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Abstract Creative self-concept, intimately intertwined with the personality traits and plays a pivotal role in shaping individuals’ behavioral tendencies. Personality traits are largely responsible to influence how people perceive and navigate their creative abilities and self-expression. Moreover, attitudes towards emotions are another key facet of one’s psychological landscape, impacting their inclination to perceive, process, and manage emotional experiences. Keeping this view, the present research attempts to explore the interconnectedness of creative self-concept, personality traits, and attitudes towards emotions among young adults, as well as focuses on exploring the predictors of creative self concept. For this purpose participants consisted of 200 young adults with a mean age of 21.20 years. Statistical outcomes revealed that creative self concept is a significant positive correlate of openness, conscientiousness, extraversion, agreeableness, attitude towards sadness, and attitude towards fear. Additionally, stepwise multiple regression analysis confirmed that openness (R2 = 27%), neuroticism (R2 = 2%) and attitude towards sadness (R2 = 2%) emerged as the significant predictors of creative self concept. Findings from the current research concludes that for young adults to have self-perception in the realm of creativity, personality traits and attitude towards emotions are significant contributing factors. By recognizing and employing these connections, individuals, educators, counselors, and practitioners can contribute to the cultivation of creativity and personal development.

Abstract Background Cancer treatments have many adverse effects on patient’s health leading to poor cardiorespiratory capacity, muscular- degeneration, fatigue, loss of strength and physical function, altered body-composition, compromised immune-function, peripheral neuropathy, and reduced quality of life (QOL). Exercise programs can significantly increase functional capacity when tailored to individual needs, thus improving health. Exercise interventions in cancer rehabilitation, when supported by appropriate nutrition can be effective in attaining a healthy weight and body-composition. The successful rehabilitation program should also include psycho-social education aimed to reduce anxiety and improve motivation. Methods The current study aimed to collect information on the post-treatment needs of cancer patients including barriers and expectations facing them, their caregivers and their families through consultation in focus group interviews. Cancer survivors living in the Republic of Ireland were recruited from the University Hospital Galway, community-based cancer centres, cancer support groups and social media platforms to participate in the study and attend a focus group interview. The focus group discussions were designed to obtain information on the collective views of cancer survivors on relevant topics selected. The topics were developed in consultation with a patient and public involvement (PPI) group supporting the study. The topics list was circulated to all participants prior to the focus group. The interviews were audio recorded and transcribed verbatim. Focus group transcripts were analysed subjected to a thematic framework analysis using NVivo. Results Thirty-six participants took part in 9 focus groups. Our analysis uncovered two main themes. The first theme ‘cast adrift with no direction’ was grouped into three sub-themes: everything revolves around treatment; panic and fear; and what exercise should I be doing? The second theme ‘everybody is different’ was clustered into two sub-themes: side effects get in the way; and personalised exercise program. Conclusion The study highlighted the lack of information and support needed by patients living with and beyond cancer. The study also highlighted the need for a personalised exercise programme designed to target the individual patient symptoms that would be ideal for the mitigation of long term symptoms and in improving QOL.

Summary: Background: The increasing prevalence of diet-related non-communicable diseases (NCDs) in South Asia is concerning, with type 2 diabetes projected to rise to 68%, compared to the global increase of 44%. Encouraging healthy diets requires stronger policies for healthier food environments. Methods: This study reviewed and assessed food environment policies in Bangladesh, India, Pakistan, and Sri Lanka from 2020 to 2022 using the Healthy Food Environment Policy Index (Food-EPI) and compared them with global best practices. Seven policy domains and six infrastructure support domains were considered, employing 47 good practice indicators to prevent NCDs. Stakeholders from government and non-governmental sectors in South Asia (n = 148) were invited to assess policy and infrastructure support implementation using the Delphi method. Findings: Implementation of food environment policies and infrastructure support in these countries was predominantly weak. Labelling, monitoring, and leadership policies received a moderate rating, with a focus on food safety, hygiene, and quality rather than obesity prevention. Key policy gaps prioritized for attention included front-of-pack labelling, healthy food subsidies, unhealthy food taxation, restrictions on unhealthy food promotion, and improvements in school nutrition standards to combat NCDs. Interpretation: Urgent action is required to expand food policies beyond hygiene and food security measures. Comprehensive strategies targeting NCD prevention are crucial to combat the escalating burden of NCDs in the region. Funding: This research was funded by the NIHR (16/136/68 and 132960) with aid from the UK Government for global health research. Petya Atanasova also acknowledges funding from the Economic and Social Research Council (ESRC) (ES/P000703/1). The views expressed are those of the authors and not necessarily of the NIHR, the UK government or the ESRC.

Summary: Malnutrition is a significant challenge among cancer patients, with 30%–85% being reported as malnourished. A decreased desire to consume food, driven in part by a reduction in sensory perception due to the interference of cancer therapy, is a significant driving force behind malnutrition experienced by cancer patients. Cancer treatment-induced dysgeusia, accompanied by fatigue, muscular degeneration, and altered body composition, reduces cancer patients' quality of life. This review aims to highlight the impact of treatment-induced dysgeusia and understand how it affects food intake and maintenance of nutritional status amongst cancer patients. One of the approaches towards preventing malnutrition can be to improve the prescription and consumption of oral nutrition supplements in pre-cachectic cancer patients. The second part of the review summarises the currently available and commonly prescribed oral nutritional supplements and their efficacy in managing malnutrition in cancer patients. The review summarises the impact of the nutritional challenges faced by cancer patients such as cancer pre-cachexia, dietary deficiencies, insufficient oral food intake, and changes in sensory taste perception, in order to develop a deeper understanding of their nutritional needs. It is also important to evaluate how the sensory taste perceptions are altered due to treatment, affecting food consumption and nutritional supplements leading to malnutrition. The review's findings underscore the need to analyse further the changes in sensory taste perceptions amongst cancer patients through qualitative research. Such research will inform the future development and prescription of a more effective nutritional intervention.

Abstract Background Endocrine-resistant breast cancers have elevated expression of XBP1, where it drives endocrine resistance by controlling the expression of its target genes. Despite the in-depth understanding of the biological functions of XBP1 in ER-positive breast cancer, effectors of endocrine resistance downstream of XBP1 are poorly understood. The aim of this study was to identify the XBP1-regulated genes contributing to endocrine resistance in breast cancer. Methods XBP1 deficient sub-clones in MCF7 cells were generated using the CRISPR-Cas9 gene knockout strategy and were validated using western blot and RT-PCR. Cell viability and cell proliferation were evaluated using the MTS assay and colony formation assay, respectively. Cell death and cell cycle analysis were determined using flow cytometry. Transcriptomic data was analysed to identify XBP1-regulated targets and differential expression of target genes was evaluated using western blot and qRT-PCR. Lentivirus and retrovirus transfection were used to generate RRM2 and CDC6 overexpressing clones, respectively. The prognostic value of the XBP1-gene signature was analysed using Kaplan–Meier survival analysis. Results Deletion of XBP1 compromised the upregulation of UPR-target genes during conditions of endoplasmic reticulum (EnR) stress and sensitized cells to EnR stress-induced cell death. Loss of XBP1 in MCF7 cells decreased cell growth, attenuated the induction of estrogen-responsive genes and sensitized them to anti-estrogen agents. The expression of cell cycle associated genes RRM2, CDC6, and TOP2A was significantly reduced upon XBP1 deletion/inhibition in several ER-positive breast cancer cells. Expression of RRM2, CDC6, and TOP2A was increased upon estrogen stimulation and in cells harbouring point-mutants (Y537S, D538G) of ESR1 in steroid free conditions. Ectopic expression of RRM2 and CDC6 increased cell growth and reversed the hypersensitivity of XBP1 KO cells towards tamoxifen conferring endocrine resistance. Importantly, increased expression of XBP1-gene signature was associated with poor outcome and reduced efficacy of tamoxifen treatment in ER-positive breast cancer. Conclusions Our results suggest that RRM2 and CDC6 downstream of XBP1 contribute to endocrine resistance in ER-positive breast cancer. XBP1-gene signature is associated with poor outcome and response to tamoxifen in ER-positive breast cancer.

The ADP ribosyltransferases (PARPs 1–17) regulate diverse cellular processes, including DNA damage repair. PARPs are classified on the basis of their ability to catalyze poly-ADP-ribosylation (PARylation) or mono-ADP-ribosylation (MARylation). Although PARP9 mRNA expression is significantly increased in progressive tuberculosis (TB) in humans, its participation in host immunity to TB is unknown. Here, we show that PARP9 mRNA encoding the MARylating PARP9 enzyme was upregulated during TB in humans and mice and provide evidence of a critical modulatory role for PARP9 in DNA damage, cyclic GMP–AMP synthase (cGAS) expression, and type I IFN production during TB. Thus, Parp9-deficient mice were susceptible to Mycobacterium tuberculosis infection and exhibited increased TB disease, cGAS and 2′3′-cyclic GMP-AMP (cGAMP) expression, and type I IFN production, along with upregulation of complement and coagulation pathways. Enhanced M. tuberculosis susceptibility is type I IFN dependent, as blockade of IFN α receptor (IFNAR) signaling reversed the enhanced susceptibility of Parp9–/– mice. Thus, in sharp contrast to PARP9 enhancement of type I IFN production in viral infections, this member of the MAR family plays a protective role by limiting type I IFN responses during TB.

Introduction: Cancer and its treatment using various chemotherapeutic agents can have many adverse side effects. These side effects often result in significant changes in haematological and biochemical composition of blood. As a result, the regular monitoring of serum biochemical and haematological changes plays an important role in management of disease. The present study aimed to determine the relationship between haematological and biochemical changes in neutropenic cancer patients following chemotherapy. Specifically we evaluated the association between neutrophil count and serum proteins and electrolytes. Methods: For this purpose we analysed retrospectively collected laboratory results from two independent patient cohorts. Each cohort was divided into a control group consisting of patients with normal haematological parameters and a study group which included patients with reduced neutrophil counts. Neutropenic patients (study group) were cancer patients on chemotherapy. Results and conclusion: Blood samples of cancer patients in study group showed reduction in haemoglobin, neutrophils and platelets. Neutropenic group showed a significant reduction in serum albumin, total protein, calcium, and potassium. Our results show that patients with severe neutropenia had pronounced changes in serum protein and electrolytes and increased incidence of abnormal serum protein and electrolyte level. The changes in the neutrophil counts showed a positive correlation with the changes in serum protein and electrolyte levels. A similar trend was seen in both the patient cohorts: the discovery set (176 patients) and the validation set (200 patients). Taken together our results suggest that chemotherapy-induced neutropenia is associated with dysregulation in haemoglobin, platelets, serum proteins and electrolytes.

Converting a vaccine into a thermostable dry powder is advantageous as it reduces the resource burden linked with the cold chain and provides flexibility in dosage and administration through different routes. Such a dry powder presentation may be especially useful in the development of a vaccine towards the respiratory infectious disease tuberculosis (TB). This study assesses the immunogenicity and protective efficacy of spray-dried ID93+GLA-SE, a promising TB vaccine candidate, against Mycobacterium tuberculosis (Mtb) in a murine model when administered via different routes. Four administration routes for the spray-dried ID93+GLA-SE were evaluated along with relevant controls—1) reconstitution and intramuscular injection, 2) reconstitution and intranasal delivery, 3) nasal dry powder delivery via inhalation, and 4) pulmonary dry powder delivery via inhalation. Dry powder intranasal and pulmonary delivery was achieved using a custom nose-only inhalation device, and optimization using representative vaccine-free powder demonstrated that approximately 10 and 44% of the maximum possible delivered dose would be delivered for intranasal delivery and pulmonary delivery, respectively. Spray-dried powder was engineered according to the different administration routes including maintaining approximately equivalent delivered doses of ID93 and GLA. Vaccine properties of the different spray-dried lots were assessed for quality control in terms of nanoemulsion droplet diameter, polydispersity index, adjuvant content, and antigen content. Our results using the Mtb mouse challenge model show that both intranasal reconstituted vaccine delivery as well as pulmonary dry powder vaccine delivery resulted in Mtb control in infected mice comparable to traditional intramuscular delivery. Improved protection in these two vaccinated groups over their respective control groups coincided with the presence of cytokine-producing T cell responses. In summary, our results provide novel vaccine formulations and delivery routes that can be harnessed to provide protection against Mtb infection.

MicroRNAs (miRNAs) are non-coding RNAs which modulate gene expression via multiple post-transcriptional mechanisms. They are involved in a variety of biological processes, including cell proliferation, metastasis, metabolism, tumorigenesis, and apoptosis. Dysregulation of miRNA expression has been implicated in human cancers, and they may also serve as biomarkers of disease progression and prognosis. The miR-17-92 cluster is one of the most widely studied miRNA clusters, which was initially reported as an oncogene, but was later reported to exhibit tumour suppressive effects in some human cancers. This review summarizes the recent progress and context-dependant role of this cluster in various cancers. We summarize the known mechanisms which regulate miR-17-92 expression and molecular pathways that are in turn controlled by it. We discuss examples where it acts as an oncogene or a tumour suppressor along with key targets affecting hallmarks of cancer. We discuss how cellular contexts regulate the biological effects of miR-17-92. The plausible mechanisms of its paradoxical roles are explained, and mechanisms are described that may contribute to cell fate regulation by miR-17-92. Further, we discuss recently developed strategies to target miR-17-92 cluster in human cancers. MiR-17-92 may serve as a potential biomarker for prognosis and response to therapy as well as a target for cancer prevention and therapeutics.

Somatic mutations of the estrogen receptor 1 gene (ESR1) is an emerging mechanism of acquired resistance to endocrine therapy in hormonal breast cancers. Hotspot point mutations in the ligand- binding domain of estrogen receptor α (ER) and genomic rearrangements producing ESR1 fusion genes are the two major types of mutations that are associated with endocrine resistance. The crosstalk between X-box binding protein 1 (XBP1), a key transcription factor of the unfolded protein response (UPR) and ER signalling creates a positive feedback loop that results in increased expression of XBP1 in ER-positive breast cancer. Here we report that XBP1 co-operated with point mutants (Y537S, D538G) and fusion mutants (ESR1-YAP1, ESR1-DAB2) of ESR1 to increase their transcriptional activity. XBP1 was required for optimal expression of estrogen-regulated genes, and up to 40% of XBP1-dependent genes were estrogen-responsive genes. Knockdown of XBP1 in genome-edited MCF7 cells expressing Y537S mutant reduced their growth, re-sensitized them to anti-estrogens and attenuated the constitutive and estrogen-stimulated expression of estrogen-regulated genes. Our study provides a rationale for overcoming endocrine resistance in breast cancers expressing ESR1 mutation by combining the XBP1 targeting agents with anti-estrogen agents.

Recent evidence has shown that the miR-17–92 cluster can function either as oncogene or tumor suppressor in human cancers. The function of miR-17–92 in subtypes of breast cancer remains largely unknown. The expression of miR-17–92 is elevated in triple negative breast cancer (TNBC) but reduced in estrogen receptor (ER)-positive breast cancer (ERPBC). We show that increased expression of miRNAs belonging to the miR-17–92 cluster is associated with poor outcome in TNBC, whereas the expression of miR-17–92 miRNAs is with good outcome in ERPBC. We show that ectopic expression of miR-17–92 inhibited cell growth and invasion of ER-positive and HER2-enriched cells. On the contrary, miR-17–92 expression enhanced cell growth and invasion of TNBC cells. Further, we found that miR-17–92 expression sensitized MCF7 cells to chemotherapeutic compounds, whereas it rendered SKBR3 cells resistant to them. We found that expression of ADORA1 was reduced by miR-17–92-expressing breast cancer cells, specifically in ERPBC. We observed an inverse correlation between the expression of ADORA1 and miR-17–92 in human breast cancer. Treatment with DPCPX, a selective ADORA1 antagonist, abolished the difference in the growth of control and miR-17–92 overexpressing MCF7 cells and identified ADORA1 as a key functional target of miR-17–92 in ERPBC. Furthermore, increased expression of ADORA1 in ERPBC is associated with a poor outcome. Our observations underscore the context-dependent role of miR-17–92 in breast cancer subtypes and suggest that miR-17–92 could serve as novel prognostic markers in breast cancer.

Anemia is a condition that affects over 1.6 billion people worldwide untreated, the disease could lead to increased morbidity and mortality during pregnancy, affecting both the mother and the unborn child. This paper presents the measured dielectric properties of whole blood samples from 176 patients obtained from a hematology clinic; with 80 samples from male patients and 96 samples from female patients. Measurements were performed using a Keysight slim form probe and Keysight network analyzer to obtain the dielectric properties over a wide frequency range (500 MHz-8.5 GHz). A multiple linear regression analysis is performed to identify which components of the blood show the highest correlation with changes in the dielectric properties. Hemoglobin (Hgb) is shown to be the biggest predictor of changes in complex permittivity, demonstrating that permittivity measurements at a single frequency can potentially be used to detect anemia. A support vector machines algorithm is trained and tested to classify between blood samples from healthy patients and blood samples from patients with anemia. The classifier is optimized using a Bayesian-optimization approach during 10-fold cross-validation and then the average performance of the final trained classifier is evaluated through 10-fold testing on unseen data sets. Using a clinical definition of anemia defined as patients having a concentration of Hgb

Expression and functions of microRNAs (miRNAs) have been widely investigated in cancer treatment-induced complications and as a response to physical activity, respectively, but few studies focus on the application of miRNAs as biomarkers in exercise-based cancer rehabilitation. Research has shown that certain miRNA expression is altered substantially due to tissue damage caused by cancer treatment and chronic inflammation. MiRNAs are released from the damaged tissue and can be easily detected in blood plasma. Levels of the miRNA present in peripheral circulation can therefore be used to measure the extent of tissue damage. Moreover, damage to tissues such as cardiac and skeletal muscle significantly affects the individual’s health-related fitness, which can be determined using physiologic functional assessments. These physiologic parameters are a measure of tissue health and function and can therefore be correlated with the levels of circulating miRNAs. In this paper, we reviewed miRNAs whose expression is altered during cancer treatment and may correlate to physiological, physical, and psychological changes that significantly impact the quality of life of cancer survivors and their role in response to physical activity. We aim to identify potential miRNAs that can not only be used for monitoring changes that occur in health-related fitness during cancer treatment but can also be used to evaluate response to exercise-based rehabilitation and monitor individual progress through the rehabilitation programme.

The lungs are the most vulnerable site for air-borne infections. Immunologic compartmentalization of the lungs into airway lumen and interstitium has paved the way to determine the immune status of the site of pathogen entry, which is crucial for the outcome of any air-borne infections. Vaccination via the nasal route with Mycobacterium indicus pranii (MIP), a prospective candidate vaccine against tuberculosis (TB), has been reported to confer superior protection as compared to the subcutaneous (s.c.) route in small-animal models of TB. However, the immune mechanism remains only partly understood. Here, we showed that intranasal (i.n.) immunization of mice with MIP resulted in a significant recruitment of CD4+ and CD8+ T-cells expressing activation markers in the lung airway lumen. A strong memory T-cell response was observed in the lung airway lumen after i.n. MIP vaccination, compared with s.c. vaccination. The recruitment of these T-cells was regulated primarily by CXCR3–CXCL11 axis in “MIP i.n.” group. MIP-primed T-cells in the lung airway lumen effectively transferred protective immunity into naïve mice against Mycobacterium tuberculosis (M.tb) infection and helped reducing the pulmonary bacterial burden. These signatures of protective immune response were virtually absent or very low in unimmunized and subcutaneously immunized mice, respectively, before and after M.tb challenge. Our study provides mechanistic insights for MIP-elicited protective response against M.tb infection.

An important event in the unfolded protein response (UPR) is activation of the endoplasmic reticulum (ER) kinase PERK. The PERK signalling branch initially mediates a prosurvival response, which progresses to a proapoptotic response upon prolonged ER stress. However, the molecular mechanisms of PERK-mediated cell death are not well understood. Here we show that expression of the primary miR-17-92 transcript and mature miRNAs belonging to the miR-17-92 cluster are decreased during UPR. We found that miR-17-92 promoter reporter activity was reduced during UPR in a PERK-dependent manner. Furthermore, we show that activity of the miR-17-92 promoter is repressed by ectopic expression of ATF4 and NRF2. Promoter deletion analysis mapped the region responding to UPR-mediated repression to a site in the proximal region of the miR-17-92 promoter. Hypericin-mediated photo-oxidative ER damage reduced the expression of miRNAs belonging to the miR-17-92 cluster in wild-type but not in PERK-deficient cells. Importantly, ER stress-induced apoptosis was inhibited upon miR-17-92 overexpression in SH-SY5Y and H9c2 cells. Our results reveal a novel function for ATF4 and NRF2, where repression of the miR-17-92 cluster plays an important role in ER stress-mediated apoptosis. Mechanistic details are provided for the potentiation of cell death via sustained PERK signalling mediated repression of the miR-17-92 cluster.

BCG (Bacillus Calmette-Guérin) is the only available vaccine against TB and is also used for the treatment of superficial bladder cancer. BCG-mediated protection against TB and bladder cancer has been shown to rely on its ability to induce superior CD4+ and CD8+ T cell responses. As the magnitude of T cell responses is defined by dendritic cell (DC) lifespan, we examined the effect of BCG on DC survival and its underlying mechanisms. It was observed that BCG stimulation enhanced DC survival and prolonged DC lifespan in a dose-dependent manner. Live BCG led to a higher DC survival compared with heat-killed BCG. FITC-Annexin V staining showed that BCG promoted DC survival by inhibiting apoptosis. Consistently, higher expressions of anti-apoptotic proteins Bcl-2 and Bcl-xL were observed in BCG-stimulated DCs. Pharmacological inhibition of Bcl-2 and Bcl-xL drastically reduced the DC survival efficacy of BCG. Comparable survival of BCG-stimulated wild-type and MyD88−/− DCs suggested that MyD88 signaling is dispensable for BCG-induced DC survival. NF-κB is one of the key regulators of innate immune responses. We observed that pharmacological inhibition of NF-κB abrogated BCG-mediated increase in DC survival and expression of anti-apoptotic proteins. These findings provide a novel insight into the effect of BCG on DC physiology.

Mycobacterium indicus pranii (MIP) is a potent vaccine candidate against tuberculosis (TB) as it has demonstrated significant protection in animal models of tuberculosis as well as in clinical trials. Higher protective efficacy of MIP against TB as compared to BCG provoked the efforts to gain insight into the molecular mechanisms underlying MIP mediated protection against Mycobacterium tuberculosis (M.tb). Autophagy, initially described as a cell survival mechanism during starvation, also plays a key role in host resistance to M.tb. Virulent mycobacteria like M.tb, suppresses host autophagy response to increase its survival in macrophages. Since mycobacterial species have been shown to vary widely in their autophagy-inducing properties, in the present study, we examined the autophagy inducing efficacy of MIP and its role in MIP-mediated protection against M.tb. MIP was found to be potent inducer of autophagy in macrophages. Induced autophagy was responsible for reversal of the phagosome maturation block and phagolysosome fusion inhibition in M.tb infected macrophages, which ultimately lead to significantly enhanced clearance of M.tb from the macrophages. This is an important study which further delineated the underlying mechanisms for significant immunotherapeutic activity observed in TB patients / animal models of tuberculosis, given MIP therapy along with chemotherapy.