bluuebunny/crossref_metadata_2025 huggingface dataset:
The dance of macrophage death: the interplay between the inevitable and the microenvironment
Authors: Makuch Magdalena , Stepanechko Mariia , Bzowska Małgorzata
Published: March 2024

Macrophages are highly plastic cells ubiquitous in various tissues, where they perform diverse functions. They participate in the response to pathogen invasion and inflammation resolution following the immune response, as well as the maintenance of homeostasis and proper tissue functions. Macrophages are generally considered long-lived cells with relatively strong resistance to numerous cytotoxic factors. On the other hand, their death seems to be one of the principal mechanisms by which macrophages perform their physiological functions or can contribute to the development of certain diseases. In this review, we scrutinize three distinct pro-inflammatory programmed cell death pathways – pyroptosis, necroptosis, and ferroptosis – occurring in macrophages under specific circumstances, and explain how these cells appear to undergo dynamic yet not always final changes before ultimately dying. We achieve that by examining the interconnectivity of these cell death types, which in macrophages seem to create a coordinated and flexible system responding to the microenvironment. Finally, we discuss the complexity and consequences of pyroptotic, necroptotic, and ferroptotic pathway induction in macrophages under two pathological conditions – atherosclerosis and cancer. We summarize damage-associated molecular patterns (DAMPs) along with other microenvironmental factors, macrophage polarization states, associated mechanisms as well as general outcomes, as such a comprehensive look at these correlations may point out the proper methodologies and potential therapeutic approaches.
Generalized pustular psoriasis in a toddler with IL36RN mutation: a case report
Authors: Adi Ghaith , Shaath Mohammed Rami , Adi Kareem , Obaid Zaki , Aldosari Egab , AlKateb Faten Ahmed
Published: March 2024

Generalized Pustular Psoriasis (GPP) is a dermatological autoinflammatory disease that rarely occurs in children and is associated with complex genetic factors. GPP pathogenesis has been associated with mutations in IL36RN gene, which encodes an interleukin-36 receptor antagonist. GPP usually occurs without a history of psoriasis in the patients or their family members. This case report describes the clinical course of a 3-year-old toddler with GPP. The diagnosis of GPP was confirmed through a comprehensive series of examinations, and genetic testing revealed an IL36RN mutation, providing further insight into the genetic basis of the condition. This case highlights the importance of a genetic perspective for diagnosing GPP, particularly in children.
Discovery of an independent poor-prognosis subtype associated with tertiary lymphoid structures in breast cancer
Authors: Liu Ruiqi , Huang Xiaoqian , Yang Shiwei , Du Wenbo , Chen Xiaozhou , Li Huamei
Published: March 2024

Introduction

Tertiary lymphoid structures (TLSs) are ectopic lymphoid formations that arise in non-lymphoid tissues due to chronic inflammation. The pivotal function of TLSs in regulating tumor invasion and metastasis has been established across several cancers, such as lung cancer, liver cancer, and melanoma, with a positive correlation between increased TLS presence and improved prognosis. Nevertheless, the current research about the clinical significance of TLSs in breast cancer remains limited.

Methods

In our investigation, we discovered TLS-critical genes that may impact the prognosis of breast cancer patients, and categorized breast cancer into three distinct subtypes based on critical gene expression profiles, each exhibiting substantial differences in prognosis (p = 0.0046, log-rank test), with Cluster 1 having the best prognosis, followed by Cluster 2, and Cluster 3 having the worst prognosis. We explored the impact of the heterogeneity of these subtypes on patient prognosis, the differences in the molecular mechanism, and their responses to drug therapy and immunotherapy. In addition, we designed a machine learning-based classification model, unveiling highly consistent prognostic distinctions in several externally independent cohorts.

Results

A notable marker gene CXCL13 was identified in Cluster 3, potentially pivotal in enhancing patient prognosis. At the single-cell resolution, we delved into the adverse prognosis of Cluster 3, observing an enhanced interaction between fibroblasts, myeloid cells, and basal cells, influencing patient prognosis. Furthermore, we identified several significantly upregulated genes (CD46, JAG1, IL6, and IL6R) that may positively correlate with cancer cells' survival and invasive capabilities in this subtype.

Discussion

Our study is a robust foundation for precision medicine and personalized therapy, presenting a novel perspective for the contemporary classification of breast cancer.
Identifying antinuclear antibody positive individuals at risk for developing systemic autoimmune disease: development and validation of a real-time risk model
Authors: Barnado April , Moore Ryan P. , Domenico Henry J. , Green Sarah , Camai Alex , Suh Ashley , Han Bryan , Walker Katherine , Anderson Audrey , Caruth Lannawill , Katta Anish , McCoy Allison B. , Byrne Daniel W.
Published: March 2024

Objective

Positive antinuclear antibodies (ANAs) cause diagnostic dilemmas for clinicians. Currently, no tools exist to help clinicians interpret the significance of a positive ANA in individuals without diagnosed autoimmune diseases. We developed and validated a risk model to predict risk of developing autoimmune disease in positive ANA individuals.

Methods

Using a de-identified electronic health record (EHR), we randomly chart reviewed 2,000 positive ANA individuals to determine if a systemic autoimmune disease was diagnosed by a rheumatologist. A priori, we considered demographics, billing codes for autoimmune disease-related symptoms, and laboratory values as variables for the risk model. We performed logistic regression and machine learning models using training and validation samples.

Results

We assembled training (n = 1030) and validation (n = 449) sets. Positive ANA individuals who were younger, female, had a higher titer ANA, higher platelet count, disease-specific autoantibodies, and more billing codes related to symptoms of autoimmune diseases were all more likely to develop autoimmune diseases. The most important variables included having a disease-specific autoantibody, number of billing codes for autoimmune disease-related symptoms, and platelet count. In the logistic regression model, AUC was 0.83 (95% CI 0.79-0.86) in the training set and 0.75 (95% CI 0.68-0.81) in the validation set.

Conclusion

We developed and validated a risk model that predicts risk for developing systemic autoimmune diseases and can be deployed easily within the EHR. The model can risk stratify positive ANA individuals to ensure high-risk individuals receive urgent rheumatology referrals while reassuring low-risk individuals and reducing unnecessary referrals.
Epidemiological monitoring and genetic variation analysis of pathogens associated with porcine viral diarrhea in southern China from 2021 to 2023
Authors: Zhang Fanfan , Luo Yangyang , Lin Cui , Tan Meifang , Wan Peiwei , Xie Baobao , Xiong Ligen , Ji Huayuan
Published: March 2024

Large-scale outbreaks of virus-associated severe diarrhea have occurred in pig populations since 2010. To investigate the prevalence and genetic evolution of the diarrhea-associated viruses responsible for the outbreaks, we tested 1,791 diarrhea samples collected from 213 pig farms in five provinces in southern China between 2021 and 2023. The test results showed that porcine epidemic diarrhea virus (PEDV) was the most frequently detected virus. The prevalence rates ranged from 47.40 to 52.22% in samples and 76.06% (162/213) in pig farms. Porcine rotavirus (PoRV) was the second common virus, with prevalence rates ranging from 25.81 to 50.81% in samples and 72.77%(155/213) in pig farms. Porcine delta coronavirus (PDCoV) was the third common virus, with prevalence rates ranging from 16.33 to 17.48% in samples and 38.50% (82/213) in pig farms. The detection rates of both transmissible gastroenteritis virus (TGEV) and porcine acute diarrheal syndrome coronavirus (SADS-CoV) were very low, less than 1.01% in samples and less than 3.76% in pig farms. In this study, we found SADS-CoV only in piglet diarrhea samples from Jiangxi, Guangdong, and Guangxi provinces in China, with a prevalence rate of 5.16% (11/213) in pig farms. Co-infection with these diarrhea-associated viruses is a common occurrence. The most common co-infections were PEDV and PoRV, with a prevalence rate of 6.64% (119/1,791), followed by PDCoV and PoRV, with a prevalence rate of 4.19% (75/1,791). Phylogenetic analyses showed that PEDV and PEDV variants prevalent in southern China during the past three years clustered into genotype GIIb and recombinant PEDV subtypes. Among the currently endemic PEDV, the most common mutations occurred in the collagenase equivalent (COE) and epitope regions of the spike gene. PoRV strains were mainly dominated by the G9 subtype, followed by the G5, G3 and G4 subtypes. Our results suggest that variant PEDV, PDCoV and PoRV are the main pathogens of swine diarrhea, and singular- or co-infection with pathogenic enteric CoV is common in pig herds in southern China. Therefore, prevention and control of porcine viral diarrhea should be given high attention.
The geomicrobiology of limestone, sulfuric acid speleogenetic, and volcanic caves: basic concepts and future perspectives
Authors: Turrini Paolo , Chebbi Alif , Riggio Filippo Pasquale , Visca Paolo
Published: March 2024

Caves are ubiquitous subterranean voids, accounting for a still largely unexplored surface of the Earth underground. Due to the absence of sunlight and physical segregation, caves are naturally colonized by microorganisms that have developed distinctive capabilities to thrive under extreme conditions of darkness and oligotrophy. Here, the microbiomes colonizing three frequently studied cave types, i.e., limestone, sulfuric acid speleogenetic (SAS), and lava tubes among volcanic caves, have comparatively been reviewed. Geological configurations, nutrient availability, and energy flows in caves are key ecological drivers shaping cave microbiomes through photic, twilight, transient, and deep cave zones. Chemoheterotrophic microbial communities, whose sustenance depends on nutrients supplied from outside, are prevalent in limestone and volcanic caves, while elevated inorganic chemical energy is available in SAS caves, enabling primary production through chemolithoautotrophy. The 16S rRNA-based metataxonomic profiles of cave microbiomes were retrieved from previous studies employing the Illumina platform for sequencing the prokaryotic V3-V4 hypervariable region to compare the microbial community structures from different cave systems and environmental samples. Limestone caves and lava tubes are colonized by largely overlapping bacterial phyla, with the prevalence of Pseudomonadota and Actinomycetota, whereas the co-dominance of Pseudomonadota and Campylobacterota members characterizes SAS caves. Most of the metataxonomic profiling data have so far been collected from the twilight and transient zones, while deep cave zones remain elusive, deserving further exploration. Integrative approaches for future geomicrobiology studies are suggested to gain comprehensive insights into the different cave types and zones. This review also poses novel research questions for unveiling the metabolic and genomic capabilities of cave microorganisms, paving the way for their potential biotechnological applications.
Astrocyte expression of aging-associated markers positively correlates with neurodegeneration in the frontal lobe of the rhesus macaque brain
Authors: Horn Miranda D. , Forest Sophia C. , Saied Ahmad A. , MacLean Andrew G.
Published: March 2024

Introduction

As the population over the age of 65 increases, rates of neurodegenerative disorders and dementias will rise – necessitating further research into the cellular and molecular mechanisms that contribute to brain aging. With the critical importance of astrocytes to neuronal health and functioning, we hypothesized that alterations in astrocyte expression of aging-associated markers p16INK4a (p16) and sirtuin 1 (SIRT1) with age would correlate with increased rates of neurodegeneration, as measured by FluoroJade C (FJC) staining.

Methods

To test this hypothesis, 19 rhesus macaques at the Tulane National Primate Research Center were selected based on the following criteria: archival FFPE CNS tissue available to use, no noted neuropathology, and an age range of 5–30 years. Tissues were cut at 5 μm and stained for GFAP, p16, SIRT1, and FJC, followed by whole-slide imaging and HALO® image analysis for percentage of marker-positive cells and relative intensity of each stain.

Results

We found the percentage of p16+ cells increases with age in total cells and astrocytes of the frontal (p = 0.0021, p = 0.0012 respectively) and temporal (p = 0.0226, p = 0.0203 respectively) lobes, as well as the relative intensity of p16 staining (frontal lobe: p = 0.0060; temporal lobe: p = 0.0269). For SIRT1, we found no correlation with age except for an increase in the relative intensity of SIRT1 in the temporal lobe (p = 0.0033). There was an increase in neurodegeneration, as measured by the percentage of FJC+ cells in the frontal lobe with age (p = 0.0057), as well as in the relative intensity of FJC staining in the frontal (p = 0.0030) and parietal (p = 0.0481) lobes. Importantly, increased p16 and SIRT1 expression in astrocytes correlated with increasing neurodegeneration in the frontal lobe (p = 0.0009, p = 0.0095 respectively).

Discussion

Together, these data suggest that age-associated alterations in astrocytes contribute to neurodegeneration and provide a target for mechanistic studies in the future.
Motor imagery for paediatric neurorehabilitation: how much do we know? Perspectives from a systematic review
Authors: Gentile Amalia Egle , Rinella Sergio , Desogus Eleonora , Verrelli Cristiano Maria , Iosa Marco , Perciavalle Vincenzo , Ruggieri Martino , Polizzi Agata
Published: March 2024

Background

Motor Imagery (MI) is a cognitive process consisting in mental simulation of body movements without executing physical actions: its clinical use has been investigated prevalently in adults with neurological disorders.

Objectives

Review of the best-available evidence on the use and efficacy of MI interventions for neurorehabilitation purposes in common and rare childhood neurological disorders.

Methods

systematic literature search conducted according to PRISMA by using the Scopus, PsycArticles, Cinahl, PUBMED, Web of Science (Clarivate), EMBASE, PsychINFO, and COCHRANE databases, with levels of evidence scored by OCEBM and PEDro Scales.

Results

Twenty-two original studies were retrieved and included for the analysis; MI was the unique or complementary rehabilitative treatment in 476 individuals (aged 5 to 18 years) with 10 different neurological conditions including, cerebral palsies, stroke, coordination disorders, intellectual disabilities, brain and/or spinal cord injuries, autism, pain syndromes, and hyperactivity. The sample size ranged from single case reports to cohorts and control groups. Treatment lasted 2 days to 6 months with 1 to 24 sessions. MI tasks were conventional, graded or ad-hoc. MI measurement tools included movement assessment batteries, mental chronometry tests, scales, and questionnaires, EEG, and EMG. Overall, the use of MI was stated as effective in 19/22, and uncertain in the remnant studies.

Conclusion

MI could be a reliable supportive/add-on (home-based) rehabilitative tool for pediatric neurorehabilitation; its clinical use, in children, is highly dependent on the complexity of MI mechanisms, which are related to the underlying neurodevelopmental disorder.
Diffusion of brain metabolites highlights altered brain microstructure in type C hepatic encephalopathy: a 9.4 T preliminary study
Authors: Mosso Jessie , Briand Guillaume , Pierzchala Katarzyna , Simicic Dunja , Sierra Alejandra , Abdollahzadeh Ali , Jelescu Ileana O. , Cudalbu Cristina
Published: March 2024

Introduction

Type C hepatic encephalopathy (HE) is a decompensating event of chronic liver disease leading to severe motor and cognitive impairment. The progression of type C HE is associated with changes in brain metabolite concentrations measured by 1H magnetic resonance spectroscopy (MRS), most noticeably a strong increase in glutamine to detoxify brain ammonia. In addition, alterations of brain cellular architecture have been measured ex vivo by histology in a rat model of type C HE. The aim of this study was to assess the potential of diffusion-weighted MRS (dMRS) for probing these cellular shape alterations in vivo by monitoring the diffusion properties of the major brain metabolites.

Methods

The bile duct-ligated (BDL) rat model of type C HE was used. Five animals were scanned before surgery and 6- to 7-week post-BDL surgery, with each animal being used as its own control. 1H-MRS was performed in the hippocampus (SPECIAL, TE = 2.8 ms) and dMRS in a voxel encompassing the entire brain (DW-STEAM, TE = 15 ms, diffusion time = 120 ms, maximum b-value = 25 ms/μm2) on a 9.4 T scanner. The in vivo MRS acquisitions were further validated with histological measures (immunohistochemistry, Golgi-Cox, electron microscopy).

Results

The characteristic 1H-MRS pattern of type C HE, i.e., a gradual increase of brain glutamine and a decrease of the main organic osmolytes, was observed in the hippocampus of BDL rats. Overall increased metabolite diffusivities (apparent diffusion coefficient and intra-stick diffusivity—Callaghan’s model, significant for glutamine, myo-inositol, and taurine) and decreased kurtosis coefficients were observed in BDL rats compared to control, highlighting the presence of osmotic stress and possibly of astrocytic and neuronal alterations. These results were consistent with the microstructure depicted by histology and represented by a decline in dendritic spines density in neurons, a shortening and decreased number of astrocytic processes, and extracellular edema.

Discussion

dMRS enables non-invasive and longitudinal monitoring of the diffusion behavior of brain metabolites, reflecting in the present study the globally altered brain microstructure in BDL rats, as confirmed ex vivo by histology. These findings give new insights into metabolic and microstructural abnormalities associated with high brain glutamine and its consequences in type C HE.
APOE3 Christchurch modulates β-catenin/Wnt signaling in iPS cell-derived cerebral organoids from Alzheimer’s cases
Authors: Perez-Corredor Paula , Vanderleest Timothy E. , Vacano Guido N. , Sanchez Justin S. , Villalba-Moreno Nelson D. , Marino Claudia , Krasemann Susanne , Mendivil-Perez Miguel A. , Aguillón David , Jiménez-Del-Río Marlene , Baena Ana , Sepulveda-Falla Diego , Lopera Francisco , Quiroz Yakeel T. , Arboleda-Velasquez Joseph F. , Mazzarino Randall C.
Published: March 2024

A patient with the PSEN1 E280A mutation and homozygous for APOE3 Christchurch (APOE3Ch) displayed extreme resistance to Alzheimer’s disease (AD) cognitive decline and tauopathy, despite having a high amyloid burden. To further investigate the differences in biological processes attributed to APOE3Ch, we generated induced pluripotent stem (iPS) cell-derived cerebral organoids from this resistant case and a non-protected control, using CRISPR/Cas9 gene editing to modulate APOE3Ch expression. In the APOE3Ch cerebral organoids, we observed a protective pattern from early tau phosphorylation. ScRNA sequencing revealed regulation of Cadherin and Wnt signaling pathways by APOE3Ch, with immunostaining indicating elevated β-catenin protein levels. Further in vitro reporter assays unexpectedly demonstrated that ApoE3Ch functions as a Wnt3a signaling enhancer. This work uncovered a neomorphic molecular mechanism of protection of ApoE3 Christchurch, which may serve as the foundation for the future development of protected case-inspired therapeutics targeting AD and tauopathies.
A natural sustained-intestinal release formulation of red chili pepper extracted capsaicinoids (Capsifen®) safely modulates energy balance and endurance performance: a randomized, double-blind, placebo-controlled study
Authors: Roopashree N. , Syam Das S. , Krishnakumar I. M. , Mala K. N. , Fleenor Bradley S. , Thomas Jestin
Published: March 2024

Introduction

Overweight and obesity are major public health concerns, with a sharp increase in prevalence over the last few decades. The primary cause is an imbalance between calorie intake and expenditure due to a rise in calorie-rich processed food and reduced physical activity. Energy balance in humans involves complex processes including thermogenesis, a crucial factor in regulating energy expenditure.

Methods

In this randomized, double-blinded, placebo-controlled three-arm three-sequence study, we investigated the efficacy of Capsifen® (CapF), a pungency-masked sustained-intestinal release formulation of red chili extract, on energy expenditure, fat oxidation, and endurance using the Quark C-PET system in healthy overweight participants, with and without exercise. In the study, 105 healthy participants were randomized to receive either placebo, CapF 100 mg/day, or CapF 200 mg/day for 28 days.

Results

CapF demonstrated a dose-dependent response to increased energy expenditure and fatty acid oxidation with a concomitant reduction in body weight. Both CapF 100 and CapF 200 also increased the time to exhaustion.

Discussion

These results demonstrate the plausible efficacy of CapF in energy expenditure and physical performance in otherwise healthy adults who have a high body mass index.

Clinical trial registration

https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MjQzNTg=&Enc=&userName=CTRI/2018/04/013157 dated 04 October 2018.
Tumor treating fields in glioblastoma: long-term treatment and high compliance as favorable prognostic factors
Authors: Wang Junjie , Du Quan , Chen Jiarui , Liu Jianjian , Gu Zhaowen , Wang Xiaoyu , Zhang Anke , Gao Shiqi , Shao Anwen , Zhang Jianmin , Wang Yongjie
Published: March 2024

Introduction

Tumor treating fields (TTFields) have earned substantial attention in recent years as a novel therapeutic approach with the potential to improve the prognosis of glioblastoma (GBM) patients. However, the impact of TTFields remains a subject of ongoing debate. This study aimed to offer real-world evidence on TTFields therapy for GBM, and to investigate the clinical determinants affecting its efficacy.

Methods

We have reported a retrospective analysis of 81 newly diagnosed Chinese GBM patients who received TTFields/Stupp treatment in the Second Affiliated Hospital of Zhejiang University. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan–Meier method. Cox regression models with time-dependent covariates were utilized to address non-proportional hazards and to assess the influence of clinical variables on PFS and OS.

Results

The median PFS and OS following TTFields/STUPP treatment was 12.6 months (95% CI 11.0-14.1) and 21.3 months (95% CI 10.0–32.6) respectively. Long-term TTFields treatment (>2 months) exhibits significant improvements in PFS and OS compared to the short-term treatment group (≤2 months). Time-dependent covariate COX analysis revealed that longer TTFields treatment was correlated with enhanced PFS and OS for up to 12 and 13 months, respectively. Higher compliance to TTFields (≥ 0.8) significantly reduced the death risk (HR=0.297, 95%CI 0.108-0.819). Complete surgical resection and MGMT promoter methylation were associated with significantly lower risk of progression (HR=0.337, 95% CI 0.176-0.643; HR=0.156, 95% CI 0.065-0.378) and death (HR=0.276, 95% CI 0.105-0.727; HR=0.249, 95% CI 0.087-0.710).

Conclusion

The TTFields/Stupp treatment may prolong median OS and PFS in GBM patients, with long-term TTFields treatment, higher TTFields compliance, complete surgical resection, and MGMT promoter methylation significantly improving prognosis.
Prediction of pCR based on clinical-radiomic model in patients with locally advanced ESCC treated with neoadjuvant immunotherapy plus chemoradiotherapy
Authors: Wang Xiaohan , Gong Guanzhong , Sun Qifeng , Meng Xue
Published: March 2024

Background

The primary objective of this research is to devise a model to predict the pathologic complete response in esophageal squamous cell carcinoma (ESCC) patients undergoing neoadjuvant immunotherapy combined with chemoradiotherapy (nICRT).

Methods

We retrospectively analyzed data from 60 ESCC patients who received nICRT between 2019 and 2023. These patients were divided into two cohorts: pCR-group (N = 28) and non-pCR group (N = 32). Radiomic features, discerned from the primary tumor region across plain, arterial, and venous phases of CT, and pertinent laboratory data were documented at two intervals: pre-treatment and preoperation. Concurrently, related clinical data was amassed. Feature selection was facilitated using the Extreme Gradient Boosting (XGBoost) algorithm, with model validation conducted via fivefold cross-validation. The model’s discriminating capability was evaluated using the area under the receiver operating characteristic curve (AUC). Additionally, the clinical applicability of the clinical-radiomic model was appraised through decision curve analysis (DCA).

Results

The clinical-radiomic model incorporated seven significant markers: postHALP, ΔHB, post-ALB, firstorder_Skewness, GLCM_DifferenceAverage, GLCM_JointEntropy, GLDM_DependenceEntropy, and NGTDM_Complexity, to predict pCR. The XGBoost algorithm rendered an accuracy of 0.87 and an AUC of 0.84. Notably, the joint omics approach superseded the performance of solely radiomic or clinical model. The DCA further cemented the robust clinical utility of our clinical-radiomic model.

Conclusion

This study successfully formulated and validated a union omics methodology for anticipating the therapeutic outcomes of nICRT followed by radical surgical resection. Such insights are invaluable for clinicians in identifying potential nICRT responders among ESCC patients and tailoring optimal individualized treatment plans.
Understanding the perceived benefits, barriers, and cues to action for lung cancer screening among Latinos: A qualitative study
Authors: Alaniz-Cantú Edgar I. , Goodwin Kalese , Smith London , Acosta Eliany , Chávez-Iñiguez Arlette , Evans Mary Jo , Gaitán Marcela , Lei Fang , Yousefi-Nooraie Reza , Fiscella Kevin A. , Rivera M. Patricia , Cupertino Ana Paula , Cartujano-Barrera Francisco
Published: March 2024

Introduction

Rates of lung cancer screening among Latinos remain low. The purpose of the study was to understand the perceived benefits, barriers, and cues to action for lung cancer screening among Latinos.

Methods

Participants (N=20) were recruited using community-based recruitment strategies. Eligibility criteria included: 1) self-identified as Hispanic/Latino, 2) spoke English and/or Spanish, and 3) met the USA Preventive Services Task Force eligibility criteria for lung cancer screening. Interviews were conducted in Spanish and English, audio recorded, and transcribed verbatim. Using the health belief model, a qualitative theoretical analysis was used to analyze the interviews.

Results

Participants’ mean age was 58.3 years old (SD=5.8), half of the participants were female, 55% had completed high school or lower educational level, and 55% reported speaking more Spanish than English. All participants were currently smoking. Fourteen participants (70%) were unaware of lung cancer screening, and eighteen (90%) did not know they were eligible for lung cancer screening. Regarding lung cancer screening, participants reported multiple perceived benefits (e.g., smoking cessation, early detection of lung cancer, increased survivorship) and barriers (e.g., fear of outcomes, cost, lung cancer screening not being recommended by their clinician). Lastly, multiple cues to actions for lung cancer screening were identified (e.g., family as a cue to action for getting screened).

Conclusions

Most Latinos who were eligible for lung cancer screening were unaware of it and, when informed, they reported multiple perceived benefits, barriers, and cues to action. These factors provide concrete operational strategies to address lung cancer screening among Latinos.
High costs, low quality of life, reduced survival, and room for improving treatment: an analysis of burden and unmet needs in glioma
Authors: Pöhlmann Johannes , Weller Michael , Marcellusi Andrea , Grabe-Heyne Kristin , Krott-Coi Lucia , Rabar Silvia , Pollock Richard F.
Published: March 2024

Gliomas are a group of heterogeneous tumors that account for substantial morbidity, mortality, and costs to patients and healthcare systems globally. Survival varies considerably by grade, histology, biomarkers, and genetic alterations such as IDH mutations and MGMT promoter methylation, and treatment, but is poor for some grades and histologies, with many patients with glioblastoma surviving less than a year from diagnosis. The present review provides an introduction to glioma, including its classification, epidemiology, economic and humanistic burden, as well as treatment options. Another focus is on treatment recommendations for IDH-mutant astrocytoma, IDH-mutant oligodendroglioma, and glioblastoma, which were synthesized from recent guidelines. While recommendations are nuanced and reflect the complexity of the disease, maximum safe resection is typically the first step in treatment, followed by radiotherapy and/or chemotherapy using temozolomide or procarbazine, lomustine, and vincristine. Immunotherapies and targeted therapies currently have only a limited role due to disappointing clinical trial results, including in recurrent glioblastoma, for which the nitrosourea lomustine remains the de facto standard of care. The lack of treatment options is compounded by frequently suboptimal clinical practice, in which patients do not receive adequate therapy after resection, including delayed, shortened, or discontinued radiotherapy and chemotherapy courses due to treatment side effects. These unmet needs will require significant efforts to address, including a continued search for novel treatment options, increased awareness of clinical guidelines, improved toxicity management for chemotherapy, and the generation of additional and more robust clinical and health economic evidence.
Prospects and challenges of CAR-T cell therapy combined with ICIs
Authors: Lv Yufan , Luo Xinyu , Xie Zhuoyi , Qiu Jieya , Yang Jinsai , Deng Yuqi , Long Rou , Tang Guiyang , Zhang Chaohui , Zuo Jianhong
Published: March 2024

Immune checkpoint molecules are a group of molecules expressed on the surface of immune cells that primarily regulate their immune homeostasis. Chimeric antigen receptor (CAR) T cell therapy is an immunotherapeutic technology that realizes tumor-targeted killing by constructing synthetic T cells expressing specific antigens through biotechnology. Currently, CAR-T cell therapy has achieved good efficacy in non-solid tumors, but its treatment of solid tumors has not yielded the desired results. Immune checkpoint inhibitors (ICIs) combined with CAR-T cell therapy is a novel combination therapy with high expectations to defeat solid tumors. This review addresses the challenges and expectations of this combination therapy in the treatment of solid tumors.
Leading in times of crisis and remote work: perceived consideration leadership behavior and its effect on follower work engagement
Authors: Sedefoglu Didem , Ohly Sandra , Schmitt Antje , Göritz Anja S.
Published: March 2024

Based on the job-demands resources theory, we examine whether leadership behavior affects followers' work engagement in the context of remote work during times of crisis, and how this effect can be explained. We focus on consideration leadership and its impact on followers' engagement under conditions of enforced remote work during the COVID-19 pandemic. Therein, we examine the role of optimism as a potential mediator. To better understand how the impact of consideration leadership behavior unfolds during crises, we examine whether being new to remote work and feeling personally impacted by COVID-19 amplified the proposed relationship between consideration leadership and followers' engagement. A sample of 729 German employees participated in a three-wave study across 6 weeks in May and June 2020. Longitudinal structural equation modeling uncovered direct positive effects of consideration leadership on changes in followers' work engagement in the second time lag (T2 to T3), while optimism did not mediate this effect. Multigroup comparisons revealed that employees who worked from home were particularly responsive to consideration leadership. No moderating effects were found for whether the COVID-19 pandemic personally impacted employees. The discussion highlights the critical role of leadership in followers' motivation and wellbeing in times of crisis and remote work.
Perspectives on community-based system change for people living with persistent pain: insights from developing the “Rethinking Pain service”
Authors: Johnson Mark I. , Page Kerry , Woodall James , Thompson Kate
Published: March 2024

In this perspective article we advocate community-based system change for people living with persistent pain. Our view is that greater use of the voluntary and community sector, in partnership with the clinical sector, creates the conditions for a “whole person” approach to pain management, leading to greater personalised care for adults living with long-term pain whilst having the potential to ease some of the pressures on General Practitioners and other clinical services. We advocate pain care that is socially connected, meaningful within socio-cultural contexts and aligned with the principles of salutogenesis. We provide an example of a UK National Health Service (NHS) commissioned pain service called “Rethinking Pain” that operationalises this perspective. Led by the voluntary and community sector, Rethinking Pain works in partnership with the clinical sector to provide a central holistic pathway of care for people experiencing persistent pain. This is the first time that this model of care has been commissioned for persistent pain in this area of England. The Rethinking Pain service is underpinned by core values to work with people to manage their pain holistically. The Rethinking Pain team proactively engage with people in the community, actively approaching and engaging those who experience the biggest health inequalities. In this article we provide an overview of the context of pain services in the UK, the rationale and supporting evidence for community-based system change, and the context, pathway, values, goals, and aspirations of the Rethinking Pain service.
The pharmacokinetics and pharmacodynamics of fentanyl administered via transdermal patch in horses
Authors: Reed Rachel A. , Berghaus Londa J. , Reynolds Rose M. , Holmes Brittany T. , Krikorian Anna M. , Sakai Daniel M. , Ishikawa Yushun , Knych Heather K.
Published: March 2024

Introduction

Understanding the pharmacokinetics and pharmacodynamics of fentanyl in horses is crucial for optimizing pain management strategies in veterinary medicine.

Methods

Six adult horses were enrolled in a randomized crossover design. Treatments included: placebo, two 100 mcg/h patches (LDF), four 100 mcg/h patches (MDF), and six 100 mcg/h patches (HDF). Patches were in place for 72 h. Blood was obtained for fentanyl plasma concentration determination, thermal threshold, mechanical threshold, heart rate, respiratory rate, and rectal temperature were obtained prior patch placement and at multiple time points following patch placement for the following 96 h. Fentanyl plasma concentration was determined using LC-MS/MS. Data were analyzed using a generalized mixed effects model.

Results

Mean (range) maximum plasma concentration (Cmax), time to Cmax, and area under the curve extrapolated to infinity were 1.39 (0.82–1.82), 2.64 (1.21–4.42), 4.11 (2.78–7.12) ng/ml, 12.7 (8.0–16.0), 12.7 (8.0–16.0), 12 (8.0–16.0) h, 42.37 (27.59–55.56), 77.24 (45.62–115.06), 120.34 (100.66–150.55) h ng/ml for LDF, MDF, and HDF, respectively. There was no significant effect of treatment or time on thermal threshold, mechanical threshold, respiratory rate, or temperature (p > 0.063). There was no significant effect of treatment on heart rate (p = 0.364). There was a significant effect of time (p = 0.003) on heart rate with overall heart rates being less than baseline at 64 h.

Conclusions

Fentanyl administered via transdermal patch is well absorbed and well tolerated but does not result in an anti-nociceptive effect as measured by thermal and mechanical threshold at the doses studied.
Antibody-drug conjugates targeting HER2 for the treatment of urothelial carcinoma: potential therapies for HER2-positive urothelial carcinoma
Authors: Shih Chia-Hsien , Lin Yu-Hua , Luo Hao-Lun , Sung Wen-Wei
Published: March 2024

Urothelial carcinoma (UC) is a common cancer characterized by high morbidity and mortality rates. Despite advancements in treatment, challenges such as recurrence and low response rates persist. Antibody-drug conjugates (ADCs) have emerged as a promising therapeutic approach for various cancers, although their application in UC is currently limited. This review focuses on recent research regarding ADCs designed to treat UC by targeting human epidermal growth factor receptor 2 (HER2), a surface antigen expressed on tumor cells. ADCs comprise three main components: an antibody, a linker, and a cytotoxic payload. The antibody selectively binds to tumor cell surface antigens, facilitating targeted delivery of the cytotoxic drug, while linkers play a crucial role in ensuring stability and controlled release of the payload. Cleavable linkers release the drug within tumor cells, while non-cleavable linkers ensure stability during circulation. The cytotoxic payload exerts its antitumor effect by disrupting cellular pathways. HER2 is commonly overexpressed in UCs, making it a potential therapeutic target. Several ADCs targeting HER2 have been approved for cancer treatment, but their use in UC is still being tested. Numerous HER2 ADCs have demonstrated significant growth inhibition and induction of apoptosis in translational models of HER2-overexpressing bladder cancer. Ongoing clinical trials are assessing the efficacy and safety of ADCs targeting HER2 in UC, with the aim of determining tumor response and the potential of ADCs as a treatment option for UC patients. The development of effective therapies with improved response rates and long-term effectiveness is crucial for advanced and metastatic UC. ADCs targeting HER2 show promise in this regard and merit further investigation for UC treatment.
Globally optimal interferometry with lossy twin Fock probes
Authors: Volkoff T. J. , Ryu Changhyun
Published: March 2024

Parity or quadratic spin (e.g., Jz2) readouts of a Mach–Zehnder (MZ) interferometer probed with a twin Fock (TF) input state allow saturating the optimal sensitivity attainable among all mode-separable states with a fixed total number of particles but only when the interferometer phase θ is near zero. When more general Dicke state probes are used, the parity readout saturates the quantum Fisher information (QFI) at θ = 0, whereas better-than-standard quantum limit performance of the Jz2 readout is restricted to an o(N) occupation imbalance. We show that a method of moments readout of two quadratic spin observables Jz2 and J+2+J−2 is globally optimal for Dicke state probes; i.e., the error saturates the QFI for all θ. In the lossy setting, we derive the time-inhomogeneous Markov process describing the effect of particle loss on TF states, showing that the method of moments readout of four at-most-quadratic spin observables is sufficient for globally optimal estimation of θ when two or more particles are lost. The analysis culminates in a numerical calculation of the QFI matrix for distributed MZ interferometry on the four-mode state |N4,N4,N4,N4〉 and its lossy counterparts, showing that an advantage for the estimation of any linear function of the local MZ phases θ1 and θ2 (compared to independent probing of the MZ phases by two copies of |N4,N4〉) appears when more than one particle is lost.
Spin glass dynamics through the lens of the coherence length
Authors: He J. , Orbach R. L.
Published: March 2024

Spin glass coherence lengths can be extracted from experiment and from numerical simulations. They encompasses the correlated region, and their growth in time makes them a useful tool for exploration of spin glass dynamics. Because they play the role of a fundamental length scale, they control the transition from the reversible to the chaotic state. This review explores their use for spin glass properties, ranging from scaling laws to rejuvenation and memory.
SCSONet: spatial-channel synergistic optimization net for skin lesion segmentation
Authors: Chen Haoyu , Li Zexin , Huang Xinyue , Peng Zhengwei , Deng Yichen , Tang Li , Yin Li
Published: March 2024

In the field of computer-assisted medical diagnosis, developing medical image segmentation models that are both accurate and capable of real-time operation under limited computational resources is crucial. Particularly for skin disease image segmentation, the construction of such lightweight models must balance computational cost and segmentation efficiency, especially in environments with limited computing power, memory, and storage. This study proposes a new lightweight network designed specifically for skin disease image segmentation, aimed at significantly reducing the number of parameters and floating-point operations while ensuring segmentation performance. The proposed ConvStem module, with full-dimensional attention, learns complementary attention weights across all four dimensions of the convolution kernel, effectively enhancing the recognition of irregularly shaped lesion areas, reducing the model’s parameter count and computational burden, thus promoting model lightweighting and performance improvement. The SCF Block reduces feature redundancy through spatial and channel feature fusion, significantly lowering parameter count while improving segmentation results. This paper validates the effectiveness and robustness of the proposed SCSONet on two public skin lesion segmentation datasets, demonstrating its low computational resource requirements. https://github.com/Haoyu1Chen/SCSONet.
Quadrat soil pollen signal reflects plant important values in forests and shrublands from subtropical China
Authors: Li Kai , Tan Bin , Liao Mengna , Ni Jian
Published: March 2024

Pollen analysis, a crucial tool in botany and ecology for examining historical biotic dynamics, has elicited debate owing to its complex link with vegetation. The challenge lies in discerning the ecological significance of pollen data. In this study, we conducted detailed quadrat surveys on Jinhua Mountain, subtropical China, analyzing topsoil pollen to determine whether pollen signals accurately reflect key ecological components in the forests and shrublands. We performed direct comparisons between pollen and plant compositions and calculated pollen percentages and plant Important Values (IVs) for each quadrat. The results indicate greater homogeneity in pollen composition across the study area compared to plant composition, particularly in the high percentage of Pinus pollen. However, distinct plant communities exhibited significantly different pollen compositions, as evidenced by the multi-response permutation test. This divergence aligns with variations in the dominant plant species across different communities. There were significant correlations between pollen percentages and plant IVs, with correlation coefficients of 0.55 (p < 0.001) at the quadrat level and 0.78 (p < 0.001) at the taxon level. These results support the utility of pollen analysis for representing ecologically significant values in subtropical Chinese forests and shrublands. Such correlations might also be extrapolated to pollen-based paleoecological studies.
Working memory training improves episodic memory in older people: transfer based on controlled retrieval processes
Authors: Zamarreño Patricia , Mateos Pedro M. , Valentín Alberto
Published: March 2024

Introduction

The results of working memory (WM) training to improve episodic memory in older people are inconsistent. This inconsistency could be due to the fact that the episodic memory tests used do not share the same cognitive resources as the trained WM task. The aim of this study was to assess whether performance on an episodic memory test will improve only when this test requires controlled processes of retrieval of information from secondary memory or recollection, similar to the processes exercised during WM training.

Method

Fifty-five people over 60 years of age participated in the study: 27 were randomly assigned to the experimental group (EG) and the rest to the control group (CG). The EG was trained in complex span tasks. Before and after training, both groups were tested on episodic memory tests (a verbal and a visuospatial recognition test) and WM span tasks (reading, digit and spatial location).

Results

ANOVAs revealed a greater improvement of recollection estimates in the EG than in the CG for both verbal recognition (p = 0.023) and visuospatial recognition (p = 0.014).

Discussion

Our results provide support for a cognitive mechanism whose shared presence favored transfer from training on a WM task to a test of episodic memory. Consistent with our predictions, training on complex span tasks improved performance on recognition tests only when recall required a controlled search process in secondary memory, or recollection. We therefore stress the importance of identifying other cognitive resources that are susceptible to transfer from a training task to other untrained tasks. A better understanding of the phenomenon of transfer is crucial for the design of increasingly effective intervention programs for older people.
Word order and context in sentence processing: evidence from L1 and L2 Russian
Authors: Slioussar Natalia , Harchevnik Maria
Published: March 2024

Introduction

In this paper, we studied how native (L1) speakers of Russian and speakers of Mandarin Chinese learning Russian as a foreign language (L2) process Russian sentences with different word orders. We compared SVO (canonical) and OVS (non-canonical) orders in isolation and in context. Experiments focusing on the L2 processing of different word orders are still not very numerous, and those using context are extremely rare.

Methods

In Experiment 1, target sentences were presented in isolation. In Experiment 2, one-sentence contexts introduced one NP mentioned in the target sentence, either the first (so that given information preceded new information, which is characteristic for Russian and many other languages) or the second. As a result, two factors could be compared: the syntactic (word order) and the contextual (whether the context is appropriate from the information-structural perspective). We used different measures to capture online and offline effects: word-by-word reading times, question-answering accuracy and sentence rating on a 1 to 5 scale (for L1 participants).

Results and discussion

In both experiments, RTs and question-answering accuracy data showed that non-canonical orders were difficult for L2 participants, but not for L1 participants. However, L1 participants gave non-canonical orders lower ratings in isolation, presumably because in naturally occurring texts, they are used only in particular contexts. As for the context factor in Experiment 2, some effects were the same for L1 and L2 processing: all participants read given NPs faster than new ones and preferred sentences with a ‘given – new’ word order. The latter may reflect the universal principles of narrative coherence. However, unlike native speakers, L2 readers are not sensitive to more subtle contextual requirements of different word orders.