bluuebunny/crossref_metadata_2025 huggingface dataset:
Can counter-advertising exposing alcohol sponsorship and harms influence sport spectators’ support for alcohol policies? An experimental study
Authors: Scully Maree , Dixon Helen , Brennan Emily , Niederdeppe Jeff , O’Brien Kerry , Pettigrew Simone , Vandenberg Brian , Wakefield Melanie
Published: February 2023

Background

Exposure to alcohol advertising and sponsorship through elite sport is associated with harmful use of alcohol. Owing to strong financial and cultural ties between alcohol and sport in Australia, policy action to restrict alcohol sport sponsorship is unlikely to occur without strong public support for change. This study tested whether exposure to counter-advertising exposing industry marketing of harmful products—a technique shown to be effective in tobacco control—promotes higher support for policy change and less favourable beliefs about the alcohol industry among sport spectators.

Methods

A sample of 1,075 Australian adults aged 18–49 years who planned to watch an National Rugby League (NRL) State of Origin series game, featuring prominent alcohol sponsorship, was recruited through an online panel and randomly assigned to one of three conditions: control (neutral advertisement); counter-advertisement exposing alcohol harms; counter-advertisement exposing alcohol sponsorship and harms. Participants completed a pre-test questionnaire and viewed their assigned counter-advertisement multiple times in the 5–7 days before the NRL game. Within four days of watching the game, participants completed post-test measures.

Results

Compared to both the control advertisement and the counter-advertisement exposing alcohol harms, participants who viewed the counter-advertisement exposing alcohol sponsorship and harms were significantly more likely to indicate support for each of four policies aimed at restricting sports-related alcohol marketing, including the complete removal of alcohol sponsorship from sport (51% vs. 32% and 37%). They were also significantly less likely to agree with statements such as “alcohol companies should be allowed to sponsor sport since their products are legal” (39% vs. 63% and 60%) and significantly less likely to report liking alcohol companies in general (38% vs. 59% and 54%). There were no significant differences in policy support or industry beliefs between participants who saw the counter-advertisement exposing alcohol harms and those who saw the control advertisement.

Conclusion

Counter-advertising employing messages that expose and critique the intent and impact of pervasive alcohol sponsorship in sport has potential to bolster public support for policies targeting alcohol sport sponsorship, diminish beliefs supportive of alcohol industry marketing strategies and enhance negative views of alcohol companies and their marketing practices.
COVID-19 vaccination coverage in Egypt: a large-scale national survey – to help achieving vaccination target, March-May, 2022
Authors: Kandeel Amr , Eldeyahy Ibrahim , Abu ElSood Hanaa , Fahim Manal , Afifi Salma , Abu Kamar Shaimaa , BahaaEldin Hala , Ahmed ElSabbah , Mohsen Amira , Abdelghaffar Khaled
Published: February 2023

Background

Only 57 countries have vaccinated 70% of their population against COVID-19, most of them in high-income countries, whereas almost one billion people in low-income countries remained unvaccinated. In March–May 2022, Egypt's Ministry of Health and Population (MoHP) conducted a nationwide community-based survey to determine COVID-19 vaccine coverage and people's perceptions of vaccination in order to improve COVID-19 vaccination uptake and confidence among Egyptians, as well as to prioritize interventions.

Methods

A cross-sectional population-based household survey among Egyptians ≥ 18 years of age was implemented in two phases using a multistage random sampling technique in all of Egypt’s 27 governorates. A sample of 18,000 subjects divided into 450 clusters of 20 households each was calculated in proportion to each governorate and the main occupation of the population. Participants were interviewed using a semistructured questionnaire that included demographics, vaccination information from the vaccination card, history of COVID-19 infection, reasons for vaccine refusal among the unvaccinated, and vaccination experience among vaccinated subjects. Vaccination coverage rates were calculated by dividing numbers by the total number of participants. Bivariate and multivariate analyses were performed by comparing the vaccinated and unvaccinated to identify the risk factors for low vaccine uptake.

Results

Overall 18,107 were interviewed, their mean age was 42 ± 16 years and 58.8% were females. Of them, 8,742 (48.3%) had COVID-19 vaccine and 8,020 (44.3%) were fully vaccinated. Factors associated with low vaccination uptake by multivariate analysis included: age groups (18–29 and 30–39) (ORs 2.0 (95% C.I. 1.8–2.2) and 1.3 (95% C.I.1.2–1.4), respectively), residences in urban or frontier governorates (ORs 1.6 (95% C.I. 1.5–1.8) and 1.2 (95% C.I. 1.1–1.4), respectively), housewives and self-employed people (ORs 1.3 (95% C.I. 1.2–1.4) and 1.2 (95% C.I. 1.1–1.4), respectively), married people (ORs 1.3 (95% C.I. 1.2–1.4), and primary and secondary educated (ORs 1.1 (95% C.I. 1.01–1.2) and 1.1(1.04–1.2) respectively). Vaccine hesitancy was due to fear of adverse events (17.5%), mistrust of vaccine (10.2%), concern over safety during pregnancy and lactation (6.9%), and chronic diseases (5.0%).

Conclusions

Survey identified lower vaccination coverage in Egypt compared to the WHO 70% target. Communication programs targeting the groups with low vaccine uptake are needed to eliminate barriers related to vaccination convenience, side effects, and safety to effectively promote vaccine uptake. Findings from the survey could contribute significantly to vaccination promotion by guiding decision-making efforts on the risky groups and preventing vaccine hesitancy.
Evaluating and comparing critical thinking skills of residents of Tehran University of Medical Sciences
Authors: Mehrpour Saeed Reza , Hoseini Shavoun Amin , Kheiltash Azita , Masoomi Rasoul , Nasle Seraji Roya
Published: February 2023

Background

Today’s complexities and diversity in the clinical setting have revealed the need to pay attention to strengthening critical thinking (CT) skills. The present study aimed to evaluate and compare CT skills in the residents of the Tehran University of Medical Sciences.

Methods

This is a cross-sectional study. The study's statistical population included 284 residents in orthopedic, internal medicine, and surgery groups studying in the PGY1 to PGY4 years of residency. The data collection tool was the California Critical Thinking Skills Test (CCTST) form B. The collected data were entered into SPSS-16 software and analyzed using descriptive (mean and standard deviation) and inferential (one-way ANOVA) statistics. The significant level in all tests was considered at P < 0.05.

Results

189 out of 284 residents completed and returned the questionnaire, and the response rate was 66%. The mean CT skill score of residents (M = 13.81, SD = 3.52) was lower than the optimal level (M = 17.1 SD = 5.0). Comparing the mean CT skill scores of the residents separately for the residency year revealed a significant decrease in CT scores in the 4 years. A significant difference was found between the CT skill scores in the three groups (internal medicine, general surgery, and orthopedic surgery).

Conclusion

The CT skills of the residents of Tehran University of Medical Sciences were generally below the optimal level. The CT score of the residents show an increase in PGY2, but a decrease in PGY3 and PGY4. Due to the emphasis of accreditation institutions, the World Federation for Medical Education, and other international educational institutions on the importance of critical thinking, it is recommended to pay more attention to the factors related to the promotion and development of CT skills in residency programs.
Reasons clinical education directors intend to leave their jobs
Authors: Klein Alicia , Schrode Katrina , Kibe Lucy , Kayingo Gerald
Published: February 2023

Objectives

The goals of this study were to characterize clinical coordinators compared to other Physician Assistant (PA) faculty, and investigate factors associated with intent to leave their position, institution, and academia in the U.S.

Methods

This was a secondary analysis of data obtained from the 2019 Physician Assistant Education Association (PAEA) Faculty and Directors Survey. We examined bivariate associations with faculty role and conducted multiple logistic regression to identify predictors of intent to leave among clinical directors.

Results

Clinical directors indicated an intention to leave their position more often than other faculty. Factors influencing intent to leave were a lack of satisfaction with professional development and moderate to high levels of burnout. Clinical directors with severe burnout had 27x the odds of intending to leave academia.

Conclusions

Our results suggest why clinical directors intend to leave and underscore the need for professional development opportunities and faculty mentoring. Faculty-centered work arrangements are needed to reduce burnout among clinical directors.
Dynamics of career intentions in a medical student cohort: a four-year longitudinal study
Authors: Pfarrwaller Eva , Voirol Lionel , Karemera Mucyo , Guerrier Stéphane , Baroffio Anne
Published: February 2023

Background

Medical students’ career intentions often change between matriculation and graduation, yet little is known about the precise timing and dynamics of individual students’ career decisions. This study expands on previous research by exploring the stability of individual students’ career intentions over four years and by analyzing associations between unstable career intentions and students’ characteristics.

Methods

Medical students from two classes were recruited into a cohort during their first academic year and completed a yearly survey over a four-year period (end of pre-clinical curriculum to graduation). Measures included career intention (specialty and practice type), personality, coping strategies, empathy, and motives for becoming a physician. The authors developed a score ranging from 0 to 10 quantifying instability of career intentions (0 = stable; 10 = unstable). The distribution of the score was analyzed descriptively, and the association between the score and other variables was quantified using a stepwise beta regression model.

Results

The sample included 262 students (61% females). The mean score was 3.07 with a median of 3. 18% of students (N = 46) did not change their specialty intention over the four years, whereas 10% (N = 26) changed every year. No further subgroups were identified between these extremes. An intention to work in private practice in year 3 and the motive care for patients were significantly associated with more stable career intentions.

Conclusion

Most students are situated on a continuum between the two extremes of being firmly committed and undecided. Extrinsic factors may be more important drivers of these fluctuations than personal characteristics and should be explored in future research. This study’s findings also provide avenues for supporting students in their career decision-making.
Evaluation of the Training in Early Detection for Early Intervention (TEDEI) e-learning course using Kirkpatrick’s method
Authors: Officer Eleanor , Johnson Maisie , Blickwedel Jessica , Reynolds Ashley , Pearse Rachel , Pearse Janice , Basu Anna Purna
Published: February 2023

Background

Early intervention in cerebral palsy could improve motor outcome but is only possible following early identification of those affected. There is a need for training of healthcare professionals (HCPs) in early detection of atypical motor development. We developed a video-based e-learning course - Training in Early Detection for Early Intervention (TEDEI) - to address this need. We evaluated whether participation in the course improved knowledge and changed behaviour of HCPs.

Methods

Participants were 332 HCPs (38% physiotherapists, 35.8% occupational therapists), predominantly UK-based (83.7%). Analysis of training effects used mixed methods and followed Kirkpatrick’s model, first assessing “Reaction” through a feedback questionnaire involving Likert scale and free text responses (n = 141). “Learning” was assessed through multiple choice questions (MCQs): all 332 HCPs completed a pre-course quiz of 6 MCQs followed by the course, then a 16 item post-course quiz including the 6 pre-course questions. “Behaviour” was assessed through in-depth qualitative interviewing of 23 participants.

Results

“Reaction”: TEDEI was found to be effective, engaging and well structured. “Learning”: Scores improved significantly between the pre-course and post-course quiz, median improvement 1/6 (z = 5.30, p < 0.001). HCPs also reported a perceived improvement in their knowledge, confidence and ability. “Behaviour”: HCPs could see how TEDEI would improve their clinical practice through having an assessment framework, ways of working better with parents, and developing observational skills useful for tele-health assessments.

Conclusion

Our brief e-learning course on early detection for early intervention was viewed positively, improved knowledge and showed potential for positive changes in practice. Kirkpatrick’s model provided a useful framework for undertaking this evaluation.
Spontaneous autoimmune subepidermal blistering diseases in animals: a comprehensive review
Authors: Bizikova Petra , Olivry Thierry , Linder Keith , Rybnicek Jan
Published: February 2023

Autoimmune subepidermal blistering diseases (AISBDs) are rare skin disorders of animals that were first identified in dogs but several AISBDs are now recognised in other companion animal species. Most AISBDs in animals are homologues of the human diseases and are thought to share similar pathomechanisms of epidermal and/or mucosal blister formation caused by autoantibodies targeting structural proteins of the basement membrane zone (BMZ). Disruption of their structural function by the autoantibodies and/or recruited inflammation leads to BMZ fragility, which presents clinically as vesicles, bullae and, later, deep erosions and ulcers. Canine AISBDs are the best characterised, particularly the more common variants such as mucous membrane pemphigoid (48%), epidermolysis bullosa acquisita (EBA) (26%), and bullous pemphigoid (10%). Exceedingly rare AISBDs in the dog are junctional EBA, mixed AISBD, type-1 bullous systemic lupus erythematosus, linear IgA dermatosis, and pemphigus gestationis. The diagnosis of a specific AISBD is made by combining the clinical features (breed, age, lesion distribution) with histological evidence of subepithelial clefting, but not all AISBDs can be differentiated in this manner and specialised immunological testing is required. This latter, unfortunately, is not readily available and, therefore, the specific AISBD diagnosis often remains unconfirmed. While this limits further understanding of these diseases, it does not prevent clinicians from treating their patients, as the treatment approaches are similar for the different AISBDs in dogs. This review primarily focuses on canine AISBDs, the species for which these diseases have been best characterised, and shorter descriptions of variants in other species are also provided.
New biomarkers exploration and nomogram construction of prognostic and immune-related adverse events of advanced non-small cell lung cancer patients receiving immune checkpoint inhibitors
Authors: Lin Xuwen , Chen Xi , Long Xiang , Zeng Chao , Zhang Zhihan , Fang Weiyi , Xu Ping
Published: February 2023

Background

Immune checkpoint inhibitors (ICIs) are regarded as the most promising treatment for advanced-stage non-small cell lung cancer (aNSCLC). Unfortunately, there has been no unified accuracy biomarkers and systematic model specifically identified for prognostic and severe immune-related adverse events (irAEs). Our goal was to discover new biomarkers and develop a publicly accessible method of identifying patients who may maximize benefit from ICIs.

Methods

This retrospective study enrolled 138 aNSCLC patients receiving ICIs treatment. Progression-free survival (PFS) and severe irAEs were end-points. Data of demographic features, severe irAEs, and peripheral blood inflammatory-nutritional and immune indices before and after 1 or 2 cycles of ICIs were collected. Independent factors were selected by least absolute shrinkage and selection operator (LASSO) combined with multivariate analysis, and incorporated into nomogram construction. Internal validation was performed by applying area under curve (AUC), calibration plots, and decision curve.

Results

Three nomograms with great predictive accuracy and discriminatory power were constructed in this study. Among them, two nomograms based on combined inflammatory-nutritional biomarkers were constructed for PFS (1 year-PFS and 2 year-PFS) and severe irAEs respectively, and one nomogram was constructed for 1 year-PFS based on immune indices. ESCLL nomogram (based on ECOG PS, preSII, changeCAR, changeLYM and postLDH) was constructed to assess PFS (1-, 2-year-AUC = 0.893 [95% CI 0.837–0.950], 0.828 [95% CI 0.721–0.935]). AdNLA nomogram (based on age, change-dNLR, changeLMR and postALI) was constructed to predict the risk of severe irAEs (AUC = 0.762 [95% CI 0.670–0.854]). NKT-B nomogram (based on change-CD3+CD56+CD16+NKT-like cells and change-B cells) was constructed to assess PFS (1-year-AUC = 0.872 [95% CI 0.764–0.965]). Although immune indices could not be modeled for severe irAEs prediction due to limited data, we were the first to find CD3+CD56+CD16+NKT-like cells were not only correlated with PFS but also associated with severe irAEs, which have not been reported in the study of aNSCLC-ICIs. Furthermore, our study also discovered higher change-CD4+/CD8+ ratio was significantly associated with severe irAEs.

Conclusions

These three new nomograms proceeded from non-invasive and straightforward peripheral blood data may be useful for decisions-making. CD3+CD56+CD16+NKT-like cells were first discovered to be an important biomarker for treatment and severe irAEs, and play a vital role in distinguishing the therapy response and serious toxicity of ICIs.
Effective production of kojic acid in engineered Aspergillus niger
Authors: Wu Liu , Zhang Licheng , Li Xiaojie , Lv Ruitong , Cao Wei , Gao Weixia , Liu Jiao , Xie Zhoujie , Liu Hao
Published: February 2023

Background

Kojic acid (KA) is a widely used compound in the cosmetic, medical, and food industries, and is typically produced by Aspergillus oryzae. To meet increasing market demand, it is important to optimize KA production through seeking alternatives that are more economic than current A. oryzae-based methods.

Results

In this study, we achieved the first successful heterologous production of KA in Aspergillus niger, an industrially important fungus that does not naturally produce KA, through the expression of the kojA gene from A. oryzae. Using the resulting KA-producing A. niger strain as a platform, we identified four genes (nrkA, nrkB, nrkC, and nrkD) that negatively regulate KA production. Knocking down nrkA or deleting any of the other three genes resulted in a significant increase in KA production in shaking flask cultivation. The highest KA titer (25.71 g/L) was achieved in a pH controlled batch bioreactor using the kojA overexpression strain with a deletion of nrkC, which showed a 26.7% improvement compared to the KA titer (20.29 g/L) that was achieved in shaking flask cultivation.

Conclusion

Our study demonstrates the potential of using A. niger as a platform for studying KA biosynthesis and regulation, and for the cost-effective production of KA in industrial strain development.
Sensor-based assessment of social isolation in community-dwelling older adults: a scoping review
Authors: Khan Shehroz S. , Gu Tiancheng , Spinelli Lauren , Wang Rosalie H.
Published: February 2023

Social isolation (SI) is a state of low social interaction with peers associated with various adverse health consequences in older adults living in the community. SI is most often assessed through retrospective self-reports, which can be prone to recall or self-report biases and influenced by stigma. Ambient and wearable sensors have been explored to objectively assess SI based on interactions of a person within the environment and physiological data. However, because this field is in its infancy, there is a lack of clarity regarding the application of sensors and their data in assessing SI and the methods to develop these assessments. To understand the current state of research in sensor-based assessment of SI in older adults living in the community and to make recommendations for the field moving forward, we conducted a scoping review. The aims of the scoping review were to (i) map the types of sensors (and their associated data) that have been used for objective SI assessment, and (ii) identify the methodological approaches used to develop the SI assessment. Using an established scoping review methodology, we identified eight relevant articles. Data from motion sensors and actigraph were commonly applied and compared and correlated with self-report measures in developing objective SI assessments. Variability exists in defining SI, feature extraction and the use of sensors and self-report assessments. Inconsistent definitions and use of various self-report scales for measuring SI create barriers to studying the concept and extracting features to build predictive models. Recommendations include establishing a consistent definition of SI for sensor-based assessment research and development and consider capturing its complexity through innovative domain-specific features.
“They talked to me rudely”. Women perspectives on quality of post-abortion care in public health facilities in Kenya
Authors: Ouedraogo Ramatou , Kimemia Grace , Igonya Emmy Kageha , Athero Sherine , Wanjiru Shelmith , Bangha Martin , Juma Kenneth
Published: February 2023

Background

Access to safe abortion is legally restricted in Kenya. Therefore, majority women seeking abortion services in such restrictive contexts resort to unsafe methods and procedures that result in complications that often require treatment in health facilities. Most women with abortion-related complications end up in public health facilities. Nevertheless, evidence is limited on the quality of care provided to patients with abortion complications in public health facilities in Kenya.

Methods

Data for this paper are drawn from a qualitative study that included interviews with 66 women who received post-abortion care in a sample of primary, secondary and tertiary public health facilities in Kenya between November 2018 and February 2019. The interviews focused on mechanisms of decision-making while seeking post-abortion care services, care pathways within facilities, and perceptions of patients on quality of care received including respect, privacy, confidentiality, communication and stigma.

Findings

The participants’ perceptions of the quality of care were characterized as either “bad care” or “good care”, with the good care focusing on interpersonal aspects such as friendliness, respect, empathy, short waiting time before receiving services, as well as the physical or functional aspects of care such as resolution of morbidity and absence of death. Majority of participants initially reported that they received “good care” because they left the facility with their medical problem resolved. However, when probed, about half of them reported delays in receiving care despite their condition being an emergency (i.e., severe bleeding and pain). Participants also reported instances of abuse (verbal and sexual) or absence of privacy during care and inadequate involvement in decisions around the nature and type of care they received. Our findings also suggest that healthcare providers treated patients differently based on their attributes (spontaneous versus induced abortion, single versus married, young versus older). For instance, women who experienced miscarriages reported supportive care whereas women suspected to have induced their abortions felt stigmatized.

Conclusion

These findings have far reaching implications on efforts to improve uptake of post-abortion care, care seeking behaviors and on how to assess quality of abortion care. There should be emphasis on interventions meant to enhance processes and structural indicators of post-abortion care services meant to improve patients’ experiences throughout the care process. Moreover, more efforts are needed to advance the tools and approaches for assessing women experiences during post-abortion care beyond just the overriding clinical outcomes of care.
VLPs containing stalk domain and ectodomain of matrix protein 2 of influenza induce protection in mice
Authors: Shi Lili , Long Ying , Zhu Yanyan , Dong Jingjian , Chen Yan , Feng Hao , Sun Xianliang
Published: February 2023

Background

As a result of antigenic drift, current influenza vaccines provide limited protection against circulating influenza viruses, and vaccines with broad cross protection are urgently needed. Hemagglutinin stalk domain and ectodomain of matrix protein 2 are highly conserved among influenza viruses and have great potential for use as a universal vaccine.

Methods

In this study, we co-expressed the stalk domain and M2e on the surface of cell membranes and generated chimeric and standard virus-like particles of influenza to improve antigen immunogenicity. We subsequently immunized BALB/c mice through intranasal and intramuscular routes.

Results

Data obtained demonstrated that vaccination with VLPs elicited high levels of serum-specific IgG (approximately 30-fold higher than that obtained with soluble protein), induced increased ADCC activity to the influenza virus, and enhanced T cell as well as mucosal immune responses. Furthermore, mice immunized by VLP had elevated level of mucosal HA and 4M2e specific IgA titers and cytokine production as compared to mice immunized with soluble protein. Additionally, the VLP-immunized group exhibited long-lasting humoral antibody responses and effectively reduced lung viral titers after the challenge. Compared to the 4M2e-VLP and mHA-VLP groups, the chimeric VLP group experienced cross-protection against the lethal challenge with homologous and heterologous viruses. The stalk domain specific antibody conferred better protection than the 4M2e specific antibody.

Conclusion

Our findings demonstrated that the chimeric VLPs anchored with the stalk domain and M2e showed efficacy in reducing viral loads after the influenza virus challenge in the mice model. This antibody can be used in humans to broadly protect against a variety of influenza virus subtypes. The chimeric VLPs represent a novel approach to increase antigen immunogenicity and are promising candidates for a universal influenza vaccine.
DEPDC1 and KIF4A synergistically inhibit the malignant biological behavior of osteosarcoma cells through Hippo signaling pathway
Authors: Yang Mingming , Zhang Hang , Gao Shichang , Huang Wei
Published: February 2023

The treatment of osteosarcoma (OS) is still mainly surgery combined with systematic chemotherapy, and gene therapy is expected to improve the survival rate of patients. This study aimed to explore the effect of DEP domain 1 protein (DEPDC1) and kinesin super-family protein 4A (KIF4A) in OS and understand its mechanism. Th expression of DEPDC1 and KIF4A in OS cells was detected by RT-PCR and western blot. The viability, proliferation, invasion and migration of OS cells and tube formation of human umbilical vein endothelial cells (HUVECs) after indicated treatment were in turn detected by CCK-8 assay, EdU staining, wound healing assay, transwell assay and tube formation assay. The interaction between DEPDC1 and KIF4A was predicted by STRING and confirmed by co-immunoprecipitation. The expression of epithelial-mesenchymal transition (EMT)-related proteins, tube formation-related proteins and Hippo signaling pathway proteins was detected by western blot. As a result, the expression of DEPDC1 and KIF4A was all increased in U2OS cells. Down-regulation of DEPDC1 suppressed the viability, proliferation, invasion and migration of U2OS cells and tube formation of HUVECs, accompanied by the increased expression of E-cadherin and decreased expression of N-cadherin, Vimentin and VEGF. DEPDC1 was confirmed to be interacted with KIF4A. Upregulation of KIF4A partially reversed the effect of DEPDC1 interference on the above biological behaviors of U2OS cells. Down-regulation of DEPDC1 promoted the expression of p-LATS1 and p-YAP in Hippo signaling pathway, which was reversed by upregulation of KIF4A. In conclusion, down-regulation of DEPDC1 inhibited the malignant biological behavior of OS cells through the activation of Hippo signaling pathway, which could be reversed by upregulation of KIF4A.
Broadly applicable TCR-based therapy for multiple myeloma targeting the immunoglobulin J chain
Authors: Meeuwsen Miranda H. , Wouters Anne K. , Wachsmann Tassilo L. A. , Hagedoorn Renate S. , Kester Michel G. D. , Remst Dennis F. G. , van der Steen Dirk M. , de Ru Arnoud H. , van Hees Els P. , Kremer Martijn , Griffioen Marieke , van Veelen Peter A. , Falkenburg J. H. Frederik , Heemskerk Mirjam H. M.
Published: February 2023

Background

The immunoglobulin J chain (Jchain) is highly expressed in the majority of multiple myeloma (MM), and Jchain-derived peptides presented in HLA molecules may be suitable antigens for T-cell therapy of MM.

Methods

Using immunopeptidomics, we identified Jchain-derived epitopes presented by MM cells, and pHLA tetramer technology was used to isolate Jchain-specific T-cell clones.

Results

We identified T cells specific for Jchain peptides presented in HLA-A1, -A24, -A3, and -A11 that recognized and lysed JCHAIN-positive MM cells. TCRs of the most promising T-cell clones were sequenced, cloned into retroviral vectors, and transferred to CD8 T cells. Jchain TCR T cells recognized target cells when JCHAIN and the appropriate HLA restriction alleles were expressed, while JCHAIN or HLA-negative cells, including healthy subsets, were not recognized. Patient-derived JCHAIN-positive MM samples were also lysed by Jchain TCR T cells. In a preclinical in vivo model for established MM, Jchain-A1, -A24, -A3, and -A11 TCR T cells strongly eradicated MM cells, which resulted in 100-fold lower tumor burden in Jchain TCR versus control-treated mice.

Conclusions

We identified TCRs targeting Jchain-derived peptides presented in four common HLA alleles. All four TCRs demonstrated potent preclinical anti-myeloma activity, encouraging further preclinical testing and ultimately clinical development.
Targeting STAT3-VISTA axis to suppress tumor aggression and burden in acute myeloid leukemia
Authors: Mo Jianshan , Deng Lin , Peng Keren , Ouyang Shumin , Ding Wen , Lou Linlin , Lin Ziyou , Zhu Jianzheng , Li Jingwei , Zhang Qiyi , Wang Pengyan , Wen Yuanzhen , Chen Xiaobing , Yue Peibin , Lu Jin-Jian , Zhu Kai , Zheng Yongjiang , Wang Yuanxiang , Zhang Xiaolei
Published: February 2023

The acute myeloid leukemia (AML) patients obtain limited benefits from current immune checkpoint blockades (ICBs), although immunotherapy have achieved encouraging success in numerous cancers. Here, we found that V-domain Ig suppressor of T cell activation (VISTA), a novel immune checkpoint, is highly expressed in primary AML cells and associated with poor prognosis of AML patients. Targeting VISTA by anti-VISTA mAb boosts T cell-mediated cytotoxicity to AML cells. Interestingly, high expression of VISTA is positively associated with hyperactive STAT3 in AML. Further evidence showed that STAT3 functions as a transcriptional regulator to modulate VISTA expression by directly binding to DNA response element of VISTA gene. We further develop a potent and selective STAT3 inhibitor W1046, which significantly suppresses AML proliferation and survival. W1046 remarkably enhances the efficacy of VISTA mAb by activating T cells via inhibition of STAT3 signaling and down-regulation of VISTA. Moreover, combination of W1046 and VISTA mAb achieves a significant anti-AML effect in vitro and in vivo. Overall, our findings confirm that VISTA is a potential target for AML therapy which transcriptionally regulated by STAT3 and provide a promising therapeutic strategy for immunotherapy of AML.
Radiographic damage in early rheumatoid arthritis is associated with increased disability but not with pain—a 5-year follow-up study
Authors: Eberhard Anna , Rydell Emil , Forslind Kristina , Bergman Stefan , Mandl Thomas , Olofsson Tor , Jacobsson Lennart T. H. , Turesson Carl
Published: February 2023

Objectives

To evaluate how radiographic damage, overall and measured as joint space narrowing score (JSNS) and erosion score (ES), as well as other clinical and laboratory measures, relate to disability and pain in early rheumatoid arthritis (RA).

Methods

An inception cohort of 233 patients with early RA, recruited in 1995–2005, was followed for 5 years. Disability was assessed with the Health Assessment Questionnaire (HAQ), and pain with a visual analogue scale (VAS; 0–100 mm). Radiographs of hands and feet were evaluated using the Sharp-van der Heijde score (SHS), including JSNS and ES. The relation for radiographic scores and other clinical parameters with pain and HAQ were evaluated cross-sectionally by multivariate linear regression analysis and over time using generalized estimating equations.

Results

ES was significantly associated with HAQ cross-sectionally at inclusion, after 2 and after 5 years, and over time. Associations for HAQ with SHS and JSNS were weaker and less consistent compared with those for ES. There was no association between radiographic scores and pain at any visit. Both HAQ and pain were associated with parameters of disease activity. The strongest cross-sectional associations were found for the number of tender joints (adjusted p<0.001 at all visits).

Conclusion

Joint damage was associated with disability already in early RA. Erosions of hands and feet appear to have a greater influence on disability compared with joint space narrowing early in the disease. Pain was associated with other factors than joint destruction in early RA, in particular joint tenderness—suggesting an impact of pain sensitization.
DU-Net-Cloud: a smart cloud-edge application with an attention mechanism and U-Net for remote sensing images and processing
Authors: Kong Jiayuan , Zhang Yanjun
Published: February 2023

In recent ages, the use of deep learning approaches to extract ground object information from remote sensing high-resolution images has attracted extensive attention in many fields. Nevertheless, due to the high similarity of features between roads, prevailing deep learning semantic segmentation networks commonly demonstrate reduced continuity in road segmentation. Besides this, the role of advanced computing technologies including cloud and edge infrastructures has also become very important due to large number of images and their storage requirements. In order to better study the road details in images related to remote sensing, this paper suggests a road extraction technique which is basically founded on Dimensional U-Net (DU-Net) network. At the deepening level of the U-Net network, a parallel attention mechanism, known as ProCBAM, is added and implemented to the feature transmission step of the classical U-Net network. Moreover, we use and implement the edge-cloud architecture to develop and construct a unique remote sensing image service system that integrates several datacenters and their related edge infrastructure. In the proposed system, the edge network is primarily used for caching and distributing the processed remote sensing images, while the remote datacenter serves as the cloud platform and is responsible for the storage and processing of original remote sensing images. The results show that the proposed cloud enabled DU-Net model has achieved good performance in road segmentation. We observed that it can achieve improved road segmentation and resolve the issue of reduced continuity of road segmentation when compared with other state-of-the-art learning networks. Moreover, our empirical evaluations suggest that the proposed system not only distributes the workload of processing tasks across the edges but also achieves data efficiency among them, which enhances image processing efficiency and reduces data transmission costs.
Analysis of the differential expression and prognostic relationship of DEGs in AML based on TCGA database
Authors: Gao Yue , Jia Yinnong , Yu Zhengmin , Ji Xinyu , Liu Xiaowen , Han Lei , Zhang Hengdong , Zhu Baoli , Xu Ming
Published: February 2023

Background

Acute myeloid leukemia (AML) is a common and lethal hematological malignant hyperplastic disease originating from hematopoietic stem cells. The purpose of this study is to obtain the key differentially expressed gene (DEG) related to the survival of AML by The Cancer Genome Atlas (TCGA) database and to verify these genes by a clinical follow-up investigation, in order to identify valuable predictive and prognostic biomarkers for early diagnosis of AML and predict the survival rates.

Methods

The RNA sequencing (RNA-Seq) data and clinical information of TCGA-LAML were downloaded from the TCGA database. After that we (1) screened the survival-related DEGs by Cox regression analysis, (2) selected the cytogenetics risk-related DEGs by DESeq2 R package, and (3) filtrated the genes in the top10 pathways of up-regulated and down-regulated of Normalization Enrichment Score (NES) by Gene Set Enrichment Analysis (GSEA). Finally, we focused the intersectional genes of above three parts as the key gene of the present study. The following Multivariate.
Longitudinal study of the short- and long-term effects of hospitalisation and oral trimethoprim-sulfadiazine administration on the equine faecal microbiome and resistome
Authors: Theelen Mathijs J. P. , Luiken Roosmarijn E. C. , Wagenaar Jaap A. , Sloet van Oldruitenborgh-Oosterbaan Marianne M. , Rossen John W. A. , Schaafstra Femke J. W. C. , van Doorn David A. , Zomer Aldert L.
Published: February 2023

Background

Hospitalisation and antimicrobial treatment are common in horses and significantly impact the intestinal microbiota. Antimicrobial treatment might also increase levels of resistant bacteria in faeces, which could spread to other ecological compartments, such as the environment, other animals and humans. In this study, we aimed to characterise the short- and long-term effects of transportation, hospitalisation and trimethoprim-sulfadiazine (TMS) administration on the faecal microbiota and resistome of healthy equids.

Methods

In a longitudinal experimental study design, in which the ponies served as their own control, faecal samples were collected from six healthy Welsh ponies at the farm (D0–D13-1), immediately following transportation to the hospital (D13-2), during 7 days of hospitalisation without treatment (D14–D21), during 5 days of oral TMS treatment (D22–D26) and after discharge from the hospital up to 6 months later (D27–D211). After DNA extraction, 16S rRNA gene sequencing was performed on all samples. For resistome analysis, shotgun metagenomic sequencing was performed on selected samples.

Results

Hospitalisation without antimicrobial treatment did not significantly affect microbiota composition. Oral TMS treatment reduced alpha-diversity significantly. Kiritimatiellaeota, Fibrobacteres and Verrucomicrobia significantly decreased in relative abundance, whereas Firmicutes increased. The faecal microbiota composition gradually recovered after discontinuation of TMS treatment and discharge from the hospital and, after 2 weeks, was more similar to pre-treatment composition than to composition during TMS treatment. Six months later, however, microbiota composition still differed significantly from that at the start of the study and Spirochaetes and Verrucomicrobia were less abundant. TMS administration led to a significant (up to 32-fold) and rapid increase in the relative abundance of resistance genessul2,tetQ,ant6-1a, andaph(3”)-lb.lnuCsignificantly decreased directly after treatment. Resistance genes sul2(15-fold) andtetQ(six-fold) remained significantly increased 6 months later.

Conclusions

Oral treatment with TMS has a rapid and long-lasting effect on faecal microbiota composition and resistome, making the equine hindgut a reservoir and potential source of resistant bacteria posing a risk to animal and human health through transmission. These findings support the judicious use of antimicrobials to minimise long-term faecal presence, excretion and the spread of antimicrobial resistance in the environment.
YULINK regulates vascular formation in zebrafish and HUVECs
Authors: Lin Hsin-Hung , Kuo Ming-Wei , Fan Tan-Chi , Yu Alice L. , Yu John
Published: February 2023

Background

The distinct arterial and venous cell fates are dictated by a combination of various genetic factors which form diverse types of blood vessels such as arteries, veins, and capillaries. We report here that YULINK protein is involved in vasculogenesis, especially venous formation.

Methods

In this manuscript, we employed gene knockdown, yeast two-hybrid, FLIM-FRET, immunoprecipitation, and various imaging technologies to investigate the role of YULINK gene in zebrafish and human umbilical vein endothelial cells (HUVECs).

Results

Knockdown ofYULINKduring the arterial-venous developmental stage of zebrafish embryos led to the defective venous formation and abnormal vascular plexus formation. Knockdown ofYULINKin HUVECs impaired their ability to undergo cell migration and differentiation into a capillary-like tube formation. In addition, the phosphorylated EPHB4 was decreased inYULINKknockdown HUVECs. Yeast two-hybrid, FLIM-FRET, immunoprecipitation, as well as imaging technologies showed that YULINK colocalized with endosome related proteins (EPS15, RAB33B or TICAM2) and markers (Clathrin and RHOB). VEGF-induced VEGFR2 internalization was also compromised inYULINKknockdown HUVECs, demonstrating to the involvement of YULINK.

Conclusion

This study suggests that YULINK regulates vasculogenesis, possibly through endocytosis in zebrafish and HUVECs.
Microbial bioremediation as a tool for the removal of heavy metals
Authors: Abo-Alkasem Mohamed I. , Hassan Ne’mat H. , Abo Elsoud Mostafa Mostafa
Published: February 2023

Background

The demand for designing a new technology that can emphasize the complete removal of heavy metals increased as a result of the industrial revolution. Bioremediation was found to have a potent impact on the degradation of organic and inorganic environmental pollutants.

Main body

Bioremediation is a multidisciplinary technology that possesses safe, efficient, and low-cost characteristics. Also, one of the important features of bioremediation technology is the in-situ treatment which reduces the possibility of transmitting the contaminants to another site. The application of genetic engineering, to engineer a microorganism to acquire the ability to remove different types of heavy metals at a time or to generate a transgenic plant, is considered one of the new promising bioremediation approaches.

Short conclusion

Removal of heavy metal pollution still represents a big challenge for ecologists that’s why this review shed some light on bioremediation technology; its importance, mechanism of action, and prospects.
Robustness optimization for rapid prototyping of functional artifacts based on visualized computing digital twins
Authors: Xu Jinghua , Liu Kunqian , Wang Linxuan , Guo Hongshuai , Zhan Jiangtao , Liu Xiaojian , Zhang Shuyou , Tan Jianrong
Published: February 2023

This study presents a robustness optimization method for rapid prototyping (RP) of functional artifacts based on visualized computing digital twins (VCDT). A generalized multiobjective robustness optimization model for RP of scheme design prototype was first built, where thermal, structural, and multidisciplinary knowledge could be integrated for visualization. To implement visualized computing, the membership function of fuzzy decision-making was optimized using a genetic algorithm. Transient thermodynamic, structural statics, and flow field analyses were conducted, especially for glass fiber composite materials, which have the characteristics of high strength, corrosion resistance, temperature resistance, dimensional stability, and electrical insulation. An electrothermal experiment was performed by measuring the temperature and changes in temperature during RP. Infrared thermographs were obtained using thermal field measurements to determine the temperature distribution. A numerical analysis of a lightweight ribbed ergonomic artifact is presented to illustrate the VCDT. Moreover, manufacturability was verified based on a thermal-solid coupled finite element analysis. The physical experiment and practice proved that the proposed VCDT provided a robust design paradigm for a layered RP between the steady balance of electrothermal regulation and manufacturing efficacy under hybrid uncertainties.
Usefulness of combined diffusion tensor imaging, arterial spin labelling and spectroscopic interictal analysis in refractory epilepsy
Authors: Reda Alaa Mohamed , Elsharkawy Ahmed , Hasby Sara Essam
Published: February 2023

Background

Epilepsy is a common neurological disorder especially in pediatric population. Patients with non-lesional epilepsy have normal conventional MRI findings. In the recent era of advances in neuroimaging studies, diffusion tensor imaging (DTI) and MR spectroscopy (MRS) can assess the tissue microstructure. Also, arterial spin labeling (ASL) is a noninvasive modality that evaluates cerebral blood flow. Multiple recent publications aimed at use of single or two new modalities in lateralization of epileptogenic focus in epilepsy, but the current study aimed to evaluate the added value of combined (DTI, ASL and MRS) in vivo localization of interactable epilepsy with negative conventional MRI findings.

Results

This prospective case control study was carried out in the period from January 1st, 2022 to October 1st, 2022 after approval of local ethical committee in our institution. Written informed consent was obtained from patients and healthy volunteers who were enrolled in this study. The current study included 46 patients with temporal lobe epilepsy and 20 age- and sex-matched healthy volunteers as a control group. The mean age in the patient group was 22.3 ± 12.2 years, and in the control group, it was 23.8 ± 15.1 years. The highest area under the curve (AUC) was for spectroscopy (0.913), the difference in NAA/Cr showed sensitivity of 94.1% and a specificity of 90%, while NAA/Cho + Cr showed a sensitivity of 91.8% and a specificity of 88%, the difference in rCBF showed an AUC of 0.89, with a cutoff value of 3.815 had a sensitivity of 80.4% and a specificity of 85%. As regards DTI, the changes in DTI parameters show sensitivity of 79.6% and a specificity of 80% in lateralization of the epileptic focus. The difference in FA only showed an AUC of 0.86, with a cutoff value of 0.01 had a sensitivity of 77% and a specificity of 75% and the difference in MD only showed an AUC of 0.771, with a cutoff value of 0.545 had a sensitivity of 67.4% and a specificity of 70%. The diagnostic performance of MRS in terms of the AUC was significantly higher than ASL parameters (difference in NAA/Cr, p = 0.033 and difference in NAA/Cho + Cr, p = 0.044), and MD (p = 0.02). No other statistically significant differences were shown between the studied parameters. When the three methods were combined, all patients’ epileptogenic foci were correctly localized and lateralized.

Conclusions

Combining ASL, DTI and H-MRS provided excellent diagnostic performance in localization and lateralization of the epileptogenic focus. If this combination is not applicable in clinical practice, ASL could provide a considerably accurate and feasible method in this context. The present study supported the value of the new noninvasive MRI techniques in the elaboration of hidden brain pathology.