bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are investigators’ access to trial data and rights to publish restricted and are potential trial participants informed about this? A comparison of trial protocols and informed consent materials
Authors: Paludan-Müller Asger S. , Ogden Michelle C. , Marquardsen Mikkel , Jørgensen Karsten J. , Gøtzsche Peter C. 
Published: August 2021

Abstract
Objectives
To determine to which degree industry partners in randomised clinical trials own the data and can constrain publication rights of academic investigators.

Methods
Cohort study of trial protocols, publication agreements and other documents obtained through Freedom of Information requests, for a sample of 42 trials with industry involvement approved by ethics committees in Denmark. The main outcome measures used were: proportion of trials where data was owned by the industry partner, where the investigators right to publish were constrained and if this was mentioned in informed consent documents, and where the industry partner could review data while the trial was ongoing and stop the trial early.

Results
The industry partner owned all data in 20 trials (48%) and in 16 trials (38%) it was unclear. Publication constraints were described for 30 trials (71%) and this was not communicated to trial participants in informed consent documents in any of the trials. In eight trials (19%) the industry partner could review data during the trial, for 20 trials (48%) it was unclear. The industry partner could stop the trial early without any specific reason in 23 trials (55%).

Conclusions
Publication constraints are common, and data is often owned by industry partners. This is rarely communicated to trial participants. Such constraints might contribute to problems with selective outcome reporting. Patients should be fully informed about these aspects of trial conduct.
Apomixis and genetic background affect distinct traits in Hieracium pilosella L. grown under competition
Authors: Sailer Christian , Tiberi Simone , Schmid Bernhard , Stöcklin Jürg , Grossniklaus Ueli 
Published: August 2021

Abstract
Background
Apomixis, the asexual reproduction through seeds, occurs in over 40 plant families and avoids the hidden cost of sex. Apomictic plants are thought to have an advantage in sparse populations and when colonizing new areas but may have a disadvantage in changing environments because they propagate via fixed genotypes.
In this study, we separated the influences of different genetic backgrounds (potentially reflecting local adaptation) from those of the mode of reproduction, i.e., sexual vs. apomictic, on nine fitness-related traits in Hieracium pilosella L. We aimed to test whether apomixis per se may provide a fitness advantage in different competitive environments in a common garden setting.

Results
To separate the effects of genetic background from those of reproductive mode, we generated five families of apomictic and sexual full siblings by crossing two paternal with four maternal parents. Under competition, apomictic plants showed reproductive assurance (probability of seeding, fertility), while offspring of sexual plants with the same genetic background had a higher germination rate. Sexual plants grew better (biomass) than apomictic plants in the presence of grass as a competitor but apomictic plants spread further vegetatively (maximum stolon length) when their competitors were sexual plants of the same species. Furthermore, genetic background as represented by the five full-sibling families influenced maximum stolon length, the number of seeds, and total fitness. Under competition with grass, genetic background influenced fecundity, the number of seeds, and germination rate.

Conclusions
Our results suggest that both the mode of reproduction as well as the genetic background affect the success of H. pilosella in competitive environments. Total fitness, the most relevant trait for adaptation, was only affected by the genetic background. However, we also show for the first time that apomixis per se has effects on fitness-related traits that are not confounded by—and thus independent of—the genetic background.
Prevalence and in vitro antifungal susceptibility of commensal yeasts in the external ear canal of cats
Authors: Niae Sara , Yurayart Chompoonek , Thengchaisri Naris , Sattasathuchana Panpicha 
Published: August 2021

Abstract
Background
Lifestyle factors such as hair length, the frequency of ear cleaning and bathing, age, cat rearing, and sex may contribute to opportunistic yeast infections in the external ear canal of cats. This study aimed to determine the prevalence of commensal yeast organisms in cats’ external ear canals, evaluate their predisposing lifestyle factors, and test the susceptibility of Malassezia pachydermatis to antifungal agents.

Results
A total of 53 cats (33 male and 20 female) seronegative for feline leukemia virus and feline immunodeficiency virus were enrolled in this study. Their mean age (± standard deviation) was 6.04 (± 3.49) years. Fungal cultures and polymerase chain reaction tests were performed to identify the yeast species derived from the external ear canal. The association between lifestyle factors and the presence of M. pachydermatis was evaluated using Fisher’s exact test. The susceptibility of M. pachydermatis to antifungal agents was also analyzed. M. pachydermatis was the most frequently recovered yeast species, with a prevalence of 50.94 % (95 % confidence interval [CI]: 36.84–64.94 %). There was an association between hair length and a positive culture for M. pachydermatis (p = 0.0001). The odds of a negative culture for M. pachydermatis among short-haired cats was 11.67 (95 % CI, 3.22–42.24) times higher than that among long-haired cats (p = 0.0002). There was also an association between the frequency of ear cleaning and the presence of M. pachydermatis (p = 0.007). The odds of a negative culture for M. pachydermatis in cats that were receiving ear cleaning at intervals of ≤ 2 weeks was 5.78 (95 % CI, 1.67–19.94) times greater than that of cats receiving ear cleaning at intervals greater than 2 weeks or never (p = 0.0055). Ranges of minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations for itraconazole, ketoconazole, miconazole, and terbinafine against M. pachydermatis were ≤ 0.063–4 and ≤ 0.063–≥32, ≤ 0.063–8 and 0.125–≥32, ≤ 0.063–≥32 and 0.5–≥32, and ≤ 0.016–1 and 0.125–8 µg/ml, respectively.

Conclusions
M. pachydermatis was the most commonly identified yeast organism in the external ear canal of healthy cats. Hair length and the frequency of ear cleaning played a role in the colonization of M. pachydermatis. The M. pachydermatis isolates had various MIC levels for common fungicides.
Pan-cancer analysis of the oncogenic role of discs large homolog associated protein 5 (DLGAP5) in human tumors
Authors: Tang Neng , Dou Xiaolin , You Xing , Shi Qiman , Ke Mujing , Liu Guodong 
Published: August 2021

Abstract
Background
In recent years, there have been many studies on the relationship between DLGAP5 and different types of cancers, yet there is no pan-cancer analysis of DLGAP5. Therefore, this study aims to analyze the roles of DLGAP5 in human tumors.

Methods
Firstly, we evaluated the expression level of DLGAP5 in 33 types of tumors throughout the datasets of TCGA (Cancer Genome Atlas) and GEO (Gene Expression Synthesis). Secondly, we used the GEPIA2 and Kaplan-Meier plotter to conduct Survival prognosis analysis. Additionally, cBioPortal web was utilized to analyze the genetic alteration of DLGAP5, after which we selected hepatocellular carcinoma (HCC) cell lines to define the function of DLGAP5. Last but not least, we performed immune infiltration analysis and DLGAP5-related gene enrichment analysis.

Results
DLGAP5 is highly expressed in most type of cancers, and there is a significant correlation between the expression of DLGAP5 and the prognosis of cancer patients. We have observed that DLGAP5 promotes the proliferation and invasion of hepatocellular carcinoma (HCC) cell lines. We also found that DLGAP5 expression was related with the CD8+ T-cell infiltration status in kidney renal clear cell carcinoma, uveal melanoma, and thymoma, and cancer-associated fibroblast infiltration was observed in breast invasive carcinoma, kidney renal papillary cell carcinoma and testicular germ cell tumors. In addition, enrichment analysis revealed that cell cycle- and oocyte meiosis-associated functions were involved in the functional mechanism of DLGAP5.

Conclusions
Taken together, our unpresented pan-cancer analysis of DLGAP5 provides a relatively integrative understanding of the oncogenic role of DLGAP5 in various tumors. DLGAP5 may prompt HCC cellular proliferation, invasion and metastasis. All of these provides solid basement and will promote more advanced understanding the role of DLGAP5 in tumorigenesis and development from the perspective of clinical tumor samples and cells.
Maternal mortality reduction: a need to focus actions on the prevention of hypertensive disorders of pregnancy
Authors: Belizán José M. , Gibbons Luz , Cormick Gabriela 
Published: August 2021

AbstractMaternal mortality (MM) reflects one of the most striking global health inequalities. Global figures of MM fell significantly from 1990 to 2017. The reduction was largely due to a 70% fall in haemorrhages, and a limited (18.2%) improvement in hypertensive disorders of pregnancy (HDP). If this trend continues, by 2021 HDP will be the main cause of global MM.MM reductions due to haemorrhage is reassuring, however MM due to HDP show a more complex situation as early detection of HDP requires regular contact of pregnant women with the health system. In order to reduce MM due to HDP, population wide preventive actions such as low dose aspirin and adequate calcium intake are required, especially in areas where women have little contact with the health systems.Calcium supplementation for women with low calcium intake has reduced the risk of pre-eclampsia, with further reductions starting daily supplementation with 500 mg of calcium preconceptionally, however adherence to supplementation is limited.To reduce global inequities in calcium intake and consequently in the HDP, food fortification seem to be an attractive strategy to achieve an increase of calcium intake.
The neuroprotective effect of pretreatment with carbon dots from Crinis Carbonisatus (carbonized human hair) against cerebral ischemia reperfusion injury
Authors: Zhang Yue , Wang Suna , Lu Fang , Zhang Meiling , Kong Hui , Cheng Jinjun , Luo Juan , Zhao Yan , Qu Huihua 
Published: August 2021

Abstract
Background
Cerebral infarction and cerebral hemorrhage, also known as “stroke”, is one of the leading cause of death. At present, there is no real specific medicine for stroke. Crinis Carbonisatus (named Xue-yu-tan in Chinese), produced from carbonized hair of healthy human, and has been widely applied to relieve pain and treat epilepsy, stroke and other diseases in China for thousands of years.

Results
In this work, a new species of carbon dots derived from Crinis Carbonisatus (CrCi-CDs) were separated and identified. And the neuroprotective effect of carbon dots from CrCi were evaluated using the middle cerebral artery occlusion (MCAO) model. Neurological deficit score and infarction volume was assessed, evans blue content of ischemic hemispheres was measured, the concentrations of inflammatory factors, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) in the cortex were measured, and the levels of neurotransmitters in the brain were determined. Preconditioning of CrCi-CDs significantly reduced ischemic lesion volume and blood–brain-barrier (BBB) permeability, improved neurologic deficits, decreased the level of TNF-α and IL-6 in MCAO rats, inhibited excitatory neurotransmitters aspartate (Asp) and glutamate (Glu), and increased the level of 5-hydroxytryptamine (5-HT). The RNA-Sequencing results reveal that further potential mechanisms behind the activities may be related to the anti-inflammation effects and inhibition of neuroexcitatory toxicity.

Conclusion
CrCi-CDs performs neuroprotective effect on cerebral ischemia and reperfusion injury, and the mechanisms may correlate with its anti-inflammatory action, which suggested that CrCi-CDs have potential value in clinical therapy on the acute apoplexy cases in combination with thrombolytic drugs.

Graphic abstract
Anxiety, trauma and well-being in health-care professionals during COVID-19 first wave in Spain: the moderating role of personal protection equipment availability
Authors: Bajo Miriam , Gallego Pilar , Stavraki Maria , Lamprinakos Grigorios , Luna Pablo , Díaz Darío 
Published: August 2021

Abstract
Background
The effect of COVID-19 on Health-Care Professionals’ mental health has received increased attention in the last year’s literature. However, previous studies essentially evaluated psychopathological symptoms and not the presence of positive mental health. Therefore, the first objective of the present research is to evaluate health-care professionals’ mental illness (i.e., anxiety and traumatic intensity) and positive mental health (i.e., well-being) using the Complete State Model of Health. Our second objective is to study the effect of Personal Protection Equipment availability on professionals’ mental health.

Methods
Two-hundred and thirty-two health-care professionals working in Spain in the first line of COVID-19 patient care participated in the study. To measure anxiety, traumatic intensity and well-being participants completed the State Trait Anxiety Inventory, the Davidson Trauma Scale, and the Mental Health Continuum-Short Form. Pearson correlations were used to examine the relationships between all scales. In order to test the two continua model of mental health, we used parallel analysis and exploratory factor analysis. To analyze anxiety, traumatic intensity, and well-being differences between health-care professionals with and without Personal Protection Equipment availability we conducted different ANOVAS. To test our hypothesis regarding the moderating role of Personal Protection Equipment availability in the effect of mental illness on positive mental health, data were subjected to a hierarchical regression analysis.

Results
As in previous studies, health-care professionals showed high levels of anxiety and traumatic intensity. They also presented low levels of well-being indicators. According to our hypothesis, results of parallel analysis and exploratory factorial analysis indicated that the measures of mental illness and positive mental health loaded on separate but correlated factors. Finally, Personal Protection Equipment availability moderated the effects of state anxiety and traumatic intensity on professionals’ well-being.

Conclusions
Health-care professionals’ mental illness and positive mental health reflect distinct continua, rather than the extreme ends of a single spectrum. Therefore, it is essential to measure both psychopathology and the presence of positive health to comprehensively evaluate professionals’ mental health. Finally, our results indicated that Personal Protection Equipment availability is essential not only for professionals’ physical health, but also for their mental health.
Calibrated automated thrombogram II: removing barriers for thrombin generation measurements
Authors: Giesen P. L. A. , Gulpen A. J. W. , van Oerle R. , ten Cate H. , Nagy M. , Spronk H. M. H. 
Published: August 2021

AbstractBackgroundThrombin generation (TG) assessed by Calibrated Automated Thrombogram (CAT-I) reflects the overall capacity of plasma to generate thrombin, thus evaluating the balance between the anti- and procoagulant processes. However, with this method the calibrator curve is usually not measured until completion which has a severe impact on the calculation of the TG parameters, especially under conditions where almost all substrate is consumed. In addition, direct thrombin inhibitor (DTI) cannot be present in the calibration sample due to inhibition of the calibrator. We have developed a modified TG assay (CAT-II) and performed head-to-head comparison with the CAT-I method using the same fluorometer. Furthermore, we have compared our CAT-II method to a new automated TG instrument (ST®-Genesia) using the same calibration method.MethodsTG was assessed with CAT-I and CAT-II using the same fulorometer and with ST®-Genesia in control plasma and plasma containing different anticoagulants (dabigatran, rivaroxaban, apixaban) and plasmas to which common interfering substances, bilirubin, hemoglobin and lipids were added. In CAT-I, calibration was against the same plasma containing calibrator in the presence of fluorogenic substrate (Z-GGR-AMC). In contrast, CAT-II method and ST®-Genesia used a standard concentration of thrombin in buffer and 7-amino-4-methylcoumarin (AMC) in a separate plasma sample for calibration.ResultsTG obtained from CAT-I using anticoagulant-free plasmas was lower compared with TG from CAT-II but both methods demonstrated an intra-assay variation less than 5% on all measured parameters. When comparing the two different calibration methods in the presence of different anticoagulants, a high correlation was seen in the presence of rivaroxaban and apixaban (R2 > 0.97), but not with dabigatran, a direct thrombin inhibitor. CAT-II method showed dose-dependent inhibition of TG in the presence of dabigatran, while CAT-I was not able to detect it. Both methods were able to correct for the interfering substances.ConclusionsOur results showed high similarity between the results of CAT-I and CAT-II method when it is applied in control plasmas and plasmas not inhibited with a direct thrombin inhibitor. Furthermore, both the CAT-II method and ST-Genesia using the same calibration method were able to detect the effect of all oral anticoagulants. Taken together, applying a new calibration method is a significant improvement for monitoring patients on direct thrombin inhibitors while not introducing any bias to results obtained on other types of samples.
Associations of immune cell homing gene signatures and infiltrates of lymphocyte subsets in human melanomas: discordance with CD163+ myeloid cell infiltrates
Authors: Kwak Minyoung , Erdag Gulsun , Leick Katie M. , Bekiranov Stefan , Engelhard Victor H. , Slingluff Craig L. 
Published: August 2021

AbstractBackgroundImmune cells in the tumor microenvironment have prognostic value. In preclinical models, recruitment and infiltration of these cells depends on immune cell homing (ICH) genes such as chemokines, cell adhesion molecules, and integrins. We hypothesized ICH ligands CXCL9-11 and CCL2-5 would be associated with intratumoral T-cells, while CXCL13 would be more associated with B-cell infiltrates.MethodsSamples of human melanoma were submitted for gene expression analysis and immune cells identified by immunohistochemistry. Associations between the two were evaluated with unsupervised hierarchical clustering using correlation matrices from Spearman rank tests. Univariate analysis performed Mann–Whitney tests.ResultsFor 119 melanoma specimens, analysis of 78 ICH genes revealed association among genes with nonspecific increase of multiple immune cell subsets: CD45+, CD8+and CD4+T-cells, CD20+B-cells, CD138+plasma cells, and CD56+NK-cells. ICH genes most associated with these infiltrates included ITGB2, ITGAL, CCL19, CXCL13, plus receptor/ligand pairs CXCL9 and CXCL10 with CXCR3; CCL4 and CCL5 with CCR5. This top ICH gene expression signature was also associated with genes representing immune-activation and effector function. In contrast, CD163+M2-macrophages was weakly associated with a different ICH gene signature.ConclusionThese data do not support our hypothesis that each immune cell subset is uniquely associated with specific ICH genes. Instead, a larger set of ICH genes identifies melanomas with concordant infiltration of B-cell and T-cell lineages, while CD163+M2-macrophage infiltration suggesting alternate mechanisms for their recruitment. Future studies should explore the extent ICH gene signature contributes to tertiary lymphoid structures or cross-talk between homing pathways.
Contraception needs and pregnancy termination in sub-Saharan Africa: a multilevel analysis of demographic and health survey data
Authors: Adde Kenneth Setorwu , Dickson Kwamena Sekyi , Ameyaw Edward Kwabena , Amo-Adjei Joshua 
Published: August 2021

Abstract
Background
Women in sub-Saharan Africa (SSA) have a higher risk of unintended pregnancies that are more likely to be terminated, most of which are unsafe with associated complications. Unmet need for contraception is highest in SSA and exceeds the global average. This study investigates the association between unmet/met need for contraception and pregnancy termination SSA.

Methods
We used pooled data from Demographic and Health Surveys conducted from January 2010 to December 2018 in 32 countries in SSA. Our study involved 265,505 women with diverse contraception needs and with complete data on all variables of interest. Multilevel logistic regression at 95% CI was used to investigate the association between individual and community level factors and pregnancy termination.

Results
We found an overall pregnancy termination rate of 16.27% ranging from 9.13% in Namibia to 38.68% in Gabon. Intriguingly, women with a met need for contraception were more likely to terminate a pregnancy [aOR = 1.11; 95% CI 1.07–1.96] than women with unmet needs. Women with secondary education were more likely to terminate a pregnancy as compared to those without education [aOR = 1.23; 95% CI 1.19–1.27]. With regards to age, we observed that every additional age increases the likelihood of terminating a pregnancy. At the contextual level, the women with female household heads were less likely to terminate a pregnancy [aOR = 0.95; 95% CI 0.92–0.97]. The least socio-economically disadvantaged women were less likely to terminate a pregnancy compared to the moderately and most socio-economically disadvantaged women.

Conclusions
Our study contributes towards the discussion on unmet/met need for contraception and pregnancy termination across SSA. Women with met need for contraception have higher odds of terminating a pregnancy. The underlying cause of this we argued could be poor adherence to the protocols of contraceptives or the reluctance of women to utilise contraceptives after experiencing a failure. Governments of SSA and non-governmental organisations need to take pragmatic steps to increase met needs for contraception and also utilise mass media to encourage women to adhere to the prescription of contraceptives in order to reduce the incidence of unplanned pregnancies and unsafe abortions.