bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual role of EZH2 in megakaryocyte differentiation
Authors: Mazzi Stefania , Dessen Philippe , Vieira Mathieu , Dufour Virginie , Cambot Marie , El Khoury Mira , Antony-Debré Iléana , Arkoun Brahim , Basso-Valentina Francesca , BenAbdoulahab Salwa , Edmond Valerie , Rameau Philippe , Petermann Rachel , Wittner Monika , Cassinat Bruno , Plo Isabelle , Debili Najet , Raslova Hana , Vainchenker William
Published: June 2021

EZH2, the enzymatic component of PRC2, has been identified as a key factor in hematopoiesis. EZH2 loss-of-function mutations have been found in myeloproliferative neoplasms, particularly in myelofibrosis, but the precise function of EZH2 in megakaryopoiesis is not fully delineated. Here, we show that EZH2 inhibition by small molecules and short hairpin RNA induces megakaryocyte (MK) commitment by accelerating lineage marker acquisition without change in proliferation. Later in differentiation, EZH2 inhibition blocks proliferation and polyploidization and decreases proplatelet formation. EZH2 inhibitors similarly reduce MK polyploidization and proplatelet formation in vitro and platelet levels in vivo in a JAK2V617F background. In transcriptome profiling, the defect in proplatelet formation was associated with an aberrant actin cytoskeleton regulation pathway, whereas polyploidization was associated with an inhibition of expression of genes involved in DNA replication and repair and an upregulation of cyclin-dependent kinase inhibitors, particularly CDKN1A and CDKN2D. The knockdown of CDKN1A and to a lesser extent CDKN2D could partially rescue the percentage of polyploid MKs. Moreover, H3K27me3 and EZH2 chromatin immunoprecipitation assays revealed that CDKN1A is a direct EZH2 target and CDKN2D expression is not directly regulated by EZH2, suggesting that EZH2 controls MK polyploidization directly through CDKN1A and indirectly through CDKN2D.
Single-cell analysis of ploidy and the transcriptome reveals functional and spatial divergency in murine megakaryopoiesis
Authors: Sun Shu , Jin Chen , Si Jia , Lei Ying , Chen Kunying , Cui Yueli , Liu Zhenbo , Liu Jiang , Zhao Meng , Zhang Xiaohui , Tang Fuchou , Rondina Matthew T. , Li Yueying , Wang Qian-fei
Published: June 2021

Megakaryocytes (MKs), the platelet progenitor cells, play important roles in hematopoietic stem cell (HSC) maintenance and immunity. However, it is not known whether these diverse programs are executed by a single population or by distinct subsets of cells. Here, we manually isolated primary CD41+ MKs from the bone marrow (BM) of mice and human donors based on ploidy (2N-32N) and performed single-cell RNA sequencing analysis. We found that cellular heterogeneity existed within 3 distinct subpopulations that possess gene signatures related to platelet generation, HSC niche interaction, and inflammatory responses. In situ immunostaining of mouse BM demonstrated that platelet generation and the HSC niche–related MKs were in close physical proximity to blood vessels and HSCs, respectively. Proplatelets, which could give rise to platelets under blood shear forces, were predominantly formed on a platelet generation subset. Remarkably, the inflammatory responses subpopulation, consisting generally of low-ploidy LSP1+ and CD53+ MKs (≤8N), represented ∼5% of total MKs in the BM. These MKs could specifically respond to pathogenic infections in mice. Rapid expansion of this population was accompanied by strong upregulation of a preexisting PU.1- and IRF-8–associated monocytic-like transcriptional program involved in pathogen recognition and clearance as well as antigen presentation. Consistently, isolated primary CD53+ cells were capable of engulfing and digesting bacteria and stimulating T cells in vitro. Together, our findings uncover new molecular, spatial, and functional heterogeneity within MKs in vivo and demonstrate the existence of a specialized MK subpopulation that may act as a new type of immune cell.
A novel approach to perioperative risk assessment for patients with pulmonary hypertension
Authors: Hassan Hussein J. , Housten Traci , Balasubramanian Aparna , Simpson Catherine E. , Damico Rachel L. , Mathai Stephen C. , Hassoun Paul M. , Steppan Jochen , Leary Peter J. , Kolb Todd M.
Published: June 2021

Rationale

Pulmonary hypertension (PH) is associated with significant perioperative morbidity and mortality. We hypothesised that pulmonary arterial hypertension (PAH) composite risk assessment scores could estimate perioperative risk for PH patients when adjusted for inherent procedural risk.

Methods

We identified patients in the Johns Hopkins PH Center Registry that had noncardiac surgery (including endoscopies) between September 2015 and January 2020. We collected information on preoperative patient-level and procedural variables and used logistic regression to evaluate associations with a composite outcome of death within 30 days or serious postoperative complication. We generated composite patient-level risk assessment scores for each subject and used logistic regression to estimate the association with adverse surgical outcomes. We adjusted multivariable models for inherent procedural risk of major cardiovascular events and used these models to generate a numerical PH perioperative risk (PHPR) score.

Results

Among 150 subjects, 19 (12.7%) reached the primary outcome, including 7 deaths (4.7%). Individual patient-level and procedural variables were associated with the primary outcome (all p<0.05). A composite patient-level risk assessment score built on three noninvasive parameters was strongly associated with reduced risk for poor outcomes (OR=0.4, p=0.03). This association was strengthened after adjusting the model for procedural risk. A PHPR score derived from the multivariable model stratified patients into low (0%), intermediate (≤10%), or high (>10%) risk of reaching the primary outcome.

Conclusion

Composite PAH risk assessment scores can predict perioperative risk for PH patients after accounting for inherent procedural risk. Validation of the PHPR score in a multicentre, prospective cohort is warranted.
RNA analysis based on a small number of manually isolated fixed cells (RNA-snMIFxC) to profile stem cells from human deciduous tooth-derived dental pulp cells
Authors: Inada Emi , Saitoh Issei , Kubota Naoko , Iwase Yoko , Kiyokawa Yuki , Noguchi Hirofumi , Yamasaki Youichi , Sato Masahiro
Published: June 2021

Background

Expression of stemness factors, such as octamer-binding transcription factor 3/4 (OCT3/4), sex determining region Y-box 2 (SOX2), and alkaline phosphatase (ALP) in human deciduous tooth-derived dental pulp cells (HDDPCs) can be assessed through fixation and subsequent immuno- or cytochemical staining. Fluorescence-activated cell sorting (FACS), a powerful system to collect cells of interest, is limited by the instrument cost and difficulty in handling. Magnetic-activated cell sorting is inexpensive compared to FACS, but is confined to cells with surface expression of the target molecule. In this study, a simple and inexpensive method was developed for the molecular analysis of immuno- or cytochemically stained cells with intracellular expression of a target molecule, through isolation of a few cells under a dissecting microscope using a mouthpiece-controlled micropipette.

Results

Two or more colored cells (~ 10), after staining with a chromogen such a 3,3′-diaminobenzidine, were successfully segregated from unstained cells. Expression of glyceraldehyde 3-phosphate dehydrogenase, a housekeeping gene, was discernible in all samples, while the expression of stemness genes (such as OCT3/4, SOX2, and ALP) was confined to positively stained cells.

Conclusion

These findings indicate the fidelity of these approaches in profiling cells exhibiting cytoplasmic or nuclear localization of stemness-specific gene products at a small-scale.
COVID-19 and gastrointestinal symptoms in Mexico, a systematic review: does location matter?
Authors: Pizuorno Antonio , Fierro Nora A. , Copado-Villagrana Edgar D. , Herrera-Solís María E. , Oskrochi Gholamreza , Brim Hassan , Ashktorab Hassan
Published: June 2021

Background

Covid-19 in Mexico is on the rise in different parts of the country. We aimed to study the symptoms and comorbidities that associate with this pandemic in 3 different regions of Mexico.

Methods

We analyzed data from SARS-CoV-2 positive patients evaluated at healthcare centers and hospitals of Mexico (n = 1607) including Northwest Mexico (Sinaloa state), Southeast Mexico (Veracruz state) and West Mexico (Jalisco state) between March 1 and July 30, 2020. Mexico consists of a total population that exceeds 128 million. Demographics, comorbidities and clinical symptoms were collected. Statistical descriptive analysis and correlation analyses of symptoms, comorbidities and mortality were performed.

Results

A total of 1607 hospitalized patients positive for COVID-19 across all 3 regions of Mexico were included. The average age was 54.6 years and 60.4% were male. A mortality rate of 33.1% was observed. The most common comorbidities were hypertension (43.2%), obesity (30.3%) and diabetes (31.4%). Hypertension was more frequent in West (45%), followed by Northwest (37%) and Southeast Mexico (29%). Obesity was around 30% in Northwest and West whereas an 18% was reported in Southeast. Diabetes was most common in West (34%) followed by Northwest (22%) and Southeast (13%). This might be related to the highest mortality rate in Northwest (31%) and West (37%) when compared to Southeast. Most common symptoms in our overall cohort were fever (80.8%), cough (79.8%), headache (66%), dyspnea (71.1%), myalgia (53.8%), joints pain (50.8%) and odynophagia (34.8%). Diarrhea was the main gastrointestinal (GI) symptom (21.3%), followed by abdominal pain (18%), and nausea/ vomiting (4.5%). Diarrhea and abdominal pain were more common in West (23.1 and 21%), followed by Southeast (17.8, and 9.8%) and Northwest (11.4 and 3.1%).

Conclusion

Our study showed a high mortality rate likely related to high frequencies of comorbidities (hypertension, obesity and diabetes). Mortality was different across regions. These discrepancies might be related to the differences in the frequencies of comorbidities, and partially attributed to differences in socio-economic conditions and quality of care. Thus, our findings stress the need for improved strategies to get better outcomes in our population.
Dapagliflozin: a sodium–glucose cotransporter 2 inhibitor, attenuates angiotensin II-induced cardiac fibrotic remodeling by regulating TGFβ1/Smad signaling
Authors: Zhang Yuze , Lin Xiaoyan , Chu Yong , Chen Xiaoming , Du Heng , Zhang Hailin , Xu Changsheng , Xie Hong , Ruan Qinyun , Lin Jinxiu , Liu Jie , Zeng Jinzhang , Ma Ke , Chai Dajun
Published: June 2021

Background

Cardiac remodeling is one of the major risk factors for heart failure. In patients with type 2 diabetes, sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of the first hospitalization for heart failure, possibly through glucose-independent mechanisms in part, but the underlying mechanisms remain largely unknown. This study aimed to shed light on the efficacy of dapagliflozin in reducing cardiac remodeling and potential mechanisms.

Methods

Sprague–Dawley (SD) rats, induced by chronic infusion of Angiotensin II (Ang II) at a dose of 520 ng/kg per minute for 4 weeks with ALZET® mini-osmotic pumps, were treated with either SGLT2 inhibitor dapagliflozin (DAPA) or vehicle alone. Echocardiography was performed to determine cardiac structure and function. Cardiac fibroblasts (CFs) were treated with Ang II (1 μM) with or without the indicated concentration (0.5, 1, 10 μM) of DAPA. The protein levels of collagen and TGF-β1/Smad signaling were measured along with body weight, and blood biochemical indexes.

Results

DAPA pretreatment resulted in the amelioration of left ventricular dysfunction in Ang II-infused SD rats without affecting blood glucose and blood pressure. Myocardial hypertrophy, fibrosis and increased collagen synthesis caused by Ang II infusion were significantly inhibited by DAPA pretreatment. In vitro, DAPA inhibit the Ang II-induced collagen production of CFs. Immunoblot with heart tissue homogenates from chronic Ang II-infused rats revealed that DAPA inhibited the activation of TGF-β1/Smads signaling.

Conclusion

DAPA ameliorates Ang II-induced cardiac remodeling by regulating the TGF-β1/Smad signaling in a non-glucose-lowering dependent manner.
Symbolic annihilation of Syrian refugees by Turkish news media during the COVID-19 pandemic
Authors: Yücel Alev
Published: June 2021

Background

This article presents a discussion about the representation of Syrian refugees in Turkish news media during the COVID-19 pandemic. Media play a critical role during pandemics by affecting values, opinions, public knowledge about stigmatized groups. When media ignore and stereotypically represent a social group, the social value of the group decreases, and their problems are trivialized.

Method

I analyzed data provided by Media Monitoring Center which is an independent media company in Turkey. Sample was selected to reveal news representation of Syrian refugees between March 11, 2020 (the first confirmed case of COVID-19 in Turkey) and August 20, 2020 (the time of this research). Mostly watched television evening (prime) news, the most widely circulated newspapers, and the most visited online news platforms were analyzed. By using content analysis method, the news stories about Syrian refugees were examined.

Results

It has been revealed that Turkish news media overwhelmingly acclaimed for Turkey’s polices on Syrian refugees and the criticized the European Union policies towards refugees in the news stories. Even though almost 4 million Syrian refugees live in Turkey, with the largest refugee population in the world, Turkish news media ignored the plight of Syrian refugees.

Conclusion

Results of the study demonstrate that Syrian refugees were symbolically annihilated by Turkish news media during the COVID-19 pandemic. The concealment of information and symbolic annihilation of disadvantaged groups could potentially cause health disparities and irreparable harm to public health. Moreover, inequities exacerbate when predicaments of stigmatized groups are ignored in the news media. Further studies are needed to reveal the impact of the media on health disparities among stigmatized groups during the pandemics.
Interstitial lung disease associated with adjuvant and neoadjuvant chemotherapy in early breast cancer
Authors: Tezuka Kenji , Miura Kotaro , Nakano Yusuke , Ueda Takahiro , Yagyu Kyoko , Matsuyama Shimako , Shirai Masami , Okuda Hiroshi , Ujikawa Miho , Ota Takayo
Published: June 2021

Background

Interstitial lung disease (ILD) is a rare adverse event in patients receiving adjuvant or neoadjuvant chemotherapy (NAC) for breast cancer. Few studies have reported the frequency of ILD in detail, and only small numbers of cases have been described in the literature.

Given these previous findings concerning ILD, we retrospectively examined the clinicopathological characteristics of five cases of ILD who had received epirubicin and cyclophosphamide (EC) and compared their findings with non-ILD cases.

Methods

The present single-center retrospective study included breast cancer patients who underwent adjuvant chemotherapy or NAC at our hospital between January 2014 and January 2021.

Results

Thirty-nine patients who had received EC for operable breast cancer were enrolled in this study. ILD developed 5 out of 39 patients (12.8%). The incidence of ILD in patients with non-dose-dense (dd) or dd chemotherapy was statistically significantly different (p= 0.0149). ILD occurred in three patients during dd EC treatment and two during weekly paclitaxel (wPTX) after dd EC. ILD was detected in one patient with high Krebs von den Lungen-6 (KL-6) levels, in two patients with continuous pyrexia, and in two patients from computed tomography imaging, which was taken to estimate the efficacy of chemotherapy, in two patients. Three of the 5 ILD patients underwent bronchoalveolar lavage, and 2 of these patients were diagnosed withPneumocystis jiroveciipneumonia (PCP). There were no cases of serious ILD that required steroid pulse therapy.

Conclusions

Dd chemotherapy may be associated with an increased ILD frequency, which may reflect developing PCP. Careful monitoring and a timely diagnosis are useful for detecting early-stage ILD.
H3.3 kinetics predicts chromatin compaction status of parental genomes in early embryos
Authors: Guo Shi-meng , Liu Xing-ping , Zhou Li-quan
Published: June 2021

Background

After fertilization, the fusion of gametes results in the formation of totipotent zygote. During sperm-egg fusion, maternal factors participate in parental chromatin remodeling. H3.3 is a histone H3 variant that plays essential roles in mouse embryogenesis.

Methods

Here, we used transgenic early embryos expressing H3.3-eGFP or H2B-mCherry to elucidate changes of histone mobility.

Results

We used FRAP analysis to identify that maternally stored H3.3 has a more significant change than H2B during maternal-to-embryonic transition. We also found that H3.3 mobile fraction, which may be regulated byde novoH3.3 incorporation, reflects chromatin compaction of parental genomes in GV oocytes and early embryos.

Conclusions

Our results show that H3.3 kinetics in GV oocytes and early embryos is highly correlated with chromatin compaction status of parental genomes, indicating critical roles of H3.3 in higher-order chromatin organization.
Where is critical analysis of power and positionality in knowledge translation?
Authors: Crosschild Chloe , Huynh Ngoc , De Sousa Ismalia , Bawafaa Eunice , Brown Helen
Published: June 2021

In Canada, the Eurocentric epistemological foundations of knowledge translation (KT) approaches and practices have been significantly influenced by the Canadian Institutes of Health Research (CIHR) KT definition. More recently, integrated knowledge translation (IKT) has emerged in part as epistemic resistance to Eurocentric discourse to critically analyse power relations between researcher and participants. Yet, despite the proliferation of IKT literature, issues of power in research relationships and strategies to equalize relationships remain largely unaddressed. In this paper, we analyse the gaps in current IKT theorizing against the backdrop of the CIHR KT definition by drawing on critical scholars, specifically those writing about standpoint theory and critical reflexivity, to advance IKT practice that worked to surface and change research-based power dynamics within the context of health research systems and policy.
Metabolic adaptation is associated with less weight and fat mass loss in response to low-energy diets
Authors: Martins Catia , Roekenes Jessica , Gower Barbara A. , Hunter Gary R.
Published: June 2021

Background

The practical relevance of metabolic adaptation remains a controversial issue. To the best of our knowledge, no study has properly evaluated the role of metabolic adaptation in modulating weight loss outcomes. Therefore, the aim of this study was to determine the association between metabolic adaptation, at the level of resting metabolic rate (RMR), and weight and fat mass (FM) loss after low-energy diets (LED), after adjusting for dietary adherence and other confounders.

Methods

71 individuals with obesity (BMI: 34.6 ± 3.4 kg/m2; age: 45.4 ± 8.2 years; 33 males) were randomized to one of three 1000 kcal/day diets for 8 weeks. Body weight, FM and fat-free mass (FFM) (air displacement plethysmography), RMR (indirect calorimetry) and physical activity level (PAL) (armbands) were measured at baseline and at week 9. Metabolic adaptation at week 9 was defined as measured RMR minus predicted RMR at week 9. An equation to predict RMR was derived from baseline data of all participants that were part of this analysis and included age, sex, FM and FFM as predictors. Dietary adherence was calculated from RMR, PAL and body composition changes. Linear regression was used to assess the potential role of metabolic adaptation in predicting weight and FM loss after adjusting for dietary adherence, average PAL, sex, baseline FM and FFM and randomization group.

Results

Participants lost on average 14 ± 4 kg of body weight (13 ± 3%) and presented with metabolic adaptation (−92 ± 110 kcal/day, P < 0.001). Metabolic adaptation was a significant predictor of both weight (β = −0.009, P < 0.001) and FM loss (β = −0.008, P < 0.001), even after adjusting for confounders (R2 = 0.88, 0.93, respectively, P < 0.001 for both). On average, an increase in metabolic adaptation of 50 kcal/day was associated with a 0.5 kg lower weight and FM loss in response to the LED.

Conclusion

In individuals with obesity, metabolic adaptation at the level of RMR is associated with less weight and FM loss in response to LED.

Trial registration ID: NCT02944253.
Gastrostomy for infants with severe epidermolysis bullosa simplex in neonatal intensive care
Authors: Marro M. , De Smet S. , Caldari D. , Lambe C. , Leclerc-Mercier S. , Chiaverini C.
Published: June 2021

Introduction

Severe epidermolysis bullosa simplex (EBS sev) is a rare genodermatosis characterized by congenital generalized blistering and mucosal involvement. Increased needs and decreased intake quickly lead to nutritional imbalance. Enteral nutrition support is proposed, but classical nasogastric tubes are not well tolerated in these patients and gastrostomy is preferred.

Objective and methods

To report the experience with EBS sev in neonatal units of French reference centers for gastrostomy. In this retrospective multicentric study, we included all patients with EBS sev who had gastrostomy placement before age 9 months during neonatal care hospitalization.

Results

Nine infants (5 males/4 females) with severe skin and mucosal involvement were included. A gastrostomy was decided, at an early age (mean 3.7 months, range 1.4 to 8 months) in infants with mean weight 4426 g (range 3500 to 6000 g). Techniques used were endoscopy with the pull technique for 5 infants and surgery under general anesthesia for 4. Main complications were local but resolved after treatment. All infants gained weight after gastrostomy. The mean withdrawal time (n = 7) for the gastrostomy was 35.8 months (range 10.5 months to 6.5 years). Seven children had persistent oral disorders.

Conclusions

Gastrostomy in infants with EBS sev can be necessary in neonatal intensive care units. Both surgical and endoscopic pull techniques seem efficient, with good tolerance.
Plant callus-derived shikimic acid regenerates human skin through converting human dermal fibroblasts into multipotent skin-derived precursor cells
Authors: Kwon Yoo-Wook , Lee Shin-Hyae , Kim Ah-Reum , Kim Beom Joon , Park Won-Seok , Hur Jin , Jang Hyunduk , Yang Han-Mo , Cho Hyun-Jai , Kim Hyo-Soo
Published: June 2021

Background

The human skin-derived precursors (SKPs) are a good cell source for regeneration. However, the isolation of SKP from human skin is limited. To overcome this drawback, we hypothesized that the component of plant stem cells could convert human fibroblasts to SKPs.

Methods

Human dermal fibroblasts were treated with shikimic acid, a major component of Sequoiadendron giganteum callus extract. The characteristics of these reprogrammed cells were analyzed by qPCR, western blot, colony-forming assay, and immunofluorescence staining. Artificial human skin was used for CO2 laser-induced wound experiments. Human tissues were analyzed by immunohistochemistry.

Results

The reprogrammed cells expressed nestin (a neural precursor-specific protein), fibronectin, and vimentin and could differentiate into the ectodermal and mesodermal lineage. Nestin expression was induced by shikimic acid through the mannose receptor and subsequent MYD88 activation, leading to P38 phosphorylation and then CREB binding to the nestin gene promoter. Finally, we confirmed that shikimic acid facilitated the healing of cut injury and enhanced dermal reconstruction in a human artificial skin model. Moreover, in a clinical study with healthy volunteers, plant callus extracts increased the expression of stem cell markers in the basal layer of the epidermis and collagen deposit in the dermis.

Conclusions

These results indicate that shikimic acid is an effective agent for tissue regeneration.
Mathematical analysis and optimal control interventions for sex structured syphilis model with three stages of infection and loss of immunity
Authors: Momoh Abdulfatai Atte , Bala Yusuf , Washachi Dekera Jacob , Déthié Dione
Published: June 2021

In this study, we develop a nonlinear ordinary differential equation to study the dynamics of syphilis transmission incorporating controls, namely prevention and treatment of the infected males and females. We obtain syphilis-free equilibrium (SFE) and syphilis-present equilibrium (SPE). We obtain the basic reproduction number, which can be used to control the transmission of the disease, and thus establish the conditions for local and global stability of the syphilis-free equilibrium. The stability results show that the model is locally asymptotically stable if the Routh–Hurwitz criteria are satisfied and globally asymptotically stable. The bifurcation analysis result reveals that the model exhibits backward bifurcation. We adopted Pontryagin’s maximum principle to determine the optimality system for the syphilis model, which was solved numerically to show that syphilis transmission can be optimally best control using a combination of condoms usage and treatment in the primary stage of infection in both infected male and female populations.
Existence results for a general class of sequential hybrid fractional differential equations
Authors: Khan Rahmat Ali , Gul Shaista , Jarad Fahd , Khan Hasib
Published: June 2021

In this paper, we study a class of nonlinear boundary value problems (BVPs) consisting of a more general class of sequential hybrid fractional differential equations (SHFDEs) together with a class of nonlinear boundary conditions at both end points of the domain. The nonlinear functions involved depend explicitly on the fractional derivatives. We study the necessary conditions required for the unique solution to the suggested BVP under the Caratheodory conditions using the technique of measure of noncompactness and degree theory. We also develop conditions for uniqueness results and also on stability analysis.
Caution is warranted when using animal space-use and movement to infer behavioral states
Authors: Buderman Frances E. , Gingery Tess M. , Diefenbach Duane R. , Gigliotti Laura C. , Begley-Miller Danielle , McDill Marc M. , Wallingford Bret D. , Rosenberry Christopher S. , Drohan Patrick J.
Published: June 2021

Background

Identifying the behavioral state for wild animals that can’t be directly observed is of growing interest to the ecological community. Advances in telemetry technology and statistical methodologies allow researchers to use space-use and movement metrics to infer the underlying, latent, behavioral state of an animal without direct observations. For example, researchers studying ungulate ecology have started using these methods to quantify behaviors related to mating strategies. However, little work has been done to determine if assumed behaviors inferred from movement and space-use patterns correspond to actual behaviors of individuals.

Methods

Using a dataset with male and female white-tailed deer location data, we evaluated the ability of these two methods to correctly identify male-female interaction events (MFIEs). We identified MFIEs using the proximity of their locations in space as indicators of when mating could have occurred. We then tested the ability of utilization distributions (UDs) and hidden Markov models (HMMs) rendered with single sex location data to identify these events.

Results

For white-tailed deer, male and female space-use and movement behavior did not vary consistently when with a potential mate. There was no evidence that a probability contour threshold based on UD volume applied to an individual’s UD could be used to identify MFIEs. Additionally, HMMs were unable to identify MFIEs, as single MFIEs were often split across multiple states and the primary state of each MFIE was not consistent across events.

Conclusions

Caution is warranted when interpreting behavioral insights rendered from statistical models applied to location data, particularly when there is no form of validation data. For these models to detect latent behaviors, the individual needs to exhibit a consistently different type of space-use and movement when engaged in the behavior. Unvalidated assumptions about that relationship may lead to incorrect inference about mating strategies or other behaviors.
A comparative case study of MTInSAR approaches for deformation monitoring of the cultural landscape of the Shanhaiguan section of the Great Wall
Authors: Xu Hang , Chen Fulong , Zhou Wei
Published: June 2021

The Great Wall of China is one of the largest architectural heritage sites globally, and its sustainability is a significant concern. However, its large extent and diverse characteristics are challenges for deformation monitoring. In this study, the Shanhaiguan section of the Great Wall was investigated in a case study to ascertain the damage and potential hazards of the architectural site. Two standard multi-temporal synthetic aperture radar interferometry (MTInSAR) technologies, including persistent scatterer SAR interferometry (PSInSAR) and small baseline subset (SBAS) SAR interferometry, were used for deformation monitoring using high-resolution TerraSAR-X data acquired in 2015–2017. The results of the two MTInSAR approaches reveal the health condition of the Great Wall. The Shanhaiguan section was stable, but local instabilities caused by rock falls were detected in some mountainous areas. In addition, the applicability of PSInSAR and SBAS was evaluated. The performance analysis of the two approaches indicated that a more reliable and adaptable MTInSAR technique needs to be developed for monitoring the Great Wall. This study demonstrates the potential of MTInSAR technology with high-resolution data for the health diagnosis of heritage sites with a linear structure, such as the Great Wall.
A simple, precise, and sensitive HPLC method for quantification of letrozole in rat plasma: development, validation, and preclinical pharmacokinetics
Authors: Hegde Aswathi R. , Padya Bharat Singh , Soman Soji , Mutalik Srinivas
Published: June 2021

A simple bioanalytical liquid chromatographic method was developed and validated to quantify letrozole (LTZ) in rat plasma. Protein precipitation using acidified chilled acetonitrile (containing 0.1% orthophosphoric acid) was used to extract LTZ from the plasma. Chromatographic separation was carried out on Kinetex C18 reverse phase (RP) column (250 mm × 4.6 mm i.d., 5 μm) using a mixture of 20 mM acetate buffer (pH 5.5) and acetonitirile (60:40 %v/v) eluting at 1.0 mL/min flow rate with the method responses measured at 240 nm. The optimized method was selective and established good linearity with recovery ranging between 91.16 and 99.44%. The validation experiments revealed that the method showed acceptable precision (2.61–7.48%) and accuracy (97.44–102.70%) and was found to be stable. The sensitivity of the method was demonstrated by the lowest concentration (LLOQ) detected at 75 ng/mL. Using the developed method, single-dose oral pharmacokinetics in Sprague-Dawley rats was carried out to successfully confirm the applicability of the method for the quantification of LTZ in biological matrix.
Identification and resolution of drug-related problems among diabetic patients attending a referral hospital: a prospective observational study
Authors: Sheleme Tadesse , Sahilu Tamiru , Feyissa Desalegn
Published: June 2021

Background

People living with diabetes are more vulnerable to drug-related problems due to the presence of multiple diseases. This study aimed to identify drug-related problems and contributing factors among diabetic patients.

Methods

This study used a prospective observational study design. The study was conducted among diabetic patients during follow-up at Mettu Karl Referral Hospital from 15 April to 09 August 2019. The consecutive sampling was utilized to collect data. The identification of drug-related problems was performed using the Pharmaceutical Care Network Europe version 8.03. Following data collection, data were entered into Epidata manager version 4.4.2 and exported to the SPSS version 24.0 for analysis. Multivariable logistic regression analysis was done to identify predictors of drug-related problems.

Results

A total of 330 people with diabetes were included in the study, among whom 279 (84.5%) had at least one drug-related problem. A total of 455 drug-related problems were identified. Effects of drug treatment not being optimal (52.7%) and untreated symptoms or indications (30.1%) were the most commonly identified drug-related problems. About 865 interventions were provided for identified drug-related problems and 79.8% was accepted. Diabetes duration$$\ge 7$$≥7 years [AOR = 2.02; 95% CI (1.06, 3.85);p = 0.033] and the presence of comorbidity [AOR: 2.33; 95% CI (1.18, 4.60);p = 0.015] were factors identified as predictors of drug-related problems.

Conclusion

The present study identified that drug-related problems are common among diabetic patients. Effects of drug treatment not being optimal and untreated symptoms or indications were the most commonly identified drug-related problems. Longer diabetes duration and the presence of comorbidities were predictors of drug-related problems.
Equity-Oriented Conceptual Framework for K-12 STEM literacy
Authors: Jackson Christa , Mohr-Schroeder Margaret J. , Bush Sarah B. , Maiorca Cathrine , Roberts Thomas , Yost Caitlyn , Fowler Abigail
Published: June 2021

We introduce a conceptual framework of K-12 STEM literacy that rightfully and intentionally positions each and every student, particularly minoritized groups, as belonging in STEM. In order to conceptualize the equity-based framework of STEM literacy, we conducted a systematic review of literature related to STEM literacy, which includes empirical studies that contribute to STEM literacy. The literature on the siloed literacies within STEM (i.e., science, technology, engineering, and mathematics literacy) also contributed to formulate the necessity of and what it means to develop STEM literacy. The Equity-Oriented STEM Literacy Framework illuminates the complexities of disrupting the status quo and rightfully transforming integrated STEM education in ways that provide equitable opportunities and access to all learners. The Equity-Oriented STEM Literacy Framework is a research-based, equity and access-focused framework that will guide research, inform practice, and provide a lens for the field that will ensure each and every student, especially minoritized students, develop, and are developing STEM literacy.
Relationships between motor scores and cognitive functioning in FMR1 female premutation X carriers indicate early involvement of cerebello-cerebral pathways
Authors: Storey Elsdon , Bui Minh Q. , Stimpson Paige , Tassone Flora , Atkinson Anna , Loesch Danuta Z.
Published: June 2021

Background

Smaller expansions of CGG trinucleotide repeats in theFMR1X-linked gene termed ‘premutation’ lead to a neurodegenerative disorder: Fragile X Associated Tremor/Ataxia Syndrome (FXTAS) in nearly half of aged carrier males, and 8–16% females. Core features include intention tremor, ataxia, and cognitive decline, and white matter lesions especially in cerebellar and periventricular locations. A ‘toxic’ role of elevated and expandedFMR1mRNA has been linked to the pathogenesis of this disorder. The emerging issue concerns the trajectory of the neurodegenerative changes: is the pathogenetic effect confined to overt clinical manifestations? Here we explore the relationships between motor and cognitive scale scores in a sample of 57 asymptomatic adult female premutation carriers of broad age range.

Methods

Three motor scale scores (ICARS-for tremor/ataxia, UPDRS-for parkinsonism, and Clinical Tremor) were related to 11 cognitive tests using Spearman’s rank correlations. Robust regression, applied in relationships between all phenotypic measures, and genetic molecular and demographic data, identified age and educational levels as common correlates of these measures, which were then incorporated as confounders in correlation analysis.

Results

Cognitive tests demonstrating significant correlations with motor scores were those assessing non-verbal reasoning on Matrix Reasoning (p-values from 0.006 to 0.011), and sequencing and alteration on Trails-B (p-values from 0.008 to 0.001). Those showing significant correlations with two motor scores-ICARS and Clinical Tremor- were psychomotor speed on Symbol Digit Modalities (p-values from 0.014 to 0.02) and working memory on Digit Span Backwards (p-values from 0.024 to 0.011).

Conclusions

Subtle motor impairments correlating with cognitive, particularly executive, deficits may occur in female premutation carriers not meeting diagnostic criteria for FXTAS. This pattern of cognitive deficits is consistent with those seen in other cerebellar disorders. Our results provide evidence that more than one category of clinical manifestation reflecting cerebellar changes – motor and cognitive - may be simultaneously affected by premutation carriage across a broad age range in asymptomatic carriers.
Variation for caffeic acid and phenolic content in different plant parts of Solanum xanthocarpum Schrad. and Wendl. – a commercially important dashmool species
Authors: Saxena Hari Om , Parihar Samiksha , Mohammad Naseer , Pawar Ganesh
Published: June 2021

Background

Environmental factors have profound effect on quantity vis-a-vis quality of phytochemicals in medicinal plants.Solanum xanthocarpumSchrad. and Wendl. is among the 10 dashmool species which is utilized in more than hundreds of Ayurvedic preparations including ‘Dashmoolarishta’. Phenolics are the pharmacologically valuable compounds. Therefore, the present study was undertaken to assess the total phenolic (TP) and Caffeic acid (CA) contents in four different plant parts i.e., leaves, fruits, stem and roots ofS. xanthocarpumsampled randomly from different locations of Madhya Pradesh, a central Indian state.

Methods

Plant samples were collected from 99 places of 29 districts falling in 11 agroclimatic regions of Madhya Pradesh through random sampling. UV-VIS spectrophotometer and HPTLC were used to determine TP and CA contents, respectively. Phytochemical screening was carried out using standard methods.

Results

Preliminary phytochemical screening indicates the presence of alkaloids, cardiac glycosides, flavonoids, phenols, steroids and terpenoids in all plant parts. Quantification of TP and CA contents revealed that both varied significantly between agroclimatic zones as well as within plant parts ofS. xanthocarpum. Results revealed that among analysed plant parts, roots and stem harbored highest content of CA while fruits and leaves had the highest TP content. Among agroclimatic regions, accessions of Satpura plateau can be considered rich in CA and TP contents for fruits (0.030%; 28.70 mg CE/g), leaves (0.058%; 27.90 mg CE/g) and roots (0.161%; 5.17 mg CE/g). For stem, highest CA (0.100%) and TP (13.23 mg CE/g) contents were observed in samples of Malwa Plateau and Central Narmada Valley, respectively.

Conclusion

We conclude that agroclimatic regions have significant effect on studied phytochemicals and Satpura plateau agroclimatic zone may be targeted for conservation and sustainable utilization of this valuable dashmool species if the target plant parts are fruits, leaves and roots. While, Malwa Plateau and Central Narmada Valley zones may be targeted for stem. Further, fruits and roots may be utilized for extraction of TP compounds and CA respectively.
Perioperative management of a patient undergoing resection of interleukin-6 producing pheochromocytoma
Authors: Kuroki Masahiro , Suzuki Hiroto , Kurota Misato , Nakane Masaki , Kawamae Kaneyuki
Published: June 2021

Background

Pheochromocytomas produce hormones, cytokines, and catecholamines. We report perioperative anesthetic management of a rare interleukin-6 (IL-6)-producing pheochromocytoma.

Case presentation

A 32-year-old female was scheduled for laparoscopic adrenalectomy for pheochromocytoma. She had a sustained high fever with elevated serum noradrenaline and IL-6 levels. The persistent high inflammatory state, followed by anemia, malnutrition, and coagulopathy, led us to prepone her date of surgery. During general anesthesia, alpha-blockers allowed hemodynamic fluctuations to be controlled. During surgery, simultaneous increases in noradrenaline and IL-6 levels were observed, which rapidly declined after tumor removal. Her postoperative course was uneventful, without pulmonary edema caused by cytokine storms.

Conclusions

The conventional pheochromocytoma strategy allowed surgical removal of an IL-6-producing pheochromocytoma under general anesthesia. However, management of high inflammatory states that induce anemia and coagulopathy is necessary.
Diffuse leptomeningeal glioneuronal tumor with high-grade features masquerading as tubercular meningitis—a case report
Authors: Peer Sameer , Murumkar Vivek , Kulanthaivelu Karthik , Prasad Chandrajit , Rao Shilpa , Santosh Vani
Published: June 2021

Background

Diffuse leptomeningeal glioneuronal tumor (DLGNT) has been recently described in the literature. The complete neuroimaging spectrum and histopathological characteristics of this entity are yet to be elucidated. In an endemic region, diffuse leptomeningeal enhancement on neuroimaging with associated communicating hydrocephalus is usually suggestive of infective meningitis and the patients are started on empirical anti-microbial therapy. However, it is important to consider other differential diagnosis of leptomeningeal enhancement in such cases, particularly if the clinical condition does not improve on anti-microbial therapy. An early diagnosis of a neoplastic etiology may be of particular importance as the treatment regimens vary considerably depending on the underlying disease condition.

Case presentation

In this case report, we describe a case of DLGNT with high-grade histopathological features which was initially managed as tubercular meningitis based on the initial neuroimaging findings. Due to worsening of the clinical course and subsequent imaging findings at follow-up, a diagnosis of DLGNT was considered and subsequently proven to be DLGNT with features of anaplasia on histopathological examination of leptomeningeal biopsy specimen.

Conclusion

This case highlights the importance of recognizing certain subtle finding on MRI which may help in an early diagnosis of DLGNT which is crucial for appropriate treatment.
Detecting COVID-19 in chest images based on deep transfer learning and machine learning algorithms
Authors: Rezaeijo Seyed Masoud , Ghorvei Mohammadreza , Abedi-Firouzjah Razzagh , Mojtahedi Hesam , Entezari Zarch Hossein
Published: June 2021

Background

This study aimed to propose an automatic prediction of COVID-19 disease using chest CT images based on deep transfer learning models and machine learning (ML) algorithms.

Results

The dataset consisted of 5480 samples in two classes, including 2740 CT chest images of patients with confirmed COVID-19 and 2740 images of suspected cases was assessed. The DenseNet201 model has obtained the highest training with an accuracy of 100%. In combining pre-trained models with ML algorithms, the DenseNet201 model and KNN algorithm have received the best performance with an accuracy of 100%. Created map by t-SNE in the DenseNet201 model showed not any points clustered with the wrong class.

Conclusions

The mentioned models can be used in remote places, in low- and middle-income countries, and laboratory equipment with limited resources to overcome a shortage of radiologists.
Frequency and Prognostic Impact of ALK Amplifications and Mutations in the European Neuroblastoma Study Group (SIOPEN) High-Risk Neuroblastoma Trial (HR-NBL1)
Authors: Bellini Angela , Pötschger Ulrike , Bernard Virginie , Lapouble Eve , Baulande Sylvain , Ambros Peter F. , Auger Nathalie , Beiske Klaus , Bernkopf Marie , Betts David R. , Bhalshankar Jaydutt , Bown Nick , de Preter Katleen , Clément Nathalie , Combaret Valérie , Font de Mora Jaime , George Sally L. , Jiménez Irene , Jeison Marta , Marques Barbara , Martinsson Tommy , Mazzocco Katia , Morini Martina , Mühlethaler-Mottet Annick , Noguera Rosa , Pierron Gaelle , Rossing Maria , Taschner-Mandl Sabine , Van Roy Nadine , Vicha Ales , Chesler Louis , Balwierz Walentyna , Castel Victoria , Elliott Martin , Kogner Per , Laureys Geneviève , Luksch Roberto , Malis Josef , Popovic-Beck Maja , Ash Shifra , Delattre Olivier , Valteau-Couanet Dominique , Tweddle Deborah A. , Ladenstein Ruth , Schleiermacher Gudrun
Published: June 2021

PURPOSE

In neuroblastoma (NB), the ALK receptor tyrosine kinase can be constitutively activated through activating point mutations or genomic amplification. We studied ALK genetic alterations in high-risk (HR) patients on the HR-NBL1/SIOPEN trial to determine their frequency, correlation with clinical parameters, and prognostic impact.

MATERIALS AND METHODS

Diagnostic tumor samples were available from 1,092 HR-NBL1/SIOPEN patients to determine ALK amplification status (n = 330), ALK mutational profile (n = 191), or both (n = 571).

RESULTS

Genomic ALK amplification ( ALKa) was detected in 4.5% of cases (41 out of 901), all except one with MYCN amplification (MNA). ALKa was associated with a significantly poorer overall survival (OS) (5-year OS: ALKa [n = 41] 28% [95% CI, 15 to 42]; no- ALKa [n = 860] 51% [95% CI, 47 to 54], [ P < .001]), particularly in cases with metastatic disease. ALK mutations ( ALKm) were detected at a clonal level (> 20% mutated allele fraction) in 10% of cases (76 out of 762) and at a subclonal level (mutated allele fraction 0.1%-20%) in 3.9% of patients (30 out of 762), with a strong correlation between the presence of ALKm and MNA ( P < .001). Among 571 cases with known ALKa and ALKm status, a statistically significant difference in OS was observed between cases with ALKa or clonal ALKm versus subclonal ALKm or no ALK alterations (5-year OS: ALKa [n = 19], 26% [95% CI, 10 to 47], clonal ALKm [n = 65] 33% [95% CI, 21 to 44], subclonal ALKm (n = 22) 48% [95% CI, 26 to 67], and no alteration [n = 465], 51% [95% CI, 46 to 55], respectively; P = .001). Importantly, in a multivariate model, involvement of more than one metastatic compartment (hazard ratio [HR], 2.87; P < .001), ALKa (HR, 2.38; P = .004), and clonal ALKm (HR, 1.77; P = .001) were independent predictors of poor outcome.

CONCLUSION

Genetic alterations of ALK (clonal mutations and amplifications) in HR-NB are independent predictors of poorer survival. These data provide a rationale for integration of ALK inhibitors in upfront treatment of HR-NB with ALK alterations.