bluuebunny/crossref_metadata_2025 huggingface dataset:
Sibling relationships and parental interventions to sibling bullying during COVID-19: A qualitative comparison of British and Turkish families of autistic adolescents
Authors: Deniz Emre , Fox Laura , Asbury Kathryn , Toseeb Umar
Published: August 2024

Background and aims

Despite its high potential for affecting sibling relationships, few studies have explored the impact of the COVID-19 pandemic on this important family dynamic. Of these, the reported evidence has been inconsistent across cultures and lacks cross-cultural comparability. For the first time, we investigated cross-cultural variability in the impact of COVID-19, and the restrictions associated with it, on sibling relationships of autistic adolescents from a Western (United Kingdom) and non-Western (Turkey) country. We also explored how British and Turkish parents intervene in negative sibling interactions—that is, sibling bullying—when witnessed.

Methods

Parents of 164 British and 96 Turkish autistic adolescents, aged 9 to 20 years, were asked how they perceived the effects of COVID-19 on their children's sibling relationships, and how they were most likely to react to instances of sibling bullying. Free response data from parents were analyzed using qualitative content analysis.

Results

Our findings indicated more cross-cultural similarities than differences between British and Turkish families. The majority of both British and Turkish parents indicated that COVID-19 worsened sibling relationships between their autistic and nonautistic children. An overwhelming majority of British and Turkish parents also said that they would step in directly when witnessing sibling bullying. Despite the high volume of cross-cultural similarities generally, we also found some cross-cultural differences, for instance in relation to the most common negative impact of COVID-19 on sibling relationships and the most preferred parental responses to sibling bullying.

Conclusions and implication

Implications and suggestions are discussed in more detail, drawing on the Etic approach to cross-cultural psychology.
Clinical Outcomes of Pars Plana Vitrectomy and Polytetrafluoroethylene (Gore-Tex) Scleral Fixation of a Monofocal Aspheric Intraocular Lens (Akreos AO60)
Authors: Mishra Amit V. , Martens Rosanna , Loh Graeme K. , Somani Rizwan , Greve Mark D.J. , Seamone Mark E.
Published: August 2024

Purpose: To evaluate the visual outcomes and complications with a polytetrafluoroethylene (Gore-Tex)-fixated intraocular lens (IOL) (Akreos AO60, Bausch + Lomb). Methods: Eyes with inadequate capsule support for in-the-bag IOL implantation had pars plana vitrectomy (PPV) and IOL placement at a single center. The main outcome measures were the postoperative visual acuity (VA) and complication rates. Results: During the study, 783 surgeries were performed. The mean visual acuity gain was 28.5 Early Treatment Diabetic Retinopathy Study letters ( P < .01), with a mean time to best VA of 3.05 months. Statistical hypotony (intraocular pressure <6.5 mm Hg) was present in 214 cases (27.3%), and clinical features of hypotony were present in 46 cases. Five percent of the complications were directly related to the IOL. There were 3 cases of IOL opacification, 2 with silicone oil endotamponade and 1 with perfluoropropane endotamponade. Conclusions: PPV with Akreos IOL implantation was an effective technique for secondary IOL placement. Complications directly related to the IOL were uncommon.
Content Analysis of Dividend Distribution Policy of Indian Listed Companies
Authors: Inamdar Meraj , Krishnan Ranjith , Mehrotra Shweta
Published: August 2024

This study attempts to perform content analysis, which is based on specific paradigms of unobtrusive research techniques, including conceptual and document analysis of the dividend distribution policies of the top 200 listed companies by market capitalisation to assess whether the policies enunciated by the companies align with the parameters suggested in the SEBI regulation. To conduct a content analysis, the authors use a three-step methodology to collect the dividend distribution policy documents and thus evaluate their content. First, we revisited the regulatory framework for the dividend policy and the provisions laid down by the regulators. The necessary information pertaining to the divided policy as per the legislations was retrieved from the policy documents and categorised further for the analysis. Finally, the collected information in the form of a document as per different categories was used as primary data for the content analysis. Our analysis found that dividends declared by companies were largely guided by the board’s long-term strategy. Further, looking from the investors’ perspective, having in place a dividend distribution policy for companies has probably not addressed their needs.
Epigenetic agents plus anti-PD-1 reprogram the tumor microenvironment and restore antitumor efficacy in Hodgkin lymphoma
Authors: Nie Jing , Wang Chunmeng , Zheng Liangtao , Liu Yang , Wang Chengcheng , Chang Yixin , Hu Yudi , Guo Bing , Pan Yuting , Yang Qingming , Hu Xueda , Han Weidong
Published: August 2024

DNA methyltransferase inhibitor decitabine plus anti–programmed cell death 1 (DP) therapy was effective in relapsed/refractory classic Hodgkin lymphoma (cHL). However, a subset of patients experienced primary resistance or relapse/progression after DP therapy. In this study, we evaluated the efficacy and safety of a triplet regimen consisting of the histone deacetylase inhibitor chidamide, decitabine, and anti–PD-1 camrelizumab (CDP) in 52 patients who previously received DP therapy. CDP treatment was well tolerated and resulted in an objective response rate of 94% (95% confidence interval [CI], 84-99), with 50% (95% CI, 36-64) of patients achieving complete response (CR). Notably, all patients who were recalcitrant to previous DP treatment exhibited therapeutic responses after CDP therapy, although their CR rate was lower than patients responsive to prior DP. Overall, the median progression-free survival was 29.4 months. Through single-cell RNA sequencing of pretreatment and on-treatment cHL tumor biopsy samples, we observed the heterogeneity of rare malignant Hodgkin Reed/Sternberg (HRS)–like cells. The classical CD30+ HRS-like cells interacted with abundant immunosuppressive IL21+CD4+ T helper cells, forming a positive feedback loop that supported their survival. While the CD30– HRS-like cell population showed potential resistance to anti–PD-1 immunotherapy. CDP treatment promoted the activation of diverse tumor-reactive CD8+ T cells and suppressed the proliferation of IL21+CD4+ T cells by inhibiting STAT1/3 signaling, thereby alleviating their immunosuppressive effects. These findings provide insights into the cHL microenvironment that contributes to anti–PD-1 resistance and highlight the therapeutic effectiveness of dual epi-immunotherapy in overcoming immunotherapy resistance. This trial was registered at www.clinicaltrials.gov as #NCT04233294.
Neuroimmune recognition and regulation in the respiratory system
Authors: Chen Jie , Lai Xiaoyun , Song Yuanlin , Su Xiao
Published: August 2024

Neuroimmune recognition and regulation in the respiratory system is a complex and highly coordinated process involving interactions between the nervous and immune systems to detect and respond to pathogens, pollutants and other potential hazards in the respiratory tract. This interaction helps maintain the health and integrity of the respiratory system. Therefore, understanding the complex interactions between the respiratory nervous system and immune system is critical to maintaining lung health and developing treatments for respiratory diseases. In this review, we summarise the projection distribution of different types of neurons (trigeminal nerve, glossopharyngeal nerve, vagus nerve, spinal dorsal root nerve, sympathetic nerve) in the respiratory tract. We also introduce several types of cells in the respiratory epithelium that closely interact with nerves (pulmonary neuroendocrine cells, brush cells, solitary chemosensory cells and tastebuds). These cells are primarily located at key positions in the respiratory tract, where nerves project to them, forming neuroepithelial recognition units, thus enhancing the ability of neural recognition. Furthermore, we summarise the roles played by these different neurons in sensing or responding to specific pathogens (influenza, severe acute respiratory syndrome coronavirus 2, respiratory syncytial virus, human metapneumovirus, herpes viruses, Sendai parainfluenza virus,
Mycobacterium tuberculosis
,
Pseudomonas aeruginosa
,
Staphylococcus aureus
, amoebae), allergens, atmospheric pollutants (smoking, exhaust pollution), and their potential roles in regulating interactions among different pathogens. We also summarise the prospects of bioelectronic medicine as a third therapeutic approach following drugs and surgery, as well as the potential mechanisms of meditation breathing as an adjunct therapy.
Nobiletin restores HFD-induced enteric nerve injury by regulating enteric glial activation and the GDNF/AKT/FOXO3a/P21 pathway
Authors: Pang Yueshan , Zhang Li , Zhong Zhuoting , Yang Ni , Zheng Yali , Ding Weijun
Published: August 2024

Background

To explore whether nobiletin has a protective effect on high-fat diet (HFD)-induced enteric nerve injury and its underlying mechanism.

Methods

An obesity model was induced by a HFD. Nobiletin (100 mg/kg and 200 mg/kg) and vehicle were administered by gastric gavage for 4 weeks. Lee’s index, body weight, OGTT and intestinal propulsion assays were performed before sacrifice. After sampling, lipids were detected using Bodipy 493/503; lipid peroxidation was detected using MDA and SOD kits and the expression of PGP 9.5, Trem2, GFAP, β-tubulin 3, Bax, Bcl2, Nestin, P75 NTR, SOX10 and EDU was detected using immunofluorescence. The GDNF, p-AKT, AKT, p-FOXO3a, FOXO3a and P21 proteins were detected using western blotting. The relative mRNA expression levels of NOS2 were detected via qPCR. Primary enteric neural stem cells (ENSCs) were cultured. After ENSCs were treated with palmitic acid (PA) and nobiletin, CCK-8 and caspase-3/7 activity assays were performed to evaluate proliferation and apoptosis.

Results

HFD consumption caused colon lipid accumulation and peroxidation, induced enteric nerve damage and caused intestinal motor dysfunction. However, nobiletin reduced lipid accumulation and peroxidation in the colon; promoted Trem2, β-tubulin 3, Nestin, P75NTR, SOX10 and Bcl2 expression; inhibited Bax and GFAP expression; reduced NOS2 mRNA transcription; and regulated the GDNF/AKT/FOXO3a/P21 pathway. Nobiletin also promoted PA-induced impairment of ENSCs.

Conclusions

Nobiletin restored HFD-induced enteric nerve injury, which may be associated with inhibiting enteric nerve apoptosis, promoting enteric nerve survival and regulating the GDNF/AKT/FOXO3a/P21 pathway.
N6-methyladenosine-modified SRPK1 promotes aerobic glycolysis of lung adenocarcinoma via PKM splicing
Authors: Wang Anqi , Zeng Yuanyuan , Zhang Weijie , Zhao Jian , Gao Lirong , Li Jianjun , Zhu Jianjie , Liu Zeyi , Huang Jian-an
Published: August 2024

Background

The RNA N6-methyladenosine (m6A) modification has become an essential hotspot in epigenetic modulation. Serine–arginine protein kinase 1 (SRPK1) is associated with the pathogenesis of various cancers. However, the m6A modification of SRPK1 and its association with the mechanism of in lung adenocarcinoma (LUAD) remains unclear.

Methods

Western blotting and polymerase chain reaction (PCR) analyses were carried out to identify gene and protein expression. m6A epitranscriptomic microarray was utilized to the assess m6A profile. Loss and gain-of-function assays were carried out elucidate the impact of METTL3 and SRPK1 on LUAD glycolysis and tumorigenesis. RNA immunoprecipitation (RIP), m6A RNA immunoprecipitation (MeRIP), and RNA stability tests were employed to elucidate the SRPK1’s METTL3-mediated m6A modification mechanism in LUAD. Metabolic quantification and co-immunoprecipitation assays were applied to investigate the molecular mechanism by which SRPK1 mediates LUAD metabolism.

Results

The epitranscriptomic microarray assay revealed that SRPK1 could be hypermethylated and upregulated in LUAD. The main transmethylase METTL3 was upregulated and induced the aberrant high m6A levels of SRPK1. Mechanistically, SRPK1’s m6A sites were directly methylated by METTL3, which also stabilized SRPK1 in an IGF2BP2-dependent manner. Methylated SRPK1 subsequently promoted LUAD progression through enhancing glycolysis. Further metabolic quantification, co-immunoprecipitation and western blot assays revealed that SRPK1 interacts with hnRNPA1, an important modulator of PKM splicing, and thus facilitates glycolysis by upregulating PKM2 in LUAD. Nevertheless, METTL3 inhibitor STM2457 can reverse the above effects in vitro and in vivo by suppressing SRPK1 and glycolysis in LUAD.

Conclusion

It was revealed that in LUAD, aberrantly expressed METTL3 upregulated SRPK1 levels via an m6A-IGF2BP2-dependent mechanism. METTL3-induced SRPK1 fostered LUAD cell proliferation by enhancing glycolysis, and the small-molecule inhibitor STM2457 of METTL3 could be an alternative novel therapeutic strategy for individuals with LUAD.
Can supervised deep learning architecture outperform autoencoders in building propensity score models for matching?
Authors: Karim Mohammad Ehsanul
Published: August 2024

Purpose

Propensity score matching is vital in epidemiological studies using observational data, yet its estimates relies on correct model-specification. This study assesses supervised deep learning models and unsupervised autoencoders for propensity score estimation, comparing them with traditional methods for bias and variance accuracy in treatment effect estimations.

Methods

Utilizing a plasmode simulation based on the Right Heart Catheterization dataset, under a variety of settings, we evaluated (1) a supervised deep learning architecture and (2) an unsupervised autoencoder, alongside two traditional methods: logistic regression and a spline-based method in estimating propensity scores for matching. Performance metrics included bias, standard errors, and coverage probability. The analysis was also extended to real-world data, with estimates compared to those obtained via a double robust approach.

Results

The analysis revealed that supervised deep learning models outperformed unsupervised autoencoders in variance estimation while maintaining comparable levels of bias. These results were supported by analyses of real-world data, where the supervised model’s estimates closely matched those derived from conventional methods. Additionally, deep learning models performed well compared to traditional methods in settings where exposure was rare.

Conclusion

Supervised deep learning models hold promise in refining propensity score estimations in epidemiological research, offering nuanced confounder adjustment, especially in complex datasets. We endorse integrating supervised deep learning into epidemiological research and share reproducible codes for widespread use and methodological transparency.
The influence factors on pit and fissure sealing behavior of 12-year-old children: a cross-sectional study in Zhejiang, China
Authors: Ge Xin , Zhou Huan , Li Xuejing , Siow Lixuen , Xie Yanyi , Hu Yijie , Wan Yao , Fu Danli , Zhu Haihua
Published: August 2024

Background

In the 21st century, dental caries remains a global burden, particularly severely affecting the growth and quality of life of 12-year-old children. Fortunately, pit and fissure sealing (PFS) procedures can effectively prevent molars from caries. Hence, this study focused on the relationship between PFS and oral epidemiological factors in 12-year-old children.

Methods

A cross-sectional survey was conducted in 12-year-old children from 11 cities in Zhejiang Province. Their dental conditions were collected through questionnaires, as well as basic information such as relevant family information, oral health knowledge and behavior. Then, logistic regression analysis was used to identify the influencing factors associated with PFS.

Results

A total of 1204 children were included, with 252 in the PFS group and 952 in the non-PFS group. There were significant differences between the two groups in terms of decayed, missing and filled teeth (DMFT) score, first permanent molar DMFT score, residential area, educational level of parents, tooth-brushing frequency, use of dental floss, oral examination in a medical institution, having taken courses on oral health care, as well as having knowledge that tooth brushing could effectively prevent gingival inflammation, PFS could protect teeth, and oral disease may affect general health. According to further logistic regression analysis, the independent factors influencing PFS included use of dental floss [odds ratios (OR) = 1.672, 95% confidence intervals (CI) = 1.235–2.263, P = 0.001], having taken courses on oral health care (OR = 0.713, 95% CI = 0.515–0.988, P = 0.042), having knowledge that tooth brushing is effective in preventing gingival inflammation (OR = 0.627, 95% CI = 0.389–0.987, P = 0.044) and having knowledge that PFS can protect teeth (OR = 0.589, 95% CI = 0.438–0.791, P < 0.001).

Conclusion

PFS can reduce the mean DMFT score of 12-year-old children. Independent influencing factors of PFS consist of use of dental floss, having taken courses on oral health care, oral health behavior and knowledge level.
Role of systemic immune-inflammatory index and systemic inflammatory response index in predicting the diagnosis of necrotizing pneumonia in children
Authors: Elmeazawy Rehab , Ayoub Dalia , Morad Lamia M. , EL-Moazen Ahmed Mohammed Farid
Published: August 2024

Background

Necrotizing pneumonia (NP) is a rare serious complication of community-acquired pneumonia (CAP) in children, which is characterized by a protracted course of the disease and a prolonged hospital stay. This study aimed to assess the role of systemic immune-inflammatory index and systemic inflammatory response index in predicting early lung necrotization in children with CAP.

Methods

This study included all children hospitalized in Pediatric Pulmonology Unit, Tanta University, Egypt, with CAP between the ages of two months and 18 years. Systemic inflammatory indices, including the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), systemic immune-inflammatory index (SII), and systemic inflammation response index (SIRI), were calculated on patients’ admission.

Results

The study involved a total of 228 children, 42 patients had NP, 46 patients had parapneumonic effusion, and 140 patients had non-complicated CAP. Patients with NP were substantially younger (p = 0.002), stayed in the hospital longer (p < 0.001), had a longer duration of symptoms before hospital admission (p < 0.001), and had fever for a longer duration than those in the other groups (p < 0.001). Regarding the inflammatory ratios, patients with NP had significantly higher MLR, PLR, SII, and SIRI than those in the other groups (p = 0.020, p = 0.007, p = 0.001, p = 0.037, respectively). ROC curve analysis showed that the combined SII + SIRI + D-dimer showed the highest AUC with a good specificity in predicting the diagnosis of NP.

Conclusions

SII, SIRI, and D-dimer may be beneficial biomarkers for predicting the occurrence of NP in children when performed on patients’ admission. In addition, it was found for the first time that combined SII + SIRI + D-dimer had a good sensitivity and specificity in the diagnosis of NP.
In vitro evaluation of PLGA loaded hesperidin on colorectal cancer cell lines: an insight into nano delivery system
Authors: Yaghoubi Narges , Gholamzad Amir , Naji Tahere , Gholamzad Mehrdad
Published: August 2024

Background

Colorectal cancer is a common disease worldwide with non-specific symptoms such as blood in the stool, bowel movements, weight loss and fatigue. Chemotherapy drugs can cause side effects such as nausea, vomiting and a weakened immune system. The use of antioxidants such as hesperidin could reduce the side effects, but its low bioavailability is a major problem. In this research, we aimed to explore the drug delivery and efficiency of this antioxidant on the HCT116 colorectal cancer cell line by loading hesperidin into PLGA nanoparticles.

Materials and methods

Hesperidin loaded PLGA nanoparticles were produced by single emulsion evaporation method. The physicochemical properties of the synthesized hesperidin-loaded nanoparticles were determined using SEM, AFM, FT-IR, DLS and UV-Vis. Subsequently, the effect of the PLGA loaded hesperidin nanoparticles on the HCT116 cell line after 48 h was investigated by MTT assay at three different concentrations of the nanoparticles.

Result

The study showed that 90% of hesperidin were loaded in PLGA nanoparticles by UV-Vis spectrophotometry and FT-IR spectrum. The nanoparticles were found to be spherical and uniform with a hydrodynamic diameter of 76.2 nm in water. The release rate of the drug was about 93% after 144 h. The lowest percentage of cell viability of cancer cells was observed at a concentration of 10 µg/ml of PLGA nanoparticles loaded with hesperidin.

Conclusion

The results indicate that PLGA nanoparticles loaded with hesperidin effectively reduce the survival rate of HCT116 colorectal cancer cells. However, further studies are needed to determine the appropriate therapeutic dosage and to conduct animal and clinical studies.
Patients’ motives and considerations on treatment decision-making for heavy menstrual bleeding: a qualitative study
Authors: Oderkerk T. J. , Singotani R. G. , Zuidema L. , van der Hijden E. J.E. , Geomini P. M.A.J. , Bongers M. Y. , Donker M. H.
Published: August 2024

Background

Several treatment modalities for heavy menstrual bleeding are available. However, many women report being unsatisfied in their search for an appropriate and effective treatment. The aim of this study is to gain insights in the experienced impact of heavy menstrual bleeding and the motives and considerations of women during the decision-making process for treating heavy menstrual bleeding.

Methods

An interpretative qualitative study was performed, using in-depth interviews. In total, 14 semi-structured interviews were conducted with patients who consulted a physician for treatment of heavy menstrual bleeding. Participants were recruited via the Netherlands Patients Federation (N = 10) or via the outpatient clinic in the Máxima Medical Center (N = 4). The interviews were conducted by phone or online between February 2020 and March 2021. In the interviews three topics were addressed: (1) participant’s experience with heavy menstrual bleeding, (2) experience with patient journey of treatment decision-making and (3) elaborating on alternative treatments for heavy menstrual bleeding. A thematic analysis was conducted.

Results

Fourteen participants aged between 30 and 59 years old were interviewed. Three main themes emerged; “Considerations in taking the (next) step to seek help”, “Various sources of information can contribute, confuse or frighten decision-making process” and “A physician’s understanding and a relationship of trust are needed to guide the decision-making process”.

Conclusion

Our results show that women’s considerations and decision making strongly depend on the obtained information and experience, the relationship with the physician, the influence of the social environment, the pre-visit expectations/desires, the fear of treatment complications and uncertainty of the effect of the treatment. It is a physicians role to create a trusting and open atmosphere during consultation. Patient-centered communication is helpful to share knowledge, and gain insights into a patient’s hopes, fears and worries.
Extract of Phyllanthus emblica L. fruit stimulates basal glucose uptake and ameliorates palmitate-induced insulin resistance through AMPK activation in C2C12 myotubes
Authors: Li Hai-yan , Li Chun-fei , Liu Chun-hui , Chen Sun-ce , Liu Yi-fan , Lv Quan-he , Zhang Wen
Published: August 2024

Background

The fruit of Phyllanthus emblica L., a traditional medicine in China and India, is used to treat diabetes mellitus. Its water extract (WEPE) has demonstrated hypoglycemic effects in diabetic rats, but its mechanisms on glucose utilization and insulin resistance in skeletal muscle remain unclear. Therefore, this study aims to investigate the effects and underlying mechanisms of WEPE on glucose utilization and insulin resistance using C2C12 myotubes.

Methods

Effects of WEPE on glucose uptake, GLUT4 translocation, and AMPK and AKT phosphorylation were investigated in C2C12 myotubes and palmitate-treated myotubes. An AMPK inhibitor and siRNA were used to explore the mechanisms of WEPE. Glucose uptake was determined using a 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxyglucose (2-NBDG) uptake assay, and protein expression and GLUT4 translocation were assessed via western blotting.

Results

In normal myotubes, WEPE significantly stimulated glucose uptake and GLUT4 translocation to the plasma membrane at concentrations of 125 and 250 µg/mL. This was accompanied by an increase in the phosphorylation of AMPK and its downstream targets. However, both compound C and AMPK siRNA blocked the WEPE-induced GLUT4 translocation and glucose uptake. Moreover, pretreatment with STO-609, a calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ) inhibitor, inhibited WEPE-induced AMPK phosphorylation and attenuated the WEPE-stimulated glucose uptake and GLUT4 translocation. In myotubes treated with palmitate, WEPE prevented palmitate-induced insulin resistance by enhancing insulin-mediated glucose uptake and AKT phosphorylation. It also restored the insulin-mediated translocation of GLUT4 from cytoplasm to membrane. However, these effects of WEPE on glucose uptake and GLUT4 translocation were blocked by pretreatment with compound C.

Conclusions

WEPE significantly stimulated basal glucose uptake though CaMKKβ/AMPK pathway and markedly ameliorated palmitate-induced insulin resistance by activating the AMPK pathway in C2C12 myotubes.
The role of mindfulness in stress, productivity and wellbeing of foundation year doctors: a mixed-methods feasibility study of the mindful resilience and effectiveness training programme
Authors: Matthias Chanais , Bu Christopher , Cohen Matt , Jones Marc V. , Hearn Jasmine H.
Published: August 2024

Background

Medical Foundation Year (FY) doctors demonstrate greater psychological distress compared with the general population and other student groups. This feasibility study investigated FY doctors’ perceptions of mindfulness and the impact of a mindful resilience and effectiveness training (MRET) programme on stress, wellbeing, and performance.

Methods

Mixed-methods study utilising a questionnaire (study 1, N = 144) and a pre-post analysis design of MRET programme (study 2, N = 13), along with focus groups (N = 7).

Results

In study 1 28.5% of FY’s reported using mindfulness. All five mindfulness facets were significantly, and positively, associated with mental wellbeing (p < 0.05). Acting with awareness (AA) and non-reactivity (NR) were significantly, positively associated with a challenge responses to stress (p < 0.05). Threat and loss appraisals were negatively associated with AA, NR, and non-judging (p < 0.01). Perceived productivity was positively associated with mindfulness facets: describing, AA, and NR (p < 0.001). In study 2, there were significant increases in wellbeing and mindfulness facets observing, describing, AA, and NR, and threat appraisals decreased (p < 0.05). The main themes identified across the focus group included Reframed Mindset, Values-Based Action, Embodied Leadership and Pedagogy.

Conclusions

There exists a relationship between mindfulness, psychological wellbeing, and performance in FYs. The MRET prorgamme improved psychological wellbeing and reduced threat appraisals. Future work could focus resources on enhancing the skills of AA and NR, as this may be sufficient to bring about meaningful improvements in wellbeing, percieved productivity and cognitive reappraisal of stressful life events.
Enhancing patient informed consent in elective skin cancer surgeries: a comparative study of traditional and digital approaches in a German public hospital
Authors: Schulz Alexandra , Bohnet-Joschko Sabine
Published: August 2024

Background

This study aims to investigate the integration of modern sources of patient information, such as videos, internet-based resources, and scientific abstracts, into the traditional patient informed consent process in outpatient elective surgeries. The goal is to optimize the informed consent experience, enhance patient satisfaction, and promote shared decision making (SDM) between patients and surgeons. By exploring different patient informed consent formats and their impact on patient satisfaction, this research seeks to improve healthcare practices and ultimately enhance patient outcomes. The findings of this study will contribute to the ongoing efforts to improve the informed consent process in public hospitals and advance patient-centred care.

Methods

Data collection occurred at the day care clinic of a prominent German public hospital, forming an integral component of a prospective clinical investigation. The study exclusively focused on individuals who had undergone surgical intervention for skin cancer. For the purpose of meticulous data examination, the statistical software SPSS version 21 was harnessed. In the course of this study, a chi-square test was aptly employed. Its purpose was to scrutinize the nuances in patient experiences pertaining to informed consent across four distinct categories, viz., oral informed consent discussion (Oral ICD), written informed consent discussion (Written ICD), video-assisted informed consent discussion (video-assisted ICD), and digitally assisted informed consent discussion (digital-assisted ICD). The primary dataset of this inquiry was diligently gathered via a structured questionnaire administered to a targeted cohort of 160 patients. Within this sample, a balanced representation of genders was observed, encompassing 82 males and 78 females. Their collective age span ranged from 18 to 92 years, with an average age of 71 years. A randomized selection methodology was employed to include participants in this study during the period spanning from July 2017 to August 2018.

Results

Significant differences were observed across the groups for all research questions, highlighting variations in patient responses. Video-assisted and digital-assisted IC were rated as superior in patient satisfaction with information compared to written and oral IC. Demographic profiles of the four study groups were found to be comparable.

Conclusion

The findings of this study indicate that the incorporation of digital technologies in the informed consent process can enhance patient understanding during outpatient elective skin cancer surgeries. These results have important implications for increasing patient satisfaction and improving the SDM process within the hospital environment.
“I didn’t even wonder why I was on the floor” – mixed methods exploration of stroke awareness and help-seeking behaviour at stroke symptom onset
Authors: Busetto Loraine , Stang Christina , Herzog Franziska , Sert Melek , Hoffmann Johanna , Purrucker Jan , Seker Fatih , Bendszus Martin , Wick Wolfgang , Ungerer Matthias , Gumbinger Christoph
Published: August 2024

Introduction

To better target stroke awareness efforts (pre and post first stroke) and thereby decrease the time window for help-seeking, this study aims to assess quantitatively whether stroke awareness is associated with appropriate help-seeking at symptom onset, and to investigate qualitatively why this may (not) be the case.

Methods

This study conducted in a German regional stroke network comprises a convergent quantitative-dominant, hypothesis-driven mixed methods design including 462 quantitative patient questionnaires combined with qualitative interviews with 28 patients and seven relatives. Quantitative associations were identified using Pearson’s correlation analysis. Open coding was performed on interview transcripts before the quantitative results were used to further focus qualitative analysis. Joint display analysis was conducted to mix data strands. Cooperation with the Patient Council of the Department of Neurology ensured patient involvement in the study.

Results

Our hypothesis that stroke awareness would be associated with appropriate help-seeking behaviour at stroke symptom onset was partially supported by the quantitative data, i.e. showing associations between some dimensions of stroke awareness and appropriate help-seeking, but not others. For example, knowing stroke symptoms is correlated with recognising one’s own symptoms as stroke (r = 0.101; p = 0.030*; N = 459) but not with no hesitation before calling help (r = 0.003; p = 0.941; N = 457). A previous stroke also makes it more likely to recognise one’s own symptoms as stroke (r = 0.114; p = 0.015*; N = 459), but not to be transported by emergency ambulance (r = 0.08; p = 0.872; N = 462) or to arrive at the hospital on time (r = 0.02; p = 0.677; N = 459). Qualitative results showed concordance, discordance or provided potential explanations for quantitative findings. For example, qualitative data showed processes of denial on the part of patients and the important role of relatives in initiating appropriate help-seeking behaviour on patients’ behalf.

Conclusions

Our study provides insights into the complexities of the decision-making process at stroke symptom onset. As our findings suggest processes of denial and inabilities to translate abstract disease knowledge into correct actions, we recommend to address relatives as potential saviours of loved ones, increased use of specific situational examples (e.g. lying on the bathroom floor) and the involvement of patient representatives in the preparation of informational resources and campaigns. Future research should include mixed methods research from one sample and more attention to potential reporting inconsistencies.
Translational modeling-based evidence for enhanced efficacy of standard-of-care drugs in combination with anti-microRNA-155 in non-small-cell lung cancer
Authors: Dogra Prashant , Shinglot Vrushaly , Ruiz-Ramírez Javier , Cave Joseph , Butner Joseph D. , Schiavone Carmine , Duda Dan G. , Kaseb Ahmed O. , Chung Caroline , Koay Eugene J. , Cristini Vittorio , Ozpolat Bulent , Calin George A. , Wang Zhihui
Published: August 2024

Background

Elevated microRNA-155 (miR-155) expression in non-small-cell lung cancer (NSCLC) promotes cisplatin resistance and negatively impacts treatment outcomes. However, miR-155 can also boost anti-tumor immunity by suppressing PD-L1 expression. Therapeutic targeting of miR-155 through its antagonist, anti-miR-155, has proven challenging due to its dual molecular effects.

Methods

We developed a multiscale mechanistic model, calibrated with in vivo data and then extrapolated to humans, to investigate the therapeutic effects of nanoparticle-delivered anti-miR-155 in NSCLC, alone or in combination with standard-of-care drugs.

Results

Model simulations and analyses of the clinical scenario revealed that monotherapy with anti-miR-155 at a dose of 2.5 mg/kg administered once every three weeks has substantial anti-cancer activity. It led to a median progression-free survival (PFS) of 6.7 months, which compared favorably to cisplatin and immune checkpoint inhibitors. Further, we explored the combinations of anti-miR-155 with standard-of-care drugs, and found strongly synergistic two- and three-drug combinations. A three-drug combination of anti-miR-155, cisplatin, and pembrolizumab resulted in a median PFS of 13.1 months, while a two-drug combination of anti-miR-155 and cisplatin resulted in a median PFS of 11.3 months, which emerged as a more practical option due to its simple design and cost-effectiveness. Our analyses also provided valuable insights into unfavorable dose ratios for drug combinations, highlighting the need for optimizing dose regimens to prevent antagonistic effects.

Conclusions

This work bridges the gap between preclinical development and clinical translation of anti-miR-155 and unravels the potential of anti-miR-155 combination therapies in NSCLC.
Genome-wide CRISPR screening identifies tyrosylprotein sulfotransferase-2 as a target for augmenting anti-PD1 efficacy
Authors: Oh Yumi , Kim Sujeong , Kim Yunjae , Kim Hyun , Jang Dongjun , Shin Seungjae , Lee Soo-Jin , Kim Jiwon , Lee Sang Eun , Oh Jaeik , Yang Yoojin , Kim Dohee , Jung Hae Rim , Kim Sangjin , Kim Jihui , Min Kyungchan , Cho Beomki , Seo Hoseok , Han Dohyun , Park Hansoo , Cho Sung-Yup
Published: August 2024

Background

Immune checkpoint therapy (ICT) provides durable responses in select cancer patients, yet resistance remains a significant challenge, prompting the exploration of underlying molecular mechanisms. Tyrosylprotein sulfotransferase-2 (TPST2), known for its role in protein tyrosine O-sulfation, has been suggested to modulate the extracellular protein-protein interactions, but its specific role in cancer immunity remains largely unexplored.

Methods

To explore tumor cell-intrinsic factors influencing anti-PD1 responsiveness, we conducted a pooled loss-of-function genetic screen in humanized mice engrafted with human immune cells. The responsiveness of cancer cells to interferon-γ (IFNγ) was estimated by evaluating IFNγ-mediated induction of target genes, STAT1 phosphorylation, HLA expression, and cell growth suppression. The sulfotyrosine-modified target gene of TPST2 was identified by co-immunoprecipitation and mass spectrometry. The in vivo effects of TPST2 inhibition were evaluated using mouse syngeneic tumor models and corroborated by bulk and single-cell RNA sequencing analyses.

Results

Through in vivo genome-wide CRISPR screening, TPST2 loss-of-function emerged as a potential enhancer of anti-PD1 treatment efficacy. TPST2 suppressed IFNγ signaling by sulfating IFNγ receptor 1 at Y397 residue, while its downregulation boosted IFNγ-mediated signaling and antigen presentation. Depletion of TPST2 in cancer cells augmented anti-PD1 antibody efficacy in syngeneic mouse tumor models by enhancing tumor-infiltrating lymphocytes. RNA sequencing data revealed TPST2’s inverse correlation with antigen presentation, and increased TPST2 expression is associated with poor prognosis and altered cancer immunity across cancer types.

Conclusions

We propose TPST2’s novel role as a suppressor of cancer immunity and advocate for its consideration as a therapeutic target in ICT-based treatments.
Home environment factors associated with child BMI changes during COVID-19 pandemic
Authors: McCabe Carolyn F. , Wood G. Craig , Welk Gregory J. , Cook Adam , Franceschelli-Hosterman Jennifer , Bailey-Davis Lisa
Published: August 2024

Background

The influence of home obesogenic environments, as assessed by the validated Family Nutrition and Physical Activity (FNPA) tool, and child obesity during the COVID pandemic were evaluated using electronic health records in this retrospective cohort study.

Methods

Historical data on BMI and the FNPA screening tool were obtained from annual well-child visits within the Geisinger Health System. The study examined youth ages 2–17 that had a BMI record and an FNPA assessment prior to the pandemic (BMI 3/1/19–2/29/20), 1 BMI record 3 months into the pandemic (6/1/20–12/31/20) and 1 BMI in the second year of the pandemic (1/1/21–12/31/21). Tertiles of obesity risk by FNPA score were examined. Mixed-effects linear regression was used to examine change in BMI slope (kg/m2 per month) pre-pandemic to pandemic using FNPA summary and subscales scores as predictors and adjusting for confounding factors.

Results

The analyses included 6,746 children (males: 51.7%, non-Hispanic white: 86.6%, overweight:14.8%, obesity:10.3%, severe obesity: 3.9%; mean(SD) age: 5.7(2.8) years). The rate of BMI change in BMI was greatest from early pandemic compared to pre-pandemic for children in lowest versus highest tertiles of FNPA summary score (0.079 vs. 0.044 kg/m2), FNPA-Eating (0.068 vs. 0.049 kg/m2), and FNPA-Activity (0.078 vs. 0.052 kg/m2). FNPA summary score was significantly associated with change in BMI from the pre-pandemic to early pandemic period (p = 0.014), but not associated with change in BMI during the later pandemic period.

Conclusions

This study provides additional insight into the changes in the rate of BMI change observed among children and adolescents in the United States during the COVID-19 pandemic. The FNPA provides ample opportunity to continue our exploration of the negative impact of the COVID-19 pandemic on the longitudinal growth patterns among children and adolescents.
Toxoplasma infection induces an aged neutrophil population in the CNS that is associated with neuronal protection
Authors: Bergersen Kristina V. , Kavvathas Bill , Ford Byron D. , Wilson Emma H.
Published: August 2024

Background

Infection with the protozoan parasite Toxoplasma gondii leads to the formation of lifelong cysts in neurons that can have devastating consequences in the immunocompromised. In the immunocompetent individual, anti-parasitic effector mechanisms and a balanced immune response characterized by pro- and anti-inflammatory cytokine production establishes an asymptomatic infection that rarely leads to neurological symptoms. Several mechanisms are known to play a role in this successful immune response in the brain including T cell production of IFNγ and IL-10 and the involvement of CNS resident cells. This limitation of clinical neuropathology during chronic infection suggests a balance between immune response and neuroprotective mechanisms that collectively prevent clinical manifestations of disease. However, how these two vital mechanisms of protection interact during chronic Toxoplasma infection remains poorly understood.

Main text

This study demonstrates a previously undescribed connection between innate neutrophils found chronically in the brain, termed “chronic brain neutrophils” (CBNeuts), and neuroprotective mechanisms during Toxoplasma infection. Lack of CBNeuts during chronic infection, accomplished via systemic neutrophil depletion, led to enhanced infection and deleterious effects on neuronal regeneration and repair mechanisms in the brain. Phenotypic and transcriptomic analysis of CBNeuts identified them as distinct from peripheral neutrophils and revealed two main subsets of CBNeuts that display heterogeneity towards both classical effector and neuroprotective functions in an age-dependent manner. Further phenotypic profiling defined expression of the neuroprotective molecules NRG-1 andErbB4 by these cells, and the importance of this signaling pathway during chronic infection was demonstrated via NRG-1 treatment studies.

Conclusions

In conclusion, this work identifies CBNeuts as a heterogenous population geared towards both classical immune responses and neuroprotection during chronic Toxoplasma infection and provides the foundation for future mechanistic studies of these cells.
Impact of an intervention for perinatal anxiety on breastfeeding: findings from the Happy Mother—Healthy Baby randomized controlled trial in Pakistan
Authors: Nisar Anum , Xiang Haoxue , Perin Jamie , Malik Abid , Zaidi Ahmed , Atif Najia , Rahman Atif , Surkan Pamela J.
Published: August 2024

Background

The study examined the effects of Happy Mother—Healthy Baby (HMHB), a cognitive-behavioural therapy (CBT) intervention on breastfeeding outcomes for Pakistani women with prenatal anxiety.

Methods

Breastfeeding practices were evaluated in a randomized controlled trial between 2019 and 2022 in a public hospital in Pakistan. The intervention group was randomized to receive six HMHB sessions targeted towards prenatal anxiety (with breastfeeding discussed in the final session), while both groups also received enhanced usual care. Breastfeeding was defined in four categories: early breastfeeding, exclusive early breastfeeding, recent breastfeeding, and exclusive recent breastfeeding. Early breastfeeding referred to the first 24 h after birth and recent breastfeeding referred to the last 24 h before an assessment at six-weeks postpartum. Potential confounders included were mother’s age, baseline depression and anxiety levels, stress, social support, if the first pregnancy (or not) and history of stillbirth or miscarriage as well as child’s gestational age, gender. Both intent-to-treat and per-protocol analyses were examined. Stratified analyses were also used to compare intervention efficacy for those with mild vs severe anxiety.

Results

Out of the 1307 eligible women invited to participate, 107 declined to participate and 480 were lost to follow-up, resulting in 720 women who completed the postpartum assessment. Both intervention and control arms were similar on demographic characteristics (e.g. sex, age, income, family structure). In the primary intent-to-treat analysis, there was a marginal impact of the intervention on early breastfeeding (OR 1.38, 95% CI: 0.99–1.92; 75.4% (N = 273) vs. 69.0% (N = 247)) and a non-significant association with other breastfeeding outcomes (OR1.42, 95% CI: 0.89–2.27; (47) 12.9% vs. (34) 9.5%, exclusive early breastfeeding; OR 1.48, 95% CI: 0.94–2.35; 90% (N = 327) vs. 86% (N = 309), recent breastfeeding; OR1.01, 95% CI: 0.76–1.35; 49% (N = 178) vs 49% (N = 175) exclusive recent breastfeeding). Among those who completed the intervention’s six core sessions, the intervention increased the odds of early breastfeeding (OR1.69, 95% CI:1.12–2.54; 79% (N = 154) vs. 69% (N = 247)) and recent breastfeeding (OR 2.05, 95% CI:1.10–3.81; 93% (N = 181) vs. 86% (N = 309)). For women with mild anxiety at enrolment, the intervention increased the odds of recent breastfeeding (OR 2.41, 95% CI:1.17–5.00; 92% (N = 137) vs. 83% (N = 123).

Conclusions

The study highlights the potential of CBT-based interventions like HMHB to enhance breastfeeding among women with mild perinatal anxiety, contingent upon full participation in the intervention.

Trial registration

ClinicalTrials.gov NCT03880032.
Phosphodiesterase type 5 inhibitor tadalafil reduces prostatic fibrosis via MiR-3126-3p/FGF9 axis in benign prostatic hyperplasia
Authors: Li Tiewen , Zhang Yu , Zhou Zeng , Guan Lvxin , Zhang Yichen , Zhou Zhiyuan , Wang Wenhao , Zhou Xuehao , Cui Di , Jiang Chenyi , Ruan Yuan
Published: August 2024

Myofibroblast buildup and prostatic fibrosis play a crucial role in the development of benign prostatic hyperplasia (BPH). Treatments specifically targeting myofibroblasts could be a promising approach for treating BPH. Tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor, holds the potential to intervene in this biological process. This study employs prostatic stromal fibroblasts to induce myofibroblast differentiation through TGFβ1 stimulation. As a result, tadalafil significantly inhibited prostatic stromal fibroblast proliferation and fibrosis process, compared to the control group. Furthermore, our transcriptome sequencing results revealed that tadalafil inhibited FGF9 secretion and simultaneously improved miR-3126-3p expression via TGFβ1 suppression. Overall, TGFβ1 can trigger pro-fibrotic signaling through miR-3126-3p in the prostatic stroma, and the use of tadalafil can inhibit this process.