bluuebunny/crossref_metadata_2025 huggingface dataset:
A Two‐Stage Flow Cytometry Strategy to Distinguish Single Cells from Doublets in Heterogeneous Cell Mixtures and Improve Cell Cluster Identification: Application to Human Monocyte Subpopulations
Authors: Merah‐Mourah Fadila , Cohen Shannon O. , Haziot Alain
Published: August 2021

Flow cytometry is a powerful method, widely used to identify cell types present in tissues, to describe their phenotypes, and to purify cells for functional analyses. As a single cell technique, flow cytometry relies on identifying and excluding cell doublets and aggregates present in samples in the initial gating steps. This identification is based on detection of events generating electrical pulses falling outside of linear variations of pulse height, width, and area in a singlet population with increasing cell sizes. In heterogeneous cell mixtures, however, with cell types varying extensively in size and granularity, exclusion of doublets has the risk of removing single cells that co‐localize with doublets of another cell type. This is particularly the case when doublets of a smaller cell type overlap with large cells of a distinct, larger cell type. Here, we describe a gating method to reduce this risk. In this protocol, initial gating steps aim to segregate cells according to physical characteristics (such as size and granularity) and gene expression properties in order to obtain more homogeneous cell clusters. Doublet exclusion is then performed separately in each cluster, minimizing the risk of confusion between single cells and doublets. To illustrate this protocol, human blood monocytes are separated and analyzed. By implementing this protocol, we were able to reveal the existence of a population of large monocytes previously unrecognized using conventional gating strategies. In subsequent functional assays, we have shown that this novel population exhibits unique inflammatory responses, highlighting the need and pertinence of this approach to identify and characterize infrequent—yet functionally relevant—cell populations present in complex cell mixtures. © 2021 Wiley Periodicals LLC.

Basic Protocol: Distinguishing single cells from doublets in heterogeneous cell mixtures by flow cytometry
Receptor interacting protein kinase 4 promotes cell proliferation, migration, and invasion in ovarian cancer via targeting protein kinase C delta
Authors: Jin Aihong , Zhang Longhui , Fang Guangguang , Chen Yinzi
Published: August 2021

Receptor interacting protein kinase 4 (RIPK4) has been reported to function as an oncogenic role in several types of cancers. The aim of this study was to evaluate the role of RIPK4 in ovarian cancer (OC) cells and to elucidate the mechanism behind this effect. In this study, the GEPIA database was used to analyze the RIPK4 expressions in OC tissues and overall survival. qRT‐PCR and western blot assay were performed to detect the expressions of RIPK4 and protein kinase C delta (PRKCD) in OC cells. In addition, cell proliferation was assessed by CCK‐8 and colony formation assay while cell invasion and migration were evaluated by transwell, wound healing and western blot assay. The interaction of RIPK4 and PRKCD was analyzed by the STRING database and the bioGRID database, and verified with co‐immunoprecipitation. Herein, we describe that RIPK4 expression was upregulated in OC tissues and cells and was associated with poor overall survival. RIPK4 silencing repressed the proliferation, migration, and invasion of OC cells. Mechanistically, PRKCD was highly expressed in OC cells and was combined with RIPK4. PRKCD was highly positively associated with RIPK4 in OC and was regulated by RIPK4. Moreover, PRKCD overexpression reversed the inhibitory effects of RIPK4 silencing on OC cell proliferation, migration, and invasion. RIPK4 functions as an oncogene in OC cells via at least partially binding to PRKCD, which might represent a novel therapeutic strategy for improving survival for patients with OC.
Conventional and microwave‐assisted organic synthesis of novel antimycobacterial agents bearing furan and pyridine hybrids
Authors: Desai Nisheeth C. , Bhatt Kandarp , Jadeja Dharmpalsinh J. , Mehta Harsh K. , Khedkar Vijay M. , Sarkar Dhiman
Published: August 2021

Drug resistance in tuberculosis poses a serious threat to humanity because currently available antitubercular drugs are ineffective against Mycobacterium tuberculosis (M. tuberculosis). As a result, the approval of Bedaquiline and Delamanid for the treatment of drug‐resistant tuberculosis was accelerated. Still, there is an urgent need to search for new antitubercular drugs with novel mechanisms of action (MoA). Due to this, we have designed a synthetic strategy by utilizing microwave‐assisted organic synthesis. We have compared our method with the conventional procedure, and the data show that our procedure is more effective in the preparation of title compounds. A unique series of 1‐(2‐(furan‐2‐yl)‐5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐3(2H)‐yl)‐3‐(aryl)‐prop‐2‐en‐1‐ones (5a‐o) was synthesized utilizing conventional and microwave‐assisted techniques. Synthetic compounds were investigated for antitubercular activity against Mycobacterium TB H37Ra and Mycobacterium bovis (M. bovis). Compound 5b was reported to be the most effective against M. tuberculosis H37Ra (97.69 percent inhibition at 30 μg/ml) and M. bovis (97.09 percent inhibition at 30 μg/ml). An in silico binding affinity study of mycobacterial enoyl‐acyl carrier protein reductase (InhA) reveals the binding mechanism and thermodynamic interactions that determine these molecule's binding affinity. Compound 5b had a high glide score of −8.991 and low glide energy of −49.893 kcal/mol.
Use of high‐frequency repetitive transcranial magnetic stimulation to probe the neural circuitry of food choice in anorexia nervosa: A proof‐of‐concept study
Authors: Muratore Alexandra F. , Bershad Mariya , Steinglass Joanna E. , Foerde Karin E. , Gianini Loren , Broft Allegra , Attia Evelyn
Published: August 2021

Repetitive transcranial magnetic stimulation (rTMS) is used to modulate neural systems and provides the opportunity for experimental tests of hypotheses regarding mechanisms underlying anorexia nervosa (AN). The present pilot study has investigated whether high‐frequency repetitive transcranial magnetic stimulation (HF‐rTMS) to a region of the right dorsolateral prefrontal cortex (DLPFC) might be associated with change in food selection among adult inpatients with AN. Ten women received one session of sham and one session of HF‐rTMS targeting the right DLPFC while completing a computerized Food Choice Task. Compared to sham, HF‐rTMS was associated with changes in food ratings and food choice: inpatients reported higher healthiness ratings of low‐ and high‐fat foods and selected a significantly greater proportion of high‐fat foods over a neutrally rated reference item while receiving HF‐rTMS. Findings suggest that HF‐rTMS to the right DLPFC was associated with a reduction of fat avoidance on a food choice task among inpatients with AN and provide additional support for the possibility that this region, and related neural circuits, may underlie restrictive food choice. Research using rTMS to experimentally test neural mechanisms is needed to elucidate the underpinnings of AN and supports the development of novel treatment targets.
Association of COVID‐19 with impaired endothelial glycocalyx, vascular function and myocardial deformation 4 months after infection
Authors: Lambadiari Vaia , Mitrakou Asimina , Kountouri Aikaterini , Thymis John , Katogiannis Konstantinos , Korakas Emmanouil , Varlamos Charalampos , Andreadou Ioanna , Tsoumani Maria , Triantafyllidi Helen , Bamias Aristotelis , Thomas Konstantinos , Kazakou Pinelopi , Grigoropoulou Sotiria , Kavatha Dimitra , Antoniadou Anastasia , Dimopoulos Meletios‐Athanasios , Ikonomidis Ignatios
Published: August 2021

Aims

SARS‐CoV‐2 infection may lead to endothelial and vascular dysfunction. We investigated alterations of arterial stiffness, endothelial coronary and myocardial function markers 4 months after COVID‐19 infection.

Methods and results

In a case‐control prospective study, we included 70 patients 4 months after COVID‐19 infection, 70 age‐ and sex‐matched untreated hypertensive patients (positive control) and 70 healthy individuals. We measured (i) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced endothelial glycocalyx thickness), (ii) flow‐mediated dilatation (FMD), (iii) coronary flow reserve (CFR) by Doppler echocardiography, (iv) pulse wave velocity (PWV), (v) global left and right ventricular longitudinal strain (GLS), and (vi) malondialdehyde (MDA), an oxidative stress marker, thrombomodulin and von Willebrand factor as endothelial biomarkers. COVID‐19 patients had similar CFR and FMD as hypertensives (2.48 ± 0.41 vs. 2.58 ± 0.88, P = 0.562, and 5.86 ± 2.82% vs. 5.80 ± 2.07%, P = 0.872, respectively) but lower values than controls (3.42 ± 0.65, P = 0.0135, and 9.06 ± 2.11%, P = 0.002, respectively). Compared to controls, both COVID‐19 and hypertensives had greater PBR5–25 (2.07 ± 0.15 µm and 2.07 ± 0.26 µm, P = 0.8 vs. 1.89 ± 0.17 µm, P = 0.001), higher PWV (carotid–femoral PWV 12.09 ± 2.50 vs. 11.92 ± 2.94, P = 0.7 vs. 10.04 ± 1.80 m/s, P = 0.036) and impaired left and right ventricular GLS (−19.50 ± 2.56% vs. −19.23 ± 2.67%, P = 0.864 vs. −21.98 ± 1.51%, P = 0.020 and −16.99 ± 3.17% vs. −18.63 ± 3.20%, P = 0.002 vs. −20.51 ± 2.28%, P < 0.001). MDA and thrombomodulin were higher in COVID‐19 patients than both hypertensives and controls (10.67 ± 0.32 vs 1.76 ± 0.03, P = 0.003 vs. 1.01 ± 0.05 nmol/L, P = 0.001 and 3716.63 ± 188.36 vs. 3114.46 ± 179.18 pg/mL, P = 0.017 vs. 2590.02 ± 156.51 pg/mL, P < 0.001). Residual cardiovascular symptoms at 4 months were associated with oxidative stress and endothelial dysfunction markers.

Conclusions

SARS‐CoV‐2 may cause endothelial and vascular dysfunction linked to impaired cardiac performance 4 months after infection.
Revamp your onboarding experience to better serve incoming students
Authors: Pavlik Amelia
Published: August 2021

A disconnect. That's what was occurring for adult and transfer students from the time they were admitted to Carlow University until classes started. “When  I was promoted from University Registrar to Assistant Provost and supervisor of the Student Hub — which includes the Registrar's Office, financial aid, and student accounts, I noticed that the coordinator of advising position that was in place to work with this incoming population of students wasn't meeting their needs,” said Jason Krall, Assistant Provost for Online and Academic Operations. “Sure the position helped faculty advisors with advising‐related matters, but what I was seeing was a true gap in these students getting off to a strong start when it came to onboarding.”
Impacts of in‐stream aggregate mining on the distributary channels of the alluvial fans of Tafí valley (Northwest Argentina)
Authors: Sampietro‐Vattuone María Marta , Peña‐Monné José Luis , Rodríguez Graciela , Medina Paula Lucía , Vattuone Marta Amelia
Published: August 2021

In‐stream mining is a common aggregate mining practice around the world. However, the impacts of such practice are not always taken into account when the mines are established, and the environmental cost of in‐stream aggregate mining is generally not assessed. The purpose of this study was to evaluate the impacts of aggregate mining conducted in La Puerta River (Tafí valley, Northwest Argentina), a dry‐pit in‐stream mine, by considering the geomorphological, geoarchaeological, and human effects. Multitemporal analysis of the area using remote sensors (aerial photographs and satellite images 1970–2020), high‐resolution drone digital elevation models and orthomosaics (2018–2019), and an intensive survey demonstrated that the mining area grew exponentially between 2002 and 2020 under unregulated mining. As a result, this practice exerts great environmental impact, including channel section alterations and destabilization of riverbanks, soil loss, river profile changes, and the formation of lag deposits of discarded materials, thus increasing environmental hazard under unpredictable flows. Finally, this is a highly touristic area that has suffered substantial landscape degradation and irreversible archaeological damage.
Option prices for risk‐neutral density estimation using nonparametric methods through big data and large‐scale problems
Authors: Monteiro Ana M. , Santos António A. F.
Published: August 2021

Option pricing theory determines the structure of call and put option pricing functions. In nonparametric risk‐neutral density estimation based on kernel functions, local constraints cannot induce a second derivative function that must integrate one. Convexity and monotonicity of pricing functions also cannot be enforced. A large‐scale (optimization) approach is proposed for the risk‐neutral density estimation, imposing an enlarged set of no‐arbitrage constraints. We considered simulations using Heston's model and hypergeometric functions. The method is applied to samples of intraday data from VIX and S&P500 indexes.
A review of CO2adsorbents performance for different carbon capture technology processes conditions
Authors: Lai Jia Yen , Ngu Lock Hei , Hashim Siti Salwa
Published: August 2021

The utilization of various conventional and emerging solid adsorbents is an attractive carbon capture method for post‐combustion and direct air capture (DAC). This review aims to identify adsorbents with the highest CO2adsorption performance at various CO2capture conditions inclusive of pre‐combustion, post‐combustion, and DAC to aid the selection of adsorbents. It presents the various adsorbents’ physical and chemical properties, their synthesis methods, CO2adsorption performance, and their advantages as CO2adsorbents. Findings of the review show that NaX@NaA core‐shell microspheres possess the highest CO2adsorption capacity at 5.60 mmol g−1for adsorption at DAC conditions. MOF‐177‐TEPA exhibited the highest post‐combustion condition CO2adsorption capacity at 4.60 mmol g−1given tetraethylenepentamine properties leading to low diffusion resistance for CO2and easy access to active sites. Approximation of these adsorbents’ adsorption capacity within pre‐combustion capture temperature at 1 bar for oxy‐combustion process was 0.0000026–48.71 mmol g−1. It is crucial to understand and evaluate these adsorbents’ characteristics for application in the appropriate adsorption conditions. This considers their usage limitations on pilot‐scale CO2capture because of low productivity, poor durability, and stability for prolonged cyclic adsorption–desorption, expensive adsorption system, high gas flow rate, high adsorbate accommodation requirement, longer flow switching time, and low tolerance towards water and impurities present in flue gas. This paper hence presents future enhancements in overcoming their limitations to accommodate pilot scale carbon capture. These are beneficial in providing insights for capturing CO2from flue gases emitted in industries. © 2021 Society of Chemical Industry and John Wiley & Sons, Ltd.
Fe3O4@C@prNHSO3H: A novel magnetically recoverable heterogeneous catalyst in green synthesis of diverse triazoles
Authors: Nasehi Niloufar , Mirza Behrooz , Soleimani‐Amiri Somayeh
Published: August 2021

The core–shell magnetic nano‐catalyst of Fe3O4@C@PrNHSO3H was proposed, synthesized, and fully described by transmission electron microscopy, field‐emission scanning electron microscope, energy‐dispersive X‐ray, vibrating sample magnetometer, thermal gravimetric analysis, X‐ray diffraction, Fourier transform infrared, and X‐ray photoelectron spectroscopy analysis. Nontoxic texture, magnetic recovery capability, high thermal stability as well as low‐cost synthesis method were found as the unique features of the synthesized core–shell magnetic nano‐catalyst. Fe3O4@C@PrNHSO3H NPs were introduced as a modern magnetic heterogeneous catalyst in the solvent‐free synthesis of triazole derivatives through one‐pot, three‐component condensation of aldehyde, ammonium acetate, and nicotinic hydrazide. The pleasant yield of products, straightforward work‐up, mild reaction conditions, along with magnetically recoverable catalyst were enumerated as the most important advantages of the method. The Fe3O4@C@PrNHSO3H could be easily separated from the reaction mixture by an external magnet and reused six times with the desired catalytic activity.
Integrated process development for the efficient and industrial production of 2,3‐butanediol and bioethanol using dried cassava chips as commercial biomass
Authors: Moon Se‐Kwon , Chung Jin Ho , Min Jiho
Published: August 2021

BACKGROUND

For the efficient use of cassava as industrial material in the fermentation business, an integrated process was developed to produce 2,3‐butanediol (2,3‐BDO) and bioethanol (BE) by a highly efficient and economical method. After separating the liquefied cassava into a solid and a liquid part, the liquid part was used to produce 2,3‐BDO, and the solid part was then used to produce BE.

RESULTS

The integrated process efficiently fermented 1000 g of dried cassava to 288 g of 2,3‐BDO (120.1 g L−1 titer and 2.39 L fermented broth) and 57 g of BE (38.4 g L−1 titer and 1.49 L fermented broth). Also, fermentable sugar of cassava was 100% available for this process, and the byproduct of BE production, condensed distillers solubles (CDS), was used as a potential nutrient source for the economical production of 2,3‐BDO.

CONCLUSION

An integrated process with simultaneous saccharification and fermentation (SSF), pH shift, and rpm shift was developed to enhance 2,3‐BDO production and to reduce the production cost of 2,3‐BDO and BE. The strategy of employing cassava as a starchy biomass‐based biorefinery resource for 2,3‐BDO and BE production was successfully performed. © 2021 Society of Chemical Industry (SCI).
An enzyme immobilized microreactor for continuous‐flow biocatalysis of ginsenoside Rb1
Authors: Kazan Aslihan , Hu Xihua , Stahl Alina , Frerichs Heike , Smirnova Irina , Yesil‐Celiktas Ozlem
Published: August 2021

BACKGROUND

Ginsenoside Rb1 is one of the major bioactive components of Panax ginseng C.A. Meyer (Araliaceae), a medicinal plant that has been used for therapeutic purposes for thousands of years in Asian countries. The pharmaceutical activity of ginsenoside Rb1 highly depends on molecular structure and its deglycosylated metabolites are known to be more potent bioactive compounds. However, these deglycosylated ginsenosides do not exist naturally so they are usually obtained by poorly selective methods, like chemical hydrolysis.

RESULTS

In this study, the development and characterization of an alginate‐based immobilized enzyme microreactor for the catalytic conversion of ginsenoside Rb1 to more bioactive metabolites have been reported. Enzyme kinetic parameters were calculated and characterization tests (such as determination of surface area of alginate matrix, long‐term use, and effect of residence time on conversion yield) were conducted. The system was operated under continuous‐flow conditions and compared with acidic and batch enzymatic hydrolysis experiments, as conventional approaches. The enzymatic microreactor showed an enhanced activity by producing 13‐fold higher amount of ginsenoside F2 than batch enzymatic hydrolysis.

CONCLUSION

Obtained results indicated that the newly developed enzymatic microreactor could successfully convert ginsenoside Rb1 to more active metabolites and have a potential for the biocatalysis of multiple ginsenosides, as well as pharmaceutically active compounds. © 2021 Society of Chemical Industry (SCI).
Proof of concept of a novel in tandem biofilter photobioreactor system for valorization of volatile organic compounds: mineralization of methanol vapors coupled with use of CO2 as a carbon source for Arthrospira maxima growth
Authors: Cruz‐García Blanca , Aizpuru Aitor
Published: August 2021

BACKGROUND

Methanol, a common air pollutant, can be converted to CO2 by biofiltration. In turn, biofilter CO2 streams, contributing to the greenhouse effect, could represent a zero‐cost carbon source for microalgal production. To assess the potential of the combination of both bioprocesses, cultivation of Arthrospira maxima, a major source of added‐value natural products, was carried out with three different carbon sources (bicarbonate mineral medium, CO2 from ambient air, and CO2 from a methanol biofilter outlet).

RESULTS

Methanol vapors were almost completely treated in the biofilter, achieving an elimination capacity of 148 ± 18 g m−3 h−1 for an inlet load of 157 ± 12 g m−3 h−1, while producing an average of 152 ± 42 g m−3 h−1 of CO2. Compared to cultivation in classic bicarbonate mineral medium, the resulting CO2 concentration in the biofilter outlet (0.5 ± 0.1% (v/v)) allowed for a 20% higher final production of A. maxima (1.3 g dry weight (DW) L−1 of medium). Moreover, the cultivation of A. maxima significantly reduced the carbon footprint of the biofilter, with a fixation rate of 302 mg CO2 L−1 h−1. Additionally, enriched CO2 concentrations coming from the biofilter outlet allowed for a 117% higher A. maxima productivity rate than ambient air (76.5 ± 2.9 vs. 35.3 ± 1.3 mg DW L−1 d−1).

CONCLUSION

Substantial reduction of the cost of microalgae production and treatment of gaseous contaminants can be carried out in tandem. Further optimization of hybrid bioprocesses could represent a win–win opportunity from both environmental and economic viewpoints. © 2021 Society of Chemical Industry (SCI).
Intestinal fatty acid‐binding protein is a biomarker for diagnosis of biliary tract infection
Authors: Weng Yu‐Chieh , Chen Wei‐Ting , Lee Jung‐Chieh , Huang Yung‐Ning , Yang Chih‐Kai , Hsieh Hui‐Shan , Chang Chih‐Jung , Lu Yang‐Bor
Published: August 2021

Background and Aim

Biliary tract infection (BTI) is an inflammatory disease and commonly associated with bacteremia. Delays in diagnosis or treatment of BTI cause high morbidity and mortality. However, an early diagnosis depends on appropriate clinical investigations. Appropriate biomarkers are urgently needed to improve the BTI diagnostic rate. We hypothesized that intestinal fatty acid‐binding protein (I‐FABP) might be a potential biomarker for BTI diagnosis.

Methods

We examined data from subjects aged ≥18 years diagnosed with BTI, including cholangitis and cholecystitis, whose blood samples were adequate for I‐FABP and zonulin assessment. We also collected blood samples from healthy volunteers as the control group. We excluded subjects in both groups who received steroids, antibiotics, or probiotics within 1 month before hospital admission (BTI cohort) or participation in this research (controls). The main study endpoint was to compare the diagnostic ability of I‐FABP to detect BTI in comparison with high‐sensitivity C‐reactive protein (hs‐CRP) and zonulin.

Results

The study collected the data of 51 patients with BTI and 35 healthy subjects. The receiver operating characteristic (ROC) area under the curve (AUC) for I‐FABP was 0.884 (95% confidence interval [CI]: 0.814–0.954), numerically higher than that for hs‐CRP (0.880; 0.785–0.976) and zonulin (0.570; 0.444–0.697). We estimated that the optimal cutoff value of I‐FABP was 2.1 ng/mL (sensitivity: 0.804; specificity: 0.829) for the diagnosis of BTI.

Conclusions

In summary, this study suggests that I‐FABP may be a potential alternative biomarker to hs‐CRP for diagnosing BTI. Further research should verify the use of I‐FABP as a marker for BTI diagnosis, but also for other inflammatory diseases.
Liver and Spleen Stiffness Surveillance Through Elastography During and After Direct‐Acting Antiviral Therapy in Patients With Chronic Hepatitis C
Authors: Chen Sheng‐Hung , Lai Hsueh‐Chou , Su Wen‐Pang , Kao Jung‐Ta , Chuang Po‐Heng , Hsu Wei‐Fan , Wang Hung‐Wei , Tsai Tsung‐Yu , Chen Hung‐Yao , Peng Cheng‐Yuan
Published: August 2021

Objectives

Direct‐acting antiviral agents achieve a high cure rate, resulting in early hepatic necroinflammatory resolution and sustained fibrosis regression. This study aimed to obtain longitudinal, concurrent within‐subject measurements of liver stiffness (LS) and spleen stiffness (SS) and their correlates over time.

Methods

Participants with hepatitis C (n = 592) receiving direct‐acting antiviral‐based therapy were monitored through point shear‐wave elastography from the treatment baseline (TW0) across follow‐up visits in terms of LS and SS.

Results

Generalized linear mixed modeling indicated that all LS values (2301 visits) were negatively correlated with the follow‐up times (all P < .05) from TW0 to 24 weeks (PW24) after the end of treatment (EOT) and positively correlated with baseline LS values (P < .001). The slopes of declines (preceding minus next) differed significantly (P < .001) between TW0–TW4 (treatment week 4) (0.060 [−0.050 to 0.225] meter/second/month [m/s/mo]) and TW4–EOT (0.010 [−0.030 to 0.075] m/s/mo). All SS values (1704 visits) were negatively correlated with time only at PW24 (P < .001) and positively correlated with baseline SS values (P < .001). The slopes of the SS values differed significantly (P < .001) only between EOT–PW12 (−0.010 [−0.110 to 0.083] m/s/mo) and PW12–PW24 (0.043 [−0.063 to 0.160] m/s/mo).

Conclusions

The biphasic fast‐to‐slow decline in LS occurred early in the on‐treatment phase, which is consistent with the resolution of hepatic necroinflammation. The slow‐to‐fast decline in SS occurred off treatment. Future studies should investigate the association with regressions in liver fibrosis and portal hypertension.
The Demographics of Patients Presenting for Laryngological Care at an Academic Medical Center
Authors: Madden Lyndsay L. , Hernandez Brian O. , Russell Gregory B. , Wright S. Carter , Kiell Eleanor P.
Published: August 2021

Objectives/Hypothesis

Few studies address the demographics/epidemiology/socioeconomic status of patients presenting to a laryngologist at a tertiary care center for treatment. To identify any possible disparities in voice, airway, and swallowing care, we sought to analyze the aforementioned data for new patients presenting to the voice center at an academic medical center.

Methods

This is a retrospective cohort study of prospectively collected data from an institutional database of 4,623 new adult patients presenting for laryngological care at a tertiary care, academic medical center from 2015 to 2020. Demographic data were analyzed.

Results

Of 4,623 patients, 62.8% were female and 37.2% were male with ages ranging from 19 to 99 years (Avg 59.51, standard deviation 15.83). Patients were 81.8% white, 13% black, and 5.2% other, compared with 56.3% white, 34.8% black, 20% other in the local municipality from US Census Data. Payer mix included 46.98% Medicare, 42.59% commercial insurance, 3.22% Medicaid, 5.19% other, and 2.01% uninsured/self‐insured. Patient demographics based on primary diagnosis codes were also examined. A majority of patients presented with voice‐related complaints.

Conclusions

Understanding the demographics of those with laryngological disorders will help to develop targeted interventions and effective outreach programs for underrepresented patient populations. Future multicenter studies could provide further insight into the distribution of healthcare disparities in laryngology.

Level of Evidence

3 Laryngoscope, 132:626–632, 2022
Comparison of the Signal Intensity of Vestibular Schwannoma Between Growing and Nongrowing Tumors
Authors: Yamada Hiroyuki , Kai Naruhiko , Hiratsuka Yoshiyasu , Mitani Sohei , Suehiro Satoshi , Shiraishi Yasuhiro , Kimura Takuya , Takagi Taro , Iwata Shinji , Teraoka Masato , Wakisaka Hiroyuki , Hato Naohito
Published: August 2021

Objectives/Hypothesis

To determine the relationship between signal intensity on gadolinium (Gd)‐enhanced magnetic resonance images and growth of vestibular schwannomas (VSs).

Study Design

Cross‐sectional study.

Methods

In this cross‐sectional study, we retrospectively reviewed the data of 31 patients with VSs who underwent magnetic resonance imaging (MRI). The mean signal intensities within the regions of interest in the tumor, pons, and temporal muscles were measured on Gd‐enhanced T1‐weighted MRI. Relative intensity ratios were calculated as follows: T/N pons ratio (T/Np) is the tumor signal intensity/pons signal intensity and T/N muscle ratio (T/Nm) is the tumor signal intensity/temporal muscle signal intensity. Volume measurements were used to assess the tumor size. Growth rate was determined by assessing previous imaging studies. Growing VS was defined as a tumor with a growth rate >100 mm3/year.

Results

The mean (standard deviation) T/Np and T/Nm were 1.47 (0.27) and 1.50 (0.24), respectively, in nongrowing tumors and 1.78 (0.17) and 1.90 (0.12), respectively, in growing tumors. The T/Np and T/Nm differed significantly between the two groups (T/Np, P < .001; T/Nm, P < .001). Receiver operating characteristic curve analysis showed that cutoffs of 1.56 and 1.76 for T/Np (93.33% sensitivity, 75.00% specificity) and T/Nm (100.00% sensitivity, 93.75% specificity), respectively, could be used to diagnose a growth rate of >100 mm3/year. The area under the curve was 0.85 (95% confidence interval, 0.70–1.00) for T/Np and 0.94 (0.82–1.00) for T/Nm.

Conclusion

Growing VSs show higher signal intensities on Gd‐enhanced MRI. Thus, measuring the signal intensity of VS on Gd‐enhanced MRI may aid in predicting VS growth.

Level of Evidence

3 Laryngoscope, 132:198–203, 2022
Does MDS‐UPDRS Provide Greater Sensitivity to Mild Disease than UPDRS in De Novo Parkinson's Disease?
Authors: Tosin Michelle H.S. , Stebbins Glenn T. , Comella Cynthia , Patterson Charity G. , Hall Deborah A. ,   the SPARX Study Group
Published: August 2021

Background

The Movement Disorder Society revision of the Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) was designed to be more sensitive to mild motor severity than the Unified Parkinson's Disease Rating Scale (UPDRS).

Objective

To test whether MDS‐UPDRS Part III items provide increased sensitivity to mild motor severity when compared to the same items of the UPDRS in de novo PD patients.

Method

Using a sample of 129 de novo PD patients assessed at one time point simultaneously with both scales, we compared the scale's scores on the 17 items measuring the same motor function. The scaling anchors for the MDS‐UPDRS were Slight, Mild, Moderate and Severe, and for the UPDRS were Mild, Moderate, Severe and Marked. Using Classical Test Theory (CTT) we compared the distributions of the scaling anchors from the individual items. Using Item Response Theory (IRT), we examined the sensitivity of the scaling anchors from each scale to the latent‐trait measurement of overall parkinsonian motor severity.

Results

There was 2193 observations of individual scaling anchors from the 17 items in both scales. The CTT approach revealed frequent floor effects with only the item assessing Gait demonstrating a significance difference in the scaling distribution between the scales (P = 0.005). The IRT analyses revealed similar levels of sensitivity to the latent trait of PD motor function.

Conclusion

These results do not support increased sensitivity of MDS‐UPDRS over the UPDRS for assessing mild motor severity in de novo PD patients, with significant difference in the scaling only for the item assessing gait.
Can pay‐performance sensitivity cure zombie firms? Evidence from China
Authors: Wu Yumeng , Pan Haiying
Published: August 2021

The proper disposal of zombie firms is the key to supply‐side structural reform. Based on data of A‐share markets from 2009 to 2018, this study explores the impact of pay‐performance sensitivity (PPS) of executives on curing zombie firms. The findings show that PPS has a significant effect on curing zombie firms, and the innovation performance plays a partially mediating role between PPS and cured zombie firms. Further analysis shows that the above effects are heterogeneous, demonstrating that the effects of PPS on curing zombie firms are more pronounced for technology‐intensive industrial firms and non‐state‐owned firms.
Academic partners see benefit in collaborative training
Authors: Enos Gary
Published: August 2021

Partners in a mental health workforce development initiative in central New York believe greater collaboration among mental health disciplines can help improve quality of care to the underserved while also easing a shortage of clinical professionals in the region. An initiative funded by the federal Health Resources and Services Administration (HRSA) is establishing a multidisciplinary training program designed to improve services for high‐need populations.
Homogeneous generalized Einstein manifolds in dimension four
Authors: García‐Río Eduardo , Mariño‐Villar Rodrigo , Vázquez‐Abal Maria Elena , Vázquez‐Lorenzo Ramon
Published: August 2021

We classify homogeneous four‐dimensional manifolds satisfying a curvature condition which naturally generalizes the Einstein one. Our work leads to new examples of self‐similar solutions of the two‐loop renormalization group flow.
D'Alembert type traveling wave solution for wave equations on a finite interval with coupled initial boundary conditions
Authors: Chen Songlin , Ma Wenran
Published: August 2021

In this paper, we study coupled wave equations which are defined on a semi‐infinite interval and a finite interval, respectively, and obtain their d'Alembert type traveling wave solutions with finite closed forms. We also illustrate the results by concrete examples. These results generalized the corresponding ones for single wave equation wherein the solution is usually expressed by Fourier series.
Registration of ‘Plainsmen’ tall wheatgrass
Authors: Trammell Michael A. , Hopkins Andrew A. , Butler Twain J. , Walker Dennis
Published: August 2021

‘Plainsmen’ (Reg. no. CV‐288, PI 698191) tall wheatgrass [Thinopyrum ponticum (Podp.) Z.‐W. Liu & R.‐C. Wang], also tested under the experimental designations NFTW6020 and Jose FYLD C1, was developed by the Noble Research Institute and released in 2014. A population was developed from selections from the cultivar ‘Jose’ for persistence under grazing and two cycles of selection for digestibility. The parents of Plainsmen were selected using within‐ and among‐family selection from this population based on autumn forage yield greater than 100% of the nursery mean. The heading date of Plainsmen in Ardmore, OK, is on average 5 d earlier than that of Jose. Seed size, as indicated by 1,000‐seed weight, of Plainsmen (4,724 mg) was greater than that of Jose (4,161 mg) and ‘Platte’ (3,143 mg). Persistence was improved by selection, with stands of Plainsmen ranging from 90 to 294% greater than stands of Jose across three locations. Total autumn forage yields of Plainsmen were greater by 45 and 53% than those of Jose at Iowa Park, TX, and Ardmore, OK, respectively. Crude protein and digestibility of Plainsmen and Jose were similar in both the autumn and spring, despite earlier maturity of Plainsmen. Seedling vigor, using a visual rating scale of 0–5, was greater for Plainsmen (4.3) than Jose (2.7). Plainsmen was released due to its improved autumn forage yield and persistence under grazing relative to Jose.
Model dynamic covalent organogels based on end‐linked three‐armed oligo(ethylene glycol) star macromonomers
Authors: Apostolides Demetris E. , Patrickios Costas S.
Published: August 2021

Dynamic covalent polymer networks represent a rapidly emerging class of polymeric materials, capable of self‐repairing when mechanically damaged. These materials also possess the ability to being dissolved and reformed, conferring upon objects made of such materials a longer service life, with positive economic and environmental impacts. While most such materials developed to date have a poorly‐defined structure, as they are randomly cross‐linked, better‐defined dynamic covalent polymer networks comprising model building blocks attract increasing interest, both because of enhanced mechanical properties and offering themselves for more precise studies. This investigation presents the development of model dynamic covalent polymer networks, cross‐linked via acylhydrazone bonds, and based on end‐linked star oligomers, that is, having a size intermediate between polymeric stars and monomers. After their appropriate end‐functionalization and purification, the oligomeric star building blocks were used to form polymeric networks in an organic solvent (organogels), which were subsequently characterized in terms of their swelling, mechanical, and dynamic properties.
Computational modeling reveals key molecular properties and dynamic behavior of disruptor of telomeric silencing 1‐like (DOT1L) and partnering complexes involved in leukemogenesis
Authors: Stodola Timothy J. , Chi Young‐In , De Assuncao Thiago M. , Leverence Elise N. , Tripathi Swarnendu , Dsouza Nikita R. , Mathison Angela J. , Volkman Brian F. , Smith Brian C. , Lomberk Gwen , Zimmermann Michael T. , Urrutia Raul
Published: August 2021

Disruptor of telomeric silencing 1‐like (DOT1L) is the only non‐SET domain histone lysine methyltransferase (KMT) and writer of H3K79 methylation on nucleosomes marked by H2B ubiquitination. DOT1L has elicited significant attention because of its interaction or fusion with members of the AF protein family in blood cell biology and leukemogenic transformation. Here, our goal was to extend previous structural information by performing a robust molecular dynamic study of DOT1L and its leukemogenic partners combined with mutational analysis. We show that statically and dynamically, D161, G163, E186, and F223 make frequent time‐dependent interactions with SAM, while additional residues T139, K187, and N241 interact with SAM only under dynamics. Dynamics models reveal DOT1L, SAM, and H4 moving as one and show that more than twice the number of DOT1L residues interacts with these partners, relative to the static structure. Mutational analyses indicate that six of these residues are intolerant to substitution. We describe the dynamic behavior of DOT1L interacting with AF10 and AF9. Studies on the dynamics of a heterotrimeric complex of DOT1L1‐AF10 illuminated describe coordinated motions that impact the relative position of the DOT1L HMT domain to the nucleosome. The molecular motions of the DOT1L–AF9 complex are less extensive and highly dynamic, resembling a swivel‐like mechanics. Through molecular dynamics and mutational analysis, we extend the knowledge previous provided by static measurements. These results are important to consider when describing the biochemical properties of DOT1L, under normal and in disease conditions, as well as for the development of novel therapeutic agents.
Machine Learning‐Based and Experimentally Validated Optimal Adhesive Fibril Designs
Authors: Son Donghoon , Liimatainen Ville , Sitti Metin
Published: August 2021

Setae, fibrils located on a gecko's feet, have been an inspiration of synthetic dry microfibrillar adhesives in the last two decades for a wide range of applications due to unique properties: residue‐free, repeatable, tunable, controllable and silent adhesion; self‐cleaning; and breathability. However, designing dry fibrillar adhesives is limited by a template‐based‐design‐approach using a pre‐determined bioinspired T‐ or wedge‐shaped mushroom tip. Here, a machine learning‐based computational approach to optimize designs of adhesive fibrils is shown, exploring a much broader design space. A combination of Bayesian optimization and finite element methods creates novel optimal designs of adhesive fibrils, which are fabricated by two‐photon‐polymerization‐based 3D microprinting and double‐molding‐based replication out of polydimethylsiloxane. Such optimal elastomeric fibril designs outperform previously proposed designs by maximum 77% in the experiments of dry adhesion performance on smooth surfaces. Furthermore, finite‐element‐analyses reveal that the adhesion of the fibrils is sensitive to the 3D fibril stem shape, tensile deformation, and fibril microfabrication limits, which contrast with the previous assumptions that mostly neglect the deformation of the fibril tip and stem, and focus only on the fibril tip geometry. The proposed computational fibril design could help design future optimal fibrils with less help from human intuition.
Acetylcholinesterase inhibitors and risk of bleeding and acute ischemic events in non‐hypertensive Alzheimer's patients
Authors: Al‐Hamed Faez Saleh , Kouniaris Stamatis , Tamimi Iskandar , Lordkipanidzé Marie , Madathil Sreenath Arekunnath , Kezouh Abbas , Karp Igor , Nicolau Belinda , Tamimi Faleh
Published: August 2021

Introduction

Acetylcholinesterase inhibitors (AChEIs) are commonly used to treat mild to moderate cases of Alzheimer disease (AD). To the best of our knowledge, there has been no study estimating the risk of bleeding and cardiovascular events in patients with non‐hypertensive AD. Therefore, this study aimed to estimate the association between AChEIs and the risk of bleeding and cardiovascular ischemic events in patients with non‐hypertensive AD.

Methods

A nested case‐control study was conducted to estimate the risk of bleeding and ischemic events (angina, myocardial infarction [MI], and stroke) in patients with AD. This study was conducted using the UK Clinical Practice Research Datalink and Hospital Episode Statistics (HES) databases. The study cohort consisted of AD patients ≥65 years of age. The case groups included all AD subjects in the database who had a bleeding or ischemic event during the cohort follow‐up. Four controls were selected for each case. Patients were classified as current users or past users based on a 60‐day threshold of consuming the drug. Simple and multivariable conditional logistic regression analyses were used to calculate the adjusted odds ratio for bleeding events and cardiovascular events.

Results

We identified 507 cases and selected 2028 controls for the bleeding event cohort and 555 cases and 2220 controls for the ischemic event cohort. The adjusted odds ratio (OR) (95% confidence interval [CI]) for the association of AChEI use was 0.93 (0.75 to 1.16) for bleeding events, 2.58 (1.01 to 6.59) for angina, and 1.89 (1.07 to 3.33) for MI. Past users of AChEIs were also at increased risk of stroke (1.51 [1.00 to 2.27]).

Discussion

This is the first study assessing the risk of bleeding and cardiovascular events in patients with non‐hypertensive AD. Our findings could be of great interest for clinicians and researchers working on AD.
From practice, pharma and politics to president
Authors: Loeb Josh
Published: August 2021

Making ‘connections that count’ is the theme of Kate Richards' presidential year, as she takes the reins at the top of the RCVS. Here, Josh Loeb chats to her about her background, her varied career and her plans for the future.
Introduction: Music, from Intangible Cultural Heritage to the Music Industry
Authors: de-Miguel-Molina Blanca , Boix-Doménech Rafael
Published: August 2021

Our first contact with music is almost certainly in our childhood when our parents sing lullabies to us at bedtime. In a community where music is important, these songs are likely to be successfully transmitted from one generation to the next. This is similar to the concept of intangible cultural heritage and how it is transmitted.
Non-flat elliptic four-folds, three-form cohomology and strongly coupled theories in four dimensions
Authors: Oehlmann Paul-Konstantin
Published: August 2021

Abstract

In this note we consider smooth elliptic Calabi-Yau four-folds whose fiber ceases to be flat over compact Riemann surfaces of genus g in the base. These non-flat fibers contribute Kähler moduli to the four-fold but also add to the three-form cohomology for g > 0. In F-/M-theory these sectors are to be interpreted as compactifications of six/five dimensional $$ \mathcal{N} $$
N
= (1, 0) superconformal matter theories. The three-form cohomology leads to additional chiral singlets proportional to the dimension of five dimensional Coulomb branch of those sectors. We construct explicit examples for E-string theories as well as higher rank cases. For the E-string theories we further investigate conifold transitions that remove those non-flat fibers. First we show how non-flat fibers can be deformed from curves down to isolated points in the base. This removes the chiral singlet of the three-forms and leads to non-perturbative four-point couplings among matter fields which can be understood as remnants of the former E-string. Alternatively the non-flat fibers can be avoided by performing birational base changes analogous to 6D tensor branches. For compact bases these transitions alternate all Hodge numbers but leave the Euler number invariant.
Endoskopische Ohrchirurgie in Deutschland
Authors: Agha-Mir-Salim Parwis , Kropp Miriam , Müller Alexander
Published: August 2021

Hintergrund

International hat sich die endoskopische Ohrchirurgie („endoscopic ear surgery“, EES) fest etabliert. In Deutschland wird sie kontrovers diskutiert und unterschiedlich angewendet. Daher erfolgte eine Umfrage zu Angebot, Indikationen, Kontraindikationen und zum zukünftigen Stellenwert der EES.

Methodik

An 141 deutsche Universitäts- und Hauptabteilungen für HNO-Heilkunde, Kopf- und Halschirurgie wurde ein Fragebogen mit 20 Fragen versendet. Die Ergebnisse wurden anhand aktueller Literatur gemäß Suche in PubMed und Google Scholar erörtert.

Ergebnisse

Der Umfragerücklauf betrug 32 % (45 Kliniken). Die EES meist flankierend durchzuführen, gaben 27 Kliniken (60 % der Antwortenden) an. Nur eine Klinik führte alle Ohreingriffe ausschließlich endoskopisch durch. Bei Auftreten intraoperativer Blutungen, Bohrarbeiten am Mastoid oder bei Notwendigkeit bimanuellen Arbeitens wurde zur mikroskopischen Technik („microscopic ear surgery“, MES) gewechselt. Als häufigste Indikationen für die EES wurden Tympanoskopie, Cholesteatom, Retraktionstasche, Eingriffe am Trommelfell und am Gehörgang angegeben. Der Aufwand bei der EES wurde in rund 50 % aller Antworten höher als in der MES eingeschätzt. Bei den EES-Kliniken dominierte mit 78 % der Tragusknorpel als rekonstruktives Transplantat. Nur 4 von 45 antwortenden Kliniken schätzten den zukünftigen Stellenwert der EES in Deutschland als hoch ein.

Schlussfolgerung

Die EES wird in Deutschland zwar eingesetzt, jedoch nur in wenigen HNO-Kliniken in größerem Umfang angewendet. Als problematisch gelten das einhändige Arbeiten, die Durchführung von Bohrarbeiten, Beherrschung von Blutungen und der insgesamt als höher eingeschätzte Aufwand. Häufig wird deshalb die EES flankierend am Ohr angewendet und zwischen EES und MES gewechselt.
Nonclinical pharmacology of daridorexant: a new dual orexin receptor antagonist for the treatment of insomnia
Authors: Roch Catherine , Bergamini Giorgio , Steiner Michel A. , Clozel Martine
Published: August 2021

Dual orexin receptor antagonists (DORAs) represent a novel type of sleep medication that provide an alternative to the traditionally used positive allosteric gamma-aminobutyric acid (GABA)-A receptor modulators. Daridorexant is a new DORA that exhibited in phase 3 trials in insomnia not only a beneficial effect on sleep variables, measured objectively and assessed subjectively, but also an improvement in daytime functioning. Daridorexant was discovered through a tailored research program aimed at identifying an optimized sleep-promoting molecule with pharmacokinetic properties appropriate for covering the whole night while avoiding next-morning residual activity at efficacious doses. By specific binding to both orexin receptors, daridorexant inhibits the actions of the wake-promoting orexin (also called hypocretin) neuropeptides. This mechanism avoids a more widespread inhibition of neuronal pathways and associated side effects that are intrinsic to positive allosteric GABA-A receptor modulators. Here, we review the general pharmacology of daridorexant, based on nonclinical pharmacology studies of daridorexant, unpublished or already described, or based on work with other DORAs. Some unique features of daridorexant will be highlighted, such as the promotion of natural and surmountable sleep, the preservation of memory and cognition, the absence of tolerance development or risk of physical dependence, and how it can benefit daytime functioning.