bluuebunny/crossref_metadata_2025 huggingface dataset:
Community interpreting in Germany: results of a nationwide cross-sectional study among interpreters
Authors: Hanft-Robert Saskia , Mösko Mike
Published: June 2024

Background

Community interpreters (CIPs) play a crucial role in various community services, including healthcare, when service providers and users do not share a common language. However, there is a lack of evidence-based data on this population globally. This explorative cross-sectional study aims to gain a better understanding of CIPs and their work in Germany.

Methods

A nationwide online survey was conducted among CIPs in Germany to collect data on their qualification background, working conditions, mental health, interpreting-related psychosocial distress and sociodemographics. Participants were recruited through interpreting pools, training institutions and migrant organizations. Data were analyzed descriptively, dependent t-test, multiple logistic and hierarchical stepwise regression analyses were performed to predict participation in interpreting-specific training, interpreting competence and interpreting-related psychosocial distress.

Results

Across all 16 federal states, N = 873 responses were used for analysis. Most participants are female (74%), born abroad (77%) and have a high level of education (69%). The vast majority interpret occasionally in their leisure time (44%) and are self-employed/freelance (51%). 34% interpret solely or additional on a voluntary basis (unpaid). The median hours of interpreting per month are 10 h, 75% do not exceed 30 h. On average interpreters work in four different settings. 69% attended any kind of interpreting training with a median of 25 h in total. Interpreting in more settings emerged as an associated factor with participation in training. Of those who have never attended any training, 69% consider themselves as rather/very competent in interpreting. Interpreting more frequently, having less severe anxiety symptoms, getting higher and more often paid and being less satisfied with the payment is associated with self-reported interpreting competence. In total, 36% reported moderate or severe psychosocial distress regarding interpreting. Higher general psychosocial distress and depressive symptoms, higher interpreting frequency and lower payment satisfaction were found to be associated with higher distress regarding interpreting. Additionally, factors such as precarious work conditions, lack of recognition and discrimination (e.g. racism and sexism) were reported as distressing.

Conclusion

This study provides a first comprehensive evidence-based national database on CIPs in Germany. The findings can be valuable for the development of qualifications, guidelines, policies and the process of professionalizing the field of CIPs.
Can #chatsafe support parents and carers beyond Australia? A qualitative study
Authors: La Sala Louise , Sabo Amanda Vittoria , Lamblin Michelle , Robinson Jo
Published: June 2024

Background

Rates of self-harm and suicide are rising for young people globally and many implicate social media in this problem. To address this concern and to increase the confidence of adults to communicate safely about suicide and social media with young people, the #chatsafe Guide for Parents and Carers was developed in Australia. With significant uptake of the resource among Australian adults, the aim of the current study was to update and contextualise the #chatsafe Guide for Parents and Carers for audiences in 15 countries globally. To improve the relevance of this resource for parents and carers in these countries, the present study sought to understand the concerns held by parents, carers and suicide prevention professionals around the world about these topics and to explore the extent to which a resource such as #chatsafe would be helpful within their communities.

Methods

Seven focus groups were conducted via Zoom with parents, carers and suicide prevention professionals (n = 40) from 15 countries. Transcribed data were coded and thematically analysed using both inductive and deductive processes.

Results

Six themes are reported: (1) Two scary ‘S’ words; (2) Country and culture impact who talks (or is silent) about self-harm and suicide; (3) The need for a protective social ecosystem; (4) #chatsafe is a tool that can help parents, carers and young people worldwide; (5) #chatsafe should consider local context and end users to improve its relevance for parents and carers worldwide; and (6) A range of marketing and dissemination strategies are needed to reach adults with #chatsafe information. Findings of this study informed the update and contextualisation of the #chatsafe Guide for Parents and Carers for adult audiences in 15 countries.

Conclusions

The findings from this study underscore a universal need for psychoeducation initiatives that provide adults with the skills and knowledge to support the mental health of young people, both online and offline, and that resources like #chastafe can play an important role in providing reliable information about these topics to adults across a range of cultures and contexts.
Using unfolding case studies to develop critical thinking for Graduate Entry Nursing students: an educational design research study
Authors: Macdiarmid Rachel , Merrick Eamon , Winnington Rhona
Published: June 2024

Background

Graduate Entry Nursing (GEN) programmes have been introduced as another entry point to nurse registration. In the development of a new GEN programme, a problem-based approach to learning was used to develop critical thinking and clinical reasoning skills of motivated and academically capable students.

Objective

To explore and evaluate the design and delivery of course material delivered to GEN students embedded in authentic learning pedagogy from the perspectives of both GEN students and academic staff using an unfolding case study approach.

Methods

An educational design research approach was used to explore the learning experiences of GEN students using an unfolding case study approach situated in experiential pedagogy and the teaching experiences of the academics who designed it. Data were collected through semi-structured interviews with students once they had finished the course and weekly reflective diary recordings by academic staff throughout implementation. Thematic analysis was used to analyse the data.

Findings

Student reflections highlighted that this cohort had insight into how they learned and were comfortable voicing their needs to academic staff. While the unfolding case studies were not liked by all participants, for some it offered a unique learning opportunity; particularly when scaffolded with podcasts, simulation labs, tutorials and clinical placements. Staff reflections primarily aligned with student experiences.

Conclusion

The gaps highlighted in the delivery of the course suggest that a blended pedagogical approach to graduate entry nurse education is required. Specifically, GEN students are aware of the learning needs and are happy to express these to academic staff, thus suggesting that engaging with a co-design curriculum approach will benefit future cohorts.
Network proximity analysis as a theoretical model for identifying potential novel therapies in primary sclerosing cholangitis
Authors: Leighton Jessica , Jones David E. J. , Dyson Jessica K. , Cordell Heather J.
Published: June 2024

Primary Sclerosing Cholangitis (PSC) is a progressive cholestatic liver disease with no licensed therapies. Previous Genome Wide Association Studies (GWAS) have identified genes that correlate significantly with PSC, and these were identified by systematic review. Here we use novel Network Proximity Analysis (NPA) methods to identify already licensed candidate drugs that may have an effect on the genetically coded aspects of PSC pathophysiology.

Over 2000 agents were identified as significantly linked to genes implicated in PSC by this method. The most significant results include previously researched agents such as metronidazole, as well as biological agents such as basiliximab, abatacept and belatacept. This in silico analysis could potentially serve as a basis for developing novel clinical trials in this rare disease.
Adipocyte pyroptosis occurs in omental tumor microenvironment and is associated with chemoresistance of ovarian cancer
Authors: Lin Chang-Ni , Liang Yu-Ling , Tsai Hsing-Fen , Wu Pei-Ying , Huang Lan-Yin , Lin Yu-Han , Kang Chieh-Yi , Yao Chao-Ling , Shen Meng-Ru , Hsu Keng-Fu
Published: June 2024

Background

Ovarian carcinoma (OC) is a fatal malignancy, with most patients experiencing recurrence and resistance to chemotherapy. In contrast to hematogenous metastasizing tumors, ovarian cancer cells disseminate within the peritoneal cavity, especially the omentum. Previously, we reported omental crown-like structure (CLS) number is associated with poor prognosis of advanced-stage OC. CLS that have pathologic features of a dead or dying adipocyte was surrounded by several macrophages is well known a histologic hallmark for inflammatory adipose tissue. In this study, we attempted to clarify the interaction between metastatic ovarian cancer cells and omental CLS, and to formulate a therapeutic strategy for advanced-stage ovarian cancer.

Methods

A three-cell (including OC cells, adipocytes and macrophages) coculture model was established to mimic the omental tumor microenvironment (TME) of ovarian cancer. Caspase-1 activity, ATP and free fatty acids (FFA) levels were detected by commercial kits. An adipocyte organoid model was established to assess macrophages migration and infiltration. In vitro and in vivo experiments were performed for functional assays and therapeutic effect evaluations. Clinical OC tissue samples were collected for immunochemistry stain and statistics analysis.

Results

In three-cell coculture model, OC cells-derived IL-6 and IL-8 could induce the occurrence of pyroptosis in omental adipocytes. The pyroptotic adipocytes release ATP to increase macrophage infiltration, release FFA into TME, uptake by OC cells to increase chemoresistance. From OC tumor samples study, we demonstrated patients with high gasdermin D (GSDMD) expression in omental adipocytes is highly correlated with chemoresistance and poor outcome in advanced-stage OC. In animal model, by pyroptosis inhibitor, DSF, effectively retarded tumor growth and prolonged mice survival.

Conclusions

Omental adipocyte pyroptosis may contribute the chemoresistance in advanced stage OC. Omental adipocytes could release FFA and ATP through the GSDMD-mediate pyroptosis to induce chemoresistance and macrophages infiltration resulting the poor prognosis in advanced-stage OC. Inhibition of adipocyte pyroptosis may be a potential therapeutic modality in advanced-stage OC with omentum metastasis.
Causal association between circulating blood cell traits and pulmonary embolism: a mendelian randomization study
Authors: Jiang Chen , Lin Jianing , Xie Bin , Peng Meijuan , Dai Ziyu , Mai Suyin , Chen Qiong
Published: June 2024

Background

Pulmonary embolism (PE) is a life-threatening thromboembolic disease for which there is limited evidence for effective prevention and treatment. Our goal was to determine whether genetically predicted circulating blood cell traits could influence the incidence of PE.

Methods

Using single variable Mendelian randomization (SVMR) and multivariate Mendelian randomization (MVMR) analyses, we identified genetic associations between circulating blood cell counts and lymphocyte subsets and PE. GWAS blood cell characterization summary statistics were compiled from the Blood Cell Consortium. The lymphocyte subpopulation counts were extracted from summary GWAS statistics for samples from 3757 individuals that had been analyzed by flow cytometry. GWAS data related to PE were obtained from the FinnGen study.

Results

According to the SVMR and reverse MR, increased levels of circulating white blood cells (odds ratio [OR]: 0.88, 95% confidence interval [CI]: 0.81-0.95, p = 0.0079), lymphocytes (OR: 0.90, 95% CI: 0.84-0.97, p = 0.0115), and neutrophils (OR: 0.88, 95% CI: 0.81–0.96, p = 0.0108) were causally associated with PE susceptibility. MVMR analysis revealed that lower circulating lymphocyte counts (OR: 0.84, 95% CI: 0.75-0.94, p = 0.0139) were an independent predictor of PE. According to further MR results, this association may be primarily related to HLA-DR+ natural killer (NK) cells.

Conclusions

Among European populations, there is a causal association between genetically predicted low circulating lymphocyte counts, particularly low HLA-DR+ NK cells, and an increased risk of PE. This finding supports observational studies that link peripheral blood cells to PE and provides recommendations for predicting and preventing this condition.

Graphical Abstract
Targeting mTOR signaling pathways in multiple myeloma: biology and implication for therapy
Authors: Wang Yanmeng , Vandewalle Niels , De Veirman Kim , Vanderkerken Karin , Menu Eline , De Bruyne Elke
Published: June 2024

Multiple Myeloma (MM), a cancer of terminally differentiated plasma cells, is the second most prevalent hematological malignancy and is incurable due to the inevitable development of drug resistance. Intense protein synthesis is a distinctive trait of MM cells, supporting the massive production of clonal immunoglobulins or free light chains. The mammalian target of rapamycin (mTOR) kinase is appreciated as a master regulator of vital cellular processes, including regulation of metabolism and protein synthesis, and can be found in two multiprotein complexes, mTORC1 and mTORC2. Dysregulation of these complexes is implicated in several types of cancer, including MM. Since mTOR has been shown to be aberrantly activated in a large portion of MM patients and to play a role in stimulating MM cell survival and resistance to several existing therapies, understanding the regulation and functions of the mTOR complexes is vital for the development of more effective therapeutic strategies. This review provides a general overview of the mTOR pathway, discussing key discoveries and recent insights related to the structure and regulation of mTOR complexes. Additionally, we highlight findings on the mechanisms by which mTOR is involved in protein synthesis and delve into mTOR-mediated processes occurring in MM. Finally, we summarize the progress and current challenges of drugs targeting mTOR complexes in MM.
Impact of background music listening on anxiety in cancer patients undergoing initial radiation therapy: a randomized clinical trial
Authors: Yang Huei-Fan , Chang Wen-Wei , Chou Ying-Hsiang , Huang Jing-Yang , Liao Yu-Shiun , Liao Ting-En , Tseng Hsien-Chun , Chang Shih-Tsung , Chen Hsin Lin , Ke Ya-Fang , Tsai Pei-Fang , Chan Hsiu-Man , Chang Bo-Jiun , Hwang Yi-Ting , Tsai Hsueh-Ya , Lee Yueh-Chun
Published: June 2024

Background

Patients undergoing radiation therapy (RT) often experience anxiety, which may jeopardize the treatment success. The efficacy of music interventions in reducing anxiety remains contentious. This randomized trial aimed to evaluate the impact of music listening on anxiety symptoms in patients undergoing initial RT.

Methods

First-time RT patients were randomly allocated to experimental and control groups. The Brief Symptom Rating Scale (BSRS-5), Distress Thermometer (DT), and Beck Anxiety Inventory (BAI-C) were administered pre- and post-RT. Changes in physiological anxiety symptoms were monitored over 10 consecutive days starting from the first day of RT. The experimental group received music during RT; the control group did not. The generalized linear mixed model was used to estimate the pre–post difference in the BSRS-5, DT, and BAI-C scores between the music intervention and control group.

Results

This study included 50 patients each in the experimental and control groups. BSRS-5 and DT scores were significantly reduced in the experimental group post-RT (p = 0.0114 and p = 0.0023, respectively). When music listening was discontinued, these scores rebounded. While the posttest BAI-C score was significantly lower in the experimental group (p < 0.0001), the pre–post difference between the two groups was not significant (p = 0.0619). On cessation of music listening, the BAI-C score also rebounded.

Conclusions

For cancer patients undergoing initial RT, music listening intervention significantly reduced anxiety symptoms measured using the BSRS-5, DT, and BAI-C scores after two weeks. Our results demonstrate the effectiveness of music listening intervention in reducing anxiety symptoms, thereby potentially improving the quality of life of cancer patients undergoing RT.
Xinbao Pill ameliorates heart failure via regulating the SGLT1/AMPK/PPARα axis to improve myocardial fatty acid energy metabolism
Authors: Pan Linjie , Xu Zhanchi , Wen Min , Li Minghui , Lyu Dongxin , Xiao Haiming , Li Zhuoming , Xiao Junhui , Cheng Yuanyuan , Huang Heqing
Published: June 2024

Background

Heart failure (HF) is characterized by a disorder of cardiomyocyte energy metabolism. Xinbao Pill (XBW), a traditional Chinese medicine formulation integrating “Liushen Pill” and “Shenfu Decoction,” has been approved by China Food and Drug Administration for the treatment of HF for many years. The present study reveals a novel mechanism of XBW in HF through modulation of cardiac energy metabolism.

Methods

In vivo, XBW (60, 90, 120 mg/kg/d) and fenofibrate (100 mg/kg/d) were treated for six weeks in Sprague–Dawley rats that were stimulated by isoproterenol to induce HF. Cardiac function parameters were measured by echocardiography, and cardiac pathological changes were assessed using H&E, Masson, and WGA staining. In vitro, primary cultured neonatal rat cardiomyocytes (NRCMs) were induced by isoproterenol to investigate the effects of XBW on myocardial cell damage, mitochondrial function and fatty acid energy metabolism. The involvement of the SGLT1/AMPK/PPARα signalling axis was investigated.

Results

In both in vitro and in vivo models of ISO-induced HF, XBW significantly ameliorated cardiac hypertrophy cardiac fibrosis, and improved cardiac function. Significantly, XBW improved cardiac fatty acid metabolism and mitigated mitochondrial damage. Mechanistically, XBW effectively suppressed the expression of SGLT1 protein while upregulating the phosphorylation level of AMPK, ultimately facilitating the nuclear translocation of PPARα and enhancing its transcriptional activity. Knockdown of SGLT1 further enhanced cardiac energy metabolism by XBW, while overexpression of SGLT1 reversed the cardio-protective effect of XBW, highlighting that SGLT1 is probably a critical target of XBW in the regulation of cardiac fatty acid metabolism.

Conclusions

XBW improves cardiac fatty acid energy metabolism to alleviate HF via SGLT1/AMPK/PPARα signalling axis.
Effect of essential phospholipids on hepatic steatosis in metabolic dysfunction-associated steatotic liver disease associated with type 2 diabetes mellitus and/or hyperlipidemia and/or obesity: study protocol of a randomized, double-blind, phase IV clinical trial
Authors: Stefan Norbert , Hartleb Marek , Popovic Branko , Varona Rafael
Published: June 2024

Background

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a predominant chronic liver condition globally and is strongly associated with obesity, diabetes mellitus, and dyslipidemia. Essential phospholipids (EPL) are recommended as supportive treatment for managing liver conditions, including MASLD or metabolic dysfunction-associated steatohepatitis, cirrhosis, and viral hepatitis. While efficacy of EPL as an adjunctive therapy in MASLD treatment has been established earlier, certain aspects of its usage such as the impact of standard-of-care parameters, effect of EPL on quality of life (QoL) and change in symptoms evaluation in patients with MASLD remain unexplored. The proposed trial aims to assess the efficacy and safety of EPL and the subsequent QoL of patients with MASLD associated with type 2 diabetes mellitus (T2DM) and/or hyperlipidemia and/or obesity.

Methods

This is a multicenter, multinational, double-blind, randomized, two-arm, placebo-controlled, parallel-group, phase IV clinical trial. The trial is being conducted in approximately 190 patients who are randomized on a 1:1 basis either to the EPL arm (Essentiale® 1800 mg/day orally + standard of care) or placebo arm (placebo + standard of care). The primary outcome is to assess the efficacy of EPL on hepatic steatosis, as measured by transient elastography, from baseline to 6 months. The secondary outcomes include change in QoL parameters, as measured by the Chronic Liver Disease Questionnaire–metabolic dysfunction-associated steatotic liver disease/ metabolic dysfunction-associated steatohepatitis and change in symptom evaluation (using the Global Overall Symptom scale) from baseline to 6 months for symptoms, including asthenia, feeling depressed, abdominal pain/discomfort, or fatigue.

Discussion

The current protocol design will allow to comprehensively explore the efficacy of EPL added to the standard of care on hepatic steatosis and QoL and its safety in patients with MASLD associated with T2DM and/or hyperlipidemia and/or obesity by assessing various outcome measures.

Trial registration

European Union Clinical Trials Register, EudraCT, 2021–006069-39. Registered on March 13, 2022.
Interannual radial growth response of Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) to severe droughts: an analysis along a gradient of soil properties and rooting characteristics
Authors: Spangenberg Göran , Zimmermann Reiner , Küppers Manfred , Schäffer Jürgen , Hein Sebastian
Published: June 2024

Key message

We analyzed stem growth responses of Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) to severe drought in 2003/04 and 2018. The results showed high drought tolerance in sandy, loamy, and most silty soils, with limitations on clayey soils. This study indicates the susceptibility of Douglas-firs with shallow root systems to extreme drought and the importance of deep rooting for high drought resilience.

Context

Although Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) is considered a more drought-tolerant substitute for Norway spruce (Picea abies (L.) Karst.) in Europe, there is considerable uncertainty about the drought tolerance of Douglas-fir under climate change, specifically concerning soil properties.

Aims

This study aimed to assess the influence of soil texture, plant-available water capacity, and rooting characteristics on the interannual stem growth response of Douglas-fir when exposed to severe drought.

Methods

Along a soil texture gradient from sand to clay, we selected seven closely spaced sites at elevations of approximately 500 m a.s.l. in southern Germany. Mixed-effects models were used to analyze the effects of soil physical and rooting characteristics on growth response indices (resistance, recovery, resilience) related to the severe to extreme droughts in 2003/04 and 2018.

Results

Douglas-fir showed high drought tolerance in sandy, loamy, and most silty soils. However, the results suggest a higher drought stress risk on clayey soils, as well as at specific silty sites with shallow root systems. A higher effective rooting depth increased the resilience of Douglas-fir during the extreme drought in 2018.

Conclusion

Douglas-fir demonstrated its drought tolerance in most soil textures. In addition, this study supports the need for combined above- and below-ground investigations on factors influencing drought tolerance and the importance of rooting for drought resilience.
Subjective performance evaluation of bitrate allocation strategies for MPEG and JPEG Pleno point cloud compression
Authors: Lazzarotto Davi , Testolina Michela , Ebrahimi Touradj
Published: June 2024

The recent rise in interest in point clouds as an imaging modality has motivated standardization groups such as JPEG and MPEG to launch activities aiming at developing compression standards for point clouds. Lossy compression usually introduces visual artifacts that negatively impact the perceived quality of media, which can only be reliably measured through subjective visual quality assessment experiments. While MPEG standards have been subjectively evaluated in previous studies on multiple occasions, no work has yet assessed the performance of the recent JPEG Pleno standard in comparison to them. In this study, a comprehensive performance evaluation of JPEG and MPEG standards for point cloud compression is conducted. The impact of different configuration parameters on the performance of the codecs is first analyzed with the help of objective quality metrics. The results from this analysis are used to define three rate allocation strategies for each codec, which are employed to compress a set of point clouds at four target rates. The set of distorted point clouds is then subjectively evaluated following two subjective quality assessment protocols. Finally, the obtained results are used to compare the performance of these compression standards and draw insights about best coding practices.
Whole-tumoral metabolic heterogeneity in 18F-FDG PET/CT is a novel prognostic marker for neuroblastoma
Authors: Liu Jun , Ren Qinghua , Xiao Haonan , Li Siqi , Zheng Lingling , Yang Xu , Feng Lijuan , Zhou Ziang , Wang Huanmin , Yang Jigang , Wang Wei
Published: June 2024

Background

Neuroblastoma (NB) is a highly heterogeneous tumor, and more than half of newly diagnosed NB are associated with extensive metastases. Accurately characterizing the heterogeneity of whole-body tumor lesions remains clinical challenge. This study aims to quantify whole-tumoral metabolic heterogeneity (WMH) derived from whole-body tumor lesions, and investigate the prognostic value of WMH in NB.

Methods

We retrospectively enrolled 95 newly diagnosed pediatric NB patients in our department. Traditional semi-quantitative PET/CT parameters including the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean), the peak standardized uptake value (SUVpeak), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured. These PET/CT parameters were expressed as PSUVmax, PSUVmean, PSUVpeak, PMTV, PTLG for primary tumor, WSUVmax, WSUVmean, WSUVpeak, WMTV, WTLG for whole-body tumor lesions. The metabolic heterogeneity was quantified using the areas under the curve of the cumulative SUV-volume histogram index (AUC-CSH index). Intra-tumoral metabolic heterogeneity (IMH) and WMH were extracted from primary tumor and whole-body tumor lesions, respectively. The outcome endpoints were overall survival (OS) and progression-free survival (PFS). Survival analysis was performed utilizing the univariate and multivariate Cox proportional hazards regression. The optimal cut-off values for metabolic parameters were obtained by receiver operating characteristic curve (ROC).

Results

During follow up, 27 (28.4%) patients died, 21 (22.1%) patients relapsed and 47 (49.5%) patients remained progression-free survival, with a median follow-up of 35.0 months. In survival analysis, WMTV and WTLG were independent indicators of PFS, and WMH was an independent risk factor of PFS and OS. However, IMH only showed association with PFS and OS. In addition to metabolic parameters, the International Neuroblastoma Staging System (INSS) was identified as an independent risk factor for PFS, and neuron-specific enolase (NSE) served as an independent predictor of OS.

Conclusion

WMH was an independent risk factor for PFS and OS, suggesting its potential as a novel prognostic marker for newly diagnosed NB patients.
The role of sexual self-esteem, sexual desire, and sexual assertiveness in the female sexual function
Authors: Chesli Shokoufeh Roshan , Bostani Khalesi Zahra , Chenari Sara Shirzad
Published: June 2024

Background

Sexual function plays a very important role in the sexual health of people, and the determination of their related factors reflects the importance of paying attention to sexual function in the cultural context.

Objective

The present study aimed to the role of sexual self-esteem, sexual desire, and sexual assertiveness in the female sexual function.

Methods

In this descriptive-analytical cross-sectional study, 592 married women of reproductive age referring to comprehensive health centers in Rasht city (North of Iran) and eligible for the inclusion criteria were selected by cluster random sampling. The data collection tools were demographic information form, Halbert’s Sexual Rights Questionnaires, Women’s Sexual Self-Esteem (short form), Halbert’s Sexual Desire, and Female Sexual Function Index. Data analysis was done with descriptive and inferential statistical tests at a significant level (p < 0.05).

Results

The mean and standard deviation of sexual assertiveness, sexual desire, and sexual self-esteem scores were 56.79 ± 18.24, 49.12 ± 26.04, and 98.52 ± 6.11, respectively. Sexual assertiveness (p < 0.01, r = 0.13), sexual desire (p < 0.001, r = 0.178), sexual self-esteem (p < 0.01, r = 0.34) of the participants with the total score, and all areas of female sexual function had a significant positive correlation.

Conclusion

Based on the findings, there is a direct and statistically significant relationship between sexual assertiveness, sexual desire, the adaptability of sexual self-esteem, and family income with sexual function in participants. However, the unemployment of the spouse had a negative effect on the female sexual function.
A post-hoc analysis of outcomes of patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) who received oral azacitidine (Oral-AZA) maintenance therapy in the QUAZAR AML-001 study.
Authors: Voso Maria Teresa , De Botton Stéphane , Pfeilstöcker Michael , Figuera Alvarez Angela , Wang Kefeng , L. See Wendy , Ugidos Guerrero Manuel , Lopes de Menezes Daniel , Petrlik Erica , Prebet Thomas , Roboz Gail J.
Published: June 2024

6522

Background: AML-MRC represents 25%–34% of all AML cases, and patients with this AML subtype generally have poor outcomes. In this subanalysis of the QUAZAR AML-001study, we report outcomes of patients with AML-MRC who received Oral-AZA vs placebo (PBO). Methods: QUAZAR AML-001 was a phase 3 study of Oral-AZA maintenance therapy in patients with AML in first remission after intensive chemotherapy who were not eligible for hematopoietic stem cell transplantation (HSCT). Patients ≥ 55 years of age with AML and intermediate- or poor-risk cytogenetics received Oral-AZA 300 mg or PBO QD for 14 d per 28-d cycles. In this analysis, WHO 2008 criteria were used to identify patients with secondary AML and/or patients with AML-MRC (both groups are referred to as AML-MRC in this analysis). Data on mutational profiles at diagnosis were not available. Overall survival (OS) from time of randomization to time of death from any cause after censoring for HSCT, and relapse-free survival (RFS) from time of randomization, were calculated using the Kaplan–Meier method. Duration of measurable residual disease (MRD) negativity achieved on treatment was calculated from the first MRD-negative assessment. Results: Overall, 101/472 patients had AML-MRC; 56/238 (23.5%) patients in the Oral-AZA arm and 45/234 (19.2%) patients in the PBO arm. Karyotype/cytogenetics data at diagnosis were available for 87/101 (86.1%) patients with AML-MRC and 331/371 (89.2%) patients with non-AML-MRC. A greater proportion of AML-MRC than non-AML-MRC patients had poor-risk cytogenetics (20/101 [19.8%] vs 46/371 [12.4%]), del(5q) (10/87 [11.5%] vs 9/331 [2.7%]), and monosomy 7/del(7q) (9/87 [10.3%] vs 14/331 [4.2%]). Median OS did not significantly differ in patients with AML-MRC vs non-AML-MRC in either treatment arm (Oral-AZA: 19.9 mo vs 25.1 mo, P = 0.2694; PBO: 14.8 mo vs 14.9 mo, P = 0.2099). In both treatment arms, the median RFS was inferior for patients with AML-MRC vs non-AML-MRC (Oral-AZA 7.5 mo vs 10.5 mo, P = 0.0430; PBO: 3.7 mo vs 4.9 mo, P = 0.0109). Oral-AZA significantly prolonged median OS and RFS, and the duration of MRD negativity for patients with AML-MRC compared with PBO (Table). Conclusions: Oral-AZA significantly improved OS and RFS compared with PBO for patients with AML-MRC indicating that Oral-AZA maintenance is an effective treatment option for these patients with particularly poor prognosis. Clinical trial information: NCT01757535 . [Table: see text]
Evaluation of the toxicity and outcomes of the combination of midostaurin and CLAG-M in patients with FLT3-mutated acute myeloid leukemia (AML): A multi-center retrospective analysis.
Authors: Chen Ashley Wen , Baek Grace Tonghwa , Palmer Shannon , Rasmussen Jack , Bubalo Joseph S. , Namburi Swathi , Schwarz Tenley , Tsomo Tenzin , Cohen Jonathan , Russell Kathryn , Shaw Carole , Othus Megan , Halpern Anna B.
Published: June 2024

6523

Background: FLT3-mutated AML is associated with poor outcomes. Addition of midostaurin (multi-targeted kinase inhibitor) to standard “7+3” with cytarabine and daunorubicin significantly prolongs overall and event-free survival for these patients (Stone 2017). At the University of Washington/Fred Hutchinson Cancer Center (UW/FHCC), the standard regimen for newly diagnosed (ND) and relapsed/refractory (r/r) AML is cladribine, high-dose cytarabine, GCSF, and mitoxantrone (CLAG-M); midostaurin is added if FLT3-mutated (Halpern 2018). There is currently no peer-reviewed literature to support this combination for these patients. The purpose of this study is to evaluate the safety and efficacy of the combination of midostaurin with CLAG-M in FLT3-mutated AML patients and compare the toxicity profile to midostaurin plus 7+3. Methods: This is a retrospective multi-center review conducted at three major cancer centers. Through pharmacy records and/or an institutional AML database, we identified adults with FLT3-mutated AML undergoing (re)induction chemotherapy who received either CLAG-M (UW/FHCC, Swedish) or 7+3 (OHSU, Swedish). The primary outcome was toxicity profile of the combination as measured by rate of adverse events ([AE], CTCAE Version 5.0). Secondary outcomes included disease response per ELN2017 AML working group criteria and 28-day mortality (TRM) (Döhner 2017). Patients treated on a clinical trial and in whom midostaurin was started > 30 days after day 1 of chemotherapy were excluded. Rates of AEs were compared using Fisher’s exact test. Results: Eighty patients treated between 10/2022-12/2023 were included; 35 patients received CLAG-M, and 44 patients 7+3. Baseline characteristics were similar across all institutions, with most patients having adverse or intermediate risk disease. AE rates were similar between the two cohorts, (Table 1) except diarrhea and bleeding events were more common in the 7+3 vs. CLAG-M cohort (p = 0.004 and p = 0.037, respectively). The rate of complete remission (CR) plus CR with incomplete blood count recovery (CRi) did not significantly differ between the two cohorts: CLAG-M, 86% versus 7+3, 70% for 7+3 (p =0.11). No TRM occurred. Conclusions: The toxicity profile of CLAG-M combined with midostaurin is comparable to the combination of 7+3 with midostaurin, and induces high remissions rates in adults with FLT3-mutated AML. [Table: see text]
Trajectories of patient-reported outcomes after prolonged stays for hematopoietic cell transplant.
Authors: Gao Lucy , DeFilipp Zachariah Michael , Chen Yi-Bin Albert , Lee Stephanie , LeBlanc Thomas William , Amonoo Hermioni L. , El-Jawahri Areej , Newcomb Richard
Published: June 2024

6553

Background: Patients hospitalized for hematopoietic cell transplantation (HCT) may have prolonged length of stay (PLOS). The longitudinal effect of PLOS in this population on quality of life (QOL) and psychological distress is unknown. Methods: We conducted secondary analyses of data from three prospective studies of patients undergoing HCT (2011-2022) at three academic centers. We defined PLOS as ≥30 days for allogeneic and ≥21 days for autologous HCT from date of admission. We collected patient-reported outcomes (PROs) for QOL, anxiety, depression, and posttraumatic stress disorder (PTSD) symptoms at baseline, 2 weeks, 3 and 6 months post-HCT. We used multivariate logistic regression to assess the effect of change in PROs from baseline to week 2 on PLOS adjusting for age, transplant type, donor, and diagnosis. We then fit linear mixed effects models to characterize the trajectory of PROs by PLOS over time. Results: 593 patients (mean age 56 years) were included, the majority of whom were male (57%), white (82%), and underwent allogeneic HCT (52%). The most common diagnosis was acute leukemia (28%). Patients with PLOS (26%) were younger (57 [range 18-78 yrs], 53 [19-75 yrs], p = 0.002), had acute leukemia (26%, 34%, p = 0.001), received myeloablative conditioning (21%, 41%, p < 0.001), and underwent allogeneic HCT (50%, 60%, p < 0.001). At baseline, patients with PLOS had lower QOL (108, 102, p = 0.001) and more depression symptoms (4.4, 5.3, p = 0.02). There was no difference in baseline anxiety or PTSD symptoms. An increase in depression symptoms from baseline to week 2 was associated with greater odds of PLOS (adjusted OR = 1.08, p = 0.04). The table depicts longitudinal differences in PROs by PLOS. Compared to those without PLOS, patients with PLOS reported lower QOL (time*PLOS interaction, ∆ = -6.6, SE = 2.1, p = 0.001) and greater increase in depression symptoms (time*PLOS interaction, ∆ = 1.9, SE = 0.6, p < 0.001) at week 2. Lower QOL in those with PLOS persisted through 6 months (Table). PLOS was associated with more re-admissions (0.8, 1.1, p = 0.02) and mortality (9%, 19%, p = 0.001) within 1 year of HCT. No difference was seen in rate of relapse and severe acute or chronic graft- versus-host disease. Conclusions: Patients with PLOS experienced worse QOL and increased psychological distress. Increase in depression symptoms from admission to week 2 may be an early indicator of PLOS and supports mental health screening during the index HCT hospitalization. Patients with PLOS may benefit from enhanced supportive care during and after HCT.[Table: see text]
Comparison of the efficacy of immunotherapy at different time points during the perioperative period for stage II-III NSCLC.
Authors: Zhang Yajuan , Jia Xiaohui , Liu Mengjie , Ni Yunfeng , Dang Chengxue , Liu Jia , Mao Ziyang , Li Yanlin , Fu Xiaolan , Guo Hui
Published: June 2024

e20009

Background: The application of immune checkpoint inhibitors (ICIs) in early-stage lung cancer is fraught with unresolved issues, and there are no clinical studies directly comparing the efficacy of ICIs used in neoadjuvant, adjuvant, and neoadjuvant followed by adjuvant therapy across different perioperative time points in non-small cell lung cancer (NSCLC). Consequently, the optimal timing for immunotherapy in surgically resectable NSCLC remains uncertain. Methods: This study encompassed 536 patients with stage II-III NSCLC, diagnosed and treated across multiple centers from January 2019 to December 2022. Clinical data for all patients ultimately included in the study were retrospectively collected. The primary endpoints evaluated were event-free survival (EFS)/disease-free survival (DFS) and overall survival (OS) . Secondary endpoints included pathological complete response (pCR) and major pathological response (MPR). Propensity score matching was utilized to mitigate confounding factors, comparing the efficacy of ICIs across different treatment modalities and time dimensions during the perioperative period of lung cancer. Results: The integration of neoadjuvant ICIs with chemotherapy was observed to significantly enhance pCR ( p < 0.001), MPR ( p < 0.001), EFS ( p = 0.002), and OS ( p < 0.001) in comparison to neoadjuvant chemotherapy alone. Similarly, the combination of adjuvant ICIs with chemotherapy markedly improved DFS ( p = 0.034) and OS ( p = 0.021) relative to adjuvant chemotherapy alone. Building on these insights, we further delineated the efficacy of ICIs across distinct temporal dimensions within the perioperative interval, categorizing patients into three groups: neoadjuvant ICIs plus chemotherapy, adjuvant ICIs plus chemotherapy, and a sequential regimen of neoadjuvant followed by adjuvant ICIs plus chemotherapy. The analysis revealed no significant differences in DFS and OS among the three patient groups for stage II NSCLC. In contrast, for stage III NSCLC, both neoadjuvant ( p = 0.015) and sequential treatment approaches ( p = 0.047) demonstrated significantly improved DFS outcomes compared to the adjuvant protocol, with no substantial statistical difference noted between the neoadjuvant and sequential treatments ( p = 0.274). Furthermore, the sequential regimen outperformed the adjuvant strategy in OS ( p = 0.020). However, when comparing the neoadjuvant strategy with either the adjuvant ( p = 0.054) or sequential approaches ( p = 0.717), there were no statistically significant variances detected. Conclusions: For individuals with resectable stage III NSCLC, perioperative administration of neoadjuvant and sequential adjuvant ICIs appears to confer enhanced survival advantages. Future efforts should focus on refining treatment strategies for early-stage NSCLC, aiming to deliver enhanced survival benefits to patients.
Single-cell landscape of the immune microenvironment of leptomeningeal metastases in non-small cell lung cancer treated with pemetrexed sheath injection.
Authors: Xu Yiquan
Published: June 2024

e20026

Background: The incidence of leptomeningeal metastasis (LM) is increasing in non-small cell lung cancer (NSCLC) and pemetrexed injection is an important treatment for LM. Here, we used single-cell RNA sequencing (scRNA-seq) to define the immune landscape of LM in NSCLC treated with pemetrexed sheath injection. Methods: scRNA-seq was utilized on 27 cerebrospinal fluid (CSF) samples from 20 patients, including 7 pairs of pre- and post-treatment samples. Detailed immune landscapes were mapped, and key results were confirmed by flow cytometry and IHC. Biomarkers for the efficacy of pemetrexed sheath injection was analyzed. Results: The LM microenvironment was characterized by macrophages and cancer cells with decreased significantly after pemetrexed injection. The cancer cells in LM was highly expressed CEACAM6, SFTPB and NAPSA, and chemokines liked CXCL16 in macrophages decreased significantly after receiving pemetrexed sheath treatment than pre- treatment, which was validated by flow cytometry and IHC. In the signal pathway enrichment analysis, significant changes of metabolism and cell cycle genes occurred before and after pemetrexed injection. Moreover, the analysis of tumor cells and immune cells interaction showed that CSF1-CSF1R, AREG/HBEGF-EGFR, FD1-Intergrin_a2B1_complex, CCL5-CCR1, CD55_ADGRE play a key role in tumor cells recruiting monocytes and inhibiting macrophages. Gene set based on the efficacy of pemetrexed sheath injection was enriched, including C15orf48, CCL5, DUSP6, FLNA, TXNIP, TNNT1, was confirmed associating with increased overall survival. Conclusions: Our study characterizes the immune cell landscape of LM from NSCLC, and provided the biomarkers for the efficacy of pemetrexed injection.
Clinical and genomic characteristics of multiple primary lung cancers with germline mutations.
Authors: Yang Yingshun , Li Mingwei , Ma Xiaoxue , Wang Shuai , Pei Guotian , Qin Jiayue , Liu Jun , Huang Yuqing
Published: June 2024

e20054

Background: The number of multiple primary lung cancer (MPLC) patients has rapidly increased in recent years. However, germline mutations and information regarding the etiology of MPLC is very rare. In this study, we sought to determine the prevalence and clinical significance of germline pathogenic/likely pathogenic (P/LP) variants in patients with MPLC. Methods: A total of 111 MPLC patients undergoing radical surgery were enrolled in this study and 625 patients with single-focus lung cancer (SFLC) were analyzed as a control. Tumor and blood lymphocyte DNA from patients were sequenced using next-generation sequencing (NGS) platform interrogating up to 808 cancer-associated genes. Interpretation of sequence variations was classified according to the American College of Medical Genetics and Genomics guidelines. Results: A total of 15 germline P/LP mutations in 12.6% (14/111) of MPLC patients were observed, including one patient with 2 germline alterations; of these, 9 patients (64.3%) had germline mutations in DNA-damage repair (DDR) pathway genes in which the most commonly genes were WRN (14.3%, 2/14) and BRCA1/2 (14.3%, 2/14), followed by RAD50 and MSH3. Similarly, 68 germline mutations were identified in 67 (10.7%)SFLCs, and 54 (79.4%) mutation genes were DDR genes including RAD50 (10.4%, 7/67) showed the highest frequency. The somatic mutations of EGFR (59.5% vs. 48.5%) were enriched in P/LP alterations carriers, while TP53 (12.4% vs. 4.8%) was more common in MPLC patients without P/LP alterations. Besides, lower BRAF and MET mutation frequency were observed in SPLC with germline alterations (p < 0.05), compared to those who did not. MPLC were more likely to be patients with family history of cancers (32.4% vs. 25.0%, p = 0.099) than SFLC, while the proportion of patients with family history of cancers found no significant difference between P/LP and non-P/LP groups. MPLC patients with germline P/LP variances were diagnosed at younger age ( < 40 years old) compared to non-carriers. For MPLC, the ratio of males is not associated with P/LP variations. However, significantly higher proportion of germline P/LP mutations was detected in males in SFLC (61.2% vs. 48.4%, p = 0.048). Patients with a history of smoking were significantly less enriched in MPLC (p = 0.030) compared to SPLC but were independent of whether harbored germline mutations. Conclusions: Taken together, ur results show that in the first large Chinese cohort of MPLC, 12.6% of patients carry germline variants. In addition, a more detailed analysis of the spectrum of germline mutations and clinical characteristics of MPLC may provide clues for the oncology treatment strategy and cancer prevention for MPLC.