bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation of carboxymethyl cellulose (CMC) derived from palm fiber waste: Effect of ozone pretreatment on CMC properties
Authors: Pujokaroni Agustu Sholeh , Ichiura Hideaki
Published: May 2023

Carboxymethyl cellulose (CMC) was prepared using cellulose extracted from palm fiber (CPF). The effect of ozone pretreatment on the CMC properties degree of substitution (DS) and viscosity was investigated. After treatment of CPF with ozone, CMC was prepared by alkalization followed by etherification using sodium hydroxide (NaOH) and sodium monochloroacetic acid (NaMCA) in an alcoholic medium. The DS of CMC increased with increased ozone pretreatment time and with increased amounts of NaOH and NaMCA reagents. The CMC solubility increased with increasing DS. Therefore, the solubility increased with ozone pretreatment time. The favored treatment conditions were ozone pretreatment for 3 h, followed by the addition of 10 mL of 30% NaOH and 38.6 mM of NaMCA. Under these conditions, the DS, purity, and solubility were 1.05, 79.6%, and 94.6%, respectively. The viscosity of CMC prepared using cellulose treated with ozone decreased with increasing ozone pretreatment time, which was caused by the reduced degree of polymerization. Therefore, use of ozone pretreatment for CMC preparation is an effective method for controlling CMC properties.
Advances in the mTOR signaling pathway and its inhibitor rapamycin in epilepsy
Authors: Zhao Wei , Xie Cong , Zhang Xu , Liu Ju , Liu Jinzhi , Xia Zhangyong
Published: May 2023

Introduction

Epilepsy is one of the most common and serious brain syndromes and has adverse consequences on a patient's neurobiological, cognitive, psychological, and social wellbeing, thereby threatening their quality of life. Some patients with epilepsy experience poor treatment effects due to the unclear pathophysiological mechanisms of the syndrome. Dysregulation of the mammalian target of the rapamycin (mTOR) pathway is thought to play an important role in the onset and progression of some epilepsies.

Methods

This review summarizes the role of the mTOR signaling pathway in the pathogenesis of epilepsy and the prospects for the use of mTOR inhibitors.

Results

The mTOR pathway functions as a vital mediator in epilepsy development through diverse mechanisms, indicating that the it has great potential as an effective target for epilepsy therapy. The excessive activation of mTOR signaling pathway leads to structural changes in neurons, inhibits autophagy, exacerbates neuron damage, affects mossy fiber sprouting, enhances neuronal excitability, increases neuroinflammation, and is closely associated with tau upregulation in epilepsy. A growing number of studies have demonstrated that mTOR inhibitors exhibit significant antiepileptic effects in both clinical applications and animal models. Specifically, rapamycin, a specific inhibitor of TOR, reduces the intensity and frequency of seizures. Clinical studies in patients with tuberous sclerosis complex have shown that rapamycin has the function of reducing seizures and improving this disease. Everolimus, a chemically modified derivative of rapamycin, has been approved as an added treatment to other antiepileptic medicines. Further explorations are needed to evaluate the therapeutic efficacy and application value of mTOR inhibitors in epilepsy.

Conclusions

Targeting the mTOR signaling pathway provides a promising prospect for the treatment of epilepsy.
Automatic assessment of object oriented programming assignments with unit testing in Python and a real case assignment
Authors: Climent Laura , Arbelaez Alejandro
Published: May 2023

In this paper, we focus on developing automatic assessment (AA) for a topic that has some difficulties in its practical assessment: object oriented programming (OOP). For evaluating that the OOP principles have been correctly applied to a real application, we use unit testing. In this paper, we focus on prioritizing that the students understand and apply correctly complex OOP principles and that they design properly the classes (including their relationships). In addition, we focus on the Python programming language rather than the typical previous works' focus in this area. Thus, we present a real case study of a practical assignment, in which the students have to implement characters for a video game. This assignment has the particularities and advantages that it is incremental and that it applies all four OOP principles within a single assignment. We also present its solution with the UML class diagram description. Furthermore, we provide unit testing for this case study and give general advice for generalizing the unit tests to other real case scenarios. Finally, we corroborate the effectiveness of our approach with positive student evaluations.
Transient downregulation of NR4A1 leads to impaired osteoblast differentiation through the TGF‐ß pathway, and Elesclomol (STA‐4783) rescues this phenotype
Authors: Muthurangan Manikandan , Elsafadi Mona , Siyal Abdulaziz , Kaimkhani Zahid Ali , Umrani Arbila , AlMuraikhi Nihal A. , Alfayez Musaad , Abdelhady Essam Eldin , Alqahtani Hamad , Basavarajappa Santhosh , Aboul‐Soud Mourad A. M. , Mahmood Amer
Published: May 2023

Bone formation is regulated by numerous factors, such as transcription factors, cytokines, and extracellular matrix molecules. Human hormone nuclear receptors (hHNR) are a family of ligand‐regulated transcription factors that are activated by steroid hormones, such as estrogen and progesterone, and various lipid‐soluble signals, including retinoic acid, oxysterols, and thyroid hormone. We found that an hHNR called NR4A1 was the most highly expressed after human MSC differentiation into osteoblasts by whole‐genome microarray. NR4A1 knockout decreased the osteoblastic differentiation of hMSCs in terms of ALPL expression and key marker gene expression. Whole‐genome microarray analysis further confirmed the decrease in key pathways when we knocked down NR4A1. Further studies with small molecule activators identified a novel molecule called Elesclomol (STA‐4783), which could activate and enhance osteoblast differentiation. Elesclomol activation of hMSCs also induced the gene expression of NR4A1 and rescued the phenotype of NR4A1 KD. In addition, Elesclomol activated the TGF‐ß pathway by regulating key marker genes. In conclusion, we first identified the role of NR4A1 in osteoblast differentiation and that Elesclomol is a positive regulator of NR4A1 through activation of the TGF‐ß signalling pathway.
Are weeds a concern when dredged ditch sediments are applied to agricultural fields?
Authors: Simmons Mathew D. , Witter Jonathan D. , Voltz Daniel C. , Haden Van Ryan , Lindsey Alexander J.
Published: May 2023

Core Ideas

Dredging is a common maintenance practice in agricultural ditches and spoil management is a challenge for farmers.

Farmers are concerned that application of sediments to fields poses a risk for redistribution of weed seed.

Weeds germinated from ditch sediments in this study are controlled by commonly used herbicides.
Substitution Effects on the Photophysical and Photoredox Properties of Tetraaza[7]helicenes
Authors: Rocker Johannes , Dresel Johannes A. , Krieger Leonie A. , Eckhardt Paul , Ortuño Ana M. , Kitzmann Winald R. , Clever Guido H. , Heinze Katja , Opatz Till
Published: May 2023

A series of substituted derivatives of tetraaza[7]helicenes were synthesized and the influence of the substitution on their photophysical and photoredox‐catalytic properties was studied. The combination of their high fluorescence quantum yields of up to 0.65 and their circularly polarized luminescence (CPL) activity results in CPL brightness values (BCPL) that are among the highest recorded for [7]helicenes so far. A sulfonylation/hetarylation reaction using cyanopyridines as substrates for photoinduced electron transfer (PET) from the excited helicenes was conducted to test for viability in photoredox catalysis. DFT calculations predict the introduction of electron withdrawing substituents to yield more oxidizing catalysts.
ACHEMA: Impulsgeberin der Prozessindustrie
Authors: Mathes Björn
Published: May 2023

No abstract.
Computational fluid dynamics based Taguchi analysis on shear stress in microfluidic cerebrovascular channels
Authors: Garud Kunal Sandip , Jeong Sehoon , Lee Moo‐Yeon
Published: May 2023

The cerebrovascular blood vessels feed necessary agents such as oxygen, glucose, and so forth. to the brain which maintains the smooth functioning of the human body. However, the blood–brain barrier as a vascular border restricts the entry of drugs that can be necessary for the treatment of neurological disorders. The fluid shear stress in the cerebrovascular blood vessels may regulate the drug delivery in the interface between the cerebrovascular blood vessels and the brain. The intensity of influence by various factors that affects the shear stress in the cerebrovascular blood vessels is scarcely addressed in the present study. A hybrid approach of computational fluid dynamics and Taguchi analysis is proposed to evaluate the influence of various geometrical and operating factors on the shear stress in the microfluidic cerebrovascular channel. Furthermore, the non‐Newtonian behavior of blood flow is considered to evaluate the shear stress in the microfluidic cerebrovascular channel. The Newtonian and six non‐Newtonian fluids models of Carreau, Carreau–Yasuda, Casson, Cross, Ostwald–de Waele, and Herschel–Bulkley are numerically tested under various conditions of the flow rate, width, and height of the channel to find the viscosity influence on the shear stress. The Taguchi analysis consisting of range and variance analyses is applied to the L16 orthogonal array to evaluate the effect of various factors on shear stress in terms of influence order, range, F value, and percentage contribution. The parameters for the considered six non‐Newtonian fluid models are proposed to accurately map the viscosity behavior with shear strain compared to the actual blood flow behavior. The Newtonian, Carreau, and Carreau–Yasuda non‐Newtonian fluid models are found accurately with maximum errors between the experimental and numerical shear stress results as 2.17%, 1.30%, and 1.48%, respectively. The shear stress decreases with an increase in the width and height of the channel and a decrease in the viscosity for all flow rates. The porosity is evaluated as a highly influential factor followed by the flow rate, width, and height of the channel in decreasing order based on their effects on the shear stress. The modified shear stress equation is proposed with an accuracy of 0.96 by integrating the effect of porosity in addition to width, height, flow rate, and viscosity. The in‐vitro microfluidic cerebrovascular model could be designed and manufactured based on the proposed results on influence order, F value, and percentage contribution of various factors in direction of achieving the in‐vivo level shear stress.
Breeding cereal rye (Secale cereale) for quality traits
Authors: Brzozowski Lauren J. , Szuleta Elżbieta , Phillips Timothy D. , Van Sanford David A. , Clark Anthony J.
Published: May 2023

Cereal rye (Secale cereale) is a multi‐purpose crop, harvested for grain (for food, feed, and other products) as well as used as a forage or cover crop. The functionality of rye across these spheres is due to its abiotic and biotic stress tolerance and unique phytochemical composition. In this review, we focus on the current state and prospects of breeding rye for quality traits, where we define quality traits as grain, feed, or forage quality. Rye grain for human consumption has numerous healthful compounds, notably high dietary fiber content in grain and unique flavors that contribute to the signature properties of rye baked products and distilled spirits. As a forage, rye is useful in marginal environments and has high quality, including high crude protein, and is thus valuable for livestock production. While yield remains a major focus of breeding efforts, due to recent improvements in rye genomic and phenotypic resources, there are now opportunities for increased attention on breeding high‐quality ryes for multiple end uses. Through genetic improvement of quality traits, cereal rye has the potential to expand and serve multiple markets as a climate‐resilient crop.
C1q/TNF‐related protein 4 mediates proliferation and migration of vascular smooth muscle cells during vascular remodelling
Authors: Liu Jingying , Long Xingbo , Li Hexin , Yan Qiuxia , Wang Lu , Qin Ziyu , Zhang Hong
Published: May 2023

Background

Vascular remodelling is an essential pathophysiological state in many circulatory diseases. Abnormal vascular smooth muscle cell (VSMC) behaviour leads to neointimal formation and may eventually results in major adverse cardiovascular events. The C1q/TNF‐related protein (C1QTNF) family is closely associated with cardiovascular disease. Notably, C1QTNF4 has unique two C1q domains. However, the role of C1QTNF4 in vascular diseases remains unclear.

Methods

C1QTNF4 expression was detected in human serum and artery tissues using ELISA and multiplex immunofluorescence (mIF) staining. Scratch assay, transwell assay and confocal microscopy were used to investigate C1QTNF4 effects on VSMC migration. EdU incorporation, MTT assay and cell counting experiment revealed C1QTNF4 effects on VSMC proliferation. C1QTNF4‐transgenic, C1QTNF4−/− and AAV9‐mediated VSMC‐specific C1QTNF4 restoration C1QTNF4−/‐ mouse and rat disease models were generated. RNA‐seq, quantitative real‐time PCR, western blot, mIF, proliferation and migration assays were used to investigate the phenotypic characteristics and underlying mechanisms.

Results

Serum C1QTNF4 levels were decreased in patients with arterial stenosis. C1QTNF4 shows colocalisation with VSMC in human renal arteries. In vitro, C1QTNF4 inhibits VSMC proliferation and migration and alters VSMC phenotype. In vivo, an adenovirus‐infected rat balloon injury model, C1QTNF4‐transgenic and C1QTNF4−/− mouse wire‐injury models with or without VSMC‐specific C1QTNF4 restoration were established to mimic the VSMC repair and remodelling. The results show that C1QTNF4 decreases intimal hyperplasia. Especially, we displayed the rescue effect of C1QTNF4 in vascular remodelling using AAV vectors. Next, transcriptome analysis of artery tissue identified the potential mechanism. In vitro and in vivo experiments confirm that C1QTNF4 ameliorates neointimal formation and maintains vascular morphology by downregulating the FAK/PI3K/AKT pathway.

Conclusions

Our study demonstrated that C1QTNF4 is a novel inhibitor of VSMC proliferation and migration that acts by downregulating the FAK/PI3K/AKT pathway, thus protecting blood vessels from abnormal neointima formation. These results provide new insights into promising potent treatments for vascular stenosis diseases.
Application of habitat association models across regions: Useful explanatory power retained in wetland bird case study
Authors: Elliott Lisa H. , Bracey Annie M. , Niemi Gerald J. , Johnson Douglas H. , Gehring Thomas M. , Gnass Giese Erin E. , Fiorino Giuseppe E. , Howe Robert W. , Lawrence Gregory J. , Norment Christopher J. , Tozer Douglas C. , Igl Lawrence D.
Published: May 2023

Species often exhibit regionally specific habitat associations, so habitat association models developed in one region might not be accurate or even appropriate for other regions. Three programs to survey wetland‐breeding birds covering (respectively) Great Lakes coastal wetlands, inland Great Lakes wetlands, and the Prairie Pothole Region offer an opportunity to test whether regionally specific models of habitat use by wetland‐obligate breeding birds are transferrable across regions. We first developed independent, regional population density models for four species of wetland‐obligate birds: Pied‐billed Grebe (Podilymbus podiceps), Virginia Rail (Rallus limicola), Sora (Porzana carolina), and American Bittern (Botaurus lentiginosus). We then used adjusted pseudo‐R2 values to compare the amount of variation explained by each model when applied to data collected in each of the three regions. Although certain habitat characteristics, such as emergent vegetation and wetland area, were consistently important across regions, models for each species differed by region—both in variables selected for inclusion and often in the directionality of relationships for common variables—indicating that habitat associations for these species are regionally specific. When we applied a model developed in one region to data collected in another region, we found that explanatory power was reduced in most (71%) models. Therefore, we suggest that ecological analyses should emphasize regionally specific habitat association models whenever possible. Nonetheless, models created from inland Great Lakes wetland data had higher median explanatory power when applied to other regions, and the amount of explanatory power lost by other transferred models was relatively small. Thus, while regionally specific habitat association models are preferable, in the absence of reliable regional data, habitat association models developed in one region may be applied to another region, but the results need to be cautiously interpreted. Additionally, we found that median explanatory power was higher when local‐scale habitat characteristics were included in the models, indicating that regionally specific models should ideally be based on a combination of local‐ and landscape‐scale habitat characteristics. Conservation practitioners can leverage such regionally specific models and associated monitoring data to help prioritize areas for management activities that contribute to regional conservation efforts.
Managing for ecological resilience of pinyon–juniper ecosystems during an era of woodland contraction
Authors: Redmond Miranda D. , Urza Alexandra K. , Weisberg Peter J.
Published: May 2023

Dryland woodland ecosystems worldwide have experienced widespread drought‐ and heat‐related tree mortality events coupled with extreme wildfire behavior. In contrast to other forest types where the emphasis has been on the silvicultural enhancement of ecosystem resilience and restoration of structural heterogeneity, limited frameworks are available for management to improve drought resilience in semiarid woodlands. This challenge is especially acute in pinyon–juniper woodlands, a dominant vegetation type across western North America that has experienced extensive tree die‐off over the past several decades while simultaneously undergoing expansion in portions of its range. In this paper, we describe the critical and urgent need to manage for future drought resilience in these highly vulnerable ecosystems and synthesize the current state of knowledge on how to enhance woodland resilience to drought coupled with high temperatures and associated disturbances. We present a landscape prioritization framework for guiding management goals and practices that requires prioritization of efforts based on the need for action and the probability of a positive outcome. Four guiding factors include historical woodland structure and drivers of long‐term landscape change, current vegetation structure and composition, future climate suitability, and habitat and resource value. In summarizing the strength of evidence supporting our recommendations, we identify critical knowledge gaps and highlight the importance of adaptive management strategies that reflect current uncertainties. This will ultimately allow for improved management of diverse semiarid woodland ecosystems that are undergoing substantial changes due to past and present land use, biological invasions, and climate change.
Writing statistical methods for ecologists
Authors: Davis Amy J. , Kay Shannon
Published: May 2023

TheMethodssection is a key component of any ecology research publication containing detailed information on how the data were collected and analyzed. However, descriptions of which statistical methods were used and how they were applied can substantially vary and may not provide enough information for the analyses to be reproducible. Computational and statistical programming advances have allowed ecological researchers without a strong statistical or mathematical background to access and use increasingly complex statistical methods. Thus, statistical methods are written by and need to be accessible to researchers across a range of quantitative expertise. Poorly writtenMethodssections can incorrectly inflate the strength of or call into question the results of an analysis. Although there are resources available, we have not found one that is specific to writing statistical methods, includes all the elements we discuss, and is targeted for ecologists. Here we provide guidelines for ecological researchers when writing statistical methods and review frequent errors made inStatistical Methodssections. We highlight some common dos and don'ts when writingStatistical Methodssections and present a simple checklist to help guide authors with their writing to ensure reproducibility. We illustrate the use of this guidance with two examples.
Synthesis, characterization of cross‐linked poly(ethylene glycol dimethacrylate‐methyl methacrylate‐N‐(1‐phenylethyl) acrylamide) copolymer and removal of copper(II), cobalt(II) ions from aqueous solutions via this copolymer
Authors: Canpolat Mutlu , Topal Giray
Published: May 2023

This study investigates the synthesis and evaluation of a new polymeric adsorbent for adsorbing Cu2+ and Co2+ ions from aqueous solutions. In this study, R‐(+)‐methylbenzylamine and acryloyl chloride were used to synthesize N‐(1‐phenylethyl)‐acrylamide (PEA) monomer, and the synthesized PEA was characterized by FTIR, 1H‐NMR and 13C‐NMR. Then, using PEA, ethylene glycol dimethacrylate (EGDMA) and methyl methacrylate (MMA) monomers by radical polymerization reaction, cross‐linked poly(ethylene glycol dimethacrylate‐methyl methacrylate‐N‐(1‐phenylethyl)acrylamide) (poly(EGDMA‐co‐ MMA‐co‐PEA) copolymer was obtained. FTIR, solid‐NMR, and elemental analysis methods were used to characterize the poly(EGDMA‐co‐MMA‐co‐PEA) obtained. Poly(EGDMA‐co‐MMA)‐co‐PEA) copolymer was used as an adsorbent in the final stage of the study to remove copper (Cu2+) and cobalt (Co2+) ions from aqueous solutions. The study examined the effects of various variables including contact time, initial metal ion concentration, and pH on adsorption efficiency. The initial concentration, contact time, and solution pH that were found to be most effective for Cu2+ ion removal were 1000 mg/L, 20 min, and 6, respectively. The ideal working parameters for Co2+ removal were determined to be an initial concentration of 1000 mg/L, a contact period of 50 min, and a solution with a pH of 6. While the adsorption capacity of Cu2+ was 185.44 mg/g at 25°C, the adsorption capacity of Co2+ was 123.76 mg/g under the same conditions. The kinetic data were best described by the theoretical adsorption capacity, which was close to the experimentally determined value for the adsorption of Cu2+ and Co2+ ions, and the pseudo‐second‐order with the highest regression coefficient.
Thermal and combustion characteristics of honge, jatropha, and honge‐jatropha mixed biodiesels
Authors: Atgur Vinay , Manavendra G. , Rao B. Nageswara , Veza Ibham , Fattah I. M. Rizwanul
Published: May 2023

Thermal characteristics of biodiesels are useful in system design, modeling, and operation. Such investigations are extensively being carried out in combustors, engine, and process industries. This article examines the thermal characteristics of jatropha (Jatropha curcas), honge (Pongamia pinnata), and their equal mixing from thermogravitometry and differential scanning calorimetry (TG‐DSC) curves for the specific 10°C/min heating rate under atmospheric air. Fuel properties are measured following ASTM standards to compare with diesel properties. Each experiment was repeated three times, and the properties showed insignificant scatter. The average properties of the repeated tests are presented. Two phases of decomposition were observed for diesel, whereas three (viz., devolatilization of aqueous fractions, combustion of methyl esters, and combustion of carbonaceous residues) in biodiesels. Jatropha oil methyl ester (JOME) is thermally stable compared to honge oil methyl ester (HOME). Mixed biodiesel (JOME+HOME) is prone to oxidation due to the high content of oleic and linoleic acids. Recorded onset and offset temperatures of mixed biodiesel are low compared to pure biodiesel. Mixed biodiesel exhibited high volatility resembling diesel characteristics. It exhibited an enthalpy of 240 J/g, whereas the enthalpy of diesel, jatropha, and honge exhibited enthalpies of 130, 321, and 570 J/g, respectively. The combustion index (S) of diesel, jatropha, honge, and mixed biodiesel was 41.6, 82.8, 77.74, and 64.6, respectively. Mixed biodiesel reduces the intensity of combustion (Hf), promising better combustion characteristics. Thus, mixed biodiesel shows the potential of an efficient alternative energy source.
Chemogenetic modulation of astrocytes and microglia: State‐of‐the‐art and implications in neuroscience
Authors: Bossuyt Jo , Van Den Herrewegen Yana , Nestor Liam , Buckinx An , De Bundel Dimitri , Smolders Ilse
Published: May 2023

Insights into the role astrocytes and microglia play in normal and diseased brain functioning has expanded drastically over the last decade. Recently, chemogenetic tools have emerged as cutting‐edge techniques, allowing targeted and spatiotemporal precise manipulation of a specific glial cell type. As a result, significant advances in astrocyte and microglial cell function have been made, showing how glial cells can intervene in central nervous system (CNS) functions such as cognition, reward and feeding behavior in addition to their established contribution in brain diseases, pain, and CNS inflammation. Here, we discuss the latest insights in glial functions in health and disease that have been made through the application of chemogenetics. We will focus on the manipulation of intracellular signaling pathways induced by activation of the designer receptors exclusively activated by designer drugs (DREADDs) in astrocytes and microglia. We will also elaborate on some of the potential pitfalls and the translational potential of the DREADD technology.
Adequate enrichment of extracellular vesicles in laboratory medicine
Authors: Zhang Limin , Ma Wencui , Gan Xinyi , Chen Wanyu , Guo Jiahui , Cui Yizhi , Wang Tong
Published: May 2023

Extracellular vesicles (EVs) and their clinical applications have been recognized as one of the most fast‐growing and promising fields. Numerous groups including us have expressed their concerns on the idea of isolating “pure” EVs for different purposes, as there are no specific markers to date that can examine the exact EV purity. Typically, major instrument need and EV yielding loss are primary compensations of getting EVs with higher purity. As such, especially in biomarker‐based clinical tests, ceaseless efforts for obtaining more pure EV are worth of discussion. We here propose alternative philosophy to tone down the importance of purity, but to emphasize the significance in clinical laboratory medicine to measure EVs obtained by well‐controlled isolation methods. As a result, EVs are enriched to the adequate degree to meet certain clinical applications such as disease diagnosis and/or prognosis. In this review, we will justify the adequate enrichment rationale with advances of EV definitions, markers and contaminants, EV isolation methods, as well as the conclusions acquired from clinical research using less pure but ease‐to‐operate EV isolation methods.
Effects of collagen, chitosan and mixture on fibroblast responses and angiogenic activities in 2D and 3D in vitro models
Authors: Binlateh Thunwa , Hutamekalin Pilaiwanwadee , Yongsawatdigul Jirawat , Yamabhai Montarop , Jitprasertwong Paiboon
Published: May 2023

Despite accumulating evidences have demonstrated the potential of collagen and chitosan on tissue repair, it remains unclear on their combination effects. Here, we examined the regenerative effects of single collagen, chitosan and their mixture on fibroblasts and endothelial cells at cellular levels. The results showed that fibroblast responses, as indicated by high proliferative rate, increased spheroid diameter and migrated area existing from spheroid edge, and decreased wound area, were significantly promoted by either collagen or chitosan stimulation. Similarly, both collagen and chitosan resulted in increased endothelial cell proliferation and migration with accelerated tube‐like network formation and upregulated VE‐cadherin expression, although collagen strongly provided this effect. While the 1:1 mixture (100:100 μg/mL of chitosan to collagen) treatment caused a reduction in fibroblast viability, the lower ratio of chitosan (1:10 mixture; 10:100 μg/mL) did not produce any impact on both fibroblast and endothelial cell viabilities. The 1:10 mixture also significantly enhanced the additional effects on fibroblast responses and angiogenic activities as shown by higher endothelial growth, proliferation and migration with accelerated capillary‐like network formation than those treated with the single substance. Further investigation of signaling proteins found that collagen significantly increased expressions of p‐Fak, p‐Akt and Cdk5 whereas chitosan upregulated p‐Fak and Cdk5 expressions. Comparing to the single treatments, p‐Fak, p‐Akt and Cdk5 were higher expressed in the 1:10 mixture. These observations indicate that proper collagen‐chitosan mixture provides the combination effects on fibroblast responses and angiogenic activities when a high concentration of collagen is used, possibly through Fak/Akt and Cdk5 signaling pathways. Therefore, this study helps to define the clinical use of collagen and chitosan as promising biomaterials for tissue repair.
Evaluating the experiences and impact of the Health Access for Refugees (HARP) project on peer volunteers in Northern England
Authors: Balaam Marie‐Clare , Haith‐Cooper Melanie , Mathew Dinah , McCarthy Rose
Published: May 2023

Community‐based peer volunteer interventions are increasingly used with people who are asylum seekers and refugees accessing health services. There is a dearth of evidence evaluating the benefits of volunteering for asylum seeking or refugee volunteers. Volunteers may have poor mental health and feel socially isolated due to their experiences as refugees and asylum seekers and may struggle or be unable to obtain paid employment. Volunteering in other contexts has been found to be beneficial to the health and well‐being of the volunteer. This paper reports on an aspect of a wider study evaluating the community‐based Health Access for Refugees Project, with the aim of exploring the impact of volunteering on the health and well‐being of the peer (asylum seeker or refugee) volunteer. In 2020, we conducted qualitative semistructured interviews by phone with 15 volunteers who were asylum seekers or refugees. The interviews were audio recorded, data were transcribed verbatim and the data set was thematically analysed. We found that the positive relationships which developed and the training received through volunteering boosted volunteers' mental well‐being. They felt motivated and confident in helping others, felt a sense of belonging and this reduced their social isolation. They also believed they benefited personally, helping their access to health services, and preparing them for future education, training or a career. In light of the beneficial nature of volunteering identified in this study, establishing more volunteering opportunities for this population and other marginalised groups with poor mental health is recommended. However, more research is needed to assess both the long‐term impact of the role in terms of the peer volunteer's health and well‐being, and the societal benefit of people moving on, integrating and contributing to society.
Physical exercise attenuates age‐related muscle atrophy and exhibits anti‐ageing effects via the adiponectin receptor 1 signalling
Authors: Chen Yuan‐Li , Ma Yi‐Cheng , Tang Jie , Zhang Dan , Zhao Qiu , Liu Jian‐Jun , Tang Hong‐Shu , Zhang Jin‐Yu , He Guang‐Hui , Zhong Chi‐Hui , Wu Yu‐Tong , Wen Heng‐Ruo , Ma Lan‐Qing , Zou Cheng‐Gang
Published: May 2023

Background

Although the adiponectin signalling exerts exercise‐mimicking effects, whether this pathway contributes to the anti‐ageing benefits of physical exercise has not been established yet.

Methods

Swim exercise training and wheel running were used to measure lifespan in the nematode Caenorhabditis elegans and skeletal muscle quality in mice, respectively. Muscle weight, muscle fibre cross‐sectional area (CSA) and myonuclei number were used to evaluate muscle mass. RNA sequencing (RNA‐Seq) analysis of skeletal muscle in exercised mice was used to study the underlying mechanisms. Western blot and immunofluorescence were performed to explore autophagy‐ and senescence‐related markers.

Results

The C. elegans adiponectin receptor PAQR‐1/AdipoR1, but not PAQR‐2/AdipoR2, was activated (3.55‐fold and 3.48‐fold increases in p‐AMPK on Days 1 and 6, respectively, P < 0.001), which was involved in lifespan extension in exercised worms. Exercise training increased skeletal muscle mass index (1.29‐fold, P < 0.01), muscle weight (1.75‐fold, P < 0.001), myonuclei number (1.33‐fold, P < 0.05), muscle fibre CSA (1.39‐fold, P < 0.05) and capillary abundance (2.19‐fold, P < 0.001 for capillary density; 1.58‐fold, P < 0.01 for capillary number) in aged mice. Physical exercise reduced protein (2.94‐fold, P < 0.001) and mRNA levels (1.70‐fold, P < 0.001) of p16INK4a, a marker for cellular senescence, in skeletal muscle of aged mice. These beneficial effects of exercise on skeletal muscle of mice were dependent on AdipoR1. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis for differentially expressed genes in skeletal muscle between exercised mice with and without AdipoR1 knockdown by RNA‐Seq analysis revealed that several KEGG pathways, such as ‘AMPK signalling pathway’ (P < 0.001), ‘FOXO signalling pathway’ (P < 0.001) and ‘autophagy’ (P < 0.001) were overrepresented. Knockdown of FoxO3a inhibited exercise‐mediated beneficial effects on skeletal muscle quality of mice by inhibiting autophagy/mitophagy (3.81‐fold reduction in LC3‐II protein, P < 0.001; 1.53‐fold reduction in BNIP3 protein, P < 0.05). Knockdown of daf‐16, the FoxO homologue in C. elegans, reduced autophagy (2.77‐fold and 2.06‐fold reduction in GFP::LGG‐1 puncta in seam cells and the intestine, respectively, P < 0.05) and blocked lifespan extension by exercise in worms.

Conclusions

Our findings provide insights into how the AdipoR1 pathway has an impact on the anti‐ageing benefits of exercise and implicate that activation of the AdipoR1 signalling may represent a potential therapeutic strategy for reducing age‐related loss of skeletal muscle.
Counselling behavioural interventions for HIV, STI and viral hepatitis among key populations: a systematic review of effectiveness, values and preferences, and cost studies
Authors: Kennedy Caitlin E. , Yeh Ping Teresa , Verster Annette , Luhmann Niklas , Konath Nabeel Mangadan , Mello Maeve Brito de , Baggaley Rachel , Macdonald Virginia
Published: May 2023

Introduction

Key populations (sex workers, men who have sex with men, people who inject drugs, people in prisons and other closed settings, and trans and gender diverse individuals) are disproportionately affected by HIV, sexually transmitted infections (STIs) and viral hepatitis (VH). Counselling behavioural interventions are widely used, but their impact on HIV/STI/VH acquisition is unclear.

Methods

To inform World Health Organization guidelines, we conducted a systematic review and meta‐analysis of effectiveness, values and preferences, and cost studies about counselling behavioural interventions with key populations. We searched CINAHL, PsycINFO, PubMed and EMBASE for studies published between January 2010 and December 2022; screened abstracts; and extracted data in duplicate. The effectiveness review included randomized controlled trials (RCTs) with HIV/STI/VH incidence outcomes; secondary review outcomes of unprotected sex, needle/syringe sharing and mortality were captured if studies also included primary review outcomes. We assessed the risk of bias using the Cochrane Collaboration tool, generated pooled risk ratios through random effects meta‐analysis and summarized findings in GRADE evidence profiles. Values and preferences and cost data were summarized descriptively.

Results

We identified nine effectiveness, two values and preferences, and two cost articles. Meta‐analysis of six RCTs showed no statistically significant effect of counselling behavioural interventions on HIV incidence (1280 participants; combined risk ratio [RR]: 0.70, 95% confidence interval [CI]: 0.41–1.20) or STI incidence (3783 participants; RR: 0.99; 95% CI: 0.74–1.31). One RCT with 139 participants showed possible effects on hepatitis C virus incidence. There was no effect on secondary review outcomes of unprotected (condomless) sex (seven RCTs; 1811 participants; RR: 0.82, 95% CI: 0.66–1.02) and needle/syringe sharing (two RCTs; 564 participants; RR 0.72; 95% CI: 0.32–1.63). There was moderate certainty in the lack of effect across outcomes. Two values and preferences studies found that participants liked specific counselling behavioural interventions. Two cost studies found reasonable intervention costs.

Discussion

Evidence was limited and mostly on HIV, but showed no effect of counselling behavioural interventions on HIV/VH/STI incidence among key populations.

Conclusions

While there may be other benefits, the choice to provide counselling behavioural interventions for key populations should be made with an understanding of the potential limitations on incidence outcomes.
Preferences and acceptability for long‐acting PrEP agents among pregnant and postpartum women with experience using daily oral PrEP in South Africa and Kenya
Authors: Wara Nafisa J. , Mvududu Rufaro , Marwa Mary M. , Gómez Laurén , Mashele Nyiko , Orrell Catherine , Moucheraud Corrina , Kinuthia John , John‐Stewart Grace , Myer Landon , Hoffman Risa , Pintye Jillian , Davey Dvora L. Joseph
Published: May 2023

Introduction

Long‐acting pre‐exposure prophylaxis (PrEP) options could overcome barriers to oral PrEP persistence during pregnancy and postpartum. We evaluated long‐acting PrEP preferences among oral PrEP‐experienced pregnant and postpartum women in South Africa and Kenya, countries with high PrEP coverage with pending regulatory approvals for long‐acting injectable cabotegravir and the dapivirine vaginal ring (approved in South Africa, under review in Kenya).

Methods

From September 2021 to February 2022, we surveyed pregnant and postpartum women enrolled in oral PrEP studies in South Africa and Kenya. We evaluated oral PrEP attitudes and preferences for long‐acting PrEP methods in multivariable logistic regression models adjusting for maternal age and country.

Results

We surveyed 190 women in South Africa (67% postpartum; median age 27 years [IQR = 22–32]) and 204 women in Kenya (79% postpartum; median age 29 years [IQR = 25–33]). Seventy‐five percent of participants reported oral PrEP use within the last 30 days. Overall, forty‐nine percent of participants reported negative oral PrEP attributes, including side effects (21% South Africa, 30% Kenya) and pill burden (20% South Africa, 25% Kenya). Preferred PrEP attributes included long‐acting method, effectiveness, safety while pregnant and breastfeeding, and free medication. Most participants (75%, South Africa and Kenya) preferred a potential long‐acting injectable over oral PrEP, most frequently for a longer duration of effectiveness in South Africa (87% South Africa, 42% Kenya) versus discretion in Kenya (5% South Africa, 49% Kenya). Eighty‐seven percent of participants preferred oral PrEP over a potential long‐acting vaginal ring, mostly due to concern about possible discomfort with vaginal insertion (82% South Africa, 48% Kenya). Significant predictors of long‐acting PrEP preference included past use of injectable contraceptive (aOR = 2.48, 95% CI: 1.34, 4.57), disliking at least one oral PrEP attribute (aOR = 1.72, 95% CI: 1.05, 2.80) and preferring infrequent PrEP use (aOR = 1.58, 95% CI: 0.94, 2.65).

Conclusions

Oral PrEP‐experienced pregnant and postpartum women expressed a theoretical preference for long‐acting injectable PrEP over other modalities, demonstrating potential acceptability among a key population who must be at the forefront of injectable PrEP rollout. Reasons for PrEP preferences differed by country, emphasizing the importance of increasing context‐specific options and choice of PrEP modalities for pregnant and postpartum women.
Factors associated with mobile app‐based ordering of HIV self‐test kits among men who have sex with men in Atlanta, Detroit and New York City: an exploratory secondary analysis of a randomized control trial
Authors: Mancuso Noah , Mansergh Gordon , Stephenson Rob , Horvath Keith J. , Hirshfield Sabina , Bauermeister Jose A. , Chiasson Mary Ann , Downing Martin J. , Sullivan Patrick S.
Published: May 2023

Introduction

The United States Centers for Disease Control and Prevention currently recommends HIV screening at least annually among sexually active gay, bisexual and other men who have sex with men (MSM), but only half report being tested in the past year in the United States. As HIV self‐test kits are becoming more available around the United States via web and app‐based interventions, it is important to understand who is willing and able to order them. This analysis sought to better understand predictors of free HIV self‐test kit utilization among MSM in M‐cubed, an HIV prevention mobile app intervention trial in Atlanta, Detroit and New York City.

Methods

We conducted an exploratory secondary analysis of self‐report and in‐app data collected from the intervention arm of the M‐Cubed study from 24 January 2018 to 31 October 2019. Behavioural, demographic and other potential predictors of HIV self‐test ordering were identified from Social Cognitive Theoretical underpinnings of the app, and from the literature. Significant predictor variables in bivariate analyses were considered for inclusion in the empiric multivariable model. Demographic variables chosen a priori were then added to a final model estimating adjusted prevalence ratios (aPR).

Results

Over half of the 417 intervention participants ordered an HIV self‐test kit during the study. In bivariate analyses, ordering a kit was associated with HIV testing history, plans to get tested and reported likelihood of getting tested. In the final model, participants were more likely to order a kit if they reported plans to get tested in the next 3 months (aPR = 1.58, 95% CI: 1.18–2.11) or had not tested for HIV in the past 3 months (aPR = 1.38, 95% CI: 1.13–1.70). There was no difference in HIV self‐test kit ordering by income, race/ethnicity or age.

Conclusions

HIV testing is an important tool in ending the HIV epidemic and must be accessible and frequent for key populations. This study demonstrates the effectiveness of HIV self‐test kits in reaching populations with suboptimal testing rates and shows that self‐testing may supplement community‐based and clinical testing while helping overcome some of the structural barriers that limit access to annual HIV prevention services for MSM.
Poverty at a distance: Supply and demand side factors and the formation of civil society organizations in Iraq
Authors: Hamoudi Ali Bakir , Köppe Stephan , Winston Nessa
Published: May 2023

This paper contributes empirically to the international debate on the drivers for the formation of civil society organizations (CSOs) by testing three separate hypotheses: demand, supply and integration. To investigate this question, we analyse the CSO sector in Iraq, which transformed since 2003 from being implicitly banned to being a central pillar of poverty alleviation and social service provision with thousands of formally registered organizations. Using OLS regression analysis with district level and official register data, we examine the geographic distribution of CSOs in relation to poverty levels in Iraq. We find no significant confirmation for demand side drivers that social service providing CSOs form in high poverty districts. Instead, we find strong support for CSO formation in governorate administrative centres, which confirms supply‐side drivers of CSO development. However, we do find some support for a higher concentration of human rights‐based CSOs in high poverty areas. The findings raise important policy implications for the UN Sustainable Development Goal of no poverty in an Iraqi context and internationally, but also how to fund CSOs to meet the demands of the primary recipients.
IGF1 synthesis after CO2 fractional laser resurfacing (FLR): New insights in the treatment of scalp actinic keratoses
Authors: Trovato Emanuele , Fiorani Diletta , Cartocci Alessandra , Cinotti Elisa , Rubegni Pietro
Published: May 2023

Objectives

Actinic keratosis have a high risk of progression to a squamous cell carcinoma. Insulin‐like growth factor 1 and its receptor play a relevant role in restoring repair of ultraviolet‐induced cell damage. This pathway is reduced in patients older than 65 years. Ablative fractional laser resurfacing could normalize insulin‐like growth factor 1 (IGF‐1) secretion in elderly by recruiting new fibroblasts. The aim of the study is to evaluate restoration of IGF1 values by PCR in senescent fibroblasts after ablative fractional laser resurfacing.

Methods

We enrolled 30 male patients with multiple actinic keratosis on the scalp, equally divided into two mirror areas of up to 50 cm2, treating only the right one. We performed one skin biopsy for each area 30 days after treatment. Real‐time PCR in fibroblasts was performed to assess the change in IGF1. At baseline and after 6 months, in vivo reflectance confocal microscopy examination was performed in all patients.

Results

IGF1 values were increased in the treated side by about 60%. The right areas had fairly complete resolution of actinic keratosis at the last follow‐up visit after 6 months with no appearance of new lesions. The mean number of actinic keratosis in the right area was reduced by more than 75% at four‐ and six‐follow‐up visits compared to the left area. The improvement in the right area was also evidenced by lower values of the mean AKASI (actinic keratosis area and severity index) score. Reflectance confocal microscopy showed a reduction of keratinocytic disarray and scales after treatment.

Discussion

Taken together, all the clinical, laboratory, and in vivo results of our study allowed us to confirm that ablative fractional laser resurfacing is a valuable tool for the treatment of actinic keratosis and cancerization field, both for the management of clinically evident lesions and for preventing the occurrence of squamous cell carcinoma.
KRAS mutations upregulate Runx1 to promote occurrence of head and neck squamous cell carcinoma
Authors: Deng Miao , Guo Jiaxin , Ling Zihang , Zhang Chi , He Lihong , Fan Zhaona , Cheng Bin , Xia Juan
Published: May 2023

Gene mutations play an important role in head and neck squamous cell carcinoma (HNSCC) by not only promoting the occurrence and progression of HNSCC but also affecting sensitivity to treatment and prognosis. KRAS is one of the most frequently mutated oncogenes, which has been reported to have a mutation rate from 1.7% to 12.7% and may lead to poor prognosis in HNSCC, but its role remains unclear. Here, we found that the KRAS mutation can promote HNSCC generation through synergism with 4‐Nitroquinoline‐1‐Oxide(4NQO). Mechanistically, KRAS mutations can significantly upregulate Runx1 to promote oral epithelial cell proliferation and migration and inhibit apoptosis. Runx1 inhibitor Ro 5‐3335 can effectively inhibit KRAS‐mutated HNSCC progression both in vitro and in vivo. These findings suggest that the KRAS mutation plays an important role in HNSCC and that Runx1 may be a novel therapeutic target for KRAS‐mutated HNSCC.