bluuebunny/crossref_metadata_2025 huggingface dataset:
Barriers And Challenges Of Multidisciplinary Teams In Oncology Management: A Scoping Review Protocol
Authors: Law Nicholas Lee Wei , Hong Lai Wei , Tan Shirley Siang Ning , Foo Chuan Jie , Lee Daniel , Voon Pei Jye
Published: February 2024

Introduction

Multidisciplinary teams (MDTs) are integral to oncology management, involving specialised healthcare professionals who collaborate to develop individualised treatment plans for patients. However, as cancer care grows more complex, MDTs must continually adapt to better address patient needs. This scoping review will explore barriers and challenges MDTs have encountered in the past decade; and propose strategies for optimising their utilisation to overcome these obstacles and improve patient care.

Methods and analysis

The scoping review will follow Arksey and O’Malley’s framework and begin with a literature search using keywords in electronic databases such as PubMed/MEDLINE, Scopus and PsychINFO, covering the period from January 2013 to December 2022 and limited to English language publications. Four independent reviewers will screen titles and abstracts based on predefined inclusion criteria, followed by full-text review of selected titles. Relevant references cited in the publications will also be examined. A Preferred Reporting Items for Systematic reviews and Meta-Analyses flow diagram will be utilised to illustrate the methodology. Data from selected publications will be extracted, analysed, and categorised for further analysis.

Ethics and dissemination

The results of the scoping review will provide a comprehensive overview of the barriers and challenges encountered by oncology MDTs over the past decade. These findings will contribute to the existing literature and provide insights into areas that require improvement in the functioning of MDTs in oncology management. The results will be disseminated through publication in a scientific journal, which will help to share the findings with the wider healthcare community and facilitate further research and discussion in this field.

Trial registration details

The protocol for this scoping review is registered with Open Science Framework, available at DOI 10.17605/OSF.IO/R3Y8U.
Enhanced active case finding of drug-resistant tuberculosis in Namibia: a protocol for the hotspots, hospitals, and households (H3TB) study
Authors: Shavuka Olga , Iipumbu Etuhole , Boois Lorraine , Günther Gunar , Hoddinott Graeme , Lin Hsien-Ho , Nepolo Emmanuel , Niemann Stefan , Ruswa Nunurai , Seddon James , Claassens Mareli M
Published: February 2024

Introduction

Namibia is a high tuberculosis (TB)-burden country with an estimated incidence of 460/100 000 (around 12 000 cases) per year. Approximately 4.5% of new cases and 7.9% of previously treated TB cases are multidrug resistant (MDR) and 47% of patients with MDR-TB are HIV coinfected. Published data suggest a clustering of MDR-TB transmission in specific areas. Identifying transmission clusters is key to implementing high-yield and cost-effective interventions. This includes knowing the yield of finding TB cases in high-transmission zones (eg, community hotspots, hospitals or households) to deliver community-based interventions. We aim to identify such transmission zones for enhanced case finding and evaluate the effectiveness of this approach.

Methods and analysis

H3TB is an observational cross-sectional study evaluating MDR-TB active case finding strategies. Sputum samples from MDR-TB cases in three regions of Namibia will be evaluated by whole genome sequencing (WGS) in addition to routine sputum investigations (Xpert MTB/RIF, culture and drug susceptibility testing). We will collect information on household contacts, use of community spaces and geographical map intersections between participants, synthesising these data to identify transmission hotspots. We will look at the feasibility, acceptability, yield and cost of case finding strategies in these hotspots, and in households of patients with MDR-TB and visitors of hospitalised patients with MDR-TB. A compartmental transmission dynamic model will be constructed to evaluate the impact and cost-effectiveness of the strategies if scaled.

Ethics and dissemination

Ethics approval was obtained. Participants will give informed consent. H3TB will capitalise on a partnership with the Ministry of Health and Social Services to follow up individuals diagnosed with MDR-TB and integrate WGS data with innovative contact network mapping, to allow enhanced case finding. Study data will contribute towards a systems approach to TB control. Equally important, it will serve as a role model for similar studies in other high-incidence settings.
Acute kidney injury, the present on admission (POA) indicator and sex disparities: observational study of inpatient real-world data in a Swiss tertiary healthcare system. Explorative analysis
Authors: Triep Karen , Musy Sarah N , Simon Michael , Endrich Olga
Published: February 2024

Background

Regarding kidney disease (KD), sex differences in epidemiology and clinical relevance have been reported. Related to absolute and relative changes of baseline creatinine, different criteria for staging may induce underdiagnosis or overdiagnosis related to sex. At the largest Swiss provider of inpatient acute healthcare, a clinic decision support algorithm ensures exact staging of KD (2012 KDIGO Kidney Disease Improving Global Outcomes Clinical Practice Guideline). Coding of the indicator ‘Present On Admission’ (POA) was introduced at this institution in 2018 to flag postadmission conditions.

Objective

The explorative analysis aimed at differences in diagnosis groups. Defined indicators and the distribution of stages in acute kidney injury (AKI) were analysed using the POA flag. Sex differences were reported.

Methods

Retrospective observational study. Explorative analysis. Routinely collected health data, 2019 and 2020 (121 757 cases) on the patient history and intensive care treatment duration, comorbidity levels, coded diagnoses, age and sex.

Software and statistic: program R, V.4.1.1, SD; median, IQR; prop.test; standardised mean difference.

Results

The reporting of postadmission diagnoses showed more interhospital transfers, more intensive care stays, higher scores of severity and treatment intensity, more often mechanical ventilation, a higher age, a higher number of diagnoses, a higher complexity level of the related cases and mortality. This observation could be made to a lesser degree for the female population. However, for the female population mortality was higher (stage III AKI 41.6%).

Conclusion

Using the POA flag, the results reflect the clinical situation of complications and comorbidities evolving unexpectedly. As our results show sex differences, that is, a lower morbidity of female patients for each stage, but a higher mortality, a deeper evaluation of the implied sex differences in staging of KD should follow.

The general results confirm the necessity of a diagnosis-onset reporting in health statistics.
Estimating rare disease prevalence and costs in the USA: a cohort study approach using the Healthcare Cost Institute claims data
Authors: Cutillo Christine M , Tisdale Ainslie , Baghbanzadeh Mahdi , Crandall Keith A , Stidd Reva L , Khural Manpreet S , Hartman Laurie J , Greenberg Jeff , Zhang Kevin B , Rahnavard Ali
Published: February 2024

Objective

The study capitalised on national insurance claims data to gather information on patient characteristics and associated costs to better understand the diagnosis and treatment of rare diseases (RDs).

Materials and methods

Data from the Healthcare Cost Institute (HCCI) data enclave were analysed using R statistical software and filtered by the International Classification of Diseases, 10th edition (ICD-10), current procedural terminology codes and the National Drug Code associated with 14 RDs and disease-modifying therapy options. Data were aggregated by prevalence, costs, patient characteristics and effects of treatment modification.

Results

The prevalence and costs of RDs in the HCCI commercial claims database varied significantly across the USA and between urban and rural areas. Pharmacy costs increased when a new treatment was initiated, while non-pharmacy costs decreased.

Discussion

Prevalence and cost estimations are highly variable due to the small number of patients with RDs, and the lack of a national healthcare database limits inferences for such patient populations. Accurate assessments require a diverse population, which can likely be achieved by analysing multiple databases. RDs face challenges in prevalence estimation due to a lack of specific disease coding and a small patient population, compounded by issues like data standardisation and privacy concerns. Addressing these through improved data management in healthcare systems, increased research and education will lead to better diagnosis, care management and quality of life for patients with RD.

Conclusion

Data on patients with RD in the HCCI database were analysed for prevalence, costs, patient characteristics and treatment modification effects. Significant heterogeneity in each of these factors was found across RDs, geography and locality (eg, urban and rural). Building capabilities to use machine learning to accelerate the diagnosis of RDs would vastly improve with changes to healthcare data, such as standardising data input, linking databases, addressing privacy issues and assigning ICD-10 codes for all RDs, resulting in more robust data for RD analytics.
Mental health effects of working as a legal professional in the field of asylum law: a systematic review
Authors: Holt Leah , Mulcaire Jessie , O'Driscoll Ciarán , Zard Sana , Brady Francesca
Published: February 2024

Aims

Legal professionals work closely with asylum seekers at many points during an asylum claim. While there is an increasing literature examining the mental health effects of working with traumatised populations, there has been limited evidence focusing on the field of asylum law. This review aims to synthesise the current qualitative and quantitative literature on the mental health effects of working in asylum law.

Method

A systematic search from inception to 24 August 2023 was completed on the following databases: Web of Science, PsycINFO, MEDLINE, PubMed, SCOPUS, Westlaw UK, Index to Foreign Legal Periodicals and Index to Legal Periodicals and Books. The search retrieved 11 studies (6 qualitative, 3 quantitative and 2 mixed methods). A thematic synthesis was completed for the qualitative research and a narrative synthesis was completed for the quantitative research, before the findings were integrated into a combined synthesis.

Results

Four main themes and 13 subthemes were generated by the qualitative research. The main themes were as follows: emotional labour, working in a broken system, emotions do not mix with law and detachment. The quantitative synthesis found a variety of measures used in the literature, indicating that common mental health concerns, such as burn-out, depression, anxiety, post-traumatic stress disorder and secondary trauma symptoms, are present across this professional group. The synthesis also provides preliminary findings relating to possible predictors of poor mental health.

Conclusions

Despite limited evidence and methodological flaws in the literature, this review indicates that legal professionals are exposed to traumatised clients and difficult working conditions, both of which can negatively impact mental health. It also highlights a number of factors which may predict or perpetuate difficulties. Clinical implications, limitations and suggestions for future research are discussed.
Embodiment of discrimination: a cross-sectional study of threats, humiliating treatment and ethnic discrimination in relation to somatic health complaints among Sámi in Sweden
Authors: San Sebastian Miguel , Gustafsson Per Erik , Stoor Jon Petter Anders
Published: February 2024

Background

Ethnic discrimination is acknowledged as a social determinant of health for Indigenous populations worldwide. This study aimed to investigate embodiment of perceived ethnic discrimination among the Sámi population in Sweden.

Methods

A population-based health study was conducted among the Sámi population aged 18–84 years in 2021. Perceived discrimination was assessed by three variables: exposure to threat, humiliation treatment and ethnic discrimination. To capture current physical health, complaints of headache, back pain, stomach pain, sleeping problems, dizziness and tiredness were used. An overall somatic complaints score was created by summing up the six individual symptoms. The magnitude of the association between the independent variables and the outcomes was summarised with the β coefficients and prevalence ratios using 95% credible intervals (95% CrI) for inferential purposes.

Results

Overall, 4.3% reported to have been exposed to threat, 26.1% to humiliation and 11.2% and 32.3% to ethnic discrimination in the last 12 months and beyond 12 months, respectively. After mutual adjustment, threat (β=1.25; 95% CrI=0.88 to 1.60), humiliation (β=1.29; 95% CrI: 1.14 to 1.44) and the two categories of discrimination (β=0.92; 95% CI: 0.64 to 1.21 in the last 12 months and β=0.68; 95% CI: 0.54 to 0.83 beyond) remained significantly associated to the overall somatic complaints score. Similar results were found for individual complaints.

Conclusions

This study has shown a strong relationship between different expressions of perceived ethnic discrimination and a series of somatic complaints among the Sámi in Sweden. Efforts to alleviate interpersonal and institutional discrimination against the Sámi would contribute to improve their health.
Exploring the molecular pathways linking sleep phenotypes andPOGZ-associated neurodevelopmental disorder
Authors: Marquezini Bruna Pereira , Moysés-Oliveira Mariana , Kloster Anna , Cunha Lais , Deconto Tais Bassani , Mosini Amanda Cristina , Guerreiro Pedro , Paschalidis Mayara , Adami Luana Nayara Gallego , Andersen Monica Levy , Tufik Sergio
Published: February 2024

Pogo transposable element-derived protein with ZNF domain (POGZ) gene encodes a chromatin regulator and rare variants on this gene have been associated with a broad spectrum of neurodevelopmental disorders, such as White-Sutton syndrome. Patient clinical manifestations frequently include developmental delay, autism spectrum disorder and obesity. Sleep disturbances are also commonly observed in these patients, yet the biological pathways which link sleep traits to thePOGZ-associated syndrome remain unclear. We screened for sleep implications among individuals with causativePOGZvariants previously described. Sleep disturbances were observed in 52% of patients, and being obese was not observed as a risk factor for sleep problems. Next, we identified genes associated with sleep-associated traits among thePOGZregulatory targets, aiming to uncover the molecular pathways that, when disrupted byPOGZloss of function, contribute to the aetiology of sleep phenotypes in these patients. The intersect betweenPOGZtargets and sleep-related genes was used in a pathway enrichment analysis. Relevant pathways among these overlapping genes are involved in the regulation of circadian rhythm, tau protein binding, ATPase activator activity. This study may represent the beginning for novel functional investigations on shared molecular mechanisms between sleep disturbances and rare developmental syndromes related toPOGZand its regulatory targets.
Do pulmonary rehabilitation programmes improve outcomes in patients with COPD posthospital discharge for exacerbation: a systematic review and meta-analysis
Authors: Jenkins Alex R , Burtin Chris , Camp Pat G , Lindenauer Peter , Carlin Brian , Alison Jennifer A , Rochester Carolyn , Holland Anne E
Published: February 2024

Introduction

Previous systematic reviews have provided heterogeneous and differing estimates for the efficacy of pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease (COPD). The aim of this review was to examine the efficacy of pulmonary rehabilitation programmes initiated within 3 weeks of hospital discharge following an exacerbation of COPD.

Methods

An update of a previous Cochrane review was undertaken using the Cochrane Airways Review Group Specialised Register. Searches were conducted from October 2015 to August 2023 for studies that initiated pulmonary rehabilitation within 3 weeks of hospital discharge. Studies assessing the impact of solely inpatient pulmonary rehabilitation were excluded. Forest plots were generated using a generic inverse variance random effects method.

Results

Seventeen studies were included. Posthospital discharge pulmonary rehabilitation reduced hospital re-admissions (OR 0.48, 95% CI 0.30 to 0.77, I2=67%), improved exercise capacity (6 min walk test, mean difference (MD) 57 m, 95% CI 29 to 86, I2=89%; incremental shuttle walk test, MD 43 m, 95% CI 6 to 79, I2=81%), health-related quality of life (St. George’s Respiratory Questionnaire, MD −8.7 points, 95% CI −12.5 to −4.9, I2=59%; Chronic Respiratory Disease Questionnaire (CRQ)-emotion, MD 1.0 points, 95% CI 0.4 to 1.6, I2=74%; CRQ-fatigue, MD 0.9 points, 95% CI 0.1 to 1.6, I2=91%), and dyspnoea (CRQ-dyspnoea, MD 1.0 points, 95% CI 0.3 to 1.7, I2=87%; modified Medical Research Council Dyspnoea Scale, MD −0.3 points, 95% CI −0.5 to −0.1, I2=60%). Significant effects were not observed for CRQ-mastery, COPD assessment test, EuroQol-5 Dimension-5 Level and mortality. No intervention-related adverse events were reported.

Discussion

Pulmonary rehabilitation delivered posthospital discharge for exacerbation of COPD results in a reduction in hospital re-admissions and improvements in exercise capacity, health-related quality of life and dyspnoea in the absence of any intervention-related adverse events.

Trial registration number

CRD42023406397.
On parity decision trees for Fourier-sparse Boolean functions
Authors: Mande Nikhil Shekhar , Sanyal Swagato
Published: February 2024

We study parity decision trees for Boolean functions. The motivation of our study is the log-rank conjecture for XOR functions and its connection to Fourier analysis and parity decision tree complexity. Our contributions are as follows: Let

\(f : \mathbb {F}_2^n \rightarrow \lbrace -1, 1\rbrace\)

be a Boolean function with Fourier support 𝒮 and Fourier sparsity
k
.
Learning to Detect Attended Objects in Cultural Sites with Gaze Signals and Weak Object Supervision
Authors: Mazzamuto* Michele , Ragusa* Francesco , Furnari* Antonino , Farinella* Giovanni Maria
Published: February 2024

Cultural sites such as museums and monuments are popular tourist destinations worldwide. Visitors come to these places to learn about the cultures, histories, and arts of a particular region or country. However, for many cultural sites, traditional visiting approaches are limited and may fail to engage visitors. To enhance visitors’ experiences, previous works have explored how wearable devices can be exploited in this context. Among the many functions that these devices can offer, understanding which artwork or detail the user is attending to is fundamental to provide additional information on the observed artworks, understand the visitor’s tastes, and provide recommendations. This motivates the development of algorithms for understanding visitor attention from egocentric images. We considered the attended object detection task, which involves detecting and recognizing the object observed by the camera wearer, from an input RGB image and gaze signals. To study the problem, we collect a dataset of egocentric images collected by subjects visiting a museum. Since collecting and labeling data in cultural sites for real applications is a time-consuming problem, we present a study comparing unsupervised, weakly supervised, and fully supervised approaches for attended object detection. We evaluate the considered approaches on the collected dataset, assessing also the impact of training models on external datasets such as COCO and EGO-CH. The experiments show that weakly supervised approaches requiring only a 2D point label related to the gaze can be an effective alternative to fully supervised approaches for attended object detection. To encourage research on the topic, we publicly release the code and the dataset at the following url:
https://iplab.dmi.unict.it/EGO-CH-Gaze/
.
Out-of-distribution Detection in Dependent Data for Cyber-physical Systems with Conformal Guarantees
Authors: Kaur Ramneet , Yang Yahan , Sokolsky Oleg , Lee Insup
Published: February 2024

Uncertainty in the predictions of learning-enabled components hinders their deployment in safety-critical cyber-physical systems (CPS). A shift from the training distribution of a learning-enabled component (LEC) is one source of uncertainty in the LEC’s predictions. Detection of this shift or out-of-distribution (OOD) detection on individual datapoints has therefore gained attention recently. But in many applications, inputs to CPS form a temporal sequence. Existing techniques for OOD detection in time-series data for CPS either do not exploit temporal relationships in the sequence or do not provide any guarantees on detection. We propose using deviation from the in-distribution temporal equivariance as the non-conformity measure in conformal anomaly detection framework for OOD detection in time-series data for CPS. Computing independent predictions from multiple conformal detectors based on the proposed measure and combining these predictions by Fisher’s method leads to the proposed detector CODiT with bounded false alarms.

CODiT performs OOD detection on fixed-length windows of consecutive time-series datapoints by using Fisher value of the input window. We further propose performing OOD detection on real-time time-series traces of variable lengths with bounded false alarms. This can be done by using CODiT to compute Fisher values of the sliding windows in the input trace and combining these values by a merging function. Merging functions such as Harmonic Mean, Arithmetic Mean, Geometric Mean, Bonferroni Method, and so on, can be used to combine Fisher values of the sliding windows in the input trace, and the combined value can be used for OOD detection on the trace with bounded false alarm rate guarantees.

We illustrate the efficacy of CODiT by achieving state-of-the-art results in two case studies for OOD detection on fixed-length windows. The first one is on an autonomous driving system with perception (or vision) LEC. The second case study is on a medical CPS for walking pattern or GAIT analysis where physiological (non-vision) data is collected with force-sensitive resistors attached to the subject’s body. For OOD detection on variable length traces, we consider the same case studies on the autonomous driving system and medical CPS for GAIT analysis. We report our results with four merging functions on the Fisher values computed by CODiT on the sliding windows of the input trace. We also compare the false alarm rate guarantees by these four merging functions in the autonomous driving system case study. Code, data, and trained models are available at
https://github.com/kaustubhsridhar/time-series-OOD
.
Choiceless Polynomial Time with Witnessed Symmetric Choice
Authors: Lichter Moritz , Schweitzer Pascal
Published: February 2024

We extend Choiceless Polynomial Time (CPT), the currently only remaining promising candidate in the quest for a logic capturing
Ptime
, so that this extended logic has the following property: for every class of structures for which isomorphism is definable, the logic automatically captures
Ptime
.

For the construction of this logic, we extend CPT by a witnessed symmetric choice operator. This operator allows for choices from definable orbits. But, to ensure polynomial-time evaluation, automorphisms have to be provided to certify that the choice set is indeed an orbit.

We argue that, in this logic, definable isomorphism implies definable canonization. Thereby, our construction removes the non-trivial step of extending isomorphism definability results to canonization. This step was a part of proofs that show that CPT or other logics capture
Ptime
on a particular class of structures. The step typically required substantial extra effort.
Stabilization of a Rao–Nakra Sandwich Beam System by Coleman–Gurtin’s Thermal Law and Nonlinear Damping of Variable-Exponent Type
Authors: Al-Gharabli Mohammed M. , Al-Omari Shadi , Al-Mahdi Adel M.
Published: February 2024

In this paper, we explore the asymptotic behavior of solutions in a thermoplastic Rao–Nakra (sandwich beam) beam equation featuring nonlinear damping with a variable exponent. The heat conduction in this context adheres to Coleman–Gurtin’s thermal law, encompassing linear damping, Fourier, and Gurtin–Pipkin’s laws as specific instances. By employing the multiplier approach, we establish general energy decay results, with exponential decay as a particular manifestation. These findings extend and generalize previous decay results concerning the Rao–Nakra sandwich beam equations.
KIF26B and CREB3L1 Derived from Immunoscore Could Inhibit the Progression of Ovarian Cancer
Authors: Cong Shanshan , Fu Yao , Zhao Xibo , Guo Qiuyan , Liang Tian , Wu Di , Wang Jing , Zhang Guangmei
Published: February 2024

Background. Ovarian cancer (OV) is characteristic of high incidence rate and fatality rate in the malignant tumors of female reproductive system. Researches on pathogenesis and therapeutic targets for OV need to be continued. This study mainly analyzed the immune‐related pathogenesis and discovered the key immunotherapy targets for OV. Methods. WGCNA was used for excavating hub gene modules and hub genes related to the immunity of OV. Enrichment analysis was aimed to analyze the related pathways of hub gene modules. Biological experiments were used for exploring the effect of hub genes on SKOV3 cells. Results. We identified two hub gene modules related to the immunoscore of OV and found that these genes in the modules were related to the extracellular matrix and viral infections. At the same time, we also discovered six hub genes related to the immunity of OV. Among them, KIF26B and CREB3L1 can affect the proliferation, migration, and invasion of SKOV3 cells by the Wnt/β‐catenin pathway. Conclusions. The local infection or inflammation of ovarian may affect the immunity of OV. KIF26B and CREB3L1 are expected to be potential targets for the immunotherapy of OV.
Bio-Based Disposable Containers for Food Services
Authors: Barretto Roselle , Qi Guangyan , Jones Christopher , Li Yonghui , Sun Xiuzhi Susan , Wang Donghai
Published: February 2024

Currently, petrochemical plastics dominate the food service industry due to their good mechanical properties and barrier against heat, water vapor, carbon dioxide, and oxygen. This widespread use is not only harmful to humans but also to the ecosystem as synthetic plastics disrupt ecological balance and deplete petroleum-based oil resources. Researchers and manufacturers are continuously addressing this problem by developing bio-based alternatives that provide numerous advantages including structural flexibility, biodegradability, and effective barrier properties. However, the high cost of production and unavailability of equipment for batch processing impede the potential for widespread manufacturing. Natural fibers mixed with bio-based adhesives derived from plants provide one of the biggest potential sources of bio-based materials for the food container industry. Not only does this address the issue of high raw material cost but it also has the potential to become sustainable once processing steps have been optimized. In this review, the current findings of several research related to the production of bio-based disposable food containers, packaging, and composites made from bio-based materials and bio-based adhesives are critically discussed. Several properties and characteristics important to the production of food service containers and primary packaging, as well as the existing challenges and future perspectives, are also highlighted.
Metagenomic Characterization of Poultry Cloacal and Oropharyngeal Swabs in Kenya Reveals Bacterial Pathogens and Their Antimicrobial Resistance Genes
Authors: Panyako Philip M. , Ommeh Sheila C. , Kuria Stephen N. , Lichoti Jacqueline K. , Musina Johns , Nair Venugopal , Nene Vish , Munir Muhammad , Oyola Samuel O.
Published: February 2024

Poultry enteric bacterial diseases are of significant economic importance because they are responsible for production losses due to weight loss, increased morbidity and mortality, and increased cost of production arising from poor feed conversion and treatment. This cross‐sectional purposive study characterized enteric bacterial pathogens in poultry from selected agroclimatic regions in Kenya and investigated their antimicrobial resistance gene profiles. Cloacal (n = 563) and oropharyngeal (n = 394) swabs were collected and pooled into 16 and 14 samples, respectively, to characterize bacterial pathogens and their antimicrobial resistance gene profiles. We report that Proteobacteria, Chlamydiae, and Firmicutes are the most dominant phyla present in both cloacal and oropharyngeal swabs of the six poultry species studied, indicating the colonization of the poultry gut by many pathogenic bacteria. Using KEGG and COG databases, some pathways related to metabolism, genetic information, and cellular processing were detected. We also report the abundance of antimicrobial resistance genes that confer resistance to β‐lactamases, aminoglycosides, and tetracycline in most of the poultry analyzed, raising concern about the dangers associated with continuous and inappropriate use of these antibiotics in poultry production. The antimicrobial resistance gene data generated in this study provides a valuable indicator of the use of antimicrobials in poultry in Kenya. The information generated is essential for managing bacterial diseases, especially in backyard poultry raised under scavenging conditions.
Stromal Signals Dominate Gene Expression Signature Scores That Aim to Describe Cancer Cell–intrinsic Stemness or Mesenchymality Characteristics
Authors: Kreis Julian , Aybey Bogac , Geist Felix , Brors Benedikt , Staub Eike
Published: February 2024

Epithelial-to-mesenchymal transition (EMT) in cancer cells confers migratory abilities, a crucial aspect in the metastasis of tumors that frequently leads to death. In multiple studies, authors proposed gene expression signatures for EMT, stemness, or mesenchymality of tumors based on bulk tumor expression profiling. However, recent studies suggested that noncancerous cells from the microenvironment or macroenvironment heavily influence such signature profiles. Here, we strengthen these findings by investigating 11 published and frequently referenced gene expression signatures that were proposed to describe EMT-related (EMT, mesenchymal, or stemness) characteristics in various cancer types. By analyses of bulk, single-cell, and pseudobulk expression data, we show that the cell type composition of a tumor sample frequently dominates scores of these EMT-related signatures. A comprehensive, integrated analysis of bulk RNA sequencing (RNA-seq) and single-cell RNA-seq data shows that stromal cells, most often fibroblasts, are the main drivers of EMT-related signature scores. We call attention to the risk of false conclusions about tumor properties when interpreting EMT-related signatures, especially in a clinical setting: high patient scores of EMT-related signatures or calls of “stemness subtypes” often result from low cancer cell content in tumor biopsies rather than cancer cell–specific stemness or mesenchymal/EMT characteristics.

Significance:

Cancer self-renewal and migratory abilities are often characterized via gene module expression profiles, also called EMT or stemness gene expression signatures. Using published clinical tumor samples, cancer cell lines, and single cancer cells, we highlight the dominating influence of noncancer cells in low cancer cell content biopsies on their scores. We caution on their application for low cancer cell content clinical cancer samples with the intent to assign such characteristics or subtypes.
ОСОБЛИВОСТІ ЛАБОРАТОРНИХ ДОСЛІДЖЕНЬ ЕРИТЕМНИХ ТА БЕЗЕРИТЕМНИХ ФОРМ ХВОРОБИ ЛАЙМА У ДІТЕЙ
Authors: Литвин Г. О. , Баса Н. Р.
Published: February 2024

Мета дослідження – проаналізувати клінічно-лабораторні особливості еритемних та безеритемних форм хвороби Лайма у дітей Львівщини.
Матеріали та методи. У роботі проведено проспективне дослідження за участю 102 дітей віком від 1 рік 4 місяці (16 місяців) до 17 років із підтвердженим діагнозом ранньої локалізованої, ранньої дисемінованої та пізньої стадій хвороби Лайма.
Результати дослідження та їх обговорення. Середнє значення віку пацієнтів складало 8 років у групі 1; 5,5 року – в групі 2 та 8 років – у групі 3.
Середні значення показників периферичної крові були у межах норми в пацієнтів усіх клінічних груп. Встановлено, що С-реактивний протеїн був найвищим у пацієнтів групи 3 і становив 5,0 мг/л. IL- 6 у групі 3 був достовірно вищим порівняно із групами 1 та 2. Серединний рівень КФК–МВ у пацієнтів групи 2 становив 28,0 Од/л і виявився достовірно вищим, аніж такий у дітей клінічних груп 1 та 3. Найвищий серединний рівень антистрептолізин О зареєстровано у пацієнтів групи 3, де цей показник становив 178 МО/мл. У чверті дітей груп 1 та 2 було виявлено рівні IgM >200 Од/мл, тоді як у групі 3 таких показників не було виявлено у жодного із пацієнтів. В усіх клінічних групах найвищими були частки виявлених IgM до p41 та OspC Ba та IgG до p41, VlsE Bb та VlsE Ba.
Висновки. У дітей з Лайм-бореліозом найчастіше діагностовано ізольовану мігруючу еритему (62,75 %). Маркери запального процесу були достовірно вищими у дітей з безеритемною формою хвороби Лайма. IgM>200 Од/мл виявляли лише у пацієнтів з еритемними формами Лайм-бореліозу. Серединні рівні IgG в осіб з безеритемними формами хвороби Лайма були у вісім разів вищими, ніж в дітей з мігруючою еритемою. IgG до VlsE Bа найчастіше виявляли в пацієнтів з безеритемними формами хвороби Лайма.
Association of Socioeconomic Status With Life's Essential 8 in the National Health and Nutrition Examination Survey: Effect Modification by Sex
Authors: Williams Amaris , Nolan Timiya S. , Luthy Jacsen , Brewer LaPrincess C. , Ortiz Robin , Venkatesh Kartik K. , Sanchez Eduardo , Brock Guy N. , Nawaz Saira , Garner Jennifer A. , Walker Daniel M. , Gray Darrell M. , Joseph Joshua J.
Published: February 2024

Background

Higher scores for the American Heart Association Life's Essential 8 (LE8) metrics, blood pressure, cholesterol, glucose, body mass index, physical activity, smoking, sleep, and diet, are associated with lower risk of chronic disease. Socioeconomic status (SES; employment, insurance, education, and income) is associated with LE8 scores, but there is limited understanding of potential differences by sex. This analysis quantifies the association of SES with LE8 for each sex, within Hispanic Americans, non‐Hispanic Asian Americans, non‐Hispanic Black Americans, and non‐Hispanic White Americans.

Methods and Results

Using cross‐sectional data from the National Health and Nutrition Examination Survey, years 2011 to 2018, LE8 scores were calculated (range, 0–100). Age‐adjusted linear regression quantified the association of SES with LE8 score. The interaction of sex with SES in the association with LE8 score was assessed in each racial and ethnic group. The US population representatively weighted sample (13 529 observations) was aged ≥20 years (median, 48 years). The association of education and income with LE8 scores was higher in women compared with men for non‐Hispanic Black Americans and non‐Hispanic White Americans (
P
for all interactions <0.05). Among non‐Hispanic Asian Americans and Hispanic Americans, the association of SES with LE8 was not different between men and women, and women had greater LE8 scores than men at all SES levels (eg, high school or less, some college, and college degree or more).

Conclusions

The factors that explain the sex differences among non‐Hispanic Black Americans and non‐Hispanic White Americans, but not non‐Hispanic Asian Americans and Hispanic Americans, are critical areas for further research to advance cardiovascular health equity.
Associations of Abdominal Muscle Density and Area and Incident Cardiovascular Disease, Coronary Heart Disease, and Stroke: The Multi‐Ethnic Study of Atherosclerosis
Authors: Larsen Britta , Bellettiere John , Allison Matthew , Ryu Rita , Tam Rowena M. , McClelland Robyn L. , Miljkovic Iva , Vella Chantal , Ouyang Pamela , Criqui Michael , Unkart Jonathan
Published: February 2024

Background

Muscle density is inversely associated with all‐cause mortality, but associations with cardiovascular disease (CVD) risk are not well understood. This study evaluated the association between muscle density and muscle area and incident total CVD, coronary heart disease (CHD), and stroke in diverse men and women.

Methods and Results

Adult participants (N=1869) in the Multi‐Ethnic Study of Atherosclerosis Ancillary Body Composition Study underwent computer tomography scans of the L2‐L4 region of the abdomen. Muscle was quantified by density (Hounsfield units) and area in cm
2
. Sex‐stratified Cox proportional hazard models assessed associations between incident total CVD, incident CHD, and incident stroke across sex‐specific percentiles of muscle area and density, which were entered simultaneously into the model. Mean age for men and women at baseline were 64.1 and 65.1 years, respectively, and median follow‐up time was 10.3 years. For men, associations between muscle density and incident CVD were inverse but not significant in fully adjusted models (
P
trend=0.15). However, there was an inverse association between density and CHD (
P
trend=0.02; HR, 0.26 for 95th versus 10th percentile), and no association with stroke (
P
trend=0.78). Conversely, for men, there was a strong positive association between muscle area and incident CVD (HR, 4.19 for 95th versus 10th percentile;
P
trend<0.001). Associations were stronger for CHD (HR, 6.18 for 95th versus 10th percentile;
P
trend<0.001), and null for stroke (
P
trend=0.67). Associations for women were mostly null.

Conclusions

For men, abdominal muscle density is associated with lower CHD risk, whereas greater muscle area is associated with markedly increased risk of CHD.
Long‐Term Functional Outcome in Patients With Isolated Thalamic Stroke: The KOSCO Study
Authors: Lee Ho Seok , Sohn Min Kyun , Lee Jongmin , Kim Deog Young , Shin Yong‐Il , Oh Gyung‐Jae , Lee Yang‐Soo , Joo Min Cheol , Lee So Young , Song Min‐Keun , Han Junhee , Ahn Jeonghoon , Kim Dae Hyun , Kim Yun‐Hee , Chang Won Hyuk
Published: February 2024

Background

Information on the long‐term prognosis in patients with isolated thalamic stroke is sparse. We report the functional outcomes of patients with thalamic stroke up to 24 months from the KOSCO (Korean Stroke Cohort for Functioning and Rehabilitation) study.

Methods and Results

Isolated thalamic stroke was defined as the presence of lesions solely in the thalamus, excluding cases with lesions in other brain parenchyma areas apart from the thalamus, as identified by brain magnetic resonance imaging or computed tomography scans. The Fugl‐Meyer Assessment, the Functional Ambulatory Category, the Korean Mini‐Mental State Examination, the American Speech‐Language‐Hearing Association National Outcome Measurement System Swallowing Scale, and the short version of the Korean Frenchay Aphasia Screening Test were used to assess physical impairment. The Functional Independence Measure and modified Rankin Scale were used to assess functional outcomes. All measurements were conducted up to 24 months poststroke. A total of 297 patients were included, consisting of 235 with ischemic and 62 with hemorrhagic stroke. Except for the Functional Ambulatory Category and Functional Independence Measure, all physical impairments showed significant improvement up to 3 months poststroke (
P
<0.001) and reached a plateau. The Functional Ambulatory Category and Functional Independence Measure scores continued to improve up to 12 months poststroke (
P
<0.05) and reached a plateau. At 7 days poststroke, 47.5% of patients had no disability (modified Rankin Scale score<2), whereas at 24 months poststroke, 76.4% of patients had no significant disability.

Conclusions

Patients showed rapid recovery from physical impairment up to 3 months poststroke, with additional improvements in ambulatory function and independence observed up to 12 months poststroke. Additionally, relatively favorable long‐term functional prognosis at 24 months after onset was demonstrated. These results could provide insights into the proper management regarding functional outcomes of patients with isolated thalamic stroke.
Effect of His Bundle Pacing on Abnormal Myocardial Fatty Acid and Glucose Metabolism Induced by Right Ventricular Pacing
Authors: Lin Yu‐Sheng , Chen Huang‐Chung , Lee Wei‐Chieh , Ho Wan‐Chun , Chang Shun‐Fu , Chen Yung‐Lung , Yang Teng‐Yao , Chen Mien‐Cheng
Published: February 2024

Background

Metabolic disorder is noted for pacing‐induced cardiomyopathy. The benefits of His bundle pacing over right ventricular (RV) pacing in preventing pacing‐induced cardiomyopathy from a metabolic perspective are yet to be fully understood.

Method and Results

Three pig groups were established for this study: sham control, RV pacing (RV pacing for 6 months), and His pacing (RV pacing for 6 months, followed by His bundle pacing for 3 months). Complete atrioventricular block was created in the last 2 groups. Left ventricular function and dyssynchrony were assessed via echocardiography, while proteins linked to metabolism, endoplasmic reticulum stress, and inflammation in left ventricular myocardium were examined. The RV pacing group had significantly more left ventricular mechanical dyssynchrony compared with the other groups. The RV pacing group exhibited triglyceride and diacylglycerol accumulation in cardiomyocytes and higher expression of binding immunoglobulin protein and tumor necrosis factor‐α than the other groups. Additionally, the expression of CD36 was activated, while the expression of hormone‐sensitive lipase was downregulated in the RV pacing group compared with the His pacing and sham control groups. Furthermore, the expressions of GLUT4 and
pyruvate dehydrogenase
were higher in the RV pacing group than the sham control and His pacing groups. Notably, the abnormal fatty acid and glucose metabolic pathways in the left ventricular myocardium during RV pacing could be corrected by His bundle pacing.

Conclusions

His bundle pacing can mitigate the abnormal metabolism disorders, endoplasmic reticulum stress, and inflammation induced during RV pacing and may contribute to the superiority of conduction system pacing over RV pacing in reducing heart failure hospitalization.
Angiotensin Receptor–Neprilysin Inhibition (Sacubitril/Valsartan) Reduces Structural Arterial Stiffness in Middle‐Aged Mice
Authors: Schellinger Isabel N. , Dannert Angelika , Hoffmann Annet , Chodisetti Giriprakash , Mattern Karin , Petzold Anne , Klöting Nora , Schuster Andreas , Wagenhäuser Markus U. , Emrich Fabian , Stumvoll Michael , Hasenfuß Gerd , Raaz Uwe
Published: February 2024

Background

Increasing arterial stiffness is a prominent feature of the aging cardiovascular system. Arterial stiffening leads to fundamental alterations in central hemodynamics with widespread detrimental implications for organ function resulting in significant morbidity and death, and specific therapies to address the underlying age‐related structural arterial remodeling remain elusive. The present study investigates the potential of the recently clinically available dual angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan (LCZ696) to counteract age‐related arterial fibrotic remodeling and stiffening in 1‐year‐old mice.

Methods and Results

Treatment of in 1‐year‐old mice with ARNI (sacubitril/valsartan), in contrast to angiotensin receptor blocker monotherapy (valsartan) and vehicle treatment (controls), significantly decreases structural aortic stiffness (as measured by in vivo pulse‐wave velocity and ex vivo aortic pressure myography). This phenomenon appears, at least partly, independent of (indirect) blood pressure effects and may be related to a direct antifibrotic interference with aortic smooth muscle cell collagen production. Furthermore, we find aortic remodeling and destiffening due to ARNI treatment to be associated with improved parameters of cardiac diastolic function in aged mice.

Conclusions

This study provides preclinical mechanistic evidence indicating that ARNI‐based interventions may counteract age‐related arterial stiffening and may therefore be further investigated as a promising strategy to improve cardiovascular outcomes in the elderly.
Association of Rare
NOTCH3
Variants With Prevalent and Incident Stroke and Dementia in the General Population
Authors: Wang Pei , Yao Ming , Yuan Jing , Han Fei , Zhai Fei‐Fei , Zhang Ding‐Ding , Zhou Li‐Xin , Ni Jun , Zhang Shu‐Yang , Cui Li‐Ying , Zhu Yi‐Cheng
Published: February 2024

Background

It is uncertain whether rare
NOTCH3
variants are associated with stroke and dementia in the general population and whether they lead to alterations in cognitive function. This study aims to determine the associations of rare
NOTCH3
variants with prevalent and incident stroke and dementia, as well as cognitive function changes.

Methods and Results

In the prospective community‐based Shunyi Study, a total of 1007 participants were included in the baseline analysis. For the follow‐up analysis, 1007 participants were included in the stroke analysis, and 870 participants in the dementia analysis. All participants underwent baseline brain magnetic resonance imaging, carotid ultrasound, and whole exome sequencing. Rare
NOTCH3
variants were defined as variants with minor allele frequency <1%. A total of 137 rare
NOTCH3
carriers were enrolled in the baseline study. At baseline, rare
NOTCH3
variant carriers had higher rates of stroke (8.8% versus 5.6%) and dementia (2.9% versus 0.8%) compared with noncarriers. After adjustment for associated risk factors, the epidermal growth factor‐like repeats (EGFr)‐involving rare
NOTCH3
variants were associated with a higher risk of prevalent stroke (odds ratio [OR], 2.697 [95% CI, 1.266–5.745];
P
=0.040) and dementia (OR, 8.498 [95% CI, 1.727–41.812];
P
=0.032). After 5 years of follow‐up, we did not find that the rare
NOTCH3
variants increased the risk of incident stroke and dementia. There was no statistical difference in the change in longitudinal cognitive scale scores.

Conclusions

Rare
NOTCH3
EGFr‐involving variants are genetic risk factors for stroke and dementia in the general Chinese population.