bluuebunny/crossref_metadata_2025 huggingface dataset:
A Cas12a ortholog with stringent PAM recognition followed by low off-target editing rates for genome editing
Authors: Chen Peng , Zhou Jin , Wan Yibin , Liu Huan , Li Yongzheng , Liu Zhaoxin , Wang Hongjian , Lei Jun , Zhao Kai , Zhang Yiliang , Wang Yan , Zhang Xinghua , Yin Lei
Published: March 2020

Background

AsCas12a and LbCas12a nucleases are reported to be promising tools for genome engineering with protospacer adjacent motif (PAM) TTTV as the optimal. However, the C-containing PAM (CTTV, TCTV, TTCV, etc.) recognition by Cas12a might induce extra off-target edits at these non-canonical PAM sites.

Results

Here, we identify a novel Cas12a nuclease CeCas12a from Coprococcus eutactus, which is a programmable nuclease with genome-editing efficiencies comparable to AsCas12a and LbCas12a in human cells. Moreover, CeCas12a is revealed to be more stringent for PAM recognition in vitro and in vivo followed by very low off-target editing rates in cells. Notably, CeCas12a renders less off-target edits located at C-containing PAM at multiple sites compared to LbCas12a and AsCas12a, as assessed by targeted sequencing methods.

Conclusions

Our study shows that CeCas12a nuclease is active in human cells and the stringency of PAM recognition could be an important factor shaping off-target editing in gene editing. Thus, CeCas12a provides a promising candidate with distinctive characteristics for research and therapeutic applications.
Tumor in the veins: an abdominal perspective with an emphasis on CT and MR imaging
Authors: Karaosmanoglu Ali Devrim , Onur Mehmet Ruhi , Uysal Aycan , Akata Deniz , Ozmen Mustafa Nasuh , Karcaaltincaba Musturay
Published: March 2020

Endovenous tumor thrombus in abdomen should be accurately diagnosed as it is a significant finding that may change medical and surgical treatment approaches. As some underlying reasons for endovenous tumor thrombi are relatively rare and imaging findings may be quite subtle, they can be easily overlooked which may have important clinical consequences. In this paper, we described the various imaging aspects of endovenous tumor thrombi originating from various tumor types in different venous structures of the abdomen.
LAMA2 regulates the fate commitment of mesenchymal stem cells via hedgehog signaling
Authors: Zhu Yuan , Zhang Xiao , Gu Ranli , Liu Xuenan , Wang Siyi , Xia Dandan , Li Zheng , Lian Xiaomin , Zhang Ping , Liu Yunsong , Zhou Yongsheng
Published: March 2020

Background

Bone defects are a common clinical condition that has gained an increasing amount of attention in recent years. Causes of bone defect include tumors, inflammation, and fractures. Bone tissue engineering is a novel treatment of bone defect, and human mesenchymal stem cells (hMSCs) are the ideal seed cells for bone tissue engineering due to their multi-lineage differentiation potential and immunogenicity. The laminin α2 (LAMA2) gene encodes the α2 subunit of laminins. Mutations in this gene have been reported to cause muscular dystrophy, but thus far no studies have elucidated the role of LAMA2 in the fate choices of MSCs. Here, we aimed to investigate the critical role of LAMA2 in the osteogenesis and adipogenesis of mesenchymal stem cells (MSCs).

Methods

We investigated LAMA2 function in osteogenic and adipogenic differentiation of MSCs in vitro and in vivo through loss- and gain-of-function experiments. In addition, molecular mechanism was clarified by Western blot and siRNA.

Results

Our results demonstrated that LAMA2 was a critical regulator for fate commitment of MSCs. Both in vitro and in vivo studies indicate that LAMA2 inhibits osteogenesis and promotes adipogenesis.Mechanistically, we found that LAMA2 regulated osteogenesis and adipogenesis of MSCs by modulating the hedgehog signaling pathway.

Conclusions

The present work confirms that LAMA2 is a new molecular target for MSC-based bone regeneration.
Using the spike protein feature to predict infection risk and monitor the evolutionary dynamic of coronavirus
Authors: Qiang Xiao-Li , Xu Peng , Fang Gang , Liu Wen-Bin , Kou Zheng
Published: March 2020

Background

Coronavirus can cross the species barrier and infect humans with a severe respiratory syndrome. SARS-CoV-2 with potential origin of bat is still circulating in China. In this study, a prediction model is proposed to evaluate the infection risk of non-human-origin coronavirus for early warning.

Methods

The spike protein sequences of 2666 coronaviruses were collected from 2019 Novel Coronavirus Resource (2019nCoVR) Database of China National Genomics Data Center on Jan 29, 2020. A total of 507 human-origin viruses were regarded as positive samples, whereas 2159 non-human-origin viruses were regarded as negative. To capture the key information of the spike protein, three feature encoding algorithms (amino acid composition, AAC; parallel correlation-based pseudo-amino-acid composition, PC-PseAAC and G-gap dipeptide composition, GGAP) were used to train 41 random forest models. The optimal feature with the best performance was identified by the multidimensional scaling method, which was used to explore the pattern of human coronavirus.

Results

The 10-fold cross-validation results showed that well performance was achieved with the use of the GGAP (g = 3) feature. The predictive model achieved the maximum ACC of 98.18% coupled with the Matthews correlation coefficient (MCC) of 0.9638. Seven clusters for human coronaviruses (229E, NL63, OC43, HKU1, MERS-CoV, SARS-CoV, and SARS-CoV-2) were found. The cluster for SARS-CoV-2 was very close to that for SARS-CoV, which suggests that both of viruses have the same human receptor (angiotensin converting enzyme II). The big gap in the distance curve suggests that the origin of SARS-CoV-2 is not clear and further surveillance in the field should be made continuously. The smooth distance curve for SARS-CoV suggests that its close relatives still exist in nature and public health is challenged as usual.

Conclusions

The optimal feature (GGAP, g = 3) performed well in terms of predicting infection risk and could be used to explore the evolutionary dynamic in a simple, fast and large-scale manner. The study may be beneficial for the surveillance of the genome mutation of coronavirus in the field.
Hemostatic agents for prehospital hemorrhage control: a narrative review
Authors: Peng Henry T.
Published: March 2020

Hemorrhage is the leading cause of preventable death in combat trauma and the secondary cause of death in civilian trauma. A significant number of deaths due to hemorrhage occur before and in the first hour after hospital arrival. A literature search was performed through PubMed, Scopus, and Institute of Scientific Information databases for English language articles using terms relating to hemostatic agents, prehospital, battlefield or combat dressings, and prehospital hemostatic resuscitation, followed by cross-reference searching. Abstracts were screened to determine relevance and whether appropriate further review of the original articles was warranted. Based on these findings, this paper provides a review of a variety of hemostatic agents ranging from clinically approved products for human use to newly developed concepts with great potential for use in prehospital settings. These hemostatic agents can be administered either systemically or locally to stop bleeding through different mechanisms of action. Comparisons of current hemostatic products and further directions for prehospital hemorrhage control are also discussed.
Memorial functional foods: a new concept from Bavi tribe
Authors: Amiri Ardekani Ehsan , Askari Hossein , Mohagheghzadeh Abdolali
Published: March 2020

The use of functional foods (FFs) for maintaining health and preventing or treating illnesses—in recent years—has been dramatically increased in the literature. There are available valuable examples of FFs in ethno medicine from different tribes. Ethnic FFs can be valuable resources for developing FFs science, e.g., introducing memorial FFs as an interdisciplinary ethnopharmacological concept. In this paper, ethnic FFs from Bavi tribe (Kohgiluyeh va Boyerahmad province of Iran) have been studied, and their medical potentials are reported. Data gathering was done by interview with Bavi tribe local healers using a questionnaire. Plant materials were collected and identified, and Bavi FFs were prepared according to local procedures. Information of 21 Bavi tribe FFs was collected which are including 20 different plant species.The results showed that most FFs are used to treat chronic diseases including kidney problems like kidney stones, liver disease, neurological complaints, and GI ulcers and are used as lactogogue, while lesser FFs are used to treat acute diseases and symptoms (43%), including nausea and vomiting, common cold, diarrhea, sore throat, and allergy. Most FFs of Bavi tribe are prepared using aromatic plants (75%) responsible for aroma in the final FF. Probably, aromatic FFs increase patient acceptance, without mimicking unpleasant memory of drug recommendation. Plants that are used in FF are mostly perennial (80%) and wild growing (80%), indicating continuous contact of natives and so having memory with such habitant herbals. Treating diseases by homemade FFs which are prepared by well-known aromatic herbals is a routine procedure among natives like the Bavi tribe. Such easily made FFs with well-known taste and flavors which may change the patient’s mood should be studied in a new approach, “memorial FFs”, as a novel opportunity for healthcare and curing.
Status Update on Data Required to Build a Learning Health System
Authors: Bertagnolli Monica M. , Anderson Brian , Norsworthy Kelly , Piantadosi Steven , Quina Andre , Schilsky Richard L. , Miller Robert S. , Khozin Sean
Published: March 2020

Wide adoption of electronic health records (EHRs) has raised the expectation that data obtained during routine clinical care, termed “real-world” data, will be accumulated across health care systems and analyzed on a large scale to produce improvements in patient outcomes and the use of health care resources. To facilitate a learning health system, EHRs must contain clinically meaningful structured data elements that can be readily exchanged, and the data must be of adequate quality to draw valid inferences. At the present time, the majority of EHR content is unstructured and locked into proprietary systems that pose significant challenges to conducting accurate analyses of many clinical outcomes. This article details the current state of data obtained at the point of care and describes the changes necessary to use the EHR to build a learning health system.
Autogenous regulation in vivo of the rpmE gene encoding ribosomal protein L31 (bL31), a key component of the protein–protein intersubunit bridge B1b
Authors: Aseev Leonid V. , Koledinskaya Ludmila S. , Boni Irina V.
Published: March 2020

Bacterial ribosomal proteins (r-proteins) encoded by nonessential genes often carry out very important tasks in translation. In particular, this is the case of a small basic bacteria-specific r-protein L31 (bL31). Recent studies revealed a crucial role of bL31 in formation of the protein–protein intersubunit bridge B1b and hence its contribution to ribosome dynamics. Our goal was to study in vivo regulation of the rpmE operon encoding bL31. We used a previously developed approach based on chromosomally integrated fusions with the lacZ reporter. E. coli rpmE is transcribed from two promoter regions, and translation of both mRNA transcripts was shown to be feedback regulated by bL31, indicating that the autogenous operator is located within the shorter transcript. The bL31-mediated control of rpmE is gene-specific, as no regulation was found for rpmE-unrelated reporters. Thus, bL31, as many other r-proteins, possesses dual activity in living cells, acting both as an integral ribosome component and an autogenous repressor. Phylogenetic studies revealed the presence of a highly conserved stem–loop structure in the rpmE 5′UTR, a presumable translational operator targeted by bL31, which was further confirmed by site-directed mutagenesis. This stable operator stem–loop separates an AU-rich translational enhancer from a Shine-Dalgarno element, which is a rare case of a noncontiguous translation initiation region. Sequence/structure computational approaches classify bL31 as an RNA-binding protein, consistent with its repressor function discovered here. Mutational analysis of bL31 showed that its unstructured amino-terminal part enriched in lysine is necessary for the repressor activity.
Diagnostic and therapeutic options in recurrent implantation failure
Authors: Moustafa Sarah , Young Steven
Published: March 2020

Recurrent implantation failure (RIF) is an uncommon, imprecisely defined clinical disorder characterized by failure to achieve pregnancy after repeated embryo transfers. The diverse etiologies and incomplete understanding of RIF provide significant diagnostic and therapeutic challenges to patients and providers. Careful clinical evaluation prior to assisted reproduction can uncover many treatable causes, including thyroid dysfunction, submucosal myomas, and tobacco use. The more-subtle causes often require a more-targeted assessment. Undetected, small polyps or small areas of intrauterine synechiae are relatively common and easily treated contributors to RIF. Molecular and cellular abnormalities pose a greater therapeutic challenge. Putative causes of RIF, including progesterone resistance, shifted window of receptivity, decreased integrin expression, and immunologic disturbances, should be considered in the evaluation of a patient with otherwise unexplained RIF. It may also be true that a more complex and standardized definition of RIF would be helpful in these cases. In this paper, we review the diagnostic and therapeutic approaches to RIF, with emphasis on disorders of endometrial receptivity.
Data extraction methods for systematic review (semi)automation: A living review protocol
Authors: Schmidt Lena , Olorisade Babatunde K. , McGuinness Luke A. , Higgins Julian P. T.
Published: March 2020

Background: Researchers in evidence-based medicine cannot keep up with the amounts of both old and newly published primary research articles. Conducting and updating of systematic reviews is time-consuming. In practice, data extraction is one of the most complex tasks in this process. Exponential improvements in computational processing speed and data storage are fostering the development of data extraction models and algorithms. This, in combination with quicker pathways to publication, led to a large landscape of tools and methods for data extraction tasks.

Objective: To review published methods and tools for data extraction to (semi)automate the systematic reviewing process.

Methods: We propose to conduct a living review. With this methodology we aim to do monthly search updates, as well as bi-annual review updates if new evidence permits it. In a cross-sectional analysis we will extract methodological characteristics and assess the quality of reporting in our included papers.

Conclusions: We aim to increase transparency in the reporting and assessment of machine learning technologies to the benefit of data scientists, systematic reviewers and funders of health research. This living review will help to reduce duplicate efforts by data scientists who develop data extraction methods. It will also serve to inform systematic reviewers about possibilities to support their data extraction.
Performance monitoring and accountability: The Agile Project’s protocol, record and experience
Authors: Tsui Amy , Anglewicz Philip , Akinlose Titilope , Srivatsan Varsha , Akilimali Pierre , Alzouma Souleymane , Bazie Fiacre , Gichangi Peter , Guiella Georges , Kayembe Patrick , Mehrotra Anupam , OlaOlorun Funmilola , Omoluabi Elizabeth , Oumarou Sani , Sodani P. R. , Thiongo Mary , Byrne Meagan , Dreger Kurt , Decker Michele , Cardona Carolina , Muhoza Pierre , Combs Carolyn , Koffi Alain K. , Radloff Scott
Published: March 2020

The Performance Monitoring and Accountability 2020 (PMA2020) project implemented a multi-country sub-project called PMA Agile, a system of continuous data collection for a probability sample of urban public and private health facilities and their clients that began November 2017 and concluded December 2019.  The objective was to monitor the supply, quality and consumption of family planning services.  In total, across 14 urban settings, nearly 2300 health facilities were surveyed three to six times in two years and a total sample of 48,610 female and male clients of childbearing age were interviewed in Burkina Faso, Democratic Republic of Congo, India, Kenya, Niger and Nigeria.  Consenting female clients with access to a cellphone were re-interviewed by telephone after four months; two rounds of the client exit, and follow-up interviews were conducted in nearly all settings.  This paper reports on the PMA Agile data system protocols, coverage and early experiences.  An online dashboard is publicly accessible, analyses of measured trends are underway, and the data are publicly available.
Tasks for independent work and control of students ' knowledge of children's Phthisiology
Authors: Askarova Roza
Published: March 2020

The textbook is prepared taking into account modern achievements of TB in accordance with the curriculum for children's Phthisiology for independent work and control of knowledge of students as an additional educational literature on the main theoretical issues, methods of detection of tuberculosis, clinical manifestations and course of tuberculosis of the respiratory system, differential diagnosis of tuberculosis with non-specific pathology of the respiratory system, complications of tuberculosis, the combination of pulmonary tuberculosis with other diseases, treatment of tuberculosis.
For students of the pediatric faculty, residents, TB doctors.
Nationwide Hospital Performance on Publicly Reported Episode Spending Measures
Authors: Liao Joshua M , Zhou Lingmei , Navathe Amol S
Published: March 2020

BACKGROUND

Medicare has implemented strategies to improve value by containing hospital spending for episodes of care. Compared with payment models, publicly reported episode‐based spending measures are underrecognized strategies.

OBJECTIVE

To provide the first nationwide description of hospitals' episode‐based spending based on publicly reported Clinical Episode‐Based Payment (CEBP) measures.

DESIGN, SETTING, AND PARTICIPANTS

We used 2017 Hospital Compare data to assess spending on six CEBPs among 1,778 hospitals. We examined spending variation and its drivers, correlation between CEBPs, and spending by cost performance categories (for individual CEBPs, below vs above average spending; for across‐CEBP comparisons, high vs low vs mixed cost). We also compared hospital spending performance on CEBPs with a global Medicare Spending Per Beneficiary measure.

MAIN OUTCOMES AND MEASURES

Episode spending.

RESULTS

Episode spending varied by CEBP type, with skilled nursing facility (SNF) care accounting for the majority of spending variation for procedural episodes but not for condition episodes. Across CEBPs, greater proportions of episode spending were attributed to SNF care at high‐(18.1%) vs mixed‐ (10.7%) vs low‐cost (9.2%) hospitals (P > .001). There was low within‐hospital CEBP correlation and low correlation and concordance between hospitals' CEBP and Medicare Spending Per Beneficiary performance.

CONCLUSIONS

Variation reduction and savings opportunities in SNF care for procedural episodes suggest that they may be better suited for existing payment models than condition episodes are. Spending performance was not hospital specific, which highlights the potential utility of episode spending measures beyond global measures.
Stereoselective synthesis of alkyl pyranosides on a laboratory scale
Authors: Serbian Immo , Prell Erik , Al-Harrasi Ahmed , Csuk Rene
Published: March 2020

The one-pot reaction of per-acetylated glycopyranosyl bromides with alcohols in light-protected flask leads to the stereoselective synthesis of deacetylated alkyl pyranosides in good yields.
La educación abierta en Europa: avances, integración con la ciencia abierta y rol bibliotecario.
Authors: Santos Hermosa Gema
Published: March 2020

This paper provides an overview of open education in Europe, focusing on higher education. It begins by considering how the notion of ‘contemporary open education’ has evolved over time. It then reviews the various open education-related initiatives that have been promoted by the European Commission, from the institution of an open education framework to the current development of education policies. It also reports on specific initiatives and makes a series of recommendations about policy design oriented to opening up education. It analyses the relationship between open education and the open science movement, specifically the manner in which open education can be contextualised in the emergent paradigm of open science. Finally, the paper considers how academic libraries should be supporting open education and examines the influence that information professionals can bring to bear in this field.
Modeling retinal detachment associated with hemorrhage by Monte Carlo simulation
Authors: Al-Saeed Tarek A.
Published: March 2020

In this work we study fundus reflection in the case of retinal detachment. Vitreous humor builds up beneath the retina through a break in the retina or when there is traction on the retina. Further, we assume that this detachment is associated with hemorrhage in regions both above and below the retina. To investigate hemorrhage, we assume erythrocytes to be spheres of different radii. Then we apply Mie scattering theory to these spheres and calculate the scattering coefficient, the absorption coefficient, and the anisotropy factor. Using these parameters, we apply Monte Carlo simulation to calculate reflection. In order to model fundus reflection under retinal detachment, we define three types of reflection: reflection from the vitreous body, retinal reflection where photons are reflected from the retinal vitreous interface once, and retinal reflection where photons are reflected many times from the retinal vitreous interface.
Experimental investigation on aero-optical effects of a hypersonic optical dome under different exposure times
Authors: Ding Haolin , Yi Shihe , Zhao Xinhai , Xu Yao
Published: March 2020

The aero-optical effects induced by the complex flow structure around a hypersonic optical dome is highly unsteady, which leads to significant differences in the imaging quality under different exposure times. It is of great significance to study the influence of exposure time on imaging quality for guiding the design of imaging guidance seekers and improving imaging guidance accuracy. Based on the hypersonic gun wind tunnel, an aero-optical effect measurement platform was built to measure the wavefront from transient exposure to long exposure. With the increase of exposure time, the accuracy of high-order optical path difference (OPD) reconstruction by low-order Zernike polynomials increased from 62.2% to 88.6%. The increase of exposure time was helpful to reduce the complexity of the wavefront spatial distribution structure. In principle, it could reduce the difficulty of wavefront adaptive correction systems. With the increase of exposure time, the

O
P
D

r
m
s

corresponding to

O
P
D

h
i
g
h
−
o
r
d
e
r

increased gradually, the amplitude decreased gradually, and the difference of

O
P
D

r
m
s

decreased gradually at different times. Under different exposure times, the large-aperture approximation principle could achieve a better prediction of Strehl ratio values. With the increase of exposure time, the imaging integral resolution,

R

, decreased obviously, and it was stable at about

1.43

R
0

. Compared with that,

R

was improved by about 30% when the exposure time was 6 ns.
Ubiquity of Fourier transformation in optical sciences
Authors: Mansuripur Masud
Published: March 2020

Fourier transformation is an important conceptual as well as
computational tool in the arsenal of every practitioner of physical
and mathematical sciences. I discuss some of its applications in
optical science and engineering to provide a broad perspective on the
intimate relation between the physical and mathematical concepts that
are elegantly interwoven within the theory of Fourier transforms.
Dynamically tunable directional subwavelength beam propagation based on photonic spin Hall effect in graphene-based hyperbolic metamaterials
Authors: Su Zengping , Wang Yueke , Shi Hangyu
Published: March 2020

Photonic spin Hall effect (PSHE) of type II hyperbolic metamaterials is achieved due to near filed interference, which provides a way to decide the propagation direction of subwavelength beam. In this paper, we propose graphene-based hyperbolic metamaterials (GHMMs), which is composed of the alternating graphene/SiO2 multilayer. The numerical results show that when a dipole emitter is placed at the boundary of the GHMMs, the subwavelength beam with λ/40 full-with half maximum can be excited and propagates along the left or right channel, which is dependent on polarization handedness. In addition, we further demonstrate that the unidirectional propagation angle can be dynamically tuned by changing the external electric field bias applied to graphene.
Underwater visible light communication at 3.24 Gb/s using novel two-dimensional bit allocation
Authors: Zou Peng , Zhao Yiheng , Hu Fangchen , Chi Nan
Published: March 2020

Underwater visible light communication (UVLC) systems suffer from a strong nonlinear effect and high inter-symbol interference (ISI). In this study, to improve the performance of a UVLC system under such conditions, we propose a novel nonlinear hybrid modulation scheme named two-dimensional bit allocation (2DBA). By comparing the performance of 2DBA with the famous Levin-Campello (LC) algorithm and the quadrature amplitude modulation (QAM)–based time-domain hybrid modulation (TDHQ) algorithm, we have proved by analysis and experiment that 2DBA can outperform the power allocation–based LC algorithm and the TDHQ algorithm below the 3.8×10−3 hard decision forward error correction threshold (HD-FEC) when the system has a severe nonlinear effect and ISI. The data rate 3.24 Gb/s of 2DBA is measured after 1.2 m underwater transmission; as far as we know, this is the highest data rate reported in a blue LED chip based UVLC system.
Tunable hard x-ray nanofocusing with Fresnel zone plates fabricated using deep etching
Authors: Li Kenan , Ali Sajid , Wojcik Michael , De Andrade Vincent , Huang Xiaojing , Yan Hanfei , Chu Yong S. , Nazaretski Evgeny , Pattammattel Ajith , Jacobsen Chris
Published: March 2020

Fresnel zone plates are used widely for x-ray nanofocusing, due to
their ease of alignment and energy tunability. Their spatial
resolution is limited in part by their outermost zone width

d

r
N

, while their efficiency is limited in
part by their thickness

t

z
p

. We demonstrate the use of Fresnel
zone plate optics for x-ray nanofocusing with

d

r

N

=
16

n
m

outermost zone width and a thickness
of about

t

z
p

=
1.8

µ

m

(or an aspect ratio of 110) with an
absolute focusing efficiency of 4.7% at 12 keV, and 6.2% at 10 keV.
Using partially coherent illumination at 12 keV, the zone plate
delivered a FWHM focus of

46
×
60

n
m

at 12 keV, with the first-order
coherent mode in a ptychographic reconstruction showing a probe size
of 16 nm FWHM. These optics were fabricated using a combination of
metal-assisted chemical etching and atomic layer deposition for the
diffracting structures, and silicon wafer back-thinning to produce
optics useful for real applications. This approach should enable new
higher resolution views of thick materials, especially when energy
tunability is required.
Label-free biochemical quantitative phase imaging with mid-infrared photothermal effect
Authors: Tamamitsu Miu , Toda Keiichiro , Shimada Hiroyuki , Honda Takaaki , Takarada Masaharu , Okabe Kohki , Nagashima Yu , Horisaki Ryoichi , Ideguchi Takuro
Published: March 2020

Label-free optical imaging is valuable in biology and medicine because
of its non-destructive nature. Quantitative phase imaging (QPI) and
molecular vibrational imaging (MVI) are the two most successful
label-free methods, providing morphological and biochemical
information, respectively. These techniques have enabled numerous
applications as they have matured over the past few decades; however,
their label-free contrasts are inherently complementary and difficult
to integrate due to their reliance on different light–matter
interactions. Here we present a unified imaging scheme with
simultaneous and in situ acquisition of
quantitative phase and molecular vibrational contrasts of single cells
in the QPI framework using the mid-infrared photothermal effect. The
robust integration of subcellular morphological and biochemical
label-free measurements may enable new analyses, especially for
studying complex and fragile biological phenomena such as drug
delivery, cellular disease, and stem cell development, where long-time
observation of unperturbed cells is needed under low
phototoxicity.
Qualitative Research Methodology and its Scope in Health Services Research
Authors: Patel Naiya
Published: March 2020

Health services research is a multidisciplinary field which involves policy makers, health care providers, as well as quality outcomes professionals of the health services provided in an organizational setting to name some. Using qualitative research methodology to get insights of both the provider and patient experience down the pipeline can help strengthen what is lacking. Bridging the gap of translation research by not just surveys 1 might be an appropriate research methodology, however, inclusion of case studies, ethnographies might help stakeholders in the field, to visualize in depth phenomenon occurring in health services research field. Telly medicine, commercial digital health status trackr might be some of the inetrventions to improvise health care services, however, knowing what are the actual needs at individual level might efficiently help in redistribution of resources or policy laws. Recruiting for clinical trials through story telling communication technology2,3, might help in recruitment for novel drug therapies to explore possibilities, however, exploring the barriers to enroll for the clinical trials, or why the drug might work effectively in some cultural population and why not on others, can only be efficiently explored through qualitative research methodologies.
ACCURACY ASSESSMENT WHILE USING THE GLUCOSE METER “SATELLITE EXPRESS” FOR GLYCEMIC CONTROL OF CHILDREN WITH SUGAR DIABETES
Authors: Dianov Oleg A. , Maltsev Vadim , Murina Elena , Anfilov Ilya
Published: March 2020

Backgraund: Monitoring glycemic control in diabetes includes daily measurements of glucose levels at home, along with periodic monitoring of glycemia indicators on the whole. The main purpose of monitoring glycemic control is to accurately and authentically assess the glycemic level reached by each patient in order to ensure the glycemic goals achievement. Glycemic control assessment at a certain point in time is best achieved by self-monitoring the level of glucose in the blood, in that allows you to assess the presence of hyperglycemia and hypoglycemia to optimize the treatment strategy.
Aims: Accuracy assessment of a medical device Portable blood glucose concentration meter with electrochemical single-use strip PKG-03 Satellite Express for glycemic control of children with diabetes.
Materials and methods: In a group of children with diabetes (n = 105, age from 1 month to 17 years), simultaneously was taken capillary blood from one drop to assess the accuracy of glycemia levels on the "Satellite Express" glucose meter and on the laboratory glucose and lactate analyzer SUPER GL.
Results: In a comparative analysis of 660 blood samples on the Clark error scale, was found that all deviations of glycemia values ​​obtained with the "Satellite Express" glucose meter were in zones A (99.7% - clinically correct values) and B (0.3% - safe deviations). The limits of permissible systematic error of measurements that meet the requirements of the National Standard of Russian Federation GOST R ISO 15197-2015 in terms of clause 6.3 System Accuracy amounted to 96.8% of deviations of glucose meter indications from reference values, which matches to areas of clinically correct and safe deviations.
Conclusion: Using the "Satellite Express" glucose meter in clinical practice makes it possible to control glycemia qualitatively and it is safe for children aged from 1 month to 17 years.
El pensamiento histórico en contextos escolares. Hacia una definición compleja de la enseñanza de Clío
Authors: Ibagón Martín Nilson Javier , Minte Münzenmayer Andrea Renate
Published: March 2020

El artículo analiza desde una perspectiva teórica las potencialidades formativas que se derivan de los principios disciplinares y pedagógicos que definen la estructuración del pensamiento histórico en la escuela. Para ello, se definen tres ejes de discusión: el primer eje, establece un balance de las principales dificultades disciplinares y pedagógicas que han limitado en la escuela el alcance formativo de la enseñanza-aprendizaje de la historia; en segundo lugar, se analiza la formación de pensamiento histórico como una alternativa a la enseñanza tradicional de la historia; finalmente, se exploran los retos que implica el desarrollo de este tipo de pensamiento en la definición de la Historia a enseñar, la Historia enseñada, y la Historia aprendida. A partir de este ejercicio analítico se concluye que, el desarrollo del pensamiento histórico permite construir una alternativa teórica y práctica a los principios limitados y restringidos.
Von der Lausitz lernen: Wie sich die Nachhaltigkeitsforschung für Demokratiefragen öffnen kann
Authors: Herberg Jeremias , Gabler Julia , Gürtler Konrad , Haas Tobias , Staemmler Johannes , Beer David Löw , Luh Victoria
Published: March 2020

In der Klimadebatte kommen integrative Konzepte der Nachhaltigkeitsforschung kaum zum Zuge. Dies zeigt der Lausitzer Kohleausstieg beispielhaft: Soziales und Umwelt werden gegeneinander ausgespielt. Eine integrierte Modellregion kann nur entstehen, wenn öffentlich über strittige
Fragen diskutiert wird. Generell müssen sich Nachhaltigkeitsforscher(innen) verstärkt mit sozial-ökologischen Konflikten und Demokratiefragen auseinandersetzen.
Solvable problems or problematic solvability? Problem conceptualization in transdisciplinary sustainability research and a possible epistemological contribution
Authors: Meyer Esther
Published: March 2020

Problems are a major focal point in transdisciplinary sustainability research (TSR). As a text analysis shows, the term “problem” is most commonly used in the context of analyzing research processes that are directed towards societal problem-solving. At the same time, these
findings imply that TSR does not follow the idea that problems are solvable. Instead, TSR should transgress the general tension between the solution imperative and the insolvability of complex problems by rather tackling each problem as situated and specific.Problem orientation plays a
significant role in emerging transdisciplinary sustainability research (TSR), where the assumption of solvability resonates with the term “problem” yet is not questioned from a sustainability perspective. This paper questions the meaning of “problems” in and for TSR
from a discourse studies perspective. The results of a collocation and concordance analysis of the term “problem(s)” in GAIA articles show that sustainability-oriented problem-solving is explicated normatively as a key research goal. In the analyzed articles, emphasis is
put on how to proceed towards this goal through research process analysis. This paper begins by analyzing the meaning of “problems” before seeking to orientate TSR in terms of how knowledge could be conceptualized. This is supported by the epistemological concept of the problematic,
which originates from 20th century French philosophy. It proves helpful to discuss how TSR can be epistemologically grasped, and thereby strengthened in its transformative potential.
Time-to-Target Simplifies Optimal Control of Visuomotor Feedback Responses
Authors: Česonis Justinas , Franklin David W.
Published: March 2020

Visuomotor feedback responses vary in intensity throughout a reach, commonly explained by optimal control. Here, we show that the optimal control for a range of movements with the same goal can be simplified to a time-to-target dependent control scheme. We measure our human participants’ visuomotor responses in five reaching conditions, each with different hand or cursor kinematics. Participants only produced different feedback responses when these kinematic changes resulted in different times-to-target. We complement our experimental data with a range of finite and non-finite horizon optimal feedback control (OFC) models, finding that the model with time-to-target as one of the input parameters best replicates the experimental data. Overall, this suggests that time-to-target is a critical control parameter in online feedback control. Moreover, we propose that for a specific task and known dynamics, humans can instantly produce a control signal without any additional online computation allowing rapid response onset and close to optimal control.
Comparative Transcriptomic Analyses of Developing Melanocortin Neurons Reveal New Regulators for the Anorexigenic Neuron Identity
Authors: Chen Xiameng , Wyler Steven C. , Li Li , Arnold Amanda G. , Wan Rong , Jia Lin , Landy Mark A. , Lai Helen C. , Xu Pin , Liu Chen
Published: March 2020

Despite their opposing actions on food intake, POMC and NPY/AgRP neurons in the arcuate nucleus of the hypothalamus (ARH) are derived from the same progenitors that give rise to ARH neurons. However, the mechanism whereby common neuronal precursors subsequently adopt either the anorexigenic (POMC) or the orexigenic (NPY/AgRP) identity remains elusive. We hypothesize that POMC and NPY/AgRP cell fates are specified and maintained by distinct intrinsic factors. In search of them, we profiled the transcriptomes of developing POMC and NPY/AgRP neurons in mice. Moreover, cell-type-specific transcriptomic analyses revealed transcription regulators that are selectively enriched in either population, but whose developmental functions are unknown in these neurons. Among them, we found the expression of the PR domain-containing factor 12 (Prdm12) was enriched in POMC neurons but absent in NPY/AgRP neurons. To study the role ofPrdm12 in vivo,we developed and characterized a floxedPrdm12allele. Selective ablation ofPrdm12in embryonic POMC neurons led to significantly reducedPomcexpression as well as early-onset obesity in mice of either sex that recapitulates symptoms of human POMC deficiency. Interestingly, however, specific deletion ofPrdm12in adult POMC neurons showed that it is no longer required forPomcexpression or energy balance. Collectively, these findings establish a critical role forPrdm12in the anorexigenic neuron identity and suggest that it acts developmentally to program body weight homeostasis. Finally, the combination of cell-type-specific genomic and genetic analyses provides a means to dissect cellular and functional diversity in the hypothalamus whose neurodevelopment remains poorly studied.

SIGNIFICANCE STATEMENTPOMC and NPY/AgRP neurons are derived from the same hypothalamic progenitors but have opposing effects on food intake. We profiled the transcriptomes of genetically labeled POMC and NPY/AgRP neurons in the developing mouse hypothalamus to decipher the transcriptional codes behind the versus orexigenic neuron identity. Our analyses revealed 29 transcription regulators that are selectively enriched in one of the two populations. We generated new mouse genetic models to selective ablate one of POMC-neuron enriched transcription factorsPrdm12in developing and adult POMC neurons. Our studies establish a previously unrecognized role forPrdm12in the anorexigenic neuron identity and suggest that it acts developmentally to program body weight homeostasis.
Cardiovascular prognostic value of echocardiography and N terminal pro B-type natriuretic peptide in type 1 diabetes: the Thousand & 1 Study
Authors: Rørth Rasmus , Jørgensen Peter Godsk , Andersen Henrik Ullits , Christoffersen Christina , Gøtze Jens Peter , Køber Lars , Rossing Peter , Jensen Magnus Thorsten
Published: March 2020

Aims

Patients with type 1 diabetes have a high risk of cardiovascular disease. Yet, the importance of routine assessment of myocardial function in patients with type 1 diabetes is not known. Thus, we examined the prognostic importance of NT-proBNP and E/e′, an echocardiographic measure of diastolic function, in type 1 diabetes patients with preserved left ventricular ejection fraction (LVEF) and without known heart disease.

Methods and results

Type 1 diabetes patients without known heart disease and LVEF ≥45% enrolled in the Thousand and 1 study were included and followed through nationwide registries. The risk of major cardiovascular events (MACE) and death associated with levels of NT-proBNP and E/e′ was examined. Of 960 patients, median follow-up of 6.3 years (Q1–Q3: 5.7–7.0), 121 (12%) experienced MACE and 51 (5%) died. Increased levels of both NT-proBNP and E/e′ were associated with worse outcomes (adjusted hazard ratios for MACE = 1.56 (1.23–1.98) and 4.29 (2.25–8.16) per Loge increase for NT-proBNP and E/e′, respectively). NT-proBNP and E/e′ combined significantly improved the discrimination power of the Steno T1D risk engine (MACE, C-index: 0.813 (0.779–0.847) vs 0.779 (0.742–0.816); P = 0.0001; All-cause mortality, C-index 0.855 (0.806–0.903) vs 0.828 (0.776–0.880); P = 0.03).

Conclusion

In patients with type 1 diabetes, preserved ejection fraction, and no known heart disease, NT-proBNP and E/e′ were associated with increased risk of MACE and all-cause mortality. The risks associated with NT-proBNP and E/e′ combined identified patients at remarkably high risk.
90 YEARS OF PROGESTERONE: Steroid receptors as MAPK signaling sensors in breast cancer: let the fates decide
Authors: Dwyer Amy R , Truong Thu H , Ostrander Julie H , Lange Carol A
Published: March 2020

Steroid hormone receptors (SRs) are classically defined as ligand-activated transcription factors that function as master regulators of gene programs important for a wide range of processes governing adult physiology, development, and cell or tissue homeostasis. A second function of SRs includes the ability to activate cytoplasmic signaling pathways. Estrogen (ER), androgen (AR), and progesterone (PR) receptors bind directly to membrane-associated signaling molecules including mitogenic protein kinases (i.e. c-SRC and AKT), G-proteins, and ion channels to mediate context-dependent actions via rapid activation of downstream signaling pathways. In addition to making direct contact with diverse signaling molecules, SRs are further fully integrated with signaling pathways by virtue of their N-terminal phosphorylation sites that act as regulatory hot-spots capable of sensing the signaling milieu. In particular, ER, AR, PR, and closely related glucocorticoid receptors (GR) share the property of accepting (i.e. sensing) ligand-independent phosphorylation events by proline-directed kinases in the MAPK and CDK families. These signaling inputs act as a ‘second ligand’ that dramatically impacts cell fate. In the face of drugs that reliably target SR ligand-binding domains to block uncontrolled cancer growth, ligand-independent post-translational modifications guide changes in cell fate that confer increased survival, EMT, migration/invasion, stemness properties, and therapy resistance of non-proliferating SR+ cancer cell subpopulations. The focus of this review is on MAPK pathways in the regulation of SR+ cancer cell fate. MAPK-dependent phosphorylation of PR (Ser294) and GR (Ser134) will primarily be discussed in light of the need to target changes in breast cancer cell fate as part of modernized combination therapies.
Space is the Place: Effects of Continuous Spatial Structure on Analysis of Population Genetic Data
Authors: Battey C J , Ralph Peter L , Kern Andrew D
Published: March 2020

Real geography is continuous, but standard models in population genetics are based on discrete, well-mixed populations. As a result, many methods of analyzing genetic data assume that samples are a random draw from a well-mixed population, but are applied to clustered samples from populations that are structured clinally over space. Here, we use simulations of populations living in continuous geography to study the impacts of dispersal and sampling strategy on population genetic summary statistics, demographic inference, and genome-wide association studies (GWAS). We find that most common summary statistics have distributions that differ substantially from those seen in well-mixed populations, especially when Wright’s neighborhood size is < 100 and sampling is spatially clustered. “Stepping-stone” models reproduce some of these effects, but discretizing the landscape introduces artifacts that in some cases are exacerbated at higher resolutions. The combination of low dispersal and clustered sampling causes demographic inference from the site frequency spectrum to infer more turbulent demographic histories, but averaged results across multiple simulations revealed surprisingly little systematic bias. We also show that the combination of spatially autocorrelated environments and limited dispersal causes GWAS to identify spurious signals of genetic association with purely environmentally determined phenotypes, and that this bias is only partially corrected by regressing out principal components of ancestry. Last, we discuss the relevance of our simulation results for inference from genetic variation in real organisms.
Comparison of stress induced in mandible around an implant-supported overdenture with locator attachment and telescopic crowns – a finite element analysis
Authors: Abbasi Meer Rownaq Ali , Vinnakota Dileep Nag , Sankar V Vijaya , Kamatham Rekhalakshmi
Published: March 2020

Introduction. One of the principle factors for the success of implant supported/retained overdentures (IOs) is the manner in which the stresses are transferred to the surrounding bone. Hence, the aim of the present study is to compare the stress induced in the mandible around IOs, using two different attachment systems, locator and telescopic.

Methods. 3D finite element models were prepared using Pro/ENGINEER or PTC Creo to simulate 4 clinical situations: IOs using two different attachment systems, locator and telescopic, with and without splinting. A vertical compressive load of 35N was directed toward the central fossa in the molar region of each overdenture. Non-linear static contact analysis was carried out to determine the stress distribution in various components of IOs. Then, the models were analyzed by a finite element program ABAQUS, and displayed using Von Mises stress patterns.

Results. The contact stress values developed on the implant and attachment components were lower with locator attachment, in both splinted and non-splinted models. On the other hand, the stress distribution to the cortical bone was more with non-splinted/splinted locator attachments (3.73/4.12 Mega Pascals) when compared to the non-splinted/splinted telescopic attachments (2.66/3.7 Mega Pascals). The stresses in all the components of overdenture were greater with the splinted model compared to non-splinted, in both the attachment systems. 

Conclusion. The locator attachment might demonstrate superior clinical performance, as the stresses on implant and attachment components were less compared to telescopic. Non-splinted model showed better results in both the attachment types.