bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of physical and psychological symptoms on cancer-related fatigue among esophageal cancer patients
Authors: Cui ChunYing , Wang Lie , Wang XiaoXi
Published: March 2024

Background

Cancer-related fatigue (CRF) is considered one of the most prevalent and distressing symptoms among cancer patients and may vary among patients with different cancer types. However, few studies have explored the influence of physical and psychological symptoms on CRF among esophageal cancer (EC) patients without esophagectomy. Therefore, this study aimed to examine the effects of physical and psychological symptoms on CRF among EC patients without esophagectomy.

Methods

In the present study, a cross-sectional study was conducted from February 2021 to March 2022 in Liaoning Province, China. Among the 112 included participants, 97 completed our investigation. The questionnaires used consisted of the Brief Fatigue Inventory (BFI), the MD Anderson Symptom Inventory Gastrointestinal Cancer Module (MDASI-GI), the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder-7 (GAD-7), and demographic and clinical information. Multivariate linear regression was conducted to test the relationships between physical and psychological symptoms and CRF.

Results

Of the 97 EC patients, 60.8% reported CRF (BFI ≥ 4). The mean age of the participants was 64.92 years (SD = 8.67). According to the regression model, all the variables explained 74.5% of the variance in CRF. Regression analysis indicated that physical symptoms, including constipation, diarrhoea, and difficulty swallowing, contributed to CRF. On the other hand, depressive symptoms increased the level of CRF among EC patients without esophagectomy.

Conclusions

Given the high prevalence of CRF among EC patients without esophagectomy, it is urgent to emphasize the importance of fatigue management interventions based on physical and psychological symptoms to alleviate CRF in EC patients.
Enhancing knowledge mastery in resident students through peer-teaching: a study in respiratory medicine
Authors: Zhu Chen , Tian Heshen , Yan Fugui , Xue Jing , Li Wen
Published: March 2024

Aim

The transition from medical students to competent physicians requires comprehensive training during residency programs. In China, resident students typically undergo 2- or 3-year training programs. While they learn from patient interactions under the guidance of experienced doctors, integrating theoretical knowledge from textbooks into practical cases remains a challenge. This study aimed to explore the impact of medical interns acting as peer-students on the knowledge mastery of resident students.

Method

The participants of this study consisted of resident students specializing in respiratory medicine at the Second Affiliated Hospital of Zhejiang University, School of Medicine. Resident students were given the opportunity to volunteer as peer-teachers for medical interns in the respiratory department. Those who chose to instruct interns were automatically placed into the test group, while those who opted not to partake in intern instruction formed the control group. In their role as peer-teachers, resident students assumed the responsibility of guiding interns in patient management throughout the entire continuum, spanning from initial engagement to discharge, a commitment that extended over a minimum period of 2 weeks. The resident students' academic performance was evaluated through a departmental examination consisting of 50 multiple-choice questions, which was administered upon completing their rotation. Statistical analysis was performed to assess the impact of peer-teaching on the resident students’ performance.

Results

Between January 2023 and June 2023, a total of 158 resident students completed their rotation in the respiratory department. Among them, 40 resident students willingly took on the responsibility of instructing medical interns, while 118 resident students did not participate in intern teaching. With a "one-to-one" teaching policy in place, the overall satisfaction rate of the interns was an impressive 95.35%. Pre-rotation test scores for the test group averaged 81.66 ± 8.325 (Mean ± SD) and the control group averaged 81.66 ± 8.002, without significance. The departmental examination scores of the test group averaged 85.60 ± 7.886, while the control group scored an average of 82.25 ± 8.292, with a statistically significant difference (p = 0.027).

Conclusion

In conclusion, our study underscores the positive influence of peer-teaching on the knowledge mastery of resident students.
A collaborative endeavour to integrate leadership and person-centred ethics: a focus group study on experiences from developing and realising an educational programme to support the transition towards person-centred care
Authors: Lood Qarin , Carlström Eric , Klinga Charlotte , Barenfeld Emmelie
Published: March 2024

Background

Ensuring the transition towards person-centred care is a growing focus in health and social care systems globally. Presented as an ethical framework for health and social care professionals, such a transition requires strong leadership and organisational changes. However, there is limited guidance available on how to assist health and social care leaders in promoting person-centred practices. In response to this, the Swedish Association of Health Professionals and the University of Gothenburg Centre for Person-Centred Care collaborated to develop an educational programme on person-centred leadership targeting health and social care leaders to support the transition towards person-centred care in Sweden. The aim with this study was to explore programme management members’ experiences from the development and realisation of the programme.

Methods

Focus group discussions were conducted, involving 12 members of the programme management team. Data from the discussions were analysed using a structured approach with emphasis the collaborative generation of knowledge through participant interaction.

Results

The analysis visualises the preparations and actions involved in programme development and realisation as a collaborative endeavour, aimed at integrating leadership and person-centred ethics in a joint learning process. Participants described the programme as an ongoing exploration, extending beyond its formal duration. Leadership was thoughtfully interwoven with person-centred ethics throughout the programme, encompassing both the pedagogical approach and programme curriculum, to provide leaders with tangible tools for their daily use.

Conclusions

According to our analysis, we conclude that a person-centred approach to both development and realisation of educational initiatives to support person-centred leadership is essential for programme enhancement and daily implementation of person-centred leadership. Our main message is that educational initiatives on the application of person-centred ethics is an ongoing and collaborative process, characterised by an exchange of ideas and collective efforts.
Persistent epigenetic signals propel a senescence-associated secretory phenotype and trained innate immunity in CD34+ hematopoietic stem cells from diabetic patients
Authors: Vinci Maria Cristina , Costantino Sarah , Damiano Giulia , Rurali Erica , Rinaldi Raffaella , Vigorelli Vera , Sforza Annalisa , Carulli Ermes , Pirola Sergio , Mastroiacovo Giorgio , Raucci Angela , El-Osta Assam , Paneni Francesco , Pompilio Giulio
Published: March 2024

Background

Diabetes-induced trained immunity contributes to the development of atherosclerosis and its complications. This study aimed to investigate in humans whether epigenetic signals involved in immune cell activation and inflammation are initiated in hematopoietic stem/progenitor cells (HSPCs) and transferred to differentiated progeny.

Methods and results

High glucose (HG)-exposure of cord blood (CB)-derived HSPCs induced a senescent-associated secretory phenotype (SASP) characterized by cell proliferation lowering, ROS production, telomere shortening, up-regulation of p21 and p27genes, upregulation of NFkB-p65 transcription factor and increased secretion of the inflammatory cytokines TNFα and IL6. Chromatin immunoprecipitation assay (ChIP) of p65 promoter revealed that H3K4me1 histone mark accumulation and methyltransferase SetD7 recruitment, along with the reduction of repressive H3K9me3 histone modification, were involved in NFkB-p65 upregulation of HG-HSPCs, as confirmed by increased RNA polymerase II engagement at gene level. The differentiation of HG-HSPCs into myeloid cells generated highly responsive monocytes, mainly composed of intermediate subsets (CD14hiCD16+), that like the cells from which they derive, were characterized by SASP features and similar epigenetic patterns at the p65 promoter. The clinical relevance of our findings was confirmed in sternal BM-derived HSPCs of T2DM patients. In line with our in vitro model, T2DM HSPCs were characterized by SASP profile and SETD7 upregulation. Additionally, they generated, after myeloid differentiation, senescent monocytes mainly composed of proinflammatory intermediates (CD14hiCD16+) characterized by H3K4me1 accumulation at NFkB-p65 promoter.

Conclusions

Hyperglycemia induces marked chromatin modifications in HSPCs, which, once transmitted to the cell progeny, contributes to persistent and pathogenic changes in immune cell function and composition.
Genomic insights into the evolution and mechanisms of carbapenem-resistant hypervirulent Klebsiella pneumoniae co-harboring blaKPC and blaNDM: implications for public health threat mitigation
Authors: Wang Qian , Liu Yue , Chen Ran , Zhang Meng , Si Zaifeng , Wang Yueling , Jin Yan , Bai Yuanyuan , Song Zhen , Lu Xinglun , Hao Mingju , Hao Yingying
Published: March 2024

Background

Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) co-producing blaKPC and blaNDM poses a serious threat to public health. This study aimed to investigate the mechanisms underlying the resistance and virulence of CR-hvKP isolates collected from a Chinese hospital, with a focus on blaKPC and blaNDM dual-positive hvKP strains.

Methods

Five CR-hvKP strains were isolated from a teaching hospital in China. Antimicrobial susceptibility and plasmid stability testing, plasmid conjugation, pulsed-field gel electrophoresis, and whole-genome sequencing (WGS) were performed to examine the mechanisms of resistance and virulence. The virulence of CR-hvKP was evaluated through serum-killing assay and Galleria mellonella lethality experiments. Phylogenetic analysis based on 16 highly homologous carbapenem-resistant K. pneumoniae (CRKP) producing KPC-2 isolates from the same hospital was conducted to elucidate the potential evolutionary pathway of CRKP co-producing NDM and KPC.

Results

WGS revealed that five isolates individually carried three unique plasmids: an IncFIB/IncHI1B-type virulence plasmid, IncFII/IncR-type plasmid harboring KPC-2 and IncC-type plasmid harboring NDM-1. The conjugation test results indicated that the transference of KPC-2 harboring IncFII/IncR-type plasmid was unsuccessful on their own, but could be transferred by forming a hybrid plasmid with the IncC plasmid harboring NDM. Further genetic analysis confirmed that the pJNKPN26-KPC plasmid was entirely integrated into the IncC-type plasmid via the copy-in route, which was mediated by TnAs1 and IS26.

Conclusion

KPC-NDM-CR-hvKP likely evolved from a KPC-2-CRKP ancestor and later acquired a highly transferable blaNDM-1 plasmid. ST11-KL64 CRKP exhibited enhanced plasticity. The identification of KPC-2-NDM-1-CR-hvKP highlights the urgent need for effective preventive strategies against aggravated accumulation of resistance genes.
Self-delivery photothermal-boosted-nanobike multi-overcoming immune escape by photothermal/chemical/immune synergistic therapy against HCC
Authors: Yang Huizhen , Mu Weiwei , Yuan Shijun , Yang Han , Chang Lili , Sang Xiao , Gao Tong , Liang Shuang , Liu Xiaoqing , Fu Shunli , Zhang Zipeng , Liu Yongjun , Zhang Na
Published: March 2024

Immune checkpoint inhibitors (ICIs) combined with antiangiogenic therapy have shown encouraging clinical benefits for the treatment of unresectable or metastatic hepatocellular carcinoma (HCC). Nevertheless, therapeutic efficacy and wide clinical applicability remain a challenge due to “cold” tumors’ immunological characteristics. Tumor immunosuppressive microenvironment (TIME) continuously natural force for immune escape by extracellular matrix (ECM) infiltration, tumor angiogenesis, and tumor cell proliferation. Herein, we proposed a novel concept by multi-overcoming immune escape to maximize the ICIs combined with antiangiogenic therapy efficacy against HCC. A self-delivery photothermal-boosted-NanoBike (BPSP) composed of black phosphorus (BP) tandem-augmented anti-PD-L1 mAb plus sorafenib (SF) is meticulously constructed as a triple combination therapy strategy. The simplicity of BPSP's composition, with no additional ingredients added, makes it easy to prepare and presents promising marketing opportunities. (1) NIR-II-activated BPSP performs photothermal therapy (PTT) and remodels ECM by depleting collagen I, promoting deep penetration of therapeutics and immune cells. (2) PTT promotes SF release and SF exerts anti-vascular effects and down-regulates PD-L1 via RAS/RAF/ERK pathway inhibition, enhancing the efficacy of anti-PD-L1 mAb in overcoming immune evasion. (3) Anti-PD-L1 mAb block PD1/PD-L1 recognition and PTT-induced ICD initiates effector T cells and increases response rates of PD-L1 mAb. Highly-encapsulated BPSP converted 'cold' tumors into 'hot' ones, improved CTL/Treg ratio, and cured orthotopic HCC tumors in mice. Thus, multi-overcoming immune escape offers new possibilities for advancing immunotherapies, and photothermal/chemical/immune synergistic therapy shows promise in the clinical development of HCC.

Graphical Abstract
Establishing conditions for the generation and maintenance of estrogen receptor-positive organoid models of breast cancer
Authors: Oliphant Michael U J , Akshinthala Dipikaa , Muthuswamy Senthil K.
Published: March 2024

Patient-derived organoid models of estrogen receptor-positive (ER+) breast cancer would provide a much-needed tool to understand drug resistance and disease progression better. However, the establishment and long-term maintenance of ER expression, function, and response in vitro remains a significant challenge. Here, we report the development of an ER+ breast tumor organoid medium (BTOM-ER) that conserves ER expression, estrogen responsiveness, and dependence, as well as sensitivity to endocrine therapy of ER+ patient-derived xenograft organoids (PDXO). Our findings demonstrate the utility of subtype-specific culture conditions that better mimic the characteristics of the breast epithelial biology and microenvironment, providing a powerful platform for investigating therapy response and disease progression of ER+ breast cancer.
Evaluation of feline heartworm disease based on gross necropsy, serology, pulmonary histopathology, and radiographic evidence in adult shelter cats in northeastern Alabama
Authors: Nelson C. Thomas , Johnson Calvin M.
Published: March 2024

Background

: Veterinary knowledge regarding feline heartworm has been increasing significantly over the past two decades. Necropsy surveys of shelter cats have shown feline adult heartworm infection prevalence to be 5–20% of the rate in unprotected dogs; however, other studies have shown feline heartworm antibody prevalence up to 33%, reflecting higher exposure rates and potential immature adult infections. Thus, the true prevalence of feline heartworm infection is likely underestimated due to the limitations of current diagnostic techniques, inadequate testing protocols, and the high likelihood of cats exhibiting transient clinical signs or dying without confirmation of infection. Diagnosing Feline Heartworm Disease (FHWD), also referred to as Heartworm Associated Respiratory Disease (HARD), is one of the conundrums of veterinary medicine. The purpose of this study was to evaluate and characterize the occurrence of Heartworm Associated Respiratory Disease [HARD] in shelter cats, naturally-infected with D.immitis.

Methods

Fifty shelter cats slated for euthanasia between December 2009 and June 2010 were investigated by gross necropsy, radiography, serology, and lung histopathology using techniques that have been established in experimental models of cat heartworm infection. The relationship between pulmonary vascular disease and serological markers for heartworm was also examined using correlations and statistical modeling. Serology included standard heartworm antigen test and a commonly used heartworm antibody test. Also included were heat-treated heartworm antigen test and two additional heartworm antibody tests previously evaluated on experimentally-infected cats.

Results

None of the cats were heartworm antibody (HW Ab) positive on a commonly used HW Ab test used by many reference laboratories even though 20% of the study cats were heartworm antigen (HW Ag) positive on heat-treated samples. Two additional HW Ab test were positive on 26% and 22% of the study cats. The combination of heat-treated HW Ag, HW Ab tests, and histopathology indicated 34% of the study cats had HARD.

Conclusions

Utilizing both, the above tests, and thoracic radiographs, enhanced the ability to predict vascular disease, possibly caused by infection with immature and adult heartworms and supported the premise that cats develop heartworm disease at the same rate as dogs.

Graphical Abstract
Optimizing malaria vector control in the Greater Mekong Subregion: a systematic review and mathematical modelling study to identify desirable intervention characteristics
Authors: Wang Yuqian , Chitnis Nakul , Fairbanks Emma L.
Published: March 2024

Background

In the Greater Mekong Subregion (GMS), new vector-control tools are needed to target mosquitoes that bite outside during the daytime and night-time to advance malaria elimination.

Methods

We conducted systematic literature searches to generate a bionomic dataset of the main malaria vectors in the GMS, including human blood index (HBI), parity proportion, sac proportion (proportion with uncontracted ovary sacs, indicating the amount of time until they returned to host seeking after oviposition) and the resting period duration. We then performed global sensitivity analyses to assess the influence of bionomics and intervention characteristics on vectorial capacity.

Results

Our review showed that Anopheles minimus, An. sinensis, An. maculatus and An. sundaicus display opportunistic blood-feeding behaviour, while An. dirus is more anthropophilic. Multivariate regression analysis indicated that environmental, climatic and sampling factors influence the proportion of parous mosquitoes, and resting duration varies seasonally. Sensitivity analysis highlighted HBI and parity proportion as the most influential bionomic parameters, followed by resting duration. Killing before feeding is always a desirable characteristic across all settings in the GMS. Disarming is also a desirable characteristic in settings with a low HBI. Repelling is only an effective strategy in settings with a low HBI and low parity proportion. Killing after feeding is only a desirable characteristic if the HBI and parity proportions in the setting are high.

Conclusions

Although in general adopting tools that kill before feeding would have the largest community-level effect on reducing outdoor transmission, other modes of action can be effective. Current tools in development which target outdoor biting mosquitoes should be implemented in different settings dependent on their characteristics.

Graphical Abstract
Determinants of COVID-19 vaccine uptake: evidence from a vulnerable global South setting
Authors: Amoah John Oti , Abraham Susanna Aba , Adongo Charles Atanga , Sekimpi Deogratias Kaheeru , Adukpo David Cudjoe , Obiri-Yeboah Dorcas , Doku David Teye
Published: March 2024

Objective

Studies are paying increasing attention to complex social determinants in explaining the variation in the rates COVID-19 vaccine uptake. This study examines the influence of various individual, contextual, and vaccine-related factors on COVID-19 vaccine uptake behaviour in a resource-scarce and vulnerable setting using a quantitative research approach. Using a multi-staged cluster sampling approach, 408 individuals from 204 households in Cape Coast, Ghana’s tourism hub, were surveyed. Probit and logistic regression models were estimated to test the vaccine-related factors.

Results

A significant difference is observed between wait time and vaccination status (χ2 = 21.17; p = 0.000). Moreover, age and religion, as controlled variables, equally played significant roles in influencing the adoption of the vaccine. Other factors encompass the perceived risk of contracting COVID-19, the perceived benefits of the vaccine in relation to its side effects, and the level of trust individuals have in the concern of vaccine producers for their health. These findings call for targeted campaigns by the Ministry of Health, health facilities and other institutions promoting the COVID-19 vaccine. These actors should emphasize the benefits of vaccination, prioritize trust-building initiatives, and provide clear guidance on vaccination schedules, and manage waiting time.
From voice to ink (Vink): development and assessment of an automated, free-of-charge transcription tool
Authors: Tolle Hannah , Castro Maria del Mar , Wachinger Jonas , Putri Agrin Zauyani , Kempf Dominic , Denkinger Claudia M. , McMahon Shannon A.
Published: March 2024

Background

Verbatim transcription of qualitative audio data is a cornerstone of analytic quality and rigor, yet the time and energy required for such transcription can drain resources, delay analysis, and hinder the timely dissemination of qualitative insights. In recent years, software programs have presented a promising mechanism to accelerate transcription, but the broad application of such programs has been constrained due to expensive licensing or “per-minute” fees, data protection concerns, and limited availability of such programs in many languages. In this article, we outline our process of adapting a free, open-source, speech-to-text algorithm (Whisper by OpenAI) into a usable and accessible tool for qualitative transcription. Our program, which we have dubbed “Vink” for voice to ink, is available under a permissive open-source license (and thus free of cost).

Results

We conducted a proof-of-principle assessment of Vink’s performance in transcribing authentic interview audio data in 14 languages. A majority of pilot-testers evaluated the software performance positively and indicated that they were likely to use the tool in their future research. Our usability assessment indicates that Vink is easy-to-use, and we performed further refinements based on pilot-tester feedback to increase user-friendliness.

Conclusion

With Vink, we hope to contribute to facilitating rigorous qualitative research processes globally by reducing time and costs associated with transcription and by expanding free-of-cost transcription software availability to more languages. With Vink running on standalone computers, data privacy issues arising within many other solutions do not apply.
The multifaceted therapeutic value of targeting steroid receptor coactivator-1 in tumorigenesis
Authors: Chen Qiang , Guo Peng , Hong Yilin , Mo Pingli , Yu Chundong
Published: March 2024

Steroid receptor coactivator-1 (SRC-1, also known as NCOA1) frequently functions as a transcriptional coactivator by directly binding to transcription factors and recruiting to the target gene promoters to promote gene transcription by increasing chromatin accessibility and promoting the formation of transcriptional complexes. In recent decades, various biological and pathological functions of SRC-1 have been reported, especially in the context of tumorigenesis. SRC-1 is a facilitator of the progression of multiple cancers, including breast cancer, prostate cancer, gastrointestinal cancer, neurological cancer, and female genital system cancer. The emerging multiorgan oncogenic role of SRC-1 is still being studied and may not be limited to only steroid hormone-producing tissues. Growing evidence suggests that SRC-1 promotes target gene expression by directly binding to transcription factors, which may constitute a novel coactivation pattern independent of AR or ER. In addition, the antitumour effect of pharmacological inhibition of SRC-1 with agents including various small molecules or naturally active compounds has been reported, but their practical application in clinical cancer therapy is very limited. For this review, we gathered typical evidence on the oncogenic role of SRC-1, highlighted its major collaborators and regulatory genes, and mapped the potential mechanisms by which SRC-1 promotes primary tumour progression.
Clinical description and outcome of overall varicella-zoster virus-related organ dysfunctions admitted in intensive care units: the VAZOREA cohort study
Authors: Malherbe Jolan , Godard Pierre , Lacherade Jean-Claude , Coirier Valentin , Argaud Laurent , Hyvernat Hervé , Schneider Francis , Charpentier Julien , Wallet Florent , Pocquet Juliette , Plantefeve Gaëtan , Quenot Jean-Pierre , Bay Pierre , Delbove Agathe , Georges Hugues , Urbina Tomas , Schnell David , Le Moal Charlène , Stanowski Matthieu , Muris Corentin , Jonas Maud , Sauneuf Bertrand , Lesieur Olivier , Lhermitte Amaury , Calvet Laure , Gueguen Ines , du Cheyron Damien
Published: March 2024

Background

Due to aging population and increasing part of immunocompromised patients, a raise in life-threatening organ damage related to VZV can be expected. Two retrospective studies were already conducted on VZV in ICU but focused on specific organ injury. Patients with high-risk of VZV disease still must be identified. The objective of this study was to report the clinical features and outcome of all life-threatening VZV manifestations requiring intensive care unit (ICU) admission. This retrospective cohort study was conducted in 26 French ICUs and included all adult patients with any life-threatening VZV-related event requiring ICU admission or occurring in ICU between 2010 and 2019.

Results

One-hundred nineteen patients were included with a median SOFA score of 6. One hundred eight patients (90.8%) were admitted in ICU for VZV disease, leaving 11 (9.2%) with VZV disease occurring in ICU. Sixty-one patients (51.3%) were immunocompromised. Encephalitis was the most prominent organ involvement (55.5%), followed by pneumonia (44.5%) and hepatitis (9.2%). Fifty-four patients (45.4%) received norepinephrine, 72 (60.5% of the total cohort) needed invasive mechanical ventilation, and 31 (26.3%) received renal-replacement therapy. In-hospital mortality was 36.1% and was significantly associated with three independent risk factors by multivariable logistic regression: immunosuppression, VZV disease occurring in ICU and alcohol abuse. Hierarchical clustering on principal components revealed five phenotypically distinct clusters of patients: VZV-related pneumonia, mild encephalitis, severe encephalitis in solid organ transplant recipients, encephalitis in other immunocompromised hosts and VZV disease occurring in ICU. In-hospital mortality was highly different across phenotypes, ranging from zero to 75% (p < 0.001).

Conclusion

Overall, severe VZV manifestations are associated with high mortality in the ICU, which appears to be driven by immunosuppression status rather than any specific organ involvement. Deciphering the clinical phenotypes may help clinicians identify high-risk patients and assess prognosis.
A precise mathematical approach for analyzing the performance of MIMO space–time block code systems over Weibull fading channels
Authors: Bessate Abdelmajid , Miftah Youssef , Ben-Azza Hussain , El Bouanani Faissal
Published: March 2024

Multiple-input–multiple-output (MIMO) systems have effectively addressed today’s high demand for 5G communications and beyond. Further, MIMO-assisted space–time block codes (STBCs) have been shown to enhance the system’s performance and provide a complete variety of coherent flat-fading channels. Additionally, the closed-form expression of the probability density function of the summation of correlated Weibull random variables remains unknown. In this work, we investigate the performance analysis of MIMO-STBC-enabled systems subject to the Weibull fading channel. New tight approximate expressions for numerous system performance metrics, e.g., outage probability, average capacity under various rate adaption methods, and average symbol/bit error rate, have been obtained. The Monte Carlo simulation method has corroborated all the presented results.
VISTA drives macrophages towards a pro-tumoral phenotype that promotes cancer cell phagocytosis yet down-regulates T cell responses
Authors: Lin Yusheng , Choukrani Ghizlane , Dubbel Lena , Rockstein Lena , Freile Jimena Alvarez , Qi Yuzhu , Wiersma Valerie , Zhang Hao , Koch Karl-Wilhelm , Ammatuna Emanuele , Schuringa Jan Jacob , van Meerten Tom , Huls Gerwin , Bremer Edwin
Published: March 2024

Background

VISTA is a well-known immune checkpoint in T cell biology, but its role in innate immunity is less established. Here, we investigated the role of VISTA on anticancer macrophage immunity, with a focus on phagocytosis, macrophage polarization and concomitant T cell activation.

Methods

Macrophages, differentiated from VISTA overexpressed THP-1 cells and cord blood CD34+ cell-derived monocytes, were used in phagocytosis assay using B lymphoma target cells opsonized with Rituximab. PBMC-derived macrophages were used to assess the correlation between phagocytosis and VISTA expression. qRT-PCR, flow cytometry, and enzyme-linked immunosorbent assay were performed to analyze the impact of VISTA on other checkpoints and M1/M2-like macrophage biology. Additionally, flow cytometry was used to assess the frequency of CD14+ monocytes expressing VISTA in PBMCs from 65 lymphoma patients and 37 healthy donors.

Results

Ectopic expression of VISTA in the monocytic model cell line THP-1 or in primary monocytes triggered differentiation towards the macrophage lineage, with a marked increase in M2-like macrophage-related gene expression and decrease in M1-like macrophage-related gene expression. VISTA expression in THP-1 and monocyte-derived macrophages strongly downregulated expression of SIRPα, a prominent ‘don’t eat me’ signal, and augmented phagocytic activity of macrophages against cancer cells. Intriguingly, expression of VISTA’s extracellular domain alone sufficed to trigger phagocytosis in ∼ 50% of cell lines, with those cell lines also directly binding to recombinant human VISTA, indicating ligand-dependent and -independent mechanisms. Endogenous VISTA expression was predominantly higher in M2-like macrophages compared to M0- or M1-like macrophages, with a positive correlation observed between VISTA expression in M2c macrophages and their phagocytic activity. VISTA-expressing macrophages demonstrated a unique cytokine profile, characterized by reduced IL-1β and elevated IL-10 secretion. Furthermore, VISTA interacted with MHC-I and downregulated its surface expression, leading to diminished T cell activation. Notably, VISTA surface expression was identified in monocytes from all lymphoma patients but was less prevalent in healthy donors.

Conclusions

Collectively, VISTA expression associates with and drives M2-like activation of macrophages with a high phagocytic capacity yet a decrease in antigen presentation capability to T cells. Therefore, VISTA is a negative immune checkpoint regulator in macrophage-mediated immune suppression.
Vaccination with a combination of STING agonist-loaded lipid nanoparticles and CpG-ODNs protects against lung metastasis via the induction of CD11bhighCD27low memory-like NK cells
Authors: Khalifa Alaa M. , Nakamura Takashi , Sato Yusuke , Harashima Hideyoshi
Published: March 2024

Background

Natural killer (NK) cells are effective in attacking tumor cells that escape T cell attack. Memory NK cells are believed to function as potent effector cells in cancer immunotherapy. However, knowledge of their induction, identification, and potential in vivo is limited. Herein, we report on the induction and identification of memory-like NK cells via the action of a combination of a stimulator of interferon genes (STING) agonist loaded into lipid nanoparticles (STING-LNPs) and cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG-ODNs), and the potential of the inducted memory-like NK cells to prevent melanoma lung metastasis.

Methods

The antitumor effects of either the STING-LNPs, CpG-ODNs, or the combination therapy were evaluated using a B16-F10 lung metastasis model. The effect of the combined treatment was evaluated by measuring cytokine production. The induction of memory-like NK cells was demonstrated via flow cytometry and confirmed through their preventative effect.

Results

The combination of STING-LNPs and CpG-ODNs tended to enhance the production of interleukin 12 (IL-12) and IL-18, and exerted a therapeutic effect against B16-F10 lung metastasis. The combination therapy increased the population of CD11bhighCD27low NK cells. Although monotherapies failed to show preventative effects, the combination therapy induced a surprisingly strong preventative effect, which indicates that CD11bhighCD27low cells could be a phenotype of memory-like NK cells.

Conclusion

As far as could be ascertained, this is the first report of the in vivo induction, identification, and confirmation of a phenotype of the memory-like NK cells through a prophylactic effect via the use of an immunotherapeutic drug. Our findings provide novel insights into the in vivo induction of CD11bhighCD27low memory-like NK cells thus paving the way for the development of efficient immunotherapies.

Graphical Abstract
The financial and social impacts of the COVID-19 pandemic on youth with eating disorders, their families, clinicians and the mental health system: a mixed methods cost analysis
Authors: Obeid Nicole , Silva-Roy Patricia , Booij Linda , Coelho Jennifer S. , Dimitropoulos Gina , Katzman Debra K.
Published: March 2024

Background

The onset of the COVID-19 pandemic has had an adverse impact on children, youth, and families with eating disorders (EDs). The COVID-19 pandemic exacerbated pre-existing personal and financial costs to youth, caregivers, and health professionals accessing or delivering ED services. The objectives of this mixed methods study were to (1) understand the indirect, direct medical and non-medical costs reported by youth, caregivers, and clinicians; (2) understand how the COVID-19 pandemic may have impacted these costs, and (3) explore implications of these costs with regards to barriers and resources to inform future decisions for the ED system of care.

Methods

Youth (aged 16–25 years) with lived/living experience, primary caregivers, clinicians, and decision-makers were recruited with support from various partners across Canada to complete group specific surveys. A total of 117 participants responded to the survey. From those respondents, 21 individuals volunteered to further participate in either a discussion group or individual interview to provide additional insights on costs.

Results

Youth and primary caregivers reported costs relating to private services, transportation and impacts of not attending school or work. Additionally, primary caregivers reported the top direct medical cost being special food or nutritional supplements (82.8%). In discussion groups, youth and caregivers elaborated further on the challenges with long waitlists and cancelled services, impact on siblings and effect on family dynamics. Clinicians and decision-makers reported increased work expectations (64.3%) and fear/isolation due to COVID-19 in the workplace (58.9%). Through discussion groups, clinicians expanded further on the toll these expectations took on their personal life. Approximately 1 in 3 health professionals reported contemplating leaving their position in 1–2 years, with greater than 60% of this group stating this is directly related to working during the pandemic.

Conclusions

Findings demonstrate the need for increased support for youth and caregivers when accessing ED services both during crisis and non-crisis times. Additionally, attention must be given to acknowledging the experience of health professionals to support better retention and resource management as they continue to navigate challenges in the health care system.
Agricultural habitat use and selection by a sedentary bird over its annual life cycle in a crop-depredation context
Authors: Chambon Rémi , Paillisson Jean-Marc , Fournier-Sowinski Jérôme , Dugravot Sébastien
Published: March 2024

Background

Modern agriculture has undoubtedly led to increasing wildlife-human conflicts, notably concerning bird damage in productive and attractive crops during some parts of the annual cycle. This issue requires utmost attention for sedentary birds that may impact agricultural crops at any stage of their annual life cycle. Reducing bird-human conflicts requires a better understanding of the relationship between bird foraging activity and the characteristics of agricultural areas, notably with respect to changes in food-resource availability and crop sensitivity across the year.

Methods

We explored how GPS-tagged adult male western jackdaws– sedentary corvids– utilize agricultural areas throughout their annual cycle, in a context of crop depredation. More precisely, we described their daily occurrence distribution and the extent of habitat use and selection consistency with respect to landscape composition across time.

Results

Jackdaws moved in the close agricultural surroundings of their urban nesting place over the year (< 2.5 km from the nest, on average). Daily occurrence distributions were restricted (< 2.2 km2), relatively centered on the nesting locality (distance between the daily occurrence centroid and the nest < 0.9 km), and rather spatially stable during each annual life-cycle period (overlap range: 63.4–76.1%). Their foraging patterns highlighted that they fed mainly in grasslands all year round, and foraged complementarily and opportunistically in maize (during sowing– coinciding with the first stages of the birds’ breeding period) and cereal crops (during harvesting– their post-fledging period).

Conclusions

Our findings demonstrate the very limited space use by breeding male jackdaws which foraged preferentially in grasslands. We call for future investigations in other agricultural contexts and also considering non-breeders for extrapolation purposes.
Quantitative analysis of the use of virtual reality environments among higher education professors
Authors: Antón-Sancho Álvaro , Vergara Diego , Fernández-Arias Pablo
Published: March 2024

Virtual Reality (VR) is a computer-generated environment with noteworthy didactic applications in different educational levels and areas of knowledge. The study of the perceptions of the agents involved about the use of VR in lectures is a fruitful line of research because it has implications in terms of the measures to be taken to improve the training and competence of professors in its use. In this paper, a quantitative, descriptive, and correlational research is carried out on the assessments of a sample of 1638 Latin American university professors on both (i) the didactic use of VR and (ii) the influence of the professors' area of knowledge on these assessments. For this purpose, a validated questionnaire was used, the responses to which were subjected to statistical analysis. As a result, it was found that the ratings of VR are very high, but professors believe that their digital skills for its use are insufficient. In addition, the professors' area of knowledge significantly influences their ratings, being higher in the areas of knowledge in which professors have a better self-concept of their digital skills. Furthermore, gender gaps have also been identified in the answers given, which behave differently according to the area of knowledge. Finally, some conclusions, implications, and recommendations are drawn from the results obtained.
Optimal Implant Sizing Using Machine Learning Is Associated With Increased Range of Motion After Cervical Disk Arthroplasty
Authors: Lakomkin Nikita , Pennington Zach , Bhandarkar Archis , Mikula Anthony L. , Michalopoulos Giorgos D. , Katsos Konstantinos , Chen Selby , McClendon Jamal , Freedman Brett A. , Bydon Mohamad
Published: March 2024

BACKGROUND AND OBJECTIVES:

Cervical disk arthroplasty (CDA) offers the advantage of motion preservation in the treatment of focal cervical pathology. At present, implant sizing is performed using subjective tactile feedback and imaging of trial cages. This study aims to construct interpretable machine learning (IML) models to accurately predict postoperative range of motion (ROM) and identify the optimal implant sizes that maximize ROM in patients undergoing CDA.

METHODS:

Adult patients who underwent CDA for single-level disease from 2012 to 2020 were identified. Patient demographics, comorbidities, and outcomes were collected, including symptoms, examination findings, subsidence, and reoperation. Affected disk height, healthy rostral disk height, and implant height were collected at sequential time points. Linear regression and IML models, including bagged regression tree, bagged multivariate adaptive regression spline, and k-nearest neighbors, were used to predict ROM change. Model performance was assessed by calculating the root mean square error (RMSE) between predicted and actual changes in ROM in the validation cohort. Variable importance was assessed using RMSE loss. Area under the curve analyses were performed to identify the ideal implant size cutoffs in predicting improved ROM.

RESULTS:

Forty-seven patients were included. The average RMSE between predicted and actual ROM was 7.6° (range: 5.8-10.1) in the k-nearest neighbors model, 7.8° (range: 6.5-10.0) in the bagged regression tree model, 7.8° (range: 6.2-10.0) in the bagged multivariate adaptive regression spline model, and 15.8° (range: 14.3-17.5°) in a linear regression model. In the highest-performing IML model, graft size was the most important predictor with RMSE loss of 6.2, followed by age (RMSE loss = 5.9) and preoperative caudal disk height (RMSE loss = 5.8). Implant size at 110% of the normal adjacent disk height was the optimal cutoff associated with improved ROM.

CONCLUSION:

IML models can reliably predict change in ROM after CDA within an average of 7.6 degrees of error. Implants sized comparably with the healthy adjacent disk may maximize ROM.
Local Ties in Spatial Equilibrium
Authors: Zabek Mike
Published: March 2024

Someone who lives in an economically depressed place was probably born there. And having workers with local ties who prefer to live in their birthplaces leads to smaller migration responses in depressed places. Smaller migration responses lead to lower real incomes and make incomes more volatile, a form of hysteresis. Local ties can also persist for generations. Subsidies to economically depressed places cause smaller distortions, because few people want to move to depressed places. Finally, subsidies to productive places increase aggregate productivity, as they induce more migration. (JEL J22, J23, J31, J61, R23, Z13)
Sectoral Heterogeneity in Nominal Price Rigidity and the Origin of Aggregate Fluctuations
Authors: Pastén Ernesto , Schoenle Raphael , Weber Michael
Published: March 2024

We study the role of heterogeneity in nominal price rigidity for aggregate fluctuations in a model with sectoral productivity shocks. Theoretically, sectoral heterogeneity in the pricing friction has an ambiguous effect on GDP and aggregate price volatility. Quantitatively, (i) GDP volatility is amplified when the friction is heterogeneous rather than homogeneous; (ii) sectoral shocks can jointly rationalize the volatility of sectoral prices, aggregate prices, and GDP, unlike aggregate shocks; and (iii) shocks to the largest or most central sectors may not matter in the aggregate as heterogeneous pricing frictions may alter the identity of the most important sectors for aggregate fluctuations. (JEL E12, E23, E31, E32)
How to Construct Nationally Representative Firm-Level Data from the Orbis Global Database: New Facts on SMEs and Aggregate Implications for Industry Concentration
Authors: Kalemlİ-Özcan Şebnem , Sørensen Bent E. , Villegas-Sanchez Carolina , Volosovych Vadym , Yeşiltaş Sevcan
Published: March 2024

We construct nationally representative firm-level longitudinal data for European countries using financial statements from the Orbis database. We validate our data by comparing its coverage and firm size distribution to official statistics. We showcase two applications to show the importance of firm representativeness in understanding macroeconomic outcomes. First, we show that small and medium-sized firms account for a large share of aggregate economic activity. Second, we document that firm representativeness is important for calculating industry concentration trends over time as the share of economic activity accounted by top firms in an industry changes with the firm samples used. (JEL C81, D22, G30, L11, L25, L60)
Uncertainty and Information Acquisition: Evidence from Firms and Households
Authors: Mikosch Heiner , Roth Christopher , Sarferaz Samad , Wohlfart Johannes
Published: March 2024

We leverage the small open economy Switzerland as a testing ground for basic premises of macroeconomic models of endogenous information acquisition, using tailored surveys of firms and households. Firms and households perceiving a greater exposure to exchange rate fluctuations acquire more information about the exchange rate. Moreover, higher perceived costs of acquiring or processing information are associated with lower levels of information acquisition. Finally, an exogenous increase in the perceived uncertainty of the exchange rate increases firms’ demand for a report about exchange rate developments, but not households’. Our findings inform the modeling of information frictions in macroeconomics. (JEL D12, D22, D81, D83, D84, E71, F31)