Risk factors for invasive pulmonary aspergillosis in patients with severe fever with thrombocytopenia syndrome: A multicenter retrospective study.

Invasive pulmonary aspergillosis (IPA) is a life-threatening complication in patients with severe fever with thrombocytopenia syndrome (SFTS), yet SFTS-associated IPA (SAPA)'s risk factors remain undefined. A multicenter retrospective cohort study across Hubei and Anhui provinces (May 2013-September 2022) utilized least absolute shrinkage and selection operator (LASSO) regression for variable selection. Multivariable logistic regression identified independent predictors of SAPA, Cox regression highlighted mortality-related risk factors. Of the 1775 screened SFTS patients, 1650 were included, with 169 developing IPA, leading to a 42-day mortality rate of 26.6% among SAPA patients. Multivariable logistic regression revealed SAPA risk factors including advanced age, petechia, hemoptysis, tremor, low albumin levels, elongated activated partial thromboplastin time (APTT), intensive care unit (ICU) admission, glucocorticoid usage, intravenous immunoglobulin (IVIG) and prolonged hospital stays. Cox regression identified predictors of 42-day mortality, including ecchymosis at venipuncture sites, absence of ICU admission, elongated prothrombin time (PT), vasopressor and glucocorticoid use, non-antifungals. Nomograms constructed on these predictors registered concordance indexes of 0.855 (95% CI: 0.826-0.884) and 0.778 (95% CI: 0.702-0.854) for SAPA onset and 42-day mortality, respectively. Lower survival rates for SAPA patients treated with glucocorticoids (p < 0.001) and improved 14-day survival with antifungal therapy (p = 0.036). Improving IPA management in SFTS-endemic areas is crucial, with effective predictive tool.

Decreased circulating IPA levels identify subjects with metabolic comorbidities: A multi-omics study.

In recent years several experimental observations demonstrated that the gut microbiome plays a role in regulating positively or negatively metabolic homeostasis. Indole-3-propionic acid (IPA), a Tryptophan catabolic product mainly produced by C. Sporogenes, has been recently shown to exert either favorable or unfavorable effects in the context of metabolic and cardiovascular diseases. We performed a study to delineate clinical and multiomics characteristics of human subjects characterized by low and high IPA levels. Subjects with low IPA blood levels showed insulin resistance, overweight, low-grade inflammation, and features of metabolic syndrome compared to those with high IPA. Metabolomics analysis revealed that IPA was negatively correlated with leucine, isoleucine, and valine metabolism. Transcriptomics analysis in colon tissue revealed the enrichment of several signaling, regulatory, and metabolic processes. Metagenomics revealed several OTU of ruminococcus, alistipes, blautia, butyrivibrio and akkermansia were significantly enriched in highIPA group while in lowIPA group Escherichia-Shigella, megasphera, and Desulfovibrio genus were more abundant. Next, we tested the hypothesis that treatment with IPA in a mouse model may recapitulate the observations of human subjects, at least in part. We found that a short treatment with IPA (4 days at 20/mg/kg) improved glucose tolerance and Akt phosphorylation in the skeletal muscle level, while regulating blood BCAA levels and gene expression in colon tissue, all consistent with results observed in human subjects stratified for IPA levels. Our results suggest that treatment with IPA may be considered a potential strategy to improve insulin resistance in subjects with dysbiosis.

The therapeutic potential of dietary intervention: based on the mechanism of a tryptophan derivative-indole propionic acid on metabolic disorders.

Tryptophan (TRP) contributes to individual immune homeostasis and good condition via three complex metabolism pathways (5-hydroxytryptamine (5-HT), kynurenine (KP), and gut microbiota pathway). Indole propionic acid (IPA), one of the TRP derivatives of the microbiota pathway, has raised more attention because of its impact on metabolic disorders. Here, we retrospect increasing evidence that TRP metabolites/IPA derived from its proteolysis impact host health and disease. IPA can activate the immune system through aryl hydrocarbon receptor (AHR) and/or Pregnane X receptor (PXR) as a vital mediator among diet-caused host and microbe cross-talk. Different levels of IPA in systemic circulation can predict the risk of NAFLD, T2DM, and CVD. IPA is suggested to alleviate cognitive impairment from oxidative damage, reduce gut inflammation, inhibit lipid accumulation and attenuate the symptoms of NAFLD, putatively enhance the intestinal epithelial barrier, and maintain intestinal homeostasis. Now, we provide a general description of the relationships between IPA and various physiological and pathological processes, which support an opportunity for diet intervention for metabolic diseases.

The agreement of phonetic transcriptions between paediatric speech and language therapists transcribing a disordered speech sample.

BACKGROUND: Speech and language therapists (SLTs) regularly use phonetic transcription to record and analyse typical and disordered speech. Phonetic transcription is highly demanding of auditory perceptual skills so researchers are sceptical about its accuracy and reliability. The literature describes how phonetic transcription is prone to auditory illusions and biases, such as a preference to transcribe speech sounds from the transcriber's own language. Few empirical research studies have calculated agreement amongst transcribers where a range of agreement scores have been reported (51%-97%). There is a consensus that agreement rates decrease as phonetic detail increases. Vowels and consonants are characterised by different perceptual features within the International Phonetic Alphabet (IPA) so they may differ in agreement rates, and thus far there is contradictory evidence as to whether vowels or consonants are more agreed upon. Transcription agreement studies to date have most commonly recruited phoneticians rather than SLTs so further research is warranted to determine transcription agreement amongst SLTs and its impact on clinical practice. AIMS: The study's primary aim was to calculate agreement scores from a group of English-speaking SLTs who transcribed disordered speech samples in an ecologically valid setting. The study also sought to contribute to the pre-existing contradictory evidence base regarding whether vowels or consonants may be more agreed upon by comparing their agreement scores. The researcher aimed to comment on SLTs' use of diacritics and non-native speech symbols (symbols not included in the English phonetic inventory) in terms of their frequency and agreement of use. By analysing transcriptions, the study aimed to discuss the impact transcription variability has on speech sound error patterns and thus its impact on clinical decision-making such as diagnosis, choice of intervention and therapy targets. METHODS: Twelve paediatric SLTs were recruited via a convenience sample at two National Health Service trusts, two of whom were specialists in Speech Sound Disorders (SSDs). Participants transcribed 16 words from a video of a boy with disordered speech completing the Diagnostic Evaluation of Articulation and Phonology (DEAP, Dodd et al., 2006) from a telehealth appointment. The use of diacritics and non-English IPA symbols were manually analysed. A classic agreement score was calculated for each target word using a Python script, and then for vowels and consonants in isolation. Datasets were manually analysed to determine whether differences in transcription resulted in the identification of different speech sound error patterns. The researcher considered the implications this had within clinical practice. RESULTS: The average classic agreement score was 56.3%. Consonants were more agreed upon than vowels with agreement scores of 62.8% and 48.6%, respectively. Nine participants (75%) used diacritics (most commonly length marks) and eight participants (67%) transcribed non-native IPA symbols at least once in their datasets, but generally with low frequencies and agreements amongst their use. Transcriptions captured the occurrence of typical and atypical error patterns but only three error patterns, out of the 20 identified, were present in all 12 participants' transcriptions. CONCLUSIONS: The agreement score of 56.3% questions the accuracy and reliability of transcription amongst SLTs which is an essential skill of the profession. The findings highlight SLTs should be more cautious of interpreting vowels than consonants given lower agreement rates. The frequency of use of non-native symbols and diacritics was relatively low which could reflect a low accuracy of their use or reduced confidence in transcribing these. The study discussed how variations in transcriptions can impact phonological and phonetic analysis, which in turn can influence clinical decision-making such as diagnosing SSDs, selecting further diagnostic assessments and choosing therapy targets and interventions. The Royal College of Speech and Language Therapists-endorsed transcription guidelines (Child Speech Disorder Research Network, 2017) could be revised to convey realistic expectations of SLTs' transcription skills, or SLTs should be offered more training to improve transcription skills to meet current expectations. Other suggestions to improve transcription accuracy are discussed such as via instrumental methods, yet these come with their own limitations such as practicality, costs and need for specialist training. WHAT THIS PAPER ADDS: What is already known on this subject Phonetic transcription is highly demanding of human perceptual skills, and researchers are sceptical about its reliability. There are few empirical research studies calculating agreement amongst transcribers, and a range of agreement scores have been reported (51%-97%) dependent on the research conditions. Research mostly involves experienced transcribers (e.g., phoneticians) rather than speech and language therapists (SLTs), a profession expected to regularly use phonetic transcription to record and analyse typical and disordered speech. What this study adds to existing knowledge A range of transcription agreement scores have been reported in previous studies, mainly comparing pairs or small groups of specialist transcribers rather than SLTs. This study provides an agreement score of 56.3% when a group of 12 SLTs transcribed a disordered speech sample in an ecologically valid setting (where speech samples were taken from a real-life speech sound assessment over a telehealth appointment using the Diagnostic Evaluation of Articulation and Phonology). The study found consonants are more agreed upon than vowels, adding to the contradictory evidence base. Unlike other studies, the researcher analysed transcriptions to identify error patterns to examine the impact that transcription variation has on clinical decision-making. What are the potential or actual clinical implications of this work? The researcher questions whether SLTs are meeting the expectations of 'accurate transcription' as listed by the Royal College of Speech and Language Therapists (RCSLT) endorsed transcription guidelines (Child Speech Disorder Research Network, 2017) given the relatively low agreement score of 56.3%. The study also questions the reliability of the use of diacritics and non-English International Phonetic Alphabet (IPA) symbols and whether SLTs should be expected to use these due to perceptual limitations. Twenty phonological processes emerged from the datasets, only three of which were agreed upon across all 12 participants. The researcher therefore discusses how transcription variations could result in different diagnoses, therapy targets and interventions choices. The paper suggests more training is required to enhance transcription accuracy, and also considers the appropriateness of utilising instrumental methods whilst recognising its limitations such as feasibility, costs and specialist training needs.

Optimizing Antifungal Treatment Strategies to Prevent Invasive Pulmonary Aspergillosis Infection-Related Deaths in Intensive Care Unit Patients: The Need for Standardization of Research Definitions.

The clinical spectrum of invasive pulmonary aspergillosis (IPA) has expanded in recent decades. A large group of patients admitted to intensive care units (ICU) is indeed susceptible to the development of IPA. Although timely diagnosis and antifungal therapy of IPA in this expanding population is crucial to prevent IPA-related deaths, the magnitude of the favorable prognostic impact of antifungal therapy is difficult to measure precisely. In our opinion, the development of standardized research definitions could have favorable implications for further improving our ability both to measure the favorable effect of antifungal treatment and to prevent IPA-related death in ICU patients.

"He is changing, but I'm changing too": An interpretative phenomenological analysis of spouse caregivers' identity in the context of dementia.

OBJECTIVE: This study explores the process through which informal caregivers, particularly spouses, construct their identity within the context of caregiving for individuals with dementia. Despite extensive research in psychology aimed at defining caregiving (e.g. tasks, consequences), few informal caregivers identify themselves as such. For instance, the affective bond shared between caregivers and care-recipients often imbues caregiving responsibilities with a sense of "naturalness," especially if the care-recipient is a spouse. METHODS: To investigate the nature of caregiver identity construction, eight semi-structured interviews were conducted with spouse caregivers of dementia patients. The collected data underwent interpretative phenomenological analysis (IPA). RESULTS: Three interconnected themes emerged from the analysis: (1) Perceiving changes in my partner, which involves recognising alterations in the care-receiver's characteristics due to dementia; (2) Processing changes, encompassing the experience of grieving losses and reminiscing about the past; and (3) Perceiving changes in myself, referring to the acknowledgement of personal changes due to caregiving. CONCLUSION: The study emphasises the dynamic and ongoing nature of caregiver identity construction, which begins with the early recognition of changes in the care-receiver. Interestingly, spouse caregivers oscillate between their identity as a spouse and caregiver, influenced by how they process changes undergone by their partner. Contrasting with previous theories on caregivers' identity, our results focus of caregivers' perceptions rather than their relationship with the care-recipient or caregiving tasks.

Moderate India Pale Ale beer consumption promotes antigenotoxic and non-mutagenic effects in ex vivo and in vivo mice models.

BACKGROUND: Discussion of the benefits of moderate alcohol consumption is ongoing. Broadly, research focusing on ethanol consumption tends to report no benefits. However, studies that distinguish between different types of alcoholic beverages, particularly beers, often reveal positive effects. The present study evaluated the genotoxic and mutagenic effects of moderate chronic consumption of India Pale Ale (IPA) craft beer. Sixty-four adult male Swiss mice were used and divided into control and treatment groups receiving water, IPA beer with 55.23 g of ethanol per liter of beer, aqueous solution with 55.23 g of ethanol per liter, and hop infusion ad libitum for 30 days. After this period, the animals were genetically evaluated with a comet assay. For the ex vivo comet assay, blood was collected and exposed to hydrogen peroxide (H2O2). For the in vivo assay, the alkylating agent cyclophosphamide (CP) was administered to the groups after blood collection and sacrificed after 24 h. Brain, liver, and heart tissues were analyzed. Bone marrow was collected and submitted to the micronucleus test. RESULTS: The groups treated with IPA beer, ethanol, and hops did not show genotoxic and mutagenic action in the blood, brain, heart, or liver. The antigenotoxic action of IPA beer and hops was observed in both in vivo and ex vivo models, showing a similar reduction in DNA damage caused by CP. There was no significant difference between the groups with regard to the formation of micronuclei by CP. CONCLUSION: Moderate chronic consumption of IPA beer and hops infusion showed antigenotoxic effects in mice but no antimutagenic action. © 2024 Society of Chemical Industry.

Improve the satisfaction of medical staff on the use of home nursing mobile APP by using a hybrid multi-standard decision model.

OBJECTIVE: To identify critical satisfaction gaps in a home nursing mobile application (APP) using a systematic decision-making model. METHODS: Initially, the decision-making trial and evaluation laboratory method was used to analyze the relationship structure and corresponding weights among the indicators. The Importance-Performance Analysis (IPA) method was used to identify the categories of all indicators and their corresponding strategic directions. Twenty-six home nursing specialists currently providing home nursing services were recruited for this study. RESULTS: The IPA results revealed that "Assurance," "Reliability," and "Personal security protection" are critical satisfaction gaps. From the influence network and weight results, "information quality" and "system quality" were the critical quality factors in the home nursing mobile APP. The influence of the network relationship structure and weight demonstrated a 98.12% significance level, indicating good stability. CONCLUSION: Continuous improvement in information and system quality is recommended to optimize the overall quality of the home nursing mobile APP. Additionally, user demands should be considered, and personal safety guarantee functions should be developed and integrated into the system to ensure the safety of home nursing workers.

In search of the 'like-minded' people: pregnant women's sense-making of their physical activity-related social experiences.

AIMS/BACKGROUND: Social factors are increasingly recognised as influential on antenatal physical activity. While pregnant women describe the people and support they require to remain physically active, little is known about how pregnant women select and make sense of their social experiences throughout pregnancy. This study followed pregnant women's sense-making of their physical activity-related social experiences as pregnancy progressed, and physical activity declined. DESIGN/METHODS: This study used a qualitative design. Four pregnant women were recruited in their second trimester, participated in three individual semi-structured interviews and submitted diary entries throughout trimesters two and three. Data were analysed using longitudinal interpretative phenomenological analysis. RESULTS: To facilitate physical activity, pregnant women were 'searching for the "like-minded" people who motivate, share and understand', namely pregnant women and prenatally trained exercise professionals. When making sense of social experiences, pregnant women were 'grading and critiquing the quality and paucity of "active pregnancy" information', and'cherry-picking social experiences necessary for "nesting", obtaining support and protecting self-esteem as physical activity declined'. This involved disengaging from social experiences, and consequently, some pregnant women found themselves 'lamenting interactions with the "like-minded" people, contending with grief and inner conflict'. CONCLUSION: Pregnant women proactively seek and make sense of social experiences to facilitate physical activity. In an increasingly digitalised society, interventions should support pregnant women to utilise social media constructively and safely to access 'like-minded' people, provide in-person and virtual networks to meet individual support needs throughout pregnancy and encourage health professionals to demonstrate interest in the 'active pregnancy' to maximise influence.

Comparative study between Salkowski reagent and chromatographic method for auxins quantification from bacterial production.

Introduction: The Salkowski reagent method is a colorimetric technique used to determine auxin production, specifically as indole-3-acetic acid (IAA). It was developed to determine indoles rapidly; however, it does not follow Beer's law at high concentrations of IAA. Thus, there could be an overestimation of IAA with the Salkowski technique due to the detection of other indole compounds. Methods: This study aims to compare the Salkowski colorimetric method versus a chromatographic method to evidence the imprecision or overestimation obtained when auxins, such as indole-acetic acid (IAA), are determined as traits from promoting growth plant bacteria (PGPB), using ten different strains from three different isolation sources. The analysis used the same bacterial culture to compare the Salkowski colorimetric and chromatographic results. Each bacterium was cultivated in the modified TSA without or with tryptophan for 96 h. The same supernatant culture was used in both methods: Salkowski reagent and ultra-performance liquid chromatography coupled with a Mass Spectrometer (LC-MS/MS). Results: The first method indicated 5.4 to 27.4 mg L-1 without tryptophan in ten evaluated strains. When tryptophan was used as an inductor of auxin production, an increase was observed with an interval from 4.4 to 160 mg L-1. The principal auxin produced by all strains was IAA from that evaluated by the LC-MS/MS method, with significantly higher concentration with tryptophan addition than without. Strains belonging to the Kocuria genus were highlighted by high IAA production. The indole-3-propionic acid (IPA) was detected in all the bacterial cultures without tryptophan and only in K. turfanensis As05 with tryptophan, while it was not detected in other strains. In addition, indole-3-butyric acid (IBA) was detected at trace levels (13-16 µg L-1). Conclusions: The Salkowski reagent overestimates the IAA concentration with an interval of 41-1042 folds without tryptophan and 7-16330 folds with tryptophan as inductor. In future works, it will be necessary to determine IAA or other auxins using more suitable sensitive techniques and methodologies.

"It's changed forever": the lived experience of sexuality and sexual functioning in women with cauda equina syndrome (CES).

PURPOSE: To explore women's lived experiences of intimacy, sexuality and sexual functioning in the context of cauda equina syndrome (CES). METHODS: Ten women completed an in-depth semi-structured interview exploring the psychosocial impact of CES on their sexuality and data were analyzed using Interpretative Phenomenological Analysis (IPA). RESULTS: One superordinate theme was generated: "Sexuality forever altered, it's changed completely," reflecting the enduring impact of CES on women's sexuality. Five subordinate themes emerged reflecting a range of changed roles and relationships, primarily associated with loss of sexual identity and a sense that health professionals did not prioritize sexual functioning (1): Loss of worth as a sexual being: "Feel like a nothing" (2) Relationships have changed: "It's not a meeting of equals anymore" (3) Lack of professional support: "We don't like to talk about anything below the waist" (4) Challenges for motherhood: "What kind of future will they have with a mother like me…" and (5) Finding ways of coping: "Closed the door on it." CONCLUSION: Findings highlight the detrimental effect of CES, directly and indirectly, on women's sexuality. There is a need for a multidisciplinary approach to address the physical, emotional, cognitive, and behavioural effects experienced in relation to sexuality as part of a rehabilitative process.

The lived experience of sexuality and sexual function is negatively affected in women with cauda equina syndrome (CES).Some women make positive adjustments in terms of alternative forms of intimate expression while others "close off" their sexuality as a coping response.Women perceive that sexuality and sexual function is not adequately addressed by health professionals.Rehabilitation should include a multidisciplinary focus on sexuality after CES.

N6-isopentenyladenosine inhibits aerobic glycolysis in glioblastoma cells by targeting PKM2 expression and activity.

Glioblastoma (GBM) is a primary tumor in the central nervous system with poor prognosis. It exhibits elevated glucose uptake and lactate production. This metabolic state of aerobic glycolysis is known as the Warburg effect. N6-isopentenyladenosine (iPA), a natural cytokine modified with an isopentenyl moiety derived from the mevalonate pathway, has well-established anti-tumor activity. It inhibits cell proliferation in glioma cells, inducing cell death by apoptosis and/or necroptosis. In the present study, we found that iPA inhibits aerobic glycolysis in unmodified U87MG cells and in the same cell line engineered to over-express wild-type epidermal growth factor receptor (EGFR) or EGFR variant III (vIII), as well as in a primary GBM4 patient-derived cell line. The detection of glycolysis showed that iPA treatment suppressed ATP and lactate production. We also evaluated the response of iPA treatment in normal human astrocyte primary cells, healthy counterpart cells of the brain. Aerobic glycolysis in treated normal human astrocyte cells did not show significant changes compared to GBM cells. To determine the mechanism of iPA action on aerobic glycolysis, we investigated the expression of certain enzymes involved in this metabolic pathway. We observed that iPA reduced the expression of pyruvate kinase M2 (PKM2), which plays a key role in the regulation of aerobic glycolysis, promoting tumor cell proliferation. The reduction of PKM2 expression is a result of the inhibition of the inhibitor of nuclear factor kappa-B kinase subunit, beta/nuclear factor-kappa B pathway upon iPA treatment. In conclusion, these experimental results show that iPA may inhibit aerobic glycolysis of GBM in stabilized cell lines and primary GBM cells by targeting the expression and activity of PKM2.

An exploration of the emotional impact of working in an adult hospice service for Irish healthcare professionals.

PURPOSE: An ageing population and a global pandemic has placed greater demands on palliative care services. Numerous studies describe the patient experience in palliative care, however, few explore the healthcare professional's experience of caring in this setting. This study explored the emotional challenges faced by palliative care professionals working in adult hospice services in Ireland. DESIGN/METHODOLOGY/APPROACH: A narrative phenomenological approach was adopted, using interpretative phenomenological analysis to analyse results from five participants' semi-structured interviews. FINDINGS: The type of challenge experienced reflected the impact it had on the participant's emotional wellbeing. Challenges perceived as achievable contributed to high levels of emotional wellbeing. These challenges often offered the opportunity for skill development and elicited positive feelings. Challenges perceived as uncontrollable negatively impacted the professional's emotional wellbeing and increased their risk of burnout. Examples of this included the shift in service provision and professional expectations. The challenges palliative care professionals experience on a daily basis can negatively or positively impact their emotional wellbeing. CONCLUSION: Overall, this study highlighted challenges and their impacts experienced by palliative care professionals, illustrating key areas for improvement to prioritise staff wellbeing.

"It's a learning curve throughout your entire life": Experiences and impact of FASD in adolescence explored in online photovoice research.

BACKGROUND: Research into the lived experience and disability of Fetal Alcohol Spectrum Disorder (FASD) is sparse in adolescence, despite its relevance to supports and life outcomes. AIMS: The study explored adolescents' lived experiences of FASD and access to support across home, school, and community. METHODS AND PROCEDURES: An online photovoice study was undertaken with eight young people (age 12-19, in education), integrating an Interpretative Phenomenological Analysis (IPA) approach. The research process comprised two individual interviews, group training, individual photo-taking, and group sessions for photo analysis/ dissemination. OUTCOMES AND RESULTS: Participant-led analysis of their photos identified how activities at home and in the community had functions of relaxation, sensory gratification, and enabled concentration. Researcher-led analysis found that young people identified with the disability of FASD through experiences at home and school. While they acknowledged the value of support and relationships, education was not always an inclusive experience. CONCLUSIONS AND IMPLICATIONS: Participatory online research allowed insight into the impact of FASD as a disability and underlines a consistent need for support in adolescence and the transition into adulthood. Young people with FASD require explicit support to develop their advocacy skills to improve educational outcomes.

Whole transcriptome sequencing identifies key lncRNAs,circRNAs, and mRNAs for exploring the pathogenesis and therapeutic target of mouse pneumoconiosis.

BACKGROUND: Pneumoconiosis is a kind of lung dysfunction caused by the inhalation of mineral dust. However, the potential molecular mechanism of pneumoconiosis have not been fully elucidated. METHODS: In this study, the silica-treated pneumoconiosis mice model was constructed and the transcriptome sequencing data including lncRNA, circRNA, and mRNA were obtained. Firstly, differentially expressed lncRNA, circRNA, and mRNA (DElncRNA, DEcircRNA, DEGs) between control and pneumoconiosis/silicosis samples were screened, the target miRNAs (co-pre-miRNAs) were obtained by intersecting the miRNAs predicted by DElncRNA and DEcircRNA, respectively, and the target mRNAs (co-mRNA) were obtained by intersecting the mRNAs predicted by target miRNA and DEGs. Then, the lncRNA/circRNA-miRNA-mRNA networks were constructed by Cytoscape. Next, the key mRNAs were obtained by protein-protein interaction (PPI) analysis, and the key lncRNAs/circRNAs were selected by correlation analysis. Moreover, the expression of the key lncRNAs, circRNAs and mRNAs on chromosome were studied by the "circlize" package. Furthermore, the TFs-miRNA-mRNA network was constructed and the function of DEGs were explored by Ingenuity Pathway Analysis (IPA). To demonstrate the feasibility and value of the constructed ceRNA networks, we validated key genes and mmu-miR-682 pathway. Finally, We used the Drug-Gene Interaction database to predict potential drugs that could interfere with key genes,which may help to find promising treatment. RESULTS: There were 427 DElncRNAs, 107 DEcircRNAs and 1,597 DEGs between silicosis and control groups. Totals of 77 co-pre-miRNAs and 96 co-mRNA were screened, and the lncRNA/circRNA-miRNA-mRNA networks were constructed with 27 lncRNA/25 circRNAs, 74 miRNAs and 96 mRNAs. Then, 6 key mRNAs including Igf1, Klf4, Ptgs2, Epas1, Gnao1, and Il1a were obtained by PPI, and all of these key mRNAs and 10 key lncRNAs and 8 circRNAs were significantly different between the pneumoconiosis and normal groups, in which 10 lncRNAs and 9 circRNA that have not been previously studied in pneumoconiosis/silicosis can be used as new potential therapeutic targets. Moreover, the TFs-miRNA-mRNA network were constructed with 11 TFs, 1 key miRNA (mmu-miR-682) and 3 key mRNAs (Igf1, Epas1, Ptgs2). And the validation of key genes revealing by RNA-seq through experimental approaches shows the the predictive power of this study. Finally, IPA results indicated that 41 pathways were activated and 2 pathways were suppressed in pneumoconiosis/silicosis groups, and Pathogen Induced Cytokine Storm Signaling Pathway was the most significant pathway affected by pneumoconiosis/silicosis. In addition, 93 drugs were screened out by Drug-Gene Interaction database. Among them, Hydroxychloroquine was a kind of drug which associated with Il1a and Ptgs2, may be a promising treatment. CONCLUSION: This study constructed the lncRNA/circRNA-miRNA-mRNA and TFs-miRNA-mRNA networks, which could deepen the potential molecular regulatory mechanism of pneumoconiosis/silicosis.

Community case studies: an interpretative phenomenological analysis on sexual abuse in urban Chennai.

This study attempts to explore the lived experiences of sexual abuse during COVID-19 in a big metropolitan city in India, with a special interest in understanding the contemporary problems faced by teenagers. Any Phenomenological enquiry begins with identifying and determining the suitability of the participants. In this case, the participants are teenage girls and boys, who have experienced one or other forms of sexual abuse during the COVID-19 pandemic. By restricting the act of sexual abuse that happened during a pandemic, this research brings attention to the medium (material), social conditions, and the role of the cultural world in the act of sexual abuse. It begins by distributing a questionnaire to 500 participants to identify the participants who had experienced one or other forms of sexual abuse during the aforementioned time. Secondly, brief interviews with the identified participants are conducted to record their lived experience of sexual abuse. Using this collected narrated experience as a reservoir for phenomenological reflection, this research aims to uncover moments of lived experience emphasizing spatial, corporeal, and temporal aspects as well as provide greater depth in understanding sexual abuse in the context of teenage lives. It helps to understand the different forms of sexual abuse experienced by teenagers as well as portrays how space plays a major role in the act. This article aims to highlight the role of the material world in the act as well as how the social, political, and cultural contexts are materialized in the act of sexual abuse. Also, this article analyses how the existing intervention mechanisms support the prevention of sexual abuse in different social settings as well as emphasizes the gaps in the intervention mechanisms apropos the chosen narrative data. To sum up, this study aims to create awareness, provides prevention mechanisms considering the role of the material world, and advocates for SDG 16 (Promote justice, peaceful and inclusive societies) and SDG 5 (Achieve gender equality and empower all women and girls).

'It's like tumbleweeds everywhere': An Interpretative Phenomenological Analysis of the lived experience of being diagnosed with and living with narcolepsy.

There is a lack of awareness of how sleep health and sleep disorders are experienced. Previous research has found that living with narcolepsy has a debilitating impact on several areas of an individual's life alongside significant diagnostic delays. This study uses a phenomenological, qualitative methodology to explore experiences of being diagnosed with and living with narcolepsy. Six women with type 1 narcolepsy participated in semi-structured interviews. Transcripts were analysed using Interpretative Phenomenological Analysis. Capturing the whole illness experience of narcolepsy, our analysis illuminated three superordinate themes; 'minimising, dismissing and downplaying symptoms', 'navigating the winding journey to diagnosis' and 'a different way of living'. Through our analysis, we are able to demonstrate the affective impact lack of awareness of sleep and sleep disorders has; resulting in significant diagnostic delays and a lack of support post-diagnosis. Findings demonstrate a need for greater awareness and increased support.

Deep learning based automatic segmentation of the Internal Pudendal Artery in definitive radiotherapy treatment planning of localized prostate cancer.

Background and purpose: Radiation-induced erectile dysfunction (RiED) commonly affects prostate cancer patients, prompting clinical trials across institutions to explore dose-sparing to internal-pudendal-arteries (IPA) for preserving sexual potency. IPA, challenging to segment, isn't conventionally considered an organ-at-risk (OAR). This study proposes a deep learning (DL) auto-segmentation model for IPA, using Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) or CT alone to accommodate varied clinical practices. Materials and methods: A total of 86 patients with CT and MRI images and noisy IPA labels were recruited in this study. We split the data into 42/14/30 for model training, testing, and a clinical observer study, respectively. There were three major innovations in this model: 1) we designed an architecture with squeeze-and-excite blocks and modality attention for effective feature extraction and production of accurate segmentation, 2) a novel loss function was used for training the model effectively with noisy labels, and 3) modality dropout strategy was used for making the model capable of segmentation in the absence of MRI. Results: Test dataset metrics were DSC 61.71 ± 7.7 %, ASD 2.5 ± .87 mm, and HD95 7.0 ± 2.3 mm. AI segmented contours showed dosimetric similarity to expert physician's contours. Observer study indicated higher scores for AI contours (mean = 3.7) compared to inexperienced physicians' contours (mean = 3.1). Inexperienced physicians improved scores to 3.7 when starting with AI contours. Conclusion: The proposed model achieved good quality IPA contours to improve uniformity of segmentation and to facilitate introduction of standardized IPA segmentation into clinical trials and practice.

Effects of multi-walled carbon nanotubes on message and Micro-RNA in human lung BEAS-2B cells.

Multi-walled Carbon nanotubes (MWCNTs) lack sufficient quality cytotoxicity, toxicity, genotoxicity and genomic data on which to make environmental and regulatory decisions. Therefore, we did a multidisciplinary in vitro study of 3 MWCNTs in human lung cells (BEAS-2B) with the following endpoints: cytotoxicity, DNA damage, reactive oxygen and nitrogen species, lipid peroxidation and mRNA and microRNA expression analyses. The MWCNTs were either unfunctionalized or functionalized with either -OH or -COOH. Doses studied ranged from 0.3 to 100 ug/ml and were exposed to a human lung cell line in vitro for 72 h., with genomic studies being done from 30 ug/ml downward. Some of the genomic pathways that were altered by MWCNT exposure were NRF2 mediated oxidative stress response, DNA damage repair, nuclear excision repair, base excision repair, mitochondrial dysfunction, oxidative phosphorylation, HIF1α signaling, unfolded protein response, protein ubiquitination, ferroptosis and sirtuin signaling pathways. The data suggested that OH functionalized MWCNT caused more and larger gene/microRNA changes, followed by COOH functionalized MWCNT and unfunctionalized MWCNT being the least biologically active. From microRNA target filter analysis, there were altered signaling hubs. MYC is the only hub that altered by all 3 MWCNTs. Signaling hubs that are common to OH and COOH functionalized MWCNTs are GRB2, AR, TP63 and AGO2. The signaling hubs that were only present in OH functionalized MWCNTs are TP53, STAT3 and BRCA1. These signaling pathways and hubs we found in vitro correlated well with the published in vivo pathological effects like oxidative stress DNA damage, inflammation and cancer in MWCNTs treated mice.

An assessment of the perceptual elements of urban streets based on the context of urban tourism - The case of Sheffield.

Background: After COVID-19, more and more travelers are more inclined to walk in cities, and the sensory elements of streets can have a significant impact on urban tourism. Local residents and travelers have different perceptions of the street and preferences for its use. The purpose of this study is to evaluate and analyse the streets from the perspective of locals and travelers. Method: In this study, a questionnaire was designed to obtain local residents' and travelers' evaluations of the sensory elements of the street and a quadrant analysis of the street's sensory elements was carried out using the IPA-Kano model. Results: The results of the study show that travelers are particularly concerned about maps and signage guidance, while local residents are more concerned about the green environment of the surroundings and how well it is maintained. Conclusion: There is a difference in the indicators chosen by the two groups in the results of the comparison between locals and travelers, and this study is hoped to provide some data support for future urban managers and designers to learn from and refer to for street improvements and renewal.