bluuebunny/crossref_metadata_2025 huggingface dataset:
Residual alterations of cardiac and endothelial function in patients who recovered from Takotsubo cardiomyopathy
Authors: Zilberman Liaz , Zalik Adi , Fugenfirov Irina , Shimoni Sara , George Jacob , Goland Sorel
Published: May 2021

Introduction

Takotsubo cardiomyopathy (TCM) is characterized by transient left ventricle dysfunction.

Hypothesis

A residual cardiac and endothelial dysfunction is present in patients who recovered from TCM.

Methods

In this single‐center prospective study, patients with prior TCM were included and followed for 6.4 ± 1.6 years. All underwent comprehensive cardiac function assessment, including tissue Doppler imaging (TDI) and 2‐dimensional strain (2DS) echocardiography at their first visit. The number of circulating endothelial progenitor cells and levels of proangiogenic vascular endothelial growth factor (VEGF) and its receptor (VEGF‐R) were measured. All measurements were compared with healthy controls.

Results

Forty‐two women (age 58. ±8.6 years, LVEF 58.1 ± 6.1%) comprised the TCM group. Patients post‐TCM had significantly lower early velocities E′ (6 (5.0–8.0) vs. 9 (7.0–11.0) cm/s, p = .001) by TDI and higher E/E′ ratio (p = .002), lower LV global average longitudinal strain (LGS) (−18.9 ± 3.5% vs. −21.7 ± 2.3%, p = .002) and RV LGS (−20.1 ± 3.9% vs. −23.4 ± 2.8%, p = .003) were evident. There was a trend toward a higher VEGF‐R (p = .09) along with decreased VEGF/VEGF‐R ratio representing inadequate VEGF production. In‐hospital mortality was not reported and only two non‐cardiac deaths occurred at long‐term follow‐up.

Conclusions

Altered TDI and 2DS indices suggest residual biventricular myocardial injury in post‐TCM patients with the apparent LV function recovery. Inappropriate production of VEGF and VEGF‐R were observed, suggesting a possible underlying endothelial dysfunction in these patients.
Dental tray adhesives and their role as potential transmission medium for microorganisms
Authors: Schierz Oliver , Müller Henrik , Stingu Catalina Suzana , Hahnel Sebastian , Rauch Angelika
Published: May 2021

Objectives

This study aimed to evaluate the possible ability of dental impression tray adhesives to serve as a transmission medium for bacteria and fungi when reusable adhesive applicators are utilized.

Materials and methods

Ten flasks with tray adhesive were monitored over a period of 12 weeks during clinical use for contamination with bacteria or fungi. Adhesive fluid samples were cultivated on eight different culture media. All grown colonies were identified by using mass spectrometry (MALDI‐TOF). Isolates without reliable identification were either identified by Rapid ID 32 API‐STREP V3.0 or by sequencing the 16S rRNA genes.

Results

After 4 weeks, bacterial growth was detected on chocolate blood agar plates in five different samples. The bacterial species were identified as Staphylococcus warnerii, Staphylococcus epidermidis, Staphylococcus pasteuri, Ralstonia insidiosa, and Alloiococcus otitidis. After 8 weeks Streptococcus oralis grew on a blood agar plate. In all samples, no fungi were identified.

Conclusions

The disinfectant component of the tested tray adhesive seems to be effective. However, some bacteria survived in the flask for a clinically relevant time, which might result in a potential transmission to a new host.
Heterogeneous magnitude of immunological memory to SARS‐CoV‐2 in recovered individuals
Authors: Mazzoni Alessio , Maggi Laura , Capone Manuela , Vanni Anna , Spinicci Michele , Salvati Lorenzo , Tekle Kiros Seble , Semeraro Roberto , Pengue Luca , Colao Maria Grazia , Magi Alberto , Rossolini Gian Maria , Liotta Francesco , Cosmi Lorenzo , Bartoloni Alessandro , Annunziato Francesco
Published: May 2021

Objective

Although the adaptive immune response to SARS‐CoV‐2 has been characterised in the acute and early convalescent phase of the disease, few studies explore whether natural infection elicits long‐lasting immunological memory in recovered individuals. In this work, we aimed to assess the maintenance of immunological memory to SARS‐CoV‐2.

Methods

We evaluated the long‐term virus‐specific cellular and humoral immune response in the members of an Italian Serie A football team, who experienced a cluster of COVID‐19 in March 2020, which was strictly evaluated in the following months.

Results

Our results highlight a heterogeneous magnitude of immunological memory at 5 months after infection. Indeed, 20% of the subjects displayed a weak cellular and humoral memory to SARS‐CoV‐2, suggesting that they may be at higher risk of reinfection. In addition, a history of symptomatic COVID‐19 was associated with higher levels of SARS‐CoV‐2‐reactive CD4+ T cells and specific antibody levels than in asymptomatic individuals.

Conclusion

Collectively, these data demonstrate that immunity to SARS‐CoV‐2 is maintained five months postinfection even if the magnitude of response is heterogeneous among individuals. This finding suggests that some COVID‐19‐recovered subjects may benefit from vaccination.
GSK‐3β S9A overexpression leads murine hippocampal neural precursors to acquire an astroglial phenotype in vivo
Authors: Flor‐García Miguel , Ávila Jesús , Llorens‐Martín María
Published: May 2021

The addition of new neurons to the existing hippocampal circuitry persists in the adult dentate gyrus (DG). During this process, named adult hippocampal neurogenesis (AHN), adult hippocampal progenitor cells (AHPs) give rise to newborn dentate granule cells (DGCs). The acquisition of a neuronal lineage by AHPs is tightly regulated by numerous signaling molecules and transcription factors. In this regard, glycogen synthase kinase 3β (GSK‐3β) is a master regulator of the maturation of AHPs in vitro. Here we analyzed the cell‐autonomous effects of overexpressing a constitutively active form of GSK‐3β (GSK‐3β S9A) in AHPs in vivo. To this end, we stereotaxically injected a GSK‐3β S9A‐encoding retrovirus (GSK‐3β‐V5) into the DG of young adult C57BL6/J Ola Hsd female mice and studied the cell lineage acquisition, migratory and marker expression patterns, and the morphological maturation of the infected cells over time. Strikingly, GSK‐3β S9A‐transduced cells expressed glial fibrillary acidic protein (GFAP) and NG2, thereby acquiring an immature astroglial phenotype, which differed markedly from the neuronal phenotype observed in cells transduced with a control retrovirus that encoded GFP. Accordingly, the morphology and migration patterns of cells transduced by the two retroviruses are remarkably divergent. These observations support the role of GSK‐3β as a cornerstone that regulates the balance between new astocytes/neurons generated in the adult murine DG.
Alike and different: Associations between orthorexic eating behaviors and exercise addiction
Authors: Strahler Jana , Wachten Hanna , Stark Rudolf , Walter Bertram
Published: May 2021

Objective

Symptoms of exercise addiction, a state of compulsively engaging in intense exercise, and orthorexic eating attitudes, the obsession with eating only healthy foods, often occur together. It is assumed that some more general psychological traits underlie this association. Main aim of this report was to examine similarities and differences between orthorexic eating and addictive exercising.

Method

Six hundred and eight individuals completed an online survey (mean age: 27.5, SD = 11.0 years; 76.5% women) measuring exercise addiction (Exercise Addiction inventory, EAI), orthorexic eating (Düsseldorfer Orthorexie Skala, DOS), personality domains (Big‐Five Inventory‐10), anxiety and depression (Hospital Anxiety and Depression Scale).

Results

Correlations between the DOS and EAI were .43 in women and .62 in men. Structural equation models identified gender‐specific as well as behavior‐specific psychological correlates. Among women, anxiety correlated with both EAI and DOS. In addition, the DOS correlated with depression and neuroticism while the EAI correlated with conscientiousness. In men, both scales were associated with conscientiousness and the EAI also correlated with extraversion. Clusterability analysis provided no evidence for clusters based on DOS and EAI.

Discussion

Present results showed a substantial correlation between addictive exercising and orthorexic eating, however, coefficients were smaller than expected and appeared higher in men. Both behaviors shared few psychological traits (anxiety in women, conscientiousness in men) thereby questioning the assumption of a similar origin. Additionally, gender‐specific psychological correlates point to the need for different disease management approaches in women and men.
Including tree spatial extension in the evaluation of neighborhood competition effects in Bornean rain forest
Authors: Newbery David M. , Stoll Peter
Published: May 2021

Classical tree neighborhood models use size variables acting at point distances. In a new approach here, trees were spatially extended as a function of their crown sizes, represented impressionistically as points within crown areas. Extension was accompanied by plasticity in the form of crown removal or relocation under the overlap of taller trees. Root systems were supposedly extended in a similar manner. For the 38 most abundant species in the focal size class (10–<100 cm stem girth) in two 4‐ha plots at Danum (Sabah), for periods P1 (1986–1996) and P2 (1996–2007), stem growth rate and tree survival were individually regressed against stem size, and neighborhood conspecific (CON) and heterospecific (HET) basal areas within incremented steps in radius. Model parameters were critically assessed, and statistical robustness in the modeling was set by randomization testing. Classical and extended models differed importantly in their outcomes. Crown extension weakened the relationship of CON effect on growth versus plot species’ abundance, showing that models without plasticity overestimated negative density dependence. A significant negative trend of difference in CON effects on growth (P2−P1) versus CON or HET effect on survival in P1 was strongest with crown extension. Model outcomes did not then support an explanation of CON and HET effects being due to (asymmetric) competition for light alone. An alternative hypothesis is that changes in CON effects on small trees, largely incurred by a drought phase (relaxing light limitation) in P2, and following the more shaded (suppressing) conditions in P1, were likely due to species‐specific (symmetric) root competition and mycorrhizal processes. The very high variation in neighborhood composition and abundances led to a strong “neighborhood stochasticity” and hence to largely idiosyncratic species’ responses. A need to much better understand the roles of rooting structure and processes at the individual tree level was highlighted.
Glucose patterns following alcohol and illicit drug use in young adults with type 1 diabetes: A flash glucose monitoring study
Authors: Pastor Adam , Conn Jennifer , Loh Margaret , O'Brien Casey L , Teng Jessie , Finch Sue , Collins Lisa , MacIsaac Richard J , Bonomo Yvonne
Published: May 2021

Introduction

To assess the effects of alcohol and illicit drug use in young adults (age 18–35) with type 1 diabetes (T1D) on flash glucose monitor sensor glucose (SG) readings.

Methods

Twenty young adults with T1D were enrolled from a tertiary referral hospital outpatient department in Melbourne, Australia for a 6‐week prospective observational study using flash glucose monitoring (FGM). Glucometrics comparing substance using days (SUEDs) to those without substance use (non‐SUEDS) were analysed. The primary outcomes were the difference in mean SG values, its standard deviation and minutes/24‐h period out of range (SG <3.9 mmol/L or >10.0 mmol/L) between matched SUEDs vs non‐SUEDs. An interaction model with the primary effect of HbA1c on SG values was also performed.

Results

There were no differences in the primary outcome measures between SUEDS and non‐SUEDs. However, there were differences in the regression coefficients for HbA1c and glucometrics between non‐SUEDs and SUEDs for mean SG, time out of range and time with SG > 10 mmol/L. This difference was also identified between non‐SUEDS and days of ≥40 g alcohol for mean SG.

Conclusions

While there was no difference between glucometrics for SUEDs and non‐SUEDs on primary outcomes, HbA1C was found to be a less reliable predictor of glucose patterns in the 24‐h period following substance use than control days. Young adults with T1D need to monitor and respond to their glucose levels following substance use and engage in harm minimisation practices irrespective of baseline glucose control.
Development of a method for calculating the transmission‐line constants of a three‐phase enclosure‐type gas insulated bus taking the proximity effect into account
Authors: Tanaka Yohei , Yonezawa Rikido , Noda Taku
Published: May 2021

Accurately calculating the transmission‐line constants of underground cables and gas insulated bus (GIB) is important for various types of power system simulations. When calculating the transmission‐line constants of a three‐phase enclosure‐type GIB, the Cable Constants supporting routine of EMTP is usually used. However, this routine could cause numerical errors, since the proximity effect is ignored for the calculation of series impedances and shunt admittances. In this paper, a method for calculating the transmission‐line constants of a three‐phase enclosure‐type GIB considering the proximity effect is proposed. Then, series impedances and shunt admittances are accurately calculated by the method of moments with a surface admittance operator (MoM‐SO) and method of moments (MoM), respectively. In this paper, the proposed method is verified by experiments using the small‐scale model of a three‐phase enclosure‐type GIB. Calculated results obtained by the proposed method agree well with the measured results.
Study on cyber‐security for IoT edge utilizing pattern match accelerator
Authors: Kashiyama Masamori , Kashiyama Reo , Seki Hiroto , Hosono Hiroyuki
Published: May 2021

A malware detection algorithm that can be embedded in IoT edge computing is proposed in this study and validated using an emulator. This algorithm, with a pattern match accelerator, reduces the computing cost while maintaining a relatively high detection accuracy. For autonomous driving, complicated IoT edge computing must have a huge amount of embedded program codes. In such a situation, the invasion of malware can lead to compromised cybersecurity. In this study, a pattern match accelerator is implemented for such issues, thereby offering IoT edge computing that detects malware automatically. Edge computing is designed to apply simply structural level analysis algorithms using HLAC mask pattern. We developed a pseudo‐emulator system environment and conducted performance confirmation of the proposed technique using 641 chosen samples from six types of malware families. The algorithm's efficiencies demonstrated an identification performance of approximately 80%. In comparison to characteristic extraction using AI, the computing cost was reduced and these processes enable edge computing with high cybersecurity features.
Serum creatinine and cystatin C‐based estimates of glomerular filtration rate are misleading in acute heart failure
Authors: Swolinsky Jutta S. , Nerger Niklas P. , Leistner David M. , Edelmann Frank , Knebel Fabian , Tuvshinbat Enkhtuvshin , Lemke Caroline , Roehle Robert , Haase Michael , Costanzo Maria Rosa , Rauch Geraldine , Mitrovic Veselin , Gasanin Edis , Meier Daniel , McCullough Peter A. , Eckardt Kai‐Uwe , Molitoris Bruce A. , Schmidt‐Ott Kai M.
Published: May 2021

Aims

We aimed to test whether the endogenous filtration markers serum creatinine or cystatin C and equation‐based estimates of glomerular filtration rate (GFR) based on these markers appropriately reflect changes of measured GFR in patients with acute heart failure.

Methods

In this prospective cohort study of 50 hospitalized acute heart failure patients undergoing decongestive therapy, we applied an intravenous visible fluorescent injectate (VFI), consisting of a low molecular weight component to measure GFR and a high molecular weight component to correct for measured plasma volume. Thirty‐eight patients had two sequential GFR measurements 48 h apart. The co‐primary endpoints of the study were safety of VFI and plasma stability of the high molecular weight component. A key secondary endpoint was to compare changes in measured GFR (mGFR) to changes of serum creatinine, cystatin C and estimated GFR.

Results

VFI‐based GFR measurements were safe and consistent with plasma stability of the high molecular weight component and glomerular filtration of the low molecular weight component. Filtration marker‐based point estimates of GFR, when compared with mGFR, provided only moderate correlation (Pearson's r, range 0.80–0.88, depending on equation used), precision (r2, range 0.65–0.78) and accuracy (56%–74% of estimates scored within 30% of mGFR). Correlations of 48‐h changes GFR estimates and changes of mGFR were significant (P < 0.05) but weak (Pearson's r, range 0.35–0.39). Observed decreases of eGFR by more than 15% had a low sensitivity (range 38%–46%, depending on equation used) in detecting true worsening mGFR, defined by a >15% decrease in mGFR.

Conclusions

In patients hospitalized for acute heart failure, serum creatinine‐ and cystatin C‐based predictions performed poorly in detecting actual changes of GFR. These data challenge current clinical strategies to evaluate dynamics of kidney function in acute heart failure.
Fortifying of probiotic yogurt with free and microencapsulated extract of Tragopogon Collinus and its effect on the viability of Lactobacillus casei and Lactobacillus plantarum
Authors: Maleki Mohammad , Ariaii Peiman , Sharifi Soltani Mahdi
Published: May 2021

In this study, the effect of free and microencapsulation of Tragopogon Collins extract (TPE) on the properties of probiotic yogurt was investigated. For this purpose, first, TPE was extracted by ultrasound method. The amounts of phenolic and flavonoid compounds in TPE were 890.04 mg/g gallic acid and 512.76 mg/g extract (respectively), and it had high antioxidant and antimicrobial properties. Then, the extract was encapsulated by maltodextrin–whey protein concentrate. The results related to the particle size, zeta‐potential, and microencapsulation efficiency of the TPE microencapsulation were 93.87 nm, 18.99 MV, and 64.35% respectively. In order to investigate the effect of nano‐ and free TPE on the properties of yogurt during a 15‐day storage period of 5 treatments including control, nano‐ and free TPE at 750 and 1,000 ppm were provided and the physicochemical properties, probiotic bacteria viability, and sensory properties were investigated. The results showed that adding TPE to yogurt affects the physicochemical properties, probiotic bacterial viability, and sensory properties were investigated. The results showed that adding TPE to yogurt affects the physicochemical properties. TPE samples had lower pH, less syneresis, and more acidity, viscosity, and antioxidant properties compared to the control sample (p < .05). Furthermore, in these samples, the viability of probiotic bacteria during storage was higher than the control treatment and the sensory properties were acceptable. In most cases, better results were observed in nano‐TPE treatment. Therefore, by industrial production of probiotic yogurt containing nano‐TPE as a functional food, a new choice will be provided for consumers of dairy products that would have more desirable nutritional value and sensory properties.
Impact of Obeticholic acid Exposure on Decompensation and Mortality in Primary Biliary Cholangitis and Cirrhosis
Authors: John Binu V. , Schwartz Kaley , Levy Cynthia , Dahman Bassam , Deng Yangyang , Martin Paul , Taddei Tamar H. , Kaplan David E.
Published: May 2021

Obeticholic acid (OCA) is approved for the treatment of patients with primary biliary cholangitis (PBC) who are partial responders or intolerant to ursodeoxycholic acid. Reports of serious liver injury have raised concerns about its safety in cirrhosis. We investigated the effects of treatment with OCA on hepatic decompensation and liver‐related mortality or transplantation in a cohort with compensated PBC cirrhosis. This was a retrospective cohort study using national data of US veterans with PBC and cirrhosis. We performed a propensity score model using variables associated with OCA prescription to control for baseline risk of decompensation. New OCA users were matched to nonusers. We identified 509 subjects with compensated PBC cirrhosis. We developed a propensity score model using variables associated with OCA prescription; 21 OCA users were matched with 84 nonusers. Over 569 and 3,847 person‐months, respectively, of follow‐up, 5 (23.8%) OCA users and 22 (26.2%) OCA nonusers decompensated. The C‐statistic of the propensity score model was 0.87. On multivariable analysis, after adjusting for potential confounders, OCA use was associated with an increased risk of hepatic decompensation (adjusted hazard ratio, 3.9; 95% confidence interval, 1.33‐11.57; P = 0.01). There was no association between OCA use and liver‐related mortality or transplantation (adjusted hazard ratio, 1.35; 95% confidence interval, 0.35‐5.21; P = 0.66). Conclusion: OCA use was associated with an increase in hepatic decompensation but not liver‐related mortality or transplantation in patients with compensated PBC cirrhosis. Additional studies are recommended to prospectively investigate these findings.
Expression of OPN3 in acral lentiginous melanoma and its associated with clinicohistopathologic features and prognosis
Authors: Zeng Wen , Zhang Wei , Feng Jianglong , He Xiaoyan , Lu Hongguang
Published: May 2021

Background

OPN3 upregulation associated with metastasis was recently described in two subtypes of lung cancers. And OPN3 identified in light‐independent functions in epidermal melanocytes has already shown promise. However, in malignant melanocytic tissues, the expression and characterization of OPN3 remain uncharacterized.

Objectives

We investigated the clinico‐histopathologic features in relation to OPN3 expression of acral lentiginous melanoma (ALM), which is a rare cutaneous melanoma subtype and not associated with prior sunlight exposure.

Methods

In all, 84 samples of junctional melanocytic nevi (JMN, n = 12), primary ALMs (n = 39) and inguinal lymph node metastasis (ILNM, n = 23) from ALMs were evaluated for the immunohistochemical expression of OPN3. OPN3 messenger RNA and protein level were further determined in melanocytic tumors using quantitative real‐time PCR, multiimmunofluorescence and Western blot assays. We also estimated the associations OPN3 expression between clinicopathological features and prognosis.

Results

ILNMs, in contrast to JMN and ALMs, had higher OPN3 expression scores (p < .001) by immunohistochemistry analysis. High OPN3 score was associated with presence of ulceration, increased Breslow depth and Clark level (p = .025, p = .042, and p = .012, respectively). Furthermore, a remarkable difference (p = .037) of patient overall survival was found when comparing the OPN3 expression of immunohistochemical score between equal to or larger than 100 and below 100 groups. Also, Cox regression models showed that high OPN3 scores were associated with worse melanoma survival.

Conclusion

High OPN3 expression is significantly associated with ALMs and metastatic phenotype as well as a poor prognosis.
An Antioxidant Sesquiterpene Inhibits Osteoclastogenesis Via Blocking IPMK/TRAF6 and Counteracts OVX-Induced Osteoporosis in Mice
Authors: Wang Shiyu , Ma Qingliang , Xie Ziang , Shen Yang , Zheng Bingjie , Jiang Chao , Yuan Putao , An Qin , Fan Shunwu , Jie Zhiwei
Published: May 2021

Excessive bone resorption induced by increased osteoclast activity in postmenopausal women often causes osteoporosis. Although the pharmacological treatment of osteoporosis has been extensively developed, a safer and more effective treatment is still needed. Here, we found that curcumenol (CUL), an antioxidant sesquiterpene isolated from Curcuma zedoaria, impaired receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis in vitro, whereas the osteoblastogenesis of MC3T3-E1 cells was not affected. We further demonstrated that CUL treatment during RANKL-induced osteoclastogenesis promotes proteasomal degradation of TRAF6 by increasing its K48-linked polyubiquitination, leading to suppression of mitogen-activated protein kinases (MAPKs) and NF-κB pathways and the production of reactive oxygen species (ROS). We also showed that inositol polyphosphate multikinase (IPMK) binds with TRAF6 to reduce its K48-linked polyubiquitination under RANKL stimulation. Concurrently, IPMK deficiency inhibits osteoclast differentiation. The binding between IPMK and TRAF6 blocked by CUL treatment was found in our study. Finally, we confirmed that CUL treatment prevented ovariectomy (OVX)-induced bone loss in mice. In summary, our study demonstrates that CUL could impair the stability of TRAF6 enhanced by IPMK and suppress excessive osteoclast activity in estrogen-deficient mice to treat osteoporosis. © 2021 American Society for Bone and Mineral Research (ASBMR).
Compound heterozygous p. Arg949Trp and p. Gly970Ala mutations deteriorated the function of PEX1p: A study on PEX1 in a patient with Zellweger syndrome
Authors: Alamatsaz Marzieh , Jalalypour Farzaneh , Hashemi Motahare‐Sadat , Shafeghati Yousef , Nasr‐Esfahani Mohammad Hossein , Ghaedi Kamran
Published: May 2021

The peroxisome is responsible for a variety of vital pathways in primary metabolism, including the very long‐chain fatty‐acid oxidation and plasmalogen lipid biosynthesis. Autosomal recessive disorder of the Zellweger spectrum (ZSD) is a major subset of peroxisome biogenesis disorders (PBDs) that can be caused by mutations in any of the 14 PEX genes. Zellweger syndrome (ZS) is the foremost common and severe phenotype within the heterogeneous ZSD. However, missense mutations encode proteins with residual functions, which are associated with phenotypes that are milder than ZS. Mutations in the PEX1 gene are among the most prevalent. PEX1 and PEX6 proteins, belonging to the AAA family of ATPases, form a hexameric complex, which is associated with peroxisome membranes and essential for peroxisome biology. In this study, a two‐month‐old Iranian boy with hypotonia, poor feeding, and difficulty in breathing was diagnosed with Zellweger syndrome. The parents of the patient were second cousins and healthy and no similar cases were observed in the parents' family. The PEX1 gene was sequenced in the patient and his parents. The compound heterozygous mutations, p. Arg949Trp and p. Gly970Ala, were identified in the patient, while the parents were heterozygous for these alleles. Sequence analysis of the mutant PEX1 D2 domain revealed that mutation p. Arg949Trp precisely occurred in a conserved arginine residue (P4 Arg), which hinders the substrate processing of the complex. Several database records have reported mutation p. Arg949Trp(R949W) but its clinical significance is given as uncertain. We report here a novel mutation, p. Gly970Ala, which is not recorded before and may prevent proper interaction of PEX1 and PEX6 proteins. In summary, the clinical findings and peroxisome profile of the patient suggested that compound heterozygosity for these two missense mutations resulted in a nonfunctional PEX1/PEX6 complex causing the severe ZS phenotype.
Identification of seven tumor‐educated platelets RNAs for cancer diagnosis
Authors: Ge Xinxin , Yuan Liuxia , Cheng Bin , Dai Kesheng
Published: May 2021

Background

Tumor‐educated platelets (TEPs) may enable blood‐based cancer diagnosis. This study aimed to identify diagnostic TEPs genes involved in carcinogenesis.

Materials and Methods

The TEPs differentially expressed genes (DEGs) between healthy samples and early/advanced cancer samples were obtained using bioinformatics. Gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were used to identify the pathways and functional annotation of TEPs DEGs. Protein‐protein interaction of these TEPs DEGs was analyzed based on the STRING database and visualized by Cytoscape software. The correlation analysis and diagnostic analysis were performed to evaluate the diagnostic value of TEPs mRNAs expression for early/advanced cancers. Quantitative real‐time PCR (qRT‐PCR) was applied to validate the role of DEGs in cancers.

Results

TEPs mRNAs were mostly involved in protein binding, extracellular matrix, and cellular protein metabolic process. RSL24D1 was negatively correlated to early‐stage cancers compared to healthy controls and may be potentially used for early cancer diagnosis. In addition, HPSE, IFI27, LGALS3BP, CRYM, HBD, COL6A3, LAMB2, and IFITM3 showed an upward trend in the expression from early to advanced cancer stages. Moreover, ARL2, FCGR2A, and KLHDC8B were positively associated with advanced, metastatic cancers compared to healthy controls. Among the 12 selected DEGs, the expression of 7 DEGs, including RSL24D1, IFI27, CRYM, HBD, IFITM3, FCGR2A, and KLHDC8B, were verified by the qRT‐PCR method.

Conclusion

This study suggests that the 7‐gene TEPs liquid‐biopsy biomarkers may be used for cancer diagnosis and monitoring.
Automation and miniaturization: enabling tools for fast, high‐throughput process development in integrated continuous biomanufacturing
Authors: Silva Tiago Castanheira , Eppink Michel , Ottens Marcel
Published: May 2021

Process development in the biotech industry leads to investments around hundred of millions of dollars. It is important to mitigate costs without neglecting the quality of process development. Biopharmaceutical process development is important for companies to develop new processes and be first to market, improve a pre‐established process, or start manufacturing a product available by patent expiry (biosimilars). Laboratory automation enables methodical and standardized process development. Miniaturization and parallelization empower laboratories to screen several experimental conditions and define operating windows for purification processes, improving process robustness. Together, they allow for fast and accurate process development in a fraction of the time and cost of nonminiaturized/nonparallel process development approaches. The most widely used High‐Throughput Screening technique is a liquid‐handling station and microfluidics is taking its first steps in process development. Both are attractive scale‐down tools for the characterization of bioprocesses and allow thousands of experiments to be performed per day. High‐Throughput Process Development (HTPD) has helped to achieve major breakthroughs in process optimization, both for upstream and downstream processing. Continuous processing is the next step in process development which leads to cost reduction, higher productivity and better quality control; the integration of upstream and downstream processes is seen as a major challenge. In this review, we will focus on the state‐of‐the‐art of miniaturized techniques for process development in the biotechnology industry, and how automation and miniaturization drive process development. A comparison between liquid‐handling stations and microfluidics is made and an indication is given of which tools are still lacking for HTPD in the context of Integrated Continuous Biomanufacturing. © 2021 The Authors. Journal of Chemical Technology and Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI).
Correlative nanoscopy: A multimodal approach to molecular resolution
Authors: Jadavi Samira , Bianchini Paolo , Cavalleri Ornella , Dante Silvia , Canale Claudio , Diaspro Alberto
Published: May 2021

Atomic force microscopy (AFM) is a nano‐mechanical tool uniquely suited for biological studies at the molecular scale. AFM operation is based on mechanical interaction between the tip and the sample, a mechanism of contrast capable of measuring different information, including surface topography, mechanical, and electrical properties. However, the lack of specificity highlights the need to integrate AFM data with other techniques providing compositional hints. In particular, optical microscopes based on fluorescence as a mechanism of contrast can access the local distribution of specific molecular species. The coupling between AFM and super‐resolved fluorescence microscopy solves the resolution mismatch between AFM and conventional fluorescence optical microscopy. Recent advances showed that also the inherently label‐free imaging capabilities of the AFM are fundamental to complement the fluorescence images. In this review, we have presented a brief historical view on correlative microscopy, and, finally, we have summarized the progress of correlative AFM‐super‐resolution microscopy in biological research.
Non‐negative assisted principal component analysis: A novel method of data analysis for raman spectroscopy
Authors: Blee Astrid L. , Day John C. C. , Flewitt Peter E. J. , Jeketo Alejandro , Megson‐Smith David
Published: May 2021

A novel method for the analysis of multivariate Raman spectroscopy data is presented. The method combines non‐negative matrix factorisation and principal component analysis, integrating the advantages and combating the disadvantages of both techniques. It involves the derivation of physically realistic spectra and the analysis of chemical and spatial trends across a sample surface. Proof of concept is demonstrated through two investigations. The first is a set of Raman spectra taken from a powder sample containing potassium sulphate, calcium carbonate and sodium sulphate. A second uses Raman data taken from an artificially corroded sample of superalloy material commonly used in gas turbine engines. This successful proof of concept for samples with unknown surface content sets the way for future development of the technique.
TRPV4 mediates cell damage induced by hyperphysiological compression and regulates COX2/PGE2 in intervertebral discs
Authors: Cambria Elena , Heusser Sally , Scheuren Ariane C. , Tam Wai Kit , Karol Agnieszka A. , Hitzl Wolfgang , Leung Victor Y. , Müller Ralph , Ferguson Stephen J. , Wuertz‐Kozak Karin
Published: May 2021

Background

Aberrant mechanical loading of the spine causes intervertebral disc (IVD) degeneration and low back pain. Current therapies do not target the mediators of the underlying mechanosensing and mechanotransduction pathways, as these are poorly understood. This study investigated the role of the mechanosensitive transient receptor potential vanilloid 4 (TRPV4) ion channel in dynamic compression of bovine nucleus pulposus (NP) cells in vitro and mouse IVDs in vivo.

Methods

Degenerative changes and the expression of the inflammatory mediator cyclooxygenase 2 (COX2) were examined histologically in the IVDs of mouse tails that were dynamically compressed at a short repetitive hyperphysiological regime (vs sham). Bovine NP cells embedded in an agarose‐collagen hydrogel were dynamically compressed at a hyperphysiological regime in the presence or absence of the selective TRPV4 antagonist GSK2193874. Lactate dehydrogenase (LDH) and prostaglandin E2 (PGE2) release, as well as phosphorylation of mitogen‐activated protein kinases (MAPKs), were analyzed. Degenerative changes and COX2 expression were further evaluated in the IVDs of trpv4‐deficient mice (vs wild‐type; WT).

Results

Dynamic compression caused IVD degeneration in vivo as previously shown but did not affect COX2 expression. Dynamic compression significantly augmented LDH and PGE2 releases in vitro, which were significantly reduced by TRPV4 inhibition. Moreover, TRPV4 inhibition during dynamic compression increased the activation of the extracellular signal‐regulated kinases 1/2 (ERK) MAPK pathway by 3.13‐fold compared to non‐compressed samples. Trpv4‐deficient mice displayed mild IVD degeneration and decreased COX2 expression compared to WT mice.

Conclusions

TRPV4 therefore regulates COX2/PGE2 and mediates cell damage induced by hyperphysiological dynamic compression, possibly via ERK. Targeted TRPV4 inhibition or knockdown might thus constitute promising therapeutic approaches to treat patients suffering from IVD pathologies caused by aberrant mechanical stress.
Stopover Ecology of Red Knots in Southwestern James Bay During Southbound Migration
Authors: Macdonald Amelia J. , Smith Paul A. , Friis Christian A. , Lyons James E. , Aubry Yves , Nol Erica
Published: May 2021

Many shorebirds rely on small numbers of staging sites during long annual migrations. Numerous shorebird species are declining and understanding the importance of these staging sites is important for successful conservation. We surveyed endangered rufa red knots (Calidris canutus rufa) staging in James Bay, Ontario, Canada, during southbound migration in 2017 and 2018. We used mark‐resight data and count data in an integrated Bayesian analysis to quantify migration phenology, estimate passage population size, and model the age structure of the stopover population. Many adult red knots arrived in James Bay in a single wave in early August in 2017, whereas adult red knots arrived in multiple smaller waves in July and mid‐August in 2018. These waves may correspond with breeding phenology where more red knots bred successfully and arrived in one large event in 2017 and the higher number of earlier arrivals in July 2018 may have been failed breeders. We included a binomial generalized linear model in the integrated analysis to estimate that 20% and 10% of staging red knots were juveniles in 2017 and 2018, respectively. In future applications, this method could provide a metric to assess breeding performance and develop our understanding of its role in population declines. Overall, we estimated that up to 23% of the estimated rufa red knot population staged in southwestern James Bay for an average of 10–12 days. The region is a key staging site for endangered red knots and could be included in conservation planning. © 2021 The Wildlife Society.
Food web structure in relation to environmental drivers across a continental shelf ecosystem
Authors: Walters Andrea , Robert Marianne , Cresson Pierre , Le Bris Hervé , Kopp Dorothée
Published: May 2021

Quantification of the physical and biological factors that influence the spatial structuring of food webs is central to inform effective resource management. We used baseline‐corrected stable isotope ratios (δ13C and δ15N) of 63 invertebrate and fish to investigate food web structure across a continental shelf gradient—the Celtic Sea Shelf in the Northeast Atlantic Ocean. Hierarchical clustering on δ13C and δ15N showed that the shelf food web is characterized by four trophic levels with trophic groups spread across pelagic and benthic trophic pathways. Four biomass‐weighted isotopic diversity metrics provided indicators on the status of the system, showing a relatively complex food web with high trophic redundancy at intermediate trophic levels suggesting resilience to disturbances. Two sets of statistical models, at the community scale and for each trophic group, identified five distinct trophic assemblages associated with different chlorophyll a concentrations, water depth, and bottom temperature. A cold, vertically mixed‐water assemblage over the outer shelf comprised the largest habitat and most diverse assemblage, highlighting the importance of cold productive conditions in the Celtic Sea. Trophic group model results were used to generate spatial area predictions to compare functioning of groups using isotopic overlap (similarity and nestedness) metrics. Isotopic niche area was larger (spanning two trophic levels) in shallow habitats, but not in habitats underlying high primary production or nutrient‐rich water masses, suggesting stronger benthic‐pelagic trophic coupling in inner shelf habitats. Results suggest that depth and intensity of pelagic production are major drivers of trophic structure and functioning of Celtic Sea communities.
Influence of nitrogen uptake and heat treatment on the microstructural characteristics and corrosion performance of X190CrVMo20‐4‐1 steel produced by supersolidus liquid‐phase sintering
Authors: Farayibi Peter K. , van gen Hassend Frederic , Blüm Michael , Weber Sebastian
Published: May 2021

Martensitic stainless steel powder exhibits a high nitrogen uptake when densified by supersolidus liquid‐phase sintering in a nitrogen atmosphere, but the optimum uptake, which is beneficial to its resistance to corrosion, is unknown. In this study, the resistance of high‐carbon martensitic stainless steel X190CrVMo20‐4‐1 densified in a nitrogen atmosphere against pitting corrosion was explored. This was to clarify the impact of nitrogen uptake in the steel matrix in the quenched and tempered condition on its corrosion resistance in an aqueous solution. Samples were subjected to potentiodynamic polarisation tests in a de‐aerated, 1 wt% NaCl solution. Results revealed that the X190 steel densified in a nitrogen atmosphere at 40‐kPa pressure, subjected to deep cryogenic treatment in liquid nitrogen at an austenitising temperature of 1150°C and tempered at 200°C, had the best pitting corrosion resistance with a breakdown potential of 142 ± 11 mV/SCE and a hardness of 738 ± 4 HV10. The matrix around the M7C3 carbides and MX carbonitrides suffered high pitting susceptibility. The implications of this study serve as a basis for the improvement of the functional properties of steels.
Numerical solutions of wavelet neural networks for fractional differential equations
Authors: Wu Mingqiu , Zhang Jinlei , Huang Zhijie , Li Xiang , Dong Yumin
Published: May 2021

Neural network has good self‐learning and adaptive capabilities. In this paper, a wavelet neural network is proposed to be used to solve the value problem of fractional differential equations (FDE). We construct a wavelet neural network (WNN) with the structure 1 ×N× 1 based on the wavelet function and give the conditions for the convergence of the given algorithm. This method uses the truncated power series of the solution function to transform the original differential equation into an approximate solution, then, using WNN, update the parameters, and finally get the FDE solution. Simulation results prove the validity of WNN.
Quantitative muscle echointensity: A practical approach using ultrasound to evaluate children with suspected neuromuscular disorders
Authors: Zaidman Craig M. , Hobson‐Webb Lisa D.
Published: May 2021

See article on pages 50–58 in this issue.
Microporosity mediated proliferation of preosteoblast cells on 3D printed bone scaffolds
Authors: Li Jian , Chong Yi Ting , Teng Choon Peng , Liu Jinyan , Wang FuKe
Published: May 2021

Microporous structure plays a significant role in bone tissue engineering, to influence inductive bone formation and elevate bone ingrowth inside microporous scaffolds. We hereby fabricated microporous scaffolds by 3D printing with mixture of porogens and photopolymerizing resin. Our method can tune the microporosity of scaffolds from 0% to 36% by varying the porogen concentration in the inks from zero to 60 vol%. The microporosity and microspore size of scaffolds can affect in vitro expansion of preosteoblast cells. We evaluated the attachment, spreading and proliferation of MC3T3‐E1 mouse preosteoblast cells on the printed porous scaffolds. Our studies revealed that preosteoblast cells’ in vitro adhesion and proliferation were significantly mediated by the printed scaffolds. Cells proliferation on scaffolds with 20%–30% microporosity showed much higher rate than on other scaffolds. In this microporosity range, scaffolds also showed much better cell spreading and morphologies. At a low level of microporosity (< 7%), the cell proliferation rate was even lower than the solid scaffolds, which indicates that the microporous structure is “toxic” for cells at low microporosity range. A higher microporosity (> 35%) led to very poor cell attachment and is unfavorable for the proliferation of MC3T3‐E1 cells. Furthermore, the printed dual macro‐/micro‐porous scaffolds showed higher proliferation rate of MC3T3‐E1 cells as compared to mono‐pore sized scaffolds, either the macro‐porous or microporous structure.
Graphene oxide grafted with polydimethylsiloxane modified polyurethane
Authors: Liu Danian , Wang Jingwen , Gao Xinhua , Wang Houqing , Ren Hua
Published: May 2021

In order to improve the dispersion of graphene oxide (GO) in polymers, we synthesized polyurethane (PU) chains with long polydimethylsiloxane (PDMS) chains as the “soft segment” and hexamethylene diisocyanate (HDI) as the “hard segment”, then the PU chains were grafted onto GO. The results of compatibility in solvents and TEM images of composites indicated that the modified GO (GO‐PU) would present two different shapes in non‐polar and polar solvents (cocoon‐like shape and stretched shape, respectively). The two shapes made it have a good dispersion in both non‐polar and polar polymers, it was expected to be applied in both non‐polar and polar polymer matrixes. This provided a method for covalent modification of GO.
Chemogenetic suppression of anterior cingulate cortical neurons projecting to the visual cortex disrupts attentional behavior in mice
Authors: Norman Kevin J. , Koike Hiroyuki , McCraney Sarah E. , Garkun Yury , Bateh Julia , Falk Elisa N. , Im Susanna , Caro Keaven , Demars Michael P. , Morishita Hirofumi
Published: May 2021

Aim

Attention is a goal‐directed cognitive process that facilitates the detection of task‐relevant sensory stimuli from dynamic environments. Anterior cingulate cortical area (ACA) is known to play a key role in attentional behavior, but the specific circuits mediating attention remain largely unknown. As ACA modulates sensory processing in the visual cortex (VIS), we aim to test a hypothesis that frontal top‐down neurons projecting from ACA to VIS (ACAVIS) contributes to visual attention behavior through chemogenetic approach.

Methods

Adult, male mice were trained to perform the 5‐choice serial reaction time task (5CSRTT) using a touchscreen system. An intersectional viral approach was used to selectively express inhibitory designer receptors exclusively activated by designer drugs (iDREADD) or a static fluorophore (mCherry) in ACAVIS neurons. Mice received counterbalanced injections (i.p.) of the iDREADD ligand (clozapine‐N‐oxide; CNO) or vehicle (saline) prior to 5CSRTT testing. Finally, mice underwent progressive ratio testing and open field testing following CNO or saline administration.

Results

Chemogenetic suppression of ACAVIS neuron activity decreased correct task performance during the 5CSRTT mainly driven by an increase in omission and a trending decrease in accuracy with no change in behavioral outcomes associated with motivation, impulsivity, or compulsivity. Breakpoint during the progressive ratio task and distance moved in the open field test were unaffected by ACAVIS neuron suppression. CNO administration itself had no effect on task performance in mCherry‐expressing mice.

Conclusion

These results identify long‐range frontal‐sensory ACAVIS projection neurons as a key enactor of top‐down attentional behavior and may serve as a beneficial therapeutic target.
How Does AWWA's Small Systems Division Benefit Small Systems?
Authors: Elliott Stephanie , Macler Bruce
Published: May 2021

According to the US Environmental Protection Agency, there are about 35,000 small community water systems (defined as serving fewer than 10,000 people) and another 105,000 noncommunity water systems that serve transient and workplace populations. Although these systems face most of the same challenges as larger water utilities, they generally have fewer resources to successfully address them. For the noncommunity systems especially, drinking water isn't usually even the principal reason they exist.
Reap the Benefits of Performing a Water Audit
Authors: Van Arsdel John
Published: May 2021

Water audits help utilities track water use and water loss to improve performance over time. AWWA resources, including the association's Free Water Audit Software, help utilities realize the many benefits of an annual audit.