bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational fluid dynamics based digital twins of fixed bed bioreactors validate scaling principles for recombinant adeno‐associated virus gene therapy manufacturing
Authors: Hill Michael , White Colten , Wang Shaoying , Thomas John , DeVincentis Brian , Singh Nripen
Published: May 2024

Gene therapy using recombinant adeno‐associated virus (rAAV) as delivery vehicles has garnered much interest in recent years. There are still significant gaps in our fundamental understanding of the manufacturing processes to deliver sufficient products. Manufacturing efforts of rAAV using HEK293 cells have commonly relied on fixed bed falling film bioreactors like the iCELLis®. We used computational fluid dynamics (CFD) to validate the operating conditions required for a predictive iCELLis® 500 scale‐down model. The small‐scale and at‐scale systems have different flow paths causing validation of the corresponding agitation rates required to achieve the same linear flow through the fixed bed across scales to be non‐trivial. Therefore, we used CFD to predict the theoretical scaling relationship. In addition, CFD could predict kLa differences between the two systems and the operating conditions required to match kLa between scales. We also confirmed that the location of DO control must be the same in both systems to achieve proper scaling. Experimental runs confirming the validity of the novel scale‐down model showed that based on the modifications to the iCELLis® Nano system, we achieved similar DO, key metabolite, pH, and GC titer trends in both systems.
Impact of business strategy on carbon emissions: Empirical evidence from U.S. firms
Authors: Houqe Muhammad Nurul , Abdelfattah Tarek , Zahir‐ul‐Hassan Muhammad Kaleem , Ullah Subhan
Published: May 2024

This study examines the nexus between business strategy and carbon emissions by utilising a dataset of U.S. firms from 2007 to 2020. It focuses on two broad types of firms, that is, prospectors and defenders. Regarding carbon emissions, we consider total emissions (Scope 1 & 2), direct emissions (Scope 1) and indirect emissions (Scope 2). The results reveal a significant association between business strategy and total carbon emissions as well as direct carbon emissions. Notably, the results suggest that prospectors, compared to defenders, display higher levels of total and direct carbon emissions. Our findings contribute to the debate on whether prospectors in developed countries mismanage sustainability issues. The study offers valuable insights into the interplay between business strategy and carbon emissions and provides empirical evidence that business strategy is an important determinant of total and direct carbon emissions.
Structural Characterization and Screening for Anti‐inflammatory Activity of Polysaccharides with Different Molecular Weights from Astragali Radix
Authors: Fan Xinhui , Li Ke , Qin Xuemei , Li Zhenyu , Du Yuguang
Published: May 2024

Astragali Radix polysaccharides (APSs) exhibit a broad spectrum of biological activity, which is mainly related to immune regulation. At present, most available studies focus on total APSs or a certain component of APSs. However, systematic structural study and screening for the anti‐inflammatory activity of polysaccharides with different molecular weights (MW) have yet to be conducted. In this study, lipopolysaccharide (LPS)‐induced RAW264.7 macrophages were used as a model to investigate the anti‐inflammatory activity of APSs and its fractions. The results revealed that fraction APS‐I had better anti‐inflammatory effects than APS‐II. After APS‐I was hydrolyzed by trifluoroacetic acid (TFA), the resulting degradation products oligosaccharides were fully methylated. These derivatized oligosaccharides were further analyzed by MALDI‐TOF‐MS and UPLC‐Q‐Exactive‐MS/MS. The results showed that APS‐I was a hetero‐polysaccharide with a molecular weight of about 2.0×106 Da, mainly consisting of glucose (46.8 %) and galactose (34.4 %). The degree of polymerization of Astragali Radix oligosaccharides (APOS) was 2–16. APOS were identified as 1,4‐glucooligosaccharides and 1,4‐galactooligosaccharides. The findings of this study lay the foundation for further elucidation of structure‐function relationships of APSs and provide guidance for the development of anti‐inflammatory drugs.
Amplification‐ and Enzyme‐Free Magnetic Diagnostics Circuit for Whole‐Genome Detection of SARS‐CoV‐2 RNA
Authors: Rösch Enja Laureen , Sack Rebecca , Chowdhury Mohammad Suman , Wolgast Florian , Zaborski Margarete , Ludwig Frank , Schilling Meinhard , Viereck Thilo , Rand Ulfert , Lak Aidin
Published: May 2024

Polymerase chain reaction (PCR) requires thermal cycling and enzymatic reactions for sequence amplification, hampering their applications in point‐of‐care (POC) settings. Magnetic bioassays based on magnetic particle spectroscopy (MPS) and magnetic nanoparticles (MNPs) are isothermal, wash‐free, and can be quantitative. Realizing them amplification‐ and enzyme‐free on a benchtop device, they will become irreplaceable for POC applications. Here we demonstrate a first‐in‐class magnetic signal amplification circuit (MAC) that enables detection of whole genome of SARS‐CoV‐2 by combining the specificity of toehold‐mediated DNA strand displacement with the magnetic response of MNPs to declustering processes. Using MAC, we detect the N gene of SARS‐CoV‐2 samples at a concentration of 104 RNA copies/μl as determined by droplet digital PCR. Further, we demonstrate that MAC can reliably distinguish between SARS‐CoV‐2 and other human coronaviruses. Being a wash‐, amplification‐ and enzyme‐free biosensing concept and working at isothermal conditions (25 °C) on a low‐cost benchtop MPS device, our MAC biosensing concept offers several indispensable features for translating nucleic acid detection to POC applications.
A high‐throughput screen in mESCs to identify the cross‐talk between signaling, endocytosis, and pluripotency
Authors: Mote Ridim D. , Tiwari Mahak , Yadavalli Narayana , Rajan Raghav , Subramanyam Deepa
Published: May 2024

Embryonic stem cell fate is regulated by various cellular processes. Recently, the process of endocytosis has been implicated in playing a role in the maintenance of self‐renewal and pluripotency of mouse embryonic stem cells. A previous siRNA‐based screen interrogated the function of core components of the endocytic machinery in maintaining the pluripotency of embryonic stem cells, revealing a crucial role for clathrin mediated endocytosis. A number of other proteins involved in key signaling pathways have also been shown to both regulate and be regulated by endocytosis. We collated a list of 1141 genes in connection to the term “endocytosis” from Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), excluding those previously interrogated, and examined the effect of their knockdown on the pluripotency of mouse embryonic stem cells (mESCs) using levels of green fluorescent protein driven by the Oct4 promoter. We used high‐throughput screening followed by an automated MATrix LABoratory (MATLAB)‐based analysis pipeline and assessed changes in GFP fluorescence as a readout for ESC pluripotency. Through this screen we identified a number of genes, many hitherto not associated with stem cell pluripotency, which upon knockdown either resulted in a significant increase or decrease of GFP fluorescence. We further present validation for some of these hits. We present a workflow aimed to identify genes involved in signaling pathways which can be regulated by endocytosis, and that affect the pluripotency of ESCs.
DRESS syndrome without eosinophilia presented with extensive skin rash and acute respiratory failure
Authors: Chaisrimaneepan Nattanicha , Pruneda Corley , Elmassry Marwan , Abdelnabi Mahmoud
Published: May 2024

Key Clinical Message

This case demonstrated the complex pathophysiology of DRESS syndrome presenting with latent human herpes virus infection reactivation due to exposure to sulfasalazine and/or hydroxychloroquine. Patients who do not initially fulfill the diagnostic criteria on admission may evolve and eventually fulfill the criteria. Steroid dose tapering is required to prevent flaring.
Mechanistic Insights into the Copper‐Catalyzed Cross‐Dehydrogenative Allylic Alkynylation Reaction
Authors: Hünemörder Paul , Alvarez Gustavo , Gräber Leo , Logotheti Maria , Höhne Matthias , Mejía Esteban
Published: May 2024

Allylic functionalization reactions are an important tool for constructing many organic compounds, as they allow for the insertion of the versatile allyl group. Numerous catalytic processes have been developed, primarily utilizing noble metals such as palladium and pre‐functionalized substrates. Conversely, the copper‐catalyzed oxidative C−H derivatization route, whether thermal or photocatalyzed, remains relatively underdeveloped. This is mostly due to the lack of a general concept and corresponding mechanistic understanding. Here we present a comprehensive analysis of the mechanism of this transformation. We utilized a range of spectroscopic techniques, including UV‐Vis, NMR, and EPR, single crystal x‐ray diffraction, as well as cyclovoltammetry, and DFT calculations. We propose that there are no free organic radicals involved in this cross‐dehydrogenative coupling, and that the reaction pathway is analogous to the well‐known Karash‐Sosnovsky reaction.
Nitrogen Fixation by Manganese Complexes – Waiting for the Rush?
Authors: Le Dé Quentin , Valyaev Dmitry A. , Simonneau Antoine
Published: May 2024

Manganese is currently experiencing a great deal of attention in homogeneous catalysis as a sustainable alternative to platinum group metals due to its abundance, affordable price and low toxicity. While homogeneous nitrogen fixation employing well‐defined transition metal complexes has been an important part of coordination chemistry, manganese derivatives have been only sporadically used in this research area. In this contribution, the authors systematically cover manganese organometallic chemistry related to N2 activation spanning almost 60 years, identify apparent pitfalls and outline encouraging perspectives for its future development.
The Diversity and Evolution of Chiral Brønsted Acid Structures
Authors: Handjaya Jasemine P. , Patankar Niraja , Reid Jolene P.
Published: May 2024

The chemical space of chiral Brønsted acid catalysts is defined by quantity and complexity, reflecting the diverse synthetic challenges confronted and the innovative molecular designs introduced. Here, we detail how this successful outcome is a powerful demonstration of the benefits of utilizing both local structure searches and a comprehensive understanding of catalyst performance for effective and efficient exploration of Brønsted acid properties. In this concept article we provide an evolutionary overview of this field by summarizing the approaches to catalyst optimization, the resulting structures, and functions.
Metastatic germ cell tumors in serous cavities and cerebrospinal fluid: A single‐center experience
Authors: Hou Tieying , Collins Katrina , Liang Guohua , Segura Sheila E. , Ulbright Thomas M. , Mesa Hector , Cramer Harvey M.
Published: May 2024

Background

Metastatic germ cell tumors (GCTs) involving body cavity effusions and cerebrospinal fluid (CSF) are rare. Diagnosis is challenging because of limited morphological and clinicopathological information in the literature.

Methods

A database search of our institution from 1990 to 2024 identified 27 cases of metastatic GCTs, comprising five pediatric and 22 adolescent and adult patients, in serous cavities or the CSF, including peritoneal (15), pleural (nine), CSF (two), and pericardial (one) fluid.

Results

The most common primary site was the testis (n = 10), followed by the ovaries (n = 7), mediastinum (n = 4), retroperitoneum (n = 3), pineal gland (n = 2), and sacrum/coccyx (n = 1). The primary tumors in 14 patients were mixed GCTs (six with a seminoma component), followed by immature teratomas (six), yolk sac tumors (three), embryonal carcinomas (two), pure seminomas (one), and postpubertal teratomas (one). The median interval between primary tumor diagnosis and diagnosis of fluid positivity was 7 months (range: 0–134 months). In nine cases, the malignant fluid was diagnosed simultaneously with or within 1 month of the primary tumor. GCT subtyping was performed on 23 of the 27 cytological specimens. Twenty‐four patients (89%) also had metastases to other sites. Thirteen patients died of the disease (48%), with a median survival time of 4 months.

Conclusions

Metastatic GCTs in serous effusions and CSF are often associated with disseminated disease and poor prognosis. Subtyping can be performed by cytomorphology combined with immunohistochemistry.
Leapfrogging vortex rings for the three‐dimensional incompressible Euler equations
Authors: Dávila Juan , Pino Manuel del , Musso Monica , Wei Juncheng
Published: May 2024

A classical problem in fluid dynamics concerns the interaction of multiple vortex rings sharing a common axis of symmetry in an incompressible, inviscid three‐dimensional fluid. In 1858, Helmholtz observed that a pair of similar thin, coaxial vortex rings may pass through each other repeatedly due to the induced flow of the rings acting on each other. This celebrated configuration, known as leapfrogging, has not yet been rigorously established. We provide a mathematical justification for this phenomenon by constructing a smooth solution of the 3D Euler equations  exhibiting this motion pattern.
Effect of Food, Crushing of Tablets, and Antacid Coadministration on Maribavir Pharmacokinetics in Healthy Adult Participants: Results From 2 Phase 1, Open‐Label, Randomized, Crossover Studies
Authors: Sun Kefeng , Ilic Katarina , Xu Peixin , Ye Ran , Wu Jingyang , Song Ivy H.
Published: May 2024

The effect of food composition, tablet crushing, and antacid coadministration on maribavir pharmacokinetics was assessed in 2 Phase 1 studies in healthy adults. In the first, a single maribavir 400‐mg dose was administered under fasting conditions, with a low‐fat/low‐calorie or a high‐fat/high‐calorie meal. In the second, a single maribavir 100‐mg dose was administered under fasting conditions, as a crushed tablet, or as a whole tablet alone or with an antacid. The 90% confidence intervals of the geometric mean ratios were within 80%‐125% for area under the concentration‐time curve (AUC), but not for maximum plasma concentration (Cmax) for low‐fat/low‐calorie and high‐fat/high‐calorie meals versus fasting or for whole tablet with antacid versus whole tablet alone. The 90% confidence intervals of the geometric mean ratios for AUC and Cmax were within 80%‐125% for crushed versus whole tablet. Maribavir median time to Cmax value in plasma under fed conditions was delayed versus fasting conditions, but there was no statistical difference for crushed versus whole tablet or with versus without antacid. As the antiviral efficacy of maribavir is driven by AUC but not Cmax, findings suggest that maribavir can be administered with food or antacids or as a crushed tablet.
Goal‐Directed Treatment of Patients With Anxiety and Mood Disorders in a Regular Curative Mental Health Care Setting
Authors: van Santen‐Bauer Paulette Regina , de Beurs Edwin , Deen Mathijs , Korrelboom Kees , van der Heiden Colin
Published: May 2024

This study examined whether goal‐directed treatment leads to improved treatment outcomes for patients with a primary mood or anxiety disorder and whether beneficial outcomes are achieved sooner compared to treatment as usual. In a quasi‐experimental controlled study with a nested design, 17 therapists received training in goal‐directed treatment and treated 105 patients with anxiety or mood disorders using principles of goal‐directed treatment. Treatment results on a generic self‐report instrument were compared with two control groups: a historical control group consisting of 16 of the 17 participating therapists, who provided treatment as usual to 97 patients before having received training in goal‐directed treatment, and a parallel control group consisting of various therapists, who provided treatment as usual to 105 patients. Symptom reduction on a self‐report measure was compared using multilevel analysis. A survival analysis was performed to assess whether a satisfactory end state had been reached sooner after goal‐directed treatment. The results of this study show that goal‐directed treatment only led to a significantly better overall treatment outcome compared to the parallel treatment as usual group. Furthermore, goal‐directed treatment was significantly shorter than both treatment as usual groups. In conclusion, this research suggest that goal‐directed treatment led to a similar or better treatment outcome in a shorter amount of time.
Analysis of integrated magnetics for input series output series DC–DC converter
Authors: Ali Yaqoob , Zheng Yan , Khan Muhammad Mansoor , Ali Abdar , Jing Zhao
Published: May 2024

Multi‐module isolated converters (MMICs) find extensive applications in various DC–DC applications owing to their exceptional features of galvanic isolation, bidirectional power flow, high‐power density, and enhanced efficiency. However, voltage and current sharing among the converter modules are the most significant issues in MMICs. This paper proposes multiport integrated‐magnetics transformers (MpIMTs) which address the input–output DC‐link voltage imbalances within an ISOS converter. The proposed transformers ensure the input voltage sharing (IVS) and output voltage sharing (OVS) through balancing windings within their structures, thus substitutes the complicated active control scheme with the balancing winding. Besides, the input side and output side modules are decoupled from each other; thus, the impact of parameters variation and intermodule energy transfer during a transient of one side does not reflect to the other side. These properties are achieved by proposing a custom‐designed core and an off the shelf available U‐core assembled MpIMTs. The magnetic and electrical equivalent circuit along with the design criteria of the balancing winding are also presented. Furthermore, the paper includes the comparative analysis of the proposed transformers which reveals that while the U‐core MpIMT offers simplified construction, it comes at the expense of slightly reduced efficiency compared with the custom‐designed MpIMT. Finally, the proposed U‐core MpIMT is validated through a laboratory prototype.
The role of long non‐coding RNAs in the development of diabetic kidney disease and the involved clinical application
Authors: Hou Qizhuo , Yi Bin
Published: May 2024

Diabetic kidney disease (DKD), one of the common microvascular complications of diabetes, is increasing in prevalence worldwide and can lead to End‐stage renal disease. However, there are still gaps in our understanding of the pathophysiology of DKD, and both current clinical diagnostic methods and treatment strategies have drawbacks. According to recent research, long non‐coding RNAs (lncRNAs) are intimately linked to the developmental process of DKD and could be viable targets for clinical diagnostic decisions and therapeutic interventions. Here, we review recent insights gained into lncRNAs in pathological changes of DKD such as mesangial expansion, podocyte injury, renal tubular injury, and interstitial fibrosis. We also discuss the clinical applications of DKD‐associated lncRNAs as diagnostic biomarkers and therapeutic targets, as well as their limitations and challenges, to provide new methods for the prevention, diagnosis, and treatment of DKD.
Combining mesocosms with models reveals effects of global warming and ocean acidification on a temperate marine ecosystem
Authors: Ullah Hadayet , Fordham Damien A. , Goldenberg Silvan U. , Nagelkerken Ivan
Published: May 2024

Ocean warming and species exploitation have already caused large‐scale reorganization of biological communities across the world. Accurate projections of future biodiversity change require a comprehensive understanding of how entire communities respond to global change. We combined a time‐dynamic integrated food web modeling approach (Ecosim) with previous data from community‐level mesocosm experiments to determine the independent and combined effects of ocean warming, ocean acidification and fisheries exploitation on a well‐managed temperate coastal ecosystem. The mesocosm parameters enabled important physiological and behavioral responses to climate stressors to be projected for trophic levels ranging from primary producers to top predators, including sharks. Through model simulations, we show that under sustainable rates of fisheries exploitation, near‐future warming or ocean acidification in isolation could benefit species biomass at higher trophic levels (e.g., mammals, birds, and demersal finfish) in their current climate ranges, with the exception of small pelagic fishes. However, under warming and acidification combined, biomass increases at higher trophic levels will be lower or absent, while in the longer term reduced productivity of prey species is unlikely to support the increased biomass at the top of the food web. We also show that increases in exploitation will suppress any positive effects of human‐driven climate change, causing individual species biomass to decrease at higher trophic levels. Nevertheless, total future potential biomass of some fisheries species in temperate areas might remain high, particularly under acidification, because unharvested opportunistic species will likely benefit from decreased competition and show an increase in biomass. Ecological indicators of species composition such as the Shannon diversity index decline under all climate change scenarios, suggesting a trade‐off between biomass gain and functional diversity. By coupling parameters from multilevel mesocosm food web experiments with dynamic food web models, we were able to simulate the generative mechanisms that drive complex responses of temperate marine ecosystems to global change. This approach, which blends theory with experimental data, provides new prospects for forecasting climate‐driven biodiversity change and its effects on ecosystem processes.
Effects of microclimate on disease prevalence across an urbanization gradient
Authors: Fox Quinn N. , Farah Keiko N. , Shaw Olivia S. , Pollowitz Michelle , Sánchez‐Conde Armando , Goodson Carrie , Penczykowski Rachel M.
Published: May 2024

Increased temperatures associated with urbanization (the “urban heat island” effect) have been shown to impact a wide range of traits across diverse taxa. At the same time, climatic conditions vary at fine spatial scales within habitats due to factors including shade from shrubs, trees, and built structures. Patches of shade may function as microclimate refugia that allow species to occur in habitats where high temperatures and/or exposure to ultraviolet radiation would otherwise be prohibitive. However, the importance of shaded microhabitats for interactions between species across urbanized landscapes remains poorly understood. Weedy plants and their foliar pathogens are a tractable system for studying how multiple scales of climatic variation influence infection prevalence. Powdery mildew pathogens are particularly well suited to this work, as these fungi can be visibly diagnosed on leaf surfaces. We studied the effects of shaded microclimates on rates of powdery mildew infection on Plantago host species in (1) “pandemic pivot” surveys in which undergraduate students recorded shade and infection status of thousands of plants along road verges in urban and suburban residential neighborhoods, (2) monthly surveys of plant populations in 22 parks along an urbanization gradient, and (3) a manipulative field experiment directly testing the effects of shade on the growth and transmission of powdery mildew. Together, our field survey results show strong positive effects of shade on mildew infection in wild Plantago populations across urban, suburban, and rural habitats. Our experiment suggests that this relationship is causal, where microclimate conditions associated with shade promote pathogen growth. Overall, infection prevalence increased with urbanization despite a negative association between urbanization and tree cover at the landscape scale. These findings highlight the importance of taking microclimate heterogeneity into account when establishing links between macroclimate or land use context and prevalence of disease.
A novel electrochemical labeled immunosensor for the detection of gliadin based on graphene oxide and silver nanoparticles
Authors: Şenol Betül , Koyuncu Zeybek Derya
Published: May 2024

In this study, a labeled electrochemical immunosensor was developed to determine gliadin protein. Herein, the glassy carbon electrode (GCE) surface was modified by the graphene oxide (GO) dispersion followed by electrochemical deposition of silver nanoparticles (AgNPs). Anti‐gliadin antibody (Gli‐Ab1) was immobilized on this electrode (GCE/GO/AgNPs); subsequently, this platform was incubated with bovine serum albumin (BSA) to prevent non‐specific interactions. Gliadin antigen (Gli) followed by horseradish peroxidase‐labeled secondary antibody (HRP−Ab2) solutions were added to the GCE/GO/AgNPs/Gli‐Ab1/BSA immunosensor surface. Scanning Electron Microscope (SEM) was utilized to investigate the surface properties of the prepared electrodes, and cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and differential pulse voltammetry (DPV) techniques were utilized to investigate their electrochemical properties. The experimental conditions have been optimized to form the appropriate immunosensor structure. The gliadin antigen was determined using DPV after the HRP enzyme substrates (hydroquinone and hydrogen peroxide) were added to the electrochemical cell. The gliadin protein′s linear working range was 0.5–200 μg mL−1. The subjected immunosensor displayed convenient reproducibility and selectivity to the possible interfering substances.
Effect of jujube powder addition on the aroma profile of quinoa snacks (QS)
Authors: Song Jianxin , Liu Jiayi , Wang Kaile , Gao Lei , Wang Xiaodong , Peng Jian , Wang Ning
Published: May 2024

Quinoa is a full‐nutrition food; however, its poor flavor and small size make it not the best food option for direct consumption. In this study, a quinoa snack (QS, a cake) was developed, and the aroma profile of the products was improved by adding jujube fruit powder (made from dried jujube fruits, from 5% to 30%). Gas chromatography mass spectrum (GC–MS) combined with electronic nose (e‐nose) was applied for characterizing the aroma profiles of QS samples. Results showed a total of 26 aroma compounds were identified in QS samples by GC–MS, and 3‐methylbutanol (from 1525 μg/kg in QS‐30 to 3487 μg/kg in QS‐0), ethanol (from 1126 μg/kg in QS‐0 to 3581 μg/kg in QS‐30), hexanal (from 125.6 μg/kg in QS‐30 to 984.1 μg/kg in QS‐0), and acetaldehyde (from 531.9 μg/kg in QS‐30 to 191.1 μg/kg in QS‐0) were common. The e‐nose response of W1S (sensitive to methane, from 17.50 of QS‐0 to 93.85 of QS‐30) and W1W (sensitive to sulfur‐organic compounds of e‐nose, from 15.57 of QS‐0 to 39.50 of QS‐30) were significantly higher, and significant differences were presented among QS samples. In conclusion, the aroma profile of the QS sample was significantly (p < .05) enhanced by the addition of jujube powder, and QS‐30 with the highest jujube content (30%) presented the strongest aroma profile. Moreover, QS samples with different additions of jujube powders could be well distinguished by principal component analysis (PCA), and the combination of e‐nose and GC–MS was effective in the volatile profile analysis of QS samples.
Encapsulation of felty germander (Teucrium polium L.) extract using the freeze‐drying method
Authors: Zeidvand Sima , Movahhed Sara , Ahmadi Chenarbon Hossein , Rajaei Peyman
Published: May 2024

Extracts with antimicrobial and antioxidant properties are limited in their application in food products due to their inability to withstand harsh environmental conditions, such as high temperatures and oxygen exposure. Therefore, the present study investigated the nanoencapsulation of Teucrium polium L. extract using the freeze‐drying method to facilitate its application and protection against environmental factors. In this regard, an emulsion containing Teucrium polium L. extract at concentrations of 10%, 20%, and 30% and a mixture of maltodextrin/Persian gum in three ratios of 1:2, 1:1, and 2:1 as the coating wall were produced and then dried in a freeze dryer. In the following, the properties of emulsions and produced nanocapsules were studied. According to the results, emulsions with high amounts of Persian gum showed more stability, zeta potential, and viscosity. However, their particle size and polydisparity index were lower than those of other emulsions. As the extract concentration increased, there was a decrease in stability, zeta potential, and viscosity, accompanied by an increase in particle size and polydispersity index. Concurrently, elevated concentrations of maltodextrin, Persian gum, and extract resulted in higher humidity, density, encapsulation efficiency, and antioxidant activity of the capsules. The most optimal properties of emulsions and nanocapsules were achieved at the 10% concentration of Teucrium polium L. extract and the 1:1 ratio of maltodextrin/Persian gum mixture as the wall material. It is noteworthy that the release rate of phenolic compounds reached its maximum value (88%) after 60 days.
The value of instream stable water isotope and nitrate concentration data for calibrating a travel time‐based water quality model
Authors: Borriero A. , Musolff A. , Kumar R. , Fleckenstein J. H. , Lutz S. R. , Nguyen T. V.
Published: May 2024

Transit time‐based water quality models using StorAge Selection (SAS) functions are crucial for nitrate (NO3−) management. However, relying solely on instream NO3− concentration for model calibration can result in poor parameter identifiability. This is due to the interaction, or correlation, between transport parameters, such as SAS function parameters, and denitrification rate, which challenges accurate parameters identification and description of catchment‐scale hydrological processes. To tackle this issue, we conducted three Monte‐Carlo experiments for a German mesoscale catchment by calibrating a SAS‐based model with daily instream NO3− concentrations (Experiment 1), monthly instream stable water isotopes (e.g. δ18O) (Experiment 2) and both datasets (Experiment 3). Our findings revealed comparable ranges of SAS transport parameters and median water transit times (TT50) across the experiments. This suggests that, despite their distinct reactive or conservative nature, and sampling strategies, the NO3− and δ18O time series offer similar information for calibration. However, the absolute values of transport parameters and TT50 time series, as well as the degree of parameter interaction differed. Experiment 1 showed greater interaction between certain transport parameters and denitrification rate, leading to greater equifinality. Conversely, Experiment 3 yielded reduced parameters interaction, which enhanced transport parameters identifiability and decreased uncertainty in TT50 time series. Hence, even a modest effort to incorporate only monthly δ18O values in model calibration for highly frequent NO3−, improved the description of hydrological transport. This study showcased the value of combining NO3− and δ18O model results to improve transport parameter identifiability and model robustness, which ultimately enhances NO3− management strategies.
Mornings with the highest non‐rainfall water during 2 years of measurements in the Negev–Ecological implications
Authors: Kidron Giora J. , Kronenfeld Rafael , Starinsky Abraham
Published: May 2024

By providing water during the long dry rainless season, non‐rainfall water (NRW), principally dew and fog, is commonly thought to serve as an important water source for arid soil biocrusts, which require water threshold of 0.05 (for lichens) and 0.1 mm (for cyanobacteria) for growth. Such values are commonly reported in the literature. Moreover, values of >0.45 mm/d (considered as the practical theoretical threshold for dew) are also reported. Following an analysis of limited (29 days) dewy mornings, it was recently reported that dew is incapable of forming on the soil surface. Being of limited scope, we therefore analyse days that yielded the highest amounts of NRW during 2 years (2021–2023) of measurements (22 days with NRW ≥0.15 mm). We conducted measurements at 1 m above ground, cobbles, rocks, and the soil surface, and compared them to the cloth‐plate method. Additionally, periodical temperature measurements were conducted, and the dewpoint temperature (Td) was calculated. Our findings indicate that (a) dew yield never surpassed 0.4 mm, (b) while the water threshold amounts were reached on the rocks and especially on the cobbles, these thresholds were seldom reached on soil (a single morning with 0.1 mm and 3 days with ≥0.05 mm), (c) in comparison to air temperatures at 0.05 m and especially at 1 m‐height above ground, surface nocturnal soil temperatures were 2–3°C warmer, thus eliminating possible vapour condensation. Our data cast doubt on values of >0.45 mm reported from various deserts. Additionally, while supporting the view that NRW may provide water for the growth of rock‐dwelling lichens, NRW in the Negev does not provide the soil biocrusts with sufficient water for growth.
Relationships between snowpack, low flows and stream temperature in mountain watersheds of the US west coast
Authors: Boisramé Gabrielle , Harpold Adrian , Tague Christina
Published: May 2024

Water temperatures in mountain streams are likely to rise under future climate change, with negative impacts on ecosystems and water quality. However, it is difficult to predict which streams are most vulnerable due to sparse historical records of mountain stream temperatures as well as complex interactions between snowpack, groundwater, streamflow and water temperature. Minimum flow volumes are a potentially useful proxy for stream temperature, since daily streamflow records are much more common. We confirmed that there is a strong inverse relationship between annual low flows and peak water temperature using observed data from unimpaired streams throughout the montane regions of the United States' west coast. We then used linear models to explore the relationships between snowpack, potential evapotranspiration and other climate‐related variables with annual low flow volumes and peak water temperatures. We also incorporated previous years' flow volumes into these models to account for groundwater carryover from year to year. We found that annual peak snowpack water storage is a strong predictor of summer low flows in the more arid watersheds studied. This relationship is mediated by atmospheric water demand and carryover subsurface water storage from previous years, such that multi‐year droughts with high evapotranspiration lead to especially low flow volumes. We conclude that watershed management to help retain snow and increase baseflows may help counteract some of the streamflow temperature rises expected from a warming climate, especially in arid watersheds.
Strategies for Detecting Aminoacylation and Aminoacyl‐tRNA Editing In Vitro and In Cells
Authors: Watkins Rylan R. , Kavoor Arundhati , Musier‐Forsyth Karin
Published: May 2024

Aminoacyl‐tRNA synthetases (aaRSs) maintain translational fidelity by ensuring the formation of correct aminoacyl‐tRNA pairs. Numerous point mutations in human aaRSs have been linked to disease phenotypes. Structural studies of aaRSs from human pathogens encoding unique domains support these enzymes as potential candidates for therapeutics. Studies have shown that the identity of tRNA pools in cells changes between different cell types and under stress conditions. While traditional radioactive aminoacylation analyses can determine the effect of disease‐causing mutations on aaRS function, these assays are not amenable to drug discovery campaigns and do not take into account the variability of the intracellular tRNA pools. Here, we review modern techniques to characterize aaRS activity in vitro and in cells. The cell‐based approaches analyse the aminoacyl‐tRNA pool to observe trends in aaRS activity and fidelity. Taken together, these approaches allow high‐throughput drug screening of aaRS inhibitors and systems‐level analyses of the dynamic tRNA population under a variety of conditions and disease states.
Display Technologies for Expanding the Pharmaceutical Applications of Cyclotides
Authors: Xie Jing , Kan Meng‐Wei , de Veer Simon J. , Wang Conan , Craik David J.
Published: May 2024

Cyclotides are ultra‐stable peptides originally discovered in plants based on their medicinal applications. Their natural function is as host defence agents. They are amenable to chemical synthesis for use as scaffolds for drug design applications. Cyclotides comprise ~30 amino acids and in addition to having a head‐to‐tail cyclic backbone, incorporate six conserved cystine residues connected in a cystine knot motif. The cyclic backbone and cystine knot contribute to their exceptional resistance to proteases or thermal denaturation, making them useful scaffolds for drug design applications. The backbone segments, or loops, between the conserved cysteine residues are amenable to combinatorial variation in native cyclotides and have also been used to incorporate selected bioactive peptide epitopes into a range of synthetic cyclotides and cyclotide‐like scaffolds. In the past this was largely done via low throughput structure‐based design approaches, but the discovery of novel cyclotide binders has been greatly enhanced by the use of combinatorial display approaches on cyclotide scaffolds using phage, bacterial, yeast and mRNA technologies, as reviewed herein.
Association between cytokine polymorphisms and recurrent pregnancy loss: A review of current evidence
Authors: Stavros Sofoklis , Panagopoulos Periklis , Machairiotis Nikolaos , Potiris Anastasios , Mavrogianni Despoina , Sfakianakis Antonios , Drakaki Eirini , Christodoulaki Chrysi , Panagiotopoulos Dimitrios , Sioutis Dimos , Karampitsakos Theodoros , Antonakopoulos Nikolaos , Christopoulos Panagiotis , Drakakis Peter
Published: May 2024

Cytokines are a type of protein that play an important role in the immune response and can also affect many physiological processes in the body. Cytokine polymorphisms refer to genetic variations or mutations that occur within the genes that code for cytokines, which may affect the level of cytokine production and function. Some cytokine polymorphisms have been associated with an increased risk of developing certain diseases, while others may be protective or have no significant effect on health. In recent years, the role of cytokine polymorphisms in the development of recurrent pregnancy loss (RPL) has been studied. RPL or miscarriage is defined as the occurrence of two or more consecutive pregnancy losses before the 20th week of gestation. There are diverse causes leading to RPL, including genetic, anatomical, hormonal, and immunological factors. With regard to cytokine polymorphisms, a few of them have been found to be associated with an increased risk of RPL, for instance, variations in the genes that code for interleukin‐6, tumor necrosis factor‐alpha, and interleukin‐10. The exact mechanisms by which cytokine polymorphisms affect the risk of recurrent miscarriage are still being studied, and further research is essential to fully understand this complex condition. This brief review aims to summarize the recent literature on the association between cytokine polymorphisms and RPL.
Effect of hysteroscopic surgery on IVF/ICSI pregnancy outcomes for different cesarean scar diverticulum severity: A retrospective cohort study
Authors: Pan Xinyi , Xu Linan , Liu Ziyu , Li Nijie , Liu Qianru , Shi Hao , Yang Xing
Published: May 2024

Objective

To investigate associations between hysteroscopic surgery for patients with varying cesarean scar diverticulum (CSD) severity and in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) embryo transfer (ET) pregnancy outcomes, focusing also on the correlation between the CSD size with its severity, and pregnancy outcomes.

Methods

A retrospective study was conducted on patients with CSD who underwent IVF/ICSI‐ET at a university‐based hospital between January 2017 and July 2023. Patients were categorized into four groups based on CSD severity and whether they received hysteroscopic surgery: a mild surgical group (Group A, n = 86), a mild non‐surgical group (Group B, n = 30), a moderate‐to‐severe surgical group (Group C, n = 173), and a moderate‐to‐severe non‐surgical group (Group D, n = 96). Baseline characteristics and pregnancy outcomes were compared among these groups. Correlation assessments were conducted to explore relationships between CSD size with its severity, and pregnancy outcomes.

Results

Compared with Group D, Group C exhibited significantly increased rates of biochemical pregnancy (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.03–3.51, P = 0.041), clinical pregnancy (OR 2.30; 95% CI1.18–4.45; P = 0.014), and live birth (OR 2.77; 95% CI 1.10–7.00, P = 0.031). However, no differences in pregnancy outcomes were observed between Groups A and B. Correlation analyses revealed significant positive associations between CSD severity and its depth, length, width, and volume.

Conclusions

Patients with moderate‐to‐severe CSD achieved favorable IVF/ICSI pregnancy outcomes following hysteroscopic surgery. The CSD size was significantly related to its severity.
Kaempferide triggers apoptosis and paraptosis in pancreatic tumor cells by modulating the ROS production, SHP‐1 expression, and the STAT3 pathway
Authors: Jung Young Yun , Son Ninh The , Mohan Chakrabhavi Dhananjaya , Bastos Jairo Kenupp , Luyen Nguyen Dinh , Huong Le Mai , Ahn Kwang Seok
Published: May 2024

Pancreatic cancer is one of the deadliest diseases with a poor prognosis and a five‐survival rate. The STAT3 pathway is hyperactivated which contributes to the sustained proliferative signals in pancreatic cancer cells. We have isolated kaempferide (KF), an O‐methylated flavonol, from the green propolis of Mimosa tenuiflora and examined its effect on two forms of cell death namely, apoptosis and paraptosis. KF significantly increased the cleavage of caspase‐3 and PARP. It also downmodulated the expression of Alix (an intracellular inhibitor of paraptosis) and increased the expression of CHOP and ATF4 (transcription factors that promote paraptosis) indicating that KF promotes apoptosis as well as paraptosis. KF also increased intracellular reactive oxygen species (ROS) suggesting the perturbance of the redox state. N‐acetylcysteine reverted the apoptosis‐ and paraptosis‐inducing effects of KF. Some ROS inducers are known to suppress the STAT3 pathway and investigation revealed that KF downmodulates STAT3 and its upstream kinases (JAK1, JAK2, and Src). Additionally, KF also elevated the expression of SHP‐1, a tyrosine phosphatase which is involved in the negative modulation of the STAT3 pathway. Knockdown of SHP‐1 prevented KF‐driven STAT3 inhibition. Altogether, KF has been identified as a promoter of apoptosis and paraptosis in pancreatic cancer cells through the elevation of ROS generation and SHP‐1 expression.
Ocular Pharmacology
Authors: Novack Gary D. , Robin Alan L.
Published: May 2024

Treatment of ocular diseases presents unique challenges and opportunities for the clinician and for the clinical pharmacologist. Ophthalmic pharmaceuticals, typically given as liquids, require consideration of solubility, physiological pH, and osmolarity, as well as sterility and stability, which in turn requires optimal pharmaceutics. Ocular tissue levels are challenging to obtain in humans, and the clinical pharmacokinetics is typically blood levels, which are primarily related to safety, rather than efficacy. The eye is a closed compartment with multiple physiological barriers with esterases and transporters, but relatively little cytochrome oxidases. Delivery routes include topical, intravitreal, and systemic. Patient dosing involves not only adherence issues common to all chronic diseases, but also performance requirements on eye drop instillation. Therapeutically, ocular diseases and their pharmacological treatments include both those analogous to systemic diseases (e.g., inflammation, infection, and neuronal degeneration) and those unique to the eye (e.g., cataract and myopia).
The use of shear‐wave elastography for the assessment of muscle spasticity in patients with cerebral palsy, a systematic review
Authors: Cesaro Edoardo , Saliba Thomas , Simoni Paolo
Published: May 2024

We explore the use of shear wave elastography (SWE) for assessing muscle stiffness and treatment response in cerebral palsy (CP) children by way of a systematic review. SWE offers real‐time muscle stiffness measurements, showing significant differences between CP patients and controls. Studies suggest that SWE can be used to follow muscle stiffness post‐botulinum toxin treatment, correlating with clinical improvement. However, methodological variations and small sample sizes prevent comparison between different studies. Standardized protocols could enhance SWE's clinical utility. In conclusion, SWE holds promise for CP management, though standardized methodologies and larger studies are needed to validate its efficacy and integration into clinical practice.
Exploring the dynamics of physician‐patient relationships: Factors affecting patient satisfaction and complaints
Authors: Mostafapour Mehrnaz , Fortier Jacqueline H. , Garber Gary
Published: May 2024

This review identifes the factors influencing the relationship between physicians and patients that can lead to patients' dissatisfaction and medical complaints. Utilizing a systemic approach 92 studies were retrieved which included quantitative, qualitative, and mixed method studies. Through a thematic analysis of the literature, we identified three interrelated main themes that can influence the relationship between physicians and patients, patients' satisfaction, and the decision to file a medico‐legal complaint. The main themes include patient and physician characteristics; the interpersonal relationship between physicians and patients; and the health care system and policies, with relevant subthemes. These themes are demonstrated in a descriptive model. The review suggests areas of focus for physicians who may wish to increase their awareness around the potential sources of relational problems with their patients. Identifying these issues may assist in improvements in the therapeutic relationship with patients, can reduce their medico‐legal risk, and enhance the quality of their clinical practice. The findings can also be utilized to support andragogical principles for medical learners. The article can serve as a structured framework to identify potential problems and gaps to design and test effective interventions to mitigate these potential relational problems between physician‐patient.