bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre- and intratherapeutic predictors of overall survival in patients with advanced metastasized castration-resistant prostate cancer receiving Lu-177-PSMA-617 radioligand therapy
Authors: Wrenger Robin , Jüptner Michael , Marx Marlies , Zhao Yi , Zuhayra Maaz , Caliebe Amke , Osmonov Daniar , Lützen Ulf 
Published: July 2022

Abstract
Background
Systemic Lutetium-177 prostate-specific membrane antigen-617 radioligand therapy (Lu-177-PSMA-617-RLT) is a novel treatment approach in patients suffering from metastasized castration-resistant prostate cancer. Nonetheless, a therapeutic response may fail to appear in a proportion of patients. This study aims to identify routinely obtainable pre- and intratherapeutic parameters to allow a prediction of overall survival in patients receiving Lu-177-PSMA-617 radioligand therapy.

Methods
Between January 2015 and December 2020 52 patients treated with a total of 146 cycles Lu-177-PSMA-617-RLT were retrospectively analysed in a single-center trial. The median overall survival time (OS) was compared to pre-therapeutic serological parameters, the extend of metastatic spread and previously performed therapies using Kaplan–Meier estimators and multivariate Cox-regression. Bonferroni-Holm correction was performed on all statistical tests.

Results
The median OS of all patients was 55.6 weeks. Multivariate Cox-regression revealed significant lower survival for decreased pretherapeutic hemoglobin levels (HR 0.698 per g/dl; 95%-CI 0.560–0.872; p = 0.001), increased lactate dehydrogenase (LDH) levels (HR 1.073 per 25 U/l; 95%-CI 1.024–1.125; p = 0.003) and the presence of hepatic metastasis (HR 6.981; 95%-CI 2.583–18.863; p < 0.001). Increased pretherapeutic c-reactive protein (CRP), alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) levels were also associated with a shorter survival. A prostate-specific antigen decline after one therapy cycle did not significantly correlate with an increased survival. No significant relations were observed between overall survival time and other serological parameters or previously performed therapies.

Conclusion
Pre-therapeutic hemoglobin and LDH levels, as well as the presence of hepatic metastasis are independent predictors of overall survival in patients receiving Lu-177-PSMA-617-RLT. CRP, ALP and GGT levels cloud be utilized as additional decision aids when a Lu-177-PSMA-617-RLT is intended.
Trial Registration Not applicable (retrospective observational study).
The association between body fat distribution and bone mineral density: evidence from the US population
Authors: Ma Ming , Liu Xiaolong , Jia Gengxin , Geng Bin , Xia Yayi 
Published: July 2022

Abstract
Objective
To investigate the association between different body fat distribution and different sites of BMD in male and female populations.

Methods
Use the National Health and Nutrition Examination Survey (NHANES) datasets to select participants. The weighted linear regression model investigated the difference in body fat and Bone Mineral Density (BMD) in different gender. Multivariate adjusted smoothing curve-fitting and multiple linear regression models were used to explore whether an association existed between body fat distribution and BMD. Last, a subgroup analysis was performed according to age and gender group.

Results
Overall, 2881 participants were included in this study. Compared to males, female participants had lower BMD (P < 0.05) and higher Gynoid fat mass (P < 0.00001), while there was no difference between Android fat mass (P = 0.91). Android fat mass was positively associated with Total femur BMD (Males, β = 0.044, 95% CI = 0.037, 0.051, P < 0.00001; Females, β = 0.044, 95% CI = 0.039, 0.049, P < 0.00001), Femoral neck BMD (Males, β = 0.034, 95% CI = 0.027, 0.041, P < 0.00001; Females, β = 0.032, 95% CI = 0.027, 0.037, P < 0.00001), and Total spine BMD (Males, β = 0.036, 95% CI = 0.029, 0.044, P < 0.00001; Females, β = 0.025, 95% CI = 0.019, 0.031, P < 0.00001). The Gynoid fat mass, subgroup analysis of age and ethnicity reached similar results.

Conclusion
Body fat in different regions was positively associated with BMD in different sites, and this association persisted in subgroup analyses across age and race in different gender.
Experiences and perceptions of nurses participating in an interprofessional, videoconference-based educational programme on concurrent mental health and substance use disorders: a qualitative study
Authors: Chicoine Gabrielle , Côté José , Pepin Jacinthe , Boyer Louise , Rouleau Geneviève , Jutras-Aswad Didier 
Published: July 2022

Abstract
Background
Individuals with co-occurring mental health and substance use disorders (i.e., concurrent disorders) have complex healthcare needs, which can be challenging for nurses to manage. Providing optimal care for this subpopulation requires nurses to develop high-level competencies despite limited resources at their disposal and the isolated settings in which many of them work. The Extension for Healthcare Community Outcomes (ECHO®) is a promising collaborative learning and capacity building model that uses videoconference technology to support and train healthcare professionals in the management of complex and chronic health conditions. The aim of this study was to explore the experiences and perceptions of nurses participating in a Canadian ECHO programme on concurrent disorders about the competencies they developed and used in their clinical practice, and which factors have influenced this process.

Methods
The study was qualitative, guided by an interpretive description approach. Individual semi-structured interviews were held with ten nurses who had participated in the programme between 2018 and 2020. A thematic analysis was conducted iteratively using an inductive approach to progressive data coding and organization.

Results
Four themes and eighteen sub-themes were identified. During their participation in ECHO, the nurses perceived as having further developed eight clinical nursing competencies. Nurses viewed ECHO as a unique opportunity to open themselves to their peers’ experiences and reflect on their own knowledge. Learning from experts in the field of concurrent disorders helped them to build their confidence in managing complex clinical situations. The nurses’ sense of belonging to a community further enhanced their engagement in the programme, and learning was facilitated through the programme’s interprofessional environment. Nevertheless, the lack of contextualized educative content linked to local realities, the limited resources in concurrent disorders, and time constraints were experienced as factors limiting competency development.

Conclusions
ECHO is a promising alternative to conventional, in-person continuing education programmes to improve the development of advanced competencies among nurses providing care to individuals with chronic and complex health conditions. These findings can inform clinicians, educators, researchers, and decision makers who are developing, implementing, evaluating, and escalating future educational interventions in the field of CDs.
A mixed-method study exploring experiences, perceptions, and acceptability of using a safe delivery mHealth application in two district hospitals in Rwanda
Authors: Nishimwe Aurore , Conco Daphney Nozizwe , Nyssen Marc , Ibisomi Latifat 
Published: July 2022

Abstract
Background
Innovative use of mobile health (mHealth) technology in timely management of childbirth complications is a promising strategy, but its evidence base is limited. The Safe Delivery mHealth Application (SDA) is one of the recent mhealth applications (loaded in smartphones) which is a clinical decision support and training tool for basic emergency obstetric and newborn care (BEmONC). This paper describes, the health providers’ experiences, perceptions, and acceptability of using the SDA, as well as the perceptions of key stakeholders.

Methods
A mixed-methods approach was utilized. Quantitative methods consisted of a self-reported acceptability survey, administered to 54 nurses and midwives, including questions on their usage and perceptions of the SDA. Descriptive statistics were employed to analyze the survey data. Qualitative methods included two focus group discussions with 24 nurses and midwives, and six key informant interviews with stakeholders (maternity matrons, responsible for maternal and child health, and district hospital managers). Thematic analysis was performed and selected quotations used to illustrate themes. The study took place in two district hospitals in Rwanda.

Results
Quantitative results found that 31 (57.4%) participants used the SDA four to six times per week. Many participants felt more confident (53.7%) and better at their job (40.7%) since having the SDA. Likert scale survey responses (1–5, 1 = Strongly Disagree, 5 = Strongly Agree) indicated general agreement that SDA is easy to use (Mean = 4.46), is an effective decision support tool (4.63), and training tool (4.65). Qualitative results included themes on perceived usefulness; professional growth acquired through the use of the SDA; SDA, an empowering, intuitive, and user-friendly technology; desired SDA features and functions; benefits of SDA as perceived by key informants, and future use of the SDA.

Conclusions
The nurses and midwives perceive the SDA as having improved their ability to manage childbirth complications. Key stakeholders also perceive the SDA as a useful tool with a reasonable cost and recommend its implementation in routine practices. This study deepens the understanding of the potential benefits of mHealth such as the SDA in low-income settings, like Rwanda. It also provides more evidence on the impact of mHealth in assuring quality BEmONC.
Association of SNPs in the FK-506 binding protein (FKBP5) gene among Han Chinese women with polycystic ovary syndrome
Authors: Ma Xinyue , Wang Zhao , Zhang Changming , Bian Yuehong , Zhang Xin , Liu Xin , Cao Yongzhi , Zhao Yueran 
Published: July 2022

Abstract
Background
Polycystic ovary syndrome (PCOS) is a common endocrine disorder in premenopausal women, whose etiology remains uncertain, although it is known to be highly heterogeneous and genetically complex. PCOS often presents with hyperandrogenism symptoms. The present study aimed to determine whether polymorphisms in the FK-506 binding protein 5 (FKBP5) gene (androgen target gene) are associated with an association for PCOS and hyperandrogenism.

Methods
This is a case–control study, and association analyses were conducted. A total of 13 single-nucleotide polymorphisms (SNPs) in the FKBP5 gene were evaluated in 775 PCOS patients who were diagnosed based on the Rotterdam Standard and 783 healthy Chinese Han women. Associations between FKBP5 SNPs and hormone levels were investigated. These 13 SNPs were genotyped using the Sequenom MassARRAY system, and an association analysis between the phenotype and alleles and genotypes were conducted.

Results
The genotype frequencies for the rs1360780 and rs3800373 SNPs differed significantly between the PCOS cases and healthy controls (p = 0.025, OR is 1.63 (1.05–2.53) and p = 0.029, OR is 1.59 (1.03–2.45) respectively under co-dominant model). Moreover, the genotype frequencies and genetic model analysis for the SNPs rs1360780, rs9470080, rs9296158, rs1043805 and rs7757037 differed significantly between the hyperandrogenism and non-hyperandrogenism groups of PCOS patients. The TT genotype of rs1360780, the TT genotype of rs9470080, the TT genotype of rs1043805 or the GG genotype of rs7705037 (ORs are 2.13 (1.03–4.39), 1.81 (1.03–3.17), 2.94 (1.32–6.53) and 1.72 (1.04–2.84) respectively) were correlated with androgen level of PCOS patients.

Conclusion
Our study showed that FKBP5 gene polymorphisms are associated with PCOS generally (rs1360780 and rs3800373) and with the hyperandrogenism subtype specifically (rs1360780, rs9470080, rs9296158, rs1043805 and rs7757037).
Liver function markers predict cardiovascular and renal outcomes in the CANVAS Program
Authors: Ferrannini Giulia , Rosenthal Norman , Hansen Michael K. , Ferrannini Ele 
Published: July 2022

Abstract
Background
Raised liver function tests (LFTs) have been correlated with multiple metabolic abnormalities and variably associated with cardiorenal outcomes. We sought to systematically test the relationship between LFT levels within the accepted range and major cardiorenal outcomes in a large clinical trial in type 2 diabetes, and the possible impact of placebo-controlled canagliflozin treatment.

Methods
We measured serum alanine aminotransferase (ALT), aspartic aminotransferase (AST), gamma-glutamyl transferase (γGT), alkaline phosphatase (ALP), and bilirubin concentrations in 10,142 patients, at baseline and repeatedly over follow-up. The relation of LFTs to first hospitalized heart failure (HHF), cardiovascular (CV) and all-cause mortality, and progression of renal impairment was investigated using multivariate proportional-hazards models.

Results
In univariate association, ALT was reciprocally predictive, and ALP was positively predictive, of all adjudicated outcomes; γGT also was directly associated with CV—but not renal—outcomes. In multivariate models including all 5 LFTs and 19 potential clinical confounders, ALT was independently associated with lower, and γGT with higher, CV outcomes risk. Canagliflozin treatment significantly reduced ALT, AST, and γGT over time. In a fully adjusted model including updated LFT levels and treatment, γGT was independently associated with CV and all-cause mortality, ALP with renal dysfunction progression, and canagliflozin treatment with significant reduction in HHF and renal risk.

Conclusions
Higher γGT levels are top LFT markers of risk of HHF and death in patients with diabetes and high CV risk, while ALT are protective. Canagliflozin lowers the risk of HHF and renal damage independently of LFTs and potential confounders.
Benefits of the Cybathlon 2020 experience for a prosthetic hand user: a case study on the Hannes system
Authors: Caserta Giulia , Boccardo Nicolò , Freddolini Marco , Barresi Giacinto , Marinelli Andrea , Canepa Michele , Stedman Samuel , Lombardi Lorenzo , Laffranchi Matteo , Gruppioni Emanuele , De Michieli Lorenzo 
Published: July 2022

Abstract
Background
Cybathlon championship aims at promoting the development of prosthetic and assistive devices capable to meet users’ needs. This paper describes and analyses possible exploitation outcomes of our team’s (REHAB TECH) experience into the Powered Arm Prosthesis Race of the Cybathlon 2020 Global Edition, with the novel prosthetic system Hannes. In detail, we present our analysis on a concurrent evaluation conducted to verify if the Cybathlon training and competition positively influenced pilot’s performance and human-technology integration with Hannes, with respect to a non-runner Hannes user.

Methods
Two transradial amputees were recruited as pilots (Pilot 1 and Pilot 2) for the Cybathlon competition and were given the polyarticulated myoelectric prosthetic hand Hannes. Due to COVID-19 emergency, only Pilot 1 was trained for the race. However, both pilots kept Hannes for Home Use for seven weeks. Before this period, they both participated to the evaluation of functionality, embodiment, and user experience (UX) related to Hannes, which they repeated at the end of the Home Use and right after the competition. We analysed Pilot 1’s training and race outcomes, as well as changes in the concurrent evaluation, and compared these results with Pilot 2’s ones.

Results
The Cybathlon training gradually improved Pilot 1’s performances, leading to the sixth place with a single error in task 5. In the parallel evaluation, both pilots had an overall improvement over time, whereas Pilot 2 experienced a deterioration of embodiment. In detail, Pilot 1, who followed the training and raced the Cybathlon, improved in greater way.

Conclusion
Hannes demonstrated to be a valuable competitor and to perform grasps with human-like behaviors. The higher improvements of Pilot 1, who actively participated in the Cybathlon, in terms of functionality, embodiment and UX, may depend on his training and engagement in the effort of achieving a successful user-prosthesis interaction during the competition. Tasks based on Cybathlon’s ones could improve the training phase of a prosthetic user, stimulating dexterity, prosthetic integration, and user perception towards the prosthesis. Likewise, timed races or competitions could facilitate and accelerate the learning phase, improving the efficiency and efficacy of the process.
Road tunnel-derived coarse, fine and ultrafine particulate matter: physical and chemical characterization and pro-inflammatory responses in human bronchial epithelial cells
Authors: Skuland Tonje , Grytting Vegard Sæter , Låg Marit , Jørgensen Rikke Bræmming , Snilsberg Brynhild , Leseman Daan L. A. C. , Kubátová Alena , Emond Jessica , Cassee Flemming R. , Holme Jørn A. , Øvrevik Johan , Refsnes Magne 
Published: July 2022

Abstract
Background
Traffic particulate matter (PM) comprises a mixture of particles from fuel combustion and wear of road pavement, tires and brakes. In countries with low winter temperatures the relative contribution of mineral-rich PM from road abrasion may be especially high due to use of studded tires during winter season. The aim of the present study was to sample and characterize size-fractioned PM from two road tunnels paved with different stone materials in the asphalt, and to compare the pro-inflammatory potential of these fractions in human bronchial epithelial cells (HBEC3-KT) in relation to physicochemical characteristics.

Methods
The road tunnel PM was collected with a vacuum pump and a high-volume cascade impactor sampler. PM was sampled during winter, both during humid and dry road surface conditions, and before and after cleaning the tunnels. Samples were analysed for hydrodynamic size distribution, content of elemental carbon (EC), organic carbon (OC) and endotoxin, and the capacity for acellular generation of reactive oxygen species. Cytotoxicity and pro-inflammatory responses were assessed in HBEC3-KT cells after exposure to coarse (2.5–10 μm), fine (0.18–2.5 μm) and ultrafine PM (≤ 0.18 μm), as well as particles from the respective stone materials used in the pavement.

Results
The pro-inflammatory potency of the PM samples varied between road tunnels and size fractions, but showed more marked responses than for the stone materials used in asphalt of the respective tunnels. In particular, fine samples showed significant increases as low as 25 µg/mL (2.6 µg/cm2) and were more potent than coarse samples, while ultrafine samples showed more variable responses between tunnels, sampling conditions and endpoints. The most marked responses were observed for fine PM sampled during humid road surface conditions. Linear correlation analysis showed that particle-induced cytokine responses were correlated to OC levels, while no correlations were observed for other PM characteristics.

Conclusions
The pro-inflammatory potential of fine road tunnel PM sampled during winter season was high compared to coarse PM. The differences between the PM-induced cytokine responses were not related to stone materials in the asphalt. However, the ratio of OC to total PM mass was associated with the pro-inflammatory potential.
Prenatal diagnosis and genetic counseling of a paternally inherited chromosome 15q11.2 microdeletion in a Chinese family
Authors: Tang Wenjuan , Chen Guowei , Xia Jingshu , Zhang Ying 
Published: July 2022

Abstract
Background
Proximal region of chromosome 15 long arm is rich in duplicons that, define five breakpoints (BP) for 15q rearrangements. 15q11.2 microdeletion has been previously associated with developmental delay, mental retardation, epilepsy, autism, schizophrenia and congenital heart defects. The literature on this microdeletion is extensive and confusing, which is a challenge for genetic counselling.

Case presentation
We have performed prenatal diagnosis and genetic counseling of a paternally inherited 15q11.2 microdeletion. In this family, father with normal phenotype and fetus with abnormal phenotype have the same microdeletion.

Conclusion
Chromosomal microdeletions and microduplications are difficult to detect by conventional cytogenetics, combination of prenatal ultrasound, karyotype analysis, CMA and genetic counseling is helpful for the prenatal diagnosis of chromosomal microdeletions/microduplications.
Combined nature and human selections reshaped peach fruit metabolome
Authors: Cao Ke , Wang Bin , Fang Weichao , Zhu Gengrui , Chen Changwen , Wang Xinwei , Li Yong , Wu Jinlong , Tang Tang , Fei Zhangjun , Luo Jie , Wang Lirong 
Published: July 2022

Abstract
Background
Plant metabolites reshaped by nature and human beings are crucial for both their lives and human health. However, which metabolites respond most strongly to selection pressure at different evolutionary stages and what roles they undertake on perennial fruit crops such as peach remain unclear.

Results
Here, we report 18,052 significant locus-trait associations, 12,691 expression-metabolite correlations, and 294,676 expression quantitative trait loci (eQTLs) for peach. Our results indicate that amino acids accumulated in landraces may be involved in the environmental adaptation of peaches by responding to low temperature and drought. Moreover, the contents of flavonoids, the major nutrients in fruits, have kept decreasing accompanied by the reduced bitter flavor during both domestication and improvement stages. However, citric acid, under the selection of breeders’ and consumers’ preference for flavor, shows significantly different levels between eastern and western varieties. This correlates with differences in activity against cancer cells in vitro in fruit from these two regions. Based on the identified key genes regulating flavonoid and acid contents, we propose that more precise and targeted breeding technologies should be designed to improve peach varieties with rich functional contents because of the linkage of genes related to bitterness and acid taste, antioxidant and potential anti-cancer activity that are all located at the top of chromosome 5.

Conclusions
This study provides powerful data for future improvement of peach flavor, nutrition, and resistance in future and expands our understanding of the effects of natural and artificial selection on metabolites.
Population-genomic analyses reveal bottlenecks and asymmetric introgression from Persian into iron walnut during domestication
Authors: Ding Ya-Mei , Cao Yu , Zhang Wei-Ping , Chen Jun , Liu Jie , Li Pan , Renner Susanne S. , Zhang Da-Yong , Bai Wei-Ning 
Published: July 2022

Abstract
Background
Persian walnut, Juglans regia, occurs naturally from Greece to western China, while its closest relative, the iron walnut, Juglans sigillata, is endemic in southwest China; both species are cultivated for their nuts and wood. Here, we infer their demographic histories and the time and direction of possible hybridization and introgression between them.

Results
We use whole-genome resequencing data, different population-genetic approaches (PSMC and GONE), and isolation-with-migration models (IMa3) on individuals from Europe, Iran, Kazakhstan, Pakistan, and China. IMa3 analyses indicate that the two species diverged from each other by 0.85 million years ago, with unidirectional gene flow from eastern J. regia and its ancestor into J. sigillata, including the shell-thickness gene. Within J. regia, a western group, located from Europe to Iran, and an eastern group with individuals from northern China, experienced dramatically declining population sizes about 80 generations ago (roughly 2400 to 4000 years), followed by an expansion at about 40 generations, while J. sigillata had a constant population size from about 100 to 20 generations ago, followed by a rapid decline.

Conclusions
Both J. regia and J. sigillata appear to have suffered sudden population declines during their domestication, suggesting that the bottleneck scenario of plant domestication may well apply in at least some perennial crop species. Introgression from introduced J. regia appears to have played a role in the domestication of J. sigillata.