bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of constitutive and inducible oncogene-containing iPSCs as surrogates for transgenic mice to study breast oncogenesis
Authors: Nguyen Christine , Nguyen Julie P. T. , Modi Arnav P. , Ahmad Ihsaan , Petrova Sarah C. , Ferrell Stuart D. , Wilhelm Sabrina R. , Ye Yin , Schaue Dorthe , Barsky Sanford H. 
Published: May 2021

Abstract
Background
Powerful constitutive and inducible transgenic / bitransgenic / tritransgenic murine models of breast cancer have been used over the past two decades to shed light on the molecular mechanisms by which the given transgenic oncogenes have interacted with other cellular genes and set in motion breast cancer initiation and progression. However, these transgenic models, as in vivo models only, are expensive and restrictive in the opportunities they provide to manipulate the experimental variables that would enable a better understanding of the molecular events related to initial transformation and the target cell being transformed.

Methods
To overcome some of these limitations, we derived oncogene-containing induced pluripotent stem cell (iPSC) clones from tail vein fibroblasts of these transgenic mice and manipulated them both in vitro and in vivo in non-transgenic background mice. We created the iPSC clones with a relatively low M.O.I, producing retroviral integrations which averaged only 1 to 2 sites per retroviral plasmid construct used.

Results
Most iPSC clones derived from each group displayed an essentially normal murine karyotype, strong expression of the exogenous reprogrammable genes and significant expression of characteristic endogenous murine surface stem cell markers including SSEA-1 (CD15), PECAM-1 (CD31), Ep-Cam (CD326), and Nectin (CD112), but no expression of their transgene. A majority (75%) of iPSC clones displayed a normal murine karyotype but 25% exhibited a genomically unstable karyotype. However, even these later clones exhibited stable and characteristic iPSC properties. When injected orthotopically, select iPSC clones, either constitutive or inducible, no longer expressed their exogenous pluripotency reprogramming factors but expressed their oncogenic transgene (PyVT or ErbB2) and participated in both breast ontogenesis and subsequent oncogenesis. When injected non-orthotopically or when differentiated in vitro along several different non-mammary lineages of differentiation, the iPSC clones failed to do so. Although many clones developed anticipated teratomas, select iPSC clones under the appropriate constitutive or inducible conditions exhibited both breast ontogenesis and oncogenesis through the same stages as exhibited by their transgenic murine parents and, as such, represent transgenic surrogates.

Conclusions
The iPSC clones offer a number of advantages over transgenic mice including cost, the ability to manipulate and tag in vitro, and create an in vitro model of breast ontogeny and oncogenesis that can be used to gain additional insights into the differentiated status of the target cell which is susceptible to transformation. In addition, the use of these oncogene-containing iPSC clones can be used in chemopreventive studies of breast cancer.
A cross-cohort analysis of autosomal DNA methylation sex differences in the term placenta
Authors: Inkster Amy M. , Yuan Victor , Konwar Chaini , Matthews Allison M. , Brown Carolyn J. , Robinson Wendy P. 
Published: May 2021

Abstract
Background
Human placental DNA methylation (DNAme) data is a valuable resource for studying sex differences during gestation, as DNAme profiles after delivery reflect the cumulative effects of gene expression patterns and exposures across gestation. Here, we present an analysis of sex differences in autosomal DNAme in the uncomplicated term placenta (n = 343) using the Illumina 450K array.

Results
At a false discovery rate < 0.05 and a mean sex difference in DNAme beta value of > 0.10, we identified 162 autosomal CpG sites that were differentially methylated by sex and replicated in an independent cohort of samples (n = 293). Several of these differentially methylated CpG sites were part of larger correlated regions of sex differential DNAme. Although global DNAme levels did not differ by sex, the majority of significantly differentially methylated CpGs were more highly methylated in male placentae, the opposite of what is seen in differential methylation analyses of somatic tissues. Patterns of autosomal DNAme at these 162 CpGs were significantly associated with maternal age (in males) and newborn birthweight standard deviation (in females).

Conclusions
Our results provide a comprehensive analysis of sex differences in autosomal DNAme in the term human placenta. We report a list of high-confidence autosomal sex-associated differentially methylated CpGs and identify several key features of these loci that suggest their relevance to sex differences observed in normative and complicated pregnancies.
A novel technique to avoid intraoperative giant tear slippage: the bimanual double aspiration technique
Authors: Placeres Daban Javier , Artieda García Daniel , Yaluff Portilla Sebastian , Belda Sanchís José Isidro 
Published: May 2021

Abstract
Background
The aim of this paper is to present a novel bimanual double aspiration technique to avoid intraoperative giant tear slippage. The major problem of giant retinal tears (GRT) surgery is the mobility of the posterior flap (slippage), which has been classically solved by the use of intraoperative perfluorocarbon liquid (PFCL). However, avoiding slippage of the posterior flap can be a serious technical challenge when the PFCL is removed, especially when a GRT circumference is > 180°.

Methods
Conventional three-port 23-gauge pars plana vitrectomy (PPV) plus chandelier was performed in three patients with giant retinal tears (GRT), using the “bimanual double aspiration technique” with non-contact wide field viewing systems. All surgeries were performed by the same surgeon.

Results
None of the three cases presented with a retinal slippage after the bimanual aspiration technique.

Discussion
GRT are full thickness retinal tears that extend circumferentially more than 90° of the retina. Management of GRT is a challenge for the vitreoretinal surgeons because the higher risk of proliferative vitreoretinopathy (PVR), re-detachment and increased risk of retinal slippage; this last can occur intraoperative or postoperative. Retinal slippage is not uncommon but far under-reported and can lead to various complications such as hypotony, retinal folds, and may exacerbate PVR formation. We performed bimanual double aspiration technique to avoid intraoperative giant tear slippage. We believe that this maneuver may avoid slippage by drying the posterior edge of the GRT. There were no complications related with the technique, and no additional equipment was needed.

Conclusion
In summary, “bimanual double aspiration technique”, is a simple, effective, safe and economic maneuver that could be a good option to avoid intraoperative slippage in giant retinal detachment surgery, thus achieving the stabilization of the posterior retinal flap.
Do concerns about COVID-19 impair sustained attention?
Authors: Jun Jihyang , Toh Yi Ni , Sisk Caitlin A. , Remington Roger W. , Lee Vanessa G. 
Published: May 2021

AbstractThe novel coronavirus disease 2019 (COVID-19) has considerably heightened health and financial concerns for many individuals. Similar concerns, such as those associated with poverty, impair performance on cognitive control tasks. If ongoing concerns about COVID-19 substantially increase the tendency to mind wander in tasks requiring sustained attention, these worries could degrade performance on a wide range of tasks, leading, for example, to increased traffic accidents, diminished educational achievement, and lower workplace productivity. In two pre-registered experiments, we investigated the degree to which young adults’ concerns about COVID-19 correlated with their ability to sustain attention. Experiment 1 tested mainly European participants during an early phase of the pandemic. After completing a survey probing COVID-related concerns, participants engaged in a continuous performance task (CPT) over two, 4-min blocks, during which they responded to city scenes that occurred 90% of the time and withheld responses to mountain scenes that occurred 10% of the time. Despite large and stable individual differences, performance on the scene CPT did not significantly correlate with the severity of COVID-related concerns obtained from the survey. Experiment 2 tested US participants during a later phase of the pandemic. Once again, CPT performance did not significantly correlate with COVID concerns expressed in a pre-task survey. However, participants who had more task-unrelated thoughts performed more poorly on the CPT. These findings suggest that although COVID-19 increased anxiety in a broad swath of society, young adults are able to hold these concerns in a latent format, minimizing their impact on performance in a demanding sustained attention task.
Care Patterns and Overall Survival in Patients With Early-Onset Metastatic Colorectal Cancer
Authors: Kanter Katie , Fish Madeleine , Mauri Gianluca , Horick Nora K. , Allen Jill N. , Blaszkowsky Lawrence S. , Clark Jeffrey W. , Ryan David P. , Nipp Ryan D. , Giantonio Bruce J. , Goyal Lipika , Dubois Jon , Murphy Janet E. , Franses Joseph , Klempner Samuel J. , Roeland Eric J. , Weekes Colin D. , Wo Jennifer Y. , Hong Theodore S. , Van Seventer Emily E. , Corcoran Ryan B. , Parikh Aparna R. 
Published: May 2021

PURPOSE: Colorectal cancer (CRC) incidence in patients younger than 50 years of age, commonly defined as early-onset (EO-CRC), is rising. EO-CRC often presents with distinct clinicopathologic features. However, data on prognosis are conflicting and outcomes with modern treatment approaches for metastatic disease are still limited. MATERIALS AND METHODS: We prospectively enrolled patients with metastatic CRC (mCRC) to a biobanking and clinical data collection protocol from 2014 to 2018. We grouped the cohort based on age at initial diagnosis: < 40 years, 40-49 years, and ≥ 50 years. We used regression models to examine associations among age at initial diagnosis, treatments, clinicopathologic features, and survival. RESULTS: We identified 466 patients with mCRC (45 [10%] age < 40 years, 109 [23%] age 40-49 years, and 312 [67%] age ≥ 50 years). Patients < 40 years of age were more likely to have received multiple metastatic resections (odds ratio [OR], 3.533; P = .0066) than their older counterparts. Patients with EO-CRC were more likely to receive triplet therapy than patients > 50 years of age (age < 40 years: OR, 6.738; P = .0002; age 40-49 years: OR, 2.949; P = .0166). Patients 40-49 years of age were more likely to have received anti-EGFR therapy (OR, 2.633; P = .0016). Despite differences in care patterns, age did not predict overall survival. CONCLUSION: Despite patients with EO-CRC receiving more intensive treatments, survival was similar to the older counterpart. However, EO-CRC had clinical and molecular features associated with worse prognoses. Improved biologic understanding is needed to optimize clinical management of EO-CRC. The cost-benefit ratio of exposing patients with EO-CRC to more intensive treatments has to be carefully evaluated.
Association Between Medicare's National Coverage Determination and Utilization of Next-Generation Sequencing
Authors: Sheinson Daniel M. , Wong William B. , Flores Carlos , Ogale Sarika , Gross Cary P. 
Published: May 2021

PURPOSE:In 2018, Medicare issued a national coverage determination (NCD) providing reimbursement for next-generation sequencing (NGS) tests for beneficiaries with advanced or metastatic cancer and no previous NGS testing. We examined the association between NCD implementation and NGS utilization trends in Medicare beneficiaries versus commercially insured patients.METHODS:This was a retrospective study of patients with advanced non–small-cell lung cancer (aNSCLC), metastatic colorectal cancer (mCRC), metastatic breast cancer (mBC), or advanced melanoma with a de novo or recurrent advanced diagnosis from January 1, 2011, through December 30, 2019, using a nationwide US electronic health record–derived deidentified database. Patients were classified by insurance and by advanced diagnosis date. NGS testing was assessed by receipt of first NGS test result ≤ 60 days of advanced diagnosis. Interrupted time series analysis assessed NGS utilization pre- and post-NCD effective date by insurance type.RESULTS:The utilization and repeat NGS testing analysis included 70,290 and 4,295 patients, respectively. Use of NGS rose from < 1% in 2011 to > 45% in Q4 2019 in aNSCLC while remaining < 20% in mBC and advanced melanoma. Among patients with aNSCLC, mCRC, or mBC, NGS testing increased post-NCD versus pre-NCD ( P < .05). There was no significant difference in trends pre- and post-NCD between Medicare beneficiaries and commercially insured patients in any tumor. Repeat NGS testing was similar before the NCD (Medicare v commercial: 24.8% v 28.5%). Post-NCD, fewer Medicare beneficiaries had repeat NGS testing (27.7% v 36.0%; P < .01).CONCLUSION:Trends in NGS utilization significantly changed post-NCD, although the magnitude of change was not significantly different by insurance type, indicating private insurers may also be incorporating NCD guidance. Implementation of the NCD may have limited use of repeat NGS testing in Medicare beneficiaries.
Early warning systems in maternity care: protocol for a qualitative evidence synthesis of maternity care providers’ views and experiences
Authors: Smith Valerie , Cithambaram Kumaresan , O'Malley Deirdre 
Published: May 2021

Background: Early warning systems (EWS) have been widely adopted for use in maternity settings internationally. The idea in using these systems is early recognition of potential or actual clinical deterioration in pregnant or postpartum women, and escalation of care. Barriers to successful implementation and use of EWS, however, have been identified. If EWS are to be applied consistently, a greater understanding of the views and experiences of EWS from the perspectives of those using and applying EWS in maternity practice is needed. This protocol describes a qualitative evidence synthesis of maternity care providers’ (midwives, obstetricians, and allied maternity care professionals) views and experiences of EWS use and application in practice. Methods: Studies will be included in the review if they report on maternity care providers use and application of EWS in any birth setting. Qualitative studies and studies of mixed methods design, where qualitative data can be extracted separately, will be included. To source relevant literature the electronic databases of MEDLINE, CINHAL, Web of Science Core Collection (incorporating Social Science Citation Index) and Maternity and Infant Care (MIDIRS), from date of inception, will be searched. The methodological quality of the included studies will be appraised using the 12-criteria of the assessment tool developed by the Evidence for Policy and Practice Information and Co-ordinating Centre. Thematic synthesis will be used for synthesising the qualitative data from included studies. The confidence in the findings will be assessed using the Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative research. Conclusions: The findings of this qualitative evidence synthesis may provide valuable information on the barriers, challenges, and facilitators for EWS use based on the experiences of those directly involved in EWS application in maternity care provision. PROSPERO registration: CRD42021235137 (08/04/2021)
Record linkage of population-based cohort data from minors with national register data: a scoping review and comparative legal analysis of four European countries
Authors: Doetsch Julia Nadine , Dias Vasco , Indredavik Marit S. , Reittu Jarkko , Devold Randi Kallar , Teixeira Raquel , Kajantie Eero , Barros Henrique 
Published: May 2021

Background: The General Data Protection Regulation (GDPR) was implemented to build an overarching framework for personal data protection across the European Union/Economic Area (EU/EEA). Linkage of data directly collected from cohort participants based on individual consent must respect data protection rules and privacy rights of data subjects. Our objective was to investigate possibilities of linking cohort data of minors with routinely collected education and health data comparing EU/EEA member states. Methods: A legal comparative analysis and scoping review was conducted of openly online accessible published laws and regulations in EUR-Lex and national law databases on GDPR’s implementation in Portugal, Finland, Norway, and the Netherlands and its connected national regulations purposing record linkage for health research that have been implemented up until April 30, 2021. Results: EU/EEA has limited legislative authority over member states. The GDPR offers flexibility for national legislation. Exceptions to process personal data, e.g., public interest and scientific research, must be laid down in EU/EEA or national law. Differences in national interpretation caused obstacles in cross-national research and record linkage: Portugal requires written consent and ethical approval; Finland allows linkage mostly without consent through the national Data Protection Supervisory Authority; Norway when based on regional ethics committee’s approval and adequate information technology safeguarding confidentiality; the Netherlands mainly bases linkage on the opt-out system and Data Protection Impact Assessment. Conclusions: Though the GDPR is the most important legal framework, national legislation execution matters most when linking cohort data with routinely collected health and education data. As national interpretation varies, legal intervention balancing individual right to informational self-determination and public good is gravely needed for scientific research. More harmonization across EU/EEA could be helpful but should not be detrimental in those member states which already opened a leeway for registries and research for the public good without explicit consent.
THE STUDENT’S METACOGNITIVE SKILLS OF PROSPECTIVE PRIMARY SCHOOL TEACHERS
Authors: Maryani Ika , Alhakim Muhamad Arif , Gestiardi Rivan 
Published: May 2021

Metacognitive skill is essential to have by every individual, including the prospective teachers' students. Some teachers who have not trained in metacognitive ability would be caused by the lack of understanding of the stages in carrying out metacognitive ability. It has not realised that metacognitive ability can affect students' learning process and learning outcome. The students who have the excellent metacognitive ability can develop metacognitive domain-oriented learning. This study aims to know the metacognitive skills of prospective primary school teachers in Universitas Ahmad Dahlan. This research used a quantitative approach to descriptive type and survey method. The samples are 100 students of elementary school educations of Universitas Ahmad Dahlan consisted of the semester II, IV, and VI. The instrument used Metacognitive Ability Inventory (MAI) with the Likert scale(1-5). Data were analysed using descriptive statistics to determine the Mean, standard deviation, percentage, and metacognitive categorisation of elementary school education students. The research result showed a low-medium range category. It influenced by some factors related to the inadequate metacognitive development of prospective primary school teachers. Judging from the cognitive knowledge aspect, the high category of the percentage calculation of cognitive knowledge aspects is in the declarative knowledge aspect. In the cognitive regulation aspect, planning becomes the highest percentage of cognitive regulation aspect.
MRI-based assessment of acetabular version and coverage after previous Pemberton osteotomy in skeletally mature patients
Authors: Bellova Petri , Blum Sophia , Hartmann Albrecht , Thielemann Falk , Günther Klaus-Peter , Goronzy Jens 
Published: May 2021

Purpose In hip dysplasia the Pemberton osteotomy can modify the shape of the acetabulum and is indicated for children aged between two and 12 when the triradiate cartilage is still open. However, there have been concerns about acetabular retroversion following this type of osteotomy. The studies, however, have been based on plain radiographs. The aim of our investigation was to assess the 3D acetabular orientation in patients with previous Pemberton osteotomy after skeletal maturation. Methods Ten patients with 12 operated hips were included who received Pemberton osteotomy for hip dysplasia between January 3, 2005 and March 25, 2011. Mean age at surgery and at follow-up were 7.2 years (sd 3.7) and 19.2 years (sd 3.7), respectively. MRIs were conducted with 1.5 T. Besides the measurement of acetabular version, the analysis included alpha angles, acetabular sector angles (ASAs) as well as modified ASAs (cartilage covered area angles). Furthermore, the presence of osteoarthritis (OA) as well as acetabular retroversion was determined on plain radiographs. Patient-related outcome measures included the international Hip Outcome Tool (iHOT) and EuroQol-5-Dimensions (EQ5D) scores. Results In comparison with the contralateral native and healthy hips the operated hips showed similar version (19.5° (sd 4.6°) versus 18.6° (sd 7.0°); p = 0.974). Also, there were no differences in terms of femoral head sphericity (alpha angles) and acetabular coverage (ASA angles). Five of 12 Pemberton hips showed signs of beginning OA (Kellgren-Lawrence classification I or II) while none of the non-operated hips did. Patients who received surgery before the age of six years had similar functional and radiological results when compared with patients who were older than six years at surgery. Among all patients, iHOT was 91.9 (sd 10.0) and EQ5D was 90.3 (sd 7.3)). Conclusion The Pemberton osteotomy provides good long-term radiographic and functional results without compromising acetabular version or coverage. Level of Evidence Level III: retrospective comparative study
Knockdown of hsa_circ_0001275 reverses dexamethasone-induced osteoblast growth inhibition via mediation of miR-377/CDKN1B axis
Authors: Xu Yan , Sun Liqin , Hu Juncheng , Xu Sai 
Published: May 2021

BackgroundOsteoporosis affects the quality of life among middle-aged and elderly individuals. In addition, dysfunction of osteoblasts can lead to the progression of osteoporosis. Circular (circ)RNAs are involved in various types of diseases, including osteoporosis. Moreover, it has been reported that hsa_circ_0001275 expression is upregulated in osteoporosis. However, the effects of hsa_circ_0001275 on the growth of osteoblasts remain unclear.MethodsIn the present study, the gene and protein expression levels in hFOB1.19 cells were detected via reverse transcription-quantitative (RT-qPCR) and western blot analyses, respectively. In addition, alkaline phosphatase (ALP) activity and calcium nodules were examined by ALP and alizarin red staining, respectively. Cell proliferation was measured using the Cell Counting Kit-8 assay. Cell apoptosis and cell cycle were analyzed by flow cytometry. Furthermore, dual luciferase reporter and RNA pull-down assay were used to confirm the association among hsa_circ_0001275, microRNA (miR)-377 and CDKN1B.ResultsDEX-induced hFOB1.19 cell growth inhibition was significantly reversed by silencing hsa_circ_0001275. Moreover, DEX significantly increased ALP activity and calcium nodules in hFOB1.19 cells, while this effect was significantly reversed in the presence of hsa_circ_0001275 small interfering RNA. In addition, miR-377 was sponged by hsa_circ_0001275 and CDKN1B was directly targeted by miR-377 in hFOB1.19 cells. Furthermore, the therapeutic effect of hsa_circ_0001275 knockdown on osteoporosis was notably reversed by miR-377 antagomir.ConclusionThe data demonstrated that knockdown of hsa_circ_0001275 reversed DEX-induced osteoblast growth inhibition via activation of the miR-377/CDKN1B axis. Therefore, this study might shed new lights on the treatment of osteoporosis.