bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Follow-Up of CD19-CAR T-Cell Therapy in Children and Young Adults With B-ALL
Authors: Shah Nirali N. , Lee Daniel W. , Yates Bonnie , Yuan Constance M. , Shalabi Haneen , Martin Staci , Wolters Pamela L. , Steinberg Seth M. , Baker Eva H. , Delbrook Cindy P. , Stetler-Stevenson Maryalice , Fry Terry J. , Stroncek David F. , Mackall Crystal L. 
Published: March 2021

PURPOSE CD19 chimeric antigen receptor (CD19-CAR) T cells induce high response rates in children and young adults (CAYAs) with B-cell acute lymphoblastic leukemia (B-ALL), but relapse rates are high. The role for allogeneic hematopoietic stem-cell transplant (alloHSCT) following CD19-CAR T-cell therapy to improve long-term outcomes in CAYAs has not been examined. METHODS We conducted a phase I trial of autologous CD19.28ζ-CAR T cells in CAYAs with relapsed or refractory B-ALL. Response and long-term clinical outcomes were assessed in relation to disease and treatment variables. RESULTS Fifty CAYAs with B-ALL were treated (median age, 13.5 years; range, 4.3-30.4). Thirty-one (62.0%) patients achieved a complete remission (CR), 28 (90.3%) of whom were minimal residual disease−negative by flow cytometry. Utilization of fludarabine/cyclophosphamide–based lymphodepletion was associated with improved CR rates (29/42, 69%) compared with non–fludarabine/cyclophosphamide–based lymphodepletion (2/8, 25%; P = .041). With median follow-up of 4.8 years, median overall survival was 10.5 months (95% CI, 6.3 to 29.2 months). Twenty-one of 28 (75.0%) patients achieving a minimal residual disease−negative CR proceeded to alloHSCT. For those proceeding to alloHSCT, median overall survival was 70.2 months (95% CI, 10.4 months to not estimable). The cumulative incidence of relapse after alloHSCT was 9.5% (95% CI, 1.5 to 26.8) at 24 months; 5-year EFS following alloHSCT was 61.9% (95% CI, 38.1 to 78.8). CONCLUSION We provide the longest follow-up in CAYAs with B-ALL after CD19-CAR T-cell therapy reported to date and demonstrate that sequential therapy with CD19.28ζ-CAR T cells followed by alloHSCT can mediate durable disease control in a sizable fraction of CAYAs with relapsed or refractory B-ALL (ClinicalTrials.gov identifier: NCT01593696 ).
Phase III, Randomized, Placebo-Controlled Trial of CC-486 (Oral Azacitidine) in Patients With Lower-Risk Myelodysplastic Syndromes
Authors: Garcia-Manero Guillermo , Santini Valeria , Almeida Antonio , Platzbecker Uwe , Jonasova Anna , Silverman Lewis R. , Falantes Jose , Reda Gianluigi , Buccisano Francesco , Fenaux Pierre , Buckstein Rena , Diez Campelo Maria , Larsen Stephen , Valcarcel David , Vyas Paresh , Giai Valentina , Olíva Esther Natalie , Shortt Jake , Niederwieser Dietger , Mittelman Moshe , Fianchi Luana , La Torre Ignazia , Zhong Jianhua , Laille Eric , Lopes de Menezes Daniel , Skikne Barry , Beach C. L. , Giagounidis Aristoteles 
Published: March 2021

PURPOSE Treatment options are limited for patients with lower-risk myelodysplastic syndromes (LR-MDS). This phase III, placebo-controlled trial evaluated CC-486 (oral azacitidine), a hypomethylating agent, in patients with International Prognostic Scoring System LR-MDS and RBC transfusion–dependent anemia and thrombocytopenia. METHODS Patients were randomly assigned 1:1 to CC-486 300-mg or placebo for 21 days/28-day cycle. The primary end point was RBC transfusion independence (TI). RESULTS Two hundred sixteen patients received CC-486 (n = 107) or placebo (n = 109). The median age was 74 years, median platelet count was 25 × 109/L, and absolute neutrophil count was 1.3 × 109/L. In the CC-486 and placebo arms, 31% and 11% of patients, respectively, achieved RBC-TI ( P = .0002), with median durations of 11.1 and 5.0 months. Reductions of ≥ 4 RBC units were attained by 42.1% and 30.6% of patients, respectively, with median durations of 10.0 and 2.3 months, and more CC-486 patients had ≥ 1.5 g/dL hemoglobin increases from baseline (23.4% v 4.6%). Platelet hematologic improvement rate was higher with CC-486 (24.3% v 6.5%). Underpowered interim overall survival analysis showed no difference between CC-486 and placebo (median, 17.3 v 16.2 months; P = .96). Low-grade GI events were the most common adverse events in both arms. In the CC-486 and placebo arms, 90% and 73% of patients experienced a grade 3-4 adverse event. Overall death rate was similar between arms, but there was an imbalance in deaths during the first 56 days (CC-486, n = 16; placebo, n = 6), most related to infections; the median pretreatment absolute neutrophil count for the 16 CC-486 patients was 0.57 × 109/L. CONCLUSION CC-486 significantly improved RBC-TI rate and induced durable bilineage improvements in patients with LR-MDS and high-risk disease features. More early deaths occurred in the CC-486 arm, most related to infections in patients with significant pretreatment neutropenia. Further evaluation of CC-486 in MDS is needed.
Vortices in Maxwell-Higgs models with a global factor
Authors: Andrade I. , Marques M. A. , Menezes R. 
Published: March 2021

Abstract
This paper deals with planar vortices in a generalized model that presents a global factor which depends on the scalar field in the Nielsen-Olesen Lagrange density. We show that the system supports a first-order framework. Contrary to what occurs with kinks in the line, planar vortices require the presence of constraints that brings modifications into the first-order equations. Novel features are unveiled, such as finite energy configurations with infinite energy density at the origin and the presence of parameters that modifies the energy, keeping the solutions unchanged.
Arid1a regulates cell cycle exit of transit-amplifying cells by inhibiting the Aurka-Cdk1 axis in mouse incisor
Authors: Du Jiahui , Jing Junjun , Chen Shuo , Yuan Yuan , Feng Jifan , Ho Thach-Vu , Sehgal Prerna , Xu Jian , Jiang Xinquan , Chai Yang 
Published: March 2021

ABSTRACT
Stem cells self-renew or give rise to transit-amplifying cells (TACs) that differentiate into specific functional cell types. The fate determination of stem cells to TACs and their transition to fully differentiated progeny is precisely regulated to maintain tissue homeostasis. Arid1a, a core component of the switch/sucrose nonfermentable complex, performs epigenetic regulation of stage- and tissue-specific genes that is indispensable for stem cell homeostasis and differentiation. However, the functional mechanism of Arid1a in the fate commitment of mesenchymal stem cells (MSCs) and their progeny is not clear. Using the continuously growing adult mouse incisor model, we show that Arid1a maintains tissue homeostasis through limiting proliferation, promoting cell cycle exit and differentiation of TACs by inhibiting the Aurka-Cdk1 axis. Loss of Arid1a overactivates the Aurka-Cdk1 axis, leading to expansion of the mitotic TAC population but compromising their differentiation ability. Furthermore, the defective homeostasis after loss of Arid1a ultimately leads to reduction of the MSC population. These findings reveal the functional significance of Arid1a in regulating the fate of TACs and their interaction with MSCs to maintain tissue homeostasis.
Metabolic response of dolphins to short-term fasting reveals physiological changes that differ from the traditional fasting model
Authors: Houser Dorian S. , Derous Davina , Douglas Alex , Lusseau David 
Published: March 2021

ABSTRACT
Bottlenose dolphins (Tursiops truncatus) typically feed on prey that are high in lipid and protein content and nearly devoid of carbohydrate, a dietary feature shared with other marine mammals. However, unlike fasted-adapted marine mammals that predictably incorporate fasting into their life history, dolphins feed intermittently throughout the day and are not believed to be fasting-adapted. To assess whether the physiological response to fasting in the dolphin shares features with or distinguishes them from those of fasting-adapted marine mammals, the plasma metabolomes of eight bottlenose dolphins were compared between post-absorptive and 24-h fasted states. Increases in most identified free fatty acids and lipid metabolites and reductions in most amino acids and their metabolites were consistent with the upregulation of lipolysis and lipid oxidation and the downregulation of protein catabolism and synthesis. Consistent with a previously hypothesized diabetic-like fasting state, fasting was associated with elevated glucose and patterns of certain metabolites (e.g. citrate, cis-aconitate, myristoleic acid) indicative of lipid synthesis and glucose cycling to protect endogenous glucose from oxidative disposal. Pathway analysis predicted an upregulation of cytokines, decreased cell growth and increased apoptosis including apoptosis of insulin-secreting β-cells. Metabolomic conditional mutual information networks were estimated for the post-absorptive and fasted states and ‘topological modules’ were estimated for each using the eigenvector approach to modularity network division. A dynamic network marker indicative of a physiological shift toward a negative energy state was subsequently identified that has the potential conservation application of assessing energy state balance in at-risk wild dolphins.
Sound detection by the American lobster (Homarus americanus)
Authors: Jézéquel Youenn , Jones Ian T. , Bonnel Julien , Chauvaud Laurent , Atema Jelle , Mooney T. Aran 
Published: March 2021

ABSTRACT
Although many crustaceans produce sounds, their hearing abilities and mechanisms are poorly understood, leaving uncertainties regarding whether or how these animals use sound for acoustic communication. Marine invertebrates lack gas-filled organs required for sound pressure detection, but some of them are known to be sensitive to particle motion. Here, we examined whether the American lobster (Homarus americanus) could detect sound and subsequently sought to discern the auditory mechanisms. Acoustic stimuli responses were measured using auditory evoked potential (AEP) methods. Neurophysiological responses were obtained from the brain using tone pips between 80 and 250 Hz, with best sensitivity at 80–120 Hz. There were no significant differences between the auditory thresholds of males and females. Repeated controls (recordings from deceased lobsters, moving electrodes away from the brain and reducing seawater temperature) indicated the evoked potentials' neuronal origin. In addition, AEP responses were similar before and after antennules (including statocysts) were ablated, demonstrating that the statocysts, a long-proposed auditory structure in crustaceans, are not the sensory organs responsible for lobster sound detection. However, AEPs could be eliminated (or highly reduced) after immobilizing hairfans, which cover much of lobster bodies. These results suggest that these external cuticular hairs are likely to be responsible for sound detection, and imply that hearing is mechanistically possible in a wider array of invertebrates than previously considered. Because the lobsters' hearing range encompasses the fundamental frequency of their buzzing sounds, it is likely that they use sound for intraspecific communication, broadening our understanding of the sensory ecology of this commercially vital species. The lobsters' low-frequency acoustic sensitivity also underscores clear concerns about the potential impacts of anthropogenic noise.
Utility of minimum intensity projection images based on three-dimensional CUBE T
1 weighted imaging for evaluating middle cerebral artery stenosis
Authors: Wu Yejun , Li Fangbing , Wang Yilin , Hu Tianxiang , Xiao Liang 
Published: March 2021

Objective:
This study investigated the diagnostic performance of MinIP images based on three-dimensional variable-flip-angle turbo spin echo T 1 weighted imaging (3D CUBE T 1WI) from high-resolution vessel wall magnetic resonance imaging for detecting middle cerebral artery (MCA) stenosis.

Methods:
A total of 63 consecutive patients were included in this study. MinIP images were reconstructed using 3D CUBE T 1WI as the source images. The degree and length of MCA stenosis were measured on MinIP images and were compared with digital subtraction angiography (DSA) as the reference standard.

Results:
The intra- and interobserver agreement for both the rate and length of MCA stenosis were excellent for the MinIP images. There was also excellent agreement in the degree of MCA stenosis calculated using MinIP images and DSA. MinIP images had a high sensitivity, specificity for diagnosing MCA stenosis. There was a good correlation between the two methods for measuring the rate and length of MCA stenosis.

Conclusion:
MinIP images based on 3D CUBE T 1WI are highly consistent with DSA for evaluating the degree and length of MCA stenosis.

Advances in knowledge:
MinIP images can be produced as a derivative from vessel wall imaging and implemented as an adjunct to vessel wall imaging without extra acquisition time.
In silico prediction of structure and function for a large family of transmembrane proteins that includes human Tmem41b
Authors: Mesdaghi Shahram , Murphy David L. , Sánchez Rodríguez Filomeno , Burgos-Mármol J. Javier , Rigden Daniel J. 
Published: March 2021

Background: Recent strides in computational structural biology have opened up an opportunity to understand previously uncharacterised proteins. The under-representation of transmembrane proteins in the Protein Data Bank highlights the need to apply new and advanced bioinformatics methods to shed light on their structure and function. This study focuses on a family of transmembrane proteins containing the Pfam domain PF09335 ('SNARE_ASSOC'/ ‘VTT ‘/’Tvp38’/'DedA'). One prominent member, Tmem41b, has been shown to be involved in early stages of autophagosome formation and is vital in mouse embryonic development as well as being identified as a viral host factor of SARS-CoV-2. Methods: We used evolutionary covariance-derived information to construct and validate ab initio models, make domain boundary predictions and infer local structural features. Results: The results from the structural bioinformatics analysis of Tmem41b and its homologues showed that they contain a tandem repeat that is clearly visible in evolutionary covariance data but much less so by sequence analysis. Furthermore, cross-referencing of other prediction data with covariance analysis showed that the internal repeat features two-fold rotational symmetry. Ab initio modelling of Tmem41b and homologues reinforces these structural predictions. Local structural features predicted to be present in Tmem41b were also present in Cl-/H+ antiporters. Conclusions: The results of this study strongly point to Tmem41b and its homologues being transporters for an as-yet uncharacterised substrate and possibly using H+ antiporter activity as its mechanism for transport.
Designing the Profile of a Student of a General Education School in the Context of the System-Activity and Outcome-Based Approach
Authors: Nikolaev V. 
Published: March 2021

At present goals and objectives of the education development are associated with ensuring the global competitiveness of the Russian education in general and guaranteeing the entry of the Russian Federation into the top 10 countries in the world in terms of the quality of general education, in particular.
To achieve these national goals and objectives aimed at the development of education, the purposeful activity of general education institutions is required. They should focus on the design of modern school models to transform them into a new type of schools that will be able to improve the quality of education and ensure the school graduates’ training and preparation for their future adult life in the context of sustainable technological changes in the production, economic and social spheres.
The article presents the approaches used by the staff of the Educational Complex "Nasha Shkola" in Novosibirsk to the construction of the Student’s Profile as a target reference point for the educational content standard of the System "Nasha Shkola" in the context of the system-activity and outcome-based approaches.
The paper also considers the list of universal competencies and literacy groups that are formed by the educational and technological environment of the school and allow creating conditions for the personal and professional success of each student.
Spectral processing techniques for efficient monitoring in optical networks
Authors: Locatelli Fabiano , Christodoulopoulos Konstantinos , Svaluto Moreolo Michela , Fàbrega Josep M. , Nadal Laia , Spadaro Salvatore 
Published: March 2021

Having ubiquitous optical monitors in dense wavelength-division multiplexing (DWDM) or flex-grid networks allows the estimation in real time of crucial parameters. Such monitoring would be even more important in disaggregated optical networks, to inspect performance issues related to inter-vendor interoperability. Several important parameters can be retrieved using optical spectrum analyzers (OSAs). However, omnipresent OSAs represent an infeasible solution. Nevertheless, the advent of new, relatively cheap, compact and medium-resolution optical channel monitors (OCMs) enable a more intensive deployment of these devices. In this paper, we identify two main scenarios for the placement of such monitors: at the ingress and at the egress of the optical nodes. In the ingress scenario, we can directly estimate the parameters related to the signals, but not those related to the filters. On the contrary, in the egress scenario, the filter-related parameters can be easily detected, but not those related to amplified spontaneous emission. Therefore, we present two methods that, leveraging a curve fitting and a machine learning regression algorithm, allow detection of the missing parameters. We verify the proposed solutions with spectral data acquired in simulation and experimental setups. We obtained good estimation accuracy for both setups and for both studied placement scenarios. It is noteworthy that in the experimental assessment of the ingress scenario, we achieved a maximum absolute error (MAE) lower than 1 GHz in filter bandwidth estimation and a MAE lower than 0.5 GHz in filter frequency shift estimation. In addition, by comparing the relative errors of the considered parameters, we identified the ingress scenario as the more beneficial. In particular, we estimated the filter central frequency shift with 84% and the filter 6 dB bandwidth with 75% higher accuracy, with respect to datasheet/reference values. This translates into a total reduction of the estimated signal-to-noise ratio (SNR) penalty, introduced by a single optical filter, of 0.24 dB.
Transverse mode instability and thermal effects in thulium-doped fiber amplifiers under high thermal loads
Authors: Gaida Christian , Gebhardt Martin , Heuermann Tobias , Wang Ziyao , Jauregui Cesar , Limpert Jens 
Published: March 2021

We experimentally analyze the average-power-scaling capabilities of ultrafast, thulium-doped fiber amplifiers. It has been theoretically predicted that thulium-doped fiber laser systems, with an emission wavelength around 2 µm, should be able to withstand much higher heat-loads than their Yb-doped counterparts before the onset of transverse mode instability (TMI) is observed. In this work we experimentally verify this theoretical prediction by operating thulium doped fibers at very high heat-load. In separate experiments we analyze the performance of two different large-core, thulium-doped fiber amplifiers. The first experiment aims at operating a short, very-large core, thulium-doped fiber amplifier at extreme heat-load levels of more than 300 W/m. Even at this extreme heat-load level, the onset of TMI is not observed. The second experiment maximizes the extractable average-output power from a large-core, thulium-doped, fiber amplifier. We have achieved a pump-limited average output power of 1.15 kW without the onset of TMI. However, during a longer period of operation at this power level the amplifier performance steadily degraded and TMI could be observed for average powers in excess of 847 W thereafter. This is the first time, to the best of our knowledge, that TMI has been reported in a thulium-doped fiber amplifier.
Vector scanning subtractive manufacturing technology for laser rapid fabrication
Authors: Lu Yi-Ming , Liu Xue-Qing , Zhu Lin , Chen Qi-Dai , Juodkazis Saulius , Sun Hong-Bo 
Published: March 2021

Herein, a vector scanning subtractive manufacturing technology is proposed to rapidly fabricate smooth micro-optical components, which is based on the vector scanning method and wet etching. Compared with the raster scanning method, the vector scanning method increases processing efficiency by nearly two orders and mitigates a buildup of stress around the laser processed region, avoiding the generation of cracks. The Letter demonstrates the fabrication of three-dimensional (3D) micro-structures with various sizes and morphologies. For example, micro-concave lenses with diameters of 20 µm to 140 µm, heights of 10 µm to 70 µm, and surface roughness of 29 nm are flexibly fabricated on sapphire by vector scanning subtractive manufacturing technology. The results indicate that the technology has broad prospects in the field of monolithic integrated 3D all-solid-state micro-optics.
Laser-induced fluorescence thermometry of supercritical CO2 flows inside a micro-channel
Authors: Park Suhyeon , Parahovnik Anatoly , Peles Yoav , Vasu Subith S. 
Published: March 2021

This work demonstrates a thermometric technique using laser-induced fluorescence (LIF) in supercritical carbon dioxide flows in a micro-channel. Rhodamine 6G was used as a temperature-sensitive fluorescent dye. The flow conditions were at a pressure of 7.9 MPa and temperature in the range of 23°–90°C. 2D spatial distributions and time-resolved temperature profiles were obtained at this high pressure. Measured LIF signals showed close relations to the temperatures obtained from resistance temperature detectors.
Enhanced 3.9  µm emission from diode pumped
Ho3+/Eu3+ codoped fluoroindate glasses
Authors: Zhang Zhi , Wang Ruicong , Liu Mo , Wang Shunbin , Zhang Jie , Brambilla Gilberto , Jia Shijie , Wang Pengfei 
Published: March 2021

The use of

E
u

3
+

codoping for enhancing the

H
o

3
+

:

5

I

5

→

5

I

6

emission in fluoroindate glasses shows that

E
u

3
+

could depopulate the lower laser state

H
o

3
+

:

5

I

6

while having little effect on the upper state

H
o

3
+

:

5

I

5

, resulting in greater population inversion. The

H
o

3
+

/

E
u

3
+

codoped glass has high spontaneous transition probability (

6.31

s

−
1

) together with large emission cross section (

7.68

×

10

−
21

c
m

2

). This study indicates that codoping of

H
o

3
+

with

E
u

3
+

is a feasible alternative to quench the lower energy level of the 3.9 µm emission and the

H
o

3
+

/

E
u

3
+

codoped fluoroindate glass is a promising material for efficient 3.9 µm fiber lasers.