bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA methylation and gene expression changes in mouse pre- and post-implantation embryos generated by intracytoplasmic sperm injection with artificial oocyte activation
Authors: Yin Mingru , Yu Weina , Li Wenzhi , Zhu Qianqian , Long Hui , Kong Pengcheng , Lyu Qifeng 
Published: November 2021

Abstract
Background
The application of artificial oocyte activation (AOA) after intracytoplasmic sperm injection (ICSI) is successful in mitigating fertilization failure problems in assisted reproductive technology (ART). Nevertheless, there is no relevant study to investigate whether AOA procedures increase developmental risk by disturbing subsequent gene expression at different embryonic development stages.

Methods
We used a mouse model to explore the influence of AOA treatment on pre- and post-implantation events. Firstly, the developmental potential of embryos with or without AOA treatment were assessed by the rates of fertilization and blastocyst formation. Secondly, transcriptome high-throughput sequencing was performed among the three groups (ICSI, ICSI-AOA and dICSI-AOA groups). The hierarchical clustering and Principal Component Analysis (PCA) analysis were used. Subsequently, Igf2r/Airn methylation analysis were detected using methylation-specific PCR sequencing following bisulfite treatment. Finally, birth rate and birth weight were examined following mouse embryo transfer.

Results
The rates of fertilization and blastocyst formation were significantly lower in oocyte activation-deficient sperm injection group (dICSI group) when compared with the ICSI group (30.8 % vs. 84.4 %, 10.0 % vs. 41.5 %). There were 133 differentially expressed genes (DEGs) between the ICSI-AOA group and ICSI group, and 266 DEGs between the dICSI-AOA group and ICSI group. In addition, the imprinted gene, Igf2r is up regulated in AOA treatment group compared to control group. The Igf2r/Airn imprinted expression model demonstrates that AOA treatment stimulates maternal allele-specific mehtylation spreads at differentially methylated region 2, followed by the initiation of paternal imprinted Airn long non-coding (lnc) RNA, resulting in the up regulated expression of Igf2r. Furthermore, the birth weight of newborn mice originating from AOA group was significantly lower compared to that of ICSI group. The pups born following AOA treatment did not show any other abnormalities during early development. All offspring mated successfully with fertile controls.

Conclusions
AOA treatment affects imprinted gene Igf2r expression and mehtylation states in mouse pre- and post-implantation embryo, which is regulated by the imprinted Airn. Nevertheless, no significant differences were found in post-natal growth of the pups in the present study. It is hoped that this study could provide valuable insights of AOA technology in assisted reproduction biology.
Potential value of the calibrated automated thrombogram in patients after a cerebral venous sinus thrombosis; an exploratory study
Authors: van der Bruggen Myrthe M. , Kremers Bram , van Oerle Rene , van Oostenbrugge Robert J. , ten Cate Hugo 
Published: November 2021

AbstractBackgroundCerebral venous sinus thrombosis (CVST) is a relatively rare, but potentially lethal condition. In approximately 15% of the patients, the cause of CVST remains unclear. Conventional clotting tests such as prothrombin time and activated partial thromboplastin time are not sensitive enough to detect prothrombotic conditions nor mild haemostatic abnormalities. The calibrated automated thrombogram (CAT) is a physiological function test that might be able to detect minor aberrations in haemostasis. Therefore, we aimed to detect the presence of a prothrombotic state in patients who endured idiopathic CVST with the CAT assay.MethodsFive adult patientswith an idiopathic, radiologically proven CVST that had been admitted during the past 3 years were included in this study. The control group consisted offiveage/gender matched healthy volunteers. Exclusion criteria were known haematological disorders, malignancy (current/past) or hormonal and anticoagulant therapy recipients. We obtained venous blood samples from all participants following cessation of anticoagulation. Using the CAT assay, we determined lag time, normalized endogenous thrombin potential (ETP), ETP reduction and normalized peak height. In addition, prothrombin concentrations were determined.ResultsWe found no significant differences in lag time (4.7 min [4.5–4.9] vs 5.3 min [3.7–5.7],p = 0.691), normalized ETP (142% [124–148] vs 124% [88–138],p = 0.222), ETP reduction (29% [26–35] vs 28% [24–58],p > 0.999), and normalized peak height (155% [153–175] vs 137 [94–154],p = 0.056) between patients and their age/gender matched controls. In addition, prothrombin concentrations did not significantly differ between patients and controls (120% [105–132] vs 127% [87–139],p > 0.999).ConclusionReasons for absent overt hypercoagulability within this study population may be the small patient sample, long time since the event (e.g. 3 years) and avoidance of acquired risk factors like oral contraception. Given the fact that CVST is a serious condition with a more than negligible risk of venous thrombosis event recurrence, exclusion of clinically relevant hypercoagulability remains a challenging topic to further study at the acute and later time points, particularly in patients with idiopathic CVST.
Addressing missing values in routine health information system data: an evaluation of imputation methods using data from the Democratic Republic of the Congo during the COVID-19 pandemic
Authors: Feng Shuo , Hategeka Celestin , Grépin Karen Ann 
Published: November 2021

Abstract
Background
Poor data quality is limiting the use of data sourced from routine health information systems (RHIS), especially in low- and middle-income countries. An important component of this data quality issue comes from missing values, where health facilities, for a variety of reasons, fail to report to the central system.

Methods
Using data from the health management information system in the Democratic Republic of the Congo and the advent of COVID-19 pandemic as an illustrative case study, we implemented seven commonly used imputation methods and evaluated their performance in terms of minimizing bias in imputed values and parameter estimates generated through subsequent analytical techniques, namely segmented regression, which is widely used in interrupted time series studies, and pre–post-comparisons through paired Wilcoxon rank-sum tests. We also examined the performance of these imputation methods under different missing mechanisms and tested their stability to changes in the data.

Results
For regression analyses, there were no substantial differences found in the coefficient estimates generated from all methods except mean imputation and exclusion and interpolation when the data contained less than 20% missing values. However, as the missing proportion grew, k-NN started to produce biased estimates. Machine learning algorithms, i.e. missForest and k-NN, were also found to lack robustness to small changes in the data or consecutive missingness. On the other hand, multiple imputation methods generated the overall most unbiased estimates and were the most robust to all changes in data. They also produced smaller standard errors than single imputations. For pre–post-comparisons, all methods produced p values less than 0.01, regardless of the amount of missingness introduced, suggesting low sensitivity of Wilcoxon rank-sum tests to the imputation method used.

Conclusions
We recommend the use of multiple imputation in addressing missing values in RHIS datasets and appropriate handling of data structure to minimize imputation standard errors. In cases where necessary computing resources are unavailable for multiple imputation, one may consider seasonal decomposition as the next best method. Mean imputation and exclusion and interpolation, however, always produced biased and misleading results in the subsequent analyses, and thus, their use in the handling of missing values should be discouraged.
Age at diagnosis in patients with chronic congenital endocrine conditions: a regional cohort study from a reference center for rare diseases
Authors: Kallali Wafa , Messiaen Claude , Saïdi Roumaisah , Lessim Soucounda , Viaud Magali , Dulon Jerome , Nedelcu Mariana , Samara Dinane , Houang Muriel , Donadille Bruno , Courtillot Carine , de Filippo GianPaolo , Carel Jean-Claude , Christin-Maitre Sophie , Touraine Philippe , Netchine Irene , Polak Michel , Léger Juliane 
Published: November 2021

Abstract
Background
For chronic congenital endocrine conditions, age at diagnosis is a key issue with implications for optimal management and psychological concerns. These conditions are associated with an increase in the risk of comorbid conditions, particularly as it concerns growth, pubertal development and fertility potential. Clinical presentation and severity depend on the disorder and the patient’s age, but diagnosis is often late.

Objective
To evaluate age at diagnosis for the most frequent congenital endocrine diseases affecting growth and/or development.

Patients and Methods
This observational cohort study included all patients (n = 4379) with well-defined chronic congenital endocrine diseases—non-acquired isolated growth hormone deficiency (IGHD), isolated congenital hypogonadotropic hypogonadism (ICHH), ectopic neurohypophysis (NH), Turner syndrome (TS), McCune-Albright syndrome (MAS), complete androgen insensitivity syndrome (CAIS) and gonadal dysgenesis (GD)—included in the database of a single multisite reference center for rare endocrine growth and developmental disorders, over a period of 14 years. Patients with congenital hypothyroidism and adrenal hyperplasia were excluded as they are generally identified during neonatal screening.

Results
Median age at diagnosis depended on the disease: first year of life for GD, before the age of five years for ectopic NH and MAS, 8–10 years for IGHD, TS (11% diagnosed antenatally) and CAIS and 17.4 years for ICHH. One third of the patients were diagnosed before the age of five years. Diagnosis occurred in adulthood in 22% of cases for CAIS, 11.6% for TS, 8.8% for GD, 0.8% for ectopic NH, and 0.4% for IGHD. A male predominance (2/3) was observed for IGHD, ectopic NH, ICHH and GD.

Conclusion
The early recognition of growth/developmental failure during childhood is essential, to reduce time-to-diagnosis and improve outcomes.
Burden of anemia and its underlying causes in 204 countries and territories, 1990–2019: results from the Global Burden of Disease Study 2019
Authors: Safiri Saeid , Kolahi Ali-Asghar , Noori Maryam , Nejadghaderi Seyed Aria , Karamzad Nahid , Bragazzi Nicola Luigi , Sullman Mark J. M. , Abdollahi Morteza , Collins Gary S. , Kaufman Jay S. , Grieger Jessica A. 
Published: November 2021

Abstract
Background
Anemia is a common disease which affects around 40% of children and 30% of reproductive age women and can have major health consequences. The present study reports the global, regional and national burden of anemia and its underlying causes between 1990 and 2019, by age, sex and socio-demographic index (SDI).

Methods
Publicly available data on the point prevalence and years lived with disability (YLDs) were retrieved from the global burden of disease (GBD) 2019 study for 204 countries and territories between 1990 and 2019. The point prevalence, YLD counts and rates per 100,000 population were presented, along with their corresponding 95% uncertainty intervals.

Results
In 2019, the global age-standardized point prevalence and YLD rates for anemia were 23,176.2 (22,943.5–23,418.6) and 672.4 (447.2–981.5) per 100,000 population, respectively. Moreover, the global age-standardized point prevalence and YLD rate decreased by 13.4% (12.1–14.5%) and 18.8% (16.9–20.8%), respectively, over the period 1990–2019. The highest national point prevalences of anemia were found in Zambia [49327.1 (95% UI: 46,838.5–51,700.1)], Mali [46890.1 (95% UI: 44,301.1–49,389.8)], and Burkina Faso [46117.2 (95% UI: 43,640.7–48,319.2)]. In 2019, the global point prevalence of anemia was highest in the 15–19 and 95+ age groups in females and males, respectively. Also, the burden of anemia was lower in regions with higher socio-economic development. Globally, most of the prevalent cases were attributable to dietary iron deficiency, as well as hemoglobinopathies and hemolytic anemias.

Conclusions
Anemia remains a major health problem, especially among females in less developed countries. The implementation of preventive programs with a focus on improving access to iron supplements, early diagnosis and the treatment of hemoglobinopathies should be taken into consideration.
The emerging role of ISWI chromatin remodeling complexes in cancer
Authors: Li Yanan , Gong Han , Wang Pan , Zhu Yu , Peng Hongling , Cui Yajuan , Li Heng , Liu Jing , Wang Zi 
Published: November 2021

AbstractDisordered chromatin remodeling regulation has emerged as an essential driving factor for cancers. Imitation switch (ISWI) family are evolutionarily conserved ATP-dependent chromatin remodeling complexes, which are essential for cellular survival and function through multiple genetic and epigenetic mechanisms. Omics sequencing and a growing number of basic and clinical studies found that ISWI family members displayed widespread gene expression and genetic status abnormalities in human cancer. Their aberrant expression is closely linked to patient outcome and drug response. Functional or componential alteration in ISWI-containing complexes is critical for tumor initiation and development. Furthermore, ISWI-non-coding RNA regulatory networks and some non-coding RNAs derived from exons of ISWI member genes play important roles in tumor progression. Therefore, unveiling the transcriptional regulation mechanism underlying ISWI family sparked a booming interest in finding ISWI-based therapies in cancer. This review aims at describing the current state-of-the-art in the role of ISWI subunits and complexes in tumorigenesis, tumor progression, immunity and drug response, and presenting deep insight into the physiological and pathological implications of the ISWI transcription machinery in cancers.
Pediatric eye emergency department activity during the first wave of Covid-19 pandemic
Authors: Franzolin Elia , Longo Rosa , Gusson Elena , Ficial Benjamim , Marchini Giorgio 
Published: November 2021

AbstractBackgroundWe investigated the volume and the characteristics of pediatric eye emergency department (PEED) consultations performed at our tertiary eye center during the early months of the COVID-19 pandemic and we compared them to those carried out in the same time interval of the previous three years.MethodsOphthalmic emergency examinations of patients aged ≤18 years old and done during the national COVID-19 lockdown (March 9th, 2020 – May 3rd, 2020) and in the corresponding date range of the previous three years (2017, 2018, and 2019) have been considered and reviewed. The following features were retrieved and analyzed: age, gender, duration and type of accused symptoms, traumatic etiology, and the discharge diagnosis.Results136, 133, and 154 PEED visits have been performed respectively in 2017, 2018, and 2019, while 29 patients presented in 2020. Therefore, the volume of PEED activity decreased by 79.4% (p < 0.0001). Demographical and clinical characteristics were comparable to those of the pre-COVID period. Despite the absolute reduction in the number of traumas, urgent conditions increased significantly from 30.7 to 50.7% (p = 0.024).ConclusionsPEED activity decreased consistently after the onset of the pandemic and it was mainly attended by those children whose conditions required prompt assistance, reducing the number of patients diagnosed with milder pathologies. At the end of the emergency, better use of PEED could avoid overcrowding and minimize waste, allowing resource optimization for the management of urgent cases.
Pediatric emergency department visits during the COVID-19 pandemic: a large retrospective population-based study
Authors: Barbiellini Amidei Claudio , Buja Alessandra , Bardin Andrea , Bonaldi Filippo , Paganini Matteo , Manfredi Mariagiovanna , Favaro Andrea , Baldo Vincenzo , Saia Mario , Da Dalt Liviana 
Published: November 2021

Abstract
Background
COVID-19 pandemic has stretched healthcare system capacities worldwide and deterred people from seeking medical support at Emergency Departments (ED). Nevertheless, population-based studies examining the consequences on children are lacking.

Methods
All ED visits from 2019 to 2020 in Veneto, Italy (4.9 million residents) were collected. Anonymized records of pediatric (≤14 years) ED visits included patient characteristics, arrival mode, triage code, clinical presentation, and discharge mode. Year-on-year variation of the main ED visit characteristics, and descriptive trends throughout the study period have been examined.

Results
Overall, 425,875 ED presentations were collected, 279,481 in 2019, and 146,394 in 2020 (− 48%), with a peak (− 79%) in March–April (first pandemic wave), and a second peak (below − 60%) in November–December (second pandemic wave). Burn or trauma, and fever were the two most common clinical presentations. Visits for nonurgent conditions underwent the strongest reduction during both pandemic waves, while urgent conditions reduced less sharply. ED arrival by ambulance was more common in 2020 (4.5%) than 2019 (3.5%), with a higher proportion of red triage codes (0.5%, and 0.4% respectively), and hospitalizations following ED discharge (9.1%, and 5.9% respectively).

Conclusion
Since the beginning of the COVID-19 pandemic, pediatric ED presentations underwent a steeper reduction than that observed for adults. Lockdown and fear of contagion in hospital-based services likely deterred parents from seeking medical support for their children. Given COVID-19 could become endemic, it is imperative that public health experts guarantee unhindered access to medical support for urgent, and less urgent health conditions, while minimizing infectious disease risks, to prevent children from suffering direct and indirect consequences of the pandemic.
Hypoxia-inducible factor-1α expression and breast cancer recurrence in a Danish population-based case control study
Authors: Collin Lindsay J. , Maliniak Maret L. , Cronin-Fenton Deirdre P. , Ahern Thomas P. , Christensen Kristina B. , Ulrichsen Sinna P. , Damkier Per , Hamilton-Dutoit Stephen , Yacoub Rami , Christiansen Peer M. , Sørensen Henrik Toft , Lash Timothy L. 
Published: November 2021

Abstract
Background
Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that facilitates the adaptation of cancer cells to hypoxic conditions and may be prognostic of breast cancer recurrence. We evaluated the association of HIF-1α expression with breast cancer recurrence, and its association with timing of breast cancer recurrence.

Methods
In this population-based case-control study, we included women diagnosed with stage I–III breast cancer between 1985 and 2001, aged 35–69 years, registered in the Danish Breast Cancer Group. We identified 541 cases of breast cancer recurrence among women with estrogen receptor (ER)-positive disease who were treated with tamoxifen for at least 1 year (ER+ TAM+). We also enrolled 300 breast cancer recurrence cases among women with ER-negative disease, not treated with tamoxifen, who survived at least 1 year (ER−/TAM−). Controls were recurrence-free breast cancer patients at the time of case diagnosis, matched to recurrence cases on ER/TAM status, date of surgery, menopausal status, cancer stage, and county of residence. Expression of HIF-1α was measured by immunohistochemistry on tissue microarrays. We fitted logistic regression models to compute odds ratios (ORs) and 95% confidence intervals (CIs) associating HIF-1α expression with recurrence, and with timing of recurrence.

Results
HIF-1α expression was observed in 23% of cases and 20% of controls in the ER+/TAM+ stratum, and in 47% of cases and 48% of controls in the ER−/TAM− stratum. We observed a near-null association between HIF-1α expression in both ER/TAM groups (ER+/TAM+ OR = 1.21, 95%CI 0.88, 1.67 and ER−/TAM− OR = 0.97, 95%CI 0.68, 1.39). HIF-1α expression was not associated with time to recurrence among women in the ER+/TAM+ stratum, but was associated with early recurrence among women in the ER−/TAM− stratum.

Conclusion
In this study, HIF-1α expression was not associated with breast cancer recurrence overall but may be associated with early recurrence among women diagnosed with ER− breast cancer.
High-quality reference genome sequences of two coconut cultivars provide insights into evolution of monocot chromosomes and differentiation of fiber content and plant height
Authors: Wang Shouchuang , Xiao Yong , Zhou Zhi-Wei , Yuan Jiaqing , Guo Hao , Yang Zhuang , Yang Jun , Sun Pengchuan , Sun Lisong , Deng Yuan , Xie Wen-Zhao , Song Jia-Ming , Qamar Muhammad Tahir ul , Xia Wei , Liu Rui , Gong Shufang , Wang Yong , Wang Fuyou , Liu Xianqing , Fernie Alisdair R. , Wang Xiyin , Fan Haikuo , Chen Ling-Ling , Luo Jie 
Published: November 2021

AbstractBackgroundCoconut is an important tropical oil and fruit crop whose evolutionary position renders it a fantastic species for the investigation of the evolution of monocot chromosomes and the subsequent differentiation of ancient plants.ResultsHere, we report the assembly and annotation of reference-grade genomes ofCn. tallandCn. dwarf, whose genome sizes are 2.40 Gb and 2.39 Gb, respectively. The comparative analysis reveals that the two coconut subspecies diverge about 2–8 Mya while the conserved Arecaceae-specific whole-genome duplication (ω WGD) occurs approximately 47–53 Mya. It additionally allows us to reconstruct the ancestral karyotypes of the ten ancient monocot chromosomes and the evolutionary trajectories of the 16 modern coconut chromosomes. Fiber synthesis genes inCn. tall, related to lignin and cellulose synthesis, are found at a higher copy number and expression level than dwarf coconuts. Integrated multi-omics analysis reveals that the difference in coconut plant height is the result of altered gibberellin metabolism, with both the GA20ox copy number and a single-nucleotide change in the promoter together leading to the difference in plant height betweenCn. tallandCn. dwarf.ConclusionWe provide high-quality coconut genomes and reveal the genetic basis of trait differences between two coconuts through multi-omics analysis. We also reveal that the selection of plant height has been targeted for the same gene for millions of years, not only in natural selection of ancient plant as illustrated in coconut, but also for artificial selection in cultivated crops such as rice and maize.
Inverse problem for cracked inhomogeneous Kirchhoff–Love plate with two hinged rigid inclusions
Authors: Lazarev Nyurgun 
Published: November 2021

AbstractWe consider a family of variational problems on the equilibrium of a composite Kirchhoff–Love plate containing two flat rectilinear rigid inclusions, which are connected in a hinged manner. It is assumed that both inclusions are delaminated from an elastic matrix, thus forming an interfacial crack between the inclusions and the surrounding elastic media. Displacement boundary conditions of an inequality type are set on the crack faces that ensure a mutual nonpenetration of opposite crack faces. The problems of the family depend on a parameter specifying the coordinate of a connection point of the inclusions. For the considered family of problems, we formulate a new inverse problem of finding unknown coordinates of a hinge joint point. The continuity of solutions of the problems on this parameter is proved. The solvability of this inverse problem has been established. Using a passage to the limit, a qualitative connection between the problems for plates with flat and bulk hinged inclusions is shown.