bluuebunny/crossref_metadata_2025 huggingface dataset:
Shortness of breath as a diagnostic factor for acute coronary syndrome in male and female callers to out-of-hours primary care
Authors: Spek Michelle , Venekamp Roderick P , Erkelens Daphne C A , van Smeden Maarten , Wouters Loes T C M , den Ruijter Hester M , Rutten Frans H , Zwart Dorien L
Published: October 2023

Objective

Chest discomfort and shortness of breath (SOB) are key symptoms in patients with acute coronary syndrome (ACS). It is, however, unknown whether SOB is valuable for recognising ACS during telephone triage in the out-of-hours primary care (OHS-PC) setting.

Methods

A cross-sectional study performed in the Netherlands. Telephone triage conversations were analysed of callers with chest discomfort who contacted the OHS-PC between 2014 and 2017, comparing patients with SOB with those who did not report SOB. We determine the relation between SOB and (1) High urgency allocation, (2) ACS and (3) ACS or other life-threatening diseases.

Results

Of the 2195 callers with chest discomfort, 1096 (49.9%) reported SOB (43.7% men, 56.3% women). In total, 15.3% men (13.2% in those with SOB) and 8.4% women (9.2% in those with SOB) appeared to have ACS. SOB compared with no SOB was associated with high urgency allocation (75.9% vs 60.8%, OR: 2.03; 95% CI 1.69 to 2.44, multivariable OR (mOR): 2.03; 95% CI 1.69 to 2.44), but not with ACS (10.9% vs 12.0%; OR: 0.90; 95% CI 0.69 to 1.17, mOR: 0.91; 95% CI 0.70 to 1.19) or ‘ACS or other life-threatening diseases’ (15.0% vs 14.1%; OR: 1.07; 95% CI 0.85 to 1.36, mOR: 1.09; 95% CI 0.86 to 1.38). For women the relation with ACS was 9.2% vs 7.5%, OR: 1.25; 95% CI 0.83 to 1.88, and for men 13.2% vs 17.4%, OR: 0.72; 95% CI 0.51 to 1.02. For ‘ACS or other life-threatening diseases’, this was 13.0% vs 8.5%, OR: 1.60; 95% CI 1.10 to 2.32 for women, and 7.5% vs 20.8%, OR: 0.81; 95% CI 0.59 to 1.12 for men.

Conclusions

Men and women with chest discomfort and SOB who contact the OHS-PC more often receive high urgency than those without SOB. This seems to be adequate in women, but not in men when considering the risk of ACS or other life-threatening diseases.
Antagonism of contractile forces in left ventricular hypertrophy: a diagnostic challenge for better pathophysiological and clinical understanding
Authors: Lunkenheimer Paul Peter , Hagendorff Andreas , Lunkenheimer Jean-Marc , Gülker Hartmut Karl , Niederer Peter
Published: October 2023

Cardiac function is characterised by haemodynamic parameters in the clinical scenario. Due to recent development in imaging techniques, the clinicians focus on the quantitative assessment of left ventricular size, shape and motion patterns mostly analysed by echocardiography and cardiac magnetic resonance. Because of the physiologically known antagonistic structure and function of the heart muscle, the effective performance of the heart remains hidden behind haemodynamic parameters. In fact, a smaller component of oblique transmural netting of cardiac muscle fibres simultaneously engenders contracting and dilating force vectors, while the predominant mass of the tangentially aligned fibres only acts in one direction. In case of hypertrophy, an increased influence of the dilating transmural fibre component might counteract systolic wall thickening, thereby counteract cardiac output. A further important aspect is the response to inotropic stimulation that is different for the tangentially aligned fibre component in comparison to the transmural component. Both aspects highlight the importance to integrate the analysis of intramural fibre architecture into the clinical cardiac diagnostics.
Correction: calibration of the PM4Sand model for hard-rock mine tailings based on laboratory and field testing results
Authors: Contreras Carlos Andrés , Yniesta Samuel , Jahanbakhshzadeh Abtin , Aubertin Michel
Published: October 2023

Une campagne d“essais en laboratoire et sur le terrain a été réalisée pour caractériser le comportement des résidus miniers de roche dure. Des essais cycliques triaxiaux, de cisaillement direct simple et de cisaillement simple triaxial ont montré que les résidus contractants sont susceptibles de se liquéfier et que leur comportement est similaire à un sable lâche malgré leur pourcentage de fines plus élevé. Afin de modéliser le comportement des parcs à résidus dans des simulations dynamiques, la loi de comportement PM4Sand est calibré à partir de l”ensemble de données présenté ici. Certains des paramètres du modèle sont définis sur la base d“essais de consolidation et de compression, tandis que la ligne d”état critique est définie sur la base des résultats d“essais de cisaillement direct et triaxial monotones. La ligne d”état critique est plus basse pour les résidus que pour la plupart des sables naturels, ce qui est cohérent avec les études précédentes. Le modèle calibré peut reproduire de manière raisonnable le comportement monotone, et fournit un excellent ajustement des courbes de résistance cyclique mesurées en laboratoire à différentes pressions de confinement et indices de densité. Les résultats présentés dans l'article indiquent que la loi de comportement PM4Sand peut être utilisée pour simuler le comportement cyclique des résidus de mines en roches dures de faible plasticité. La procédure proposée fournie aussi des lignes directives générales pour calibrer le modèle pour d'autres types de résidus miniers.1 Ceci est une traduction fournie par l'auteur du résumé en anglais.
Outcrossing rates in the permanent translocation heterozygote Oenothera biennis L. (Onagraceae)
Authors: Johnson Marc T.J. , Godfrey Ryan M.
Published: October 2023

In species that primarily reproduce asexually, occasional sex can have important evolutionary consequences. Many plant species in the genus Oenothera have a genetic system called permanent translocation heterozygosity (PTH), which renders plants functionally asexual when they self-fertilize. PTH results from reciprocal translocations of chromosomes that suppress recombination and a balanced lethal mortality of homozygous gametes that prevents independent assortment of alleles. When PTH plants self-fertilize, the offspring are genetically identical to the parents, but when they outcross they can create new genotypes. Here, we sought to determine the outcrossing rate of natural populations of PTH Oenothera biennis L. (Onagraceae). We genotyped 46 parents from 14 populations in Tompkins County, NY, USA, and 754 of their offspring at highly polymorphic microsatellite loci. 99.5% of offspring were genetically identical to their seed parents, whereas 4 offspring out of 754 exhibited allelic mismatches with their seed parent. The estimated outcrossing rate ranged from 0.1% to 0.4%. Our study design also permitted us to estimate mutation rate of microsatellite loci, which ranged from 1.33 × 10−3 to 3.98 × 10−3. These results show that O. biennis typically exhibits a functionally asexual genetic system, but rare outcrossing events can generate novel genotypes that may have important evolutionary consequences.
Theoretical corrections of $$R_D$$ and $$R_{D^*}$$
Authors: Long Xin-Xin , Zhao Shu-Min , Liu Ming-Yue , Wang Xi , Wang Yi-Tong , Yang Zhong-Jun , Dong Xing-Xing , Feng Tai-Fu
Published: October 2023

$$R_{D^{(*)}}$$

R

D

(

∗
)

is the ratio of branching ratio $$\overline{B} \rightarrow D^{(*)}\tau \overline{\nu }_{\tau }$$

B
¯

→

D

(

∗
)

τ

ν
¯

τ

to $$\overline{B} \rightarrow D^{(*)}l\overline{\nu }_{l}~(l=e,~\mu )$$

B
¯

→

D

(

∗
)

l

ν
¯

l

(
l
=
e
,

μ
)

. There is a gap of 2$$\sigma _{exp}$$

σ

exp

or more between its experimental value and the prediction under the standard model (SM). People extend the MSSM with the local gauge group $$U(1)_X$$

U

(
1
)

X

to obtain the $$U(1)_X$$

U

(
1
)

X

SSM. Compared with MSSM, $$U(1)_X$$

U

(
1
)

X

SSM has more superfields and effects. In $$U(1)_X$$

U

(
1
)

X

SSM, we research the semileptonic decays $$\overline{B} \rightarrow D^{(*)}l\overline{\nu }_{l}$$

B
¯

→

D

(

∗
)

l

ν
¯

l

and calculate $$R_{D^{(*)}}$$

R

D

(

∗
)

. The numerical results of $$R_{D^{(*)}}$$

R

D

(

∗
)

are further corrected under $$U(1)_X$$

U

(
1
)

X

SSM, which are much better than the SM predictions. After correction, the theoretical value of $$R_{D^{(*)}}$$

R

D

(

∗
)

can reach one $$\sigma _{exp}$$

σ

exp

range of the averaged experiment central value.
INVESTIGATING THE VARIATIONS IN THE BRAIN ACTIVITY BETWEEN HEALTHY SUBJECTS AND MILD COGNITIVE IMPAIRMENT (MCI) PATIENTS
Authors: PAKNIYAT NAJMEH , RAMAKRISHNAN BALAMURALI , PALLAVI V. , KREJCAR ONDREJ , FRISCHER ROBERT , NAMAZI HAMIDREZA
Published: October 2023

Analysis of brain activity for patients with brain disorders is an important research area. Mild cognitive impairment (MCI) is a condition in which patients have more memory or thinking problems compared to healthy people of the same age. In this work, we studied the alterations in brain activity among control subjects and patients with MCI. Three complexity techniques, namely sample entropy, approximate entropy, and fractal dimension, were employed to study electroencephalogram (EEG) signals recorded from 102 control (healthy) subjects, and seven subjects with MCI in a comfortable position, on a bed, with their eyes closed. The results showed that the EEG signals of patients with MCI show greater complexity than the EEG signals of healthy subjects. This analysis method can be applied to compare brain activity among healthy subjects and patients with other brain diseases.
Community and Facility Health Information System Integration in Malawi: A Comparison of Machine Learning and Probabilistic Record Linkage Methods
Authors: Dixon Anna , Thengo Limbani , Kitsao Emmanuel , Matiya Kondwani , Barasa Mourice , Nyirongo Revelation , Muli Jennifer , Kamanga Funny , Kachimanga Chiyembekezo , Munyaneza Fabien , Ngari Phillip , Makungwa Henry , Chimpukuso Jones , Amulele Mercy , Karari Elijah , Mbae Simon
Published: October 2023

Accurate and efficient record linkage methods are essential to link patients between community health worker digital health apps and an EMR system, facilitating information flow and improving coordination of care. This study presents the eTrace workflow as an illustrative example, highlighting the benefits of enhanced coordination of care for patients in antiretroviral and non-communicable disease programs in rural Neno district, Malawi. This research focuses on the following major contributions: (1) development of a machine learning-based record linkage model for electronic health information systems, (2) comparison between the machine learning-based and probabilistic approaches to record linkage and (3) a concrete evaluation of our approach on real data for the eTrace workflow. A review of the standard record linkage architecture and its application to health information exchange systems is also presented. An empirical comparison conducted of logistic regression and the Fellegi-Sunter algorithms for this use case reveals comparable results. Both classifiers demonstrate an average precision of 0.86, while logistic regression achieves a higher recall at a fixed 0.90 precision of 0.74.
Hate Speech Detection in Limited Data Contexts Using Synthetic Data Generation
Authors: Khullar Aman , Nkemelu Daniel , Nguyen V. Cuong , Best Michael L.
Published: October 2023

A growing body of work has focused on text classification methods for detecting the increasing amount of hate speech posted online. This progress has been limited to only a select number of highly resourced languages causing detection systems to either under-perform or not exist in limited data contexts. This is mostly caused by a lack of training data, which are expensive to collect and curate in these settings. In this work, we propose a data augmentation approach that addresses the problem of lack of data for online hate speech detection in limited data contexts using synthetic data generation techniques. Given a handful of hate speech examples in a high-resource language such as English, we present three methods to synthesize new examples of hate speech data in a target language that retains the hate sentiment in the original examples but transfers the hate targets. We apply our approach to generate training data for hate speech classification tasks in Hindi and Vietnamese. Our findings show that a model trained on synthetic data performs comparably to, and in some cases outperforms, a model trained only on the samples available in the target domain. This method can be adopted to bootstrap hate speech detection models from scratch in limited data contexts. As the growth of social media within these contexts continues to outstrip response efforts, this work furthers our capacities for detection, understanding, and response to hate speech.Disclaimer:This work contains terms that are offensive and hateful. These, however, cannot be avoided due to the nature of the work.
Explainable Activity Recognition in Videos using Deep Learning and Tractable Probabilistic Models
Authors: Roy Chiradeep , Nourani Mahsan , Arya Shivvrat , Shanbhag Mahesh , Rahman Tahrima , Ragan Eric D. , Ruozzi Nicholas , Gogate Vibhav
Published: October 2023

We consider the following video activity recognition (VAR) task: given a video, infer the set of activities being performed in the video and assign each frame to an activity. Although VAR can be solved accurately using existing deep learning techniques, deep networks are neither interpretable nor explainable and as a result their use is problematic in high stakes decision-making applications (in healthcare, experimental Biology, aviation, law, etc.). In such applications, failure may lead to disastrous consequences and therefore it is necessary that the user is able to either understand the inner workings of the model or probe it to understand its reasoning patterns for a given decision. We address these limitations of deep networks by proposing a new approach that feeds the output of a deep model into a tractable, interpretable probabilistic model called a dynamic conditional cutset network that is defined over the explanatory and output variables and then performing joint inference over the combined model. The two key benefits of using cutset networks are: (a) they explicitly model the relationship between the output and explanatory variables and as a result, the combined model is likely to be more accurate than the vanilla deep model and (b) they can answer reasoning queries in polynomial time and as a result, they can derive meaningful explanations by efficiently answering explanation queries. We demonstrate the efficacy of our approach on two datasets, Textually Annotated Cooking Scenes (TACoS), and wet lab, using conventional evaluation measures such as the Jaccard Index and Hamming Loss, as well as a human-subjects study.
Immune Responses in Controllers of HIV Infection
Authors: Kwaa Abena K. , Blankson Joel N.
Published: October 2023

Elite controllers are a heterogeneous group of people living with HIV who control viral replication without antiretroviral therapy. There is substantial evidence that at least some elite controllers are infected with replication-competent virus, thus they may serve as a model of a functional cure of HIV. The mechanisms responsible for virologic control have been actively studied. The most objective data support CD8+ T cell–based mechanisms of control, but other immune responses, mediated by antibodies and natural killer cells, may also play a role in controlling viral replication. In this article, we review the evidence for different mechanisms of immune control in these remarkable individuals.
The Electrochemical Behavior of Zr(IV) and Y(III) in NaCl-KCl-K2ZrF6-YCl3 Molten Salt
Authors: Wang Yanli , Sun Rongfa , Yang Lingxu , Liu Huijun , Zeng Chaoliu
Published: October 2023

In this paper, the electrochemical behavior of Zr(IV) and Y(III) in NaCl-KCl-K2ZrF6-YCl3 molten salts is studied by cyclic voltammetry, linear sweep voltammetry, and chronopotentiometry methods, which will provide a theoretical foundation for the preparation of Zr-Y alloy coating by molten salt electrodeposition method. Results show that the reduction of Zr(IV) on molybdenum electrode is a three-step charge-transfer process, while the reduction of Y(III) is a single-step diffusion-controlled three-electron quasi-reversible process at −0.30 V vs Pt. In addition, the diffusion coefficient of Y(III) in the melt at 750 °C is calculated as 2.15 × 10−5 cm2·s−1. The reduction of Zr(IV) and Y(III) on molybdenum electrode in NaCl-KCl-K2ZrF6-YCl3 molten salts has also been studied by cyclic voltammetry method. Results indicate that the Zr-Y alloy coating can be obtained on molybdenum electrode by galvanostatic electrolysis at −1.50 V vs Pt for 30 min.
Understanding the Degradation of La1−x
Sr
x
FeO3−δ
(0 ≤ x ≤ 1) Perovskite Oxides during the Oxygen Evolution Reaction in Alkaline Solution
Authors: Qing Geletu , Thompson David , Heske Clemens , F. Greenlee Lauren , Chen Jingyi
Published: October 2023

Perovskite oxides are an emerging class of highly active catalysts for the oxygen evolution reaction (OER); however, their electrochemical stability remains poorly understood. Here, we report a systematic evaluation of the OER activity and stability of La1−x
Sr
x
FeO3-δ
perovskites in 1 M KOH. Their initial OER activity first increases with increasing Sr content (from x = 0 to 0.8), and then decreases when the Sr content is increased to 1. Their stability evaluated by monitoring the element leaching from the electrodes show that La does not leach at a detectable rate, but Sr and Fe leach substantially. The leaching of Sr occurs at similar rates under open circuit potential (OCP) and OER potential, suggesting a nonelectrochemical dissolution process. The leaching of Fe is, however, strongly dependent on the electrode potential. More Fe leaching is observed under the OER potential than OCP. Additionally, the electrode with higher initial OER activity leaches more Fe. These results indicate that OER facilitates the dissolution of Fe from the electrode. The leaching of Fe, in turn, is considered responsible for the activity loss of La1-x
Sr
x
FeO3−δ
during OER. This study brings new insight into the degradation mechanism of La1-x
Sr
x
FeO3−δ
and their related perovskite oxides during electro-oxidation processes.
Exploring the Impact of Structural and Physical Properties of Layered Molybdenum Disulfide on Electrochemical Characteristics and The Sensitive Response to Chloramphenicol Detection
Authors: Pham Tuyet Nhung , Ong Van Hoang , Tien Van Manh , Le Nhat Trang Nguyen , Hoa Nguyen Quang , Oanh Vu Thi Kim , Lam Vu Dinh , Le Anh-Tuan
Published: October 2023

This report focuses on evaluating the influence of structural and physical properties of MoS2 material on electrochemical behaviors as well as sensing performance toward the detection of targeted chloramphenicol (CAP) molecules. The various MoS2 samples were fabricated via a simple ultrasonication route at different experimental times. Through using X-ray diffraction (XRD), Raman, and scanning electron microscopy (SEM), structural and chemophysical characterizations were analyzed and discussed. Furthermore, from electrochemical measurements such as CV, EIS, DPV, and CA, the recorded results exhibited strong differences in the current response and the kinetic parameters of redox reactions among the proposed electrodes. It is also interesting to note that the proposed possible hypotheses and suitable mechanisms are particularly necessary to explain in more detail the important changes in kinetic parameters and sensing performance at MoS2-modified electrodes. Among them, the MoS2-3 sample with good crystallinity, high purity, low intrinsic thickness, and particularly, a defect-rich structure offered remarkable advances compared with that of other materials. As a result, this electrode exhibited an extended linear range (0.5 − 50 μM), a lower detection limit (0.1 μM), good repeatability, and high selectivity.
Generation of Atp6v1g3-Cre mice for investigation of intercalated cells and the collecting duct
Authors: Saxena Vijay , Arregui Samuel , Zhang Shaobo , Canas Jorge , Qin Xuebin , Hains David S. , Schwaderer Andrew L.
Published: October 2023

This study details the development, validation, and experimental use of a new mouse model to study the collecting duct and intercalated cells. Kidney intercalated cells are a cell type increasingly recognized to be important in several human diseases including kidney infections, acid-base disorders, and acute kidney injury.
Farnesoid X receptor prevents neutrophil extracellular traps via reduced sphingosine-1-phosphate in chronic kidney disease
Authors: Jones Bryce A. , Myakala Komuraiah , Guha Mahilan , Davidson Shania , Adapa Sharmila , Lopez Santiago Isabel , Schaffer Isabel , Yue Yang , Allegood Jeremy C. , Cowart L. Ashley , Wang Xiaoxin X. , Rosenberg Avi Z. , Levi Moshe
Published: October 2023

Many preclinical studies have shown that the farnesoid X receptor (FXR) reduces renal inflammation, but the mechanism is poorly understood. This report identifies FXR as a novel regulator of neutrophilic inflammation and NETosis via the inhibition of sphingosine-1-phosphate signaling. Additionally, NETosis severity in human Alport kidney biopsies correlates with clinical markers of kidney disease. A better understanding of this signaling axis may lead to novel treatments that prevent renal inflammation and chronic kidney disease.
Angiotensin II type 2 receptor-mediated dilation is greater in the cutaneous microvasculature of premenopausal women compared with men
Authors: Schwartz Kelsey S. , Lang James A. , Stanhewicz Anna E.
Published: October 2023

Premenopausal women have greater protection against cardiovascular disease than age-matched men. However, the role of vasoconstrictor angiotensin II type 1 receptors (AT1R) and vasodilatory angiotensin II type 2 receptors (AT2R) in mediating these sex differences is unclear. Here, we demonstrate that women have greater AT2R-mediated vasodilation than men and that AT1R negates AT2R-mediated dilation in men, but not in women.
Supporting evidence for an “arterial pump” venous return mechanism in humans
Authors: Cohen Jeremy N. , Samra Rose A. , Au Jason S.
Published: October 2023

Venous return mechanisms have classically considered muscle and respiratory pumps; however, recent ex vivo evidence suggests that pulsatile energy imparted from arteries to adjacent bundled veins can increase venous flow under certain driving pressures. We tested this concept in humans by manipulating hydrostatic pressures and measuring flow in bundled and nonbundled veins. The bundled vein exhibited flow preservation at the highest hydrostatic pressure. We suggest a novel conservation of energy mechanism within the circulatory system.
Nonhuman primates exploit the prior assumption that the visual world is vertical
Authors: Khazali Mohammad Farhan , Daddaoua Nabil , Thier Peter
Published: October 2023

Here we show that the principles that characterize the human perception of the vertical are shared by another old world primate species, the rhesus monkey, suggesting phylogenetic continuity. In both species the integration of visual and vestibular information on the orientation of the head relative to the world is similarly constrained by the prior assumption that the visual world is vertical in the sense of having an orientation that is congruent with the gravity vector.
Description of the Cattle and Small Ruminants Trade Network in Senegal and Implication for the Surveillance of Animal Diseases
Authors: Ciss Mamadou , Giacomini Alessandra , Diouf Mame Nahé , Delabouglise Alexis , Mesdour Asma , Garcia Garcia Katherin , Muñoz Facundo , Cardinale Eric , Lo Mbargou , Gaye Adji Marème , Fall Mathioro , Ndiaye Khady , Fall Assane Gueye , Cetre-Sossah Catherine , Apolloni Andrea
Published: October 2023

Livestock mobility, particularly that of small and large ruminants, is one of the main pillars of production and trade in West Africa: livestock is moved around in search of better grazing or sold in markets for domestic consumption and for festival-related activities. These movements cover several thousand kilometers and have the capability of connecting the whole West African region, thus facilitating the diffusion of many animal and zoonotic diseases. Several factors shape mobility patterns even in normal years and surveillance systems need to account for such changes. In this paper, we present an approach based on temporal network theory to identify possible sentinel locations, i.e., locations where pathogens circulation can be detected in the early phase of the epidemic (before the peak), using two indicators: vulnerability (i.e., the probability of being reached by the disease) and time of infection (i.e., the time of first arrival of the disease). Using these indicators in our structural analysis of the changing network enabled us to identify a set of nodes that could be used in an early warning system. As a case study, we simulated the introduction of transboundary animal diseases in Senegal and used data taken from 2020 Sanitary certificates (laissez-passer sanitaire (LPS)) issued by the Senegalese Veterinary Services to reconstruct the national mobility network. Our analysis showed that a static approach can significantly overestimate the speed and the extent of disease propagation, whereas temporal analysis revealed that the reachability and vulnerability of the different administrative departments (used as nodes of the mobility network) change over the course of the year. For this reason, several sets of sentinel nodes were identified in different periods of the year, underlining the role of temporality in shaping patterns of disease diffusion.
The Solution of Two-Dimensional Coupled Burgers’ Equation by
G
-Double Laplace Transform
Authors: Alhefthi Reem K. , Eltayeb Hassan
Published: October 2023

The two-dimensional coupled Burgers’ equation, a foundational partial differential equation, boasts widespread relevance across numerous scientific domains. Attaining precise solutions to this equation stands as a pivotal endeavor, fostering a comprehensive understanding of both physical phenomena and mathematical models. In this article, we underscore the paramount significance of the

G

-double Laplace transform, a transformative mathematical tool. Leveraging this innovative technique, we furnish dependable and exact solutions, addressing both homogeneous and nonhomogeneous variants of the coupled Burgers’ equations. This approach not only delivers reliability but also serves as an invaluable instrument for delving deeper into the equation’s intricate behavior and its profound implications across diverse disciplinary landscapes.
Comprehensive Analysis of METTLs (METTL1/13/18/21A/23/25/2A/2B/5/6/9) and Associated mRNA Risk Signature in Hepatocellular Carcinoma
Authors: Wang Haoyu , Hu Shangshang , Nie Junjie , Qin Xiaodan , Zhang Xu , Wang Qian , Li John Zhong
Published: October 2023

Currently, 80%–90% of liver cancers are hepatocellular carcinomas (HCC). HCC patients develop insidiously and have an inferior prognosis. The methyltransferase‐like (METTL) family principal members are strongly associated with epigenetic and tumor progression. The present study mainly analyzed the value of METTLs (METTL1/13/18/21A/23/25/2A/2B/5/6/9) and associated mRNA risk signature for HCC. METTLs expression is upregulated in HCC and is a poor prognostic factor in HCC. METTLs were upregulated in patients older than 60 and associated with grade. Except for METTL25, the remaining 10 genes were associated with the HCC stage, invasion depth (T). In addition, METTLs showed an overall alteration rate of 50%. Except for METTL13/2A/25/9, the expression of the other seven genes was significantly associated with overall survival, disease‐specific survival, and progression‐free survival. Multivariate studies have shown that METTL21A/6 can be an independent prognostic marker in HCC. A total of 664 mRNAs were selected based on Pearson correlation coefficient (R > 0.5), unsupervised consensus clustering, weighted coexpression network analysis, and univariate Cox analysis. These mRNAs were significantly associated with METTLs and were poor prognostic factors in HCC patients. The least absolute shrinkage and selection operator (lasso) was used to construct the best METTLs associated with mRNA risk signature. The mRNA risk signature was significantly associated with age, stage, and t grade. The mRNA high‐risk group had higher TP53 and RB1 mutations. This study constructed a nomogram with the mRNA risk profile and clinicopathological features, which could better predict the OS of individuals with HCC. We also analyzed associations between METTLs and mRNA risk signatures in epithelial‐mesenchymal transition, immune checkpoints, immune cell infiltration, tumor mutational burden, microsatellite instability, cancer stem cells, tumor pathways, and drug sensitivity. In addition, this study constructed a protein interaction network network including METTLs and mRNA risk signature genes related to tumor microenvironment remodeling based on single‐cell sequencing. In conclusion, this study provides a theoretical basis for the mechanism, biomarker screening, and treatment of HCC.
Relationship between Nonhepatic Serum Ammonia Levels and Sepsis-Associated Encephalopathy: A Retrospective Cohort Study
Authors: Wang Pei , Yan Jia , Shi Qiqing , Yang Fei , Li Xuguang , Shen Yuehao , Liu Haiying , Xie Keliang , Zhao Lina
Published: October 2023

Objectives. Nonhepatic hyperammonemia often occurs in patients with sepsis. Ammonia plays an essential role in the occurrence of hepatic encephalopathy. However, the relationship between nonhepatic serum ammonia levels and sepsis-associated encephalopathy (SAE) remains unclear. Thus, we aimed to evaluate the association between serum ammonia levels and patients with SAE. Methods. Data of critically ill adults with sepsis who were admitted to the intensive care unit were retrieved from the Medical Information Mart for Intensive Care IV (MIMIC IV) between 2008 and 2019 and retrospectively analyzed. Data of patients with sepsis patients and serum ammonia not related to acute or chronic liver disease were not included. Results. Data from 720 patients with sepsis were included. SAE was found to have a high incidence (64.6%). After adjusting for other risk factors, a serum ammonia level of ≥45 μmol/L (odds ratio (OR): 3.508, 95% confidence interval (CI): 2.336–5.269,

p
<
0.001

) was found to be an independent risk factor for patients with SAE; moreover, as the serum ammonia level increased, the hospital mortality of SAE gradually increased in a certain range (serum ammonia <150 μmol/L). Serum ammonia levels of ≥45 μmol/L were associated with higher Simplified Acute Physiology Score II and Sequential Organ Failure Assessment (SOFA) scores in patients with SAE. Besides, our study found that patients with SAE used opioid analgesics (OR:3.433, 95% CI: 1.360–8.669,

p
=
0.009

) and the SOFA scores of patients with SAE (OR: 1.126, 95% CI: 1.062–1.194,

p
<
0.001

) were significantly higher than those without SAE. Conclusions. Nonhepatic serum ammonia levels of ≥45 μmol/L evidently increased the incidence of SAE. Serum ammonia levels should be closely monitored in patients with sepsis.
Asymptomatic Esophageal Eosinophilia in an 11-Year-Old with Severe Persistent Asthma
Authors: Hofstaedter Casey E. , Watkins Runa , Kotwal Nidhi
Published: October 2023

Asymptomatic esophageal eosinophilia (aEE) is a rare presentation, where patients have increased eosinophils in esophageal mucosa but lack any esophagus-related symptoms. Cases of aEE have only been documented in adults, and little is known about its clinical significance and whether treatment is warranted. We report a case of an 11-year-old patient with uncontrolled severe persistent asthma who underwent flexible bronchoscopy and upper endoscopy as a part of complete aerodigestive evaluation. Elevated intraepithelial eosinophils in the esophageal mucosa were noted, suggesting an aEE-like presentation. This case documents a pediatric patient with aEE and highlights the importance of combined aerodigestive assessment with pulmonology and gastroenterology teams for the evaluation of severe asthma.
EhretiaSpecies Phytoconstituents as Potential Lead Compounds againstKlebsiella pneumoniaeCarbapenemase: A Computational Approach
Authors: Oselusi Samson O. , Sibuyi Nicole R. S. , Meyer Mervin , Madiehe Abram M.
Published: October 2023

The evolution of antibiotic‐resistant carbapenemase has negatively impacted the management of critical healthcare‐associated infections.K. pneumoniaecarbapenemase‐2‐ (KPC‐2‐) expressing bacteria have developed resistance to conventional therapeutic options, including those used as a last resort for life‐threatening diseases. In this study,Ehretiaspecies phytoconstituents were screened for their potential to inhibit KPC‐2 protein usingin silicoapproaches. Molecular docking was used to identify strong KPC‐2 protein binding phytoconstituents retrieved from the literature. The best‐docked conformation of the ligands was selected based on their glide energy and binding interactions. To determine their binding free energies, these hit compounds were subjected to molecular mechanics with generalized born and surface area (MM‐GBSA) in the PRIME module. Pharmacological assessments of the ligands were performed to evaluate their drug‐likeness. Molecular dynamic (MD) simulations were used to analyze the conformational stability of the selected druglike compounds within the active site of the KPC‐2 protein. Overall, a total of 69 phytoconstituents were compiled from the literature. Fourteen of these compounds exhibited a stronger binding affinity for the protein target than the reference drugs. Four of these top hit compounds, DB09, DB12, DB28, and DB66, revealed the highest efficacy in terms of drug‐likeness properties. The MD simulation established that among the druglike compounds, DB66 attained stable conformations after 150 ns simulation in the active site of the protein. We concluded that DB66 fromEhretiaspecies could play a significant role in therapeutic efforts against KPC‐2‐expressing bacteria.
Machine Learning-Based Jamming Detection for Safety Applications in Vehicular Networks: Individual Detection?
Authors: Nguyen-Minh Huong , Tran Hoang Tung , Pham Thanh Giang
Published: October 2023

Intelligent transportation system (ITS) refers to advanced applications to make transportation safer and more intelligent. The dynamic and diverse natures of the system have been creating many challenges in ITS deployment and security. The progression in recent years of machine learning provides potentially strong methods to exploit data sources from transportation networks. Machine learning-based approaches promise to deal with various challenges in networks thanks to their ability to adapt to the changing network topology and network scale. This paper investigates the application of machine-learning models in jamming detection by analyzing how the approach works on individual observations of vehicles in different scenarios. We propose a machine learning-based approach that explores hidden rules of how the observation changes under a reactive jamming attack. Our proposed machine learning-based approach improves detection accuracy compared to existing methods. The performance of the proposed method depends closely on dataset selection. Though we evaluate our approach with synthetic data, the data are generated with justifiable simulations calibrated to match a real-referenced dataset. Our analysis provides a connection between the machine-learning domain and vehicular networks by utilizing specific domain techniques for jamming detection.
Long-Term Seismic Monitoring of a Passively-Controlled Steel Building on Performance Assessment under Strong Earthquake
Authors: Tong Yunjia , Xue Songtao , Xie Liyu , Tang Hesheng
Published: October 2023

Analysis of recorded seismic response of an eight-story passively-controlled steel building located in Sendai is reported in this paper. Vibration monitoring system has been instrumented to test the effectiveness of dampers and actual performance of passively-controlled structures under earthquake since it was constructed in 2003. A data-driven stochastic subspace identification methodology with an alternative strategy to remove spurious modes is developed and implemented to the recorded actual earthquake response to extract dynamic properties of the passively-controlled eight-story steel building from the recorded floor acceleration data. Thus, the inherent damping characteristic of the building is identified under various earthquakes. Moreover, the variation of the estimated natural frequencies, mode shapes, and damping ratios for all the earthquake recordings are illustrated. To further investigate serviceability of the passively-controlled steel building during an earthquake, probabilistic model updating is developed to estimate the model parameters and infer the response of the structure based on the identified modes. Besides, seismic performance assessment of the passively-controlled steel building from the estimated dynamic characteristics and model parameters during service period is also discussed.
Supplementary Figure 11 from Peritumoral Immune-suppressive Mechanisms Impede Intratumoral Lymphocyte Infiltration into Colorectal Cancer Liver versus Lung Metastases
Authors: Ye Jian , Guo Weihua , Wang Chongkai , Egelston Colt A. , D'Apuzzo Massimo , Shankar Geereesh , Fakih Marwan G. , Lee Peter P.
Published: October 2023

Analysis of immune cells between paired primary and liver metastases.
Supplementary Figure 1 from Peritumoral Immune-suppressive Mechanisms Impede Intratumoral Lymphocyte Infiltration into Colorectal Cancer Liver versus Lung Metastases
Authors: Ye Jian , Guo Weihua , Wang Chongkai , Egelston Colt A. , D'Apuzzo Massimo , Shankar Geereesh , Fakih Marwan G. , Lee Peter P.
Published: October 2023

Characterization of TME in CRC primary and metastatic tumors with mIF.
Graphic Summary from Peritumoral Immune-suppressive Mechanisms Impede Intratumoral Lymphocyte Infiltration into Colorectal Cancer Liver versus Lung Metastases
Authors: Ye Jian , Guo Weihua , Wang Chongkai , Egelston Colt A. , D'Apuzzo Massimo , Shankar Geereesh , Fakih Marwan G. , Lee Peter P.
Published: October 2023

Graphic Summary
FIGURE 7 from Peritumoral Immune-suppressive Mechanisms Impede Intratumoral Lymphocyte Infiltration into Colorectal Cancer Liver versus Lung Metastases
Authors: Ye Jian , Guo Weihua , Wang Chongkai , Egelston Colt A. , D'Apuzzo Massimo , Shankar Geereesh , Fakih Marwan G. , Lee Peter P.
Published: October 2023

Higher immune activity in lung metastasis, while more immune suppressive in the liver and peritoneal metastases. A, Representative image of ROI selection in GeoMx digital spatial profiling from a colorectal cancer lung metastasis. Cancer island and stroma within tumor core were identified by the expression of Pan-CK. Cell identity markers from metastatic colorectal cancer tumors (B) and markers highly expressing in the liver (C), lung (D), and peritoneal (E) metastases in GeoMx assay. Paired comparison of gene expression between each two organs in the different histologic regions shown in bottom row. F, GeoMx markers expressing in the LA. Statistical significance was determined by Wilcoxon signed-rank test for B–F.
Data from Peritumoral Immune-suppressive Mechanisms Impede Intratumoral Lymphocyte Infiltration into Colorectal Cancer Liver versus Lung Metastases
Authors: Ye Jian , Guo Weihua , Wang Chongkai , Egelston Colt A. , D'Apuzzo Massimo , Shankar Geereesh , Fakih Marwan G. , Lee Peter P.
Published: October 2023

Abstract
Patients with microsatellite stable (MSS) colorectal cancer with liver metastases are resistant to immune checkpoint inhibitor (ICI) therapy, while about one-third of patients with colorectal cancer without liver metastases, particularly those with lung-only metastases, respond to ICI. We analyzed primary colorectal cancer tumors and major metastatic sites (liver, lung, peritoneal) using multiplex immunofluorescence and whole-slide spatial analyses to identify variations in immune contexture and regional localization within the tumor microenvironment. While levels of T and B cells within peritumoral regions were similar, their levels were significantly lower within the tumor core of liver and peritoneal metastases compared with lung metastases. In contrast, antigen-presenting cells (APC) and APC–T cell interactions were more abundant in all regions of lung metastases. We also identified an abundance of lymphoid aggregates throughout lung metastases, but these were present only within peritumoral regions of liver and peritoneal metastases. Larger lymphoid aggregates consistent with features of tertiary lymphoid structures were observed within or adjacent to primary tumors, but not metastatic lesions. Our findings were validated using NanoString GeoMx DSP, which further showed that liver metastases had higher expression of immune-suppressive markers, while lung metastases showed higher proinflammatory activity and T-cell activation markers. Peritoneal metastases demonstrated higher expression of cancer-associated fibroblast–related proteins and upregulated PD-1/PD-L1 signaling molecules. Our results demonstrate that functional status and spatial distribution of immune cells vary significantly across different metastatic sites. These findings suggest that metastatic site–dependent immune contexture may underlie discordant responses to ICI therapy in patients with MSS colorectal cancer.
Significance:
Our results demonstrate that functional status and spatial distribution of immune cells vary significantly across different metastatic sites in MSS colorectal cancer. These findings suggest that metastatic site–dependent immune contexture may underlie discordant responses to ICI therapy in patients with MSS colorectal cancer.
Ewing Sarcoma Single-cell Transcriptome Analysis Reveals Functionally Impaired Antigen-presenting Cells
Authors: Visser Lindy L. , Bleijs Margit , Margaritis Thanasis , van de Wetering Marc , Holstege Frank C. P. , Clevers Hans
Published: October 2023

Novel therapeutic strategies are urgently needed for patients with high-risk Ewing sarcoma and for the reduction of severe side effects for all patients. Immunotherapy may fill this need, but its successful application has been hampered by a lack of knowledge on the composition and function of the Ewing sarcoma immune microenvironment. Here, we explore the immune microenvironment of Ewing sarcoma, by single-cell RNA sequencing of 18 Ewing sarcoma primary tissue samples. Ewing sarcoma is infiltrated by natural killer, T, and B cells, dendritic cells, and immunosuppressive macrophages. Ewing sarcoma–associated T cells show various degrees of dysfunction. The antigen-presenting cells found in Ewing sarcoma lack costimulatory gene expression, implying functional impairment. Interaction analysis reveals a clear role for Ewing sarcoma tumor cells in turning the Ewing sarcoma immune microenvironment into an immunosuppressive niche. These results provide novel insights into the functional state of immune cells in the Ewing sarcoma tumor microenvironment and suggest mechanisms by which Ewing sarcoma tumor cells interact with, and shape, the immune microenvironment.

Significance:

This study is the first presenting a detailed analysis of the Ewing sarcoma microenvironment using single-cell RNA sequencing. We provide novel insight into the functional state of immune cells and suggests mechanisms by which Ewing tumor cells interact with, and shape, their immune microenvironment. These insights provide help in understanding the failures and successes of immunotherapy in Ewing sarcoma and may guide novel targeted (immuno) therapeutic approaches.
Comprehensive Analysis of the Relationship between Cuproptosis-Related Gene GCSH and Prognosis, Tumor Microenvironment Infiltration, and Therapy Response in Endometrial Cancer
Authors: Zhao Mengya , Nie Haihang , Qiu Peishan , Yu Yali , Wang Haizhou , Wang Fan , Fang Jun , Zhao Qiu
Published: October 2023

Introduction: Cuproptosis is a novel form of cell death regulated by protein lipoylation and implicated in mitochondrial metabolism. However, further research is needed to explore the influence of the cuproptosis-related gene γ-glutamylcysteine synthetase (GCSH) on the prognosis of endometrial cancer (EC), the tumor immune microenvironment, and therapeutic response. Methods: The differential expression of GCSH between EC and normal tissues was analyzed using multiple public databases. Additionally, cancer and adjacent tissues were prospectively collected from 17 EC patients, and immunohistochemical analysis was performed to further investigate GCSH expression differences. The relationship between GCSH and the prognosis and clinicopathological characteristics of EC patients was evaluated, and a nomogram was constructed to predict patient survival based on GCSH expression. Subsequently, Gene set variation analysis was used to explore the potential biological functions of GCSH in EC. The impact of GCSH on the tumor microenvironment (TME) was estimated. Finally, the effect of GCSH on the response to immunotherapy and chemotherapeutic drugs in EC was investigated. Results: The expression of GCSH was significantly upregulated in EC. High GCSH expression was associated with poor prognosis in EC patients. Enrichment analysis revealed an association between high GCSH and immune suppression. Furthermore, high GCSH was found to be associated with a non-inflamed TME, leading to decreased infiltration levels of immune cells. Lastly, it was observed that patients with high GCSH exhibited insensitivity to both immunotherapy and chemotherapeutic drugs. Conclusion: This study revealed the role of GCSH in TME, response to therapy, and clinical prognosis in EC, which provided novel insights for the therapeutic application in EC.
The Balance of CD8-Positive T Cells and PD-L1 Expression in the Myocardium Predicts Prognosis in Lymphocytic Fulminant Myocarditis
Authors: Hiraiwa Hiroaki , Morimoto Ryota , Tsuyuki Yuta , Ushida Kaori , Ito Ryota , Kazama Shingo , Kimura Yuki , Araki Takashi , Mizutani Takashi , Oishi Hideo , Kuwayama Tasuku , Kondo Toru , Okumura Takahiro , Murohara Toyoaki
Published: October 2023

Introduction: The clinical significance and prognostic value of T cell involvement and programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) have not been established in lymphocytic fulminant myocarditis (FM). We investigated the prognostic impact of the number of CD4+, CD8+, FoxP3+, and PD-1+ T cells, as well as PD-L1 expression, in cardiomyocytes in lymphocytic FM. Methods: This is a single-center observational cohort study. Myocardial tissue was obtained from 16 consecutive patients at lymphocytic FM onset. The median follow-up was 140 days. Cardiac events were defined as a composite of cardiac death and left ventricular-assist device implantation. CD4, CD8, FoxP3, PD-1, and PD-L1 immunostaining were performed on myocardial specimens. Results: The median age of the patients was 52 years (seven men and nine women). There was no significant difference in the number of CD4+ cells. The number of CD8+ cells and the CD8+/CD4+ T cell ratio were higher in the cardiac event group (Event+) than in the group without cardiac events (Event−) (p = 0.048 and p = 0.022, respectively). The number of FoxP3+ T cells was higher in the Event+ group (p = 0.049). Although there was no difference in the number of PD-1+ cells, cardiomyocyte PD-L1 expression was higher in the Event+ group (p = 0.112). Event-free survival was worse in the group with a high CD8+ cell count (p = 0.012) and high PD-L1 expression (p = 0.049). When divided into three groups based on the number of CD8+ cells and PD-L1 expression (CD8highPD-L1high [n = 8], CD8lowPD-L1high [n = 1], and CD8lowPD-L1low [n = 7]), the CD8highPD-L1high group demonstrated the worst event-free survival, while the CD8lowPD-L1high group had a favorable prognosis without cardiac events (p = 0.041). Conclusion: High myocardial expression of CD8+ T cells and PD-L1 may predict a poor prognosis in lymphocytic FM.