bluuebunny/crossref_metadata_2025 huggingface dataset:
Empagliflozin inhibits Na+/H+ exchanger activity in human atrial cardiomyocytes
Authors: Trum Maximilian , Riechel Johannes , Lebek Simon , Pabel Steffen , Sossalla Samuel T. , Hirt Stephan , Arzt Michael , Maier Lars S. , Wagner Stefan
Published: September 2020

Aims

Recent clinical trials have proven gliflozins to be cardioprotective in diabetic and non‐diabetic patients. However, the underlying mechanisms are incompletely understood. A potential inhibition of cardiac Na+/H+ exchanger 1 (NHE1) has been suggested in animal models. We investigated the effect of empagliflozin on NHE1 activity in human atrial cardiomyocytes.

Methods and results

Expression of NHE1 was assessed in human atrial and ventricular tissue via western blotting. NHE activity was measured as the maximal slope of pH recovery after NH4+ pulse in isolated carboxy‐seminaphtarhodafluor 1 (SNARF1)‐acetoxymethylester‐loaded murine ventricular and human atrial cardiomyocytes. NHE1 is abundantly expressed in human atrial and ventricular tissue. Interestingly, compared with patients without heart failure (HF), atrial NHE1 expression was significantly increased in patients with HF with preserved ejection fraction and atrial fibrillation. The largest increase in atrial and ventricular NHE1 expression, however, was observed in patients with end‐stage HF undergoing heart transplantation. Importantly, acute exposure to empagliflozin (1 μmol/L, 10 min) significantly inhibited NHE activity to a similar extent in human atrial myocytes and mouse ventricular myocytes. This inhibition was also achieved by incubation with the well‐described selective NHE inhibitor cariporide (10 μmol/L, 10 min).

Conclusions

This is the first study systematically analysing NHE1 expression in human atrial and ventricular myocardium of HF patients. We show that empagliflozin inhibits NHE in human cardiomyocytes. The extent of NHE inhibition was comparable with cariporide and may potentially contribute to the improved outcome of patients in clinical trials.
Sex‐based differences in biomarkers, health status, and reverse cardiac remodelling in patients with heart failure with reduced ejection fraction treated with sacubitril/valsartan
Authors: Ibrahim Nasrien E. , Piña Ileana L. , Camacho Alexander , Bapat Devavrat , Felker G. Michael , Maisel Alan S. , Butler Javed , Prescott Margaret F. , Abbas Cheryl A. , Solomon Scott D. , Januzzi James L. ,   Prospective Study of Biomarkers, Symptom Improvement and Ventricular Remodeling During Entresto Therapy for Heart Failure (PROVE‐HF) Study Investigators
Published: September 2020

Aims

We sought to determine sex‐based differences in biomarkers, self‐reported health status, and magnitude of longitudinal changes in measures of reverse cardiac remodelling among patients with heart failure with reduced ejection fraction (HFrEF, left ventricular ejection fraction ≤40%) treated with sacubitril/valsartan (S/V).

Methods and results

This was a subgroup analysis of patients initiated on S/V in the Prospective Study of Biomarkers, Symptom Improvement and Ventricular Remodeling During Entresto Therapy for Heart Failure (PROVE‐HF) study. There were 226 (28.5%) women in the study. Though women had lower baseline N‐terminal pro B‐type natriuretic peptide (NT‐proBNP), they had more rapid early reduction in the biomarker after initiation of S/V. Compared to men, women had lower average baseline Kansas City Cardiomyopathy Questionnaire (KCCQ)‐23 Total Symptom score (67.6 vs. 71.9; P = 0.003) but showed greater linear improvement (7.4 vs. 5.5 points; P < 0.001) and faster pace of KCCQ change (P < 0.001) over the course of the trial. Women and men demonstrated similar degrees of reverse left ventricular remodelling following S/V initiation; however, women did so earlier than men with more consistent changes. These results remained unchanged with adjustment for relevant covariates. Reduction in NT‐proBNP was associated with reverse cardiac remodelling in both women and men. Treatment with S/V was well tolerated in all.

Conclusions

In women with HFrEF, treatment with S/V was associated with significant NT‐proBNP reduction, health status improvement and reverse cardiac remodelling.
Effect of multi‐axial hot forging process on mechanical, and corrosion resistance behavior of Mg‐3Zn alloy for temporary orthopedic implants
Authors: Jaiswal Satish , Agrawal Shubham , Dubey Anshu , Lahiri Debrupa
Published: September 2020

Magnesium (Mg) is a load‐bearing biocompatible material which has the ability to reduce stress shielding effect and facilitate osteocompatibility and biodegradation in the presence of body fluids. However, Mg is highly susceptible to corrosion in the physiological environment, hence leading to poor mechanical integrity. In this study, the multi‐axial hot forging (MAHF) process is performed on Mg‐3Zn alloys to study its grain refinement and possible improvement in mechanical, corrosion, and bioactivity behavior. The average grain size of the sample becomes significantly refined after the third cycle of MAHF. The yield and ultimate compressive strength of Mg‐3Zn alloys are found to increase by 70% and 41%, respectively, after the third cycle of MAHF, which is potentially due to the grain size refinement. Accelerated corrosion studies show improvements in the corrosion resistance with the refined grain structure. Additionally, in‐vitro immersion studies in the simulated body fluid for 14 days showed a reduction in the degradation rate after third cycle of MAHF, due to the increased grain boundary area, which offered more nucleation sites for apatite precipitation. This study underscores and lays the foundation for a new branch of severely deformed fine‐grained Mg‐3Zn alloy for temporary orthopedic implants.
Felt power: Can Mexican Indigenous women finally be powerful?
Authors: Whittaker Catherine
Published: September 2020

Too often, women from the Global South have been portrayed as victims of gender violence in need of empowerment. Yet in the rural south of Mexico City, many Indigenous women expressed feeling strong, even powerful, despite their varied experiences of violence. Based on fifteen months of ethnographic fieldwork, I argue that their felt power was often rooted in their realities. Nahuatl‐speaking communities have historically recognized certain kinds of power in women (including healing magic) and others in men (including political power). Women's narratives revealed complex interactions between women's and men's power. Women often represented themselves not as helpless victims but as having the power to change their circumstances, for better or worse. I introduce felt power as a conceptual tool for centering Indigenous women's experiential, embodied, and spiritual knowledge in addressing the gender‐based violence they often experienced. Felt power is derived from Dian Million's framework of felt theory, which represents Indigenous people's narratives as feeling‐based theory‐making, rather than raw data to be theorized into abstraction by non‐Indigenous thinkers. I suggest that considering and respecting Indigenous women's felt power in the face of violence will contribute to decolonizing the study of gender violence and development agencies’ responses to it.
A meta‐analysis: Does vitamin D play a promising role in sleep disorders?
Authors: Yan Shoumeng , Tian Zhenwei , Zhao Hantong , Wang Changcong , Pan Yingan , Yao Nan , Guo Yinpei , Wang Han , Li Bo , Cui Weiwei
Published: September 2020

Background

Sleep disorders, one of the most common problems in the general population, have been related to a series of harmful health consequences. Vitamin D appears to be associated with sleep disorders. However, the difference in vitamin D levels between sleep disorder subjects and people without a sleep disorder is unclear. Simultaneously, the influence of vitamin D replenishment on sleep disorders remains controversial.

Methods

PubMed, MEDLINE, Web of Science, and Cochrane Library were searched for literatures published until October 2019. Using a random effects model, a meta‐analysis was conducted to calculate the standard mean difference to evaluate the difference in vitamin D concentrations between sleep disorder subjects and normal people and the efficacy of vitamin D supplementation on sleep disorders.

Results

Our study found that the serum vitamin D levels in the sleep disorder subjects were lower than that in the normal people (SMD = −0.75 ng/ml, 95% CI = −0.93, −0.57 ng/ml). Moreover, the Pittsburgh Sleep Quality Index (PSQI)in the subjects with vitamin D supplementation was lower than that in the controls (SMD = −0.45, 95% CI = −0.76, −0.13).

Conclusions

Vitamin D could play a promising role in sleep disorders. More data are required to confirm the efficacy of vitamin D supplementation for improving sleep disorders.
Physicochemical composition, lipid oxidation, and microbiological quality of ram mortadella supplemented with Smallanthus sonchifolius meal
Authors: do Santos Junior Alexandre Cristiano , Oliveira Rodrigo Fortunato de , Henry Fabio da Costa , Maia Junior Jonhny de Azevedo , Moulin Monique Moreira , Della Lucia Suzana Maria , Quirino Célia Raquel , Martins Meire Lelis Leal , Rampe Maria Cecília Cabral
Published: September 2020

This study evaluated the physicochemical, lipid peroxidation, and microbiological quality of mortadellas prepared with ram and supplemented with different amounts of Smallanthus sonchifolius meal. Three mutton mortadella formulations supplemented with 1.25%, 2.50%, and 5% yacón meal and control formulation without yacón meal was included. The physicochemical, lipid peroxidation, and microbiological analyses were carried out in the time periods 10, 45 days, three, and six month after the preparation of mortadella. The control formulation presenting lighter and more intense red tone compared with the other formulations. All formulations presenting lipid peroxidation increased 90 days after processing; already the pH and Aw values were constant for all formulations at the experimental times stipulated. All formulations had the physicochemical characterization and microbiological quality standards, according to defined in regulations for mortadella production in Brazil. The results show that mutton mortadella supplemented with yacón meal is a promising alternative in the manufacture of healthy meat products.
Orthogonal arrays of particle assembly are essential for normal aquaporin‐4 expression level in the brain
Authors: de Bellis Manuela , Cibelli Antonio , Mola Maria Grazia , Pisani Francesco , Barile Barbara , Mastrodonato Maria , Banitalebi Shervin , Amiry‐Moghaddam Mahmood , Abbrescia Pasqua , Frigeri Antonio , Svelto Maria , Nicchia Grazia Paola
Published: September 2020

Astrocyte endfeet are endowed with aquaporin‐4 (AQP4)‐based assemblies called orthogonal arrays of particles (OAPs) whose function is still unclear. To investigate the function of OAPs and of AQP4 tetramers, we have generated a novel “OAP‐null” mouse model selectively lacking the OAP forming M23‐AQP4 isoform. We demonstrated that AQP4 transcript levels were not reduced by using qPCR. Blue native (BN)/SDS‐PAGE and Western blot performed on OAP‐null brain and primary astrocyte cultures showed the complete depletion of AQP4 assemblies, the selective expression of M1‐AQP4‐based tetramers, and a substantial reduction in AQP4 total expression level. Fluorescence quenching and super‐resolution microscopy experiments showed that AQP4 tetramers were functionally expressed in astrocyte plasma membrane and their dimensions were reduced compared to wild‐type assemblies. Finally, as shown by light and electron microscopy, OAP depletion resulted in a massive reduction in AQP4 expression and a loss of perivascular AQP4 staining at astrocyte endfeet, with only sparse labeling throughout the brain areas analyzed. Our study relies on the unique property of AQP4 to form OAPs, using a novel OAP‐null mouse model for the first time, to show that (a) AQP4 assembly is essential for normal AQP4 expression level in the brain and (b) most of AQP4 is organized into OAPs under physiological conditions. Therefore, AQP4 tetramers cannot be used by astrocytes as an alternative to OAPs without affecting AQP4 expression levels, which is important in the physiological and pathological conditions in which OAP aggregation/disaggregation dynamics have been implicated.
Neuroinflammatory inhibition of synaptic long‐term potentiation requires immunometabolic reprogramming of microglia
Authors: York Elisa M. , Zhang Jingfei , Choi Hyun B. , MacVicar Brian A.
Published: September 2020

Immunometabolism refers to the rearrangement of metabolic pathways in response to immune stimulation, and the ability of these metabolic pathways themselves to control immune functions. Many aspects of immunometabolism have been revealed through studies of peripheral immune cells. However, immunometabolic reprogramming of microglia, the resident immune cell of the central nervous system, and the consequential outcome on neuronal activity have remained difficult to unravel. Microglia are highly sensitive to subtle changes in their environment, limiting the techniques available to study their metabolic and inflammatory profiles. Here, using fluorescence lifetime imaging of endogenous NAD(P)H, we measure the metabolic activity of individual microglia within acute hippocampal slices. We observed an LPS‐induced increase in aerobic glycolysis, which was blocked by the addition of 5 mM 2‐deoxyglucose (2DG). This LPS‐induced glycolysis in microglia was necessary for the stabilization of hypoxia inducible factor‐1α (HIF‐1α) and production of the proinflammatory cytokine, interleukin‐1β (IL‐1β). Upon release, IL‐1β acted via the neuronal interleukin‐1 receptor to inhibit the formation of synaptic long‐term potentiation (LTP) following high frequency stimulation. Remarkably, the addition of 2DG to blunt the microglial glycolytic increase also inhibited HIF‐1α accumulation and IL‐1β production, and therefore rescued LTP in LPS‐stimulated slices. Overall, these data reveal the importance of metabolic reprogramming in regulating microglial immune functions, with appreciable outcomes on cytokine release and neuronal activity.
Prognostic models integrating quantitative parameters from baseline and interim positron emission computed tomography in patients with diffuse large B‐cell lymphoma: post‐hoc analysis from the SAKK38/07 clinical trial
Authors: Zucca Emanuele , Cascione Luciano , Ruberto Teresa , Facchinelli Davide , Schär Sämi , Hayoz Stefanie , Dirnhofer Stefan , Giovanella Luca , Bargetzi Mario , Mamot Christoph , Ceriani Luca
Published: September 2020

Positron emission computed tomography (PET/CT) in patients with diffuse large B‐cell lymphoma (DLBCL) enrolled in a prospective clinical trial were reviewed to test the impact of quantitative parameters from interim PET/CT scans on overall (OS) and progression‐free (PFS) survival. We centrally reviewed baseline and interim PET/CT scans of 138 patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone given every 14 days (R‐CHOP14) in the SAKK38/07 trial (ClinicalTrial.gov identifier: NCT00544219). Cutoff values for maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and metabolic heterogeneity (MH) were defined by receiver operating characteristic analysis. Responses were scored using the Deauville scale (DS). Patients with DS 5 at interim PET/CT (defined by uptake >2 times higher than in normal liver) had worse PFS (P = 0.014) and OS (P < 0.0001). A SUVmax reduction (Δ) greater than 66% was associated with longer PFS (P = 0.0027) and OS (P < 0.0001). Elevated SUVmax, MTV, TLG, and MH at interim PET/CT also identified patients with poorer outcome. At multivariable analysis, ΔSUVmax and baseline MTV appeared independent outcome predictors. A prognostic model integrating ΔSUVmax and baseline MTV discriminated three risk groups with significantly (log‐rank test for trend, P < 0.0001) different PFS and OS. Moreover, the integration of MH and clinical prognostic indices could further refine the prediction of OS. PET metrics‐derived prognostic models perform better than the international indices alone. Integration of baseline and interim PET metrics identified poor‐risk DLBCL patients who might benefit from alternative treatments.
DNMT1 maintains the methylation of miR‐152‐3p to regulate TMSB10 expression, thereby affecting the biological characteristics of colorectal cancer cells
Authors: Wang Chenchen , Ma Xiaoji , Zhang Jieyun , Jia Xiaobin , Huang Mingzhu
Published: September 2020

Objective

DNA methyltransferases (DNMTs) take on a relevant role in epigenetic control of cancer proliferation and cell survival. However, the molecular mechanisms underlying the establishment and maintenance of DNA methylation in human cancer remain to be fully elucidated. This study was to investigate that how DNMT1 affected the biological characteristics of colorectal cancer (CRC) cells via modulating methylation of microRNA (miR)‐152‐3p and thymosin β 10 (TMSB10) expression.

Methods

DNMT1, miR‐152‐3p, and TMSB10 expression, and the methylation of miR‐152‐3p in CRC tissues and cells were detected. SW‐480 and HCT‐116 CRC cells were transfected with DNMT1 or miR‐152‐3p‐related sequences or plasmids to explore their characters in biological functions of CRC cells. The binding relationship between DNMT1 and miR‐152‐3p and the targeting relationship between miR‐152‐3p and TMSB10 were analyzed. The tumor growth was also detected in vivo.

Results

Upregulated DNMT1, TMSB10, reduced miR‐152‐3p, and methylated miR‐152‐3p were detected in CRC tissues and cells. Silenced DNMT1 or upregulated miR‐152‐3p reduced TMSB10 expression and suppressed CRC progression and tumor growth. Moreover, elevated DNMT1 could reverse the effect of miR‐152‐3p upregulation on CRC development and tumor growth. DNMT1 maintained methylation of miR‐152‐3p. TMSB10 was the direct target gene of miR‐152‐3p.

Conclusion

The study highlights that silenced DNMT1 results in non‐methylated miR‐152‐3p to depress TMSB10 expression, thereby inhibiting CRC development, which provides a new approach for CRC therapy.
Effects of Self‐Compassion and Social Support on Lesbian, Gay, and Bisexual College Students' Positive Identity and Career Decision‐Making
Authors: Jang Hansori , Woo Hongryun , Lee Injung
Published: September 2020

The purpose of this study was to explore the serial mediating effects of self‐compassion and social support on the relationship between positive identity and career decision‐making self‐efficacy (CDMSE) among lesbian, gay, and bisexual (LGB) college students. A total of 222 LGB (109 bisexual, 113 lesbian/gay) students participated in the study. Results supported the mediating roles of self‐compassion and social support. Specifically, self‐compassion and social support sequentially mediated the relationship between positive identity and CDMSE, and the patterns of the sequence of the mediators were different between the bisexual and lesbian/gay groups. Implications for career counselors and future research are discussed.
Synthesis, in vitro cytotoxicity, ADME, and molecular docking studies of benzimidazole‐bearing furanone derivatives
Authors: Husain Asif , Bhutani Medha , Parveen Shazia , Khan Shah Alam , Ahmad Aftab , Iqbal Md Azhar
Published: September 2020

A series of benzimidazole‐derived–furanones (4a–l) were synthesized, characterized, and explored for their in vitro anticancer activities. The pharmacokinetic parameters assessed revealed that all the compounds followed the Lipinski's rule of five, making them potential drug candidates. Further, the results of anticancer activity revealed that (E)‐5‐(1H‐benzo[d]imidazol‐2‐yl)‐3‐(3,4,5‐trimethoxybenzylidene)furan‐2(3H)‐one (4a), was active against A549, MCF7, and DU145 with an IC50 values of 10.4 ± 0.39, 11.1 ± 0.43, and 10.7 ± 0.19 μM, respectively. While another compound (E)‐5‐(1H‐benzo[d]imidazol‐2‐yl)‐3‐([5‐phenyl]furan‐2‐yl)furan‐2(3H)‐one (4k) also exhibited good activity against A549, MCF7, and DU145 with IC50 values of 11.4 ± 0.39, 9.1 ± 0.43, and 12.7 ± 0.19 μM, respectively. Doxorubicin was used as the standard drug. Further, molecular docking studies were carried out to provide binding mode into the binding sites of vascular endothelial growth factor receptor (VEGFR). Docking scores and binding energies corroborated well with the results of experimental anticancer activity. Pharmacokinetic (ADME) parameters of the potent derivatives were also found to be in an acceptable range. The benzimidazole‐furanonone conjugates seem to be a potential source for the further development of potent cytotoxic agents.
Meaning profiles and the perception of the working alliance at the start of outpatient person‐centered, experiential, and existential psychotherapies
Authors: Golovchanova Nadezhda , Dezutter Jessie , Vanhooren Siebrecht
Published: September 2020

Objective(s)

Quantitative research on meaning in life in the context of psychotherapy is relatively limited. The current study aims to investigate the profiles of the meaning of clients and their perception of the working alliance and initial symptomatology at the start of therapy.

Design

In a sample of 145 clients (62.1% female; mean age, 34.77) who started person‐centered psychotherapy, the relationship between meaning, search for meaning, symptomatology, and the working alliance was analyzed. The assessment took place after the second session.

Results

Cluster analysis revealed four profiles: Low Presence High Search, High Presence Low Search, High Presence High Search, and Low Presence Low Search. These meaning profiles are distinguished in terms of symptomatology but not in terms of the working alliance perception. However, the experience of meaning is significantly associated with the working alliance.

Conclusions

Results show the relevance of meaning‐related questions for certain groups of clients at the start of therapy.
Validation of a description of sarcopenic obesity defined as excess adiposity and low lean mass relative to adiposity
Authors: Baker Joshua F. , Harris Tamara , Rapoport Allegra , Ziolkowski Susan L. , Leonard Mary B. , Long Jin , Zemel Babette , Weber David R.
Published: September 2020

Background

This study aims to assess the construct validity of a body composition‐defined definition of sarcopenic obesity based on low appendicular lean mass relative to fat mass (ALMIFMI) and high fat mass index (FMI) and to compare with an alternative definition using appendicular lean mass index (ALMI) and percent body fat (%BF).

Methods

This is a secondary analysis of two cohort studies: the National Health and Examination Survey (NHANES) and the Health, Aging, and Body Composition study (Health ABC). Sarcopenic obesity was defined as low ALMIFMI combined with high FMI and was compared with a widely used definition based on ALMI and %BF cut‐points. Body composition Z‐scores, self‐reported disability, physical functioning, and incident disability were compared across body composition categories using linear and logistic regression and Cox proportional hazards models.

Results

Among 14, 850 participants from NHANES, patients with sarcopenic obesity defined by low ALMIFMI and high FMI (ALMIFMI‐FMI) had above‐average FMI Z‐scores [mean (standard deviation): 1.00 (0.72)]. In contrast, those with sarcopenic obesity based on low ALMI and high %BF (ALMI‐%BF) had below‐average FMI Z‐scores. A similar pattern was observed for 2846 participants from Health ABC. Participants with sarcopenic obesity based on ALMIFMI‐FMI had a greater number of disabilities, worse physical function, and a greater risk of incident disability compared with those defined based on ALMI‐%BF.

Conclusions

Body composition‐defined measures of sarcopenic obesity defined as excess adiposity and lower‐than‐expected ALMI relative to FMI are associated with functional deficits and incident disability and overcome the limitations of using %BF in estimating obesity in this context.
Cancer cachexia in a mouse model of oxidative stress
Authors: Brown Jacob L. , Lawrence Marcus M. , Ahn Bumsoo , Kneis Parker , Piekarz Katarzyna M. , Qaisar Rizwan , Ranjit Rojina , Bian Jan , Pharaoh Gavin , Brown Chase , Peelor Fredrick F. , Kinter Michael T. , Miller Benjamin F. , Richardson Arlan , Van Remmen Holly
Published: September 2020

Background

Cancer is associated with muscle atrophy (cancer cachexia) that is linked to up to 40% of cancer‐related deaths. Oxidative stress is a critical player in the induction and progression of age‐related loss of muscle mass and weakness (sarcopenia); however, the role of oxidative stress in cancer cachexia has not been defined. The purpose of this study was to examine if elevated oxidative stress exacerbates cancer cachexia.

Methods

Cu/Zn superoxide dismutase knockout (Sod1KO) mice were used as an established mouse model of elevated oxidative stress. Cancer cachexia was induced by injection of one million Lewis lung carcinoma (LLC) cells or phosphate‐buffered saline (saline) into the hind flank of female wild‐type mice or Sod1KO mice at approximately 4 months of age. The tumour developed for 3 weeks. Muscle mass, contractile function, neuromuscular junction (NMJ) fragmentation, metabolic proteins, mitochondrial function, and motor neuron function were measured in wild‐type and Sod1KO saline and tumour‐bearing mice. Data were analysed by two‐way ANOVA with Tukey–Kramer post hoc test when significantFratios were determined andαwas set at 0.05. Unless otherwise noted, results in abstract are mean ±SEM.

Results

Muscle mass and cross‐sectional area were significantly reduced, in tumour‐bearing mice. Metabolic enzymes were dysregulated in Sod1KO mice and cancer exacerbated this phenotype. NMJ fragmentation was exacerbated in tumour‐bearing Sod1KO mice. Myofibrillar protein degradation increased in tumour‐bearing wild‐type mice (wild‐type saline, 0.00847 ± 0.00205; wildtype LLC, 0.0211 ± 0.00184) and tumour‐bearing Sod1KO mice (Sod1KO saline, 0.0180 ± 0.00118; Sod1KO LLC, 0.0490 ± 0.00132). Muscle mitochondrial oxygen consumption was reduced in tumour‐bearing mice compared with saline‐injected wild‐type mice. Mitochondrial protein degradation increased in tumour‐bearing wild‐type mice (wild‐type saline, 0.0204 ± 0.00159; wild‐type LLC, 0.167 ± 0.00157) and tumour‐bearing Sod1KO mice (Sod1KO saline, 0.0231 ± 0.00108; Sod1 KO LLC, 0.0645 ± 0.000631). Sciatic nerve conduction velocity was decreased in tumour‐bearing wild‐type mice (wild‐type saline, 38.2 ± 0.861; wild‐type LLC, 28.8 ± 0.772). Three out of eleven of the tumour‐bearing Sod1KO mice did not survive the 3‐week period following tumour implantation.

Conclusions

Oxidative stress does not exacerbate cancer‐induced muscle loss; however, cancer cachexia may accelerate NMJ disruption.
Developments in evidence creation for treatments of inborn errors of metabolism
Authors: Stockler‐Ipsiroglu Sylvia , Potter Beth K. , Yuskiv Nataliya , Tingley Kylie , Patterson Marc , van Karnebeek Clara
Published: September 2020

Inborn errors of metabolism (IEM) represent the first group of genetic disorders, amenable to causal therapies. In addition to traditional medical diet and cofactor treatments, new treatment strategies such as enzyme replacement and small molecule therapies, solid organ transplantation, and cell‐and gene‐based therapies have become available. Inherent to the rare nature of the single conditions, generating high‐quality evidence for these treatments in clinical trials and under real‐world conditions has been challenging. Guidelines developed with standardized methodologies have contributed to improve the practice of care and long‐term clinical outcomes. Adaptive trial designs allow for changes in sample size, group allocation and trial duration as the trial proceeds. n‐of‐1 studies may be used in small sample sized when participants are clinically heterogeneous. Multicenter observational and registry‐based clinical trials are promoted via international research networks. Core outcome and standard data element sets will enhance comparative analysis of clinical trials and observational studies. Patient‐centered outcome‐research as well as patient‐led research initiatives will further accelerate the development of therapies for IEM.
Effectiveness and surface changes of different decontamination protocols at smooth and minimally rough titanium surfaces
Authors: Stuani Vitor T. , Kim David M. , Nagai Masazumi , Chen Chia‐Yu , Sant'Ana Adriana C.P.
Published: September 2020

Background

The objective of this study is to evaluate titanium decontamination after different protocols while assessing changes in surface roughness, chemical composition, and wettability.

Methods

Ninety‐six smooth (S) and 96 minimally rough (R) titanium microimplants were used. Pristine microimplants were reserved for negative control (S‐nC/R‐nC, n = 9), while the remaining microimplants were incubated in Escherichia coli culture. Non‐decontaminated microimplants were used as positive control (S‐pC/R‐pC, n = 3). The other microimplants were divided into seven different decontamination protocols (12 S/R per group): 24% EDTA, 2% chlorhexidine (CHL), gauze soaked in 2% chlorhexidine (GCHL), gauze soaked in ultrapure water (GMQ), scaling (SC), titanium brush (TiB), and implantoplasty (IP). Contaminated areas were assessed by scanning electron microscope images, chemical composition by energy dispersive X‐ray spectroscopy, wettability by meniscus technique, and roughness by an optical profiler.

Results

Higher residual bacteria were observed in R‐pC compared with S‐pC (P <0.0001). When comparing S and R with their respective pC groups, the best results were obtained with GCHL, SC, TiB, and IP, with no difference between these protocols (P >0.05). Changes in surface roughness were observed after all treatments, with S/R‐IP presenting the smoother and a less hydrophilic surface (P <0.05). Apart from IP protocol, all the other groups presented a more hydrophilic surface in R than in S microimplants (P <0.003). All decontamination protocols resulted in a lower percentage of superficial Ti when compared with S/R‐nC (P <0.002).

Conclusions

All decontamination protocols resulted in changes in roughness, wettability, and chemical composition, but GCHL, SC, TiB, an IP presented the best decontamination outcomes.
Comparison of the pharmacokinetic profiles of 13 phenolic acids and 6 triterpenes in normal and leukopenia rats after oral administration of Sanguisorba officinalis L. extract by LC‐MS/MS
Authors: Fan Linzi , Wang Xiaotong , Huang Jing , Gan Chunli , Jiang Shuang , Yang Xinrong , Yang Chunjuan , Yao Meicun
Published: September 2020

A selective, accurate, and efficient liquid chromatography‐tandem mass spectrometry method was developed for the simultaneous determination of 13 phenolic acids. Additionally, for more comprehensively determining the chemical constituents in Sanguisorba officinalis L. extract, a previously developed method was employed for the simultaneous determination of six triterpenes. Thus, two methods were used to ensure the comprehensiveness and reliability of this study. Based on these methods, the pharmacokinetic profiles of the 13 phenolic acids and 6 triterpenes in normal and leukopenia rats after oral administration of S. officinalis L. extract were compared for the first time in the present study. Quantitative detection of the 13 phenolic acids and 6 triterpenes was performed using the multiple reaction monitoring mode with the electrospray ion source in negative and positive electrospray ionization, respectively. Chromatographic separation was performed on an Agilent Eclipse Plus C18 RRHD column (50 × 2.1 mm, 1.8 µm) using gradient elution with a mobile phase composed of methanol–0.1% aqueous formic acid. The pharmacokinetic results demonstrated that the pharmacokinetic characteristics of the 19 analytes in leukopenia rats differed significantly from those determined in normal rats, which could provide a helpful reference for the clinical application of S. officinalis L. in the prevention and treatment of leucopenia.
Supraglottic Carcinoma in Intravenous Opioid Drug Abusers: A Distinct Disease with Improved Survival
Authors: Yaniv Dan , Reuven Yonatan , Lahav Yonatan , Cohen Oded , Hamzany Yaniv , Moore Assaf , Rapana Olga G. , Argaman Natan , Halperin Doron , Popovtzer Aron , Bachar Gideon , Shoffel‐Havakuk Hagit
Published: September 2020

Objectives/Hypothesis

Recent evidence indicates an increased prevalence of intravenous opioid drug abusers (IVDAs) among supraglottic squamous cell carcinoma (SG‐SCC) patients. This study investigates whether the clinical course of SG‐SCC in IVDA differs from SG‐SCC in non‐IVDA.

Study Design

A retrospective case–control study conducted in a in two tertiary referral centers.

Methods

This case–control study compares IVDA with non‐IVDA patients diagnosed and treated for SG‐SCC in between 2005 and 2018. Disease‐free survival (DFS) and overall survival (OS) were calculated using the Kaplan–Meier estimator. Adjusted odds ratios (ORs) for mortality were calculated using multivariant analyses.

Results

A total of 124 patients were included; 21% (26) were IVDA, and 79% (98) were non‐IVDA. Age at diagnosis in the IVDA group versus the non‐IVDA group was 53 and 66 years, respectively (P = .001). Nevertheless, the age hazard ratio for OS was calculated and found to have minimal to no effect, 1.05 (95% Cl: 1.025–1.076). Otherwise, the two groups were comparable regarding demographics, other risk factors (i.e., gender, smoking, and alcohol), and comorbidities status, as well as the comparable stage at diagnosis, histologic grading, and treatment modalities. Although the DFS was comparable in both groups, the 5‐year OS was 55% in the IVDA group compared with 34% among the non‐IVDA patients (P = .04). In multivariant analyses for mortality, positive IVDA history was found to be protective, adjusted OR: 0.263 (95% CI: 0.081–0.854). Similarly, within the subgroup of 100 patients with advanced‐stage disease (III and IV), the adjusted OR was 0.118 (95% CI: 0.028–0.495).

Conclusions

SG‐SCC in IVDA patients has a distinct clinical course, presenting at a younger age, and may have improved prognosis.

Level of Evidence

NA Laryngoscope, 131:E1190–E1197, 2021
A novel GABRB3 variant in Dravet syndrome: Case report and literature review
Authors: Pavone Piero , Pappalardo Xena Giada , Marino Simona D. , Sciuto Laura , Corsello Giovanni , Ruggieri Martino , Parano Enrico , Piccione Maria , Falsaperla Raffaele
Published: September 2020

Background

Mutations in GABRB3 have been identified in subjects with different types of epilepsy and epileptic syndromes, including West syndrome (WS), Dravet syndrome (DS), Lennox‐Gastaut syndrome (LGS), myoclonic‐atonic epilepsy (MAE), and others.

Methods and results

We herewith report on a girl affected by DS, who has been followed from infancy to the current age of 18 years. Next‐generation sequencing (NGS)‐based genetic testing for multigene analysis of neurodevelopmental disorders identified two likely de novo pathogenic mutations, a missense variant in GABRB3 gene (c.842 C>T; p.Thr281IIe) and a nonsense variant found in BBS4 gene (c.883 C>T; p.Arg295Ter).

Conclusion

A likely relationship between the novel GABRB3 gene variant and the clinical manifestations presented by the girl is proposed. Previously, one case of DS and two of DS‐like linked with GABRB3 mutations have been reported. To the best of our knowledge, this is the first report of DS associated with this novel variant. A literature review of clinical cases with various types of epileptic encephalopathies (EEs) related to GABRB3 mutations is reported.
Laplace‐based variational iteration method for nonlinear oscillators in microelectromechanical system
Authors: Zhang Yanni , Pang Jing
Published: September 2020

A nonlinear oscillator arising in a microelectromechanical system (MEMS) is difficult to be solved analytically due to the zero conditions. So the main objective of this work is to analyze the mathematical model of this system, and its approximate analytical solution is solved via the coupling variational iteration method and Laplace transform (LVIM). This method provides an efficient way to obtain the approximate nonlinear frequency and approximate solutions of MEMS. Moreover, LVIM also approximates the pull‐in threshold in terms of model parameters. Finally, the results are compared with the exact one, and a good result is obtained.
Stimulation of Gastric Transit Function Driven by Hydrolyzed Casein Increases Small Intestinal Carbohydrate Availability and Its Microbial Metabolism
Authors: Shen Junhua , Mu Chunlong , Wang Huisong , Huang Zan , Yu Kaifan , Zoetendal Erwin G , Zhu Weiyun
Published: September 2020

Gastrointestinal (GI) functions affect gut nutrient flow and microbial metabolism. Dietary peptides modulate GI functions and improve small intestinal health, but the mechanism remains elusive. This study aims to investigate whether dietary peptides affect small intestinal microbial metabolism, and the underlying mechanisms. An ileal‐cannulated pig model is adopted to explore the relationship between gut nutrient flow and microbial metabolism after treatment with hydrolyzed casein (peptides) or intact casein (Control)‐based diet. The results demonstrate that hydrolyzed casein enhances microbial carbohydrate metabolism with higher Streptococcus abundance and higher lactate level in the ileum. Meanwhile, hydrolyzed casein increases ileal flows of nutrients, especially carbohydrate, leading to a higher carbohydrate availability in ileal digesta. To unveil the mechanisms, it is found that the hydrolyzed casein enhances the ghrelin signal and improves development of interstitial cells of Cajal and muscular layer in gastric corpus, indicating the enhanced upper GI transit function. In addition, hydrolyzed casein improves small intestinal health, as indicated by higher villus heights and luminal lactate concentrations in the jejunum and ileum. In conclusion, hydrolyzed casein stimulates upper GI transit function, enhances gut nutrient flow, and increases small intestinal carbohydrate availability and its microbial metabolism, which favor the small intestinal health.
Printed planar tunable composite right/left‐handed leaky‐wave antenna based on a tunable polymer‐BST substrate
Authors: Hajisaeid Ehsan , Deshmukh Shruti , Burbine Stephen J. , Keaney Erin E. , Lepont Claire , Herndon Mary , Barry Carol , Mead Joey , Akyurtlu Alkim
Published: September 2020

This article presents a printed tunable right/left‐handed leaky wave antenna (LWA) on a new flexible, tunable low density polyethylene‐barium strontium titanate composite substrate using an aerosol jet printer. The new substrate had a dielectric constant of 16 and tunability of 3.5% at f = 10 GHz. Interdigital capacitors (IDC) were utilized in the leaky wave antenna design not only to act as shunt capacitor in CRLH transmission line design but also as tunability element to implement tuning capability of the LDPE‐BST substrate for antenna beam steerability for a fixed operated frequency in X‐band frequency range. Up to 15° beam steering was achieved by applying DC voltage through the printed leaky wave antenna.
Monitoring of the sedimentation kinetics of vaccine adjuvants using water proton NMR relaxation
Authors: Taraban Marc B. , Yu Yihua Bruce
Published: September 2020

Suspensions of solid particles find applications in many areas—mining, waste treatment, and in pharmaceutical formulations. Pharmaceutical suspensions include aluminum‐adjuvanted vaccines are widely administered to millions of people worldwide annually. Hence, the stability parameters of such suspensions, for example, sedimentation rate and the compactness of the formed sediments, are of great interest to achieve the most optimal and stable formulations. Unlike currently used analytical techniques involving visual observations and/or monitoring of several optical properties using specialized glassware, water proton nuclear magnetic resonance (wNMR) used in this work allows one to analyze samples in their original sealed container regardless of its opacity and/or labeling. It was demonstrated that the water proton transverse relaxation rate could be used to monitor in real time the sedimentation process of two widely used aluminum adjuvants—Alhydrogel® and Adju‐Phos®. Using wNMR, we obtained valuable information on the sedimentation rate, dynamics of the supernatant and sediment formation, and the sedimentation volume ratio (SVR) reflecting the compactness of the formed sediment. Results on SVR from wNMR were verified by caliper measurements. Verification of the sedimentation rate results from wNMR by other analytical techniques is challenging due to differences in the measured attributes and even units of the reported rate. Nonetheless, our results demonstrate the practical applicability of wNMR as an analytical tool to study pharmaceutical suspensions, for example, aluminum‐adjuvanted vaccines, to provide higher quality and more efficient vaccines. Such analyses could be carried out in the original container of a suspension drug product to study its colloidal stability and to monitor its quality over time without compromising product integrity.
Randomized probabilistic approach for parametric uncertainties in unmanned helicopters
Authors: Singh Rupam , Bhushan Bharat
Published: September 2020

Parametric uncertainties and the problems associated with the design of robust state feedback control tends to be a major concern for achieving stable operation of nonlinear systems. To overcome these drawbacks, this article provides a perspective on a randomized algorithm based probabilistic control for nonlinear systems. The control approach aims at development of randomized algorithms for control of unmanned helicopters which are subjected to uncertainties. A controller gain is synthesized by developing a robust probabilistic approach using sequential randomized algorithm with the two degree of freedom helicopter system. Subsequently, the stability and reachability for the action of developed controller is validated with the help of Lyapunov asymptotic stability and reach tube analysis, and the corresponding results were analyzed. A comparative assessment of simulation and real‐time control results of projected approaches on helicopter model are presented for validation of the controller response.
Ultrastructure of cell trafficking pathways and coronavirus: how to recognise the wolf amongst the sheep
Authors: Neil Desley , Moran Linda , Horsfield Catherine , Curtis Elizabeth , Swann Olivia , Barclay Wendy , Hanley Brian , Hollinshead Michael , Roufosse Candice
Published: September 2020

The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic has resulted in an urgent need to understand the pathophysiology of SARS‐CoV‐2 infection, to assist in the identification of treatment strategies. Viral tissue tropism is an active area of investigation, one approach to which is identification of virus within tissues by electron microscopy of post‐mortem and surgical specimens. Most diagnostic histopathologists have limited understanding of the ultrastructural features of normal cell trafficking pathways, which can resemble intra‐ and extracellular coronavirus; in addition, viral replication pathways make use of these trafficking pathways. Herein, we review these pathways and their ultrastructural appearances, with emphasis on structures which may be confused with coronavirus. In particular, we draw attention to the fact that, when using routine fixation and processing, the typical ‘crown’ that characterises a coronavirus is not readily identified on intracellular virions, which are located in membrane‐bound vacuoles. In addition, the viral nucleocapsid is seen as black dots within the virion and is more discriminatory in differentiating virions from other cellular structures. The identification of the viral replication organelle, a collection of membranous structures (convoluted membranes) seen at a relatively low scanning power, may help to draw attention to infected cells, which can be sparse. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Personality Sensing for Theory Development and Assessment in the Digital Age
Authors: Harari Gabriella M. , Vaid Sumer S. , Müller Sandrine R. , Stachl Clemens , Marrero Zachariah , Schoedel Ramona , Bühner Markus , Gosling Samuel D.
Published: September 2020

People around the world own digital media devices that mediate and are in close proximity to their daily behaviours and situational contexts. These devices can be harnessed as sensing technologies to collect information from sensor and metadata logs that provide fine–grained records of everyday personality expression. In this paper, we present a conceptual framework and empirical illustration for personality sensing research, which leverages sensing technologies for personality theory development and assessment. To further empirical knowledge about the degree to which personality–relevant information is revealed via such data, we outline an agenda for three research domains that focus on the description, explanation, and prediction of personality. To illustrate the value of the personality sensing research agenda, we present findings from a large smartphone–based sensing study ( N = 633) characterizing individual differences in sensed behavioural patterns (physical activity, social behaviour, and smartphone use) and mapping sensed behaviours to the Big Five dimensions. For example, the findings show associations between behavioural tendencies and personality traits and daily behaviours and personality states. We conclude with a discussion of best practices and provide our outlook on how personality sensing will transform our understanding of personality and the way we conduct assessment in the years to come. © 2020 European Association of Personality Psychology