bluuebunny/crossref_metadata_2025 huggingface dataset:
Health‐related quality of life in stage III‐IV melanoma treated with targeted therapy or immunotherapy: A systematic review on the adequacy of reporting and clinical issues in phase III randomized controlled trials
Authors: Chen Chen , Wang Zehua , Qin Yan‐Ru
Published: August 2022

Cutaneous melanoma represents around over 90% of all melanoma. With more effective treatments able to extend patients' survival, health‐related quality of life (HRQOL) is increasingly becoming an important endpoint in cancer clinical trials. They are often secondary outcomes measured in phase III randomized controlled trials and their implementation, collection, analysis, and reporting can be challenging methodologically. For these reasons, an increasing number of international recommendations introduced the standards regarding the conduct of HRQOL. In this systematic review, we appraise the adequacy of HRQOL reporting in phase III randomized controlled trials of stage III‐IV cutaneous melanoma and the clinical issues of immunotherapy and small‐molecular‐targeted therapy on HRQOL. Our search strategy totally got 55 articles, and only 13 studies met all inclusion criteria. Findings suggest that most treatments did not yield significant improvements in HRQOL but kept baseline levels, accompanied by prolonged survival and acceptable toxicity. Except for some existing limitations, reporting of HRQOL has made encouraging progress during the period covered by our search, but some aspects still need further optimization.
Anoikis in cancer: The role of lipid signaling
Authors: Raeisi Mortaza , Zehtabi Mojtaba , Velaei Kobra , Fayyazpour Parisa , Aghaei Negar , Mehdizadeh Amir
Published: August 2022

Malignantly transformed cells must alter their metabolic status to stay viable in a harsh microenvironment and maintain their ability to invade and spread. Anoikis, a specific detachment‐related form of apoptotic cell death, is a potential barrier to cancer cell metastasis. Several molecular/pathway alterations have been implicated in preventing anoikis in metastatic cancers. Specific alterations in the lipid metabolism machinery (such as an increase in fatty acid uptake and synthesis) and modifications in the carbohydrate and amino acid metabolism are partially identified mechanisms associated with the anoikis resistance in various types of cancers, among other survival benefits. Following a summary of the molecular basis of the anoikis pathway, its resistance mechanisms, and the fundamentals of lipid metabolism in cancer, this article aims to elucidate the impact of lipid metabolism deviations recruited by cancer cells to escape anoikis.
Oxidative Cleavage of Vicinal Diols Catalyzed by Monomeric Fe‐Sites Inside MFI Zeolite
Authors: Treu Philipp , Sarma Bidyut Bikash , Grunwaldt Jan‐Dierk , Saraçi Erisa
Published: August 2022

The oxidative cleavage of vicinal diols to carboxylic acids was investigated over heterogeneous Fe/MFI catalysts in aqueous medium, with green oxidant H2O2 and in mild reaction conditions. High conversions and selectivities (X=90 %, S=79 %) were achieved for the oxidative cleavage of ethylene glycol. Further substrates were also tested broadening the relevance of this catalyst. The employment of non‐noble and abundant Fe as the active metal and the MFI‐type zeolite as support has a clear advantage over the presently used homogeneous or noble metal‐based catalysts. A combination of complementary characterisation techniques with catalytic results is used to show that monomeric Fe species inside zeolite MFI are the active sites for the oxidative cleavage of C−C bonds of vicinal diols. The recyclability of the catalyst and reaction mechanism were also studied.
Comparative Studies of Oxygen‐Free Semiconductors in Photocatalytic CO2 Reduction and Alcohol Degradation
Authors: Lorenz Felix , Moustakas Nikolaos G. , Peppel Tim , Strunk Jennifer
Published: August 2022

Commercially available α‐SiC, β‐SiC, GaN, ZnTe and self‐synthesized g‐C3N4 were investigated in a comparative study regarding their photocatalytic capabilities in CO2 reduction and alcohol degradation. Under reproducible high‐purity solid‐gas conditions none of the tested materials promoted CO2 reduction using H2O as proton donor, although TiO2 P25 has been shown to produce significant amounts of CH4 under similar conditions. Replacing H2O with 2‐propanol led to hydrocarbon formation which could solely be attributed to alcohol degradation while no CO2 reduction took place.
Translocation of gasdermin D induced mitochondrial injury and mitophagy mediated quality control in lipopolysaccharide related cardiomyocyte injury
Authors: Yu Ziqing , Xiao Zilong , Guan Lichun , Bao Pei , Yu Yong , Liang Yixiu , Li Minghui , Huang Zhenzhen , Chen Xueying , Chen Ruizhen , Su Yangang , Ge Junbo
Published: August 2022

Backgrounds

Inflammation underlies the mechanism of different kinds of heart disease. Cytoplasmic membrane localized N‐terminal fragment of gasdermin‐D (GSDMD‐N) could induce inflammatory injury to cardiomyocyte. However, effects and dynamic changes of GSDMD during the process of lipopolysaccharide (LPS) related inflammatory stress induced cardiomyocyte injury are barely elucidated to date. In this study, LPS related cardiomyocyte injury was investigated based on potential interaction of GSDMD‐N induced mitochondrial injury and mitophagy mediated mitochondria quality control.

Methods

HL‐1 cardiomyocytes were treated with LPS and Nigericin to induce inflammatory stress. The dual‐fluorescence‐labelled GSDMD expressed HL‐1 cardiomyocytes were constructed to study the translocation of GSDMD. The mitochondrial membrane potential (MMP) was measured by JC‐1 staining. Mitophagy and autophagic flux were recorded by transmission electron microscopy and fluorescent image.

Results

GSDMD‐N showed a time‐dependent pattern of translocation from mitochondria to cytoplasmic membrane under LPS and Nigericin induced inflammatory stress in HL‐1 cardiomyocytes. GSDMD‐N preferred to localize to mitochondria to permeablize its membrane and dissipate the MMP. This effect couldn't be reversed by cyclosporine‐A (mPTP inhibitor), indicating GSDMD‐N pores as alternative mechanism underlying MMP regulation, in addition to mitochondrial permeability transition pore (mPTP). Moreover, the combination between GSDMD‐N and autophagy related Microtubule Associated Protein 1 Light Chain 3 Beta (LC3B) was verified by co‐immunoprecipitation. Besides, mitophagy alleviating GSDMD‐N induced mitochondrial injury was proved by pre‐treatment of autophagy antagonist or agonist in GSDMD‐knock out or GSDMD‐overexpression cells. A time‐dependent pattern of GSDMD translocation and mitochondrial GSDMD targeted mitophagy were verified.

Conclusion

Herein, our study confirmed a crosstalk between GSDMD‐N induced mitochondrial injury and mitophagy mediated mitochondria quality control during LPS related inflammation induced cardiomyocyte injury, which potentially facilitating the development of therapeutic target to myocardial inflammatory disease. Our findings support pharmaceutical intervention on enhancing autophagy or inhibiting GSDMD as potential target for inflammatory heart disease treatment.
IL‐34 deficiency impairs FOXP3+ Treg function in a model of autoimmune colitis and decreases immune tolerance homeostasis
Authors: Freuchet Antoine , Salama Apolline , Bézie Séverine , Tesson Laurent , Rémy Séverine , Humeau Romain , Règue Hadrien , Sérazin Céline , Flippe Léa , Peterson Pärt , Vimond Nadège , Usal Claire , Ménoret Séverine , Heslan Jean‐Marie , Duteille Franck , Blanchard Frédéric , Giral Magali , Colonna Marco , Anegon Ignacio , Guillonneau Carole
Published: August 2022

Background

Immune homeostasis requires fully functional Tregs with a stable phenotype to control autoimmunity. Although IL‐34 is a cytokine first described as mainly involved in monocyte cell survival and differentiation, we recently described its expression by CD8+ Tregs in a rat model of transplantation tolerance and by activated FOXP3+ CD4+ and CD8+ Tregs in human healthy individuals. However, its role in autoimmunity and potential in human diseases remains to be determined.

Methods

We generated Il34−/− rats and using both Il34−/− rats and mice, we investigated their phenotype under inflammatory conditions. Using Il34−/− rats, we further analyzed the impact of the absence of expression of IL‐34 for CD4+ Tregs suppressive function. We investigated the potential of IL‐34 in human disease to prevent xenogeneic GVHD and human skin allograft rejection in immune humanized immunodeficient NSG mice. Finally, taking advantage of a biocollection, we investigated the correlation between presence of IL‐34 in the serum and kidney transplant rejection.

Results

Here we report that the absence of expression of IL‐34 in Il34−/− rats and mice leads to an unstable immune phenotype, with production of multiple auto‐antibodies, exacerbated under inflammatory conditions with increased susceptibility to DSS‐ and TNBS‐colitis in Il34−/− animals. Moreover, we revealed the striking inability of Il34−/− CD4+ Tregs to protect Il2rg−/− rats from a wasting disease induced by transfer of pathogenic cells, in contrast to Il34+/+ CD4+ Tregs. We also showed that IL‐34 treatment delayed EAE in mice as well as GVHD and human skin allograft rejection in immune humanized immunodeficient NSG mice. Finally, we show that presence of IL‐34 in the serum is associated with a longer rejection‐free period in kidney transplanted patients.

Conclusion

Altogether, our data emphasize on the crucial necessity of IL‐34 for immune homeostasis and for CD4+ Tregs suppressive function. Our data also shows the therapeutic potential of IL‐34 in human transplantation and auto‐immunity.

Highlights

Absence of expression of IL‐34 in Il34−/− rats and mice leads to an unstable immune phenotype, with a production of multiple auto‐antibodies and exacerbated immune pathology under inflammatory conditions.

Il34−/− CD4+ Tregs are unable to protect Il2rg−/− rats from colitis induced by transfer of pathogenic cells.

IL‐34 treatment delayed EAE in mice, as well as acute GVHD and human skin allograft rejection in immune‐humanized immunodeficient NSG mice.
IT teachers' beliefs about alternative curriculum designs: Results from a mixed methods study
Authors: Drenoyianni Helen , Bekos Nikos
Published: August 2022

This paper presents the results of an exploratory sequential mixed methods research project investigating Greek IT teachers' curriculum ideologies. Following the theoretical framework proposed by Michael Schiro, two different measurement tools were designed and implemented for the identification of teachers' philosophical beliefs about the curriculum. In the qualitative phase of the study, 33 semi‐structured interviews were conducted, in which IT teachers discussed the curriculum designs underlying four different lesson plans, all regarded with the common themes of ‘Robots’ and ‘Robotics’. Based on qualitative data analysis, a survey was administered, using a modified version of Schiro's original ‘Curriculum Ideologies Inventory’, in which 157 IT teachers participated. The findings of the study illustrated a direct preference towards the well‐known, widely recognized and highly promoted ‘Social efficiency’ ideology, embellished with remodelled elements of a ‘Learner‐centred’ ideology. Both ‘Social Reconstruction’ and ‘Scholar Academic’ ideologies were perceived as the edges, or the extremes of a continuum, with the first being conceived as too radical and risky, and the second as too traditional and conservative. On the contrary, the study's results also suggested that the process of measuring teachers' curriculum ideologies remains a complex and challenging issue and that teachers' stated curriculum preferences may reflect attributes directly concerned with their professional identity and their experiences in education.
Identification of critical hemodilution by artificial intelligence in bone marrow assessed for minimal residual disease analysis in acute myeloid leukemia: The Cinderella method
Authors: Hoffmann Joerg , Thrun Michael C. , Röhnert Maximilian A. , von Bonin Malte , Oelschlägel Uta , Neubauer Andreas , Ultsch Alfred , Brendel Cornelia
Published: August 2022

Minimal residual disease (MRD) detection is a strong predictor for survival and relapse in acute myeloid leukemia (AML). MRD can be either determined by molecular assessment strategies or via multiparameter flow cytometry. The degree of bone marrow (BM) dilution with peripheral blood (PB) increases with aspiration volume causing consecutive underestimation of the residual AML blast amount. In order to prevent false‐negative MRD results, we developed Cinderella, a simple automated method for one‐tube simultaneous measurement of hemodilution in BM samples and MRD level. The explainable artificial intelligence (XAI) Cinderella was trained and validated with the digital raw data of a flow cytometric “8‐color” AML‐MRD antibody panel in 126 BM and 23 PB samples from 35 patients. Cinderella predicted PB dilution with high accordance compared to the results of the Holdrinet formula (Pearson's correlation coefficient r = 0.94, R2 = 0.89, p < 0.001). Unlike conventional neuronal networks Cinderella calculated the distributions of 12 different cell populations that were assigned to true hematopoietic counterparts as a human in the loop (HIL) approach. Besides characteristic BM cells such as myelocytes and myeloid progenitor cells the XAI identified discriminating populations, which were not specific for BM or PB (e.g., T cell/NK cell subpopulations and CD45 negative cells) and considered their frequency differences. Thus, Cinderella represents a HIL‐XAI algorithm capable to calculate the degree of hemodilution in BM samples with an AML MRD immunophenotype panel. It is explicable, transparent, and paves a simple way to prevent false negative MRD reports.
Lightweight unmanned aerial vehicle video object detection based on spatial‐temporal correlation
Authors: Zhou Pei , Liu GuanJun , Wang Jiacun , Weng QianLi , Zhang KaiWen , Zhou ZiYuan
Published: August 2022

Intelligent unmanned aerial vehicles (UAVs) are drawing more and more attention from industry to academia. UAV navigation plays an important role in the cooperative scenario where multiple UAVs are deployed, while image data that capture the information of the UAV area are often used as input for UAV navigation. Deep learning is a common and powerful technique for UAV image processing, but a complex model generated by deep learning technique is hardly suitable for the limited computing capacity of edge computing devices such as UAVs. Therefore, this paper designs an efficient deep learning model on UAVs to fit the restriction of low computational powers and low power consumption. Traditional UAV object detection methods mostly use static images as the basis for object recognition, or collect images for offline detection. Our method combines the existing fast single‐frame detection methods with the spatial‐temporal relationship of video sequences, to build an efficient end‐to‐end model. In addition, the convolutional LSTM module is used to propagate the temporal context of the video frame sequences. Based on the temporal context, we propose a module for calculating spatial correlation. At the same time, we establish our experimental dataset in our real application and conduct the experiment, which shows that the proposed method reduces the size of models and meanwhile maintains the detection rate. Compared with the existing static images approaches, our method is faster and more accurate. Inference speeds of nearly 20fps can be achieved while performing real‐time tasks.
Prey size is more representative than prey taxa when measuring dietary overlap in sympatric forest bats
Authors: Divoll Timothy J. , Brown Veronica A. , McCracken Gary F. , O'Keefe Joy M.
Published: August 2022

In temperate forests, insectivorous bats need to use variable hunting strategies as prey availability fluctuates during the growing season. At sites with variable amounts of forested habitat, sympatric bat species may exhibit high dietary overlap, but mechanisms of coexistence are unknown. We analyzed the diets of sympatric Myotis septentrionalis and Myotis sodalis in two different landscapes in central Indiana, USA: a riparian agricultural site and a managed forest site, aiming to assess interspecific dietary overlap. We collected fecal samples from 166 Myotis over four maternity seasons and used DNA metabarcoding to assess niche overlap by operational taxonomic units (OTUs, n = 708) and prey‐size taxa (n = 79). Analyzing diets by prey‐size classes, as opposed to only species, provided an alternative interpretation of dietary richness and overlap that may more accurately represent predator perceptions of prey. With overall prey sizes ranging from 2–36 mm, M. septentrionalis (n = 88) consumed larger prey (10.0 ± 5.5 mm, μ ± σ) than M. sodalis (n = 78; 8.9 ± 5.0 mm). Myotis sodalis had a more diverse diet (547 OTUs) compared to M. septentrionalis (453 OTUs) despite the smaller sample size. Of the 708 OTUs detected, 41% (292) were common across bat species. We found greater dietary overlap between species within each site than within either species across sites, suggesting both species mostly consume whatever insects are available on the landscape. Flexible hunting strategies may allow these species to coexist by consuming different sizes of prey at different rates in the tradeoff between travel cost and profitability. Prey size is an important measure for dietary overlap and resource partitioning in bats that few studies have yet considered, with implications for linking predators, prey, and habitats.
IRF8 regulates efficacy of therapeutic anti‐CD20 monoclonal antibodies
Authors: Grzelak Ludivine , Roesch Ferdinand , Vaysse Amaury , Biton Anne , Legendre Rachel , Porrot Françoise , Commère Pierre‐Henri , Planchais Cyril , Mouquet Hugo , Vignuzzi Marco , Bruel Timothée , Schwartz Olivier
Published: August 2022

Anti‐CD20 monoclonal antibodies such as Rituximab, Ofatumumab, and Obinutuzumab are widely used to treat lymphomas and autoimmune diseases. They act by depleting B cells, mainly through Fc‐dependent effectors functions. Some patients develop resistance to treatment but the underlying mechanisms are poorly understood. Here, we performed a genome‐wide CRISPR/Cas9 screen to identify genes regulating the efficacy of anti‐CD20 antibodies. We used as a model the killing of RAJI B cells by Rituximab through complement‐dependent‐cytotoxicity (CDC). As expected, the screen identified MS4A1, encoding CD20, the target of Rituximab. Among other identified genes, the role of Interferon Regulatory Factor 8 (IRF8) was validated in two B‐cell lines. IRF8 KO also decreased the efficacy of antibody‐dependent cellular cytotoxicity and phagocytosis (ADCC and ADCP) induced by anti‐CD20 antibodies. We further show that IRF8 is necessary for efficient CD20 transcription. Levels of IRF8 and CD20 RNA or proteins correlated in normal B cells and in hundreds of malignant B cells. Therefore, IRF8 regulates CD20 expression and controls the depleting capacity of anti‐CD20 antibodies. Our results bring novel insights into the pathways underlying resistance to CD20‐targeting immunotherapies.
Parametric study for N2O conversion and reduction using cobalt‐oxide‐based catalysts
Authors: Rocha‐Meneses Lisandra , Inayat Abrar , Ayoub Muhammad , Ullah Sami , Naqvi Salman R. , Farrukh Sarah , Mustafa Ahmad , Abdullah Ahmad Z. , Bhat Aamir H.
Published: August 2022

Nitrous oxide is a highly reactive gas with several well‐known environmental impacts. Its presence in the atmosphere can decrease the stratospheric ozone levels, cause an increase in the greenhouse gas emissions, and contribute to acid‐rain formation. Therefore, in this article, the potential and performance of different types of cobalt oxide (Co3O4) catalysts in N2O decomposition and conversion was studied. For this, the catalytic activity of these materials was tested in a differential fixed‐bed reactor, operated under steady state conditions. The results obtained in this study show reduced CoO achieved 100% N2O conversion at 250°C; that CoO has a great performance (>95%) in the absence of oxygen and humidity, regardless of the W/F; even at low space velocities (0.1 g−s/ml) and in the absence of humidity the N2O conversion efficiency is still very high (100%); 10%La/CoO has a higher catalytic activity than 10% Ba/CoO, 10% Na/CoO, and 10% W/CoO. The highest catalytic activity (>90%) was reported in samples with 50%La/CoO, even in the presence of 5% H2O and 15% O2.
Spillover effects and other determinants of medical device uptake in the presence of a medical guideline: An analysis of drug‐eluting stents in Germany and Italy
Authors: Möllenkamp Meilin , Pongiglione Benedetta , Rabbe Stefan , Torbica Aleksandra , Schreyögg Jonas
Published: August 2022

We investigated the role of spillover effects among hospitals in the diffusion of drug‐eluting stents (DES) in Germany and Italy during a period in which the relevant medical guideline clearly recommended their use over bare‐metal stents. We used administrative data of hospitalized patients treated with ST‐elevation myocardial infarction from 2012 to 2016 to estimate spatial panel models allowing for global spillover effects. We used an inverse‐distance weights matrix to capture the geographical proximity between neighboring hospitals and assigned a lower weight to more distant neighbors. For both countries, we found significant positive spatial autocorrelation in most years based on the global Moran's I test, and a significant, positive spatial lag parameter across model specifications, indicating positive spillover effects among neighboring hospitals. We found that private for‐profit hospital ownership and hospital competition in Germany and the number of inpatient cases with circulatory system diseases in Italy were other significant determinants of DES adoption. Our results underline the importance of spillover effects among peers for the diffusion of medical devices even in the presence of a positive guideline recommendation. Policymakers might therefore consider promoting various forms of exchange and collaboration among medical staff and hospitals to ensure the appropriate use of medical technologies.
Study of anxiety and job burnout, and awareness among young anesthetists during COVID‐19 pandemic
Authors: Yang Xi , Zuo Yunxia
Published: August 2022

To describe the psychological impact of coronavirus disease 2019 (COVID‐19) on young doctors and their job burnout in the Department of Anesthesiology during the initial days of the pandemic and examine their awareness and familiarity with this pneumonia. We conducted a cross‐sectional study in West China Hospital in February 2020. A self‐designed questionnaire was sent to all young doctors working in the department of anesthesiology. Impact of Event Scale‐Revised and Maslach Burnout Inventory General Survey were used to evaluate the psychological impact and degree of job burnout. Another questionnaire was conducted to explore the awareness and familiarity of COVID‐19. All participants were divided into five groups according to the time of clinical practice: Postgraduate year (PGY) 0.5 (less than 0.5 year), 0.6–1 (0.6–1 year), 1–2 (1–2 years), 2–3 (2–3 years), 3 (more than 3 years) groups. The results were collected and analyzed subsequently. A total of 188 questionnaires were collected. There were significant differences in distress level between PGY 0.5 and PGY 0.6–1 (17.60 ± 12.53 vs. 12.05 ± 10.65; p = 0.029), and PGY 3 and PGY 0.6–1 (19.92 ± 11.88 vs. 12.05 ± 10.65; p = 0.031). As for job burnout, there were no differences among the five subgroups. Most participants (86.70%) were kept in good working condition, and 25 participants showed a mild level of job burnout. Although all of the respondents had high awareness of the basic elements of COVID‐19, they had little knowledge about the details, such as lab tests, release criteria, and recommended therapy, and this result had no significant difference among the five groups. COVID‐19 had caused a mild level of distress and work burnout in young anesthetists. Most of the participants were not clear about the diagnostic, release criteria, and therapeutic method, which will become key teaching points in the future.
Housing: Fragile buffer to wildfire smoke in pregnancy
Authors: Sklar Rachel S. , Padula Amy M.
Published: August 2022

Synopsis

Living near or migrating to areas at high risk for wildfires may result in health consequences and increased disparities for pregnant people and their children.
Zebrafish brain and skull imaging based on polarization‐sensitive optical coherence tomography
Authors: Yang Di , Yuan Zhuoqun , Hu Muyun , Liang Yanmei
Published: August 2022

Zebrafish brain imaging is very important for the study of brain disease and regeneration. We scanned the adult zebrafish brain before and after skull removal and monitored the recovery process of a head wound by polarization‐sensitive optical coherence tomography (PS‐OCT) in this paper. We analyzed the structure and polarization characteristics of the brain and skull in PS‐OCT images, and found their internal microstructure can be clearly identified with the polarization information. Further, we estimated the pigment distribution of the skull area and found that the density of pigment in skull is a critical factor of affecting zebrafish brain in vivo polarization imaging. Our results demonstrated that more features of brain can be displayed by introducing the polarization information, and proved high‐resolution PS‐OCT will play a great potential role in studying the zebrafish brain and skull.
Remote photoplethysmography with consumer smartphone reveals temporal differences between glabrous and nonglabrous skin: Pilot in vivo study
Authors: Burton Timothy , Saiko Gennadi , Cao Meiyun , Douplik Alexandre
Published: August 2022

Photoplethysmography (PPG) is a noninvasive optical technology, with applications including vital sign extraction and patient monitoring. The PPG acquisition skin type may be of importance. Skin is either nonglabrous (~90%) or glabrous (~10%). Clinical PPG collection is typically from glabrous (fingerpad), while proliferating wearables collecting PPG, which may perform critical functions like arrythmia detection, often acquire from atypical sites. Glabrous skin has significant differences from nonglabrous, including microcirculation, yet comparisons between their PPG signals have not been well reported. Using a smartphone‐based remote/contactless PPG, a pilot dataset was collected from the hands (palmar/dorsal) of five healthy volunteers. The data shows statistically significant lead time (52 ± 36 ms) of glabrous over nonglabrous. Further, a trend of glabrous amplitude increase over nonglabrous (31%) was found. Although our study has a small number of participants, these results further the characterization of PPG skin differences, and can be used to inform development of PPG‐based devices.
Strontium‐loaded hydrogel scaffolds to promote gingival fibroblast function
Authors: Alsharif Shahad Bakheet , Wali Rofida , Vanyo Stephen T. , Andreana Sebastiano , Chen Kaiwen , Sheth Bhoomika , Swihart Mark T. , Dziak Rosemary , Visser Michelle B.
Published: August 2022

Dental implant clinical success is dependent on effective peri‐implant tissue attachment to the trans‐mucosal portion following placement. Modification of transmucosal implant surfaces can improve cellular adhesion and function leading to formation of an effective soft‐tissue seal during healing, of which gingival fibroblasts are prominent cells to migrate to repair wounds and crucial for the development of a collagen rich connective tissue. Biocompatible loaded scaffold materials have been developed to allow local release of molecules with effective biological activity. Our previous studies indicate that strontium can promote gingival fibroblast metabolism, decrease apoptosis and support adhesion to titanium healing abutments. In this study, we developed a strontium‐loaded alginate hydrogel scaffold which can be easily personalized to fit over any size and shape of implant transmucosal collar or healing abutment. Results indicate that biologically active strontium ions are effectively released from loaded alginate hydrogel material to promote fibroblast viability and migration to repair in vitro wounds similar to that of strontium citrate solution. Overall, this novel strontium‐loaded alginate scaffold device displays good biocompatibility and functionality, demonstrating high potential as a system to provide local delivery of strontium to improve peri‐implant mucosal healing following implant placement and clinical success.
Potentially functional genetic variants of VAV2 and PSMA4 in the immune‐activation pathway and non‐small cell lung cancer survival
Authors: Bai Yushun , Zheng Ji , Cheng Lei , Liu Qi , Zhao Genming , Li Jingrao , Gu Yanzi , Xu Wanghong , Wang Mengyun , Wei Qingyi , Zhang Ruoxin
Published: August 2022

Background

Lung cancer has the highest mortality among cancers, represented by a low 5‐year survival rate. The function of the immune system has a profound influence on the development and progression of lung cancer. Thus genetic variants of the immune‐related genes may serve as potential predictors of non‐small cell lung cancer (NSCLC) survival.

Methods

In the present study, we conducted a two‐stage survival analysis in 1,531 NSCLC patients and assessed the associations between genetic variants in the immune‐activation gene set and the overall survival (OS) of NSCLC patients. The validated variants were further subjected to functional annotation and in vitro experiments.

Results

We identified 25 SNPs spanning six loci associated with NSCLC OS after multiple‐testing corrections in all datasets, in which two variants, PSMA4 rs12901682 A > C and VAV2 rs12002767 C > T, were shown to potentially affect lung cancer OS by cis‐regulating the expression of the corresponding genes [(HR (95% CI) = 0.76 (0.65–0.89) and 1.36 (1.12–1.65), p = 4.29 × 10−4 and 0.002, respectively].

Conclusion

Our findings provide new insights into the role of genetic variants in the immune‐activation pathway genes in lung cancer progression.
Single-cell phenotypic profiling to identify a set of immune cell protein biomarkers for relapsed and refractory diffuse large B cell lymphoma: A single-center study
Authors: Shi Yuan , Ding Weidong , Gu Weiying , Shen Yangling , Li Haiqian , Zheng Zhuojun , Zheng Xiao , Liu Yan , Ling Yun
Published: August 2022

Diffuse large B-cell lymphoma (DLBCL) is the most common invasive type of non-Hodgkin lymphoma. Cell-of-origin (COO) classification is related to patients’ prognoses. Primary drug resistance in treatment for DLBCL has been observed. The specific serum biomarkers in these patients who suffer from relapsed and refractory (R/R)-DLBCL remains unclear. In the current study, using single-cell RNA sequencing (scRNA-seq) and mass cytometry (CyTOF), we determined and verified immune cell biomarkers at the mRNA and protein levels in single-cell resolution from 18 diagnostic PBMC specimens collected from patients with R/R DLBCL. As controls, 5 PBMC specimens from healthy volunteers were obtained. We identified a panel of 35 surface marker genes for the features of R/R DLBCL unique cell cluster by scRNA-seq of 8 R/R DLBCL patient samples and validated its efficiency in an external cohort consisting of 10 R/R DLBCL patients by CyTOF. The cell clustering and dimension reduction were compared among R/R DLBCL samples in CyTOF Space with COO as well as the C-MYC expression designation. Immune cells from each patient occupied unique regions in the 32-dimensional phenotypic space with no apparent clustering of samples into discrete subtypes. Significant heterogeneity observed in subgroups was mainly attributed to individual differences among samples and not to expression differences in a single, homogeneous immune cell subpopulation. The marker panel showed reliability in labeling R/R DLBCL without any influence from COO stratification and C-MYC expression designation. Furthermore, we compared all the markers between R/R DLBCL and normal samples. A total of 12 biomarkers were significantly overexpressed in R/R DLBCL relative to the normal samples. Therefore, we further optimized the diagnostic biomarker panel of R/R DLBCL comprising CD82, CD55, CD36, CD63, CD59, IKZF1, CD69, CD163, CD14, CD226, CD84, and CD31. In summary, we developed a novel set of biomarkers for the diagnoses of patients with R/R DLBCL. Detections procedures at single-cell resolution provide precise biomarkers, which may substantially overcome intertumoral and intratumoral heterogeneity among primary samples. The findings confirmed that each case was unique and may comprise multiple, genetically distinct subclones.
Inhibition of MEK signaling prevents SARS‐CoV2‐induced lung damage and improves the survival of infected mice
Authors: Xie Jingwu , Klemsz Michael J. , Kacena Melissa A. , Sandusky George , Zhang Xiaoli , Kaplan Mark H.
Published: August 2022

Coronavirus disease 2019 (COVID‐19) is the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Over 500 million confirmed cases of COVID‐19 have been recorded, with six million deaths. Thus, reducing the COVID‐19‐related medical burden is an unmet need. Despite a vaccine that is successful in preventing COVID‐19‐caused death, effective medication to relieve COVID‐19‐associated symptoms and alleviate disease progression is still in high demand. In particular, one in three COVID‐19 patients have signs of long COVID syndrome and are termed, long haulers. At present, there are no effective ways to treat long haulers. In this study, we determine the effectiveness of inhibiting mitogen‐activated protein kinase (MEK) signaling in preventing SARS‐CoV‐2‐induced lung damage in mice. We showed that phosphorylation of extracellular signal‐regulated kinase, a marker for MEK activation, is high in SARS‐CoV‐2‐infected lung tissues of mice and humans. We also showed that selumetinib, a specific inhibitor of the upstream MEK kinases, reduces cell proliferation, reduces lung damage following SARS‐CoV‐2 infection, and prolongs the survival of the infected mice. Selumetinib has been approved by the US Food and Drug Administration to treat cancer. Further analysis indicates that amphiregulin, an essential upstream molecule, was upregulated following SARS‐CoV‐2 infection. Our data suggest that MEK signaling activation represents a target for therapeutic intervention strategies against SARS‐CoV‐2‐induced lung damage and that selumetinib may be repurposed to treat COVID‐19.
Inter‐Rater Reliability of Thyroid Ultrasound Risk Criteria: A Systematic Review and Meta‐Analysis
Authors: Staibano Phillip , Ham Jennifer , Chen Jennifer , Zhang Han , Gupta Michael K.
Published: August 2022

Objective

The most commonly employed diagnostic criteria for identifying thyroid nodules include Thyroid Imaging and Reporting Data System (TI‐RADS) and American Thyroid Association (ATA) guidelines. The purpose of this systematic review and meta‐analysis is to determine the inter‐rater reliability of thyroid ultrasound criteria.

Methods

We performed a library search of MEDLINE (Ovid), EMBASE (Ovid), and Web of Science for full‐text articles published from January 2005 to June 2022. We included full‐text primary research articles that used TI‐RADS and/or ATA guidelines to evaluate thyroid nodules in adults. These included studies must have calculated inter‐rater reliability using any validated metric. The Quality Appraisal for Reliability Studies (QAREL) was used to assess study quality. We planned for a random‐effects meta‐analysis, in addition to covariate and publication bias analyses. This study was performed in accordance with Preferred Reporting Items for a Systematic Review and Meta‐analysis guidelines and registered prior to conduction (International prospective register of systematic reviews—PROSPERO: CRD42021275072).

Results

Of the 951 articles identified via the database search, 35 met eligibility criteria. All studies were observational. The most commonly utilized criteria were ACR Thyroid Imaging and Reporting Data System (TI‐RADS) and/or ATA criteria, while the majority of studies employed Κ statistics. For ACR TI‐RADS, the pooled Κ was 0.51 (95% confidence interval [CI]: 0.42, 0.57; n = 7) while for ATA, the pooled Κ was 0.52 (95% CI: 0.37, 0.67; n = 3). Due to the small number of studies, covariate or publication bias analyses were not performed.

Conclusion

Ultrasound criteria demonstrate moderate inter‐rater reliability, but these findings are impacted by poor study quality and a lack of standardization. Laryngoscope, 133:485–493, 2023
Operationalizing an integrative socio‐ecological framework in support of global monitoring of land degradation
Authors: Pricope Narcisa G. , Daldegan Gabriel A. , Zvoleff Alex , Mwenda Kevin M. , Noon Monica , Lopez‐Carr David
Published: August 2022

Despite sustained global efforts to avoid, reduce, and reverse land degradation, estimates of land degradation nationally and regionally vary considerably. Land degradation reduces agricultural productivity, impacts the provision of vital ecosystem services, and disproportionately affects vulnerable populations. The 2030 Agenda for Sustainable Development, through Sustainable Development Goal 15.3, sets out to achieve land degradation neutrality (LDN) by improving the livelihoods of those most affected and building resilience in areas affected by or at risk from degradation. The United Nations Convention to Combat Desertification (UNCCD) leads the charge in creating a spatially explicit framework for monitoring and reporting on LDN goals that countries can integrate into their land planning policies. However, it remains difficult to operationalize the integration of biophysical indicators of land degradation with climatic and socio‐economic indicators to assess the impact of land degradation on vulnerable populations. We present an integrative framework that demonstrates how freely available global geospatial data sets can be leveraged through an open‐source platform (Trends.Earth) to simplify and operationalize monitoring and reporting on progress towards achieving LDN. Then, we summarize a suite of data sets and approaches that can be used to understand and quantify the socio‐ecological interactions between drought, land degradation and population exposed to desertification, land degradation and drought. We discuss how improvements in Earth observation data sets and algorithms will allow UNCCD land‐based progress sub‐indicators (changes in primary productivity, land cover, soil organic carbon, drought, and population exposure) to be computed at enhanced spatial resolutions.
Chemical Cascading Between Polymersomal Nanoreactor Populations
Authors: Altay Yigit , Llopis‐Lorente Antoni , Abdelmohsen Loai K. E. A. , van Hest Jan C.M.
Published: August 2022

Harnessing interactions of functional nano‐compartments to generate larger particle assemblies allows studying diverse biological behaviors based on their population states and can lead to the development of smart materials. Herein, thiol‐functionalized polymersome nanoreactors are utilized as responsive organelle‐like nano‐compartments—with inherent capacity to associate into larger aggregates in response to change in the redox state of their environment—to study the kinetics of cascade reactions and explore functions of their collective under different population states. Two nanoreactor populations, glucose oxidase‐ and horseradish peroxidase‐loaded polymersomes, are prepared, and the results of their cascading upon addition of glucose are investigated. The kinetics of resorufin production in associated polymersomes and non‐associated polymersome populations are compared, observing a decreased rate upon association. For the associated populations, faster chemical cascading is found when the two types of nanoreactors are associated in a concerted step, as compared to sequential association. The addition of competing agents such as catalase impacts the communication between non‐associated polymersomes, whereas such an effect is less pronounced for the associated ones. Altogether, the results showcase the impact of collective associations on enzymatic cascading between organelle‐like nanoreactors.
Automorphism invariant measures and weakly generic automorphisms
Authors: Sági Gábor
Published: August 2022

Let be a countable ℵ0‐homogeneous structure. The primary motivation of this work is to study different amenability properties of (subgroups of) the automorphism group of ; the secondary motivation is to study the existence of weakly generic automorphisms of . Among others, we present sufficient conditions implying the existence of automorphism invariant probability measures on certain subsets of A and of ; we also present sufficient conditions implying that the theory of is amenable. More concretely, we show that if the set of locally finite automorphisms of is dense (in particular, if has weakly generic tuples of automorphisms of arbitrary finite length), then there exists a finitely additive probability measure μ on the subsets of definable with parameters such that μ is invariant under . Moreover, if is saturated and the set of its locally finite automorphisms is dense (in particular, if is saturated and has weak generics), then the theory of is amenable.
Yeast β‐Glucan Improves Insulin Sensitivity and Hepatic Lipid Metabolism in Mice Humanized with Obese Type 2 Diabetic Gut Microbiota
Authors: Mitchelson Kathleen A. J. , Tran Tam T. T. , Dillon Eugene T. , Vlckova Klara , Harrison Sabine M. , Ntemiri Alexandra , Cunningham Katie , Gibson Irene , Finucane Francis M. , O'Connor Eibhlís M. , Roche Helen M. , O'Toole Paul W.
Published: August 2022

Scope

Gut microbiota alterations are associated with obesity and type 2 diabetes. Yeast β‐glucans are potential modulators of the innate immune‐metabolic response, by impacting glucose, lipid, and cholesterol homeostasis. The study examines whether yeast β‐glucan interacts differentially with either an obese healthy or obese diabetic gut microbiome, to impact metabolic health through hepatic effects under high‐fat dietary challenge.

Methods and results

Male C57BL/6J mice are pre‐inoculated with gut microbiota from obese healthy (OBH) or obese type 2 diabetic (OBD) subjects, in conjunction with a high‐fat diet (HFD) with/without yeast β‐glucan. OBD microbiome colonization adversely impacts metabolic health compared to OBH microbiome engraftment. OBD mice are more insulin resistant and display hepatic lipotoxicity compared to weight matched OBH mice. Yeast β‐glucan supplementation resolves this adverse metabolic phenotype, coincident with increasing the abundance of health‐related bacterial taxa. Hepatic proteomics demonstrates that OBD microbiome transplantation increases HFD‐induced hepatic mitochondrial dysfunction, disrupts oxidative phosphorylation, and reduces protein synthesis, which are partly reverted by yeast β‐glucan supplementation.

Conclusions

Hepatic metabolism is adversely affected by OBD microbiome colonization with high‐fat feeding, but partially resolved by yeast β‐glucan. More targeted dietary interventions that encompass the interactions between diet, gut microbiota, and host metabolism may have greater treatment efficacy.
Voxel‐based finite elements with hourglass control in fast Fourier transform‐based computational homogenization
Authors: Schneider Matti
Published: August 2022

The power of fast Fourier transform (FFT)‐based methods in computational micromechanics critically depends on a seamless integration of discretization scheme and solution method. In contrast to solution methods, where options are available that are fast, robust and memory‐efficient at the same time, choosing the underlying discretization scheme still requires the user to make compromises. Discretizations with trigonometric polynomials suffer from spurious oscillations in the solution fields and lead to ill‐conditioned systems for complex porous materials, but come with rather accurate effective properties for finitely contrasted materials. The staggered grid discretization, a finite‐volume scheme, is devoid of bulk artifacts in the solution fields and works robustly for porous materials, but does not handle anisotropic materials in a natural way. Fully integrated finite‐element discretizations share the advantages of the staggered grid, but involve a higher memory footprint, require a higher computational effort due to the increased number of integration points and typically overestimate the effective properties. Most widely used is the rotated staggered grid discretization, which may also be viewed as an underintegrated trilinear finite element discretization, which does not impose restrictions on the constitutive law, has fewer artifacts than Fourier‐type discretizations and leads to rather accurate effective properties. However, this discretization comes with two downsides. For a start, checkerboard artifacts are still present. Second, convergence problems occur for complex porous microstructures. The work at hand introduces FFT‐based solution techniques for underintegrated trilinear finite elements with hourglass control. The latter approach permits to suppress local hourglass modes, which stabilizes the convergence behavior of the solvers for porous materials and removes the checkerboards from the local solution field. Moreover, the hourglass‐control parameter can be adjusted to “soften” the material response compared to fully integrated elements, using only a single integration point for nonlinear analyses at the same time. To be effective, the introduced technology requires a displacement‐based implementation. The article exposes an efficient way for doing so, providing minimal interfaces to the most commonly used solution techniques and the appropriate convergence criterion.
Ghanaian nurses' and midwives' perspectives on technology adoption in nursing and midwifery education
Authors: Adjei Charles Ampong , Adjorlolo Samuel , Kyei Josephine , Ohene Lillian Akorfa , Dzansi Gladys , Acheampong Angela Kwartemaa , Asante Isabella Naana Akyaa , Woolley Philomena , Nyante Felix , Aziato Lydia
Published: August 2022

Aim

The purpose of this study was to explore the perceived benefits and challenges of online distance education and computer‐based testing (CBT) among registered nurses and midwives in a sample of government‐owned health facilities and health training institutions in Ghana.

Design

Exploratory descriptive qualitative design.

Methods

Individual semi‐structured interviews were conducted with 45 participants (i.e. 25 nurses and 20 midwives). The data were manually processed and analysed using Braun and Clarke’s thematic analysis approach (November 2019‐February 2020).

Results

Nurses and midwives prefer online distance education for three reasons: convenience, cost‐effectiveness and learning centre proximity to the workplace. The course schedule’s flexibility allowed participants to work and study simultaneously. Others acknowledged online distance education as a viable option for overcoming the challenges of obtaining study leave. However, the lack of recognition of certificates by some employers, poor Internet connectivity and perceived excessive course load were noted as deterrents. Regarding the CBT, many of the participants said that it was useful. Among the advantages of CBT are: (1) a decrease in examination malpractices, (2) a decrease in examination costs and (3) a rise in students’ interest in information, communication and technology (ICT). This finding emphasizes the necessity of integrating ICT into nursing and midwifery education and examinations, as well as maximizing its benefits.