bluuebunny/crossref_metadata_2025 huggingface dataset:
DDR1 associates with TRPV4 in cell‐matrix adhesions to enable calcium‐regulated myosin activity and collagen compaction
Authors: Wang Andrew Y. , Coelho Nuno M. , Arora Pamma D. , Wang Yongqiang , Eymael Denise , Ji Chenfan , Wang Qin , Lee Wilson , Xu Jessica , Kapus Andras , Carneiro Karina M. M. , McCulloch Christopher A.
Published: February 2022

Tissue fibrosis manifests as excessive deposition of compacted, highly aligned collagen fibrils, which interfere with organ structure and function. Cells in collagen‐rich lesions often exhibit marked overexpression of discoidin domain receptor 1 (DDR1), which is linked to increased collagen compaction through the association of DDR1 with the Ca2+‐dependent nonmuscle myosin IIA (NMIIA). We examined the functional relationship between DDR1 and the transient receptor potential vanilloid type 4 (TRPV4) channel, a Ca2+‐permeable ion channel that is implicated in collagen compaction. Fibroblasts expressing high levels of DDR1 were used to model cells in lesions with collagen compaction. In these cells, the expression of the β1 integrin was deleted to simplify studies of DDR1 function. Compared with DDR1 wild‐type cells, high DDR1 expression was associated with increased Ca2+ influx through TRPV4, enrichment of TRPV4 in collagen adhesions, and enhanced contractile activity mediated by NMIIA. At cell adhesion sites to collagen, DDR1 associated with TRPV4, which enhanced DDR1‐mediated collagen alignment and compaction. We conclude that DDR1 regulates Ca2+ influx through the TRPV4 channel to promote critical, DDR1‐mediated processes that are important in lesions with collagen compaction and alignment.
The WNK1 kinase regulates the stability of transcription factors during wound healing of human corneal epithelial cells
Authors: Desjardins Pascale , Le‐Bel Gaëtan , Ghio Sergio C. , Germain Lucie , Guérin Sylvain L.
Published: February 2022

Due to its superficial anatomical localization, the cornea is continuously subjected to injuries. Damages to the corneal epithelium trigger important changes in the composition of the extracellular matrix to which the basal human corneal epithelial cells (hCECs) attach. These changes are perceived by membrane‐bound integrins and ultimately lead to re‐epithelialization of the injured epithelium through intracellular signalin. Among the many downstream targets of the integrin‐activated signaling pathways, WNK1 is the kinase whose activity is the most strongly increased during corneal wound healing. We previously demonstrated that pharmacological inhibition of WNK1 prevents proper closure of wounded human tissue‐engineered cornea in vitro. In the present study, we investigated the molecular mechanisms by which WNK1 contributes to corneal wound healing. By exploiting transcription factors microarrays, electrophoretic mobility‐shift assay, and gene profiling analyses, we demonstrated that the DNA binding properties and expression of numerous transcription factors (TFs), including the well‐known, ubiquitous TFs specific protein 1 (Sp1) and activator protein 1 (AP1), were reduced in hCECs upon WNK1 inhibition by WNK463. This process appears to be mediated at least in part by alteration in both the ubiquitination and glycosylation status of these TFs. These changes in TFs activity and expression impacted the transcription of several genes, including that encoding the α5 integrin subunit, a well‐known target of both Sp1 and AP1. Gene profiling revealed that only a moderate number of genes in hCECs had their level of expression significantly altered in response to WNK463 exposition. Interestingly, analysis of the microarray data for these deregulated genes using the ingenuity pathway analysis software predicted that hCECs would stop migrating and proliferating but differentiate more when they are grown in the presence of the WNK1 inhibitor. These results demonstrate that WNK1 plays a critical function by orienting hCECs into the appropriate biological response during the process of corneal wound healing.
Hyperglycemic environment disrupts phosphate transporter function and promotes calcification processes in podocytes and isolated glomeruli
Authors: Kulesza Tomasz , Typiak Marlena , Rachubik Patrycja , Audzeyenka Irena , Rogacka Dorota , Angielski Stefan , Saleem Moin A. , Piwkowska Agnieszka
Published: February 2022

Soft tissue calcification is a pathological phenomenon that often occurs in end‐stage chronic kidney disease (CKD), which is caused by diabetic nephropathy, among other factors. Hyperphosphatemia present during course of CKD contributes to impairments in kidney function, particularly damages in the glomerular filtration barrier (GFB). Essential elements of the GFB include glomerular epithelial cells, called podocytes. In the present study, we found that human immortalized podocytes express messenger RNA and protein of phosphate transporters, including NaPi 2c (SLC34A3), Pit 1 (SLC20A1), and Pit 2 (SLC20A2), which are sodium‐dependent and mediate intracellular phosphate (Pi) transport, and XPR1, which is responsible for extracellular Pi transport. We found that cells that were grown in a medium with a high glucose (HG) concentration (30 mM) expressed less Pit 1 and Pit 2 protein than podocytes that were cultured in a standard glucose medium (11 mM). We found that exposure of the analyzed transporters in the cell membrane of the podocyte is altered by HG conditions. We also found that the activity of tissue nonspecific alkaline phosphatase increased in HG, causing a rise in Pi generation. Additionally, HG led to a reduction of the amount of ectonucleotide pyrophosphatase/phosphodiesterase 1 in the cell membrane of podocytes. The extracellular concentration of pyrophosphate also decreased under HG conditions. These data suggest that a hyperglycemic environment enhances the production of Pi in podocytes and its retention in the extracellular space, which may induce glomerular calcification.
The electrophoretic deposition of TiB2 nanoparticles produced by pulsed laser ablation: Case study on microstructural features and micromorphology properties
Authors: Teimouri Elahe , Darabi Elham , Hantehzadeh Mohammadreza , Khajehnezhad Ana
Published: February 2022

In the last decade, laser Ablation technique (Nd:YAG) has been considered as a perfect method for producing nanostructures with high purity. In the present study, Titanium diboride nanoparticles (TiB2 NPs) have been deposited on Aluminum (Al) and their micromorphology and microstructural properties have been investigated. The synthesis of TiB2 NPs has been carried out by the Laser Ablation technique (Nd:YAG) which has not been reported so far. Moreover, the effects of laser energy on improving the synthesis of TiB2 NPs have been examined. In this regard, five samples of TiB2 NPs were prepared by Laser Ablation method in different values of laser fluency in the range of 0.4–1.2 J/cm2. The structural properties of prepared nanoparticles were detected by grazing incidence X‐ray diffraction, transmission electron microscopy, and energy dispersive X‐ray spectroscopy. The morphology of samples was also investigated by field effect scanning electron microscopy. The results demonstrate the formation of spherical nanoparticles in all samples. Based on the results of the GIXRD patterns, pulsed laser energy is an effective parameter for the size of ablated nanoparticles. As can be seen, increasing the energy of laser beam decreases the average size of nanoparticles from 79.41 to 4 nm. As the next step, the as‐prepared nanoparticles were deposited on Aluminum substrate with electrophoretic deposition technique at constant applied voltage (30 Volt) and constant deposition time (30 min). The X‐ray diffraction pattern of TiB2 NPs deposited onto Al substrate confirmed the formation of the TiB2 thin films on all Al substrates. Also, the roughness and average particle size of deposited films were measured by atomic force microscopy images and MountainsMap® Premium software. Increasing the fluency of laser beam made the surface more irregular and the maximum value of fractal dimension and hence, the most irregular topography has been observed in the sample produced by maximum laser fluency.

Research Highlights

Titanium diboride nanoparticles have been synthesized by the laser ablation technique.

The effects of laser energy on improving the synthesis of TiB2 NPs have been investigated.

The micromorphology of samples have been investigated by analyzing AFM and SEM images.
Application of motivational interviewing strategies with the extended parallel process model to improve risk communication for parents of children with familial hypercholesterolemia
Authors: Winchester Bridget , Cragun Deborah , Redlinger‐Grosse Krista , Walters Scott T. , Ash Erin , Baldry Emma , Zierhut Heather
Published: February 2022

Current genetic counseling practice has not been found to significantly increase risk communication between family members. A more diverse set of genetic counseling approaches may be needed. A genetic counseling intervention based on motivational interviewing principles and the extended parallel process model was utilized to increase cascade outcomes within families with familial hypercholesterolemia, a common, underdiagnosed, and treatable condition. Parents of children with familial hypercholesterolemia were invited to participate in an online pre‐survey, single‐session genetic counseling intervention, and post‐intervention surveys as a part of the CHEERS (Cholesterol Evaluation to Explore Risk Screening) intervention. This study investigated the efficacy of a genetic counselor delivered motivational interviewing intervention and how parents of children with familial hypercholesterolemia react by assessing family member cholesterol screening and risk communication to at‐risk relatives. Transcripts were audio‐recorded, transcribed, and analyzed for change talk using the Motivational Interviewing Skill Code version 2.1. Participant surveys were analyzed for self‐reported extended parallel process constructs and motivations. Coincidence analysis was conducted to explore differences between those with and without positive cascade outcomes within 12 months after the intervention. On average, change talk increased during the session in order of the extended parallel process constructs (perceived severity, susceptibility, response efficacy, self‐efficacy). Coincidence analysis revealed that 6 of the 7 cases with positive cascade outcomes were explained by either the presence of high change talk during the intervention or presence of positive motivations shortly after, while 5 of the 5 cases without a positive outcome lacked both of these key factors that were associated with cascade outcomes. Results of this study suggest that incorporating motivational interviewing and the extended parallel process model increases change talk and that the presence of either high levels of change talk or positive motivations is associated with positive cascade outcomes.
No effect of oral ketone ester supplementation on exercise capacity in patients with McArdle disease and healthy controls: A randomized placebo‐controlled cross‐over study
Authors: Løkken Nicoline , Storgaard Jesper H. , Revsbech Karoline L. , Voermans Nicol C. , Van Hall Gerrit , Vissing John , Ørngreen Mette C.
Published: February 2022

Patients with glycogen storage disease type V (GSDV), also known as McArdle disease, have blocked glycogen breakdown due to myophosphorylase deficiency, leading to exercise intolerance, muscle pain, and risk of muscle damage. Blood‐derived ketone bodies (KBs) constitute an alternative energy source that could fuel the muscle independent of glycogenolysis. However, except for long‐time fasting or ketogenic dieting, KBs are present in low quantities. This led us to explore the effects of a drink containing exogenously produced KBs in the form of D‐β‐hydroxybutyrate esters (KE) on exercise capacity and metabolism in patients with GSDV. Eight GSDV patients and four healthy controls (HC) were included in this placebo‐controlled, cross‐over study where subjects were randomized to receive a KE drink with 395 mgKE/kg or placebo drink on two separate days 25 min before a submaximal cycle exercise test. The primary outcome was exercise capacity as indicated by heart rate response (HR) to exercise. Secondary outcomes included perceived exertion (PE) and measures of KB, carbohydrate, and fat metabolism during exercise. In GSDV, the KE drink vs. placebo increased plasma KBs and KB oxidation (p ≤ 0.0001) but did not improve exercise capacity as judged from HR (p = 0.120) and PE (p = 0.109). In addition, the KE drink lowered plasma glucose, free fatty acids, and lowered lipolytic rate and glucose rate of appearance compared with placebo. Similar results were found in the HC group. The present study indicates that an increase in KB oxidation by oral KE supplementation does not improve exercise capacity in GSDV possibly because of KB‐induced inhibition of lipolysis and liver glucose output. Thus, oral KE supplementation alone cannot be recommended as a treatment option for patients with GSDV.
Ppt1‐deficiency dysregulates lysosomal Ca++ homeostasis contributing to pathogenesis in a mouse model of CLN1 disease
Authors: Mondal Avisek , Appu Abhilash P. , Sadhukhan Tamal , Bagh Maria B. , Previde Rafael M. , Sadhukhan Sriparna , Stojilkovic Stanko , Liu Aiyi , Mukherjee Anil B.
Published: February 2022

Inactivating mutations in the PPT1 gene encoding palmitoyl‐protein thioesterase‐1 (PPT1) underlie the CLN1 disease, a devastating neurodegenerative lysosomal storage disorder. The mechanism of pathogenesis underlying CLN1 disease has remained elusive. PPT1 is a lysosomal enzyme, which catalyzes the removal of palmitate from S‐palmitoylated proteins (constituents of ceroid lipofuscin) facilitating their degradation and clearance by lysosomal hydrolases. Thus, it has been proposed that Ppt1‐deficiency leads to lysosomal accumulation of ceroid lipofuscin leading to CLN1 disease. While S‐palmitoylation is catalyzed by palmitoyl acyltransferases (called ZDHHCs), palmitoyl‐protein thioesterases (PPTs) depalmitoylate these proteins. We sought to determine the mechanism by which Ppt1‐deficiency may impair lysosomal degradative function leading to infantile neuronal ceroid lipofuscinosis pathogenesis. Here, we report that in Ppt1−/− mice, which mimic CLN1 disease, low level of inositol 3‐phosphate receptor‐1 (IP3R1) that mediates Ca++ transport from the endoplasmic reticulum to the lysosome dysregulated lysosomal Ca++ homeostasis. Intriguingly, the transcription factor nuclear factor of activated T‐cells, cytoplasmic 4 (NFATC4), which regulates IP3R1‐expression, required S‐palmitoylation for trafficking from the cytoplasm to the nucleus. We identified two palmitoyl acyltransferases, ZDHHC4 and ZDHHC8, which catalyzed S‐palmitoylation of NFATC4. Notably, in Ppt1−/− mice, reduced ZDHHC4 and ZDHHC8 levels markedly lowered S‐palmitoylated NFATC4 (active) in the nucleus, which inhibited IP3R1‐expression, thereby dysregulating lysosomal Ca++ homeostasis. Consequently, Ca++‐dependent lysosomal enzyme activities were markedly suppressed. Impaired lysosomal degradative function impaired autophagy, which caused lysosomal storage of undigested cargo. Importantly, IP3R1‐overexpression in Ppt1−/− mouse fibroblasts ameliorated this defect. Our results reveal a previously unrecognized role of Ppt1 in regulating lysosomal Ca++ homeostasis and suggest that this defect contributes to pathogenesis of CLN1 disease.
Quantification and evaluation of ion transmission efficiency in two‐stage vacuum chamber miniature mass spectrometer
Authors: Guo Chengan , Diao Zhaoyin , Liu Jianli , Yang Baokun , Zhang Jian
Published: February 2022

Miniature mass spectrometer is more compact and portable than traditional commercial mass spectrometry, with more potential for application outside the laboratory. However, a miniature mass spectrometer is less sensitive than a commercial instrument, limiting its application scenarios. The ion transmission efficiency of the instrument is an essential factor affecting the sensitivity. Still, there are few works of literature on the quantitative study of the ion transmission efficiency of each component from a systematic perspective. In this paper, the Faraday cup coupled with a microcurrent signal testing instrument was used to measure the ions generated by nanoelectrospray ionization (nano‐ESI), which have successfully gone through several components. Then the ion transmission efficiency of each component was quantified. Results showed that the front lens had the highest ion transmission efficiency of 39.7%, whereas the inlet and skimmer had the lowest ion transfer efficiency of 0.8% and 17.1%. Next, the influence of control parameters on ion transmission efficiency of critical components was investigated. If optimized, the ion funnel and the skimmer had the potential to improve their transmission efficiency by 120% and 79%, respectively. This paper shows the decreasing intensity distribution of ions in the whole transmission process and the transmission efficiency of each component, which can guide for improving the sensitivity of the miniature mass spectrometer.
vFLIP‐regulated competing endogenous RNA (ceRNA) networks targeting lytic induction for KSHV‐associated malignancies
Authors: Sheng Liuxue , Chen Chen , Chen Yuheng , He Yujia , Zhuang Ruoyu , Gu Yang , Yan Qin , Li Wan , Lu Chun
Published: February 2022

Kaposi's sarcoma‐associated herpesvirus (KSHV) causes life‐long latent infection and malignancies, including KS commonly found in AIDS patients. Lytic replication can be induced to kill tumor cells harboring latent KSHV, through viral cytopathic effects and the subsequent antiviral immune responses. Viral FLICE‐inhibitory protein (vFLIP), encoded by KSHV ORF K13, inhibits KSHV lytic reactivation, implying that the competing endogenous RNA (ceRNA) networks regulated by vFLIP can be modulated to induce the lytic reactivation of latent KSHV, a promising strategy for KSHV‐associated malignancies. Here, we performed whole‐transcriptome sequencing to reveal the global landscape of noncoding RNAs and messenger RNAs (mRNAs) in iSLK‐RGB‐BAC16 cells and iSLK‐RGB‐K13 mutant cells. It showed that vFLIP regulated 227 differentially expressed (DE) long non‐coding RNAs (lncRNAs), 57 DE circular RNAs (circRNAs), 20 DE microRNAs (miRNAs), and 1371 DE mRNAs. Enrichment analysis verified that riboflavin metabolism was simultaneously enriched in DE genes related to miRNAs, lncRNAs, and circRNAs. The upregulated hsa‐miR‐378i and hsa‐miR‐3654, and downregulated miR‐4467, miR‐3163, miR‐4451, and miR‐4257 were significantly enriched in the ceRNA complex network, which contained 9 upregulated and 7 downregulated circRNAs, 5 upregulated and 85 downregulated lncRNAs, 5 upregulated and 35 downregulated mRNAs. Finally, we constructed and validated two vFLIP‐regulated ceRNA networks: circRNA hsa_circ_0070049/hsa‐miR‐378i/SPEG/FOXQ1 and lncRNA AL031123.1/hsa‐miR‐378i/SPEG/FOXQ1. Taken together, the two ceRNA networks may mediate KSHV reactivation. These novel findings refreshed the present understanding of ceRNA network in KSHV lytic induction and provided potential therapeutic targets for KSHV‐associated malignancies.
Adverse events following immunization of COVID‐19 (Covaxin) vaccine at a tertiary care center of India
Authors: Parida Swayam Pragyan , Sahu Dinesh Prasad , Singh Arvind Kumar , Alekhya G. , Subba Sonu Hangma , Mishra Abhisek , Padhy Biswa Mohan , Patro Binod Kumar
Published: February 2022

The study aimed to assess the adverse events following COVID‐19 vaccine (Covaxin) immunization at a tertiary care institution and also assess the predictors of the adverse events following immunization (AEFI). The prospective observational study was conducted in a tertiary care institute among the Covaxin beneficiaries between June 28 and September 6, 2021. A total of 1826 participants were assessed for any local or systemic adverse events after seven days of vaccination. A telephonic interview was conducted, and the beneficiaries were assessed according to the adverse event grading. A total of 1826 participants were assessed for AEFI, and 544 (29.8%) reported at least one of the AEFI. No severe adverse events were reported, and about 1.6% had moderate AEFI. Pain at the injection site (14.6%), fever (9.7%), and myalgia (5.9%) were the common adverse events reported by the participants. AEFI incidence was higher in the first dose (38.1%) when compared to the second dose (26.4%), and this finding was significant with a p < 0.001. The major factors associated with AEFI were female sex, history of an allergic reaction, presence of comorbidities, acute infection in the past 3 months, and intake of chronic medications. Precaution needs to be taken while vaccinating individuals having allergies, comorbidities, acute infection in the last 3 months, and individuals on chronic medication.
Novel statistics predict the COVID‐19 pandemic could terminate in 2022
Authors: Chen Ji‐Ming
Published: February 2022

Many people want to know when the COVID‐19 pandemic will end and life will return to normal. This question is highly elusive and distinct predictions have been proposed. In this study, the global mortality and case fatality rate of COVID‐19 were analyzed using nonlinear regression. The analysis showed that the COVID‐19 pandemic could terminate in 2022, but COVID‐19 could be one or two times more deadly than seasonal influenza by 2023. The prediction considered the possibility of the emergence of new variants of SARS‐CoV‐2 and was supported by the features of the Omicron variant and other facts. As the herd immunity against COVID‐19 established through natural infections and mass vaccination is distinct among countries, COVID‐19 could be more or less deadly in some countries in the coming years than the prediction. Although the future of COVID‐19 will have multiple possibilities, this statistics‐based prediction could aid to make proper decisions and establish an example on the prediction of infectious diseases.
Clinicopathological and prognostic significance of HER2 status in surgically resected colorectal liver metastases
Authors: Han Jiahao , Wang Xiangyu , Zhang Chong , Wu Qian , Ma Xiaochen , Li Yitong , Chen Zhenmei , Zhang Rui , Zhang Guo , Lin Jing , Lu Lu , Zhu Wenwei , Jia Huliang , Zhang Jubo , Fan Jie , Chen Jinhong
Published: February 2022

Background

The clinicopathological and prognostic significance of human epidermal growth factor receptor 2 (HER2) status in surgically resected colorectal liver metastases (CRLM) remains uncertain.

Methods

HER2 expression was evaluated by immunohistochemical (IHC) in two CRLM tissue microarrays (TMAs). For samples with an IHC score of 2+ or 3+, fluorescence in situ hybridization (FISH) was performed to assess HER2 amplification. The association of HER2 amplification with clinicopathological parameters and prognosis was assessed using Fisher's exact test and Kaplan–Meier method, respectively.

Results

HER2 expression was consistent between primary tumor and liver metastases in 66.9% (85/127) cases (r = 0.643, p = 0.001). After FISH validation, HER2 amplification was identified in 6.25% (13/208) patients. HER2 amplification was significantly associated with age (p = 0.017), bilobar involvement (p = 0.005) and left‐sided RAS/RAF wild‐type status (p = 0.002). In the overall cohort, HER2 amplification was correlated with significantly worse relapse‐free survival (RFS). Further stratification revealed that among left‐sided RAS/RAF wild‐type cases, HER2 amplification was significantly associated with worse overall survival (OS) (30.2 vs. 50.9 months, p = 0.040) and RFS (5.77 vs. 19.97 months, p = 0.017).

Conclusion

HER2 amplification is more enriched in CRLMs with younger age, left‐sided RAS/RAF wild‐type, and bilobar involvement. Moreover, HER2 amplification predicts a poorer prognosis especially in left‐sided RAS/RAF wild‐type CRLMs.
The impact of neurotoxicant exposures on posttraumatic stress disorder trajectories: The Ft. Devens Gulf War Veterans Cohort
Authors: Zundel Clara G. , Price Kathryn , Grasso Claudia M. , Spiro Avron , Heeren Timothy , Sullivan Kimberly , Krengel Maxine H.
Published: February 2022

Gulf War veterans (GWVs) were exposed to neurotoxicants, including sarin nerve gas, anti–nerve agent pills, pesticides, oil well fires, and fumes from unvented tent heaters, all of which have been associated with subsequent adverse health. Posttraumatic stress disorder (PTSD) symptoms have also been associated with GW deployment; however, associations between exposures and PTSD symptoms have not been investigated. We assessed PTSD symptom trajectories and associations with neurotoxicant exposures in Ft. Devens Cohort (FDC) veterans (N = 259) who endorsed trauma exposure during deployment and completed the PTSD Checklist at three follow‐ups (1992–1993, 1997–1998, 2013–2017). Results indicate that among veterans with more severe initial PTSD symptoms, symptoms remained significantly higher across follow‐ups, Bs = −1.489–1.028, whereas among those with low initial PTSD symptoms, symptom severity increased significantly over time, Bs = 1.043–10.304. Additionally, neurotoxicant exposure was associated with a significant increase in PTSD symptoms, Bs = −1.870–9.003. Significant interactions between time and exposures were observed for PTSD symptom clusters, suggesting that among participants with high initial PTSD symptom, unexposed veterans experienced symptom alleviation, whereas exposed veterans’ PTSD symptoms remained high. In GWVs with low initial PTSD symptoms, both unexposed and exposed veterans experienced PTSD symptom exacerbations over time; however, this occurred at a faster rate among exposed veterans. These findings suggest that in the years following deployment, GWVs who were exposed to both traumatic events and neurotoxicants may experience more severe and chronic PTSD symptoms than those without neurotoxicant exposures.
Pore‐water exchange flushes blue carbon from intertidal saltmarsh sediments into the sea
Authors: Chen Xiaogang , Santos Isaac R. , Hu Duofei , Zhan Lucheng , Zhang Yan , Zhao Ze , Hu Shengjie , Li Ling
Published: February 2022

We quantified whether pore‐water exchange flushes out saltmarsh sediment carbon, driving carbon outwelling into the ocean and outgassing into the atmosphere. Radon‐derived pore‐water exchange released 1.8 times more sediment carbon in the wet than in dry season. Both crab burrow flushing and delayed seepage of surface water infiltrating sediments during the spring tide released sediment carbon to surface waters. The outwelling flux of dissolved inorganic carbon exceeded dissolved organic carbon. Carbon dioxide and methane emissions were 169 and 0.25 mmol m−2 d−1, respectively. Pore‐water carbon fluxes exceeded carbon outwelling. This requires some carbon processing within the saltmarsh (e.g., degradation or outgassing to the atmosphere) before pore‐water carbon is exported to the ocean. Overall, pore‐water exchange and outwelling are key components of saltmarsh carbon budgets and should be considered when assessing their carbon sequestration potential and strategies to mitigate climate change.
Properties of Hastelloy joint welded via laser wire‐filling
Authors: Zhang Wulin , Wang Xuanguo , Si Jiaqiang
Published: February 2022

In this study, UNS N10003 Hastelloy is welded using laser wire‐filling welding. The welded joint exhibits favorable tensile strength at room and high temperatures. A molten salt corrosion experiment is performed, and it is discovered that the corrosion depth increases gradually as corrosion progresses, although the growth rate decreases. When the corrosion time reaches 96 h, the corrosion depths of the weld bead and base metal are 23.39 and 24.71 μm, respectively, indicating their similar corrosion resistance. The main corrosion mechanism of N10003 Hastelloy in molten salt is the diffusion of Cr and Mo. Ni3Fe and pure Ni phases appear near the outer surface area after corrosion, which can reduce the corrosion rate.
CP‐generic expansions of models of Peano Arithmetic
Authors: Abdul‐Quader Athar , Schmerl James H.
Published: February 2022

We study notions of genericity in models of , inspired by lines of inquiry initiated by Chatzidakis and Pillay and continued by Dolich, Miller and Steinhorn in general model‐theoretic contexts. These papers studied the theories obtained by adding a “random” predicate to a class of structures. Chatzidakis and Pillay axiomatized the theories obtained in this way. In this article, we look at the subsets of models of which satisfy the axiomatization given by Chatzidakis and Pillay; we refer to these subsets in models of as CP‐generics. We study a more natural property, called strong CP‐genericity, which implies CP‐genericity. We use an arithmetic version of Cohen forcing to construct (strong) CP‐generics with various properties, including ones in which every element of the model is definable in the expansion, and, on the other extreme, ones in which the definable closure relation is unchanged.
Effect of External Magnetic Field on Bulk Heterojunction Polymer Solar Cells
Authors: Wu Dezhen , Shen Lenning , Zhang Dong , Zhu Tao , Zheng Jie , Gong Xiong
Published: February 2022

Polymer solar cells (PSCs) with a bulk heterojunction (BHJ) device structure have incredible advantages, such as low‐cost fabrication and flexibility. However, the power conversion efficiency (PCE) of BHJ PSCs needs to be further improved to realize their practical applications. In this study, boosted PCEs from PSCs based on BHJ composites incorporated with Fe3O4 magnetic nanoparticles (MNPs), aligned by an external magnetic field (EMF), are reported. It is found that the coercive electric field within the Fe3O4 MNPs generated by the EMF has a strong and positive influence on the charge generation, which results in a more than 10% increase in free charge carriers. Moreover, the coercive electric field speeds up the charge carrier transport and suppresses charge carrier recombination within PSCs. In addition, a shortened extraction time makes charge carriers more likely to make it to the electrodes. As a result, more than 15% enhancement in PCE is observed from the PSCs based on the BHJ composite incorporated with the Fe3O4 MNPs and the EMF as compared with that based on the BHJ composite thin film. This work indicates that the incorporation of MNPs and the EMF is a facile way to enhance the PCEs of PSCs.
A multidisciplinary approach and consensus statement to establish standards of care for Angelman syndrome
Authors: Duis Jessica , Nespeca Mark , Summers Jane , Bird Lynne , Bindels‐de Heus Karen G.C.B. , Valstar M. J. , de Wit Marie‐Claire Y. , Navis C. , ten Hooven‐Radstaake Maartje , van Iperen‐Kolk Bianca M. , Ernst Susan , Dendrinos Melina , Katz Terry , Diaz‐Medina Gloria , Katyayan Akshat , Nangia Srishti , Thibert Ronald , Glaze Daniel , Keary Christopher , Pelc Karine , Simon Nicole , Sadhwani Anjali , Heussler Helen , Wheeler Anne , Woeber Caroline , DeRamus Margaret , Thomas Amy , Kertcher Emily , DeValk Lauren , Kalemeris Kristen , Arps Kara , Baym Carol , Harris Nicole , Gorham John P. , Bohnsack Brenda L. , Chambers Reid C. , Harris Sarah , Chambers Henry G. , Okoniewski Katherine , Jalazo Elizabeth R. , Berent Allyson , Bacino Carlos A. , Williams Charles , Anderson Anne
Published: February 2022

Background

Angelman syndrome (AS) is a rare neurogenetic disorder present in approximately 1/12,000 individuals and characterized by developmental delay, cognitive impairment, motor dysfunction, seizures, gastrointestinal concerns, and abnormal electroencephalographic background. AS is caused by absent expression of the paternally imprinted gene UBE3A in the central nervous system. Disparities in the management of AS are a major problem in preparing for precision therapies and occur even in patients with access to experts and recognized clinics. AS patients receive care based on collective provider experience due to limited evidence‐based literature. We present a consensus statement and comprehensive literature review that proposes a standard of care practices for the management of AS at a critical time when therapeutics to alter the natural history of the disease are on the horizon.

Methods

We compiled the key recognized clinical features of AS based on consensus from a team of specialists managing patients with AS. Working groups were established to address each focus area with committees comprised of providers who manage >5 individuals. Committees developed management guidelines for their area of expertise. These were compiled into a final document to provide a framework for standardizing management. Evidence from the medical literature was also comprehensively reviewed.

Results

Areas covered by working groups in the consensus document include genetics, developmental medicine, psychology, general health concerns, neurology (including movement disorders), sleep, psychiatry, orthopedics, ophthalmology, communication, early intervention and therapies, and caregiver health. Working groups created frameworks, including flowcharts and tables, to help with quick access for providers. Data from the literature were incorporated to ensure providers had review of experiential versus evidence‐based care guidelines.

Conclusion

Standards of care in the management of AS are keys to ensure optimal care at a critical time when new disease‐modifying therapies are emerging. This document is a framework for providers of all familiarity levels.
Novel homozygous nonsynonymous variant of CNNM4 gene in a Chinese family with Jalili syndrome
Authors: Li Huajin , Huang Yanfeng , Li Jing , Xie Maosong
Published: February 2022

Background

Jalili syndrome (JS) is a rare autosomal‐recessive inherited disorder characterized by cone‐rod dystrophy and amelogenesis imperfecta. It is often misdiagnosed in clinical practice due to its heterogeneity and rarity.

Methods

Two JS patients from a consanguineous family were included in this study. Detailed ophthalmic examinations were performed. Oral photography was taken. The DNA sample of the proband was sequenced using the customized capture panel, which includes 338 retinal disease genes. Sanger sequencing was performed for validation and segregation.

Results

The patients had poor vision, photophobia, and nystagmus from childhood. Fundus examination revealed diffused chorioretinal atrophy with a prominent macular coloboma. OCT showed a deep staphyloma, severely reduced retinal thickness, retinoschisis, loss of photoreceptor layer, and retinal pigment epithelium in the macular region. Amelogenesis imperfecta, dental decay, staining, irregular shapes, and loss of teeth were present. Next‐generation sequencing combined with Sanger validation identified a novel homozygous nonsynonymous variant c.598T>C (p.S200P) in CNNM4 gene (NM_020184.3).

Conclusions

We described the clinical features of a Chinese family with JS and identified a novel disease‐causing mutation. Our findings broadened the phenotypes and mutation spectrums of JS in Chinese population, as well as are helpful in the diagnosis of this rare disease.
Autosomal recessive nonsyndromic hearing impairment in two Finnish families due to the population enriched CABP2 c.637+1G>T variant
Authors: Bharadwaj Thashi , Schrauwen Isabelle , Acharya Anushree , Nouel‐Saied Liz M. , Väisänen Marja‐Leena , Kraatari Minna , Rahikkala Elisa , Jarvela Irma , Kotimäki Jouko , Leal Suzanne M.
Published: February 2022

Background

The genetic architecture of hearing impairment in Finland is largely unknown. Here, we investigated two Finnish families with autosomal recessive nonsyndromic symmetrical moderate‐to‐severe hearing impairment.

Methods

Exome and custom capture next‐generation sequencing were used to detect the underlying cause of hearing impairment.

Results

In both Finnish families, we identified a homozygous pathogenic splice site variant c.637+1G>T in CAPB2 that is known to cause autosomal recessive nonsyndromic hearing impairment. Four CABP2 variants have been reported to underlie autosomal recessive nonsyndromic hearing impairment in eight families from Iran, Turkey, Pakistan, Italy, and Denmark. Of these variants, the pathogenic splice site variant c.637+1G>T is the most prevalent. The c.637+1G>T variant is enriched in the Finnish population, which has undergone multiple bottlenecks that can lead to the higher frequency of certain variants including those involved in disease.

Conclusion

We report two Finnish families with hearing impairment due to the CABP2 splice site variant c.637+1G>T.
Mdr3 gene mutation in preterm infants with parenteral nutrition‐associated cholestasis
Authors: Yang Xiufang , Liu Guosheng , Yi Bing
Published: February 2022

To investigate the relationship of multidrug resistance 3 (Mdr3) gene mutation and parenteral nutrition‐associated cholestasis (PNAC) in preterm infants. Preterm infants who had received total parenteral nutrition for at least 14 days were enrolled: 76 preterm infants in the PNAC group and 80 preterm infants in the non‐PNAC group. Genomic DNA was extracted from white blood cells. Twenty‐eight exons of the Mdr3 gene were amplified by polymerase chain reaction. PNAC infants of 1 month corrected age with the Mdr3 gene mutation and abnormal liver biochemistry were selected for the experimental liver biopsy group. Five normal adult living liver transplantation donors were enrolled in a normal donor group. The Mdr3 missense mutations c.1031G>A, c.3347G>A, and c.485T>A, and the Mdr3 frameshift mutation c.2793_2794insA were found in the PNAC group. The allele frequency and genotype frequency of c.1031G>A, c.3347G>A, and c.485T>A in the Mdr3 gene in the PNAC group were significantly higher than those in non‐PNAC group (p < 0.05). The rate of Mdr3 gene mutations c.1031G>A, c.485T>A, c.3347G>A, and c.2793_2794insA in the PNAC group was higher than in the non‐PNAC group (21.05% vs. 1.25%, respectively, χ2 = 15.747, p < 0.05). Mdr3 gene mutations c.2793_2794insA, c.1031G>A, c.3347G>A, and c.485T>A may be the genetic cause of PNAC.
BH leadership development program to advance equity launches
Authors: Canady Valerie A.
Published: February 2022

Preparing behavioral health leaders to take measurable action to create equitable systems and empowering these leaders to thrive as change agents to unravel systemic racism and inequity are key goals of a new initiative launched by The College for Behavioral Health Leadership (CBHL).
Program reaches rural youths through telehealth at school
Authors: Enos Gary
Published: February 2022

The University of Montana is taking advantage of schoolchildren's growing familiarity with pandemic‐era technology to make mental health counseling services more available to young people in the state's remote communities.
Massachusetts BCBS report highlights BH disparities
Authors: Canady Valerie A.
Published: February 2022

Observing Massachusetts as a longtime national leader in health care reform and the push toward universal health insurance coverage, a new report released Feb. 8 from the Blue Cross Blue Shield of Massachusetts (BCBSMA) Foundation found gaps in access to health care persist and disproportionately impact people on race, ethnicity, income and other factors. This situation particularly holds true for mental health and substance use disorders, where the delivery system is fragmented and difficult to navigate, the survey stated.
Study finds high levels of MI in people with disabilities
Authors: Canady Valerie A.
Published: February 2022

While emerging research has highlighted sources of magnified stress and trauma for people with disabilities during the pandemic compared to others in the population, few studies have examined the mental health impact of the pandemic on people with disabilities in relation to disability‐related stigma, social isolation and demographic characteristics, Oregon State University researchers said of a new study published in Rehabilitation Psychology.
Protein and peptide engineering for chemical exchange saturation transfer imaging in the age of synthetic biology
Authors: Gilad Assaf A. , Bar‐Shir Amnon , Bricco Alexander R. , Mohanta Zinia , McMahon Michael T.
Published: February 2022

At the beginning of the millennium, the first chemical exchange saturation transfer (CEST) contrast agents were bio‐organic molecules. However, later, metal‐based CEST agents (paraCEST agents) took center stage. This did not last too long as paraCEST agents showed limited translational potential. By contrast, the CEST field gradually became dominated by metal‐free CEST agents. One branch of research stemming from the original work by van Zijl and colleagues is the development of CEST agents based on polypeptides. Indeed, in the last 2 decades, tremendous progress has been achieved in this field. This includes the design of novel peptides as biosensors, genetically encoded recombinant as well as synthetic reporters. This was a result of extensive characterization and elucidation of the theoretical requirements for rational designing and engineering of such agents. Here, we provide an extensive overview of the evolution of more precise protein‐based CEST agents, review the rationalization of enzyme‐substrate pairs as CEST contrast enhancers, discuss the theoretical considerations to improve peptide selectivity, specificity and enhance CEST contrast. Moreover, we discuss the strong influence of synthetic biology on the development of the next generation of protein‐based CEST contrast agents.
Mechanical, thermogravimetric, and dynamic mechanical analysis of basalt and flax fibers intertwined vinyl ester polymer composites
Authors: Selvaraj Gokulraj , Kaliyamoorthy Rajkumar , Kirubakaran Ramraji
Published: February 2022

The selection of fibers and their stacking sequence, which affect structural integrity and functional properties, are critical parts of polymer composite design. In this work, the influence of various stacking sequences made of basalt and flax fiber layers on the mechanical, thermal, and dynamic mechanical analyses of vinyl ester polymer composites was investigated. The stacking sequence designed by alternate basalt and flax layers showed higher tensile and flexural strengths, with basalt layers in the outer positions. The high‐strength basalt fiber retains considerable stress, particularly in the outer layer, reducing stress transfer to the remaining core layers. The basalt and flax fiber alternative layered sequence with outer basalt layers shows a slightly lower thermal degradation temperature (467°C) than the only basalt layered sequence composite (474°C). Because of the high thermal resistance of the outer basalt layers, heat flow to the next fiber layers is reduced. The dynamic mechanical analysis reveals that the polymer composite intertwined with only basalt fiber was found to have a higher storage modulus. On the other hand, the outer basalt layers intertwined with the core flax layers composite showed a 122% higher damping value than the stacking sequence made of only basalt fiber due to the porous structure of flax fibers dissipating more vibration energy.
Mothers' and teachers' experience of school re‐entry after a child's prolonged absence due to severe illness
Authors: Hen Meirav
Published: February 2022

School re‐entry of children who have been absent from school due to severe illness is a complex process and requires effort and adjustment from the child and his parents, teachers, school systems, and classmates. To contribute to the understanding and accuracy of the school re‐entry process of ill children, and to the development of re‐entry programs in Israel, the present study examined the re‐entry experience from the viewpoint of mothers and teachers. The study included 27 semi‐structured interviews with mothers and teachers of children who re‐entered school after a prolonged absence due to childhood cancer. The study findings suggest that changes in the child's self‐perception, physical limitations brought on by the illness, as well as social difficulties, and altered academic abilities make it very difficult to re‐enter school. School re‐entry is more optimal when the sick child's relationship with the teacher and classmates is maintained during the absence, and when it is tailored and continuous learning support from the school. These findings emphasize the importance of maintaining an ongoing relationship during the ill child's absence from school and setting a clear re‐entry plan by the school in accordance with the child and his parents.
Advancing mental health screening in schools: Innovative, field‐tested practices and observed trends during a 15‐month learning collaborative
Authors: Connors Elizabeth H. , Moffa Kathryn , Carter Taneisha , Crocker John , Bohnenkamp Jill H. , Lever Nancy A. , Hoover Sharon A.
Published: February 2022

Schools are well positioned to facilitate early identification and intervention for youth with emerging mental health needs through universal mental health screening. Early identification of mental health concerns via screening can improve long‐term student development and success, but schools face logistical challenges and lack of pragmatic guidance to develop local screening policies and practices. This study summarizes mental health screening practices tested by six school districts participating in a 15‐month learning collaborative. Qualitative analysis of 42 Plan‐Do‐Study‐Act cycles revealed that districts tested quality improvement changes across seven screening practice areas, with all teams conducting at least one test to (1) build a foundation and (2) identify resources, logistics, and administration processes. Quantitative data indicated that the average percentage of total students screened increased from 0% to 22% (range = 270–4850 students screened at follow‐up). Together, these results demonstrate how school districts not currently engaged in mental health screening can apply small, specific tests of change to develop a locally‐tailored, practical, and scalable process to screen for student mental health concerns. Lessons learned are provided to inform future directions for school‐based teams.
The reliability of four standardized concern for falling scales among adults with a major lower extremity amputation
Authors: Nugent Kristin , Payne Michael W. , Viana Ricardo , Hunter Susan W.
Published: February 2022

Introduction

More than 52.4% of people with a lower extremity amputation (PLEA) will fall at least once each year. Previously established standardized scales that evaluate a concern for falling (CFF) were developed primarily among community‐dwelling older adults. The reliability of commonly used scales to evaluate a CFF among PLEA is needed.

Objective

To evaluate test‐retest relative and absolute reliability, and agreement of the Modified Survey of Activities and Fear of Falling in the Elderly (mSAFFE), Falls Efficacy Scale ‐ International (FES‐I), Consequences of Falling (COF) Scale, Perceived Control Over Falling (PCOF) Scale, and Perceived Ability to Manage Falls (PAMF) Scale among PLEA.

Design

Web‐based cross‐sectional repeated‐measures study.

Setting

Rehabilitation hospital.

Participants

Adults with a transtibial or transfemoral level amputation, who had completed a prosthetic rehabilitation program, and at minimum of 1 year using a prosthesis for ambulation were recruited after regularly scheduled appointments (N = 22, mean age ± SD, 63.5 ± 12.9 years).

Interventions

Not applicable.

Main Outcome Measure(s)

Initial and re‐test scores on the mSAFFE, FES‐I, COF, PCOF, and PAMF.

Results

Intraclass correlation coefficients (ICCs) demonstrated excellent relative reliability of the mSAFFE (ICC = 0.92, 95% confidence interval [CI]: 0.82‐0.97), good relative reliability of the FES‐I (ICC = 0.87, 95% CI: 0.70‐0.94), and fair relative reliability of the COF (ICC = 0.78, 95% CI: 0.53‐0.90) and PAMF (ICC = 0.73, 95% CI: 0.46‐0.88) scales. The ICC value of the PCOF scale could not be validly calculated and was not further analyzed. Calculated standard error of measurement values for the mSAFFE, FES‐I, COF, and PAMF scales were small in magnitude, and Bland‐Altman graphs demonstrated good agreement of initial and re‐test scores for all scales.

Conclusion

This study provides initial evidence on the suitability and reliable use of the mSAFFE, FES‐I, COF, and PAMF scales within this population. Further evaluation of the validity of these scales is needed.