bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydration and pore structure characteristics of concrete incorporating internal curing materials in a dry and large-temperature-difference environment
Authors: Lu Yan , Wang Kun , Zhu Duo , Meng Qingxin , Cui Liyan
Published: March 2022

The climate in the Central Asian area is extreme dry, with a large temperature difference between day and night, and the concrete is easy to crack during the construction period under the conditions of traditional external curing. Therefore, this study concerns understanding the application of internal curing materials in a dry and large-temperature-difference environment. The effects of three internal curing materials, namely, Super Absorbent Polymer (SAP), Light Weight Aggregate (LWA) and Perforated Cenospheres (PCs), on hydration and pore structure characteristics of concrete were investigated. Scanning electron microscope (SEM) and x-ray diffractometer (XRD)were used to observe the microscopic morphology and physical phase composition of concrete, and the evolution of pore characteristics was analyzed using mercury intrusion porosimeter (MIP) to explore the mechanism of pore structure refinement. Results show that the pores formed by the release of water provide space for the accumulation of hydration products, thereby accelerating the formation of ettringite crystals. Results indicate that the continuous release of internal curing materials allows the interior of the concrete to continue to be hydrated, which greatly promotes the overall hydration of the cement. The effect of supplementary cementitious materials (GGBS, FA) and implications of large-temperature-difference environment on concrete durability are discussed.
3DG/Se4.7S3.3 composites with different morphologies as new all-solid-state lithium storage electrode materials
Authors: Shen Zhongli , Liu Fangchao , Hu Han , Fu Zhengwen
Published: March 2022

Selenium-sulfur(SexSy) composites can be used as energy storage materials for lithium batteries benefit from their integration of the high capacity of sulfur and the high conductivity of selenium. Herein, we prepared amorphous three dimensional reduced graphene oxide/selenium sulfide(a-3DG/Se4.7S3.3) composites and crystalline 3DG/Se4.7S3.3(c-3DG/Se4.7S3.3) composites by in situ synthesis and hydrothermal methods, respectively, in order to research the effect of different morphologies of 3DG/Se4.7S3.3 composites on the electrochemical properties of all-solid-state lithium batteries. Our study found that the a-3DG/Se4.7S3.3 cathodes displayed greater capacity and outstanding rate performance, with an initial discharge capacity of 926 mAh g−1 and utilization rate of 103% at 1/2C. And a first discharge capacity of up to 706 mAh g−1 at 7 C. Although the first discharge capacity of c-3DG/Se4.7S3.3 was 523 mAh g−1, its cycling stability was significantly improved compared with that of a-3DG/Se4.7S3.3 cathodes, and the Coulombic efficiency remained above 97% after 60 cycles at ½ C. In this work, we investigate the performance of solid-state batteries by preparing new SexSy composites with different morphologies and rational design of electrodes in terms of structure and morphology, which provides ideas for the preparation of electrodes in the future.
Effect of bimodal grain size and gradient structure on heterogeneous deformation induced (HDI) stress and mechanical properties of Cu
Authors: Yang Yi , Gong Yulan , Li Xingfu , Liu Huan , Li Cong , Yang Jingran , Pan Hongjiang , Shu Baipo , Deng Chao , Fang Junqi , Zhu Xinkun
Published: March 2022

In this study, two different types of heterogeneous structures were prepared by controlling different surface mechanical attrition treatment (SMAT) time (5 s, 10 s, 30 s, 60 s). The effect of heterogeneous Cu with bimodal grain size structure (BGSS) and gradient structure (GS) on heterogeneous deformation induced (HDI) stress and mechanical properties was investigated systematically. By combining surface morphology with microhardness distribution, it was found that the surface grains of the SMAT-ed Cu (5 s and 10 s) were partially refined to exhibit BGSS, while the surface grains of SMAT-ed Cu (30 s and 60 s) were sufficiently refined to form GS. The load-unload-reload (LUR) tests results showed that HDI stress for SMAT 60s Cu was much higher than that of the SMAT 10s Cu. Furthermore, microstructure characterizations revealed that SMAT-ed Cu with BGSS and GS suppressed strain localization, which resulted in high strength and reasonable ductility.
Machine learning-based method to adjust electron anomalous conductivity profile to experimentally measured operating parameters of Hall thruster
Authors: SHASHKOV Andrey , TYUSHEV Mikhail , LOVTSOV Alexander , TOMILIN Dmitry , KRAVCHENKO Dmitrii
Published: March 2022

The problem of determining the electron anomalous conductivity profile in a Hall thruster, when its operating parameters are known from the experiment, is considered. To solve the problem, we propose varying the parametrically set anomalous conductivity profile until the calculated operating parameters match the experimentally measured ones in the best way. The axial 1D3V hybrid model was used to calculate the operating parameters with parametrically set conductivity. Variation of the conductivity profile was performed using Bayesian optimization with a Gaussian process (machine learning method), which can resolve all local minima, even for noisy functions. The calculated solution corresponding to the measured operating parameters of a Hall thruster in the best way proved to be unique for the studied operating modes of KM-88. The local plasma parameters were calculated and compared to the measured ones for four different operating modes. The results show the qualitative agreement. An agreement between calculated and measured local parameters can be improved with a more accurate model of plasma-wall interaction.
Phase polynomials synthesis algorithms for NISQ architectures and beyond
Authors: Vandaele Vivien , Martiel Simon , Goubault de Brugière Timothée
Published: March 2022

We present a framework for the synthesis of phase polynomials that addresses both cases of full connectivity and partial connectivity for NISQ architectures. In most cases, our algorithms generate circuits with lower CNOT count and CNOT depth than the state of the art or have a significantly smaller running time for similar performances. We also provide methods that can be applied to our algorithms in order to trade an increase in the CNOT count for a decrease in execution time, thereby filling the gap between our algorithms and faster ones.
Qsun: an open-source platform towards practical quantum machine learning applications
Authors: Nguyen Quoc Chuong , Ho Le Bin , Nguyen Tran Lan , Nguyen Hung Q
Published: March 2022

Currently, quantum hardware is restrained by noises and qubit numbers. Thus, a quantum virtual machine (QVM) that simulates operations of a quantum computer on classical computers is a vital tool for developing and testing quantum algorithms before deploying them on real quantum computers. Various variational quantum algorithms (VQAs) have been proposed and tested on QVMs to surpass the limitations of quantum hardware. Our goal is to exploit further the VQAs towards practical applications of quantum machine learning (QML) using state-of-the-art quantum computers. In this paper, we first introduce a QVM named Qsun, whose operation is underlined by quantum state wavefunctions. The platform provides native tools supporting VQAs. Especially using the parameter-shift rule, we implement quantum differentiable programming essential for gradient-based optimization. We then report two tests representative of QML: quantum linear regression and quantum neural network.
Error estimates for a class of continuous Bonse-type inequalities
Authors: Marques Diego , Trojovský Pavel
Published: March 2022

Let

p
n

p_n

be the

n
n

th prime number. In 2000, Papaitopol proved that the inequality

p
1

⋯

p
n

>

p

n
+
1

n
−
π
(
n
)

p_1\cdots p_n>p_{n+1}^{n-\pi (n)}

holds, for all

n
≥
2

n\geq 2

, where

π
(
x
)

\pi (x)

is the prime counting function. In 2021, Yang and Liao tried to sharpen this inequality by replacing

n
−
π
(
n
)

n-\pi (n)

by

n
−
π
(
n
)
+
π
(
n
)

/

π
(
log
⁡
n
)
−
2
π
(
π
(
n
)
)

n-\pi (n)+\pi (n)/\pi (\log n)-2\pi (\pi (n))

, however there is a small mistake in their argument. In this paper, we exploit properties of the logarithm error term in inequalities of the type

p
1

⋯

p
n

>

p

n
+
1

k
(
n
,
x
)

p_1\cdots p_n>p_{n+1}^{k(n,x)}

, where
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="k left-parenthesis n comma x right-parenthesis equals n minus pi left-parenthesis n right-parenthesis plus pi left-parenthesis n right-parenthesis slash pi left-parenthesis log n right-parenthesis minus x pi left-parenthesis pi left-parenthesis n right-parenthesis right-parenthesis">

k
(
n
,
x
)
=
n
−
π
(
n
)
+
π
(
n
)

/

π
(
log
⁡
n
)
−
x
π
(
π
(
n
)
)

k(n,x)=n-\pi (n)+\pi (n)/\pi (\log n)-x\pi (\pi (n))

. In particular, we improve Yang and Liao estimate, by showing that the previous inequality at

x
=
1.4

x=1.4

holds for all

n
≥
21

n\geq 21

.
On the regularity of the complex Hessian equation
Authors: Åhag Per , Czyż Rafał
Published: March 2022

This note aims to investigate the regularity of a solution to the Dirichlet problem for the complex Hessian equation, which has a density of the

m
m

-Hessian measure that belongs to

L
q

L^q

, for

q
≤

n
m

q\leq \frac nm

.
Roots of the identity operator and proximal mappings: (Classical and phantom) cycles and gap vectors
Authors: Bauschke Heinz , Wang Xianfu
Published: March 2022

Recently, Simons provided a lemma for a support function of a closed convex set in a general Hilbert space and used it to prove the geometry conjecture on cycles of projections. In this paper, we extend Simons’s lemma to closed convex functions, show its connections to Attouch–Théra duality, and use it to characterize (classical and phantom) cycles and gap vectors of proximal mappings.
Critical value asymptotics for the contact process on random graphs
Authors: Nam Danny , Nguyen Oanh , Sly Allan
Published: March 2022

Recent progress in the study of the contact process (see Shankar Bhamidi, Danny Nam, Oanh Nguyen, and Allan Sly [Ann. Probab. 49 (2021), pp. 244–286]) has verified that the extinction-survival threshold

λ
1

\lambda _1

on a Galton-Watson tree is strictly positive if and only if the offspring distribution

ξ
\xi

has an exponential tail. In this paper, we derive the first-order asymptotics of

λ
1

\lambda _1

for the contact process on Galton-Watson trees and its corresponding analog for random graphs. In particular, if

ξ
\xi

is appropriately concentrated around its mean, we demonstrate that

λ
1

(
ξ
)
∼
1

/

E

ξ

\lambda _1(\xi ) \sim 1/\mathbb {E} \xi

as

E

ξ
→
∞

\mathbb {E}\xi \rightarrow \infty

, which matches with the known asymptotics on

d
d

-regular trees. The same results for the short-long survival threshold on the Erdős-Rényi and other random graphs are shown as well.
On the multiparameter Falconer distance problem
Authors: Du Xiumin , Ou Yumeng , Zhang Ruixiang
Published: March 2022

We study an extension of the Falconer distance problem in the multiparameter setting. Given

ℓ
≥
1

\ell \geq 1

and

R

d

=

R

d
1

×
⋯
×

R

d
ℓ

\mathbb {R}^{d}=\mathbb {R}^{d_1}\times \cdots \times \mathbb {R}^{d_\ell }

,

d
i

≥
2

d_i\geq 2

. For any compact set

E
⊂

R

d

E\subset \mathbb {R}^{d}

with Hausdorff dimension larger than

d
−

min
⁡
(

d
i

)

2

+

1
4

d-\frac {\operatorname {min}(d_i)}{2}+\frac {1}{4}

if

min
⁡
(

d
i

)

\operatorname {min}(d_i)

is even,

d
−

min
⁡
(

d
i

)

2

+

1
4

+

1

4
min
⁡
(

d
i

)

d-\frac {\operatorname {min}(d_i)}{2}+\frac {1}{4} +\frac {1}{4\operatorname {min}(d_i)}

if

min
⁡
(

d
i

)

\operatorname {min}(d_i)

is odd, we prove that the multiparameter distance set of

E
E

has positive

ℓ
\ell

-dimensional Lebesgue measure. A key ingredient in the proof is a new multiparameter radial projection theorem for fractal measures.
Surfaces on the Severi line in positive characteristic
Authors: Gu Yi , Sun Xiaotao , Zhou Mingshuo
Published: March 2022

Let

k

\mathbf {k}

be an algebraically closed field, a minimal surface

X
X

over

k

\mathbf {k}

of maximal Albanese dimension is called on the Severi line if the ‘Severi equality’:

K
X
2

=
4
χ
(

O

X

)

K^2_X=4\chi (\mathcal {O}_X)

holds. We prove that

X
X

is on the Severi line if and only if its canonical model

X

c
a
n

X_{\mathrm {can}}

admits a flat double cover over an Abelian surface.
On 𝐿¹² square root cancellation for exponential sums associated with nondegenerate curves in ℝ⁴
Authors: Demeter Ciprian
Published: March 2022

We prove sharpL12L^{12}estimates for exponential sums associated with nondegenerate curves inR4\mathbb {R}^4. We place Bourgain’s seminal result [J. Amer. Math. Soc. 30 (2017), pp. 205–224] in a larger framework that contains a continuum of estimates of different flavor. We enlarge the spectrum of methods by combining decoupling with quadratic Weyl sum estimates, to address new cases of interest. All results are proved in the general framework of real analytic curves.
The Adams spectral sequence for the image-of-𝐽 spectrum
Authors: Bruner Robert , Rognes John
Published: March 2022

We show that if we factor the long exact sequence in cohomology of a cofiber sequence of spectra into short exact sequences, then the

d
2

d_2

-differential in the Adams spectral sequence of any one term is related in a precise way to Yoneda composition with the 2-extension given by the complementary terms in the long exact sequence. We use this to give a complete analysis of the Adams spectral sequence for the connective image-of-

J
J

spectrum, finishing a calculation that was begun by D. Davis [Bol. Soc. Mat. Mexicana (2) 20 (1975), pp. 6–11].
The microtubule plus-end tracking protein Bik1 is required for chromosome congression
Authors: Julner Alexander , Abbasi Marjan , Menéndez-Benito Victoria
Published: March 2022

Bik1, the budding yeast homolog of CLIP-170, is a microtubule plus-end tracking protein involved in spindle positioning. Here we reveal that Bik1 also has a crucial role in the alignment of chromosomes in metaphase, a process known as chromosome congression.
Circulating Cell-Free DNA and DNA Integrity as Molecular Diagnostic Tools in Hepatocellular Carcinoma
Authors: Elzehery Rasha , Effat Narmin , El Farahaty Reham , Elsayed Farag Raghda , Abo-Hashem Ekbal M , Elhelaly Rania
Published: March 2022

Objectives

We assessed the ability to use circulating cell-free DNA (cfDNA) and the DNA integrity index (DNAII) to detect the transition from liver cirrhosis (LC) to hepatocellular carcinoma (HCC).

Methods

Circulating cfDNA and DNAII were measured in 50 patients with advanced LC and 50 patients with HCC who were followed for 1 month after transarterial chemoembolization (TACE). Fifty healthy participants served as a control group. Real-time quantitative polymerase chain reaction (PCR) was used to measure circulating cfDNA concentration, and Alu-PCR was used to measure the concentration of Alu repeats, both short fragments (115 base pairs [bp]) and long fragments (247 bp). We compared liquid biopsy results with the relevant traditional markers.

Results

The HCC group showed significantly higher circulating cfDNA concentrations and DNAII values compared with the LC and control groups. No significant differences were found in circulating cfDNA concentrations and DNAII values between the LC and control groups. Circulating cfDNA concentrations decreased significantly after treatment (TACE); areas under the curve of circulating cfDNA concentration and DNAII values were significantly better than those of ɑ-fetoprotein and vascular endothelial growth factor in discriminating between LC and HCC.

Conclusions

The combined use of DNAII with proteins induced by vitamin K absence or antagonist showed better diagnostic performance in HCC. Circulating cfDNA could have a potential role in monitoring HCC treatment.
An updated vancomycin dosing protocol for initiating therapy in patients undergoing intermittent high-flux hemodialysis
Authors: Zelenitsky Sheryl A , Ariano Robert E
Published: March 2022

Purpose

To design an updated vancomycin dosing protocol for initiating therapy in patients undergoing chronic intermittent high-flux hemodialysis (iHFHD) that is congruent with the revised 2020 consensus guidelines for therapeutic drug monitoring (TDM).

Methods

Monte Carlo simulation methods were used to study vancomycin dosing for patients on iHFHD. Vancomycin regimens were constructed as intravenous infusions (for intradialytic administration) of a loading dose and maintenance doses 3 times weekly during subsequent dialysis sessions. Vancomycin plasma concentrations were simulated, and the probability of target attainment (PTA) for a 24-hour area under the time-concentration curve (AUC24) of 400 to 700 mg · h/L was determined. Standardized weight-based (ie, dose-banding) regimens were investigated, and an optimized protocol was selected based on TDM target attainment and practical considerations for use in the dialysis setting.

Results

The proposed vancomycin dosing protocol (for intradialytic administration) specifies 3 regimens: (1) a 1,500-mg loading dose and 750-mg maintenance doses for patients weighing 50 kg to 69 kg; (2) a 2,000-mg loading dose and 1,000-mg maintenance doses for patients weighing 70 kg to 89 kg; and (3) a 2,500-mg loading dose and 1,250-mg maintenance doses for patients weighing 90 kg to 110 kg. In a simulated hemodialysis population (n = 5,000), the proposed protocol delivered median (interquartile range [IQR]) loading and maintenance doses of 25.0 (23.4-26.6) mg/kg and 12.5 (11.8-13.3) mg/kg, respectively. The PTA for an AUC24 of 400 to 700 mg · h/L was 74.7% on day 1 and 70.8% on day 8, with less than 10% of values exceeding the target range.

Conclusion

Our proposed dosing protocol for patients undergoing iHFHD offers an updated and practical approach for initiating vancomycin therapy that can be optimized with early TDM.
Effectiveness of telepharmacy diabetes services: A systematic review and meta-analysis
Authors: Cao Diana X , Tran Rebecca J C , Yamzon Joycelyn , Stewart Tania L , Hernandez Elvin A
Published: March 2022

Purpose

Although pharmacist-provided diabetes services have been shown to be effective, the effectiveness of telepharmacy (TP) in diabetes management has not been clearly established. This systematic review and meta-analysis aims to evaluate the effectiveness of diabetes TP services.

Methods

PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched (from inception through September 2021) to identify published studies that evaluated the effect of TP services in patients with diabetes mellitus and reported either glycosylated hemoglobin (HbA1c) or fasting blood glucose (FBG) outcomes. Mean difference (MD), weighted mean difference (WMD), relative risk (RR), and 95% confidence intervals were calculated using the DerSimonian and Laird random-effects model.

Results

36 studies involving 13,773 patients were included in the systematic review, and 23 studies were included in the meta-analysis. TP was associated with a statistically significant decrease in HbA1c (MD, –1.26%; 95% CI, –1.69 to –0.84) from baseline. FBG was not significantly affected (MD, –25.32 mg/dL; 95% CI, –57.62 to 6.98). Compared to non-TP service, TP was associated with a lower risk of hypoglycemia (RR, 0.48; 95% CI, 0.30-0.76). In a subset of studies that compared TP to face-to-face (FTF) pharmacy services, no significant difference in HbA1c lowering was seen between the 2 groups (WMD, –0.09%; 95% CI, –1.07 to 0.90).

Conclusion

Use of TP was associated with reduction of HbA1c and the risk of hypoglycemia in patients with diabetes mellitus. High-quality randomized controlled trials are needed to validate the effectiveness of diabetes TP services relative to FTF services.
Development of a system-wide pharmacy operational weighted workload model at a large academic health system
Authors: Petersen Autumn E , Zeeman Jacqueline M , Vest Mary-Haston , Schenkat Daniel H , Colmenares Evan W
Published: March 2022

Purpose

The purpose of this study is to develop a standard operational and distributional weighted workload model that is applicable across an integrated, diverse healthcare system. This model aims to not only demonstrate the operational intensity of pharmacy practice but also to inform opportunities to decrease waste, increase efficiency, facilitate growth, and demonstrate value across operational and distributional pharmacy services.

Time studies were conducted at 8 hospitals within the UNC Health system to objectively measure time spent within each operational process in order to create a system-wide weighted workload model. Time study results informed the development of a system-wide weighted workload model. Data from December 29, 2019, through December 26, 2020, was then applied to this weighted workload model. With this model, acute care hospital and infusion center operational areas were compared in thousands of combinations within single operational areas and across any and all operational areas by dispense code, weighted work, and ratio of weighted work to total sum of dispenses at each site.

Conclusion

The model successfully achieved the objective to develop a standard operational weighted workload model that is applicable across the integrated, diverse care system. This model provides a foundation for UNC Health to further productivity measurement and fills a gap in the literature by offering a novel method of developing a system-level operational workload model that can be used to evaluate and compare operational workloads across health-system sites.
Phylogenetic position of Ligusticopsis (Apiaceae, Apioideae): evidence from molecular data and carpological characters
Authors: Li Zi-Xuan , Guo Xian-Lin , Price Megan , Zhou Song-Dong , He Xing-Jin
Published: March 2022

Ligusticopsis (Apiaceae, Apioideae) is now considered to have an East-Asia and Sino–Himalaya distribution. The genus was not recognized as a natural and separate genus and was treated as a synonym of Ligusticum both in Flora Reipublicae Popularis Sinicae and Flora of China since first established, though Pimenov et al. have made many taxonomic revisions to Ligusticopsis, phylogenetic relationships between Ligusticopsis and Ligusticum have been in dispute. Thirty-four plastomes and 35 nrITS from Apioideae were analysed by RAxML and MrBayes to reconstruct the phylogenetic relationships, along with carpology of 10 species and comparative analyses of 17 plastomes to investigate the evidence supporting the independence of Ligusticopsis. As a result, nine species suggested to be Ligusticopsis formed a highly supported monophyletic branch (Subclade A) inside Selineae both in maximum likelihood and Bayesian inference; the results of the comparative analyses further supported the monophyly of Subclade A, mainly in the location of genes at the IRa/LSC boundary, the sequence diversity exhibited by various genes (e.g. trnH-GUG–psbA and ycf2) and same codon biases in terminator TAA (relative synonymous codon usage = 1.75). Species in Subclade A also had shared characters in mericarps, combined with other characters of the plant, ‘base clothed in fibrous remnant sheaths, pinnate bracts, pinnate bracteoles longer than rays of umbellule, mericarps strongly compressed dorsally, median and lateral ribs filiform or keeled, marginal ribs winged, and numerous vittae in commissure and each furrow’ should be the most important and diagnostic characters of Ligusticopsis. Our phylogenetic trees and other analyses supported the previous taxonomic treatments of Pimenov et al. that Ligusticopsis should be a natural and separate genus rather than a synonym of Ligusticum.
BioDKG–DDI: predicting drug–drug interactions based on drug knowledge graph fusing biochemical information
Authors: Ren Zhong-Hao , Yu Chang-Qing , Li Li-Ping , You Zhu-Hong , Guan Yong-Jian , Wang Xin-Fei , Pan Jie
Published: March 2022

The way of co-administration of drugs is a sensible strategy for treating complex diseases efficiently. Because of existing massive unknown interactions among drugs, predicting potential adverse drug–drug interactions (DDIs) accurately is promotive to prevent unanticipated interactions, which may cause significant harm to patients. Currently, numerous computational studies are focusing on potential DDIs prediction on account of traditional experiments in wet lab being time-consuming, labor-consuming, costly and inaccurate. These approaches performed well; however, many approaches did not consider multi-scale features and have the limitation that they cannot predict interactions among novel drugs. In this paper, we proposed a model of BioDKG–DDI, which integrates multi-feature with biochemical information to predict potential DDIs through an attention machine with superior performance. Molecular structure features, representation of drug global association using drug knowledge graph (DKG) and drug functional similarity features are fused by attention machine and predicted through deep neural network. A novel negative selecting method is proposed to certify the robustness and stability of our method. Then, three datasets with different sizes are used to test BioDKG–DDI. Furthermore, the comparison experiments and case studies can demonstrate the reliability of our method. Upon our finding, BioDKG–DDI is a robust, yet simple method and can be used as a benefic supplement to the experimental process.
Integrated multi-cohorts for characterizing the immunogenomic landscape and predicting drug response in triple-negative breast cancer
Authors: Su Dongqing , Chi Meng , Wang Shiyuan , Di Shuhong , Zhang Haoxing , Lu Qianzi , Yu Yao , Xiong Yuqiang , Wei Haodong , Lv Yingli , Zuo Yongchun , Yang Lei
Published: March 2022

Triple-negative breast cancer (TNBC) is the breast cancer subtype with the highest fatality rate, and it seriously threatens women’s health. Recent studies found that the level of immune cell infiltration in TNBC was associated with tumor progression and prognosis. However, due to practical constraints, most of these TNBC immune infiltration studies only used a small number of patient samples and a few immune cell types. Therefore, it is necessary to integrate more TNBC patient samples and immune cell types to comprehensively study immune infiltration in TNBC to contribute to the prognosis and treatment of patients. In this study, 12 TNBC datasets were integrated and an extensive collection of 182 gene sets with immune-related signatures were included to comprehensively investigate tumor immune microenvironment of TNBC. A single sample gene set enrichment analysis was performed to calculate the infiltration score of each immune-related signature in each patient, and an immune-related risk scoring model for TNBC was constructed to accurately assess patient prognosis. Significant differences were found in immunogenomic landscape between different immune risk subtypes. In addition, the immunotherapy response and chemotherapy drug sensitivity of patients with different immune risk subtypes were also analyzed. The results showed that there were significant differences in these characteristics. Finally, a prediction model for immune risk subtypes of TNBC patients was constructed to accurately predict patients with unknown subtypes. Based on the aforementioned findings, we believed that the immune-related risk score constructed in this study can assist in providing personalized medicine to TNBC patients.
ProSAP: a GUI software tool for statistical analysis and assessment of thermal stability data
Authors: Ji Hongchao , Lu Xue , Zheng Zhenxiang , Sun Siyuan , Tan Chris Soon Heng
Published: March 2022

The Cellular Thermal Shift Assay (CETSA) plays an important role in drug-target identification, and statistical analysis is a crucial step significantly affecting conclusion. We put forward ProSAP (Protein Stability Analysis Pod), an open-source, cross-platform and user-friendly software tool, which provides multiple methods for thermal proteome profiling (TPP) analysis, nonparametric analysis (NPA), proteome integral solubility alteration and isothermal shift assay (iTSA). For testing the performance of ProSAP, we processed several datasets and compare the performance of different algorithms. Overall, TPP analysis is more accurate with fewer false positive targets, but NPA methods are flexible and free from parameters. For iTSA, edgeR and DESeq2 identify more true targets than t-test and Limma, but when it comes to ranking, the four methods show not much difference. ProSAP software is available at https://github.com/hcji/ProSAP and https://zenodo.org/record/5763315.
An efficient curriculum learning-based strategy for molecular graph learning
Authors: Gu Yaowen , Zheng Si , Xu Zidu , Yin Qijin , Li Liang , Li Jiao
Published: March 2022

Computational methods have been widely applied to resolve various core issues in drug discovery, such as molecular property prediction. In recent years, a data-driven computational method-deep learning had achieved a number of impressive successes in various domains. In drug discovery, graph neural networks (GNNs) take molecular graph data as input and learn graph-level representations in non-Euclidean space. An enormous amount of well-performed GNNs have been proposed for molecular graph learning. Meanwhile, efficient use of molecular data during training process, however, has not been paid enough attention. Curriculum learning (CL) is proposed as a training strategy by rearranging training queue based on calculated samples' difficulties, yet the effectiveness of CL method has not been determined in molecular graph learning. In this study, inspired by chemical domain knowledge and task prior information, we proposed a novel CL-based training strategy to improve the training efficiency of molecular graph learning, called CurrMG. Consisting of a difficulty measurer and a training scheduler, CurrMG is designed as a plug-and-play module, which is model-independent and easy-to-use on molecular data. Extensive experiments demonstrated that molecular graph learning models could benefit from CurrMG and gain noticeable improvement on five GNN models and eight molecular property prediction tasks (overall improvement is 4.08%). We further observed CurrMG’s encouraging potential in resource-constrained molecular property prediction. These results indicate that CurrMG can be used as a reliable and efficient training strategy for molecular graph learning.

Availability: The source code is available in https://github.com/gu-yaowen/CurrMG.
DeepTTA: a transformer-based model for predicting cancer drug response
Authors: Jiang Likun , Jiang Changzhi , Yu Xinyu , Fu Rao , Jin Shuting , Liu Xiangrong
Published: March 2022

Identifying new lead molecules to treat cancer requires more than a decade of dedicated effort. Before selected drug candidates are used in the clinic, their anti-cancer activity is generally validated by in vitro cellular experiments. Therefore, accurate prediction of cancer drug response is a critical and challenging task for anti-cancer drugs design and precision medicine. With the development of pharmacogenomics, the combination of efficient drug feature extraction methods and omics data has made it possible to use computational models to assist in drug response prediction. In this study, we propose DeepTTA, a novel end-to-end deep learning model that utilizes transformer for drug representation learning and a multilayer neural network for transcriptomic data prediction of the anti-cancer drug responses. Specifically, DeepTTA uses transcriptomic gene expression data and chemical substructures of drugs for drug response prediction. Compared to existing methods, DeepTTA achieved higher performance in terms of root mean square error, Pearson correlation coefficient and Spearman’s rank correlation coefficient on multiple test sets. Moreover, we discovered that anti-cancer drugs bortezomib and dactinomycin provide a potential therapeutic option with multiple clinical indications. With its excellent performance, DeepTTA is expected to be an effective method in cancer drug design.
Exploring the Effects of Geopolitical Shifts on Global Wildlife Trade
Authors: Ribeiro Joana , Bingre Pedro , Strubbe Diederik , Santana Joana , Capinha César , Araújo Miguel B , Reino Luís
Published: March 2022

International wildlife trade is a major driver of species extinction and biological invasions. Anticipating environmental risks requires inferences about trade patterns, which are shaped by geopolitics. Although the future cannot be predicted, scenarios can help deal with the uncertainty of future geopolitical dynamics. We propose a framework for generating and analyzing scenarios based on four geopolitical storylines, distinguished by combinations of international trade barrier strength and domestic law enforcement degree across countries supplying and demanding wildlife. We then use historical data on bird trade to classify countries into geopolitical profiles and confirm that trade barriers and law enforcement allow predicting bird trade patterns, supporting our scenarios’ plausibility and enabling projections for future global bird trade. Our framework can be used to examine the consequences of geopolitical changes for wildlife trade and to advise policy and legislation. Reducing demand for wildlife and ameliorating global inequality are key for curbing trade related risks.
Fighting a Fire versus Waiting for the Wave: Useful and Not-So-Useful Analogies in Times of SARS-CoV-2
Authors: Archer Louise C , Standley Claire J , Molnár Péter K
Published: March 2022

As SARS-CoV-2 has swept the planet, intermittent lockdowns have become a regular feature to control transmission. References to so-called recurring waves of infections remain pervasive among news headlines, political messaging, and public health sources. We explore the power of analogies to facilitate understanding of biological models and processes by reviewing strengths and limitations of analogies used throughout the COVID-19 pandemic. We consider how, when analogies fall short, their ability to persuade can mislead public perception, even if unintentionally. Although waves can convey patterns of disease outbreak, we suggest process-based analogies might be more effective communication tools, given that they can be easily mapped to underlying epidemiological concepts and extended to include complex dynamics. Although no single analogy perfectly captures disease dynamics, fire is particularly suitable for visualizing epidemiological models, underscoring the importance and reasoning behind control strategies and potentially conveying a sense of urgency that can galvanize individual and collective action.
Distinct brainstem to spinal cord noradrenergic pathways inversely regulate spinal neuronal activity
Authors: Kucharczyk Mateusz W , Di Domenico Francesca , Bannister Kirsty
Published: March 2022

Brainstem to spinal cord noradrenergic pathways include a locus coeruleus origin projection and diffuse noxious inhibitory controls. While both pathways are traditionally viewed as exerting an inhibitory effect on spinal neuronal activity, the locus coeruleus was previously shown to have a facilitatory influence on thermal nocioception according to the subpopulation of coerulean neurons activated. Coupled with knowledge of its functional modular organisation and the fact that diffuse noxious inhibitory controls are not expressed in varied animal models of chronicity, we hypothesized a regulatory role for the locus coeruleus on non-coerulean, discrete noradrenergic cell group(s).

We implemented locus coeruleus targeting strategies by microinjecting canine adenovirus encoding for channelrhodopsin-2 under a noradrenaline-specific promoter in the spinal cord (retrogradely labelling a coeruleospinal module) or the locus coeruleus itself (labelling the entire coerulean module). Coeruleospinal module optoactivation abolished diffuse noxious inhibitory controls (two-way ANOVA, P < 0.0001), which were still expressed following locus coeruleus neuronal ablation.

We propose that the cerulean system interacts with, but does not directly govern, diffuse noxious inhibitory controls. This mechanism may underlie the role of the locus coeruleus as a ‘chronic pain generator’. Pinpointing the functionality of discrete top-down pathways is crucial for understanding sensorimotor modulation in health and disease.
Different computational relations in language are captured by distinct brain systems
Authors: Fu Ze , Wang Xiaosha , Wang Xiaoying , Yang Huichao , Wang Jiahuan , Wei Tao , Liao Xuhong , Liu Zhiyuan , Chen Huimin , Bi Yanchao
Published: March 2022

A critical way for humans to acquire information is through language, yet whether and how language experience drives specific neural semantic representations is still poorly understood. We considered statistical properties captured by 3 different computational principles of language (simple co-occurrence, network-(graph)-topological relations, and neural-network-vector-embedding relations) and tested the extent to which they can explain the neural patterns of semantic representations, measured by 2 functional magnetic resonance imaging experiments that shared common semantic processes. Distinct graph-topological word relations, and not simple co-occurrence or neural-network-vector-embedding relations, had unique explanatory power for the neural patterns in the anterior temporal lobe (capturing graph-common-neighbors), inferior frontal gyrus, and posterior middle/inferior temporal gyrus (capturing graph-shortest-path). These results were relatively specific to language: they were not explained by sensory-motor similarities and the same computational relations of visual objects (based on visual image database) showed effects in the visual cortex in the picture naming experiment. That is, different topological properties within language and the same topological computations (common-neighbors) for language and visual inputs are captured by different brain regions. These findings reveal the specific neural semantic representations along graph-topological properties of language, highlighting the information type-specific and statistical property-specific manner of semantic representations in the human brain.
Molnupiravir and Nirmatrelvir-Ritonavir: Oral Coronavirus Disease 2019 Antiviral Drugs
Authors: Saravolatz Louis D , Depcinski Shawn , Sharma Mamta
Published: March 2022

At a crucial time with rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant globally, the United States Food and Drug Administration has issued an emergency use authorization for 2 oral antivirals, molnupiravir (in persons aged ≥18 years) and nirmatrelvir-ritonavir (Paxlovid) (in persons aged ≥12 years weighing ≥40 kg), for the outpatient treatment of patients with mild to moderate coronavirus disease 2019 (COVID–19) who are at risk for progression. Molnupiravir is a nucleoside analogue, whereas nirmatrelvir is a SARS-CoV-2 main protease inhibitor, and ritonavir is a human immunodeficiency virus type 1 protease inhibitor. Drug interactions are a major concern for nirmatrelvir-ritonavir. Nirmatrelvir-ritonavir demonstrated a greater risk reduction in hospitalization and death than molnupiravir compared to placebo. Both drugs need to be started within 5 days of symptoms onset and given for 5 days’ duration. This article reviews the 2 oral COVID-19 antiviral drugs including the mechanisms of action, antiviral activity, pharmacokinetics, drug interactions, clinical experience including trials, adverse events, recommended indications, and formulary considerations.
Mental Health, Work Presenteeism, and Exercise in Inflammatory Bowel Disease
Authors: Sciberras Martina , Karmiris Konstantinos , Nascimento Catarina , Tabone Trevor , Nikolaou Penelope , Theodoropoulou Angeliki , Mula Abigail , Goren Idan , Yanai Henit , Amir Hadar , Mantzaris Gerassimnos J , Georgiadi Tereza , Foteinogiannopoulou Kalliopi , Koutroubakis Ioannis , Allocca Mariangela , Fiorino Gionata , Furfaro Federica , Katsanos Konstantinos , Fousekis Fotios , Michalopoulos George , Camilleri Liberato , Torres Joana , Ellul Pierre
Published: March 2022

Background

Chronic diseases, such as IBD, can lead to anxiety and depression which can have a significant impact on productivity at work [presenteeism]. The aim of this study was to assess the prevalence of depression/anxiety, presenteeism and exercise levels among IBD patients.

Methods

This was a multicentre study whereby adult IBD patients, in clinical remission, were asked to answer a questionnaire anonymously. Hospital Anxiety and Depression Score [HADS], Stanford Presenteeism Scale [SPS-6] and Godin Exercise Score were also collected.

Results

A total of 585 patients were recruited. The majority had Crohn’s disease [CD, 62.2%] and were male [53.0%], with a median age of 39 years [IQR 30-49]. A psychiatric diagnosis was present in 10.8% of patients prior to their IBD diagnosis. A further 14.2% of patients were psychiatrically diagnosed after IBD diagnosis, this being commoner in CD patients [41.6% of CD, p <0.01]. A raised HADS-Anxiety or a HADS-Depression score ≥8 was present in 46.1% of patients, with 27.4% having a score ≥11. Low presenteeism at work was present in 34.0%. Patients diagnosed with depression/anxiety had a more sedentary lifestyle [p <0.01], lower presenteeism at work [p <0.01] and a higher rate of unemployment [p <0.01].

Conclusions

A significant percentage of IBD patients in remission suffer from anxiety and/or depression. Risk factors for these are CD, female gender, use of biologic medications, long-standing and/or perianal disease. Depression/anxiety was associated with a sedentary lifestyle, lower presenteeism at work and unemployment. Validated screening tools and appropriate referrals to psychologists and/or psychiatrists should be employed within IBD clinics.
Risk of depression after coronary artery bypass grafting: a SWEDEHEART population-based cohort study
Authors: Stenman Malin , Jeppsson Anders , Pivodic Aldina , Sartipy Ulrik , Nielsen Susanne J
Published: March 2022

Aims

A diagnosis of depression in patients with coronary heart disease is associated with worse outcomes. This study examined the long-term risk for new onset of depression after coronary artery bypass grafting (CABG) compared to an age- and sex-matched control group from the general population.

Methods and results

In total, 125 418 primary isolated CABG patients and 495 371 matched controls were included from 1992 to 2017. The SWEDEHEART registry and three other national registers were used to acquire information about baseline characteristics and depression. The adjusted risk of depression was estimated by using Cox regression models adjusted for patient characteristics, and socioeconomic variables, described by hazard ratios (HR) and 95% confidence intervals (CI). In total, 6202 (4.9%) CABG patients and 17 854 (3.6%) controls developed depression. The cumulative incidence of depression was higher in CABG patients than in the control population [6.1%, 95% CI 6.0–6.3 vs. 4.7% (4.7–4.8), P < 0.0001]. Overall, the CABG group had a marginally increased adjusted risk of depression compared to controls [adjusted HR (aHR): 1.05 (1.01–1.09), P = 0.0091]. In age-specific analyses, the increased risk compared to controls was only present in patients <65 years [aHR: 1.19 (1.11–1.27), P <0.0001] and was only evident during the first 5 years after surgery.

Conclusion

Patients who underwent CABG had a higher risk of new onset of depression compared to sex- and age-matched controls in the general population. The risk of depression was especially pronounced in younger patients during the first 5 years after surgery.
A forgotten pioneer: Eugene Marteney and the American renaissance of hautboy-making, 1962–1969
Authors: Howe Robert
Published: March 2022

Coming from a background in science and philosophy, the American electrical engineer Eugene Marteney (1934–2008) stumbled into hautboy-making in 1961–2, inspired by the playing of Josef Marx. Marteney learned the techniques of woodwind manufacture from Friedrich von Huene, who ultimately referred potential buyers to him. Selling hautboys after 1964, he did everything himself, from measuring antique specimens to designing and making the instruments and their reeds. He made connections with Marx, von Huene, Bruce Haynes, Paul Hailperin and, through him, with Michel Piguet and Bernhard Schermer, which would set off modern hautboy-making at original pitches. Marteney did this all half a decade before anyone else. In so doing he influenced all of the people we remember today as modern hautboy pioneers, laying the foundations for the Baroque revival of the 1970s and 80s.

In 1969, as Schermer and Haynes started making quality hautboys at original pitches, Marteney stopped doing so. His work was then forgotten until 2010. This article explores the hautboy-making of this remarkable man and shows how he influenced more well-known figures.
The relationship between mutuality and contributions to self-care in family caregivers of patients with heart failure: multiple mediating effects of resilience and self-efficacy
Authors: Chen Cancan , Zhao Qiuge , Zhang Xiuting , Yang Qiaofang , Dong Xiaoyu , Zhang Yilin , Fan Xiuzhen
Published: March 2022

Aims

Previous studies have indicated a positive association between mutuality and caregiver contributions to heart failure self-care (CC-HFSC). However, little is known about the underlying mechanisms in the relationship. This study aimed to determine whether resilience and self-efficacy play multiple mediating roles in the association between mutuality and CC-HFSC.

Methods and results

In this cross-sectional, correlational study, a self-reported survey was conducted in 259 patient–caregiver dyads recruited from two hospitals in China using a convenience sampling method. Better mutuality (r = 0.27, P < 0.01), resilience (r = 0.23, P < 0.01), and self-efficacy (r = 0.34, P < 0.01) were correlated with greater CC-HFSC maintenance. Better mutuality (r = 0.29, P < 0.01), resilience (r = 0.20, P < 0.01), and self-efficacy (r = 0.35, P < 0.01) were correlated with greater CC-HFSC management. In multiple mediation models, self-efficacy independently [effect = 0.061, 95% confidence interval (CI) (0.024–0.119)] and resilience and self-efficacy serially [effect = 0.017, 95% CI (0.007–0.036)] mediated the association between mutuality and CC-HFSC maintenance. Meanwhile, self-efficacy independently [effect = 0.058, 95% CI (0.020–0.113)] and resilience and self-efficacy serially [effect = 0.018, 95% CI (0.007–0.038)] mediated the association between mutuality and CC-HFSC management.

Conclusions

Resilience and self-efficacy were multiple mediators in the association between mutuality and CC-HFSC. Interventions targeting the facilitation of mutuality, and then increasing resilience and self-efficacy may be beneficial for improving CC-HFSC.
Dual roles for nuclear RNAi Argonautes in Caenorhabditis elegans dosage compensation
Authors: Davis Michael B , Jash Eshna , Chawla Bahaar , Haines Rebecca A , Tushman Lillian E , Troll Ryan , Csankovszki Györgyi
Published: March 2022

Dosage compensation involves chromosome-wide gene regulatory mechanisms which impact higher order chromatin structure and are crucial for organismal health. Using a genetic approach, we identified Argonaute genes which promote dosage compensation in Caenorhabditis elegans. Dosage compensation in C. elegans hermaphrodites is initiated by the silencing of xol-1 and subsequent activation of the dosage compensation complex which binds to both hermaphrodite X chromosomes and reduces transcriptional output by half. A hallmark phenotype of dosage compensation mutants is decondensation of the X chromosomes. We characterized this phenotype in Argonaute mutants using X chromosome paint probes and fluorescence microscopy. We found that while nuclear Argonaute mutants hrde-1 and nrde-3, as well as mutants for the piRNA Argonaute prg-1, exhibit derepression of xol-1 transcripts, they also affect X chromosome condensation in a xol-1-independent manner. We also characterized the physiological contribution of Argonaute genes to dosage compensation using genetic assays and found that hrde-1 and nrde-3 contribute to healthy dosage compensation both upstream and downstream of xol-1.