bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Validity of a Serious Game (VirtualTer) for Postural Balance Rehabilitation in Older Adults
Authors: Medeiros Candice Simões Pimenta de , Pacheco Thaiana Barbosa Ferreira , Dantas Rummenigge Rudson , Cavalcanti Fabrícia Azevêdo da Costa 
Published: November 2021

Background Physiological changes resulting from aging can impair postural balance. Exergames have been used to treat balance disorders, enabling sensory-motor training due to their content, and with targeted goals and purposes beyond entertainment. Aim The aim of this investigation was to describe the development of a serious game, VirtualTer, and to test content validity. Methods A Brazilian group from the Federal University of Rio Grande do Norte developed a serious game called VirtualTer for postural balance rehabilitation in older adults. In game navigation, the avatar needed to save the environment from catching harmful energy that destroys nature. The avatar performs stationary walking, lateral reaching, and climbing up and down steps to capture the energies. Content validity was determined using content matter experts by the Delphi method. Eleven content matter experts played the game and expressed their opinions using the assessment instruments: VirtualTer Dimensions (VD) and System Usability Scale (SUS). Results VirtualTer was designed with regard to variability in practice, since the game was constructed under three levels and offers continuous and terminal feedback. The participants needed to achieve at least 70% of the total score to advance to the next phase. The limits of stability for lateral reach test were right 23.2 ± 4.77 cm and left 22.9 ± 4.86 cm, which was applied in the game. The content validity index of the VD was 0.8, and Cronbach’s alpha coefficient was 0.924. The content matter experts reported the game as having a 67.73 satisfaction with the SUS. Conclusion This game has good usability, low-cost investment, and supports access to innovative and valid technology for rehabilitation in countries with little investment in technology for health.
Missed nursing care and complexity theory: a conceptual paper
Authors: Albsoul Rania Ali , FitzGerald Gerard , Hughes James A , Ahmed Alshyyab Muhammad 
Published: November 2021

Background Missed nursing care is a complex healthcare problem. Extant literature in this area identifies several interventions that can be used in acute hospital settings to minimise the impact of missed nursing care. However, controversy still exists as to the effectiveness of these interventions on reducing the occurrence of missed nursing care. Aim This theoretical paper aimed to provide a conceptual understanding of missed nursing care using complexity theory. Methods The method utilised for this paper is based on a literature review on missed care and complexity theory in healthcare. Results We found that the key virtues of complexity theory relevant to the missed nursing care phenomenon were adaptation and self-organisation, non-linear interactions and history. It is suggested that the complex adaptive systems approach may be more useful for nurse managers to inform and prepare nurses to meet uncertain encounters in their everyday clinical practice and therefore reduce instances of missed care. Conclusions This paper envisions that it is time that methods used to explore missed care changed. Strategies proposed in this paper may have an important impact on the ability of nursing staff to provide quality and innovative healthcare in the modern healthcare system.
Long non-coding RNA TUG1 promotes proliferation and migration in PDGF-BB-stimulated HASMCs by regulating miR-216a-3p/SMURF2 axis
Authors: Wang Xinfang , Chen Junsong 
Published: November 2021

Abstract
Background
Abnormal proliferation and migration of human airway smooth muscle cells (HASMCs) play an important role in the development of childhood asthma. Long non-coding RNAs (lncRNAs) have been demonstrated to participate in HASMC proliferation and migration. We aimed to explore more effects and molecular mechanism of taurine upregulated gene 1 (TUG1) in childhood asthma.

Results
TUG1 and SMURF2 were overexpressed and miR-216a-3p was downregulated in childhood asthma patients and PDGF-BB-stimulated HASMCs. TUG1 knockdown attenuated PDGF-BB-triggered proliferation and migration of HASMCs. MiR-216a-3p was targeted by TUG1, and miR-216a-3p suppression counteracted the repressive effects of TUG1 interference on proliferation and migration in PDGF-BB-treated HASMCs. SMURF2 was a downstream target of miR-216a-3p, and SMURF2 upregulation abated the inhibiting effects of miR-216a-3p on migration and proliferation in PDGF-BB-exposed HASMCs. TUG1 sponged miR-216a-3p to positively regulate SMURF2 expression.

Conclusion
TUG1 downregulation inhibited PDGF-BB-induced HASMC proliferation and migration by regulating miR-216a-3p/SMURF2 axis, offering novel insight into the potential application of TUG1 for childhood asthma treatment.
RETRACTED ARTICLE: The association between neutrophil–lymphocyte ratio and poor outcomes following infant cardiac surgery
Authors: Gao Peng , Liu Jinping , Wang Xu , Zhang Peiyao , Jin Yu , Bai Liting , Li Yixuan 
Published: November 2021

Abstract
Background
Neutrophil–lymphocyte ratio (NLR) is a valuable indicator for evaluating inflammation and adverse outcomes after cardiac surgery. The objective of this study was to evaluate the association of perioperative NLR with clinical outcomes in infants undergoing congenital heart surgery with cardiopulmonary bypass.

Methods
We performed a retrospective review of 424 consecutive infants (≤ 1 year) undergoing cardiac surgery between January 2019 and September 2019. Neonates (≤ 28 days) and patients with incomplete NLR data were excluded. The study endpoint was a composite of poor outcomes after surgery. We assess the correlation between perioperative NLR and clinical outcomes. A receiver operating characteristic curve and multivariable logistic regression were applied to identify the prognosis performance of postoperative NLR for poor outcomes.

Results
A total of 68 (16%) infants experienced at least one of the poor outcomes. Postoperative NLR on the third day after the surgery showed the best prognostic significance (AUC = 0.763, 95%CI 0.700–0.826) among perioperative period, with a cut-off value of 2.05. Postoperative NLR was also strongly correlated with mechanical ventilation time, length of ICU and hospital stay (p < 0.001). Multivariable logistic regression revealed that elevated postoperative NLR (OR 3.722, 95%CI 1.895–7.309, p < 0.001) was an independent risk factor for poor outcomes in infants after cardiac surgery.

Conclusions
Postoperative NLR was correlated with increased mechanical ventilation time, length of ICU and hospital stay. Elevated postoperative NLR was an independent predictor for poor outcomes after cardiac surgery in infants.
Frequency and characteristics of promissory conference abstracts, i.e. abstracts without results, accepted at Cochrane Colloquia 1994-2020
Authors: Novak Darko , Puljak Livia 
Published: November 2021

Abstract
Background
The purpose of a conference abstract is to summarize the main points of a research-related report that will be presented at an academic conference. However, some conferences accept and publish abstracts without results, which is contrary to the basic idea of a conference abstract as a dissemination tool. A conference abstract without results included is called a “promissory abstract”. This study aimed to analyze the frequency and characteristics of promissory conference abstracts, i.e. abstracts submitted without results, accepted at Cochrane Colloquia.

Methods
We analyzed 8297 conference abstracts accepted at 25 Cochrane Colloquia, organized in 1994–2020, which were publicly available on the website of the Cochrane Library. Two authors screened abstracts to identify promissory abstracts. We extracted characteristics of promissory abstracts.

Results
Among abstracts accepted for Cochrane Colloquia, 8.7% were promissory; 475 (66%) were accepted as poster presentations, 241 (34%) as oral presentations and 1 as a workshop. The median number of authors in promissory abstracts was 4 (interquartile range: 3 to 6 authors). In 245 (34%) promissory abstracts, affiliations of authors were not reported. The authors were most commonly affiliated with the following countries: UK (472; 36%), Canada (N = 123; 26%), China (N = 76; 16%), United States (N = 66; 14%) and Australia (N = 53; 11%). There were 512 (71%) promissory abstracts in which study design was not reported.

Conclusion
Promissory abstracts were commonly accepted at Cochrane Colloquia. Such abstracts deserve further attention, as they are detrimental in terms of the dissemination of new knowledge presented at a conference. Conference organizers could ask authors to update the abstract results subsequently to enable the dissemination of information presented at a conference.
PGRMC1-dependent lipophagy promotes ferroptosis in paclitaxel-tolerant persister cancer cells
Authors: You Ji Hyeon , Lee Jaewang , Roh Jong-Lyel 
Published: November 2021

Abstract
Background
Progesterone receptor membrane component 1 (PGRMC1) is a heme-binding protein inducing dimerization with cytochrome P450, which mediates chemoresistance. Increased PGRMC1 expression is found in multiple types of resistant cancers, but the role of PGRMC1 in the ferroptosis of cancer cells remains unrevealed. Therefore, we examined the role of PGRMC1 in promoting ferroptosis in paclitaxel-tolerant persister cancer cells (PCC).

Methods
The effects of ferroptosis inducers and PGRMC1 gene silencing/overexpression were tested on head and neck cancer (HNC) cell lines and mouse tumor xenograft models. The results were analyzed about cell viability, death, lipid ROS and iron production, mRNA/protein expression and interaction, and lipid assays.

Results
PCC had more free fatty acids, lipid droplets, and fatty acid oxidation (FAO) than their parental cells. PCC was highly sensitive to inhibitors of system xc− cystine/glutamate antiporter (xCT), such as erastin, sulfasalazine, and cyst(e)ine deprivation, but less sensitive to (1S,3R)-RSL3. PGRMC1 silencing in PCC reduced ferroptosis sensitivity by xCT inhibitors, and PGRMC1 overexpression in parental cells increased ferroptosis by xCT inhibitors. Lipid droplets were degraded along with autophagy induction and autophagosome formation by erastin treatment in PCC. Lipophagy was accompanied by increased tubulin detyrosination, which was increased by SIRT1 activation but decreased by SIRT1 inhibition. FAO and lipophagy were also promoted by the interaction between lipid droplets and mitochondria.

Conclusion
PGRMC1 expression increased FAO and ferroptosis sensitivity from in vivo mice experiments. Our data suggest that PGRMC1 promotes ferroptosis by xCT inhibition in PCC.
Beech tree masting explains the inter-annual variation in the fall and spring peaks of Ixodes ricinus ticks with different time lags
Authors: Bregnard Cindy , Rais Olivier , Herrmann Coralie , Kahl Olaf , Brugger Katharina , Voordouw Maarten J. 
Published: November 2021

AbstractBackgroundThe tickIxodes ricinusis an important vector of tick-borne diseases including Lyme borreliosis. In continental Europe, the nymphal stage ofI. ricinusoften has a bimodal phenology with a large spring peak and a smaller fall peak. There is consensus about the origin of the spring nymphal peak, but there are two alternative hypotheses for the fall nymphal peak. In the direct development hypothesis, larvae quest as nymphs in the fall of the same year that they obtained their larval blood meal. In the developmental diapause hypothesis, larvae overwinter in the engorged state and quest as nymphs one year after they obtained their larval blood meal. These two hypotheses make different predictions about the time lags that separate the larval blood meal and the density of questing nymphs (DON) in the spring and fall.MethodsInter-annual variation in seed production (masting) by deciduous trees is a time-lagged index for the density of vertebrate hosts (e.g., rodents) which provide blood meals for larval ticks. We used a long-term data set on the masting of the European beech tree and a 15-year study on the DON at 4 different elevation sites in western Switzerland to differentiate between the two alternative hypotheses for the origin of the fall nymphal peak.ResultsQuestingI. ricinusnymphs had a bimodal phenology at the three lower elevation sites, but a unimodal phenology at the top elevation site. At the lower elevation sites, the DON in the fall was strongly correlated with the DON in the spring of the following year. The inter-annual variation in the densities ofI. ricinusnymphs in the fall and spring was best explained by a 1-year versus a 2-year time lag with the beech tree masting index. Fall nymphs had higher fat content than spring nymphs indicating that they were younger. All these observations are consistent with the direct development hypothesis for the fall peak ofI. ricinusnymphs at our study site. Our study provides new insight into the complex bimodal phenology of this important disease vector.ConclusionsPublic health officials in Europe should be aware that following a strong mast year, the DON will increase 1 year later in the fall and 2 years later in the spring. Studies ofI. ricinuspopulations with a bimodal phenology should consider that the spring and fall peak in the same calendar year represent different generations of ticks.Graphical Abstract
Global diversity of the gene encoding the Pfs25 protein—a Plasmodium falciparum transmission-blocking vaccine candidate
Authors: Sookpongthai Pornpawee , Utayopas Korawich , Sitthiyotha Thassanai , Pengsakul Theerakamol , Kaewthamasorn Morakot , Wangkanont Kittikhun , Harnyuttanakorn Pongchai , Chunsrivirot Surasak , Pattaradilokrat Sittiporn 
Published: November 2021

AbstractBackgroundVaccines against the sexual stages of the malarial parasitePlasmodium falciparumare indispensable for controlling malaria and abrogating the spread of drug-resistant parasites. Pfs25, a surface antigen of the sexual stage ofP. falciparum, is a leading candidate for transmission-blocking vaccine development. While clinical trials have reported that Pfs25-based vaccines are safe and effective in inducing transmission-blocking antibodies, the extent of the genetic diversity ofPfs25in malaria endemic populations has rarely been studied. Thus, this study aimed to investigate the global diversity ofPfs25inP. falciparumpopulations.MethodsA database of 307Pfs25sequences ofP. falciparumwas established. Population genetic analyses were performed to evaluate haplotype and nucleotide diversity, analyze haplotypic distribution patterns ofPfs25in different geographical populations, and construct a haplotype network. Neutrality tests were conducted to determine evidence of natural selection. Homology models of thePfs25haplotypes were constructed, subjected to molecular dynamics (MD), and analyzed in terms of flexibility and percentages of secondary structures.ResultsThePfs25gene ofP. falciparumwas found to have 11 unique haplotypes. Of these, haplotype 1 (H1) and H2, the major haplotypes, represented 70% and 22% of the population, respectively, and were dominant in Asia, whereas only H1 was dominant in Africa, Central America, and South America. Other haplotypes were rare and region-specific, resulting in unique distribution patterns in different geographical populations. The diversity inPfs25originated from ten single-nucleotide polymorphism (SNP) loci located in the epidermal growth factor (EGF)-like domains and anchor domain. Of these, an SNP at position 392 (GGA/GCA), resulting in amino acid substitution 131 (Gly/Ala), defined the two major haplotypes. The MD results showed that the structures of H1 and H2 variants were relatively similar. Limited polymorphism inPfs25could likely be due to negative selection.ConclusionsThe study successfully established aPfs25sequence database that can become an essential tool for monitoring vaccine efficacy, designing assays for detecting malaria carriers, and conducting epidemiological studies ofP. falciparum. The discovery of the two major haplotypes, H1 and H2, and their conserved structures suggests that the current Pfs25-based vaccines could be used globally for malaria control.Graphical Abstract
Multiscale heterogeneity in gastric adenocarcinoma evolution is an obstacle to precision medicine
Authors: Röcken Christoph , Amallraja Anu , Halske Christine , Opasic Luka , Traulsen Arne , Behrens Hans-Michael , Krüger Sandra , Liu Anne , Haag Jochen , Egberts Jan-Hendrik , Rosenstiel Philip , Meißner Tobias 
Published: November 2021

Abstract
Background
Cancer is a somatic evolutionary disease and adenocarcinomas of the stomach and gastroesophageal junction (GC) may serve as a two-dimensional model of cancer expansion, in which tumor subclones are not evenly mixed during tumor progression but rather spatially separated and diversified. We hypothesize that precision medicine efforts are compromised when clinical decisions are based on a single-sample analysis, which ignores the mechanisms of cancer evolution and resulting intratumoral heterogeneity. Using multiregional whole-exome sequencing, we investigated the effect of somatic evolution on intratumoral heterogeneity aiming to shed light on the evolutionary biology of GC.

Methods
The study comprised a prospective discovery cohort of 9 and a validation cohort of 463 GCs. Multiregional whole-exome sequencing was performed using samples form 45 primary tumors and 3 lymph node metastases (range 3–10 tumor samples/patient) of the discovery cohort.

Results
In total, the discovery cohort harbored 16,537 non-synonymous mutations. Intratumoral heterogeneity of somatic mutations and copy number variants were present in all tumors of the discovery cohort. Of the non-synonymous mutations, 53–91% were not present in each patient’s sample; 399 genes harbored 2–4 different non-synonymous mutations in the same patient; 175 genes showed copy number variations, the majority being heterogeneous, including CD274 (PD-L1). Multi-sample tree-based analyses provided evidence for branched evolution being most complex in a microsatellite instable GC. The analysis of the mode of evolution showed a high degree of heterogeneity in deviation from neutrality within each tumor. We found evidence of parallel evolution and evolutionary trajectories: different mutations of SMAD4 aligned with different subclones and were found only in TP53 mutant GCs.

Conclusions
Neutral and non-neutral somatic evolution shape the mutational landscape in GC along its lateral expansions. It leads to complex spatial intratumoral heterogeneity, where lymph node metastases may stem from different areas of the primary tumor, synchronously. Our findings may have profound effects on future patient management. They illustrate the risk of mis-interpreting tumor genetics based on single-sample analysis and open new avenues for an evolutionary classification of GC, i.e., the discovery of distinct evolutionary trajectories which can be utilized for precision medicine.
Patient-focused pathogen genetic counselling—has the time come?
Authors: Ferdinand Angeline S , Hocking Jane S , Denholm Justin T. , Howden Benjamin P. , Williamson Deborah A. 
Published: November 2021

AbstractEnsuring accordance with principles of healthcare ethics requires improved communication of pathogen genomic data. This could include educating healthcare professionals in communicating pathogen genomic information to individuals, developing ethical frameworks for reporting pathogen genomic results to individuals, responsible media reporting guidelines, and counselling for individuals (‘pathogen genetic counselling’).
Disseminated tuberculosis with myelofibrosis presentation: a case report
Authors: Khatuni Mahdi , Ghalamkari Marziyeh , Ameli Fereshteh , Yekehtaz Habibeh 
Published: November 2021

Abstract
Background
Primary myelofibrosis is a rare myeloproliferative disorder in middle-aged and old adults and should be distinguished from secondary and reactive causes of bone marrow fibrosis because, in reactive fibrosis, treatment approaches depend on the underlying etiology.

Case presentation
Here we report the case of a middle-aged Iranian man who was diagnosed and treated as primary myelofibrosis at presentation, and whose final diagnosis was disseminated tuberculosis with reactive bone marrow fibrosis.

Conclusions
It is prudent to evaluate the potential causes of myelofibrosis in any patient with the diagnosis primary myelofibrosis. Tuberculosis can be an important etiology of bone marrow fibrosis, especially in endemic areas.
Alternative method’s results for the non targeted determination of xenobiotics in food by means of high resolution and accuracy mass spectrometry
Authors: Scarpone Rossana , Rocchi Rachele , Bacà Federico , Rosato Roberta , Chiumiento Francesco , Migliorati Giacomo 
Published: November 2021

AbstractThe application of a high resolution and accurate mass spectrometry (HRAMS) approach to detect xenobiotics in different food matrices by means of non targeted determination by UHPLC-Orbitrap followed by data processing analysis was described. Three case studies were reported to demonstrate the possibility to identify unexpected substances in different food commodities overcomes targeted method. This innovative approach could lay the foundation for its applicability to routine analysis in the near future giving the possibility to open new horizons to the research of a wide range of xenobiotics.
What motivates informal carers to be actively involved in research, and what obstacles to involvement do they perceive?
Authors: Malm Camilla , Andersson Stefan , Kylén Maya , Iwarsson Susanne , Hanson Elizabeth , Schmidt Steven M. 
Published: November 2021

Abstract
Background
Due to demographic changes and a strained public sector operating in many countries globally, informal care is increasing. Currently, at least 1.3 million adults in Sweden regularly provide help, support and/or care to a family member/significant other. With no sign of an imminent decrease in their caring activities, it is important that informal carers are considered as a key stakeholder group within research that affects them, e.g., the co-design of carer and/or dyadic support interventions. The objective of this descriptive, quantitative study was to investigate informal carers’ perceived motivations and obstacles to become involved in research.

Methods
A cross-sectional survey design was adopted, using first-wave data from a panel study. The data, collected in Sweden between September 2019 and March 2020, included survey responses from 147 informal carers who were either aged 60+ years themselves or were caring for someone who was aged 60+ years.

Results
Our main results showed that informal carers are, in general, interested in research. Slightly fewer were interested in becoming actively involved themselves, but older age was the only characteristic significantly associated with less interest of being actively involved. Two latent motivational dimensions emerged from the factor analysis: ‘family motivation’ and ‘the greater good motivation’. These, according to our results, almost equally valued dimensions, described the differing reasons for informal carers to become involved in research. The most common perceived obstacle was lack of time and it was reported by more women than men.

Conclusion
Our study contributes with new knowledge of informal carers’ perceived motivations and obstacles regarding carer involvement in research. Paying attention to the differing motivational dimensions held by informal carers could help researchers create conditions for more inclusive and systematic participation of informal carers within research. Thereby, increasing the opportunities for research that is deemed to be of higher societal impact. IRRID (International Registered Report Identifier): RR2-10.2196/17759.