bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemically defined and small molecules-based generation of sinoatrial node-like cells
Authors: Hou Xiaojie , Ma Shuhong , Fan Wei , Li Fang , Xu Miaomiao , Yang Chao , Liu Feng , Yan Ying , Wan Juyi , Lan Feng , Liao Bin 
Published: April 2022

Abstract
Background
Existing methods for in vitro differentiation of human pluripotent stem cells (hPSCs) into sinoatrial node-like cells (SANLCs) require complex and undefined medium constituents. This might hinder the elucidation of the molecular mechanisms involved in cardiac subtype specification and prevent translational application. In our study, we aimed to establish a chemically defined differentiation methods to generate SANLCs effectively and stably.

Methods
We induced human embryonic stem cells (hESCs)/induced PSCs (hiPSCs) to pan-cardiomyocytes by temporal modulation of the WNT/β-catenin (WNT) signaling pathway with GSK3 inhibitor and WNT inhibitor. During cardiac mesoderm stage of the differentiation process, signaling of WNT, retinoid acid (RA), and fibroblast growth factor (FGF) was manipulated by three specific molecules. Moreover, metabolic selection was designed to improve the enrichment of SANLCs. Finally, RT-PCR, immunofluorescence, flow cytometry, and whole cell patch clamp were used to identify the SANLCs.

Results
WNT, RA, and FGF signaling promote the differentiation of hPSCs into SANLCs in a concentration- and time window-sensitive manner, respectively. Synergetic modulation of WNT, FGF, and RA signaling pathways enhance the pacemaker phenotype and improve the differentiation efficiency of SANLCs (up to 45%). Moreover, the purification based on lactate metabolism and glucose starvation further reached approximately 50% of SANLCs. Finally, the electrophysiological data demonstrate that cells differentiated with the proposed protocol produce a considerable number of SANLCs that display typical electrophysiological characteristics of pacemaker cells in vitro.

Conclusion
We provide an optimized and chemically defined protocol to generate SANLCs by combined modulation of WNT, RA, and FGF signaling pathways and metabolic selection by lactate enrichment and glucose starvation. This chemically defined method for generating SANLCs might provide a platform for disease modeling, drug discovery, predictive toxicology, and biological pacemaker construction.
Obesogenic and diabetic effects of CD44 in mice are sexually dimorphic and dependent on genetic background
Authors: VerHague Melissa , Albright Jody , Barron Keri , Kim Myungsuk , Bennett Brian J. 
Published: April 2022

AbstractIntroductionCD44 is a candidate gene for obesity and diabetes development and may be a critical mediator of a systemic inflammation associated with obesity and diabetes.MethodsWe investigated the relationship of CD44 with obesity in CD44-deficient mice challenged with a high-fat diet.ResultsIn mice fed a diet high in fat, cholesterol, and sucrose for 12 weeks fat mass accumulation was reduced in CD44-deficient mice bred onto both a C57BL/6J and the naturally TLR deficient C3H/HeJ background. Reduced fat mass could not be attributed to lower food intake or an increase in energy expenditure as measured by indirect calorimetry. However, we observed a 40–60% lower mRNA expression of the inflammation markers, F4/80, CD11b, TNF-α, and CD14, in adipose tissue of CD44-deficient mice on the C57BL/6J background but not the C3H/HeJ background, perhaps indicating that alternative factors may be affecting adiposity in this model. Measures of hepatic steatosis and insulin sensitivity were improved in CD44-deficient mice on a C57BL/6J but not in the C3H/HeJ mice. These results were highly sexually dimorphic as there were no detectable effects of CD44 inactivation in female mice on a C57BL/6 J or C3H/HeJ background.ConclusionCD44 was associated with adiposity, liver fat, and glucose in male mice. However, the effects of CD44 on obesity may be independent of TLR4 signaling.
Comparison of absorbed dose extrapolation methods for mouse-to-human translation of radiolabelled macromolecules
Authors: Cicone Francesco , Viertl David , Denoël Thibaut , Stabin Michael G. , Prior John O. , Gnesin Silvano 
Published: April 2022

Abstract
Background
Extrapolation of human absorbed doses (ADs) from biodistribution experiments on laboratory animals is used to predict the efficacy and toxicity profiles of new radiopharmaceuticals. Comparative studies between available animal-to-human dosimetry extrapolation methods are missing. We compared five computational methods for mice-to-human AD extrapolations, using two different radiopharmaceuticals, namely [111In]CHX-DTPA-scFv78-Fc and [68Ga]NODAGA-RGDyK. Human organ-specific time-integrated activity coefficients (TIACs) were derived from biodistribution studies previously conducted in our centre. The five computational methods adopted are based on simple direct application of mice TIACs to human organs (M1), relative mass scaling (M2), metabolic time scaling (M3), combined mass and time scaling (M4), and organ-specific allometric scaling (M5), respectively. For [68Ga]NODAGA-RGDyK, these methods for mice-to-human extrapolations were tested against the ADs obtained on patients, previously published by our group. Lastly, an average [68Ga]NODAGA-RGDyK-specific allometric parameter αnew was calculated from the organ-specific biological half-lives in mouse and humans and retrospectively applied to M3 and M4 to assess differences in human AD predictions with the α = 0.25 recommended by previous studies.

Results
For both radiopharmaceuticals, the five extrapolation methods showed significantly different AD results (p < 0.0001). In general, organ ADs obtained with M3 were higher than those obtained with the other methods. For [68Ga]NODAGA-RGDyK, no significant differences were found between ADs calculated with M3 and those obtained directly on human subjects (H) (p = 0.99; average M3/H AD ratio = 1.03). All other methods for dose extrapolations resulted in ADs significantly different from those calculated directly on humans (all p ≤ 0.0001). Organ-specific allometric parameters calculated using combined experimental [68Ga]NODAGA-RGDyK mice and human biodistribution data varied significantly. ADs calculated with M3 and M4 after the application of αnew = 0.17 were significantly different from those obtained by the application of α = 0.25 (both p < 0.001).

Conclusions
Available methods for mouse-to-human dosimetry extrapolations provided significantly different results in two different experimental models. For [68Ga]NODAGA-RGDyK, the best approximation of human dosimetry was shown by M3, applying a metabolic scaling to the mouse organ TIACs. The accuracy of more refined extrapolation algorithms adopting model-specific metabolic scaling parameters should be further investigated.
Cardiovascular drug shortages in Lebanon: a broken heart
Authors: Khattar Georges , Hallit Jennifer , El Chamieh Carolla , Bou Sanayeh Elie 
Published: April 2022

AbstractFor nearly 3 years now, Lebanon has been assailed by compounded crises. With the economic instability, the coronavirus pandemic, and the explosion of the Beirut Port on August 4, 2020; the fragile Lebanese healthcare system has found itself at massive risk of a catastrophic public health crisis secondary to cardiovascular drug shortages. The time has come for public health authorities to find urgent solutions for this national trajedy that is projected to last for years.
Antimicrobial resistance and one health in the post COVID-19 era: What should health students learn?
Authors: Elmahi Osman Kamal Osman , Uakkas Saad , Olalekan Babatunde Yusuf , Damilola Ibrahim Abdulmumin , Adedeji Oluwakorede Joshua , Hasan Mohammad Mehedi , dos Santos Costa Ana Carla , Ahmad Shoaib , Essar Mohammad Yasir , Thomson Deborah Janine 
Published: April 2022

AbstractAntimicrobial resistance (AMR) is a critical worldwide health issue that jeopardizes our ability to fight illnesses. However, despite being a natural phenomenon, AMR is exacerbated in the world by inappropriate administration of an antimicrobial medication such as under-use or overuse by the general population, farmers, and various health professionals. The onset of the COVID-19 pandemic has put the world in a shocking state. The pandemic exacerbated the problem of antimicrobial resistance, which was largely caused by irrational off-label use of antivirals, anthelmintics, antimalarials, and, most notably, macrolide antibiotics. As a result, monitoring the AMR progression during the pandemic has been critical. The One Health Approach is progressively becoming the most widely utilized and recommended approach in the ongoing fight against AMR. The aim of this article is to address the lack of teachings in AMR and the One Health Approach in health student training curricula, as well as to provide recommendations that can be implemented as we progress beyond the COVID-19 era.
Body-size dependent foraging strategies in the Christmas Island flying-fox: implications for seed and pollen dispersal within a threatened island ecosystem
Authors: Todd Christopher M. , Westcott David A. , Martin John M. , Rose Karrie , McKeown Adam , Hall Jane , Welbergen Justin A. 
Published: April 2022

Abstract
Background
Animals are important vectors for the dispersal of a wide variety of plant species, and thus play a key role in maintaining the health and biodiversity of natural ecosystems. On oceanic islands, flying-foxes are often the only seed dispersers or pollinators. However, many flying-fox populations are currently in decline, particularly those of insular species, and this has consequences for the ecological services they provide. Knowledge of the drivers and the scale of flying-fox movements is important in determining the ecological roles that flying-foxes play on islands. This information is also useful for understanding the potential long-term consequences for forest dynamics resulting from population declines or extinction, and so can aid in the development of evidence-based ecological management strategies. To these ends, we examined the foraging movements, floral resource use, and social interactions of the Critically Endangered Christmas Island flying-fox (Pteropus natalis).

Methods
Utilization distributions, using movement-based kernel estimates (MBKE) were generated to determine nightly foraging movements of GPS-tracked P. natalis (n = 24). Generalized linear models (GLMs), linear mixed-effect models (LMMs), and Generalized linear mixed-effects model (GLMMs) were constructed to explain how intrinsic factors (body mass, skeletal size, and sex) affected the extent of foraging movements. In addition, we identified pollen collected from facial and body swabs of P. natalis (n = 216) to determine foraging resource use. Direct observations (n = 272) of foraging P. natalis enabled us to assess the various behaviors used to defend foraging resources.

Results
Larger P. natalis individuals spent more time foraging and less time traveling between foraging patches, traveled shorter nightly distances, and had smaller overall foraging ranges than smaller conspecifics. Additionally, larger individuals visited a lower diversity of floral resources.

Conclusions
Our findings suggest that smaller P. natalis individuals are the primary vectors of long-distance dispersal of pollen and digested seeds in this species, providing a vital mechanism for maintaining the flow of plant genetic diversity across Christmas Island. Overall, our study highlights the need for more holistic research approaches that incorporate population demographics when assessing a species’ ecological services.
Detection of astrocytic tau pathology facilitates recognition of chronic traumatic encephalopathy neuropathologic change
Authors: Ameen-Ali Kamar E. , Bretzin Abigail , Lee Edward B. , Folkerth Rebecca , Hazrati Lili-Naz , Iacono Diego , Keene C. Dirk , Kofler Julia , Kovacs Gabor G. , Nolan Amber , Perl Daniel P. , Priemer David S. , Smith Douglas H. , Wiebe Douglas J. , Stewart William ,   CONNECT-TBI Investigators, Al-Sarraj Safa , Cortes Etty , Crary John , Dams-O’Connor Kristin , Diaz-Arrastia Ramon , Dollé Jean-Pierre , Edlow Brian , Fischl Bruce , Hinds Col. Sidney , Johnson Victoria E. , Manley Geoffrey , Meaney David , Okonkwo David , Schneider Andrea L. C. , Schneider Julie , Troakes Claire , Trojanowski John Q. , van der Kouwe Andre , Yaffe Kristine 
Published: April 2022

AbstractTraumatic brain injury (TBI) is associated with the development of a range of neurodegenerative pathologies, including chronic traumatic encephalopathy (CTE). Current consensus diagnostic criteria define the pathognomonic cortical lesion of CTE neuropathologic change (CTE-NC) as a patchy deposition of hyperphosphorylated tau in neurons, with or without glial tau in thorn-shaped astrocytes, typically towards the depths of sulci and clustered around small blood vessels. Nevertheless, although incorporated into consensus diagnostic criteria, the contribution of the individual cellular components to identification of CTE-NC has not been formally evaluated. To address this, from the Glasgow TBI Archive, cortical tissue blocks were selected from consecutive brain donations from contact sports athletes in which there was known to be either CTE-NC (n = 12) or Alzheimer’s disease neuropathologic change (n = 4). From these tissue blocks, adjacent tissue sections were stained for tau antibodies selected to reveal either solely neuronal pathology (3R tau; GT-38) or mixed neuronal and astroglial pathologies (4R tau; PHF-1). These stained sections were then randomised and independently assessed by a panel of expert neuropathologists, blind to patient clinical history and primary antibody applied to each section, who were asked to record whether CTE-NC was present. Results demonstrate that, in sections stained for either 4R tau or PHF-1, consensus recognition of CTE-NC was high. In contrast, recognition of CTE-NC in sections stained for 3R tau or GT-38 was poor; in the former no better than chance. Our observations demonstrate that the presence of both neuronal and astroglial tau pathologies facilitates detection of CTE-NC, with its detection less consistent when neuronal tau pathology alone is visible. The combination of both glial and neuronal pathologies, therefore, may be required for detection of CTE-NC.
Effects of academic achievement and group composition on the quality of student-generated questions and online procedural prompt usage patterns
Authors: Yu Fu-Yun , Cheng Wen-Wen 
Published: April 2022

AbstractThis study aims to examine if and how academic achievement and gender group composition affect the quality of online SGQ and the use patterns of procedural prompts provided to support SGQ activities. Forty-one university sophomores enrolled in an English as a foreign language class participated in a four-week study. All questions generated were categorized based on the revised Bloom’s taxonomy for quality evaluation, and a content analysis along the set of integrated online procedural prompts was conducted to reveal usage patterns. Five key findings were obtained: First, the provision of the online procedural prompts served as an efficacious learning scaffold to help the participants at both high- and low-academic achievement levels generate the most questions at high-cognitive levels. Second, based on the results of the Fisher’s exact test, no significant relationships were found between academic achievement and the quality of SGQ. Third, the participants in the all-male and mixed-gender groups generated the majority of their questions at high-cognitive levels, whereas the all-female group generated an equal number of questions at both low- and high-cognitive levels. Fourth, no significant relationships between the gender group composition and the quality of SGQ were found according to the chi-square test of independence. Fifth, the results of the content analysis revealed that while some same usage patterns related to online procedural prompts were exhibited by students at both low- and high-academic achievement levels and with different gender group compositions, slightly different usage patterns were observed.
Technology facilitated sexual violence: a comparative study between working and non-working females in Egypt before and during the COVID-19 pandemic
Authors: Zagloul Nancy M. , Farghaly Rasha M. , ELKhatib Hossam , Issa Sahar Y. , El-Zoghby Safaa M. 
Published: April 2022

Abstract
Background
During the COVID-19 pandemic, quarantine measures policies increased Internet usage, leading to technological hazards as technology facilitated sexual violence (TFSV).

Aim
The current work aimed to assess TFSV among working and non-working Egyptian females before and during COVID-19.

Methods
The current work is a cross-sectional observational comparative study using an anonymous online questionnaire distributed through social platforms among working and non-working Egyptian females.

Results
TFSV was reported by 50.3% of the participants; however, regarding some forms of digital sexual violence, there was a significant decrease during COVID-19 lockdown than before it, considering; threatened creation form (7.8%, 12.0%; p = 0.017); non-consensual pornography (31.4%, 51.9%; p < 0.001) and online sexual harassment and cyber-stalking types (80.9%, 89.4%; p < 0.001). Only 17.3% of the study participants knew the identity of the perpetrator. TFSV led 6.4% to abstain from social media, and 3.9% reported the incident to a law agency.

Conclusions
The current study revealed that almost half of women experienced TFSV. Although time spent on the Internet by the whole participants during the pandemic was significantly higher than before, there was a significant decrease in some types of TFSV. The current study revealed that divorced females working in non-governmental sectors experienced harassment more significantly than others. There is crucial importance to set laws and penalties against perpetrators of TFSV to provide a safe technological environment for women.
A mobile battery-powered brain perfusion ultrasound (BPU) device designed for prehospital stroke diagnosis: correlation to perfusion MRI in healthy volunteers
Authors: Kilic Mustafa , Scalzo Fabien , Lyle Chandler , Baldaranov Dobri , Dirnbacher Maximilian , Honda Tristan , Liebeskind David S. , Schlachetzki Felix 
Published: April 2022

Abstract
Background
Early prehospital stroke identification is crucial for goal directed hospital admission especially in rural areas. However, clinical prehospital stroke scales are designed to identify any stroke but cannot sufficiently differentiate hemorrhagic from ischemic stroke, including large vessel occlusion (LVO) amenable to mechanical thrombectomy. We report on a novel small, portable and battery driven point-of-care ultrasound system (SONAS®) specifically developed for mobile non-invasive brain perfusion ultrasound (BPU) measurement after bolus injection of an echo-enhancing agent suitable for the use in prehospital stroke diagnosis filling a current, unmet and critical need for LVO identification.

Methods
In a phase I study of healthy volunteers we performed comparative perfusion-weighted magnetic resonance imaging (PWI) and BPU measurements, including safety analysis.

Results
Twelve volunteers (n = 7 females, n = 5 males, age ranging between 19 and 55 years) tolerated the measurement extremely well including analysis of blood–brain barrier integrity, and the correlation coefficient between the generated time kinetic curves after contrast agent bolus between PWI and BPU transducers ranged between 0.89 and 0.76.

Conclusions
Mobile BPU using the SONAS® device is feasible and safe with results comparable to PWI. When applied in conjunction with prehospital stroke scales this may lead to a more accurate stroke diagnosis and patients bypassing regular stroke units to comprehensive stroke centers. Further studies are needed in acute stroke patients and in the prehospital phase including assessment of immediate and long-term morbidity and mortality in stroke.
Trial registration: Clinical trials.gov, registered 28.Sep.2017, Identifier: NCT03296852.
Analysis of microstructural characteristics and components of red and yellow ink pigments used in permanent makeup
Authors: Jin Hyun Sook , Chang Byung Soo 
Published: April 2022

AbstractOur purpose in this study is to analyze the microstructural characteristics and constituent elements of inorganic substances added to the yellow ink and red ink pigments used in permanent makeup. We observed the microstructural properties of inorganic pigments added to the ink using a scanning electron microscopy (SEM) and analyzed the constituent elements of the inorganic pigment particles using an energy dispersive X-ray spectroscopy (EDX). In red wine-colored ink, cubic titanium dioxide with a diameter of 110 to 200 nm was the major component, and rod-shaped iron oxide was rarely observed. Most of the ingredients of taupe yellow ink were rod-shaped yellow iron oxide, and a small amount of cubic titanium dioxide was observed. Red wine-colored ink and taupe yellow ink contained lumps composed of titanium dioxide particles. In red wine-colored ink, lumps were formed by agglomeration. However, we observed that the surface of the lump composed of titanium dioxide in the taupe yellow ink had a smooth surface caused by external physical compression. The titanium dioxide particle mass which found in taupe yellow ink in this study is an artificial product. When this mass accumulates in the dermis, it may cause a color mismatch. Therefore, permanent makeup using fine pigments should be free of foreign substances that may cause trouble in the skin. In addition, there is a need to improve the quality of the ink so that the required color can be safe and long lasting in the dermis.
Maulana and sekanjabin (oxymel): a ceremonial relationship with gastronomic and health perspectives
Authors: Orhan Halil İbrahim , Yılmaz İlkay , Tekiner İsmail Hakkı 
Published: April 2022

AbstractSekanjabin, also known as Oxymel, is an ancient beverage including honey, fermented vinegar, water, and various fruits and herbs. Great physicians Hippocrates, Galen, and Avicenna recommended treating gastrointestinal disorders, pain, asthma, thoracic, cough, sore throat, foul, and breath. Furthermore, Maulana, a symbol of tolerance that is humanism-flexible and non-violent, frequently mentions this beverage in his great masterpieces “Divan-ı Kebir” and “Masnavi.” Therefore, it can be evaluated as an intangible cultural heritage of Western and near Asian civilizations and has a significant and ceremonial role in Maulana and Maulawi Culture. From a gastronomic and health perspective, this study explored the ceremonial relationship between Maulana and sekanjabin.
Prenatal diagnosis of accessory mitral valve tissue in a fetus with persistent dysrhythmia
Authors: Hematian Mohammad Nasir , Torabi Shirin , Hantoushzadeh Sedigheh , Dehestani Alireza , Dadkhah Minoo , Shabanian Reza 
Published: April 2022

Abstract
Background
Accessory mitral valve tissue (AMVT) is a rare congenital cardiac anomaly that mainly diagnosed in the first decade of life. However, asymptomatic cases may not be diagnosed even up to adulthood. We report a fetus with AMVT to show the diagnostic ability of the fetal echocardiography for detection of this pathology in the prenatal period.

Case presentation
AMVT was diagnosed in a 26-week-old male fetus with persistent dysrhythmia. Dysrhythmia could not be aborted and controlled by sotalol till the third trimester evaluation. Apical left ventricular (LV) diverticulum was the additional finding in his fetal echocardiogram. After birth, he was in sinus rhythm and echocardiography confirmed the presence of AMVT, however, without any evidence of LV apical diverticulum.

Conclusions
The diagnosis of AMVT in the prenatal period is possible by fetal echocardiography.