bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioequivalence and Pharmacokinetics Study of Two Zidovudine/Lamivudine Tablets in Chinese Healthy Volunteers
Authors: Huang Xiaomei , Wang Gongzhu , Huang Jian , Liang Wu , Guan Huiyu , Liu Haisha , Deng Yuan , You Yu , Zhang Bikui
Published: November 2023

Zidovudine/lamivudine tablets are nucleoside reverse transcriptase inhibitors that are used to treat human immunodeficiency virus. The objective of this study was to investigate the bioequivalence and pharmacokinetics (PKs) of test and reference preparations of zidovudine/lamivudine tablets in healthy Chinese subjects. We designed a randomized, open, single‐center, single‐dose, 2‐crossover experiment with a 7‐day washout period involving 20 healthy subjects. The subjects were given a single dose of the test or reference preparation after fasting overnight for 10 hours. Blood samples were subsequently collected at scheduled time points from 0 hour (preadministration) up to 24 hours postadministration. The plasma concentrations of zidovudine and lamivudine were determined by a validated ultra‐performance liquid chromatography‐tandem mass spectrometry method. Analysis of variance (ANOVA) was used to compare differences in the mean values of key PK parameters between the 2 preparations. Bioequivalence was evaluated by 2 one‐sided t‐tests and 90% confidence intervals (CIs) of the geometric mean ratio (GMR). In total, 19 of the 20 subjects completed the trial. Based on the analysis of PK parameters, the relative bioavailability of zidovudine and lamivudine was 101.1% ± 2.0% and 100.3% ± 1.5%, respectively. ANOVA found no significant difference in primary PK parameters when compared between the 2 formulations, and the 90% CIs of the GMR of the 2 formulations were within the bioequivalence margins of 80%–125%. No serious adverse events occurred. Thus, we confirmed that the 2 preparations were bioequivalent in healthy Chinese volunteers. Our analysis demonstrated that both products showed good tolerance in all subjects.
Bioequivalence of 200 mg Amisulpride Tablets in Healthy Chinese Volunteers under Fasting and Fed Conditions
Authors: Cao Yi , Su Jianfen
Published: November 2023

In this study, we compared the pharmacokinetics and safety of a new generic product and a branded reference product of amisulpride tablets. Additionally, we assessed the bioequivalence of the 2 products in healthy Chinese volunteers to acquire sufficient evidence for the marketing approval of the generic drug. Thirty volunteers under fasting and fed conditions were randomly administered a single dose of the test or reference drug orally, followed by a 7‐day washout period. The pharmacokinetic parameters were obtained by the concentration‐time profiles, including the area under the plasma concentration‐time curve (AUC) over the dosing interval, AUC from time zero to infinity, maximum plasma concentration, time to achieve maximum plasma concentration, and elimination half‐life. AUC from time zero to infinity of amisulpride in the postprandial group was reduced by approximately 25%, suggesting that a high‐fat diet can affect this parameter. In the aspect of safety, no serious adverse events occurred. This study demonstrated that generic and reference products of amisulpride tablets were bioequivalent in healthy Chinese volunteers under fasting and fed conditions.
Implementation and evaluation of two parallel computational models for the simulation of a long‐haul DWDM system limited by FWM
Authors: Sánchez‐Lara Rafael , López‐Martínez José L. , Trejo‐Sánchez Joel A. , Offerhaus Herman L. , Álvarez‐Chávez José A.
Published: November 2023

Four‐Wave Mixing (FWM) is one of the non‐linear phenomena affecting long‐reach communication systems and high bandwidth. Research communities use simulation tools for parameter optimization. Unfortunately, such a simulation is time‐consuming and requires more time as the number of channels increases. This paper proposes two fast implementations of Dense Wavelength Division Multiplexing (DWDM) system, limited by FWM and the intrinsic Amplified Spontaneous Emission (ASE) noise of optical amplifiers employed in each segment. Additionally, this work compares the efficiency and speed improvement of the proposed parallelization model versus an earlier sequential model. We present the computational complexity analysis of sequential and parallel models. The paper considers two different parallel implementations: a multicore processor using Open MultiProcessing (OpenMP) and Compute Unified Device Architecture (CUDA), which is based on the use of a Graphics Processing Unit (GPU). Results show that parallelism using CUDA improves by up to 70 times the simulation performance compared to the sequential model. Parallelism with CUDA is up to 15 times compared to OpenMP using 12 logical processors. It is possible to simulate an increased number of channels within our parallel execution, which was impractical in the sequential simulation.
Creating a Roadmap to Quantitative Systems Pharmacology–Informed Rare Disease Drug Development: A Workshop Report
Authors: Bai Jane P.F. , Stinchcomb Audra L. , Wang Jie , Earp Justin , Stern Sydney , Schuck Robert N.
Published: November 2023

One of the goals of the Accelerating Rare Disease Cures (ARC) program in the Center for Drug Evaluation and Research (CDER) at the US Food and Drug Administration (FDA) is the development and use of regulatory and scientific tools, including drug/disease modeling, dose selection, and translational medicine tools. To facilitate achieving this goal, the FDA in collaboration with the University of Maryland Center of Excellence in Regulatory Science and Innovation (M‐CERSI) hosted a virtual public workshop on May 11, 2023, entitled “Creating a Roadmap to Quantitative Systems Pharmacology–Informed Rare Disease Drug Development.” This workshop engaged scientists from pharmaceutical companies, academic institutes, and the FDA to discuss the potential utility of quantitative systems pharmacology (QSP) in rare disease drug development and identify potential challenges and solutions to facilitate its use. Here, we report the main findings from this workshop, highlight the key takeaways, and propose a roadmap to facilitate the use of QSP in rare disease drug development.
Overview of Determination of Biopharmaceutical Properties for Development Candidate Selection
Authors: Yazdanian Mehran
Published: November 2023

The physicochemical and biopharmaceutical properties of putative drug molecules impact their performance in both in vitro and in vivo studies. The design and selection of molecules with drug‐like properties assist in the selection of drug candidates with a higher probability of success in the development process. Described in this overview are commonly used approaches for measuring compound solubility, permeability, and partitioning in drug discovery and development. The utility of these methods in the drug discovery process and product development is discussed. The evaluation of crystallinity and physicochemical stability in relation to biopharmaceutical properties and in assessing the potential for successful development is also discussed. © 2023 Wiley Periodicals LLC.
Genotyping Protocols for Genetically Engineered Mice
Authors: Limaye Advait , Cho Kyoungin , Hall Bradford , Khillan Jaspal S. , Kulkarni Ashok B.
Published: November 2023

Historically, the laboratory mouse has been the mammalian species of choice for studying gene function and for modeling diseases in humans. This was mainly due to their availability from mouse fanciers. In addition, their short generation time, small size, and minimal food consumption compared to that of larger mammals were definite advantages. This led to the establishment of large hubs for the development of genetically modified mouse models, such as the Jackson Laboratory. Initial research into inbred mouse strains in the early 1900s revolved around coat color genetics and cancer studies, but gene targeting in embryonic stem cells and the introduction of transgenes through pronuclear injection of a mouse zygote, along with current clustered regularly interspaced short palindromic repeat (CRISPR) RNA gene editing, have allowed easy manipulation of the mouse genome. Originally, to distribute a mouse model to other facilities, standard methods had to be developed to ensure that each modified mouse trait could be consistently identified no matter which laboratory requested it. The task of establishing uniform protocols became easier with the development of the polymerase chain reaction (PCR). This chapter will provide guidelines for identifying genetically modified mouse models, mainly using endpoint PCR. In addition, we will discuss strategies to identify genetically modified mouse models that have been established using newer gene‐editing technology such as CRISPR. Published 2023. This article is a U.S. Government work and is in the public domain in the USA.

Basic Protocol 1: Digestion with proteinase K followed by purification of genomic DNA using phenol/chloroform

Alternate Protocol: Digestion with proteinase K followed by crude isopropanol extraction of genomic DNA for tail biopsy and ear punch samples

Basic Protocol 2: Purification of genomic DNA using a semi‐automated system

Basic Protocol 3: Purification of genomic DNA from semen, blood, or buccal swabs

Basic Protocol 4: Purification of genomic DNA from mouse blastocysts to assess CRISPR gene editing

Basic Protocol 5: Routine endpoint‐PCR‐based genotyping using DNA polymerase and thermal cycler

Basic Protocol 6: T7E1/Surveyor assays to detect insertion or deletions following CRISPR editing

Basic Protocol 7: Detecting off‐target mutations following CRISPR editing

Basic Protocol 8: Detecting genomic sequence deletion after CRISPR editing using a pair of guide RNAs

Basic Protocol 9: Detecting gene knock‐in events following CRISPR editing

Basic Protocol 10: Screening of conditional knockout floxed mice
Aniline Derivatives from Lignin under Mild Conditions Enabled by Electrochemistry
Authors: Castillo‐Garcia Antonio A. , Kappe Christian Oliver , Cantillo David , Barta Katalin
Published: November 2023

The development of environmentally friendly methods for the valorization of important phenolic platform chemicals originating directly from lignin‐first depolymerization into value‐added N‐chemicals, such as aniline derivatives, is of high industrial interest. In this work, we tackle this challenging transformation by the judicious combination of electrochemical conversion and chemical functionalization steps. In the first step, lignin‐derived para‐substituted guaiacols and syringols undergo an atom‐efficient, room‐temperature anodic oxidation using methanol both as solvent and reagent towards the formation of the corresponding cyclohexadienone derivatives, which are subsequently converted to synthetically challenging ortho‐methoxy substituted anilines by reaction with ethyl glycinate hydrochloride under mild conditions. The developed method was applied to crude lignin depolymerization bio‐oils, derived from reductive catalytic fractionation (RCF) mediated either by copper‐doped porous metal oxide (Cu20PMO) or Ru/C, allowing the selective production of 4‐propanol‐2‐methoxyaniline (1Gb) and 4‐propyl‐2‐methoxyaniline (2Gb), respectively, from pine lignocellulose. Finally, the application of 2Gb was further studied in the synthesis of carbazole 2Gc, a lignin‐derived analogue of biologically active alkaloid murrayafoline A.
The potential clinical impact of cell type‐specific genetic regulation: Crohn's disease
Authors: Tyebally Rika , Xue Angli , Powell Joseph E.
Published: November 2023

Complex diseases are heterogenous due to variation in their genetic and environmental underpinnings, leading to varied treatment responses. Genome‐wide association studies (GWAS) integrated with single‐cell expression quantitative trait loci analyses (eQTL) can pinpoint cell‐type specific candidate disease‐relevant genes and pathways. This knowledge can be applied to patient stratification and novel therapeutic target identification. Here, we describe the translational potential of cell‐type specific genetic regulation, using Crohn's disease as an example.
Anti‐allodynic and anti‐hyperalgesic activity of (±)‐licarin A in neuropathic rats via NO‐cyclic‐GMP‐ATP‐sensitive K+ channel pathway
Authors: Hernández‐Vázquez Liliana , Colín‐Martínez Brian , Lara‐Ruíz María Guadalupe , Cordova‐Alonso Beatriz , González‐Morales Estefanía , Godínez‐Chaparro Beatriz
Published: November 2023

The study aimed to examine the effect of intraperitoneal and intrathecal (±)‐licarin A in neuropathic pain induced by L5 and L6 spinal nerve ligation (SNL) in male Wistar rats and the possible involvement of the NO‐cGMP‐ATP‐sensitive K+ channel pathway. Neuropathic pain signs (allodynia and hyperalgesia) were evaluated on postoperative Day 14 using von Frey filaments. Single intraperitoneal (0.01, 0.1, 1, and 10 mg/kg) and intrathecal (0.01, 0.1, 1, and 10 µg/rat) administration of (±)‐licarin A improved allodynia and hyperalgesia. The (±)‐licarin A‐induced anti‐allodynic and anti‐hyperalgesic activity was prevented by the intrathecal injection of 
l‐NAME (100 µg/rat; nonselective nitric oxide synthase inhibitor), ODQ (10 µg/rat; guanylate cyclase inhibitor), and glibenclamide (50 µg/rat; adenosine triphosphate (ATP)‐sensitive K+ channel blocker). The data suggest that (±)‐licarin A exerts its anti‐allodynic and anti‐hyperalgesic activity by activating the NO‐cGMP‐ATP‐sensitive K+ channel pathway.
The Circular Economy in European Union Policy: Explaining an idea's success through policy learning
Authors: Pinyol Alberich Josep , Hartley Sarah
Published: November 2023

The circular economy (CE) was adopted in 2015 by the European Union (EU). Since its emergence, the CE has proved to be a remarkably powerful idea that has shifted the understanding of the economy, and consequently, it has shaped the EU's economic and environmental policies. The public policy literature theorises such shifts in collective understanding through the concept of policy learning, a process through which ideas are understood and adopted. Yet this literature lacks clarity on the factors that can explain policy learning within a policy community. We use the case of the EU's adoption of the CE to address this gap, exploring the factors that account for the EU's adoption of the CE from the policy‐learning perspective. We show how actors in the policy community have constructed, championed, supported and pioneered the CE and argue that these four factors have mutually reinforced each other, leading to policy learning and the wide acceptance of this idea within EU policy‐making. Revealing these factors helps advance policy learning theory and contributes to the CE literature and environmental policy and governance literature more generally by furthering our understanding of how and why certain policy ideas are adopted.
Transjugular tricuspid valve‐in‐ring replacement using the novel system under three‐dimensional printing guidance
Authors: Wang Yiwei , Liu Yang , Yang Jian
Published: November 2023

Recurrent tricuspid regurgitation after failed ring annuloplasty is associated with high mortality rates and unfavourable clinical outcomes. Transcatheter tricuspid valve‐in‐ring (TVIR) replacement offers an alternative to high‐risk surgical reoperation, but challenges remain. We present a case of a 67‐year‐old male who underwent tricuspid annuloplasty 3 years ago and developed severe recurrent tricuspid regurgitation (regurgitation volume = 36 mL) 6 months ago. To avoid a high‐risk thoracotomy, we finally performed TVIR replacement using the novel device, LuX‐Valve Plus system, via the transjugular approach. Cardiovascular three‐dimensional printing technology was utilized to investigate the distinct advantages offered by the new device in this specific intervention, as well as to simulate the procedure. Successful TVIR replacement resulted in significant symptomatic improvement. TVIR replacement with the LuX‐Valve Plus system is feasible for failed annuloplasty ring cases. Patient‐specific three‐dimensional printed models enable personalized procedural planning, enhancing safety and precision.
Bioinspired Photoredox Oxidation of Alcohols with Copper‐Containing Galactose Oxidase Analog
Authors: Chiang Chien‐Wei , Chou Yi‐Hsien , Chou Chih‐Hui , Chen Hung‐Chi , Chen Jeng‐Lung , Hsu Liang‐Ching , Huang Wei‐Hsiang , Li Hung‐Li , Liu Yu‐Hao
Published: November 2023

Enzyme mimic studies are driven by a variety of factors, including understanding the function of the active site, replicating enzyme activity, and constructing bio‐inspired catalysts. In this study, we present a ferrocene‐conjugated copper complex (FcTrpCOO)Cu(bpy) that not only serves as a structural analog of Galactose oxidase (GOase) but also demonstrates impressive catalytic efficiency for alcohol oxidation via a photoredox process. Mechanistic investigations of the reaction were carried out using a range of spectroscopic techniques, including UV‐Vis, IR, CV, LC‐MS, XAS, and EPR. These findings offer valuable insights into the mechanism of alcohol oxidation in biological systems and provide a promising approach for developing efficient and eco‐friendly catalysts for chemical synthesis.
Electrochemically Driven Tandem Cyclization Reaction of Unsaturated Sulfoximines with Diselenides
Authors: Yang Jie , Gao Wenchao , Teng Yong , Yu Lintao , Huang Kexin , Li Qiyang , Xie Huanping , Li Ting
Published: November 2023

An electrochemically enabled tandem cyclization reaction of unsaturated sulfoximines with diselenides has been well developed, affording metal‐ and external oxidant‐free access to sulfoximidoyl‐based heterocycles containing selenium in moderate to good yields. With nBu4NBr as the role of catalyst and electrolyte, this methodology shows broad substrate scope and functional group tolerance under mild conditions.
Divergent Synthesis of (Benzo[b][1,4]diazepin‐2‐yl)phosphonates and (Quinoxalin‐2‐yl)methylphosphonates from Phosphoryl‐Substituted Conjugated Ynones
Authors: Mitrofanov Alexander Yu. , Gontcharenko Victoria E. , Beletskaya Irina P.
Published: November 2023

It is shown that the reaction of conjugated ynones containing a phosphoryl group with o‐phenylenediamines can, depending on the conditions, lead to the selective formation of phosphorylated 1,5‐benzodiazepines and quinoxalines. Phosphorylated quinoxalines can be used for synthesis of substituted vinyl quinoxalines.
Evans’ Chiral Auxiliary‐Based Asymmetric Synthetic Methodology and Its Modern Extensions
Authors: Chen Ling‐Yan , Huang Pei‐Qiang
Published: November 2023

Although the asymmetric catalysis has made a spurt of progress, the use of chiral auxiliaries remains crucial in asymmetric synthesis due to both the reliability and versatility of the methods, and the predictability of stereochemistry of the reactions. Up to date, Evans’ chiral non‐racemic oxazolidinone‐based asymmetric synthetic methodology is still widely used in asymmetric synthesis. More importantly, the Evans asymmetric synthetic methodology turned out to be a fruitful source of inspiration for the development of related asymmetric synthetic methodologies. However, although reviews on the application of Evans’ asymmetric synthetic methodology in both organic synthesis and medicinal chemistry continually to appear in the literature, a comprehensive review dedicating to the extensions of Evans’ chiral non‐racemic oxazolidinone‐based asymmetric methodology remains elusive. In this review, we summarize the extensions of the Evans asymmetric methodology, which cover: (1) the modification of the chiral oxazolidinone auxiliaries; (2) the extension of the Evans’ asymmetric aldol reaction from Evans’ syn‐aldol to other diastereomeric aldol adducts; (3) the extension of the asymmetric reaction types; (4) the extension of chiral imide‐type substrates to N‐alkenyl, N‐allenenyl and N‐alkynyl oxazolidinones; (5) the achiral oxazolidinone‐based asymmetric catalysis; (6) the catalytic transformation of Evans’ products; and (7) the straightforward transformations of Evans’ chiral products to other classes of compounds than the chiral carboxylic acids, esters, alcohols, and Weinreb amides.
The intra‐individual power of contact: Investigating when, how and why intergroup contact and intergroup outcomes fluctuate together
Authors: Boin Jessica , Fuochi Giulia , Voci Alberto , Hewstone Miles
Published: November 2023

Intergroup contact research has rarely considered the intra‐individual (within‐person) variability of contact. Using a three‐wave longitudinal dataset (N = 565), this research aimed to (a) test the within‐person simultaneous associations between positive and negative contacts and several intergroup outcomes (i.e. attitudes, prejudice, perceived variability, anxiety, empathy and deprovincialization), while controlling for between‐person associations; (b) understand whether and how within‐person simultaneous associations are mediated by empathy, anxiety and deprovincialization, and moderated by between‐person contact and social dominance orientation (SDO). We found that within‐ and between‐person variations in positive and negative contacts were associated with all intergroup outcomes, except intergroup anxiety for within‐person contact. These associations were mainly mediated by the same processes (i.e., empathy and deprovincialization); the associations of within‐person variations in contact with intergroup outcomes were largely independent of between‐person contact and SDO. Intra‐individual contact fluctuations matter for simultaneous prejudice reduction, suggesting the importance of frequent positive contact.
Coupling capillary electrophoresis with mass spectrometry for the analysis of oxidized phospholipids in human high‐density lipoproteins
Authors: Chen Chao‐Jung , Chang Chiz‐Tzung , Lin Zhi‐Ru , Chiu Wen‐Chien , Liu Jia‐Yuan , Ye Zhi‐Cheng , Wang Chuan‐Jun , Shieh Ying‐Tzu , Liu Mine‐Yine
Published: November 2023

The oxidized 1‐palmitoyl‐2‐arachidonoyl‐sn‐glycero‐3‐phosphocholine (ox‐PAPC) products in human high‐density lipoproteins (HDLs) were investigated by low‐flow capillary electrophoresis‐mass spectrometry (low‐flow CE‐MS). To accelerate the optimization, native PAPC (n‐PAPC) standard was first analyzed by a commercial CE instrument with a photodiode array detector. The optimal separation buffer contained 60% (v/v) acetonitrile, 40% (v/v) methanol, 20 mM ammonium acetate, 0.5% (v/v) formic acid, and 0.1% (v/v) water. The selected separation voltage and capillary temperature were 20 kV and 23°C. The optimal CE separation buffer was then used for the low‐flow CE‐MS analysis. The selected MS conditions contained heated capillary temperature (250°C), capillary voltage (10 V), and injection time (1 s). No sheath gas was used for MS. The linear range for n‐PAPC was 2.5–100.0 µg/mL. The coefficient of determination (R2) was 0.9918. The concentration limit of detection was 1.52 µg/mL, and the concentration limit of quantitation was 4.60 µg/mL. The optimal low‐flow CE‐MS method showed good repeatability and sensitivity. The ox‐PAPC products in human HDLs were determined based on the in vitro ox‐PAPC products of n‐PAPC standard. Twenty‐one ox‐PAPC products have been analyzed in human HDLs. Uremic patients showed significantly higher levels of 15 ox‐PAPC products than healthy subjects.
Cough syncope: A coughing fit, but not quite!
Authors: Asranna Ajay , Sureshbabu Sachin , Mittal Gaurav , Peter Sudhir , Sobhana Chindripu , Akhthar Shamim
Published: November 2023

Content available: Video
Rocking induced axial response and performance of lead‐rubber bearings in seismically isolated nuclear plants
Authors: Kumar Satyam , Kumar Manish
Published: November 2023

Seismic isolation using lead‐rubber (LR) bearings can be an effective earthquake mitigation technique to ensure the safety of Nuclear Power Plants (NPPs) against extreme earthquake events. Accurate estimation of the axial and rocking response of NPPs is critical to the design of the safety‐related secondary components, piping, and auxiliary system crossing the interface of the isolation system. The isolators along the periphery of the isolation interface are especially susceptible to buckling in compression and cavitation in tension due to the rocking motion of the structure. No study so far has looked into rocking response of base‐isolated NPP and its consequence on isolator's performance. This paper investigates the axial and rocking behavior of base‐isolated NPPs at a site of high seismic hazard. A numerical study is conducted on the different representations of NPP models with the varying height of the center of mass isolated using a range of isolation systems of different periods and characteristic strengths. The rocking responses are obtained using simplified and advanced isolator models, which consider the interaction between the axial and shear response. The results provide estimates of the rocking responses and their influence on the axial response of isolators. It was observed that the rocking response of a base‐isolated NPP increases with an increase in the isolation period and the characteristics strength of the isolation system. Rocking effects may amplify the axial forces in the lead‐rubber isolators by more than 100% and need to be considered for true performance assessment of isolators when the horizontal to vertical shaking intensity exceeds a ratio of 0.5.
The optimal interval combination prediction model based on vectorial angle cosine and a new aggregation operator for social security level prediction
Authors: Peng Kexin , Kang Chao , Ru Xiwen , Zhou Ligang
Published: November 2023

This paper puts forwards the induced generalized ordered weighted multiple continuous ordered weighted geometric averaging (IGOWMC‐OWGA) operator, which overcomes the deficiency that the ordered weighted geometric averaging (C‐OWGA) operator can only integrate a single interval. Main properties of the proposed operator are investigated. In order to integrate interval data and obtain more accurate prediction results, an optimal model based on IGOWMC‐OWGA operator and vectorial angle cosine is constructed. Finally, the model is applied to an empirical analysis of the moderate measure value of social security level about a certain province in China. The sensitivity and comparisons of results are analyzed which shows that the established model is of good stability and can effectively improve the accuracy of prediction.
The influence of carboxymethyl cellulose and hydroxypropyl methylcellulose on physicochemical, texture, and sensory characteristics of gluten‐free pancake
Authors: Maghsoud Maryam , Heshmati Ali , Taheri Mehdi , Emamifar Aryou , Esfarjani Fatemeh
Published: November 2023

In this study, gluten‐free pancakes were prepared using rice flour and potato starch at a ratio of 50:50. Due to a lack of gluten networks in these ingredients, the hydrocolloid gums including carboxymethyl cellulose (CMC) at 0.5%, 1%, and 1.5% and hydroxypropyl methylcellulose (HPMC) at 1%, 2%, and 3% were added to improve the quality of the final products. The effects of these hydrocolloid gums on the physicochemical, textural, and sensory properties of the gluten‐free pancakes were evaluated. Pancakes prepared with wheat flour were used as a control sample. The results showed that the addition of both gums decreased the hardness and chewiness of the gluten‐free pancakes while increasing the springiness and their moisture content. Increasing the concentration of the gums resulted in an L* value (lightness) reduction, which produced a darker crust on the pancakes. Moreover, the gluten‐free pancakes containing CMC and HPMC had higher specific volumes than the gluten‐free samples made without CMC and HPMC. From a sensory point of view, the samples containing 2%, 3% HPMC and 1% CMC received the highest overall acceptance score. Thus, CMC and HPMC can be used as improvers in gluten‐free pancakes.
Factors influencing concentrations of risperidone and 9‐hydroxyrisperidone in psychiatric outpatients taking immediate‐release formulations of risperidone
Authors: Guo Zhihao , Chen Chunxiu , Deng Shuhua , Lu Haoyang , Ni Xiaojia , Zhang Ming , Huang Shanqing , Wen Yuguan , Shang Dewei , Wang Zhanzhang
Published: November 2023

Objectives

To analyze the factors affecting the concentrations of the active moiety of risperidone (RIS) and its active metabolite 9‐hydroxyrisperidone (9‐OH‐RIS) in psychiatric outpatients taking immediate‐release formulations.

Methods

This is a retrospective study on the therapeutic drug monitoring (TDM) data regarding RIS and 9‐OH‐RIS in adult psychiatric outpatients. TDM data with simultaneous RIS and 9‐OH‐RIS monitoring from March 2018 to February 2020 and relevant medical records (including dosage, dosage form, sex, age, diagnosis, combined medication, and comorbid disease) from 399 adult psychiatric outpatients (223 males and 176 females) were included in this study.

Results

The daily dose of RIS was 5.56 ± 2.05 mg, the concentration of total active moiety was 42.35 ± 25.46 ng/mL, and the dose‐adjusted plasma concentration (C/D) of active moiety was 7.83 ± 3.87 (ng/ml)/(mg/day). Dose, sex, and age were identified as important factors influencing concentrations of RIS and 9‐OH‐RIS in adult psychiatric outpatients.

Conclusions

Individualized medication adjustments should be made according to the specific conditions of psychiatric outpatients. The findings strongly support the use of TDM to guide dosing decisions in psychiatric outpatients taking RIS.
A shift from individual species to ecosystem services effect: Introducing the Eco-indicator Sensitivity Distribution (EcoSD) as an ecosystem services approach to redefining the species sensitivity distribution (SSD) for soil ecological risk assessment
Authors: Fajana Hamzat O. , Lamb Eric G. , Siciliano Steven D.
Published: November 2023

Incorporating the ecosystem services (ES) approach into soil ecological risk assessment (ERA) has been advocated over the years, but implementing the approach in ERA faces some challenges. However, several researchers have made significant improvements to the soil ERA, such as applying the species sensitivity distribution (SSD) to discern chemical effects on the soil ecosystem. Despite the considerable contributions of SSD to ERA, SSD fails to relate chemical impact on individual species to ES and account for functional redundancy as well as soil ecosystem complexity. Here, we introduce the Eco-indicator Sensitivity Distribution (EcoSD). An EcoSD fits ecological functional groups and soil processes, termed “eco-indicators,” instead of individual species responses to a statistical distribution. These eco-indicators are related directly to critical ecosystem functions that drive ES. We derived an EcoSD for cadmium as a model chemical and estimated a soil ecosystem protection value (EcoPVSoil) based on the eco-indicator dataset for cadmium from the literature. The EcoSD identified nitrogen cycling as the critical process disrupted by cadmium. A key advantage of EcoSD is that it identifies key ecological and chemical indicators of an ES effect. In doing so, it links chemical monitoring results to sensitive ecological functions. The estimated EcoPVSoil for cadmium was slightly more protective of the soil ecosystem than most regional soil values derived from this study's dataset and soil guideline values from the literature. Thus, EcoSD has proven to be a practical and valuable ES concept with the potential to serve as an initial step of the tiered ERA approach. Integr Environ Assess Manag 2024;20:1166–1179. © 2023 SETAC

Key Points

The proposed Eco-indicator Sensitivity Distribution (EcoSD) demonstrated that cadmium significantly affected soil's eco-indicators of nitrogen cycling. Soil processes were the most sensitive eco-indicators of cadmium toxicity in soil. The EcoSD approach should be adopted to better understand the soil ecological pathways of chemical effects on ecosystem function and service delivery.
Novel multidisciplinary cooperation model for obstetric medical quality control: A quasi‐experimental study
Authors: Zhao Li‐Rong , Sun Li‐Hong , Wei Jing , Yu Ying‐Chun
Published: November 2023

Objective

To explore the impact of a novel multidisciplinary cooperation model in obstetric medical quality control.

Methods

This quasi‐experimental study analyzed the quality indicators of full‐term pregnant women who underwent vaginal trial labor in Zibo Maternal and Child Health Hospital between July 2021 and June 2022. The pregnant women were divided into two groups based on implementation of novel multidisciplinary cooperation: multidisciplinary and non‐multidisciplinary. We compared the rate of labor analgesia, postpartum hemorrhage in vaginal delivery, transfer to cesarean section, and the 5‐min Apgar score ≤7 in full‐term neonates.

Results

A total of 3751 pregnant women were enrolled into the study, of whom 2004 were included in the non‐multidisciplinary group and 1747 in the multidisciplinary group. The analgesic rate of delivery of the multidisciplinary group was higher than that of the non‐multidisciplinary group (P = 0.000). We established that the rate of postpartum bleeding (P = 0.040), transfer cesarean section (P = 0.003) and the incidence of Apgar score ≤7 in 5 min of full‐term neonates (P = 0.038) of the multidisciplinary group was lower than that of the non‐multidisciplinary group. There was no significant difference in the mean ages (29.40 ± 3.99 vs. 29.90 ± 4.27 years; P = 0.126), mean delivery gestational ages (39.65 ± 0.87 vs. 39.64 ± 1.06; P = 0.221), mean gravidity values (1.93 ± 1.09 vs. 2.00 ± 1.18; P = 0.586) and mean parity (1.40 ± 0.56 vs. 1.42 ± 0.59; P = 0.635) of the women in the two groups.

Conclusion

Multidisciplinary cooperation in delivery management can significantly improve some quality indicators. We established the analgesic rate of delivery can be increased and the rate of postpartum bleeding, transfer cesarean section and the incidence of Apgar score ≤7 in 5 min of full‐term neonates can be decreased with the implementation of novel multidisciplinary cooperation.
Mucin‐producing urothelial‐type adenocarcinoma of the prostate with sarcomatoid features and novel molecular phenotype
Authors: Renavikar Pranav S , Auen Thomas J , Wagner David G , Lele Subodh M
Published: November 2023

Introduction

Mucin‐producing urothelial‐type adenocarcinoma of the prostate is a rare tumor that may not elevate serum prostate‐specific antigen, creating significant diagnostic and monitoring challenges. We evaluate our case in detail and review prior studies to demonstrate that the pathologic and molecular features of this tumor are distinct from conventional prostate adenocarcinoma.

Case presentation

Our patient had a remote history of radiation‐treated conventional prostate adenocarcinoma and presented many years later with an abscess‐like prostate mass leading to urinary obstruction and hematuria. Biopsy revealed mucin‐producing urothelial‐type adenocarcinoma of the prostate with concurrent sarcomatoid features. Molecular studies showed a unique phenotype involving alterations in the KRAS, PTEN, RAD21, and TP53 genes.

Conclusions

To our knowledge, this is the first report that describes sarcomatoid features and molecular mutations in mucin‐producing urothelial‐type adenocarcinoma of the prostate.
Matrine alleviates hypoxia‐induced inflammation and pulmonary vascular remodelling via RPS5/NF‐κB signalling pathway
Authors: Li Mingxing , Ying Miaofa , Gu Shenglong , Zhou Zheng , Zhao Rui
Published: November 2023

Hypoxia‐induced vasoconstriction and vascular remodelling are the main pathological features of hypoxic pulmonary arterial hypertension (HPAH), and inflammation is participated in the occurrence of pulmonary vascular remodelling (PVR). Matrine is an alkaloid with the effects of anti‐inflammation, antifibrosis and antitumour. But, few studies have explored the role of matrine in regulating PVR, and the related mechanisms are still unknown. In this study, we found that hypoxia‐induced pulmonary artery smooth muscle cells (PASMCs) proliferation and inhibited its apoptosis, reduced the expression of ribosomal protein s5 and activated the nuclear factor kappa‐B (NF‐κB) signalling. Matrine, sildenafil and NF‐κB inhibitor Bay 11‐7082 could reverse these changes and impel the cell cycle in phase S retardation, and reduced the expression of p50, p65, proliferating cell nuclear antigen (PCNA), Bcl‐2. In addition, matrine could lower right ventricular systolic pressure and mean pulmonary artery pressure of rats, α‐smooth muscle actin and PCNA expression in pulmonary artery media, the levels of tumor necrosis factor‐α and interleuki‐1β, thus improved hypoxia‐induced PVR. This study indicated that matrine could alleviate inflammation and improve PVR through reversing the imbalance of proliferation and apoptosis of PASMCs, thus it had a therapeutic effect on HPAH.
Simple versus nonsimple loops on random regular graphs
Authors: Dozier Benjamin , Sapir Jenya
Published: November 2023

In this note, we solve the “birthday problem” for loops on random regular graphs. Namely, for fixed , we prove that on a random ‐regular graph with vertices, as approaches infinity, with high probability: (i) almost all primitive nonbacktracking loops of length are simple, that is, do not self‐intersect, and (ii) almost all primitive nonbacktracking loops of length self‐intersect.
Radial and longitudinal meniscus tears show different gapping patterns under stance phase conditions
Authors: Sukopp Matthias , Frey Julian , Schwer Jonas , Kalbitz Miriam , Ignatius Anita , Seitz Andreas Martin
Published: November 2023

Meniscal tearing can increase the contact pressure between the tibia and femur by causing gapping of torn meniscus tissue. The aim of this study was to quantify gapping behavior of radial and longitudinal tears and their impact on peak contact pressure and mean contact area. Twelve porcine knee joints underwent unicondylar, convertible osteotomy for exact tear application and consecutive suturing. Six tantalum marker beads were positioned along meniscus tears. The joints were preloaded with sinusoidal loading cycles ranging between 0 N and 350 N. Peak load was held constant and two synchronized Roentgen stereophotogrammetric analysis x‐ray images were obtained to evaluate gapping, peak contact pressure and mean contact area in the native, torn and repaired states. There was no change in gapping or peak contact pressure in longitudinal tear. By contrast, the radial tear led to a significant gapping when compared to the native state, while the inside‐out suture was able to restore gapping in parts of the meniscus. An increase in contact pressure after radial tear was detected, which was again normalized after suturing. The most important finding of the study is that longitudinal tears did not gap under pure axial loading, whereas radial tears tended to separate the tear interfaces.
Non‐volatile and volatile compound changes in blueberry juice inoculated with different lactic acid bacteria strains
Authors: Wang Jun , Wei Bo‐Cheng , Zhai Yan‐Rong , Li Ke‐Xin , Wang Chu‐Yan
Published: November 2023

BACKGROUND

Lactic acid bacteria (LABs) are widely present in foods and affect the flavour of fermented cultures. This study investigates the effects of fermentation with Lactobacillus acidophilus JYLA‐16 (La), Lactobacillus plantarum JYLP‐375 (Lp), and Lactobacillus rhamnosus JYLR‐005 (Lr) on the flavour profile of blueberry juice.

RESULTS

This study showed that all LABs strains preferentially used glucose rather than fructose as the carbon source during fermentation. Lactic acid was the main fermentation product, reaching 7.76 g L−1 in La‐fermented blueberry juice, 5.86 g L−1 in Lp‐fermented blueberry juice, and 6.41 g L−1 in Lr‐fermented blueberry juice. These strains extensively metabolized quinic acid, whereas oxalic acid metabolism was almost unaffected. Sixty‐four volatile compounds were identified using gas chromatography–ion mobility spectrometry (GC–IMS). All fermented blueberry juices exhibited decreased aldehyde levels. Furthermore, fermentation with La was dominated by alcohols, Lp was dominated by esters, and Lr was dominated by ketones. Linear discriminant analysis of the electronic nose and principal component analysis of the GC–IMS data effectively differentiated between unfermented and fermented blueberry juices.

CONCLUSION

This study informs LABs selection for producing desirable flavours in fermented blueberry juice and provides a theoretical framework for flavour detection. © 2023 Society of Chemical Industry.
Effect of low‐voltage electrostatic field‐assisted partial freezing on large yellow croaker protein properties and metabolomic analysis during storage
Authors: Fei Lifeng , Ma Ze , Yue Aodong , Cui Pengbo , Qiu Yue , Lyu Fei , Zhang Jianyou
Published: November 2023

Background

Large yellow croaker is highly perishable during storage because of high protein and moisture content. The degradation of the fish is mainly attributed to microbial growth and enzyme activity, so it is important to find an efficient storage method to extend its shelf life.

Methodology

This study investigated the effect of a low‐voltage electrostatic field combined with partial freezing treatment on the physicochemical properties of myofibrillar protein (MP) and metabolomic analysis of large yellow croaker during preservation. The samples in chilled storage (C), partial freezing storage (PF) and 6 kV/m low‐voltage electrostatic field partial freezing storage (LVEF‐PF) were analyzed during an 18 day storage period.

Results

In comparison with the C and PF groups, LVEF‐PF delayed the oxidation of MP by inhibiting the formation of carbonyl groups (2.25 nmol/mg pro), and maintaining higher sulfhydryl content (29.73 nmol/mg pro). Fourier transform infrared (FTIR) spectroscopy and fluorescence spectroscopy analysis also demonstrated that the LVEF‐PF treatment maintained the stability of the protein structure by increasing the a‐helix ratio (19.88%) and reducing the random coil ratio (17.83%). Scanning electron microscopy showed that, compared with the LVEF‐PF group, there was more degeneration and aggregation of MP in the C and PF groups after 18 days’ storage. The results of untargeted metabolomic analysis showed that 415 kinds of differential metabolites were identified after storage, and the difference levels of differential metabolites were least between the samples treated with LVEF‐PF stored on the ninth day and the fresh samples. The main differential metabolic pathways during storage were amino acid metabolism and lipid metabolism.

Conclusion

The LVEF‐PF treatment could maintain the stability of myofibrillar protein in large yellow croaker during storage. These results showed a potential application of the LVEF‐PF method for aquatic product preservation. © 2023 Society of Chemical Industry.
The effect of surgical timing in nonmetastatic melanoma
Authors: Kakish Hanna , Drigotas Claire , Ahmed Fasih Ali , Elshami Mohamedraed , Bordeaux Jeremy S. , Rothermel Luke D. , Hoehn Richard S.
Published: November 2023

Background and Objectives

There is no consensus guidelines on the best timing to perform Sentinel lymph node biopsy (SLNB) in high‐risk melanoma patients. We aimed to understand the impact of surgical timing on nodal upstaging in patients with cutaneous melanoma.

Methods

We queried the National Cancer Database from 2004 to 2018 for patients with T2–T4, N0, M0 melanomas, who underwent melanoma excision and nodal surgery. We included patients who underwent surgery within 2–19 weeks postdiagnosis. We aimed to determine the association of surgical delay (weeks) with nodal positivity.

Results

A total of 53 355 patients were included, of whom 20.9% had positive lymph nodes. Patients underwent surgery at a median of 5 (4–7) weeks after diagnosis. The rate of positive nodes increased with increased weeks to surgery (line of best‐fit slope = 0.38). Multivariable regression analysis identified an association between time to surgery and nodal positivity (2.4% increased risk per week, p < 0.05). Our analysis showed significantly increased likelihood of nodal positivity beginning 9 weeks after diagnosis (odds ratio [OR] = 1.3, p < 0.05). Furthermore, patients with T2–3 tumors had a significant increase in nodal positivity with increased time to surgery (OR = 1.03 per week, p < 0.001). However, no significant trend in nodal positivity was identified for patients with T4 melanomas (OR = 1.01 per week, p = 0.596).

Conclusion

Surgery within 9 weeks of melanoma diagnosis was not associated with increased likelihood of nodal positivity. These data can guide clinical conversations regarding the importance of surgical timing for melanoma.
Contributing factors to secondary traumatic stress and vicarious posttraumatic growth in therapists
Authors: Cleary Eimear , Curran David , Dyer Kevin , Simms Jane , Hanna Donncha
Published: November 2023

Alongside the recognized potential negative repercussions of working as a psychological therapist, there is growing interest in the potential positive impacts of engaging in such work. The current study used a cross‐sectional online survey design to explore the impact of a range of demographic, work‐related, and compassion‐related factors on levels of secondary traumatic stress (STS) and vicarious posttraumatic growth (VPTG) in an international sample of 359 psychological therapists. Hierarchical multiple regressions demonstrated that burnout, lower levels of self‐compassion, having a personal trauma history, reporting a higher percentage of working time with a trauma focus, and being female were the statistically significant contributors to STS scores, explaining 40.8% of the variance, F(9, 304) = 23.2, p <.001. For VPTG, higher compassion satisfaction, higher self‐compassion, higher STS, a higher percentage of working time with a trauma focus, fewer years qualified, being male, and having a personal trauma history were all statistically significant contributors, explaining 27.3% of the variance, F (10, 304) = 11.37, p <.001. The findings illustrate the potential risk and protective factors for developing STS and clarify factors that may increase the likelihood of experiencing VPTG. Implications for psychological therapists and the organizations and institutions for which they work are considered along with potential directions for future research in the discussion.
Nanoparticle Concentration in Surgical Plume During Tonsillectomy: A Comparison of Four Techniques
Authors: Law Richard H. , Cena Lorenzo , Sporn Alec , Buzi Adva , Rizzi Mark D. , Ruiz Ryan L. , Fedrigo Sabrina , Giordano Terri , Fahmy Alexander N. , Dedhia Kavita
Published: November 2023

Objective

Surgical plume has known potential occupational health hazards. This study compares nanoparticle concentrations in surgical plumes generated between different pediatric tonsillectomy surgical techniques and assesses the efficacy of mitigation measures.

Methods

This is a cross‐sectional study performed at a tertiary care academic center. Extracapsular or intracapsular tonsillectomy was performed in 60 patients using four techniques and in 10 additional patients using mitigation measures. Two nanoparticle counters were used to measure particulate concentrations: CPC™ and DiSCmini™. Tonsillectomy techniques included: (1) microdebrider (MD), (2) Bovie with manual suctioning by an assistant (B), (3) Bovie with built‐in smoke evacuation system (BS), and (4) Coblator™ (CB). An additional Yankauer suction was used in the mitigation groups (BSY) and (CBY). Comparative analysis was performed using one‐way ANOVA on ranks and pairwise comparisons between the groups.

Results

The mean concentrations (particles/cm3) and coefficient of variants for the DiSCmini particulate counter were MD: 5140 (1.6), B: 30700 (1.5), BS: 25001 (0.8), CB: 54814 (1.7), CBY: 2395 (1.3) and BSY: 11552 (1.0). Mean concentrations for the CPC particulate counter were MD: 1223 (1.4), B: 3405 (0.7), BS: 5002 (0.9), CB: 13273 (1.0), CBY: 1048 (1.2) and BSY: 3046 (0.6). The lowest mean concentrations were noted in cases using MD and the highest in cases using CB. However, after mitigation, CBY had the lowest overall levels.

Conclusion

Tonsillectomy technique does impact the levels of nanoparticles emitted within the surgical plume, which may present an occupational hazard for operating room personnel.

Level of Evidence

3 Laryngoscope, 134:2444–2448, 2024