bluuebunny/crossref_metadata_2025_split huggingface dataset:
Doxycycline Significantly Enhances Induction of Induced Pluripotent Stem Cells to Endoderm by Enhancing Survival Through Protein Kinase B Phosphorylation
Authors: Peaslee Caitlin , Esteva‐Font Cristina , Su Tao , Munoz‐Howell Antonio , Duwaerts Caroline C. , Liu Zhe , Rao Sneha , Liu Ke , Medina Marisa , Sneddon Julie B. , Maher Jacquelyn J. , Mattis Aras N. 
Published: May 2021

Background and Aims
Induced pluripotent stem cells (iPSCs) provide an important tool for the generation of patient‐derived cells, including hepatocyte‐like cells, by developmental cues through an endoderm intermediate. However, most iPSC lines fail to differentiate into endoderm, with induction resulting in apoptosis.

Approach and Results
To address this issue, we built upon published methods to develop an improved protocol. We discovered that doxycycline dramatically enhances the efficiency of iPSCs to endoderm differentiation by inhibiting apoptosis and promoting proliferation through the protein kinase B pathway. We tested this protocol in >70 iPSC lines, 90% of which consistently formed complete sheets of endoderm. Endoderm generated by our method achieves similar transcriptomic profiles, expression of endoderm protein markers, and the ability to be further differentiated to downstream lineages.

Conclusions
Furthermore, this method achieves a 4‐fold increase in endoderm cell number and will accelerate studies of human diseases in vitro and facilitate the expansion of iPSC‐derived cells for transplantation studies.
Analytical study of heat and mass transfer effects on unsteady Casson fluid flow over an oscillating plate with thermal and solutal boundary conditions
Authors: Endalew Mehari Fentahun 
Published: May 2021

AbstractIn this study, the impacts of heat and mass transfer characteristics on an isotropic incompressible Casson fluid flow over an oscillatory plate with the incidences of solutal and thermal boundary conditions have been investigated. Exact solutions of the fundamental equations governing the fluid flow are determined by using the Laplace transform technique. Numerical results based on analytical solutions are presented in graphical and tabular illustrations to clarify the behaviors of the fluid. Most interestingly, both fluid velocity and species concentration increase with an increment of mass transfer coefficient, whereas the fluid velocity diminishes as oscillating frequency increases near the surface of the plate. This happens due to the presence of high fluctuation of the plate in the flow system. Finally, this investigation is helpful to the scientific community, and the obtained results can be used as benchmark solutions for solving nonlinear flow governing problems fully via various numerical methods.
Induction of dormancy by confinement: An agarose‐silica biomaterial for isolating and analyzing dormant cancer cells
Authors: Preciado Julian , Lam Tiffany , Azarin Samira M. , Lou Emil , Aksan Alptekin 
Published: May 2021

AbstractThe principal cause of cancer deaths is the residual disease, which eventually results in metastases. Certain metastases are induced by disseminated dormancy‐capable single cancer cells that can reside within the body undetected for months to years. Awakening of the dormant cells starts a cascade resulting in the patient's demise. Despite its established clinical significance, dormancy research and its clinical translation have been hindered by lack of in vitro models that can identify, isolate, and analyze dormancy‐capable cells. We have previously shown that immobilization of cells in a stiff microenvironment induces dormancy in dormancy‐capable cell lines. In this communication, we present a novel biomaterial and an in vitro immobilization method to isolate, analyze, and efficiently recover dormancy‐capable cancer cells. MCF‐7, MDA‐MB‐231, and MDA‐MB‐468 cells were individually coated with agarose using a microfluidic flow‐focusing device. Coated cells were then immobilized in a rigid and porous silica gel. Dormancy induction by this process was validated by decreased Ki‐67 expression, increased p38/ERK activity ratio, and reduced expression of CDK‐2, cyclins D1, and E1. We showed that we can reliably and repeatedly induce dormancy in dormancy‐capable MCF‐7 cells and enhance the dormancy‐capable sub‐population in MDA‐MB‐231 cells. As expected, dormancy‐resistant MDA‐MB‐468 cells did not survive immobilization. The dormant cells could be awakened on demand, by digesting the agarose gel in situ, and efficiently recovered by magnetically separating the silica gel, making the cells available for downstream analysis and testing. The awakened cells were shown to regain motility immediately, proliferating, and migrating normally.
Age‐stratified and gender‐specific reference intervals of six tumor markers panel of lung cancer: A geographic‐based multicenter study in China
Authors: Li Yan , Li Ming , Zhang Yi , Zhou Jianping , Jiang Li , Yang Chen , Li Gang , Qu Wei , Li Xinhui , Chen Yong , Chen Qing , Wang Wei , Wang Shukui , liang Xing Jin , Huang Huayi 
Published: May 2021

AbstractBackgroundSerum biomarkers have been widely adopted in clinical practice for assisting lung cancer diagnoses, therapeutic monitoring, and prognostication. The function of a well‐performing tumor biomarker depends on a reliable reference interval (RI) with consideration of the study subjects’ age, gender, and geographical location. This study aimed to establish a RI for each of 6 lung cancer biomarkers for use in the whole country of China on Mindray platform.MethodsThe levels of serum 6 lung cancer biomarkers—namely progastrin‐releasing peptide (ProGRP), neuron‐specific enolase (NSE), squamous cell carcinoma antigen (SCC), carcinoembryonic antigen (CEA), cytokeratin‐19 fragment (CYFRA21‐1), and human epididymis protein 4 (HE4)—were measured utilizing the chemiluminescence immunoassay on the Mindray CL‐6000i platform following the laboratory standard operating procedures in apparently healthy Chinese individuals on large cohort, multicenter, and geographical consideration bases. The CLSI EP28‐A3C guideline was followed for the enrollment of study subjects.ResultsThe age‐stratified, gender‐specific RIs for ProGRP, NSE, SCC, CEA, CYFRA21‐1, and HE4 lung cancer biomarkers in the Chinese population have been established as described in the results and discussion in this work. In addition, various levels of the six lung cancer biomarkers among nine geographical locations in China have been observed.ConclusionsThe sample volume of study cohort, age, and geographical location should be considered upon establishing a reliable biomarker RI. A RI for each of six lung cancer biomarkers has been established. The results from this study would be helpful for clinical laboratories in interpreting the analytical results and for clinicians in patient management.
Applicability of Western protocols in resource‐limited setting: Real‐world data of long‐term outcome of intensive treatment of adult acute myeloid leukaemia in Sri Lanka
Authors: Hewamana Saman , Kandabadage Lakmali , Skandarajah Thurairajah , Pieris Natasha , Perera Eranga , Harischandra Mahesh , Wijewickrama Ananda , Wickramarathna Chandana , Somasundaram Gnani , Srinivasan Vadivelu , Somiah Surjit , Jayawardena Priyankara , Perera Mehendra , Gunasekera Dehan , Jayasinghe Chathuri , Constantine Godvin , Munasinghe Sanjeewa , De Silva Chandu , Wijesiriwardena Bandula , Balawardena Jayantha 
Published: May 2021

AbstractThere are no published data on long‐term survival and applicability of treatment protocols from developed countries in acute myeloid leukaemia (AML) in Sri Lanka. Eighty‐seven AML patients were reviewed; there were 56 newly diagnosed patients between 18 and 65 years. Thirty‐one out of 33 who started treatment achieved complete remission after first cycle of treatment. The induction mortality was one of 33. Twelve out of 20 patients who completed treatment are alive at the time of analysis. The estimated 5‐year overall survival rate is 0.629. Strict infection control and treatment and superior clinical experience may have contributed towards better outcome.
Intensity and microphysical properties surrounding the rapid intensification in landfalling Super Typhoons over China during the summer and autumn seasons
Authors: Deng Lin , Zhao Yang , Gao Wenhua , Xue Lulin , Duan Yihong 
Published: May 2021

AbstractThis study investigates the seasonal intensity variabilities of typhoons (TYs) over the western North Pacific that made landfall in the mainland China during the summer (June–August) and autumn (September–November) seasons for the period of 1979–2017. Using the latest climate reanalysis dataset (ERA5), cloud microphysical properties surrounding the rapid intensification (RI) period within the Super TYs (the maximum wind speed exceeding 51 ms−1) are explored to verify whether there exists microphysical precursor in TY intensity change like RI. The major results are: (a) The total number of landfalling TYs in summer is 188, almost two times of the number in autumn, and 25.5% of them can reach the Super TYs category, while 39.5% of the landfalling TYs in autumn became Super TYs with a shorter lifespan. (b) At least half of the summer and autumn cases have undergone the RI before they reached their maximum intensity, and more autumn cases experienced RI as they approached the coastal areas. (c) Snow and rain contents within the vortex exhibit consistent increasing trends during the RI period in both seasons. It is found that ice and snow contents show relatively distinct increase prior to the intensity change during the RI period in autumn cases, while no obvious signal exists in summer. The short‐term microphysical change and the released latent heat may be insufficient in supporting the onset of RI in Super TYs, and the differences of large‐scale environmental conditions between summer and autumn are mostly responsible for the distinct evolutions of intensity and microphysical characteristics in such strong systems.
Raman characterization of phonon confinement and strain effects from latent ion tracks in α‐quartz
Authors: Garcia Toro Maria C. , Crespillo Miguel L. , Olivares Jose , Graham Joseph T. 
Published: May 2021

AbstractThis study reports phonon confinement and strain effects in the Raman spectrum of ion‐irradiated and subsequently etched α‐quartz. Y‐ and Z‐cut α‐quartz single crystals were irradiated at room temperature with 20‐MeV Ni6+ and 40‐MeV I7+ ions. Latent ion tracks were produced with areal densities ranging from the isolated track regime to the overlapping track regime (nominal fluences of 1 × 109, 1 × 1010, and 1 × 1011 ions cm−2). Nanowell structures were revealed after vapor etching with hydrofluoric acid (HF) aqueous solutions. A phonon confinement model was invoked to explain the observed changes in the shape of the strong Raman peak located around 463 cm−1. Phonon coherence lengths of the irradiated samples were determined by fitting the confinement model to the experimental data. It was found that the phonon coherence lengths (L) decreased with increasing fluence (L ~ 66 nm for samples irradiated with 1 × 109 ions cm−2, L ~ 58 nm at 1 × 1010 ions cm−2, and L ~ 45 nm at 1 × 1011 ions cm−2), suggesting that ion tracks may confine optical phonons in quartz. An additional contribution to the upshift was observed at the highest fluence. This was attributed to a contribution from lattice strain when track separations are small and the overlapping strain fields around ion tracks extend through a large volume fraction of the crystal. Through an empirical correlation, the induced stress was estimated to be on the order of 100 MPa.
Identification of microduplications at Xp21.2 and Xq13.1 in neurodevelopmental disorders
Authors: Kokkonen Hannaleena , Siren Auli , Määttä Tuomo , Kamila Kadlubowska Magda , Acharya Anushree , Nouel‐Saied Liz M. , Leal Suzanne M. , Järvelä Irma , Schrauwen Isabelle 
Published: May 2021

AbstractBackgroundMicroduplications are a rare cause of disease in X‐linked neurodevelopmental disorders but likely have been under reported due challenges in detection and interpretation.MethodsWe performed exome sequencing and subsequent microarray analysis in two families with a neurodevelopmental disorder.ResultsHere, we report on two families each with unique inherited microduplications at Xp21.2 and Xq13.1, respectively. In the first family, a 562.8‐kb duplication at Xq13.1 covering DLG3, TEX11, SLC7A3, GDPD2, and part KIF4A was identified in a boy whose phenotype was characterized by delayed speech development, mild intellectual disability (ID), mild dysmorphic facial features, a heart defect, and neuropsychiatric symptoms. By interrogating all reported Xq13.1 duplications in individuals affected with a neurodevelopmental disorder, we provide evidence that this genomic region and particularly DLG3 might be sensitive to an increased dosage. In the second family with four affected males, we found a noncontinuous 223‐ and 204‐kb duplication at Xp21.2, of which the first duplication covers exon 6 of IL1RAPL1. The phenotype of the male patients was characterized by delayed speech development, mild to moderate ID, strabismus, and neurobehavioral symptoms. The carrier daughter and her mother had learning difficulties. IL1RAPL1 shows nonrecurrent causal structural variation and is located at a common fragile site (FRAXC), prone to re‐arrangement.ConclusionIn conclusion, we show that comprehensive clinical and genetic examination of microduplications on the X‐chromosome can be helpful in undiagnosed cases of neurodevelopmental disease.
LAMB2 novel variant c.2885‐9 C>A affects RNA splicing in a minigene assay
Authors: Wang Xiaoyuan , Xiao Huijie , Su Baige , Ren Yali , Ding Jie , Wang Fang 
Published: May 2021

AbstractBackgroundBoth Pierson syndrome (PS) and isolated nephrotic syndrome can be caused by LAMB2 biallelic pathogenic variants. Only 15 causative splicing variants in the LAMB2 gene have been reported. However, the pathogenicity of most of these variants has not been verified, which may lead to incorrect interpretation of the functional consequence of these variants.MethodsUsing high‐throughput DNA sequencing and Sanger sequencing, we detected variants in a female with clinically suspected PS. A minigene splicing assay was performed to assess the effect of LAMB2 intron 20 c.2885‐9C>A on RNA splicing. We also performed the immunohistochemical analysis of laminin beta‐2 in kidney tissues.ResultsTwo novel LAMB2 heteroallelic variants were found: a paternally inherited variant c.2885‐9C>A in intron 20 and a maternally inherited variant c. 3658C>T (p. (Gln1220Ter)). In vitro minigene assay showed that the variant c.2885‐9C>A caused erroneous integration of a 7 bp sequence into intron 20. Immunohistochemical analysis revealed the absence of glomerular expression of laminin beta‐2, the protein encoded by LAMB2.ConclusionWe demonstrated the impact of a novel LAMB2 intronic variant on RNA splicing using the minigene assay firstly. Our results extend the mutational spectrum of LAMB2.
Approximation algorithms for Steiner forest: An experimental study
Authors: Ghalami Laleh , Grosu Daniel 
Published: May 2021

AbstractIn the Steiner forest problem, we are given a set of terminal pairs and need to find the minimum cost subgraph that connects each of the terminal pairs together. Motivated by the recent work on greedy approximation algorithms for the Steiner forest, we provide efficient implementations of existing approximation algorithms and conduct a thorough experimental study to characterize their performance. We consider several approximation algorithms: the influential primal‐dual 2‐approximation algorithm due to Agrawal, Klein, and Ravi, the greedy algorithm due to Gupta and Kumar, and a randomized algorithm based on probabilistic approximation by tree metrics. We also consider the simplest heuristic greedy algorithm for the problem, which picks the closest unconnected pair of terminals and connects it using the shortest path between the terminals in the current graph. To characterize the performance of the algorithms, we created a new library with more than one thousand Steiner forest problem instances and conducted an extensive experimental analysis on those instances. Our analysis reveals that for the majority of instances the primal‐dual algorithm is the fastest among all the algorithms considered here, and obtains solutions that are very close to the optimal solutions obtained by solving the integer program formulation of the problem.
Predictors of long‐term weight loss trajectories during a behavioral weight loss intervention: An exploratory analysis
Authors: Ostendorf Danielle M. , Blankenship Jennifer M. , Grau Laura , Arbet Jaron , Mitchell Nia S. , Creasy Seth A. , Caldwell Ann E. , Melanson Edward L. , Phelan Suzanne , Bessesen Daniel H. , Catenacci Victoria A. 
Published: May 2021

AbstractBackgroundSubstantial interindividual variability in response to behavioral weight loss interventions remains a critical challenge in obesity treatment. An improved understanding of the complex factors that contribute to this variability may improve obesity treatment outcomes.ObjectiveTo identify weight change trajectories during a behavioral weight loss intervention and to explore differences between trajectory groups in sociodemographic, biologic, behavioral, and psychosocial factors.MethodsAdults (n = 170, 40 ± 9 years, BMI 34 ± 4 kg/m2, 84% female) participated in an 18‐month behavioral weight loss intervention. Weight was measured at 0, 3, 6, 9, 12, 15, 18, and 24 months. Among participants with at least two weights after baseline (n = 140), clusters of longitudinal trajectories of changes in weight were identified using a latent class growth mixture model. The association between baseline factors or changes in factors over time and trajectory group was examined.ResultsTwo weight change trajectories were identified: “weight regainers” (n = 91) and “weight loss maintainers” (n = 49). Black participants (90%, 19/21) were more likely than non‐Black participants to be regainers versus maintainers (p < 0.01). Maintainers demonstrated greater increases in device‐measured physical activity, autonomous motivation for exercise, diet self‐efficacy, cognitive restraint, and engagement in weight management behaviors and greater reductions in barriers for exercise, disinhibition, and depressive symptoms over 24 months versus regainers (p < 0.05).ConclusionMaintainers and regainers appear to be distinct trajectories that are associated with specific sociodemographic, behavioral, and psychosocial factors. Study results suggest potential targets for more tailored, multifaceted interventions to improve obesity treatment outcomes.
Communication in dyads of adult children at the end of life with their parents and parents at the end of life with their adult children: Findings from a mixed‐methods study
Authors: Gawinski Laura , Stiel Stephanie , Schneider Nils , Herbst Franziska A. 
Published: May 2021

AbstractObjectivePatient–family member communication plays a decisive role in coping with an end‐of‐life situation and is strongly influenced by the dyadic relationship. There is a lack of research exploring and comparing the specifics of communication between (1) terminally ill adult children and their parents and (2) terminally ill parents and their adult children. The present study aimed at describing and comparing communication specifics within these two dyads.MethodsAs part of the research project Dy@EoL on parent–adult child interactions, this mixed‐methods study combined qualitative interviews and the Berlin Social Support Scales self‐report questionnaire. Participants in both dyads were recruited via 12 inpatient and ambulatory palliative/hospice care providers between February 2018 and September 2019.ResultsParticipants included 65 patients (dyad 1: 19; dyad 2: 46) and 42 family members (dyad 1: 13; dyad 2: 29). Qualitative interviews revealed communication changes in the terminal illness situation and provided insight into each dyad partner's perception of openness and avoidance in the dyadic communication. The quantitative results showed that patients in both dyads provided significantly less informational support relative to family members. A strong similarity present in both dyads was the central motivation for limiting information sharing.ConclusionsIndividual preferences for information sharing suggest that the divergent needs of dyad partners must be carefully negotiated to ensure that patients are able to address important topics without putting too great an emotional burden on their family members. Tailored psychosocial support measures are needed to achieve this goal.The study was registered prospectively in the German Clinical Trials Register (registration N° DRKS00013206).
Rock glacier inventory of the western Nyainqêntanglha Range, Tibetan Plateau, supported by InSAR time series and automated classification
Authors: Reinosch Eike , Gerke Markus , Riedel Björn , Schwalb Antje , Ye Qinghua , Buckel Johannes 
Published: May 2021

AbstractThe western Nyainqêntanglha Range on the Tibetan Plateau reaches an elevation of 7,162 m and is characterized by an extensive periglacial environment under semi‐arid climatic conditions. Rock glaciers play an important part of the water budget in high mountain areas and recent studies suggest that they may even act as climate‐resistant water storages. In this study we present the first rock glacier inventory of this region containing 1,433 rock glaciers over an area of 4,622 km. To create the most reliable inventory we combine manually created rock glacier outlines with an automated classification approach. The manual outlines were generated based on surface elevation data, optical satellite imagery and a surface velocity estimation. This estimation was generated via InSAR time series analysis with Sentinel‐1 data from 2016 to 2019. Our pixel‐based automated classification was able to correctly identify 87.8% of all rock glaciers in the study area at a true positive rate of 69.5%. In total, 65.9% of rock glaciers are classified as transitional with surface velocities of 1–10 cm/yr. In total, 18.5% are classified as active with higher velocities of up to 87 cm/yr. The southern windward side of the mountain range contains more numerous and more active rock glaciers. We attribute this to higher moisture availability supplied by the Indian Monsoon.
SCLpred‐MEM: Subcellular localization prediction of membrane proteins by deep N‐to‐1 convolutional neural networks
Authors: Kaleel Manaz , Ellinger Liam , Lalor Clodagh , Pollastri Gianluca , Mooney Catherine 
Published: May 2021

AbstractThe knowledge of the subcellular location of a protein is a valuable source of information in genomics, drug design, and various other theoretical and analytical perspectives of bioinformatics. Due to the expensive and time‐consuming nature of experimental methods of protein subcellular location determination, various computational methods have been developed for subcellular localization prediction. We introduce “SCLpred‐MEM,” an ab initio protein subcellular localization predictor, powered by an ensemble of Deep N‐to‐1 Convolutional Neural Networks (N1‐NN) trained and tested on strict redundancy reduced datasets. SCLpred‐MEM is available as a web‐server predicting query proteins into two classes, membrane and non‐membrane proteins. SCLpred‐MEM achieves a Matthews correlation coefficient of 0.52 on a strictly homology‐reduced independent test set and 0.62 on a less strict homology reduced independent test set, surpassing or matching other state‐of‐the‐art subcellular localization predictors.