bluuebunny/crossref_metadata_2025 huggingface dataset:
Additive manufacturing with fibre-reinforcement – design guidelines and investigation into the influence of infill patterns
Authors: Plocher Janos , Wioland Jean-Baptiste , Panesar Ajit Singh
Published: February 2022

Purpose

Fibre-reinforced additive manufacturing (FRAM) with short and continuous fibres yields light and stiff parts and thus increasing industry acceptance. High material anisotropy and specific manufacturing constraints shift the focus towards design for AM (DfAM), particularly on toolpath strategies. Assessing the design-property-processing relations of infill patterns is fundamental to establishing design guidelines for FRAM.

Design/methodology/approach

Subject to the DfAM factors performance, economy and manufacturability, the efficacy of two conventional infill patterns (grid and concentric) was compared with two custom strategies derived from the medial axis transformation (MAT) and guided by the principal stresses (MPS). The recorded stiffness and strength, the required CPU and print time, and the degree of path undulation and effective fibre utilisation (minimum printable fibre length) associated with each pattern, served as assessment indices for different case studies. Moreover, the influence of material anisotropy was examined, and a stiffness-alignment index was introduced to predict a pattern’s performance.

Findings

The highest stiffnesses and strengths were recorded for the MPS infill, emphasising the need for tailoring print paths rather than using fixed patterns. In contrast to the grid infill, the concentric infill offered short print times and reasonable utilisation of continuous fibres. The MAT-based infill yielded an excellent compromise between the three DfAM factors and experimentally resulted in the best performance.

Originality/value

This constitutes the first comprehensive investigation into infill patterns under DfAM consideration for FRAM, facilitating design and processing choices.
Propagule size and sex ratio influence colonisation dynamics after introduction of a non‐native lizard
Authors: Fargevieille Amélie , Reedy Aaron M. , Kahrl Ariel F. , Mitchell Timothy S. , Durso Andrew M. , Delaney David M. , Pearson Phillip R. , Cox Robert M. , Warner Daniel A.
Published: February 2022

The composition of founding populations plays an important role in colonisation dynamics and can influence population growth during early stages of biological invasion. Specifically, founding populations with small propagules (i.e. low number of founders) are vulnerable to the Allee effect and have reduced likelihood of establishment compared to those with large propagules. The founding sex ratio can also impact establishment via its influence on mating success and offspring production.

Our goal was to test the effects of propagule size and sex ratio on offspring production and annual population growth following introductions of a non‐native lizard species (Anolis sagrei). We manipulated propagule composition on nine small islands, then examined offspring production, population growth and survival rate of founders and their descendants encompassing three generations.

By the third reproductive season, per capita offspring production was higher on islands seeded with a relatively large propagule size, but population growth was not associated with propagule size. Propagule sex ratio did not affect offspring production, but populations with a female‐biased propagule had positive growth, whereas those with a male‐biased propagule had negative growth in the first year. Populations were not affected by propagule sex ratio in subsequent years, possibly due to rapid shifts towards balanced (or slightly female biased) population sex ratios.

Overall, we show that different components of population fitness have different responses to propagule size and sex ratio in ways that could affect early stages of biological invasion. Despite these effects, the short life span and high fecundity of A. sagrei likely helped small populations to overcome Allee effects and enabled all populations to successfully establish.

Our rare experimental manipulation of propagule size and sex ratio can inform predictions of colonisation dynamics in response to different compositions of founding populations, which is critical in the context of population ecology and invasion dynamics.
Homeownership and taxes: How the TCJA altered the tax code's treatment of housing
Authors: Ambrose Brent W. , Hendershott Patric H. , Ling David C. , McGill Gary A.
Published: February 2022

The federal government has long promoted homeownership through various provisions in the US income tax code. The Tax Cuts and Jobs Act of 2017 (TCJA) renewed interest and debate about the treatment of housing via the tax code, particularly with respect to the mortgage interest deduction and the limitation on deductions for state and local taxes. We document the extent that the TCJA magnifies the long‐standing unequal treatment of debt and equity financing of homeownership in the tax code. Our analysis indicates that most households no longer benefit from mortgage interest and property tax deductions. We also show how the limitations on the deduction of state and local taxes alter the costs associated with homeownership across geographic areas, and we provide detailed calculations of the average and marginal tax rates at which housing‐related expenses are deducted. The former are relevant to the tenure choice decision, the latter to the quantity demanded decision. Finally, we document that the lost tax savings associated with the inability to benefit from mortgage interest and property tax expenditures are often small relative to the primary tax benefit owners still enjoy: the nontaxation of the return on equity invested in the home.
Using cadaver temperatures to estimate time of death: A case‐specific numerical approach
Authors: Abraham John , Cheng Lijing , Vallez Lauren , Wei Tie
Published: February 2022

A new approach is taken to estimating the time of death based on cadaver temperatures. The predictions are obtained by using numerical simulation that can be performed in a case‐by‐case scenario. Such a method enables time‐of‐death predictions for persons of any size and weight and in any thermal environment. An added advantage of the method is that it is not dependent upon an identification of the individual tissue layers and regions. Rather, a homogeneous tissue model is used, and the results that are obtained agree closely with the results of prior estimation methods and also with a prior published case study. Among the results presented in this study are various convective environments in both air and water (or a combination for a partially submerged body). The orientation of the body (face down vs face up) is investigated. It is found that when a body is face up, its body core temperature is more responsive to the ambient conditions, compared with a face‐down orientation, at least for some partial‐submergence depths. The method disclosed here can also be used to handle situations, where the environmental conditions are changing (such as diurnal temperature variations, variation in cloudy or sunny skies, etc.). Current nomogram methods are not able to handle such timewise variations.
Metagenomics indicate that public health risk may be higher from flooding following dry versus rainy periods
Authors: Kim Minjae , Kienast Yvonne , Hatt Janet K. , Kirby Amy E. , Konstantinidis Konstantinos T.
Published: February 2022

Urban floodwater could lead to significant risk for public and environmental health from mobilization of microbial pathogens and overflow of wastewater treatment systems. Here, we attempted to assess this risk by obtaining metagenomic profiles of antibiotic resistance genes (ARGs), virulence factors (VFs) and pathogens present in floodwater samples collected in urban Atlanta, GA that were categorized in two distinct groups: floods that occurred after periods of drought and those after regular (seasonal) rain events. Even though no major (known) pathogens were present at the limit of detection of our sequencing effort (~3 Gbp/sample), we observed that floodwaters after drought showed a 2.5‐fold higher abundance of both ARGs and VFs compared to floodwater after rainy days. These differences were mainly derived by several novel species of the Pseudomonas genus, which were more dominant in the former versus the latter samples and carried several genes to cope with osmotic stress in addition to ARGs and VFs. These results revealed that there are previously undescribed species that become mobilized after flooding events in the Southeast US urban settings and could represent an increased public health risk, especially after periods of drought, which warrants further attention.
Predicting aquatic animal movements and behavioural states from acoustic telemetry arrays
Authors: Whoriskey Kim , Baktoft Henrik , Field Chris , Lennox Robert J. , Babyn Jonathan , Lawler Ethan , Mills Flemming Joanna
Published: February 2022

Fine‐scale tracking with passive acoustic telemetry can yield great insights into the movement ecology of aquatic animals. To predict fine‐scale positions of tagged animals in continuous space from spatially‐discrete detection data, state‐space modelling through the R package YAPS provides a promising alternative to frequently used positioning algorithms. However, YAPS cannot currently classify multiple kinds of movement that may be used as proxies for individual behaviours of study animals (behavioural states), an endeavour that is of increasing interest to movement ecologists.

We advance YAPS by incorporating the functionality to predict behavioural states by using an iterative maximization framework. Our model, which we call YAMS, occurs in continuous time and therefore we adapt current hidden Markov model (HMM) machinery to accommodate this while remaining within a likelihood framework that provides rapid fitting. We test our model using simulations and approximately 6 days’ worth of Northern pike data from Hald Lake, Denmark.

YAMS is shown to produce accurate parameter estimates and random effect predictions when model results were compared to simulated data, with behavioural state accuracies of 0.94 and 0.79 for two‐ and three‐state models, respectively, and location state root mean squared errors of 1.8 m for both models. In addition, the behavioural states are shown to reflect varying speeds of the pike, yielding a highly interpretable classification.

This research has the potential to be broadly applicable to both ecologists interested in identifying fine‐scale space use and behavioural states from acoustic telemetry data, as well as to statisticians who may wish to use standard HMM machinery to fit continuous‐time HMMs to animal movement data.
CFOs’ audit experience and corporate disclosure quality: evidence from China
Authors: Li Piao , Song Chang , Wang Jenny Jing , Zheng Hongrui
Published: February 2022

This paper examines the effect of the prior audit experience of chief financial officers (CFOs) on corporate information disclosure. Utilising a sample of 25,480 firm‐annual observations of A‐share Chinese listed companies over the period 2007–2019, we find that CFOs with audit experience improve the quality of corporate information disclosure. We also find that Big 4 auditor CFOs have a more positive influence on corporate information. Finally, we find that the power of CEOs influences the effect of CFOs’ audit experience on corporate disclosure quality. This study contributes to the selection of CFOs by listed companies with the aim to improve corporate governance mechanisms.
The impact of changes in COVID‐19 lockdown restrictions on alcohol consumption and drinking occasion characteristics in Scotland and England in 2020: an interrupted time‐series analysis
Authors: Hardie Iain , Stevely Abigail K. , Sasso Alessandro , Meier Petra S. , Holmes John
Published: February 2022

Background and Aims

Early evidence suggests that COVID‐19 lockdown restrictions affect alcohol consumption. However, existing studies lack data on how drinking practices changed as restrictions disrupted people’s work, family life and socializing routines. We examined changes in consumption and drinking occasion characteristics during three periods of changing restrictions in Scotland/England.

Design

Interrupted time‐series analysis of repeat cross‐sectional market research data (assessing step‐level changes).

Setting

Scotland/England, January 2009–December 2020.

Participants

Scotland: 41 507 adult drinkers; England: 253 148 adult drinkers.

Measurements

Three intervention points: March 2020 lockdown, July 2020 easing of restrictions and October 2020 re‐introduction of some restrictions. Primary outcome: mean units consumed per week (total/off‐trade/on‐trade; 1 unit = 8 g ethanol). Secondary outcomes: drinking > 14 units per week, heavy drinking, drinking days per week, solitary drinking, drinking with family/partners, drinking with friends/colleagues, own‐home drinking, drinking in someone else’s home and drinking start times.

Findings

In Scotland, March 2020’s lockdown was associated with a 2.32 [95% confidence interval (CI) = 0.61, 4.02] increase in off‐trade (i.e. shop‐bought) units per week, a −2.84 (95% CI = −3.63, −2.06) decrease in on‐trade (i.e. licensed venues) units per week, but no statistically significant change in total units per week. July 2020’s easing of restrictions was associated with a 1.33 (95% CI = 0.05, 2.62) increase in on‐trade units per week, but no statistically significant total/off‐trade consumption changes. October 2020’s re‐introduction of some restrictions was not associated with statistically significant consumption changes. Results for England were broadly similar. Lockdown restrictions were also associated with later drinking start times, fewer occasions in someone else’s home and with friends/colleagues, more own‐home drinking and (in Scotland only) more solitary drinking.

Conclusions

Reductions in on‐trade alcohol consumption following COVID‐19 lockdown restrictions in Scotland/England in 2020 were mainly offset by increased own‐home drinking. This largely persisted in periods of greater/lesser restrictions. The shift towards off‐trade drinking involved significant changes in the characteristics of drinking occasions.
Impact of an opioid prescribing alert system on patients with posttraumatic stress disorder
Authors: Bestha Durga , Tomatsu Shizuka , Hutcheson Bradford , Blankenship Kelly , Yu Ziqing , Wally Meghan K. , Wyatt Stephen , Seymour Rachel B. , Hsu Joseph R. , Rachal James ,   PRIMUM Group
Published: February 2022

Background and Objectives

Posttraumatic stress disorder (PTSD) is associated with higher rates of chronic pain and increased risk of developing Opioid use disorder. This paper evaluates the impact of PRIMUM, an electronic health record‐embedded (EHR) clinical decision support intervention on opioid prescribing patterns for patients with diagnosis of PTSD.

Methods

Inpatient, emergency department (ED), urgent care, and outpatient encounters with ICD‐10 codes F43.1 (PTSD), F43.10 (PTSD, unspecified), F43.11 (PTSD, acute), and F43.12 (PTSD, chronic) at Atrium Health between 1/1/2016 and 12/29/2018 were included in the study.

Results

A total of 3121 patients with a diagnosis of PTSD were seen in 37,443 encounters during the study period. Ten percent (n = 3761) of the encounters resulted in prescriptions for opioids and PRIMUM alerts were triggered in 1488 of these encounters. These alerts resulted in “decision influenced” for 17% of patients (n = 255) or no prescriptions for opioids or benzodiazepines for 5.8% (n = 86). The majority of the prescriptions were below 50 Morphine milligram equivalents (MME)/day, but there were 570 (15.5%) prescriptions for doses of 50–90 MME and 721 (19.6%) prescriptions for >90 MME/day.

Discussion and Conclusion

The PRIMUM alert system helps improve patient safety. PRIMUM affected clinician decisions 17% of the time, and the effect was greater in patients with opioid overdose history and those presenting for early refills.

Scientific Significance

The effectiveness of clinical support interventions for opioid prescribing for patients with PTSD has not been documented previously. Our findings provide novel evidence that the EHR can be used to improve patient safety among patients with PTSD in the context of substance use.
Mutational scanning identified amino acids of the CLOCK exon 19‐domain essential for circadian rhythms
Authors: Abdo Ashraf N. , Rintisch Carola , Gabriel Christian H. , Kramer Achim
Published: February 2022

Aim

In the mammalian circadian clock, the CLOCK/BMAL1 heterodimer binds to E‐box enhancer elements in the promoters of its target genes to activate transcription. The classical Clock mice, the first circadian mouse mutant discovered, are behaviourally arrhythmic. In this mutant, CLOCK lacks a 51 amino acid domain corresponding to exon 19 (CLOCKΔ19), which is required for normal transactivation. While the importance of this CLOCK domain for circadian rhythms is well established, the exact molecular mechanism is still unclear.

Methods

Using CRISPR/Cas9 technology, we created a CLOCK knockout – CLOCK rescue system in human circadian reporter cells and performed systematic mutational scanning to assess the functionality of individual amino acids within the CLOCK exon 19‐domain.

Results

CLOCK knockout cells were arrhythmic, and circadian rhythms could be rescued by introducing wild‐type CLOCK, but not CLOCKΔ19. In addition, we identified several residues, whose mutation failed to rescue rhythms in CLOCK knockout cells. Many of these are part of the hydrophobic binding interface of the predicted dimer of the CLOCK exon 19‐domain.

Conclusion

Our data not only indicate that CLOCK/BMAL1 oligomerization mediated by the exon 19‐domain is important for circadian dynamics but also suggest that the exon 19‐domain provides a platform for binding coactivators and repressors, which in turn is required for normal circadian rhythms.
Coping with changing plant–plant interactions in restoration ecology: Effect of species, site, and individual variation
Authors: Garrote Pedro José , Castilla Antonio Ramón , Fedriani Jose Maria
Published: February 2022

Question

Nurse–beneficiary plant interactions are often used to restore degraded habitats. However, whether and how shifts in plant–plant interactions along the facilitation–competition continuum alter revegetation success has been seldom considered. To test whether and how shifts in plant–plant interactions (due to woody species identity, study site, early life stage, and individual nurse) might alter plant recruitment and thus the success of revegetation projects, we chose a system comprising the Mediterranean dwarf palm (Chamaerops humilis) and seven common woody plant species.

Location

Two human‐degraded sites within Doñana National Park (southwestern Spain).

Methods

We carried out several well‐replicated field experiments to compare plant performance (seed survival, seedling emergence, seedling survival, seedling recruitment) in the presence and absence of Chamaerops humilis.

Results

Chamaerops humilis had marked effects on the performance of woody species that, however, changed among life stages. Depending on woody species identity, seed survival was up to 193 times greater in adjacent open spaces than beneath Chamaerops humilis. Conversely, seedling survival and recruitment were up to 19 times greater beneath Chamaerops humilis than in open spaces. Importantly, none of the studied woody species showed greater accumulated recruitment in open spaces than beneath Chamaerops humilis. Interestingly, we found strong inter‐individual palm variation in the sign and strength of their effect on woody plant performance.

Conclusions

We found strong seed–seedling conflicts the strength of which was species‐specific. The strong inter‐individual palm variation depicts a facilitation–competition continuum with important implications for restoration. We propose several management recommendations across different hierarchical levels (i.e., from individuals to communities) that may increase plant recruitment and therefore the success of revegetation projects. Our results are particularly relevant for restoring arid, semi‐arid and alpine landscapes worldwide where the nurse–beneficiary plant interactions are critical to ameliorating stressful conditions.
MAP Bayesian modelling combining striatal dopamine receptor occupancy and plasma concentrations to optimize antipsychotic dose regimens in individual patients
Authors: Ismail Mohamed , Straubinger Thomas , Uchida Hiroyuki , Graff‐Guerrero Ariel , Nakajima Shinichiro , Suzuki Takefumi , Caravaggio Fernando , Gerretsen Philip , Mamo David , Mulsant Benoit H. , Pollock Bruce G. , Bies Robert
Published: February 2022

Aims

Develop a robust and user‐friendly software tool for the prediction of dopamine D2 receptor occupancy (RO) in patients with schizophrenia treated with either olanzapine or risperidone, in order to facilitate clinician exploration of the impact of treatment strategies on RO using sparse plasma concentration measurements.

Methods

Previously developed population pharmacokinetic models for olanzapine and risperidone were combined with a pharmacodynamic model for D2 RO and implemented in the R programming language. Maximum a posteriori Bayesian estimation was used to provide predictions of plasma concentration and RO based on sparse concentration sampling. These predictions were then compared to observed plasma concentration and RO.

Results

The average (standard deviation) response times of the tools, defined as the time required for the application to predict parameter values and display the output, were 2.8 (3.1) and 5.3 (4.3) seconds for olanzapine and risperidone, respectively. The mean error (95% confidence interval) and root mean squared error (95% confidence interval) of predicted vs. observed concentrations were 3.73 ng/mL (−2.42–9.87) and 10.816 ng/mL (6.71–14.93) for olanzapine, and 0.46 ng/mL (−4.56–5.47) and 6.68 ng/mL (3.57–9.78) for risperidone and its active metabolite (9‐OH risperidone). Mean error and root mean squared error of RO were −1.47% (−4.65–1.69) and 5.80% (3.89–7.72) for olanzapine and −0.91% (−7.68–5.85) and 8.87% (4.56–13.17) for risperidone.

Conclusion

Our monitoring software predicts concentration–time profiles and the corresponding D2 RO from sparsely sampled concentration measurements in an accessible and accurate form.
Network properties of intracortical myelin associated with psychosocial functioning in bipolar I disorder
Authors: Sehmbi Manpreet , Suh Jee Su , Rowley Christopher D. , Minuzzi Luciano , Kapczinski Flavio , Bock Nicholas A. , Frey Benicio N.
Published: February 2022

Objective

Psychosocial functioning in bipolar disorder (BD) persists even during euthymia and has repeatedly been associated with illness progression and cognitive function. Its neurobiological correlates remain largely unexplored. Using a structural covariance approach, we explored whole cortex intracortical myelin (ICM) and psychosocial functioning in 39 BD type I and 58 matched controls.

Method

T1‐weighted images (3T) optimized for ICM measurement were analyzed using a surface‐based approach. The ICM signal was sampled at cortical mid‐depth using the MarsAtlas parcellation, and psychosocial functioning was measured via the Functioning Assessment Short Test (FAST). Following construction of structural covariance matrices, graph theoretical measures were calculated for each subject. Within BD and HC groups separately, correlations between network measures and FAST were explored. After accounting for multiple comparisons, significant correlations were tested formally using rank‐based regressions accounting for sex differences.

Results

In BD only, psychosocial functioning was associated with global efficiency (β = −0.312, pcorr = 0.03), local efficiency in the right rostral dorsolateral prefrontal cortex (β = 0.545, pcorr = 0.001) and clustering coefficient in this region (β = 0.497, pcorr = 0.0002) as well as in the right ventromedial prefrontal cortex (β = 0.428, pcorr = 0.002). All results excepting global efficiency remained significant after accounting for severity of depressive symptoms. In contrast, no significant associations between functioning and network measures were observed in the HC group.

Conclusion

These results uncovered a novel brain–behaviour relationship between intracortical myelin signal changes and psychosocial functioning in BD.
Suppression of non‐small‐cell lung cancer A549 tumor growth by an mtDNA mutation‐targeting pyrrole‐imidazole polyamide‐triphenylphosphonium and a senolytic drug
Authors: Tsuji Kohei , Kida Yuki , Koshikawa Nobuko , Yamamoto Seigi , Shinozaki Yoshinao , Watanabe Takayoshi , Lin Jason , Nagase Hiroki , Takenaga Keizo
Published: February 2022

Certain somatic mutations in mtDNA were associated with tumor progression and frequently found in a homoplasmic state. We recently reported that pyrrole‐imidazole polyamide conjugated with the mitochondria‐delivering moiety triphenylphosphonium (PIP‐TPP) targeting an mtDNA mutation efficiently induced apoptosis in cancer cells with the mutation but not normal cells. Here, we synthesized the novel PIP‐TPP, CCC‐021‐TPP, targeting ND6 14582A > G homoplasmic missense mutation that is suggested to enhance metastasis of non‐small‐cell lung cancer A549 cells. CCC‐021‐TPP did not induce apoptosis but caused cellular senescence in the cells, accompanied by a significant induction of antiapoptotic BCL‐XL. Simultaneous treatment of A549 cells with CCC‐021‐TPP and the BCL‐XL selective inhibitor A‐1155463 resulted in apoptosis induction. Importantly, the combination induced apoptosis and suppressed tumor growth in an A549 xenografted model. These results highlight the potential of anticancer therapy with PIP‐TPPs targeting mtDNA mutations to induce cell death even in apoptosis‐resistant cancer cells when combined with senolytics.
Measuring oral health—How can the International Classification of Functioning help?
Authors: Faulks Denise , Scambler Sasha , Daly Blánaid , Jamieson Lisa , Hennequin Martine , Tsakos Georgios
Published: February 2022

There is a need for a theoretically informed, contextualized approach to measuring oral health from a multidisciplinary perspective that goes beyond the commonly used clinical indices and sociodental measures. This commentary aims to discuss the potential for the WHO's International Classification of Functioning, Disability and Health (ICF) to provide a model for the development of indicators for oral health. It is suggested that the ICF might provide both a theoretical model and an operational classification for indicators of oral health. The ICF model states that human experience of physical, cognitive and social functioning is universal and, thus, can be described and qualified. Human function is given social and environmental context within the model at both an individual and population level. The ICF can not only capture data regarding oral health and function at the physiological level (e.g. chewing) but also at the social level (e.g. sharing meals). It is able not only to capture aspects of preventive behaviour (e.g. caring for teeth) but also aspects of social facilitation (e.g. economic self‐sufficiency) or ability to fulfil a social role (e.g. remunerative employment). It also includes aspects of social environment, such as healthcare services or political, economic and legal systems. Case studies are given as examples of the potential use of the ICF in the oral health domain. Examples are also given of the first steps that have been made towards operationalization of the ICF in data collection and oral health research. The challenges of encompassing such a comprehensive model into a practical oral health measure are discussed.
Reliability and accuracy of dynamic navigation for zygomatic implant placement
Authors: Wu Yiqun , Tao Baoxin , Lan Kengliang , Shen Yihan , Huang Wei , Wang Feng
Published: February 2022

Objectives

To assess the accuracy of a real‐time dynamic navigation system applied in zygomatic implant (ZI) surgery and summarize device‐related negative events and their management.

Material and methods

Patients who presented with severely maxillary atrophy or maxillary defects and received dynamic navigation‐supported ZI surgery were included. The deviations of entry, exit, and angle were measured after image data fusion. A linear mixed‐effects model was used. Statistical significance was defined as p < .05. Device‐related negative events and their management were also recorded and analyzed.

Results

Two hundred and thirty‐one zygomatic implants (ZIs) with navigation‐guided placement were planned in 74 consecutive patients between Jan 2015 and Aug 2020. Among them, 71 patients with 221 ZIs received navigation‐guided surgery finally. The deviations in entry, exit, and angle were 1.57 ± 0.71 mm, 2.1 ± 0.94 mm and 2.68 ± 1.25 degrees, respectively. Significant differences were found in entry and exit deviation according to the number of ZIs in the zygomata (p = .03 and .00, respectively). Patients with atrophic maxillary or maxillary defects showed a significant difference in exit deviation (p = .01). A total of 28 device‐related negative events occurred, and one resulted in 2 ZI failures due to implant malposition. The overall survival rate of ZIs was 98.64%, and the mean follow‐up time was 24.11 months (Standard Deviation [SD]: 12.62).

Conclusions

The navigation‐supported ZI implantation is an accurate and reliable surgical approach. However, relevant technical negative events in the navigation process are worthy of attention.
A retrospective study of 12,538 internal conical connection implants focused on the long‐term integrity of implant–abutment complexes
Authors: Jin Xiaoting , Guan Ye , Ren Jie , Zhao Yanwei , Wang Xiaoxiang , He Fuming
Published: February 2022

Objective

To evaluate the long‐term integrity of implant–abutment complexes in implant systems with two internal conical angles.

Material and Methods

12,538 bone‐level implants of two systems placed between January 2012 and December 2018 were retrospectively analyzed. Cumulative abutment/implant fracture rates in systems with larger (LA, 7.5°) and smaller (SA, 5.7°) internal conical angles were estimated using the Kaplan–Meier analysis and compared between groups. The association between implant systems and jammed abutment retrievability was evaluated by multivariable generalized estimating equation logistic regression modeling.

Results

For LA, the 8‐year cumulative incident rate was 0.10% (95% confidence interval (CI): 0–0.24%) for implant fracture and 0.26% (95% CI: 0.11%–0.41%) for abutment fracture, demonstrating a significant difference in gender (p = .03), implant diameter (p = .01), jaw (p = .006), and antagonist tooth (p < .001). For SA, the 8‐year cumulative incident rate was 0.38% (95% CI: 0–0.79%) for implant fracture and 2.62% (95% CI: 0.05%–5.13%) for abutment fracture, which was influenced by implant diameter (p < .001) and site (p = .03). The cumulative implant/abutment fracture rate was lower for LA implants, particularly for LA implant‐supported single crowns (SCs) (p < .05). The abutment‐retrieval success rate was 92.9% for LA and 57.1% for SA (p = .055).

Conclusion

LA implants exhibited a lower incidence of fracture in abutment–implant complexes and a relatively higher retrievability success rate for jammed abutments.
The effect of propofol on hypoxia‐ and TNF‐α‐mediated BDNF/TrkB pathway dysregulation in primary rat hippocampal neurons
Authors: Tao Weiping , Zhang Xuesong , Ding Juan , Yu Shijian , Ge Peiqing , Han Jingfeng , Luo Xing , Cui Wei , Chen Jiawei
Published: February 2022

Aims

Hypoxia and inflammation may lead to BDNF/TrkB dysregulation and neurological disorders. Propofol is an anesthetic with neuroprotective properties. We wondered whether and how propofol affected BDNF/TrkB pathway in hippocampal neurons and astrocytes.

Methods

Primary rat hippocampal neurons and astrocytes were cultured and exposed to propofol followed by hypoxia or TNF‐α treatment. The expression of BDNF and the expression/truncation/phosphorylation of TrkB were measured. The underlying mechanisms were investigated.

Results

Hypoxia and TNF‐α reduced the expression of BDNF, which was reversed by pretreatment of 25 μM propofol in hippocampal neurons. Furthermore, hypoxia and TNF‐α increased the phosphorylation of ERK and phosphorylation of CREB at Ser142, while reduced the phosphorylation of CREB at Ser133, which were all reversed by 25 μM propofol and 10 μM ERK inhibitor. In addition, hypoxia or TNF‐α did not affect TrkB expression, truncation, or phosphorylation in hippocampal neurons and astrocytes. However, in hippocampal neurons, 50 μM propofol induced TrkB phosphorylation, which may be mediated by p35 expression and Cdk5 activation, as suggested by the data showing that blockade of p35 or Cdk5 expression mitigated propofol‐induced TrkB phosphorylation.

Conclusions

Propofol modulated BDNF/TrkB pathway in hippocampal neurons via ERK/CREB and p35/Cdk5 under the condition of hypoxia or TNF‐α exposure.
Can we Save the rectum by watchful waiting or TransAnal surgery following (chemo)Radiotherapy versus Total mesorectal excision for early REctal Cancer (STAR‐TREC)? Protocol for the international, multicentre, rolling phase II/III partially randomized patient preference trial evaluating long‐course concurrent chemoradiotherapy versus short‐course radiotherapy organ preservation approaches
Authors: Bach Simon P. ,   the STAR‐TREC Collaborative
Published: February 2022

Aim

Organ‐saving treatment for early‐stage rectal cancer can reduce patient‐reported side effects compared to standard total mesorectal excision (TME) and preserve quality of life. An optimal strategy for achieving organ preservation and longer‐term oncological outcomes are unknown; thus there is a need for high quality trials.

Method

Can we Save the rectum by watchful waiting or TransAnal surgery following (chemo)Radiotherapy versus Total mesorectal excision for early REctal Cancer (STAR‐TREC) is an international three‐arm multicentre, partially randomized controlled trial incorporating an external pilot. In phase III, patients with cT1‐3b N0 tumours, ≤40 mm in diameter, who prefer organ preservation are randomized 1:1 between mesorectal long‐course chemoradiation versus mesorectal short‐course radiotherapy, with selective transanal microsurgery. Patients preferring radical surgery receive TME. STAR‐TREC aims to recruit 380 patients to organ preservation and 120 to TME surgery. The primary outcome is the rate of organ preservation at 30 months. Secondary clinician‐reported outcomes include acute treatment‐related toxicity, rate of non‐operative management, non‐regrowth pelvic tumour control at 36 months, non‐regrowth disease‐free survival at 36 months and overall survival at 60 months, and patient‐reported toxicity, health‐related quality of life at baseline, 12 and 24 months. Exploratory biomarker research uses circulating tumour DNA to predict response and relapse.

Discussion

STAR‐TREC will prospectively evaluate contrasting therapeutic strategies and implement new measures including a smaller mesorectal target volume, two‐step response assessment and non‐operative management for complete response. The trial will yield important information to guide routine management of patients with early‐stage rectal cancer.
Covered versus uncovered metal stent for endoscopic drainage of a malignant distal biliary obstruction: Meta‐analysis
Authors: Yamashita Yasunobu , Tachikawa Ayaka , Shimokawa Toshio , Yamazaki Hirofumi , Itonaga Masahiro , Sakai Yuji , Sugiyama Harutoshi , Nakai Yousuke , Tanaka Kiyohito , Isayama Hiroyuki , Kitano Masayuki
Published: February 2022

Objectives

The role of a covered vs. an uncovered self‐expandable metal stent (SEMS) for malignant distal biliary obstruction (MDBO) is not clear. This meta‐analysis compared the efficacy of covered vs. uncovered SEMS for patients with MDBO after endoscopic insertion.

Methods

A systematic meta‐analysis of all relevant articles listed in PubMed, the Cochrane Library, and Google Scholar databases was performed. Fixed effects or random effects models were used to investigate pooled effects with 95% confidence intervals (CIs).

Results

The meta‐analysis included 2358 patients from 12 eligible studies. Time to recurrent biliary obstruction (RBO) was significantly longer for covered SEMS (mean difference, 45.51 days; 95% CI 11.79–79.24). Although there was no significant difference in the RBO rate, subgroup analysis in pancreatic cancer occupying more than 90% (PC) revealed that the RBO rates were significantly lower for covered SEMS (odds ratio [OR] 0.43, 95% CI 0.25–0.74). Stent migration, sludge formation, and overgrowth were significantly more common with a covered SEMS (OR 7.92, 95% CI 4.01–15.64; OR 3.25, 95% CI 1.89–5.59; OR 2.03, 95% CI 1.20–3.43, respectively). The rate of ingrowth was significantly lower for covered SEMS. There was no significant difference in total procedure‐related adverse events between the two types of SEMS.

Conclusions

A covered SEMS is superior to an uncovered SEMS with respect to prevention of RBO in patients with MDBO, particularly those caused by PC.
Efficacy and safety of alogliptin versus acarbose in Chinese type 2 diabetes patients with high cardiovascular risk or coronary heart disease treated with aspirin and inadequately controlled with metformin monotherapy or drug‐naive: A multicentre, randomized, open‐label, prospective study (ACADEMIC)
Authors: Gao Bin , Gao Weiguo , Wan Hailong , Xu Fengmei , Zhou Rong , Zhang Xia , Ji Qiuhe
Published: February 2022

Aims

To demonstrate the noninferiority of alogliptin to acarbose, in terms of antidiabetic efficacy, in Chinese people with uncontrolled type 2 diabetes (T2D) and high cardiovascular risk.

Materials and Methods

ACADEMIC (NCT03794336) was a randomized, open‐label, phase IV study conducted at 46 sites in China. Antidiabetic treatment‐naive or metformin‐treated adults with uncontrolled T2D (glycated haemoglobin [HbA1c] 58.0–97.0 mmol/mol) were randomized 2:1 to alogliptin 25 mg once daily or acarbose 100 mg three times daily for 16 weeks. All participants had a documented history of coronary heart disease or high cardiovascular risk at screening and received aspirin (acetylsalicylic acid) 100 mg daily throughout the trial. The primary endpoints were change in HbA1c versus baseline, and the incidence of gastrointestinal adverse events (AEs). Safety and tolerability were also assessed.

Results

A total of 1088 participants were randomized. Alogliptin was noninferior to acarbose for the change in Week‐16 HbA1c (least‐squares mean change [standard error] –11.9 [0.4] vs. –11.4 [0.5] mmol/mol, respectively; difference between arms –0.5 [0.7] mmol/mol; 95% confidence interval –1.9 to 0.8 mmol/mol), and was associated with a lower incidence of gastrointestinal AEs (8.9% vs. 33.6%, respectively; P < 0.0001). More alogliptin than acarbose recipients achieved HbA1c <53.0 mmol/mol without gastrointestinal AEs (48.0% vs. 32.7%; P < 0.0001). Discontinuations due to treatment‐related AEs were less frequent with alogliptin than acarbose (0.3% vs. 2.5%).

Conclusions

Glycaemic control was comparable between alogliptin and acarbose, but the gastrointestinal tolerability of alogliptin was better. More patients achieved target HbA1c without gastrointestinal AEs with alogliptin, suggesting that this agent may be preferred in clinical practice.
Changes in pedometer‐measured physical activity are associated with weight loss and changes in body composition and fat distribution in response to reduced‐energy diet interventions: ThePOUNDS Losttrial
Authors: Xue Qiaochu , Li Xiang , Ma Hao , Tao Zhou , Heianza Yoriko , Rood Jennifer C. , Bray George A , Sacks Frank M , Qi Lu
Published: February 2022

Aims

To examine whether changes in objectively measured physical activity (PA) are associated with weight loss and changes in body composition and fat distribution in response to weight‐loss diet interventions.

Methods

This study included 535 participants with overweight/ obesity, who were randomly assigned to four weight‐loss diets varying in macronutrients. PA was measured objectively with pedometers, and body composition and fat distribution were measured using dual‐energy X‐ray absorptiometry and computed tomography scans at baseline, 6 months and 24 months.

Results

From baseline to 6 months, when the maximum weight loss was achieved, each 1000‐steps/d increment in PA was associated with a greater reduction in body weight (β[SE] = −0.48[0.11]) and waist circumference (β[SE] = −0.49[0.12]). Similar inverse associations were found in changes in body composition and fat distribution (P < 0.05 and false discovery rateqvalue < 0.1 for all). The trajectory of the above adiposity measures across the 24‐month intervention period differed between the patterns of PA change. Participants with the largest increase in PA maintained their weight loss from 6 months to 24 months, while those with a smaller increase in PA regained their weight. In addition, dietary fat or protein intake significantly modified the associations between changes in PA and changes in body weight and waist circumference over 24 months (P∆PA*diet < 0.05).

Conclusions

Changes in objectively measured PA were inversely related to changes in body weight, body composition and fat distribution in response to weight‐loss diets, and such associations were more evident in people on a high‐fat or average‐protein diet compared with a low‐fat or high‐protein diet.
Age‐related differences in bottom‐up and top‐down attention: Insights from EEG and MEG
Authors: ElShafei Hesham A. , Masson Rémy , Fakche Camille , Fornoni Lesly , Moulin Annie , Caclin Anne , Bidet‐Caulet Aurélie
Published: February 2022

Attention operates through top‐down and bottom‐up processes, and a balance between these processes is crucial for daily tasks. Imperilling such balance could explain ageing‐associated attentional problems such as exacerbated distractibility. In this study, we aimed to characterize this enhanced distractibility by investigating the impact of ageing upon event‐related components associated with top‐down and bottom‐up attentional processes. MEG and EEG data were acquired from 14 older and 14 younger healthy adults while performing a task that conjointly evaluates top‐down and bottom‐up attention. Event‐related components were analysed on sensor and source levels. In comparison with the younger group, the older mainly displayed (1) reduced target anticipation processes (reduced CMV), (2) increased early target processing (larger P50 but smaller N1) and (3) increased processing of early distracting sounds (larger N1 but reduced P3a), followed by a (4) prolonged reorientation towards the main task (larger RON). Taken together, our results suggest that the enhanced distractibility in ageing could stem from top‐down deficits, in particular from reduced inhibitory and reorientation processes.
An intersectionality lens is needed to establish a global view of equity, diversity and inclusion
Authors: Khelifa Rassim , Mahdjoub Hayat
Published: February 2022

Equity, diversity, and inclusion (EDI) have become essential considerations in different academic fields in recent years, attracting an increasing number of voices and perspectives from different groups. There is a need for an intersectionality framework that is inclusive of both the local and global diversity of researchers. Here, we present an intersectionality framework called KLOB which structures barriers to academic success into four components: knowledge exchange (K), language (L), obligations (O), and biases (B), and thus helps to think about the cumulative effect of multiple barriers that individuals from different backgrounds encounter to succeed in academic activities such as scientific publishing, which is the primary currency of academic success in our current system. This framework highlights both local and global disparities in socioeconomic, linguistic, and discriminatory factors that determine the opportunity of individual researchers to succeed in academia. We emphasise that individual researchers have no control over most barriers they face because of where and how they were born. Implementing solutions to address barriers associated with KLOB requires a multiscale vision and initiatives that tackle local and global inequities.
From sneaking to striding: Combatting competence creep and consolidating the EU legislative process
Authors: Garben Sacha
Published: February 2022

This paper argues that the EU legislative process should be used for taking all decisions at European level that matter, banning the various backroads of European decision‐making (competence creep) that are currently legal but not legitimate. This is a silver bullet, resolving at once a range of seemingly disparate but intimately connected legitimacy problems across all areas of EU activity, that ultimately result from an incorrectly calibrated state of transnational constitutional democracy at EU level, where certain aspects are over‐constitutionalised while others remain fundamentally under‐constitutionalised. This is therefore the key transversal issue that the Conference on the Future of Europe and its ensuing changes should address. The paper makes various concrete proposals to this effect, including for a general legislative competence.
Chromosome counting in the mouse zygote using low‐invasive super‐resolution live‐cell imaging
Authors: Hatano Yu , Mashiko Daisuke , Tokoro Mikiko , Yao Tatsuma , Yamagata Kazuo
Published: February 2022

In preimplantation embryos, an abnormal chromosome number causes developmental failure and a reduction in the pregnancy rate. Conventional chromosome testing methods requiring biopsy reduce the risk of associated genetic diseases; nevertheless, the reduction in cell number also reduces the pregnancy rate. Therefore, we attempted to count the chromosomes in mouse embryos using super‐resolution live‐cell imaging as a new method of chromosome counting that does not reduce the cell number or viability. We counted the 40 chromosomes at the first mitosis by injecting embryos with histone H2B‐mCherry mRNA under conditions by which pups could be obtained; however, the results were often an underestimation of chromosome number and varied by embryo and time point. Therefore, we developed a method to count the chromosomes via CRISPR/dCas‐mediated live‐cell fluorescence in situ hybridization targeting the sequence of the centromere region, enabling us to count the chromosomes more accurately in mouse embryos. The methodology presented here may provide useful information for assisted reproductive technologies, such as those used in livestock animals/humans, as a technique for assessing the chromosomal integrity of embryos prior to transfer.