bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of game-based interventions on functional capacity in acutely hospitalised older adults: results of an open-label non-randomised clinical trial
Authors: Cuevas-Lara César , Sáez de Asteasu Mikel L , Ramírez-Vélez Robinson , Izquierdo Mikel , Zambom-Ferraresi Fabiola , Antoñanzas-Valencia Cristina , Galbete Arkaitz , Zambom-Ferraresi Fabricio , Martínez-Velilla Nicolás 
Published: November 2021

Abstract

Background
Hospitalisation-associated disability due to reduced physical activity levels and prolonged bedrest episodes are highly prevalent in older adults.

Objective
To assess the effect of gamified interventions on functional capacity in hospitalised older adults.

Methods
A three-armed non-randomised controlled trial with two experimental intervention groups and a control group was conducted in a tertiary public hospital in Navarre, Spain. Participants were allocated to a simple gamification group (SGG) (n = 21), a technology-based gamification group (TGG) (n = 23) or a control group (CG) (n = 26). The end points were changes in functional capacity, muscle strength, cognition, mood status and quality of life.

Results
Seventy patients (mean age 86.01 ± 4.27 years old) were included in the study; 29 (41.4%) were women. At discharge, compared to CG, a mean increase of 1.47 points (95%CI, 0.15–2.80 points) and 2.69 points (95%CI, 1.32–4.06 points) was observed (SGG and TGG, respectively) in the SPPB test; as well as an increase of 5.28 points (95%CI, 0.70–9.76 points) in the Barthel Index and 2.03 kg (95%CI, 0.33–3.72 kg) in handgrip strength in the TGG. Regression mediation analyses demonstrated that muscle strength changes (β = 1.30; 95%CI, 0.45–2.14; indirect effect 0.864; 95%CI, 0.09–1.90) significantly mediated the TGG effect on the SPPB score.

Conclusions
The TGG intervention programme may provide significant benefits in physical and muscle function over usual care and seems to reverse the functional decline frequently associated with acute hospitalisation in older adults.
Declining daily functioning as a prelude to a hip fracture in older persons—an individual patient data meta-analysis
Authors: Ravensbergen Willeke M , Blom Jeanet W , Kingston Andrew , Robinson Louise , Kerse Ngaire , Teh Ruth O , Groenwold Rolf H H , Gussekloo Jacobijn ,   the TULIPS consortium
Published: November 2021

Abstract

Background
Daily functioning is known to decline after a hip fracture, but studies of self-reported functioning before the fracture suggest this decline begins before the fracture.

Objective
Determine whether change in functioning in the year before a hip fracture in very old (80+) differs from change in those without a hip fracture.

Design
Two-stage individual patient data meta-analysis including data from the Towards Understanding Longitudinal International older People Studies (TULIPS)-consortium.

Setting
Four population-based longitudinal cohorts from the Netherlands, New Zealand and the UK.

Subjects
Participants aged 80+ years.

Methods
Participants were followed for 5 years, during which (instrumental) activities of daily living [(I)ADL] scores and incident hip fractures were registered at regular intervals. Z-scores of the last (I)ADL score and the change in (I)ADL in the year before a hip fracture were compared to the scores of controls, adjusted for age and sex.

Results
Of the 2,357 participants at baseline, the 161 who sustained a hip fracture during follow-up had a worse (I)ADL score before the fracture (0.40 standard deviations, 95% CI 0.19 to 0.61, P = 0.0002) and a larger decline in (I)ADL in the year before fracture (−0.11 standard deviations, 95% CI −0.22 to 0.004, P = 0.06) compared to those who did not sustain a hip fracture.

Conclusions
In the very old a decline in daily functioning already starts before a hip fracture. Therefore, a hip fracture is a sign of ongoing decline and what full recovery is should be seen in light of the pre-fracture decline.
Adult sex ratio and male body condition affect alternative reproductive tactics in a spider
Authors: Heimerl Daniel , Dudová Pavla , Wacker Karoline , Schenkel Elisa , Despréaux Garance , Tuni Cristina 
Published: November 2021

AbstractBiases in adult sex ratios can alter the intensity of sexual selection by enhancing competition for mates. Under intense competition males increase their investment in behaviors to outcompete rivals (e.g., fighting). Yet, given that in male-biased environments mating opportunities are rare males may alternatively reduce costly courtship and/or adopt alternative reproductive tactics (ARTs). Males of the spider Pisaura mirabilis adopt different mating tactics, offering females genuine nuptial gifts (prey), nutritionally worthless gifts (prey leftovers), or no gifts. To test whether behavioral shifts between gift tactics are triggered by changes in the competitive environment, we established replicate spider populations under natural conditions at varying adult sex ratios (male-biased, female-biased and equal) and sampled gift tactics repeatedly over time. We additionally explored how male individual traits, such as body size and condition, affect the expression of ARTs. In male-biased populations males produced more gifts but of low quality, suggesting competition to trigger increased mating effort to ensure mate acquisition and fertilizations, but through a worthless gift tactic. Production of gifts and of genuine gifts was favored by high body condition, pointing to energetic limitations as being central for male reproductive capacity. We hence highlight two co-existing mechanisms at play to explain ARTs in this system, the competitive social environment where expression of gift tactics is based on optimal-decision making to overcome competition, and a conditional strategy linked to the individual’s energetic state.
HINGRL: predicting drug–disease associations with graph representation learning on heterogeneous information networks
Authors: Zhao Bo-Wei , Hu Lun , You Zhu-Hong , Wang Lei , Su Xiao-Rui 
Published: November 2021

AbstractIdentifying new indications for drugs plays an essential role at many phases of drug research and development. Computational methods are regarded as an effective way to associate drugs with new indications. However, most of them complete their tasks by constructing a variety of heterogeneous networks without considering the biological knowledge of drugs and diseases, which are believed to be useful for improving the accuracy of drug repositioning. To this end, a novel heterogeneous information network (HIN) based model, namely HINGRL, is proposed to precisely identify new indications for drugs based on graph representation learning techniques. More specifically, HINGRL first constructs a HIN by integrating drug–disease, drug–protein and protein–disease biological networks with the biological knowledge of drugs and diseases. Then, different representation strategies are applied to learn the features of nodes in the HIN from the topological and biological perspectives. Finally, HINGRL adopts a Random Forest classifier to predict unknown drug–disease associations based on the integrated features of drugs and diseases obtained in the previous step. Experimental results demonstrate that HINGRL achieves the best performance on two real datasets when compared with state-of-the-art models. Besides, our case studies indicate that the simultaneous consideration of network topology and biological knowledge of drugs and diseases allows HINGRL to precisely predict drug–disease associations from a more comprehensive perspective. The promising performance of HINGRL also reveals that the utilization of rich heterogeneous information provides an alternative view for HINGRL to identify novel drug–disease associations especially for new diseases.
DeepDISOBind: accurate prediction of RNA-, DNA- and protein-binding intrinsically disordered residues with deep multi-task learning
Authors: Zhang Fuhao , Zhao Bi , Shi Wenbo , Li Min , Kurgan Lukasz 
Published: November 2021

AbstractProteins with intrinsically disordered regions (IDRs) are common among eukaryotes. Many IDRs interact with nucleic acids and proteins. Annotation of these interactions is supported by computational predictors, but to date, only one tool that predicts interactions with nucleic acids was released, and recent assessments demonstrate that current predictors offer modest levels of accuracy. We have developed DeepDISOBind, an innovative deep multi-task architecture that accurately predicts deoxyribonucleic acid (DNA)-, ribonucleic acid (RNA)- and protein-binding IDRs from protein sequences. DeepDISOBind relies on an information-rich sequence profile that is processed by an innovative multi-task deep neural network, where subsequent layers are gradually specialized to predict interactions with specific partner types. The common input layer links to a layer that differentiates protein- and nucleic acid-binding, which further links to layers that discriminate between DNA and RNA interactions. Empirical tests show that this multi-task design provides statistically significant gains in predictive quality across the three partner types when compared to a single-task design and a representative selection of the existing methods that cover both disorder- and structure-trained tools. Analysis of the predictions on the human proteome reveals that DeepDISOBind predictions can be encoded into protein-level propensities that accurately predict DNA- and RNA-binding proteins and protein hubs. DeepDISOBind is available at https://www.csuligroup.com/DeepDISOBind/
Artificial intelligence in clinical research of cancers
Authors: Shao Dan , Dai Yinfei , Li Nianfeng , Cao Xuqing , Zhao Wei , Cheng Li , Rong Zhuqing , Huang Lan , Wang Yan , Zhao Jing 
Published: November 2021

AbstractSeveral factors, including advances in computational algorithms, the availability of high-performance computing hardware, and the assembly of large community-based databases, have led to the extensive application of Artificial Intelligence (AI) in the biomedical domain for nearly 20 years. AI algorithms have attained expert-level performance in cancer research. However, only a few AI-based applications have been approved for use in the real world. Whether AI will eventually be capable of replacing medical experts has been a hot topic. In this article, we first summarize the cancer research status using AI in the past two decades, including the consensus on the procedure of AI based on an ideal paradigm and current efforts of the expertise and domain knowledge. Next, the available data of AI process in the biomedical domain are surveyed. Then, we review the methods and applications of AI in cancer clinical research categorized by the data types including radiographic imaging, cancer genome, medical records, drug information and biomedical literatures. At last, we discuss challenges in moving AI from theoretical research to real-world cancer research applications and the perspectives toward the future realization of AI participating cancer treatment.
AMDBNorm: an approach based on distribution adjustment to eliminate batch effects of gene expression data
Authors: Zhang Xu , Ye Zhiqiang , Chen Jing , Qiao Feng 
Published: November 2021

Abstract
Batch effects explain a large part of the noise when merging gene expression data. Removing irrelevant variations introduced by batch effects plays an important role in gene expression studies. To obtain reliable differential analysis results, it is necessary to remove the variation caused by technical conditions between different batches while preserving biological variation. Usually, merging data directly with batch effects leads to a sharp rise in false positives. Although some methods of batch correction have been developed, they have some drawbacks. In this study, we develop a new algorithm, adjustment mean distribution-based normalization (AMDBNorm), which is based on a probability distribution to correct batch effects while preserving biological variation. AMDBNorm solves the defects of the existing batch correction methods. We compared several popular methods of batch correction with AMDBNorm using two real gene expression datasets with batch effects and analyzed the results of batch correction from the visual and quantitative perspectives. To ensure the biological variation was well protected, the effects of the batch correction methods were verified by hierarchical cluster analysis. The results showed that the AMDBNorm algorithm could remove batch effects of gene expression data effectively and retain more biological variation than other methods. Our approach provides the researchers with reliable data support in the study of differential gene expression analysis and prognostic biomarker selection.
The Nation-State: Not Yet Ready For the Dustbin of History?
Authors: Müllerson Rein 
Published: November 2021

Abstract
At the turn of the millennia, the ideas of withering away of the Nation-State became, once again, widespread. The latest wave of globalisation was supposed to lead to a borderless world, where goods, money, capital and workforce would move without hindrance. Multinational companies, non-governmental organisations (NGOs), big cities, regions (e.g., California or Bavaria), supranational entities, like the European Union, and even individuals would replace States as important decision-makers. This should have also been a triumph of liberal-democracy and the end of history à la Francis Fukuyama. This was also meant to be an American century where the only remaining superpower would lead the world either by example, by persuasion, or, if necessary, by punishing those who disobeyed. However, this was not to be the case. Excesses of globalisation, marked by financial and economic crises, the arrogant and naïve triumphalism of the West that attempted to remake the world in accordance with its own image, often using military power to carry out regime change, soon made it clear that the world is too big, complex and diverse to have its rich tapestry to be flattened into a carpet where only one pattern, be it of a Judeo-Christian, Anglo-Saxon, Confucian, Muslim or even secular liberal-democratic, would dominate. Moreover, the Nation-State, as a cradle of democracy and the main subject of international law, has made its comeback even in the Old Continent where it had emerged and was meant to make way for more progressive political arrangements. In places where the State authority was weakened or had collapsed, often as a result of foreign interference, chaos reigned instead of democracy and attempts to replace international law with imperial rule failed. It is becoming more and more obvious that democracy can be restored and reinforced by strengthening Statehood, not weakening it, and peace can be best guaranteed by balance of power between sovereign States cooperating with each other notwithstanding differences in their domestic arrangements.
Pharmacogenetics of the Late-Onset Efavirenz Neurotoxicity Syndrome (LENS)
Authors: van Rensburg Roland , Nightingale Sam , Brey Naeem , Albertyn Christine H , Kellermann Tracy A , Taljaard Jantjie J , Esterhuizen Tonya M , Sinxadi Phumla Z , Decloedt Eric H 
Published: November 2021

Abstract

Background
The late-onset efavirenz neurotoxicity syndrome (LENS) presents as ataxia and/or encephalopathy with supratherapeutic efavirenz plasma concentrations (&gt;4 µg/mL). Efavirenz is primarily metabolized by cytochrome P450 2B6 (CYP2B6), with CYP2A6 as an accessory pathway. We hypothesized that participants with LENS would predominantly be CYP2B6 slow metabolizers. The aim of our study was to determine the frequency of CYP2B6 slow metabolizers in participants with LENS.

Methods
Adult HIV-positive participants on efavirenz-based antiretroviral therapy presenting with LENS were prospectively enrolled. Genetic polymorphisms known to be associated with increased efavirenz plasma concentrations in CYP2B6 (rs3745274, rs28399499, rs4803419) and CYP2A6 (rs28399433) were selected and used to determine proportions of slow metabolizers. Pharmacokinetic analyses were performed using liquid chromatography–tandem mass spectrometry. Median (IQR) plasma efavirenz and 8-hydroxyefavirenz were described.

Results
Fifteen participants were enrolled. Thirteen (13/15) were Black-African and 13 were female. Median weight was 49.9kg with a median duration on efavirenz of 2.2 years. All 15 participants were successfully genotyped as slow CYP2B6 metabolizers, with 6 participants additionally having CYP2A6 heterozygous genotype. Thirteen were receiving the CYP2A6 enzyme inhibitor isoniazid, and all 15 were genotypic NAT2 slow or intermediate acetylators. Efavirenz plasma concentration was markedly increased at 50.5 (47.0–65.4) µg/mL; 8-hydroxyefavirenz concentration was markedly decreased at 0.10 (0.07–0.15) µg/mL.

Conclusions
Our cohort provides definitive evidence that LENS is associated with the CYP2B6 slow metabolizer genotype, with a median efavirenz plasma concentration &gt;12-fold higher than the defined upper limit of the therapeutic range. Isoniazid and low body weight are important contributors to LENS development.
Metformin induces lactate accumulation and accelerates renal cyst progression in Pkd1-deficient mice
Authors: Chang Ming-Yang , Tsai Chung-Ying , Chou Li-Fang , Hsu Shen-Hsing , Yang Huang-Yu , Hung Cheng-Chieh , Tian Ya-Chung , Ong Albert C M , Yang Chih-Wei 
Published: November 2021

Abstract
Metabolic reprogramming is a potential treatment strategy for autosomal dominant polycystic kidney disease (ADPKD). Metformin has been shown to inhibit the early stages of cyst formation in animal models. However, metformin can lead to lactic acidosis in diabetic patients with advanced chronic kidney disease, and its efficacy in ADPKD is still not fully understood. Here, we investigated the effect of metformin in an established hypomorphic mouse model of PKD that presents stable and heritable knockdown of Pkd1. The Pkd1 miRNA transgenic mice of both genders were randomized to receive metformin or saline injections. Metformin was administrated through daily intraperitoneal injection from postnatal day 35 for 4 weeks. Unexpectedly, metformin treatment at a concentration of 150 mg/kg increased disease severity, including kidney-to-body weight ratio, cystic index and plasma BUN levels, and was associated with increased renal tubular cell proliferation and plasma lactate levels. Functional enrichment analysis for cDNA microarrays from kidney samples revealed significant enrichment of several pro-proliferative pathways including β-catenin, hypoxia-inducible factor-1α, protein kinase Cα and Notch signaling pathways in the metformin-treated mutant mice. The plasma metformin concentrations were still within the recommended therapeutic range for type 2 diabetic patients. Short-term metformin treatment in a second Pkd1 hypomorphic model (Pkd1RC/RC) was however neutral. These results demonstrate that metformin may exacerbate late-stage cyst growth associated with the activation of lactate-related signaling pathways in Pkd1 deficiency. Our findings indicate that using metformin in the later stage of ADPKD might accelerate disease progression and call for the cautious use of metformin in these patients.
Something Ventured, Nothing Gained?—Remedies before the ECtHR and Their Potential for Climate Change Cases
Authors: Keller Helen , Heri Corina , Piskóty Réka 
Published: November 2021

Abstract
The European Court of Human Rights stands before what may be its greatest challenge: addressing current and impending human rights violations stemming from climate change. As the first climate cases trickle into the Court’s docket, and speculation about the Court’s response grows, many questions remain to be answered. Perhaps the matter of greatest uncertainty relates to the type and degree of redress that the Court can offer in this context. This article argues that the Court’s often deferential, inconsistent and unreasoned remedial practice is in urgent need of overhaul. It studies the Court’s remedial practice in environmental cases to draw conclusions about the Court’s existing approach to remedies and its self-perception in this context, i.e. its own understanding of the possibilities and limitations of its role. From this, it extrapolates the remedial approaches that could potentially be taken in climate cases, and discusses the advantages and disadvantages of each one.
Retrospective modelling of hospital bed capacities associated with the administration of remdesivir during the first wave of COVID-19 in a German metropolitan city
Authors: Jeck Julia , Jakobs Florian , Kron Anna , Cornely Oliver A , Kron Florian 
Published: November 2021

Abstract

Objectives
Internationally, healthcare systems are confronted by an ever-increasing scarcity of medical resources due to the ongoing novel coronavirus disease 2019 (COVID-19) pandemic. The aim of this study was to investigate the impact of remdesivir on the demand of hospital bed capacities for hospitalized COVID-19 patients and to evaluate the potentially created capacities for treating additional COVID-19 patients or elective treatments at the hospital.

Methods
An epidemiological model was developed that utilized the population of Cologne (Germany) during the first COVID-19 wave (first hospitalized patient—30 September 2020) to compare two scenarios: no administration of remdesivir (A) and the administration of remdesivir according to the EMA label (B). The results of the Adaptive COVID-19 Treatment Trial were used to evaluate the potential impact of remdesivir on hospital capacity.

Results
With the first recorded patient on 2 March 2020, a total of 576 COVID-19 hospitalized patients were detected during the first wave in Cologne. Comparing both scenarios (A versus B) of the model, the administration of remdesivir increased the number of discharges from 259 to 293 (+5.8%) and fewer patients needed ICU admission [214 versus 178 (−6.3%)]. In addition, the model estimated 20 fewer deaths (scenario B). Based on a reduced length of stay, 31.4 hospital beds (57.0 versus 25.6) could have been freed by administering remdesivir to eligible patients. This would have allowed either the treatment of an additional 730 COVID-19 patients or 660 elective treatments.

Conclusions
In our model, remdesivir administration profoundly contributed to free hospital capacities in the metropolitan city Cologne in Germany.