bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of (Epi)genetic Predisposing Factors in a 5-Year Unselected National Wilms Tumor Cohort: A Comprehensive Clinical and Genomic Characterization
Authors: Hol Janna A. , Kuiper Roland P. , van Dijk Freerk , Waanders Esmé , van Peer Sophie E. , Koudijs Marco J. , Bladergroen Reno , van Reijmersdal Simon V. , Morgado Lionel M. , Bliek Jet , Lombardi Maria Paola , Hopman Saskia , Drost Jarno , de Krijger Ronald R. , van den Heuvel-Eibrink Marry M. , Jongmans Marjolijn C.J. 
Published: March 2022

PURPOSE Wilms tumor (WT) is associated with (epi)genetic predisposing factors affecting a growing number of WT predisposing genes and loci, including those causing Beckwith-Wiedemann spectrum (BWSp) or WT1-related syndromes. To guide genetic counseling and testing, we need insight into the prevalence of WT predisposing (epi)genetic factors. PATIENTS AND METHODS All children diagnosed with WT in the Netherlands between 2015 and 2020 were referred to a clinical geneticist. Phenotypic data, disease characteristics, and diagnostic test results were collected. If no genetic predisposition was identified by targeted diagnostic testing, germline (trio-)whole-exome sequencing and BWSp testing on normal kidney-derived DNA were offered. RESULTS A total of 126 cases were analyzed of 128 identified patients. (Epi)genetic predisposing factors were present in 42 of 126 patients (33.3%) on the basis of a molecular diagnosis in blood-derived DNA (n = 26), normal kidney-derived DNA (n = 12), or solely a clinical diagnosis of BWSp (n = 4). Constitutional, heterozygous DIS3L2 variants were identified as a recurrent predisposing factor in five patients (4%), with a second somatic hit in 4 of 5 tumors. Twenty patients (16%) were diagnosed with BWSp while four additional patients without BWSp features harbored chromosome 11p15 methylation defects in normal kidney tissue. Remaining findings included WT1-related syndromes (n = 10), Fanconi anemia (n = 1), neurofibromatosis type 1 (n = 1), and a pathogenic REST variant (n = 1). In addition, (likely) pathogenic variants in adult-onset cancer predisposition genes ( BRCA2, PMS2, CHEK2, and MUTYH) were identified in 5 of 56 (8.9%) patients with available whole-exome sequencing data. Several candidate WT predisposition genes were identified, which require further validation. CONCLUSION (Epi)genetic WT predisposing factors, including mosaic aberrations and recurrent heterozygous DIS3L2 variants, were present in at least 33.3% of patients with WT. On the basis of these results, we encourage standard genetic testing after counseling by a clinical geneticist.
An optimized retroviral toolbox for overexpression and genetic perturbation of primary lymphocytes
Authors: van der Donk Lieve E. H. , van der Spek Jet , van Duivenvoorde Tom , ten Brink Marieke S. , Geijtenbeek Teunis B. H. , Kuijl Coenraad P. , van Heijst Jeroen W. J. , Ates Louis S. 
Published: March 2022

ABSTRACT
Genetic manipulation of primary lymphocytes is crucial for both clinical purposes and fundamental research. Despite their broad use, we encountered a paucity of data on systematic comparison and optimization of retroviral vectors, the workhorses of genetic modification of primary lymphocytes. Here, we report the construction and validation of a versatile range of retroviral expression vectors. These vectors can be used for the knockdown or overexpression of genes of interest in primary human and murine lymphocytes, in combination with a wide choice of selection and reporter strategies. By streamlining the vector backbone and insert design, these publicly available vectors allow easy interchangeability of the independent building blocks, such as different promoters, fluorescent proteins, surface markers and antibiotic resistance cassettes. We validated these vectors and tested the optimal promoters for in vitro and in vivo overexpression and knockdown of the murine T cell antigen receptor. By publicly sharing these vectors and the data on their optimization, we aim to facilitate genetic modification of primary lymphocytes for researchers entering this field.
The Paget's disease of bone risk gene PML is a negative regulator of osteoclast differentiation and bone resorption
Authors: Wani Sachin , Daroszewska Anna , Salter Donald M. , van ‘t Hof Rob J. , Ralston Stuart H. , Albagha Omar M. E. 
Published: March 2022

ABSTRACT
Paget's disease of bone (PDB) is characterized by focal increases in bone remodelling. Genome-wide association studies identified a susceptibility locus for PDB tagged by rs5742915, which is located within the PML gene. Here, we have assessed the candidacy of PML as the predisposing gene for PDB at this locus. We found that the PDB-risk allele of rs5742915 was associated with lower PML expression and that PML expression in blood cells from individuals with PDB was lower than in controls. The differentiation, survival and resorptive activity of osteoclasts prepared from Pml−/− mice was increased compared with wild type. Furthermore, the inhibitory effect of IFN-γ on osteoclast formation from Pml−/− was significantly blunted compared with wild type. Bone nodule formation was also increased in osteoblasts from Pml−/− mice when compared with wild type. Although microCT analysis of trabecular bone showed no differences between Pml−/− mice and wild type, bone histomorphometry showed that Pml−/− mice had high bone turnover with increased indices of bone resorption and increased mineral apposition rate. These data indicate that reduced expression of PML predisposes an individual to PDB and identify PML as a novel regulator of bone metabolism.
This article has an associated First Person interview with the first author of the paper.
Hg(II) Ion-Selective Electrodes with PVC Membranes Based on Bis-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one
Authors: Isildak Omer , Yildiz Ilyas , Erenler Ramazan , Dag Besir , Isildak Ibrahim 
Published: March 2022

Abstract
A new solid-state contact potentiometric membrane electrode was developed based on bis-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one (ionophore), which acts selectively towards the mercury(II) ion. The ionophore was synthesized by the treatment of an amino derivative with oxybis dibenzaldehyde. The potentiometric behavior of an electrode was investigated in the concentration range from 1.0 × 10−2 to 1.0 × 10−6 mol L−1 for mercury(II) ion. The electrode displayed a good linearity (R2 = 0.9997) with the detection limit of 1.2 × 10−7 mol L−1 and showed a very high selectivity against Hg(II) ion without being affected by the presence of interfering ions. The electrode exhibited a potential change of 62.0 ± 2.0 mV for each ten-fold increase in concentration of mercury(II) ion. Potentiometric response of the electrode was investigated in the pH range from 3.0 to 10.0. In addition to this electrode being used to determine mercury(II) in different water samples, it can also be used with EDTA as an indicator electrode in the potentiometric titration of mercury(II) ion. Since the developed electrode displayed good potentiometric performance, it has potential to be used in environmental and biological samples for detection of mercury(II) ions.
Validation of different protocols of inferior alveolar canal tracing using cone beam computed tomography (CBCT)
Authors: Fahd Ali , Temerek Ahmed Talaat , Kenawy Sarah Mohammed 
Published: March 2022

Objectives The objective of this study was to evaluate, compare and validate different protocols of inferior alveolar canal tracing. Methods 60 DICOM files with a total of 80 inferior alveolar canals were retrieved and imported to a third-party software where all proposed protocols can be performed. Initially, inferior alveolar canal was traced by two oral and maxillofacial radiologists together on cone beam CT cross-sectional images and considered as the baseline for future comparisons. Oral and maxillofacial surgeon performed the proposed different protocols. The protocols were color-coded differently by the surgeon before being compared with the baseline canal by the radiologists through a 5-point scale. Results Results showed that no single protocol was successful in all cases, even the cross-sectional protocol. According to the present study, the hybrid protocol was the most accurate while the automatic protocol was the least accurate. Conclusions The hybrid protocol was reliable and showed the highest number of successful applications followed by the commonly used cross-sectional protocol. Dental practitioners should be aware of the application of multiple protocols and their pros and cons as no single protocol was successful in all the cases. Applying the same protocols on a larger sample size using different cone beam CT and multislice CT machines with different exposure parameters is recommended.
The differentiation of mesenchymal bone marrow stem cells into nerve cells induced by Chromolaena odorata extracts
Authors: Eriani Kartini , Desriani Desriani , Suhartono Suhartono , Br Sibarani Miftahul Jannah , Ichsan Ichsan , Syafrizal Dedy , Asmara Hadhymulya 
Published: March 2022

Background: Mesenchymal stem cells (MSCs) can differentiate into nerve cells with an induction from chemical compounds in medium culture. Chromolaena odorata contains active compounds, such as alkaloids and flavonoids, that can initiate the transformation of MSCs into nerve cells. The aim of this study was to determine the potential of methanol extracted C. odorata leaf to induce the differentiation of bone marrow MSCs into nerve cells. Methods: A serial concentration of C. odorata leaf extract (0.7–1.0 mg/mL) with two replications was used. The parameters measured were the number of differentiated MSCs into nerve cells (statistically analyzed using ANOVA) and cell confirmation using reverse transcription polymerase chain reaction (RT-PCR). Results: The results showed that the C. odorata extract had a significant effect on the number MSCs differentiating into nerve cells (p < 0.05) on the doses of 0.8 mg/ml with 22.6%. Molecular assay with RT-PCR confirmed the presence of the nerve cell gene in all of the samples. Conclusions: In conclusion, this study showed the potential application of C. odorata leaf extract in stem cell therapy for patients experiencing neurodegeneration by inducing the differentiation of MSCs into nerve cells.
Light wave filtration by colored cellophane to optimize microscopic contrast ratio in pulmonary tuberculosis sputum observation
Authors: Edbert Daniel , Mertaniasih Ni Made , Endraswari Pepy Dwi , Koendhori Eko Budi 
Published: March 2022

Introduction: Indonesia has the second highest number of Tuberculosis (TB) in the world and tuberculosis still pose as a global health priority problem. For the diagnostics, microscopy is still one of important modalities in TB diagnosis especially in peripheral areas for screening, case-finding, and treatment evaluation. The use of microscopy is limited to operator visual burden and specimen load. This study aims to modify the use of the microscope by using everyday item to increase microscope operator workload. Method: This is an analytic study of the use of colored cellophane in microscopic examination of sputum smear from 24 pulmonary TB patients from Jakarta and Surabaya. The sputum samples were confirmed positive by standardized ZN-AFB microscopy and/or Xpert MTB/RIF. Each sputum were made into two slides, for each slide, 10 oil immersion fields were captured using Optilab microscope camera mounted on microscope. A total of 480 data pairs were analysed by comparing color characteristic of acid-fast bacilli pixels and its adjacent background pixels and by counting Acid fast Bacilli for each observation field. IUATLD scale were also observed by 3 operators. Results: Contrast ratio for each AFB and its adjacent pixels were significantly higher in groups using cellophane filter than without using filter (p = 0.001). AFB identification per image acquired using filter were not significantly higher (p=0.815). Conclusion: Colored cellophane increases contrast ratio and eases microscopic examination, thus increases sputum smear microscopic observation capability. Also it might increase identification capability with digital image processing.
Protocol for a feasibility study of longitudinal surveys to assess the impact of policies on tobacco use among school-going adolescents in South Asia
Authors: Mishu Masuma Pervin , Siddiqi Kamran , McNeill Ann , Kanaan Mona , Jackson Cath , Huque Rumana , Kanan Sushama , Abdullah S.M. , Fieroze Fariza , Garg Suneela , Singh M. Meghachandra , Borle Amod L. , Deshmukh Chetana , Akhter Zohaib , Mazhar Laraib , Khan Zohaib , Rehman Khalid , Ullah Safat , Han Lu , Readshaw Anne , Iqbal Romaina 
Published: March 2022

Background: Smokeless tobacco (ST) use is common among youth in South Asia where 85% of the world’s 300 million ST users live and use the most lethal ST forms. Little is known about the impact of tobacco control policies on the youth ST uptake in those countries. We planned to conduct longitudinal surveys among school going adolescents to evaluate existing tobacco control policies on tobacco uptake and use, and a feasibility study for that prospective, observational cohort study. Study objectives: (1) To demonstrate the feasibility of selection, recruitment and retention of schools and of study participants; (2) To assess the feasibility and acceptability of the study procedure and study tool (questionnaire); (3) To evaluate if the questionnaire can assess tobacco uptake and use, and their potential predictors. Methods and analysis: The feasibility study will be conducted in two administrative areas within each of three South Asian countries: Bangladesh, India and Pakistan. We will use both quantitative and qualitative data collection methods. Eight eligible schools will be randomly selected within purposively selected sub-districts from each country. We plan to conduct one baseline and one follow up survey among students of grade 6-8, one year apart. At each time point, data on tobacco uptake and potential predictors will be collected from students via self-administered questionnaires that were designed for the longitudinal study. The qualitative component will be embedded into the study with each round of data collection to assess the acceptability of the study instrument (questionnaire) and data collection methods, via focus group discussions with students and semi-structured interviews with schoolteachers. Recruitment and retention rates, completeness of the questionnaires, frequencies and associations of tobacco use and explanatory variables will be reported. Data gathered from the focus group and interviews will be analysed using the framework approach.
Inductive Representation Learning on Dynamic Stock Co-Movement Graphs for Stock Predictions
Authors: Tian Hu , Zheng Xiaolong , Zhao Kang , Liu Maggie Wenjing , Zeng Daniel Dajun 
Published: March 2022

Co-movement among individual firms’ stock prices can reflect complex interfirm relationships. This paper proposes a novel method to leverage such relationships for stock price predictions by adopting inductive graph representation learning on dynamic stock graphs constructed based on historical stock price co-movement. To learn node representations from such dynamic graphs for better stock predictions, we propose the hybrid-attention dynamic graph neural network, an inductive graph representation learning method. We also extended mini-batch gradient descent to inductive representation learning on dynamic stock graphs so that the model can update parameters over mini-batch stock graphs with higher training efficiency. Extensive experiments on stocks from different markets and trading simulations demonstrate that the proposed method significantly improves stock predictions. The proposed method can have important implications for the management of financial portfolios and investment risk. Summary of Contribution: Accurate predictions of stock prices have important implications for financial decisions. In today’s economy, individual firms are increasingly connected via different types of relationships. As a result, firms’ stock prices often feature synchronous co-movement patterns. This paper represents the first effort to leverage such phenomena to construct dynamic stock graphs for stock predictions. We develop hybrid-attention dynamic graph neural network (HAD-GNN), an inductive graph representation learning framework for dynamic stock graphs to incorporate temporal and graph attention mechanisms. To improve the learning efficiency of HAD-GNN, we also extend the mini-batch gradient descent to inductive representation learning on such dynamic graphs and adopt a t-batch training mechanism (t-BTM). We demonstrate the effectiveness of our new approach via experiments based on real-world data and simulations.
Price Optimization Under the Finite-Mixture Logit Model
Authors: van de Geer Ruben , den Boer Arnoud V. 
Published: March 2022

We consider price optimization under the finite-mixture logit model. This model assumes that customers belong to one of a number of customer segments, where each customer segment chooses according to a multinomial logit model with segment-specific parameters. We reformulate the corresponding price optimization problem and develop a novel characterization. Leveraging this new characterization, we construct an algorithm that obtains prices at which the revenue is guaranteed to be at least [Formula: see text] times the maximum attainable revenue for any prespecified [Formula: see text]. Existing global optimization methods require exponential time in the number of products to obtain such a result, which practically means that the prices of only a handful of products can be optimized. The running time of our algorithm, however, is exponential in the number of customer segments and only polynomial in the number of products. This is of great practical value, because in applications, the number of products can be very large, whereas it has been found in various contexts that a low number of segments is sufficient to capture customer heterogeneity appropriately. The results of our numerical study show that (i) ignoring customer segmentation can be detrimental for the obtained revenue, (ii) heuristics for optimization can get stuck in local optima, and (iii) our algorithm runs fast on a broad range of problem instances. This paper was accepted by Omar Besbes, revenue management and market analytics.
Mid-term improvement of cognitive performance after total hip arthroplasty in patients with osteoarthritis of the hip
Authors: Strahl André , Kazim Murteza Ali , Kattwinkel Nils , Hauskeller Wiebke , Moritz Steffen , Arlt Sönke , Niemeier Andreas 
Published: March 2022

AimsThe aim of this study was to determine whether total hip arthroplasty (THA) for chronic hip pain due to unilateral primary osteoarthritis (OA) has a beneficial effect on cognitive performance.MethodsA prospective cohort study was conducted with 101 patients with end-stage hip OA scheduled for THA (mean age 67.4 years (SD 9.5), 51.5% female (n = 52)). Patients were assessed at baseline as well as after three and months. Primary outcome was cognitive performance measured by d2 Test of Attention at six months, Trail Making Test (TMT), FAS-test, Rivermead Behavioural Memory Test (RBMT; story recall subtest), and Rey-Osterrieth Complex Figure Test (ROCF). The improvement of cognitive performance was analyzed using repeated measures analysis of variance.ResultsAt six months, there was significant improvement in attention, working speed and concentration (d2-test; p < 0.001), visual construction and visual memory (ROCF; p < 0.001), semantic memory (FAS-test; p = 0.009), verbal episodic memory (RBMT; immediate recall p = 0.023, delayed recall p = 0.026), as well as pain (p < 0.001) with small to large effect sizes. Attention, concentration, and visual as well as verbal episodic memory improved significantly with medium effect sizes over η2partial= 0.06. In these cognitive domains the within-group difference exceeded the minimum clinically important difference.ConclusionTHA is associated with clinically relevant postoperative improvement in the cognitive functions of attention, concentration, and memory. These data support the concept of a broad interaction of arthroplasty with central nervous system function. Cite this article: Bone Joint J 2022;104-B(3):331–340.
High revision rates following repeat septic revision after failed one-stage exchange for periprosthetic joint infection in total knee arthroplasty
Authors: Neufeld Michael E. , Liechti Emanuel F. , Soto Fernando , Linke Philip , Busch Sophia-Marlene , Gehrke Thorsten , Citak Mustafa 
Published: March 2022

Aims The outcome of repeat septic revision after a failed one-stage exchange for periprosthetic joint infection (PJI) in total knee arthroplasty (TKA) remains unknown. The aim of this study was to report the infection-free and all-cause revision-free survival of repeat septic revision after a failed one-stage exchange, and to determine whether the Musculoskeletal Infection Society (MSIS) stage is associated with subsequent infection-related failure. Methods We retrospectively reviewed all repeat septic revision TKAs which were undertaken after a failed one-stage exchange between 2004 and 2017. A total of 33 repeat septic revisions (29 one-stage and four two-stage) met the inclusion criteria. The mean follow-up from repeat septic revision was 68.2 months (8.0 months to 16.1 years). The proportion of patients who had a subsequent infection-related failure and all-cause revision was reported and Kaplan-Meier survival for these endpoints was determined. Patients were categorized according to the MSIS staging system, and the association with subsequent infection was analyzed. Results At the most recent follow-up, 17 repeat septic revisions (52%) had a subsequent infection-related failure and the five-year infection-free survival was 59% (95% confidence interval (CI) 39 to 74). A total of 19 underwent a subsequent all-cause revision (58%) and the five-year all-cause revision-free survival was 47% (95% CI 28 to 64). The most common indication for the first subsequent aseptic revision was loosening. The MSIS stage of the host status (p = 0.663) and limb status (p = 1.000) were not significantly associated with subsequent infection-related failure. Conclusion Repeat septic revision after a failed one-stage exchange TKA for PJI is associated with a high rate of subsequent infection-related failure and all-cause revision. Patients should be counselled appropriately to manage expectations. The host and limb status according to the MSIS staging system were not associated with subsequent infection-related failure. Cite this article: Bone Joint J 2022;104-B(3):386–393.