bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘It is designed for everybody to find their own level and to improve themselves’; views of older people and instructors of the Falls Management Exercise (FaME) programme
Authors: Gumber Leher , Timmons Stephen , Coupland Carol , Gladman John R F , Iliffe Steve , Kendrick Denise , Lafond Natasher , Logan Pip , Masud Tahir , Skelton Dawn A , Timblin Clare , Orton Elizabeth 
Published: January 2022

Abstract

Background
Older adults are at increased risk of falls due to ageing, decreased muscle strength and impaired balance. Clinical trials have demonstrated the efficacy and effectiveness of the Falls Management Exercise (FaME) programme in improving functioning and preventing falls. However, programme completion is often low, impacting the potential benefits of FaME.

Objective
To explore the barriers and facilitators for participation and completion of the FaME programme from an instructor and participant perspective.

Methods
Semi-structured interviews were conducted with 20 FaME users and seven Postural Stability Instructors from the East Midlands region of England, UK. Interviews were conducted using a topic guide and explored their views of the programme, intended benefits, reasons for participating, instructor’s approach and venue facilities. Data were transcribed verbatim and analysed using thematic analysis. Written informed consent was obtained from all participants and instructors.

Results
Common themes identified by participants and instructors for adherence related to perceived health benefits, psychological well-being, intervention characteristics, cost, instructors’ qualities, opportunity to socialise, venue accessibility and facilities. Further factors such as maintaining independence, discipline, relationship with peers and caring responsibilities influenced participants’ engagement with the programme. Instructor factors such as progression were also reported as important predictors.

Conclusions
Instructor and participant factors influence uptake, attendance and adherence of FaME. The findings from this study can inform the development and improvement of additional falls-prevention programmes. It can also guide marketing strategies to promote uptake of exercise-based falls-prevention programmes among older adults.
‘Unprepared for the depth of my feelings’ - Capturing grief in older people through research poetry
Authors: Gerber Katrin , Brijnath Bianca , Lock Kayla , Bryant Christina , Hills Danny , Hjorth Larissa 
Published: January 2022

Abstract

Background
Older people are more likely to experience bereavements than any other age group. However, in healthcare and society, their grief experiences and support needs receive limited attention. Through innovative, arts-based research poetry, this study aimed to capture older people’s bereavement stories and the effects of grief on their physical and mental health.

Method
Semi-structured in-depth interviews with 18 bereaved older adults were analysed using thematic and poetic narrative analysis, following a five-step approach of immersion, creation, critical reflection, ethics and engagement.

Results
Research poems were used to illustrate three themes of bereavement experiences among older adults: feeling unprepared, accumulation of losses and ripple effects of grief. While half of participants reported that the death of their family member was expected, many felt unprepared despite having experienced multiple bereavements throughout their life. Instead, the accumulation of losses had a compounding effect on their health and well-being. While these ripple effects of grief focussed on emotional and mental health consequences, many also reported physical health effects like the onset of a new condition or the worsening of an existing one. In its most extreme form, grief was connected with a perceived increased mortality risk.

Conclusions
By using poetry to draw attention to the intense and often long-lasting effects of grief on older people’s health and well-being, this article offers emotional, engaging and immersive insights into their unique bereavement experiences and thereby challenges the notion that grief has an expiry date.
SAM-TB: a whole genome sequencing data analysis website for detection of Mycobacterium tuberculosis drug resistance and transmission
Authors: Yang Tingting , Gan Mingyu , Liu Qingyun , Liang Wenying , Tang Qiqin , Luo Geyang , Zuo Tianyu , Guo Yongchao , Hong Chuangyue , Li Qibing , Tan Weiguo , Gao Qian 
Published: January 2022

Abstract
Whole genome sequencing (WGS) can provide insight into drug-resistance, transmission chains and the identification of outbreaks, but data analysis remains an obstacle to its routine clinical use. Although several drug-resistance prediction tools have appeared, until now no website integrates drug-resistance prediction with strain genetic relationships and species identification of nontuberculous mycobacteria (NTM). We have established a free, function-rich, user-friendly online platform for MTB WGS data analysis (SAM-TB, http://samtb.szmbzx.com) that integrates drug-resistance prediction for 17 antituberculosis drugs, detection of variants, analysis of genetic relationships and NTM species identification. The accuracy of SAM-TB in predicting drug-resistance was assessed using 3177 sequenced clinical isolates with results of phenotypic drug-susceptibility tests (pDST). Compared to pDST, the sensitivity of SAM-TB for detecting multidrug-resistant tuberculosis was 93.9% [95% confidence interval (CI) 92.6–95.1%] with specificity of 96.2% (95% CI 95.2–97.1%). SAM-TB also analyzes the genetic relationships between multiple strains by reconstructing phylogenetic trees and calculating pairwise single nucleotide polymorphism (SNP) distances to identify genomic clusters. The incorporated mlstverse software identifies NTM species with an accuracy of 98.2% and Kraken2 software can detect mixed MTB and NTM samples. SAM-TB also has the capacity to share both sequence data and analysis between users. SAM-TB is a multifunctional integrated website that uses WGS raw data to accurately predict antituberculosis drug-resistance profiles, analyze genetic relationships between multiple strains and identify NTM species and mixed samples containing both NTM and MTB. SAM-TB is a useful tool for guiding both treatment and epidemiological investigation.
Cross-dependent graph neural networks for molecular property prediction
Authors: Ma Hehuan , Bian Yatao , Rong Yu , Huang Wenbing , Xu Tingyang , Xie Weiyang , Ye Geyan , Huang Junzhou 
Published: January 2022

Abstract

Motivation
The crux of molecular property prediction is to generate meaningful representations of the molecules. One promising route is to exploit the molecular graph structure through graph neural networks (GNNs). Both atoms and bonds significantly affect the chemical properties of a molecule, so an expressive model ought to exploit both node (atom) and edge (bond) information simultaneously. Inspired by this observation, we explore the multi-view modeling with GNN (MVGNN) to form a novel paralleled framework, which considers both atoms and bonds equally important when learning molecular representations. In specific, one view is atom-central and the other view is bond-central, then the two views are circulated via specifically designed components to enable more accurate predictions. To further enhance the expressive power of MVGNN, we propose a cross-dependent message-passing scheme to enhance information communication of different views. The overall framework is termed as CD-MVGNN.

Results
We theoretically justify the expressiveness of the proposed model in terms of distinguishing non-isomorphism graphs. Extensive experiments demonstrate that CD-MVGNN achieves remarkably superior performance over the state-of-the-art models on various challenging benchmarks. Meanwhile, visualization results of the node importance are consistent with prior knowledge, which confirms the interpretability power of CD-MVGNN.

Availability and implementation
The code and data underlying this work are available in GitHub at https://github.com/uta-smile/CD-MVGNN.

Supplementary information
Supplementary data are available at Bioinformatics online.
SCONCE: a method for profiling copy number alterations in cancer evolution using single-cell whole genome sequencing
Authors: Hui Sandra , Nielsen Rasmus 
Published: January 2022

Abstract

Motivation
Copy number alterations (CNAs) are a significant driver in cancer growth and development, but remain poorly characterized on the single cell level. Although genome evolution in cancer cells is Markovian through evolutionary time, CNAs are not Markovian along the genome. However, existing methods call copy number profiles with Hidden Markov Models or change point detection algorithms based on changes in observed read depth, corrected by genome content and do not account for the stochastic evolutionary process.

Results
We present a theoretical framework to use tumor evolutionary history to accurately call CNAs in a principled manner. To model the tumor evolutionary process and account for technical noise from low coverage single-cell whole genome sequencing data, we developed SCONCE, a method based on a Hidden Markov Model to analyze read depth data from tumor cells using matched normal cells as negative controls. Using a combination of public data sets and simulations, we show SCONCE accurately decodes copy number profiles, and provides a useful tool for understanding tumor evolution.

Availabilityand implementation
SCONCE is implemented in C++11 and is freely available from https://github.com/NielsenBerkeleyLab/sconce.

Supplementary information
Supplementary data are available at Bioinformatics online.
Surgical method to prevent early death of neonatal rat pups with Hirschsprung disease, thus permitting development of long-term therapeutic approaches
Authors: Stamp Lincon A , Lei Enie , Liew Jamie J M , Pustovit Ruslan V , Hao Marlene M , Croaker David H , Furness John B , Adams Cameron D 
Published: January 2022

Abstract
Hirschsprung disease occurs when children are born with no intrinsic nerve cells in varying lengths of the large intestine. In the most severe cases, neurons are also missing from the distal part of the small intestine. Nerve-mediated relaxation of the aganglionic bowel fails and fecal matter accumulates in the more proximal regions of the intestine. This is life threatening. Perforation of the bowel can ensue, causing sepsis and in some cases, death of the infant. Repopulation of the colon with neural stem cells is a potential therapy, but for this to be successful the patient or experimental animal needs to survive long enough for neural precursors to differentiate and make appropriate connections. We have developed a surgical procedure that can be applied to rats with Hirschsprung disease. A stoma was created to allow the normal bowel to empty and a second stoma leading to the aganglionic bowel was also created. This allowed homozygous mutants that would usually die at less than 3 weeks of age to survive into adulthood. During this time, the rats also required post-operative care of their stomas. The interventions we describe provide an animal model of Hirschsprung disease that is suited to assess the effectiveness of cell therapies in the treatment of this condition.
Semisupervised Calibration of Risk with Noisy Event Times (SCORNET) using electronic health record data
Authors: Ahuja Yuri , Liang Liang , Zhou Doudou , Huang Sicong , Cai Tianxi 
Published: January 2022

Summary
Leveraging large-scale electronic health record (EHR) data to estimate survival curves for clinical events can enable more powerful risk estimation and comparative effectiveness research. However, use of EHR data is hindered by a lack of direct event time observations. Occurrence times of relevant diagnostic codes or target disease mentions in clinical notes are at best a good approximation of the true disease onset time. On the other hand, extracting precise information on the exact event time requires laborious manual chart review and is sometimes altogether infeasible due to a lack of detailed documentation. Current status labels—binary indicators of phenotype status during follow-up—are significantly more efficient and feasible to compile, enabling more precise survival curve estimation given limited resources. Existing survival analysis methods using current status labels focus almost entirely on supervised estimation, and naive incorporation of unlabeled data into these methods may lead to biased estimates. In this article, we propose Semisupervised Calibration of Risk with Noisy Event Times (SCORNET), which yields a consistent and efficient survival function estimator by leveraging a small set of current status labels and a large set of informative features. In addition to providing theoretical justification of SCORNET, we demonstrate in both simulation and real-world EHR settings that SCORNET achieves efficiency akin to the parametric Weibull regression model, while also exhibiting semi-nonparametric flexibility and relatively low empirical bias in a variety of generative settings.
Excision and suture in the midline versus Karydakis flap surgery for pilonidal sinus: randomized clinical trial
Authors: Hemmingsson Oskar , Binnermark Felix , Odensten Christoffer , Rutegård Martin , Franklin Karl A. , Haapamäki Markku M. 
Published: January 2022

Abstract

Background
There are several surgical options for the management of pilonidal disease, including midline and off midline closure, but prospective studies are rare. The study hypothesis was that Karydakis flap surgery would result in shorter wound healing and fewer recurrences than excision of pilonidal sinus and suture in the midline.

Methods
A randomized clinical trial was conducted in two hospitals in Sweden between 2006 and 2015 to compare excision and suture in the midline with Karydakis flap surgery. Adult patients with a chronic pilonidal sinus disease were randomized 1:1 at the outpatient clinic without blinding. Power calculation based on recurrence of 2 per cent for Karydakis flap and 10 per cent for excision and primary closure in the midline required 400 patients with 90 per cent statistical power at 5 per cent significance assuming 10 per cent loss during follow-up. Participants were followed up until complete wound healing; late follow-up after 6–13 years was performed by telephone by two blinded assessors. The two co-primary outcomes were time to complete wound healing and recurrence rate.

Results
The study was terminated early at a planned interim analysis due slow recruitment and a significant difference in primary outcome. In total, 125 patients were randomized, of whom 116 were available for the present analysis. Median wound healing time was 49 days (95 per cent confidence interval (c.i.) 32 to 66) for excision with suture in the midline and 14 days (95 per cent c.i. 12 to 20) for Karydakis flap surgery (P &lt; 0.001). There were five recurrences in each group, after a median follow-up of 11 years (P = 0.753).

Conclusion
Karydakis flap surgery for pilonidal sinus disease led to a shorter wound healing time than excision and suture in the midline but no difference in recurrence rates.
Registration number: NCT00412659 (http://www.clinicaltrials.gov)
‘The WOW factors’: comparing workforce organization and well-being for doctors, nurses, midwives and paramedics in England
Authors: Taylor Cath , Mattick Karen , Carrieri Daniele , Cox Anna , Maben Jill 
Published: January 2022

AbstractBackgroundHigh rates of poor mental health in healthcare staff threatens the quality and sustainability of healthcare delivery. Multi-factorial causes include the nature and structure of work. We conducted a critical review of UK NHS (England) data pertaining to: doctors, nurses, midwives and paramedics.Sources of dataKey demographic, service architecture (structural features of work) and well-being indicators were identified and reviewed by a stakeholder group. Data searching prioritized NHS whole workforce sources (focusing on hospital and community health services staff), which were rated according to strength of evidence.FindingsKey differences between professions were: (i) demographics: gender (nursing and midwifery female-dominated, doctors and paramedics more balanced); age (professions other than doctors had ageing workforces); ethnicity (greater diversity among doctors and nurses); (ii) service architecture: despite net staffing growth, turnover and retention were problematic in all professions; 41.5% doctors were consultants but smaller proportions held high grade/band roles in other professions; salaries were higher for doctors; (iii) well-being: all reported high job stress, particularly midwives and paramedics; sickness absence rates for nurses, midwives and paramedics were three times those of doctors, and presenteeism nearly double.Growing pointsSociocultural factors known to increase risk of poor mental health may explain some of the differences reported between professions. These factors and differences in service architecture are vital considerations when designing strategies to improve well-being.Areas timely for developing researchMulti-level systems approaches to well-being are required that consider intersectionality and structural differences between professions; together with inter-professional national databases to facilitate monitoring.
Frontostriatothalamic effective connectivity and dopaminergic function in the psychosis continuum
Authors: Sabaroedin Kristina , Razi Adeel , Chopra Sidhant , Tran Nancy , Pozaruk Andrii , Chen Zhaolin , Finlay Amy , Nelson Barnaby , Allott Kelly , Alvarez-Jimenez Mario , Graham Jessica , Yuen Hok P , Harrigan Susy , Cropley Vanessa , Sharma Sujit , Saluja Bharat , Williams Rob , Pantelis Christos , Wood Stephen J , O’Donoghue Brian , Francey Shona , McGorry Patrick , Aquino Kevin , Fornito Alex 
Published: January 2022

Abstract
Dysfunction of fronto-striato-thalamic (FST) circuits is thought to contribute to dopaminergic dysfunction and symptom onset in psychosis, but it remains unclear whether this dysfunction is driven by aberrant bottom-up subcortical signalling or impaired top-down cortical regulation.
We used spectral dynamic causal modelling of resting-state functional MRI to characterize the effective connectivity of dorsal and ventral FST circuits in a sample of 46 antipsychotic-naïve first-episode psychosis patients and 23 controls and an independent sample of 36 patients with established schizophrenia and 100 controls. We also investigated the association between FST effective connectivity and striatal 18F-DOPA uptake in an independent healthy cohort of 33 individuals who underwent concurrent functional MRI and PET.
Using a posterior probability threshold of 0.95, we found that midbrain and thalamic connectivity were implicated as dysfunctional across both patient groups. Dysconnectivity in first-episode psychosis patients was mainly restricted to the subcortex, with positive symptom severity being associated with midbrain connectivity. Dysconnectivity between the cortex and subcortical systems was only apparent in established schizophrenia patients. In the healthy 18F-DOPA cohort, we found that striatal dopamine synthesis capacity was associated with the effective connectivity of nigrostriatal and striatothalamic pathways, implicating similar circuits to those associated with psychotic symptom severity in patients.
Overall, our findings indicate that subcortical dysconnectivity is evident in the early stages of psychosis, that cortical dysfunction may emerge later in the illness, and that nigrostriatal and striatothalamic signalling are closely related to striatal dopamine synthesis capacity, which is a robust marker for psychosis.
Matrix metalloproteinase 10 is linked to the risk of progression to dementia of the Alzheimer’s type
Authors: Martino Adami Pamela V , Orellana Adelina , García Pablo , Kleineidam Luca , Alarcón-Martín Emilio , Montrreal Laura , Aguilera Nuria , Espinosa Ana , Abdelnour Carla , Rosende-Roca Maitee , Pablo Tartari Juan , Vargas Liliana , Mauleón Ana , Esteban-De Antonio Ester , López-Cuevas Rogelio , Dalmasso Maria Carolina , Campos Martin Rafael , Parveen Kayenat , Andrade Fuentes Victor M , Amin Najaf , Ahmad Shahzad , Ikram M Arfan , Lewczuk Piotr , Kornhuber Johannes , Peters Oliver , Frölich Lutz , Rüther Eckart , Wiltfang Jens , Tarraga Lluis , Boada Merce , Maier Wolfgang , de Rojas Itziar , Cano Amanda , Sanabria Angela , Alegret Montserrat , Hernández Isabel , Marquié Marta , Valero Sergi , van Duijn Cornelia M , Wagner Michael , Jessen Frank , Schneider Anja , Sáez Goñi María Eugenia , González Pérez Antonio , Ruiz Agustín , Ramírez Alfredo 
Published: January 2022

Abstract
Alzheimer’s disease has a long asymptomatic phase that offers a substantial time window for intervention. Using this window of opportunity will require early diagnostic and prognostic biomarkers to detect Alzheimer’s disease pathology at predementia stages, thus allowing identification of patients who will most probably progress to dementia of the Alzheimer’s type and benefit from specific disease-modifying therapies. Consequently, we searched for CSF proteins associated with disease progression along with the clinical disease staging.
We measured the levels of 184 proteins in CSF samples from 556 subjective cognitive decline and mild cognitive impairment patients from three independent memory clinic longitudinal studies (Spanish ACE, n = 410; German DCN, n = 93; German Mannheim, n = 53). We evaluated the association between protein levels and clinical stage, and the effect of protein levels on the progression from mild cognitive impairment to dementia of the Alzheimer’s type.
Mild cognitive impairment subjects with increased CSF level of matrix metalloproteinase 10 (MMP-10) showed a higher probability of progressing to dementia of the Alzheimer’s type and a faster cognitive decline. CSF MMP-10 increased the prediction accuracy of CSF amyloid-β 42 (Aβ42), phospho-tau 181 (P-tau181) and total tau (T-tau) for conversion to dementia of the Alzheimer’s type. Including MMP-10 to the [A/T/(N)] scheme improved considerably the prognostic value in mild cognitive impairment patients with abnormal Aβ42, but normal P-tau181 and T-tau, and in mild cognitive impairment patients with abnormal Aβ42, P-tau181 and T-tau. MMP-10 was correlated with age in subjects with normal Aβ42, P-tau181 and T-tau levels.
Our findings support the use of CSF MMP-10 as a prognostic marker for dementia of the Alzheimer’s type and its inclusion in the [A/T/(N)] scheme to incorporate pathologic aspects beyond amyloid and tau. CSF level of MMP-10 may reflect ageing and neuroinflammation.