bluuebunny/crossref_metadata_2025 huggingface dataset:
RNA-Binding Protein Expression Alters Upon Differentiation of Human B Cells and T Cells
Authors: Zandhuis Nordin D. , Nicolet Benoit P. , Wolkers Monika C.
Published: November 2021

B cells and T cells are key players in the defence against infections and malignancies. To exert their function, B cells and T cells differentiate into effector and memory cells. Tight regulation of these differentiation processes is key to prevent their malfunction, which can result in life-threatening disease. Lymphocyte differentiation relies on the appropriate timing and dosage of regulatory molecules, and post-transcriptional gene regulation (PTR) is a key player herein. PTR includes the regulation through RNA-binding proteins (RBPs), which control the fate of RNA and its translation into proteins. To date, a comprehensive overview of the RBP expression throughout lymphocyte differentiation is lacking. Using transcriptome and proteome analyses, we here catalogued the RBP expression for human B cells and T cells. We observed that even though the overall RBP expression is conserved, the relative RBP expression is distinct between B cells and T cells. Differentiation into effector and memory cells alters the RBP expression, resulting into preferential expression of different classes of RBPs. For instance, whereas naive T cells express high levels of translation-regulating RBPs, effector T cells preferentially express RBPs that modulate mRNA stability. Lastly, we found that cytotoxic CD8+ and CD4+ T cells express a common RBP repertoire. Combined, our study reveals a cell type-specific and differentiation-dependent RBP expression landscape in human lymphocytes, which will help unravel the role of RBPs in lymphocyte function.
Kinase Inhibition as Treatment for Acute and Chronic Graft-Versus-Host Disease
Authors: Braun Lukas M. , Zeiser Robert
Published: November 2021

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a potentially curative therapy for patients suffering from hematological malignanciesviathe donor immune system driven graft-versus-leukemia effect. However, the therapy is mainly limited by severe acute and chronic graft-versus-host disease (GvHD), both being life-threatening complications after allo-HCT. GvHD develops when donor T cells do not only recognize remaining tumor cells as foreign, but also the recipient’s tissue, leading to a severe inflammatory disease. Typical GvHD target organs include the skin, liver and intestinal tract. Currently all approved strategies for GvHD treatment are immunosuppressive therapies, with the first-line therapy being glucocorticoids. However, therapeutic options for glucocorticoid-refractory patients are still limited. Novel therapeutic approaches, which reduce GvHD severity while preserving GvL activity, are urgently needed. Targeting kinase activity with small molecule inhibitors has shown promising results in preclinical animal models and clinical trials. Well-studied kinase targets in GvHD include Rho-associated coiled-coil-containing kinase 2 (ROCK2), spleen tyrosine kinase (SYK), Bruton’s tyrosine kinase (BTK) and interleukin-2-inducible T-cell kinase (ITK) to control B- and T-cell activation in acute and chronic GvHD. Janus Kinase 1 (JAK1) and 2 (JAK2) are among the most intensively studied kinases in GvHD due to their importance in cytokine production and inflammatory cell activation and migration. Here, we discuss the role of kinase inhibition as novel treatment strategies for acute and chronic GvHD after allo-HCT.
CircRNA75 and CircRNA72 Function as the Sponge of MicroRNA-200 to Suppress Coelomocyte Apoptosis Via Targeting Tollip in Apostichopus japonicus
Authors: Liu Jiqing , Zhao Xuelin , Duan Xuemei , Zhang Weiwei , Li Chenghua
Published: November 2021

Circular RNAs (circRNAs) act as essential regulators in many biological processes, especially in mammalian immune response. Nonetheless, the functions and mechanisms of circRNAs in the invertebrate immune system are largely unclarified. In our previous work, 261 differentially expressed circRNAs potentially related to the development of Apostichopus japonicus skin ulceration syndrome (SUS), which is a major problem restricting the sea cucumber breeding industry, were identified by genome-wide screening. In this study, via miRanda analysis, both circRNA75 and circrRNA72 were shown to share the miR-200 binding site, a key microRNA in the SUS. The two circRNAs were verified to be increased significantly in LPS-exposed primary coelomocytes, similar to the results of circRNA-seq in sea cucumber under Vibrio splendidus-challenged conditions. A dual-luciferase assay indicated that both circRNA75 and circRNA72 could bind miR-200 in vivo, in which circRNA75 had four binding sites of miR-200 and only one for circRNA72. Furthermore, we found that miR-200 could bind the 3’-UTR of Toll interacting protein (Tollip) to negatively mediate the expression of Tollip. Silencing Tollip increased primary coelomocyte apoptosis. Consistently, inference of circRNA75 and circRNA72 could also downregulate Tollip expression, thereby increasing the apoptosis of primary coelomocytes, which could be blocked by miR-200 inhibitor treatment. Moreover, the rate of si-circRNA75-downregulated Tollip expression was higher than that of si-circRNA72 under an equivalent amount. CircRNA75 and circRNA72 suppressed coelomocyte apoptosis by sponging miR-200 to promote Tollip expression. The ability of circRNA to adsorb miRNA might be positively related to the number of binding sites for miRNA.
Using the T Cell Receptor as a Biomarker in Type 1 Diabetes
Authors: Nakayama Maki , Michels Aaron W.
Published: November 2021

T cell receptors (TCRs) are unique markers that define antigen specificity for a given T cell. With the evolution of sequencing and computational analysis technologies, TCRs are now prime candidates for the development of next-generation non-cell based T cell biomarkers, which provide a surrogate measure to assess the presence of antigen-specific T cells. Type 1 diabetes (T1D), the immune-mediated form of diabetes, is a prototypical organ specific autoimmune disease in which T cells play a pivotal role in targeting pancreatic insulin-producing beta cells. While the disease is now predictable by measuring autoantibodies in the peripheral blood directed to beta cell proteins, there is an urgent need to develop T cell markers that recapitulate T cell activity in the pancreas and can be a measure of disease activity. This review focuses on the potential and challenges of developing TCR biomarkers for T1D. We summarize current knowledge about TCR repertoires and clonotypes specific for T1D and discuss challenges that are unique for autoimmune diabetes. Ultimately, the integration of large TCR datasets produced from individuals with and without T1D along with computational ‘big data’ analysis will facilitate the development of TCRs as potentially powerful biomarkers in the development of T1D.
Effect of Fibre Types on the Tensile Behaviour of Engineered Cementitious Composites
Authors: Lan Mingzhang , Zhou Jian , Xu Mingfeng
Published: November 2021

Engineered cementitious composite (ECC) is a group of ultra-ductile fibre-reinforced cementitious composites, characterised by high ductility and moderate content of short discontinuous fibre. The unique tensile strain-hardening behaviour of ECC results from a deliberate design based on the understanding of micromechanics between fibre, matrix, and fibre–matrix interface. To investigate the effect of fibre properties on the tensile behaviour of ECCs is, therefore, the key to understanding the composite mechanical behaviour of ECCs. This paper presents a study on the fibre-bridging behaviour and composite mechanical properties of ECCs with three types of fibres, including oil-coated polyvinyl alcohol (PVA) fibre, untreated PVA fibre, and polypropylene (PP) fibre. The experimental result reveals that various fibres with different properties result in difference in the fibre-bridging behaviour and composite mechanical properties of ECCs. The difference in the composite mechanical properties of ECCs with different fibres was interpreted by analysing the fibre-bridging behaviour.
Association Between Sarcopenia and Depressive Symptoms in Chinese Older Adults: Evidence From the China Health and Retirement Longitudinal Study
Authors: Gao Ke , Ma Wen-Zhuo , Huck Scarlett , Li Bo-Lin , Zhang Li , Zhu Jiao , Li Tian , Zhou Dan
Published: November 2021

Background: Little is known about whether sarcopenia predicts incident depressive symptoms in older adults. Using the nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), we conducted cross-sectional and longitudinal analyses to estimate the association between sarcopenia and depressive symptoms among older adults.

Methods: The sample comprised 7,706 participants aged at least 60 years (50.6% women; mean age 68.0 ± 6.5) from the CHARLS 2015. Based on the Asian Working Group for Sarcopenia 2019 (AWGS 2019) criteria, sarcopenia status was classified into three types: no-sarcopenia, possible sarcopenia, and sarcopenia. Depressive symptoms were assessed using the validated 10-items of the Center for Epidemiologic Studies Depression Scale. A cross-sectional analysis was used to examine the relationship between sarcopenia status and depressive symptoms. A total of 4,652 participants without depressive symptoms were recruited from the same cohort in 2015 and were followed up in 2018. Cox proportional hazards regression models were conducted to examine the effect of sarcopenia status on subsequent depressive symptoms with the report of hazard ratio (HR).

Results: The prevalence of depressive symptoms in total populations, no-sarcopenia, possible sarcopenia, and sarcopenia individuals were 27.1% (2085/7706), 21.5% (927/4310), 33.6% (882/2627), and 35.9% (276/769), respectively. Both possible sarcopenia (OR: 1.75, 95% CI: 1.46–2.10) and sarcopenia (OR: 1.64, 95% CI: 1.23–2.19) were positively associated with higher odds of depressive symptoms (all p < 0.01). During the 3.7 years of follow-up, 956 cases (20.6%) with incident depressive symptoms were identified. In the longitudinal analysis, individuals with the diagnosed possible sarcopenia (HR: 1.27, 95% CI: 1.01–1.58) and sarcopenia participants (HR: 1.49, 95% CI: 1.06–2.09) were more likely to have new onset depressive symptoms than no-sarcopenia peers.

Conclusions: Both possible sarcopenia and sarcopenia, assessed using the AWGS 2019 criteria, were independent predictors for the occurrence of depressive symptoms among Chinese older adults. Our findings provided new evidence supporting the longitudinal connection between sarcopenia and mental health problems, it also provides further justification for timely identification and management of both possible sarcopenia and sarcopenia as part of comprehensive strategies to fight against depressive symptoms.
Cerebrovascular Disease in the Setting of Posterior Reversible Encephalopathy Syndrome
Authors: Cheng XiaoQing , Li JianRui , Lan Ying , Liu Jia , Chen Sui , Lu GuangMing
Published: November 2021

Overlap between the pathogenesis of posterior reversible encephalopathy syndrome and that of cerebrovascular disease can confound their clinical and radiological presentations, posing a diagnostic challenge. This article presents a literature review and discussion of the clinical manifestations, pathological mechanisms, and imaging manifestations of subarachnoid hemorrhage and vasculitis leading to posterior reversible encephalopathy syndrome, coexistence of posterior reversible encephalopathy syndrome with reversible cerebral vasoconstriction syndrome, and hemorrhage and infarction secondary to posterior reversible encephalopathy syndrome. The findings show that posterior reversible encephalopathy syndrome shares some overlapping pathophysiological mechanisms with cerebrovascular disease. Importantly, neuroimaging plays an important role in identifying this entity in a timely manner and differentiating it from other diseases.
How Much Tumor Volume Is Responsible for Development of Clinical Symptoms in Patients With Convexity, Parasagittal, and Falx Meningiomas?
Authors: Yamada Shuhei , Kijima Noriyuki , Nakagawa Tomoyoshi , Hirayama Ryuichi , Kinoshita Manabu , Kagawa Naoki , Kishima Haruhiko
Published: November 2021

Purpose: Meningiomas are the most common primary intracranial neoplasms and clinical symptom appearance depends on their volume and location. This study aimed to identify factors that influence clinical symptoms and to determine a specific threshold tumor volume for the prediction of symptomatic progression in patients with convexity, parasagittal, and falx meningiomas.

Materials and Methods: We retrospectively studied patients with radiologically suspected convexity, parasagittal, or falx meningiomas at our institution.

Results: The data of three hundred thirty-three patients were analyzed. We further divided patients into two groups based on clinical symptoms: an asymptomatic group (250 cases) and a symptomatic group (83 cases). Univariate analysis revealed significant differences between the groups in terms of sex (p = 0.002), age at the time of volumetric analysis (p < 0.001), hyperintense lesions on T2-weighted images (p = 0.029), peritumoral edema (p < 0.001), maximum tumor diameter (p < 0.001), and tumor volume (p < 0.001). Further multivariate analysis revealed significant differences between the groups in terms of age at the time of volumetric analysis (p = 0.002), peritumoral edema (p < 0.001), and tumor volume (p < 0.001). The receiver operating characteristic curve revealed a threshold tumor volume of 21.1 ml for predicting whether a patient would develop symptoms (sensitivity 0.843, specificity 0.880, an area under the curve 0.919 [95% confidence interval: 0.887–0.951]).

Conclusion: We identified factors predictive of clinical symptoms in patients with convexity, parasagittal, and falx meningiomas and determined the first-ever threshold tumor volume for predicting symptomatic progression in such patients.
Highlighting the Place of Metastasis-Directed Therapy in Isolated Liver Metastases in Prostate Cancer: A Case Report
Authors: Yeo Anne-Emmanuella , Hendrix Aurore , Confente Caterina , Christian Nicolas , Mansvelt Baudouin , Pairet Géraldine , Seront Emmanuel
Published: November 2021

Metastatic prostate cancer remains a challenge for clinicians. Metastases involve mainly the bone compartment and can manifest as oligometastatic disease. In this setting, the role of metastasis-directed therapies (MDT) including surgery and/or stereotactic body radiotherapy is currently evaluated. Visceral metastases are less common and have very poor prognosis in mPC. Whether treating isolated visceral metastases such as liver metastases with MDT could increase the prognosis remains unknown. We report the management of a prostate cancer patient who progressed on androgen deprivation therapy with apparition of two liver metastases. We describe the feasibility of combining MDT with abiraterone acetate and prednisone in a patient with metastatic castration-resistant prostate cancer. MDT allowed the interruption of abiraterone acetate, preventing cumulative toxicity of this agent.
Reproducibility and Repeatability of CBCT-Derived Radiomics Features
Authors: Wang Hao , Zhou Yongkang , Wang Xiao , Zhang Yin , Ma Chi , Liu Bo , Kong Qing , Yue Ning , Xu Zhiyong , Nie Ke
Published: November 2021

Purpose

This study was conducted in order to determine the reproducibility and repeatability of cone-beam computed tomography (CBCT) radiomics features.

Methods

The first-, second-, and fifth-day CBCT images from 10 head and neck (H&N) cancer patients and 10 pelvic cancer patients were retrospectively collected for this study. Eighteen common radiomics features were extracted from the longitudinal CBCT images using two radiomics packages. The reproducibility of CBCT-derived radiomics features was assessed using the first-day image as input and compared across the two software packages. The site-specific intraclass correlation coefficient (ICC) was used to quantitatively assess the agreement between packages. The repeatability of CBCT-based radiomics features was evaluated by comparing the following days of CBCT to the first-day image and quantified using site-specific concordance correlation coefficient (CCC). Furthermore, the correlation with volume for all the features was assessed with linear regression and R2 as correlation parameters.

Results

The first-order histogram-based features such as skewness and entropy showed good agreement computed in either software package (ICCs ≥ 0.80), while the kurtosis measurements were consistent in H&N patients between the two software tools but not in pelvic cases. The ICCs for GLCM-based features showed good agreement (ICCs ≥ 0.80) between packages in both H&N and pelvic groups except for the GLCM-correction. The GLRLM-based texture features were overall less consistent as calculated by the two different software packages compared with the GLCM-based features. The CCC values of all first-order and second-order GLCM features (except GLCM-energy) were all above 0.80 from the 2-day part test–retest set, while the CCC values all dropped below the cutoff after 5-day treatment scans. All first-order histogram-based and GLCM-texture-based features were not highly correlated with volume, while two GLRLM features, in both H&N and pelvic cohorts, showed R2 ≥0.8, meaning a high correlation with volume.

Conclusion

The reproducibility and repeatability of CBCT-based radiomics features were assessed and compared for the first time on both H&N and pelvic sites. There were overlaps of stable features in both disease sites, yet the overall stability of radiomics features may be disease-/protocol-specific and a function of time between scans.
HOTAIR Modulated Pathways in Early-Stage Breast Cancer Progression
Authors: Abba Martin C. , Fabre María Laura , Lee Jaeho , Tatineni Pradeep , Kil Hyunsuk , Aldaz C. Marcelo
Published: November 2021

The long-non-coding HOX transcript antisense intergenic RNA (HOTAIR) was identified as significantly upregulated in breast ductal carcinoma in situ (DCIS). The aim of this study was to characterize the phenotypic effects and signaling pathways modulated by HOTAIR in early-stage breast cancer progression. We determined that HOTAIR induces premalignant phenotypic changes by increasing cell proliferation, migration, invasion and in vivo growth in normal and DCIS breast cell lines. Transcriptomic studies (RNA-seq) identified the main signaling pathways modulated by HOTAIR which include bioprocesses related to epithelial to mesenchymal transition, cell migration, extracellular matrix remodeling and activation of several signaling pathways (HIF1A, AP1 and FGFR). Similar pathways were identified as activated in primary invasive breast carcinomas with HOTAIR over-expression. We conclude that HOTAIR over-expression behaves as a positive regulator of cell growth and migration both in normal and DCIS breast cells involved with early-stage breast cancer progression.
Lipid Metabolism and its Mechanism Triggered by Supercritical CO2 Extract of Adlay (Coix lacryma-jobi var. ma-yuen (Rom. Caill.) Stapf) Bran in High-Fat Diet Induced Hyperlipidemic Hamsters
Authors: Huang Chiao-Chih , Lin Tzu-Ching , Liu Chiung-Hui , Hu Hao-Chun , Yu Szu-Yin , Wu Shu-Jing , Yen Ming-Hong , Tsai Yi-Hong , Chang Fang-Rong
Published: November 2021

Adlay (Coix lacryma-jobi var. ma-yuen (Rom. Caill.) Stapf) seeds are edible crop classified as Traditional Chinese Medicine (TCM). Adlay bran (AB) is one of the wastes generated during adlay refining processes. In this work, supercritical fluid extract of AB (AB-SCF) was investigated to reveal its lipid regulating potential and decode its bifunctional ingredients. AB-SCF×0.5 (30.84 mg/kg/body weight), AB-SCF×1 (61.67 mg/kg/BW), AB-SCF×5 (308.35 mg/kg/BW) and AB-SCF×10 (616.70 mg/kg/BW) were administrated to high fat-diet (HFD) induced hyperglycemic hamsters for 8 weeks. The results indicates that AB-SCF displays a prevention of dramatic body weight gains, lower levels of serum TG, TC, LDL-C and higher in HDL-C, amelioration of cardiovascular risk, alleviation of hepatic TG, TC and lipid peroxidation, and enhancement on cholesterol metabolism with higher bile acid excretion. Investigations on energy metabolic mechanism demonstrates that the hyperlipidemia mitigating capacities of AB-SCF are up-regulated on lipoprotein lipase, AMPK, p-AMPK and down-regulated at fatty acid synthase. Major bio-functional lipid compositions are identified as linoleic acid (28.59%) and oleic acid (56.95%). Non-lipid chemical and active markers are confirmed as 3-O-(trans-4-feruloyl)-β-sitostanol (1463.42 ppm), 3-O-(cis-4-feruloyl)-β-sitostanol (162.60 ppm), and β-sitosterol (4117.72 ppm). These compositions might synergistically responsible for the mentioned activities and can be regarded as analytical targets in quality control. AB-SCF may be considered as a promising complementary supplement, and developed as a functional food or new botanical drug in the future.
The Circadian Clock in Lepidoptera
Authors: Brady Daniel , Saviane Alessio , Cappellozza Silvia , Sandrelli Federica
Published: November 2021

With approximately 160,000 identified species of butterflies and moths, Lepidoptera are among the most species-rich and diverse insect orders. Lepidopteran insects have fundamental ecosystem functions as pollinators and valuable food sources for countless animals. Furthermore, Lepidoptera have a significant impact on the economy and global food security because many species in their larval stage are harmful pests of staple food crops. Moreover, domesticated species such as the silkwormBombyx moriproduce silk and silk byproducts that are utilized by the luxury textile, biomedical, and cosmetics sectors. Several Lepidoptera have been fundamental as model organisms for basic biological research, from formal genetics to evolutionary studies. Regarding chronobiology, in the 1970s, Truman’s seminal transplantation experiments on different lepidopteran species were the first to show that the circadian clock resides in the brain. With the implementation of molecular genetics, subsequent studies identified key differences in core components of the molecular circadian clock of Lepidoptera compared to the dipteranDrosophila melanogaster, the dominant insect species in chronobiological research. More recently, studies on the butterflyDanaus plexippushave been fundamental in characterizing the interplay between the circadian clock and navigation during the seasonal migration of this species. Moreover, the advent of Next Generation Omic technologies has resulted in the production of many publicly available datasets regarding circadian clocks in pest and beneficial Lepidoptera. This review presents an updated overview of the molecular and anatomical organization of the circadian clock in Lepidoptera. We report different behavioral circadian rhythms currently identified, focusing on the importance of the circadian clock in controlling developmental, mating and migration phenotypes. We then describe the ecological importance of circadian clocks detailing the complex interplay between the feeding behavior of these organisms and plants. Finally, we discuss how the characterization of these features could be useful in both pest control, and in optimizing rearing of beneficial Lepidoptera.
Does One Treatment Fit All? Effectiveness of a Multicomponent Cognitive Behavioral Therapy Program in Data-Driven Subtypes of Perinatal Depression
Authors: Waqas Ahmed , Rahman Atif
Published: November 2021

Background: Current diagnostic systems of mental disorders are criticized for their poor validity and reliability, owing to the within disorder heterogeneity and between disorder homogeneity. The issue is important if treatments for mental disorders are to be tailored to individual needs. There is little information in this area on perinatal depression (PND), a highly prevalent condition globally.

Aims: i) Quantify heterogeneity attributable to the polythetic diagnostic framework for PND and, ii) present evidence for the effectiveness of a multicomponent and low-intensity cognitive behavioral Thinking Healthy Programme (THP) across the heterogeneous presentations of PND.

Methods: This investigation presents secondary analyses of a cluster randomized controlled trial, conducted in Kallar Syedan, Pakistan. A total of 903 pregnant women were randomized to an intervention group receiving the THP intervention or control group receiving enhanced usual care. Principal component analyses and clustering algorithm were utilized to identify heterogenous subtypes of PND. Linear mixed effects models were used to assess effectiveness of the intervention across the identified subtypes of PND.

Results: Four different clusters of PND were identified: mixed anxiety-depression, somatic depression, mild depression, and atypical depression. All clinical phenotypes responded well to the THP intervention. Compared to their counterparts in the control group, mothers with mild depression in the treatment group yielded lowest risk ratios 0.24 (95% CI: 0.15 to 0.37), followed by mothers with anxiety-depression 0.50 (95% CI: 0.37 to 0.68), atypical depression 0.51 (95% CI: 0.27 to 0.99) and somatic depression 0.59 (95% CI: 0.42 to 0.83).

Conclusion: The Thinking Healthy Programme was found to be effective in reducing severity of depressive symptoms and disability across the four subtypes of PND.
A Biopsychosocial and Interprofessional Approach to the Treatment of Family and Intimate Partner Violence: It Takes a Village
Authors: Poleshuck Ellen , Wittink Marsha N. , Crean Hugh , Juskiewicz Iwona , ReQua Michelle A. , Cerulli Catherine
Published: November 2021

Family and intimate partner violence and abuse (FIPV) is a critical public health problem with repercussions for mental and physical health. FIPV exposure also is associated with social difficulties such as low socioeconomic status, legal issues, poor access to employment and education, housing instability, and difficulty meeting other basic needs. As a biopsychosocial problem, one discipline alone cannot adequately address FIPV. While individuals who experience FIPV traditionally seek respite, care and safety through domestic violence shelters, social services or courts, they also often present to health care settings. Building on the medical-legal partnership model with critical input from a community advisory board of individuals with lived experiences of FIPV, we implemented a person-centered approach in the health care context to cohesively integrate legal, safety, social, psychological and physical health needs and concerns. The purpose of this paper is to describe the Healing through Health, Education, Advocacy and Law (HEAL) Collaborative for individuals who have experienced psychological abuse, physical abuse, sexual abuse, or neglect related to child maltreatment, intimate partner violence, and/or elder abuse, and review our real-world challenges and successes. We describe our interprofessional team collaboration and our pragmatic biopsychosocial framework for bringing together: professional and stakeholder perspectives; psychological, medical, legal, and personal perspectives; and clinical, evidence-based, and educational perspectives. There is no doubt that creating a program with biopsychosocial components like HEAL requires professionals appreciating each other's contributions and the need to begin working from a common goal. Furthermore, such a program could not be successful without the contributions of individuals with the lived experience we seek to treat, coupled with the external health care clinicians' input. We describe lessons learned to date in an effort to ease the burden for those seeking to implement such a program. Lessons include HEAL's more recent clinical adaptions to serve patients both in-person and via telehealth in the wake of COVID-19.
Brucella Seroprevalence and Associated Risk Factors in Occupationally Exposed Humans in Selected Districts of Southern Province, Zambia
Authors: Mubanga Melai , Mfune Ruth L. , Kothowa John , Mohamud Ahmed S. , Chanda Chitalu , Mcgiven John , Bumbangi Flavien N. , Hang'ombe Bernard M. , Godfroid Jacques , Simuunza Martin , Muma John B.
Published: November 2021

Background: Brucellosis is a neglected debilitating zoonosis widely recognized as an occupational health hazard. The seroprevalence of human anti-Brucella antibodies in high-risk populations, as well as their risk factors, have not been well-documented in Zambia. This study aimed at estimating the Brucella seroprevalence in herdsmen and abattoir workers and assess the associated risk factors.

Methods: A cross-sectional seroepidemiological study was carried out between May and December 2020 among abattoir workers and herdsmen in Namwala, Monze and Choma districts of Southern Province in Zambia. Seroprevalence was assessed by indirect enzyme-linked immunosorbent assay (i-ELISA) or competitive enzyme-linked immunosorbent assay (c-ELISA) while a questionnaire was administered to obtain epidemiological data.

Results: A total of 153 individuals were recruited in the study. The overall Brucella seroprevalence was 20.3% (95% CI: 14.6–27.5). Seropositivity among herdsmen and abattoir workers was 14.4% (95% CI: 9.2–21.8) and 46.4%, (95% CI: 28.8–65.0), respectively. Comparable seropositive results among districts showed Namwala with 26.9%, which was the highest, seconded by Monze 19.0%, and the least was Choma with 11.36%, seropositivity. The multivariate logistic regression model showed that occupation, age category, and district of residence were predictors of being seropositive to Brucella spp. antibodies. The odds of abattoir workers being seropositive to Brucella antibodies were 8.6 (95% CI: 2.6–28.2) higher than that of herdsmen being the reference group. The odds of age category 17–50 years being seropositive to Brucella antibodies were 7.0 (95% CI: 0.7–72.2) higher than being <16 years as the reference group. The odds of one having attained primary level of education being seropositive to Brucella were 1.3 (95% CI: 0.1–14.7) or secondary level of education were 6.2 (95% CI: 0.5–72.6) or tertiary level of education were 5.1 (95% CI: 0.2, 113.3) higher than that of no level of education as the reference group. Furthermore, the odds of a respondent being seropositive to Brucella antibodies were 4.5 (95% CI: 1.3–15.7) for Namwala and 4.9 (95% CI: 1.1–21.7) for Monze higher than that of Choma as the reference group.

Conclusion: Anti-Brucella antibodies are prevalent among herdsmen and abattoir workers in the study areas of Zambia (20.26%), a sign of exposure to Brucella pathogens. Type of profession, age and level of education seem to influence the exposure to Brucella pathogens. This zoonosis should be considered as one of the differential diagnosis in humans presenting intermittent fever, malaria-like signs and general pain in humans.
Animal-Based Factors Prior to Infection Predict Histological Disease Outcome in Porcine Reproductive and Respiratory Syndrome Virus- and Actinobacillus pleuropneumoniae-Infected Pigs
Authors: van Dixhoorn Ingrid D. E. , te Beest Dennis E. , Bolhuis Jantina E. , Parmentier Hendrik K. , Kemp Bas , van Mourik Simon , Stockhofe-Zurwieden Norbert , van Reenen Cornelis G. , Rebel Johanna M. J.
Published: November 2021

A large variety of clinical manifestation in individual pigs occurs after infection with pathogens involved in porcine respiratory disease complex (PRDC). Some pigs are less prone to develop respiratory disease symptoms. The variation in clinical impact after infection and the recovery capacity of an individual animal are measures of its resilience. In this paper, we examined which ones of a range of animal-based factors (rectal temperature, body weight, skin lesion scores, behavior, natural antibody serum levels, serum levels of white blood cells, and type of T and granulocyte subsets) when measured prior to infection are related to disease severity. These animal-based factors and the interaction with housing regimen of the piglets (conventional or enriched) were modeled using linear regression to predict disease severity using a dataset acquired from a previous study using a well-established experimental coinfection model of porcine reproductive and respiratory syndrome virus (PRRSV) and Actinobacillus pleuropneumoniae. Both PRRSV and A. pleuropneumoniae are often involved in PRDC. Histological lung lesion score of each animal was used as a measure for PRDC severity after infection. Prior to infection, higher serum levels of lymphocytes (CD3+), naïve T helper (CD3+CD4+CD8−), CD8+ (as well as higher relative levels of CD8+), and memory T helper (CD3+CD4+CD8+) cells and higher relative levels of granulocytes (CD172a) were related to reduced disease severity in both housing systems. Raised serum concentrations of natural IgM antibodies binding to keyhole limpet hemocyanin (KLH) were also related to reduced disease severity after infection. Increased levels of skin lesions at the central body part (after weaning and before infection) were related to increased disease severity in conventional housing systems only. High resisters showed a lower histological lung lesion score, which appeared unrelated to sex. Body temperature, behavior, and growth prior to infections were influenced by housing regimen but could not explain the variation in lung lesion scores after infection. Raised basal lymphocyte counts and lower skin lesion scores are related to reduced disease severity independent of or dependent on housing system, respectively. In conclusion, our study identifies intrinsic animal-based measures using linear regression analysis that predicts resilience to infections in pigs.
Contact Dermatitis in Nail Cosmetics
Authors: Lipman Zoe M. , Tosti Antonella
Published: November 2021

Many ingredients found within nail cosmetic products are capable of sensitizing patients’ immune systems and causing contact dermatitis (CD). These include but are not limited to tosylamide, (meth)acrylates, and formaldehyde. A clear temporal relationship between nail cosmetic procedures and an eczematous outbreak on the hands, face, or other ectopic body regions can be a key indicator of CD secondary to nail cosmetic exposure. Once an inciting allergen is identified through patch testing, elimination and avoidance becomes a mainstay of treatment alongside the use of emollients and topical anti-inflammatory therapies. Patients should be counselled to approach future nail cosmetic products and procedures with caution and careful attention to ingredients, regardless of whether or not it has a “hypoallergenic” label.
An Appraisal of the Field of Metallomics and the Roles of Metal Ions in Biochemistry and Cell Signaling
Authors: Maret Wolfgang
Published: November 2021

Humans require about 20 chemical elements. Half of them are essential metal ions. Many additional, non-essential metal ions are present in our bodies through environmental exposures, including in our diet, with functional consequences. Their accumulation is accelerated due to the increasing pollution of soil, air, water and manufacturing processes that employ chemical elements to which we have not been exposed in our evolutionary history. Yet other metal ions are essential for other forms of life, which calls on life scientists to consider the interactions of life processes with most of the chemical elements in the periodic table. Only in this century have attempts been made to integrate specialty disciplines into a science of bioelements called metallomics. Metallomics forms a fifth group when added to the traditional four building blocks of living cells and their areas of investigations, i.e., sugars (glycomics), fats (lipidomics), proteins (proteomics) and nucleic acids (genomics). Neither an understanding of all the essential metals and their interactions nor the functional impacts of the non-essential metals for life, except established toxic elements such as lead, are widely perceived as important in the basic science communities and in the applied sciences such as medicine and engineering. It is a remarkable oversight that this article attempts to address with representative examples.
The Characteristics of Heavy Ozone Pollution Episodes and Identification of the Primary Driving Factors Using a Generalized Additive Model (GAM) in an Industrial Megacity of Northern China
Authors: Diao Liuli , Bi Xiaohui , Zhang Wenhui , Liu Baoshuang , Wang Xuehan , Li Linxuan , Dai Qili , Zhang Yufen , Wu Jianhui , Feng Yinchang
Published: November 2021

Tropospheric ozone is the only normal pollutant with a continuously increasing annual average concentration worldwide. In this study, data were monitored at the Nankai University Air Quality Research Supersite (NKAQRS) (38.99° N, 117.33° E) between 1 April, and 31 August from 2018 to 2020, 33 O3 episodes from 2018 to 2020 were analyzed to reveal the characteristics of O3, VOCs and OFP during O3 episodes and to evaluate the driving factors. The O3 episodes showed a decreasing trend in terms of pollution frequency, days, heavy pollution duration and peak concentration. Ethane, acetylene, cyclopentane, and methylcyclopentane were the major types in 2020, while 1-hexene was the main component in 2019. The main ozone-contributing species in 2020 were propene cyclopentane methylcyclopentane and ethylene. Alkenes were important contributors to ozone formation. Using generalized additive models (GAMs), the explanatory variables in the study are divided into environmental and meteorological factors, and 16 impact factors are selected as explanatory variables. We found that the influence of these meteorological factors on O3 pollution was nonlinear and impacted by the interaction between variables. O3 episodes were mainly driven by meteorological and precursor (NO) factors in 2018, while meteorological conditions (T), followed by precursor (NO2) were the driving factors in 2019 and 2020, suggesting that O3 episodes were mainly driven by meteorological conditions.
Virtual Detection of Mechanically Induced Short Circuits in a Cylindrical Lithium-Ion Battery Cell Based on Finite Element Simulation
Authors: Jantscher Klemens , Breitfuß Christoph , Miklau Martin , Ismail Khaled , Dobusch Peter
Published: November 2021

Lithium-ion batteries (LIBs) are commonly used in today’s electric vehicles. Studying their behaviour under mechanical loading, including short circuits, is vital for vehicle safety. This paper covers three major topics, (1) a general literature review for the state-of-the-art of LIBs, (2) physical cell tests for model validation are performed, wherein the occurrence of short circuits is detected and (3) creating a finite element model (FEM) of an 18650 cylindrical LIB using the most recent testing and simulation techniques. A variety of short-circuit criteria based on stresses, strains and geometric parameters have been implemented in the simulation and compared to the test results. It will be demonstrated that a combination of two geometric criteria, in the radial and axial directions of the cell, is best suited for virtual short-circuit detection in the simulation. Finally, the short-circuit criteria are implemented in a post-processing tool that allows fast short-circuit analysis of cells of different loadings. In the future, this method of short-circuit detection will be used to analyse an assembly of several battery cells such as, for instance, an automotive or maritime battery pack. Furthermore, the developed method enables mechanical integration with respect to crash safety in vehicles.
Biological Effects of BET Inhibition by OTX015 (MK-8628) and JQ1 in NPM1-Mutated (NPM1c) Acute Myeloid Leukemia (AML)
Authors: Djamai Hanane , Berrou Jeannig , Dupont Mélanie , Coudé Marie-Magdelaine , Delord Marc , Clappier Emmanuelle , Marceau-Renaut Alice , Kaci Anna , Raffoux Emmanuel , Itzykson Raphaël , Berthier Caroline , Wu Hsin-Chieh , Hleihel Rita , Bazarbachi Ali , de Thé Hugues , Baruchel André , Gardin Claude , Dombret Hervé , Braun Thorsten
Published: November 2021

BET inhibitors (BETi) including OTX015 (MK-8628) and JQ1 demonstrated antileukemic activity including NPM1c AML cells. Nevertheless, the biological consequences of BETi in NPM1c AML were not fully investigated. Even if of better prognosis AML patients with NPM1c may relapse and treatment remains difficult. Differentiation-based therapy by all trans retinoic acid (ATRA) combined with arsenic trioxide (ATO) demonstrated activity in NPM1c AML. We found that BETi, similar to ATO + ATRA, induced differentiation and apoptosis which was TP53 independent in the NPM1c cell line OCI-AML3 and primary cells. Furthermore, BETi induced proteasome-dependent degradation of NPM1c. BETi degraded NPM1c in the cytosol while BRD4 is degraded in the nucleus which suggests that restoration of the NPM1/BRD4 equilibrium in the nucleus of NPM1c cells is essential for the efficacy of BETi. While ATO + ATRA had significant biological activity in NPM1c IMS-M2 cell line, those cells were resistant to BETi. Gene profiling revealed that IMS-M2 cells probably resist to BETi by upregulation of LSC pathways independently of the downregulation of a core BET-responsive transcriptional program. ATO + ATRA downregulated a NPM1c specific HOX gene signature while anti-leukemic effects of BETi appear HOX gene independent. Our preclinical results encourage clinical testing of BETi in NPM1c AML patients.
Highly Sensitive Surface Plasmon Resonance Humidity Sensor Based on a Polyvinyl-Alcohol-Coated Polymer Optical Fiber
Authors: Wang Ying , Wang Jingru , Shao Yu , Liao Changrui , Wang Yiping
Published: November 2021

A surface-plasmon-resonance-based fiber device is proposed for highly sensitive relative humidity (RH) sensing and human breath monitoring. The device is fabricated by using a polyvinyl alcohol (PVA) film and gold coating on the flat surface of a side-polished polymer optical fiber. The thickness and refractive index of the PVA coating are sensitive to environmental humidity, and thus the resonant wavelength of the proposed device exhibits a redshift as the RH increases. Experimental results demonstrate an average sensitivity of 4.98 nm/RH% across an ambient RH ranging from 40% to 90%. In particular, the sensor exhibits a linear response between 75% and 90% RH, with a sensitivity of 10.15 nm/RH%. The device is suitable for human breath tests and shows an average wavelength shift of up to 228.20 nm, which is 10 times larger than that of a silica-fiber-based humidity sensor. The corresponding response and recovery times are determined to be 0.44 s and 0.86 s, respectively. The proposed sensor has significant potential for a variety of practical applications, such as intensive care and human health analysis.
Characterizing and Exploiting Tumor Microenvironments to Optimize Treatment Outcomes
Authors: Allott Emma H. , Dean Kellie , Robson Tracy , Meaney Claire
Published: November 2021

Our understanding of cancer initiation, progression, and treatment is continually progressing through dedicated research achieved through laboratory investigation, clinical trials, and patient engagement. The importance and complexity of the microenvironment and its role in tumor development and behavior is pivotal to the understanding of tumor growth and the best course of treatment. The 57th Irish Association for Cancer Research (IACR) Annual Conference collected key researchers, clinicians, and patient advocates together to highlight and discuss the recognized importance of the microenvironment and treatment advances in cancer. In this article, we describe the key components of the microenvironment that influence tumor development and treatment, including the microbiome, metabolism, and immune response and the progress of preclinical models to reflect these complex environments. From a psycho-social oncology perspective, we highlight expert opinion and data on the process of shared decision-making in the context of emerging cancer treatments.
Interstitial Photodynamic Therapy for Glioblastomas: A Standardized Procedure for Clinical Use
Authors: Leroy Henri-Arthur , Baert Gregory , Guerin Laura , Delhem Nadira , Mordon Serge , Reyns Nicolas , Vignion-Dewalle Anne-Sophie
Published: November 2021

Glioblastomas (GBMs) are high-grade malignancies with a poor prognosis. The current standard of care for GBM is maximal surgical resection followed by radiotherapy and chemotherapy. Despite all these treatments, the overall survival is still limited, with a median of 15 months. For patients harboring inoperable GBM, due to the anatomical location of the tumor or poor general condition of the patient, the life expectancy is even worse. The challenge of managing GBM is therefore to improve the local control especially for non-surgical patients. Interstitial photodynamic therapy (iPDT) is a minimally invasive treatment relying on the interaction of light, a photosensitizer and oxygen. In the case of brain tumors, iPDT consists of introducing one or several optical fibers in the tumor area, without large craniotomy, to illuminate the photosensitized tumor cells. It induces necrosis and/or apoptosis of the tumor cells, and it can destruct the tumor vasculature and produces an acute inflammatory response that attracts leukocytes. Interstitial PDT has already been applied in the treatment of brain tumors with very promising results. However, no standardized procedure has emerged from previous studies. Herein, we propose a standardized and reproducible workflow for the clinical application of iPDT to GBM. This workflow, which involves intraoperative imaging, a dedicated treatment planning system (TPS) and robotic assistance for the implantation of stereotactic optical fibers, represents a key step in the deployment of iPDT for the treatment of GBM. This end-to-end procedure has been validated on a phantom in real operating room conditions. The thorough description of a fully integrated iPDT workflow is an essential step forward to a clinical trial to evaluate iPDT in the treatment of GBM.
Prognostic Matrisomal Gene Panel and Its Association with Immune Cell Infiltration in Head and Neck Carcinomas
Authors: Belotti Yuri , Lim Su Bin , Iyer Narayanan Gopalakrishna , Lim Wan-Teck , Lim Chwee Teck
Published: November 2021

Squamous cell carcinoma of the head and neck (SCCHN) is common worldwide and related to several risk factors including smoking, alcohol consumption, poor dentition and human papillomavirus (HPV) infection. Different etiological factors may influence the tumor microenvironment and play a role in dictating response to therapeutics. Here, we sought to investigate whether an early-stage SCCHN-specific prognostic matrisome-derived gene signature could be identified for HPV-negative SCCHN patients (n = 168), by applying a bioinformatics pipeline to the publicly available SCCHN-TCGA dataset. We identified six matrisome-derived genes with high association with prognostic outcomes in SCCHN. A six-gene risk score, the SCCHN TMI (SCCHN-tumor matrisome index: composed of MASP1, EGFL6, SFRP5, SPP1, MMP8 and P4HA1) was constructed and used to stratify patients into risk groups. Using machine learning-based deconvolution methods, we found that the risk groups were characterized by a differing abundance of infiltrating immune cells. This work highlights the key role of immune infiltration cells in the overall survival of patients affected by HPV-negative SCCHN. The identified SCCHN TMI represents a genomic tool that could potentially aid patient stratification and selection for therapy in these patients.