bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ability to increase the base of support and recover stability is limited in its generalisation for different balance perturbation tasks
Authors: Bosquée Jil , Werth Julian , Epro Gaspar , Hülsdünker Thorben , Potthast Wolfgang , Meijer Kenneth , Ellegast Rolf , Karamanidis Kiros 
Published: October 2021

Abstract
Background
The assessment of stability recovery performance following perturbations contributes to the determination of fall resisting skills. This study investigated the association between stability recovery performances in two perturbation tasks (lean-and-release versus tripping).

Methods
Healthy adults (12 young: 24 ± 3 years; 21 middle-aged: 53 ± 5 years; 11 old: 72 ± 5 years) were suddenly released from a forward-inclined position attempting to recover stability with a single step. In a second task, all participants experienced a mechanically induced trip during treadmill walking. To assess dynamic stability performance, the antero-posterior margin of stability (MoS), the base of support (BoS), and the rate of increase in BoS were determined at each foot touchdown (TD) for both tasks.

Results
Only weak to moderate correlations in dynamic stability performance parameters were found between the two tasks (0.568 > r > 0.305, 0.001 < p < 0.04). A separation of participants according to the number of steps required to regain stability in the lean-and-release task revealed that multiple- (more than one step) compared to single-steppers showed a significantly lower MoS at TD (p = 0.003; g = 1.151), lower BoS at TD (p = 0.019; g = 0.888) and lower rate of increase in BoS until TD (p = 0.002; g = 1.212) after release. Despite these profound subgroup differences in the lean-and-release task, no differences between multiple- and single-steppers were observed in the stability recovery performance during tripping.

Conclusion
The results provide evidence that the ability to effectively control dynamic stability following a sudden balance disturbance in adults across a wide age range is limited in its generalisation for different perturbation tasks.
Wavelet Screening: a novel approach to analyzing GWAS data
Authors: Denault William R. P. , Gjessing Håkon K. , Juodakis Julius , Jacobsson Bo , Jugessur Astanand 
Published: October 2021

Abstract
Background
Traditional methods for single-variant genome-wide association study (GWAS) incur a substantial multiple-testing burden because of the need to test for associations with a vast number of single-nucleotide polymorphisms (SNPs) simultaneously. Further, by ignoring more complex joint effects of nearby SNPs within a given region, these methods fail to consider the genomic context of an association with the outcome.

Results
To address these shortcomings, we present a more powerful method for GWAS, coined ‘Wavelet Screening’ (WS), that greatly reduces the number of tests to be performed. This is achieved through the use of a sliding-window approach based on wavelets to sequentially screen the entire genome for associations. Wavelets are oscillatory functions that are useful for analyzing the local frequency and time behavior of signals. The signals can then be divided into different scale components and analyzed separately. In the current setting, we consider a sequence of SNPs as a genetic signal, and for each screened region, we transform the genetic signal into the wavelet space. The null and alternative hypotheses are modeled using the posterior distribution of the wavelet coefficients. WS is enhanced by using additional information from the regression coefficients and by taking advantage of the pyramidal structure of wavelets. When faced with more complex genetic signals than single-SNP associations, we show via simulations that WS provides a substantial gain in power compared to both the traditional GWAS modeling and another popular regional association test called SNP-set (Sequence) Kernel Association Test (SKAT). To demonstrate feasibility, we applied WS to a large Norwegian cohort (N=8006) with genotypes and information available on gestational duration.

Conclusions
WS is a powerful and versatile approach to analyzing whole-genome data and lends itself easily to investigating various omics data types. Given its broader focus on the genomic context of an association, WS may provide additional insight into trait etiology by revealing genes and loci that might have been missed by previous efforts.
Activation of Toll-like receptor 2 enhances peripheral and tumor-infiltrating CD8+ T cell cytotoxicity in patients with gastric cancer
Authors: Xu Junli , Guo Rongya , Jia Jing , He Yun , He Shuixiang 
Published: October 2021

Abstract
Background
Toll-like receptors (TLRs) play central roles in the initiation of innate immune response, and also control adaptive immunity activation. Thus, the aim of the study was to investigate the regulation of TLR activation to CD8+ T cells has not been fully elucidated in gastric cancer (GC).

Materials and methods
Thirty-two GC patients and twenty-three healthy controls were enrolled. Expression profile of TLRs in peripheral and tumor-infiltrating CD8+ T cells was investigated. Purified CD8+ T cells were stimulated with Pam3Csk4, an agonist of TLR2, and cytotoxic and co-inhibitory molecules in CD8+ T cells was measured. Direct and indirect contact coculture system between CD8+ T cells and AGS cells was set up. Modulation of TLR2 activation to CD8+ T cells was assessed by measuring lactate dehydrogenase release and cytokine secretion.

Results
TLR2 mRNA and TLR2+ cell percentage was down-regulated in GC derived peripheral and tumor-infiltrating CD8+ T cells. CD8+ T cells from GC patients showed exhausted phenotype, which presented as decreased perforin/granzyme B, increased programmed death-1, and reduced cytotoxicity to AGS cells. TLR2 activation by Pam3Csk4 enhanced perforin and granzyme B expression in CD8+ T cells, however, did not affect either proinflammatory cytokine production or co-inhibitory molecules expression. Pam3Csk4 stimulation enhanced cytolytic activation of peripheral and tumor-infiltrating CD8+ T cells from GC, but not those from healthy individuals.

Conclusion
The present data revealed an important immunomodulatory activity of TLR2 to CD8+ T cells in GC patients.
Drivers of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) in nine southern African countries: a modelling study
Authors: Riou Julien , Dupont Carole , Bertagnolio Silvia , Gupta Ravindra K. , Kouyos Roger D. , Egger Matthias , L. Althaus Christian 
Published: October 2021

Abstract
Introduction
The rise of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTI) threatens antiretroviral therapy's long-term success (ART). NNRTIs will remain an essential drug for the management of HIV-1 due to safety concerns associated with integrase inhibitors. We fitted a dynamic transmission model to historical data from 2000 to 2018 in nine countries of southern Africa to understand the mechanisms that have shaped the HIV-1 epidemic and the rise of pretreatment NNRTI resistance.

Methods
We included data on HIV-1 prevalence, ART coverage, HIV-related mortality, and survey data on pretreatment NNRTI resistance from nine southern Africa countries from a systematic review, UNAIDS and World Bank. Using a Bayesian hierarchical framework, we developed a dynamic transmission model linking data on the HIV-1 epidemic to survey data on NNRTI drug resistance in each country. We estimated the proportion of resistance attributable to unregulated, off-programme use of ART. We examined each national ART programme's vulnerability to NNRTI resistance by defining a fragility index: the ratio of the rate of NNRTI resistance emergence during first-line ART over the rate of switching to second-line ART. We explored associations between fragility and characteristics of the health system of each country.

Results
The model reliably described the dynamics of the HIV-1 epidemic and NNRTI resistance in each country. Predicted levels of resistance in 2018 ranged between 3.3% (95% credible interval 1.9–7.1) in Mozambique and 25.3% (17.9–33.8) in Eswatini. The proportion of pretreatment NNRTI resistance attributable to unregulated antiretroviral use ranged from 6% (2–14) in Eswatini to 64% (26–85) in Mozambique. The fragility index was low in Botswana (0.01; 0.0–0.11) but high in Namibia (0.48; 0.16–10.17), Eswatini (0.64; 0.23–11.8) and South Africa (1.21; 0.83–9.84). The combination of high fragility of ART programmes and high ART coverage levels was associated with a sharp increase in pretreatment NNRTI resistance.

Conclusions
This comparison of nine countries shows that pretreatment NNRTI resistance can be controlled despite high ART coverage levels. This was the case in Botswana, Mozambique, and Zambia, most likely because of better HIV care delivery, including rapid switching to second-line ART of patients failing first-line ART.
Variations in disease burden of laryngeal cancer attributable to alcohol use and smoking in 204 countries or territories, 1990–2019
Authors: Zhang Qiang-Wei , Wang Jing-Yuan , Qiao Xiao-Feng , Li Tong-Li , Li Xin 
Published: October 2021

Abstract
Background
Alcohol consumption and smoking are the leading risk factors for laryngeal cancer (LC). Understanding the variations in disease burden of LC attributable to alcohol use and smoking is critical for LC prevention.

Methods
Disease burden data of LC were retrieved from the Global Burden of Disease Study 2019. We used estimated average percentage change (EAPC) to measure the temporal trends of the age-standardized mortality rate (ASMR) of LC.

Results
Globally, while the ASMR of LC decreased by 1.49% (95% CI, 1.41–1.57%) per year between 1990 and 2019, the number of deaths from LC has increased 41.0% to 123.4 thousand in 2019. In 2019, 19.4 and 63.5% of total LC-related deaths were attributable to alcohol use and smoking worldwide, respectively. The ASMR of alcohol- and smoking-related LC decreased by 1.78 and 1.93% per year, whereas the corresponding death number has increased 29.2 and 25.1% during this period, respectively. The decreasing trend was more pronounced in developed countries. In some developing countries, such as Guinea and Mongolia, the LC mortality has shown an unfavorable trend.

Conclusion
The ubiquitous decrease in LC mortality was largely attributed to the smoking control and highlighted the importance of smoking control policies. However, the disease burden of LC remained in increase and more effective strategies are needed to combat the global increase of alcohol consumption.
Stapled versus hand-sewn intestinal anastomosis in pediatric patients: a systematic review and meta-analysis
Authors: Fujii Takayuki , Tanaka Aya , Katami Hiroto , Shimono Ryuichi 
Published: October 2021

Abstract
Background
The safety and feasibility of stapled intestinal anastomosis have been widely reported in adults. However, the efficacy of stapled anastomosis (SA) in children is unclear. The aim of this study was to perform a systematic review and meta-analysis to evaluate the safety and effectiveness of SA compared with hand-sewn anastomosis (HA) in pediatric patients.

Methods
A systematic literature search was performed using PubMed, the Cochrane Library, and Scopus databases. Studies comparing outcomes of children aged < 7 years and subgroups of children aged < 1 year who underwent SA or HA were included. Primary outcomes were anastomotic leakage and anastomotic stricture. Mean differences (MDs) with 95 % confidence intervals (CIs) were calculated for continuous variables. Odds ratios (ORs) with 95 % CIs were calculated for dichotomous variables. Interstudy heterogeneity was assessed using the chi-squared test and was quantified using the I² statistic.

Results
One randomized control trial and five retrospective cohort studies, comprising 633 cases (229 SA cases and 404 HA cases), were included. No significant differences were observed in anastomotic leakage (6.5 % vs. 7.4 %; OR, 0.93; 95 % CI, 0.37–2.34; p = 0.88), anastomotic stricture (4.1 % vs. 9.3 %; OR, 0.54; 95 % CI, 0.19–1.51; p = 0.24), ileus (7.1 % vs. 9.3 %, OR, 2.35; 95 % CI, 0.15–37.51; p = 0.54), anastomosis-related complications (9.5 % vs. 10.9 %, OR, 0.98; 95 % CI, 0.52–1.86; p = 0.96; I2 = 39 %), and time until full-feeding (MD = -3.57 days; 95 % CI, -11.36 to 4.23; p = 0.37) between SA and HA. Operative time was significantly shorter in SA than in HA in children aged < 1 year (MD = -20.36 min; 95 % CI, -26.13 to -14.59).

Conclusions
SA required shorter operative time and was comparable to HA in the overall complication rate. Although the evidence was insufficient, SA could be an option for intestinal anastomosis in children.
Firearm laws and the network of firearm movement among US states
Authors: Takada Sae , Choi Kristen R. , Natsui Shaw , Saadi Altaf , Buchbinder Liza , Easterlin Molly , Zimmerman Frederick J. 
Published: October 2021

Abstract
Background
The movement of firearm across state lines may decrease the effectiveness of state-level firearm laws. Yet, how state-level firearm policies affect cross-state movement have not yet been widely explored. This study aims to characterize the interstate movement of firearms and its relationship with state-level firearm policies.

Methods
We analyzed the network of interstate firearm movement using Bureau of Alcohol, Tobacco, Firearms, and Explosives firearm trace data (2010–2017). We constructed the network of firearm movement between 50 states. We used zero-inflated negative binomial regression to estimate the relationship between the number of a state’s firearm laws and number of states for which it was the source of 100 or more firearms, adjusting for state characteristics. We used a similar model to examine the relationship between firearm laws and the number of states for which a given state was the destination of 100 or more firearms.

Results
Over the 8-year period, states had an average of 26 (Standard Deviation [SD] 25.2) firearm laws. On average, a state was the source of 100 or more crime-related firearms for 2.2 (SD 2.7) states and was the destination of 100 or more crime-related firearms for 2.2 (SD 3.4) states. Greater number of firearm laws was associated with states being the source of 100 or more firearms to fewer states (Incidence Rate Ratio [IRR] 0.58 per SD, p < 0.001) and being the destination of 100 or more firearms from more states (IRR1.73 per SD, p < 0.001).

Conclusions
Restrictive state-level firearm policies are associated with less movement of firearms to other states, but with more movement of firearms from outside states. The effectiveness of state-level firearm-restricting laws is complicated by a network of interstate firearm movement.
Physicochemical characterization, cytotoxic effect and toxicity evaluation of nanostructured lipid carrier loaded with eucalyptol
Authors: Izham Mira Nadiah Mohd , Hussin Yazmin , Rahim Nurul Fattin Che , Aziz Muhammad Nazirul Mubin , Yeap Swee Keong , Rahman Heshu Sulaiman , Masarudin Mas Jaffri , Mohamad Nurul Elyani , Abdullah Rasedee , Alitheen Noorjahan Banu 
Published: October 2021

Abstract
Background
Eucalyptol is an active compound of eucalyptus essential oil and was reported to have many medical attributes including cytotoxic effect on breast cancer cells. However, it has low solubility in aqueous solutions which limits its bioavailability and cytotoxic efficiency. In this study, nanostructured lipid carrier loaded with eucalyptol (NLC-Eu) was formulated and characterized and the cytotoxic effect of NLC-Eu towards breast cancer cell lines was determined. In addition, its toxicity in animal model, BALB/c mice was also incorporated into this study to validate the safety of NLC-Eu.

Methods
Eucalyptol, a monoterpene oxide active, was used to formulate the NLC-Eu by using high pressure homogenization technique. The physicochemical characterization of NLC-Eu was performed to assess its morphology, particle size, polydispersity index, and zeta potential. The in vitro cytotoxic effects of this encapsulated eucalyptol on human (MDA MB-231) and murine (4 T1) breast cancer cell lines were determined using the MTT assay. Additionally, acridine orange/propidium iodide assay was conducted on the NLC-Eu treated MDA MB-231 cells. The in vivo sub-chronic toxicity of the prepared NLC-Eu was investigated using an in vivo BALB/c mice model.

Results
As a result, the light, translucent, milky-colored NLC-Eu showed particle size of 71.800 ± 2.144 nm, poly-dispersity index of 0.258 ± 0.003, and zeta potential of − 2.927 ± 0.163 mV. Furthermore, the TEM results of NLC-Eu displayed irregular round to spherical morphology with narrow size distribution and relatively uniformed particles. The drug loading capacity and entrapment efficiency of NLC-Eu were 4.99 and 90.93%, respectively. Furthermore, NLC-Eu exhibited cytotoxic effects on both, human and mice, breast cancer cells with IC50 values of 10.00 ± 4.81 μg/mL and 17.70 ± 0.57 μg/mL, respectively at 72 h. NLC-Eu also induced apoptosis on the MDA MB-231 cells. In the sub-chronic toxicity study, all of the studied mice did not show any signs of toxicity, abnormality or mortality. Besides that, no significant changes were observed in the body weight, internal organ index, hepatic and renal histopathology, serum biochemistry, nitric oxide and malondialdehyde contents.

Conclusions
This study suggests that the well-characterized NLC-Eu offers a safe and promising carrier system which has cytotoxic effect on breast cancer cell lines.
Learning to diagnose accurately through virtual patients: do reflection phases have an added benefit?
Authors: Fink Maximilian C. , Heitzmann Nicole , Siebeck Matthias , Fischer Frank , Fischer Martin R. 
Published: October 2021

Abstract
Background
Simulation-based learning with virtual patients is a highly effective method that could potentially be further enhanced by including reflection phases. The effectiveness of reflection phases for learning to diagnose has mainly been demonstrated for problem-centered instruction with text-based cases, not for simulation-based learning. To close this research gap, we conducted a study on learning history-taking using virtual patients. In this study, we examined the added benefit of including reflection phases on learning to diagnose accurately, the associations between knowledge and learning, and the diagnostic process.

Methods
A sample of N = 121 medical students completed a three-group experiment with a control group and pre- and posttests. The pretest consisted of a conceptual and strategic knowledge test and virtual patients to be diagnosed. In the learning phase, two intervention groups worked with virtual patients and completed different types of reflection phases, while the control group learned with virtual patients but without reflection phases. The posttest again involved virtual patients. For all virtual patients, diagnostic accuracy was assessed as the primary outcome. Current hypotheses were tracked during reflection phases and in simulation-based learning to measure diagnostic process.

Results
Regarding the added benefit of reflection phases, an ANCOVA controlling for pretest performance found no difference in diagnostic accuracy at posttest between the three conditions, F(2, 114) = 0.93, p = .398. Concerning knowledge and learning, both pretest conceptual knowledge and strategic knowledge were not associated with learning to diagnose accurately through reflection phases. Learners’ diagnostic process improved during simulation-based learning and the reflection phases.

Conclusions
Reflection phases did not have an added benefit for learning to diagnose accurately in virtual patients. This finding indicates that reflection phases may not be as effective in simulation-based learning as in problem-centered instruction with text-based cases and can be explained with two contextual differences. First, information processing in simulation-based learning uses the verbal channel and the visual channel, while text-based learning only draws on the verbal channel. Second, in simulation-based learning, serial cue cases are used to gather information step-wise, whereas, in text-based learning, whole cases are used that present all data at once.
Equitable data sharing in epidemics and pandemics
Authors: Pratt Bridget , Bull Susan 
Published: October 2021

Abstract
Background
Rapid data sharing can maximize the utility of data. In epidemics and pandemics like Zika, Ebola, and COVID-19, the case for such practices seems especially urgent and warranted. Yet rapidly sharing data widely has previously generated significant concerns related to equity. The continued lack of understanding and guidance on equitable data sharing raises the following questions: Should data sharing in epidemics and pandemics primarily advance utility, or should it advance equity as well? If so, what norms comprise equitable data sharing in epidemics and pandemics? Do these norms address the equity-related concerns raised by researchers, data providers, and other stakeholders? What tensions must be balanced between equity and other values?

Methods
To explore these questions, we undertook a systematic scoping review of the literature on data sharing in epidemics and pandemics and thematically analyzed identified literature for its discussion of ethical values, norms, concerns, and tensions, with a particular (but not exclusive) emphasis on equity. We wanted to both understand how equity in data sharing is being conceptualized and draw out other important values and norms for data sharing in epidemics and pandemics.

Results
We found that values of utility, equity, solidarity, and reciprocity were described, and we report their associated norms, including researcher recognition; rapid, real-time sharing; capacity development; and fair benefits to data generators, data providers, and source countries. The value of utility and its associated norms were discussed substantially more than others. Tensions between utility norms (e.g., rapid, real-time sharing) and equity norms (e.g., researcher recognition, equitable access) were raised.

Conclusions
This study found support for equity being advanced by data sharing in epidemics and pandemics. However, norms for equitable data sharing in epidemics and pandemics require further development, particularly in relation to power sharing and participatory approaches prioritizing inclusion. Addressing structural inequities in the wider global health landscape is also needed to achieve equitable data sharing in epidemics and pandemics.