bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

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

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.
Discursos de seguridad en Argentina y Brasil: un análisis desde la teoría de la securitización
Authors: Cardinale María Eugenia
Published: March 2021

Los gobiernos conservadores de Argentina y Brasil se han respaldado en discursos securitarios frente a amenazas o peligros calificados de graves y existenciales. Nos proponemos describir los discursos y las prácticas llevadas a cabo en nombre de la seguridad, y analizarlos a través de la teoría de la securitización, buscando identificar elementos propios de esta en ambas coyunturas. Para ello nos centramos en distinguir en las enunciaciones: actor securitizador, sujeto amenazante, audiencias habilitadoras y medidas extraordinarias implicadas. Estos elementos constituyen una guía para poder dilucidar si estamos ante un efectivo proceso de securitización en los dos casos bajo estudio. Este es un estudio descriptivo-interpretativo que se basa en la teoría de la securitización, seleccionando algunos de sus componentes, para el análisis de los casos de Mauricio Macri y Jair Bolsonaro, a modo de evaluar si estamos ante la aplicabilidad de dicho enfoque.
Technical Note–A Simple Heuristic Policy for Stochastic Distribution Inventory Systems with Fixed Shipment Costs
Authors: Zhu Han , Chen Youhua (Frank) , Hu Ming , Yang Yi
Published: March 2021

Inventory Management in Stochastic Distribution Systems
Reliability and security at the dawn of electronic bank transfers in the 1970s-1980s.
Authors: Maixé-Altés Juan Carlos
Published: March 2021

Desde una perspectiva histórica, el concepto de fiabilidad y seguridad informática a principios de la década de 1970, cuando los procesos de transferencia electrónica de datos estaban en sus primeras etapas, permite observar un cambio de paradigma sobre dichos aspectos en la banca. Los equipos y los programas, considerados como activos informáticos, cobran mayor importancia frente al tradicional concepto de seguridad ligado al dinero depositado o a la identificación de los clientes en la oficina bancaria. El estudio de estos cambios en los casos de Japón,España y Alemania, en relación con el despliegue de sus primeras redes interbancarias, junto al papel de los estándares bancarios en dichos procesos, ofrecen un interesante campo de análisis. En este marco, las consideraciones sobre fiabilidad y seguridad de los procesos constituyen factores clave en una nueva conceptualización de la actividad financiera, dentro de los procesos de desmaterialización de los activos que están afectando al negocio bancario en las últimas décadas.
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.
Rotated rectangular aperture imaging through multi-frame blind deconvolution with Hyper-Laplacian priors
Authors: Zhou Hao , Chen Yueting , Feng Huajun , Lv Guomian , Xu Zhihai , Li Qi
Published: March 2021

Rotated rectangular aperture imaging has many advantages in large aperture telephoto systems due to its lower cost and lower complexity. This technology makes it possible to build super large aperture telescopes. In this paper, we combine the ideas of deblurring with rotated rectangular aperture imaging and propose an image synthesis algorithm based on multi-frame deconvolution. In the specific reconstruction process, Hyper-Laplacian priors and sparse priors are used, and an effective solution is developed. The simulation and real shooting experiments show that our algorithm has excellent performance in visual effect and objective evaluation. The synthetic images are significantly sharper than the results of the existing methods.
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.
Non-iterative complex wave-field reconstruction based on Kramers–Kronig relations
Authors: Shen Cheng , Liang Mingshu , Pan An , Yang Changhuei
Published: March 2021

A non-iterative and non-interferometric computational imaging method to reconstruct a complex wave field called synthetic aperture imaging based on Kramers–Kronig relations (KKSAI) is reported. By collecting images through a modified microscope system with pupil modulation capability, we show that the phase and amplitude profile of the sample at pupil limited resolution can be extracted from as few as two intensity images by using Kramers–Kronig (KK) relations. It is established that as long as each subaperture’s edge crosses the pupil center, the collected raw images are mathematically analogous to off-axis holograms. This in turn allows us to adapt a recently reported KK-relations-based phase recovery framework in off-axis holography for use in KKSAI. KKSAI is non-iterative, free of parameter tuning, and applicable to a wider range of samples. Simulation and experiment results have proved that it has much lower computational burden and achieves the best reconstruction quality when compared with two existing phase imaging methods.
Parameters and determinants of responses to selection in antibody libraries
Authors: Schulz Steven , Boyer Sébastien , Smerlak Matteo , Cocco Simona , Monasson Rémi , Nizak Clément , Rivoire Olivier
Published: March 2021

The sequences of antibodies from a given repertoire are highly diverse at few sites located on the surface of a genome-encoded larger scaffold. The scaffold is often considered to play a lesser role than highly diverse, non-genome-encoded sites in controlling binding affinity and specificity. To gauge the impact of the scaffold, we carried out quantitative phage display experiments where we compare the response to selection for binding to four different targets of three different antibody libraries based on distinct scaffolds but harboring the same diversity at randomized sites. We first show that the response to selection of an antibody library may be captured by two measurable parameters. Second, we provide evidence that one of these parameters is determined by the degree of affinity maturation of the scaffold, affinity maturation being the process by which antibodies accumulate somatic mutations to evolve towards higher affinities during the natural immune response. In all cases, we find that libraries of antibodies built around maturated scaffolds have a lower response to selection to other arbitrary targets than libraries built around germline-based scaffolds. We thus propose that germline-encoded scaffolds have a higher selective potential than maturated ones as a consequence of a selection for this potential over the long-term evolution of germline antibody genes. Our results are a first step towards quantifying the evolutionary potential of biomolecules.
Pulmonary Madurella mycetomatis mycetoma secondary to knee eumycetoma, Senegal
Authors: Diongue Khadim , Diallo Mamadou Alpha , Sarr Lamine , Seck Mame Cheikh , Bréchard Ludivine , Ndiaye Mouhamadou , Badiane Aida Sadikh , Ranque Stéphane , Ndiaye Daouda
Published: March 2021

Mycetoma is a neglected tropical disease which is endemic in Senegal. Although this subcutaneous mycosis is most commonly found on the foot, extrapodal localisations have also been found, including on the leg, knee, thigh, hand, and arm. To our knowledge, no case of blood-spread eumycetoma has been reported in Senegal. Here, we report a case of pulmonary mycetoma secondary to a Madurella mycetomatis knee eumycetoma. The patient was a 41-year-old farmer living in Louga, Senegal, where the Sudano-Sahelian climate is characterised by a short and unstable rainy season and a steppe vegetation. He suffered a trauma to the right more than 20 years previously and had received treatment for more than 10 years with traditional medicine. He consulted at Le Dantec University Hospital in Dakar for treatment of a right knee mycetoma which had been diagnosed more than 10 years ago. He had experienced a chronic cough for more than a year; tuberculosis documentation was negative. Grains collected from the knee and the sputum isolated M. mycetomatis, confirmed by the rRNA gene ITS regions nucleotide sequence analysis. An amputation above the knee was performed, and antibacterial and antifungal therapy was started with amoxicillin-clavulanic acid and terbinafine. The patient died within a month of his discharge from hospital.
Impact of onset-to-door time on outcomes and factors associated with late hospital arrival in patients with acute ischemic stroke
Authors: Lee Eung-Joon , Kim Seung Jae , Bae Jeonghoon , Lee Eun Ji , Kwon Oh Deog , Jeong Han-Yeong , Kim Yongsung , Jeong Hae-Bong
Published: March 2021

Background and purpose

Previous studies have reported that early hospital arrival improves clinical outcomes in patients with acute ischemic stroke; however, whether early arrival is associated with favorable outcomes regardless of reperfusion therapy and the type of stroke onset time is unclear. Thus, we investigated the impact of onset-to-door time on outcomes and evaluated the predictors of pre-hospital delay after ischemic stroke.

Methods

Consecutive acute ischemic stroke patients who arrived at the hospital within five days of onset from September 2019 to May 2020 were selected from the prospective stroke registries of Seoul National University Hospital and Chung-Ang University Hospital of Seoul, Korea. Patients were divided into early (onset-to-door time, ≤4.5 h) and late (>4.5 h) arrivers. Multivariate analyses were performed to assess the effect of early arrival on clinical outcomes and predictors of late arrival.

Results

Among the 539 patients, 28.4% arrived early and 71.6% arrived late. Early hospital arrival was significantly associated with favorable outcomes (three-month modified Rankin Scale [mRS]: 0−2, adjusted odds ratio [aOR]: 2.03, 95% confidence interval: [CI] 1.04–3.96) regardless of various confounders, including receiving reperfusion therapy and type of stroke onset time. Furthermore, a lower initial National Institute of Health Stroke Scale (NIHSS) score (aOR: 0.94, 95% CI: 0.90–0.97), greater pre-stroke mRS score (aOR: 1.58, 95% CI: 1.18–2.13), female sex (aOR: 1.71, 95% CI: 1.14–2.58), unclear onset time, and ≤6 years of schooling (aOR: 1.76, 95% CI: 1.03–3.00 compared to >12 years of schooling) were independent predictors of late arrival.

Conclusions

Thus, the onset-to-door time of≤4.5 h is crucial for better clinical outcome, and lower NIHSS score, greater pre-stroke mRS score, female sex, unclear onset times, and ≤6 years of schooling were independent predictors of late arrival. Therefore, educating about the importance of early hospital arrival after acute ischemic stroke should be emphasized. More strategic efforts are needed to reduce the prehospital delay by understanding the predictors of late arrival.
Long term risk and costs of bleeding in men and women treated with triple antithrombotic therapy–An observational study
Authors: Holm Anna , Henriksson Martin , Alfredsson Joakim , Janzon Magnus , Johansson Therese , Swahn Eva , Vial Dominique , Sederholm Lawesson Sofia
Published: March 2021

Objectives

Bleeding is the most common non-ischemic complication in patients with coronary revascularisation procedures, associated with prolonged hospitalisation and increased mortality. Many factors predispose for bleeds in these patients, among those sex. Anyhow, few studies have characterised the population receiving triple antithrombotic therapy (TAT) as well as long term bleeds from a sex perspective. We investigated the one year rate of bleeds in patients receiving TAT, potential sex disparities and premature discontinuation of TAT. We also assessed health care costs in bleeders vs non-bleeders.

Setting

Three hospitals in the County of Östergötland, Sweden during 2009–2015.

Participants

All patients discharged with TAT registered in the SWEDEHEART registry.

Primary and secondary outcome measures

All bleeds receiving medical attention during one-year follow-up were collected by retrieving relevant information about each patient from medical records. Resource use associated with bleeds was assigned unit cost to estimate the health care costs associated with bleeding episodes.

Results

Among 272 patients, 156 bleeds occurred post-discharge, of which 28.8% were gastrointestinal. In total 54.4% had at least one bleed during or after the index event and 40.1% bled post discharge of whom 28.7% experienced a TIMI major or minor bleeding. Women discontinued TAT prematurely more often than men (52.9 vs 36.1%, p = 0.01) and bled more (48.6 vs. 37.1%, p = 0.09). One-year mean health care costs were EUR 575 and EUR 5787 in non-bleeding and bleeding patients, respectively.

Conclusion

The high bleeding incidence in patients with TAT, especially in women, is a cause of concern. There is a need for an adequately sized randomised, controlled trial to determine a safe but still effective treatment for these patients.
Experience of gender-based violence and its effect on depressive symptoms among Indian adolescent girls: Evidence from UDAYA survey
Authors: Patel Ratna , Gupte Samriddhi S. , Srivastava Shobhit , Kumar Pradeep , Chauhan Shekhar , Govindu Mani Deep , Dhillon Preeti
Published: March 2021

Background

Violence against women has been one of the most prominent issue and a major public health concern. It is a principle violation of basic human rights and has both physical and mental effect on the victim. This study focuses on married and unmarried girls aged 15 to 19 years, belonging to Uttar Pradesh and Bihar, India. This study attempts to examine depression level among married and unmarried girls who have faced violence against them. With the unprecedented growth in social networking, online digital platform and its accessibility, the study also brings out the pertinent aspect of internet based violence and its psychological outcome on adolescent girls. Hence, the study can be seen as an important and needed value addition to the existing pool of knowledge on the subject.

Methods

The study uses Understanding the lives of adolescents and young adults (UDAYA) project data for Uttar Pradesh and Bihar. Depressive symptoms among adolescent girl is the outcome variable of the study. Descriptive statistic and bivariate analysis has been used to get to preliminary results. Chi-squared test is used to test the significant of variables. Further, multi-variate analysis (logistic regression) was used.

Results

Almost 29, 23 and 26 percent of married adolescent girls had faced emotional, physical and sexual violence respectively. It was found that about five per cent of unmarried and eight per cent of married girls had high depressive symptoms. It was found that unmarried adolescent girls who had witnessed their father beating mother were 71 percent more likely to suffer from higher depressive symptoms [OR: 1.71, 1.09–2.69]. Adolescents who faced perpetrated bullying had 90 per cent [OR: 1.90, 1.32–2.72] and 86 per cent [OR: 1.86, 0.98–3.52] higher likelihood to suffer from higher depressive symptoms.

Conclusion

The study goes beyond intimate partner violence and includes various covariates to explain the association between violence and depressive symptoms among married and unmarried adolescents. Hence, more inclusive policies are needed to address the issue of violence against women as the spectrum of the violence is expanding with time.
Macular pigment changes after cataract surgery with yellow-tinted intraocular lens implantation
Authors: Obana Akira , Gohto Yuko , Asaoka Ryo
Published: March 2021

Purpose

We previously reported that macular pigment optical density (MPOD) levels decreased during a long follow-up period after clear intraocular lens (IOL) implant surgery presumably due to excessive light exposure. We examined changes in MPOD levels in the eyes that received yellow-tinted IOL implant surgery.

Subjects and methods

This was a prospective, observational study. Fifty-five eyes of 35 patients were studied. MPOD levels were measured with a dual-wavelength autofluorescence technique on day 4; months 1, 3, and 6; and years 1 and 2 postoperatively. The average optical densities at 0°- 2° eccentricities (local MPODs) and total volumes of MPOD (MPOVs) in the area within 1.5° and 9° eccentricities were analyzed.

Results

The mean local MPOD at baseline (on day 4) was 0.79 at 0°, 0.71 at 0.5°, 0.68 at 0.9°, and 0.32 at 2°. The mean MPOV within 1.5° and 9° at baseline was 2950 and 18,897, respectively. Local MPOD at 0.9° and 2° and MPOVs were slightly decreased at month 1 and increased after that. The increase reached statistical significance in local MPOD at 0.5° and 2° and MPOVs (Tukey–Kramer test). The changes in MPOV within 9° at year 2 [(MPOV on year 2 − MPOV on day 4) / MPOV on day 4] were from −0.21 to 1.18 (mean and standard deviation: 1.14 ± 0.28). The MPOV of 15 eyes increased more than 10% from the initial value, was maintained within 10% in 21 eyes, and deteriorated more than 10% in only 3 eyes.

Conclusions

Local MPOD and MPOV tended to slightly decrease month 1 postoperatively and gradually increased after that, but the rates of increases in MPOD levels were small. Yellow-tinted IOLs that have a lower transmittance of blue light might be preferable for preserving MPOD levels after surgery.
DRP1 haploinsufficiency attenuates cardiac ischemia/reperfusion injuries
Authors: Bouche Laura , Kamel Rima , Tamareille Sophie , Garcia Gabriel , Villedieu Camille , Pillot Bruno , Gueguen Naïg , Chehaitly Ahmad , Chao de la Barca Juan Manuel , Beaumont Justine , Baetz Delphine , Ovize Michel , Sesaki Hiromi , Henrion Daniel , Reynier Pascal , Lenaers Guy , Prunier Fabrice , Mirebeau-Prunier Delphine
Published: March 2021

Mitochondrial dynamics is a possible modulator of myocardial ischemia/reperfusion injuries (IRI). We previously reported that mice partially deficient in the fusion protein OPA1 exhibited higher IRI. Therefore, we investigated whether deficiency in the fission protein DRP1 encoded by Dnm1l gene would affect IRI in Dnm1l+/- mouse. After baseline characterization of the Dnm1l+/- mice heart, using echocardiography, electron microscopy, and oxygraphy, 3-month-old Dnm1l+/- and wild type (WT) mice were exposed to myocardial ischemia/reperfusion (I/R). The ischemic area-at-risk (AAR) and area of necrosis (AN) were delimited, and the infarct size was expressed by AN/AAR. Proteins involved in mitochondrial dynamics and autophagy were analyzed before and after I/R. Mitochondrial permeability transition pore (mPTP) opening sensitivity was assessed after I/R. Heart weight and left ventricular function were not significantly different in 3-, 6- and 12-month-old Dnm1l+/- mice than in WT. The cardiac DRP1 protein expression levels were 60% lower, whereas mitochondrial area and lipid degradation were significantly higher in Dnm1l+/- mice than in WT, though mitochondrial respiratory parameters and mPTP opening did not significantly differ. Following I/R, the infarct size was significantly smaller in Dnm1l+/- mice than in WT (34.6±3.1% vs. 44.5±3.3%, respectively; p<0.05) and the autophagic markers, LC3 II and P62 were significantly increased compared to baseline condition in Dnm1l+/- mice only. Altogether, data indicates that increasing fusion by means of Dnm1l deficiency was associated with protection against IRI, without alteration in cardiac or mitochondrial functions at basal conditions. This protection mechanism due to DRP1 haploinsufficiency increases the expression of autophagic markers.
Neutralizing antibodies for SARS-CoV-2 in stray animals from Rio de Janeiro, Brazil
Authors: Dias Helver Gonçalves , Resck Maria Eduarda Barreto , Caldas Gabriela Cardoso , Resck Alessandro Fioretti , da Silva Natália Valente , dos Santos Aline Marcele Vieira , Sousa Thiago das Chagas , Ogrzewalska Maria Halina , Siqueira Marilda Mendonça , Pauvolid-Corrêa Alex , dos Santos Flavia Barreto
Published: March 2021

The epidemic of coronavirus disease 2019 (COVID-19), caused by a novelBetacoronavirusnamed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a public health emergency worldwide. Few reports indicate that owned pets from households with at least one human resident that was diagnosed with COVID-19 can be infected by SARS-CoV-2. However, the exposure to SARS-CoV-2 of pets from households with no COVID-19 cases or stray animals remains less assessed. Using real-time reverse transcriptase polymerase chain reaction (RT-PCR) and plaque reduction neutralization test (PRNT90), we investigated the infection and previous exposure of dogs and cats to SARS-CoV-2 during the ongoing COVID-19 epidemic in Rio de Janeiro, Brazil. From June to August 2020, 96 animals were sampled, including 49 cats (40 owned and 9 stray) and 47 dogs (42 owned and 5 stray). Regarding owned pets, 75.6% (62/82) belonged to households with no COVID-19 cases. Samples included serum, and rectal and oropharyngeal swabs. All swabs were negative for SARS-CoV-2 RNA, but serum samples of a stray cat and a stray dog presented neutralizing antibodies for SARS-CoV-2, with PRNT90titer of 80 and 40, respectively. Serological data presented here suggest that not only owned pets from households with COVID19 cases, but also stray animals are being exposed to SARS-CoV-2 during the COVID-19 pandemic.
Modeling growth and development of hydroponically grown dill, parsley, and watercress in response to photosynthetic daily light integral and mean daily temperature
Authors: Walters Kellie J. , Lopez Roberto G.
Published: March 2021

In controlled environments, crop models that incorporate environmental factors can be developed to optimize growth and development as well as conduct cost and/or resource use benefit analyses. The overall objective of this study was to model growth and development of dill ‘Bouquet’ (Anethum graveolens), parsley ‘Giant of Italy’ (Petroselinum crispum), and watercress (Nasturtium officinale) in response to photosynthetic daily light integral (DLI) and mean daily temperature (MDT). Plants were grown hydroponically in five greenhouse compartments with MDTs ranging from 9.7 to 27.2 °C under 0%, 30%, or 50% shade cloth to create DLIs ranging from 6.2 to 16.9 mol·m‒2·d‒1. MDT and DLI interacted to influence dill fresh mass and height, and watercress maximum quantum yield of dark adapted leaves (Fv/Fm), height, and branch number while only MDT affected dill leaf number and watercress fresh mass and branch length. Besides dry matter concentration (DMC), parsley was influenced by MDT and not DLI. Increasing MDT from ≈10 to 22.4 °C (parsley) or 27.2 °C (dill and watercress), linearly or near-linearly increased fresh mass. For dill, increasing DLI decreased fresh mass when MDT was low (9.7 to 13.9 °C) and increased fresh mass when MDT was high (18.4 to 27.2 °C). DMC of dill, parsley, and watercress increased as MDT decreased or DLI increased, indicating a higher proportion of plant fresh mass is water at higher MDTs or lower DLIs. With these data we have created growth and development models for culinary herbs to aid in predicting responses to DLI and MDT.
Gene flow in commercial alfalfa (Medicago sativa subsp. sativa L.) seed production fields: Distance is the primary but not the sole influence on adventitious presence
Authors: Kesoju Sandya R. , Kramer Matthew , Brunet Johanne , Greene Stephanie L. , Jordan Amelia , Martin Ruth C.
Published: March 2021

In insect-pollinated crops, gene flow is affected by numerous factors including crop characteristics, mating system, life history, pollinators, and planting management practices. Previous studies have concentrated on the impact of distance between genetically engineered (GE) and conventional fields on adventitious presence (AP) which represents the unwanted presence of a GE gene. Variables other than distance, however, may affect AP. In addition, some AP is often present in the parent seed lots used to establish conventional fields. To identify variables that influence the proportion of AP in conventional alfalfa fields, we performed variable selection regression analyses. Analyses based on a sample-level and a field-level analysis gave similar, though not identical results. For the sample-level model, distance from the GE field explained 66% of the variance in AP, confirming its importance in affecting AP. The area of GE fields within the pollinator foraging range explained an additional 30% of the variation in AP in the model. The density of alfalfa leafcutting bee domiciles influenced AP in both models. To minimize AP in conventional alfalfa seed fields, management practices should focus on optimizing isolation distances while also considering the size of the GE pollen pool within the pollinator foraging range, and the foraging behavior of pollinators.
Identifying optimal COVID-19 testing strategies for schools and businesses: Balancing testing frequency, individual test technology, and cost
Authors: Lyng Gregory D. , Sheils Natalie E. , Kennedy Caleb J. , Griffin Daniel O. , Berke Ethan M.
Published: March 2021

Background

COVID-19 test sensitivity and specificity have been widely examined and discussed, yet optimal use of these tests will depend on the goals of testing, the population or setting, and the anticipated underlying disease prevalence. We model various combinations of key variables to identify and compare a range of effective and practical surveillance strategies for schools and businesses.

Methods

We coupled a simulated data set incorporating actual community prevalence and test performance characteristics to a susceptible, infectious, removed (SIR) compartmental model, modeling the impact of base and tunable variables including test sensitivity, testing frequency, results lag, sample pooling, disease prevalence, externally-acquired infections, symptom checking, and test cost on outcomes including case reduction and false positives.

Findings

Increasing testing frequency was associated with a non-linear positive effect on cases averted over 100 days. While precise reductions in cumulative number of infections depended on community disease prevalence, testing every 3 days versus every 14 days (even with a lower sensitivity test) reduces the disease burden substantially. Pooling provided cost savings and made a high-frequency approach practical; one high-performing strategy, testing every 3 days, yielded per person per day costs as low as $1.32.

Interpretation

A range of practically viable testing strategies emerged for schools and businesses. Key characteristics of these strategies include high frequency testing with a moderate or high sensitivity test and minimal results delay. Sample pooling allowed for operational efficiency and cost savings with minimal loss of model performance.