bluuebunny/crossref_metadata_2025_split huggingface dataset:
The orthopedic characterization of cfap298tm304 mutants validate zebrafish to faithfully model human AIS
Authors: Marie-Hardy Laura , Cantaut-Belarif Yasmine , Pietton Raphaël , Slimani Lotfi , Pascal-Moussellard Hugues 
Published: April 2021

AbstractCerebrospinal fluid (CSF) circulation relies on the beating of motile cilia projecting in the lumen of the brain and spinal cord cavities Mutations in genes involved in cilia motility disturb cerebrospinal fluid circulation and result in scoliosis-like deformities of the spine in juvenile zebrafish. However, these defects in spine alignment have not been validated with clinical criteria used to diagnose adolescent idiopathic scoliosis (AIS). The aim of this study was to describe, using orthopaedic criteria the spinal deformities of a zebrafish mutant model of AIS targeting a gene involved in cilia polarity and motility, cfap298tm304. The zebrafish mutant line cfap298tm304, exhibiting alteration of CSF flow due to defective cilia motility, was raised to the juvenile stage. The analysis of mutant animals was based on micro-computed tomography (micro-CT), which was conducted in a QUANTUM FX CALIPER, with a 59 µm-30 mm protocol. 63% of the cfap298tm304 zebrafish analyzed presented a three-dimensional deformity of the spine, that was evolutive during the juvenile phase, more frequent in females, with a right convexity, a rotational component and involving at least one dislocation. We confirm here that cfap298tm304 scoliotic individuals display a typical AIS phenotype, with orthopedic criteria mirroring patient’s diagnosis.
Systematic prediction of drug resistance caused by transporter genes in cancer cells
Authors: Shen Yao , Yan Zhipeng 
Published: April 2021

AbstractTo study the drug resistance problem caused by transporters, we leveraged multiple large-scale public data sets of drug sensitivity, cell line genetic and transcriptional profiles, and gene silencing experiments. Through systematic integration of these data sets, we built various machine learning models to predict the difference between cell viability upon drug treatment and the silencing of its target across the same cell lines. More than 50% of the models built with the same data set or with independent data sets successfully predicted the testing set with significant correlation to the ground truth data. Features selected by our models were also significantly enriched in known drug transporters annotated in DrugBank for more than 60% of the models. Novel drug-transporter interactions were discovered, such as lapatinib and gefitinib with ABCA1, olaparib and NVPADW742 with ABCC3, and gefitinib and AZ628 with SLC4A4. Furthermore, we identified ABCC3, SLC12A7, SLCO4A1, SERPINA1, and SLC22A3 as potential transporters for erlotinib, three of which are also significantly more highly expressed in patients who were resistant to therapy in a clinical trial.
Description of the genetic variants identified in a cohort of patients diagnosed with localized anal squamous cell carcinoma and treated with panitumumab
Authors: Trilla-Fuertes Lucía , Gámez-Pozo Angelo , Maurel Joan , Garcia-Carbonero Rocio , Capdevila Jaume , G-Pastrián Laura , Mendiola Marta , Peña Cristina , López-Vacas Rocío , Cuatrecasas Miriam , García-Alfonso Pilar , Ramos-Ruiz Ricardo , Llorens Carlos , Ghanem Ismael , Conill Carles , Heredia-Soto Victoria , Campos-Barros Ángel , Fresno Vara Juan Ángel , Feliu Jaime 
Published: April 2021

AbstractSquamous cell carcinoma is the most frequent histologic type of anal carcinoma. The standard of care since the 1970s has been a combination of 5-fluorouracil, mitomycin C, and radiotherapy. This treatment is very effective in T1/T2 tumors (achieving complete regression in 80–90% of tumors). However, in T3/T4 tumors, the 3-year relapse free survival rate is only 50%. The VITAL trial aimed to assess the efficacy and safety of panitumumab in combination with this standard treatment. In this study, 27 paraffin-embedded samples from the VITAL trial and 18 samples from patients from daily clinical practice were analyzed by whole-exome sequencing and the influence of the presence of genetic variants in the response to panitumumab was studied. Having a moderate- or high-impact genetic variant in PIK3CA seemed to be related to the response to panitumumab. Furthermore, copy number variants in FGFR3, GRB2 and JAK1 were also related to the response to panitumumab. These genetic alterations have also been studied in the cohort of patients from daily clinical practice (not treated with panitumumab) and they did not have a predictive value. Therefore, in this study, a collection of genetic alterations related to the response with panitumumab was described. These results could be useful for patient stratification in new anti-EGFR clinical trials.
Genetic and epigenetic regulation of the non-muscle myosin light chain kinase isoform by lung inflammatory factors and mechanical stress
Authors: Sun Xiaoguang , Sun Belinda L. , Sammani Saad , Bermudez Tadeo , Dudek Steven M. , Camp Sara M. , Garcia Joe G.N. 
Published: April 2021

Abstract
Rationale: The myosin light chain kinase gene, MYLK, encodes three proteins via unique promoters, including the non-muscle isoform of myosin light chain kinase (nmMLCK), a cytoskeletal protein centrally involved in regulation of vascular integrity. As MYLK coding SNPs are associated with severe inflammatory disorders (asthma, acute respiratory distress syndrome (ARDS)), we explored clinically relevant inflammatory stimuli and promoter SNPs in nmMLCK promoter regulation. Methods: Full-length or serially deleted MYLK luciferase reporter promoter activities were measured in human lung endothelial cells (ECs). SNP-containing non-muscle MYLK (nmMYLK) DNA fragments were generated and nmMYLK promoter binding by transcription factors (TFs) detected by protein–DNA electrophoretic mobility shift assay (EMSA). Promoter demethylation was evaluated by 5-aza-2′-deoxycytidine (5-Aza). A preclinical mouse model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) was utilized for nmMLCK validation. Results: Lung EC levels of nmMLCK were significantly increased in LPS-challenged mice and LPS, tumor necrosis factor-α (TNF-α), 18% cyclic stretch (CS) and 5-Aza each significantly up-regulated EC nmMYLK promoter activities. EC exposure to FG-4592, a prolyl hydroxylase inhibitor that increases hypoxia-inducible factor (HIF) expression, increased nmMYLK promoter activity, confirmed by HIF1α/HIF2α silencing. nmMYLK promoter deletion studies identified distal inhibitory and proximal enhancing promoter regions as well as mechanical stretch-, LPS- and TNFα-inducible regions. Insertion of ARDS-associated SNPs (rs2700408, rs11714297) significantly increased nmMYLK promoter activity via increased transcription binding (glial cells missing homolog 1 (GCM1) and intestine-specific homeobox (ISX), respectively). Finally, the MYLK rs78755744 SNP (−261G/A), residing within a nmMYLK CpG island, significantly attenuated 5-Aza-induced promoter activity. Conclusion: These findings indicate nmMYLK transcriptional regulation by clinically relevant inflammatory factors and ARDS-associated nmMYLK promoter variants are consistent with nmMLCK as a therapeutic target in severe inflammatory disorders.
Spoken Vocabulary Outcomes of Toddlers With Developmental Delay After Parent-Implemented Augmented Language Intervention
Authors: Walters Casy , Sevcik Rose A. , Romski MaryAnn 
Published: April 2021

Purpose
Early intervention using augmentative and alternative communication (AAC) supports both receptive and expressive language skills. However, many parents and clinicians still worry that augmented language intervention might delay or impair speech development. This study aimed to (a) characterize and analyze the speech sound development of toddlers with developmental delay who participated in a parent-implemented language intervention; (b) examine the accuracy of speech sounds among toddlers who participated in an augmented language intervention using speech-generating devices and toddlers who participated in a traditional, spoken language intervention; and (c) examine the relationship between baseline factors (i.e., receptive and expressive language skills, vocal imitation, and number of unintelligible utterances) and the number of spoken target vocabulary words after intervention.

Method
This study used extant data from two randomized control trials of parent-implemented language interventions using AAC or spoken language. Out of 109 children who completed the intervention, 45 children produced spoken target vocabulary words at the end of the intervention. We identified and phonetically transcribed spoken target vocabulary words for each child and then classified them based on Shriberg and Kwiatkowski's (1982) developmental sound classes.

Results
Children's speech sound accuracy was not significantly different across intervention groups. Overall, children who produced more words had more speech sound errors and higher baseline language scores. Intervention group and baseline receptive and expressive language skills significantly predicted the number of spoken target vocabulary words produced at the end of intervention.

Conclusions
Participation in AAC intervention resulted in significantly more spoken target vocabulary words and no statistically significant differences in speech sound errors when compared to children who received spoken language intervention without AAC. Results support using AAC interventions for very young children without the fear that it will delay speech or spoken language development.

Supplemental Material

https://doi.org/10.23641/asha.14265365
Neuropsychiatrische Folgen der COVID-19-Pandemie
Authors: Dreßing Andrea , Hosp Jonas , Kuehner Christine , Dreßing Harald , Meyer-Lindenberg Andreas 
Published: April 2021

ZusammenfassungDie COVID-19-Pandemie hat erhebliche Auswirkungen auf die psychische Gesundheit. Neben Ängsten um die ökonomische Situation, die eigene Gesundheit und die Gesundheit anderer Menschen können auch Maßnahmen der Pandemiekontrolle wie Distanzierung und die dadurch bedingte Isolation psychosoziale Folgen haben. Schließlich kann die Infektion selbst im Rahmen einer systemischen Manifestation zu psychiatrischen und neuropsychiatrischen Symptomen führen. In dieser Arbeit werden unterschiedliche Mechanismen dargestellt, die mittelbar oder unmittelbar zu neuropsychologischen und psychopathologischen Symptomen im Kontext der COVID-19-Pandemie führen können.
Mathematical Interpretation of the Pharmacodynamics of Homoeopathic Medicines
Authors: Warner John Michel 
Published: April 2021

AbstractAccording to Hahnemann, homoeopathic medicines must be great immune responses inducers. In crude states, these medicines pose severe threats to the immune system. So, the immune-system of an organism backfires against the molecules of the medicinal substances. The complex immune response mechanism activated by the medicinal molecules can handle any threats which are similar to the threats posed by the medicinal molecules. The intersectional operation of the two sets, medicine-induced immune responses and immune responses necessary to cure diseases, shows that any effective homoeopathic medicine, which is effective against any disease, can induce immune responses which are necessary to cure the specific disease. In this article, this mechanism has been exemplified by the action of Silicea in human body. Also, a neuroimmunological assessment of the route of medicine administration shows that the oral cavity and the nasal cavity are two administration-routes where the smallest doses (sometimes even few molecules) of a particular homoeopathic medicine induce the most effective and sufficient (in amount) purgatory immune responses. Administering the smallest unitary doses of Silicea in the oral route can make significant changes in the vital force line on the dose–response relationship graph. The dose–response relationship graph further implicates that the most effective dose of a medicine must be below the lethality threshold. If multiple doses of any medicine are administered at same intervals, the immune-system primarily engages with the medicinal molecules; but along the passage of time, the engagement line splits into two: one engages with the medicinal molecules and another engages with diseases. The immune system's engagement with the diseases increases along the passage of time, though the engagement with the medicinal molecules gradually falls with the administration of descending doses. Necessarily, I have shown through mathematical logic that the descending doses, though they seem to be funny, can effectively induce the most effective immune responses.
Heparan Sulfate Proteoglycans in Diabetes
Authors: Hiebert Linda M. 
Published: April 2021

AbstractDiabetes is a complex disorder responsible for the mortality and morbidity of millions of individuals worldwide. Although many approaches have been used to understand and treat diabetes, the role of proteoglycans, in particular heparan sulfate proteoglycans (HSPGs), has only recently received attention. The HSPGs are heterogeneous, highly negatively charged, and are found in all cells primarily attached to the plasma membrane or present in the extracellular matrix (ECM). HSPGs are involved in development, cell migration, signal transduction, hemostasis, inflammation, and antiviral activity, and regulate cytokines, chemokines, growth factors, and enzymes. Hyperglycemia, accompanying diabetes, increases reactive oxygen species and upregulates the enzyme heparanase that degrades HSPGs or affects the synthesis of the HSPGs altering their structure. The modified HSPGs in the endothelium and ECM in the blood vessel wall contribute to the nephropathy, cardiovascular disease, and retinopathy seen in diabetes. Besides the blood vessel, other cells and tissues in the heart, kidney, and eye are affected by diabetes. Although not well understood, the adipose tissue, intestine, and brain also reveal HSPG changes associated with diabetes. Further, HSPGs are significantly involved in protecting the β cells of the pancreas from autoimmune destruction and could be a focus of prevention of type I diabetes. In some circumstances, HSPGs may contribute to the pathology of the disease. Understanding the role of HSPGs and how they are modified by diabetes may lead to new treatments as well as preventative measures to reduce the morbidity and mortality associated with this complex condition.
Endothelial Heparan Sulfate Proteoglycans in Sepsis: The Role of the Glycocalyx
Authors: Oshima Kaori , King Samantha I. , McMurtry Sarah A. , Schmidt Eric P. 
Published: April 2021

AbstractThere is increasing recognition of the importance of the endothelial glycocalyx and its in vivo manifestation, the endothelial surface layer, in vascular homeostasis. Heparan sulfate proteoglycans (HSPGs) are a major structural constituent of the endothelial glycocalyx and serve to regulate vascular permeability, microcirculatory tone, leukocyte and platelet adhesion, and hemostasis. During sepsis, endothelial HSPGs are shed through the induction of “sheddases” such as heparanase and matrix metalloproteinases, leading to loss of glycocalyx integrity and consequent vascular dysfunction. Less well recognized is that glycocalyx degradation releases HSPG fragments into the circulation, which can shape the systemic consequences of sepsis. In this review, we will discuss (1) the normal, homeostatic functions of HSPGs within the endothelial glycocalyx, (2) the pathological changes in HSPGs during sepsis and their consequences on the local vascular bed, and (3) the systemic consequences of HSPG degradation. In doing so, we will identify potential therapeutic targets to improve vascular function during sepsis as well as highlight key areas of uncertainty that require further mechanistic investigation.
Congenital Perineal Groove Defect in Monozygotic Twin Infants: A Literature Review
Authors: Harsono Mimily , Yanishevski David , Pourcyrous Massroor 
Published: April 2021

AbstractPerineal groove is a rare benign congenital anomaly with lesion that resembles perforation of mid-perineum or perineal raphe area. Most reported cases of congenital perineal groove presented as an isolated defect in term or early-term singleton female infants. Thus far, there is no reported case of this anomaly in monozygotic twins. Embryo pathogenesis of this female predominance congenital defect remains controversial. Many clinicians are unfamiliar with this congenital anomaly. This congenital defect tends to get self-resolved at around 2 year of age. Nevertheless, the exposed nonepithelized mucous membrane can carry risk of local infection or irritation with the possibility of requiring early surgical correction. The defect can be infrequently associated with other ano-urogenital malformations that required immediate surgical intervention. Most isolated cases tend to be asymptomatic and self-healed with expectant management. Surgical correction may be considered if not healed after 2 years of age. Early diagnosis at birth is important to avoid misdiagnoses at later age for trauma, dermatitis, sexual abuse, and risk of unnecessary aggressive intervention. Early parental counseling for providing good hygiene and close follow-up is important to prevent infection or inflammation. Presentation of this anomaly in both monozygotic twins may support the hypothesis of potential disruption during embryo morphogenesis stages.
Cantilever magnetoelectric PZT/Tb–Fe–Co resonators for magnetic sensing applications
Authors: Ngoc N. T. , Agnus G. , Matzen S. , Maroutian T. , Giang D. T. Huong , Lecoeur P. 
Published: April 2021

Magnetoelectric material-based cantilever resonators have been considered as a promising solution for magnetic sensing applications. However, most applications focus on bulk piezoelectric (e.g., PZT) laminated composites, which put a critical limit for miniaturizing into micrometer-sized devices. This work aims at demonstrating the potential of a micro-resonator approach with lower power consumption and smaller size. It reports on the fabrication and characterization of a resonant cantilever based on a freestanding multi-ferroic PZT/Tb–Fe–Co thin film multilayer, where the magnetic signal is sensed by measuring the shift of the device resonant frequency. The Tb–Fe–Co layer acts as a magnetic field sensing layer, while the PZT thin film integrated in the capacitor geometry acts as a micro-transducer to obtain an electrical signal. For a magnetic field less than 0.2 T, a sensitivity as high as 487 Hz/T is measured for the sensor under a vacuum environment. While the sensor design has to be further optimized to improve the performance, it is promising as a micro-magnetoelectric sensor for magnetic field sensing.
Composition dependence of spin–orbit torques in PtRh/ferromagnet heterostructures
Authors: Shi Guoyi , Liu Enlong , Yang Qu , Liu Yakun , Cai Kaiming , Yang Hyunsoo 
Published: April 2021

We experimentally study the spin–orbit torque (SOT) in PtRh/heterostructures by varying the composition of PtRh alloy. By performing dc-biased spin-torque ferromagnetic resonance and second-harmonic measurements in PtxRh1−x/ferromagnet heterostructures, we find that the effective damping-like spin-torque efficiency and spin Hall conductivity are 0.18 and 3.8 × 105 ℏ/2e Ω−1 m−1 for Pt0.9Rh0.1, respectively, with a low resistivity of 46.9 µΩ cm. Furthermore, current induced SOT switching in PtRh/Co is investigated. The critical current density for SOT switching decreases with an increase in the Rh composition of the PtRh alloy, which can be understood by domain wall assisted switching. Due to a large spin Hall conductivity, a relatively low resistivity, and sustainability of the high temperature process, the PtRh alloy could be an attractive spin source for SOT applications.
Effects of substrate termination on R
on increase under stress in 650 V GaN power devices
Authors: Li Feiyu , Wang Ronghua , Huang Huolin , Ren Yongshuo , Ren Guangshan , Liang Zhuang , Zhou Fubin , Cheng Wanxi , Liang Huinan 
Published: April 2021

Abstract
Buffer related electron trapping and hot electron injection are responsible for R
on degradation in devices, but the effects of substrate termination are still uncertain. In this work, both positive and negative substrate bias are applied to investigate the different vertical trapping mechanisms in 650 V gallium nitride (GaN) power devices. R
on shows an instant and significant increase under vertical bias stress, and the magnitude of downward buffer electron trapping induced R
on increase is relatively larger than that induced by upward trapping. Additionally, the substrate floated and grounded GaN devices are also submitted to both off-state and semi-on-state stresses to investigate the effects of substrate termination on hot electron injection induced R
on increase. The intensity of the upward electron trapping increases faster with temperature resulting in a higher R
on increase than the downward situation. The hot electron effect is only obvious when the substrate is grounded, suggesting that the main injection destination is not in the buffer. The substrate floated device exhibits a lower R
on increase after both off-state and semi-on-state stresses at elevated temperatures. Substrate floated packages are suggested to ensure reliable dynamic performance of device, especially for high voltage application design.
Effects of Se substitution on the Schottky barrier of a MoS
x
Se(2−x)/graphene heterostructure
Authors: Yin Kui , Huang Tao , Wu Hong-Yu , Si Yuan , Lian Ji-Chun , Xiao Yu-Wen , Zhang Zhaogang , Huang Wei-Qing , Hu Wangyu , Huang Guo-Fang 
Published: April 2021

Abstract
One of the most fundamental and challenging tasks to achieve high-performance ultra-thin atomic field effect transistors (FETs) is to obtain very low or even zero Schottky barrier height (SBH) at source/drain contact. Here, we propose that heteroatom substitution is an effective strategy to tune the performance of two-dimensional materials-based FETs, which is demonstrated by systematically exploring the effects of Se substitution on the structural and electronic properties, and SBH of MoS
x
Se(2−x)/graphene (MoS
x
Se(2−x)/G) heterostructures using first-principles calculations. Our findings suggest that the type and height of Schottky barrier can be adjusted by varying Se concentration. The transformation from n-type Schottky barrier to p-type Schottky barrier can be realized when the Se concentration is greater than 25%. With the increase of Se concentration, a lower p-type Schottky barrier can be obtained at the interface to achieve efficient charge transfer. Moreover, the Schottky barrier of MoS
x
Se(2−x)/G heterostructures with different Se concentration would disappear as the external electric field exceeds certain values. These results would provide a direction in developing high-performance FETs involving heteroatom substitution layers as contact electrodes.