bluuebunny/crossref_metadata_2025 huggingface dataset:
Conductivity and Stability Properties of Anion Exchange Membranes: Cation Effect and Backbone Effect
Authors: Han Juanjuan , Song Wenfeng , Cheng Xueqi , Cheng Qiang , Zhang Yangyang , Liu Chifeng , Zhou Xiaorong , Ren Zhandong , Hu Meixue , Ning Tianshu , Xiao Li , Zhuang Lin
Published: September 2021

The rise of heterocycle cations, a new class of stable cations, has fueled faster growth of research interest in heterocycle cation‐attached anion exchange membranes (AEMs). However, once cations are grafted onto backbones, the effect of backbones on properties of AEMs must also be taken into account. In order to comprehensively study the influence of cations effect and backbones effect on AEMs performance, a series of AEMs were prepared by grafting spacer cations, heterocycles cations, and aromatic cations onto brominated poly(2,6‐dimethyl‐1,4‐phenylene oxide) (BPPO) or poly(vinylbenzyl chloride) (PVB) backbones, respectively. Spacer cation [trimethylamine (TMA), N,N‐dimethylethylamine (DMEA)]‐attached AEMs showed general ion transportation and stability behaviors, but exhibited high cationic reaction efficiency. Heterocycle cation [1‐methylpyrrolidine (MPY), 1‐methylpiperidine (MPrD)]‐attached AEMs showed excellent chemical stability, but their ion conduction properties were unimpressive. Aromatic cation [1‐methylimidazole (MeIm), N,N‐dimethylaniline (DMAni)]‐attached AEMs exhibited superior ionic conductivity, while their poor cations stabilities hindered the application of the membranes. Besides, it was found that PVB‐based AEMs had excellent backbone stability, but BPPO‐based AEMs exhibited higher OH− conductivity and cation stability than those of the same cations grafted PVB‐based AEMs due to their higher water uptake (WU). For example, the ionic conductivities (ICs) of BPPO‐TMA and PVB‐TMA at 80 °C were 53.1 and 38.3 mS cm−1, and their WU was 152.3 and 95.1 %, respectively. After the stability test, the IC losses of BPPO‐TMA and PVB‐TMA were 21.4 and 32.2 %, respectively. The result demonstrated that the conductivity and stability properties of the AEMs could be enhanced by increasing the WU of the membranes. These findings allowed the matching of cations to the appropriate backbones and reasonable modification of the AEM structure. In addition, these results helped to fundamentally understand the influence of cation effect and backbone effect on AEM performance.
Hydrothermal Degradation of Amino Acids
Authors: Körner Paul
Published: September 2021

Within the past years, hydrothermal processes have gathered much attention as promising conversion technologies for especially wet biomass. Amino acids are an integral component of biomass, zoo biomass in particular. However, what happens to them during hydrothermal treatment? Reviewing the available literature going back to the mid of the 20th century revealed an astonishing, but still fragmentary view. In fact, two universal degradation reactions could be identified (i. e., deamination and decarboxylation), competing with each other. Thereby, small structural differences may obviously have huge impacts on the fate of individual amino acids. Nevertheless, the amount of available experimental data is relatively scarce in many cases. In this work, the available knowledge about the degradation of 20 proteinogenic amino acids under hydrothermal conditions was presented and discussed critically. The hydrothermal conversion of proteinaceus biomass as well as the Maillard reaction, both extensively reviewed elsewhere, were only touched on.
Effect of resistor tolerance on the performance of resistor network—An application of the statistical design of experiment
Authors: Pandey Vimal Kant , Tan Cher Ming
Published: September 2021

Resistors come with different tolerances, but they are generally not seriously considered in circuit simulation as only the exact resistances are used. In actual implementation of a resistor network, the tolerance of the resistors used can affect the performances of the network, especially when the network consists of large number of resistors. This work demonstrates the use of the statistical design of experiment methods combined with circuit simulator to obtain the optimum value of the tolerances for different resistors in a resistor network for an application used in proton therapy. The discretized positioning circuit consisting of 86 resistors of four different values (R1 = 1KΩ, R2 = 600 Ω, R3 = 300 Ω, and R4 = 100 Ω) is analyzed for three tolerances of 0.05%, 0.1%, and 0.5%, respectively, and maximum variation in the output signal is observed for 0.5% tolerance. Resistors with values of R1 and R4 are dominant in numbers (56 with R1 and 22 with R4 out of 86 resistors) in the network, and hence, their effect is observed to be significant on the output as expected. Significant interactions between resistors are also observed.
High expression of CD38 and MHC class II on CD8+ T cells during severe influenza disease reflects bystander activation and trogocytosis
Authors: Jia Xiaoxiao , Chua Brendon Y , Loh Liyen , Koutsakos Marios , Kedzierski Lukasz , Olshansky Moshe , Heath William R , Chang So Young , Xu Jianqing , Wang Zhongfang , Kedzierska Katherine
Published: September 2021

Objectives

Although co‐expression of CD38 and HLA‐DR reflects T‐cell activation during viral infections, high and prolonged CD38+HLA‐DR+ expression is associated with severe disease. To date, the mechanism underpinning expression of CD38+HLA‐DR+ is poorly understood.

Methods

We used mouse models of influenza A/H9N2, A/H7N9 and A/H3N2 infection to investigate mechanisms underpinning CD38+MHC‐II+ phenotype on CD8+ T cells. To further understand MHC‐II trogocytosis on murine CD8+ T cells as well as the significance behind the scenario, we used adoptively transferred transgenic OT‐I CD8+ T cells and A/H3N2‐SIINKEKL infection.

Results

Analysis of influenza‐specific immunodominant DbNP366+CD8+ T‐cell responses showed that CD38+MHC‐II+ co‐expression was detected on both virus‐specific and bystander CD8+ T cells, with increased numbers of both CD38+MHC‐II+CD8+ T‐cell populations observed in immune organs including the site of infection during severe viral challenge. OT‐I cells adoptively transferred into MHC‐II−/− mice had no MHC‐II after infection, suggesting that MHC‐II was acquired via trogocytosis. The detection of CD19 on CD38+MHC‐II+ OT‐I cells supports the proposition that MHC‐II was acquired by trogocytosis sourced from B cells. Co‐expression of CD38+MHC‐II+ on CD8+ T cells was needed for optimal recall following secondary infection.

Conclusions

Overall, our study demonstrates that both virus‐specific and bystander CD38+MHC‐II+ CD8+ T cells are recruited to the site of infection during severe disease, and that MHC‐II presence occurs via trogocytosis from antigen‐presenting cells. Our findings highlight the importance of the CD38+MHC‐II+ phenotype for CD8+ T‐cell recall.
T‐cell response after first dose of BNT162b2 SARS‐CoV‐2 vaccine among healthcare workers with previous infection or cross‐reactive immunity
Authors: Casado Jose L , Haemmerle Johannes , Vizcarra Pilar , Rodriguez‐Dominguez Mario , Velasco Tamara , Velasco Hector , Centenera Elena , Romero‐Hernandez Beatriz , Fernandez‐Escribano Marina , Vallejo Alejandro
Published: September 2021

Objectives

Antibody response to the first dose of BNT162b2 SARS‐CoV‐2 is greater in COVID‐19‐convalescent than in infection‐naïve individuals. However, there are no data about T‐cell response in individuals with pre‐existing cellular immunity.

Methods

We evaluated T‐cell responses in parallel with SARS‐CoV‐2 antibody level after first dose of BNT162b2 vaccine in 23 infection‐naïve and 27 convalescent healthcare workers (HCWs) previously included in a study about humoral and T‐cell immunity.

Results

Overall, the antibody response was lower in the infection‐naïve group than in convalescent individuals (18 895 vs 662.7 AU mL−1, P < 0.001), and intermediate but significantly lower in convalescent HCWs with previous negative serology (25 174 vs 1793 AU mL−1; P = 0.015). Indeed, anti‐spike IgG titres after the first dose correlated with baseline anti‐nucleocapsid IgG titres (rho = 0.689; P < 0.001). Pre‐existing T‐cell immunity was observed in 78% of convalescent and 65% of the infection‐naïve HCWs. T‐cell response after the first dose of the vaccine was observed in nearly all the cases with pre‐existing T‐cell immunity, reaching 94% in convalescent HCWs and 93% in those with cross‐reactive T cells. It was lower in the infection‐naïve group (50%; P = 0.087) and in convalescent HCWs with negative serology (56%; P = 0.085). Notably, systemic reactogenicity after vaccination was mainly observed in those with pre‐existing T‐cell immunity (P = 0.051).

Conclusion

Here, we report that the first dose of BTN162b2 elicits a similar S‐specific T‐cell response in cases of either past infection or cross‐reactive T cells, but lower in the rest of infection‐naïve individuals and in convalescent HCWs who have lost detectable specific antibodies during follow‐up.
Astragaloside IV enhances the sensibility of lung adenocarcinoma cells to bevacizumab by inhibiting autophagy
Authors: Li Liang , Li Gao , Chen Minbiao , Cai Renzhong
Published: September 2021

Bevacizumab (BV) has an inhibitory effect on tumor growth including lung adenocarcinoma. However, its efficacy is greatly affected by drug resistance. Astragaloside IV (AST‐IV) is effective in combination with other drugs is effective to treat cancer. This study aimed to investigate the effect of AST‐IV on enhancing the sensibility of lung adenocarcinoma cells to BV. A549 cells were treated by different concentrations of BV and AST‐IV. Cell viability, cell cycle, and apoptosis were detected by thiazolyl blue tetrazolium bromide (MTT) and flow cytometry, respectively. Quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) and western blotting were performed to detect the expression levels of autophagy‐ and apoptosis‐related proteins, protein kinase B (AKT), and mammalian target of rapamycin (mTOR). The results showed that BV or AST‐IV could inhibit the viability and promote the apoptosis of A549 cells in a concentration‐dependent manner. Moreover, BV or AST‐IV inhibited Bcl‐2 expression and increased the expressions of Bax and Cleaved caspase‐3, and promoted apoptosis. BV and AST‐IV in combination acted synergistically on viability and apoptosis of A549 cells. However, BV alone down‐regulated P62 expression, LC3I/LC3II level, the number of cells arrested at S phase and the phosphorylation levels of AKT and mTOR, but upregulated the number of cells arrested at G0/G1 phase and Beclin1 expression, whereas AST‐IV alone could reverse the effect of BV on autophagy‐related proteins, the phosphorylation levels of AKT and mTOR. This paper demonstrates that AST‐IV enhances the effect of BV on inhibiting proliferation and promoting apoptosis of lung adenocarcinoma cells through inhibiting autophagy pathway.
Efficacy of 6‐mm diameter fully covered self‐expandable metallic stents in preoperative biliary drainage for pancreatic ductal adenocarcinoma
Authors: Kataoka Fumiya , Inoue Dai , Watanabe Masato , Fukuda Keita , Nobusawa Tsubasa , Umemura Kayo , Miura Natsuki , Yokota Takuya , Yoshioka Astushi , Shimoji Kohei , Nakazono Ayano , Horike Hideyuki , Ogura Yuki , Hayashi Tatsuya , Morita Yasuhiro , Namiki Shin
Published: September 2021

Objectives

Plastic stents (PS) used for preoperative biliary drainage (PBD) of pancreatic ductal adenocarcinomas (PDAC) tend to be associated with a high incidence of recurrent biliary obstruction (RBO). Although 10‐mm diameter fully covered self‐expanding metallic stents (FCSEMS) have come into use, vigilance is still required to prevent complications, such as cholecystitis and surgical site infection. The present study examined the efficacy and safety of the 6‐mm diameter FCSEMS for PBD.

Methods

The present retrospective study compared the incidence of complications associated with the use of 6‐mm FCSEMS and PS. The inclusion criteria were a diagnosis of PDAC and preoperative endoscopic biliary tract drainage performed at our institution between April 2012 and June 2019.

Results

Of the 51 patients enrolled, 25 and 26 patients received a PS and a 6‐mm FCSEMS, respectively. The RBO incidence was significantly lower in the 6‐mm FCSEMS group (7.7%) than in the PS group (40.0%) (p = 0.009), and time to RBO was significantly longer in the 6‐mm FCSEMS group (HR = 6.008, p = 0.021). The patency rate at three months after stent placement was significantly higher in the latter group (83.5% vs. 45.3%, p = 0.009, Log‐rank test). The groups did not differ significantly in terms of complications associated with PBD, such as cholecystitis and surgical site infection.

Conclusion

The present findings suggested that the 6‐mm FCSEMS may be an effective drainage device for use in PBD in PDAC treatment.
Camera‐trap data do not indicate scaling of diel activity and cathemerality with body mass in an East African mammal assemblage
Authors: Clauss Marcus , Scriba Miriam , Kioko John , Ganzhorn Jörg U. , Kiffner Christian
Published: September 2021

Diel activity patterns of animal species reflect constraints imposed by morphological, physiological, and behavioral trade‐offs, but these trade‐offs are rarely quantified for multispecies assemblages. Based on a systematic year‐long camera‐trap study in the species‐rich mammal assemblage of Lake Manyara National Park (Tanzania), we estimated activity levels (hours active per day) and circadian rhythms of 17 herbivore and 11 faunivore species to determine the effects of body mass and trophic level on activity levels and cathemerality (the degree to which species are active throughout the day and night). Using generalized least squares and phylogenetic generalized least squares analyses, we found no support for the hypothesis that trophic level is positively associated with activity levels. We found no support for activity levels to scale positively with body mass in herbivores or to differ between ruminants and nonruminants; in faunivores, we also did not detect relationships between body mass and activity levels. Cathemerality was positively associated with activity levels but did not scale significantly with body mass. Overall, our findings caution against trophic level or body mass‐associated generalized conclusions with regard to diel activity patterns.
Benchmarking care outcomes for young adults with type 1 diabetes in Australia after transition to adult care
Authors: Rueter Phidias , Farrell Kaye , Phelan Helen , Colman Peter , Craig Maria E. , Gunton Jenny , Holmes‐Walker D. Jane ,   the ADDN study group, ANDA study group
Published: September 2021

Aim

To determine advantages conferred by a youth‐specific transition clinic model for young adults with type 1 diabetes (T1D) at Westmead Hospital (WH) as compared with Australian registry data.

Methods

Prospectively collected data included age, diabetes duration, visit frequency, post code, BMI, mode of insulin delivery, continuous glucose monitoring, HbA1c, albumin creatinine ratio, BP, retinopathy and diabetic ketoacidosis (DKA) for all WH T1D clinic attendees aged 16–25 between January 2017 and June 2018 (n = 269). Results were compared with data collected during the same time period from 2 separate Australian data registries, one longitudinal (Australasian Diabetes Data Network, ADDN) and one a spot survey (the Australian National Diabetes Audit, ANDA).

Results

Across the three cohorts, HbA1c was similar (respectively, WH, ADDN, ANDA; 8.7%[72mmol/mol], 8.7%[72mmol/mol], 8.5%[69mmol/mol]) and HbA1c was significantly higher in young adults <21 years (8.7–8.9%[73‐75mmol/mol]) as compared with ≥21 years (8.5%[69mmol/mol], p < .002). In the WH cohort, median interval between visits was shorter than in ADDN (4.5 vs. 9.0 months) and DKA was lower (respectively, 3.6 and 9.2/100 patient years; p < .001).

Conclusions

While suboptimal HbA1c was recorded in all centres, the WH model of care saw increased attendance and reduced admissions with DKA as compared with other Australian adult centres.
Unprecedented Reversal of Regioselectivity during Methanolysis and an Interception of Curtius Rearrangement
Authors: Mandal Mihirbaran , Buevich Alexei V. , Wang Hongwu , Brunskill Andrew , Orth Peter , Caldwell John P. , Liu Xiaoxiang , Mazzola Robert , Cumming Jared , McKittrick Brian , Zhu Zhaoning , Stamford Andrew
Published: September 2021

Unprecedented reversal in regioselectivity during methanolysis of anhydrides due to the change in substitution pattern of fluorine in the phenyl moiety, and the formation of nitrene intercepted intermediates during Curtius rearrangement of the acids were the major impediments for discovering bioactive molecules in beta amyloid cleaving enzyme‐1 (BACE1) program. Solutions to these synthetic challenges, and our investigation into this unexpected change in reactivity are discussed.
Combinatorial peptides: A library that continuously probes low‐abundance proteins
Authors: Boschetti Egisto , Zilberstein Gleb , Righetti Pier Giorgio
Published: September 2021

After a decade of experimental applications, it is the objective of this review to make a point on combinatorial peptide ligand libraries dedicated to low‐abundance proteins from animals to plants and to microorganism proteomics. It is, thus, at the light of the recent technical developments and applications that we will examine the state of the art, its usage within the scientific community, and its openness to unexplored fields. The improvements of the methodology and its implementation in connection with analytical determinations of combinatorial peptide ligand library (CPLL)‐treated samples are extensively reviewed and commented upon. Relevant examples covering few critical aspects describe the performance of the technology. Finally, a reflection on the technological future is attempted in particular by involving new concepts adapted to the limited availability of certain biological samples.
Effect of extraction method on the chemical profiles and bioactivities of soybean hull polysaccharides
Authors: Han Lin , Song Hong , Fu Licheng , Li Jun , Yang Lina , Liu He
Published: September 2021

The yields, properties, and bioactivities of polysaccharides extracted by three methods from soybean hulls (SSCPs) were evaluated: hot water extraction (H‐SSCP), microwave‐assisted ammonium oxalate extraction (A‐SSCP), and microwave‐assisted sodium citrate extraction (S‐SSCP). A‐SSCP gave the highest yield of polysaccharides (9.3 ± 0.5%) although all three products had similar physicochemical characteristics and FT‐IR spectra. A‐SSCP and S‐SSCP produced polysaccharides with lower molecular weight distributions and higher total reducing power and scavenging ability for ABTS+• and DPPH• free radicals. Furthermore, the effect of SSCPs on carbon tetrachloride (CCl4)‐induced liver injury was investigated in the mice. When compared with H‐SSCP and S‐SSCP, A‐SSCP significantly decreased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), and reactive oxygen (ROS) to normal (p < .05) and increased the level of glutathione (GSH) to normal (p < .05). A‐SSCP was the most effective polysaccharide, yielding an approximately normal hepatic appearance with well‐preserved cytoplasm, obvious cell boundaries, with legible nuclei and nucleoli. This study indicates that polysaccharides extracted from soybean hulls via microwave‐assisted ammonium oxalate extraction have the potential to be developed as a new functional food contributing to the alleviation of liver damage.
Preservatives from food—For food: Pea protein hydrolysate as a novel bio‐preservative against Escherichia coli O157:H7 on a lettuce leaf
Authors: Mohan Niamh M. , Zorgani Amine , Earley Leah , Chauhan Sweeny , Trajkovic Sanja , Savage John , Adelfio Alessandro , Khaldi Nora , Martins Marta
Published: September 2021

Fresh‐cut fruits and vegetables are becoming particularly popular as healthy fast‐food options; however, they present challenges such as accelerated rates of decay and increased risk for contamination when compared to whole produce. Given that food safety must remain paramount for producers and manufacturers, research into novel, natural food preservation solutions which can help to ensure food safety and protect against spoilage is on the rise. In this work, we investigated the potential of using a novel protein hydrolysate, produced by the enzymatic hydrolysis of Pisum sativum (PSH), as a novel bio‐preservative and its abilities to reduce populations of Escherichia coli O157:H7 after inoculation on a lettuce leaf. While unhydrolyzed P. sativum proteins show no antimicrobial activity, once digested, and purified, the enzymatically released peptides induced in vitro bactericidal effects on the foodborne pathogen at 8 mg/ml. When applied on an infected lettuce leaf, the PSH significantly reduced the number of bacteria recovered after 2 hr of treatment. PSH may be preferred over other preservation strategies based on its natural, inexpensive, sustainable source, environmentally friendly process, nontoxic nature, good batch to batch consistency, and ability to significantly reduce counts of E. coli both in vitro and in a lettuce leaf.
Effect of freezing treatment of soybean on soymilk nutritional components, protein digestibility, and functional components
Authors: Li Meng‐jia , Cao Ru‐ge , Tong Li‐tao , Fan Bei , Sun Ruo‐qi , Liu Li‐ya , Wang Feng‐zhong , Wang Li‐li
Published: September 2021

Soymilk is a popular beverage in many countries owing to its nutrition and health effects. To increase household consumption of soymilk, instant soybeans were developed by freezing and subsequent drying pretreatment, which overcome the time‐consuming need of soaking during soymilk preparation for home making. However, compared with the traditional soymilk making, the nutritional quality and functional properties of this soymilk made from the soybean by direct grinding in water without soaking are not clear yet. Soymilk made from untreated soybeans, soaked soybeans, and soaking, freezing, and air‐drying soybeans (FADTS) were compared on their properties including nutritional components, in vitro protein digestibility, and functional components. It was found that FADTS was the best at extracting lipid and Ca, good at extracting of protein, carbohydrate, oligosaccharides, Fe, phytic acids, and tannins, and in producing soymilks with highest in vitro protein digestibility. The soluble protein and protein digestibility of FADTS (4 day) increased significantly from 44.4% and 78.5% of control to 56.2% and 85.0%, respectively. Soymilk from 4 days FADTS contained similar protein content and higher Fe content (4.40 mg/kg) compared to soaked sample (3.82 mg/kg). The results revealed that FADTS performed better at producing soymilk than untreated and soaked soybeans.
Ovotransferrin exerts bidirectional immunomodulatory activities via TLR4‐mediated signal transduction pathways in RAW264.7 cells
Authors: Ru Zhiying , Xu Mingsheng , Zhu Gaoxiang , Tu Yonggang , Jiang Yan , Du Huaying
Published: September 2021

The immune regulation function of ovotransferrin (OVT) explored using the RAW264.7 was induced by lipopolysaccharide (LPS) as vitro model in this study. The results showed that RAW264.7 cultured with OVT (200 μg/ml) alone not only enhanced the phagocytic activity and the production and expression of inflammatory factors, but also expression of toll‐like receptor 4 (TLR4) gene was significantly promoted by OVT. OVT (50 μg/ml) significantly inhibited the secretion and expression of inflammatory factors in LPS‐stimulated RAW264.7, but CD14 and TLR4 genes expressions were no obvious effects. Inflammatory cytokines and NO secreted by OVT‐induced macrophages pretreated with inhibitors of TLR4 were down‐regulated. We further verified the effects of OVT on inflammatory signaling pathway‐related proteins through immunofluorescence and western blotting, MyD88, TLR4 and the phosphorylation of IκBα and p65 were significantly promoted by OVT, but there was no significant effects on the phosphorylation of IRF3. OVT promoted the phosphorylation of ERK and p38 in RAW264.7 and inhibited the phosphorylated expression of MAPK in LPS‐mediated inflammation. These results indicated that OVT had the bidirectional immunoregulatory function through TLR4‐mediated NF‐κB/MAPK signaling pathway, that is, anti‐inflammatory effect of low concentration and immune‐enhancing activity of high concentration were showed. That provides a theoretical utilization for the development and utilization of OVT.
The impact of primary care physician density on perinatal health: Evidence from a natural experiment
Authors: Kinge Jonas Minet , Grytten Jostein
Published: September 2021

We examined the impact of primary care physician density on perinatal health outcomes in Norway. From 1992 and onwards, primary care physicians who chose to work in selected remote municipalities were given an annual reduction in their student loan. This reduction, combined with increased supply of physicians, led to an increase in the density of primary care physicians in these selected municipalities. Our register‐based population study showed that this increase in physician density significantly improved perinatal health in terms of fewer fetal deaths and increased birth weight. The richness of the data allowed us to perform several robustness tests.
Cervical dysplasia among migrant women with female genital mutilation/cutting type III: A cross‐sectional study
Authors: Frick Albertina , Azuaga Alicia , Abdulcadir Jasmine
Published: September 2021

Objective

To assess the rate of cervical dysplasia in a population of migrant women with female genital mutilation/cutting (FGM/C) type III who attended a specialized clinic for FGM/C.

Methods

Descriptive retrospective cross‐sectional study reviewing electronic medical records of all infibulated women who attended a specialized clinic for women and girls with FGM/C at Geneva University Hospitals (2010–2016). We examined sociodemographic characteristics, parity, FGM/C subtypes, presence/grade of cervical dysplasia, colposcopy follow up/treatment, infections, and history of sexual violence.

Results

Out of 360 women reviewed, 188 women with FGM/C type III were included. Mean age of the women was 37.7 (±5.14) years. They were mostly from East Africa (n = 116, 61.7%). A total of 113 (60%) had undergone defibulation, the majority (105; 92.9%) without undergoing re‐infibulation. Cervical dysplasia was found in 20 (10.6%): 16 (8.5%) had a low‐grade grade squamous intraepithelial lesion or HPV‐positive atypical squamous cells of undetermined significance, Four (2.1%) had a high‐grade squamous intraepithelial lesions, of which one was a carcinoma in situ. Seven (35%) of the women with dysplasia underwent colposcopies regularly, five (25%) irregularly, and eight (40%) dropped out of colposcopy follow up.

Conclusion

Cervical dysplasia is frequent among women with FGM/C type III and efforts should be made to guarantee follow up for migrant women.
Survey‐based assessment of shifting trends in first solid organ transplant pharmacist jobs
Authors: Horwedel Timothy A. , Crowther Barrett R. , Lourenco Jenkins Laura M. , Doligalski Christina T. , Geyston Jennifer , Suarez Tricia , Fleming James N.
Published: September 2021

Introduction

Tremendous growth in post‐graduate year 2 (PGY2) and fellowship training opportunities in Solid Organ Transplantation has been seen throughout the 2010s, and efforts to assess the impact and ongoing needs for training are needed.

Objectives

The American College of Clinical Pharmacy Immunology/Transplantation Practice and Research Network (ACCP IMTR PRN) conducted a survey of its membership in 2018 to assess the initial positions held by its members within the solid organ transplant space in order to evaluate the job market to optimize trainee competitiveness upon graduation.

Methods

The ACCP IMTR PRN Workforce Committee developed a survey through an iterative process assessing pharmacists' first job related to solid organ transplant. Survey content was divided into questions regarding formal training, first job structure, and first job responsibilities. The final survey included 59 questions utilizing branch logic questioning, thus respondents did not answer questions that were not relevant based upon previous responses.

Results

There were 206 analyzable responses representing pharmacists starting between 1986 and 2017, with the majority starting between 2013 and 2017. Before 2013, 52% of respondents had completed a PGY2 residency specializing in solid organ transplant, compared with 68% of respondents between 2013 and 2017. When comparing responses with first jobs between 2013 and 2017 as compared with the earlier era, more jobs were purely inpatient (32 vs 24%) more were purely dedicated to the transplant population (87 vs 79%), and more had medication order entry as a job responsibility (65 vs 47%).

Conclusions

The results of this survey should be used to help guide the development of post‐graduate specialty training in solid organ transplant to prepare residency and fellowship graduates for first job responsibilities.
Medication nonadherence monitoring and management in adult kidney transplantation: A survey of practices and perceptions at US‐based transplant programs
Authors: Patel Samir J. , Hofmeyer Brooke A. , Moore Cody A. , Descourouez Jillian L. , Nguyen Duc T. , Graviss Edward A. , Taber David J.
Published: September 2021

Introduction

Medication nonadherence is a predominant contributor to graft loss, however little is known about currently utilized strategies by transplant centers to monitor or manage this issue.

Objective

Utilizing standard surveying and analysis techniques, assess health care professionals' (HCPs) perceptions of the scope and scale of medication nonadherence and strategies used to manage this issue at US‐based transplant centers.

Methods

A survey to gain insights into pre‐ and post‐transplant medication nonadherence screening, mitigation strategies and perceptions of HCPs regarding nonadherence was developed through an iterative process. This was followed by broad distribution to HCPs at US‐based adult kidney transplant centers. Standard descriptive and comparative statistics were utilized to assess responses and develop inferences and themes from participant responses.

Results

One hundred and ninety HCPs from 99 centers responded; 56.5% felt medication nonadherence was a major contributor to post‐transplant rejection and graft loss, while 71.1% acknowledged not having a prospective medication nonadherence screening protocol. Of those centers with a protocol, screening declined over time (first post‐transplant month: 92.7%; after 1‐year: <50%). Medication nonadherence management strategies also declined over time (initial transplant stay: 76%; after 1‐year: 6.5%). Few HCPs (24.1%) felt their centers had adequate resources to implement management strategies. Barriers to implement strategies included large patient volume (68.2%) and lack of a validated, easy to use, noninvasive medication nonadherence measure (65.9%).

Conclusion

While HCPs at US‐based adult kidney transplant programs feel that medication nonadherence is a significant issue, the use of systematic processes aimed at prospectively identifying and addressing medication nonadherence is uncommon. Opportunities exist to better address medication nonadherence in kidney transplantation, using feasible noninvasive monitoring and management strategies that align with current HCPs workflow and logistic constraints.
Redox ratio in the left ventricle of the growth restricted fetus is positively correlated with cardiac output
Authors: Dimasi Catherine G. , Lazniewska Joanna , Plush Sally E. , Saini Brahmdeep S. , Holman Stacey L. , Cho Steven K. S. , Wiese Michael D. , Sorvina Alexandra , Macgowan Christopher K. , Seed Mike , Brooks Doug A. , Morrison Janna L. , Darby Jack R. T.
Published: September 2021

Intrauterine growth restriction (IUGR) is a result of limited substrate supply to the developing fetus in utero, and can be caused by either placental, genetic or environmental factors. Babies born IUGR can have poor long‐term health outcomes, including being at higher risk of developing cardiovascular disease. Limited substrate supply in the IUGR fetus not only changes the structure of the heart but may also affect metabolism and function of the developing heart. We have utilised two imaging modalities, two‐photon microscopy and phase‐contrast MRI (PC‐MRI), to assess alterations in cardiac metabolism and function using a sheep model of IUGR. Two‐photon imaging revealed that the left ventricle of IUGR fetuses (at 140–141 d GA) had a reduced optical redox ratio, suggesting a reliance on glycolysis for ATP production. Concurrently, the use of PC‐MRI to measure foetal left ventricular cardiac output (LVCO) revealed a positive correlation between LVCO and redox ratio in IUGR, but not control fetuses. These data suggest that altered heart metabolism in IUGR fetuses is indicative of reduced cardiac output, which may contribute to poor cardiac outcomes in adulthood.
Structural characterization of β‐propiolactone inactivated severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) particles
Authors: Bagrov Dmitry V. , Glukhov Grigory S. , Moiseenko Andrey V. , Karlova Maria G. , Litvinov Daniil S. , Zaitsev Petr А. , Kozlovskaya Liubov I. , Shishova Anna A. , Kovpak Anastasia A. , Ivin Yury Y. , Piniaeva Anastasia N. , Oksanich Alexey S. , Volok Viktor P. , Osolodkin Dmitry I. , Ishmukhametov Aydar A. , Egorov Alexey M. , Shaitan Konstantin V. , Kirpichnikov Mikhail P. , Sokolova Olga S.
Published: September 2021

The severe COVID‐19 pandemic drives the research toward the SARS‐CoV‐2 virion structure and the possible therapies against it. Here, we characterized the β‐propiolactone inactivated SARS‐CoV‐2 virions using transmission electron microscopy (TEM) and atomic force microscopy (AFM). We compared the SARS‐CoV‐2 samples purified by two consecutive chromatographic procedures (size exclusion chromatography [SEC], followed by ion‐exchange chromatography [IEC]) with samples purified by ultracentrifugation. The samples prepared using SEC and IEC retained more spikes on the surface than the ones prepared using ultracentrifugation, as confirmed by TEM and AFM. TEM showed that the spike (S) proteins were in the pre‐fusion conformation. Notably, the S proteins could be recognized by specific monoclonal antibodies. Analytical TEM showed that the inactivated virions retained nucleic acid. Altogether, we demonstrated that the inactivated SARS‐CoV‐2 virions retain the structural features of native viruses and provide a prospective vaccine candidate.
Profiling nonhuman primate germline RNA to understand the legacy of early life stress
Authors: Morin Elyse L. , Garza Kristie M. , Aoued Hadj , Sannigrahi Soma , Siebert Erin R. , Howell Brittany R. , Walum Hasse , Sanchez Mar M. , Dias Brian G.
Published: September 2021

Exposure to stress is a risk factor for perturbed mental health, including impoverished regulation of emotional and physiological responses that accompany anxiety and mood disorders, substance abuse and behavioral disorders. Such disruptions to well‐being could be triggered by discrete environmental events or pervasive early life stress (ELS) resulting for example from adverse caregiving. Recent data mostly collected from rodents exposed to anthropogenic stressors suggest that one way via which the detrimental effects of such stress extend beyond the exposed population to future offspring is via stress‐induced alterations of RNA found in the paternal germline. In contrast, less attention has been paid to how naturally occurring stress in males might influence offspring biology and behavior. In this study, we used a translational nonhuman primate model of ELS caused by naturally occurring adverse caregiving of infant macaques to (1) profile total RNA in the adolescent male germline, and (2) identify how those RNA profiles are affected by exposure to ELS. Our findings that the top 100 transcripts identified correspond to transcripts related to germline biology and reproduction demonstrate the validity and feasibility of profiling RNA in the germline of rhesus macaques. While our small sample sizes precluded definitive assessment of stress‐induced alterations of RNA in the male germline of rhesus macaques that experienced ELS, our study sets the foundation for future investigations of how early adversity might alter the male germline, across species and in experimental protocols that involve anthropogenic vs natural stressors.
Facilitating EMA binding test performance using fluorescent beads combined with next‐generation sequencing
Authors: Glenthøj Andreas , Brieghel Christian , Nardo‐Marino Amina , van Wijk Richard , Birgens Henrik , Petersen Jesper
Published: September 2021

The eosin‐5′‐maleimide (EMA) binding test is widely used as diagnostic test for hereditary spherocytosis (HS), one of the most common haemolytic disorders in Caucasian populations. We recently described the advantages of replacing the use of healthy control blood samples with fluorescent beads in a modified EMA binding assay. In this study we further explore this novel approach. We performed targeted next‐generation sequencing, modified EMA binding test and osmotic gradient ektacytometry on consecutive individuals referred to our laboratory on the suspicion of HS. In total, 33 of 95 carried a (likely) pathogenic variant, and 24 had variants of uncertain significance (VUS). We identified a total 79 different (likely) pathogenic variants and VUS, including 43 novel mutations. Discarding VUS and recessive mutations in STPA1, we used the occurrence of (likely) pathogenic variants to generate a diagnostic threshold for our modified EMA binding test. Twenty‐one of 23 individuals with non‐SPTA1 (likely) pathogenic variants had EMA ≥ 43.6 AU, which was the optimal threshold in receiver operating characteristic (ROC) analysis. Accuracy was excellent at 93.4% and close to that of osmotic gradient ektacytometry (98.7%). In conclusion, we were able to simplify the EMA‐binding test by using rainbow beads as reference and (likely) pathogenic variants to define an accurate cut‐off value.
Routine management, healthcare resource use and patient and carer‐reported outcomes of patients with transfusion‐dependent β‐thalassaemia in the United Kingdom: A mixed methods observational study
Authors: Shah Farrukh , Telfer Paul , Velangi Mark , Pancham Shivan , Wynn Robert , Pollard Sally , Chalmers Elizabeth , Kell Jonathan , Carter Angela M. , Hickey Joe , Paramore Clark , Jobanputra Minesh , Ryan Kate
Published: September 2021

Objectives

We evaluated routine healthcare management, clinical status and patient‐ and carer‐reported outcomes in UK paediatric and adult patients with transfusion‐dependent β‐thalassaemia (TDT).

Methods

A multi‐centre, observational mixed‐methodology study evaluated 165 patients (50% male; median age 24.1 [interquartile range (IQR)] 11.8–37.2] years) from nine UK centres.

Results

Patients had a mean of 13.7 (standard deviation [SD] ±3.2) transfusion episodes/year (mean retrospective observation period 4.7 [±0.7] years). The median (IQR) for iron overload parameters at the last assessment during the observation period were: serum ferritin (n = 165) 1961.0 (1090.0–3003.0) μg/L (38% > 2500 μg/L); R2 liver iron (n = 119) 5.4 (2.9–11.6) mg/g (16% ≥15 mg/g); T2* cardiac iron (n = 132) 30.3 (22.0–37.1) ms (10% < 10 ms). All patients received ≥1 iron chelator during the observation period; 21% received combination therapy. Patients had a mean of 7.8 (±8.1) non‐transfusion‐related hospital attendances or admissions/year. Adult patients’ mean EQ‐5D utility score was 0.69 (±0.33; n = 94 [≥16 years]) and mean Transfusion‐dependent quality of life score was 58.6 (±18.4; n = 94 [≥18 years]). For Work Productivity and Activity impairment, mean activity impairment for patients ≥18 years (n = 88) was 48% (±32%) and for carers (n = 29) was 28% (±23%).

Conclusions

TDT presents significant burden on patients, carers and healthcare resources.
Differential outcomes for frontal versus posterior demyelination in childhood cerebral adrenoleukodystrophy
Authors: Gupta Ashish O. , Nascene David R. , Shanley Ryan , Kenney‐Jung Daniel L. , Eisengart Julie B. , Lund Troy C. , Orchard Paul J. , Pierpont Elizabeth I.
Published: September 2021

In the most common variant of childhood cerebral adrenoleukodystrophy (cALD), demyelinating brain lesions are distributed predominately in parieto‐occipital white matter. Less frequently, lesions first develop in frontal white matter. This matched cohort study examined whether outcomes after standard treatment with hematopoietic cell transplantation (HCT) differ in patients with early stage frontal lesions as compared to parieto‐occipital lesions. Retrospective chart review identified seven pediatric patients with frontal cALD lesions and MRI severity score < 10 who underwent a single HCT at our center between 1990 and 2019. Concurrent MRI, neurocognitive and psychiatric outcomes at last comprehensive follow‐up (mean 1.2 years; range 0.5‐2.1 years) were compared with a group of seven boys with the parieto‐occipital variant matched on pre‐HCT MRI severity score. Both groups showed similar rates of transplant complications and radiographic disease advancement. Neurocognitive outcomes were broadly similar, with more frequent working memory deficits among individuals with frontal lesions. Psychiatric problems (hyperactivity, aggression, and atypical behavior) were considerably more common and severe among patients with frontal lesions. Aligned with the critical role of the frontal lobes in emotional and behavioral regulation, functional disruption of self‐regulation skills is widely observed among patients with frontal lesions. Comprehensive care for cALD should address needs for psychiatric care and management.
Characterizing the hyper‐ and hypometabolism in temporal lobe epilepsy using multivariate machine learning
Authors: Wu Dongyan , Yang Liyuan , Gong Gaolang , Zheng Yumin , Jin Chaoling , Qi Lei , Li Yanran , Wu Di , Cui Zaixu , He Xiaosong , Ren Liankun
Published: September 2021

Mesial temporal lobe epilepsy (MTLE) is the most common type of focal epilepsy, presenting both structural and metabolic abnormalities in the ipsilateral mesial temporal lobe. While it has been demonstrated that the metabolic abnormalities in MTLE actually extend beyond the epileptogenic zone, how such multidimensional information is associated with the diagnosis of MTLE remains to be tested. Here, we explore the whole‐brain metabolic patterns in 23 patients with MTLE and 24 healthy controls using [18F]fluorodeoxyglucose PET imaging. Based on a multivariate machine learning approach, we demonstrate that the brain metabolic patterns can discriminate patients with MTLE from controls with a superior accuracy (>95%). Importantly, voxels showing the most extreme contributing weights to the classification (i.e., the most important regional predictors) distribute across both hemispheres, involving both ipsilateral negative weights over the anterior part of lateral and medial temporal lobe, posterior insula, and lateral orbital frontal gyrus, and contralateral positive weights over the anterior frontal lobe, temporal lobe, and lingual gyrus. Through region‐of‐interest analyses, we verify that in patients with MTLE, the negatively weighted regions are hypometabolic, and the positively weighted regions are hypermetabolic, compared to controls. Interestingly, despite that both hypo‐ and hypermetabolism have mutually contributed to our model, they may reflect different pathological and/or compensative responses. For instance, patients with earlier age at epilepsy onset present greater hypometabolism in the ipsilateral inferior temporal gyrus, while we find no evidence of such association with hypermetabolism. In summary, quantitative models utilizing multidimensional brain metabolic information may provide additional assistance to presurgical workups in TLE.
The Value of Contrast‐Enhanced Ultrasound in Diagnosing Small Renal Cell Carcinoma Subtypes and Angiomyolipoma
Authors: Cao Hongli , Fang Liang , Chen Lin , Zhan Jia , Diao Xuehong , Liu Yingchun , Lu Chen , Zhang Zhengwang , Chen Yue
Published: September 2021

Objectives

To retrospectively explore the value of contrast‐enhanced ultrasound (CEUS) in differentiating small renal cell carcinomas (RCCs) from angiomyolipomas (AMLs), and distinguishing between clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC).

Methods

A total of 151 patients with small renal masses (110 ccRCCs, 12 pRCCs, 9 chRCCs, and 20 AMLs) were enrolled between August 2016 and October 2019.

Results

There were significant differences in terms of enhancement intensity (EI), enhancement homogeneity, perilesional rim‐like enhancement (PRE), wash in, and wash out (WO) between RCC and AML (P = .000, .011, .000, .001, .000, respectively). Although there was no significant difference in EI between pRCC and chRCC (P = .272), EI of ccRCC was higher than that of pRCC (P = .000) and chRCC (P = .010). Multivariate regression analysis showed PRE and fast WO were related to RCC (OR = 18.189, 15.141, respectively). Although there were no significant differences in the sensitivity and area under the curve (AUC) between PRE and fast WO (95.0% vs. 95.0%, P = 1.000 and .880 vs. 0.799, P = .123, respectively), the specificity of PRE in predicting RCC was higher than that of fast WO (80.92% vs. 64.89%, P = .011). The sensitivity, specificity, and AUC of the two characteristics combination for differentiating RCC from AML were 95.0%, 90.8%, and 0.920, respectively, and that of EI for differentiating between ccRCC, pRCC, and chRCC were 81.0%, 78.2%, and 0.796, respectively.

Conclusions

CEUS has value in differentiating small RCCs from AMLs and distinguishing ccRCC, a subtype associated with a greater likelihood of malignant behavior from pRCC and chRCC.
Readability of Commonly Used Patient‐Reported Outcome Measures in Laryngology
Authors: Rao Shambavi J. , Nickel Joseph C. , Kiell Eleanor P. , Madden Lyndsay L.
Published: September 2021

Objectives

Patient‐reported outcome measures (PROMs) are used to evaluate patients' symptoms and clinical improvement after an intervention. Advocacy efforts and increased provider awareness regarding health literacy have helped to improve the readability of PROMs. Recent studies in otolaryngology in rhinology, pediatric otolaryngology, and head and neck reported PROM readability scores above the sixth‐grade level. However, there is limited data regarding the readability of laryngology PROMs. Thus, this study aims to report the readability levels of PROMs in laryngology by assessing different readability indices and describing the relationship of readability levels to equitable healthcare.

Methods

This is a bibliometric study that received approval from institutional review board (IRB) review as a nonhuman subject research study. Recent and widely utilized laryngology PROMs were selected from a publicly available literature search by reviewing laryngology systematic reviews, PubMed, and Google Scholar. Laryngology PROMs were selected from voice, dysphagia, airway, and other PROMs including voice questionnaires administered to patients seeking gender affirming voice care from systematic reviews and expert opinion. There were 37 PROMs included in this study. PROMs were analyzed via Gunning Fog, Simple Measure of Gobbledygook (SMOG), FORCAST, and Flesch Reading Ease Score.

Results

All laryngology PROMs had readabilities above the recommended sixth‐grade level. The mean and standard deviation (SD) of Gunning Fog was 7.30 (2.59), SMOG was 8.70 (1.51), FORCAST was 10.05 (1.51), and Flesch Reading Ease Score was 8.08 (2.76).

Conclusion

Laryngology PROMs are above the recommended middle school reading level. To further promote health equity, readability should be considered when developing future PROMs.

Level of Evidence

NA Laryngoscope, 132:1069–1074, 2022