bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro co-culture of Clostridium scindens with primary human colonic epithelium protects the epithelium against Staphylococcus aureus
Authors: Wang Hao , Kim Raehyun , Wang Yuli , Furtado Kathleen L. , Sims Christopher E. , Tamayo Rita , Allbritton Nancy L.
Published: April 2024

A complex and dynamic network of interactions exists between human gastrointestinal epithelium and intestinal microbiota. Therefore, comprehending intestinal microbe-epithelial cell interactions is critical for the understanding and treatment of intestinal diseases. Primary human colonic epithelial cells derived from a healthy human donor were co-cultured with Clostridium scindens (C. scindens), a probiotic obligate anaerobe; Staphylococcus aureus (S. aureus), a facultative anaerobe and intestinal pathogen; or both bacterial species in tandem. The co-culture hanging basket platform used for these experiments possessed walls of controlled oxygen (O2) permeability to support the formation of an O2 gradient across the intestinal epithelium using cellular O2 consumption, resulting in an anaerobic luminal and aerobic basal compartment. Both the colonic epithelial cells and C. scindens remained viable over 48 h during co-culture. In contrast, co-culture with S. aureus elicited significant damage to colonic epithelial cells within 24 h. To explore the influence of the intestinal pathogen on the epithelium in the presence of the probiotic bacteria, colonic epithelial cells were inoculated sequentially with the two bacterial species. Under these conditions, C. scindens was capable of repressing the production of S. aureus enterotoxin. Surprisingly, although C. scindens converted cholic acid to secondary bile acids in the luminal medium, the growth of S. aureus was not significantly inhibited. Nevertheless, this combination of probiotic and pathogenic bacteria was found to benefit the survival of the colonic epithelial cells compared with co-culture of the epithelial cells with S. aureus alone. This platform thus provides an easy-to-use and low-cost tool to study the interaction between intestinal bacteria and colonic cells in vitro to better understand the interplay of intestinal microbiota with human colonic epithelium.
Exploration of agr types, virulence−associated genes, and biofilm formation ability in Staphylococcus aureus isolates from hemodialysis patients with vascular access infections
Authors: Lai Chi-Hsiang , Wong Min Yi , Huang Tsung-Yu , Kao Chih-Chen , Lin Yu-Hui , Lu Chu-Hsueh , Huang Yao-Kuang
Published: April 2024

Introduction

Staphylococcus aureus, is a pathogen commonly encountered in both community and hospital settings. Patients receiving hemodialysis treatment face an elevated risk of vascular access infections (VAIs) particularly Staphylococcus aureus, infection. This heightened risk is attributed to the characteristics of Staphylococcus aureus, , enabling it to adhere to suitable surfaces and form biofilms, thereby rendering it resistant to external interventions and complicating treatment efforts.

Methods

Therefore this study utilized PCR and microtiter dish biofilm formation assay to determine the difference in the virulence genes and biofilm formation among in our study collected of 103 Staphylococcus aureus, isolates from hemodialysis patients utilizing arteriovenous grafts (AVGs), tunneled cuffed catheters (TCCs), and arteriovenous fistulas (AVFs) during November 2013 to December 2021.

Results

Our findings revealed that both MRSA and MSSA isolates exhibited strong biofilm production capabilities. Additionally, we confirmed the presence of agr types and virulence genes through PCR analysis. The majority of the collected isolates were identified as agr type I. However, agr type II isolates displayed a higher average number of virulence genes, with MRSA isolates exhibiting a variety of virulence genes. Notably, combinations of biofilm-associated genes, such as eno−clfA−clfB−fib−icaA−icaD and eno−clfA−clfB−fib−fnbB−icaA−icaD, were prevalent among Staphylococcus aureus, isolates obtained from vascular access infections.

Discussion

These insights contribute to a better understanding of the molecular characteristics associated with Staphylococcus aureus, infections in hemodialysis patients and provided more targeted and effective treatment approaches.
Context matters: the importance of extra-mathematical knowledge in solving mathematical problems
Authors: Sigus Hardi , Mädamürk Kaja
Published: April 2024

Extra-mathematical knowledge is often overlooked when investigating mathematical skills. This study explores profiles of mathematical skills and associations with extra-mathematical knowledge and the understanding of complex sentences. The study involved 1,288 sixth-grade students (52.1% male) from 95 classes in 58 schools in Estonia. Students completed a math test as part of their regular lessons. The profiles of mathematical skills included students’ calculation skills, standard problems, and complex problems. Three distinct profiles of students emerged: students with high skill levels, students with average skill levels, and students with low skill levels. Students with high mathematical skills also had high extra-mathematical knowledge showing the crucial role of understanding the context of the math tasks in addition to having good mathematical skills.
Global trends and spatial drivers of diabetes mellitus mortality, 1990-2019: a systematic geographical analysis
Authors: Xu Zejia , Feng Jianheng , Xing Siyi , Liu Yin , Chen Yuting , Li Jie , Feng Yunhui
Published: April 2024

Objective

Diabetes mellitus is the leading cause of death worldwide, and multiple risk factors associated with diabetes mortality.

Methods

Employing spatial statistics, we characterized the spatial distribution and patterns of diabetes mortality, and revealed the spatial relationship between diabetes mortality and 11 socioeconomic and environmental risk factors at the country level, from 1990 to 2019.

Results

Globally, significantly high rates of diabetes mortality were primarily clustered in countries with limited land areas or located on islands, such as Fiji, Kiribati, Eswatini, and Trinidad and Tobago. Countries with weaker economic independence are more likely to have higher diabetes mortality rates. In addition, the impact of socioeconomic and environmental factors was significant at the country level, involving health expenditure, number of physicians, household and ambient air pollution, smoking, and alcohol consumption. Notably, the spatial relationship between diabetes mortality and ambient air pollution, as well as alcohol consumption, showed negative correlations. Countries with high diabetes mortality rates generally had lower levels of ambient air pollution and alcohol consumption.

Conclusion

The study highlights the spatial clustering of diabetes mortality and its substantial variation. While many risk factors can influence diabetes mortality, it’s also essential to consider the level of these factors at the country level. Tailoring appropriate interventions based on specific national circumstances holds the potential to more effectively mitigate the burden of diabetes mortality.
Pegunigalsidase alfa: a novel, pegylated recombinant alpha-galactosidase enzyme for the treatment of Fabry disease
Authors: Germain Dominique P. , Linhart Ales
Published: April 2024

Fabry disease, a rare X-linked genetic disorder, results from pathogenic variants in GLA, leading to deficient lysosomal α-galactosidase A enzyme activity and multi-organ manifestations. Since 2001, enzyme replacement therapy (ERT), using agalsidase alfa or agalsidase beta, has been the mainstay treatment, albeit with limitations such as rapid clearance and immunogenicity. Pegunigalsidase alfa, a novel PEGylated recombinant alpha-galactosidase, offers promise as an alternative. Produced in plant cells, pegunigalsidase alfa exhibits enhanced stability, prolonged half-life, and reduced immunogenicity due to pegylation. A phase 1/2 clinical trial demonstrated Gb3 clearance from renal capillary endothelial cells and its 48-month extension study revealed notable outcomes in renal function preservation. Three phase 3 clinical trials (BRIDGE, BRIGHT, and BALANCE) have shown favorable efficacy and safety profile, although caution is warranted in interpreting the results of BRIDGE and BRIGHT which lacked control groups. In BALANCE, the pivotal phase 3 trial comparing pegunigalsidase alfa with agalsidase beta, an intention-to-treat analysis of the eGFR decline over 2 years showed that the intergroup difference [95%confidence interval] in the median slope was −0.36 mL/min/1.73 m2/year [−2.44; 1.73]. The confidence interval had a lower limit above the prespecified value of −3 mL/min/1.73 m2/year and included zero. Despite challenges such as occasional hypersensitivity reactions and immune-complex-mediated glomerulonephritis, pegunigalsidase alfa approval by the European Medicines Agency and the Food and Drug Administration represents a significant addition to Fabry disease therapeutic landscape providing an option for patients in whom enzyme replacement therapy with current formulations is poorly tolerated or poorly effective.
A metformin add-on clinical study in multiple sclerosis to evaluate brain remyelination and neurodegeneration (MACSiMiSE-BRAIN): study protocol for a multi-center randomized placebo controlled clinical trial
Authors: De Keersmaecker Anna-Victoria , Van Doninck Eline , Popescu Veronica , Willem Lander , Cambron Melissa , Laureys Guy , D’ Haeseleer Miguel , Bjerke Maria , Roelant Ella , Lemmerling Marc , D’hooghe Marie Beatrice , Derdelinckx Judith , Reynders Tatjana , Willekens Barbara
Published: April 2024

Introduction

Despite advances in immunomodulatory treatments of multiple sclerosis (MS), patients with non-active progressive multiple sclerosis (PMS) continue to face a significant unmet need. Demyelination, smoldering inflammation and neurodegeneration are important drivers of disability progression that are insufficiently targeted by current treatment approaches. Promising preclinical data support repurposing of metformin for treatment of PMS. The objective of this clinical trial is to evaluate whether metformin, as add-on treatment, is superior to placebo in delaying disease progression in patients with non-active PMS.

Methods and analysis

MACSiMiSE-BRAIN is a multi-center two-arm, 1:1 randomized, triple-blind, placebo-controlled clinical trial, conducted at five sites in Belgium. Enrollment of 120 patients with non-active PMS is planned. Each participant will undergo a screening visit with assessment of baseline magnetic resonance imaging (MRI), clinical tests, questionnaires, and a safety laboratory assessment. Following randomization, participants will be assigned to either the treatment (metformin) or placebo group. Subsequently, they will undergo a 96-week follow-up period. The primary outcome is change in walking speed, as measured by the Timed 25-Foot Walk Test, from baseline to 96 weeks. Secondary outcome measures include change in neurological disability (Expanded Disability Status Score), information processing speed (Symbol Digit Modalities Test) and hand function (9-Hole Peg test). Annual brain MRI will be performed to assess evolution in brain volumetry and diffusion metrics. As patients may not progress in all domains, a composite outcome, the Overall Disability Response Score will be additionally evaluated as an exploratory outcome. Other exploratory outcomes will consist of paramagnetic rim lesions, the 2-minute walking test and health economic analyses as well as both patient- and caregiver-reported outcomes like the EQ-5D-5L, the Multiple Sclerosis Impact Scale and the Caregiver Strain Index.

Ethics and dissemination

Clinical trial authorization from regulatory agencies [Ethical Committee and Federal Agency for Medicines and Health Products (FAMHP)] was obtained after submission to the centralized European Clinical Trial Information System. The results of this clinical trial will be disseminated at scientific conferences, in peer-reviewed publications, to patient associations and the general public.

Trial registration

ClinicalTrials.gov Identifier: NCT05893225, EUCT number: 2023-503190-38-00.
Case report: Rubella virus-associated cutaneous granuloma in an adult with TAP1 deficiency
Authors: Wang Qiaohui , Su Huilin , Han Jiande , Yang Juhua , Lin Naiyu
Published: April 2024

Rubella virus-associated granulomas commonly occur in immunocompromised individuals, exhibiting a diverse range of clinical presentations. These manifestations can vary from predominantly superficial cutaneous plaques or nonulcerative nodules to more severe deep ulcerative lesions, often accompanied by extensive necrosis and significant tissue destruction. TAP1 deficiency, an exceedingly rare primary immune-deficiency disorder, presents with severe chronic sino-pulmonary infection and cutaneous granulomas. This report highlights the occurrence of rubella virus-associated cutaneous granulomas in patients with TAP1 deficiency. Notably, the pathogenic mutation responsible for TAP1 deficiency stems from a novel genetic alteration that has not been previously reported. This novel observation holds potential significance for the field of diagnosis and investigative efforts in the context of immunodeficiency disorders.
MNDA, a PYHIN factor involved in transcriptional regulation and apoptosis control in leukocytes
Authors: Bottardi Stefania , Layne Taylorjade , Ramòn Ailyn C. , Quansah Norreen , Wurtele Hugo , Affar El Bachir , Milot Eric
Published: April 2024

Inflammation control is critical during the innate immune response. Such response is triggered by the detection of molecules originating from pathogens or damaged host cells by pattern-recognition receptors (PRRs). PRRs subsequently initiate intra-cellular signalling through different pathways, resulting in i) the production of inflammatory cytokines, including type I interferon (IFN), and ii) the initiation of a cascade of events that promote both immediate host responses as well as adaptive immune responses. All human PYRIN and HIN-200 domains (PYHIN) protein family members were initially proposed to be PRRs, although this view has been challenged by reports that revealed their impact on other cellular mechanisms. Of relevance here, the human PYHIN factor myeloid nuclear differentiation antigen (MNDA) has recently been shown to directly control the transcription of genes encoding factors that regulate programmed cell death and inflammation. While MNDA is mainly found in the nucleus of leukocytes of both myeloid (neutrophils and monocytes) and lymphoid (B-cell) origin, its subcellular localization has been shown to be modulated in response to genotoxic agents that induce apoptosis and by bacterial constituents, mediators of inflammation. Prior studies have noted the importance of MNDA as a marker for certain forms of lymphoma, and as a clinical prognostic factor for hematopoietic diseases characterized by defective regulation of apoptosis. Abnormal expression of MNDA has also been associated with altered levels of cytokines and other inflammatory mediators. Refining our comprehension of the regulatory mechanisms governing the expression of MNDA and other PYHIN proteins, as well as enhancing our definition of their molecular functions, could significantly influence the management and treatment strategies of numerous human diseases. Here, we review the current state of knowledge regarding PYHIN proteins and their role in innate and adaptive immune responses. Emphasis will be placed on the regulation, function, and relevance of MNDA expression in the control of gene transcription and RNA stability during cell death and inflammation.
Spatio-temporal variation in progression rates of black band disease between Pramuka Island and Pari Island of the Seribu Islands, Indonesia
Authors: Ofri Ofri Johan , Ginanjar Rendy , Rustam Agustin , Ardi Idil , Sholichah Lili , Rachmawati Rita , Siringoringo Rikoh Manogar , Abrar Muhammad , Sari Ni Wayan Purnama , Giyanto  , Samusamu Andrias Steward , Undap Nani Ingrid , Rachmawati Puput Fitri , Zamani Neviaty Putri , Sweet Michael , Kunzmann Andreas
Published: April 2024

Black band disease (BBD) is one of the oldest recognized diseases of scleractinian corals. This disease is little known on the variation of progression rates across relatively small spatial scales and how local variations in the environment can impact prevalence and spread. The purpose of this study was to explore the progression of BBD on genus Montipora in relation to spatio-temporal environmental parameters in two islands of the Seribu Islands, North Jakarta, Indonesia during dry season and rainy season. Monthly underwater pictures were taken for determining the progress of disease level. Interestingly, the progression rate of the disease recorded at Pramuka Island was higher (8.10 cm2 day-1) than the one at Pari Island (3.79 cm2 day-1). In Pramuka Island, the infected corals had almost 89% of the dead surface, compared to only 68% at Pari Island. Similar to other studies in the region, we confirmed that the disease progressed faster during the dry season, where the environmental parameters, such as temperature, light intensity, and phosphate, were starting to increase, while total organic matter, current flow rates, and turbidity were lower. Progression of the disease was significantly different between seasons (p<0.001), but not between sites (p=0.118). Therefore, the progress of BBD has a higher impact at the more populated Pramuka island than at the less populated Pari Island, in addition to the influence of environmental parameters on coral vulnerability to diseases.
Machine learning for monitoring hobbing tool health in CNC hobbing machine
Authors: Tambake Nagesh , Deshmukh Bhagyesh , Pardeshi Sujit , Mahmoud Haitham A. , Cep Robert , Salunkhe Sachin , Nasr Emad Abouel
Published: April 2024

Utilizing Machine Learning (ML) to oversee the status of hobbing cutters aims to enhance the gear manufacturing process’s effectiveness, output, and quality. Manufacturers can proactively enact measures to optimize tool performance and minimize downtime by conducting precise real-time assessments of hobbing cutter conditions. This proactive approach contributes to heightened product quality and decreased production costs. This study introduces an innovative condition monitoring system utilizing a Machine Learning approach. A Failure Mode and Effect Analysis (FMEA) were executed to gauge the severity of failures in hobbing cutters of Computer Numerical Control (CNC) Hobbing Machine, and the Risk Probability Number (RPN) was computed. This numerical value aids in prioritizing preventive measures by concentrating on failures with the most substantial potential impact. Failures with high RPN numbers were considered to implement the Machine Learning approach and artificial faults were induced in the hobbing cutter. Vibration signals (displacement, velocity, and acceleration) were then measured using a commercial high-capacity and high-frequency range Data Acquisition System (DAQ). The analysis covered operating parameters such as speed (ranging from 35 to 45 rpm), feed (ranging from 0.6 to 1 mm/rev), and depth of cut (6.8 mm). MATLAB code and script were employed to extract statistical features. These features were subsequently utilized to train seven algorithms (Decision Tree, Naive Bayes, Support Vector Machine (SVM), Efficient Linear, Kernel, Ensemble and Neural Network) as well as the application of Bayesian optimization for hyperparameter tuning and model evaluation were done. Amongst these algorithms, J48 Decision tree (DT) algorithm demonstrated impeccable accuracy, correctly classifying 100% of instances in the provided dataset. These algorithms stand out for their accuracy and efficiency in building, making them well-suited for this purpose. Based on ML model performance, it is recommended to employ J48 Decision Tree Model for the condition monitoring of a CNC hobbing cutter. The emerging confusion matrix was crucial in creating a condition monitoring system. This system can analyze statistical features extracted from vibration signals to assess the health of the cutter and classify it accordingly. The system alerts the operator when a hobbing cutter approaches a worn or damaged condition, enabling timely replacement before any issues arise.
Clostridioides difficile infection is associated with differences in transcriptionally active microbial communities
Authors: Chen See Jeremy R. , Leister Jillian , Wright Justin R. , Kruse Peter I. , Khedekar Mohini V. , Besch Catharine E. , Kumamoto Carol A. , Madden Gregory R. , Stewart David B. , Lamendella Regina
Published: April 2024

Clostridioides difficile infection (CDI) is responsible for around 300,000 hospitalizations yearly in the United States, with the associated monetary cost being billions of dollars. Gut microbiome dysbiosis is known to be important to CDI. To the best of our knowledge, metatranscriptomics (MT) has only been used to characterize gut microbiome composition and function in one prior study involving CDI patients. Therefore, we utilized MT to investigate differences in active community diversity and composition between CDI+ (n = 20) and CDI− (n = 19) samples with respect to microbial taxa and expressed genes. No significant (Kruskal-Wallis, p > 0.05) differences were detected for richness or evenness based on CDI status. However, clustering based on CDI status was significant for both active microbial taxa and expressed genes datasets (PERMANOVA, p ≤ 0.05). Furthermore, differential feature analysis revealed greater expression of the opportunistic pathogens Enterocloster bolteae and Ruminococcus gnavus in CDI+ compared to CDI− samples. When only fungal sequences were considered, the family Saccharomycetaceae expressed more genes in CDI−, while 31 other fungal taxa were identified as significantly (Kruskal-Wallis p ≤ 0.05, log(LDA) ≥ 2) associated with CDI+. We also detected a variety of genes and pathways that differed significantly (Kruskal-Wallis p ≤ 0.05, log(LDA) ≥ 2) based on CDI status. Notably, differential genes associated with biofilm formation were expressed by C. difficile. This provides evidence of another possible contributor to C. difficile’s resistance to antibiotics and frequent recurrence in vivo. Furthermore, the greater number of CDI+ associated fungal taxa constitute additional evidence that the mycobiome is important to CDI pathogenesis. Future work will focus on establishing if C. difficile is actively producing biofilms during infection and if any specific fungal taxa are particularly influential in CDI.
Analysis of the expression level and predictive value of CLEC16A|miR-654-5p|RARA regulatory axis in the peripheral blood of patients with ischemic stroke based on biosignature analysis
Authors: Hao Jiang-jie , Liu Yuan , Lu Jun-hua , Zhao Ying , Lin Ying , Ma Li-qiu , Xue Ping , Jin Bao-yun , Li Bei-bei , Zhou Zheng , Huang Xin-xin , Liu Ting , Li Meng-yue , Lai Jin-ying , Guan Hong-jun
Published: April 2024

Introduction

Ischemic stroke (IS) is a cerebrovascular disease that can be disabling and fatal, and there are limitations in the clinical treatment and prognosis of IS. It has been reported that changes in the expression profile of circRNAs have been found during injury in ischemic stroke, and circRNAs play an important role in the IS cascade response. However, the specific mechanisms involved in the pathogenesis of IS are not yet fully understood, and thus in-depth studies are needed.

Methods

In this study, one circRNA dataset (GSE161913), one miRNA dataset (GSE60319) and one mRNA dataset (GSE180470) were retrieved from the Gene Expression Omnibus (GEO) database and included, and the datasets were differentially expressed analyzed by GEO2R and easyGEO to get the DEcircRNA, DEmiRNA and DEmRNA, and DEmRNA was enriched using ImageGP, binding sites were predicted in the ENCORI database, respectively, and the competitive endogenous RNA (ceRNA) regulatory network was visualized by the cytoscape software, and then selected by MCC scoring in the cytoHubba plugin Hub genes. In addition, this study conducted a case–control study in which blood samples were collected from stroke patients and healthy medical examiners to validate the core network of ceRNAs constructed by biosignature analysis by real-time fluorescence quantitative qRT-PCR experiments.

Results

A total of 233 DEcircRNAs, 132 DEmiRNAs and 72 DEmRNAs were screened by bioinformatics analysis. circRNA-mediated ceRNA regulatory network was constructed, including 148 circRNAs, 43 miRNAs and 44 mRNAs. Finally, CLEC16A|miR-654-5p|RARA competitive endogenous regulatory axis was selected for validation by qRT-PCR, and the validation results were consistent with the bioinformatics analysis.

Discussion

In conclusion, the present study establishes a new axis of regulation associated with IS, providing new insights into the pathogenesis of IS.
Post-stroke diabetes management: a qualitative study
Authors: Hewitt Jonathan , Azhari Hala F. , O’Neill Martin , Smith Alexander , Quinn Terence , Dawson Jesse
Published: April 2024

Introduction

Diabetes is associated with an increased risk of stroke. In many cases, a diabetes diagnosis may predate a stroke; however, diabetes is often diagnosed during the hospital admission following a stroke. To explore the experiences of stroke survivors as they cope with a new diabetes diagnosis, particularly regarding developing an effective strategy for managing the disease.

Methods

A qualitative grounded theory approach was used that employed focus group interviews with participants, including clinicians and stroke survivors, to develop a holistic understanding of primary and secondary stroke care services and the experiences of those accessing them.

Results

Clinicians believed they were not optimally equipped to manage diabetes as a condition. They believed more emphasis should be placed on self-management, which would be better managed by lifestyle changes than medication alone. Conversely, stroke survivors with diabetes experienced an additional burden associated with the diagnoses but relied on clinicians to manage their diabetes and believed the clinicians were failing if they were unwilling or unable to achieve this.

Discussion

The research highlights the tensions between stroke survivors and healthcare professionals. Stroke survivors relied on the healthcare teams to provide the optimal treatment when they had recently undergone a significant health event where they had experienced a stroke and received a diabetes diagnosis. However, the healthcare teams, while recognizing the importance of a holistic and comprehensive treatment package, struggled to provide it due to resource limitations. To optimize post-stroke diabetes self-management education, a strategic framework that prioritizes patient empowerment and interdisciplinary collaboration is paramount. Tailoring educational interventions to align with individual patient profiles—considering their unique health status, personal preferences, and cultural context—is essential for fostering self-efficacy. Such a strategy not only empowers patients to take an active role in managing their diabetes post-stroke but also contributes to superior health outcomes and an elevated standard of living.
Co-learning synaptic delays, weights and adaptation in spiking neural networks
Authors: Deckers Lucas , Van Damme Laurens , Van Leekwijck Werner , Tsang Ing Jyh , Latré Steven
Published: April 2024

Spiking neural network (SNN) distinguish themselves from artificial neural network (ANN) because of their inherent temporal processing and spike-based computations, enabling a power-efficient implementation in neuromorphic hardware. In this study, we demonstrate that data processing with spiking neurons can be enhanced by co-learning the synaptic weights with two other biologically inspired neuronal features: (1) a set of parameters describing neuronal adaptation processes and (2) synaptic propagation delays. The former allows a spiking neuron to learn how to specifically react to incoming spikes based on its past. The trained adaptation parameters result in neuronal heterogeneity, which leads to a greater variety in available spike patterns and is also found in the brain. The latter enables to learn to explicitly correlate spike trains that are temporally distanced. Synaptic delays reflect the time an action potential requires to travel from one neuron to another. We show that each of the co-learned features separately leads to an improvement over the baseline SNN and that the combination of both leads to state-of-the-art SNN results on all speech recognition datasets investigated with a simple 2-hidden layer feed-forward network. Our SNN outperforms the benchmark ANN on the neuromorphic datasets (Spiking Heidelberg Digits and Spiking Speech Commands), even with fewer trainable parameters. On the 35-class Google Speech Commands dataset, our SNN also outperforms a GRU of similar size. Our study presents brain-inspired improvements in SNN that enable them to excel over an equivalent ANN of similar size on tasks with rich temporal dynamics.
The predictive ability of ABSI compared to BMI for mortality and frailty among older adults
Authors: Shafran Itamar , Krakauer Nir Y. , Krakauer Jesse C. , Goshen Abigail , Gerber Yariv
Published: April 2024

Introduction

To study the utility of A Body Shape Index (ABSI) alongside body mass index (BMI) to predict mortality and frailty in an aging community population.

Materials and methods

Participants (n = 1,580) were drawn from the first Israeli national health and nutrition survey of older adults (“Mabat Zahav”) conducted from 2005 to 2006, constituting adults aged ≥65 years. Socio-demographic, clinical, behavioral, and psychosocial data were collected. Baseline weight, height, and waist circumference (WC) were measured and expressed as the allometric indices BMI (kg/m2) and ABSI, a BMI-independent measure of abdominal obesity [WC/(BMI2/3*m1/2)]. Mortality follow-up lasted through 2019. Frailty was assessed in 2017–2019 by the Fried Biological Phenotype in a sub-cohort of 554 survivors. Cox and logistic regression models assessed associations of BMI and ABSI with mortality and frailty.

Results

At baseline, mean [SD] age was 74.5 [6.1] years, and 52.4% were women. The correlation between BMI and WC Z scores was 0.71, reduced to −0.11 for BMI and ABSI. Over a median follow-up of 13 years, 757 deaths occurred. The multivariable-adjusted hazard ratios (95% CIs) for mortality per standard deviation increase in BMI and ABSI were 1.07 (0.99;1.17) and 1.13 (1.05;1.21), respectively. Among participants assessed for frailty, 77 (14%) met the frailty criteria. After multivariable adjustment, the odds ratios (95% CIs) for frailty were 0.83 (0.69–1.01) for BMI and 1.55 (1.34–1.79) for ABSI.

Discussion

In a nationwide cohort of older adults, ABSI was independently associated with mortality risk. Furthermore, ABSI, but not BMI, was a strong predictor of frailty.
Reflections of well-being: navigating body image, chronic energy deficiency, and nutritional intake among urban and rural adolescents
Authors: Yulia Cica , Rosdiana Delita Septia , Muktiarni M. , Sari Desyane Ramadhina
Published: April 2024

Background

Adolescent growth and development is a period of very specific nutritional problems. As a result of poor growth and development, 36.3% of adolescents in Indonesia are at risk of developing CED. The purpose of this study was to determine the description of body image, the incidence of Chronic Energy Deficiency (CED), and nutritional intake in adolescents in urban and rural areas.

Methods

This study used a descriptive quantitative design with a cross-sectional study conducted in Bandung and Sumedang on 387 adolescents aged 13–15 years. The instruments used in this study were body image questionnaire Figure Rating Scale (FRS) method, 2 × 24-h food recall, and anthropometry for Measuring mid upper arm circumference (MUAC).

Results

Results of this study showed that more than half of adolescents in urban (54.0%) and rural areas (61.7%) were at risk of CED, had negative body image perceptions in urban (69.1%) and rural areas (62.3%), and underconsumption of macronutrients in both urban and rural adolescents.

Conclusion

Most adolescents in urban and rural areas still consume less energy, carbohydrates, and protein. Perceived body image and nutrient intake contribute to the incidence of CED in adolescents.
Possible interactions between selected food processing and medications
Authors: Poli Giuseppe , Bologna Ettore , Saguy I. Sam
Published: April 2024

The impact of food processing on drug absorption, metabolism, and subsequent pharmacological activity is a pressing yet insufficiently explored area of research. Overlooking food-processing-drug interactions can significantly disrupt optimal clinical patient management. The challenges extend beyond merely considering the type and timing of food ingestion as to drug uptake; the specific food processing methods applied play a pivotal role. This study delves into both selected thermal and non-thermal food processing techniques, investigating their potential interference with the established pharmacokinetics of medications. Within the realm of thermal processing, conventional methods like deep fat frying, grilling, or barbecuing not only reduce the enteric absorption of drugs but also may give rise to side-products such as acrylamide, aldehydes, oxysterols, and oxyphytosterols. When produced in elevated quantities, these compounds exhibit enterotoxic and pro-inflammatory effects, potentially impacting the metabolism of various medications. Of note, a variety of thermal processing is frequently adopted during the preparation of diverse traditional herbal medicines. Conversely, circumventing high heat through innovative approaches (e.g., high-pressure processing, pulsed electric fields, plasma technology), opens new avenues to improve food quality, efficiency, bioavailability, and sustainability. However, it is crucial to exercise caution to prevent the excessive uptake of active compounds in specific patient categories. The potential interactions between food processing methods and their consequences, whether beneficial or adverse, on drug interactions can pose health hazards in certain cases. Recognizing this knowledge gap underscores the urgency for intensified and targeted scientific inquiry into the multitude of conceivable interactions among food composition, processing methods, and pharmaceutical agents. A thorough investigation into the underlying mechanisms is imperative. The complexity of this field requires substantial scrutiny and collaborative efforts across diverse domains, including medicine, pharmacology, nutrition, food science, food technology, and food engineering.
Efficacy and safety of venetoclax plus hypomethylating agents in relapsed/refractory acute myeloid leukemia: a multicenter real-life experience
Authors: Angotzi Francesco , Lessi Federica , Leoncin Matteo , Filì Carla , Endri Mauro , Lico Albana , Visentin Andrea , Pravato Stefano , Candoni Anna , Trentin Livio , Gurrieri Carmela
Published: April 2024

Venetoclax (VEN) has been shown to play a synergistic effect in combination with hypomethylating agents (HMAs) in the frontline treatment of acute myeloid leukemia (AML). However, the potential role of this therapy in the relapsed/refractory (R/R) AML setting, still needs to be further unveiled. The aim of the current study was to retrospectively outline the safety profile, response and survival outcomes of R/R AML patients treated with VEN in association with HMAs. Clinical, biological, and molecular data were collected from 57 patients with R/R AML treated with VEN combined with azacitidine or decitabine between 2018 and 2023. The median age of patients was 63 years, 38 (66.7%) received treatment for relapsed disease while 19 (33.3%) for refractory disease, 5 (8.7%) were treated for molecular relapse. A consistent proportion of the cohort was represented by patients with unfavorable prognostic factors such as complex karyotype (36.8%), secondary AML (29.8%), previous exposure to HMAs (38.6%), and relapse after allogeneic stem cell transplant (22.8%). A total of 14 patients achieved CR (24.6%), 3 (5.3%) CRi, 3 (5.3%) MLFS, and 3 (5.3%) PR, accounting for an ORR of 40.4%. The CR/CRi rate was higher in the group treated with azacitidine than in the group treated with decitabine (37.8% vs. 15%). The median OS was 8.2 months, reaching 20.1 months among responding patients. VEN-HMAs treatment allowed to bridge to allogeneic stem cell transplantation 11 (23.9%) of eligible patients, for which a median OS of 19.8 months was shown. On multivariate analysis, ECOG performance status ≥2, complex karyotype and not proceeding to allogeneic stem cell transplantation after therapy with VEN-HMAs were the factors independently associated with shorter OS. Patients treated with the azacitidine rather than the decitabine containing regimen generally displayed a trend toward superior outcomes. The major toxicities were prolonged neutropenia and infections. In conclusion, this study showed how VEN-HMAs could represent an effective salvage therapy in patients with R/R AML, even among some of those patients harboring dismal prognostic features, with a good toxicity profile. Further prospective studies are thus warranted.
The expression of PKM1 and PKM2 in developing, benign, and cancerous prostatic tissues
Authors: Li Lin , Cheng Siyuan , Yeh Yunshin , Shi Yingli , Henderson Nikayla , Price David , Gu Xin , Yu Xiuping
Published: April 2024

Background

Neuroendocrine prostate cancer (NEPCa) is the most aggressive type of prostate cancer (PCa). However, energy metabolism, one of the hallmarks of cancer, in NEPCa has not been well studied. Pyruvate kinase M (PKM), which catalyzes the final step of glycolysis, has two main splicing isoforms, PKM1 and PKM2. The expression pattern of PKM1 and PKM2 in NEPCa remains unknown.

Methods

In this study, we used immunohistochemistry, immunofluorescence staining, and bioinformatics analysis to examine the expression of PKM1 and PKM2 in mouse and human prostatic tissues.

Results

We found that PKM2 was the predominant isoform expressed throughout prostate development and PCa progression, with slightly reduced expression in murine NEPCa. PKM1 was mostly expressed in stromal cells but low-level PKM1 was also detected in prostate basal epithelial cells. Its expression was absent in the majority of prostate adenocarcinoma (AdPCa) specimens but present in a subset of NEPCa. Additionally, we evaluated the mRNA levels of ten PKM isoforms that express exon 9 (PKM1-like) or exon 10 (PKM2-like). Some of these isoforms showed notable expression levels in PCa cell lines and human PCa specimens.

Discussion

Our study characterized the expression pattern of PKM1 and PKM2 in prostatic tissues including developing, benign, and cancerous prostate. These findings lay the groundwork for understanding the metabolic changes in different PCa subtypes.
NLRP3 inflammasome and pyroptosis in cardiovascular diseases and exercise intervention
Authors: Ding Ping , Song Yuanming , Yang Yang , Zeng Cheng
Published: April 2024

NOD-like receptor protein 3 (NLRP3) inflammasome is an intracellular sensing protein complex that possesses NACHT, leucine-rich repeat, and pyrin domain, playing a crucial role in innate immunity. Activation of the NLRP3 inflammasome leads to the production of pro-inflammatory cellular contents, such as interleukin (IL)-1β and IL-18, and induction of inflammatory cell death known as pyroptosis, thereby amplifying or sustaining inflammation. While a balanced inflammatory response is beneficial for resolving damage and promoting tissue healing, excessive activation of the NLRP3 inflammasome and pyroptosis can have harmful effects. The involvement of the NLRP3 inflammasome has been observed in various cardiovascular diseases (CVD). Indeed, the NLRP3 inflammasome and its associated pyroptosis are closely linked to key cardiovascular risk factors including hyperlipidemia, diabetes, hypertension, obesity, and hyperhomocysteinemia. Exercise compared with medicine is a highly effective measure for both preventing and treating CVD. Interestingly, emerging evidence suggests that exercise improves CVD and inhibits the activity of NLRP3 inflammasome and pyroptosis. In this review, the activation mechanisms of the NLRP3 inflammasome and its pathogenic role in CVD are critically discussed. Importantly, the purpose is to emphasize the crucial role of exercise in managing CVD by suppressing NLRP3 inflammasome activity and proposes it as the foundation for developing novel treatment strategies.
Pathogenic role of super-enhancers as potential therapeutic targets in lung cancer
Authors: Yao Zhiyuan , Song Peng , Jiao Wenjie
Published: April 2024

Lung cancer is still one of the deadliest malignancies today, and most patients with advanced lung cancer pass away from disease progression that is uncontrollable by medications. Super-enhancers (SEs) are large clusters of enhancers in the genome’s non-coding sequences that actively trigger transcription. Although SEs have just been identified over the past 10 years, their intricate structure and crucial role in determining cell identity and promoting tumorigenesis and progression are increasingly coming to light. Here, we review the structural composition of SEs, the auto-regulatory circuits, the control mechanisms of downstream genes and pathways, and the characterization of subgroups classified according to SEs in lung cancer. Additionally, we discuss the therapeutic targets, several small-molecule inhibitors, and available treatment options for SEs in lung cancer. Combination therapies have demonstrated considerable advantages in preclinical models, and we anticipate that these drugs will soon enter clinical studies and benefit patients.
Merging single-track location Elastographic imaging with the frequency shift method improves shear wave attenuation measurements
Authors: Mislati Reem , Iliza Katia T. , Gerber Scott A. , Doyley Marvin M.
Published: April 2024

The frequency shift (FS) method is emerging as the standard approach for estimating shear wave attenuation coefficient (SWA). However, measurement noise can negatively impact the FS method’s accuracy, especially when employed in vivo. We hypothesized that combining plane wave single-track location shear wave elastography imaging with the FS method would reduce this problem. To test our hypothesis, we performed studies on calibrated phantoms and two groups of in vivo murine liver: control and obese mice. We evaluated the performance of various SWA methods, including the plane wave single-track location frequency shift (pSTL-FS) method that we recently developed, the original FS method, and the attenuation-measuring-shear-wave ultrasound elastography (AMUSE) method. We also assessed the effectiveness of assuming a Gaussian distribution versus a Gamma distribution for the shear wave spectrum when estimating SWA coefficients with the pSTL-FS and FS methods. The actual SWA coefficients of the phantoms were determined by performing independent mechanical testing on representative samples. The accuracy incurred when estimating SWA ranged from 84.69% to 97.55% for pSTL-FS (Gamma), 51.37%–72.18% for pSTL-FS (Gaussian), 40.33%–57.00% for FS (Gamma), 39.33%–55.37% for FS (Gaussian), and 59.25%–99.22% for AMUSE. The results of studies performed on murine livers (n = 10) revealed that assuming a Gaussian distribution during pSTL-FS imaging resulted in lower attenuation values than when a Gamma distribution was assumed. We also observed that pSTL-FS (Gamma) resulted in the highest significant difference between control and obese mice than all other approaches (p-value <0.0001). We also observed that the standard FS method with either Gamma or Gaussians produced lower attenuation estimates than pSTL-FS, AMUSE and mechanical testing. The mean attenuation coefficients of the murine livers measured with the pSTL-FS (Gamma and Gaussian functions) methods were consistently higher than those computed with the standard FS methods but lower than those computed with the AMUSE method. Our results demonstrated that combining the pSTL method with FS method provided more robust estimates of the SWA coefficient. For the murine livers, a Gamma distribution is more representative of the shear wave frequency spectrum than a Gaussian distribution.
An epilepsy detection method based on multi-dimensional feature extraction and dual-branch hypergraph convolutional network
Authors: Liu Jiacen , Yang Yong , Li Feng , Luo Jing
Published: April 2024

Epilepsy is a disease caused by abnormal neural discharge, which severely harms the health of patients. Its pathogenesis is complex and variable with various forms of seizures, leading to significant differences in epilepsy manifestations among different patients. The changes of brain network are strongly correlated with related pathologies. Therefore, it is crucial to effectively and deeply explore the intrinsic features of epilepsy signals to reveal the rules of epilepsy occurrence and achieve accurate detection. Existing methods have faced the following issues: 1) single approach for feature extraction, resulting in insufficient classification information due to the lack of rich dimensions in captured features; 2) inability to deeply analyze the essential commonality of epilepsy signal after feature extraction, making the model susceptible to data distribution and noise interference. Thus, we proposed a high-precision and robust model for epileptic seizure detection, which, for the first time, applies hypergraph convolution to the field of epilepsy detection. Through a hypergraph network structure constructed based on relationships between channels in electroencephalogram (EEG) signals, the model explores higher-order characteristics of epilepsy EEG data. Specifically, we use the Conv-LSTM module and Power spectral density (PSD), a two-branch parallel method, to extract channel features from space-time and frequency domains to solve the problem of insufficient feature extraction, and can adequately describe the data structure and distribution from multiple perspectives through double-branch parallel feature extraction. In addition, we construct a hypergraph on the captured features to explore the intrinsic features in the high-dimensional space in an attempt to reveal the essential commonality of epileptic signal feature extraction. Finally, using the ensemble learning concept, we accomplished epilepsy detection on the dual-branch hypergraph convolution. The model underwent leave-one-out cross-validation on the TUH dataset, achieving an average accuracy of 96.9%, F1 score of 97.3%, Pre of 98.2% and Re of 96.7%. In addition, the model was generalized performance tested on CHB-MIT scalp EEG dataset with leave-one-out cross-validation, and the average ACC, F1 score, Pre and Re were 94.4%, 95.1%, 95.8%, and 93.9% respectively. Experimental results indicate that the model outperforms related literature, providing valuable reference for the clinical application of epilepsy detection.