bluuebunny/crossref_metadata_2025_split huggingface dataset:
TGF-β-R2 is required for HBP induced acute lung injury and vascular leakage for TGF-β/Smad/Rho signaling pathway activation
Authors: Liu Zixuan , Chen Mingming , Sun Yini , Li Xu , Cao Liu , Ma Xiaochun 
Published: January 2022

AbstractHeparin-binding protein (HBP), as a granule protein secreted by polymorphonuclear neutrophils (PMNs) participates in the pathophysiological process of sepsis. It has been reported that HBP is a biomarker of sepsis, which is related to the severity of septic shock and organ dysfunction. HBP binds to vascular endothelial cells as one of the primary target sites. However, it is still unclear whether HBP-binding protein receptors exist on the surface of ECs. The effect of HBP on vascular permeability in sepsis and its mechanism needs to be explored. We conducted in vivo and in vitro study. We demonstrated that HBP bound to transforming growth factor-β receptor type 2 (TGF-β-R2) as a ligand. GST pull-down analysis reveals that HBP mainly interacts with the extracellular domain of TGF-β-R2. HBP induced acute lung injury (ALI) and vascular leakage via activation of TGF-β/SMAD2/3 signaling pathway. Permeability assay suggests TGF-β-R2 is necessary for HBP-induced increased permeability. We also defined the role of HBP and its potential membrane receptor TGF-β-R2 in the blood-gas barrier in the pathogenesis of HBP-related ALI.
PRACTICE OF EARLY BREASTFEEDING INITIATION ON PRIMIGRAVIDA WITH A CULTURAL PERSPECTIVE: A SYSTEMATIC REVIEW
Authors: Dewi Tarini Ni Wayan , Rumambo Pandin Moses Glorino 
Published: January 2022

ABSTRACTOne of the health aspects in the development process is the development of human resource potential (HR). What plays a role in this potential of human resources is good nutritional status from an early age. In addition to these factors, the quality of human resource formation is also influenced by the environment that shapes human character. namely the socio-cultural environment (Soekirman, 2005). One of the cultural interactions that affect nutritional status as a condition for the formation of quality human resources is the practice of breastfeeding and the practice of early breastfeeding initiation (IMD). There have been many previous studies that have written that there are still many mothers who do not practice IMD, where one of the reasons mentioned is the belief that the first milk that comes out is dirty and unhealthy, so it is not suitable to be given to babies (Roesli, 2008). The purpose of this literature study is to determine the influence of culture in the practice of early breastfeeding initiation.The articles used in the literature review were obtained through databases of international journal providers such as Proquest, Google Scholar and Science Direct. The journal was taken from 2019 to 2021. Researchers used keywords, namely transcultural nursing, breastfeeding (according to MESH/Medical Subject Heading) and 20 articles were analyzed using PRISMA diagrams. The analysis found that most mothers did not practice early breastfeeding because of certain beliefs about early breastfeeding, such as early breastfeeding was not as good as exclusive breastfeeding, dirty early breast milk, unhealthy early breastfeeding given to babies and the habit of mothers who immediately gave additional food immediately. after the baby is born.
Modulating CRISPR-Cas genome editing using guide-complementary DNA oligonucleotides
Authors: Swartjes Thomas , Shang Peng , van den Berg Dennis , Künne Tim A. , Geijsen Niels , Brouns Stan J.J. , van der Oost John , Staals Raymond H.J. , Notebaart Richard A. 
Published: January 2022

AbstractCRISPR-Cas has revolutionized genome editing and has a great potential for applications, such as correcting human genetic disorders. To increase the safety of genome editing applications, CRISPR-Cas may benefit from strict control over Cas enzyme activity. Previously, anti-CRISPR proteins and designed oligonucleotides have been proposed to modulate CRISPR-Cas activity. Here we report on the potential of guide-complementary DNA oligonucleotides as controlled inhibitors of Cas9 ribonucleoprotein complexes. First, we show that DNA oligonucleotides down-regulate Cas9 activity in human cells, reducing both on and off-target cleavage. We then used in vitro assays to better understand how inhibition is achieved and under which conditions. Two factors were found to be important for robust inhibition: the length of the complementary region, and the presence of a PAM-loop on the inhibitor. We conclude that DNA oligonucleotides can be used to effectively inhibit Cas9 activity both ex vivo and in vitro.
Nature and Trends of Pharmaceutical Payments to the Board Certified Respiratory Specialists in Japan between 2016 and 2019
Authors: Murayama Anju , Hoshi Momoko , Saito Hiroaki , Kamamoto Sae , Tanaka Manato , Kawashima Moe , Mamada Hanano , Kusumi Eiji , Sapkota Binaya , Shrestha Sunil , Shrestha Rajeev , Bhandari Divya , Sawano Toyoaki , Yamashita Erika , Tanimoto Tetsuya , Ozaki Akihiko 
Published: January 2022

AbstractBackgroundThere are financial relationships between healthcare professionals and pharmaceutical companies, and these relationships have historically caused conflicts of interest and unduly influenced patient care. However, little was known about such relationship and its effect in clinical practice among specialists in respiratory medicine.MethodsBased on the retrospective analysis of payment data made available by all 92 pharmaceutical companies in Japan, this study evaluated the magnitude and trend of financial relationships between all board-certified Japanese respiratory specialists and pharmaceutical companies between 2016 and 2019. Magnitude and prevalence of payments for specialists were analyzed descriptively. The payment trends were assessed using the generalized estimating equations for the payment per specialist and the prevalence of specialists with payments.ResultsAmong all 7,114 respiratory specialists certified as of August, 2021, 4,413 (62.0%) received a total of USD($) 53,547,391 and 74,195 cases from 72 (78.3%) pharmaceutical companies between 2016 and 2019. The mean±SD and median (interquartile range) four-year combined payment values per specialist were $12,134±$34,045 and $2,210 ($715□$8,178) respectively. At maximum, one specialist received $495,332 personal payments over the four years. Both payments per specialist and prevalence of specialists with payments significantly increased during the four-year period, with 7.8% (95% CI: 5.5□9.8; p<0.001) in payments and 1.5% (95% CI: 0.61% □2.4%; p = 0.001) in prevalence of specialists with payments, respectively.ConclusionMajority of respiratory specialists had increasingly received substantial personal payments from pharmaceutical companies for the reimbursement of lecturing, consulting, and writing between 2016 and 2019. These increasing financial relationships with pharmaceutical companies might cause conflicts of interest among respiratory physicians.
Computed tomographic analysis of dental system of three Jurassic ceratopsians: implications for the evolution of the tooth replacement pattern and diet in early-diverging ceratopsians
Authors: Hu Jinfeng , Forster Catherine A. , Xu Xing , Zhao Qi , He Yiming , Han Fenglu 
Published: January 2022

AbstractThe dental system of ceratopsids is among the most specialized structure in Dinosauria, and includes high angled wear surfaces, split tooth roots, and multiple teeth in each tooth family. However, the early evolution of this unique dental system is generally poorly understood due to a lack of knowledge of the dental morphology and development in early-diverging ceratopsians. Here we study the dental system of three of the earliest-diverging Chinese ceratopsians: Yinlong and Hualianceratops from the early Late Jurassic of Xinjiang, and Chaoyangsaurus from the Late Jurassic of Liaoning. By using micro-computed tomographic analyses, our study has revealed significant new information regarding the dental system of these early ceratopsians, including no more than five replacement teeth in each jaw quadrant; at most one generation of replacement teeth in each alveolus; nearly full resorption of the functional tooth root during tooth replacement; and occlusion with low-angled, concave wear facets that differs significantly from the shearing occlusal system seen in ceratopsids. Yinlong displays an increase in the number of maxillary tooth alveoli and a decrease in the number of replacement teeth during ontogeny as well as the retention of remnants of functional teeth in the largest individual. Early-diverging ceratopsians thus display a relatively slow tooth replacement rate compared to late-diverging ceratopsians. Combined with paleobotany and palaeoenvironment data, Yinlong likely uses gastroliths to triturate foodstuffs, and the difference in diet strategy might have influenced the pattern of tooth replacement in later-diverging ceratopsians.
Impaired iron recycling from erythrocytes is an early hallmark of aging
Authors: Slusarczyk Patryk , Mandal Pratik Kumar , Zurawska Gabriela , Niklewicz Marta , Chouhan Komal Kumari , Macias Matylda , Szybinska Aleksandra , Cybulska Magdalena , Krawczyk Olga , Herman Sylwia , Mikula Michal , Serwa Remigiusz , Lenartowicz Malgorzata , Pokrzywa Wojciech , Mleczko-Sanecka Katarzyna 
Published: January 2022

AbstractAging affects iron homeostasis, as evidenced by tissue iron loading and toxicity and common anemia in the elderly. Iron needs in mammals are met primarily by iron-recycling from senescent red blood cells (RBCs), a task chiefly accomplished by splenic red pulp macrophages (RPMs) via erythrophagocytosis. Given that RPMs continuously process iron, their cellular functions might be susceptible to age-dependent decline, a condition that has been largely unexplored to date. Here, we found that 10-11-months-old female mice exhibit iron loading, diminished lysosomal activity, and decreased erythrophagocytosis rate in RPMs. These impairments lead to the retention of senescent hemolytic RBCs in the spleen, and the formation of undegradable iron- and heme-rich extracellular protein aggregates, likely derived from ferroptotic RPMs. We further found that feeding mice an iron-reduced diet alleviates iron accumulation in RPMs, enhances their ability to clear erythrocytes, and limits ferroptosis. Consequently, this diet ameliorates hemolysis of splenic RBCs and the formation of iron-rich aggregates, increasing serum iron availability in aging mice. Using RPM-like cells, we show that the diminished iron-recycling capacity of RPMs is underlain by iron accumulation and reduced expression of heme-catabolizing enzyme heme oxygenase 1 (HO-1). Taken together, we identified RPM collapse as an early hallmark of aging and demonstrated that dietary iron reduction improves iron turnover efficacy.
Neuron-specific protein network mapping of autism risk genes identifies shared biological mechanisms and disease relevant pathologies
Authors: Murtaza Nadeem , Cheng Annie A. , Brown Chad O. , Meka Durga Praveen , Hong Shuai , Uy Jarryll A. , El-Hajjar Joelle , Pipko Neta , Unda Brianna K. , Schwanke Birgit , Xing Sansi , Thiruvahindrapuram Bhooma , Engchuan Worrawat , Trost Brett , Deneault Eric , Calderon de Anda Froylan , Doble Bradley W. , Ellis James , Anagnostou Evdokia , Bader Gary D. , Scherer Stephen W. , Lu Yu , Singh Karun K. 
Published: January 2022

Manuscript summaryThere are hundreds of risk genes associated with autism spectrum disorder (ASD), but signaling networks at the protein level remain unexplored. We use neuron-specific proximity-labeling proteomics (BioID) to identify protein-protein interaction (PPI) networks for 41 ASD-risk genes. Neuron-specific PPI networks, including synaptic transmission proteins, are disrupted byde novomissense variants. The PPI network map reveals convergent pathways, including mitochondrial/metabolic processes, Wnt signaling, and MAPK signaling. CRISPR knockout reveal an association between mitochondrial activity and ASD-risk genes. The PPI network shows an enrichment of 112 additional ASD-risk genes and differentially expressed genes from post-mortem ASD patients. Clustering of risk genes based on PPI networks identifies gene groups corresponding to clinical behavior score severity. Our data reveal that cell type-specific PPI networks can identify individual and convergent ASD signaling networks, provide a method to assess patient variants, and reveal biological insight into disease mechanisms and sub-cohorts of ASD.
Capturing non-local through-bond effects in molecular mechanics force fields: II. Using fractional bond orders to fit torsion parameters
Authors: Stern Chaya D. , Maat Jessica , Dotson David L. , Bayly Christopher I. , Smith Daniel G. A. , Mobley David L. , Chodera John D. 
Published: January 2022

AbstractAccurate small molecule force fields are crucial for predicting thermodynamic and kinetic properties of drug-like molecules in biomolecular systems. Torsion parameters, in particular, are essential for determining conformational distribution of molecules. However, they are usually fit to computationally expensive quantum chemical torsion scans and generalize poorly to different chemical environments. Torsion parameters should ideally capture local through-space non-bonded interactions such as 1-4 steric and electrostatics and non-local through-bond effects such as conjugation and hyperconjugation. Non-local through-bond effects are sensitive to remote substituents and are a contributing factor to torsion parameters poor transferability. Here we show that fractional bond orders such as the Wiberg Bond Order (WBO) are sensitive to remote substituents and correctly captures extent of conjugation and hyperconjugation. We show that the relationship between WBO and torsion barrier heights are linear and can therefore serve as a surrogate to QC torsion barriers, and to interpolate torsion force constants. Using this approach we can reduce the number of computationally expensive QC torsion scans needed while maintaining accurate torsion parameters. We demonstrate this approach to a set of substituted benzene rings.
Assessing Myf5 and Lbx1 contribution to carapace development by reproducing their turtle-specific signatures in mouse embryos
Authors: Tekko Triin , Nóvoa Ana , Mallo Moisés 
Published: January 2022

ABSTRACTBackgroundThe turtle carapace is an evolutionary novelty resulting from changes in the processes that build ribs and their associated muscles in most tetrapod species. Turtle embryos have several unique features that might play a role in this process, including the carapacial ridge, a Myf5 gene with shorter coding region that generates an alternative splice variant lacking exon 2, and unusual expression patterns of Lbx1 and HGF.ResultsWe generated Myf5 alleles reproducing the Myf5 turtle expression features. At mid gestation, mouse embryos expressing Myf5 lacking exon 2 reproduced some early properties of turtle somites, but still developed into viable and fertile mice. Extending Lbx1 expression into the hypaxial dermomyotomal lip of trunk somites to mimic the turtle Lbx1 expression pattern, produced fusions in the distal part of the ribs.ConclusionsTurtle-like Myf5 activity might generate a plastic state in developing trunk somites under which they can either enter carapace morphogenetic routes, possibly triggered by signals from the carapacial ridge, or still engage in the development of a standard tetrapod ribcage in the absence of those signals. In addition, trunk Lbx1 expression might play a later role in the formation of the lateral border of the carapace.
Distinct roles for SOX2 and SOX21 in differentiation, distribution and maturation of pulmonary neuroendocrine cells
Authors: Eenjes Evelien , Boerema-de Munck Anne , Buscop-van Kempen Marjon , Tibboel Dick , Rottier Robbert J. 
Published: January 2022

ABSTRACTPulmonary neuroendocrine (NE) cells represent a small population in the airway epithelium, but despite this, hyperplasia of NE cells is associated with several lung diseases, such as congenital diaphragmatic hernia and bronchopulmonary dysplasia. The molecular mechanisms causing the development of NE cell hyperplasia remains poorly understood. Previously, we showed that the SOX21 modulates the SOX2-initiated differentiation of epithelial cells in the airways (Eenjes, 2021). Here, we show that precursor NE cells start to develop in the SOX2+SOX21+ airway region and that SOX21 suppresses the differentiation of airway progenitors to precursor NE cells. During development, clusters of NE cells start to form and NE cells mature by expressing neuropeptide proteins, such as CGRP. Deficiency in SOX2 resulted in decreased clustering, while deficiency in SOX21 increased both the numbers of NE ASCL1+ precursor cells early in development, and the number of cell clusters at E18.5. In addition, at the end of gestation (E18.5), a number of NE cells in Sox2 heterozygous mice, did not yet express CGRP suggesting a delay in maturation. In conclusion, SOX2 and SOX21 function in the initiation, migration and maturation of NE cells.
Rethinking Statistical Learning as a Dynamic Stochastic Process, from The Motor Systems Perspective
Authors: Vaskevich Anna , Torres Elizabeth B 
Published: January 2022

AbstractThe brain integrates streams of sensory input and builds accurate predictions, while arriving at stable percepts under disparate time scales. This stochastic process bears different dynamics for different people, yet statistical learning (SL) currently averages out, as noise, individual fluctuations in data streams registered from the brain as the person learns. We here adopt the motor systems perspective to reframe SL. Specifically, we rethink this problem using the demands that the person’s brain faces to predict, and control variations in biorhythmic activity akin to those present in bodily motions. This new approach harnesses gross data as the important signals, to reassess how individuals learn predictive information in stable and unstable environments. We find two types of learners: narrow-variance learners, who retain explicit knowledge of the regularity embedded in the stimuli -the goal. They seem to use an error-correction strategy steadily present in both stable and unstable cases. In contrast, broad-variance learners emerge only in the unstable environment. They undergo an initial period of memoryless learning characterized by a gamma process that starts out exponentially distributed but converges to Gaussian. We coin this mode exploratory, preceding the more general error-correction mode characterized by skewed-to-symmetric distributions and higher signal content from the start. Our work demonstrates that statistical learning is a highly dynamic and stochastic process, unfolding at different time scales, and evolving distinct learning strategies on demand.
Information-seeking behaviour of Tanzanians in the time of COVID-19
Authors: Elia Emmanuel Frank 
Published: January 2022

Purpose
This study aims to investigate on access and communication of COVID-19 information among Tanzanians.

Design/methodology/approach
Quantitative methods were applied to identify a total of 636 respondents.

Findings
Results show that the majority (86.9%) of respondents seek information on COVID-19. Gender, age, education and marital status did not influence individual’s information-seeking behaviour. Respondents largely used social media, particularly WhatsApp, to communicate. Respondents prefer blending professional and traditional information to combat COVID-19. The majority (51%) of respondents indicated that COVID-19 information was not communicated ethically. Employed people are more likely to ethically communicate information on the pandemic in social media.

Practical implications
Findings imply that novelty of the pandemic has enhanced active information-seeking behaviour. Respondents rely on multiple information sources to seek and collaboratively communicate COVID information. Employment status is associated with respondents’ information-seeking behaviour. Audio-visual sources are mostly preferred and relied in communicating information on the pandemic. Social media usage has enhanced timely and appropriate decision-making measures to tackle the COVID menace. Level of education has an influence on the use of credible sources and ethical communication of information on the pandemic. Utilization of COVID-19 preventive information was not statistically associated with socio-demographic variables. Availability of information infrastructures, particularly the internet, influences access, use and clear informed decision on prevention and treatment of COVID-19 disease.

Originality/value
The study contributes to knowledge and literature on response and preventive measures on COVID-19 pandemic in developing countries.
Comparing health consumer search behavior and scientific research productivity related to COVID-19 vaccines in the USA: an infodemiology study
Authors: SeyyedHosseini Shohreh , Lund Brady D. , BasirianJahromi Reza 
Published: January 2022

Purpose
While vaccines are an effective preventative measure to defend against the spread and harmful symptoms of COVID-19, information about COVID vaccines can be difficult to find and conflicting in its coverage of vaccines’ benefits and risks. This study aims to examine the extent to which Americans are searching for information about the three major vaccine producers (Pfizer-BioNTech, Moderna and Johnson & Johnson’s Janssen) in relation to the amount of reliable scholarly information that has been produced about each one.

Design/methodology/approach
Data were retrieved from Google Trends for the US Web users alongside scientific research output of the US scientists toward three Centers for Disease Control and Prevention (CDC)-authorized COVID-19 vaccines in Web of Science, Scopus and PubMed. The authors searched for descriptive statistical analyses to detect coronavirus-seeking behavior versus coronavirus releases in the USA from May 1, 2020, to April 30, 2021.

Findings
Of the three COVID-19 vaccines, Pfizer has attracted more attention from the US population. However, the greatest number of articles about COVID-19 vaccines published by the US scholars belonged to Moderna (M = 8.17), with Pfizer (M = 7.75) having slightly less, and Janssen (M = 0.83) well behind. A positive association was found between COVID-19 vaccine information-seeking behavior (ISB) on Google and the amount of research produced about that vaccine (P <0.001).

Research limitations/implications
As the researchers use the single search engine, Google, to retrieve data from the USA, thus, selection bias will be existing as Google only gathers the data of people who chose to get the information by using this search engine.

Practical implications
If the policymakers in the US Department of Health and Human Services or the US CDC desire to improve the country’s health ISB and the scientific publication behavior (SPB) of the US researchers regarding COVID-19 vaccines studies, they should reference the results of such a study.

Originality/value
From an infodemiological viewpoint, these findings may support the health policymakers, as well as researchers who work on COVID-19 vaccines in the USA.