bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of gellan gum and inulin on mixed‐gel properties and molecular structure of gelatin
Authors: Wang Juanjuan , Zhao Xue , Zhou Changyu , Wang Chong , Zheng Yanyan , Ye Keping , Li Chunbao , Zhou Guanghong
Published: January 2021

Gellan gum (GG) is often added to gelatin (GL) to improve the gel property. GG‐based or inulin (IL)‐based hydrogels were developed. Rigid and brittle gels or smooth and delicate gels were prepared with GG and IL, respectively. This study aimed to explore the properties and interaction mechanisms of the mixed‐gel system containing GL, GG, and IL, in which different ratios of GG‐IL (0.4%) (10:0, 8:2, 6:4, 5:5, 4:6, 2:8, and 0:10) were added to GL (6%). Texture profiles, rheological properties, water mobility, intermolecular forces, circular dichroism (CD) spectra, and microstructures were analyzed. The results showed that addition of GG‐IL could improve the hardness, chewiness, and cohesiveness of mixed‐gel, besides maintaining appropriate springiness. Water mobility of the mixed‐gel decreased while viscoelasticity increased upon the addition GG. At GG:IL = 2:8, the melting temperature of mixed‐gel was far higher than that of GL gel itself. The GL‐GG‐IL gel showed decrease in nonspecific bonding and increase in hydrogen bonding compared with the GL gel. CD spectra indicated the promotion of GL unfolding by GG, hence suggesting the binding of GG to GL; binding ability was better at GG:IL >5:5. Cryo‐SEM provided evidence for the formation of cross‐linked network within GL‐GG‐IL. Overall, we concluded that addition of GG‐IL to GL system would be most suitable for improving the properties of mixed‐gel. This finding may be potentially applicable in the further development of gel food products, such as meat jellies and gummy jellies.
Feasibility and preliminary effectiveness of an online training and support program for caregivers of people with dementia in India: a randomized controlled trial
Authors: Baruah Upasana , Varghese Mathew , Loganathan Santosh , Mehta Kala M. , Gallagher‐Thompson Dolores , Zandi Diana , Dua Tarun , Pot Anne Margriet
Published: January 2021

Objectives

Internet‐based interventions involving elements of cognitive behavior therapy, psychoeducation, relaxation and skills training for caregivers of people with dementia have been found to be promising in Western countries. Given these outcomes, the adapted version of a multi‐component online caregiver skills training and support program of the World Health Organization, called iSupport, was tested for feasibility and preliminary effectiveness in India.

Methods

One hundred fifty‐one caregivers of family members with a diagnosis of Alzheimer's disease or dementia were randomized to either the intervention arm (iSupport; n = 74) or to the control group (an education‐only e‐book program; n = 77). Participants were assessed using self‐rated measures of depression and perceived burden, which were the primary outcome measures, at baseline and 3‐month follow‐up. Person‐centered attitude, self‐efficacy, mastery and self‐rated health were also assessed.

Results

Fifty‐five caregivers (29 in the iSupport group and 26 in the control condition) completed the study. The recruitment and retention rate of the study were 44.67% and 36.42% respectively. No significant differences were found between the two groups at 3‐month follow‐up on the primary outcomes. Among the secondary outcomes, significant improvement was only seen in caregivers' person‐centered attitude towards persons with dementia in the iSupport group (t = 2.228; p < 0.05).

Conclusions

Despite efforts to recruit and retain participants to the online program, this study had a low recruitment and retention rate, which require closer attention and indicates a need for further adaptations of the Indian version of the iSupport program to improve its acceptability and accessibility. The lessons learned from this study will guide the further development of caregiver training and support interventions in India. The trial was registered with the Clinical Trials Registry‐India (Trial Registration No. CTRI/2017/02/007876).
Azithromycin—Spectrum of Activity, Pharmacokinetics, and Clinical Applications
Authors: Drew Richard H. , Gallis Harry A.
Published: January 2021

Azithromycin is an azalide antimicrobial agent. Structurally related to the macrolide antibiotic erythromycin, its mechanism of activity (similar to erythromycin) is interference with bacterial protein synthesis by binding to the 50S component of the 70S ribosomal subunit. Although slightly less potent than erythromycin against gram‐positive organisms, azithromycin demonstrates superior activity in vitro against a wide variety of gram‐negative bacilli, including Haemophilus influenzae. Absorption is approximately 37% after a 500‐mg oral dose. The large volume of distribution (23 L/kg) and low peak serum level (0.4 μg/ml) are consistent with data demonstrating extensive tissue distribution and intracellular accumulation. Metabolism is predominantly hepatic (to inactive metabolites), with biliary excretion a major pathway of elimination. Drug elimination is biphasic, with a terminal half‐life of up to 5 days. Published trials have examined the efficacy and safety of azithromycin in the treatment of adults with upper and lower respiratory tract infections, skin and skin structure infections, streptococcal pharyngitis, and sexually transmitted diseases. Many used a 5‐day course of 250 mg once daily, supplemented with a 250‐mg dose on the first day of therapy. Selected trials in sexually transmitted diseases examined single 1‐g doses. Promising results also were obtained with oral daily doses of 500 mg. in patients with human immunoviral infection who also had Mycobacterium avium complex infection and in animals with toxoplasmosis. Adverse reactions are primarily gastrointestinal (nausea, diarrhea, abdominal pain), with minimal laboratory abnormalities reported. Gastrointestinal tolerance is better than that of erythromycin. Drug interactions have not been observed to date, although coadministration of azithromycin with a large meal may reduce absorption by up to 50%.
Simultaneous immunofluorescence and histology in pemphigus vulgaris using ex vivo confocal laser scanning microscopy
Authors: Bağcı Işın Sinem , Aoki Rui , Vladimirova Gabriela , Sárdy Miklós , Ruzicka Thomas , French Lars E. , Hartmann Daniela
Published: January 2021

Ex vivo confocal laser scanning microscopy (ex vivo CLSM) provides rapid, high‐resolution imaging and immunofluorescence examinations of the excised tissues. We aimed to evaluate the applicability of ex vivo CLSM in histomorphological and direct immunofluorescence (DIF) examination of pemphigus vulgaris (PV). 20 PV sections were stained with fluorescent‐labeled anti‐IgG and anti‐C3 using various dilutions and incubation periods. Subsequently, the determined ideal staining protocol was applied on 20 additional PV and 20 control sections. Ex vivo CLSM identified intraepidermal blisters and acantholytic cells in 80% and 60% of PV patients, respectively. The sensitivity of ex vivo CLSM in detecting intraepidermal fluorescence was 90% both with IgG and C3. The specificity of staining for IgG and C3 was 70% and 90%, respectively. Histomorphological and immunofluorescence features of PV could be detected within the same ex vivo CSLM session showing a comparable performance to conventional histopathology and DIF microscopy.
A highly‐sensitive vascular endothelial growth factor‐A(165) immunosensor, as a tool for early detection of cancer
Authors: Taati Yengejeh Fatemeh , Shabani Shayeh Javad , Rahmandoust Moones , Fatemi Fattaneh , Arjmand Sareh
Published: January 2021

Biomarkers can be ideal indicators for assessing the risk of the presence of a disease. In this study, a label‐free electrochemical biosensor was designed to quantify the vascular endothelial growth factor A (165) (VEGF‐A(165)) antigen, using reduced graphene oxide‐gold nanoparticle for early detection of breast cancer. The conductivity of gold nanoparticle along with its biocompatibility provide an enhanced surface, suitable for anti‐VEGF antibody immobilization. 11‐mercaptoundecanoic acid was used to facilitate a single‐step and convenient bonding of the antibodies to the surface, compared to previous studies. The dynamic range of the biosensor was between 20 to 120 pg/ml and its limit of detection of the biomarker VEGF‐A(165) was obtained to be about 0.007 pg/ml, using different electric signal transduction modes. Hence, the biosensor is a beneficial immunosensor with high sensitivity and ideal dynamic range for early‐stage diagnosis of breast cancer and other cancers diseases associated with expression of VEGF‐A(165). The as‐prepared immunosensor could be efficiently employed for designing a point‐of‐care diagnostic platform.
Hepatoprotective effect of arjunolic acid against cisplatin‐induced hepatotoxicity: Targeting oxidative stress, inflammation, and apoptosis
Authors: Sherif Iman O.
Published: January 2021

Minimizing the adverse effects of chemotherapeutic agents remains a therapeutic challenge. Cisplatin (CP) induces hepatotoxicity through activation of oxidative stress, inflammation, and apoptosis cascades which is considered a significant drawback. Thus, this study aimed to highlight the possible hepatoprotective role of arjunolic acid (Arj) in a rat model of CP‐induced hepatotoxicity. Four groups of rats were included; the normal control group, Arj control group, CP group which was injected with 7.5 mg/kg CP intraperitoneally to induce hepatotoxicity, and the treated group (Arj + CP), which was orally administered 20 mg/kg Arj for 10 days with a CP hepatotoxic dose on day 5. Blood and liver tissues were assembled for analysis at the end of the study. Pretreatment with Arj exhibited a marked improvement in liver function as well as histopathology when compared with the CP group. Moreover, Arj suppressed the oxidative stress in hepatic tissue by significantly decreasing malondialdehyde and nitric oxide contents along with markedly elevating the levels of superoxide dismutase, catalase, and reduced glutathione when compared with CP injected rats. Attenuation of hepatic inflammation and apoptosis was also reported with Arj treatment through the marked reduction in the proinflammatory cytokine tumor necrosis factor α level as well as the apoptotic marker caspase‐3 protein expression in comparison to the CP group. This study explored for the first time the Arj hepatoprotective effect against CP‐induced hepatotoxicity through its antioxidant, anti‐inflammatory, and antiapoptotic activities.
When do errors in reinforcer delivery affect learning? A parametric analysis of treatment integrity
Authors: Bergmann Samantha , Kodak Tiffany , Harman Michael J.
Published: January 2021

Treatment integrity is the extent to which components of an intervention are implemented as intended (Gresham, 1989). Recent behavior‐analytic literature has begun to evaluate the effects of reduced‐treatment integrity on the efficacy and efficiency of skill‐acquisition interventions. This study extended the current literature on the effects of errors of omission and commission of reinforcer delivery by replicating and extending Hirst and DiGennaro Reed (2015). Using a randomized‐control group design, we compared undergraduate student participants' acquisition of conditional discriminations in a parametric analysis of different error values. A computer program erred in reinforcer delivery on 0%, 5%, 10%, 15%, 20%, 25% and 50% of trials. The purpose of the current study was to identify which levels of reduced integrity slowed or prevented acquisition. Our data replicated the findings of Hirst and DiGennaro Reed, and extended parametric analyses by identifying that errors in reinforcer delivery occurring on 15% or fewer trials (i.e., 85% integrity) were unlikely to prevent participants' responding from meeting the mastery criterion. These results could inform future research on how treatment‐integrity errors change behavior‐analytic procedures and the effects on skill acquisition for consumers of applied behavior analysis.
Sediment phosphorus buffering in streams at baseflow: A meta‐analysis
Authors: Simpson Zachary P. , McDowell Richard W. , Condron Leo M. , McDaniel Marshall D. , Jarvie Helen P. , Abell Jonathan M.
Published: January 2021

Phosphorus (P) pollution of surface waters remains a challenge for protecting and improving water quality. Central to the challenge is understanding what regulates P concentrations in streams. This quantitative review synthesizes the literature on a major control of P concentrations in streams at baseflow—the sediment P buffer—to better understand streamwater–sediment P interactions. We conducted a global meta‐analysis of sediment equilibrium phosphate concentrations at net zero sorption (EPC0), which is the dissolved reactive P (DRP) concentration toward which sediments buffer solution DRP. Our analysis of 45 studies and >900 paired observations of DRP and EPC0showed that sediments often have potential to remove or release P to the streamwater (83% of observations), meaning that “equilibrium” between sediment and streamwater is rare. This potential for P exchange is moderated by sediment and stream characteristics, including sorption affinity, stream pH, exchangeable P concentration, and particle sizes. The potential for sediments to modify streamwater DRP concentrations is often not realized owing to other factors (e.g., hydrologic interactions). Sediment surface chemistry, hyporheic exchange, and biota can also influence the potential exchange of P between sediments and the streamwater. Methodological choices significantly influenced EPC0determination and thus the estimated potential for P exchange; we therefore discuss how to measure and report EPC0to best suit research objectives and aid in interstudy comparison. Our results enhance understanding of the sediment P buffer and inform how EPC0can be effectively applied to improve management of aquatic P pollution and eutrophication.
Automatic quantification of lymphocyte vacuolization in peripheral blood smears of patients with Batten's disease (CLN3 disease)
Authors: Nonkes Lourens J. P. , Kuper Willemijn F. E. , Berrens‐Hogenbirk Karin , Musson Ruben E. A. , van Hasselt Peter M. , Huisman Albert
Published: January 2021

Quantifying lymphocyte vacuolization in peripheral blood smears (PBSs) serves as a measure for disease severity in CLN3 disease—a lysosomal storage disorder of childhood‐onset. However, thus far quantification methods are based on labor‐intensive manual assessment of PBSs. As machine learning techniques like convolutional neural networks (CNNs) have been deployed quite successfully in detecting pathological features in PBSs, we explored whether these techniques could be utilized to automate quantification of lymphocyte vacuolization. Here, we present and validate a deep learning pipeline that automates quantification of lymphocyte vacuolization. By using two CNNs in succession, trained for cytoplasm‐segmentation and vacuolization‐detection, respectively, we obtained an excellent correlation with manual quantification of lymphocyte vacuolization (r = 0.98, n = 40). These results show that CNNs can be utilized to automate the otherwise cumbersome task of manually quantifying lymphocyte vacuolization, thereby aiding prompt clinical decisions in relation to CLN3 disease, and potentially beyond.
Safety and efficacy of cryoballoon ablation for the treatment of paroxysmal and persistent AF in a real‐world global setting: Results from the Cryo AF Global Registry
Authors: Chun Kyoung Ryul Julian , Okumura Ken , Scazzuso Fernando , Keun On Young , Kueffer Fred J. , Braegelmann Kendra M. , Kaur Khelae Surinder , Al‐Kandari Fawzia , Földesi Csaba ,   the Cryo Global Registry Investigators
Published: January 2021

Background

Cryoballoon ablation is a commonly used approach to treat patients with atrial fibrillation (AF).

Objectives

Report on the safety and efficacy of cryoballoon ablation for the treatment of AF in the largest global cohort of cryoablated patients prospectively studied within a single registry.

Methods

The Cryo AF Global Registry is a prospective, multi‐center registry. Patients with paroxysmal AF (PAF) or persistent AF (PsAF) were treated with the cryoballoon catheter according to routine practices at 93 sites across 36 countries. Primary efficacy endpoints included freedom from AF and freedom from AF/atrial flutter (AFL)/atrial tachycardia (AT) ≥30 seconds. The primary safety endpoint was serious device‐ or procedure‐related adverse events over 12 month follow‐up.

Results

During this evaluation window, 2922 subjects completed an index cryoballoon procedure, and 1440 completed 12 month follow‐up. The cohort was 61 ± 12 years of age, 36.3% female, and 78.7% PAF. Serious device‐ and procedure‐related adverse event rates were 1.5% and 3.4%, respectively. Freedom from AF/AFL/AT after the 90 day blanking period was 86.4% (95% CI: 84.3%‐88.3%) in patients with PAF and 70.9% (95% CI: 64.6%‐76.4%) in patients with PsAF. Freedom from AF/AFL/AT in first‐line PAF and PsAF was 90.0% (95% CI: 86.4%‐92.7%) and 72.9% (95% CI: 58.6%‐83.0%) at 12 months, respectively.

Conclusions

The Cryo Global AF Registry is the largest evaluation to demonstrate cryoablation is an efficient, safe, and effective treatment for patients with AF worldwide. Cryoablation was commonly used to treat patients prior to an AAD failure and may facilitate earlier therapy for patients on the AF disease continuum.
Cervical Extension of the Normal Thymus in Children and Adolescents
Authors: Xia Chunxia , Chen Shuang , Baikpour Masoud , Pierce Theodore T. , Duan Yu , Li Qian , Chen Lei , Cheah Eugene , Samir Anthony E.
Published: January 2021

Objective

This study aims to confirm the prevalence of incidental cervical extension of normal thymus in children and adolescents undergoing neck ultrasound and describe the ultrasound appearance to minimize future misdiagnosis.

Materials and Methods

This retrospective study was conducted in a single institution. Thyroid and lower neck ultrasound images of the consecutive pediatric subjects between January 1, 2011 and September 30, 2017 were independently reviewed by 2 radiologists for the presence of cervical thymus. When identified on sonographic images, cervical thymus was described on the basis of echogenicity, location, and shape.

Results

In 278 consecutive cases, the 2 reviewers identified 105 (37.8%) and 103 (37.1%) cases respectively as having sonographically visible tissue in the expected location of cervical extension of the thymus. The internal echotexture was variable with 38.1% of cases being hypoechoic, 37.1% mixed, and 24.8% hyperechoic. Cervical extension of the thymus was most commonly (65.0%) to the left of the trachea or (30.9%) bilateral/anterior to the trachea; isolated right paratracheal thymus was uncommon. Thymic shape was variable: quadrilateral (30.9%), oval (29.9%), triangular (25.8%), and other (13.4%). The logistic regression model including age, gender, and BMI z‐scores showed that, when controlled for sex and BMI z‐scores, younger age was a predictor for the presence of cervical thymic extension (p < .001).

Conclusion

Cervical thymic extension is sonographically visible as a soft tissue mass of variable appearance in about a third of children and adolescents undergoing neck ultrasonography with decreasing prevalence with age. Sonographically visible cervical thymic tissue is more common in younger patients.
Therapeutic Ultrasound‐Enhanced Transcorneal PHMB Delivery In Vitro
Authors: Karpinecz Bianca , Edwards Natalie , Zderic Vesna
Published: January 2021

Objective

Delivery of therapeutic agents to the cornea is a difficult task in the treatment of parasitic keratitis. In this study, we looked at using different combinations of ultrasound parameters to enhance corneal permeability to polyhexamethylene biguanide (PHMB), a clinically available ophthalmic antiparasitic formulation.

Methods

Permeability of PHMB was investigated in vitro using a standard diffusion cell setup. Continuous or 25% duty‐cycle ultrasound was used at frequencies of 400 or 600 kHz, intensities of 0.5 or 0.8 W/cm2, and exposure times ranging from 1 to 5 minutes. Structural changes in the cornea were examined using light microscopy.

Results

Ultrasound exposure produced increases in transcorneal delivery in every treatment parameter combination when compared to the sham treatment. The highest increase was 2.36 times for 5 minutes of continuous ultrasound at a frequency of 600 kHz and an intensity of 0.5 W/cm2 with statistical significance (p <.001). Histological analysis showed that ultrasound application only caused structural changes in the corneal epithelium, with most damage being at the surface layers.

Conclusions

This study suggests the possibility of therapeutic ultrasound as a novel drug delivery technique for the treatment of parasitic keratitis. Further studies are needed to examine the thermal effects of these proposed ultrasound applications and the long‐term viability of this treatment.
Comorbid Dysphagia and Malnutrition in Elderly Hospitalized Patients
Authors: Bomze Laura , Dehom Salem , Lao Wilson P. , Thompson Jordan , Lee Nathan , Cragoe Andrea , Luceno Cesar , Crawley Brianna
Published: January 2021

Objective/Hypothesis

Elderly individuals account for one‐third of all hospitalizations. The goal of this study was to evaluate the prevalence of dysphagia in elderly patients admitted to a tertiary care center. It also sought to investigate how dysphagia is identified, how it covaries with malnutrition and other conditions, and how it impacts hospital stay.

Study Design

Case Series.

Methods

A retrospective chart review was performed. All patients >65 years admitted to a tertiary care center in January and February 2016 were included. Patients with primary psychiatric diagnoses and patients with upper aerodigestive tract malignancy or surgery were excluded.

Results

A total of 655 patients were identified. Mean age was 76.6 years. Twenty‐four percent (155 patients) had dysphagia while 43% (282 patients) had malnutrition. Thirteen percent (84 patients) had both dysphagia and malnutrition. Fifty percent of patients who had malnutrition were seen by speech language pathology (SLP). One hundred percent of malnourished patients that saw SLP were identified as having dysphagia. Three hundred and eighty‐two patients (58%) were seen by the dietician but not by SLP. Multiple logistic regression indicated that the presence of dysphagia was positively associated with age, presence of malnutrition, admission to either cardiology or neurology service as compared to medicine service, and history of stroke.

Conclusions

One‐quarter of elderly patients admitted to our tertiary care center had dysphagia. Dysphagia, especially when linked with malnutrition, has poorer outcomes and increased healthcare costs. Our data suggests a possible disconnect between malnutrition diagnosis and dysphagia identification. This is an important area of intervention that has the potential to improve the treatment and outcomes of these patients.

Level of Evidence

4 Laryngoscope, 131:2441–2447, 2021
A long‐term no‐tillage system can increase enzymatic activity and maintain bacterial richness in paddy fields
Authors: Carlos Filipe Selau , Schaffer Naihana , Marcolin Elio , Fernandes Rodrigo Schmitt , Mariot Roberta , Mazzurana Michael , Roesch Luiz Fernando Wurdig , Levandoski Bruno , de Oliveira Camargo Flávio Anastácio
Published: January 2021

Soil management systems cause many changes in the microenvironment that directly affect activity and diversity of microorganisms. In lowlands, there is a gap in relation to the adoption of no‐tillage (zero‐tillage) and the impact it has on soil under cultivation of irrigated rice. This study, an in‐field experiment, evaluated the microbial enzymatic activity and diversity in an Entisol cultivated with rice under different managements for 22 years. The experiment started in the 1994/95 growing season, and the treatments were no‐tillage, conventional, and pregerminated management systems. After 22 years, the data obtained on most of the evaluation dates indicated that no‐tillage increased microbial biomass carbon (+45%), microbial biomass nitrogen (+54%), and basal respiration (+54%). No‐tillage compared to management under soil tillage (pregerminated and conventional tillage) increased the activity of β‐glucosidase (+43%), acid phosphatase (+68%), diacetate fluorescein (+34%), and urease (+96%). The enzyme activity was correlated with the soil organic carbon content and particulate fraction. Despite the relatively high enzyme activity with no‐tillage, bacterial richness was maintained in this soil management system. TheProteobacteriaphylum has a greater abundance in the NT (43.2%) in relation to the CT (32.3%).Bacteroidetesphylum has a lower abundance in the NT (10.0%) in relation to the CT (15.2%). TheVerrucomicrobiaphylum has a greater abundance in NT (8.9%) in relation to CT (4.9%). The results suggest that no‐tillage is an important management tool in the recovery of irrigated rice areas whose soil has undergone microbiological degradation.
A sensitive fluorescent assay for measuring carbon‐phosphorus lyase activity in aquatic systems
Authors: Granzow Benjamin N. , Sosa Oscar A. , Gonnelli Margherita , Santinelli Chiara , Karl David M. , Repeta Daniel J.
Published: January 2021

In the oligotrophic ocean where inorganic phosphate (Pi) concentrations are low, microorganisms supplement their nutrient requirements with phosphorus (P) extracted from dissolved organic matter (DOM). Most P in DOM is bound as phosphate esters, which are hydrolyzed by phosphoesterases to Pi. However, a large fraction of DOM‐P occurs as phosphonates, reduced organophosphorus compounds with a CP bond that do not yield Pi through simple ester hydrolysis alone. Phosphonates require an additional step that cleaves the CP bond and oxidizes P(III) to P(V) to yield Pi. Most phosphonates are metabolized by the C‐P lyase pathway, which cleaves CP bonds and oxidizes phosphonates to Pi, enabling microbial assimilation. While the activity of common phosphoesterases such as alkaline phosphatase and phosphodiesterase can be measured by a fluorescent assay, a comparable method to assess C‐P lyase activity (CLA) in natural water samples does not exist. To address this, we synthesized a dansyl‐labeled phosphonate compound, and measured its hydrolysis by C‐P lyase using high performance liquid chromatography. We found that laboratory cultures of marine bacteria expressing the C‐P lyase pathway are able to hydrolyze the dansyl phosphonate, while bacteria expressing other phosphonate degradation pathways do not. Finally, we performed several field tests of the assay to measure water column profiles of CLA at Sta. ALOHA in the North Pacific Subtropical Gyre. Activity was elevated near the deep chlorophyll maximum suggesting high levels of phosphonate degradation in that region.
Loss‐of‐function or gain‐of‐function variations in VINCULIN (VCL) are risk factors of human neural tube defects
Authors: Wang Yalan , Qin Yue , Peng Rui , Wang Hongyan
Published: January 2021

Background

Neural tube defects (NTDs) are severe birth defects resulting from the failure of neural tube closure during embryogenesis. Both genetic and environmental factors contribute to the occurrence of NTDs and the heritability of NTDs is approximately 70%. As a key component of focal adhesions, Vinculin (VCL) plays pivotal roles in cell skeleton remodeling and signal transduction. Vcl deficient mice displayed NTD, but how VCL variants contribute to human NTDs has not been addressed yet.

Methods

We screened VCL variants in a Chinese cohort of 387 NTDs and 244 controls by targeted next‐generation sequencing.

Results

We identified four case‐specific VCL variations (p.M209L, p.D256fs, p.L555V and p.R586Q). VCL p.D256fs and p.L555V are novel variations that have never been reported. Our analysis revealed that p.D256fs is a loss‐of‐function variant, while p.L555V showed a gain of function in planner cell polarity (PCP) pathway regulation and cell migration, probably due to its enhanced protein stability.

Conclusion

Our study reports human NTD specific novel variations in VCL and provides the functional evaluation of VCL variants related to the etiology of human NTDs.
Kynurenine‐Induced Aryl Hydrocarbon Receptor Signaling in Mice Causes Body Mass Gain, Liver Steatosis, and Hyperglycemia
Authors: Rojas Itzel Y. , Moyer Benjamin J. , Ringelberg Carol S. , Wilkins Owen M. , Pooler Darcy B. , Ness Dylan B. , Coker Shodeinde , Tosteson Tor D. , Lewis Lionel D. , Chamberlin Mary D. , Tomlinson Craig R.
Published: January 2021

Objective

The aryl hydrocarbon receptor (AHR) plays a key role in obesity.In vitrostudies revealed that the tryptophan metabolite kynurenine (Kyn) activates AHR signaling in cultured hepatocytes. The objective of this study was to determine whether Kyn activated the AHR in mice to induce obesity.

Methods

Mice were fed a low‐fat diet and the same diet supplemented with Kyn. Body mass, liver status, and the expression of identified relevant genes were determined.

Results

Kyn caused mice to gain significant body mass, develop fatty liver and hyperglycemia, and increase expression levels of cytochrome P450 1B1 and stearoyl‐CoA desaturase 1. The hyperglycemia was accompanied with decreased insulin levels, which may have been due to the repression of genes involved in insulin secretion. Kyn plasma concentrations and BMI were measured in female patients, and a significant association was observed between Kyn and age in patients with obesity but not in patients who were lean.

Conclusions

Results show that (1) Kyn or a metabolite thereof is a ligand responsible for inducing AHR‐based obesity, fatty liver, and hyperglycemia in mice; (2) plasma Kyn levels increase with age in women with obesity but not in lean women; and (3) an activated AHR is necessary but not sufficient to attain obesity, a status that also requires fat in the diet.
Children with Severe Obesity in Family‐Based Obesity Treatment Compared with Other Participants: Conclusions Depend on Metrics
Authors: Hayes Jacqueline F. , Fowler Lauren A. , Balantekin Katherine N. , Saelens Brian E. , Stein Richard I. , Perri Michael G. , Welch R. Robinson , Epstein Leonard H. , Wilfley Denise E.
Published: January 2021

Objective

This study compares children with severe obesity and children with mild obesity/overweight participating in family‐based obesity treatment (FBT) on change in (1) relative weight and adiposity and (2) psychosocial distress.

Methods

Children 7 to 11 years old (N = 241) and their parents participated in 12 months of behavioral treatment (FBT + maintenance treatment) and completed anthropometric, adiposity, and psychosocial assessments (psychiatric disorder symptomology, quality of life). Severe obesity was defined as a baseline BMI ≥ 120% of the 95th percentile (N = 105).

Results

At 12 months, 40% of children with baseline severe obesity no longer had severe obesity. Percent overweight and fat mass index measurements showed similar magnitudes of change among children with severe obesity and children with mild obesity/overweight, whereas BMI z score and percent body fat change was lower in the group with severe obesity. Youth with severe obesity were higher on some measures of psychosocial distress at baseline but generally experienced improvements similar to children with mild obesity/overweight.

Conclusions

FBT with maintenance treatment is beneficial for children with severe obesity and is recommended for use prior to more invasive treatments in severe pediatric obesity. Future studies should assess the necessity of additional treatment, as children with severe obesity still have high relative weights post intervention.
Associations Between Self‐Reported Weight History and Sarcopenic Obesity in Adults with Knee Osteoarthritis
Authors: Godziuk Kristine , Prado Carla M. , Woodhouse Linda J. , Forhan Mary
Published: January 2021

Objective

The purpose of this study was to examine associations between self‐reported weight history and sarcopenic obesity in adults with advanced knee osteoarthritis (OA).

Methods

Self‐reported weight history was collected from n = 151 adults (58.9% female) with knee OA and BMI ≥30 kg/m2 in a cross‐sectional study. Body composition was assessed using dual‐energy x‐ray absorptiometry. Sarcopenic obesity was defined as appendicular skeletal muscle mass, adjusted by BMI, <0.51 kg/m2 in females and <0.79 kg/m2 in males; prevalence was 27.2%. Weight gain in the preceding year, weight gain ≥5% of body weight in the past decade, and multiple weight cycling events in life‐span (loss of ≥10 lb [4.5 kg] with regain ≥3 times) were examined using logistic regression (adjusted by age, sex, and %fat mass), with the dependent variable of sarcopenic obesity presence.

Results

Weight gain in the preceding year was associated with sarcopenic obesity (odds ratio [OR]: 2.45, 95% CI: 1.02‐5.87). No associations were found with weight gain in the past decade (OR: 1.04, 95% CI: 0.43‐2.5) or weight cycling (OR: 0.86, 95% CI: 0.37‐2.01).

Conclusions

In adults with obesity and advanced knee OA, self‐reported weight gain in the preceding year was associated with sarcopenic obesity. This patient population may benefit from recommendations that prioritize prevention of weight gain.
Pembrolizumab in Patients with Advanced Metastatic Germ Cell Tumors
Authors: Tsimberidou Apostolia-Maria , Vo Henry Hiep , Subbiah Vivek , Janku Filip , Piha-Paul Sarina , Yilmaz Bulent , Gong Jing , Naqvi Mohammad Faraz , Tu Shi-Ming , Campbell Matthew , Meric-Bernstam Funda , Naing Aung
Published: January 2021

Lessons Learned

Background

Advanced germ cell tumors are associated with poor prognosis. We investigated the role of pembrolizumab in patients with advanced germ cell tumors.

Methods

We analyzed a prespecified cohort of an open-label, phase II clinical trial in which patients with advanced germ cell tumors were treated with pembrolizumab (200 mg) intravenously every 21 days. The endpoints of the study were the non-progression rate (NPR) at 27 weeks, safety, and tolerability. An NPR >20% was considered successful and worthy of further pursuit.

Results

From August 2016 to February 2018, 12 patients (10 men, 2 women) were treated (median age, 35 years [range, 22–63 years]; median number of prior systemic therapies, 3.5 [range, 2–7]; median number of metastatic sites, 3 [range, 2–8]). Overall, pembrolizumab was well tolerated. One patient experienced both grade 1 immune-related skin rash and grade 3 immune-related pneumonitis. No patient died from toxicity. Three patients had radiographic stable disease that lasted for 10.9 months, 5.5 months, and 4.5 months, respectively. No objective response was noted. The median progression-free survival was 2.4 months (95% confidence interval [CI], 1.5–4.5 months), and the median overall survival was 10.6 months (95% CI, 4.6–27.1 months). The 27-week NPR was 9.0% (95% CI, 0.23–41.2%).

Conclusion

Overall, pembrolizumab was safe and had limited antitumor activity in these patients. In the advanced, metastatic setting, tumor profiling to understand the mechanisms of resistance to immunotherapy and innovative clinical trials to identify efficacious combination regimens rather than off-label use of pembrolizumab are warranted.
Statistic Replacement of Lanthanide Ions in Bis‐salicylatoborate Coordination Polymers for the Deliberate Control of the Luminescence Chromaticity
Authors: Zottnick Sven H. , Sprenger Jan A. P. , Finze Maik , Müller‐Buschbaum Klaus
Published: January 2021

Based on the strand‐like coordination polymer (CP) type 1∞[Ln(BSB)3(py)2], [BSB]−=bis‐salicylatoborate anion, mixed Eu/Tb‐containing compounds of the constitution 1∞[EuxTb1−x(BSB)3(py)2] were synthesised ionothermally for a phase width of (x=0.25–0.75) and characterized regarding structure and optical properties. Previously, known only for other lanthanides, the mixed 1D−Eu/Tb‐CPs show excellent options for statistic replacement of the Ln‐cations during synthesis yielding solid solutions. The products are highly luminescent, with the chromaticity being a direct function of the amount of the respective Ln‐ions. Corresponding to an overall addition of emission intensities, the green Tb3+ emission and the red Eu3+ emission allow for a chromaticity control that also includes yellow emission. Control of the luminescence colour renders them suitable examples of the versatility of statistic replacement of metal ions in coordination chemistry. In addition, crystallization of [EMIm]2[YCl5(py)] illuminates possible other products of the ionothermal reactions of [EMIm][BSB] with LnCl3 constituted by components not being part of the main CPs.
Extremely Low Vapor‐Pressure Data as Access to PC‐SAFT Parameter Estimation for Ionic Liquids and Modeling of Precursor Solubility in Ionic Liquids
Authors: Bülow Mark , Greive Moritz , Zaitsau Dzmitry H. , Verevkin Sergey P. , Held Christoph
Published: January 2021

Precursor solubility is a crucial factor in industrial applications, dominating the outcome of reactions and purification steps. The outcome and success of thermodynamic modelling of this industrially important property with equations of states, such as Perturbed‐Chain Statistical Associating Fluid Theory (PC‐SAFT), vastly depends on the quality of the pure‐component parameters. The pure‐component parameters for low‐volatile compounds such as ionic liquids (ILs) have been commonly estimated using mixture properties, e. g. the osmotic pressure of aqueous solutions. This leads to parameters that depend on the solvent, and transferability to other mixtures often causes poor modeling results. Mixture‐independent experimental properties would be a more suitable basis for the parameter estimation offering a way to universal parameter sets. Model parameters for ILs are available in the literature [10.1016/j.fluid.2012.05.029], but they were estimated using pure‐IL density data. The present work focuses on a step towards a more universal estimation strategy that includes new experimental vapor‐pressure data of the pure IL. ILs exhibit an almost negligible vapor pressure in magnitude of usually 10−5 Pa even at elevated temperatures. In this work, such vapor‐pressure data of a series of 1‐ethyl‐3‐methyl‐imidazolium‐based [C2mim]‐ILs with various IL‐anions (e. g. tetrafluoroborate [BF4]−, hexafluorophosphate [PF6]−, bis(trifluoromethylsulfonyl)imide [NTf2]−) were experimentally determined and subsequently used for PC‐SAFT parameter estimation. The so‐determined parameters were used to predict experimental molecular precursor solubility in ILs and infinitely diluted activity coefficients of various solvents in ILs. The parameters were further compared to modeling results using classical parametrization methods (use of liquid‐density data only for the molecular PC‐SAFT and the ion‐based electrolyte PC‐SAFT). As a result, the modeled precursor solubilities using the new approach are much more precise than using the classical parametrization methods, and required binary parameters were found to be much smaller (if needed). In sum, including the pure‐component vapor‐pressure data of ILs opens the door towards parameter estimation that is not biased by mixture data. This procedure might be suitable also for polymers and for all kind of ionic species but needs extension to ion‐specific parametrization in the long term.
Magnesium Oxide‐Catalyzed Conversion of Chitin to Lactic Acid
Authors: Kun‐asa Kodchakon , Reubroycharoen Prasert , Yamazaki Kiyoyuki , Mimura Naoki , Sato Osamu , Yamaguchi Aritomo
Published: January 2021

Although chitin, an N‐acetyl‐D‐glucosamine polysaccharide, can be converted to valuable products by means of homogeneous catalysis, most of the chitin generated by food processing is treated as industrial waste. Thus, a method for converting this abundant source of biomass to useful chemicals, such as lactic acid, would be beneficial. In this study, we determined the catalytic activities of various metal oxides for chitin conversion at 533 K and found that MgO showed the highest activity for lactic acid production. X‐ray diffraction analysis and thermogravimetry‐differential thermal analysis showed that the MgO was transformed to Mg(OH)2 during chitin conversion. The highest yield of lactic acid (10.8 %) was obtained when the reaction was carried out for 6 h with 0.5 g of the MgO catalyst. The catalyst could be recovered as a solid residue after the reaction and reused twice with no decrease in the lactic acid yield.
China–Pakistan economic corridor (CPEC), tourism demand, and environmental concerns: Policy implications for sustainable tourism in Gilgit‐Baltistan
Authors: Nazneen Shama , Hong Xu , Jenkins Carson L. , Ud Din Nizam
Published: January 2021

The mega‐infrastructural development project provides easy access to remarkable tourism destinations and keeps attracting tourists. Tourist data from the tourism department of Gilgit‐Baltistan (GB), Pakistan, show that the China–Pakistan Economic Corridor (CPEC) project's impact positively relates to tourism demand. GB is at the early stage of tourism development, and residents show a willingness to support tourism even though tourism costs outweigh benefits. Besides, the existing tourism policy of Gilgit‐Baltistan focuses explicitly on economic sustainability but overlooks the socio‐cultural and environmental concerns. Therefore, the present study based on the stakeholder theory provides policy implications to minimize adverse effects on socio‐cultural and ecological resources and achieve sustainable tourism.
On the motion of a snake‐like soft robot
Authors: Lamping Frederik , Seis Robin , de Payrebrune Kristin M.
Published: January 2021

In this work, we investigate the locomotion of a snake‐like soft robot in terms of its design. Therefore the backbone of the robot is represented by a curve in plane which is actuated by a given curvature. By adding anisotropic friction between robot and surface the robot “moves” on the surface.

With this simple model we are able to predict the locomotion of the robot for certain sets of parameters. This allows to evaluate the influence of design changes and hence to facilitate the design process. As an example, we discuss results concerning the precision of actuation, the bending radius of the robot and the influence of friction between robot and surface.
The Effect of Functionally‐Graded Voids and GNPs on the Damage Tolerance of Polyurethane Foam Core
Authors: Al-Maharma Ahmad Y. , Sendur Polat , Patil Sandeep P. , Markert Bernd
Published: January 2021

The weight of sandwich composite structures with foam cores mainly depends on the volume fraction and the distribution of air voids in its porous structure. A considerable reduction of the weight can be achieved at the expense of mechanical and strength properties by increasing the fraction of air voids in the sandwich composite's core. Therefore, high stiffness nano‐fillers such as graphene nano‐platelets (GNPs) are frequently used to improve the specific stiffness and mechanical strength of sandwich composites without sacrificing from the lightweight requirements. In this contribution, the effect of the square‐ and circle‐shaped distributions of air‐voids and GNPs on damage tolerance properties of thermoplastic polyurethane (TPU) resin is investigated. TPU foams with randomly oriented air voids and GNPs are used as a baseline to evaluate the improvement of the properties mentioned above. For that purpose, finite element based micro‐mechanical models for representative volume elements (RVEs) are used to homogenize the properties of multi‐scale models of TPU foam. The analysis results show that the air pores increase the ductility of brittle TPU resin significantly when the pores are non‐linearly distributed in circular functionally graded (FG) shape. Besides, it is concluded that Young's modulus degradation associated with the use of linearly distributed air‐voids composed of the square‐shaped FG foam can be compensated by using GNPs. The results of the study suggest that the functional grading design of TPU foam has excellent potential for applications, which require meeting the challenging weight, strength, stiffness and toughness requirements at the same time.
Virtual Testing of Geometrically Imperfect Additively Manufactured Lattice Structures
Authors: Gebhardt Ulrike , Kästner Markus , Hufenbach Julia Kristin , Kühn Uta , Berner Matthias , Holtzhausen Stefan
Published: January 2021

Additively manufactured lattice structures increase the lightweight potential of components for technical applications. When modelling the mechanical behaviour of those lattice structures, imperfections within the structures need to be considered.

In this contribution we investigate the effect of process induced pores of varying size and location inside the lattice structure during pressure tests using a 2D minimal model in two configurations. It shows that the location of pores with respect to the configuration of the model has a strong influence on whether the imperfection decreases the mechanical performance.
Simulation and Development of Biomimetic Electrospun PCL Nanofibrous Tympanic Membrane Implants
Authors: Chen Zhaoyu , Benecke Lukas , Kempert Philipp , Stoppe Thomas , Bornitz Matthias , Neudert Marcus , Aibibu Dilbar , Cherif Chokri , Zahnert Thomas
Published: January 2021

Electrospun membranes have a great potential in myringoplasty, as the special microstructure of fibers could be comparable to the fiber structure of the tympanic membrane (TM), thus, making it an potential implant for tympanic membrane reconstruction. In this work, the microscale parameters of the fiber structure were studied in a numerical homogenization procedure. The aim of the investigations was to obtain an implant that has a compromise between acoustic and mechanical properties and which at macroscale is comparable with the human TM. The numerical results were verified with experiments on first samples.
Fluid‐Structure Interaction Simulations of Aortic Dissection
Authors: Schussnig Richard , Rolf-Pissarczyk Malte , Holzapfel Gerhard A. , Fries Thomas-Peter
Published: January 2021

The numerical modeling of aortic dissection (AD) is a particularly challenging biomechanical application, since the underlying coupling of tissue deformation and blood flow has to be considered, leading to a fluid‐structure interaction (FSI) problem. To improve clinical relevance, patient‐specific data and state‐of‐the‐art constitutive models have to be incorporated. Computational methods to consider for tissue prestress and fiber orientation are presented herein.
Inverse Design Based on Nonlinear Thermoelastic Material Models
Authors: Zwicke Florian , Hohlweck Tobias , Hopmann Christian , Elgeti Stefanie
Published: January 2021

This paper describes two approaches for the optimisation of the injection moulding process. The objective of both approaches is to reduce the warpage of the produced part. One approach consists in the thermal optimisation of the injection mould in order to reduce inhomogeneities in the cooling behaviour that greatly impact on the material warpage. In the other approach, an improved mould cavity shape is determined that will lead to a part shape that is closer to the target. The combination of both of these approaches is a powerful tool for the design of injection moulds.
Dynamic load balancing for large‐scale mortar contact formulations
Authors: Mayr Matthias , Popp Alexander
Published: January 2021

Parallel computing plays a vital role when solving large problems in computational mechanics, which might not be tractable by serial computers. Yet, in order to utilize parallel computing hardware effectively, appropriate balancing of the computational work load among all parallel processes is crucial to speed up computations and to avoid waste of computational resources. The present contribution addresses the question of optimal load balancing in the context of contact problems with a particular focus on dynamic contact scenarios, i.e. contact problems with large relative motion and significant changes in the contact configuration over time. To this end, we analyze the issue of load imbalance in contact problems, propose a load balancing strategy for dynamic contact problems, and demonstrate optimal balance and scalability for some application‐driven test cases.