bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of HPV-16 in Borderline Mucinous Cystic Neoplasm of Pancreas
Authors:   Department of Pathology, Princess Margaret Hospital, Hong Kong, China, Tong Tommy R. , Chan Anthony ,   Department of Pathology, Prince of Wales Hospital, Hong Kong, China, Lai Tak-wing ,   Department of Surgery, Princess Margaret Hospital, Hong Kong, China, Chan Olivia W. ,   Department of Pathology, Nethersole Hospital, Hong Kong, China, Lee Kam-cheong , TH Lo Stephen , Lung Rosanna , Li Jackson YW , Chow Tat-chong ,   Department of Pathology, Princess Margaret Hospital, Hong Kong, China;
Published: December 2023

Pancreatic mucinous cystic neoplasms (PMCN) predominantly affect women in the reproductive age, are located in the body and tail of the pancreas, and share morphological features with similar tumors of the ovary. We report the detection of human papillomavirus (HPV) using several different PCR protocols in a borderline PMCN from a female patient. Type-specific PCR demonstrated the HPV to be type 16. If confirmed by others, this group of neoplasms might become preventable by HPV vaccination.
Medial Expression of TNF-α and TNF Receptors Precedes the Development of Atherosclerotic Lesions in Apolipoprotein E/LDL Receptor Double Knockout Mice
Authors:   Department of Biomedical Laboratory Sciences, Malmo University, Sweden, Fredrikson Gunilla Nordin , Jovinge Stefan ,   Department of Cardiology, Lund University Hospital and Lund Stem Cell Center, Lund University, Niemann-Jonsson Audrey , Soderberg Ingrid , Lindholm Marie W , Nilsson Jan ,   Department of Clinical Sciences, Malmo University Hospital, Lund University
Published: December 2023

TNF-α is present in atherosclerotic lesions, activates endothelial adhesion molecule expression, stimulates the release of proinflammatory cytokines and matrix metalloproteinases and promotes smooth muscle cell proliferation and migration. Taken together these observations suggest that TNF-α may be functionally involved in early atherosclerosis development. To further evaluate this hypothesis we compared vascular TNF-α and TNF receptor expression in atherosclerosis-susceptible apoE-/-/LDL receptor-/- mice and control C57BL/6 mice. The aortas of 8 week old apoE-/-/LDLreceptor-/- mice displayed immunoreactivity for TNF-α as well as TNF p55 and p75 receptors (2.1 ± 1.6%, 5.6 ± 1.5% and 3.6 ± 1.3% of total media area, respectively), but did not have any detectable lesions. A marginal increase in TNF-α and TNF receptor immunoreactivity was observed at 12 weeks and atherosclerotic plaques were detected in 1 out of 5 animals. At 16 weeks TNF-α expression in the media was increased more than four-fold as compared with 8 week old mice, and atherosclerosis was widespread. TNF-α immunoreactivity was also observed in all plaques. In addition, at the same age a tendency towards increased TNF-α mRNA levels was detected in the double knockout mice compared to age-matched controls. A further increase in TNF-α and TNF receptor immunoreactivity as well as plaque size was observed at 20 weeks. With only a few exceptions, no TNF-α or TNF receptor immunoreactivity was detected in C57BL/6 control mice. These findings demonstrate that medial TNF-α and TNF receptor expression precedes lesion formation in apoE-/-/LDL receptor-/- mice.
An investigation on the solid dispersions of chlordiazepoxide
Authors:   Medway School of Pharmacy, the Universities of Kent and Greenwich, Central Ave., Chatham Maritime, ME4 4TB, Kent, UK, Nokhodchi Ali , Talari Roya ,   School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran, Valizadeh Hadi , Jalali Mohammad Barzegar ,   Drug Applied Research Center and School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
Published: December 2023

The aim of this study was to prepare solid dispersions of chlordiazepoxide techniques to improve its dissolution rate. To this end, three techniques namely, two solvent methods and co-grinding technique were used. Solid dispersions of chlordiazepoxide in polyvinylpyrrolidone (PVP), Eudragit E100, Mannitol and Sorbitol with two different ratios of drug to carrier (5:5 and 1:9) were prepared. These solid dispersions were evaluated using dissolution tester to monitor dissolution behaviour and Fourier-transform infrared spectroscopy to investigate interaction between the drug and carriers in solid dispersion samples. Solid dispersion of chlordiazepoxide with all three carriers (PVP, mannitol and eudragit E) prepared by solvent method showed considerable increase in the dissolution rate of chlordiazepoxide in comparison with physical mixture and pure drug at different pH values. According to the results of this investigation cogrinding technique yields solid dispersions with a less improved dissolution rate than does the solvent deposition technique. Infrared studies showed no interaction between chlordiazepoxide and carriers in solid dispersions in solid state.
Evidence for the Effects of Xanthohumol in Disrupting Angiogenic, but not Stable Vessels
Authors:   Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal, Soares Raquel , Negrao Rita , Incio Joao , Lopes Rui , Azevedo Isabel
Published: December 2023

Angiogenesis is a complex multistep process that comprises proliferation, migration, and anastomosis of endothelial cells, followed by stabilization of the newly formed vessel through the attachment of support cells. This process is imbalanced in a large number of disorders, including cardiovascular disease, diabetes and cancer. Evidence indicates that xanthohumol (XN), a prenylated chalcone present in beer, exerts anti-angiogenic properties. However, its precise effect within the angiogenic steps is not accurately established. The purpose of the present study was to examine which features of the angiogenic process can be disturbed by XN. Human umbilical vein endothelial cells (HUVEC) and human fetal aortic smooth muscle cells (SMC) were incubated with xanthohumol at 5 and 10 mM, and cell viability, apoptosis, invasion and capillary-like structures formation were examined. Treatment with 10 mM XN significantly decreased viability and invasion capacity and increased apoptosis in both cell types as assessed by MTT, double-chamber assay and TUNEL assay respectively. The two concentrations of XN further led to a significant reduction in the number of capillary-like structures, when HUVEC were cultured on growth factor reduced-Matrigel-coated plates. Interestingly, XN exhibited the opposite effect when HUVEC were co-cultured with SMC, leading to an increase in the number of cord structures. In addition, incubation of both types of cells with XN resulted in reduced activity of NFkB, a transcription factor implicated in these cell fates. Given the absence of adverse effects in mature vasculature by XN, these findings emphasize the potential use of XN against pathological situations where angiogenesis is stimulated.
Multiple Sclerosis and HERV-W/MSRV: A multicentric Study
Authors:   Institute of Clinical Neurology, University of Sassari, Viale San Pietro 10, 07100, Sassari, Italy, Sotgiu Stefano
Published: December 2023

We designed a large multicentric study to analyse the presence of MSRV particles in blood and CSF of a large cohort of patients and controls from different European areas. 149 MS patients and 153 neurological and healthy controls were selected from Sardinia, Spain, Northern-Italy and Sweden. To avoid biological and inter-assay variability MSRV was detected within a single laboratory through nested and real-time PCR assays specific for pol and env genes. MSRV detection in blood and CSF of MS patients and controls in populations of different ethnicity gave significant differences (p<0.05 compared to neurological controls and <0.001 compared to healthy controls). The presence and viral load of MSRV are significantly associated with MS as compared to neurological and healthy controls in all ethnic groups.
First steps in the development of a new measure of attitudes toward sexual offending against children
Authors: Nunes Kevin L. , Hawthorn Danielle M. L. , Bateman Emily R. , Griffith Amy L. , Fraser Julia M.
Published: December 2023

It is unclear whether existing measures of attitudes and cognitive distortions regarding sexual offending against children (SOC) reflect evaluative attitudes toward SOC (i.e., how negatively or positively one views SOC). The purpose of the current study was to take the first steps toward creating a self-report measure of evaluative attitudes toward SOC. We created 30 items and asked 157 incarcerated people in a sexual offense treatment program to complete them. We retained the 13 items that were the least positively skewed (i.e., lowest endorsement of the most negative response option) and non-redundant (i.e., not too highly correlated with other items) for inclusion in the new measure, which we called the Evaluative Attitudes Toward Sexual Offending Against Children (EASOC) Scale. As an initial test of the relevance of the EASOC Scale, we examined its association with SOC. Participants with SOC (n = 58) reported more positive evaluative attitudes on the EASOC Scale than did those without SOC (n = 22). This expected association is a necessary (but not sufficient) indication that the EASOC Scale may be relevant for predicting and explaining SOC. Future research using more rigorous methodology should build on our modest first steps to revisit item selection and test the validity and relevance of the EASOC Scale.
Research on the Solution-Focused Approach in 2022: A Scoping Review
Authors: Żak Andreea M , Pakrosnis Rytis , Kuminskaya Evgeniya
Published: December 2023

Following an initiative started in the late ’90s by Dr Alasdair Macdonald, the European Brief Therapy Association (EBTA) continues to maintain and update a list of references to research and other relevant publications on the solution-focused approach. The current scoping review from the EBTA Research Task Group members aimed to identify trends in the methodology and results emerging from the latest research of the solution-focused practices added to the list. A total of 58 research articles published in 2022 were identified and reviewed for main trends in sample, study, intervention characteristics, and the main findings. Several trends in each of these aspects emerged from the data during the process of scoping review. Along with the summary of the main trends, related issues and questions important for practitioners, researchers, and the whole solution-focused community are discussed in the article. Finally, recommendations for future research are put forward to aid in providing answers to remaining questions relevant to the establishment of the solution-focused approach as an evidence-based practice.
AN OVERVIEW OF THE PRIMARY HEALTHCARE SYSTEM IN NIGERIA
Authors: Dada Sholadoye
Published: December 2023

This paper describes the structure and operation of the primary healthcare system in Nigeria, the sequence of its evolution from inception to what is obtainable now and the effectiveness of the system. Prior to that, a detailed description of the WHO targets through its Alma-Ata declaration in 1978 was explained and evaluated in comparison with the Nigerian healthcare system. Emphasis was laid on the concept, principle and element of the primary healthcare system as well as the challenges and the current state of the system. In conclusion, Primary healthcare in Nigeria, particularly in rural areas, has come a long way, but more work is undoubtedly still needed to realize the objective of universal health now and in the future. Priority should be given to improving people's living conditions beyond the current poverty level in order to promote healthier living. Local governments, as well as all other levels of government, must increase their allocations to the health sector among other things.
Prediction of Innovation Capability: the Role of Mediation in the Relationship between Digital Transformation and Competitiveness with the PLS-SEM Model
Authors: Firmansyah Deri , Wahdiniwaty Rahma
Published: December 2023

The importance of happiness management This study explores the mediating role of innovation capabilities (IC) on the relationship of digital transformation (DT) and competitiveness (CP), by proposing model construction. Four research questions and four hypotheses were posed. The survey method was carried out by distributing research instruments to 98 respondents, the collected data was used to analyze the relationship between digital transformation, innovation ability and competitiveness, also used to test hypotheses. Evaluation of predictions through structural equation models with partial least squares-structural equation modeling (PLS-SEM). Research findings show that digital transformation directly has a significant positive effect on competitiveness. Digital transformation directly has a significant positive effect on competitiveness. Digital transformation has a significant positive effect on innovation capabilities. The innovation capability has a significant positive influence on competitiveness. Innovation capabilities are proven to have a mediating effect on the influence of digital transformation on competitiveness.
The impact of Households Fuel Wood Energy Consumption to Forest Resources: A Case Study Ruangwa District
Authors: Mchitika Z. J.
Published: December 2023

The purpose of this paper is to evaluate the effects of household fuel wood energy dependency on village trees in Ruangwa District. The study's specific
goals  were  to  identify  energy  sources  in  Ruangwa  District,  investigate  the
consequences of home energy dependency on trees in rural areas, and evaluate strategies to alleviate the effects of household energy dependency on forests. The study used a case study in southern Tanzania to examine the effects of household fuel wood energy dependency on forest resources. The study sample constituted
96 local forest resource stakeholders. Purposive and non-probability sampling techniques were employed in data collection.  Both   quantitative and qualitative
methodologies were used. Closed and open-ended questionnaires were used to
collect both primary and secondary data including relevant documents related to village forest resource production, sales patterns, and resource control. The study established that, charcoal and firewood were the primary sources of cooking energy. Also, lack of knowledge and household poverty had a significant impact on forest management and control. The study concluded that, poverty was the primary factor driving household reliance on charcoal and firewood compounded  by forest management  authorities restricting local communities from  extracting  essential  forest  products;  and  lack  of  education  on  the importance of conserving trees in the local environment. Recommended that, local  communities  should  be  educated  on  the  negative  fuel  wood  human activities to the environment specifically excessive tree cutting for fuel wood energy. Besides, villages around forest resources and forest management on authority should jointly draw regulations and supervision mechanisms sustainable use of forest resources and products.
Mutáció és eltűnés. A térbeliség kategóriájának útja a hartmanni rétegfelépítményben
Authors:   ELTE Filozófiatudományi Doktori Iskola, Beck Tamás
Published: December 2023

The primary aim of my paper is to show how the category of spatiality appears at different levels of the strata structure outlined by Nicolai Hartmann. As a starting point, Hartmann’s connection to the Cartesian tradition leads directly to the misunderstanding that manifests itself in the accusation of hypostasis. In order to dispel this misunderstanding, I examine whether we can attach greater importance to the boundary marking the beginning of life than to the boundary between the organic and spiritual layers of existence, which is characterized, among other things, by the disappearance of the category of spatiality and the increased dominance of nova. In order to clarify this, the distinction between organic and inorganic layers of existence inevitably needs to be clarified. Next, I explain that the appearance of life on the second stage of Hartmann’s construction is devoid of any vital tendencies, and I attempt to prove that, although Hartmann draws a sharp line between the second and third layers of existence, this caesura does not result in psychophysical dualism in his system. Then I will show that the category of spatiality is already distorted shortly before its disappearance, while the living organism comes into contact with its own environment. Of course, the indirect assertion of spatiality can also be detected in non-spatial layers of existence, but its direct manifestation has interdisciplinary implications, and it can also be connected with the method of phenomenology, which I must discuss in detail. Finally, I point to the ontological consequences of the disappearance of the category in question, making it clear that the Platonic conception of existence associated with spatiality is inadequate for grasping intangible beings. After a brief description of Heidegger’s attempt, I will point out that the successful integration of intellectual entities into reality is carried out precisely by Hartmann through the real time’s ability to unite.
Homologous Series of Chemical Compounds in Three-component Systems (Aa+ – Bb+ – Cc–) and (Zn2+ - Ge4+ - P3-) in Generalized Form
Authors: Undalov Yu K
Published: December 2023

For the first time, a method for calculating formulas of homologous series of chemical compounds of the systems (Aa+ – Bb+ – Cc–) and {Zn2+ – Ge4+ – P3–} in a generalized form is presented. The calculation is confirmed by the literature experimentally obtained compounds: thirteen compounds of the system (Na+ – Ti4+ – O2–), seven – systems (Li+ – Ti4+ – O2–), five – systems (K+ – V5+ – – O2–), eight – systems (Ba2+ – Cu2+ – O2–). Homological series in (Aa+ – Bb+ – Cc–) have the following generalized form: A{t – k·r + nr – r)bcBracC{t – k·r + nr)ab and AtbcB{r – k·t + nt – t}acC (r – k·t + nt)ab. In (Zn2+ – Ge4+ – P3–) systems for the m-group the formulas of homologous series, that develops towards Ge3P4, have the following generalized form: Zn6tGe(6r – 6kt + 6n – 6t)P(8r – 8kt + 8n) and for αm-homologous series – Zn6Ge3nP4(n + 1). A method for calculating formulas of homologous series of chemical compounds in a generalized form can be used for any system of chemical elements.
Roadmap for Renewable Energy Development
Authors: Penjiyev Ahmet Myradovich
Published: December 2023

The article examines the priorities and prospects of the road map for the development of renewable energy using the example of Turkmenistan. The main scientific conditions of the goal, objectives, principles of public policy, a heterogeneous class of renewable technologies, the main scientific conditions of the road map for sustainable development, the environmental aspect of climate change, mitigation potential, and costs are presented. The compiled roadmap for the use of renewable energy sources outlines the expected energy, economic, and environmental effects from the use of renewable energy technologies in remote areas from the centralized power line. The author believes that the outlined development roadmap for the use of renewable energy sources will become the basis for drawing up programs in other countries, depending on natural, climatic, and geographical conditions. Thus, the road map for the development of renewable energy sources, the use of local renewable energy resources, can reduce the need for fossil fuels in some cases by up to 80% and will significantly reduce the anthropogenic load on the environment. The introduction of renewable energy sources is one of the most relevant and promising for the development of the desert and the fight against desertification in the Karakum.
The Use of Clustering Model to Improve Poetry Writing Skills of SMP Negeri 4 Watampone, Bone Regency, Indonesia
Authors: Safar Muh. , Andi Srimularahamah  , Arif Rahman Aulia Jamnawi  , Fahri Akbar
Published: December 2023

This research aims to describe the improvement of writing skills of students in class VIII B SMP Negeri 4 Watampone, Bone Regency through the use of clustering model. This research was conducted by pre-observation in class VIII B. The writing skills of students of class VIII B SMP Negeri 4 Watampone are still low or lacking. The targets to be given action are students of class VIII B SMP Negeri 4 Watampone in 2022/2023 academic year. This research is classroom action research. The research procedure was carried out in 2 (two) cycles and each cycle had 3 meetings. Each cycle consists of four stages, namely: planning, action implementation, observation, and reflection. The techniques of data collection in this classroom action research are observation, documents, student assignments and tests. The data analysis was conducted using qualitative and quantitative techniques. The criteria for success of classroom action is the test of writing poetry using the clustering model. The use of clustering models in learning to write poetry can improve the quality of the process and students’ learning outcomes. It shows that there is an improvement in the completeness of the ability to write poetry from pre-cycle as many as 12 or 36.4%, cycle 1 as many as 21 or 63.6% and cycle 2 as many as 33 or 100%. Based on the improvement in student learning completeness in each cycle, the use of the clustering model needs to be applied to the learning of writing poetry of students in class VIII B SMP Negeri 4 Watampone, Bone Regency.
Online learning during COVID-19: Key challenges and suggestions to enhance effectiveness
Authors: Heng Kimkong , Sol Koemhong
Published: December 2023

The COVID-19 pandemic has wreaked havoc on every aspect of society. It has caused profound disruption to the education system as governments around the world have temporarily closed educational institutions to contain the spread of the coronavirus. Face-to-face classes have been canceled and moved online, bringing about the rise of online learning that has allowed learners to continue their education. The sudden transition from face-to-face to online learning has, however, posed numerous challenges for students, teachers, administrators, and education leaders. Drawing on previously published sources, this article first attempts to explain different terms used to describe online learning. It then discusses key challenges posed by the widespread adoption of online learning during the pandemic, followed by a discussion of suggestions made by different researchers to enhance the effectiveness of online learning. The article concludes with a summary of key challenges and suggestions and brief recommendations for the broader adoption of online and blended learning in the post-COVID-19 world.
Distributed Leadership in School: A Brief Review of the Literature
Authors: Sol Koemhong
Published: December 2023

Several forms of leadership are discussed in the literature and have been practiced within schools and across different school levels. Some of those include transformative leadership, strategic leadership, distributed leadership, and participative leadership, among others. While each form of leadership has its own strengths and weaknesses and is more or less applicable depending on organizational contexts, distributed leadership has risen as an alternative form of today’s school leadership. Unlike other forms of leadership, distributed leadership is primarily concerned with the interactive and interdependent practice of leadership rather than the roles and responsibilities of those who have a formally assigned leadership position. To better understand the concept of distributed leadership, this article first reviews some literature on the topic and then offers some recommendations for practice.
The events before the event
Authors: O'Boyle Neil
Published: December 2023

This article demonstrates how the concept of paratexts can be employed in the analysis of unfolding sports events. Drawing on the work of Jonathan Gray and Matt Hills, it reflects on the “extended presence” of sports events across media, space, and time – how mean- ing is created before, during, and after their apparent conclusion, and how their mediated “centres” appear to move in the process. By way of illustration, it examines a boxing event in early 2023 involving the popular British boxers Chris Eubank Jr. and Liam Smith; how- ever, it focuses on the events before the event – namely, the preceding press conference and weigh-in – and suggests that these “entryway events” were paratextually significant in shaping expectations and attitudes towards the “main event”. The article also demon- strates how sports events feed into wider processes of social inclusion and exclusion, often acting as lightning rods for public discussions of socio-political issues, such as race, class, gender, and (in this case) sexual orientation.
Building an Ideal Theatre
Authors: Saro Anneli
Published: December 2023

Throughout the course of theatre history, many actors and directors have dreamt about an ideal theatre. Many young European theatre makers in the twenty-first century have preferred working in their own groups with like-minded colleagues instead of joining big institutional theatres or have tried to revolutionize the institutions.Dwelling on theoretical arguments about the terms “ideal”, “idealism”, and “utopia” in theatre, the article investigates what are the ideals of contemporary theatre makers, which ideals/utopias are realizable in theatre practice and how. To answer these questions, the case study of Estonian theatre NO99 is used. In 2004, Tiit Ojasoo and Ene-Liis Semper became the leaders of the state funded theatre Vanalinnastuudio and tried to reorganize it into an ideal theatre. The article investigates what were the ideals of the theatre makers of the NO99, how their ideals were realized, which ideals endured, and which ones failed during the fourteen years. Finally, a discussion on the developments of theatre institutions in the twenty-first century will be presented.
Between Linguistic Geography and Structural Linguistics
Authors: Jensen Viggo Bank , Cigana Lorenzo
Published: December 2023

In this paper, we follow the development of Coseriu’s conceptual tools for variational linguistics during the 1950s. Our starting point is Pisani’s notion of “isogloss”, which Coseriu initially regarded as a core idea for his own approach and yet progressively abandoned in favour of the more structuralist-oriented notion of “functional language”, adopted in the wake of Louis Hjelmslev’s framework, through Leiv Flydal’s mediation. Finally, we speculate about the reasons and the implications of Coseriu’s failing to acknowledge Uriel Weinreich as an important source for variational linguistics.
The appropriation of oral/spoken French by L2 learners
Authors: Paternostro Roberto
Published: December 2023

The expressions ‘oral French’ and ‘spoken French’ are often used as equivalents. However, they have implications that are far from trivial, especially when it comes to teaching the French language. In this article, we will attempt to point out the nuances behind the expressions oral and spoken French, through reflections on the diamesic and the diaphasic variational dimensions. Secondly, we shall present the implications that this perspective may entail when it comes to the teaching of French as a foreign language (FLE). This research on the teaching of spoken French will also allow us to take into consideration some issues and challenges in relation to the implementation of a ‘didactics of spoken French’. The presentation of examples from the fieldwork research will enable us to dig further into these questions.
Le régime québécois d’assurance automobile
sans égard à la responsabilité
Authors: Belleau Claude
Published: December 2023

À l’heure où l’assurance automobile est en crise dans plusieurs provinces canadiennes,
le régime québécois se présente comme un modèle à suivre. Ce texte fait la
genèse du régime québécois. Il démontre aussi que, malgré la remise en question du
principe de l’assurance sans égard à la responsabilité, le régime étatique d’indemnisation
du préjudice corporel compense pleinement les pertes éprouvées dans des
accidents d’automobile par la très grande majorité des Québécois et que le régime
privé de réparation des dommages matériels suivant le système d’indemnisation
directe fondé sur la faute connaît une grande stabilité dont les automobilistes peuvent
se réjouir.
La citoyenneté empêchée ! Freins et leviers au droit de vote face au vieillissement et au handicap
Authors: Desjeux Cyril , Viriot Durandal Jean-Philippe , Virriat Yan
Published: December 2023

Dans la littérature scientifique, l’existence d’un «disability gap» et la diminution de la participation électorale à partir de 80 ans ont souvent été traitées de manière séparée. Parce que ces deux phénomènes ont été étudiés parallèlement, les auteurs de cet article proposent un regard croisé entre les domaines du handicap et du vieillissement sur la question de l’exercice de la citoyenneté avec un attention plus particulière sur l abstention. L’article invite en substance à l’observation des convergences et divergences des obstacles au vote qui se manifestent dans les parcours biographiques des personnes âgées et/ou en situation de handicap. Loin de proposer une lecture dichotomique du sujet, il interroge aussi le caractère parfois flou des catégories en envisageant notamment les cas spécifiques des personnes âgées en situation de handicap, ainsi que des personnes en situation de handicap vieillissantes.
14-3-3 protein augments the protein stability of phosphorylated spastin and promotes the recovery of spinal cord injury through its agonist intervention
Authors: Liu Qiuling , Yang Hua , Luo Jianxian , Peng Cheng , Wang Ke , Zhang Guowei , Ji Zhisheng , Lin Hongsheng
Published: December 2023

Axon regeneration is abortive in the central nervous system following injury. Orchestrating microtubule dynamics has emerged as a promising approach to improve axonal regeneration. The microtubule severing enzyme spastin is essential for axonal development and regeneration through remodeling of microtubule arrangement. To date, however, little is known regarding the mechanisms underlying spastin action in neural regeneration after spinal cord injury. Here, we use glutathione transferase pulldown and immunoprecipitation assays to demonstrate that 14-3-3 interacts with spastin, both
in vivo
and
in vitro,
via spastin Ser233 phosphorylation. Moreover, we show that 14-3-3 protects spastin from degradation by inhibiting the ubiquitination pathway and upregulates the spastin-dependent severing ability. Furthermore, the 14-3-3 agonist Fusicoccin (FC-A) promotes neurite outgrowth and regeneration
in vitro
which needs spastin activation. Western blot and immunofluorescence results revealed that 14-3-3 protein is upregulated in the neuronal compartment after spinal cord injury
in vivo
. In addition, administration of FC-A not only promotes locomotor recovery, but also nerve regeneration following spinal cord injury in both contusion and lateral hemisection models; however, application of spastin inhibitor spastazoline successfully reverses these phenomena. Taken together, these results indicate that 14-3-3 is a molecular switch that regulates spastin protein levels, and the small molecule 14-3-3 agonist FC-A effectively mediates the recovery of spinal cord injury in mice which requires spastin participation.

The formation of the 14-3-3 and spastin protein complex requires phosphorylation of spastin at the S233 site.14-3-3 is involved in the phosphorylation-ubiquitination crosstalk of spastin, thus impacting the protein stability.14-3-3 agonists Fusicoccin-A can facilitate the repair of spinal cord injury in mice.Activation of spastin function is a prerequisite for nerve regeneration and recovery of spinal cord injury in mice.
Innovative Integration of Recycled Plastics for Flexible Pavement Design
Authors: Singh Bishwajeet , Subedi Bishal , Tiwari Nalraj , Sapkota Ram Prasad , Katuwal Shradha , Pokharel Srijan , Kafle Sudarshan , Dahal Sulav
Published: December 2023

Plastic waste is a major problem due to its non-biodegradable nature. Incorporating recycled plastic in road construction enhances mechanical properties effectively. This paper encompasses methods to solve two major issues in Nepal, largely focused in major cities of Nepal: primarily, the management of solid waste, specifically with consideration of used plastics which have engulfed main cities; secondarily, the development of potholes on roads due to heavy traffic weight and some environmental factors such as excessive precipitation and infiltration, flooding conditions. This study inspects the effect of combining waste thermoplastic polymers like High-density polyethylene (HDPE), Polyethylene Terephthalate (PET), and Polypropylene (PP) in flexible pavement design, at various plastic compositions. The plastics were grinded and mixed with the bitumen at a temperature range of 160 °C–170 °C. Various tests such as the Marshall Stability test, Penetration test, Ductility test, and, Softening Point test were carried out to find the resulting modifications from base bitumen. It was observed that the plastic mixed sample upto 10% by weight shows sufficient mechanical properties of pavements. Being a cheap and effective way of improving the capacity of flexible pavement, It is one of the alternative ways to use plastic waste.
Racial Prejudice and the Fear of the other in Amiri Baraka’s Dutchman
Authors: Alrammah Aaya Adil
Published: December 2023

This study focuses on the Racist Theory in Amiri Baraka’s Dutchman, a play that revealed how racial prejudice and fear impacted people's lifestyles in 1964. A modern stage and racial thinking interact to initialise the understanding of races and turn towards individual experiences. Baraka’s Dutchman focuses on the culture within white supremacy that has historically marginalised all other races by representing possible outcomes. This paper studies the work of Lula, who destroys the clay to symbolise the savage destruction of the white man for the cultural identity of black people. Furthermore, it displays the continuation of racial violence that has been rampant since the 1960s. This study registers racial thinking and modern stage interactions, and in doing so, the researcher has adopted a secondary qualitative data collection method. The entire process of this study has been conducted based on information collected from existing resources. Thus, this study is especially applicable for readers since it connects with prejudice and fear. Analysing several types of elements in racial prejudice based on Racist Theory, the result helps to provide a transparent viewpoint.
Effect of Esketamine Added to Propofol Sedation on Desaturation and Hypotension in Bidirectional Endoscopy
Authors: Song Nan , Yang Yi , Zheng Zhong , Shi Wen-cheng , Tan Ai-ping , Shan Xi-sheng , Liu Hong , Meng Lingzhong , Peng Ke , Ji Fu-hai
Published: December 2023

Importance

Propofol sedation is widely used for endoscopic procedures, but it poses risks of hemodynamic and respiratory depression. The addition of esketamine as an adjuvant may reduce propofol requirements and associated adverse events.

Objective

To evaluate the effects of low-dose esketamine added to propofol-based sedation on desaturation and hypotension during same-visit bidirectional endoscopy.

Design, Setting, and Participants

This multicenter, double-blind, placebo-controlled randomized clinical trial assessed patients from 3 teaching hospitals in China who were scheduled for same-visit bidirectional endoscopy between February 8 and November 30, 2022, and randomly assigned to receive esketamine or normal saline (placebo).

Interventions

After induction of sedation with 0.1 μg/kg of sufentanil and 0.5 mg/kg of propofol, patients in the esketamine group received 0.15 mg/kg of intravenous esketamine, whereas patients in the placebo group received an equivalent volume of saline. Sedation was achieved through propofol titration.

Main Outcomes and Measures

The primary outcome was the composite of desaturation and hypotension during the procedures. Secondary outcomes included desaturation, hypotension, propofol requirements, postprocedure pain and fatigue, nausea or vomiting, dizziness or headache, hallucination or nightmare, endoscopist satisfaction, and patient satisfaction.

Results

Among the 663 initially enrolled patients, 660 completed the study (median [IQR] age, 48 [36-57] years; 355 [53.8%] female), with 331 randomized to the esketamine group and 329 to the placebo group. The administration of esketamine compared with placebo significantly reduced the incidence of the composite outcome of desaturation and hypotension (8.2% vs 21.0%; difference, −12.8 percentage points; odds ratio [OR], 0.34; 95% CI, 0.21-0.54; P < .001). Additionally, esketamine led to significantly lower incidences of desaturation (OR, 0.36; 95% CI, 0.18-0.72; false discovery rate q = .01) and hypotension (OR, 0.33; 95% CI, 0.18-0.60; q < .001) and reduced propofol requirements (difference, −58.9 mg; 95% CI, −65.7 to −52.2 mg; q < .001), without significant effects on other secondary outcomes.

Conclusions and Relevance

In this randomized clinical trial of patients undergoing same-visit bidirectional endoscopy, the administration of low-dose esketamine resulted in an approximately 61% reduction in the incidence of desaturation and hypotension, accompanied by decreased propofol requirements. These findings support the use of esketamine as an adjuvant to propofol-based sedation in endoscopic procedures.

Trial Registration

Chinese Clinical Trial Registry Identifier: ChiCTR2200055938
Use of Open Science Practices in Surgical Journals
Authors: Pathak Kavya , Marwaha Jayson S. , Chen Hao Wei , Krumholz Harlan M. , Matthews Jeffrey B.
Published: December 2023

This cross-sectional study assesses the level of adoption of 5 new tools that promote high quality and transparency in surgical research.
The autophagy of stress granules
Authors: Ryan Laura , Rubinsztein David C.
Published: December 2023

Our understanding of stress granule (SG) biology has deepened considerably in recent years, and with this, increased understanding of links has been made between SGs and numerous neurodegenerative diseases. One of the proposed mechanisms by which SGs and any associated protein aggregates may become pathological is based upon defects in their autophagic clearance, and so the precise processes governing the degradation of SGs are important to understand. Mutations and disease‐associated variants implicated in amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease and frontotemporal lobar dementia compromise autophagy, whilst autophagy‐inhibiting drugs or knockdown of essential autophagy proteins result in the persistence of SGs. In this review, we will consider the current knowledge regarding the autophagy of SG.
Dosimetric effects of rotational errors for single isocenter multiple targets in HyperArc plans: A phantom and retrospective imaging analysis study
Authors: Golmakani Samane , McGrath Andrew N. , Williams Timothy J.
Published: December 2023

Purpose

This study uses a phantom to investigate the dosimetric impact of rotational setup errors for Single Isocenter Multiple Targets (SIMT) HyperArc plans. Additionally, it evaluates intra‐fractional rotational setup errors in patients treated with Encompass immobilization system.

Methods

The Varian HyperArc system (Varian Medical systems) was used to create plans targeting spherical PTVs with diameters of 5, 10, and 15 mm and with offsets of 1.3–5.3 cm from the isocenter. Dosimetric parameters, including mean and maximum dose, D99% and D95% were evaluated for various rotational setup errors ranging from 0.5° to 2° for the PTVs and certain CTVs created within PTVs. These rotational errors were applied in an order and direction that resulted in the maximum displacement of targets. The rotation was applied both uniformly around all three axes and individually around each axis. Furthermore, to link the findings to actual treatment scenarios, the intra‐fractional rotational setup errors were obtained for stereotactic cranial patients treated with the Encompass system using CBCT images acquired during treatments.

Results

The maximum displacement of 2.7 mm was observed for targets located at 4.4 and 4.5 cm from the isocenter with rotational setup errors of 2°. The dose reduction for D99% values corresponding to this displacement were about 50%, 40%, and 30% for PTVs with diameters of 5, 10, and 15 mm, respectively. Both D99% and D95% showed a consistent trend of dose reduction across various rotational errors and PTV volumes. While the maximum dose remained consistent for different targets with various rotational errors, the mean dose decreased by approximately 25%, 12%, and 6% for PTVs with diameters of 5, 10, and 15 cm, respectively, with rotational errors of 2°. In addition, by analyzing CBCT images, the absolute mean rotational setup errors obtained during treatment with Encompass for pitch, roll, and yaw were 0.17° ± 0.13°, 0.11° ± 0.10°, and 0.12° ± 0.10° respectively. This data, combined with existing studies, suggest that a 0.5° rotational setup error is a safe choice to consider for calculating additional PTV margin to ensure adequate CTV coverage.

Therefore, the assessment of maximum displacement and dosimetric parameters in this study, for a 0.5° rotational error, highlights the need for an additional 0.7 mm PTV margin for targets positioned at distances of 4.4 cm or greater from the isocenter.

Conclusions

For SIMT Plans, a 0.5° rotational setup error is recommended as a basis for calculating additional PTV margins to ensure adequate CTV coverage when using the Encompass system.
Frailty and Risk of Serious Infections in Patients With Rheumatoid Arthritis Treated With Biologic or Targeted‐Synthetic Disease‐Modifying Antirheumatic Drugs
Authors: Singh Namrata , Gold Laura S. , Lee Jiha , Wysham Katherine D. , Andrews James S. , Makris Una E. , England Bryant R. , George Michael D. , Baker Joshua F. , Jarvik Jeffrey , Heagerty Patrick J. , Singh Siddharth
Published: December 2023

Objective

It remains unknown whether frailty status portends an increased risk of adverse outcomes in patients with rheumatoid arthritis (RA) initiating biologic or targeted‐synthetic (b/ts) disease‐modifying antirheumatic drugs (DMARDs). The objective of our study was to evaluate the association between frailty and serious infections in a younger population of patients (<65 years old) with RA who initiated b/tsDMARDs.

Methods

Using MarketScan data, we identified new users of tumor necrosis factor inhibitors (TNFi), non‐TNFi biologic DMARDs, or Janus kinase inhibitors (JAKi) between 2008 and 2019 among those with RA. Patients’ baseline frailty risk score was calculated using a Claims‐Based Frailty Index (≥0.2 defined as frail) 12 months prior to drug initiation. The primary outcome was time to serious infection; secondarily, we examined time‐to‐any infection and all‐cause hospitalizations. We used Cox proportional hazards to estimate adjusted hazard ratios and 95% confidence intervals (95% CIs) and assessed the significance of interaction terms between frailty status and drug class.

Results

A total of 57,980 patients, mean (±SD) age 48.1 ± 10.1 were included; 48,139 (83%) started TNFi, 8,111 (14%) non‐TNFi biologics, and 1,730 (3%) JAKi. Among these, 3,560 (6%) were categorized as frail. Frailty was associated with a 50% increased risk of serious infections (adjusted hazard ratio [95% CI] 1.5, 1.2–1.9) and 40% higher risk of inpatient admissions (1.4 [1.3–1.6]) compared with nonfrail patients among those who initiated TNFi. Frailty was also associated with a higher risk of any infection relative to nonfrail patients among those on TNFi (1.2 [1.1–1.3]) or non‐TNFi (1.2 [1.0–1.4]) or JAKi (1.4 [1.0–2.0]).

Conclusion

Frailty is an important predictor for the risk of adverse outcomes among patients with RA treated with biologic or targeted‐synthetic DMARDs.
Targeting Cyclin‐Dependent Kinase 1 Induces Apoptosis and Cell Cycle Arrest of Activated Hepatic Stellate Cells
Authors: Kang Xinmei , Chen Huaxin , Zhou Zhuowei , Tu Silin , Cui Bo , Li Yanli , Dong Shuai , Zhang Qi , Xu Yan
Published: December 2023

Liver fibrosis is the integral process of chronic liver diseases caused by multiple etiologies and characterized by excessive deposition of extracellular matrix (ECM). During liver fibrosis, hepatic stellate cells (HSCs) transform into a highly proliferative, activated state, producing various cytokines, chemokines, and ECM. However, the precise mechanisms that license HSCs into the highly proliferative state remain unclear. Cyclin‐dependent kinase 1 (CDK1) is a requisite event for the transition of the G1/S and G2/M phases in eukaryotic cells. In this study, it is demonstrated that CDK1 and its activating partners, Cyclin A2 and Cyclin B1, are upregulated in both liver fibrosis/cirrhosis patient specimens and the murine hepatic fibrosis models, especially in activated HSCs. In vitro, CDK1 is upregulated in spontaneously activated HSCs, and inhibiting CDK1 with specific small‐molecule inhibitors (CGP74514A, RO‐3306, or Purvalanol A) orshort hairpin RNAs (shRNAs) resulted in HSC apoptosis and cell cycle arrest by regulating Survivin expression. Above all, it is illustrated that increased CDK1 expression licenses the HSCs into a highly proliferative state and can serve as a potential therapeutic target in liver fibrosis.
Janus Paper‐Based Wound Dressings for Effective Exudate Absorption and Antibiotic Delivery
Authors: Gao Yang , Elhadad Anwar , Choi Seokheun
Published: December 2023

Traditional hydrophilic wound dressings, while common, fail to effectively drain wound exudate, creating conditions favorable for bacterial growth. Similarly, newer Janus‐type dressings with hydrophobic‐hydrophilic properties also fall short, as their hydrophobic side causes excessive dryness by pulling biofluids from the wound, disrupting moisture balance. Additionally, embedding antibiotics in dressings at fixed concentrations, regardless of the infection type, reduces effectiveness and contributes to the growing problem of antibiotic resistance. In response, a single‐layered Janus paper wound dressing, designed for efficient exudate absorption and precise antibiotic delivery, is developed. The approach differs from traditional Janus‐type dressings; a hydrophilic layer is placed directly against the wound for better moisture management, while antibiotics are applied through the hydrophobic layer. To further enhance exudate management, the hydrophilic section with four extra absorbent pads is extended. The dressing's antibiotic efficacy and dosage are tailored based on antibiotic susceptibility testing, ensuring targeted treatment. The selected antibiotic is manually added but automatically delivered directly to the wound bed. The in vitro and ex vivo evaluations, using bacterial cultures on agar and porcine skin assays, respectively, confirm the dressing's superior exudate drainage and its ability to inhibit pathogen growth and reproduction, marking a significant advancement in wound care.
pH‐Responsive Chitosan Microspheres Loaded with Gemini Imidazolium‐Based Ionic Liquids as Smart Corrosion Inhibitors for N80 Steel in Hydrochloric Acid Solution
Authors: Wang Li , Wang Zhikun , Li Fengting , Liu Yueqi , Li Miantuo , Cui Nannan , Hu Songqing , Sun Shuangqing
Published: December 2023

Chitosan microspheres (CSM) loaded with synthesized Gemini imidazolium‐based ionic liquids ([C2(Bim)2]Cl2@CSM and [C6(Bim)2]Br2@CSM) are constructed as smart corrosion inhibitors to protect N80 steel in hydrochloric acid solution. The optimal inhibition efficiency of [C2(Bim)2]Cl2 and [C6(Bim)2]Br2 at 300 mg L−1 reaches 94.68% and 95.96%, respectively, indicating mixed‐type inhibition behavior. On this basis, the prepared [C2(Bim)2]Cl2@CSM and [C6(Bim)2]Br2@CSM can proactively identify corrosive environments and protect the metal. The microspheres are pH‐responsive owing to the presence of Schiff‐base C═N bonds and the loaded inhibitors can be released rapidly in acidic environment. Released inhibitors are delivered to corroded sites and synergistically interact with decomposed microspheres for enhanced corrosion inhibition effect.