bluuebunny/crossref_metadata_2025 huggingface dataset:
Dilated cardiomyopathy–associated skeletal muscle actin (ACTA1) mutation R256H disrupts actin structure and function and causes cardiomyocyte hypocontractility
Authors: Garg Ankit , Jansen Silvia , Greenberg Lina , Zhang Rui , Lavine Kory J. , Greenberg Michael J.
Published: November 2024

Skeletal muscle actin (ACTA1) mutations are a prevalent cause of skeletal myopathies consistent with ACTA1’s high expression in skeletal muscle. Rare de novo mutations in ACTA1 associated with combined cardiac and skeletal myopathies have been reported, but ACTA1 represents only ~20% of the total actin pool in cardiomyocytes, making its role in cardiomyopathy controversial. Here we demonstrate how a mutation in an actin isoform expressed at low levels in cardiomyocytes can cause cardiomyopathy by focusing on a unique ACTA1 variant, R256H. We previously identified this variant in a family with dilated cardiomyopathy, who had reduced systolic function without clinical skeletal myopathy. Using a battery of multiscale biophysical tools, we show that R256H has potent effects on ACTA1 function at the molecular scale and in human cardiomyocytes. Importantly, we demonstrate that R256H acts in a dominant manner, where the incorporation of small amounts of mutant protein into thin filaments is sufficient to disrupt molecular contractility, and that this effect is dependent on the presence of troponin and tropomyosin. To understand the structural basis of this change in regulation, we resolved a structure of R256H filaments using cryoelectron microscopy, and we see alterations in actin’s structure that have the potential to disrupt interactions with tropomyosin. Finally, we show that

ACTA1
R256H/+

human-induced pluripotent stem cell cardiomyocytes demonstrate reduced contractility and sarcomeric organization. Taken together, we demonstrate that R256H has multiple effects on ACTA1 function that are sufficient to cause reduced contractility and establish a likely causative relationship between ACTA1 R256H and clinical cardiomyopathy.
Design characteristics of integrated surveillance of antimicrobial resistance at the human, animal, and environment interfaces
Authors: Hau Erda Eni Rame , Sly Peter D. , Mikkelsen Deirdre , Taneja Neelam , Penjor Kinley , Ryu Sukhyun , Donner Erica , Mollinger Joanne , Ferreira Jorge Pinto , Schipp Mark , Soares Magalhaes Ricardo J.
Published: November 2024

Efforts have been made to strengthen national and global antimicrobial resistance (AMR) surveillance programs by integrating data collection across the human, animal, and environmental sectors. We searched the literature to review published studies reporting the implementation of integrated AMR surveillance approaches, and we identified a total of 96 articles from 36 countries published from 2000 to 2022, which met our inclusion criteria. Standard review protocols were applied in our study. Out of 96 studies, 47 (49%) articles integrated AMR analysis from human and animal (HA) populations, 24 (25%) considered human, animal, and environmental (HAE) samples together, 11 (12%) studies included animal and environment (AE) samples, and 12 (13%) integrated human and environmental (HE) surveillance. Human isolate-based and animal isolate-based surveillance were the most common study designs (38, 52.8%), with the remainder applying human case-based and isolate-based for animal populations (32, 44.4%). Finally, our results demonstrate that AMR studies on
E. coli
revealed a lower correlation between human and animal AMR prevalence compared to
Salmonella
spp. and
Campylobacter
spp. studies. Different aspects of surveillance design were associated with the level of correlation of AMR prevalence between sectors. Our study found that while global efforts for integrated AMR surveillance have increased in the past 10 years, significant variation exists between studies with regard to the epidemiological and laboratory aspects of their surveillance designs. Our findings indicate that to enable the generation of comparable epidemiological data across countries and sectors, there is a need for the development of a global protocol to support the design of surveillance programs that aim to conduct integrated surveillance of AMR.
Soil biodiversity and microbial antagonism for suppression of plant-parasitic nematodes
Authors: Colagiero Mariantonietta , Pentimone Isabella , Rosso Laura , Ciancio Aurelio
Published: November 2024

Plant parasitic nematodes (PPN) cause significant economic losses in agriculture and the use of nematicides is the most common management practice applied today. However, due to the impact of such chemicals, more sustainable methods are needed. Current trends consider the exploitation of indigenous soil microbial communities. In this review we discuss some concepts required for the conservation and management of soil microorganisms, considered as a fundamental natural resource. Co-evolution and co-speciation are basic evolutionary processes of soil taxa involved in soil ecosystem services such as nematode regulation. The microorganisms showing a host-parasite co-evolution hold potential for the insurgence or re-construction of a natural equilibrium in soil, aiming at nematode regulation. The impact on soil microbial diversity of farming intensification and PPN management through nematicides is also discussed. Some examples of soil microbial resources and their impact including antagonists like nematophagous fungi (NF), aquatic parasites and bacteria are also briefly reviewed.
Structural robustness and optimization of leader-follower coherence in star-coupled networks
Authors: Zhang Qing , Li Gaoxuan , Sun Weigang
Published: November 2024

In this paper, we investigate the structural robustness and optimization of leader-follower coherence, quantified by the eigenvalues of the grounded Laplacian matrix, which measures the deviation between leaders and followers. To examine the impacts of network couplings and leader assignments on coherence, we select star-coupled networks as base models and introduce three types of coupling forms. By utilizing regular network structures, we derive analytical expressions for leader-follower coherence with respect to network parameters and evaluate the performance of coherence under various leader assignments. In addition, for achieving the lowest coherence in a network connected by a path graph, we propose an optimization algorithm that involves adding edges among the followers to enhance coherence.
Three-state p-SOS models on binary Cayley trees
Authors: Jahnel B , Rozikov U
Published: November 2024

We consider a version of the solid-on-solid model on the Cayley tree of order two in which vertices carry spins of value

0
,
1

or 2 and the pairwise interaction of neighboring vertices is given by their spin difference to the power p > 0. We exhibit all translation-invariant splitting Gibbs measures (TISGMs) of the model and demonstrate the existence of up to seven such measures, depending on the parameters. We further establish general conditions for extremality and non-extremality of TISGMs in the set of all Gibbs measures and use them to examine selected TISGMs for a small and a large p. Notably, our analysis reveals that extremality properties are similar for large p compared to the case p = 1, a case that has been explored already in previous work. However, for the small p, certain measures that were consistently non-extremal for p = 1 do exhibit transitions between extremality and non-extremality.
1

/

f

noise in semiconductors arising from the heterogeneous detrapping process of individual charge carriers
Authors: Kononovicius Aleksejus , Kaulakys Bronislovas
Published: November 2024

We propose a model of

1

/

f

noise in semiconductors based on the drift of individual charge carriers and their interaction with the trapping centers. We assume that the trapping centers are homogeneously distributed in the material. The trapping centers are assumed to be heterogeneous and have unique detrapping rates. We show that uniform detrapping rate distribution emerges as a natural consequence of the vacant trap depths following the Boltzmann distribution, and the detrapping process obeying Arrhenius law. When these laws apply, and if the trapping rate is low in comparison to the maximum detrapping rate,

1

/

f

noise in the form of Hooge’s relation is recovered. Hooge’s parameter, α
H, is shown to be a ratio between the characteristic trapping rate and the maximum detrapping rate. The proposed model implies that

1

/

f

noise arises from the temporal charge carrier number fluctuations, not from the spatial mobility fluctuations.
Study on Corrosion Damage Behavior of 300M Ultra-high Strength Steel in Marine Atmospheric Environment
Authors: Liu Jun , Luo Laizheng , Feng Lijun , He Yupeng , Wu Shuai
Published: November 2024

The marine atmospheric environment exposure test of 300M ultra-high strength steel was carried out at Hainan test station. The corrosion damage behavior of 300M ultra-high strength steel in marine atmospheric environment was studied by macroscopic and microscopic corrosion morphology, tensile properties and stress corrosion. The results show that the comprehensive corrosion behavior of 300M ultra-high strength steel occurred in the marine atmospheric environment. The color of the corrosion products changed from red to reddish brown, dark brown and black, and the maximum corrosion depth in the three years was 400μm. The corrosion had a significant effect on the tensile properties during the test. The tensile strength and elongation of 300M ultra-high strength steel decreased by 13.3 % and 81.8 %, respectively, which indicated that the effect of corrosion on the plasticity of the material was much greater than that on the tensile strength. Corrosion also caused a decrease in fracture toughness, and the fracture toughness of 300M ultra-high strength steel decreased by 26% in 2 years. The results of stress corrosion show that the crack propagation of 300M ultra-high strength steel is very rapid in the initial stage of marine atmospheric environment test, and the crack propagation length reaches 10.836mm in 7 days. The stress corrosion threshold KISCC of 300M ultra-high strength steel is 24.48MPa•m1/2, and the relative index of stress corrosion cracking sensitivity is 0.31, which indicates that 300M ultra-high strength steel is very sensitive to stress corrosion in marine atmospheric environment. The results show that 300M ultra-high strength steel has poor adaptability to the marine environment. Therefore, it is necessary to adopt excellent surface treatment process and spray aging resistant coating to effectively protect 300M ultra-high strength steel to ensure its long-term reliable use in the marine environment.
Bending Failure Behavior of Thin-walled Composite Tube Structures
Authors: Fang Zhigang , Yin Wenchang , Cao Jingyi , Xia Chenxi , Wang Zhanbin
Published: November 2024

The bending failure, failure load and failure mode of thin-walled circular tubes made of carbon fiber reinforced resin matrix composites were investigated by experiments and numerical simulation. Three typical failure modes of circular tubes under bending load were observed in experiments, and the characteristics and mechanisms of different failure modes were analyzed. The results show that interlaminar shear induces the generation and propagation of microcracks at the interface of circular tubes, which accelerates the failure of circular tubes. In the bending failure process, because the interlayer performance of the round pipe is relatively low, it is the weak link of the structure, and the pipe wall is the first to produce interlayer delamination and splitting failure under the action of shear stress, resulting in structural instability and premature fracture failure. The lay-up and initial defects of thin-walled round pipe have great influence on the bending failure mode and failure load.
Analysis and Calculation of Cross-contact Force between Strands of Multi-layer Conductor
Authors: Qin Jian , Wang Fei , Qiao Liang , Liu Chen
Published: November 2024

As a key component of the transmission line, the inter-layer cross-contact force of the internal strand is an important factor affecting the mechanical properties of the conductor. In this paper, the cross-contact characteristics between the strands of multi-layer conductors are analyzed. According to the relationship between the contact force and the contact distance between the strands, the finite element simulation of different material strands of different conductors at different cross angles is carried out. Through the analysis, it can be seen that the cross angle between the strands and the material of the strands have a significant impact on the contact force. Then, based on the existing Hertz contact theory model, the relationship between the contact force and the contact distance between the strands is modified, and the contact force and contact distance models suitable for different cross angles of the conductor strands are obtained, that is, the modified Hertz contact model. According to the simulation results, combined with the modified Hertz contact model, the contact force coefficient between the strands is fitted, and the calculation formula of contact force and contact displacement is proposed. The formula can be applied to the calculation of contact force at any intersection angle between strands. The calculation formula provides theoretical support for the accurate structural calculation of the conductor, which is helpful to the analysis and calculation of the contact friction between the strands.
Measurement of natural radiation levels in some soil samples from the ancient city of Borsippa in Babylon Governorate, Iraq
Authors: Ibrahim Hassooni Mohammed , Hussein Ibrahem Salar , Hussein Oleiwi Mohanad
Published: November 2024

In the present study, the activity concentration of natural radionuclides was determined for 40K, 232Th, and 238U. Some samples of soil from the ancient city of Borsippa in Babylon Governorate. The detector sodium iodide activated by Thallium NaI (Tl) has been used to perform the radioactivity measurements. 15 samples had their natural radioactivity levels assessed. 40K, 232Th, and 238U had average specific activities of (167.86±1.19, 25.15±1.09, and 11.75±0.457) Bq/kg. The average radium equivalent (61.17±2.10) Bq/kg. Average internal and external risk factors were (0.15±0.00007, and 0.19±0.00027), As for the average value of the index of representative levels (Iᵧ) was (0.44±0.018) The average absorbed dose level in (nGy/h) (28.19±1.18). The results of this study were within the internationally permissible limits, according to the report of the United Nations Scientific Committee on the Effects of Atomic Radiation.
Market restructuring of agribusiness in Russia as a trigger for rapid economic growth
Authors: Moroz O N , Medvedsky D A
Published: November 2024

In the period of political tension and instability of the international economic system, the agricultural sector of Russia continues to demonstrate progressive growth and is characterized by a favorable investment climate. In many respects, this circumstance in modern conditions is facilitated by scientific research and development of an innovative and technological nature, stimulating the accelerated development of domestic agriculture, due to which there is a favorable impact on the growth of the competitive component of the industry. Modern Russian agribusiness is one of the most intensive and highly promising points for the integration of digital innovations. For the steady growth of this sphere, it is essential to provide it with high-quality material, technical, infrastructural and innovative resources for its functioning. The studied sphere of economic activity of the country conservatively includes the primary function of ensuring national food security and independence, as a result of which the state actively attaches great importance due to the influence of a set of certain factors that make agriculture unstable and extremely vulnerable. The main goal of the digital modernization of agribusiness in Russia is to provide agricultural producers with state-of-the-art technologies, as well as to digitalize management, marketing and sales activities. The digital transformation of the agricultural sector should be carried out on a comprehensive, targeted and systematic basis based on target indicators and indicators, as well as be directed to core and secondary areas of the sphere. The integration of digital innovations into agribusiness in Russia will contribute to the active and breakthrough development of not only the agro-industrial complex, but also related industries.
Trends in the development of organic production in Europe
Authors: Khoruzhy L I , Kirillova S S , Kagirova M V , Romantseva Yu N
Published: November 2024

The Sustainable Development Goals direct the activities of all sectors of the economy to preserve the environment and minimize the negative consequences of anthropogenic activities. The agro-industrial complex is a major source of pollution of soil, water, air and the entire biosphere in general, and therefore significant changes have been taking place in agriculture over the last 20 years, both in the methods of its organization and in the directions of development. Europe was chosen as the object of analysis for the study, since it is here that almost all countries use organic technologies in the agricultural sector, the area of organic land, the number of organic producers, the volume of produced, exported and imported organic products, and their consumption increase every year. As part of the work, countries are grouped (by calculating a multidimensional average from a number of indicators) according to the level of development of organic agriculture, and the reasons for the differences are established; based on the method of correlation and regression analysis, the relationship between the demand for organic products and the level of average income in the country was identified and described; the structure of exports and imports of organic products was studied; the pace of development of the production of organic products was determined according to key characteristics, the main projects adopted in the field of crop production were considered in order to increase the volume of production of organic products. Based on the analysis, a conclusion was made about the pace and directions of development of organic agriculture in the European Union.
Problems of information support for the implementation of the state program for the involvement of unused agricultural land in economic turnover and ways to solve them
Authors: Papaskiri T V , Lipski S A , Fatkulina A V
Published: November 2024

The article examines how the process of identifying unused agricultural land and their involvement in economic turnover is interconnected with the maintenance of the state register of agricultural lands, which began in 2022. It is noted that the coincidence in time of these processes not only made it possible to identify a number of long-overdue problems, but also became the best option for solving them, including through digitalization and the use of artificial intelligence.
Positive properties of a biological preparation based on the consortium genus bacillus
Authors: Timofeev Vyacheslav
Published: November 2024

An experiment to study the use of a biological preparation was carried out on spring wheat in plot experiments in the conditions of the northern forest-steppe. A fungicidal seed protectant, a bacterial preparation BP (Bacillus simplex / B. Megaterium consortium, secondary metabolites, titer 108 Coe/ml), Biocoal were studied. When treating seeds, plant development was 7 days higher than control when using BP at a rate of 2.5 l/t, where an increase in sprout length by 1.25 cm was noted. When applying the drug to day-old seedlings, the use of BP variants in pure form and with biochar at a rate of 5.0 l/t had a greater effect with an increase in the length of the sprout by 3.2-4.2 cm, a decrease in the population of pathogenic fungi in seeds at the level of 60%, stimulating effect on root length by 1.7 cm, sprout length by 1.5 cm and germination by 6-8%. The use of a bacterial preparation during seed treatment did not affect the reduction of crop root disease. Measuring plant development parameters in the tillering phase, BP with a rate of 1.5 l/t had a greater effect on the length of the upper leaf, exceeding the control by 1-2 cm. The development of morphometric parameters of the flag leaf in the filling phase - milky ripeness had a leaf length of 18-23 cm with a width of 1.0-1.2 cm, with an increase at BP rates of 2.5-5.0 l/t. For seed treatment options, the impact at this stage is minimal or absent. Taking into account biometric indicators of the mass of formed plant organs showed an excess of indicators for BP options in pure form and with biochar at a rate of 5.0 l/t when treating seeds and using them during the growing season. Structural analysis of the ear determined a significant excess of the results of the preparations used during the growing season; the weight of 1000 grains was higher by 2-3 g when the seeds were treated with a chemical disinfectant and using BP at rates of 2.5-5.0 l/t. The crop yield increased by 0.1 t/ha in variants with a rate of bacterial preparation BP of 2.5-5.0 l/t in its pure form.
Proof of the Ballantine-Merca Conjecture and theta function identities modulo 2
Authors: Hong Letong , Zhang Shengtong
Published: November 2024

For positive integers

m
m

we consider the theta functions

f
m

(
z
)
≔

∑

m
k
+
1

s
q
u
a
r
e

q
k

f_m(z)≔\sum _{mk+1\mathrm {square}}q^k

. Due to classical identities of Jacobi, it is known that

f
4

≡

f
6

f

12

(
mod

2
)
.

\begin{equation*} f_4\equiv f_6f_{12}\pmod 2. \end{equation*}

Here we prove that the only triples

(
a
,
b
,
c
)

(a,b,c)

for which

f
a

≡

f
b

f
c

(
mod

2
)

f_a\equiv f_bf_c\pmod 2

are of the form

(
2
q
,
4
q
,
4
q
)

(2q,4q,4q)

or

(
4
q
,
4
q
,
8
q
)

(4q,4q,8q)

, where

q
q

is any positive odd number, or belong to the following finite list
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="StartLayout 1st Row 1st Column left-brace 2nd Column a m p semicolon left-parenthesis 4 comma 6 comma 12 right-parenthesis comma left-parenthesis 6 comma 8 comma 24 right-parenthesis comma left-parenthesis 8 comma 12 comma 24 right-parenthesis comma left-parenthesis 10 comma 12 comma 60 right-parenthesis comma 2nd Row 1st Column Blank 2nd Column a m p semicolon left-parenthesis 15 comma 24 comma 40 right-parenthesis comma left-parenthesis 16 comma 24 comma 48 right-parenthesis comma left-parenthesis 20 comma 24 comma 120 right-parenthesis comma left-parenthesis 21 comma 24 comma 168 right-parenthesis right-brace period EndLayout">

{

a
m
p
;
(
4
,
6
,
12
)
,
(
6
,
8
,
24
)
,
(
8
,
12
,
24
)
,
(
10
,
12
,
60
)
,

a
m
p
;
(
15
,
24
,
40
)
,
(
16
,
24
,
48
)
,
(
20
,
24
,
120
)
,
(
21
,
24
,
168
)
}
.

\begin{align*} \{&(4,6,12),(6,8,24),(8,12,24),(10,12,60), \\ &(15,24,40),(16,24,48),(20,24,120),(21,24,168)\}. \end{align*}

The result is inspired by the Ballantine-Merca Conjecture on recurrence relations for the parity of the partition function

p
(
n
)

p(n)

, which we also prove here.
scDTL: enhancing single-cell RNA-seq imputation through deep transfer learning with bulk cell information
Authors: Zhao Liuyang , Jiang Landu , Xie Yufeng , Huang JianHao , Xie Haoran , Tian Jun , Zhang Dian
Published: November 2024

The increasing single-cell RNA sequencing (scRNA-seq) data enable researchers to explore cellular heterogeneity and gene expression profiles, offering a high-resolution view of the transcriptome at the single-cell level. However, the dropout events, which are often present in scRNA-seq data, remaining challenges for downstream analysis. Although a number of studies have been developed to recover single-cell expression profiles, their performance may be hindered due to not fully exploring the inherent relations between genes. To address the issue, we propose scDTL, a deep transfer learning based approach for scRNA-seq data imputation by harnessing the bulk RNA-sequencing information. We firstly employ a denoising autoencoder trained on bulk RNA-seq data as the initial imputation model, and then leverage a domain adaptation framework that transfers the knowledge learned by the bulk imputation model to scRNA-seq learning task. In addition, scDTL employs a parallel operation with a 1D U-Net denoising model to provide gene representations of varying granularity, capturing both coarse and fine features of the scRNA-seq data. Finally, we utilize a cross-channel attention mechanism to fuse the features learned from the transferred bulk imputation model and U-Net model. In the evaluation, we conduct extensive experiments to demonstrate that scDTL could outperform other state-of-the-art methods in the quantitative comparison and downstream analyses.
Gerontologic Biostatistics and Data Science: Aging Research in the Era of Big Data
Authors: Chen Chixiang , Murphy Terrence E , Speiser Jaime Lynn , Bandeen-Roche Karen , Allore Heather , Travison Thomas G , Griswold Michael , Shardell Michelle
Published: November 2024

Introduced in 2010, the subdiscipline of gerontologic biostatistics was conceptualized to address the specific challenges of analyzing data from clinical research studies involving older adults. Since then, the evolving technological landscape has led to a proliferation of advancements in biostatistics and other data sciences that have significantly influenced the practice of gerontologic research, including studies beyond the clinic. Data science is the field at the intersection of statistics and computer science, and although the term “data science” was not widely used in 2010, the field has quickly made palpable effects on gerontologic research. In this Review in Depth, we describe multiple advancements of biostatistics and data science that have been particularly impactful. Moreover, we propose the subdiscipline of “gerontologic biostatistics and data science,” which subsumes gerontologic biostatistics into a more encompassing practice. Prominent gerontologic biostatistics and data science advancements that we discuss herein include cutting-edge methods in experimental design and causal inference, adaptations of machine learning, the rigorous quantification of deep phenotypic measurement, and analysis of high-dimensional -omics data. We additionally describe the need for integration of information from multiple studies and propose strategies to foster reproducibility, replicability, and open science. Lastly, we provide information on software resources for gerontologic biostatistics and data science practitioners to apply these approaches to their own work and propose areas where further advancement is needed. The methodological topics reviewed here aim to enhance data-rich research on aging and foster the next generation of gerontologic researchers.
Picking the juiciest cherries from the blockchain tree: Is the hype still alive?
Authors: Flórez Rojas María Lorena , Langer Philipp
Published: November 2024

Over the last years, blockchain technology has been promoted to revolutionize industries through trustless transactions. However, it has recently faced scrutiny for its failure to deliver on its alleged potential. This paper shows how blockchain applications have fallen short of their claims, including trustless and fraud-less transactions, as well as transparency systems. Building on this analysis, this research inspects how Blockchain’s building blocks, such as the Merkle tree and digital signatures, are still highly relevant technological concepts since their introduction decades ago. The paper examines these aspects, the unfulfilled claims, and the salvageable features through a critical analysis, offering insights into various sectors and jurisdictions, using as an example case a public project developed in Colombia. From cases of wrongful implementations, the paper demonstrates the necessity to put specific needs and requirements of real-world applications before the urge to apply blockchain technology without diligent social analysis, especially considering public funds.
Trending in the right direction: critical access hospitals increased adoption of advanced electronic health record functions from 2018 to 2023
Authors: Apathy Nate C , Holmgren A Jay , Nong Paige , Adler-Milstein Julia , Everson Jordan
Published: November 2024

Objectives

We analyzed trends in adoption of advanced patient engagement and clinical data analytics functionalities among critical access hospitals (CAHs) and non-CAHs to assess how historical gaps have changed.

Materials and Methods

We used 2014, 2018, and 2023 data from the American Hospital Association Annual Survey IT Supplement to measure differences in adoption rates (ie, the “adoption gap”) of patient engagement and clinical data analytics functionalities across CAHs and non-CAHs. We measured changes over time in CAH and non-CAH adoption of 6 “core” clinical data analytics functionalities, 5 “core” patient engagement functionalities, 5 new patient engagement functionalities, and 3 bulk data export use cases. We constructed 2 composite measures for core functionalities and analyzed adoption for other functionalities individually.

Results

Core functionality adoption increased from 21% of CAHs in 2014 to 56% in 2023 for clinical data analytics and 18% to 49% for patient engagement. The CAH adoption gap in both domains narrowed from 2018 to 2023 (both P < .01). More than 90% of all hospitals had adopted viewing and downloading electronic data and clinical notes by 2023. The largest CAH adoption gaps in 2023 were for Fast Healthcare Interoperability Resources (FHIR) bulk export use cases (eg, analytics and reporting: 63% of CAHs, 81% of non-CAHs, P < .001).

Discussion

Adoption of advanced electronic health record functionalities has increased for CAHs and non-CAHs, and some adoption gaps have been closed since 2018. However, CAHs may continue to struggle with clinical data analytics and FHIR-based functionalities.

Conclusion

Some crucial patient engagement functionalities have reached near-universal adoption; however, policymakers should consider programs to support CAHs in closing remaining adoption gaps.
Evaluating gradient-based explanation methods for neural network ECG analysis using heatmaps
Authors: Storås Andrea Marheim , Mæland Steffen , Isaksen Jonas L , Hicks Steven Alexander , Thambawita Vajira , Graff Claus , Hammer Hugo Lewi , Halvorsen Pål , Riegler Michael Alexander , Kanters Jørgen K
Published: November 2024

Objective

Evaluate popular explanation methods using heatmap visualizations to explain the predictions of deep neural networks for electrocardiogram (ECG) analysis and provide recommendations for selection of explanations methods.

Materials and Methods

A residual deep neural network was trained on ECGs to predict intervals and amplitudes. Nine commonly used explanation methods (Saliency, Deconvolution, Guided backpropagation, Gradient SHAP, SmoothGrad, Input × gradient, DeepLIFT, Integrated gradients, GradCAM) were qualitatively evaluated by medical experts and objectively evaluated using a perturbation-based method.

Results

No single explanation method consistently outperformed the other methods, but some methods were clearly inferior. We found considerable disagreement between the human expert evaluation and the objective evaluation by perturbation.

Discussion

The best explanation method depended on the ECG measure. To ensure that future explanations of deep neural networks for medical data analyses are useful to medical experts, data scientists developing new explanation methods should collaborate tightly with domain experts. Because there is no explanation method that performs best in all use cases, several methods should be applied.

Conclusion

Several explanation methods should be used to determine the most suitable approach.
Pollen limitation influences the divergences in mating system and floral traits between two sympatric Halenia species
Authors: Yang Ming-Liu , Liu Jin-Chun , Gao Meng-Ke , Sun Yu-Rong , Zhang Zhi-Qiang
Published: November 2024

The mating systems and floral traits often among relatives of hermaphroditic plants can exhibit considerable diversity. This diversity can be influenced by the evolution of selfing and associated floral traits as a form of reproductive assurance (RA) when pollen limitation (PL) results from insufficient pollinator availability. To explore whether the degree of PL primarily drives differences in mating systems and floral traits, we conducted a comprehensive study involving two closely related species, Halenia elliptica and Halenia grandiflora, in three sympatric sites. We investigated floral characteristics, pollinator visitation, PL, autonomous selfing ability, RA and mating system in studied populations. Our findings show that H. elliptica produces smaller flowers and less nectar production than H. grandiflora, making it less attractive to pollinators. Compared with H. grandiflora, H. elliptica experienced more severe outcross pollen limitation (OPL), but compensates with a higher capacity for autonomous selfing, ensuring seed production under natural conditions. Moreover, significant differences in mating systems were detected between them, with H. elliptica exhibiting a higher selfing rate than H. grandiflora across all studied sympatric populations. These differences are also reflected in variations in herkogamy and dichogamy. Our study suggested that the degree of OPL impacts the divergence in mating systems and floral traits between sympatric closely related species, offering valuable insights into the evolution of plant mating systems and floral traits.
Potential of ex vivo organotypic slice cultures in neuro-oncology
Authors: Steindl Ariane , Valiente Manuel
Published: November 2024

Over recent decades, in vitro and in vivo models have significantly advanced brain cancer research; however, each presents distinct challenges for accurately mimicking in situ conditions. In response, organotypic slice cultures have emerged as a promising model recapitulating precisely specific in vivo phenotypes through an ex vivo approach. Ex vivo organotypic brain slice models can integrate biological relevance and patient-specific variability early in drug discovery, thereby aiming for more precise treatment stratification. However, the challenges of obtaining representative fresh brain tissue, ensuring reproducibility, and maintaining essential central nervous system (CNS)-specific conditions reflecting the in situ situation over time have limited the direct application of ex vivo organotypic slice cultures in robust clinical trials. In this review, we explore the benefits and possible limitations of ex vivo organotypic brain slice cultures in neuro-oncological research. Additionally, we share insights from clinical experts in neuro-oncology on how to overcome these current limitations and improve the practical application of organotypic brain slice cultures beyond academic research.
Private but Misunderstood? Evidence on Measuring Intimate Partner Violence via Self-Interviewing in Rural Liberia and Malawi
Authors: Park David Sungho , Aggarwal Shilpa , Jeong Dahyeon , Kumar Naresh , Robinson Jonathan , Spearot Alan
Published: November 2024

Women may underreport intimate partner violence (IPV) in surveys. In an experiment in rural Liberia and Malawi, women were asked IPV questions via self-interviewing (SI) or face-to-face interviewing. Many respondents appear to misunderstand questions in SI, and significant effects of SI were observed on innocuous placebo questions. Because the prevalence of IPV is typically well below 50 percent, such measurement error will tend to bias IPV reporting upwards. Indeed, the results show that SI increases reported incidence of IPV, but it cannot be ruled out that these increases are spurious.
Inhibition of Phosphodiesterase 10A Alleviates Pain-like Behavior in Mice
Authors: Gross Tilman , Stehle Daniel , Nagel Chantal , Zhou Fangyuan , Duman Emre , Hernandez-Olmos Victor , Sinderwald Rekia , Gerninghaus Hannah , Petersen Jonas , Feil Susanne , Kallenborn-Gerhardt Wiebke , Lu Ruirui , Metzner Katharina , Feil Robert , Proschak Ewgenij , Schmidtko Achim
Published: November 2024

Background:

Emerging evidence indicates that cyclic nucleotide phosphodiesterases exert distinct functions in pain processing and that targeting phosphodiesterases might be a novel strategy for pain relief. This study hypothesized that the phosphodiesterase isoform phosphodiesterase 10A (PDE10A) might be a target for analgesic therapy.

Methods:

In situ hybridization, immunostaining, cyclic nucleotide enzyme immunoassays, real-time cyclic guanosine monophosphate imaging, and real-time quantitative reverse transcription polymerase chain reaction were performed to investigate the expression and activity of PDE10A in the dorsal root ganglia and spinal cord. Mice of both sexes were assessed in multiple pain models after the administration of specific PDE10A inhibitors.

Results:

PDE10A is distinctly expressed in nociceptive neurons in the dorsal root ganglia and spinal cord of mice. Incubation of cultured sensory neurons with the PDE10A inhibitor, TAK-063 (150 nM), increased cyclic guanosine monophosphate levels in enzyme immunoassays and real-time imaging at the single-cell level. Strikingly, treatment with TAK-063 (0.3 mg/kg intraperitoneal) ameliorated the pain-like behavior of female and male mice in models of acute nociceptive pain after intraplantar injection of capsaicin (mean ± SD, 8.87 ± 8.78 s [TAK-063] vs. 51.24 ± 36.36 s [vehicle], P = 0.020) or allyl isothiocyanate (2.46 ± 3.43 s [TAK-063] vs. 10.36 ± 4.87 s [vehicle]; P = 0.018). Furthermore, TAK-063 (0.3 mg/kg intraperitoneal) reduced established pain-like behavior in models of inflammatory pain induced by intraplantar injection of zymosan (two-way ANOVA, group, F[1,18] = 48.51, TAK-063 vs. vehicle; P ≤ 0.0001) or complete Freund’s adjuvant (F[1,14] = 46.10, TAK-063 vs. vehicle; P ≤ 0.0001), without the development of antinociceptive tolerance. The antinociceptive effects were recapitulated using the PDE10A inhibitor PF-2545920.

Conclusions:

Collectively, the data support the idea that PDE10A is a suitable target for the development of efficacious analgesic drugs.
Safety and efficacy of Angong Niuhuang Pills in patients with moderate-to-severe acute ischemic stroke (ANGONG TRIAL): A randomized double-blind placebo-controlled pilot clinical trial
Authors: Li Shengde , Wang Anxin , Shi Lin , Liu Qin , Guo Xiaoling , Liu Kun , Wang Xiaoli , Li Jie , Zhu Jianming , Wu QiuYi , Yang QingCheng , Zhuang Xianbo , You Hui , Feng Feng , Luo Yishan , Li Huiling , Ni Jun , Peng Bin
Published: November 2024

Background:

Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke.

Methods:

This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days.

Results:

There were 57 and 60 patients in the ANP and placebo groups finally included respectively for modified intention-to-treat analysis. The median age was 66 years, and the median NIHSS score at baseline was 12. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: –7.1 mL; interquartile range [IQR]: −18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively (median difference: 3.0 mL, IQR: −1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups (P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: –12.3 mL; IQR: –27.7 to –0.3 mL, P = 0.03).

Conclusions:

ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis.

Trail Registration:

Clinicaltrials.gov, No. NCT04475328.
Predictive value of pre-treatment circulating tumor DNA genomic landscape in patients with relapsed/refractory multiple myeloma undergoing anti-BCMA CAR-T therapy: Insights from tumor cells and T cells
Authors: Chen Rongrong , Jin Chunxiang , Liu Kai , Zhao Mengyu , Yang Tingting , Zhang Mingming , Xiao Pingnan , Feng Jingjing , Hong Ruimin , Fu Shan , Cui Jiazhen , Huang Simao , Wei Guoqing , Huang He , Hu Yongxian
Published: November 2024

Background:

B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM.

Methods:

Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells.

Results:

In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow (P = 0.013), lower percentages of CAR-T cells in the peripheral blood at peak (P = 0.037), and higher percentages of CD8+ T cells (P = 0.034). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) (P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [P = 0.004], IRF4 [P = 0.024], and CREBBP [P = 0.041]), number of multisite mutations, and resistance-related mutation (ERBB4, P = 0.040) were independent risk factors for PFS.

Conclusion:

Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy.

Registeration:

Chinese Clinical Trial Registry (ChiCTR2100046474) and National Clinical Trial (NCT04670055, NCT05430945).
The Regulation of Innate Antiviral Immunity by TRIM56
Authors: Li Kui , Lee Jacob Z.
Published: November 2024

A member of the tripartite-motif (TRIM) protein family of E3 ligases, TRIM56 has increasingly been recognized as a versatile player in innate antiviral immunity that operates via catalytically-dependent and catalytically-independent mechanisms. Herein, we provide a concise overview of the various roles that TRIM56 has been demonstrated to play in host interactions with viruses, including its "direct" virus-restricting activities and "indirect" antiviral effects resulting from its positive regulation of innate immune signaling. In addition, we discuss the current understanding of the molecular determinants and underlying biology by which TRIM56 functions in these processes.
Streamlining Atrial Fibrillation Care: Building a Comprehensive Program to Provide High-Quality, Individualized Care
Authors: Lam David , Farrell Jen , Fletcher Bob , Zivin Adam
Published: November 2024

Atrial fibrillation is the most common sustained arrhythmia with a variable presentation ranging from asymptomatic incidental diagnosis by physical examination or electrocardiogram screening, to severely symptomatic requiring emergent treatment. The variation in care represents an opportunity to build a comprehensive center of excellence within a hospital system. We present our experience building the Swedish Comprehensive AFib Network and a dedicated AFib clinic at a large quaternary urban medical center. We focused on patient and referral engagement, standardized protocols to promote best practices, data collection to improve quality of care, and broad evaluation of a single but multidisciplinary disease process. We hope this can offer insight into how other programs can be started for atrial fibrillation or other disease-focused clinics. We report our experience in the first 2 years, having evaluated over 700 new patients, and demonstrated an improvement in the rate of anticoagulation usage and a reduction in hospitalizations among patients included in our program.
Investigating the impact of metabolic syndrome and its components on pancreas fat: a Bidirectional Mendelian randomization study
Authors: Su Bohan , Gao Xin , Pang Chaoyu , Dong Peng , Fan Zhiyao , Zhan Hanxiang
Published: November 2024

Objective:

Metabolic syndrome (MetS) and fatty pancreas are two prevalent health conditions that are strongly associated with an elevated risk of developing type 2 diabetes, cardiovascular disease, and pancreatic cancer. Understanding the causal relationship between these conditions is important for developing effective prevention and treatment strategies. In this study, we performed a bidirectional Mendelian randomization analysis to investigate the potential causal relationship between MetS and fatty pancreas.

Methods:

This study undertook bidirectional Mendelian randomization. Genetic instruments for obesity, glycemic, lipid, and blood pressure were identified as instrumental variables for MetS traits in order to evaluate their causal role in pancreatic fat etiology. Summary level data for pancreas fat (PF) were obtained from a genome-wide association study conducted in the UK Biobank.

Results:

There was no causal relationship between MetS as a binary trait and PF. In addition, a causal association of increasing Waist-to-Hip Ratio (WHR) with pancreatic fat risk was found [odds ratio (OR)=1.173, 95% confidence interval (CI): 1.067-1.288, p=9*10-4]. Notably, there is no evidence of a causal relationship between PF and glycemic, lipid, and blood pressure. Sensitivity analyses did not indicate that pleiotropy was an important source of bias.

Conclusion:

MetS had no causal relationship with pancreatic fat. Of the components of the metabolic syndrome, only abdominal obesity and pancreatic fat were observed to be causally related.