bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.