bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychiatric Disorder and Its Management through Ayurveda: A Review
Authors: Thakre Pooja P. , Ade Vinod , Parwe Shweta
Published: March 2022

The prevalence of psychiatric diseases is startling. According to the National Institute of Mental Health, about 25% of adults have one or more diagnosable mental disorders. Psychiatric conditions, for the most part, respond well to treatment. Many Ayurvedic remedies are beneficial in the treatment of psychiatric problems. As a system of medicine, Ayurveda cannot overlook the importance of a patient's psychological state in diagnosing and treating illnesses. Psychic tensions are the core cause of various diseases, according to medical science. Ayurveda has a well-developed area of psychiatry, with scientifically validated methods for treating mental and physical problems related to psychological imbalance. Drugs that are synthesised for human health Synthetic medications for human brain illnesses are costly, long-acting symptomatic treatments that can have substantial and unavoidable adverse effects and low patient adherence. For various individuals' mental problems, such as Alzheimer's disease, Parkinson's disease, depression, epilepsy, schizophrenia, anxiety, and others, herbal and Ayurvedic remedies are favoured over synthetic medications. The Ayurvedic school of medicine has long been utilised to treat a variety of neurological problems. Plant products have numerous advantages, including their accessibility, low frequency of side effects, and cost-effectiveness. The established traditional methods of herbal therapies for various brain illnesses are receiving a lot of attention these days, which gives sufferers hope. Ayurvedic medicines, including either one or the other plant uniqueness or a blend of plant material, have been shown to be particularly effective in treating such diseases. Plant components prescribed for these ailments range from whole plants, roots, stems, bark, leaves, flowers, fruits, and seeds to herbs and perennial trees with a variety of plant components spanning from complete plants to portions of plants, roots, stems, bark, leaves, flowers, fruits, and seeds. It's been tried before to describe Ayurvedic treatment and the problem of synthetic pharmaceutical side effects.
Condylar Height: Age and Sex Determination Using Orthopantogram in Forensics
Authors: Sushanthi L. Casilda , Arthanari Abirami , Ramani Pratibha
Published: March 2022

Background: Since time immemorial, Condyles has been the area of interest for anthropologists, and the condyle size in men is higher than that of women. The condyle measurement is usually studied in two planes, i.e. anteroposterior and mediolateral, which are more gender-alliant. Different conventional X-rays are used for condylar imaging whose panoramic views of both condyles are provided by the OPG. For the creation of biological profiles during mass disasters the skull has remained useful. However, the technical procedures must in most cases be based on fragmented skull bones, when the whole skull is not available.

Materials and Methods: The study samples were retrieved from DIAS of Saveetha Dental College and Hospitals between the retrospective months from November 2020 to February 2021. The study sample consisted of 300 OPG’s (150 males and 150 females), which were taken using Genoray Papaya machine, of age ranging from 10 to 24.9 years in which mandibular condylar height was measured using PlanmecaRomexis Software.

Results: The standard deviation for evaluation of condylar height for female is ±4.38 while for males it is ±4.91.The standard error mean for condylar height for females is 0.35808 and for males is 0.40136 with non-significant p value of 0.893.

Conclusion: By analysing the condylar mandibular height, the results of this study could improve human identification.For validation and comparison purposes, further research may be required in order to expand other associated parameters into a broader sample size.
Development and Evaluation of Extended Release Tacrolimus Tablets by Melt Granulation in Combination with Magnesium Alumino Metasilicate
Authors: Anwar Asif , Soni Priyanka , Kharia Ankit Anand
Published: March 2022

To increase the effectiveness of tacrolimus, the present study sought to develop extended-release tablets. It is used to treat mild to severe atopic dermatitis as well as to prevent organ rejection after organ transplantation. Tacrolimus, on the other hand, has a poor bioavailability and a short half-life. The current research aims to create extended-release tacrolimus tablets by melting and granulating utilizing lipid and adsorbent materials to ensure excellent flow and a hypromellose matrix system to regulate release for 12 hr. Tacrolimus granules were prepared by melting with glyceryl behenate in rapid mixer granulator in the presence of polyethylene glycol followed by magnesium alumino metasilicate for adsorption purposes. Adsorbed granules were milled, sifted, and mixed with extra granular material such as hypromellose, lactose monohydrate and magnesium stearate. Granules were compressed to tablets using oval-shaped plain tooling. In vitro dissolution profile of solid dispersion and extended release tablets were investigated. Release profile of tablets and solid dispersion were improved by melt granulation due to the polymorphic form conversion of drug substance from crystalline to amorphous.Release kinetics of tacrolimus extended release tablets were fitted with zero order release with R2 value of 0.964, which designate constant release for 12 hr. Therefore, the present findings from the study revealed that the formulation was successfully prepared and showed extended release pattern over 12 hr.
In Hospital Mortality and Adverse Events in High-risk Patients Undergoing Primary Percutaneous Coronary Intervention for St Elevation Myocardial Infarction
Authors: Kumar Ashok , Khalid Muhammad Rahman , Kumar Rajesh , Khan Kamran Ahmed , Khowaja Sanam , Hussain Altaf
Published: March 2022

Objective: To determine frequency of in hospital mortality and adverse events in high-risk patients undergoing primary percutaneous coronary intervention (PCI) for ST Elevation Myocardial Infarction (STEMI).

Study Design: Descriptive case series study

Setting: The Department of Adult Cardiology, National Institute of Cardiovascular Diseases, Karachi.

Duration: From 5thJanuary 2019 To 4thJuly 2019

Material and Methods: All the patients of acute myocardial infarction (MI), age between18 to 80 years, and undergoing Primary PCI of either gender were included. Study outcomes such as in-hospital mortality, cardiogenic shock, heart failure, no reflow phenomenon, and ventricular arrhythmia were recorded. Data was collected via study proforma and analysis was done by using SPSS version 26.

Results: There were 81.9% males and 18.1% females. 16.7% cases diabetic, 42.7% were hypertensive, 38% with family history, 24.7% with smoking and 74% with obesity. Mortality was 14.7%, cardiogenic shock was 12.0%, heart failure was 18.7%, no reflow phenomenon was 28% and ventricular arrhythmia was 16%. Significant association of mortality was found with age and obesity. Cardiogenic shock and ventricular arrhythmia were significant according to gender and heart failure findings were significantly linked to hypertension (p-<0.05).

Conclusion: Mortality rate was high among STEMI patients who underwent primary PCI. No reflow phenomenon was the most observed event among these patients.
Comparison of Video-assisted Instruction and Conventional Teaching Method’s Effects on Students’ Performance in Root Canal Obturation during COVID- 19 Pandemic
Authors: Darmiani Soheila , Ahmadi Mahla
Published: March 2022

Background: The purpose of root canal treatment is to prepare the root canal and obturate the entire the root canal reliably. The traditional method of teaching endodontics to dental students is the live conventional demonstration (CD)., Video –assisted clinical instruction in dentistry (VACID) is an educational tool that uses video-images to complement dental education. The aim of this study was to evaluate the effectiveness of VACID and CD on the performance of dental students in obturating the root canal.

Materials and Methods: In this interventional study, thirty undergraduate dental students of Birjand University of Medical Sciences in 2021 were included in the study. They were equally divided in to three groups(n=10). and received instructions on root canal obturation via CD, VICAD and CD plus VICADThen, two endodontists evaluated the clinical performance of the students based onfinal radiographs of obturated root canals.blindly . Each student's score was calculated from 20.  Data were entered into SPSS software and analyzed by ANOVA and Chi-square tests.

Results: The mean± standard deviation(SD) grade point average (GPA) of students were not significantly different from each other (P = 0.398). The mean score of students' performance in all groups was not significantly different from each other (P> 0.05). The mean score of students' performance in terms of their gender in all three groups was not significantly different from each other (P> 0.05). The mean score of students' performance in terms of GPA in terms of evaluating teachers was not significantly different from each other (P> 0.05).

Conclusion: The use of new educational methods, such as the production of educational videos, will be as effective as the usual demonstration methods for the performance of dental students during corona virus pandemic.
Metabolic Syndrome in Patients with ST Elevated Myocardial Infarction
Authors: Zahid Wajid , Bandeshah Akhtar Ali , Mian Fazzal Aziz , Noureen Fakhra , Saeed Abid , Iqbal Javed , Rasool Alishba , Saleem Amer
Published: March 2022

Introduction: ST-elevation myocardial infarction (STEMI) is a leading cause of morbidity and mortality worldwide.  Present study is designed to gather data in our population about the prevalence of metabolic syndrome (MetS) in STEMI. The gathered data will help in better understanding of association of STEMI and metabolic syndrome. This will also help the physicians to devise preventive strategies based on life style modifications to limit further progression of this syndrome particularly in individuals who are at higher risk for CAD.

Objectives: To determine the frequency of metabolic syndrome in patients presented with ST segment elevated myocardial infarction.

Study design: Cross sectional study.

Duration of Study: 6 months (01-08-2018 to 31-01-2019)

Settings: Department of Cardiology, Pakistan Institute of Medical Sciences Islamabad

Subjects and Methods: A total of two hundred and fifty-seven (n=257) patients of both gender between age 18-75 years who were diagnosed cases of ST segment elevated myocardial infarction (STEMI) were enrolled in this study. Fasting blood sugar, Serum TG, HDL, blood pressure and waist circumference was estimated and frequency of metabolic syndrome was evaluated.

Results: Metabolic syndrome was found present in 37.4% (n=96/257) patients as per our operational definition. Frequency of metabolic syndrome was significantly higher in males as compared to females (P=0.048). No significant difference noted in the frequency of metabolic syndrome when data was stratified for different age groups (P=0.717).

Conclusions: Metabolic syndrome was observed to the highly prevalent among patients presented with ST segment elevated myocardial infarction and was significantly higher in males.
Excavations in the Canongate Backlands, Edinburgh
Authors: Gooder John , Ellis Clare , Haggarty George , Heald Andrew , Campbell Stuart , Henderson David , Gallagher Dennis B , Holmes Nicholas N McQ , Turnbull Jill , Vandorpe Patrice
Published: March 2022

The following paper presents the results of two excavations undertaken in 1999 and 2000 within parts of the World Heritage Site of the Old Town of Edinburgh and the Canongate (NGR: NT 2665 7377). Excavation at Plot N of the Holyrood North Re-Development Project, Holyrood Road, unearthed evidence of medieval boundary works (including a possible 12th-century burgh ditch), a 17th-century well, a medieval graindrying kiln, refuse pits, drainage features and post-medieval cultivation soils. Excavation alongside Calton Road revealed evidence of medieval/post-medieval property divisions, cultivation soils and quarry pits. Both sites yielded significant artefact assemblages.
Sex questions SAMHSA grantees must ask cause hubbub: GPRA
Authors: Knopf Alison
Published: March 2022

For years, treatment providers funded by the Substance Abuse and Mental Health Services Administration (SAMHSA) have privately railed against the accountability measures they are required to take in order to justify their grants. But in general, as long as there are no strings attached — the money comes regardless of the reports — the recipients have been quiet.
Fast Charging Anode Materials for Lithium‐Ion Batteries: Current Status and Perspectives
Authors: Li Shengqiang , Wang Kai , Zhang Gefei , Li Shani , Xu Yanan , Zhang Xudong , Zhang Xiong , Zheng Shuanghao , Sun Xianzhong , Ma Yanwei
Published: March 2022

With the enormous development of the electric vehicle market, fast charging battery technology is highly required. However, the slow kinetics and lithium plating under fast charging condition of traditional graphite anode hinder the fast charging capability of lithium‐ion batteries. To develop anode materials with rapid Li‐ions diffusion capability and fast reaction kinetics has received widely attentions. This review summarizes the current status in the exploration of fast charging anode materials, mainly including the critical challenge of achieving fast charging capability, the inherent structures and lithium storage mechanisms of various anode materials, as well as the recent progress to improve the rate performance involving morphology regulation, structure design, surface/interface modification, as well as forming multiphase systems. Finally, the challenges and future directions of developing fast charging Li‐ion batteries are highlighted.
Engineered Spider Silk Proteins for Biomimetic Spinning of Fibers with Toughness Equal to Dragline Silks
Authors: Arndt Tina , Greco Gabriele , Schmuck Benjamin , Bunz Jessica , Shilkova Olga , Francis Juanita , Pugno Nicola M , Jaudzems Kristaps , Barth Andreas , Johansson Jan , Rising Anna
Published: March 2022

Spider silk is the toughest fiber found in nature, and bulk production of artificial spider silk that matches its mechanical properties remains elusive. Development of miniature spider silk proteins (mini‐spidroins) has made large‐scale fiber production economically feasible, but the fibers’ mechanical properties are inferior to native silk. The spider silk fiber's tensile strength is conferred by poly‐alanine stretches that are zipped together by tight side chain packing in β‐sheet crystals. Spidroins are secreted so they must be void of long stretches of hydrophobic residues, since such segments get inserted into the endoplasmic reticulum membrane. At the same time, hydrophobic residues have high β‐strand propensity and can mediate tight inter‐β‐sheet interactions, features that are attractive for generation of strong artificial silks. Protein production in prokaryotes can circumvent biological laws that spiders, being eukaryotic organisms, must obey, and the authors thus design mini‐spidroins that are predicted to more avidly form stronger β‐sheets than the wildtype protein. Biomimetic spinning of the engineered mini‐spidroins indeed results in fibers with increased tensile strength and two fiber types display toughness equal to native dragline silks. Bioreactor expression and purification result in a protein yield of ≈9 g L−1 which is in line with requirements for economically feasible bulk scale production.
Anodized Steel: The Most Promising Bifunctional Electrocatalyst for Alkaline Water Electrolysis in Industry
Authors: Zhou Pengfei , Niu Pengda , Liu Jishan , Zhang Nian , Bai Haoyun , Chen Mingpeng , Feng Jinxian , Liu Di , Wang Litong , Chen Shi , Kwok Chi Tat , Tang Yuxin , Li Ruidi , Wang Shuangpeng , Pan Hui
Published: March 2022

Electrolysis of water, especially alkaline water electrolysis (AWE), is the most promising technology to produce hydrogen in industry. However, only 4% of the total hydrogen is produced in this way because the electrode materials are expensive, inefficient, or unstable. Here, it is reported that the large‐scale 3D printed martensitic steel (AerMet100) can be the bifunctional electrode for AWE with high catalytic performance, which may dramatically increase the green‐hydrogen percentage in the market and provide strategic planning for energy management. It is found that the martensitic steel by fast anodization (3 min) can realize ultra‐high hydrogen and oxygen evolution reactions (HER and OER), and excellent stability at high current densities. Particularly, this electrocatalyst shows a low overpotential of 3.18 V and long‐term stability over 140 h at 570 mA cm−2 in overall water splitting. Additionally, the treated large‐scale steel can work well under a very high current up to 20 A. This study demonstrates that martensitic steel can be commercialized as a highly efficient catalyst for industrial hydrogen production in AWE, which should provide solutions to the energy crisis and environmental pollution.
Plasmonic Fluorescence Enhancement in Diagnostics for Clinical Tests at Point‐of‐Care: A Review of Recent Technologies
Authors: Semeniak Daria , Cruz Daniela F. , Chilkoti Ashutosh , Mikkelsen Maiken H.
Published: March 2022

Fluorescence‐based biosensors have widely been used in the life‐sciences and biomedical applications due to their low limit of detection and a diverse selection of fluorophores that enable simultaneous measurements of multiple biomarkers. Recent research effort has been made to implement fluorescent biosensors into the exploding field of point‐of‐care testing (POCT), which uses cost‐effective strategies for rapid and affordable diagnostic testing. However, fluorescence‐based assays often suffer from their feeble signal at low analyte concentrations, which often requires sophisticated, costly, and bulky instrumentation to maintain high detection sensitivity. Metal‐ and metal oxide‐based nanostructures offer a simple solution to increase the output signal from fluorescent biosensors due to the generation of high field enhancements close to a metal or metal oxide surface, which has been shown to improve the excitation rate, quantum yield, photostability, and radiation pattern of fluorophores. This article provides an overview of existing biosensors that employ various strategies for fluorescence enhancement via nanostructures and have demonstrated the potential for use as POCT. Biosensors using nanostructures such as planar substrates, freestanding nanoparticles, and metal–dielectric–metal nanocavities are discussed with an emphasis placed on technologies that have shown promise towards POCT applications without the need for centralized laboratories.
Tunable Photoelectric Properties of n‐Type Semiconducting Polymer:Small Molecule Blends for Red Light Sensing Phototransistors
Authors: Lin Chia‐Chi , Velusamy Arulmozhi , Tung Shih‐Huang , Osaka Itaru , Chen Ming‐Chou , Liu Cheng‐Liang
Published: March 2022

Semiconducting blend heterostructures, composed of conjugated polymer with photoresponsive organic crystals, provide an effective way to achieve promising photodetection devices. Here, solution‐processed n‐type N2200 conjugated polymer and quinoidal thienoisoindigo (TIIQ) small molecule blend is used to construct phototransistors for red light detection. The device performance of the optically switchable phototransistors can be tuned by the relative composition in the blend. The key feature is red light (680 nm) illuminated intensity‐tunable photodetection enabling the highest photoresponsivity (R) of 4065 A W‐1 and specific photodetectivity (D*) of 1.4 × 1013 Jones for an 88% blend device. At the same time, maintaining high mobility (μ) of 1.59 cm2 V‐1 s‐1, since the efficient extraction of photogenerated charges from blend heterointerface, benefiting from blending with higher μ and enhanced absorption of TIIQ, contributes to improvement in the red light photoresponse of the N2200:TIIQ blend phototransistor. This work demonstrates that the semiconducting blend strategies provide opportunities for developing high performance organic phototransistors.
Synthesis of Dihydro‐5H‐Benzo[c]‐Fluorenes, Dihydroindeno[c]‐Chromenes and Thiochromenes via Intramolecular Cyclization and their Effect on Human Leukemia Cells
Authors: Yan Jun , Tran Christine , Bignon Jérôme , Provot Olivier , Hamze Abdallah
Published: March 2022

In this work, we describe the construction of a series of 6,7‐dihydro‐5H‐benzo[c]fluorenes. Their synthesis is based on an intramolecular‐cyclization of tricyclic substrates, which has an alcohol functional group in acidic conditions at ambient temperature. Certain reaction optimization conditions reveal that triflic acid was the most convenient reagent for this transformation, affording a broad range of fluorene derivatives in a 37 to 93% yield. We illustrate the robustness of this methodology through a gram‐scale synthesis, and the preparation of dihydroindeno[c]‐chromenes thiochromenes, and azulenes derivatives.

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A New Stable, Explicit, Third‐Order Method for Diffusion‐Type Problems
Authors: Kovács Endre , Nagy Ádám , Saleh Mahmoud
Published: March 2022

This paper reports on a novel explicit numerical method for the spatially discretized diffusion or heat equation. After discretizing the space variables as in conventional finite difference methods, this method does not use a finite difference approximation for the time derivatives, it instead combines constant‐neighbor and linear‐neighbor approximations, which decouple the ordinary differential equations, thus they can be solved analytically. In the obtained three‐stage method, the time step size appears in exponential form with negative coefficients in the final expression. This property guarantees unconditional stability, as it is shown using von Neumann stability analysis. It is also proved that the convergence of the method is third order in the time step size. After verification, by solving Fisher's and Huxley's equations, it is demonstrated that it works for nonlinear equations as well. The new algorithm is tested against widely used numerical solvers for cases where the media is strongly inhomogeneous. According to the results, the new method is significantly more effective than the traditional explicit or implicit methods, especially for extremely large stiff systems. It is believed that this new method is unique in the sense that it is the first unconditionally stable explicit method with third‐order convergence.
Market potential of new plant‐based protein alternatives: Insights from four US consumer experiments
Authors: Tonsor Glynn T. , Lusk Jayson L. , Schroeder Ted C.
Published: March 2022

This article reports results from four studies determining the US market potential for plant‐based meat alternatives in different contexts and settings. The first study shows that a pair‐wise choice between beef and a plant‐based alternative was not significantly affected by the presence of nutrition facts panels or ingredient lists. A second study, framed as a food service meal choice, reveals that the introduction of a plant‐based burger has roughly the same effect on beef sales as does the presence of a chicken wrap. The final two studies estimate own‐ and cross‐price elasticities of retail demand. We find small cross‐price elasticities between plant‐based patties and ground beef. Each of the aforementioned results varies for regular meat consumers as compared to consumers who self‐identify with an alternative diet such as flexitarian, vegetarian, or vegan. Combined, this study increases understanding of the impact presented by plant‐based offerings in the US protein market.
Experimental animal models of pulmonary hypertension: Development and challenges
Authors: Wu Xiao‐Han , Ma Jie‐Ling , Ding Dong , Ma Yue‐Jiao , Wei Yun‐Peng , Jing Zhi‐Cheng
Published: March 2022

Pulmonary hypertension (PH) is clinically divided into 5 major types, characterized by elevation in pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR), finally leading to right heart failure and death. The pathogenesis of this arteriopathy remains unclear, leaving it impossible to target pulmonary vascular remodeling and reverse the deterioration of right ventricular (RV) function. Different animal models have been designed to reflect the complex mechanistic origins and pathology of PH, roughly divided into 4 categories according to the modeling methods: non‐invasive models in vivo, invasive models in vivo, gene editing models, and multi‐means joint modeling. Though each model shares some molecular and pathological changes with different classes of human PH, in most cases the molecular etiology of human PH is poorly known. The appropriate use of classic and novel PH animal models is essential for the hunt of molecular targets to reverse severe phenotypes.
Heterogeneity of adipose stromal vascular fraction cells from the different harvesting sites in rats
Authors: Hendawy Hanan , Kaneda Masahiro , Yoshida Tadashi , Metwally Elsayed , Hamabe Lina , Yoshida Tomohiko , Shimada Kazumi , Tanaka Ryou
Published: March 2022

In both veterinary and human health, regenerative medicine offers a promising cure for various disorders. One of the rate‐limiting challenges in regenerative medicine is the considerable time and technique required to expand and grow cells in culture. Therefore, the stromal vascular fraction (SVF) shows a significant promise for various cell therapy approaches. The present study aimed to define and investigate the optimal harvest site of freshly isolated SVF cells from various adipose tissue (AT) depot sites in the female Sprague–Dawley (S.D.) rat. First, hematoxylin and eosin (H&E) were used to analyze the morphological variations in AT samples from peri‐ovarian, peri‐renal, mesenteric, and omental sites. The presence of putative stromal cells positive CD34 was detected using immunohistochemistry. Then, the isolated SVF cells were examined for cell viability and cellular yield differences. Finally, the expression of mesenchymal stem cells and hematopoietic markers in the SVF cells subpopulation was studied using flow cytometry. The pluripotent gene expression profile was also evaluated. CD34 staining of the omental AT was substantially higher than those of other anatomical sites. Despite having the least quantity of fat, omental AT has the highest SVF cell fraction and viable cells. Along with CD90 and CD44 higher expression, Oct4, Sox2, and Rex‐1 genes levels were higher in SVF cells isolated from the omental AT. To conclude, omental fat is the best candidate for SVF cell isolation in female S.D. rats with the highest SVF cell fraction with higher MSCs phenotypes and pluripotency gene expression.
Reproductive concerns among adolescent and young adult cancer survivors: A scoping review of current research situations
Authors: Xie Jianfei , Sun Qian , Duan Yinglong , Cheng Qinqin , Luo Xiaofei , Zhou Yi , Liu Xiangyu , Xiao Panpan , Cheng Andy S. K.
Published: March 2022

Fertility is a significant concern among adolescent and young adult (AYA) cancer survivors and their caregivers, especially after their completion of cancer treatment programs. Concerns about fertility affect not only cancer patients' psychological well‐being, but also all aspects of their medical treatments, including treatment protocol, decision‐making, and treatment adherence. In this scoping review, the PubMed, CINAHL, Web of Science, Embase, CNKI, and Wanfang electronic databases were searched according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis Extension for Scoping Reviews. The searches identified 669 articles, 54 of which met the inclusion criteria. Reviewers extracted the data on the study characteristics, measurements, positive factors, negative factors, and additional themes. This scoping review included studies from 10 countries. Most studies were quantitative using a cross‐sectional design. The prevalence of reproductive concerns among AYA cancer survivors ranged from 44% to 86%, and 28% to 44% of the survivors experienced moderate to severe concerns. The specific implementation of fertility consultation, including timing, consult frequency, and content, deserves ongoing exploration.
A Novel Vascular Disrupting Agents Noncovalent Polymeric Nanomedicine: Significantly Increased Antitumor Therapeutic Efficiency
Authors: Lv Jianlin , Xu Yajun , Huang Yue , Yu Haiyang , Tang Zhaohui
Published: March 2022

Comprehensive Summary

Plinabulin, a potential vascular disrupting agent (VDA), has entered the phase III clinical trial. However, the antitumor efficacy of Plinabulin is only moderate, which is probably because of the short action time of acting on tubulin. To maintain a constant VDAs concentration around the tumor vascular endothelial cells, in this study, we developed a novel Plinabulin derivate named HBP and further prepared noncovalent HBP nanoparticles (HBP NPs). We examined and compared the antitumor efficiency of HBP and HBP NPs in 4T1 tumor‐bearing mice. HBP NPs significantly increased therapeutic efficiency than HBP, even with a quarter dose. These findings exhibited in this paper further confirmed the opinion that VDAs nanomedicine could markedly enhance tumor therapeutic effect more than small molecular VDAs.
Brightness, lightness, colorfulness, and chroma in CIECAM02 and CAM16
Authors: Hellwig Luke , Fairchild Mark D.
Published: March 2022

In the CIECAM02 and CAM16 color appearance models, brightness is computed as a nonlinear function of lightness. This paper traces the history of that nonlinearity to its roots in the Hunt color appearance model. A new, more robust, linear relationship between lightness and brightness is proposed. This new formula also prompts the reevaluation of the CAM16 equations for chroma, colorfulness, and saturation. The new formulas for these perceptual attributes are tested on experimental data from the Munsell color order system and the LUTCHI color appearance dataset and are compared to the performance of the original CAM16 equations.
Re‐evaluating the actin‐dependence of spectraplakin functions during axon growth and maintenance
Authors: Qu Yue , Alves‐Silva Juliana , Gupta Kriti , Hahn Ines , Parkin Jill , Sánchez‐Soriano Natalia , Prokop Andreas
Published: March 2022

Axons are the long and slender processes of neurons constituting the biological cables that wire the nervous system. The growth and maintenance of axons require loose microtubule bundles that extend through their entire length. Understanding microtubule regulation is therefore an essential aspect of axon biology. Key regulators of neuronal microtubules are the spectraplakins, a well‐conserved family of cytoskeletal cross‐linkers that underlie neuropathies in mouse and humans. Spectraplakin deficiency in mouse or Drosophila causes severe decay of microtubule bundles and reduced axon growth. The underlying mechanisms are best understood for Drosophila’s spectraplakin Short stop (Shot) and believed to involve cytoskeletal cross‐linkage: Shot's binding to microtubules and Eb1 via its C‐terminus has been thoroughly investigated, whereas its F‐actin interaction via N‐terminal calponin homology (CH) domains is little understood. Here, we have gained new understanding by showing that the F‐actin interaction must be finely balanced: altering the properties of F‐actin networks or deleting/exchanging Shot's CH domains induces changes in Shot function—with a Lifeact‐containing Shot variant causing remarkable remodeling of neuronal microtubules. In addition to actin‐microtubule (MT) cross‐linkage, we find strong indications that Shot executes redundant MT bundle‐promoting roles that are F‐actin‐independent. We argue that these likely involve the neuronal Shot‐PH isoform, which is characterized by a large, unexplored central plakin repeat region (PRR) similarly existing also in mammalian spectraplakins.
Urinary clearance of 11‐nor‐9‐carboxy‐Δ9‐tetrahydrocannabinol: A detailed pharmacokinetic analysis
Authors: Sempio Cristina , Huestis Marilyn A. , Kaplan Bruce , Klawitter Jost , Christians Uwe , Henthorn Thomas K.
Published: March 2022

Urine is a common matrix for screening for cannabis use. Urine assays typically measure total 11‐nor‐9‐carboxy‐Δ9‐tetrahydrocannabinol (THCCOOH) concentrations after hydrolysis cleaves the glucuronide. Urine THCCOOH concentration is adjusted by urine creatinine concentration or specific gravity, to account for variable hydration states. Therefore, we performed a population pharmacokinetic analysis of the urinary THCCOOH excretion, urinary flow rate, and creatinine excretion rate data. Urine was obtained over 168 h from six subjects who smoked low‐ (15.8 mg) and high‐dose (33.8 mg) Δ9‐tetrahydrocannabinol (THC) cigarettes on two occasions. Samples were analyzed for THCCOOH concentration by gas chromatography–mass spectrometry (GC‐MS) and volume, time, and creatinine concentration measured. A population pharmacokinetic model of the urinary clearance of THCCOOH was created from these data, and potential covariates of urine creatinine concentration and urine creatinine excretion rate were assessed. Elimination clearance of THCCOOH was estimated as 0.104 ± 0.088 L/min, and its urinary clearance was 0.0022 ± 0.0015 L/min. Total urine excretion of THCCOOH was estimated at 2.3%. Urine flow rate and urine creatinine concentrations were significantly correlated, r2 = 0.35. Creatinine excretion rate was 129.6 ± 71.0 ml/min, and the intrasubject variability was 31%–52% (SD%) during the week. Urinary creatinine excretion rate was a significant covariate for the urinary clearance of THCCOOH. Creatinine clearance is a significant covariate for urinary THCCOOH clearance. Only 2%–3% of bioavailable THC is excreted as THCCOOH and THCCOO‐glucuronide via the urine. Correction of urine drug and/or metabolite concentration with urine creatinine concentration or specific gravity may be more problematic than previously appreciated.
Flowering time advances since the 1970s in a sagebrush steppe community: Implications for management and restoration
Authors: Bloom Trevor D. S. , O'Leary Donal S. , Riginos Corinna
Published: March 2022

Climate change is widely known to affect plant phenology, but little is known about how these impacts manifest in the widespread sagebrush ecosystem of the Western United States, which supports a number of wildlife species of concern. Shifts in plant phenology can trigger consequences for the plants themselves as well as the communities of consumers that depend upon them. We assembled historical observations of first‐flowering dates for 51 species collected in the 1970s and 1980s in a montane sagebrush community in the Greater Yellowstone Ecosystem and compared these to contemporary phenological observations targeting the same species and locations (2016–2019). We also assembled regional climate data (average spring temperature, day of spring snowmelt, and growing degree days) and tested the relationship between first‐flowering time and these variables for each species. We observed the largest change in phenology in early‐spring flowers, which, as a group, bloomed on average 17 days earlier, and as much as 36 days earlier, in the contemporary data set. Mid‐summer flowers bloomed on average 10 days earlier, nonnative species 15 days earlier, and berry‐producing shrubs 5 days earlier, while late summer flowering plants did not shift. The greatest correlates of early‐spring and mid‐summer flowering were average spring temperature and day of snowmelt, which was 21 days earlier, on average, in 2016–2019 relative to the 1973–1978 observations. The shifts in flowering phenology that we observed could indicate developing asynchronies or novel synchronies of these plant resources and wildlife species of conservation concern, including Greater Sage‐grouse, whose nesting success is tied to availability of spring forbs; grizzly bears, which rely heavily on berries for their fall diet; and pollinators. This underscores the importance of maintaining a diverse portfolio of native plants in terms of species composition, genetics, phenological responsiveness to climatic cues, and ecological importance to key wildlife and pollinator species. Redundancy within ecological niches may also be important considering that species roles in the community may shift as climate change affects them differently. These considerations are particularly relevant to restoration and habitat‐enhancement projects in sagebrush communities across western North America.
Responder analysis for improvement in 6‐min walk test with ferric carboxymaltose in patients with heart failure with reduced ejection fraction and iron deficiency
Authors: Anker Stefan D. , Ponikowski Piotr , Khan Muhammad Shahzeb , Friede Tim , Jankowska Ewa A. , Fabien Vincent , Goehring Udo‐Michael , Metra Marco , Piña Ileana L. , Coats Andrew J.S. , Rosano Giuseppe , Dorigotti Fabio , Comin‐Colet Josep , Van Veldhuisen Dirk J. , Filippatos Gerasimos S. , Butler Javed
Published: March 2022

Aim

Improving functional capacity is a key goal in heart failure (HF). This pooled analysis of FAIR‐HF and CONFIRM‐HF assessed the likelihood of improvement or deterioration in 6‐min walk test (6MWT) among iron‐deficient patients with chronic HF with reduced ejection fraction (HFrEF) receiving ferric carboxymaltose (FCM).

Methods and results

Data for 760 patients (FCM: n = 454; placebo: n = 306) were analysed. The proportions of patients receiving FCM or placebo who had ≥20, ≥30, and ≥40 m improvements or ≥10 m deterioration in 6MWT at 12 and 24 weeks were assessed. Patients receiving FCM experienced a mean (standard deviation) 31.1 (62.3) m improvement in 6MWT versus 0.1 (77.1) m improvement for placebo at week 12 (difference in mean changes 26.8 [16.6–37.0]). At week 12, the odds [95% confidence interval] of 6MWT improvements of ≥20 m (odds ratio 2.16 [1.57–2.96]; p < 0.0001), ≥30 m (2.00 [1.44–2.78]; p < 0.0001), and ≥40 m (2.29 [1.60–3.27]; p < 0.0001) were greater with FCM versus placebo, while the odds of a deterioration ≥10 m were reduced with FCM versus placebo (0.55 [0.38–0.80]; p = 0.0019). Among patients who experienced 6MWT improvements of ≥20, ≥30, or ≥40 m with FCM at week 12, more than 80% sustained this improvement at week 24.

Conclusion

Ferric carboxymaltose resulted in a significantly higher likelihood of improvement and a reduced likelihood of deterioration in 6MWT versus placebo among iron‐deficient patients with HF. Of the patients experiencing clinically significant improvements at week 12, the majority sustained this improvement at week 24. These results are supportive of FCM to improve exercise capacity in HF.
A Comparative Study of Compressive Effects on the Morphology and Performance of Carbon Paper and Cloth Electrodes in Redox Flow Batteries
Authors: Tenny Kevin M. , Greco Katharine V. , van der Heijden Maxime , Pini Tommaso , Mularczyk Adrian , Vasile Alexandru-Petru , Eller Jens , Forner-Cuenca Antoni , Chiang Yet-Ming , Brushett Fikile R.
Published: March 2022

Compressing porous carbon electrodes is a common approach to improve flow battery performance, but the resulting impact on electrode structure, fluid dynamics, and cell performance is not well understood. Herein, microtomographic imaging, load cell testing, and flow cell diagnostics are employed to characterize how compression‐induced changes impact pressure drop, polarization, and mass‐transfer scaling. Five different compressions are tested, spanning ranges typically used in literature, for AvCarb 1071 cloth (0%, 9%, 20%, 25%, 32%) and Freudenberg H23 paper (0%, 8%, 12%, 17%, 22%). It is found that the two electrode structures have distinct responses to compression, resulting in differing optimal conditions identified for each material; specifically, the Freudenberg H23 exhibits lower combined ohmic, charge‐transfer, and mass‐transport values at 8% compression, resulting in improved electrochemical performance across all compressive values, as compared to the optimal AvCarb 1071 compression (20%). Overall, Freudenberg H23 exhibits a greater sensitivity to compression with peak electrochemical activity correlating with increased permeability, whereas AvCarb 1071 is insensitive to compressive loads but produces lower electrochemical performance. Herein, the trade‐offs of mechanical robustness on fluid‐dynamic and electrochemical performance between the two electrodes are demonstrated by the aforementioned findings, suggesting each could be used for specific operating environments.
Recent advances and prospects in purification and heterologous expression of lactoferrin
Authors: Cui Shixiu , Lv Xueqin , Sun Guoyun , Wu Wenyang , Xu Hong , Li Yuelong , Liu Yanfeng , Li Jianghua , Du Guocheng , Wang Miao , Liu Long
Published: March 2022

Lactoferrin is an 80 kDa iron‐binding glycoprotein of the transferrin family, which is abundant in milk and in most biological fluids. Besides the direct antimicrobial properties, lactoferrin can regulate immune responses and prevent infection and septic shock. Membrane adsorption and chromatographic methods are usually used for separating and purifying of lactoferrin from bovine milk. However, the content of lactoferrin in milk is relatively low, resulting in a high cost of producing lactoferrin. Meanwhile, as a heterologous protein applied to the human body, it may cause a certain antigen response. Therefore, obtaining a large amount of biologically active lactoferrin has always been a research hot topic. This review first introduced the physical and chemical properties, and biological activities of lactoferrin. Then, the current recombinant expression systems for lactoferrin were summarized. Finally, the current challenges and the future development trends of efficient synthesis of lactoferrin were discussed.
Recovery of superior frontal gyrus cortical thickness and resting‐state functional connectivity in abstinent heroin users after 8 months of follow‐up
Authors: Yang Wenhan , Zhang Min , Tang Fei , Du Yanyao , Fan Li , Luo Jing , Yan Cui , Wang Shicong , Zhang Jun , Yuan Kai , Liu Jun
Published: March 2022

Compared with healthy controls, heroin users (HUs) show evidence of structural and functional brain alterations. However, little is known about the possibility of brain recovery after protracted heroin abstinence. The purpose of this study was to investigate whether brain recovery is possible after protracted abstinence in HUs. A total of 108 subjects with heroin addiction completed structural and functional scans, and 61 of those subjects completed 8‐month follow‐up scans. Resting‐state data and 3D‐T1 MR images were collected for all participants, first at baseline and again after 8 months. Cognitive function and craving were measured by the Trail Making Test‐A (TMT‐A) and Visual Analog Scale for Craving, respectively. The cortical thickness and resting‐state functional connectivity (RSFC) differences were then analyzed and compared between baseline and follow‐up, and correlations were obtained between neuroimaging and behavioral changes. HUs demonstrated improved cognition (shorter TMT‐A time) and reduced craving at the follow‐up (HU2) relative to baseline (HU1), and the cortical thickness in the bilateral superior frontal gyrus (SFG) was significantly greater at HU2 than at HU1. Additionally, the RSFC of the left SFG with the inferior frontal gyrus (IFG), insula, and nucleus accumbens and that of the right SFG with the IFG, insula and orbitofrontal cortex (OFC) were increased at HU2. The changes in TMT‐A time were negatively correlated with the RSFC changes between the left SFG and the bilateral IFG, the bilateral caudate, and the right insula. The changes in craving were negatively correlated with the RSFC changes between the left OFC and the bilateral SFG. Our results demonstrated that impaired frontal‐limbic neurocircuitry can be partially restored, which might enable improved cognition as well as reduced craving in substance‐abusing individuals. We provided novel scientific evidence for the partial recovery of brain circuits implicated in cognition and craving after protracted abstinence.
The structural effects of Vitamin A deficiency on biological macromolecules due to ethanol consumption and withdrawal: An FTIR study with chemometrics
Authors: Elibol Birsen , Severcan Mete , Jakubowska‐Dogru Ewa , Dursun Ilknur , Severcan Feride
Published: March 2022

The structural effects of vitamin A‐deficiency were examined on the molecular profiles of biomolecules of male rat hippocampus during prolonged ethanol intake/withdrawal using FT‐IR spectroscopy coupled with chemometrics. Liquid ethanol diet with/without vitamin A was maintained to adult rats for 3‐months. The rats were decapitated at different ethanol withdrawal times and FT‐IR spectra were obtained. Ethanol consumption/withdrawal produced significant changes in proteins' conformations, while having insignificant structural effects on lipids. In vitamin A deficiency, ethanol produced structural changes in lipids by lipid ordering especially in the early‐ethanol withdrawal. Furthermore, an increase in lipid and protein content, saturated/unsaturated lipid ratio, a decrease in nucleic acids content and decrease in membrane fluidity were observed. These changes were less severe in the presence of Vitamin A. This study is clinically important for individuals with vitamin A deficiency because they have to be more cautious when consuming alcohol to protect themselves from cognitive dysfunctions.
Noises investigations and image denoising in femtosecond stimulated Raman scattering microscopy
Authors: Ranjan Rajeev , Costa Giovanni , Ferrara Maria Antonietta , Sansone Mario , Sirleto Luigi
Published: March 2022

In the literature of SRS microscopy, the hardware characterization usually remains separate from the image processing. In this article, we consider both these aspects and statistical properties analysis of image noise, which plays the vital role of joining links between them. Firstly, we perform hardware characterization by systematic measurements of noise sources, demonstrating that our in‐house built microscope is shot noise limited. Secondly, we analyze the statistical properties of the overall image noise, and we prove that the noise distribution can be dependent on image direction, whose origin is the use of a lock‐in time constant longer than pixel dwell time. Finally, we compare the performances of two widespread general algorithms, that is, singular value decomposition and discrete wavelet transform, with a method, that is, singular spectrum analysis (SSA), which has been adapted for stimulated Raman scattering images. In order to validate our algorithms, in our investigations lipids droplets have been used and we demonstrate that the adapted SSA method provides an improvement in image denoising.