bluuebunny/crossref_metadata_2025_split huggingface dataset:
Household income and medical help-seeking for fertility problems among a representative population in Japan
Authors: Iba Arisa , Maeda Eri , Jwa Seung Chik , Yanagisawa-Sugita Ayako , Saito Kazuki , Kuwahara Akira , Saito Hidekazu , Terada Yukihiro , Ishihara Osamu , Kobayashi Yasuki 
Published: August 2021

Abstract
Background
Fertility treatments help many infertile couples to have children. However, disparities exist in access to fertility tests and treatments. We investigated the association between household income and medical help-seeking for fertility in Japan.

Methods
We conducted a cross-sectional study using nationally representative data from the National Fertility Survey 2015. Respondents were 6598 married women younger than 50 years old. The primary outcome was medical help-seeking for fertility among those who experienced fertility problems. Multiple logistic regression models were used to assess the association between household income and medical help-seeking, adjusting for age, length of marriage, educational level, employment status, number of children, childbearing desires, living with parents, and region of residence.

Results
Among 2253 (34%) women who experienced fertility problems, 1154 (51%) sought medical help. The proportion of help-seekers increased linearly from 43% in the low-income group (< 4 million Japanese yen [JPY]) to 59% in the high-income group (≥ 8 million JPY) (P for trend < 0.001). Respondents with upper-middle (6–8 million JPY) or high household income were more likely to seek medical help, compared to those with low household income: adjusted odds ratio [aOR] 1.37 (95% confidence interval [CI]: 1.00–1.86) and aOR 1.78 (95% CI: 1.29–2.47), respectively.

Conclusions
We found that higher household income was associated with a higher probability of seeking medical help among Japanese women who experienced fertility problem. Along with policy discussion about additional financial support, further studies from societal, cultural, or psychological views are required.
Evolutionary trajectory of SARS-CoV-2 and emerging variants
Authors: Singh Jalen , Pandit Pranav , McArthur Andrew G. , Banerjee Arinjay , Mossman Karen 
Published: August 2021

AbstractThe emergence of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and more recently, the independent evolution of multiple SARS-CoV-2 variants has generated renewed interest in virus evolution and cross-species transmission. While all known human coronaviruses (HCoVs) are speculated to have originated in animals, very little is known about their evolutionary history and factors that enable some CoVs to co-exist with humans as low pathogenic and endemic infections (HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1), while others, such as SARS-CoV, MERS-CoV and SARS-CoV-2 have evolved to cause severe disease. In this review, we highlight the origins of all known HCoVs and map positively selected for mutations within HCoV proteins to discuss the evolutionary trajectory of SARS-CoV-2. Furthermore, we discuss emerging mutations within SARS-CoV-2 and variants of concern (VOC), along with highlighting the demonstrated or speculated impact of these mutations on virus transmission, pathogenicity, and neutralization by natural or vaccine-mediated immunity.
Temporal response of an injectable calcium phosphate material in a critical size defect
Authors: Landeck Jacob T. , Walsh William R. , Oliver Rema A. , Wang Tian , Gordon Mallory R. , Ahn Edward , White Colin D. 
Published: August 2021

AbstractBackgroundCalcium phosphate-based bone graft substitutes are used to facilitate healing in bony defects caused by trauma or created during surgery. Here, we present an injectable calcium phosphate-based bone void filler that has been purposefully formulated with hyaluronic acid to offer a longer working time for ease of injection into bony defects that are difficult to access during minimally invasive surgery.MethodsThe bone substitute material deliverability and physical properties were characterized, and in vivo response was evaluated in a critical size distal femur defect in skeletally mature rabbits to 26 weeks. The interface with the host bone, implant degradation, and resorption were assessed with time.ResultsThe calcium phosphate bone substitute material could be injected as a paste within the working time window of 7–18 min, and then self-cured at body temperature within 10 min. The material reached a maximum ultimate compressive strength of 8.20 ± 0.95 MPa, similar to trabecular bone. The material was found to be biocompatible and osteoconductive in vivo out to 26 weeks, with new bone formation and normal bone architecture observed at 6 weeks, as demonstrated by histological evaluation, microcomputed tomography, and radiographic evaluation.ConclusionsThese findings show that the material properties and performance are well suited for minimally invasive percutaneous delivery applications.
Role of pre-operative red cell distribution width estimation in the prediction of in-hospital mortality after off-pump coronary artery bypass grafting
Authors: Joshi Dharmendra , Chowdhury Md. Abir Tazim , Alauddin Md. , Ranjan Redoy , Khan Omar Sadeque , Hoque Md. Rezwanul 
Published: August 2021

Abstract
Background
Red cell distribution width (RDW) level is routinely provided in a simple and inexpensive complete blood count report. However, RDW is sometimes overlooked. Recently a higher RDW level is found associated with postoperative mortality after off-pump coronary artery bypass. Many risk-prediction tools are available, like the European System for Cardiac Operative Risk Evaluation, Society of Thoracic Surgeons score, etc. but all need improvement for better prediction. So, a new risk-factor should be discovered which is simple enough for clinical use and cost-effective, and improves the risk assessment tools that help to predict and avoid preventable mortality following cardiac surgery.

Methods
The prospective study was conducted, taking a total of 150 patients of coronary artery disease who underwent elective isolated off-pump coronary artery bypass. The study population was grouped according to their preoperative RDW level as Group A (RDW ≤ 14%), Group B (RDW 14–16%), and Group C (RDW ≥ 16%). The receiver operating characteristic (ROC) curve was constructed and multivariate regression analysis was done to see the predictive value of RDW for in-hospital mortality.

Results
The mortality rate was 2.7%, N = 150. ROC curve revealed Area Under the Curve 0.841 and p = 0.020 that indicates the RDW as the reliable predictor for in-hospital mortality. Multivariate regression analysis showed the RDW to be the only variable independently predicting in-hospital mortality after off-pump coronary artery bypass among possible haematological predictors. (OR 1.838, 95% CI 1.061–3.186, p = 0.030).

Conclusion
Preoperative raised RDW level is a novel predictor of in-hospital mortality after off-pump coronary artery bypass. Further studies should be done to determine the associated mechanism.
Retrospective study on growth in infants with isolated Robin sequence treated with the Tuebingen Palate Plate
Authors: Wiechers Cornelia , Iffländer Regina , Gerdes Rieke , Ciuffolotti Melissa , Arand Jörg , Weise Christina , Peters Katharina , Grandke Bärbel , Reinert Siegmar , Koos Bernd , Poets Christian F. 
Published: August 2021

AbstractBackgroundChildren with Robin sequence (RS) are at risk of growth failure, mainly due to their increased work of breathing and feeding difficulties. Various conservative and surgical treatment approaches exist, but their impact on weight gain has not yet been adequately addressed. A functional treatment concept, used in our center for > 20 years, includes a pre-epiglottic baton plate (Tuebingen palatal plate) and intensive feeding training.ObjectiveTo investigate the effect of the Tuebingen treatment protocol on growth and weight trajectories during infancy.MethodsThis retrospective study analyzed longitudinal data from infants with isolated RS admitted to Tuebingen University Children’s Hospital, Germany between 1998 and 2019. Through our electronic patient database, we evaluated anthropometric parameters until reaching 1-year follow-up. Results are shown as median (IQR).ResultsIn 307 infants analyzed, median Z-score for weight decreased from − 0.28 at birth to − 1.12 upon admission to our center at a median age of 22 days. Z-score then remained largely unchanged until discharge (Z-score difference, − 0.08), while the proportion of infants receiving tube feedings decreased from 55.1 to 13.7%. Z-score subsequently increased from − 1.17 at discharge to − 0.44 at the 1-year follow-up (p < 0.001).ConclusionBased on a comparatively large cohort, this functional treatment was associated with better weight gain and improved feeding. As RS infants often show postnatal growth failure, weight monitoring may be a valuable parameter for monitoring treatment effectiveness.Clinical Trial RegistrationNot necessary due to the retrospective design.
Endophenotypical drift in Huntington’s disease: a 5-year follow-up study
Authors: Hellem Marie N. N. , Hendel Rebecca K. , Vinther-Jensen Tua , Larsen Ida U. , Nielsen Troels T. , Hjermind Lena E. , Budtz-Jørgensen Esben , Vogel Asmus , Nielsen Jørgen E. 
Published: August 2021

AbstractBackgroundHuntington’s disease (HD) is clinically characterized by progressing motor, cognitive and psychiatric symptoms presenting as varying phenotypes within these three major symptom domains. The disease is caused by an expanded CAG repeat tract in the huntingtin gene and the pathomechanism leading to these endophenotypes is assumed to be neurodegenerative. In 2012/2013 we recruited 107 HD gene expansion carriers (HDGECs) and examined the frequency of the three cardinal symptoms and in 2017/2018 we followed up 74 HDGECs from the same cohort to describe the symptom trajectories and individual drift between the endophenotypes as well as potential predictors of progression and remission.ResultsWe found higher age to reduce the probability of improving on psychiatric symptoms; increasing disease burden score ((CAG-35.5) * age) to increase the risk of developing cognitive impairment; increasing disease burden score and shorter education to increase the risk of motor onset while lower disease burden score and higher Mini Mental State Examination increased the probability of remaining asymptomatic. We found 23.5% (N = 8) to improve from their psychiatric symptoms.ConclusionsThere is no clear pattern in the development of or drift between endophenotypes. In contrast to motor and cognitive symptoms we find that psychiatric symptoms may resolve and thereby not entirely be caused by neurodegeneration. The probability of improving from psychiatric symptoms is higher in younger age and advocates for a potential importance of early treatment.
Long-term efficacy and safety of sapropterin in patients who initiated sapropterin at < 4 years of age with phenylketonuria: results of the 3-year extension of the SPARK open-label, multicentre, randomised phase IIIb trial
Authors: Muntau Ania C. , Burlina Alberto , Eyskens François , Freisinger Peter , Leuzzi Vincenzo , Sivri Hatice Serap , Gramer Gwendolyn , Pazdírková Renata , Cleary Maureen , Lotz-Havla Amelia S. , Lane Paul , Alvarez Ignacio , Rutsch Frank 
Published: August 2021

AbstractBackgroundDuring the initial 26-week SPARK (Safety Paediatric efficAcy phaRmacokinetic with Kuvan®) study, addition of sapropterin dihydrochloride (Kuvan®; a synthetic formulation of the natural cofactor for phenylalanine hydroxylase, tetrahydrobiopterin; BH4), to a phenylalanine (Phe)-restricted diet, led to a significant improvement in Phe tolerance versus a Phe-restricted diet alone in patients aged 0–4 years with BH4-responsive phenylketonuria (PKU) or mild hyperphenylalaninaemia (HPA). Based on these results, the approved indication for sapropterin in Europe was expanded to include patients < 4 years of age. Herein, we present results of the SPARK extension study (NCT01376908), evaluating the long-term safety, dietary Phe tolerance, blood Phe concentrations and neurodevelopmental outcomes in patients < 4 years of age at randomisation, over an additional 36 months of treatment with sapropterin.ResultsAll 51 patients who completed the 26-week SPARK study period entered the extension period. Patients who were previously treated with a Phe-restricted diet only (‘sapropterin extension’ group; n = 26), were initiated on sapropterin at 10 mg/kg/day, which could be increased up to 20 mg/kg/day. Patients previously treated with sapropterin plus Phe-restricted diet, remained on this regimen in the extension period (‘sapropterin continuous’ group; n = 25). Dietary Phe tolerance increased significantly at the end of the study versus baseline (week 0), by 38.7 mg/kg/day in the ‘sapropterin continuous’ group (95% CI 28.9, 48.6;p < 0.0001). In the ‘sapropterin extension’ group, a less pronounced effect was observed, with significant differences versus baseline (week 27) only observed between months 9 and 21; dietary Phe tolerance at the end of study increased by 5.5 mg/kg/day versus baseline (95% CI − 2.8, 13.8;p = 0.1929). Patients in both groups had normal neuromotor development and growth parameters.ConclusionsLong-term treatment with sapropterin plus a Phe-restricted diet in patients who initiated sapropterin at < 4 years of age with BH4-responsive PKU or mild HPA maintained improvements in dietary Phe tolerance over 3.5 years. These results continue to support the favourable risk/benefit profile for sapropterin in paediatric patients (< 4 years of age) with BH4-responsive PKU. Frequent monitoring of blood Phe levels and careful titration of dietary Phe intake to ensure adequate levels of protein intake is necessary to optimise the benefits of sapropterin treatment.Trial registrationClinicalTrials.gov, NCT01376908. Registered 17 June 2011,https://clinicaltrials.gov/ct2/show/NCT01376908.
Preventive use of nitisinone in alkaptonuria
Authors: Wolffenbuttel Bruce H. R. , Heiner-Fokkema M. Rebecca , van Spronsen Francjan J. 
Published: August 2021

AbstractAlkaptonuria (AKU, OMIM 203500) is a rare congenital disorder caused by a deficiency of the enzyme homogentisate-1,2,-dioxygenase. The long-term consequences of AKU are joint problems, cardiac valve abnormalities and renal problems. Landmark intervention studies with nitisinone 10 mg daily, suppressing an upstream enzyme activity, demonstrated its beneficial effects in AKU patients with established complications, which usually start to develop in the fourth decade. Lower dose of nitisinone in the range of 0.2–2 mg daily will already reduce urinary homogentisic acid (uHGA) excretion by > 90%, which may prevent AKU-related complications earlier in the course of the disease while limiting the possibility of side-effects related to the increase of plasma tyrosine levels caused by nitisinone. Future preventive studies should establish the lowest possible dose for an individual patient, the best age to start treatment and also collect evidence to which level uHGA excretion should be reduced to prevent complications.
Probability calibration-based prediction of recurrence rate in patients with diffuse large B-cell lymphoma
Authors: Fan Shuanglong , Zhao Zhiqiang , Zhang Yanbo , Yu Hongmei , Zheng Chuchu , Huang Xueqian , Yang Zhenhuan , Xing Meng , Lu Qing , Luo Yanhong 
Published: August 2021

AbstractBackgroundAlthough many patients receive good prognoses with standard therapy, 30–50% of diffuse large B-cell lymphoma (DLBCL) cases may relapse after treatment. Statistical or computational intelligent models are powerful tools for assessing prognoses; however, many cannot generate accurate risk (probability) estimates. Thus, probability calibration-based versions of traditional machine learning algorithms are developed in this paper to predict the risk of relapse in patients with DLBCL.MethodsFive machine learning algorithms were assessed, namely, naïve Bayes (NB), logistic regression (LR), random forest (RF), support vector machine (SVM) and feedforward neural network (FFNN), and three methods were used to develop probability calibration-based versions of each of the above algorithms, namely, Platt scaling (Platt), isotonic regression (IsoReg) and shape-restricted polynomial regression (RPR). Performance comparisons were based on the average results of the stratified hold-out test, which was repeated 500 times. We used the AUC to evaluate the discrimination ability (i.e., classification ability) of the model and assessed the model calibration (i.e., risk prediction accuracy) using the H-L goodness-of-fit test, ECE, MCE and BS.ResultsSex, stage, IPI, KPS, GCB, CD10 and rituximab were significant factors predicting the 3-year recurrence rate of patients with DLBCL. For the 5 uncalibrated algorithms, the LR (ECE = 8.517, MCE = 20.100, BS = 0.188) and FFNN (ECE = 8.238, MCE = 20.150, BS = 0.184) models were well-calibrated. The errors of the initial risk estimate of the NB (ECE = 15.711, MCE = 34.350, BS = 0.212), RF (ECE = 12.740, MCE = 27.200, BS = 0.201) and SVM (ECE = 9.872, MCE = 23.800, BS = 0.194) models were large. With probability calibration, the biased NB, RF and SVM models were well-corrected. The calibration errors of the LR and FFNN models were not further improved regardless of the probability calibration method. Among the 3 calibration methods, RPR achieved the best calibration for both the RF and SVM models. The power of IsoReg was not obvious for the NB, RF or SVM models.ConclusionsAlthough these algorithms all have good classification ability, several cannot generate accurate risk estimates. Probability calibration is an effective method of improving the accuracy of these poorly calibrated algorithms. Our risk model of DLBCL demonstrates good discrimination and calibration ability and has the potential to help clinicians make optimal therapeutic decisions to achieve precision medicine.
SorGSD: updating and expanding the sorghum genome science database with new contents and tools
Authors: Liu Yuanming , Wang Zhonghuang , Wu Xiaoyuan , Zhu Junwei , Luo Hong , Tian Dongmei , Li Cuiping , Luo Jingchu , Zhao Wenming , Hao Huaiqing , Jing Hai-Chun 
Published: August 2021

Abstract
Background
As the fifth major cereal crop originated from Africa, sorghum (Sorghum bicolor) has become a key C4 model organism for energy plant research. With the development of high-throughput detection technologies for various omics data, much multi-dimensional and multi-omics information has been accumulated for sorghum. Integrating this information may accelerate genetic research and improve molecular breeding for sorghum agronomic traits.

Results
We updated the Sorghum Genome SNP Database (SorGSD) by adding new data, new features and renamed it to Sorghum Genome Science Database (SorGSD). In comparison with the original version SorGSD, which contains SNPs from 48 sorghum accessions mapped to the reference genome BTx623 (v2.1), the new version was expanded to 289 sorghum lines with both single nucleotide polymorphisms (SNPs) and small insertions/deletions (INDELs), which were aligned to the newly assembled and annotated sorghum genome BTx623 (v3.1). Moreover, phenotypic data and panicle pictures of critical accessions were provided in the new version. We implemented new tools including ID Conversion, Homologue Search and Genome Browser for analysis and updated the general information related to sorghum research, such as online sorghum resources and literature references. In addition, we deployed a new database infrastructure and redesigned a new user interface as one of the Genome Variation Map databases. The new version SorGSD is freely accessible online at http://ngdc.cncb.ac.cn/sorgsd/.

Conclusions
SorGSD is a comprehensive integration with large-scale genomic variation, phenotypic information and incorporates online data analysis tools for data mining, genome navigation and analysis. We hope that SorGSD could provide a valuable resource for sorghum researchers to find variations they are interested in and generate customized high-throughput datasets for further analysis.
Effectiveness of sarolaner in the clinical management of furuncular myiasis in dogs naturally infested with Dermatobia hominis (Diptera: Cuterebridae)
Authors: Andriotti Paula A. , Souza Clarissa P. , Oliveira Priscila C. , Melo Rodrigo C. , Verocai Guilherme G. , Fernandes Julio I. 
Published: August 2021

Abstract
Background
The human botfly, Dermatobia hominis, is a common cause of furuncular myiasis in dogs in Latin America. Lesions can be single or multiple, each harboring an individual larva, presented as an erythematous nodule that causes pruritus and pain. Typical treatment consists of sedation for removal of larvae by surgical incision or manual pressure. Medications to kill the larva before its extraction can reduce inflammation and discomfort and provide a less traumatic larval removal. Isoxazolines are broad-spectrum ectoparasiticides with larvicidal activity previously reported in the treatment of screwworm myiasis in companion animals. The aim of this study was to evaluate the effectiveness of sarolaner as part of the clinical management of furuncular myiasis in dogs caused by D. hominis larvae.

Methods
Ten short-haired mixed breed dogs naturally infested with D. hominis were enrolled. Clinical diagnosis was achieved by observation of skin nodules and visualization of larval motility through the lesion orifice. Sarolaner was administered at manufacturer recommended dose for fleas and ticks. Lesions were reexamined 24 h post-treatment and assessed for viability of larvae. Larvae were removed by digital compression and identified as D. hominis.

Results
Seventy-five D. hominis larvae were retrieved from ten dogs. No live larvae were observed, demonstrating 100% larvicidal efficacy of sarolaner. Skin lesions were healed 30 days post-treatment and new lesions were not observed.

Conclusions
Sarolaner seems to be effective as larvicidal treatment for dogs with furuncular myiasis, reducing discomfort caused by the presence of the larva in the skin and facilitating its safe removal.

Graphical abstract
The hepatoprotective effects of Pyrus biossieriana buhse leaf extract on tert-butyl hydroperoxide toxicity in HepG2 cell line
Authors: Mir Hamed , Elieh Ali Komi Daniel , Pouramir Mahdi , Parsian Hadi , Moghadamnia Ali Akbar , Seyfizadeh Nayer , Lakzaei Mostafa 
Published: August 2021

AbstractObjectiveIn present study, the effects of the leaf extract ofPyrus biossierianaBuhse ontert-Butyl hydroperoxide (t-BHP) induced toxicity in the HepG2 cell line were investigated.ResultsHepG2 cells were exposed to different concentrations of both extract (1.5, 2.0, and 2.5 mg/mL) and t-BHP (100, 150, and 200 μM). The total flavonoid and phenolic contents, the cell viability, lipid peroxidation, NO generation, and the total antioxidant capacity in cell media were assessed. The amount of arbutin was estimated 12.6% of the dry weight of leaves (equivalent to 126 mg/g). Additionally, the amounts of flavonoids and phenols in extract were estimated 119 mg/g and 418 mg/g, respectively. The cells incubated with t-BHP showed a significant decrease in survival (p < 0.001). Preincubation with extract (1.5 mg/mL and 2.0 mg/mL) attenuated the t-BHP toxicity and increased the cell viability in cells exposed even to the highest concentration of t-BHP (200 μM) (p value < 0.001, and p value = 0.035) respectively. Additionally, treatment with extract reduced the cell growth suppression caused by t-BHP. TheP. biossierianaBuhse leaf extract at concentrations of 1.5 and 2.0 mg/mL is capable of attenuating t-BHP-induced cytotoxicity in HepG2 cells.