bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting the RHOA pathway improves learning and memory in adult Kctd13 and 16p11.2 deletion mouse models
Authors: Martin Lorenzo Sandra , Nalesso Valérie , Chevalier Claire , Birling Marie-Christine , Herault Yann 
Published: January 2021

Abstract
Background
Gene copy number variants play an important role in the occurrence of neurodevelopmental disorders. Particularly, the deletion of the 16p11.2 locus is associated with autism spectrum disorder, intellectual disability, and several other features. Earlier studies highlighted the implication of Kctd13 genetic imbalance in 16p11.2 deletion through the regulation of the RHOA pathway.

Methods
Here, we generated a new mouse model with a small deletion of two key exons in Kctd13. Then, we targeted the RHOA pathway to rescue the cognitive phenotypes of the Kctd13 and 16p11.2 deletion mouse models in a pure genetic background. We used a chronic administration of fasudil (HA1077), an inhibitor of the Rho-associated protein kinase, for six weeks in mouse models carrying a heterozygous inactivation of Kctd13, or the deletion of the entire 16p11.2 BP4-BP5 homologous region.

Results
We found that the small Kctd13 heterozygous deletion induced a cognitive phenotype similar to the whole deletion of the 16p11.2 homologous region, in the Del/+ mice. We then showed that chronic fasudil treatment can restore object recognition memory in adult heterozygous mutant mice for Kctd13 and for 16p11.2 deletion. In addition, learning and memory improvement occurred in parallel to change in the RHOA pathway.

Limitations
The Kcdt13 mutant line does not recapitulate all the phenotypes found in the 16p11.2 Del/+ model. In particular, the locomotor activity was not altered at 12 and 18 weeks of age and the object location memory was not defective in 18-week old mutants. Similarly, the increase in locomotor activity was not modified by the treatment in the 16p11.2 Del/+ mouse model, suggesting that other loci were involved in such defects. Rescue was observed only after four weeks of treatment but no long-term experiment has been carried out so far. Finally, we did not check the social behaviour, which requires working in another hybrid genetic background.

Conclusion
These findings confirm KCTD13 as one target gene causing cognitive deficits in 16p11.2 deletion patients, and the relevance of the RHOA pathway as a therapeutic path for 16p11.2 deletion. In addition, they reinforce the contribution of other gene(s) involved in cognitive defects found in the 16p11.2 models in older mice.
Comparative analysis of mouse bone marrow and adipose tissue mesenchymal stem cells for critical limb ischemia cell therapy
Authors: Nammian Pegah , Asadi-Yousefabad Seyedeh-Leili , Daneshi Sajad , Sheikhha Mohammad Hasan , Tabei Seyed Mohammad Bagher , Razban Vahid 
Published: January 2021

Abstract
Introduction
Critical limb ischemia (CLI) is the most advanced form of peripheral arterial disease (PAD) characterized by ischemic rest pain and non-healing ulcers. Currently, the standard therapy for CLI is the surgical reconstruction and endovascular therapy or limb amputation for patients with no treatment options. Neovasculogenesis induced by mesenchymal stem cells (MSCs) therapy is a promising approach to improve CLI. Owing to their angiogenic and immunomodulatory potential, MSCs are perfect candidates for the treatment of CLI. The purpose of this study was to determine and compare the in vitro and in vivo effects of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) and adipose tissue mesenchymal stem cells (AT-MSCs) on CLI treatment.

Methods
For the first step, BM-MSCs and AT-MSCs were isolated and characterized for the characteristic MSC phenotypes. Then, femoral artery ligation and total excision of the femoral artery were performed on C57BL/6 mice to create a CLI model. The cells were evaluated for their in vitro and in vivo biological characteristics for CLI cell therapy. In order to determine these characteristics, the following tests were performed: morphology, flow cytometry, differentiation to osteocyte and adipocyte, wound healing assay, and behavioral tests including Tarlov, Ischemia, Modified ischemia, Function and the grade of limb necrosis scores, donor cell survival assay, and histological analysis.

Results
Our cellular and functional tests indicated that during 28 days after cell transplantation, BM-MSCs had a great effect on endothelial cell migration, muscle restructure, functional improvements, and neovascularization in ischemic tissues compared with AT-MSCs and control groups.

Conclusions
Allogeneic BM-MSC transplantation resulted in a more effective recovery from critical limb ischemia compared to AT-MSCs transplantation. In fact, BM-MSC transplantation could be considered as a promising therapy for diseases with insufficient angiogenesis including hindlimb ischemia.
Novel pharmacotherapy: NNI-362, an allosteric p70S6 kinase stimulator, reverses cognitive and neural regenerative deficits in models of aging and disease
Authors: Sumien Nathalie , Wells Matthew S. , Sidhu Akram , Wong Jessica M. , Forster Michael J. , Zheng Qiao-Xi , Kelleher-Andersson Judith A. 
Published: January 2021

AbstractAging is known to slow the neurogenic capacity of the hippocampus, one of only two mammalian adult neurogenic niches. The reduction of adult-born neurons with age may initiate cognitive decline progression which is exacerbated in chronic neurodegenerative disorders, e.g., Alzheimer’s disease (AD). With physiologic neurogenesis diminished, but still viable in aging, non-invasive therapeutic modulation of this neuron regeneration process remains possible. The discovery of truly novel neuron regenerative therapies could be identified through phenotypic screening of small molecules that promote adult-born neurons from human neural progenitor cells (hNPCs). By identifying neuron-generating therapeutics and potentially novel mechanism of actions, therapeutic benefit could be confirmed through in vivo proof-of-concept studies. The key aging and longevity mTOR/p70S6 kinase axis, a commonly targeted pathway, is substrate for potential selective kinase modulators to promote new hippocampal neurons from NPCs. The highly regulated downstream substrate of mTOR, p70S6 kinase, directly controls pleiotropic cellular activities, including translation and cell growth. Stimulating this kinase, selectively in an adult neurogenic niche, should promote NPC proliferation, and cell growth and survival in the hippocampus. Studies of kinase profiling and immunocytochemistry of human progenitor neurogenesis suggest that the novel small molecule NNI-362 stimulates p70S6 kinase phosphorylation, which, in turn, promotes proliferation and differentiation of NPCs to neurons. NNI-362 promoted the associative reversal of age- and disease-related cognitive deficits in aged mice and Down syndrome-modeled mice. This oral, allosteric modulator may ultimately be beneficial for age-related neurodegenerative disorders involving hippocampal-dependent cognitive impairment, specifically AD, by promoting endogenous hippocampal regeneration.
Understanding coherence and integration in integrated STEM curriculum
Authors: Roehrig Gillian H. , Dare Emily A. , Ring-Whalen Elizabeth , Wieselmann Jeanna R. 
Published: January 2021

Abstract
Background
Few tools or rubrics exist to assess the quality of integrated STEM curricula, and existing tools focus on checklists of characteristics of integrated STEM. While such instruments provide important information about the presence and quality of certain curricular components, they do not assess the level and nature of integration of the curriculum as a whole. Thus, this study explores the development of a process focused to understand the nature of integration within a STEM curriculum unit.

Findings
A conceptual flow graphic (CFG) was constructed for 50 integrated STEM curriculum units. Patterns in the nature of the interdisciplinary connections were used to categorize and understand the nature of integration and curricular coherence within each unit. The units formed four broad types of integrated STEM curricula: (i) coherent science unit with loosely connected engineering design challenge (EDC), (ii) engineering design-focused unit with limited connections to science content, (iii) engineering design unit with science content as context, and (iv) integrated and coherent STEM units. All physical science units were in the integrated and coherent category with strong conceptual integration between the main science concepts and the EDC. Curricula based in the Earth and life sciences generally lacked conceptual integration between the science content and the EDC and relied on the engineering design process to provide a coherent storyline for the unit.

Conclusions
Our study shows that engineering practices can serve as a contextual integrator within a STEM unit. The utilization of an EDC also provides the potential for conceptual integration because engineering is grounded in the application of science and mathematics. Integrated STEM curricula that purposefully include science and mathematics concepts necessary to develop solutions to the EDC engage students in authentic engineering experiences and provide conceptual integration between the disciplines. However, the alignment of grade-level science standards with the EDC can be problematic, particularly in life science and Earth science. The CFG process provides a tool for determining the nature of integration between science and mathematics content and an EDC. These connections can be conceptual and/or contextual, as both forms of integration are appropriate depending on the instructional goals.
Early childhood education in Vietnam, history, and development
Authors: Vu Thao Thi 
Published: January 2021

AbstractVietnam has an age-old history of education, and Vietnamese people have high respect for learning. However, early childhood education (ECE) in Vietnam has been the main concern only since 1945. This paper describes the process of establishment and development of ECE in Vietnam. Before and during the French colonial period in Vietnam, early childhood education was not considered a social task, and therefore, there was no formal educational system and curriculum for preschool children at this time. After 1945, with the great transformation of history, Vietnamese education has changed dramatically so that from 1945 to 1975 it was a period of political, social and educational separation. The historical events affect the education system and early childhood education in Vietnam. Consequently, the history of ECE in Vietnam is separated into two main phases, before and after 1975. Through the ups and downs of history, Vietnam has successfully built the ECE system. Over seven decades of development, ECE in Vietnam has made remarkable changes. The change comes not only from the expansion of the number of educational institutions, but also from the curriculum and pedagogy that are considered as the most important changes. Gradually escaping the influence of teacher-centered pedagogy, Vietnamese ECE is aiming to build a child-centered education, thereby helping learners to reach their full potential.
Vision-related quality of life in adults with severe peripheral vision loss: a qualitative interview study
Authors: Lange Ryan , Kumagai Abigail , Weiss Sara , Zaffke Katherine B. , Day Sherry , Wicker Donna , Howson Ashley , Jayasundera K. Thiran , Smolinski Lori , Hedlich Christina , Lee Paul P. , Massof Robert W. , Stelmack Joan A. , Carlozzi Noelle E. , Ehrlich Joshua R. 
Published: January 2021

Abstract
Background
Existing patient-reported outcome (PRO) measures may not be relevant to the full range of functional and vision-related quality of life (VR-QOL) concerns of individuals with vision impairment due to severe peripheral field loss (PFL). Measurement of VR-QOL in severe PFL is important in order to determine the effectiveness of vision rehabilitation interventions for this population. The purpose of this study was to characterize the impact of severe PFL due to retinitis pigmentosa (RP) and glaucoma on VR-QOL as the initial phase in the development of a novel PRO measure.

Methods
Individuals with severe PFL due to RP or glaucoma were recruited from the Kellogg Eye Center and the Association for the Blind and Visually Impaired. Participants completed semi-structured qualitative interviews, the Impact of Vision Impairment (IVI) questionnaire and the RAND 36-Item Health Survey. Interviews were analyzed by two coders using thematic analysis. A matrix analysis was conducted to compare VR-QOL by cause of severe PFL. Sample size was determined by thematic saturation.

Results
The study included 37 participants (19 RP, 18 glaucoma). Median best-corrected visual acuity for those with RP and glaucoma was 20/40 and 20/27.5, while Pelli-Robson contrast sensitivity was 1.2 log contrast sensitivity (logCS) and 1.1 logCS, respectively. Median domain scores on the IVI (reading, mobility, well-being) ranged from a low of − 0.2 to a high of 0.7 logits in those with RP and from 0.5 to 1.2 logits in those with glaucoma. Qualitative interviews identified six VR-QOL themes relevant across participants with both RP and glaucoma, including activity limitations, driving, emotional well-being, reading, mobility, and social function. VR-QOL concerns were largely consistent among those with severe PFL due to RP and glaucoma. These overarching themes contained content relevant to specific challenges related to severe PFL.

Conclusions
There are commonly occurring VR-QOL concerns among individuals with severe PFL due to RP and glaucoma. The outlined themes will serve as the basis for development of the Low Vision Severely Constricted Peripheral Eyesight (LV-SCOPE) Questionnaire.
Impact of endometrial microbiome on fertility
Authors: Elnashar Aboubakr Mohamed 
Published: January 2021

Abstract
Background
Next-generation sequencing isolates culturable and unculturable bacteria from the female reproductive tract. Current literatures surrounding the impact of endometrial microbiome on fertility are reviewed.

Main body
An abnormal endometrial microbiota has been associated with implantation failure pregnancy loss and other gynecological and obstetrical conditions. Identification of endometrial dysbiosis as a new cause of infertility opens a new microbiological field in the evaluation of endometrial factor, highlighting the relevance of assessing the uterine microbiota in infertile patients to restore a favorable endometrial flora in those patients with altered uterine microbiota to improve and personalize the clinical care of infertile patients. Understanding the significance of microbiome in the endometrium may completely change the therapeutic approach in the treatment of this part of the reproductive tract.

Conclusion
Investigation of the endometrial microbiota may be a future tool for improving reproductive outcomes in infertile patients. Further well-designed studies are required to establish its role in the evaluation and treatment of infertile patients
Prevalence of asthma—chronic obstructive pulmonary disease overlap in patients with airflow limitation
Authors: Shabaan Ahmed Youssef , Daabis Rasha Galal , Abdelhady Ahmed Mohamed , Ibrahim Dina Hassan 
Published: January 2021

Abstract
Background
Asthma-COPD overlap (ACO) according to GINA and GOLD is not a single disease and is described by persistent airflow limitation with several features usually associated with asthma and several features usually associated with COPD. Some different protocols were proposed to diagnose ACO, besides those reported in GINA and GOLD guidelines. Despite the discrepancy between all the proposed diagnostic protocols, the diagnosis of ACO is still worthy as it may lead to a more appropriate treatment plan. In Egypt, prevalence of ACO is hardly estimated due to lack of database of patients. Our aim of work was to detect the prevalence of ACO in patients diagnosed as having a chronic airflow limiting disease.

Results
In asthma group (75 patients), 53.3% (40 patients) were diagnosed as ACO with 3 statistically significant favoring diagnostic criteria; post-BDR test FEV1/FVC < 70%, longer disease duration, and sputum neutrophilia ≥ 57%. While in COPD group (75 patients), 42.7% (32 patients) were diagnosed as ACO with four statistically significant favoring diagnostic criteria; higher BDR, presence of personal history of either asthma or atopy and sputum eosinophils > 1%.

Conclusions
ACO has an underestimated prevalence among those diagnosed with either asthma or COPD. More consensus guidelines are needed to focus on the more effective and the more practical criteria to diagnose such hidden disease.
The association between ethnicity, environmental and lifestyle factors and chronic disease in the development of pseudoexfoliation syndrome
Authors: Ali Arif Saba , Khan Muhammad Ifraheem , Nauman Fatimah , Arif Mohammad Ali 
Published: January 2021

Objectives: To determine the association between ethnicity, environmental factors, lifestyle factors, chronic diseases and pseudoexfoliation syndrome (PEX).
Methods: A case control study conducted at four major hospitals in Pakistan from January to November 2019, with 241 cases and 294 controls, aged ≥ 40 years, who were administered a questionnaire assessing demographics, lifestyle factors, chronic diseases and ethnicity. Multivariate binary logistic regression was applied to calculate the odds ratio between cases and controls.
Results: PEX was found to be positively associated with ethnicity (p<0.001), time spent outdoors (p<0.001), educational status (p<0.001), asthma (p<0.001), mean age (p<0.001), daily tea intake (p=0.003), weighted maximum temperature (p<0.001) and weighted mean temperature (p=0.004). Poor association was found with weighted latitude (p=0.526) and weighted minimum temperature (p=0.079). Odds ratios for patients with asthma (OR=7.366, regression coefficient=1.993, p<0.001) Pathan ethnicity (OR=1.616, regression coefficient=0.48, p=0.016) and mean weighted temperature (OR=0.907, regression coefficient-0.097, p=0 0.000) were significant in diagnosed cases of PEX.
Conclusion: Individuals with Pathan ethnicity and asthmatics should be made aware of the risk of developing PEX and the importance of periodic screening. Limiting exposure to sunlight and cold and reducing the intake of tea may help in reducing in the chances of developing PEX.
doi: https://doi.org/10.12669/pjms.37.2.2216
How to cite this:Arif SA, Khan MI, Nauman F, Arif MA. The association between ethnicity, environmental and lifestyle factors and chronic disease in the development of pseudoexfoliation syndrome. Pak J Med Sci. 2021;37(2):409-414. doi: https://doi.org/10.12669/pjms.37.2.2216
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Surgical Training During The COVID-19 Pandemic
Authors: Shah Rupali , Carty Isabelle , Ugwu Francis 
Published: January 2021

doi: https://doi.org/10.12669/pjms.37.2.4119
How to cite this: Shah R, Carty I, Ugwu F. Surgical Training During The COVID-19 Pandemic. Pak J Med Sci. 2021;37(2):610-611. doi: https://doi.org/10.12669/pjms.37.2.4119
Subwavelength grating based mode (de)multiplexer for 3D photonic integrated circuits
Authors: Jiang Weifeng , Hu Jinzhu , Mao Siqiang , Feng Jiaqi , Hao Xiaoyu , Zhang Yingjia 
Published: January 2021

A broadband three-dimensional (3D) mode (de) multiplexer [(De)MUX] is proposed based on the subwavelength grating (SWG) for 3D photonic integrated circuits (PICs). The proposed 3D mode (De)MUX consists of three SWG waveguides on two vertical layers. The coupling strength and operating bandwidth can be increased benefitting from both the subwavelength structure and offset between bus and access SWGs. The proposed 3D mode (De)MUX is optimized based on the 3D full-vectorial finite difference time domain method. The 1-dB bandwidths of the optimized device are over

>

300

, 107, and 128 nm for demultiplexing

T
E

0

,

T
E

1

, and

T
E

2

modes, respectively. The coupling lengths are only 5.0 and 1.75 µm for demultiplexing the

T
E

1

and

T
E

2

modes, respectively. The insertion losses are 0.12, 0.27, and 0.29 dB, respectively. The proposed 3D mode (De)MUX is also fabrication tolerant.
Phacoemulsification of primary cataract by the second stage after vitreoretinal surgery of PDR patients.
Authors: Konovalova Karina Igorevna , Shishkin Mikhail Mikhailovich , Fayzrakhmanov Rinat Rustamovich 
Published: January 2021

BACKGROUND: The «gold standart» for surgical treatment of patients with proliferative diabetic retinopathy (PDR is vitreoretinal surgery. However, the question of the timing of the removal of primary cataract in this category of patients remains open.AIM: To evaluate the efficacy of phacoemulsification of primary cataract by the second stage after vitreoretinal surgery of PDR patientsMETHODS: 67 cases of surgery treatment of patients with PDR and complicated primary cataract were enrolled. This patients were divided into two groups depending on the treatment tactics. In the 1st group patients were subjected to a two–step surgical procedure: vitreoretinal surgery with silicone oil tamponade performed as the 1st step in their treatment; followed by the 2d step, phacoemulsifi tion surgery and silicone oil removal, and the IOL implantation, respectively. In the 2d group phacoemulsifi tion performed simultaneously with vitreoretinal surgery: phacoemulsification, IOL implantation, vitreoretinal surgery with silicone oil tamponade. The second step differed in the removal of silicone oil from the vitreous cavity.RESULTS: Visual functions improved in 88.6% of cases in group 1, and in 68.7% in group 2.CONCLUSIONS: Outcomes of the preliminary studies suggest that it is more viable to perform phacoemulsification surgery sometime later along with silicone oil removal on PDR patients with complicated primary cataract. This sequence of treatment procedure ensures a more gentle approach to the anatomic structures of the eye during the first stage (vitreoretinal surgery) and contributes to the reduction in the number of intraoperative and postoperative complications.