bluuebunny/crossref_metadata_2025_split huggingface dataset:
A qualitative study on patients’ and their support persons’ preferences for receiving one longer consultation or two shorter consultations when being informed about allogeneic hematopoietic stem cell transplantation
Authors: Herrmann Anne , Holler Ernst , Edinger Matthias , Eickmann Sascha , Wolff Daniel 
Published: June 2021

Abstract
Background
Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only potentially curative treatment option for many patients with hematological disorders but it includes a significant risk of mortality and long-term morbidity. Many patients and their support persons feel overwhelmed when being informed about alloHSCT and may benefit from improvements in consultation style and timing.

Aims
To explore, qualitatively, in a sample of hematological cancer patients and their support persons, their preferences for receiving one longer consultation or two shorter consultations when being informed about alloHSCT. Participants’ perceptions of when and how different consultation styles should be offered were also examined.

Methods
Semi-structured face-to-face and phone interviews were conducted. A purposeful sampling frame was used. Data were analysed using framework analysis.

Results
Twenty patients and 13 support persons were recruited (consent rate: 96%, response rate: 91%). Most patients (60%) and support persons (62%) preferred two shorter consultations over one longer consultation. This helped them digest and recall the information provided, remember questions they had, involve significant others and search for additional information. Patients would have liked to be offered paper and pen to take notes, take a break after 30 min and have their understanding checked at the end of the first consultation, e.g. using question prompt lists. Some patients and support persons preferred both consultations to happen on the same day to reduce waiting times as well as travel times and costs. Others preferred having a few days in-between both consultations to better help them prepare the second consultation. Participants reported varying preferences for different consultation styles depending on personal and disease-related characteristics, such as age, health literacy level and previous treatment.

Conclusion
To our knowledge, this is the first qualitative study to explore patients’ and their support persons’ preferences for having one longer consultation or two shorter consultations when being informed about alloHSCT. Receiving two shorter consultations may help patients process and recall the information provided and more actively involve their support persons. Clinicians should consider offering patients and their support persons to take a break after 30 min, provide paper and pen as well as question prompt lists.
Challenges in delivery of tuberculosis Services in Ethiopian Pastoralist Settings: clues for reforming service models and organizational structures
Authors: Getnet Fentabil , Demissie Meaza , Worku Alemayehu , Gobena Tesfaye , Tschopp Rea , Farah Alinoor Mohamed , Seyoum Berhanu 
Published: June 2021

Abstract
Background
The End-TB strategy aims to see a world free of tuberculosis (TB) by the coming decade through detecting and treating all cases irrespective of socioeconomic inequalities. However, case detections and treatment outcomes have not been as they should be in Somali pastoral settings of Ethiopia. Hence, this study aimed to explore the challenges that hinder the delivery and utilization of TB services in pastoral areas.

Methods
A qualitative study was conducted between December 2017 and October 2018 among pastoralist patients with delay of ≥2 months in seeking healthcare, healthcare providers and programme managers. Data were collected from different sources using 41 in-depth interviews, observations of facilities and a review meeting of providers from 50 health facilities. The data were transcribed, coded and analyzed to identify pre-defined and emerging sub-themes. ATLAS.ti version 7.0 was used for coding data, categorizing codes, and visualizing networks.

Results
Poor knowledge of TB and its services, limited accessibility (unreachability, unavailability and unacceptability), pastoralism, and initial healthcare-seeking at informal drug vendors that provide improper medications were the key barriers hindering the uptake of TB medical services. Inadequate infrastructure, shortage of trained and enthused providers, interruptions of drugs and laboratory supplies, scarce equipment, programme management gaps, lack of tailored approach, low private engagement, and cross-border movement were the major challenges affecting the provision of TB services for pastoral communities. The root factors were limited potential healthcare coverage, lack of zonal and district TB units, mobility and drought, strategy and funding gaps, and poor development infrastructure.

Conclusion
In pastoral settings of Ethiopia, the major challenges of TB services are limited access, illicit medication practices, inadequate resources, structural deficits, and lack of tailored approaches. Hence, for the pastoral TB control to be successful, mobile screening and treatment modalities and engaging rural drug vendors will be instrumental in enhancing case findings and treatment compliance; whereas, service expansion and management decentralization will be essential to create responsive structures for overcoming challenges.
Professionals’ views on working in the field of domestic violence and abuse during the first wave of COVID-19: a qualitative study in the Netherlands
Authors: van Gelder Nicole E. , van Haalen Ditte L. , Ekker Kyra , Ligthart Suzanne A. , Oertelt-Prigione Sabine 
Published: June 2021

AbstractBackgroundThe COVID-19 pandemic and lockdown evoked great worries among professionals in the field of domestic violence and abuse (DVA) as they expected a rise of the phenomenon. While many countries reported increased DVA, the Netherlands did not. To understand this discrepancy and the overall impact of the lockdown on DVA support services, we interviewed DVA professionals about their experiences with DVA during the rise of COVID-19, the impact of the lockdown on clients and working conditions, and views on eHealth and online tools.MethodsSemi-structured interviews were conducted among 16 DVA professionals with various specializations. This data was analyzed using open thematic coding and content analysis.ResultsMost professionals did not see an increase in DVA reports but they did notice more severe violence. They experienced less opportunities to detect DVA and worried about their clients’ wellbeing and the quality of (online) care. Furthermore, their working conditions rapidly changed, with working from home and online, and they expressed frustration, insecurity and loneliness. Professionals feel eHealth and online tools are not always suitable but they do see them as an opportunity to increase reach and maintain services when physical contact is not possible.ConclusionThis study suggests DVA was probably under-detected during the lockdown rather than not having increased. The Dutch system heavily relies on professionals to detect and report DVA, suggesting a need for critical evaluation of the accessibility of professional help. Professionals experienced significant challenges and should themselves be supported psychologically and in their changed work practices to maintain their ability to aid survivors.
Novel homozygous mutations in Pakistani families with Charcot–Marie–Tooth disease
Authors: Kanwal Sumaira , Choi Yu JIn , Lim Si On , Choi Hee Ji , Park Jin Hee , Nuzhat Rana , khan Aneela , Perveen Shazia , Choi Byung-Ok , Chung Ki Wha 
Published: June 2021

Abstract
Background
Charcot–Marie–Tooth disease (CMT) is a group of genetically and clinically heterogeneous peripheral nervous system disorders. Few studies have identified genetic causes of CMT in the Pakistani patients.

Methods
This study was performed to identify pathogenic mutations in five consanguineous Pakistani CMT families negative for PMP22 duplication. Genomic screening was performed by application of whole exome sequencing.

Results
We identified five pathogenic or likely pathogenic homozygous mutations in four genes: c.2599C > T (p.Gln867*) and c.3650G > A (p.Gly1217Asp) in SH3TC2, c.19C > T (p.Arg7*) in HK1, c.247delG (p.Gly83Alafs*44) in REEP1, and c.334G > A (p.Val112Met) in MFN2. These mutations have not been reported in CMT patients. Mutations in SH3TC2, HK1, REEP1, and MFN2 have been reported to be associated with CMT4C, CMT4G, dHMN5B (DSMA5B), and CMT2A, respectively. The genotype–phenotype correlations were confirmed in all the examined families. We also confirmed that both alleles from the homozygous variants originated from a single ancestor using homozygosity mapping.

Conclusions
This study found five novel mutations as the underlying causes of CMT. Pathogenic mutations in SH3TC2, HK1, and REEP1 have been reported rarely in other populations, suggesting ethnic-specific distribution. This study would be useful for the exact molecular diagnosis and treatment of CMT in Pakistani patients.
Immune signature-based hepatocellular carcinoma subtypes may provide novel insights into therapy and prognosis predictions
Authors: Zheng Qiuxian , Yang Qin , Zhou Jiaming , Gu Xinyu , Zhou Haibo , Dong Xuejun , Zhu Haihong , Chen Zhi 
Published: June 2021

Abstract
Background
Hepatocellular carcinoma (HCC) has a poor prognosis and has become the sixth most common malignancy worldwide due to its high incidence. Advanced approaches to therapy, including immunotherapeutic strategies, have played crucial roles in decreasing recurrence rates and improving clinical outcomes. The HCC microenvironment is important for both tumour carcinogenesis and immunogenicity, but a classification system based on immune signatures has not yet been comprehensively described.

Methods
HCC datasets from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and the International Cancer Genome Consortium (ICGC) were used in this study. Gene set enrichment analysis (GSEA) and the ConsensusClusterPlus algorithm were used for clustering assessments. We scored immune cell infiltration and used linear discriminant analysis (LDA) to improve HCC classification accuracy. Pearson's correlation analyses were performed to assess relationships between immune signature indices and immunotherapies. In addition, weighted gene co-expression network analysis (WGCNA) was applied to identify candidate modules closely associated with immune signature indices.

Results
Based on 152 immune signatures from HCC samples, we identified four distinct immune subtypes (IS1, IS2, IS3, and IS4). Subtypes IS1 and IS4 had more favourable prognoses than subtypes IS2 and IS3. These four subtypes also had different immune system characteristics. The IS1 subtype had the highest scores for IFNγ, cytolysis, angiogenesis, and immune cell infiltration among all subtypes. We also identified 11 potential genes, namely, TSPAN15, TSPO, METTL9, CD276, TP53I11, SPINT1, TSPO, TRABD2B, WARS2, C9ORF116, and LBH, that may represent potential immunological biomarkers for HCC. Furthermore, real-time PCR revealed that SPINT1, CD276, TSPO, TSPAN15, METTL9, and WARS2 expression was increased in HCC cells.

Conclusions
The present gene-based immune signature classification and indexing may provide novel perspectives for both HCC immunotherapy management and prognosis prediction.
An immune-related pseudogene signature to improve prognosis prediction of endometrial carcinoma patients
Authors: Tang Shanshan , Zhuge Yiyi 
Published: June 2021

AbstractBackgroundPseudogenes show multiple functions in various cancer types, and immunotherapy is a promising cancer treatment. Therefore, this study aims to identify immune-related pseudogene signature in endometrial cancer (EC).MethodsGene transcriptome data of EC tissues and corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA) through UCSC Xena browser. Spearman correlation analysis was performed to identify immune-related pseudogenes (IRPs) between the immune genes and pseudogenes. Univariate Cox regression, LASSO, and multivariate were performed to develop a risk score signature to investigate the different overall survival (OS) between high- and low-risk groups. The prognostic significance of the signature was assessed by the Kaplan–Meier curve, time-dependent receiver operating characteristic (ROC) curve. The abundance of 22 immune cell subtypes of EC patients was evaluated using CIBERSORT.ResultsNine IRPs were used to build a prognostic signature. Survival analysis revealed that patients in the low-risk group presented longer OS than those in the high-risk group as well as in multiple subgroups. The signature risk score was independent of other clinical covariates and was associated with several clinicopathological variables. The prognostic signature reflected infiltration by multiple types of immune cells and revealed the immunotherapy response of patients with anti-programmed death-1 (PD-1) and anti-programmed cell death 1 ligand 1 (PD-L1) therapy. Function enrichment analysis revealed that the nine IRPs were mainly involved in multiple cancer-related pathways.ConclusionWe identified an immune-related pseudogene signature that was strongly correlated with the prognosis and immune response to EC. The signature might have important implications for improving the clinical survival of EC patients and provide new strategies for cancer treatment.
Celastrol inhibits the proliferation and angiogenesis of high glucose-induced human retinal endothelial cells
Authors: Fang Jian , Chang Xiaoke 
Published: June 2021

Abstract
Background
Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes. Celastrol plays a certain role in the improvement of various diabetes complications. Therefore, this study aimed to explore whether celastrol inhibited the proliferation and angiogenesis of high glucose (HG)-induced human retinal endothelial cells (hRECs) by down-regulating the HIF1/VEGF signaling pathway.

Methods
The viability and proliferation of hRECs treated with glucose, celastrol or dimethyloxallyl glycine (DMOG) were analyzed by MTT assay. The invasion and tube formation ability of hRECs treated with glucose, celastrol or DMOG were in turn detected by transwell assay and tube formation assay. The expression of HIF1α and VEGF in hRECs after indicated treatment was analyzed by Western blot analysis and RT-qPCR analysis and ICAM-1 expression in hRECs after indicated treatment was detected by immunofluorescence assay

Results
HG induction promoted the proliferation, invasion and tube formation ability and increased the expression of HIF-1α and VEGF of hRECs, which were gradually suppressed by celastrol changing from 0.5 to 2.0 μM. DMOG was regarded as a HIF1α agonist, which attenuated the effect of celastrol on HG-induced hRECs.

Conclusion
Celastrol inhibited the proliferation and angiogenesis of HG-induced hRECs by down-regulating the HIF1α/VEGF signaling pathway.
Mixture effects of prenatal exposure to per- and polyfluoroalkyl substances and polybrominated diphenyl ethers on maternal and newborn telomere length
Authors: Eick Stephanie M. , Goin Dana E. , Cushing Lara , DeMicco Erin , Park June-Soo , Wang Yunzhu , Smith Sabrina , Padula Amy M. , Woodruff Tracey J. , Morello-Frosch Rachel 
Published: June 2021

Abstract
Background
Per- and polyfluoroalkyl substances (PFAS) and polybrominated diphenyl ethers (PBDEs) are endocrine disrupting chemicals with widespread exposures across the U.S. given their abundance in consumer products. PFAS and PBDEs are associated with reproductive toxicity and adverse health outcomes, including certain cancers. PFAS and PBDEs may affect health through alternations in telomere length. In this study, we examined joint associations between prenatal exposure to PFAS, PBDEs, and maternal and newborn telomere length using mixture analyses, to characterize effects of cumulative environmental chemical exposures.

Methods
Study participants were enrolled in the Chemicals in Our Bodies (CIOB) study, a demographically diverse cohort of pregnant people and children in San Francisco, CA. Seven PFAS (ng/mL) and four PBDEs (ng/g lipid) were measured in second trimester maternal serum samples. Telomere length (T/S ratio) was measured in delivery cord blood of 292 newborns and 110 second trimester maternal whole blood samples. Quantile g-computation was used to assess the joint associations between groups of PFAS and PBDEs and newborn and maternal telomere length. Groups considered were: (1) all PFAS and PBDEs combined, (2) PFAS, and (3) PBDEs. Maternal and newborn telomere length were modeled as separate outcomes.

Results
T/S ratios in newborn cord and maternal whole blood were moderately correlated (Spearman ρ = 0.31). In mixtures analyses, a simultaneous one quartile increase in all PFAS and PBDEs was associated with a small increase in newborn (mean change per quartile increase = 0.03, 95% confidence interval [CI] = -0.03, 0.08) and maternal telomere length (mean change per quartile increase = 0.03 (95% CI = -0.03, 0.09). When restricted to maternal–fetal paired samples (N = 76), increasing all PFAS and PBDEs combined was associated with a strong, positive increase in newborn telomere length (mean change per quartile increase = 0.16, 95% CI = 0.03, 0.28). These associations were primarily driven by PFAS (mean change per quartile increase = 0.11 [95% CI = 0.01, 0.22]). No associations were observed with maternal telomere length among paired samples.

Conclusions
Our findings suggest that PFAS and PBDEs may be positively associated with newborn telomere length.
Transcultural adaptation and psychometric properties of Family Quality of Life Survey for caregivers of people with neurodegenerative disease: a study of Spanish families who live in the rural Spain–Portugal cross-border
Authors: Badia Marta , Orgaz M. Begoña , Vicario-Molina Isabel , González-Ortega Eva , Gómez-Vela María , Aza Alba , Martín-Delgado M. Antonia 
Published: June 2021

AbstractBackgroundNeurodegenerative diseases (NDs) are one of the main causes of disability and dependence that have a great impact both on the quality of life of people with disabilities and their families. A majority of people with NDs receive care and support from the family, but there is no tool in Spain with which to measure whole-family QOL. The aim of this study was the translation, cultural adaptation, and validation of theFQOLS–Dementiainto Spanish to assess FQOL among family members of individuals with NDs who live in the Spain–Portugal cross-border area.MethodThe Spanish version was translated and adapted following the international guidelines for cross-cultural adaptation tests. A sample of 300 family caregivers was interviewed, applying an adapted version of theFamily Quality Survey(FQOLS–Dementia). Confirmatory factor analysis was performed to validate the factor structure, and convergent validity was examined with Pearson’s correlation coefficients of the global FQOL with the domains. Internal consistency reliability was determined using Cronbach’s alpha.ResultsThe domain structure of theFQOLS–NDshowed a good fit. In the convergent validity, it was found that the total score and the subscale domain scores were associated with the global FQOL score, except for theValuesdomain. Internal consistency of nine domain subscales was strong (α = 0.80 to 0.91), and excellent for the total FQOL (α = 0.85) and the global FQOL (α = 0.87).ConclusionTheFQOLS–NDpresented good validity and reliability in caregiver families with individuals with ND, so its application shows its usefulness in detecting areas of improvement and intervention strategies for FQOL in the Spain–Portugal cross-border area.
Clinicopathological features of desmoplastic small round cell tumors: clinical series and literature review
Authors: Wang Ling-Ling , Ji Zhong-He , Gao Ying , Chang Hong , Sun Ping-Ping , Li Yan 
Published: June 2021

Abstract
Background and purpose
Desmoplastic small round cell tumor (DSRCT) is a highly malignant sarcoma that occurs in the abdominopelvic cavities of adolescents. The accurate diagnosis of DSRCT is challenging owing to limited literatures. Our study aimed to investigate the relationship between clinicopathological features and prognosis in patients with DSRCTs.

Methods
Data of 8 patients with DSRCT originating from the abdominal cavity were retrospectively reviewed. The clinical manifestations, pathological characteristics, treatment approaches, and prognosis were analyzed. The histopathological (identified using hematoxylin-eosin staining), immunohistochemical, and molecular diagnostic (using fluorescence in situ hybridization) features were also reviewed.

Results
All patients were male aged between 24 and 45 years (median age, 30 years). The main clinical symptoms included abdominal distension, abdominal pain, and constipation. Seven of the 8 patients developed metastases to either distant organs or lymph nodes. Multiple gray nodules with diameters of 1–10 cm and poorly defined boundaries were scattered throughout the omentum and mesentery. Histopathological examination demonstrated well-defined nests composed of small round blue cells separated by markedly desmoplastic stroma. Immunohistochemical analysis revealed positive expressions of desmin, vimentin and C-terminal of Wilm’s tumor suppressor (WT-1). The Ewing sarcoma breakpoint region 1 gene fused with WT1 (EWSR1-WT1) gene fusion was detected in all patients. Cytoreductive surgery (CRS) was performed in 6 patients. Follow-up period ranged from 7.5 to 28.5 months with a median of 17.2 months. Three patients died during follow-up.

Conclusion
DSRCT is highly aggressive and presents distinctive morphological features. CRS is the essential therapy for DSRCT. A test for the combined expression of desmin, cytokeratins, and C-terminal of WT-1, as well as the analysis of morphologic features, might be helpful during DSRCT diagnosis, and the EWSR1-WT1 gene fusion is the gold standard for definitive diagnosis. Our work will provide new insights into the diagnosis and treatment of DSRCTs.
Src family kinases, adaptor proteins and the actin cytoskeleton in epithelial-to-mesenchymal transition
Authors: Ortiz Maria A. , Mikhailova Tatiana , Li Xiang , Porter Baylee A. , Bah Alaji , Kotula Leszek 
Published: June 2021

AbstractOver a century of scientific inquiry since the discovery of v-SRC but still no final judgement on SRC function. However, a significant body of work has defined Src family kinases as key players in tumor progression, invasion and metastasis in human cancer. With the ever-growing evidence supporting the role of epithelial-mesenchymal transition (EMT) in invasion and metastasis,
so does our understanding of the role SFKs play in mediating these processes. Here we describe some key mechanisms through which Src family kinases play critical role in epithelial homeostasis and how their function is essential for the propagation of invasive signals.