bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anticancer L-Asparaginase and Phytoactive Compounds From Plant Solanum nigrum Against MDR (Methicillindrug resistant) Staphylococcus aureus and Fungal Isolates
Authors: Aisha Ambreen , Zahra Saba , Tahir Imtiaz M. , Hussain Asim , Bano Naheed , Roobi Alishbah , Afsheen Nadia , Saleem Yasir 
Published: April 2022

L-asparaginase is used in chemotherapy for acute lymphoblastic leukemia and other cancers. L-asparaginase derived from bacterial source triggers immune responses. The current study investigates Solanum nigrum as a novel and latent source of L-asparaginase to minimize immunological reactions. The antitumor activity of SN methanol extract was determined using the potato disc assay. InterPro Chimera and InterPro were used to predict the amino acid sequence of L-asparaginase and its anticancer activity. Purification of the enzyme was carried out to homogeneity of 1.51-fold with a recovery of 61.99%. At optimal conditions of 36.5°C, pH 8.6, and 8.5 g/mL substrate, fruit (crude extract) revealed an L-asparaginase titer of 48.23 U/mL. The molecular weight of the enzyme was calculated to be 32 ± 5 kDa using SDS PAGE. The fruit’s total flavonoids and phenolic contents are 0.42 ± .030 g/mL and 94 ± 1.9 mg CAE, respectively. Anti-tumorigenic efficacy was determined to be 66% against Agrobacterium tumefaciens. Additionally, the extract possesses potent antifungal and antibacterial properties. Molecular docking provided the structural motifs and underlying interactions between L-asparaginase, N-acetylglucosamine, murine, and chitin. SN contains high levels of the enzyme L-asparaginase and phytochemicals, making it a potential source of anticancer drugs.
Comparison of conventional and transtrapezial palmar approaches for screw fixation of scaphoid waist fractures: a clinical study
Authors: Tsumura Takuya , Matsumoto Taiichi , Imanaka Toshihide , Kishimoto Katsuma , Ito Hiromu 
Published: April 2022

We investigated two palmar approaches for screw fixation of acute scaphoid waist fractures: the conventional percutaneous or transtrapezial approach. Thirty cases who underwent operation from 2013 to 2021 were reviewed (conventional group, 15; transtrapezial approach group, 15). Cross-sections were constructed along the long axis of the scaphoid on postoperative computed tomography to evaluate the screw position, relative to the centre point in the distal-third, midwaist and proximal-third of the bone. The screw could be inserted centrally in the proximal and distal regions using the transtrapezial approach. In the conventional approach, the screw was inserted radially in the distal region, but tended to be positioned centrally in the midwaist and proximal regions. As central placement of the screw in the proximal fragment offers a biomechanical advantage, both approaches can be options for some fracture patterns, while for others, the fracture pattern could influence which approach is better. Level of evidence: IV
Outcomes in Pump- and CGM-Baseline Use Subgroups in the International Diabetes Closed-Loop Trial
Authors: Ekhlaspour Laya , Raghinaru Dan , Forlenza Gregory P. , Isganaitis Elvira , Kudva Yogish C. , Lam David W. , Levister Camilla , O’Malley Grenye , Church Mei Mei , Lum John W. , Buckingham Bruce , Brown Sue A. 
Published: April 2022

Background: We investigated the potential benefits of automated insulin delivery (AID) among individuals with type 1 diabetes (T1D) in sub-populations of baseline device use determined by continuous glucose monitor (CGM) use status and insulin delivery via multiple daily injections (MDI) or insulin pump. Materials and Methods: In a six-month randomized, multicenter trial, 168 individuals were assigned to closed-loop control (CLC, Control-IQ, Tandem Diabetes Care), or sensor-augmented pump (SAP) therapy. The trial included a two- to eight-week run-in phase to train participants on study devices. The participants were stratified into four subgroups: insulin pump and CGM (pump+CGM), pump-only, MDI and CGM (MDI+CGM), and MDI users without CGM (MDI-only) users. We compared glycemic outcomes among four subgroups. Results: At baseline, 61% were pump+CGM users, 18% pump-only users, 10% MDI+CGM users, and 11% MDI-only users. Mean time in range 70-180 mg/dL (TIR) improved from baseline in the four subgroups using CLC: pump+CGM, 62% to 73%; pump-only, 61% to 70%; MDI+CGM, 54% to 68%; and MDI-only, 61% to 69%. The reduction in time below 70 mg/dL from baseline was comparable among the four subgroups. No interaction effect was detected with baseline device use for TIR ( P = .67) or time below ( P = .77). On the System Usability Questionnaire, scores were high at 26 weeks for all subgroups: pump+CGM: 87.2 ± 12.1, pump-only: 89.4 ± 8.2, MDI+CGM 87.2 ± 9.3, MDI: 78.1 ± 15. Conclusions: There was a consistent benefit in patients with T1D when using CLC, regardless of baseline insulin delivery modality or CGM use. These data suggest that this CLC system can be considered across a wide range of patients.
Dietary diversity score and associated factors among high school adolescent girls in a selected school of Yeka Sub-city, Addis Ababa
Authors: Worku Lelisa , Mamo Konjit , Bekele Teshome , Atlaw Daniel 
Published: April 2022

Introduction: Adequate dietary intake is critical for modification of eating behavior and provides nutrients required for growth particularly among adolescents. The evidence revealed the variation and unrelated data on the prevalence of dietary diversity among adolescent girls in Ethiopia. Objective: To assess the magnitude of dietary diversity and associated factors among high school adolescent girls at the selected school of Yeka Sub-city, Addis Ababa, Ethiopia 2021. Methods: A cross-sectional study was conducted in high schools of the Yeka sub-city. Self-administered questionnaires were used to collect data. Data were analyzed using SPSS and the characteristics of the study participants were reported using descriptive statistics. A logistic regression model was fitted to identify factors associated with dietary diversity. Result: The mean score of dietary diversity was 4.9 ± 1.47 with a response rate of 97.2% among a proposed number of participants. The dietary diversity score is high in 56.7% and low among 43.3% of adolescents. Stayed a long time on social media (adjusted odds ratio = 2.6), school type (adjusted odds ratio = 6.5), educational status of mother (adjusted odds ratio = 8.7), consuming more sweet food (adjusted odds ratio = 3.6), occupation of the mother (adjusted odds ratio = 2.3), household security (adjusted odds ratio = 2.3), and fear of obese/worried about shape (adjusted odds ratio = 5.0) were statistically associated with low dietary diversity score. Conclusion: The finding of the study revealed that the magnitude of low dietary diversity among adolescent girls was found to be high. Long time social media usage, school type, educational status of the mother, consuming more sweet food, occupation of mother, household food security, and fear of obese/worried about shape were statistically associated with dietary diversity score.
Utilization of cervical cancer screening service and associated factors among women of reproductive age group in Ilu Abba Bor zone, southwestern Ethiopia, 2019: Cross-sectional study
Authors: Dirirsa Dejene Edosa , Asefa Eyosiyas Yeshialem , Awol Salo Mukemil 
Published: April 2022

Introduction: Cervical cancer is one of the severest risks to women’s life. It is the main reason for more than half million of morbidity and 266,000 deaths worldwide annually. Objective: The aim of this study was to assess the level of cervical cancer screening service utilization and associated factors among women of the reproductive age group coming for health care service to public health facilities of Ilu Abba Bor zone, southwestern Ethiopia, 2019. Methods: An institutional-based cross-sectional study design was employed from 1 May to 30 May 2019. Participants were selected by systematic random sampling technique. Data were collected using a pretested questionnaire and entered into Epi data 3.1 and exported to SPSS version 23 for analysis. Multivariable logistic regression was used to observe the factors associated with cervical cancer screening utilization service. An adjusted odds ratio with a 95% confidence interval was used. Variables with a p-value of <0.05 were considered to be statistically significant. Results: From a total of 259 women involved in the study, about 19 (7.3%) of the study participants had been screened for cervical cancer at least once in the past 3 years during the study period. Educational status: primary (grade 1–8) (adjusted odds ratio = 3; 95% confidence interval = (1.15–7.91)), secondary (grade 9–12) (adjusted odds ratio = 4.21; 95% confidence interval = (1.04–7.46)), and tertiary (grade 12+) (adjusted odds ratio = 6.01; 95% confidence interval = (3.01–11.35)), nulliparous (adjusted odds ratio = 0.256; 95% confidence interval = (0.105–0.642)), and looking for information about cervical cancer (adjusted odds ratio = 3.4; 95% confidence interval = (1.8–6.2)) were significant factors associated with utilization of cervical cancer screening service. Conclusion: The study revealed that there was low cervical cancer screening service utilization in the study area. Educational status, parity, and looking for cervical cancer information were independently associated with cervical cancer screening utilization service. There is need to improve women’s education, dissemination of information about importance of cervical cancer screening, and focus on nulliparous women to have good practice of cervical cancer screening.
Tertiary experience of managing young bladder cancer patients
Authors: Brown Andrew , Burton Claudia , Ives Sarah , Elkington Isabel , Hussain Maria , Murigu Alex , Shear Ben , Warren Katherine , Burden Helena 
Published: April 2022

Objective: Bladder cancer is rare in young patients and some authors have concluded that this group have a favourable outcome. We aimed to analyse our experience with such patients. Patients and Methods: Patients aged 50 years or younger were identified via a retrospective review of pathology samples between 2016 and 2020. Data regarding demographics, symptoms, stage, grade, size and multifocality at initial transurethral resection, recurrence rate and progression were analysed. Results: 60 patients with an average age of 42 were identified. The majority of patients presented with intermediate-risk non-muscle invasive bladder cancer (NMIBC). Four patients presented with muscle invasive and three with metastatic disease. There were seven deaths. Forty-nine patients with NMIBC were followed-up for an average of 5 years and 2 months. 41% of our cohort did not have a recurrence and only four moved up the risk stratification. No patients under 40 presented with muscle invasive disease and the majority had intermediate risk NMIBC. Conclusion: Young patients typically present with intermediate-risk NMIBC which rarely progresses. Very high-risk disease and aggressive variants do occur and may benefit from upfront cystectomy. The rate of muscle-invasive disease increases with age and rarely occurs under 40. Until more data is readily available, the management of this cohort of patients should follow the well-established guidelines. Level of evidence: 4 (case series)
Prospective trial registration and publication rates of randomized clinical trials in digital health: A cross-sectional analysis of global trial registries
Authors: Al-Durra Mustafa , Nolan Robert P , Seto Emily , Cafazzo Joseph A 
Published: April 2022

Objectives We sought to examine the prevalence of prospective registration and publication rates in digital health trials. Materials and Methods We included 417 trials that enrolled participants in 2012 and were registered in any of the 17 WHO data provider registries. The evaluation of the prospective trial registration was based on the actual difference between the registration and enrollment dates. We identified existing publications through an automated PubMed search by every trial registration number as well as a pragmatic search in PubMed and Google based on extracted metadata from the trial registries. Results The prospective registration and publication rates were at (38.4%) and (65.5%), respectively. We identified a statistically significant ( p < 0.001) “Selective Registration Bias” with 95.7% of trials published within a year after registration, were registered retrospectively. We reported a statistically significant relationship ( p = 0.003) between prospective registration and funding sources, with industry-funded trials having the lowest compliance with prospective registration at (14.3%). The lowest non-publication rates were in the Middle East (26.7%) and Europe (28%), and the highest were in Asia (56.5%) and the U.S. (42.5%). We found statistically significant differences ( p < 0.001) between trial location and funding sources with the highest percentage of industry-funded trials in Asia (17.4%) and the U.S. (3.3%). Conclusion The adherence of investigators to the best practices of trial registration and result dissemination is still evolving in digital health trials. Further research is required to identify contributing factors and mitigation strategies to low compliance rate with trial publication and prospective registration in digital health trials.
A phase 1 study of donor regulatory T-cell infusion plus low-dose interleukin-2 for steroid-refractory chronic graft-vs-host disease
Authors: Whangbo Jennifer S. , Nikiforow Sarah , Kim Haesook T. , Wahl Jonathan , Reynolds Carol G. , Rai Sharmila C. , Kim Soomin , Burden Andrew , Alho Ana C. , Lacerda João F. , Alyea Edwin P. , Cutler Corey S. , Ho Vincent T. , Antin Joseph H. , Soiffer Robert J. , Ritz Jerome , Koreth John 
Published: April 2022

Abstract
Chronic graft-versus-host disease (cGVHD) remains a frequent cause of nonrelapse morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Despite recent advances, options for steroid-refractory (SR) cGVHD are limited. In previous trials of low-dose interleukin-2 (LD IL-2), the immunomodulatory properties of regulatory T cells (Tregs) have been harnessed to treat SR-cGVHD safely and effectively. In the present study, we combined a single infusion of Treg-enriched lymphocytes (Treg DLI) from the original stem cell donor with in vivo Treg expansion using LD IL-2 (1 × 106 IU/m2 per day for 8 weeks) in 25 adult patients with SR-cGVHD. Treg were not expanded ex vivo. Treg DLI was initiated at 0.1 × 106 cells per kg patient and escalated to a maximum dose of 1 × 106 cells per kg. Treg DLI plus LD IL-2 was well tolerated and led to partial responses (PR) in 5 of 25 patients (20%) after 8 weeks of therapy. Ten additional patients (40%) had stable disease with minor responses not meeting PR criteria. Patients at all dose levels had similar Treg expansion without significant changes in CD4+ conventional T cells or CD8+ T cells. High-throughput sequencing of the T-cell receptor β locus showed selective improvement of Treg diversity. A subset of DLI-derived Treg clones showed preferential expansion at week 8 and long-term persistence 1-year postinfusion. We demonstrate for the first time that infusion of polyclonal healthy donor Tregs followed by expansion with LD IL-2 is safe in patients with SR-cGVHD, thus establishing a foundation for future adoptive Treg therapies in the posttransplant setting. This trial was registered at www.clinicaltrials.gov as #NCT01937468.
Use of MS-GUIDE for identification of protein biomarkers for risk stratification of patients with prostate cancer
Authors: Goetze Sandra , Schüffler Peter , Athanasiou Alcibiade , Koetemann Anika , Poyet Cedric , Fankhauser Christian Daniel , Wild Peter J. , Schiess Ralph , Wollscheid Bernd 
Published: April 2022

AbstractBackgroundNon-invasive liquid biopsies could complement current pathological nomograms for risk stratification of prostate cancer patients. Development and testing of potential liquid biopsy markers is time, resource, and cost-intensive. For most protein targets, no antibodies or ELISAs for efficient clinical cohort pre-evaluation are currently available. We reasoned that mass spectrometry-based prescreening would enable the cost-effective and rational preselection of candidates for subsequent clinical-grade ELISA development.MethodsUsing Mass Spectrometry-GUided Immunoassay DEvelopment (MS-GUIDE), we screened 48 literature-derived biomarker candidates for their potential utility in risk stratification scoring of prostate cancer patients. Parallel reaction monitoring was used to evaluate these 48 potential protein markers in a highly multiplexed fashion in a medium-sized patient cohort of 78 patients with ground-truth prostatectomy and clinical follow-up information. Clinical-grade ELISAs were then developed for two of these candidate proteins and used for significance testing in a larger, independent patient cohort of 263 patients.ResultsMachine learning-based analysis of the parallel reaction monitoring data of the liquid biopsies prequalified fibronectin and vitronectin as candidate biomarkers. We evaluated their predictive value for prostate cancer biochemical recurrence scoring in an independent validation cohort of 263 prostate cancer patients using clinical-grade ELISAs. The results of our prostate cancer risk stratification test were statistically significantly 10% better than results of the current gold standards PSA alone, PSA plus prostatectomy biopsy Gleason score, or the National Comprehensive Cancer Network score in prediction of recurrence.ConclusionUsing MS-GUIDE we identified fibronectin and vitronectin as candidate biomarkers for prostate cancer risk stratification.
The Bursaphelenchus xylophilus effector BxML1 targets the cyclophilin protein (CyP) to promote parasitism and virulence in pine
Authors: Zhang Yan , Wen Tong-Yue , Wu Xiao-Qin , Hu Long-Jiao , Qiu Yi-Jun , Rui Lin 
Published: April 2022

AbstractBackgroundBursaphelenchus xylophilusis the causal agent of pine wilt disease (PWD) that has caused enormous ecological and economic losses in China. The mechanism in the interaction between nematodes and pine remains unclear. Plant parasitic nematodes (PPNs) secrete effectors into host plant tissues. However, it is poorly studied that role of effector in the infection of pine wood nematode (PWN).ResultsWe cloned, characterized and functionally validated theB. xylophiluseffector BxML1, containing an MD-2-related lipid-recognition (ML) domain. This protein inhibits immune responses triggered by the molecular pattern BxCDP1 ofB. xylophilus. An insitu hybridization assay demonstrated that BxML1 was expressed mainly in the dorsal glands and intestine ofB. xylophilus. Subcellular localization analysis showed the presence of BxML1 in the cytoplasm and nucleus. Furthermore, number ofB. xylophilusand morbidity of pine were significantly reduced inPinus thunbergiiinfected withB. xylophiluswhen BxML was silenced. Using yeast two-hybrid (Y2H) and coimmunoprecipitation (CoIP) assays, we found that the BxML1 interacts with cyclophilin protein PtCyP1 inP. thunbergii.ConclusionsThis study illustrated that BxML1 plays a critical role in theB. xylophilus–plant interaction and virulence ofB. xylophilus.
Performance of the SarQoL quality of life tool in a UK population of older people with probable sarcopenia and implications for use in clinical trials: findings from the SarcNet registry
Authors: Witham Miles D. , Heslop Philip , Dodds Richard M. , Clegg Andrew P. , Hope Suzy V. , McDonald Claire , Smithard David , Storey Bryony , Tan Ai Lyn , Thornhill Anna , Sayer Avan A. 
Published: April 2022

Abstract
Background
The Sarcopenia Quality of Life (SarQoL) questionnaire is a disease-specific sarcopenia quality of life tool. We aimed to independently assess SarQoL with a particular focus on its suitability as a clinical trial outcome measure.

Methods
We analysed data from the UK Sarcopenia Network and Registry. Measures of physical performance and lean mass were collected at baseline. SarQoL and the Strength, Assistance, Rise, Climb - Falls (SARC-F) questionnaire (to assess functional ability) were collected at both baseline and six-month follow-up. Global changes in fitness and quality of life at 6 months were elicited on seven-point Likert scales. Internal consistency was assessed using Cronbach’s alpha. Responsiveness (Cohen’s d and Guyatt coefficients) and minimum clinically important differences were calculated for participants reporting slight improvement or worsening in their global scores. Concurrent validity was assessed by correlating baseline SarQoL scores with measures of physical performance and functional ability.

Results
We analysed data from 147 participants, 125 of whom underwent follow up assessment; mean age 78 years; 72 (49%) were women. Internal consistency was good; Cronbach’s alpha was 0.944 at baseline and 0.732 at telephone follow-up. Correlation between baseline and follow-up SarQoL was weak (r = 0.27; p = 0.03). The minimum clinically important improvement ranged from 5 to 21 points giving trial sample size estimates of 25–100 participants. SarQoL scores were moderately correlated with handgrip (r = 0.37; p < 0.001), SARC-F (r = − 0.45; p < 0.001), short physical performance battery (r = 0.48; p < 0.001) and 4-m walk speed (r = 0.48; p < 0.001).

Conclusions
SarQoL has acceptable performance in older UK participants with probable sarcopenia and is sufficiently responsive for use in clinical trials for sarcopenia.
Markers of kidney function, genetic variation related to cognitive function, and cognitive performance in the UK Biobank
Authors: Richard Erin L. , McEvoy Linda K. , Deary Ian J. , Davies Gail , Cao Steven Y. , Oren Eyal , Alcaraz John E. , LaCroix Andrea Z. , Bressler Jan , Salem Rany M. 
Published: April 2022

Abstract
Background
Chronic kidney disease has been linked to worse cognition. However, this association may be dependent on the marker of kidney function used, and studies assessing modification by genetics are lacking. This study examined associations between multiple measures of kidney function and assessed effect modification by a polygenic score for general cognitive function.

Methods
In this cross-sectional study of up to 341,208 European ancestry participants from the UK Biobank study, we examined associations between albuminuria and estimated glomerular filtration rate based on creatinine (eGFRcre) or cystatin C (eGFRcys) with cognitive performance on tests of verbal-numeric reasoning, reaction time and visual memory. Adjustment for confounding factors was performed using multivariate regression and propensity-score matching. Interaction between kidney function markers and a polygenic risk score for general cognitive function was also assessed.

Results
Albuminuria was associated with worse performance on tasks of verbal-numeric reasoning (β(points) = -0.09, p < 0.001), reaction time (β(milliseconds) = 7.06, p < 0.001) and visual memory (β(log errors) = 0.013, p = 0.01). A polygenic score for cognitive function modified the association between albuminuria and verbal-numeric reasoning with significantly lower scores in those with albuminuria and a lower polygenic score (p = 0.009). Compared to participants with eGFRcre ≥ 60 ml/min, those with eGFRcre < 60 ml/min had lower verbal-numeric reasoning scores and slower mean reaction times (verbal numeric reasoning β = -0.11, p < 0.001 and reaction time β = 6.08, p < 0.001 for eGFRcre < 60 vs eGFRcre ≥ 60). Associations were stronger using cystatin C-based eGFR than creatinine-based eGFR (verbal numeric reasoning β = -0.21, p < 0.001 and reaction time β = 11.21, p < 0.001 for eGFRcys < 60 vs eGFRcys ≥ 60).

Conclusions
Increased urine albumin is associated with worse cognition, but this may depend on genetic risk. Cystatin C-based eGFR may better predict cognitive performance than creatinine-based estimates.