bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional health index of intrinsic capacity: multi-domain operationalisation and validation in the Singapore Longitudinal Ageing Study (SLAS2)
Authors: Cheong Chin Yee , Yap Philip , Nyunt Ma Shwe Zin , Qi Gao , Gwee Xinyi , Wee Shiou Liang , Yap Keng Bee , Ng Tze Pin 
Published: January 2022

Abstract

Background
ad hoc approaches are used to create composite indexes of intrinsic capacity (IC) based on five domains recommended by the World Health Organization for healthy ageing. We examined how combinations of domain-specific measures determine measurement performances of composite IC indexes.

Methods
in this population-based prospective cohort study, community-dwelling older persons (N = 2,906) aged 55 years and above were recruited. We used 12 domain-specific measures: cognition (Mini-Mental State Examination, MMSE), psychological (Geriatric Depression Scale, GDS), locomotion (Timed Up-and Go [TUG], GV, Knee Extension Strength, Performance Orientated Mobility Assessment), sensory (logarithm of the Minimum Angle of Resolution [LogMAR] vision and Whisper Test hearing) and vitality (forced expiratory volume in 1 second pulmonary function, Elderly Nutritional Indicators for Geriatric Malnutrition Assessment [ENIGMA], Nutritional Screening Initiative) to derive 144 composite 2- to 5-domain functional health indexes (FHI), and evaluated their abilities to predict 9-year mortality and their associations with health determinants.

Results
with 5-domain FHI, TUG, logMAR and MMSE showed the largest factor loadings (0.65–0.75). All single-domain FHI were significantly associated with mortality risks. Area under the receiver operating characteristic curve (AUC) values of mortality prediction increased with the number of domains (from mean 0.615 for single-domain FHI to mean 0.705 for 5-domain FHI), but the difference between 3-domain versus 4-domain FHI (P = 0.082) or versus 5-domain FHI (P = 0.109) was not statistically significant. Highest AUCs (P &lt; 0.001) of best performing FHI were single-domain TUG: 0.735; 2-domain TUG + ENIGMA: 0.743; 3-domain TUG + LogMAR + ENIGMA: 0.762; 4-domain TUG + MMSE + LogMAR + ENIGMA: 0.757; 5-domain TUG + MMSE + GDS + LogMAR + ENIGMA: 0.751. FHI showed excellent construct validity based on correlations with known health determinants.

Conclusions
among Singaporean older adults, cognition, sensory and locomotion are predominant IC domains. A multi-domain IC index performs better with more domain measures, but a minimalist 3-domain index performs just as robustly as a 4- or 5-domain index.
Response Letter to Koivistoet al. ‘Evaluating the Theoretical Background of STOFFENMANAGER® and the Advanced REACH Tool’
Authors: Fransman Wouter , Arnone Mario , Borghi Francesca , Cattaneo Andrea , Cavallo Domenico M , Cherrie John W , Franken Remy , Galea Karen S , van der Haar Rudolf , Heussen Gerardus A H , Jensen Keld A , Koponen Milja , Koppisch Dorothea , Kromhout Hans , Luo Yu-Syuan , McNally Kevin , Säämänen Arto , Spinazzè Andrea , van Tongeren Martie , Vanoirbeek Jeroen , Verpaele Steven , Vetter Daniel , Viegas Susana , Warren Nick 
Published: January 2022

AbstractIn this article, we have responded to the key statements in the article by Koivisto et al. (2022) that were incorrect and considered to be a biased critique on a subset of the exposure models used in Europe (i.e. ART and Stoffenmanager®) used for regulatory exposure assessment. We welcome scientific discussions on exposure modelling (as was done during the ISES Europe workshop) and criticism based on scientific evidence to contribute to the advancement of occupational exposure estimation tools. The tiered approach to risk assessment allows various exposure assessment models from screening tools (control/hazard banding) through to higher-tiered approaches. There is a place for every type of model, but we do need to recognize the cost and data requirements of highly bespoke assessments. That is why model developers have taken pragmatic approaches to develop tools for exposure assessments based on imperfect data. We encourage Koivisto et al. to focus on further scientifically robust work to develop mass-balance models and by independent external validations studies, compare these models with alternative model tools such as ART and Stoffenmanager®.
Down, then up: non-parallel genome size changes and a descending chromosome series in a recent radiation of the Australian allotetraploid plant species, Nicotiana section Suaveolentes (Solanaceae)
Authors: Chase Mark W , Samuel Rosabelle , Leitch Andrew R , Guignard Maïté S , Conran John G , Nollet Felipe , Fletcher Paul , Jakob Aljaž , Cauz-Santos Luiz A , Vignolle Gabriel , Dodsworth Steven , Christenhusz Maarten J M , Buril Maria Teresa , Paun Ovidiu 
Published: January 2022

Abstract

Background and Aims
The extent to which genome size and chromosome numbers evolve in concert is little understood, particularly after polyploidy (whole-genome duplication), when a genome returns to a diploid-like condition (diploidization). We study this phenomenon in 46 species of allotetraploid Nicotiana section Suaveolentes (Solanaceae), which formed &lt;6 million years ago and radiated in the arid centre of Australia.

Methods
We analysed newly assessed genome sizes and chromosome numbers within the context of a restriction site-associated nuclear DNA (RADseq) phylogenetic framework.

Key Results
RADseq generated a well-supported phylogenetic tree, in which multiple accessions from each species formed unique genetic clusters. Chromosome numbers and genome sizes vary from n = 2x = 15 to 24 and 2.7 to 5.8 pg/1C nucleus, respectively. Decreases in both genome size and chromosome number occur, although neither consistently nor in parallel. Species with the lowest chromosome numbers (n = 15–18) do not possess the smallest genome sizes and, although N. heterantha has retained the ancestral chromosome complement, n = 2x = 24, it nonetheless has the smallest genome size, even smaller than that of the modern representatives of ancestral diploids.

Conclusions
The results indicate that decreases in genome size and chromosome number occur in parallel down to a chromosome number threshold, n = 20, below which genome size increases, a phenomenon potentially explained by decreasing rates of recombination over fewer chromosomes. We hypothesize that, more generally in plants, major decreases in genome size post-polyploidization take place while chromosome numbers are still high because in these stages elimination of retrotransposons and other repetitive elements is more efficient. Once such major genome size change has been accomplished, then dysploid chromosome reductions take place to reorganize these smaller genomes, producing species with small genomes and low chromosome numbers such as those observed in many annual angiosperms, including Arabidopsis.
Participatory Research with Care Leavers to Explore their Support Experiences During the COVID-19 Pandemic
Authors: Dadswell Anna , O’Brien Niamh 
Published: January 2022

Abstract
The COVID-19 pandemic has perpetuated the challenges faced by care leavers and increased the need for support. Online participatory research was conducted to explore care leavers’ support experiences during the pandemic. A research team of twenty-five care leavers aged sixteen to twenty-five years and support workers from six local authorities across England identified priorities and developed an online questionnaire that was completed by ninety-four care leavers aged seventeen to twenty-six years. The research team also participated in focus groups, reflected on findings and agreed recommendations. The findings focused on four overarching themes: finances and practical issues, mental health, social connection, and support from services. The recommendations suggest that corporate parent services should provide information, offer equal opportunity to access support, facilitate connection for care leavers, and proactively reach out and ensure someone is always there for them. So that support is responsive to their needs, the continued participation of care leavers in decisions that affect them is paramount, along with commitment by the government and corporate parent services to listen and take action. By using a participatory approach that involved care leavers in the research process, this research promotes their voices and strengthens the evidence for enhancing care leaver support during the pandemic and beyond.
A neural network for tics: insights from causal brain lesions and deep brain stimulation
Authors: Ganos Christos , Al-Fatly Bassam , Fischer Jan-Frederik , Baldermann Juan-Carlos , Hennen Christina , Visser-Vandewalle Veerle , Neudorfer Clemens , Martino Davide , Li Jing , Bouwens Tim , Ackermanns Linda , Leentjens Albert F G , Pyatigorskaya Nadya , Worbe Yulia , Fox Michael D , Kühn Andrea A , Horn Andreas 
Published: January 2022

Abstract
Brain lesions are a rare cause of tic disorders. However, they can provide uniquely causal insights into tic pathophysiology and can also inform on possible neuromodulatory therapeutic targets. Based on a systematic literature review, we identified 22 cases of tics causally attributed to brain lesions and employed ‘lesion network mapping’ to interrogate whether tic-inducing lesions would be associated with a common network in the average human brain. We probed this using a normative functional connectome acquired in 1000 healthy participants. We then examined the specificity of the identified network by contrasting tic-lesion connectivity maps to those seeding from 717 lesions associated with a wide array of neurological and/or psychiatric symptoms within the Harvard Lesion Repository. Finally, we determined the predictive utility of the tic-inducing lesion network as a therapeutic target for neuromodulation. Specifically, we collected retrospective data of 30 individuals with Tourette disorder, who underwent either thalamic (n = 15; centromedian/ventrooralis internus) or pallidal (n = 15; anterior segment of globus pallidus internus) deep brain stimulation and calculated whether connectivity between deep brain stimulation sites and the lesion network map could predict clinical improvements.
Despite spatial heterogeneity, tic-inducing lesions mapped to a common network map, which comprised the insular cortices, cingulate gyrus, striatum, globus pallidus internus, thalami and cerebellum. Connectivity to a region within the anterior striatum (putamen) was specific to tic-inducing lesions when compared with control lesions. Connectivity between deep brain stimulation electrodes and the lesion network map was predictive of tic improvement, regardless of the deep brain stimulation target.
Taken together, our results reveal a common brain network involved in tic generation, which shows potential as a therapeutic target for neuromodulation.
Associating Alzheimer’s disease pathology with its cerebrospinal fluid biomarkers
Authors: Bridel Claire , Somers Charisse , Sieben Anne , Rozemuller Annemieke , Niemantsverdriet Ellis , Struyfs Hanne , Vermeiren Yannick , Van Broeckhoven Christine , De Deyn Peter P , Bjerke Maria , Nagels Guy , Teunissen Charlotte E , Engelborghs Sebastiaan 
Published: January 2022

Abstract
Alzheimer’s disease CSF biomarkers 42 amino acid long amyloid-β peptide (Aβ1–42), total tau protein (T-tau), and tau protein phosphorylated at threonine 181 (P-tau181) are considered surrogate biomarkers of Alzheimer’s disease pathology, and significantly improve diagnostic accuracy. Their ability to reflect neuropathological changes later in the disease course is not well characterized. This study aimed to assess the potential of CSF biomarkers measured in mid to late stage Alzheimer’s disease to reflect post-mortem neuropathological changes. Individuals were selected from two autopsy cohorts of Alzheimer’s disease patients in Antwerp and Amsterdam. Neuropathological diagnosis was performed according to the updated consensus National Institute on Aging-Alzheimer’s Association guidelines, which includes quantification of amyloid-β plaque, neurofibrillary tangle, and neuritic plaque load. CSF samples were analysed for Aβ1–42, T-tau, and P-tau181 by ELISA. One hundred and fourteen cases of pure definite Alzheimer’s disease were included in the study (mean age 74 years, disease duration 6 years at CSF sampling, 50% females). Median interval between CSF sampling and death was 1 year. We found no association between Aβ1–42 and Alzheimer’s disease neuropathological change profile. In contrast, an association of P-tau181 and T-tau with Alzheimer’s disease neuropathological change profile was observed. P-tau181 was associated with all three individual Montine scores, and the associations became stronger and more significant as the interval between lumbar puncture and death increased. T-tau was also associated with all three Montine scores, but in individuals with longer intervals from lumbar puncture to death only. Stratification of the cohort according to APOE ε4 carrier status revealed that the associations applied mostly to APOE ε4 non-carriers. Our data suggest that similar to what has been reported for Aβ1–42, plateau levels of P-tau181 and T-tau are reached during the disease course, albeit at later disease stages, reducing the potential of tau biomarkers to monitor Alzheimer’s disease pathology as the disease progresses. As a consequence, CSF biomarkers, which are performant for clinical diagnosis of early Alzheimer’s disease, may not be well suited for staging or monitoring Alzheimer’s disease pathology as it progresses through later stages.
Cancer among kidney transplant recipients &gt;20 years after transplantation: post-transplant lymphoproliferative disorder remains the most common cancer type in the ultra long-term
Authors: Fuhrmann Julia D , Valkova Kristyna , von Moos Seraina , Wüthrich Rudolf P , Müller Thomas F , Schachtner Thomas 
Published: January 2022

ABSTRACT

Background
Cancer risk is increased by 2- to 4-fold in kidney transplant recipients (KTRs) compared with the general population. Little attention, however, has been given to KTRs with ultra long-term survival &gt;20 years.

Methods
We studied 293 of 1241 KTRs (23.6%), transplanted between 1981 and 1999, who showed kidney allograft survival &gt;20 years. These long-term survivors were analysed for cancer development, cancer type, cancer-associated risk factors and patient and allograft outcomes.

Results
By 10, 20 and 30 years post-transplantation, these long-term KTRs showed a cancer rate of 4.4%, 14.6% and 33.2%, and a non-melanoma skin cancer (NMSC) rate of 10.3%, 33.5% and 76.8%, respectively. By recipients’ ages of 40, 60 and 80 years, KTRs showed a cancer rate of 3.4%, 14.5% 55.2%, and a NMSC rate of 1.7%, 31.6% and 85.2%, respectively. By 30 years post-transplantation, post-transplant lymphoproliferative disorder (PTLD) showed the highest incidence of 8.5%, followed by renal cell carcinoma (RCC) with 5.1%. Risk factors associated with the development of cancer were only recipient age (P = 0.016). Smoking history was associated with the risk of lung cancer (P = 0.018). Risk factors related to the development of NMSC included recipient age (P = 0.001) and thiazide diuretics (P = 0.001). Cancer increased the risk of death by 2.4-fold (P = 0.002), and PTLD increased the risk of kidney allograft loss by 6.5-fold (P = 0.001). No differences were observed concerning the development of donor-specific antibodies (P &gt; 0.05).

Conclusions
In long-term KTRs, cancer is a leading cause of death. PTLD remains the most common cancer type followed by RCC. These results emphasize the need for focused long-term cancer surveillance protocols.
Authors’ attitude toward adopting a new workflow to improve the computability of phenotype publications
Authors: Cui Hong , Ford Bruce , Starr Julian , Reznicek Anton , Zhang Limin , Macklin James A 
Published: January 2022

Abstract
Critical to answering large-scale questions in biology is the integration of knowledge from different disciplines into a coherent, computable whole. Controlled vocabularies such as ontologies represent a clear path toward this goal. Using survey questionnaires, we examined the attitudes of biologists toward adopting controlled vocabularies in phenotype publications. Our questions cover current experience and overall attitude with controlled vocabularies, the awareness of the issues around ambiguity and inconsistency in phenotype descriptions and post-publication professional data curation, the preferred solutions and the effort and desired rewards for adopting a new authoring workflow. Results suggest that although the existence of controlled vocabularies is widespread, their use is not common. A majority of respondents (74%) are frustrated with ambiguity in phenotypic descriptions, and there is a strong agreement (mean agreement score 4.21 out of 5) that author curation would better reflect the original meaning of phenotype data. Moreover, the vast majority (85%) of researchers would try a new authoring workflow if resultant data were more consistent and less ambiguous. Even more respondents (93%) suggested that they would try and possibly adopt a new authoring workflow if it required 5% additional effort as compared to normal, but higher rates resulted in a steep decline in likely adoption rates. Among the four different types of rewards, two types of citations were the most desired incentives for authors to produce computable data. Overall, our results suggest the adoption of a new authoring workflow would be accelerated by a user-friendly and efficient software-authoring tool, an increased awareness of the challenges text ambiguity creates for external curators and an elevated appreciation of the benefits of controlled vocabularies.
Outcome of esophageal atresia: inborn versus outborn patients
Authors: Schlee Denise , Theilen Till-Martin , Fiegel Henning , Hutter Martin , Rolle Udo 
Published: January 2022

Summary
Esophageal atresia (EA) is a rare congenital disease which is usually not of the detected prenatally. Due to the lack of prenatal diagnosis, some newborns with EA are born outside of specialized centers. Nevertheless, centralized care of EA has been proposed, even if a clear volume–outcome association in EA management remains unconfirmed. Furthermore, whether outcomes differ between outborn and inborn patients with EA has not been systematically investigated. Therefore, this single-center, retrospective study aimed to investigate EA management and outcomes with a special focus on inborn versus outborn patients. The following data were extracted from the medical records of infants with EA from 2009 to 2019: EA type, associated anomalies, complications, and long-term outcome. Patients were allocated into inborn and outborn groups. Altogether, 57 patients were included. Five patients were excluded (referral before surgery, loss of data, death before surgery [n = 1], and incorrect diagnosis [diverticulum, n = 1]). Among all patients, the overall survival rate was 96%, with no mortalities among outborn patients. The overall hospitalization period was shorter for outborn patients. The median follow-up durations were 3.8 years and 3.2 years for inborn and outborn patients, respectively. Overall, 15% of patients underwent delayed primary anastomosis (long-gap atresia [n = 4] and other reasons [n = 4]). Early complications included three anastomotic leakages and one post-operative fistula; 28% of patients developed strictures, which required dilatation, and 38% of patients showed relevant gastroesophageal reflux, which required fundoplication, without any differences between the groups. The two groups had comparable low mortality and expected high morbidity with no significant differences in outcome. The outborn group showed nonsignificant trends toward lower morbidity and shorter hospitalization periods, which might be explained by the overall better clinical status.
Transvalvular jet velocity, aortic valve area, mortality, and cardiovascular outcomes
Authors: Alcón Blanca , Martínez-Legazpi Pablo , Stewart Simon , Gonzalez-Mansilla Ana , Cuadrado Víctor , Strange Geoff , Yotti Raquel , Cascos Enric , Delgado-Montero Antonia , Prieto-Arévalo Raquel , Mombiela Teresa , Rodríguez-González Elena , Espinosa M Ángeles , Postigo Andrea , Gutiérrez-Ibanes Enrique , Pérez-Vallina Manuel , Fernández-Avilés Francisco , Playford David , Bermejo Javier 
Published: January 2022

Abstract

Aims
The interplay between aortic stenosis (AS), cardiovascular events, and mortality is poorly understood. In addition, how echocardiographic indices compare for predicting outcomes remains unexplored for the full range of AS severity.

Methods and results
We prospectively calculated peak jet velocity (Vmax) and aortic valve area (AVA) in 5994 adult subjects with and without AS. We linked ultrasound data to 5-year mortality and clinical events obtained from electronic medical records. Proportional-hazard and negative binomial regression models were adjusted for relevant covariables such as age, sex, comorbidities, stroke-volume, LV ejection fraction, left valve regurgitation, aortic valve sclerosis or calcification, and valve replacement. We observed a strong linear relationship between Vmax and all-cause mortality (hazard ratio: 1.26, 95% confidence interval: 1.19–1.33 per 100 cm/s), cardiovascular events, as well as incidental and recurrent heart failure (HF). Adjusted risks were highly significant even at Vmax values in the range of 150–200 cm/s, risk curves separating very early after the index exam. Vmax was not associated with coronary, arrhythmic, cerebrovascular, or non-cardiovascular events. Although risks were confirmed when AVA was entered in place of Vmax, the risks estimated for categories based on the two indices were mismatched, even in patients with normal flow. An external cohort comprising 112 690 patients confirmed augmented risks of all-cause and cardiovascular mortality starting at values of Vmax and AVA in the range of mild AS.

Conclusions
Aortic stenosis is strongly associated to all-cause mortality, cardiovascular mortality, and cardiac events, specifically HF. Risks increase in parallel to the degree of outflow obstruction but are apparent very early in patients with mild disease. Criteria for grading AS based on Vmax and AVA are mismatched in terms of outcomes.
Rethinking the roles of ELT in English-medium education in multilingual university settings: an introduction
Authors: Dafouz Emma , Gray John 
Published: January 2022

AbstractThe Introduction to this Special Issue on ELT and English-medium education in multilingual university settings provides a picture of the dynamic backdrop to the issues addressed by our contributing writers. We begin with a reflection on the nature of ELT and then move to a discussion of the specific nature of English-medium education in higher education globally. The Introduction underlines the importance of respecting and drawing on students’ multilingual repertoires, and the opportunities this affords for decolonising ELT in university settings.