogenital distance AF, measured from the anus to the posterior fourchette, was significantly associated with higher risk of endometriosis in the meta-analysis. By contrast, there was no such association for anogenital distance AC, measured from the anus to the clitoral surface. Both analyses demonstrated significant heterogeneity across studies. Too few studies were available for robust investigation of publication bias.

Conclusions

The association of short anogenital distance with endometriosis risk provides support for the hypothesis that endometriosis represents, in part, a disorder mediated by relatively low testosterone levels in early prenatal development. This conclusions has notable implications for understanding the causes and treatment of endometriosis.
Educational interventions delivered to prescribing advisers to influence primary care prescribing: a very low-cost pragmatic randomised trial using routine data from OpenPrescribing.net
Authors: Curtis Helen J , MacKenna Brian , Reddy Bhavana , Walker Alex J , Bacon Sebastian , Perera Rafael , Goldacre Ben
Published: January 2024

Background

NHS England issued commissioning guidance on 18 low-priority treatments which should not be routinely prescribed in primary care. We aimed to monitor the impact of an educational intervention delivered to regional prescribing advisors by senior pharmacists from NHS England on the primary care spend on low-priority items.

Methods

An opportunistic randomised, controlled parallel-group trial. Participants (clinical commissioning groups, CCGs) were randomised to intervention or control in a 1:1 ratio. The intervention group were invited to participate. The intervention was a one-off educational session. Our primary outcomes concerned the total prescribing of low-priority items in primary care. Secondary outcomes concerned the prescribing of specific low-priority items. We also measured the impact on information-seeking behaviour.

Results

40 CCGs were randomised, 20 allocated to intervention, with 11 receiving the intervention. There was no significant impact on any prescribing outcomes. There was some possible evidence of increased engagement with data, in the form of CCG email alert sign-ups (p=0.077). No harms were detected.

Conclusions

A one-off intervention delivered to CCGs by NHS England did not significantly influence low-priority prescribing. This trial demonstrates how routine interventions planned to improve uptake or adherence to healthcare guidance can be delivered as low-cost randomised trials and how to robustly assess their effectiveness.
Applying the Theoretical Domains Framework to the Implementation of Medicaid Coverage for Doula Services: Doulas’ Perceptions of Barriers and Facilitators in the State of Florida
Authors: Applequist Janelle , Wilson Roneé , Perkins Megan , Evans Victoria , Daniel Angela , Rookwood Averjill , Simmons Elizabeth , Louis-Jacques Adetola F.
Published: January 2024

As of September 2023, more than half of US states have either expanded Medicaid to cover doula care or are in the process of implementing doula care into Medicaid services. However, little is known about doulas’ experiences with Medicaid. Doula uptake of these services is critical to support low-income clients. We explored Florida doulas’ experiences with and perceptions of Medicaid reimbursement. We conducted seven focus groups and seven in-depth interviews with 31 doulas providing perinatal support. An inductive approach to thematic analysis was used to generate primary findings. A deductive approach was then applied to these themes, drawing on the Theoretical Domains Framework to enhance understanding. Most participants reported wanting to engage with Medicaid to support marginalized communities, but not doing so due to misinformation, low reimbursement rates and a complicated reimbursement structure. Doulas that work with Medicaid patients reflected on their frustrations with insurers and the financial impact of delayed reimbursements. Misinformation spread amongst doula communities about the Medicaid reimbursement process (often based on outdated information) was found to be a significant barrier to implementation. Doulas relied on one another for information, as they reported few resources have been made available by Medicaid or managed care organizations for guidance on reimbursement processes. This highlights an opportunity for Medicaid education to ensure client access to doula services and maintenance of the doula workforce. Doula care is associated with better perinatal outcomes, but structural barriers hinder the ability for low-income families to receive doula care in Florida, creating further health inequities.
Glymphatic flow resistance in humans measured by multifrequency impedance dispersion
Authors: Dagum Paul , Giovangrandi Laurent , Levendovszky Swati Rane , Winebaum Jake J. , Singh Tarandeep , Cho Yeilim , Kaplan Robert M. , Jaffee Michael S. , Lim Miranda M. , Vandeweerd Carla , Iliff Jeffrey J.
Published: January 2024

Glymphatic function in animal models supports the clearance of brain proteins whose mis-aggregation is implicated in neurodegenerative conditions including Alzheimer’s and Parkinson’s disease. The measurement of glymphatic function in the human brain has been elusive, limiting its potential in translational research. Here we described a non-invasive multimodal device for the first-in-human continuous measurement of sleep-active glymphatic flow resistance using repeated electrical impedance spectroscopy measurements through two separate clinical validation studies. Device measurements successfully (i) paralleled sleep-associated changes in extracellular volume that regulate glymphatic function, (ii) replicated preclinical findings showing glymphatic function is increased with increasing sleep EEG delta power, and is decreased with increasing sleep EEG beta power and heart rate, and (iii) predicted glymphatic solute exchange measured by contrast-enhanced MRI. The present investigational device permits the continuous and time-resolved assessment of glymphatic flow resistance in naturalistic settings necessary to determine the contribution of glymphatic impairment to risk and progression of Alzheimer’s disease, and to enable target-engagement studies that modulate glymphatic function in humans.
Evaluating and Improving the Performance and Racial Fairness of Algorithms for GFR Estimation
Authors: Zhang Linying , Richter Lauren R. , Kim Tevin , Hripcsak George
Published: January 2024

Data-driven clinical prediction algorithms are used widely by clinicians. Understanding what factors can impact the performance and fairness of data-driven algorithms is an important step towards achieving equitable healthcare. To investigate the impact of modeling choices on the algorithmic performance and fairness, we make use of a case study to build a prediction algorithm for estimating glomerular filtration rate (GFR) based on the patient’s electronic health record (EHR). We compare three distinct approaches for estimating GFR: CKD-EPI equations, epidemiological models, and EHR-based models. For epidemiological models and EHR-based models, four machine learning models of varying computational complexity (i.e., linear regression, support vector machine, random forest regression, and neural network) were compared. Performance metrics included root mean squared error (RMSE), median difference, and the proportion of GFR estimates within 30% of the measured GFR value (P30). Differential performance between non-African American and African American group was used to assess algorithmic fairness with respect to race. Our study showed that the variable race had a negligible effect on error, accuracy, and differential performance. Furthermore, including more relevant clinical features (e.g., common comorbidities of chronic kidney disease) and using more complex machine learning models, namely random forest regression, significantly lowered the estimation error of GFR. However, the difference in performance between African American and non-African American patients did not decrease, where the estimation error for African American patients remained consistently higher than non-African American patients, indicating that more objective patient characteristics should be discovered and included to improve algorithm performance.
A susceptibility gene signature for ERBB2-driven mammary tumor development and metastasis in Collaborative Cross mice with human translational value
Authors: Yang Hui , Wang Xinzhi , Blanco-Gómez Adrián , He Li , García-Sancha Natalia , Corchado-Cobos Roberto , Pérez-Baena Manuel Jesús , Jiménez-Navas Alejandro , Wang Pin , Inman Jamie L , Snijders Antoine M , Threadgill David W , Balmain Allan , Chang Hang , Perez-Losada Jesus , Mao Jian-Hua
Published: January 2024

Background

Deeper insights into ERBB2-driven cancers are essential to develop novel treatment avenues for ERBB2+ breast cancers (BCs). We employed Collaborative Cross (CC) mouse model, along with human translational evaluation, to unearth genetic factors underpinning Erbb2-driven mammary tumor development and metastasis.

Methods

732 F1 hybrid female mice between FVB/N MMTV-Erbb2and 30 CC strains were monitored for mammary tumor phenotypes. GWAS pinpointed SNPs that influence various tumor phenotypes. Clinical value of a mouse tumor susceptibility gene signature (mTSGS) was evaluated using public datasets, encompassing TCGA, METABRIC and I-SPY2 cohorts. The predictive power of mTSGS for response to chemotherapy was validatedin vivousing genetically diverse MMTV-Erbb2mice.

Results

Distinct variances in tumor onset, multiplicity, and metastatic patterns were observed across CC strains. Besides lung metastasis, liver and kidney metastases emerged in specific CC strains. GWAS identified 1525 SNPs, 800 SNPs, 568 SNPs, and 23 SNPs significantly associated with tumor onset, multiplicity, lung metastasis, and liver metastasis, respectively. Multivariate analyses flagged SNPs in 20 genes independently tied to various tumor characteristics, designated as mTSGS. These 20 genes were transcriptionally altered in human BCs. We then established mTSGS scores (mTSGSS) based on their transcriptional levels. The mTSGSS showed prognostic values, superseding clinical factors and PAM50 molecular subtype across cohorts. Moreover, mTSGSS predicted pathological complete response (pCR) to six of thirteen treatment regimens, including chemotherapy only, in I-SPY2 study. Importantly, the predictive value of the mTSGSS for pCR stood independent of the MammaPrint score. The power of mTSGSS for predicting chemotherapy response was validated in anin vivoMMTV-Erbb2 model, showing that like findings in human patients, mouse tumors with low mTSGSS were most likely to respond to treatment.

Conclusion

Our investigation has unveiled many novel genes predisposing individuals to ERBB2-driven cancer. Translational findings indicate that mTSGSS holds promise as a biomarker to refine treatment strategies for BC patients.
The Metabolic Role of MAP3K15: Genetic and Phenotypic Insights from the 23andMe Research Database and Genetics-Driven Recruitment
Authors: Brady Jennifer J. , Kalkus Kira , Nguyen Dominique T. , Wen Jingran , Fuller Zachary L. , Qi Yue , Deering Shaeloren S. , Selcer Leah , Shringarpure Suyash S. ,   The 23andMe Research Team, Holmes Michael V. , Wang Xin
Published: January 2024

MAP3K15 has been previously associated with protection from type 2 diabetes (T2D), prompting interest in the development of MAP3K15 inhibitors as a potential therapeutic option for diabetes. The trans-ancestry genome-wide association study (GWAS) meta-analysis and loss-of-function (LoF) burden testing methods that implicate association with T2D greatly benefit from large sample size. The direct-to-consumer genetic testing company, 23andMe, Inc., is the world’s largest research consented genetic database. We leveraged the 23andMe database to further inform the metabolic role of MAP3K15, using a variety of genetic analysis methods. We find that MAP3K15 LoF carriers show a significant delay of 4.5 years in the median age of T2D diagnosis among individuals at high polygenic risk and uncover a novel burden association of MAP3K15 LoF with protection against high cholesterol. We expanded these findings by establishing a capability to recruit consented participants on the basis of genetics unknown to them (specifically, a single LoF variant in MAP3K15, rs148312150), and obtained clinical laboratory evidence of a modest reduction in median cholesterol and LDL/HDL ratio in MAP3K15 LoF carriers. Our findings demonstrate the discovery power of the 23andMe database, including the feasibility of consented participant recruitment to inform therapeutic discovery and development.
Chronicling menstrual cycle patterns across the reproductive lifespan with real world data
Authors: Cunningham Adam C. , Pal Lubna , Wickham Aidan P. , Prentice Carley , Goddard Frederick G. B. , Klepchukova Anna , Zhaunova Liudmila
Published: January 2024

Background

The intricate hormonal and physiological changes of the menstrual cycle can influence health on a daily basis. Although prior studies have helped improve our understanding of the menstrual cycle, they often lack diversity in populations included, sample size, and the span of reproductive and life stages. This paper aims to describe the dynamic differences in menstrual cycle characteristics and associated symptoms by age in a large global cohort of period tracking application users. This work aims to contribute to our knowledge and understanding of female physiology at varying stages of reproductive aging.

Methods

This cohort study included self-reported menstrual cycle and symptom information in a sample of Flo application users aged 18-55. Cycle and period length and their variability, and frequency of menstrual cycle symptom logs are described by age of user.

Results

Based on data logged by over 19 million global users of the Flo app, the length of the menstrual cycle and period show clear age associated patterns. With higher age, cycles tend to get shorter (Cycle length: D̄ = 1.85 days, Cohen’s D= 0.59) and more variable (Cycle length SD: D̄ = 0.42 days, Cohen’s D= 0.09), until close to the chronological age (40-44) suggesting menopausal transition, when both cycles and periods become longer (Cycle length: D̄ = 0.86 days, t=48.85, Cohen’s D=0.26; Period length: D̄ =0.08, t=15.6, Cohen’s D=0.07) and more variable (Cycle length SD: D̄ =2.80 days, t=111.43, d=0.51; Period length SD: D̄ =0.23 days, t=67.81, Cohen’s D=0.31). The proportion of individuals with irregular cycles was highest in participants aged 51-55 (44.7%), and lowest in the 36-40 age group (28.3%). The spectrum of common menstrual cycle related symptoms also varies with age. Frequency of logging of cramps and acne is lower in older participants, while logs of headache, backache, stress and insomnia are higher in older users. Other symptoms show different patterns, such as breast tenderness and fatigue peaking between the ages of 20-40, or mood swings being most frequently logged in the youngest and oldest users.

Conclusion

The menstrual cycle, and related symptoms are not static throughout the lifespan. Understanding these age related differences in cycle characteristics and symptoms is important in understanding how best to care for and improve daily experience for menstruators across the reproductive life span.
Patient experiences of UK primary care online triage and consultation platforms during COVID-19: A systematic review
Authors: Roberts Christopher , George Jomin , Jenkins Judy
Published: January 2024

Background

Online triage and consultation platforms are being increasingly used by healthcare providers in the UK for patient/clinician interactions. COVID-19 accelerated the shift towards the use of these platforms to maintain healthcare provision and reduce transmission. Strict directives were introduced by the UK Government to avoid in-person contact wherever possible in March 2020.

Aim

To examine patients’ experiences of online triage and consultation in UK primary care during the COVID-19 pandemic and offer considerations for their continued use.

Design

This study follows the PRISMA framework and includes qualitative studies conducted in UK primary care based on the experiences of patient users of any such online platform during the period of March 2020 to April 2023. Studies were included using the PICO format. Three literature databases were searched for relevant studies: PubMed, Science Direct and EMBASE. CASP is used to assess data quality.

Results

540 studies were reviewed and reduced to 12 studies that met the inclusion criteria. Study characteristics were identified as: year of study, study population, disease types/conditions, patient response themes and the study’s data capture method. A thematic inductive approach identifies three overarching themes (Accessibility, Care delivery, System functionality) and 10 sub-themes (Affordability, IT literacy, Communication, Convenience, Care quality, Patient safety/privacy, Usability, Continuity of care, Inequality and Media influence).

Conclusion

This review highlights aspects of patient satisfaction and benefit but also those most concerning for patients. This study reviews the rapid, compulsory adoption of these systems during COVID-19 with implications for their future implementation beyond the pandemic.
Towards patient-relevant, trial-ready digital motor outcomes for SPG7: a cross-sectional prospective multi-center study (PROSPAX)
Authors: Beichert Lukas , Seemann Jens , Kessler Christoph , Traschütz Andreas , Müller Doreen , Dillmann-Jehn Katrin , Ricca Ivana , Satolli Sara , Nazli Başak Ayşe , Coarelli Giulia , Timmann Dagmar , Gagnon Cynthia , van de Warrenburg Bart P. ,   PROSPAX consortium, Ilg Winfried , Synofzik Matthis , Schüle Rebecca
Published: January 2024

Background and Objectives

With targeted treatment trials on the horizon, identification of sensitive and valid outcome measures becomes a priority for the >100 spastic ataxias. Digital-motor measures, assessed by wearable sensors, are prime outcome candidates for SPG7 and other spastic ataxias. We here aimed to identify candidate digital-motor outcomes for SPG7 – as one of the most common spastic ataxias – that: (i) reflect patient-relevant health aspects, even in mild, trial-relevant disease stages; (ii) are suitable for a multi-center setting; and (iii) assess mobility also during uninstructed walking simulating real-life.

Methods

Cross-sectional multi-center study (7 centers, 6 countries). Unaided walking was assessed in 65 patients with SPG7 and 50 unrelated healthy controls using 3 wearable sensors (Opal APDM). Digital gait measures were correlated to measures of disease severity (SARA, SPRS; including mobility-relevant subscores SPRS1315291292025, SARAPG) and activities of daily living (FARS-ADL). The task set included lab-based defined gait tasks, complemented by uninstructed ‘supervised free walking’.

Results

Among 30 hypothesis-based gait measures, 18 demonstrated at least moderate effect size (Cliff’s δ>0.5) in discriminating SPG7 patients from controls, and 17 even in mild disease stages (SPRSmobility≤9). Spatiotemporal variability measures such as the spatial variability composite measure SPcmp (ρ=0.67, p=<0.0001), Stride Time CV (ρ=0.67, p=<0.0001) and Swing CV (ρ=0.64, p=<0.0001) showed the highest correlations with clinician-reported mobility scores (SPRSmobility), and overall disease severity (SPRS, SARA). Overall, top-ranked measures also correlated with patient-relevant functional deficits in everyday life activities (FARS-ADL). In mild disease stages (SPRSmobility≤9, n=41), Swing CV (ρ=0.53, p=<0.0001) and SPcmp (ρ=0.50, p=<0.0001) correlated with SPRSmobility. In the uninstructed ‘supervised free walking’ task, the correlations between spatiotemporal variability measures (Stride Time CV, Stride Length CV, Swing CV) and SPRSmobilitycould be confirmed; additionally, Gait Speed (ρ=-0.59, p=<0.0001) was highly correlated with SPRSmobility.

Discussion

We here identified trial-ready digital-motor candidate outcomes for the spastic ataxia SPG7, all characterized by proven multi-center applicability, ability to discriminate patients from controls, and correlation with measures of disease severity – even in mild disease stages –, and patient-relevant everyday function. If validated longitudinally, these sensor outcomes might inform future natural history and treatment trials in SPG7 and other spastic ataxias.
Development and Validation of an Intrinsic Capacity Score in the UK Biobank Study
Authors: Beyene Melkamu Bedimo , Visvanathan Renuka , Ahmed Muktar , Benyamin Beben , Beard John R. , Amare Azmeraw T.
Published: January 2024

Background

In 2015, the World Health Organization introduced the concept of intrinsic capacity (IC) to define the individual-level characteristics that enable an older person to be and do the things they value. This study developed an IC score for UK Biobank (UKB) study participants and validated its use as a tool for health outcome prediction, understanding healthy aging trajectories, and genetic research.

Methods

Our analysis included data from 45,208 UKB participants who had a complete record of the ten variables included in the analysis. Factor adequacy was tested using Kaiser–Meyer– Olkin (KMO), Barthelt’s, and the determinant of matrix tests, and the number of factors was determined by the parallel analysis method. Exploratory and confirmatory factor analyses were employed to determine the structure and dimensionality of indicators. Finally, the IC score was generated, and its construct and predictive validities as well as reliability were assessed.

Results

The factor analysis identified a multidimensional construct comprising, one general factor (IC) and five specific factors (locomotor, vitality, cognitive, psychological, and sensory). The bifactor structure showed a better fit (comparative fit index = 0.995, Tucker Lewis index = 0.976, root mean square error of approximation = 0.025, root mean square residual = 0.009) than the conventional five-factor structure. The IC score, generated using the bifactor confirmatory factor analysis has good construct validity, as demonstrated by an inverse association with age (lower IC in older age; beta = -0.035 (95%CI: -0.036, -0.034)), frailty (lower IC score in prefrail, beta = -0.104 (95%CI: (-0.114, -0.094) and frail, beta = -0.227 (95%CI: -0.267, -0.186) than the robust), and Charlson’s comorbidity index (CCI) for incident cases (a lower IC score associated with increased CCI, beta, = -0.019 (95%CI: -0.022, -0.015). The IC score also predicted incident CCI (a one-unit increase in baseline IC score led to lower CCI, beta = 0.147 (95%CI: -0.173, - 0.121)).

Conclusion

The bifactor structure showed a better fit in all goodness of fit tests. The IC construct has strong structural, construct, and predictive validities and it is a promising tool for monitoring aging trajectories.

Highlights

Large biobank studies should be leveraged with intrinsic capacity scores developed.

Factor analysis confirmed IC as one general factor and five specific factors.

Better goodness of fit observed with the bifactor model versus conventional structure.

The bifactor model IC score has a good construct and predictive validity.

The IC score can be used as a single reliable measure of IC.
Human coronavirus HKU1 recognition of the TMPRSS2 host receptor
Authors: McCallum Matthew , Park Young-Jun , Stewart Cameron , Sprouse Kaitlin R. , Brown Jack , Tortorici M. Alejandra , Gibson Cecily , Wong Emily , Ieven Margareta , Telenti Amalio , Veesler David
Published: January 2024

The human coronavirus HKU1 spike (S) glycoprotein engages host cell surface sialoglycans and transmembrane protease serine 2 (TMPRSS2) to initiate infection. The molecular basis of HKU1 binding to TMPRSS2 and determinants of host receptor tropism remain elusive. Here, we designed an active human TMPRSS2 construct enabling high-yield recombinant production in human cells of this key therapeutic target. We determined a cryo-electron microscopy structure of the HKU1 RBD bound to human TMPRSS2 providing a blueprint of the interactions supporting viral entry and explaining the specificity for TMPRSS2 among human type 2 transmembrane serine proteases. We found that human, rat, hamster and camel TMPRSS2 promote HKU1 S-mediated entry into cells and identified key residues governing host receptor usage. Our data show that serum antibodies targeting the HKU1 RBD TMPRSS2 binding-site are key for neutralization and that HKU1 uses conformational masking and glycan shielding to balance immune evasion and receptor engagement.
Mathematical modeling of the influence ofACE I/Dpolymorphism on blood pressure and antihypertensive therapy
Authors: Kutumova Elena , Kovaleva Anna , Sharipov Ruslan , Lifshits Galina , Kolpakov Fedor
Published: January 2024

The angiotensin converting enzyme (ACE) gene (ACE) insertion/deletion (I/D) polymorphism has attracted much attention in recent years, as it raises the hope of personalizing ACE inhibitor therapy to optimize its efficiency and reduce side effects for genetically distinct subgroups. However, the extent of its influence among these subgroups remains inconclusive. Therefore, we extended our computational model of blood pressure regulation to investigate the effect of theACE I/Dpolymorphism on hemodynamic parameters in humans and antihypertensive therapy. The model showed that the dependence of blood pressure on serum ACE activity is a function of saturation. Hence, a possible reason for the lack of association betweenACE I/Dand blood pressure levels could be a fairly high ACE activity in populations. Additionally, in an extended model simulating the effects of different classes of antihypertensive drugs, we explored the relationship betweenACE I/Dand the efficacy of inhibitors of the renin-angiotensin-aldosterone system. The model predicted that the response of cardiovascular and renal parameters to treatment directly depends on ACE activity. However, significant differences in parameter changes were observed only between groups with high and low ACE levels, whileACE I/Dgenotypes within the same group had similar changes in absolute values. We conclude that a single genetic variant is responsible for only a small fraction of heredity in treatment success, so its predictive value is limited.
A mutation in the low-complexity domain of splicing factor hnRNPA1 linked to amyotrophic lateral sclerosis disrupts distinct neuronal RNA splicing networks
Authors: Lee Yeon J. , Rio Donald C.
Published: January 2024

Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disease characterized by loss of motor neurons. Human genetic studies have linked mutations in RNA-binding proteins as causative for this disease. The hnRNPA1 protein, a known pre-mRNA splicing factor, is mutated in some ALS patients. Here, two human cell models were generated to investigate how a mutation in the C-terminal low-complexity domain (LCD) of hnRNPA1 can cause splicing changes of thousands of transcripts that collectively are linked to the DNA damage response, cilium organization, and translation. We show that the hnRNPA1 D262V mutant protein binds to new binding sites on differentially spliced transcripts from genes that are linked to ALS. We demonstrate that this ALS-linked hnRNPA1 mutation alters normal RNA-dependent protein–protein interactions. Furthermore, cells expressing this hnRNPA1 mutant exhibit a cell aggregation phenotype, markedly reduced growth rates, changes in stress granule kinetics, and aberrant growth of neuronal processes. This study provides insight into how a single amino acid mutation in a splicing factor can alter RNA splicing networks of genes linked to ALS.
Momentum spectrum of Schwinger pair production in four-dimensional e-dipole fields
Authors: Degli Esposti Gianluca , Torgrimsson Greger
Published: January 2024

We calculate the momentum spectrum of electron-positron pairs created via the Schwinger mechanism by a class of four-dimensional electromagnetic fields called e-dipole fields. To the best of our knowledge, this is the first time the momentum spectrum has been calculated for 4D, exact solutions to Maxwell’s equations. Moreover, these solutions give fields that are optimally focused, and are hence particularly relevant for future experiments. To achieve this we have developed a worldline instanton formalism where we separate the process into a formation and an acceleration region.

Published by the American Physical Society
2024
Feature-rich electronic properties of three-dimensional ternary compound: Li7P3S11
Authors: Liu Hsin-Yi , Wu Jhao-Ying
Published: January 2024

Purpose

The theoretical findings serve as a foundation for further research into understanding sulfide-based solid-state electrolytes, ultimately advancing the progress of all-solid-state batteries.

Design/methodology/approach

The electronic properties of Li7P3S11 are thoroughly explored through first-principles calculations.

Findings

This investigation encompasses the intricate atom-dominated valence and conduction bands, spatial charge density distribution and the breakdown of atom and orbital contributions to van Hove singularities. Additionally, the compound’s wide and discrete energy spectra reflect the substantial variations in bond lengths and its highly anisotropic geometric structure. The complex and nonuniform chemical environment indicates the presence of intricate hopping integrals.

Originality/value

This study provides valuable insights into the critical multiorbital hybridizations occurring in the Li-S and P-S chemical bonds. To validate the theoretical predictions, experimental techniques can be employed. By combining theoretical predictions with experimental data, a comprehensive understanding of the geometric and electronic characteristics of Li7P3S11 can be achieved.
Preparation of polysulfone/sulfonated polysulfone-SiO2 nanofiltration membrane and its performance characterization
Authors: Chen Liangbin , Zhao Lihong , Ding Keren , Xu Kaibo , Tang Xianzhe
Published: January 2024

Purpose

This study aims to optimize the preparation conditions and modify the nanofiltration (NF) membranes to prepare high-performance polysulfone/sulfonated polysulfone composite nanofiltration (PSF/SPSF-NF) membranes through interfacial polymerization.

Design/methodology/approach

Investigating the impacts of anhydrous piperazine (PIP) concentration, trimesoyl chloride (TMC) concentration and basement membrane type on NF membrane performance, the optimal membrane was prepared. In addition, nano-SiO2 was added to the active separation layer to modify the NF membranes.

Findings

The comprehensive performance of PSF/SPSF-NF membranes was optimized when the concentration of PIP was 0.75 Wt.% and the concentration of TMC was 0.15 Wt.%, at which time the water flux was 66.1 L·m−2·h−1 and the retention rate of Na2SO4 was 98.1%. The comprehensive performance of polysulfone/sulfonated polysulfone-SiO2 nanofiltration (PSF/SPSF-SiO2-NF) membranes was optimized when the blending ratio of nano-SiO2 to PIP was 2:3, with a pure water flux of 81.9 L·m−2·h−1 and a Na2SO4 retention rate of 95.9%. Compared to polysulfone nanofiltration (PSF-NF) membranes and PSF/SPSF-NF membranes, NF membranes with nano-SiO2 increased the flux recovery rate by 22.9% and 8.7%.

Practical implications

PSF/SPSF-SiO2-NF membrane exhibits excellent antifouling properties.

Originality/value

There is currently no literature available on the preparation of NF membranes using polysulfone/sulfonated polysulfone (PSF/SPFS) as a substrate. This provides a method for modifying NF membranes, starting with the modification of the basement membrane and then modifying the active separation layer.
Landscape and domains of possible future threats from a societal point of view
Authors: Tähtinen Lassi , Toivonen Saija , Rashidfarokhi Anahita
Published: January 2024

We are currently amid multiple interconnected and complex crises within the different dimensions of our society—a polycrisis, and the future promises even greater complexity in terms of threats. However, the existing crisis typologies and crisis identification often have an introspective organisational focus and tend to concentrate on a limited set of historically known threats. This study takes an exploratory, futures studies‐based approach with a broader societal perspective. Through environmental scanning using 1714 literature sources and consultations with 54 experts, we have identified 153 potential future crises spanning various societal domains. We utilize the PESTLE framework to outline the possible emergence of these crises. Our findings reveal a considerably larger number of potential crisis phenomena than previously proposed, aiming for objective sensemaking of the complex crisis landscape. The results also demonstrate crises vary in their temporal development, albeit evaluating this is challenging. This study challenges the prevalent myopic and subjective prioritisation‐based crisis identification and provides a comprehensive yet comprehensible list of possible future crises. In the current context of siloed decision‐making structures, both public and private organisations can use this list to enhance their future‐oriented preparedness and assess their responsibilities in managing these crises, as well as identifying necessary stakeholders.
Influence of the cash conversion cycle on firm's financial performance: Evidence from publicly traded firms in the Latin American context
Authors: Figlioli Bruno , Antônio Rafael Moreira , Gatsios Rafael Confetti , Lima Fabiano Guasti
Published: January 2024

This study investigates the relationship between the cash conversion cycle (CCC) and the financial and market performances of publicly traded” firms in six Latin American (LatAm) countries: Argentina, Brazil, Chile, Colombia, Mexico, and Peru. The analysis covers the period from 2000 to 2018. The results indicate that increases in CCC negatively impact the generation of operating cash flows and long‐term investments, and increase financial risk. Other findings suggest that the mechanisms through which CCC affects a firm's financial performance can provide a satisfactory explanation of its market performance. The evidence is consistent with the hypothesis that CCC is a relevant driver of value in working capital management in undeveloped or emerging economies.
Inequalities in dental caries among Indigenous and non‐Indigenous children in Australia: A literature review
Authors: Wang X , Ghanbarzadegan A , Sohn W , Taylor E , Gao J , Christian B
Published: January 2024

Dental caries constitutes one of the most ubiquitous diseases in Australia, with Indigenous children presenting a notably higher prevalence than their non‐Indigenous peers. This literature review aims to update the knowledge base developed by Christian and Blinkhorn in 2012, with a particular focus on the contemporary disparities in dental caries between Indigenous and non‐Indigenous children. Our research strategy involved a thorough exploration of the Medline, PubMed, and Scopus databases to identify pertinent studies published between 2009 and 2022. Supplementary resources included various government websites and citation searches. We prioritised studies that focused on children aged 5–6 or 12 years—reflecting the World Health Organization's index ages for oral health—and that reported dental caries prevalence and experience indicators. Our review methodology was guided by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) statement. The updated search, spanning 2009 to 2023, retrieved studies that reported caries estimates exclusively from 2009 to 2014. Within this period, the prevalence of dental caries in Indigenous children's primary teeth ranged between 52% and 77%, while the prevalence in permanent teeth varied from 36% to 60%. This updated review indicated that Indigenous children continue to experience caries at an approximately twice higher rate than non‐Indigenous children, sustaining the persisting disparity in caries estimates. The findings from this review show that no discernible improvement in dental caries rates among Australian Indigenous children has been observed in comparison to the previous review; and that Indigenous children continue to experience both higher prevalence and severity of dental caries compared to non‐Indigenous children.
‘My pet can't come with me’: Pets as a barrier against moving into supported accommodation
Authors: Collier Janette , Lewis Virginia Jane , Bennett Pauleen
Published: January 2024

Objective

To determine the impact of pet ownership on older people's decision to move to supported accommodation.

Methods

Online survey.

Results

Older Australians who were current or past pet owners were invited to complete an online survey, with 193 participants providing valid data. Almost two‐thirds of the respondents who said they did not intend to move in the foreseeable future (n = 85) said their pet was an important reason. When asked to rate which factors would be hardest to come to terms with if they had to move because they needed more assistance in future, three groups emerged: the first group (37%) thought the impact on their pet of moving would not be difficult and the pet was not an important reason for staying in their current home. The second group (36%) were the opposite; they believed there would be a negative impact on their pet if they moved and the pet was an important reason for them to stay. The final group (27%) thought their pet was not an important reason to stay in their current location but if they did have to move, the impact on the pet would be quite difficult. No one fell into the category of identifying that their pet was an important reason to stay but having to move would have no impact on the animal.

Conclusions

Many older people think about their pets when making a decision to move house, including considering whether a move to supported accommodation will be difficult for their pet. A perceived absence of pet‐friendly supported accommodation may be contributing to sub‐optimal decision‐making by older people.
The prognostic validity of delirium severity as measured by Delirium Observation Screening Scale (DOS scale) on adverse outcomes
Authors: Gray Elyshia Ann , Ranasinghe Champa , Lin Hui‐Shan
Published: January 2024

Objective

To investigate whether an assessment of delirium severity at diagnosis using the Delirium Observation Screening Scale (DOS scale) predicts adverse outcomes in hospital and on discharge.

Methods

A prospective cohort study was conducted on a convenience sample of patients admitted to an acute geriatric ward with delirium over an eight‐month period. DOS scale was administered to the patients within 48 h of delirium diagnosis to measure delirium severity. Univariate logistic regression analysis was performed to evaluate the correlation between DOS scale and adverse outcomes.

Results

Fifty‐nine patients were included in the study. There was a moderate correlation between increasing DOS scores and duration of delirium (r = 0.46, p < 0.001), as well as increasing DOS scores and decline in mobility on discharge (r = 0.35, p = 0.007). There was a weak correlation between increasing DOS scores and functional decline as measured by change in Katz Index from admission to discharge (r = −0.27, p = 0.04). No statistically significant correlations were found between DOS scores and in‐hospital mortality, inpatient complication rates or discharge to higher level of care.

Conclusion

Delirium severity as measured by DOS scale may be useful in predicting delirium duration and decline in mobility and function on discharge. Further research with larger sample sizes is needed to establish if this finding can be replicated and whether delirium severity predicts additional adverse outcomes. Measuring delirium severity at diagnosis may be useful for communicating prognostic information to family members and setting expectations and treatment goals.