bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of
Burkholderia cepacia
strains that express a
Burkholderia pseudomallei
-like capsular polysaccharide
Authors: Burtnick Mary N. , Dance David A. B. , Vongsouvath Manivanh , Newton Paul N. , Dittrich Sabine , Sendouangphachanh Amphone , Woods Kate , Davong Viengmon , Kenna Dervla T. D. , Saiprom Natnaree , Sengyee Sineenart , Hantrakun Viriya , Wuthiekanun Vanaporn , Limmathurotsakul Direk , Chantratita Narisara , Brett Paul J.
Published: February 2024

Burkholderia pseudomallei
and
Burkholderia cepacia
are Gram-negative, soil-dwelling bacteria that are found in a wide variety of environmental niches. While
B. pseudomallei
is the causative agent of melioidosis in humans and animals, members of the
B. cepacia
complex typically only cause disease in immunocompromised hosts. In this study, we report the identification of
B. cepacia
strains isolated from either patients or soil in Laos and Thailand that express a
B. pseudomallei
-like 6-deoxyheptan capsular polysaccharide (CPS). These
B. cepacia
strains were initially identified based on their positive reactivity in a latex agglutination assay that uses the CPS-specific monoclonal antibody (mAb) 4B11. Mass spectrometry and
recA
sequencing confirmed the identity of these isolates as
B. cepacia
(formerly genomovar I). Total carbohydrates extracted from
B. cepacia
cell pellets reacted with
B. pseudomallei
CPS-specific mAbs MCA147, 3C5, and 4C4, but did not react with the
B. pseudomallei
lipopolysaccharide-specific mAb Pp-PS-W. Whole genome sequencing of the
B. cepacia
isolates revealed the presence of genes demonstrating significant homology to those comprising the
B. pseudomallei
CPS biosynthetic gene cluster. Collectively, our results provide compelling evidence that
B. cepacia
strains expressing the same CPS as
B. pseudomallei
co-exist in the environment alongside
B. pseudomallei
. Since CPS is a target that is often used for presumptive identification of
B. pseudomallei
, it is possible that the occurrence of these unique
B. cepacia
strains may complicate the diagnosis of melioidosis.

IMPORTANCE

Burkholderia pseudomallei
, the etiologic agent of melioidosis, is an important cause of morbidity and mortality in tropical and subtropical regions worldwide. The 6-deoxyheptan capsular polysaccharide (CPS) expressed by this bacterial pathogen is a promising target antigen that is useful for rapidly diagnosing melioidosis. Using assays incorporating CPS-specific monoclonal antibodies, we identified both clinical and environmental isolates of
Burkholderia cepacia
that express the same CPS antigen as
B. pseudomallei
. Because of this, it is important that staff working in melioidosis-endemic areas are aware that these strains co-exist in the same niches as
B. pseudomallei
and do not solely rely on CPS-based assays such as latex-agglutination, AMD Plus Rapid Tests, or immunofluorescence tests for the definitive identification of
B. pseudomallei
isolates.
Consensus on rapid screening for prodromal Alzheimer’s disease in China
Authors: Huang Lin , Li Qinjie , Lu Yao , Pan Fengfeng , Cui Liang , Wang Ying , Miao Ya , Chen Tianlu , Li Yatian , Wu Jingnan , Chen Xiaochun , Jia Jianping , Guo Qihao
Published: February 2024

Alzheimer’s disease (AD) is a common cause of dementia, characterised by cerebral amyloid-β deposition, pathological tau and neurodegeneration. The prodromal stage of AD (pAD) refers to patients with mild cognitive impairment (MCI) and evidence of AD’s pathology. At this stage, disease-modifying interventions should be used to prevent the progression to dementia. Given the inherent heterogeneity of MCI, more specific biomarkers are needed to elucidate the underlying AD’s pathology. Although the uses of cerebrospinal fluid and positron emission tomography are widely accepted methods for detecting AD’s pathology, their clinical applications are limited by their high costs and invasiveness, particularly in low-income areas in China. Therefore, to improve the early detection of Alzheimer's disease (AD) pathology through cost-effective screening methods, a panel of 45 neurologists, psychiatrists and gerontologists was invited to establish a formal consensus on the screening of pAD in China. The supportive evidence and grades of recommendations are based on a systematic literature review and focus group discussion. National meetings were held to allow participants to review, vote and provide their expert opinions to reach a consensus. A majority (two-thirds) decision was used for questions for which consensus could not be reached. Recommended screening methods are presented in this publication, including neuropsychological assessment, peripheral biomarkers and brain imaging. In addition, a general workflow for screening pAD in China is established, which will help clinicians identify individuals at high risk and determine therapeutic targets.
Locked and loaded: correlates of in-home firearm storage beliefs and behaviours
Authors: Warner Tara D
Published: February 2024

Objectives

To understand how crime and victimisation fears and risks operate alongside social status threats and motivations to shape unsafe in-home firearm storage practices and beliefs.

Methods

Using data from firearm owners identified in a nationwide sample surveyed in 2023, this study examined how in-home loaded firearm accessibility, firearm storage practice and firearm safety beliefs are associated with: fear of crime and victimisation; perceived and personal victimisation; racial resentment; cultural and status threats; and masculinity threats. Regression models also accounted for the role of gender, race, marital status, political affiliation, geographic region and protective motivation for firearm ownership.

Results

Over 40% of firearm owners reported having a loaded firearm ‘always accessible’ at home, and almost half think homes with firearms are safer than those without. About one-third of owners reported storing firearms locked but still loaded. Crime and victimisation fears and threats were unrelated to firearm storage behaviours and beliefs; however, firearm owners who experience higher levels of sociocultural anxiety are more likely to always have a loaded firearm accessible at home, store firearms locked and loaded, and believe that firearms make homes safer.

Conclusions

Identifying the barriers to safer storage beliefs and behaviours is essential for refining and enhancing effective firearm injury prevention strategies. Sociocultural anxieties may not reflect concrete threats to physical safety, but they can be experienced as feelings of insecurity, instability and distress that—for some Americans—may be managed by knowing they have a (loaded) firearm within reach.
Improved sensitivity for detection of pathogenic variants in familialNF2-related schwannomatosis
Authors: Perez-Becerril Cristina , Burghel George J , Hartley Claire , Rowlands Charles F , Evans D Gareth , Smith Miriam J
Published: February 2024

Purpose

To determine the impact of additional genetic screening techniques on the rate of detection of pathogenic variants leading to familialNF2-related schwannomatosis.

Methods

We conducted genetic screening of a cohort of 168 second-generation individuals meeting the clinical criteria forNF2-related schwannomatosis. In addition to the current clinical screening techniques, targeted next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification analysis, we applied additional genetic screening techniques, including karyotype and RNA analysis. For characterisation of a complex structural variant, we also performed long-read sequencing analysis.

Results

Additional genetic analysis resulted in increased sensitivity of detection of pathogenic variants from 87% to 95% in our second-generationNF2-related schwannomatosis cohort. A number of pathogenic variants identified through extended analysis had been previously observed after NGS analysis but had been overlooked or classified as variants of uncertain significance.

Conclusion

Our study indicates there is added value in performing additional genetic analysis for detection of pathogenic variants that are difficult to identify with current clinical genetic screening methods. In particular, RNA analysis is valuable for accurate classification of non-canonical splicing variants. Karyotype analysis and whole genome sequencing analysis are of particular value for identification of large and/or complex structural variants, with additional advantages in the use of long-read sequencing techniques.
Competitive leptomeningeal flow impact on thrombectomy reperfusion grade rating
Authors: Aboul-Nour Hassan , Dolia Jaydevsinh , Tarek Mohamed A , Grossberg Jonathan A , Pabaney Aqueel , Damiani Mateus , Al-Bayati Alhamza R , Nogueira Raul G , Haussen Diogo C
Published: February 2024

Background

Competitive leptomeningeal flow (CLF) can be observed immediately after mechanical thrombectomy (MT) reperfusion with retrograde contrast clearing of the distal leptomeningeal branches from non-contrast opacified flow through different vascular territories. We aim to evaluate the frequency of the CLF phenomenon, to determine if it has an association with the degree of leptomeningeal collateral status, and to understand the potentia impact it may have on the final expanded Treatment in Cerebral Ischemia (eTICI) score rating.

Methods

Retrospective analysis of a prospective MT database spanning November 2020 to December 2021. Consecutive cases of intracranial internal carotid (i-ICA) or middle cerebral artery (MCA) M1 occlusions were included. CLF was defined by the observation of retrograde clearing of distal MCA branches that were previously opacified by antegrade reperfusion. The clearance of the distal branches is presumed to occur due to CLF via non-contrast opacified posterior cerebral artery or anterior cerebral artery flow. The washout was considered CLF if it cleared abruptly with or without forward reconstitution of antegrade opacification.

Results

A total of 125 patients met the inclusion criteria. The median age was 64 years (IQR 52.5–75) and 64 (51%) were men. The baseline median National Institutes of Health Stroke Scale score was 17 (IQR 12–22) and the Alberta Stroke Program Early CT Score was 9 (IQR 8–10). Median last known well time to puncture was 7 hours (IQR 4–13.1) and 30.4% received tissue plasminogen activator. Final eTICI 2c–3 was achieved in 80%. CLF was present in 32 (25.6%) patients, who had comparable baseline characteristics to patients without CLF. Twelve (37.5%) patients had regional CLF and 20 (62.5%) had focal CLF. The CLF arm had better leptomeningeal single-phase CTA collaterals than the non-CLF arm (P=0.01). The inter-rater agreement for the eTICI score was moderate when CLF was present and strong in its absence (Krippendorf’s alpha=0.65 and 0.81, respectively). There was minimal agreement (Kappa=0.3) for the presence versus absence of CLF between the two operators, possibly related to reader experience.

Conclusion

CLF was observed in 32% of patients, was associated with better collateral flow, and impacted the reported procedural eTICI rating.
The influence of epigenetic biological age on key complications and outcomes in aneurysmal subarachnoid haemorrhage
Authors: Macias-Gómez Adrià , Jiménez-Balado Joan , Fernández‑Pérez Isabel , Suárez‑Pérez Antoni , Vallverdú-Prats Marta , Guimaraens Leopoldo , Vivas Elio , Saldaña Jesus , Giralt-Steinhauer Eva , Guisado-Alonso Daniel , Villalba Gloria , Gracia Maria-Pilar , Esteller Manel , Rodriguez-Campello Ana , Jiménez-Conde Jordi , Ois Angel , Cuadrado-Godia Elisa
Published: February 2024

Background

We aimed to investigate the association between DNA-methylation biological age (B-age) calculated as age acceleration (ageAcc) and key aneurysmal subarachnoid haemorrhage (aSAH) complications such as vasospasm, delayed cerebral ischaemia (DCI), poor outcome, and mortality.

Methods

We conducted a prospective study involving 277 patients with aSAH. B-age was determined in whole blood samples using five epigenetic clocks: Hannum’s, Horvath’s, Levine’s and both versions of Zhang’s clocks. Age acceleration was calculated as the residual obtained from regressing out the effect of C-age on the mismatch between C-age and B-age. We then tested the association between ageAcc and vasospasm, DCI and 12-month poor outcome (mRS 3–5) and mortality using linear regression models adjusted for confounders.

Results

Average C-age was 55.0 years, with 66.8% being female. Vasospasm occurred in 143 cases (51.6%), DCI in 70 (25.3%) and poor outcomes in 99 (35.7%), with a mortality rate of 20.6%. Lower ageAcc was linked to vasospasm in Horvath’s and Levine’s clocks, whereas increased ageAcc was associated with 12-month mortality in Hannum’s clock. No significant differences in ageAcc were found for DCI or poor outcome at 12 months with other clocks.

Conclusions

Our study indicates that B-age is independently associated with vasospasm and 12-month mortality in patients with aSAH. These findings underscore the potential role of epigenetics in understanding the pathophysiology of aSAH-related complications and outcomes.
Novel multiclass classification machine learning approach for the early-stage classification of systemic autoimmune rheumatic diseases
Authors: Wang Yun , Wei Wei , Ouyang Renren , Chen Rujia , Wang Ting , Yuan Xu , Wang Feng , Hou Hongyan , Wu Shiji
Published: February 2024

Objective

Systemic autoimmune rheumatic diseases (SARDs) encompass a diverse group of complex conditions with overlapping clinical features, making accurate diagnosis challenging. This study aims to develop a multiclass machine learning (ML) model for early-stage SARDs classification using accessible laboratory indicators.

Methods

A total of 925 SARDs patients were included, categorised into SLE, Sjögren’s syndrome (SS) and inflammatory myositis (IM). Clinical characteristics and laboratory markers were collected and nine key indicators, including anti-dsDNA, anti-SS-A60, anti-Sm/nRNP, antichromatin, anti-dsDNA (indirect immunofluorescence assay), haemoglobin (Hb), platelet, neutrophil percentage and cytoplasmic patterns (AC-19, AC-20), were selected for model building. Various ML algorithms were used to construct a tripartite classification ML model.

Results

Patients were divided into two cohorts, cohort 1 was used to construct a tripartite classification model. Among models assessed, the random forest (RF) model demonstrated superior performance in distinguishing SLE, IM and SS (with area under curve=0.953, 0.903 and 0.836; accuracy= 0.892, 0.869 and 0.857; sensitivity= 0.890, 0.868 and 0.795; specificity= 0.910, 0.836 and 0.748; positive predictive value=0.922, 0.727 and 0.663; and negative predictive value= 0.854, 0.915 and 0.879). The RF model excelled in classifying SLE (precision=0.930, recall=0.985, F1 score=0.957). For IM and SS, RF model outcomes were (precision=0.793, 0.950; recall=0.920, 0.679; F1 score=0.852, 0.792). Cohort 2 served as an external validation set, achieving an overall accuracy of 87.3%. Individual classification performances for SLE, SS and IM were excellent, with precision, recall and F1 scores specified. SHAP analysis highlighted significant contributions from antibody profiles.

Conclusion

This pioneering multiclass ML model, using basic laboratory indicators, enhances clinical feasibility and demonstrates promising potential for SARDs classification. The collaboration of clinical expertise and ML offers a nuanced approach to SARDs classification, with potential for enhanced patient care.
Safety and efficacy of colchicine in crystal-induced arthritis flare in 54 patients with severe chronic kidney disease
Authors: Bausson Johanna , Keller Nicolas , Von Hunolstein Jean-Jacques , Sacrez Matthieu , Michel Bruno , Gourieux Bénédicte , Fourtage Marion , Felten Renaud
Published: February 2024

Introduction

Colchicine, commonly used in gout flare, is contraindicated in severe chronic kidney disease (CKD) (estimated glomerular filtration rate <30 mL/min). However, in this context, there are few alternatives, and colchicine use persists. We evaluated the tolerance of colchicine and its efficacy in patients with severe CKD.

Patients and methods

All prescriptions of colchicine for managing crystal-induced arthritis flare (gout or calcium pyrophosphate deposition (CPPD) disease) in a hospitalised patient with severe CKD were screened from September 2020 to September 2021. After patient consent and treatment information, clinical and biological safety and efficacy data were prospectively collected from day 1 (D1) to D11.

Results

We included 54 patients (median age 75 years (IQR 67–83)) with 62 colchicine prescriptions (cases). Twelve (22%) patients were on dialysis. The main reason for hospitalisation was heart failure (31.5%), acute renal failure (22.2%), infection (18.5%) or an acute joint episode (9.3%). In total, 59.3% of patients had diabetes. The prescriptions concerned 58 cases of gout flares, 1 case of CPPD and 3 cases of both. Initial colchicine dosages were ≤0.5 mg/day in 47/62 (75.8%) cases; no dosage exceeded 1 mg/day (median duration of 6 days (IQR 3–11)). Colchicine was well tolerated in 47/61 (77%) cases. No serious adverse event was reported. Colchicine was considered completely effective by the medical team in 48/58 (83%) of cases.

Conclusion

The use of colchicine, at reduced doses, was mostly effective to treat crystal-induced arthritis flare in 54 patients with severe CKD and was well tolerated, without any serious adverse events.
Classical and quantum cosmology for two scalar field Brans–Dicke type theory: a Noether symmetry approach
Authors: Hembrom Shriton , Bhaumik Roshni , Dutta Sourav , Chakraborty Subenoy
Published: February 2024

The paper deals with a cosmological model containing two scalar fields which can be considered as an extension of the Brans–Dicke scalar field model. Due to highly coupled non linear field equations, Noether symmetry analysis has been imposed and as a result the Lagrangian as well as the field equations become much simple in form to have the classical solutions. The relevant cosmological parameters are analyzed graphically. Finally, quantum cosmology has been studied by constructing the Wheeler–DeWitt equation and the solution of this second order partial differential equation has been done using this symmetry analysis.
Non-perturbative suppression of chiral vortical effect in hot (s)QGP for hyperons spin polarization in heavy ion collisions
Authors: Abramchuk Ruslan A. , Selch Maik
Published: February 2024

With the field correlator method (FCM) for QCD, we show that the chiral vortical effect (CVE) in hot (strongly-interacting) quark-gluon plasma ((s)QGP) is modified by non-perturbative interactions – by color-magnetic confinement, and by remnant color-electric interaction, which is encoded in the Polyakov line. The obtained result demonstrates numerical suppression of CVE comparable to the phenomenological suppression used for numerical simulations of RHIC-STAR data on hyperons spin polarization in non-central heavy ion collision (HIC). The parameters range in the temperature – quark chemical potential plane is expected to cover ALICE and RHIC data. The chiral current is calculated for the rigidly rotating model of (s)QGP in the linear order in angular velocity at the rotation axis with account of non-perturbative interactions.
Lipofibromatous Hamartoma of the Median Nerve – A Rare Condition in the Hand
Authors: JIANMONGKOL Surut , HOMKLAI Kittiphong , SUMANANONT Chat , VINITPAIROT Chaiyos
Published: February 2024

Lipofibromatous hamartoma (LFH) of the median nerve is a rare condition in the hand and often remains asymptomatic for a significant period. MRI imaging can reveal unique tumour characteristics; however, the definitive diagnosis is confirmed through a tissue biopsy. In this report, a 38-year-old male presented with a gradually growing mass on his right hand. Physical examination revealed a large soft tissue mass extending from the thenar area to the wrist, causing compression of the median nerve. MRI confirmed the presence of a distinct soft tissue mass on the volar side of the hand. The mass was excised along with a fascicle and confirmed by histological examination. One year after surgery, sensation has improved, but weakness remains and opponensplasty was offered to the patient. Although the treatment strategy of LFH of the median nerve remains controversial, delayed treatment can result in severe compressive neuropathy and irreversible nerve damage.

Level of Evidence: Level V (Therapeutic)
Measuring Commonality in Recommendation of Cultural Content to Strengthen Cultural Citizenship
Authors: Ferraro Andres , Ferreira Gustavo , Diaz Fernando , Born Georgina
Published: February 2024

Recommender systems have become the dominant means of curating cultural content, significantly influencing the nature of individual cultural experience. While the majority of academic and industrial research on recommender systems optimizes for personalized user experience, this paradigm does not capture the ways that recommender systems impact cultural experience in the aggregate, across populations of users. Although existing novelty, diversity, and fairness studies probe how recommender systems relate to the broader social role of cultural content, they do not adequately center culture as a core concept and challenge. In this work, we introduce commonality as a new measure of recommender systems that reflects the degree to which recommendations familiarize a given user population with specified categories of cultural content. Our proposed commonality metric responds to a set of arguments developed through an interdisciplinary dialogue between researchers in computer science and the social sciences and humanities. With reference to principles underpinning public service media (PSM) systems in democratic societies, we identify universality of address and content diversity in the service of strengthening cultural citizenship as particularly relevant goals for recommender systems delivering cultural content. We develop commonality as a measure of recommender system alignment with the promotion of a shared cultural experience of, and exposure to, diverse cultural content across a population of users. Moreover, we advocate for the involvement of human editors accountable to a larger value community as a fundamental part of defining categories in the service of cultural citizenship. We empirically compare the performance of recommendation algorithms using commonality with existing utility, diversity, novelty, and fairness metrics using three different domains. Our results demonstrate that commonality captures a property of system behavior complementary to existing metrics and suggests the need for alternative, non-personalized interventions in recommender systems oriented to strengthening cultural citizenship across populations of users. Moreover, commonality demonstrates both consistent results under different editorial policies and robustness to missing labels and users. Alongside existing fairness and diversity metrics, commonality contributes to a growing body of scholarship developing “public good” rationales for digital media and machine learning systems.
Reduced On-chip Storage of Seeds for Built-in Test Generation
Authors: Pomeranz Irith
Published: February 2024

Logic built-in self-test (LBIST) approaches use an on-chip logic block for test generation and thus enable in-field testing. Recent reports of silent data corruption underline the importance of in-field testing. In a class of storage-basedLBISTapproaches, compressed tests are stored on-chip and decompressed by an on-chip decompression logic. The on-chip storage requirements may become a bottleneck when the number of compressed tests is large. In this case, using each compressed test for applying several different tests allows the storage requirements to be reduced. However, producing different tests from each compressed test has a hardware overhead. This article suggests a new on-chip storage scheme for compressed tests that eliminates the additional hardware overhead. Under the new storage scheme, a set ofNB-bit compressed tests targeting a set of faultsF0is translated into a sequenceSofN ⋅ Bbits. EveryBconsecutive bits ofSare considered as a compressed test. The sequenceSthus yields close toN ⋅ Bcompressed tests, magnifying the test data stored inSalmostBtimes. Taking advantage of the extra tests, the article describes a software procedure that is applied offline to reduceSwithout losing fault coverage ofF0. Experimental results for benchmark circuits demonstrate significant reductions in the storage requirements ofSand significant increases in the fault coverage of a second set of faults,F1.
MiSleep: Human Sleep Posture Identification from Deep Learning Augmented Millimeter-wave Wireless Systems
Authors: Adhikari Aakriti , Sur Sanjib
Published: February 2024

In this work, we propose
MiSleep
, a deep learning augmented millimeter-wave (mmWave) wireless system to monitor human sleep posture by predicting the 3D location of the body joints of a person during sleep. Unlike existing vision- or wearable-based sleep monitoring systems,
MiSleep
is not privacy-invasive and does not require users to wear anything on their body.
MiSleep
leverages knowledge of human anatomical features and deep learning models to solve challenges in existing mmWave devices with low-resolution and aliased imaging and specularity in signals.
MiSleep
builds the model by learning the relationship between mmWave reflected signals and body postures from thousands of existing samples. Since a practical sleep also involves sudden toss-turns, which could introduce errors in posture prediction,
MiSleep
designs a state machine based on the reflected signals to classify the sleeping states into rest or toss-turn and predict the posture only during the rest states.

We evaluate
MiSleep
with real data collected from Commercial-Off-The-Shelf mmWave devices for eight volunteers of diverse ages, genders, and heights performing different sleep postures

.

We observe that
MiSleep
identifies the toss-turn events start time and duration within 1.25 s and 1.7 s of the ground truth, respectively, and predicts the 3D location of body joints with a median error of 1.3 cm only and can perform even under the blankets, with accuracy on par with the existing vision-based system, unlocking the potential of mmWave systems for privacy-noninvasive at-home healthcare applications.
C-terminal fragment of fibroblast growth factor 23 improves heart function in murine models of high intact fibroblast growth factor 23
Authors: Hu Ming Chang , Reneau James A. , Shi Mingjun , Takahashi Masaya , Chen Gaozhi , Mohammadi Moosa , Moe Orson W.
Published: February 2024

There is a strong correlation between cardiovascular morbidity and high circulating fibroblast growth factor 23 (FGF23) levels, but causality was never proven. We used a murine chronic kidney disease (CKD) model to show that intact FGF23 (iFGF23) is pathogenic and contributes to both CKD progression and cardiomyopathy. Blockade of FGF23 signaling with a natural proteolytic product of iFGF23, C-terminal FGF23, alleviated kidney and cardiac histology, and function in three separate murine models of high endogenous FGF23.
Habitually wearing high heels may improve user walking economy in any footwear
Authors: Beck Owen N. , Schroeder Jordyn N. , Sawicki Gregory S.
Published: February 2024

Habitually wearing high-heeled footwear structurally remodels leg muscle tendons and improves user walking economy, regardless of worn attire.
Ceramides are fuel gauges on the drive to cardiometabolic disease
Authors: Wilkerson Joseph L. , Tatum Sean M. , Holland William L. , Summers Scott A.
Published: February 2024

Ceramides are signals of fatty acid excess that accumulate when a cell’s energetic needs have been met and its nutrient storage has reached capacity. As these sphingolipids accrue, they alter the metabolism and survival of cells throughout the body including in the heart, liver, blood vessels, skeletal muscle, brain, and kidney. These ceramide actions elicit the tissue dysfunction that underlies cardiometabolic diseases such as diabetes, coronary artery disease, metabolic-associated steatohepatitis, and heart failure. Here, we review the biosynthesis and degradation pathways that maintain ceramide levels in normal physiology and discuss how the loss of ceramide homeostasis drives cardiometabolic pathologies. We highlight signaling nodes that sense small changes in ceramides and in turn reprogram cellular metabolism and stimulate apoptosis. Finally, we evaluate the emerging therapeutic utility of these unique lipids as biomarkers that forecast disease risk and as targets of ceramide-lowering interventions that ameliorate disease.
Proteomics of the heart
Authors: Karpov Oleg A. , Stotland Aleksandr , Raedschelders Koen , Chazarin Blandine , Ai Lizhuo , Murray Christopher I. , Van Eyk Jennifer E.
Published: February 2024

Mass spectrometry-based proteomics is a sophisticated identification tool specializing in portraying protein dynamics at a molecular level. Proteomics provides biologists with a snapshot of context-dependent protein and proteoform expression, structural conformations, dynamic turnover, and protein-protein interactions. Cardiac proteomics can offer a broader and deeper understanding of the molecular mechanisms that underscore cardiovascular disease, and it is foundational to the development of future therapeutic interventions. This review encapsulates the evolution, current technologies, and future perspectives of proteomic-based mass spectrometry as it applies to the study of the heart. Key technological advancements have allowed researchers to study proteomes at a single-cell level and employ robot-assisted automation systems for enhanced sample preparation techniques, and the increase in fidelity of the mass spectrometers has allowed for the unambiguous identification of numerous dynamic posttranslational modifications. Animal models of cardiovascular disease, ranging from early animal experiments to current sophisticated models of heart failure with preserved ejection fraction, have provided the tools to study a challenging organ in the laboratory. Further technological development will pave the way for the implementation of proteomics even closer within the clinical setting, allowing not only scientists but also patients to benefit from an understanding of protein interplay as it relates to cardiac disease physiology.
The Best Fit Bayesian Hierarchical Generalized Linear Model Selection Using Information Complexity Criteria in the MCMC Approach
Authors: Ebrahim Endris Assen , Cengiz Mehmet Ali , Terzi Erol
Published: February 2024

Both frequentist and Bayesian statistics schools have improved statistical tools and model choices for the collected data or measurements. Model selection approaches have advanced due to the difficulty of comparing complicated hierarchical models in which linear predictors vary by grouping variables, and the number of model parameters is not distinct. Many regression model selection criteria are considered, including the maximum likelihood (ML) point estimation of the parameter and the logarithm of the likelihood of the dataset. This paper demonstrates the information complexity (ICOMP), Bayesian deviance information, or the widely applicable information criterion (WAIC) of the BRMS to hierarchical linear models fitted with repeated measures with a simulation and two real data examples. The Fisher information matrix for the Bayesian hierarchical model considering fixed and random parameters under maximizing a posterior estimation is derived. Using Gibbs sampling and Hybrid Hamiltonian Monte Carlo approaches, six different models were fitted for three distinct application datasets. The best-fitted candidate models were identified under each application dataset with the two MCMC approaches. In this case, the Bayesian hierarchical (mixed effect) linear model with random intercepts and random slopes estimated using the Hamiltonian Monte Carlo method best fits the two application datasets. Information complexity (ICOMP) is a better indicator of the best-fitted models than DIC and WAIC. In addition, the information complexity criterion showed that hierarchical models with gradient-based Hamiltonian Monte Carlo estimation are the best fit and have supper convergence relative to the gradient-free Gibbs sampling methods.
Effects of Mind-Body Qigong Exercise on Overall Health, Fatigue/Sleep, and Cognition in Older Chinese Immigrants in the US: An Intervention Study with Control
Authors: Liu Jianghong , Yang Yi , Li Clara , Perez Adriana , Raine Adrian , Shi Haoer , Zou Liye
Published: February 2024

Background. Culturally relevant exercises may help improve health and address disparities faced by older immigrants due to language and cultural barriers. Few studies have focused on such exercise interventions among older Chinese immigrants at US daycare centers. Methods. We conducted a 10-week nonrandomized controlled trial in older Chinese immigrants in Philadelphia, US. The intervention group practiced Chinese Qigong (Baduanjin) 5 days a week guided by trained research assistants and video instructions. The control group maintained their usual daily activities. We collected self-report assessments on overall health, sleep, and fatigue and implemented two computerized cognitive tests measuring psychomotor vigilance task (PVT) and memory twice, preintervention and postintervention. Repeated measures general linear model (GLM) and paired samples t-tests were used for data analyses. Results. Eighty-eight older adults (Qigong, n = 53; control, n = 35) with an average age of 78.13 (SD = 5.05) were included. Groups showed no significant differences at baseline evaluation. After the 10-week exercise, the intervention group showed significant improvements in overall health (p=0.032), fatigue (p<0.001), and cognitive functions including memory (p=0.01), response speed (p=0.002), and response time (p=0.012) on the PVT, as well as marginally significant benefits in sleep (p=0.058). Between-group comparisons identified significant group-by-time interactions in health (p=0.024), sleep (p=0.004), fatigue (p=0.004), and memory (p=0.004). Conclusion. We revealed significant positive effects of Qigong in older Chinese immigrants across multiple health domains. Findings highlight the potential of a culturally relevant exercise in addressing health disparities.
Determination of 60 Food-Borne Stimulant Drug Residues in Animal-Derived Foods by Solid-Phase Extraction Purification and Ultra-High-Performance Liquid Chromatography-Quadrupole/Orbitrap High-Resolution Mass Spectrometry
Authors: He Liangna , Li Qiang , Ma Junmei , Cao Meirong , Fan Lixin , Ren Xiaowei , Shi Guohua , Zhang Yan
Published: February 2024

A method for the rapid screening and confirmation of 60 food-borne stimulants in animal-derived foods was developed using the ultra-high-performance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry (UPLC-Q/Orbitrap HRMS). After enzymatic hydrolysis at 37°C for 16 h, the samples were extracted with acetonitrile solution. The extraction solution was purified by PRiME HLB pass-through solid-phase extraction cartridge and redissolved by nitrogen blowing. The target compounds of reconstitution fluid were separated by Hypersil GOLD™ VANQUISH column (2.1 mm × 100 mm, 1.9 μm). The raw data were collected for the target compounds in Full Scan-ddMS2 mode, and then the Quan Browser module under Xcalibur software can be used to analyze the quantitative results of the samples. The combination of Tracefinder and mzVault software can realize the qualitative screening and confirmation of the samples. The results showed that the relative deviation of the exact mass of the 60 food-borne stimulants was less than 5.0 × 10−6, which had a good linear relationship in the corresponding concentration, and the correlation coefficient (R2) was greater than 0.9966. The detection limit ranged from 0.05 to 0.5 μg/kg. The quantification limit ranged from 0.1 to 1 μg/kg. The method recoveries ranged from 70.2% to 111.9% with relative standard deviations of 0.05% to 9.00% (n = 6). The method is easy to operate, covers a wide range of targets, and has high efficiency and accuracy. It is suitable for rapid screening and confirmation of various food-derived stimulants in animal-derived foods and provides assistance for food safety in the major events.
Research on Direction Finding Method under Impulsive Noise Based on Nonuniform Linear Array
Authors: An Chunlian , Yang Guyue , Li Peng , Zhou Dengmei , Tian Liangliang
Published: February 2024

Direction of arrival (DOA) estimation under impulsive noise has always been an important research area in array signal processing. The traditional methods under impulsive noise mostly rely on prior parameters and have high computational complexity. Based on the filtering theory, we present an effective pretreatment filtering technology to cut out the impulse mixed in the array received data and employ the nonuniform linear array to improve the estimation performance further. First, according to the amplitude characteristics of impulse noise, the pretreatment filtering technology is proposed to cut out the impulse based on the median filter and sliding average filter, which is valid for both strong and weak impulsive noise. Second, the minimum redundant array is adopted to carry out array virtual expansion so that the array aperture can be increased and the estimation performance can be improved. Finally, based on the idea of matrix reconstruction, we propose the improved estimation of signal parameters via rotational invariance techniques algorithm and an improved root multiple signal classification algorithm for DOA estimation. Theoretical analysis and simulation results show that the proposed method has a simple processing process, small calculation load, good array expansion ability, and excellent noise adaptability. Moreover, the proposed methods greatly improve the direction-finding performance under the condition of low signal-to-noise ratio and strong impulsive noise.
Supplementary Table S3 from Osimertinib Covalently Binds to CD34 and Eliminates Myeloid Leukemia Stem/Progenitor Cells
Authors: Xia Li , Liu Jie-Yang , Yang Meng-Ying , Zhang Xue-Hong , Jiang Yue , Yin Qian-Qian , Luo Chen-Hui , Liu Hong-Chen , Kang Zhi-Jie , Zhang Cheng-Tao , Gao Bei-Bei , Zhou Ai-Wu , Cai Hai-Yan , Waller Edmund K. , Yan Jin-Song , Lu Ying
Published: February 2024

Motif analysis by Scaffold PTM of regulated tyrosine-phosphorylated peptides between vehicle or osimertinib treated CD34+ cells.
Supplementary Figure legends from PTEN Lipid Phosphatase Activity Suppresses Melanoma Formation by Opposing an AKT/mTOR/FRA1 Signaling Axis
Authors: Xu Xiaonan , Bok Ilah , Jasani Neel , Wang Kaizhen , Chadourne Manon , Mecozzi Nicol , Deng Ou , Welsh Eric A. , Kinose Fumi , Rix Uwe , Karreth Florian A.
Published: February 2024

Supplementary Figure legends
Data from Neuronal Activity Promotes Glioma Progression by Inducing Proneural-to-Mesenchymal Transition in Glioma Stem Cells
Authors: Guo Xiaofan , Qiu Wei , Wang Chaochao , Qi Yanhua , Li Boyan , Wang Shaobo , Zhao Rongrong , Cheng Bo , Han Xiao , Du Hao , Gao Zijie , Pan Ziwen , Zhao Shulin , Li Gang , Xue Hao
Published: February 2024

Abstract
Neuronal activity can drive progression of high-grade glioma by mediating mitogen production and neuron-glioma synaptic communications. Glioma stem cells (GSC) also play a significant role in progression, therapy resistance, and recurrence in glioma, which implicates potential cross-talk between neuronal activity and GSC biology. Here, we manipulated neuronal activity using chemogenetics in vitro and in vivo to study how it influences GSCs. Neuronal activity supported glioblastoma (GBM) progression and radioresistance through exosome-induced proneural-to-mesenchymal transition (PMT) of GSCs. Molecularly, neuronal activation led to elevated miR-184–3p in neuron-derived exosomes that were taken up by GSCs and reduced the mRNA N6-methyladenosine (m6A) levels by inhibiting RBM15 expression. RBM15 deficiency decreased m6A modification of DLG3 mRNA and subsequently induced GSC PMT by activating the STAT3 pathway. Loss of miR-184–3p in cortical neurons reduced GSC xenograft growth, even when neurons were activated. Levetiracetam, an antiepileptic drug, reduced the neuronal production of miR-184–3p-enriched exosomes, inhibited GSC PMT, and increased radiosensitivity of tumors to prolong survival in xenograft mouse models. Together, these findings indicate that exosomes derived from active neurons promote GBM progression and radioresistance by inducing PMT of GSCs.
Significance:
Active neurons secrete exosomes enriched with miR-184–3p that promote glioblastoma progression and radioresistance by driving the proneural-to-mesenchymal transition in glioma stem cells, which can be reversed by antiseizure medication levetiracetam.
Supplementary Data 1 from Absence of BTK, BCL2, and PLCG2 Mutations in Chronic Lymphocytic Leukemia Relapsing after First-Line Treatment with Fixed-Duration Ibrutinib plus Venetoclax
Authors: Jain Nitin , Croner Lisa J. , Allan John N. , Siddiqi Tanya , Tedeschi Alessandra , Badoux Xavier C. , Eckert Karl , Cheung Leo W.K. , Mukherjee Anwesha , Dean James P. , Szafer-Glusman Edith , Seymour John F.
Published: February 2024

Figure S1 shows number of baseline genomic risk features in patients with and without subsequent PD; Figure S2 shows correlations between baseline genomic risk features; Table S1 shows representativeness of study participants.
Supplementary Figure S2 from A Phase Ib First-In-Patient Study Assessing the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ponsegromab in Participants with Cancer and Cachexia
Authors: Crawford Jeffrey , Calle Roberto A. , Collins Susie M. , Weng Yan , Lubaczewski Shannon L. , Buckeridge Clare , Wang Ellen Q. , Harrington Magdalena A. , Tarachandani Anil , Rossulek Michelle I. , Revkin James H.
Published: February 2024

Participant disposition
Figure S2 from Clinical and Immunologic Features of Germline Pathogenic Variant–Positive Patients with Melanoma
Authors: Shen Alan , Arbesman Michelle , Lodha Roshan , Rayman Patricia , Bungo Brandon , Ni Ying , Chan Timothy , Gastman Brian , Ko Jennifer , Diaz-Montero C. Marcela , Arbesman Joshua , Funchain Pauline
Published: February 2024

MSS and PMN-MDSC differences by HRD and Non-HRD status.
Figure S2 from Paclitaxel plus Eftilagimod Alpha, a Soluble LAG-3 Protein, in Metastatic, HR+ Breast Cancer: Results from AIPAC, a Randomized, Placebo Controlled Phase IIb Trial
Authors: Wildiers Hans , Armstrong Anne , Cuypere Eveline , Dalenc Florence , Dirix Luc , Chan Steve , Marme Frederik , Schröder Carolina P. , Huober Jens , Duhoux Francois P. , Vuylsteke Peter , Jager Agnes , Brain Etienne , Kuemmel Sherko , Pápai Zsuzsanna , Menke-van der Houven van Oordt Catharina Willemien , Perjesi Luca , Mueller Christian , Brignone Chrystelle , Triebel Frederic
Published: February 2024

(A) AIPAC trial schema, and (B) patient disposition.
Supplementary Figures 1 from Impact of Rare Structural Variant Events in Newly Diagnosed Multiple Myeloma
Authors: Chojnacka Monika , Diamond Benjamin , Ziccheddu Bachisio , Rustad Even , Maclachlan Kylee , Papadimitriou Marios , Boyle Eileen M. , Blaney Patrick , Usmani Saad , Morgan Gareth , Landgren Ola , Maura Francesco
Published: February 2024

Supplementary Figures
Supplementary methods S2 from Novel Methionine Aminopeptidase 2 Inhibitor M8891 Synergizes with VEGF Receptor Inhibitors to Inhibit Tumor Growth of Renal Cell Carcinoma Models
Authors: Friese-Hamim Manja , Ortiz Ruiz Maria J. , Bogatyrova Olga , Keil Marina , Rohdich Felix , Blume Beatrix , Leuthner Birgitta , Czauderna Frank , Hahn Diane , Jabs Julia , Jaehrling Frank , Heinrich Timo , Kellner Roland , Chan Katherine , Tong Amy H.Y. , Wienke Dirk , Moffat Jason , Blaukat Andree , Zenke Frank T.
Published: February 2024

Description of effect of M8891 on HUVEC formation on 3D Matrigel methodology
Supplementary Table2 from Effects of Combined Therapeutic Targeting of AXL and ATR on Pleural Mesothelioma Cells
Authors: Hirai Soichi , Yamada Tadaaki , Katayama Yuki , Ishida Masaki , Kawachi Hayato , Matsui Yohei , Nakamura Ryota , Morimoto Kenji , Horinaka Mano , Sakai Toshiyuki , Sekido Yoshitaka , Tokuda Shinsaku , Takayama Koichi
Published: February 2024

Supplementary Table2
Figure S3 from Effects of Combined Therapeutic Targeting of AXL and ATR on Pleural Mesothelioma Cells
Authors: Hirai Soichi , Yamada Tadaaki , Katayama Yuki , Ishida Masaki , Kawachi Hayato , Matsui Yohei , Nakamura Ryota , Morimoto Kenji , Horinaka Mano , Sakai Toshiyuki , Sekido Yoshitaka , Tokuda Shinsaku , Takayama Koichi
Published: February 2024

Figure S3
Figure S11 from CD38 x ICAM-1 Bispecific Antibody Is a Novel Approach for Treating Multiple Myeloma and Lymphoma
Authors: Chen Xiaocheng , Wong Oi Kwan , Reiman Lauren , Sherbenou Daniel W. , Post Leonard
Published: February 2024

Combination studies on MM CDX models
Supplementary Figure 2 from TAS0612, a Novel RSK, AKT, and S6K Inhibitor, Exhibits Antitumor Effects in Preclinical Tumor Models
Authors: Ichikawa Koji , Ito Satoshi , Kato Emi , Abe Naomi , Machida Takumitsu , Iwasaki Junya , Tanaka Gotaro , Araki Hikari , Wakayama Kentaro , Jona Hideki , Sugimoto Tetsuya , Miyadera Kazutaka , Ohkubo Shuichi
Published: February 2024

Supplementary Figure 2. Pharmacodynamic marker inhibitions in the HCC70 tumor xenografts treated after repetitive doses of TAS0612. TAS0612, 60 mg/kg, was administered to the HCC70 tumor-bearing mice daily from Day 1 to Day 8 by oral gavage, and subcutaneously implanted tumors were dissected at 4 hour post-administration on
Day 8. After tumor sampling, immunoblot analysis was performed to detect pharmacodynamic marker inhibitions, signal feedback, and apoptosis induction. Clear inhibition of pharmacodynamic markers such as phospho-PRAS40, phospho-YB1, and phospho-S6RP by TAS0612 was observed even at Day 8 post-administration. In addition, the upregulation of phospho-AKT and phospho-RSK indicating feedback re-activation of pathway signals were also observed in tumors as seen in in vitro analysis. Regarding apoptosis induction, cleavage of PARP and caspase-3 proteins was induced to a greater extent in TAS0612-treated tumors than in the control tumors.
Supplementary Fig. S4 from Amelioration of Tumor-promoting Microenvironment via Vascular Remodeling and CAF Suppression Using E7130: Biomarker Analysis by Multimodal Imaging Modalities
Authors: Ito Ken , Yamaguchi Masayuki , Semba Taro , Tabata Kimiyo , Tamura Moe , Aoyama Muneo , Abe Takanori , Asano Osamu , Terada Yasuhiko , Funahashi Yasuhiro , Fujii Hirofumi
Published: February 2024

E7130 reduced plasma TGF-β1 levels in MCF-7,breast cancer orthotopic model in mouse
Supplementary Figure S2 from An Antibody–Drug Conjugate Directed to Tissue Factor Shows Preclinical Antitumor Activity in Head and Neck Cancer as a Single Agent and in Combination with Chemoradiotherapy
Authors: Bakema Jantine E. , Stigter-van Walsum Marijke , Harris Jeffrey R. , Ganzevles Sonja H. , Muthuswamy Anantharaman , Houtkamp Mischa , Plantinga Theo S. , Bloemena Elisabeth , Brakenhoff Ruud H. , Breij Esther C.W. , van de Ven Rieneke
Published: February 2024

Tumor growth curves FaDu xenografts