Miracle-dz/UniFAR-FTUs huggingface dataset:
Experienced, trauma-informed teachers working in remote Australia: What is required for their work to be effective?

Introduction In remote education settings in Australia, experienced teachers who can effectively support students impacted by trauma are essential. Remote communities are unique yet are in many ways vulnerable to trauma as they face higher rates of disadvantage and exposure to traumatic events, including natural disasters and domestic and family violence. This is compounded by a lack of access to effective supports due to the tyranny of distance. Also, First Nations peoples living in remote areas continue to endure the ongoing and traumatic impacts of a violent and disruptive colonization. Methods The qualitative research study detailed in this article explored the requirements for the work of experienced, trauma-informed teachers in remote Australia to be effective, adding an important and unique perspective to the research evidence that is not often considered. Seven teachers from remote Australia completed a short, online questionnaire and participated in a focus group interview which was analyzed thematically. Results Themes emerging from the focus group data indicated that specific and contextualized preparation and support for teachers is required for them to do their work effectively. For remote Australian settings this means preparing teachers with cultural awareness and relevant trauma-informed training. Further, the wellbeing of these remote educators is often compromised, and addressing systemic factors such as adequate preparation of their colleagues and support to access relevant ongoing professional learning is needed. Discussion Remote teaching work in Australia is complex, and while the current study is small and exploratory in nature, the findings highlight some of the real-world impacts of these issues at a community and individual teacher level that have not been previously explored.
The nasal microbiome in patients suffering from non-steroidal anti-inflammatory drugs-exacerbated respiratory disease in absence of corticosteroids

Chronic rhinosinusitis (CRS) is a chronic inflammatory disease phenotypically classified by the absence (CRSsNP) or presence of nasal polyps (CRSwNP). The latter may also be associated with asthma and hypersensitivity towards non-steroidal anti-inflammatory drugs (NSAID) as a triad termed NSAID-exacerbated respiratory disease (N-ERD). The role of the microbiome in these different disease entities with regard to the underlying inflammatory process and disease burden is yet not fully understood. To address this question, we measured clinical parameters and collected nasal samples (nasal mucosal fluids, microbiome swabs from middle meatus and anterior naris) of patients suffering from CRSsNP (n=20), CRSwNP (n=20) or N-ERD (n=20) as well as from patients without CRS (=disease controls, n=20). Importantly, all subjects refrained from taking local or systemic corticosteroids or immunosuppressants for at least two weeks prior to sampling. The nasal microbiome was analyzed using 16S rRNA gene amplicon sequencing, and levels of 33 inflammatory cytokines were determined in nasal mucosal fluids using the MSD platform. Patients suffering from N-ERD and CRSwNP showed significantly worse smell perception and significantly higher levels of type 2 associated cytokines IL-5, IL-9, Eotaxin and CCL17. Across all 4 patient groups, Corynebacteria and Staphylococci showed the highest relative abundances. Although no significant difference in alpha and beta diversity was observed between the control and the CRS groups, pairwise testing revealed a higher relative abundance of Staphylococci in the middle meatus in N-ERD patients as compared to CRSwNP (p<0.001), CRSsNP (p<0.01) and disease controls (p<0.05) and of Lawsonella in patients suffering from CRSwNP in middle meatus and anterior naris in comparison to CRSsNP (p<0.0001 for both locations) and disease controls (p<0.01 and p<0.0001). Furthermore, we observed a positive correlation of Staphylococci with IL-5 (Pearson r=0.548) and a negative correlation for Corynebacteria and Eotaxin-3 (r=-0.540). Thus, in patients refraining from oral and nasal corticosteroid therapy for at least two weeks known to alter microbiome composition, we did not observe differences in microbiome alpha or beta diversity between various CRS entities and disease controls. However, our data suggest a close association between increased bacterial colonization with Staphylococci and decreased colonization by Corynebacteria as well as increased type 2 inflammation.
Monitoring of kinetics and exhaustion markers of circulating CAR-T cells as early predictive factors in patients with B-cell malignancies

Purpose CAR-T cell therapy has proven to be a disruptive treatment in the hematology field, however, less than 50% of patients maintain long-term response and early predictors of outcome are still inconsistently defined. Here, we aimed to optimize the detection of CD19 CAR-T cells in blood and to identify phenotypic features as early biomarkers associated with toxicity and outcomes. Experimental design In this study, monitoring by flow cytometry and digital PCR (dPCR), and immunophenotypic characterization of circulating CAR-T cells from 48 patients treated with Tisa-cel or Axi-cel was performed. Results Validation of the flow cytometry reagent for the detection of CAR-T cells in blood revealed CD19 protein conjugated with streptavidin as the optimal detection method. Kinetics of CAR-T cell expansion in blood confirmed median day of peak expansion at seven days post-infusion by both flow cytometry and digital PCR. Circulating CAR-T cells showed an activated, proliferative, and exhausted phenotype at the time of peak expansion. Patients with increased expansion showed more severe CRS and ICANs. Immunophenotypic characterization of CAR-T cells at the peak expansion identified the increased expression of co-inhibitory molecules PD1 and LAG3 and reduced levels of the cytotoxicity marker CD107a as predictors of a better long-term disease control. Conclusions These data show the importance of CAR-T cells in vivo monitoring and identify the expression of PD1LAG3 and CD107a as early biomarkers of long-term disease control after CAR-T cell therapy.
Therapeutic mammoplasty: a “wise” oncoplastic choice—lessons from the largest single-center cohort from Asia

Introduction The majority of breast cancer patients from India usually present with advanced disease, limiting the scope of breast conservation surgery. Therapeutic mammoplasty (TM), an oncoplastic technique that permits larger excisions, is quite promising in such a scenario and well suited to breast cancer in medium-to-large-sized breasts with ptosis and in some cases of large or multifocal/multicentric tumors. Here, we describe our TM cohort of 205 (194 malignant and 11 benign) patients from 2012 to 2019 treated at a single surgeon center in India, the largest Asian dataset for TM. Methods All patients underwent treatment after careful discussions by a multidisciplinary tumor board and patient counseling. We report the clinicopathological profiles and surgical, oncological, cosmetic, and patient-related outcomes with different TM procedures. Results The median age of breast cancer patients was 49 years; that of benign disease patients was 41 years. The breast cancer cohort underwent simple (n = 84), complex (n = 71), or extreme (n = 44) TM surgeries. All resection margins were analyzed through intra-operative frozen-section assessment with stringent rad-path analysis protocols. The margin positivity rate was found to be 1.4%. A majority of the cohort was observed to have pT1–pT2 tumors, and the median resection volume was 180 cc. Low post-operative complication rates and good-to-excellent cosmetic scores were observed. The median follow-up was 39 months. We observed 2.07% local and 5.7% distal recurrences, and disease-specific mortality was 3.1%. At median follow-up, the overall survival was observed to be 95.9%, and disease-free survival was found to be 92.2%. The patient-reported outcome measures (PROMs) showed good-to-excellent scores for all types of TMs across BREAST-Q domains. Conclusion We conclude that in India, a country where women present with large and locally advanced tumors, TM safely expands the indications for breast conservation surgery. Our results show oncological and cosmetic outcomes at acceptable levels. Most importantly, PROM scores suggest improved overall wellbeing and better satisfaction with the quality of life. For patients with macromastia, this technique not only focuses on cancer but also improves self-image and reduces associated physical discomfort often overlooked by women in the Indian setting. The popularization of this procedure will enable Indian patients with breast cancer to receive the benefits of breast conservation.
Sweetening K-channels: what sugar taught us about permeation and gating

Because they enable for the modification of both viscosity and osmolarity, sugars have been used as a biophysical probe of voltage-gated K-channels for a while. Viscosity variations made it possible to measure the pore sizes in large and small conductance K-channels using techniques similar to those used in the 1980s to study the gramicidin A channel. These analyses led to the finding that the size of the internal mouth appears to be the primary cause of the conductance differences between Shaker-like channels and large conductance BK-channels. As an osmotic agent, adding sugar unilaterally causes streaming potentials that indicate H2O/K+ cotransport across the BK-channel pore. Osmotic experiments on Shaker K-channels suggest that the pore gate operation and the slow inactivation displace comparable amounts of water. Functionally isolated voltage sensors allow estimation of individual osmotic work for each voltage sensing charge during voltage-activation, reporting dramatic internal and external remodeling of the Voltage Sensing Domain´s solvent exposed surfaces. Remarkably, each charge of the VSD appears to take a unique trajectory. Thus, manipulation of viscosity and osmolarity, together with 3D structures, brings in solid grounds to harmonize function and structure in membrane proteins such as K-channels and, in a wider scope, other structurally dynamic proteins.
Consumer perception of “artificial meat” in the educated young and urban population of Africa

African’s population is expected to grow especially in cities to reach about 2.5 billion in 2050. This will create an unprecedented boom in the demand for animal products over the coming years which will need to be managed properly. Industry stakeholders worldwide have been touting the potential benefits of “artificial meat” in recent years as a more sustainable way of producing animal protein. “Artificial meat” is therefore moving into the global spotlight and this study aimed to investigate how African meat consumers of the coming generations perceive it, i.e., the urban, more educated and younger consumers. Three surveys were conducted with more than 12,000 respondents in total. The respondents came from 12 different countries (Cameroon, Congo, -DRC Democratic Republic of Congo, Ghana, Ivory Coast, Kenya, Morocco, Nigeria, Senegal South Africa, Tanzania and Tunisia). Respondents in this survey prefered the term “artificial meat”. This term was therefore used throughout the survey. “Artificial meat” proved to be fairly well known in the surveyed countries as about 64% the respondents had already heard of “artificial meat. ” Only 8.9% were definitely willing to try “artificial meat” (score of 5 on a scale of 1–5) mostly males between 31 and 50 years of age. Furthermore, 31.2% strongly agreed that “artificial meat” will have a negative impact on the rural life (score of 5 on a scale of 1–5) and 32.9% were not prepared to accept “artificial meat” as a viable alternative in the future but were still prepared to eat meat alternatives. Of all the results, we observed significant differences in responses between respondents’ countries of origin, age and education level with interactions between these factors for willingness to try. For instance, the richest and most educated countries that were surveyed tended to be more willing to try “artificial meat. ” A similar pattern was observed for willingness to pay, except that gender had no significant effect and age had only a small effect. One major observation is that a large majority of respondents are not willing to pay more for “artificial meat” than for meat from livestock.
Development of an anti-Pseudomonas aeruginosa therapeutic monoclonal antibody WVDC-5244

The rise of antimicrobial-resistant bacterial infections is a crucial health concern in the 21st century. In particular, antibiotic-resistant Pseudomonas aeruginosa causes difficult-to-treat infections associated with high morbidity and mortality. Unfortunately, the number of effective therapeutic interventions against antimicrobial-resistant P. aeruginosa infections continues to decline. Therefore, discovery and development of alternative treatments are necessary. Here, we present pre-clinical efficacy studies on an anti-P. aeruginosa therapeutic monoclonal antibody. Using hybridoma technology, we generated a monoclonal antibody and characterized its binding to P. aeruginosa in vitro using ELISA and fluorescence correlation spectroscopy. We also characterized its function in vitro and in vivo against P. aeruginosa. The anti-P. aeruginosa antibody (WVDC-5244) bound P. aeruginosa clinical strains of various serotypes in vitro, even in the presence of alginate exopolysaccharide. In addition, WVDC-5244 induced opsonophagocytic killing of P. aeruginosa in vitro in J774.1 murine macrophage, and complement-mediated killing. In a mouse model of acute pneumonia, prophylactic administration of WVDC-5244 resulted in an improvement of clinical disease manifestations and reduction of P. aeruginosa burden in the respiratory tract compared to the control groups. This study provides promising pre-clinical efficacy data on a new monoclonal antibody with therapeutic potential for P. aeruginosa infections.
Different risk and prognostic factors for liver metastasis of breast cancer patients with de novo and relapsed distant metastasis in a Chinese population

Purpose The present study aimed to identify clinicopathological characteristics of breast cancer liver metastasis (BCLM) as well as to characterize the risk and prognostic factors for the liver metastasis (LM) of breast cancer patients with de novo and relapsed distant metastasis in a Chinese population. Materials and methods Patients with metastatic breast cancer (MBC) who were hospitalized in the Breast Cancer Center at Chongqing University between January 2011 and December 2019 were included in the present study. Logistic regression analyses were conducted to identify risk factors for the presence of BCLM. Cox proportional hazard regression models were performed to determine the prognostic factors for the survival of BCLM patients. The correlation between LM and overall survival was assessed by the Kaplan–Meier method. Results In total, 1,228 eligible MBC patients, including 325 cases (26.5%) with de novo metastasis (cohort A) and 903 cases (73.5%) with relapsed metastasis (cohort B), were enrolled in the present study. In cohort A and cohort B, 81 (24.9%) and 226 (25.0%) patients had BCLM, respectively. Patients in these two cohorts had different clinicopathological features. Logistic regression analysis identified that the human epidermal growth factor receptor 2 (HER2) status in cohort A as well as the HER2 status and invasive ductal carcinoma histology in cohort B were risk factors for BCLM. The median OS of patients with LM was inferior to that of non-LM patients (17.1 vs. 37.7 months, P = 0.0004 and 47.6 vs. 84.0 months, P < 0.0001, respectively). Cox analysis identified that the primary T stage, Ki67 level, and breast surgery history were independent prognostic factors for cohorts A and B, respectively. Conclusions De novo and relapsed MBC patients have different risk and prognostic factors for LM. Patients with BCLM have an unfavorable prognosis.
BRAF-mediated brain tumors in adults and children: A review and the Australian and New Zealand experience

The mitogen-activated protein kinase (MAPK) pathway signaling pathway is one of the most commonly mutated pathways in human cancers. In particular, BRAF alterations result in constitutive activation of the rapidly accelerating fibrosarcoma–extracellular signal–regulated kinase–MAPK significant pathway, leading to cellular proliferation, survival, and dedifferentiation. The role of BRAF mutations in oncogenesis and tumorigenesis has spurred the development of targeted agents, which have been successful in treating many adult cancers. Despite advances in other cancer types, the morbidity and survival outcomes of patients with glioma have remained relatively stagnant. Recently, there has been recognition that MAPK dysregulation is almost universally present in paediatric and adult gliomas. These findings, accompanying broad molecular characterization of gliomas, has aided prognostication and offered opportunities for clinical trials testing targeted agents. The use of targeted therapies in this disease represents a paradigm shift, although the biochemical complexities has resulted in unexpected challenges in the development of effective BRAF inhibitors. Despite these challenges, there are promising data to support the use of BRAF inhibitors alone and in combination with MEK inhibitors for patients with both low-grade and high-grade glioma across age groups. Safety and efficacy data demonstrate that many of the toxicities of these targeted agents are tolerable while offering objective responses. Newer clinical trials will examine the use of these therapies in the upfront setting. Appropriate duration of therapy and durability of response remains unclear in the glioma patient cohort. Longitudinal efficacy and toxicity data are needed. Furthermore, access to these medications remains challenging outside of clinical trials in Australia and New Zealand. Compassionate access is limited, and advocacy for mechanism of action-based drug approval is ongoing.
Diagnostic value of the apparent diffusion coefficient in differentiating malignant from benign endometrial lesions

Introduction Magnetic resonance imaging (MRI) with its innovative techniques, such as diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC), increases the diagnostic accuracy in distinguishing between malignant and benign lesions of the endometrium. The aim of the study was MRI differentiation between malignant and benign endometrial lesions and correlation with histopathological findings with a special emphasis on quantitative analysis. An additional aim was to correlate the ADC values and histological tumor grades. Methods The prospective study included 119 female patients with or without vaginal bleeding and pathological values of endometrial thickness, who underwent MRI examinations. According to MRI reports the patients were divided into 45 suspicious malignant and 74 suspicious benign endometrial lesions. The radiological diagnosis was compared to the histopathological evaluation, which confirmed 37 malignant lesions while the rest were benign. Results The mean ADC value for malignant lesions was 0.761 ± 0.13×10−3 mm2/s and for benign lesions was 1.318 ± 0.20×10−3 mm2/s. The ADC values for malignant lesions were expectedly lower than those of benign lesions (p<0.001). The ADC cut-off value was 1.007×10−3 mm2/s with a sensitivity of 100%, specificity of 92.7%, a positive predictive value of 60.3%, and a negative predictive value of 100%. In comparison with the histopathological findings, the sensitivity of MRI was 100%, specificity 90.2%, positive predictive value was 82.2%, and negative predictive value was 100%. Observing the histological grades 1, 2, and 3 of endometrial carcinoma, no statistically significant differences of mean ADC values were found. The mean ADC values for histological tumor grades 1,2 and 3 were 0.803 ± 0.13×10−3 mm2/s, 0.754 ± 0.12×10−3 mm2/s and 0.728 ± 0.13×10−3 mm2/s, respectively. Conclusion DWI and ADC values represent clinically useful tools for the differentiation between malignant and benign endometrial lesions with high sensitivity and good specificity, but the results failed to demonstrate their usefulness in differentiating histological grades of endometrial cancer.
The double-edged sword of inflammation in inherited retinal degenerations: Clinical and preclinical evidence for mechanistically and prognostically impactful but treatable complications

We present retrospective data from our clinical research efforts of the past several years alongside a review of past and current clinical and preclinical data independently by several investigators supporting our clinical evidence for the importance of inflammation in inherited retinal degenerations (IRDs). We show how inflammation is a complicating factor in IRDs but, if recognized and managed, also a great opportunity to mitigate disease severity immediately, improve patient prognosis and quality of life, extend the treatment windows for gene-specific and agnostic therapeutic approaches, mitigate the impact of inflammatory complications on the accurate estimate of vision changes in IRD natural history studies, improve the chances of safer outcomes following cataract surgery, and potentially reduce the likelihood of inflammatory adverse events and augment the efficacy of viral vector-based treatment approaches to IRDs. Manuscript contribution to the field. Inflammation has been suspected to be at play in IRDs since the beginning of the 1900s and became a research focus through the early 1990s but was then largely abandoned in favor of genetic-focused research. Thanks to regained cognizance, better research tools, and a more holistic approach to IRDs, the recent reappraisal of the role of inflammation in IRDs has brought back to the surface its importance. A potential confounder in natural history studies and a limiting factor in clinical trials if not accounted for, inflammation can be managed and often offers an opportunity for immediately improved prognosis and outcomes for IRD patients. We present our retrospective clinical evidence for connections with a measurable secondary autoimmune component that can develop in IRDs and contribute to vision loss but is at least in part treatable. We also present ample lines of evidence from the literature corroborating our clinical observations at the preclinical level.