bluuebunny/crossref_metadata_2025_split huggingface dataset:
How I treat chronic lymphocytic leukemia after venetoclax
Authors: Lew Thomas E. , Tam Constantine S. , Seymour John F. 
Published: April 2021

AbstractVenetoclax-based regimens have expanded the therapeutic options for patients with chronic lymphocytic leukemia (CLL), frequently achieving remissions with undetectable measurable residual disease and facilitating time-limited treatment without chemotherapy. Although response rates are high and durable disease control is common, longer-term follow-up of patients with relapsed and refractory disease, especially in the presence of TP53 aberrations, demonstrates frequent disease resistance and progression. Although the understanding of venetoclax resistance remains incomplete, progressive disease is typified by oligoclonal leukemic populations with distinct resistance mechanisms, including BCL2 mutations, upregulation of alternative BCL2 family proteins, and genomic instability. Although most commonly observed in heavily pretreated patients with disease refractory to fludarabine and harboring complex karyotype, Richter transformation presents a distinct and challenging manifestation of venetoclax resistance. For patients with progressive CLL after venetoclax, treatment options include B-cell receptor pathway inhibitors, allogeneic stem cell transplantation, chimeric antigen receptor T cells, and venetoclax retreatment for those with disease relapsing after time-limited therapy. However, data to inform clinical decisions for these patients are limited. We review the biology of venetoclax resistance and outline an approach to the common clinical scenarios encountered after venetoclax-based therapy that will increasingly confront practicing clinicians.
The chromatin remodeler CHD8 governs hematopoietic stem/progenitor survival by regulating ATM-mediated P53 protein stability
Authors: Tu Zhaowei , Wang Chen , Davis Ashley K. , Hu Mengwen , Zhao Chuntao , Xin Mei , Lu Q. Richard , Zheng Yi 
Published: April 2021

Abstract
The Chd8 gene encodes a member of the chromodomain helicase DNA-binding (CHD) family of SNF2H-like adenosine triphosphate (ATP)-dependent chromatin remodeler, the mutations of which define a subtype of autism spectrum disorders. Increasing evidence from recent studies indicates that ATP-dependent chromatin-remodeling genes are involved in the control of crucial gene-expression programs in hematopoietic stem/progenitor cell (HSPC) regulation. In this study, we identified CHD8 as a specific and essential regulator of normal hematopoiesis. Loss of Chd8 leads to severe anemia, pancytopenia, bone marrow failure, and engraftment failure related to a drastic depletion of HSPCs. CHD8 forms a complex with ATM and its deficiency increases chromatin accessibility and drives genomic instability in HSPCs causing an activation of ATM kinase that further stabilizes P53 protein by phosphorylation and leads to increased HSPC apoptosis. Deletion of P53 rescues the apoptotic defects of HSPCs and restores overall hematopoiesis in Chd8−/− mice. Our findings demonstrate that chromatin organization by CHD8 is uniquely necessary for the maintenance of hematopoiesis by integrating the ATM-P53–mediated survival of HSPCs.
Iron homeostasis during anemia of inflammation: a prospective study of patients with tuberculosis
Authors: Cercamondi Colin I. , Stoffel Nicole U. , Moretti Diego , Zoller Thomas , Swinkels Dorine W. , Zeder Christophe , Mhimibra Francis , Hella Jerry , Fenner Lukas , Zimmermann Michael B. 
Published: April 2021

Abstract
Anemia of inflammation is a hallmark of tuberculosis. Factors controlling iron metabolism during anemia of inflammation and its resolution are uncertain. Whether iron supplements should be given during antituberculosis treatment to support hemoglobin (Hb) recovery is unclear. Before and during treatment of tuberculosis, we assessed iron kinetics, as well as changes in inflammation and iron metabolism indices. In a 26-week prospective study, Tanzanian adults with tuberculosis (N = 18) were studied before treatment and then every 2 weeks during treatment; oral and intravenous iron tracers were administered before treatment and after intensive phase (8/12 weeks) and complete treatment (24 weeks). No iron supplements were given. Before treatment, hepcidin and erythroferrone (ERFE) were greatly elevated, erythrocyte iron utilization was high (∼80%), and iron absorption was negligible (&lt;1%). During treatment, hepcidin and interleukin-6 levels decreased ∼70% after only 2 weeks (P&lt; .001); in contrast, ERFE did not significantly decrease until 8 weeks (P&lt; .05). ERFE and interleukin-6 were the main opposing determinants of hepcidin (P&lt; .05), and greater ERFE was associated with reticulocytosis and Hb repletion (P&lt; .01). Dilution of baseline tracer concentration was 2.6-fold higher during intensive phase treatment (P&lt; .01), indicating enhanced erythropoiesis. After treatment completion, iron absorption increased ∼20-fold (P&lt; .001), and Hb increased ∼25% (P&lt; .001). In tuberculosis-associated anemia of inflammation, our findings suggest that elevated ERFE is unable to suppress hepcidin, and iron absorption is negligible. During treatment, as inflammation resolves, ERFE may remain elevated, contributing to hepcidin suppression and Hb repletion. Iron is well absorbed only after tuberculosis treatment, and supplementation should be reserved for patients remaining anemic after treatment. This trial was registered at www.clinicaltrials.gov as #NCT02176772.
An Overview on Recent Progress of Metal Oxide/Graphene/CNTs-Based Nanobiosensors
Authors: Aykaç Ahmet , Gergeroglu Hazal , Beşli Büşra , Akkaş Emine Özge , Yavaş Ahmet , Güler Saadet , Güneş Fethullah , Erol Mustafa 
Published: April 2021

AbstractNanobiosensors are convenient, practical, and sensitive analyzers that detect chemical and biological agents and convert the results into meaningful data between a biologically active molecule and a recognition element immobilized on the surface of the signal transducer by a physicochemical detector. Due to their fast, accurate and reliable operating characteristics, nanobiosensors are widely used in clinical and nonclinical applications, bedside testing, medical textile industry, environmental monitoring, food safety, etc. They play an important role in such critical applications. Therefore, the design of the biosensing interface is essential in determining the performance of the nanobiosensor. The unique chemical and physical properties of nanomaterials have paved the way for new and improved sensing devices in biosensors. The growing demand for devices with improved sensing and selectivity capability, short response time, lower limit of detection, and low cost causes novel investigations on nanobiomaterials to be used as biosensor scaffolds. Among all other nanomaterials, studies on developing nanobiosensors based on metal oxide nanostructures, graphene and its derivatives, carbon nanotubes, and the widespread use of these nanomaterials as a hybrid structure have recently attracted attention. Nanohybrid structures created by combining these nanostructures will directly meet the future biosensors’ needs with their high electrocatalytic activities. This review addressed the recent developments on these nanomaterials and their derivatives, and their use as biosensor scaffolds. We reviewed these popular nanomaterials by evaluating them with comparative studies, tables, and charts.
Formation and Evaluation of Silicon Substrate with Highly-Doped Porous Si Layers Formed by Metal-Assisted Chemical Etching
Authors: Li Yijie , Van Toan Nguyen , Wang Zhuqing , Samat Khairul Fadzli Bin , Ono Takahito 
Published: April 2021

AbstractPorous silicon (Si) is a low thermal conductivity material, which has high potential for thermoelectric devices. However, low output performance of porous Si hinders the development of thermoelectric performance due to low electrical conductivity. The large contact resistance from nonlinear contact between porous Si and metal is one reason for the reduction of electrical conductivity. In this paper, p- and n-type porous Si were formed on Si substrate by metal-assisted chemical etching. To decrease contact resistance, p- and n-type spin on dopants are employed to dope an impurity element into p- and n-type porous Si surface, respectively. Compared to the Si substrate with undoped porous samples, ohmic contact can be obtained, and the electrical conductivity of doped p- and n-type porous Si can be improved to 1160 and 1390 S/m, respectively. Compared with the Si substrate, the special contact resistances for the doped p- and n-type porous Si layer decreases to 1.35 and 1.16 mΩ/cm2, respectively, by increasing the carrier concentration. However, the increase of the carrier concentration induces the decline of the Seebeck coefficient for p- and n-type Si substrates with doped porous Si samples to 491 and 480 μV/K, respectively. Power factor is related to the Seebeck coefficient and electrical conductivity of thermoelectric material, which is one vital factor that evaluates its output performance. Therefore, even though the Seebeck coefficient values of Si substrates with doped porous Si samples decrease, the doped porous Si layer can improve the power factor compared to undoped samples due to the enhancement of electrical conductivity, which facilitates its development for thermoelectric application.
White matter microstructure associations with episodic memory in adults with Down syndrome: a tract-based spatial statistics study
Authors: Bazydlo Austin , Zammit Matthew , Wu Minjie , Dean Douglas , Johnson Sterling , Tudorascu Dana , Cohen Ann , Cody Karly , Ances Beau , Laymon Charles , Klunk William , Zaman Shahid , Handen Benjamin , Alexander Andrew , Christian Bradley , Hartley Sigan 
Published: April 2021

Abstract
Background
Nearly all persons with Down syndrome will show pathology of Alzheimer’s disease in their 40s. There is a critical need for studies to identify early biomarkers of these various pathological changes of Alzheimer’s disease in the Down syndrome population and understand the relationship of these biomarkers to cognitive symptoms in order to inform clinical trials. Although Alzheimer’s disease is often considered a disease of gray matter, white matter degeneration has been documented during the preclinical stage of Alzheimer’s disease. The current study examined the association between diffusion tensor imaging (DTI) measures of white matter microstructure and episodic memory performance in 52 adults with Down syndrome.

Methods
Seventy (N = 70) participants (M = 40.13, SD = 7.77 years) received baseline scans as part of the Neurodegeneration in Aging Down Syndrome (NiAD) study at two imaging facilities (36 at the University of Wisconsin-Madison [UW-Madison] and 34 at the University of Pittsburgh Medical Center [UPMC]). All participants had genetically confirmed trisomy 21. Fifty-two (N = 52) participants remained after QC. The DTI measures, fractional anisotropy (FA) and mean diffusivity (MD), were calculated for each participant. A combined measure of episodic memory was generated by summing the z-scores of (1) Free and Cued Recall test and (2) Rivermead Behavioural Memory Test for Children Picture Recognition. The DTI data were projected onto a population-derived FA skeleton and tract-based spatial statistics analysis was conducted using the FSL tool PALM to calculate Pearson’s r values between FA and MD with episodic memory.

Results
A positive correlation of episodic memory with FA and a negative correlation of episodic memory and MD in the major association white matter tracts were observed. Results were significant (p < 0.05) after correction for chronological age, imaging site, and premorbid cognitive ability.

Conclusion
These findings suggest that white matter degeneration may be implicated in early episodic memory declines prior to the onset of dementia in adults with Down syndrome. Further, our findings suggest a coupling of episodic memory and white matter microstructure independent of chronological age.
MAPS: machine-assisted phenotype scoring enables rapid functional assessment of genetic variants by high-content microscopy
Authors: Chao Jesse T. , Roskelley Calvin D. , Loewen Christopher J. R. 
Published: April 2021

AbstractBackgroundGenetic testing is widely used in evaluating a patient’s predisposition to hereditary diseases. In the case of cancer, when a functionally impactful mutation (i.e. genetic variant) is identified in a disease-relevant gene, the patient is at elevated risk of developing a lesion in their lifetime. Unfortunately, as the rate and coverage of genetic testing has accelerated, our ability to assess the functional status of new variants has fallen behind. Therefore, there is an urgent need for more practical, streamlined and cost-effective methods for classifying variants.ResultsTo directly address this issue, we designed a new approach that uses alterations in protein subcellular localization as a key indicator of loss of function. Thus, new variants can be rapidly functionalized using high-content microscopy (HCM). To facilitate the analysis of the large amounts of imaging data, we developed a new software toolkit, named MAPS for machine-assisted phenotype scoring, that utilizes deep learning to extract and classify cell-level features. MAPS helps users leverage cloud-based deep learning services that are easy to train and deploy to fit their specific experimental conditions. Model training is code-free and can be done with limited training images. Thus, MAPS allows cell biologists to easily incorporate deep learning into their image analysis pipeline. We demonstrated an effective variant functionalization workflow that integrates HCM and MAPS to assess missense variants ofPTEN, a tumor suppressor that is frequently mutated in hereditary and somatic cancers.ConclusionsThis paper presents a new way to rapidly assess variant function using cloud deep learning. Since most tumor suppressors have well-defined subcellular localizations, our approach could be widely applied to functionalize variants of uncertain significance and help improve the utility of genetic testing.
Correlation AnalyzeR: functional predictions from gene co-expression correlations
Authors: Miller Henry E. , Bishop Alexander J. R. 
Published: April 2021

AbstractBackgroundCo-expression correlations provide the ability to predict gene functionality within specific biological contexts, such as different tissue and disease conditions. However, current gene co-expression databases generally do not consider biological context. In addition, these tools often implement a limited range of unsophisticated analysis approaches, diminishing their utility for exploring gene functionality and gene relationships. Furthermore, they typically do not provide the summary visualizations necessary to communicate these results, posing a significant barrier to their utilization by biologists without computational skills.ResultsWe present Correlation AnalyzeR, a user-friendly web interface for exploring co-expression correlations and predicting gene functions, gene–gene relationships, and gene set topology. Correlation AnalyzeR provides flexible access to its database of tissue and disease-specific (cancer vs normal) genome-wide co-expression correlations, and it also implements a suite of sophisticated computational tools for generating functional predictions with user-friendly visualizations. In the usage example provided here, we explore the role ofBRCA1-NRF2interplay in the context of bone cancer, demonstrating how Correlation AnalyzeR can be effectively implemented to generate and support novel hypotheses.ConclusionsCorrelation AnalyzeR facilitates the exploration of poorly characterized genes and gene relationships to reveal novel biological insights. The database and all analysis methods can be accessed as a web application athttps://gccri.bishop-lab.uthscsa.edu/correlation-analyzer/and as a standalone R package athttps://github.com/Bishop-Laboratory/correlationAnalyzeR.
Changes in the expression levels of elastic fibres in yak lungs at different growth stages
Authors: Li Jingyi , Meng Xiangqiong , Wang Lihan , Yu Yang , Yu Hongxian , Wei Qing 
Published: April 2021

Abstract
Background
Yaks have a strong adaptability to the plateau environment, which can be attributed to the effective oxygen utilization rate of their lung tissue. Elastic fibre confers an important adaptive structure to the alveolar tissues in yaks. However, little research has been focused on the structural development of lung tissues and the expression levels of elastic fibres in yaks after birth. Therefore, this study aimed to investigate the morphological changes of elastic fibers and expression profiles of fibre-formation genes in yak lungs at different growth stages and the relationship between these changes and plateau adaptation.

Results
Histological staining was employed to observe the morphological changes in the lung tissue structure of yaks at four different ages: 1 day old, 30 days old, 180 days old and adult. There was no significant difference in the area of a single alveolus between the 1-day-old and 30-day-old groups (P-value > 0.05). However, the single alveolar area was gradually increased with an increase in age (P-value < 0.05). Elastic fibre staining revealed that the amount of elastic fibres in alveolar tissue was increased significantly from the ages of 30 days to 180 days (P-value < 0.05) and stabilized during the adult stage. Transcriptome analysis indicated that the highest levels of differentially expressed genes were found between 30 days of age and 180 days of age. KEGG analysis showed that PI3K-Akt signalling pathway and MAPK pathway, which are involved in fibre formation, accounted for the largest proportion of differentially expressed genes between 30 days of age and 180 days of age. The expression levels of 36 genes related to elastic fibre formation and collagen fibre formation were also analysed, and most of these genes were highly expressed in 30-day-old and 180-day-old yaks.

Conclusions
The content of elastic fibres in the alveolar tissue of yaks increases significantly after birth, but this change occurs only from 30 days of age to 180 days of age. Our study indicates that elastic fibres can improve the efficiency of oxygen utilization in yaks under harsh environmental conditions.
Treatment with surfactants enables quantification of translational activity by O-propargyl-puromycin labelling in yeast
Authors: Staudacher Jennifer , Rebnegger Corinna , Gasser Brigitte 
Published: April 2021

Abstract
Background
Translation is an important point of regulation in protein synthesis. However, there is a limited number of methods available to measure global translation activity in yeast. Recently, O-propargyl-puromycin (OPP) labelling has been established for mammalian cells, but unmodified yeasts are unsusceptible to puromycin.

Results
We could increase susceptibility by using a Komagataella phaffii strain with an impaired ergosterol pathway (erg6Δ), but translation measurements are restricted to this strain background, which displayed growth deficits. Using surfactants, specifically Imipramine, instead, proved to be more advantageous and circumvents previous restrictions. Imipramine-supplemented OPP-labelling with subsequent flow cytometry analysis, enabled us to distinguish actively translating cells from negative controls, and to clearly quantify differences in translation activities in different strains and growth conditions. Specifically, we investigated K. phaffii at different growth rates, verified that methanol feeding alters translation activity, and analysed global translation in strains with genetically modified stress response pathways.

Conclusions
We set up a simple protocol to measure global translation activity in yeast on a single cell basis. The use of surfactants poses a practical and non-invasive alternative to the commonly used ergosterol pathway impaired strains and thus impacts a wide range of applications where increased drug and dye uptake is needed.
Assessment of the knowledge level and experience of healthcare personnel concerning CPR and early defibrillation: an internal survey
Authors: Spinelli G. , Brogi E. , Sidoti A. , Pagnucci N. , Forfori F. 
Published: April 2021

Abstract
Background
In‐hospital cardiac arrest (IHCA) is a major public health problem with significant mortality. Rapid cardiopulmonary resuscitation and early defibrillation is extremely connected to patient outcome. In this study, we aimed to assess the effects of a basic life support and defibrillation course in improving knowledge in IHCA management.

Methods
We performed a prospective observational study recruiting healthcare personnel working at Azienda Ospedaliero Universitaria Pisana, Pisa, Italy. Study consisted in the administration of two questionnaires before and after BLS-D course. The course was structured as an informative meeting and it was held according to European Resuscitation Council guidelines.

Results
78 participants completed pre- and post-course questionnaires. Only 31.9% of the participants had taken part in a BLS-D before our study. After the course, we found a significative increase in the percentage of participants that evaluated their skills adequate in IHCA management (17.9% vs 42.3%; p < 0.01) and in the correct use of defibrillator (38.8% vs 67.9% p < 0.001). However, 51.3% of respondents still consider their preparation not entirely appropriate after the course. Even more, we observed a significant increase in the number of corrected responses after the course, especially about sequence performed in case of absent vital sign, CPR maneuvers and use of defibrillator.

Conclusions
The training course resulted in significant increase in the level of knowledge about the general management of IHCA in hospital staff. Therefore, a simple intervention such as an informative meetings improved significantly the knowledge about IHCA and, consequently, can lead to a reduction of morbidity and mortality.