Miracle-dz/UniFAR-FTUs huggingface dataset:
Recent trends in next generation immunoinformatics harnessed for universal coronavirus vaccine design

ABSTRACT The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has globally devastated public health, the economies of many countries and quality of life universally. The recent emergence of immune-escaped variants and scenario of vaccinated individuals being infected has raised the global concerns about the effectiveness of the current available vaccines in transmission control and disease prevention. Given the high rate mutation of SARS-CoV-2, an efficacious vaccine targeting against multiple variants that contains virus-specific epitopes is desperately needed. An immunoinformatics approach is gaining traction in vaccine design and development due to the significant reduction in time and cost of immunogenicity studies and increasing reliability of the generated results. It can underpin the development of novel therapeutic methods and accelerate the design and production of peptide vaccines for infectious diseases. Structural proteins, particularly spike protein (S), along with other proteins have been studied intensively as promising coronavirus vaccine targets. Numbers of promising online immunological databases, tools and web servers have widely been employed for the design and development of next generation COVID-19 vaccines. This review highlights the role of immunoinformatics in identifying immunogenic peptides as potential vaccine targets, involving databases, and prediction and characterization of epitopes which can be harnessed for designing future coronavirus vaccines.
Tissue-resident memory T cells from a metastatic vaginal melanoma patient are tumor-responsive T cells and increase after anti-PD-1 treatment

Background Vaginal melanoma (VM) is a rare cancer and has a poor response to immune checkpoint blockade (ICB). CD8+Tissue Resident Memory (TRM) T cells proliferate in response to ICB and correlate with longer survival in metastatic cutaneous melanoma. However, their capacity to respond to VM and their neoantigens is not known. Methods Using longitudinal samples, we explored the evolution of VM mutations by whole-exome sequencing and RNAseq, we also defined the immune context using multiplex immunohistochemistry and nanostring pan cancer immune profile. Then using fresh single cell suspensions of the metastatic samples, we explored VM T cells via mass cytometry and single cell RNAseq and T cell receptor sequencing (TCRseq). Finally, we investigated TRM, pre-TRM and exhausted T cell function against melanoma neo-antigens and melanoma differentiation antigens in vitro. Results Primary VM was non-inflamed and devoid of CD8+ TRM cells. In contrast, both metastases showed proliferating CD8+ TRM were clustered at the tumor margin, with increased numbers in the second ICB-refractory metastasis. The first metastasis showed dense infiltration of CD8+ T cells, the second showed immune exclusion with loss of melanoma cell Major histocompatibility complex (MHC)-I expression associated with downregulation of antigen presentation pathway gene expression. CD8+ TRM from both metastases responded to autologous melanoma cells more robustly than all other CD8+ T cell subsets. In addition, CD8+ TRM shared TCR clones across metastases, suggesting a response to common antigens, which was supported by recognition of the same neoantigen by expanded tumor infiltrating lymphocytes. Conclusions In this study, we identified TRM clusters in VM metastases from a patient, but not primary disease. We showed TRM location at the tumor margin, and their superior functional response to autologous tumor cells, predicted neoantigens and melanoma differentiation antigens. These CD8+ TRM exhibited the highest tumor-responsive potential and shared their TCR with tumor-infiltrating effector memory T cells. This suggests VM metastases from this patient retain strong antitumor T cell functional responses; however, this response is suppressed in vivo. The loss of VG MHC-I expression is a common immune escape mechanism which was not addressed by anti-PD-1 monotherapy; rather an additional targeted approach to upregulate MHC-I expression is required.
AMI in (bi)ventricular pacing – do not discard the ECG

ABSTRACT Background There is a growing number of patients with ventricular paced rhythm, who present to the emergency department with chest pain. The diagnosis of ST-segment elevation myocardial infarction (STEMI) and subsequent percutaneous coronary intervention (PCI) is often postponed, as the 12 leads-electrocardiogram (ECG) is discarded as not interpretable. There is a growing body of literature that suggests that Smith-modified Sgarbossa criteria can be applied for the diagnosis of STEMI in patients with paced rhythms. These criteria were originally developed for the interpretation of ECGs in patients with a left bundle branch block (LBBB) and chest pain, but have been expanded to paced ECGs. Methodology We present three case reports with chest pain and right ventricular or biventricular pacing. Findings In all three cases, the Smith-modified Sgarbossa was positive and the diagnosis of STEMI could have been made early on. Implications It remains important to look for ST-segment deviations and to compare the symptomatic ECG with previous asymptomatic ECGs. As the number of patients with potential acute myocardial infarction (AMI) and paced rhythms is likely to rise in the future, these criteria should be known to emergency physicians and cardiologists.
In vitro effects of aqueous extract of unfermented rooibos on human spermatozoa

The inability to conceive is a baleful experience for thousands of couples worldwide. Among different well‐known reproductive techniques, medicinal plants have been utilized to treat male infertility. Medicinal plants, provide a therapeutic alternative, which is available and affordable for infertile couples. We investigated the direct effect of unfermented rooibos aqueous extract on human spermatozoa. Semen samples (n = 50) collected from donors and patients consulting for fertility were reassigned as normal (n = 22) and abnormal (n = 28) samples based on the outcome of the baseline semen analysis, using the World Health Organization (WHO) cut off value. Semen samples were allowed to liquefy and subsequently washed with human tubular fluid in bovine serum albumin medium. The samples were then treated with aqueous extracts of unfermented rooibos (0, 0.15, 1.5, 15, 150 μg/ml) at 37°C for 1 h and assessed thereafter. Sperm motility, vitality, DNA fragmentation, intracellular reactive oxygen species and mitochondrial membrane potential in both groups remained unchanged (p > 0.05). However, aqueous extract of unfermented rooibos (only at 1.5 μg/ml) significantly increased capacitation and acrosome reaction in the abnormal sample group (p > 0.05). Unfermented rooibos aqueous extract had no deleterious impact on human spermatozoa's function and might be attributed to its antioxidant properties.
DIFFERENTIAL EXPRESSION PATTERN OF AIP, UCKL1, AND PKN1 GENES IN PROSTATE CANCER PATIENTS.

BACKGROUND The evolution of research on the therapy of prostate cancer (PC) depends on a study of molecules that are involved in the progression of this disease. Nevertheless, there is a need for additional biomarkers that would help to refine the molecular profile of PC and propose the personalized therapeutic approach. AIM To study differential expression patterns of the AIP, UCKL1, and PKN1 genes in blood sera and tumor tissue of patients with PC with different Gleason scores. MATERIALS AND METHODS The total extracellular RNA was isolated from blood sera of 44 PC patients and 4 healthy donors. cDNAs were synthesized and quantitative polymerase chain reaction (qPCR) was performed. Immunohistochemical study of the UCKL, AIP and PKN1 proteins was performed on deparaffinized sections of tumors. The study was supplemented by a bioinformatic analysis of the publicly available databases. RESULTS The UCKL1, AIP, PKN1 genes were overexpressed at the mRNA level in blood sera of PC patients, compared to healthy donors. Extracellular mRNA levels of AIP and UCKL-1 were 100-1000-fold increased in all PC samples compared to the healthy donors but without significant inequality between the groups of PC cases differing by the Gleason score. The highest levels were detected in the samples from PC patients with the Gleason score > 9. The PKN1 expression was higher in PC patients compared with healthy donors but without significant difference between the groups. CONCLUSIONS From the three chosen genes, AIP and UCKL1 showed similar pattern of expression assessed either by extracellular mRNA levels in patient sera or the protein in PC tissues. AIP was up to 1000-fold increased in all PC samples, compared to the healthy donors, with the highest levels in PC cases with Gleason score > 9. Expression levels of the AIP and UCKL1 genes in the PC patient sera may be used as an additional criterion for prognosis of tumor progression.
Identifying the Caenorhabditis elegans vulval transcriptome

Abstract Development of the Caenorhabditis elegans vulva is a classic model of organogenesis. This system, which starts with 6 equipotent cells, encompasses diverse types of developmental event, including developmental competence, multiple signaling events to control precise and faithful patterning of three cell fates, execution and proliferation of specific cell lineages, and a series of sophisticated morphogenetic events. Early events have been subjected to extensive mutational and genetic investigations and later events to cell biological analyses. We infer the existence of dramatically changing profiles of gene expression that accompanies the observed changes in development. Yet, except from serendipitous discovery of several transcription factors expressed in dynamic patterns in vulval lineages, our knowledge of the transcriptomic landscape during vulval development is minimal. This study describes the composition of a vulva-specific transcriptome. We used tissue-specific harvesting of mRNAs via immunoprecipitation of epitope-tagged poly(A) binding protein, PAB-1, heterologously expressed by a promoter known to express GFP in vulval cells throughout their development. The identified transcriptome was small but tightly interconnected. From this data set, we identified several genes with identified functions in development of the vulva and validated more with promoter-GFP reporters of expression. For one target, lag-1, promoter-GFP expression was limited but a fluorescent tag of the endogenous protein revealed extensive expression. Thus, we have identified a transcriptome of C. elegans vulval lineages as a launching pad for exploration of functions of these genes in organogenesis.
Understanding, Experience, and Response Strategies to Sexual Harassment Among Chinese College Students

Sexual harassment is a serious problem, and with a growing population of college students in China, the phenomenon is becoming prevalent. Using the 2010 data from the Third Survey on Chinese Women’s Social Status, we examined relationships between understanding of sexual harassment and experience/response among Chinese college students. The results show that college students understand physical sexual harassment better (88%; unwanted sexual requests: 92%) than verbal and visual sexual harassment (54% and 70%, respectively). Understanding is higher among females than males, with a margin between eight to 21%. At a prevalence of 30%, the experience of verbal sexual harassment is the highest compared to other forms of harassment. Males were more likely to experience verbal and visual sexual harassment, while females were more likely to experience physical sexual harassment. In any event of sexual harassment, expressing dissatisfaction and stopping it is the response strategy that most resonates with respondents. It varied between 62% and 70% across forms of sexual harassment. Reporting to teachers or school authorities resonates least, varying between 0.30% and 2.28%. Understanding sexual harassment was strongly associated with a reduced likelihood of harassment. The equivalent odds ratios varied between 0.41 and 0.33 (p < .001), or 59–67% reduced likelihood across the forms of sexual harassment. Understanding sexual harassment was also strongly associated with an increased likelihood of not reacting passively or staying silent. Odds ratio varied between 1.99 and 3.86 (p < .001), about a minimum of twofold increased likelihood. Parents should strive to involve in their children’s sex and sexual rights education, particularly during adolescence, to help them inculcate values against sexual harassment. Also, colleges and universities can bolster their curriculum with elective courses on sex education and regularly organize symposiums on sexual harassment to create a better understanding and awareness among students.
Financial Assistance Processes and Mechanisms in Rural and Nonrural Oncology Care Settings

PURPOSE: Patients with cancer are at heightened risk of experiencing financial hardship. Financial navigation (FN) is an evidence-based approach for identifying and addressing patient and caregiver financial needs. In preparation for the implementation of a multisite FN intervention, we describe existing processes (ie, events and actions) and mechanisms (ie, how events work together) connecting patients to financial assistance, comparing rural and nonrural practices. METHODS: We conducted in-depth, semistructured interviews with stakeholders (ie, administrators, providers, and staff) at each of the 10 oncology care sites across a single state (five rural and five nonrural practices). We developed process maps for each site and analyzed stakeholder perspectives using thematic analysis. After reporting findings back to stakeholders, we synthesized themes and process maps across rural and nonrural sites separately. RESULTS: Eighty-three stakeholders were interviewed. We identified six core elements of existing financial assistance processes across all sites: distress screening (including financial concerns), referrals, resource connection points, and pharmaceutical, insurance, and community/foundation resources. Processes differed by rurality; however, facilitators and barriers to identifying and addressing patient financial needs were consistent. Open communication between staff, providers, patients, and caregivers was a primary facilitator. Barriers included insufficient staff resources, challenges in routinely identifying needs, inadequate preparation of patients for anticipated medical costs, and limited tracking of resource availability and eligibility. CONCLUSION: This study identified a clear need for systematic implementation of oncology FN to equitably address patient and caregiver financial hardship. Results have informed our current efforts to implement a multisite FN intervention, which involves comprehensive financial toxicity screening and systematization of intake and referrals.
Differences in Collagen Fiber Diameter and Waviness between Healthy and Aneurysmal Abdominal Aortas

Abstract Collagen plays a key role in the strength of aortic walls, so studying micro-structural changes during disease development is critical to better understand collagen reorganization. Second-harmonic generation microscopy is used to obtain images of human aortic collagen in both healthy and diseased states. Methods are being developed in order to efficiently determine the waviness, that is, tortuosity and amplitude, as well as the diameter, orientation, and dispersion of collagen fibers, and bundles in healthy and aneurysmal tissues. The results show layer-specific differences in the collagen of healthy tissues, which decrease in samples of aneurysmal aortic walls. In healthy tissues, the thick collagen bundles of the adventitia are characterized by greater waviness, both in the tortuosity and in the amplitude, compared to the relatively thin and straighter collagen fibers of the media. In contrast, most aneurysmal tissues tend to have a more uniform structure of the aortic wall with no significant difference in collagen diameter between the luminal and abluminal layers. An increase in collagen tortuosity compared to the healthy media is also observed in the aneurysmal luminal layer. The data set provided can help improve related material and multiscale models of aortic walls and aneurysm formation.
Genome sequencing and genomic analysis of Amycolatopsis tucumanensis DSM 45259 applicable in gray, red, and nano‐biotechnology

Through the years, the genus Amycolatopsis has demonstrated its biotechnological potential. The need to clean up the environment and produce new antimicrobial molecules led to exploit promising bacterial genera such as Amycolatopsis. In this present work, we analyze the genome of the strain Amycolatopsis tucumanensis AB0 previously isolated from copper‐polluted sediments. Phylogenomic and comparative analysis with the closest phylogenetic neighbor was performed. Our analysis showed the genetic potential of the strain to deal with heavy metals such as copper and mitigate oxidative stress. In addition, the ability to produce copper oxide nanoparticles and the presence of genes potentially involved in the synthesis of secondary metabolites suggest that A. tucumanensis may find utility in gray, red, and nano‐biotechnology. To our knowledge, this is the first genomic analysis of an Amycolatopsis strain with potential for different biotechnological fields.
Illustrating systemic change in family therapy: How therapists’ and clients’ alliance perceptions codevelop over time

Abstract Research showing that caregivers’, adolescents’ and therapists’ perceptions of the therapeutic alliance become more similar over time has not examined conceptual models, like emotional contagion and interdependence, that are theorized to account for this convergence. Objective: We modeled codevelopment in systemic family therapy to examine mutual influence and shared environment processes among the alliance perceptions of youth, caregivers, and therapists. Method: The self-report version of the System for Observing Family Therapy Alliances (SOFTA-s) was administered after sessions 3, 6 and 9–156 Spanish maltreating families and 20 therapists. Results: Using a triadic version of the repeated measures actor-partner interdependence analysis, a random intercepts cross-lagged panel model, we found significant effects of the shared environment and mutual influence in caregivers’ and therapists’ alliance scores over time, reflecting emotional contagion. Additionally, (i) therapists’ alliance scores at session 6 significantly predicted youth alliance scores at session 9, and (ii) therapist alliance at session 6 significantly mediated the relationship between caregiver alliance at session 3 and youth alliance at session 9, suggesting that therapists bridge the caregiver’s and youth’s perceptions of the alliance. In successful (compared to unsuccessful) cases, therapists’ alliance perceptions at session 6 positively influenced caregivers’ alliance perceptions at session 9. Conclusion: Therapist’s perceptions of the alliance can bridge differences in alliance perceptions of caregivers and adolescents resulting in greater similarity in alliance perceptions over time.
Reply to comment on: Massive transfusion experience, current practice and decision support: A survey of Australian and New Zealand Anaesthetists

We would like to congratulate Dr Miller and colleagues on developing a smartphone application to provide clinical decision support (CDS) for interpreting rotational thromboelastometry (ROTEMR ; TEM international GmbH, Munich, Germany), a form of viscoelastic haemostatic assay (VHA) for pointof-care coagulation assessment in the context of massive transfusion (MT). MT is a complex and multifaceted task that can occur unpredictably and require significant resources at a moment’s notice. Cognitive aids and CDS as paper-based or electronic tools are increasingly used in resuscitation scenarios. MTs are also commonly protocol-based, where institutional massive transfusion protocols (MTP) are used to direct staff, determine blood products to be transfused, provide goals of care and provide CDS to clinicians, and therefore lend themselves towards an electronic CDS solution, given their complexity. Despite the adoption of point-of-care coagulation assessment into clinical practice for the management of major haemorrhage, its benefit in MT has not yet been established. A recent trial that compared VHA-based management of major trauma haemorrhage versus use of conventional coagulation testing found no difference in patient outcomes. Smartphones are almost ubiquitous in healthcare, with a recent survey of anaesthetists demonstrating all respondents owned a smartphone and used their device during clinical practice. With each new model, specifications, connectivity and integrations have expanded, to the point where they can even be used for arrhythmia diagnosis. Given their availability and capabilities, it is no wonder that CDS is increasingly being implemented using smartphone-based medical applications. Smartphones are also an attractive option to deploy new tools rapidly in what can otherwise be difficult Electronic Medical Record software environments. The evidence to support widespread adoption of these smartphone applications for decision support, however, is lacking. A recent review of CDS smartphone applications for use across a broad range of areas demonstrated a lack of rigorous clinical trial–based evaluation and instead found that research mainly focused on diagnostic accuracy. Even if smartphone applications show benefit in a research environment, their success will still depend on addressing the real-world organisational, human and technological implementation factors faced by any medical device. In-house development of these IT solutions and other devices in medicine more generally by motivated clinicians are a great source of ingenuity, but they come with a risk of ‘MacGyver bias’—a term coined by Duggan et al. to describe the tendency to hold improvised devices in ‘high regard despite the relative absence of evidence for their efficacy’. In-house developers also need to consider regulatory requirements of medical devices relevant in their jurisdiction. In Australia, the Therapeutic Goods Administration requires registration of medical devices and CDS software before