bluuebunny/crossref_metadata_2025 huggingface dataset:
High-resolution 3D printing of angle-ply annulus fibrosus scaffolds for intervertebral disc regeneration
Authors: Liu Zhao , Wang Huan , Yuan Zhangqin , Wei Qiang , Han Fengxuan , Chen Song , Xu Hao , Li Jiaying , Wang Jiayuan , Li Zexi , Chen Qixin , Fuh Jerry , Ding Lin , Wang Hui , Li Bin
Published: November 2022

Intervertebral disc (IVD) degeneration is one of the leading causes of disability, and current therapies are mainly unsatisfactory. The key pathological feature during IVD degeneration is the dysfunction of annulus fibrosus (AF). Although tissue-engineered AF has shown great promise for IVD regeneration, the design and fabrication of biomimetic AF scaffold remains a challenge due to the complexity of its structure. Nowadays, 3D printing technology has drawn great attention due to its customizable processes and ability to produce complex tissue architecture. However, few existing 3D printing methods can accurately replicate the fine angle-ply architecture of native AF, which is one of the most critical steps for IVD regeneration, due to the limited printing resolution. In this study, we aimed to fabricate high-resolution polycaprolactone (PCL) scaffolds using a newly developed electrohydrodynamic 3D printing technique. The structural advantages of such scaffolds were verified by finite element analysis (FEA). The PCL scaffolds were further assembled into AF construct to replicate the angle-ply architecture of AF. The optimal assembling method was confirmed by FEA and mechanical tests. The in vitro experiments showed that the 3D printed AF scaffolds presented favorable biocompatibility and supported the adhesion and growth of AF cells. The in vivo performance of tissue-engineered IVDs (TE-IVDs), which consisted of 3D printed AF scaffold and GelMA hydrogel that simulated nucleus pulposus (NP), were evaluated using a rat total disc replacement model. We found that the implantation of TE-IVDs helped maintain the disc height, reduced the loss of NP water content, and partially restored the biomechanical function of IVD. In addition, the TE-IVDs achieved well integration with adjacent tissues and promoted new tissue formation. In summary, being able to accurately simulate the structural characteristics of native AF, the 3D printed angle-ply AF scaffolds hold potential for future applications in IVD regeneration.
Efficient hepatic differentiation of hydrogel microsphere-encapsulated human pluripotent stem cells for engineering prevascularized liver tissue
Authors: Deng Shuai , Zhao Xiaoyu , Zhu Yanlun , Tang Ning , Wang Rongliang , Zhang Xuerao , Qu Fuyang , Ho Yi-Ping , Lee Wayne Yuk-Wai , Chen Jiansu , Li Mingqiang , Tao Yu , Chan Hon Fai
Published: November 2022

Liver tissue engineering is promising as an alternative strategy to treat liver failure. However, generating functional hepatocytes from stem cells is conventionally restricted by the immature status of differentiated cells. Besides, embedding hepatocytes in bulk scaffold is limited by a lack of vascularity and low cell-packing density. Here, we fabricate collagen type I (COL1) microspheres for efficient hepatic differentiation of pluripotent stem cells and subsequent assembly of prevascularized liver tissue (PLT). Using a microfluidic platform, we demonstrate that hydrogel COL1 microspheres (mCOL1) encapsulating human embryonic stem cells (hESCs) can be reproducibly generated and efficiently differentiated into hepatocyte-like cells (HLCs) microspheres for the first time. Compared with other culture configurations such as encapsulation of hESC in a bulk COL1 hydrogel and 2D monolayer culture, mCOL1 with high uniformity produce HLC microspheres of improved maturity based on comprehensive analyses of cell morphology, transcriptome profile, hepatic marker expression and hepatic functions. In addition, these HLC microspheres can be applied as building blocks to self-assemble with endothelial cells to construct a dense PLT. The PLT resembles native liver tissue with high cell-packing density, shows successful engraftment in mice liver following implantation, and exhibits improved hepatic function in vivo. Overall, it is believed that this multiscale technology will advance the fabrication of stem cell-based liver tissue for regenerative medicine, drug screening, and in vitro liver modeling.
Size- and density-dependent acoustic differential bioassembly of spatially-defined heterocellular architecture
Authors: Gu Longjun , Jiang Shanqing , Xu Xiaodong , Wang Jibo , Xu Fang , Fan Han , Shang Jia , Liu Kan , Demirci Utkan , Chen Pu
Published: November 2022

Emerging acoustic bioassembly represents an attractive strategy to build cellular closely-packed organotypic constructs in a tunable manner for biofabrication. However, simultaneously assemble heterogeneous cell types into heterocellular functional units with spatially-defined cell arrangements, such as complementary and sandwich cytoarchitectures, remains a long-lasting challenge. To overcome this challenge, herein we present an acoustic differential bioassembly technique to assemble different cell types at the distinct positions of the acoustic field based on their inherent physical characteristics including cellular size and buoyant density. Specifically, different cell types can be differentially assembled beneath the nodal or the antinode regions of the Faraday wave to form complementary cytoarchitectures, or be selectively positioned at the center or edge area beneath either the nodal or the antinode regions to form sandwich cytoarchitectures. Using this technique, we assemble human induced pluripotent stem cell-derived liver spheroids and endothelial cells into hexagonal cytoarchitectures in vitro to mimic the cord and sinusoid structures in the hepatic lobules. This hepatic lobule model reconstitutes liver metabolic and synthetic functions, such as albumin secretion and urea production. Overall, the acoustic differential bioassembly technique facilitates the construction of human relevant in vitro organotypic models with spatially-defined heterocellular architectures, and can potentially find wide applications in tissue engineering and regenerative medicine.
Effects of friction stir welding process on the microstructure and mechanical properties of AA8090—T87 aluminium alloy
Authors: C Shyamlal , S Rajesh , Jappes J T Winowlin , Ravichandran M , S Syath Abuthakeer
Published: November 2022

AA8090 aluminium lithium alloy which is employed in the fuselage of airplane and in the cryogenic fuel tank was successfully welded using friction stir welding technique. Nine set of experiments were conducted by employing 700 rpm, 900 rpm, and 1100 rpm rotation speed with varying traverse speeds of 30 mm min−1, 50 mm min−1, 70 mm min−1 to arrive at the best possible combination of inputs and obtain better joint efficiency. The macroscopic, microscopic and mechanical property analysis were performed to determine the effectiveness of the joint. Based on the results of the aforementioned studies, the best combination of input parameters such as rotational speed and traverse speed for the welded specimens were determined as 700 rpm and 30 mm min−1, 700 rpm and 70 mm min−1 respectively. Tensile strength of 700 rpm and 30 mm min−1, 700 rpm and 70 mm min−1 joints were found as 238.1 MPa and 222.56 MPa, micro hardness of the afore-mentioned joints were 107.3 VHN and 123.1 VHN and are subjected to microstructural analysis using scanning electron microscopy and electron back scattered diffraction techniques in stir zone and in heat affected zone. The above studies revealed the reason for the deviation in the grain size, increase in micro hardness, tensile strength owing to precipitate formation in the grains, and grain refinement in the weld zone.
Antibacterial, efficient and sustainable CS/PVA/GA electrospun nanofiber membrane for air filtration
Authors: Yang Bochen , Wang Jing , Kang Le , Gao Xiaoping , Zhao Ke
Published: November 2022

Since the outbreak of the COVID-19 epidemic, a large number of disposable protective masks have been manufactured and used, and the abandonment of masks has caused enormous pollution. In this paper the chitosan (CS), polyvinyl alcohol (PVA), and water were used as raw materials and the nanofiber membranes were prepared by electrostatic spinning. The CS/PVA fiber membranes were crosslinked by glutaraldehyde hydrochloric acid vapour. The fiber morphology, hydrolysis resistance, antibacterial properties, chemical structure, thermal stability and filtration performance of nanofiber membranes were characterized. Results shows that the antibacterial performance of the crosslinked composite nanofibers exceeds 97%, the thermal stability is improved, and the fiber morphology is not destroyed. The hybridized fiber membrane has high filtration performance, excellent antibacterial and hydrolysis resistance, which broadening the PVA fiber membrane application. It is expected to replace traditional protective materials and relieve environmental pressure.
Investigating the binding properties of NbC/Fe-based composite layer and HT300 through experiments and simulations
Authors: Zhao Nana , Shan Rui , Wang Zihan , Yao Teli , Ren Congcong , Liu Heguang , Li Shujuan , Xu Yunhua , Cui Zhen
Published: November 2022

In this work, the hot-pressing diffusion method was used for the fabrication of a novel composite structure. More specifically, by keeping the temperature constant at 1000 °C and applying a pressure value of 40 MPa for 60 min, α 90 min and 120 min, respectively, the NbC/Fe composite layer on the surface of HT300 was formed. The microstructure, element distribution, microhardness, bonding property and scratch deformation characteristics of NbC/Fe composite layer were studied, and the fracture mode was studied by simulation and tensile test at the micro level. The results show that the main components of the NbC/Fe composite layer prepared in the experiment are α- Fe and NbC, the composition of the composite layer is pure. The thickness of NbC/Fe composite layer prepared with 60 min, 90 min and 120 min holding time is 5 μm, 15 μm and 23 μm. The hardness of the composite layer can reach 2096.4 HV0.1; The bonding property between the NbC/Fe composite layer and the matrix is the best when the heat preservation is 120 min. Because the tensile fracture is brittle and the fracture location is in the NbC/Fe composite layer, the bonding strength between the composite layer and the matrix is greater than 297MPa, which has excellent bonding properties. In the scratch test, the longer the holding time is, the stronger the bonding ability between the reinforcing layer and the matrix is, 41.2N (90 min) and 75.75N (120 min) respectively. The fracture mechanism in the NbC/Fe composite layer was simulated by abaqus. The fracture of the composite layer was caused by the propagation of microcracks caused by the stress concentration at the sharp corner of square NbC particles in the layer.
High efficiency GHz laser processing with long bursts
Authors: Audouard Eric , Mottay Eric
Published: November 2022

Bursts of GHz repetition rate pulses involve more ablation mechanisms than single femtosecond pulses. Efficient ablation by GHz laser pulses is a multi-step process, consisting of a first thermal incubation phase, followed by a highly efficient ablation phase. GHz ablation therefore combines thermal and non-thermal ablation mechanisms. With an optimal choice of the burst duration, the ablation efficiency can be highly enhanced. Long bursts, comprising tens of pulses to hundreds of pulses, are needed to take full advantage of the increase in ablation efficiency.
Contractive projections in Paley-Wiener spaces
Authors: Kulikov Aleksei , Zlotnikov Ilya
Published: November 2022

Let

S
1

S_1

and

S
2

S_2

be disjoint finite unions of parallelepipeds. We describe necessary and sufficient conditions on the sets

S
1

,

S
2

S_1,S_2

and exponents

p
p

such that the canonical projection

P
P

from

P

W

S
1

∪

S
2

p

PW_{S_1\cup S_2}^p

to

P

W

S
1

p

PW_{S_1}^p

is a contraction.
Orthogonal unitary bases and a subfactor conjecture
Authors: Crann Jason , Kribs David , Pereira Rajesh
Published: November 2022

We show that any finite dimensional von Neumann algebra admits an orthonormal unitary basis with respect to its standard trace. We also show that a finite dimensional von Neumann subalgebra of

M
n

(

C

)

M_n(\mathbb {C})

admits an orthonormal unitary basis under normalized matrix trace if and only if the normalized matrix trace and standard trace of the von Neumann subalgebra coincide. As an application, we verify a recent conjecture of Bakshi-Gupta [Glasg. Math. J. 64 (2022), pp. 586–602], showing that any finite-index regular inclusion

N
⊆
M

N\subseteq M

of

I

I
1

II_1

-factors admits an orthonormal unitary Pimsner-Popa basis.
An elementary proof of the homotopy invariance of stabilized configuration spaces
Authors: Malin Connor
Published: November 2022

In this paper we give an elementary proof of the proper homotopy invariance of the equivariant stable homotopy type of the configuration space

F
(
M
,
k
)

F(M,k)

for a topological manifold

M
M

. Our technique is to compute the Spanier-Whitehead dual of

Σ
+
∞

F
(
M
,
k
)

\Sigma ^\infty _+ F(M,k)

and use the results of Spivak and Wall on normal spherical fibrations to deduce that the Spanier-Whitehead dual is a proper homotopy invariant. This stable invariance was recently proved by Knudsen using factorization homology. Aside from being elementary, our proof has the advantage that it readily extends to “generalized configuration spaces” which have recently undergone study.
Treenome Browser: co-visualization of enormous phylogenies and millions of genomes
Authors: Kramer Alexander M , Sanderson Theo , Corbett-Detig Russell
Published: November 2022

Treenome Browser is a web browser tool to interactively visualize millions of genomes alongside huge phylogenetic trees.

Availability and implementation

Treenome Browser for SARS-CoV-2 can be accessed at cov2tree.org, or at taxonium.org for user-provided trees. Source code and documentation are available at github.com/theosanderson/taxonium and docs.taxonium.org/en/latest/treenome.html.

Supplementary information

Supplementary data are available at Bioinformatics online.
IBCOx-14 Excess weight loss variability bt age group after gastric bypass in a large volume center
Authors: Rodriguez-Quintero J , Garcia Cabrera A T , Flores F M , Choi J , Moran-Atkin E , Camach D R
Published: November 2022

Introduction

Laparoscopic Roux-en-Y Gastric Bypass (LRYGB) is one of the principal bariatric procedures performed around the world. It allows for the reduction of around 60-70% of excess weight loss at 2 years after the procedure. However, the reproducibility of these outcomes across age groups has been controversial, especially in the extremes of age. This study assessed one-year percentage of excess weight loss after LRYGB comparing the different age groups operated in our center.

Methods

Our hospital's -MBSAQIP database for years 2014 - 2017 was used. Patients were included if they underwent primary RYGB. The patient´s age underwent analysis of normality allowing for the division of our sample in four quartiles. A one-way Welch ANOVA test was conducted to determine if the percentage of excess weight loss (%EWL) one year after surgery was different between the 4 groups. Data are presented as mean +/- standard deviation. A p-value of <.05 was considered statistically significant.

Results

A total of 803 patients underwent non-revisional LRYGB in the analyzed period. Mean %EWL at one year was 59.2% in the whole sample. However, when compared between groups, there was a statistically significant difference in %EWL: 61.9 vs. 59.3 vs.60 vs. 56.1. (p=0.003)

Conclusions

There is a difference in the percentage of excess weight loss one year after LRYGB based on the age group in our patient population. The quartile of age presenting the less %EWL was the eldest.
Construction of a prognostic model for lung squamous cell carcinoma based on immune-related genes
Authors: Pu Jiangtao , Teng Zhangyu , Yang Wenxing , Zhu Peiquan , Zhang Tao , Zhang Dengguo , Wang Biao , Hu Zhi , Song Qi
Published: November 2022

Lung squamous cell carcinoma (LUSC) lacks appropriate prognostic and diagnostic strategies. Available studies suggest the effectiveness of immunotherapy for LUSC, but effective molecular markers are still insufficient. We obtained mRNA expression and clinical information of LUSC samples from The Cancer Genome Atlas (TCGA) database. Enrichment levels of immune-related genes were revealed by single sample gene set enrichment analysis. Then, differentially expressed genes (DEGs) related to immunity were obtained by differential analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. In addition, Cox regression analysis combined with LASSO method was utilized to identify immune-related prognostic genes, and an immune-related prognostic model was constructed. Kaplan–Meier and receiver operating characteristic (ROC) curves were drawn to verify the accuracy of the model. Finally, a nomogram and calibration curve were drawn to predict LUSC patients’ survival. Samples were assigned into high-, medium- and low-immune groups. Compared with low- and medium-immune groups, high-immune group enriched more immune cells, with higher immune infiltration degree, and higher expression of immune checkpoints and human leukocyte antigen. DEGs were enriched in biological processes and signaling pathways related to immunity. Eleven genes (ONECUT3, MAGED4, SULT2A1, HPR, S100A5, IRS4, DPP6, FGF8, TEX38, PLAAT1 and CLEC3A) were obtained to construct an immune-related prognostic model. Riskscore served as an independent prognostic factor. Besides, the nomogram prediction model could predict disease progression in LUSC patients. The constructed risk assessment model for LUSC immune-related genes could assess LUSC patients’ prognoses with great efficacy, providing guidance for the clinical treatment of LUSC.
Development, Robustness by Design Expert and Validation of a Method for Enantiomeric Impurity Content Determination in Pretomanid Drug Substance and Pharmaceutical Dosage Form
Authors: Surapuraju Pavan Kumar Raju , Juturu Raveendra Reddy
Published: November 2022

For the purpose of identifying enantiomeric impurities in the drug substance and pharmaceutical dosage forms of the novel anti-TB medication pretomanid, an RP-high-performance liquid chromatography method was devised. To ensure the robustness of the optimized approach, analytical quality by design was used. Studies on factor screening and risk evaluation helped pinpoint the critical method parameters (CMPs); resolution (R1), analyte retention time (R2) and tailing factor (R3) are those terms. Pareto charts, half-normal plots, 3D surface plots, 2D contour plots and 3D cube plots were used to study the effects of solo and interactive CMPs on critical analytical attributes. Analysis of variance (ANOVA) was used to verify the technique parameters’ confirmation of significance (P = 0.05). With a Chiral Cel OJ-3R (150 × 4.6 mm, 3 µm) and a mobile phase consisting of 20 mM of ammonium trifluoroacetate, pH = 2.5, and acetonitrile in a gradient mode, chromatographic separation was accomplished. At 30°C and 330 nm, the column’s temperature and wavelength, respectively, were recorded. The procedure is stability-indicating and is LC–MS compatible. According to the International Conference on Harmonization tripartite guidelines, the method demonstrated appropriate specificity, sensitivity, linearity, accuracy, precision and robustness. The LOD and LOQ were, respectively, 0.09 and 0.3 μg/mL. With a correlation coefficient of >0.990, it was discovered that the established method for enantiomeric impurity was linear over the concentration range of 0.3–2.25μg/mL. The approach exhibits adequate accuracy (%recovery = 85–115%), robustness (%RSD = 5.0) and precision (%RSD = 5.0). The method was also shown to be stability-indicating and was shown to provide effective separation in the presence of degradation products through the use of forced degradation tests.
Postural orthostatic tachycardia syndrome and orthostatic hypotension in post-acute sequelae of COVID-19 during pregnancy: a case report
Authors: Hanson Justin , Richley Michael , Hsu Jeffrey J , Lin Jeannette , Afshar Yalda
Published: November 2022

Background

Patients with post-acute sequelae of COVID-19 (PASC) often experience the addition of new symptoms after recovery from COVID-19 illness. These may include orthostatic intolerance and autonomic dysfunction, and postural orthostatic tachycardia syndrome has been described to occur in a proportion of patients with PASC.

Case summary

In this report, we present a 32-year-old pregnant woman (G3P2) who experiences severe orthostatic symptoms as part of her PASC syndrome, which is decoupled from normal physiologic changes of pregnancy. At 25 weeks of gestation, she was evaluated for increasing episodes of dyspnoea, marked tachycardia with minimal exertion, intermittent non-exertional chest pain, and presyncope. This patient had a moderate course of COVID-19 at 12 weeks of gestation, for which she received monoclonal antibody therapy (casirivimab/imdevimab). The patient then had complete resolution of COVID-19 symptoms and felt well for 1 month prior to developing orthostatic symptoms at 25 weeks of gestation. Evaluation with a NASA Lean Test revealed marked orthostatic tachycardia, as well as delayed orthostatic hypotension. Given her COVID-19 illness 4 months prior, PASC involving autonomic dysfunction was diagnosed.

Discussion

Patients with orthostatic symptoms in PASC should be carefully evaluated with dedicated active stand tests, such as the NASA Lean Test, to characterize the autonomic response to standing. In pregnant patients, an understanding of normal pregnancy physiology is crucial to correctly identify abnormal findings in such tests.
Aging-Related Multisystem Dysregulation Over the Adult Life Span and Physical Function in Later Life: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Lu Yifei , Pike James R , Kucharska-Newton Anna M , Palta Priya , Whitsel Eric A , Bey Ganga S , Zannas Anthony S , Windham B Gwen , Walker Keenan A , Griswold Michael , Heiss Gerardo
Published: November 2022

Background

Multisystem dysregulation (Dm) shows promise as a metric of aging and predicts mortality. However, Dm needs to be studied with less severe endpoints indicating modifiable aging stages. Physical function, reflecting healthy longevity rather than just longevity, is more relevant to the goals of geroscience but has not been well investigated.

Methods

We tested the association of midlife Dm and its change over ~20 years with physical function in later life in 5 583 the Atherosclerosis Risk in Communities Study cohort participants (baseline mean age 54.7). Dm quantifies the multivariate statistical deviation of 17 physiologically motivated biomarkers relative to their distribution in a young healthy sample at baseline. Physical function was assessed from grip strength and the Short Physical Performance Battery (SPPB). Associations were quantified using linear regression and ordinal logistic regression adjusting for age, sex, race, and education.

Results

Each unit increment in midlife Dm was associated with 1.71 times the odds of having a lower SPPB score. Compared to the first quartile of midlife Dm, the odds ratios of having a lower SPPB score were 1.25, 1.56, and 2.45, respectively, for the second–fourth quartiles. Similar graded association patterns were observed for each SPPB component test and grip strength. An inverse monotonic relationship also was observed between the annual growth rate of Dm and physical function.

Conclusion

Greater Dm and progression in midlife were associated with lower physical function in later life. Future studies on the factors that lead to the progression of Dm may highlight opportunities to preserve physical function.
3D-Beacons: decreasing the gap between protein sequences and structures through a federated network of protein structure data resources
Authors: Varadi Mihaly , Nair Sreenath , Sillitoe Ian , Tauriello Gerardo , Anyango Stephen , Bienert Stefan , Borges Clemente , Deshpande Mandar , Green Tim , Hassabis Demis , Hatos Andras , Hegedus Tamas , Hekkelman Maarten L , Joosten Robbie , Jumper John , Laydon Agata , Molodenskiy Dmitry , Piovesan Damiano , Salladini Edoardo , Salzberg Steven L , Sommer Markus J , Steinegger Martin , Suhajda Erzsebet , Svergun Dmitri , Tenorio-Ku Luiggi , Tosatto Silvio , Tunyasuvunakool Kathryn , Waterhouse Andrew Mark , Žídek Augustin , Schwede Torsten , Orengo Christine , Velankar Sameer
Published: November 2022

While scientists can often infer the biological function of proteins from their 3-dimensional quaternary structures, the gap between the number of known protein sequences and their experimentally determined structures keeps increasing. A potential solution to this problem is presented by ever more sophisticated computational protein modeling approaches. While often powerful on their own, most methods have strengths and weaknesses. Therefore, it benefits researchers to examine models from various model providers and perform comparative analysis to identify what models can best address their specific use cases. To make data from a large array of model providers more easily accessible to the broader scientific community, we established 3D-Beacons, a collaborative initiative to create a federated network with unified data access mechanisms. The 3D-Beacons Network allows researchers to collate coordinate files and metadata for experimentally determined and theoretical protein models from state-of-the-art and specialist model providers and also from the Protein Data Bank.
The 2015–2017 Pamir earthquake sequence: foreshocks, main shocks and aftershocks, seismotectonics, fault interaction and fluid processes
Authors: Bloch Wasja , Metzger Sabrina , Schurr Bernd , Yuan Xiaohui , Ratschbacher Lothar , Reuter Sanaa , Xu Qiang , Zhao Junmeng , Murodkulov Shokhruhk , Oimuhammadzoda Ilhomjon
Published: November 2022

A sequence of three strong (MW7.2, 6.4, 6.6) earthquakes struck the Pamir of Central Asia in 2015–2017. With a local seismic network, we recorded the succession of the foreshock, main shock and aftershock sequences at local distances with good azimuthal coverage. We located 11 784 seismic events and determined 33 earthquake moment tensors. The seismicity delineates the tectonic structures of the Pamir in unprecedented detail, that is the thrusts that absorb shortening along the Pamir’s thrust front, and the strike-slip and normal faults that dissect the Pamir Plateau into a westward extruding block and a northward advancing block. Ruptures on the kinematically dissimilar faults were activated subsequently from the initial MW 7.2 Sarez event at times and distances that follow a diffusion equation. All main shock areas but the initial one exhibited foreshock activity, which was not modulated by the occurrence of the earlier earthquakes. Modelling of the static Coulomb stress changes indicates that aftershock triggering occurred over distances of ≤90 km on favourably oriented faults. The third event in the sequence, the MW 6.6 Muji earthquake, ruptured despite its repeated stabilization through stress transfer in the order of –10 kPa. To explain the accumulation of MW > 6 earthquakes, we reason that the initial main shock may have increased nearby fault permeability, and facilitated fluid migration into the mature fault zones, eventually triggering the later large earthquakes.
Stochastic frontier approach to efficiency analysis of health facilities in providing services for non-communicable diseases in eight LMICs
Authors: Bala Muhammad Muazu , Singh Shailender , Gautam Dhruba Kumar
Published: November 2022

Background

The rising burden of non-communicable diseases presents an increasing public health challenge to many low- and middle-income countries. This problem may be compounded in health systems with lower levels of technical efficiency (TE).

Methods

This study used recent Service Provision Assessments data to estimate the level of TEs of health facilities in eight countries. Initially, the general and disease-specific service readiness indexes are estimated. Finally, the production function is estimated using the exposures and the outcomes of the model.

Results

Evidence shows that the general and disease-specific service readiness indexes are significantly associated with an increase in the number of outpatient visits. Outpatient visits may increase by 14% with an increase in health worker density. Similarly, outpatient visits may increase by 0.3% with a unit increase in the general and diabetes service readiness indexes. Furthermore, outpatient visits may increase by 0.4% and 0.8% with an increase in services readiness for cardiovascular and respiratory diseases. respectively. Overall, the level of TE score suggests the need for improvement.

Conclusions

Facility-level service readiness for chronic diseases is quite low. Therefore, improving health outcomes related to chronic diseases requires urgent investment in high-quality health systems in these countries.
HCI Research Experiences During the Pandemic: Lessons Learned for the Road Ahead
Authors: Marques Correa Claiton , Diniz Junqueira Barbosa Gabriel , Diniz Junqueira Barbosa Simone , Selbach Silveira Milene
Published: November 2022

The social interaction restrictions imposed by COVID-19 required academic researchers to rethink the design of their research projects, especially those that involved human interaction. Considering this scenario, we report here the experience of conducting four studies in Human–Computer Interaction research projects that were adapted to be executed remotely: a focus group study, a communicability evaluation study, a speculative design study and a user observation study. Considering how the studies were planned, executed and analysed, we reflect on the adaptations needed, and lessons related to our experiences. From these lessons, we believe that, even after all the pandemic restrictions are lifted, we may continue conducting at least part of our research studies remotely to increase our geographical reach, reduce costs and facilitate data capture.
Design and reporting of phase III oncology trials with prospective biomarker validation
Authors: Liang Fei , Peng Ling , Wu Zhengyu , Giamas Georgios , Stebbing Justin
Published: November 2022

Background

Phase III trials with prospective biomarker validation are essential to drug development in the era of personalized oncology. However, concerns have emerged regarding the design and reporting of phase III trials with prospective biomarker validation.

Methods

We searched MEDLINE for phase III oncology trials with prospective biomarker validation published in high-impact medical journals from 2011 to 2020. Information regarding trial design and reporting were extracted. Descriptive methods were used to summarize the results.

Results

We identified 45 phase III trials with prospective biomarker validation. There was a trend for increasing use of biomarker validation phase III trials (from 1 trial in 2011 to 12 trials in 2020). For 39 (86.7%) trials, results in biomarker-negative population were either listed as an exploratory subgroup analysis (62.2%) or not mentioned in the methods (24.4%). Twenty-one (46.7%) trials were originally designed without biomarker validation but were then apparently modified to incorporate prospective biomarker validation after trial commencement, albeit only 15 (33.3%) trials reported this change. Treatment effect and primary outcome values in biomarker-negative patients were not reported in 24.4% and 40.0% trials, respectively. For 18 trials with statistically significant results in the overall population, only 7 trials reported a hazard ratio less than 0.8 in the biomarker-negative population.

Conclusions

Although biomarker validation in phase III trials have been increasingly used in the past decade, issues regarding changes in trial design after commencement without disclosure, underreporting of results in biomarker-negative groups, and recommending treatment in biomarker negative groups despite modest effects require substantial improvement.
Composition, distribution and environmental drivers of Mongolian rangeland plant communities
Authors: Suzuki Kohei , Tungalag Radnaakhand , Narantsetseg Amartuvshin , Tsendeekhuu Tsagaanbandi , Shinoda Masato , Yamanaka Norikazu , Kamijo Takashi
Published: November 2022

In Mongolia, overgrazing and the resulting degradation of rangelands are recognized as serious issues. To address rangeland degradation, we sought to develop a broad-scale vegetation classification of Mongolian rangeland communities focusing on regional characteristics. Moreover, we sought to clarify the spatial distributions of communities and the environmental drivers of the distributions. Between 2012 and 2016, we surveyed vegetation in 278 plots (each 10 m × 10 m) in different regions of Mongolia (43–50° N, 87–119° E) in plots where grazing pressure is low relative to adjacent areas. The data were grouped into vegetation units using a modified two-way indicator species analysis (TWINSPAN). We then explored the regional characteristics of species compositions and community distributions, as well as relationships between distributions and climatic variables. The modified TWINSPAN classified the vegetation data into three cluster groups, each of which corresponds to a particular type of zonal vegetation (i.e. forest steppe, steppe and desert steppe). The aridity index was identified as an important driver of the distributions of all cluster groups, whereas longitude and elevation were important determinants of the distribution of clusters within cluster groups. Western regions, which are characterized by higher elevation and continentality compared with eastern regions, have lower mean temperature and precipitation during the wettest quarter, leading to differences in species composition within cluster groups. Regional differences in species composition reflect differences in phytogeographic origin. Thus, the framework of species composition and distributional patterns in Mongolian rangeland communities was demonstrated in relation to climatic and geographical factors.
Astraeus – VI. Hierarchical assembly of AGN and their large-scale effect during the Epoch of Reionization
Authors: Trebitsch Maxime , Hutter Anne , Dayal Pratika , Gottlöber Stefan , Legrand Laurent , Yepes Gustavo
Published: November 2022

In this work, the sixth of a series, we use the seminumerical rAdiative tranSfer coupling of galaxy formaTion and Reionization in N-body dark-matter simUlationS (astraeus) framework to investigate the nature of the sources that reionized the Universe. We extend astraeus, which already couples a galaxy formation semi-analytical model with a detailed seminumerical reionization scheme, to include a model for black-hole formation, growth, and the production of ionizing radiation from associated active galactic nuclei (AGNs). We calibrate our fiducial AGN model to reproduce the bolometric luminosity function at z ≃ 5, and explore the role of the resulting AGN population in reionizing the Universe. We find that in all the models yielding a reasonable AGN luminosity function, galaxies dominate overwhelmingly the ionizing budget during the Epoch of Reionization, with AGN accounting for 1–10 per cent of the ionizing budget at z = 6 and starting to play a role only below z ≲ 5.
Chemo-dynamical substructure in the M31 inner halo globular clusters: further evidence for a recent accretion event
Authors: Lewis Geraint F , Brewer Brendon J , Mackey Dougal , Ferguson Annette M N , Li Yuan (Cher) , Adams Tim
Published: November 2022

Based upon a metallicity selection, we identify a significant subpopulation of the inner halo globular clusters in the Andromeda Galaxy, which we name the Dulais Structure. It is distinguished as a co-rotating group of 10–20 globular clusters that appear to be kinematically distinct from, and on average more metal-poor than, the majority of the inner halo population. Intriguingly, the orbital axis of this Dulais Structure is closely aligned with that of the younger accretion event recently identified using a subpopulation of globular clusters in the outer halo of Andromeda, and this is strongly suggestive of a causal relationship between the two. If this connection is confirmed, a natural explanation for the kinematics of the globular clusters in the Dulais Structure is that they trace the accretion of a substantial progenitor (∼1011 M⊙) into the halo of Andromeda during the last few billion years, which may have occurred as part of a larger group infall.
Impact of experimental design factors on the potency of genotoxicants in in vitro tests
Authors: Sanders Julie , Thienpont Anouck , Anthonissen Roel , Vanhaecke Tamara , Mertens Birgit
Published: November 2022

Previous studies have shown that differences in experimental design factors may alter the potency of genotoxic compounds in in vitro genotoxicity tests. Most of these studies used traditional statistical methods based on the lowest observed genotoxic effect levels, whereas more appropriate methods, such as the benchmark dose (BMD) approach, are now available to compare genotoxic potencies under different test conditions. We therefore investigated the influence of two parameters, i.e. cell type and exposure duration, on the potencies of two known genotoxicants [aflatoxin B1 and ethyl methanesulfonate (EMS)] in the in vitro micronucleus (MN) assay and comet assay (CA). Both compounds were tested in the two assays using two cell types (i.e. CHO-K1 and TK6 cells). To evaluate the effect of exposure duration, the genotoxicity of EMS was assessed after 3 and 24 h of exposure. Results were analyzed using the BMD covariate approach, also referred to as BMD potency ranking, and the outcome was compared with that of more traditional statistical methods based on lowest observed genotoxic effect levels. When comparing the in vitro MN results obtained in both cell lines with the BMD covariate approach, a difference in potency was detected only when EMS exposures were conducted for 24 h, with TK6 cells being more sensitive. No difference was observed in the potency of both EMS and aflatoxin B1 in the in vitro CA using both cell lines. In contrast, EMS was more potent after 24 h exposure compared with a 3 h exposure under all tested conditions, i.e. in the in vitro MN assay and CA in both cell lines. Importantly, for several of the investigated factors, the BMD covariate method could not be used to confirm the differences in potencies detected with the traditional statistical methods, thus highlighting the need to evaluate the impact of experimental design factors with adequate approaches.
Younger Children Develop Higher Effector Antibody Responses to SARS-CoV-2 Infection
Authors: Tomasi Lisa , Thiriard Anais , Heyndrickx Leo , Georges Daphnée , Van den Wijngaert Sigi , Olislagers Véronique , Sharma Shilpee , Matagne André , Ackerman Margaret E , Ariën Kevin K , Goetghebuer Tessa , Marchant Arnaud
Published: November 2022

Background

The basis of the less severe clinical presentation of coronavirus disease 2019 (COVID-19) in children as compared with adults remains incompletely understood. Studies have suggested that a more potent boosting of immunity to endemic common cold coronaviruses (HCoVs) may protect children.

Methods

To test this hypothesis, we conducted a detailed analysis of antibodies induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children aged 2 months to 14 years.

Results

Younger children had higher titers of antibodies to SARS-CoV-2 receptor binding domain (RBD), S1 but not S2 domain, and total spike (S) protein, higher avidity RBD immunoglobulin G, and higher titers of neutralizing and complement-activating antibodies as compared with older children. In contrast, older children had higher titers of antibodies to HCoVs, which correlated with antibodies to the SARS-CoV-2 S2 domain but not with neutralizing or complement-activating antibodies.

Conclusions

These results reveal a unique capacity of young children to develop effector antibody responses to SARS-CoV-2 infection independently of their immunity to HCoVs.
Different combinations of laccase paralogs nonredundantly control the amount and composition of lignin in specific cell types and cell wall layers in Arabidopsis
Authors: Blaschek Leonard , Murozuka Emiko , Serk Henrik , Ménard Delphine , Pesquet Edouard
Published: November 2022

Vascular plants reinforce the cell walls of the different xylem cell types with lignin phenolic polymers. Distinct lignin chemistries differ between each cell wall layer and each cell type to support their specific functions. Yet the mechanisms controlling the tight spatial localization of specific lignin chemistries remain unclear. Current hypotheses focus on control by monomer biosynthesis and/or export, while cell wall polymerization is viewed as random and nonlimiting. Here, we show that combinations of multiple individual laccases (LACs) are nonredundantly and specifically required to set the lignin chemistry in different cell types and their distinct cell wall layers. We dissected the roles of Arabidopsis thaliana LAC4, 5, 10, 12, and 17 by generating quadruple and quintuple loss-of-function mutants. Loss of these LACs in different combinations led to specific changes in lignin chemistry affecting both residue ring structures and/or aliphatic tails in specific cell types and cell wall layers. Moreover, we showed that LAC-mediated lignification has distinct functions in specific cell types, waterproofing fibers, and strengthening vessels. Altogether, we propose that the spatial control of lignin chemistry depends on different combinations of LACs with nonredundant activities immobilized in specific cell types and cell wall layers.
Sleep as a Mediator Between Cannabis Use and Psychosis Vulnerability: A Longitudinal Cohort Study
Authors: Ouellet Julien , Spinney Sean , Assaf Roxane , Boers Elroy , Livet Audrey , Potvin Stéphane , Conrod Patricia
Published: November 2022

Objectives

Increasing evidence implicates cannabis consumption as a key risk factor in the development of psychosis, but the mechanisms underpinning this relationship remain understudied. This study proposes to determine whether sleep disruption acts as a mediator of the cannabis-to-psychosis relationship.

Study Design

This longitudinal study assessed measures of cannabis use frequency, sleep quality (SQ), and psychotic-like experiences (PLEs) were collected using self-reported questionnaires. Data were collected from September 2012 to September 2018. Data were collected from a general population sample of adolescents who entered the seventh grade in 31 schools in the Greater Montreal area. The study uses data collected on an annual basis from 3801 high school students from grades 7 to 11. The aforementioned measures were measured using the Detection of Alcohol and Drug Problems in Adolescents questionnaire, a SQ Likert scale, and measures the Psychotic-Like Experiences Questionnaire for Children.

Study Results

Results show a reciprocal 1-year cross-lagged effect of cannabis use and sleep (β = −0.076, 95% CI = −0.037 to −0.018, P = .000), of sleep on cannabis use (β = −.016, 95% CI = −0.025 to −0.006, P = .007), of sleep on PLEs (β = −0.077, 95%CI = −0.014 to −0.051, P = .000), and of PLEs on sleep (β = −0.027, 95% CI = −0.037 to −0.018, P = .000). We additionally found a 2 years indirect lagged-effect of cannabis use on PLEs (β = 0.068, 95% CI = 0.024 to 0.113, P = .011) mediated by 1-year sleep (β = 0.006, 95% CI = 0.003 to 0.009, P = .001).

Conclusions

Our results suggest sleep disruptions simultaneously aggravate, and are aggravated by, cannabis addiction and PLEs. The longitudinal sleep-mediated effect of cannabis use on PLEs encourages further research into the role of sleep as a potential therapeutic target in the prevention of cannabis-related psychosis.
Foliar Phosphate Applications Influence Organic Acid Composition in the Citrus Phloem and Could Reduce Huanglongbing Disease by Limiting CLas Titers
Authors: Glusberger Paula Rios , Petrone Joseph R. , Muñoz-Beristain Alam , Li Jinyun , Wang Nian , Guha Anirban , Vincent Christopher , Killiny Nabil , Triplett Eric W.
Published: November 2022

Citrus greening disease is now completely endemic to Florida citrus trees, having spread rapidly across all counties in the past 20 years and causing devastating economic losses. The disease's etiological agent is the phloem-restricted bacterium ‘ Candidatus Liberibacter asiaticus’ ( CLas). Liberibacter crescens, the closest culturable relative, was discovered to prefer citrate as its most effective carbon and energy source. Citrus plants load free citrate in response to phosphorus deficiency. In Florida's calcareous soils, supplemental phosphate fertilization is very low due to the assumption that phosphate is readily available for plants through the soil. It is likely that citrus trees are loading citrate to mine phosphorus from the soil, which could inadvertently exacerbate CLas infection. In greenhouse experiments, foliar-sprayed phosphate is taken up by the plants, resulting in decreased free-citrate levels and changes in fumaric and succinic acids in the phloem, in addition to delaying titer detection of CLas. Our field experiments—where mature trees have a well-established huanglongbing infection maintained by infected psyllids—exhibited a lower CLas titer for some of the phosphate treatments across time.
A Diagnostic Guide for Myrtle Rust
Authors: Boufleur Thaís R. , Morales João V. P. , Martins Túlio V. , Gonçalves Manoel P. , Júnior Nelson S. Massola , Amorim Lilian
Published: November 2022

Myrtle rust is associated with more than 480 host species belonging to the Myrtaceae family, including economically important genera, such as Eucalyptus, Metrosideros, Angophora, Syzygium, and Psidium, and native plant species that are part of forest biodiversity in several countries. This disease is caused by Austropuccinia psidii (G. Winter) Beenken, 2017 (synonym Puccinia psidii (G. Winter), 1884). In this publication, we provide methods for myrtle rust diagnosis and manipulation of the pathogen in field and laboratory conditions.
The Dynamic Transcription Activator-Like Effector Family of Xanthomonas
Authors: Teper Doron , White Frank F. , Wang Nian
Published: November 2022

Transcription activator-like effectors (TALEs) are bacterial proteins that are injected into the eukaryotic nucleus to act as transcriptional factors and function as key virulence factors of the phytopathogen Xanthomonas. TALEs are translocated into plant host cells via the type III secretion system and induce the expression of host susceptibility (S) genes to facilitate disease. The unique modular DNA binding domains of TALEs comprise an array of nearly identical direct repeats that enable binding to DNA targets based on the recognition of a single nucleotide target per repeat. The very nature of TALE structure and function permits the proliferation of TALE genes and evolutionary adaptations in the host to counter TALE function, making the TALE−host interaction the most dynamic story in effector biology. The TALE genes appear to be a relatively young effector gene family, with a presence in all virulent members of some species and absent in others. Genome sequencing has revealed many TALE genes throughout the xanthomonads, and relatively few have been associated with a cognate S gene. Several species, including Xanthomonas oryzae pv. oryzae and X. citri pv. citri, have near absolute requirement for TALE gene function, while the genes appear to be just now entering the disease interactions with new fitness contributions to the pathogens of tomato and pepper among others. Deciphering the simple and effective DNA binding mechanism also has led to the development of DNA manipulation tools in fields of gene editing and transgenic research. In the three decades since their discovery, TALE research remains at the forefront of the study of bacterial evolution, plant−pathogen interactions, and synthetic biology. We also discuss critical questions that remain to be addressed regarding TALEs.