bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative comprehensive geriatric assessment and optimisation prior to elective arterial vascular surgery: a health economic analysis
Authors: Partridge Judith S L , Healey Andrew , Modarai Bijan , Harari Danielle , Martin Finbarr C , Dhesi Jugdeep K 
Published: April 2021

Abstract

Background
increasing numbers of older people are undergoing vascular surgery. Preoperative comprehensive geriatric assessment and optimisation (CGA) reduces postoperative complications and length of hospital stay. Establishing CGA-based perioperative services requires health economic evaluation prior to implementation. Through a modelling-based economic evaluation, using data from a single site clinical trial, this study evaluates whether CGA is a cost-effective alternative to standard preoperative assessment for older patients undergoing elective arterial surgery.

Methods
an economic evaluation, using decision-analytic modelling, comparing preoperative CGA and optimisation with standard preoperative care, was undertaken in older patients undergoing elective arterial surgery. The incremental net health benefit of CGA, expressed in terms of quality-adjusted life-years (QALYs), was used to evaluate cost-effectiveness.

Results
CGA is a cost-effective substitute for standard preoperative care in elective arterial surgery across a range of cost-effectiveness threshold values. An incremental net benefit of 0.58 QALYs at a cost-effectiveness threshold of £30k, 0.60 QALYs at a threshold of £20k and 0.63 QALYs at a threshold of £13k was observed. Mean total pre- and postoperative health care utilisation costs were estimated to be £1,165 lower for CGA patients largely accounted for by reduced postoperative bed day utilisation.

Conclusion
this study demonstrates a likely health economic benefit in addition to the previously described clinical benefit of employing CGA methodology in the preoperative setting in older patients undergoing arterial surgery. Further evaluation should examine whether CGA-based perioperative services can be effectively implemented and achieve the same clinical and health economic outcomes at scale.
Is Pathfinder a safe alternative to the emergency department for older patients? An observational analysis
Authors: Bernard Paul , Corcoran Grace , Kenna Lawrence , O’Brien Claire , Ward Peter , Howard William , Hogan Laura , Mooney Rebecca , Masterson Siobhan 
Published: April 2021

Abstract

Background
many patients brought to emergency departments (EDs) following an emergency medical services (EMS) call have non-urgent needs that could be treated elsewhere. Older people are particularly vulnerable to adverse events while attending the ED. Alternative care pathway models can reduce ED crowding and improve outcomes. Internationally, there is no consensus on which model is recommended.

Aim
the aim of this study is to investigate the impact of the Pathfinder model on ED conveyance rates and patient safety.

Methods
the Pathfinder service is a collaboration between the National Ambulance Service and Beaumont Hospital Occupational Therapy and Physiotherapy Departments. It is supported by the Government of Ireland’s Sláintecare Integration fund. This is a retrospective cohort study of the Pathfinder service over a 5-month period.

Results
one-hundred and seventy-eight patients were responded to by the Pathfinder ‘Rapid Response Team’. Average age was 79.6 years (standard deviation 7.6), median clinical frailty score was 6 (interquartile range: 5–6). Sixty-four percent remained at home following initial review. None re-presented to the ED within 24 hours, and 10% re-presented within 7 days. The majority (67%) of patients required follow-up by the Pathfinder ‘Follow-Up Team’ and/or another community-based service. Feedback demonstrates 99% patient satisfaction with the service.

Conclusion
the Pathfinder service is a safe alternative to ED conveyance for older people following an EMS call. It is the first model of this kind to be evaluated in Ireland. The overwhelmingly positive feedback confirms that older people want this service. This model could expand, with local adaptation, nationally and internationally.
Investigation of REFINED CNN ensemble learning for anti-cancer drug sensitivity prediction
Authors: Bazgir Omid , Ghosh Souparno , Pal Ranadip 
Published: April 2021

Abstract

Motivation
Anti-cancer drug sensitivity prediction using deep learning models for individual cell line is a significant challenge in personalized medicine. Recently developed REFINED (REpresentation of Features as Images with NEighborhood Dependencies) CNN (Convolutional Neural Network)-based models have shown promising results in improving drug sensitivity prediction. The primary idea behind REFINED-CNN is representing high dimensional vectors as compact images with spatial correlations that can benefit from CNN architectures. However, the mapping from a high dimensional vector to a compact 2D image depends on the a priori choice of the distance metric and projection scheme with limited empirical procedures guiding these choices.

Results
In this article, we consider an ensemble of REFINED-CNN built under different choices of distance metrics and/or projection schemes that can improve upon a single projection based REFINED-CNN model. Results, illustrated using NCI60 and NCI-ALMANAC databases, demonstrate that the ensemble approaches can provide significant improvement in prediction performance as compared to individual models. We also develop the theoretical framework for combining different distance metrics to arrive at a single 2D mapping. Results demonstrated that distance-averaged REFINED-CNN produced comparable performance as obtained from stacking REFINED-CNN ensemble but with significantly lower computational cost.

Availability and implementation
The source code, scripts, and data used in the paper have been deposited in GitHub (https://github.com/omidbazgirTTU/IntegratedREFINED).

Supplementary information
Supplementary data are available at Bioinformatics online.
Epigenetic transgenerational inheritance, gametogenesis and germline development†
Authors: Ben Maamar Millissia , Nilsson Eric E , Skinner Michael K 
Published: April 2021

AbstractOne of the most important developing cell types in any biological system is the gamete (sperm and egg). The transmission of phenotypes and optimally adapted physiology to subsequent generations is in large part controlled by gametogenesis. In contrast to genetics, the environment actively regulates epigenetics to impact the physiology and phenotype of cellular and biological systems. The integration of epigenetics and genetics is critical for all developmental biology systems at the cellular and organism level. The current review is focused on the role of epigenetics during gametogenesis for both the spermatogenesis system in the male and oogenesis system in the female. The developmental stages from the initial primordial germ cell through gametogenesis to the mature sperm and egg are presented. How environmental factors can influence the epigenetics of gametogenesis to impact the epigenetic transgenerational inheritance of phenotypic and physiological change in subsequent generations is reviewed.
You cannot ablate the Lernaean Hydra: SCN5A mutation in a patient with multifocal ectopic Purkinje-related premature contractions syndrome treated with Flecainide and an implant of a subcutaneous defibrillator—a case report
Authors: Leventopoulos Georgios , Perperis Angelos , Karelas Dimitrios , Almpanis Georgios 
Published: April 2021

Abstract

Background
SCN5A mutations may present with different clinical phenotypes such as Brugada syndrome, long QT3 syndrome, sick sinus syndrome, atrial fibrillation, dilated cardiomyopathy, and the least known multifocal ectopic Purkinje-related premature contractions syndrome.

Case summary
We report a case of a 29-year-old woman with palpitations due to multifocal premature ventricular complexes (PVCs) and a family history of sudden death. The previous electrophysiological study had shown that PVCs arose from Purkinje fibres but catheter ablation was unsuccessful. Cardiac magnetic resonance (CMR) imaging demonstrated non-ischaemic areas of subendocardial fibrosis at multiple left ventricular (LV) segments with concomitant dilatation and mild systolic impairment. Amiodarone suppressed the ectopy but caused hyperthyroidism. Due to recent pregnancy, she received no antiarrhythmics which resulted in PVC burden increase and further deterioration of the ejection fraction (EF). After gestation, amiodarone was reinitiated and switched to flecainide after implantation of a subcutaneous defibrillator as a safety net. At follow-up, LV function had almost normalized. Genetic analysis confirmed an SCN5A mutation.

Discussion
Multifocal ectopic Purkinje-related premature contractions syndrome is associated with SCN5A mutation which in our case (R222Q) is the most common described. Flecainide can be an appropriate treatment option when ablation is ineffective. Defibrillator—even a subcutaneous type—could be implanted in cases of LV dysfunction or scar. PVCs suppression by flecainide and restoration of EF implies an arrhythmia—induced mechanism of LV impairment.
The maintenance of polygenic sex determination depends on the dominance of fitness effects which are predictive of the role of sexual antagonism
Authors: Meisel Richard P 
Published: April 2021

Abstract
In species with polygenic sex determination (PSD), multiple male- and female-determining loci on different proto-sex chromosomes segregate as polymorphisms within populations. The extent to which these polymorphisms are at stable equilibria is not yet resolved. Previous work demonstrated that PSD is most likely to be maintained as a stable polymorphism when the proto-sex chromosomes have opposite (sexually antagonistic) fitness effects in males and females. However, these models usually consider PSD systems with only two proto-sex chromosomes, or they do not broadly consider the dominance of the alleles under selection. To address these shortcomings, I used forward population genetic simulations to identify selection pressures that can maintain PSD under different dominance scenarios in a system with more than two proto-sex chromosomes (modeled after the house fly). I found that overdominant fitness effects of male-determining proto-Y chromosomes are more likely to maintain PSD than dominant, recessive, or additive fitness effects. The overdominant fitness effects that maintain PSD tend to have proto-Y chromosomes with sexually antagonistic effects (male-beneficial and female-detrimental). In contrast, dominant fitness effects that maintain PSD tend to have sexually antagonistic multi-chromosomal genotypes, but the individual proto-sex chromosomes do not have sexually antagonistic effects. These results demonstrate that sexual antagonism can be an emergent property of the multi-chromosome genotype without individual sexually antagonistic chromosomes. My results further illustrate how the dominance of fitness effects has consequences for both the likelihood that PSD will be maintained as well as the role sexually antagonistic selection is expected to play in maintaining the polymorphism.
Association of Intensive Lifestyle and Metformin Interventions With Frailty in the Diabetes Prevention Program Outcomes Study
Authors: Hazuda Helen P , Pan Qing , Florez Hermes , Luchsinger José A , Crandall Jill P , Venditti Elizabeth M , Golden Sherita H , Kriska Andrea M , Bray George A 
Published: April 2021

Abstract

Background
Frailty is a geriatric syndrome of decreased physiologic reserve and resistance to stressors that results in increased vulnerability to adverse health outcomes with aging. Diabetes and hyperglycemia are established risk factors for frailty. We sought to examine whether the odds of frailty among individuals at high risk of diabetes randomized to treatment with intensive lifestyle (ILS), metformin, or placebo differed after long-term follow-up.

Method
The sample comprised participants in the Diabetes Prevention Program (DPP) clinical trial, who continued follow-up in the DPP Outcomes Study (DPPOS) and completed frailty assessments in DPPOS Years 8 (n = 2385) and 10 (n = 2289), approximately 12 and 14 years after DPP randomization. Frailty was classified using Fried Frailty Phenotype criteria. GEE models adjusting for visit year with repeated measures pooled for Years 8 and 10 were used to estimate pairwise odds ratios (ORs) between ILS, metformin, and placebo for the outcomes of frail and prefrail versus nonfrail.

Results
Frailty prevalence by treatment group was ILS = 3.0%, metformin = 5.4%, placebo = 5.7% at Year 8, and ILS = 3.6%, metformin = 5.3%, placebo = 5.4% at Year 10. Odds ratios (95% CI) estimated with GEE models were ILS versus placebo, 0.62 (0.42–0.93), p = .022; metformin versus placebo, 0.99 (0.69–1.42), p = .976; and ILS versus metformin, 0.63 (0.42–0.94), p = .022. Odds of being frail versus nonfrail were 37% lower for ILS compared to metformin and placebo.

Conclusions
Early ILS intervention, at an average age of about 50 years, in persons at high risk of diabetes may reduce frailty prevalence in later life. Metformin may be ineffective in reducing frailty prevalence.

Clinical Trials Registration Numbers
NCT00004992 (DPP) and NCT00038727 (DPPOS).
Neighborhood Characteristics and Inflammation Among Older Black Americans: The Moderating Effects of Hopelessness and Pessimism
Authors: Nguyen Ann W , Taylor Harry Owen , Lincoln Karen D , Qin Weidi , Hamler Tyrone , Wang Fei , Mitchell Uchechi A 
Published: April 2021

Abstract

Background
Research documents the adverse health effects of systemic inflammation. Overall, older Black Americans tend to have higher inflammation than older non-Hispanic White adults. Given that inflammation is related to a range of chronic health problems that disproportionately affect Blacks compared to Whites, this racial disparity in inflammation may contribute to racial disparities in particular chronic health problems. Thus, a better understanding of its determinants in the older Black population is of critical importance. This analysis examined the association between neighborhood characteristics and inflammation in a national sample of older non-Hispanic Black Americans. An additional aim of this study was to determine whether hopelessness and pessimism moderate the association between neighborhood characteristics and inflammation.

Methods
A sample of older non-Hispanic Black Americans aged 60+ were drawn from the Health and Retirement Study (N = 1004). Neighborhood characteristics included neighborhood physical disadvantage and neighborhood social cohesion. Inflammation was assessed by C-reactive protein.

Results
The analyses indicated that neighborhood physical disadvantage and social cohesion were not associated with C-reactive protein. Hopelessness and pessimism moderated the association between neighborhood physical disadvantage and C-reactive protein.

Conclusions
Knowledge regarding the role of hopelessness and pessimism as moderator in the neighborhood–inflammation association can inform cognitive-behavioral interventions targeted at changes in cognition patterns.
Neither Leg Muscle Strength Nor Balance Is Associated With the Incidence of Falls in Middle-Aged Women: A 5-Year Population-Based Prospective Study
Authors: Wang Mengmeng , Wu Feitong , Callisaya Michele L , Jones Graeme , Winzenberg Tania M 
Published: April 2021

Abstract

Background
Muscle strength and balance are major modifiable factors of falls in older adults, but their associations with falls in middle-aged adults are underinvestigated. We aimed to examine the association of baseline and change in leg muscle strength (LMS) and balance with the incidence of falls in a cohort of middle-aged women.

Methods
This was a 5-year follow-up of a population-based sample of 273 women aged 36–57 years at baseline (2011–2012). Data on LMS (by dynamometer) and balance (timed up and go test, step test, functional reach test, and lateral reach test) were obtained at baseline and 5 years later (2017–2018). After 5 years, falls were recorded monthly for 1 year by questionnaire (2017–2019). Negative binomial/Poisson and log-binomial regressions were used as appropriate to assess associations of baseline and change in LMS and balance with any falls, injurious falls, and multiple falls.

Results
Over 1 year, 115 participants (42%) reported at least one fall. Neither baseline nor 5-year change in LMS and balance measures was associated with the risk of any falls, injurious falls, or multiple falls 5 years later, with or without adjusting for confounders at baseline (incidence rate ratio/relative risk ranging from 0.85 to 1.19, 0.90 to 1.20, and 0.82 to 1.36, respectively; p &gt; .05 for all).

Conclusions
Baseline or change in LMS and balance measures are not associated with incident falls among middle-aged women. The contributions of environmental and other intrinsic factors such as chronic conditions and gait/mobility problems need to be investigated.
Advance Directive Completion Among Older American Couples: A Dyadic Perspective on the Role of Cognitive Function and Other Factors
Authors: Lu Peiyi , Kong Dexia , Lee Jeongeun , Shelley Mack 
Published: April 2021

Abstract

Objective
Dyadic perspective is scarce in existing advance directive (AD) literature. Particularly, the significance of one’s own and/or one’s partner’s cognitive function on AD remains unknown. This study investigates the relationship of cognitive function and other factors with AD completion within the spousal context.

Method
Data from the Health and Retirement Study (2014–2015) were used. Older heterosexual couples (age ≥65) married for 10+ years were asked if they had a living will and/or appointed a durable power of attorney for health care (DPAHC). Structural equation models examined the actor and partner effects of sociodemographic, health, and couple-level characteristics on wife’s and husband’s AD, respectively.

Results
Moderate spousal interdependence was observed in living will (kappa coefficient, κ = .60) and DPAHC (κ = .53). Older age and higher education were related to both spouses having AD. Less household wealth and being racial/ethnic minority were associated with a lower probability of having AD. Notable gender contrasts in actor and partner effects were found. Wife’s higher level of cognitive function was associated with husband’s AD completion. Contrarily, husband’s lower level of cognitive function was associated with wife’s AD completion. Retirement status had primarily actor effects for both husbands and wives. More chronic conditions were linked to husband’s AD completion.

Discussion
The spousal interdependence of AD warrants practitioner efforts to facilitate family-oriented end-of-life planning. Wives and husbands may have different thoughts regarding their spouse’s cognitive capacity to surrogate. Facilitating couple-based discussions may be a feasible approach to promote engagement with AD among older adults.
Downregulation of ARID1B, a tumor suppressor in the WNT subgroup medulloblastoma, activates multiple oncogenic signaling pathways
Authors: Deogharkar Akash , Singh Satishkumar Vishram , Bharambe Harish Shrikrishna , Paul Raikamal , Moiyadi Aliasgar , Goel Atul , Shetty Prakash , Sridhar Epari , Gupta Tejpal , Jalali Rakesh , Goel Naina , Gadewal Nikhil , Muthukumar Sahana , Shirsat Neelam Vishwanath 
Published: April 2021

Abstract
Medulloblastoma, a common pediatric malignant brain tumor, consists of four distinct molecular subgroups WNT, SHH, Group 3 and Group 4. Exome sequencing of 11 WNT subgroup medulloblastomas from an Indian cohort identified mutations in several chromatin modifier genes, including genes of the mammalian SWI/SNF complex. The genome of WNT subgroup tumors is known to be stable except for monosomy 6. Two tumors, having monosomy 6, carried a loss of function mutation in the ARID1B gene located on chromosome 6. ARID1B expression is also lower in the WNT subgroup tumors compared to other subgroups and normal cerebellar tissues that could result in haploinsufficiency. The short hairpin RNA-mediated knockdown of ARID1B expression resulted in a significant increase in the malignant potential of medulloblastoma cells. Transcriptome sequencing identified upregulation of several genes encoding cell adhesion proteins, matrix metalloproteases indicating the epithelial–mesenchymal transition. The ARID1B knockdown also upregulated ERK1/ERK2 and PI3K/AKT signaling with a decrease in the expression of several negative regulators of these pathways. The expression of negative regulators of the WNT signaling like TLE1, MDFI, GPX3, ALX4, DLC1, MEST decreased upon ARID1B knockdown resulting in the activation of the canonical WNT signaling pathway. Synthetic lethality has been reported between SWI/SNF complex mutations and EZH2 inhibition, suggesting EZH2 inhibition as a possible therapeutic modality for WNT subgroup medulloblastomas. Thus, the identification of ARID1B as a tumor suppressor and its downregulation resulting in the activation of multiple signaling pathways opens up opportunities for novel therapeutic modalities for the treatment of WNT subgroup medulloblastoma.
Repeat Variation Resolves a Complete Aggregate Silk Sequence of Bolas Spider Mastophora phrynosoma
Authors: Stellwagen Sarah D , Burns Mercedes 
Published: April 2021

Abstract
Many species of spider use a modified silk adhesive, called aggregate glue, to aid in prey capture. Aggregate spidroins (spider fibroins) are modified members of the spider silk family; however, they are not spun into fibers as are their solid silk relatives. The genes that encode for aggregate spidroins are the largest of the known spidroin genes and are similarly highly repetitive. In this study, we used long read sequencing to discover the aggregate spidroin genes of the toad-like bolas spider, Mastophora phrynosoma, which employs the glue in a unique way, using only a single, large droplet to capture moths. While Aggregate Spidroin 1 (AgSp1) remains incomplete, AgSp2 is more than an extraordinary 62 kb of coding sequence, 20 kb longer than the longest spidroin on record. The structure of repeats from both aggregate silk proteins follows a similar pattern seen in other species, with the same strict conservation of amino acid residue number for much of the repeats’ lengths. Interestingly, AgSp2 lacks the elevated number and groupings of glutamine residues seen in the other reported AgSp2 of a classic orb weaving species. The role of gene length in glue functionality remains a mystery, and thus discovering length differences across species will allow understanding and harnessing of this attribute for the next generation of bio-inspired adhesives.
Evaluation of anticoagulant therapy management in a teaching hospital in Tunisia: information and education for vitamin k antagonist newly treated patients need to be improved
Authors: Jeddou Khouloud Ben , Abbassi Aïmen , M’barka Fatma Ben , Bedoui Yosra , Boukhris Imene , Baccar Hédi , Khalfallah Narjess , Ouahchi Zeineb 
Published: April 2021

Abstract

Objective
The objective of this study was to assess the level of Vitamin K antagonist (VKA) therapy knowledge among VKA newly treated patients.

Methods
Questionnaire-based interviews were administered in a university hospital to VKA newly treated patients covering both cognitive (i.e. indication, route of administration, treatment monitoring and side effects) and know-how (i.e. safety precautions, what affects anticoagulant therapy and the management of overdose signs) aspects of therapy knowledge.

Key findings
A total of 55 patients were included. The mean overall score of patients’ knowledge was 5.78 (SD = 3.425) out of 20. The mean scores of cognitive and practical knowledge were 3.8 (2.26) and 1.98 (1.78) out of 10, respectively. Factors associated with an insufficient level of VKA therapy knowledge included low level of education, lack of access to therapy information and continuous access to this information.

Conclusions
Knowledge about VKA therapy among newly treated patients is insufficient. Patient’s medication knowledge should be improved to ensure better adherence.