bluuebunny/crossref_metadata_2025 huggingface dataset:
THE INFLUENCE OF ISLAMIC SPIRITUAL EXTRACURRICULAR ON THE MORALS OF STUDENTS
Authors: Munawaroh Nenden , Fadilah Elsa , Nasrullah Yufi M , Usman Asep Tutun
Published: July 2022

The background of this study is the existence of technology that affects the nature, morals, and character of learners, for example, characterized by learners who communicate with teachers using non-formal languages, female learners who wear clothes follow trends so as not to close their aurat perfectly, learning hours 8-9 hours per day make moral education only focused on the school environment. This study aims to find out the extracurricular influence of Islamic Spiritual on the morals of students at SMAN 15 Garut. The research uses quantitative approaches and descriptive methods. The subject of this study is a student who follows Islamic spiritual extracurriculars at SMAN 15 Garut. The object of this research is the result of the influence of the Islamic Spiritual in forming student morals. This researched data collection uses observations, interviews, and documentation. Data analysis techniques use quantitative techniques. In this study, obtaining data with variable calculation X resulted in reliability and validity with a total variant of 11,375, variant items of 129,387, tcount of 20.81, and ttable of 2.01 in a Reliable decision. Calculating variable Y with a total variant of 53.53, variant items of 7.32, t-count of 16.10, and t-table of 2.01 with Realiabel decision. After the hypothesis test produced t-count data of 8.66 and a t-table of 2.01, it can be concluded that the hypothesis Ho was rejected and Ha accepted, with a determination influence of 45% with an epsilon of 55% and including medium criteria. So it can be concluded that ROHIS extracurriculars affect the morals of students at SMAN 15 Garut by 45%.
THE EFFECTIVENESS OF USING THE LABORATORY IN LEARNING SCIENCE
Authors: Wahidah Ainun Ilmi , Mardiana Alif , Iriani Siti Anisatul , Safitri Amalia , Nihaya Asya Fikriyatun , Nafiah Mufidatul
Published: July 2022

The science that studies nature and its processes are called Science. When learning about Science, the laboratory has an essential role in growing students' experimentation abilities and increasing students' enthusiasm for learning. This study aims to describe and determine the effectiveness of the use of laboratories in science learning at SMPN 2 Lumajang. This study uses an approach with the interview method. This research was carried out at SMPN 2 Lumajang, which involved subject science teachers at the SMPN. The results showed that the science laboratory at SMPN 2 Lumajang had two rooms: a laboratory room and a storage room. Judging from the aspect of the laboratory space, the science laboratory of SMPN 2 Lumajang still needs to be improved a bit, such as a space to store tools and materials, and there is no preparation room to make preparations before the practicum begins. The existing facilities and infrastructure influence the effectiveness of the use of laboratories in the learning process. With complete facilities and infrastructure, student learning activities in observations will run smoothly.
EVALUATION OF THE JUMAT TAQWA PROGRAM (JUMTAQ) TO CONSTRUCTING THE RELIGIOUS CHARACTER OF STUDENTS
Authors: Ida Ida
Published: July 2022

This study describes the Evaluation of the Jumat Taqwa Program at SMAN 13 Pandeglang. The purpose of this study is to evaluate the Jumat Taqwa program, which is routinely held every Friday morning at SMAN 13 Pandeglang as a consideration for the student and spiritual fields, to take policies regarding the development of character education in schools. This study uses a qualitative descriptive method with the evaluation model used is Countenance Stake. The result of this study is that the Jumat Taqwa program (JUMTAQ) at SMAN 13 Pandeglang received a good response from the students. This can be seen based on the percentage of students who agree and are enthusiastic about participating in the Jumtaq program, 89%. The average answer of students in the aspect of aqidah after participating in the Jumat taqwa program 92% said consistently, and 8% often said, in the element of morality there were 78% always, 14% usually and 8% sometimes, while in the aspect of increasing knowledge of fiqh the answers were obtained Yes by 87% and No by 13%. Based on the study results, the Jumat Taqwa program made a positive contribution to the cultivation of the religious character of students.
POLITICAL EFFECT IN MERDEKA BELAJAR EDUCATION ERA OF THE COVID-19 PANDEMIC
Authors: Heri Kang , Zaini Zaini
Published: July 2022

Political influence in education is like compulsory instruction, while it is difficult to create without astute individuals. Even the brightest individuals have to be framed through school. Education is directly or by implication influenced by government issues. The amalgamation of instructions and governance issues is plural. For a while, teaching can shape people who participate in political life. The reason for the school is to make students mentally minded and have great personalities. The training framework must produce millennial students who can compete in the modern-based 4.0 era. Therefore, the educational framework in Pamekasan continues to improve and change. Changes in schooling began with Nadiem Makarim's discourse, who proposed the development of "Merdeka Belajar". Nadiem's opportunity aims to make independent instructors have an essential meaning for academic units or schools for educators and their students to have the chance to advance, adapt freely, and be creative, especially during this coronavirus pandemic.
THE PORTRAIT OF EDUCATIONAL PHILOSOPHY THROUGH AN ANALYSIS OF INDONESIAN MOVIE BASED ON PESANTREN THEME
Authors: Aini Devi Nur , Shofi Millatus , Zuhriya Latifatu
Published: July 2022

The way of people educate and think of their values affect the educational system; it is found in Pesantren as the Islamic institution that holds norm, belief, and values in education system. Meanwhile, movies is one of the effective devices to promote the society learning process due to its popularity among the society, teenagers and also adults. Many movies produced intended to portray the uniqueness of educational system in pesantren and got a great attention as educational philosophy. This study examined the habits, norm, and values of educational system through the analysis of the movie Negeri 5 Menara. Document review and descriptive analysis method used as a qualitative research methods. Film observation form gathered and the decoding process of it prior to the scene identification was based on education and specific themes. The results shown by the setting, gesture, and action of each character among the other, and some of the quotation based on some verses in Al-Qur’an to improve reliability. The Findings depicted that perennials was identified as the most prominent educational philosophy up to nowadays. The central leading character plays a part of students’ belief in seeking knowledge. It is said in Javanese language as “Ngalap barokahe Kyai”.
THE STRENGTHENING OF CHARACTER EDUCATION BASED ON LOCAL WISDOM THROUGH HIKAYAT NYIMAS GAMPARAN
Authors: Haryanti Ade Siti , Hufad Achmad , Leksono Suroso Mukti
Published: July 2022

This study describes character education in developing the affective domain for students, especially for junior high school students. Important character education is instilled in junior high school children who are intensively looking for identity, this character education is expected to form students who have morals and noble character in accordance with the 2013 curriculum. Teachers can develop subject matter through a local wisdom approach, which is owned by the area. One of the local wisdoms in Balaraja is the saga Nyimas Gamparan, which is packaged in an interesting picture story book. So the benefits of this study are; 1) Providing creative and innovative ideas for teachers in developing learning materials based on local wisdom through the saga of Nyimas Gamparan; 2) Motivating schools, teachers, parents, and the community to direct students who have positive attitudes towards the surrounding culture; and 3) motivate students in the formation of characters that will be useful in their lives.
LEARNING CYCLE MANAGEMENT BASED ON LOCAL WISDOM IN INSTILLING THE CHARACTER OF RELIGIOUS STUDENTS IN MADRASA
Authors: Masruroh Siti , Bz Zakiyah
Published: July 2022

The subjects of this study were students of MI Nurur Rahmah. The data analysis technique used is descriptive qualitative analysis, and the data collection technique used is the method of observation and interviews. The local wisdom that exists at MI Nurur Rahmah is part of the habits that are believed and obeyed by students and teachers at MI Nururrahmah, which are religious habits or practices that occur every day, such as congregational prayers, dhuha prayers, and reading the Qur'an. before the KBM starts. As a source of learning and the cultivation of local wisdom character values that can be instilled in students' personalities,Based on the results of research and discussion on inculcating students' religious character, the management of the learning cycle based on local wisdom applied by MI teacher Nurur Rahmah aims to make students better understand the meaning of piety in religious rituals, so that the religious values contained therein can be instilled in students with the hope of becoming their religious character later by instilling the religious character of students through habituation in the institution.
EDUCATORS PEDAGOGICAL COMPETENCE IN ONLINE LEARNING AND ITS IMPACT ON STUDENTS' LEARNING OUTCOMES
Authors: Sholikhun Muhamad , Soraya Zulfatus , Siswanto Siswanto , Wafirah Milna
Published: July 2022

Covid-19 has a tangible impact on the learning process, namely the necessity of implementing bold learning. Bold learning ultimately requires educators to be proficient in using technology, but not all educators are ready to use technology in learning. This condition causes learning during the COVID-19 pandemic to be less than optimal, resulting in low learning outcomes. This study was conducted with the aim of analyzing how the correlation between the pedagogic competence of educators and student learning outcomes during the covid-19 pandemic. This research includes quantitative research. Research data was collected using two techniques, namely questionnaires and technical documentation. Research data that has been collected is then analyzed using statistical analysis of Product Moment correlation. Based on the data analysis, it can be said that the relationship between the pedagogic competence of educators and student learning outcomes is significant and positive. The results of this study can be achieved if bold learning during the pandemic requires adequate pedagogic competence in improving student learning outcomes
A More Welcoming Climate: How Basic Income found better Traction in Holyrood than in Westminster
Authors: Thomas Steve
Published: July 2022

Basic income has moved tentatively on to the UK agenda since 2015, but it has struggled to find a foothold in Westminster, where the dominant view of poverty is as the result of failure in the labour market, and the response remains coercive welfare conditionality. In Scotland, government-funded research into the feasibility of basic income pilots has drawn on health and well-being priorities and civic and local authority involvement, while making an explicit connection between poverty, agency, health and wealth. This article draws on literature and semi-expert interviews to argue that the nature of Scottish political institutions and culture, allied to a Nationalist party government keen to differentiate itself from Westminster, with independence as short-term or long-term goal, has created an unusual policy space that provides the conditions for basic income as a pivoting reform. While implementation of a Basic Income may be impossible without full independence, Scotland is creating an ideational climate where – unlike south of the border – it at least looks feasible.
Historians, Activists and Britain's Slave Trade Abolition Debate: The Henry Dundas Plaque Debacle
Authors: McCarthy Angela
Published: July 2022

Since the summer of 2020 debate concerning the commemoration of one of Scotland’s leading eighteenth century politicians has galvanised opinions. The heart of the controversy surrounds the wording on a new heritage marker erected in 2021 at the statue of Henry Dundas (later Viscount Melville) in St Andrew Square, Edinburgh. This article does not address the complex question of whether or not Dundas was an abolitionist, but only if he can be held accountable for a delay to abolition of the British slave trade as claimed on the plaque. My overarching argument is that Sir Geoff Palmer, the key figure behind the new plaque’s wording, has wrongly conflated arguments about whether or not Dundas was an abolitionist with assertions that he delayed abolition of Britain’s slave trade. Through identifying the flaws in his approach to the past, I highlight the problems that arise when individuals and institutions discount, marginalise and demean professional and longstanding historical expertise. Indeed, the heritage sector is grossly undermined by the lack of rigorous scrutiny for plaques and memorials erected to serve pressure group politics. Although this controversy is about one monument in one city, it has wider ramifications for how we remember and engage with the past.
The Digital Health and Wellbeing Needs, or otherwise, of a Deprived Scottish Community
Authors: McVean Scot , Yuill Chris
Published: July 2022

Healthcare is becoming increasingly digitised. Access and usage of digital health technologies however is unequal in deprived communities. Despite this disparity, research remains silent on digital health and health inequalities. The present study investigates the health and well-being needs of a deprived community and how digital health technologies could be implemented to meet those needs. An interpretative, qualitative approach was adopted. 18 residents from the deprived community of Raploch, Stirling were recruited. Participants were split into two age cohorts 26–49 (N=4) and 50+ years of age (N=14). Three focus group discussions and a semi-structured interview were used to explore the digital health needs of the residents using open-ended questions. The findings revealed that there are multitude of accessibility relations that influenced the everyday experience of the residents. The complex assemblage of relations must be understood and addressed if digital health interventions are to be successfully implemented into a deprived community.
Scotland's Catholics, A Distinctive Community?
Authors: Rosie Michael
Published: July 2022

Despite persistent debate about the status and character of Scotland’s Catholic community the question of how distinctive – if at all – Scotland’s Catholics are within a wider British Catholicism is seldom asked. Utilising the newly released Catholics in Britain Survey of 2019 this short article sketches out some comparative evidence on Catholic religiosity, moral values, family, and personal networks. It concludes that Scotland’s Catholicism is closely similar, in terms of such measures, to a wider British Catholic community.
A NOTE ON KENMOTSU MANIFOLDS ADMITTING GENERALIZED TANAKA-WEBSTER CONNECTION
Authors: YILDIRIM Mustafa , KAYA Ramazan Çınar
Published: July 2022

In the present paper, we investigate some tensor conditions of Kenmotsu manifolds with the generalized Tanaka-Webster connection. Using

the Q tensor whose trace is the well-known Z-tensor, we prove the conditions ξ − Q∗ flat, ϕ − Q∗ flat Kenmotsu manifold with respect to the generalized Tanaka-Webster connection.
Seed viability of feathertop Rhodes grass (Chloris virgata Sw.) reduced by silage, digestion, and sheep rumen digestion
Authors: Asaduzzaman Md , Piltz John , Koetz Eric , Hopwood Michael , Shephard Adam , Wu Hanwen
Published: July 2022

Weed seeds can be spread by different vectors, and seed dispersal is an important mechanism for the weed to persist. Weed seeds passaging through the digestive tract of a ruminant animal is expected to result in reduced viability. Two separate experiments were conducted to determine the germinability and viability of the mature seeds of feathertop Rhodes grass (Chloris virgata Sw.) after exposure to four treatments, that is, 3 months in silage, 48 h in the rumen of steers, silage plus digestion, and passing through the digestive tract of sheep. Our results showed that three different treatments (silage, digestion, and silage plus digestion) can inhibit 90%–100% of the seed germination of feathertop Rhodes grass. Both silage and digestion reduced seed viability by 65%–90%, depending on the population. Silage followed by digestion reduced viability by 80%–97%. The sheep feeding study showed that total viable seeds from the daily recovery of feces for 12 consecutive days after ingestion was only 0.084% and 0.022% in the 2020 and 2021 experiments, respectively. In comparison with the untreated control, the seed viability of feathertop Rhodes grass was reduced by more than 99.9% after feeding through sheep, indicating that the spreading of feathertop Rhodes grass seeds via sheep feces is minimal. These results indicate that silage, digestion, silage followed by digestion, and the ingestion of mature seeds are effective non-chemical weed management options for an integrated weed management package for feathertop Rhodes grass.
Multi-phasic life-threatening anaphylaxis refractory to epinephrine managed by extracorporeal membrane oxygenation (ECMO): A case report
Authors: Grafeneder Juergen , Ettl Florian , Warenits Alexandra-Maria , Buchtele Nina , Lobmeyr Elisabeth , Staudinger Thomas , Schwameis Michael , Sperr Wolfgang R. , Gelbenegger Georg , Schoergenhofer Christian , Jilma Bernd
Published: July 2022

We present a case of a 52-year-old patient suffering from multi-phasic life-threatening anaphylaxis refractory to epinephrine treatment. Extracorporeal membrane oxygenation (ECMO) therapy was initiated as the ultima ratio to stabilize the patient hemodynamically during episodic severe bronchospasm. ECMO treatment was successfully weaned after 4 days. Mastocytosis was diagnosed as the underlying condition. Although epinephrine is recommended as a first-line treatment for anaphylaxis, this impressive case provides clear evidence of its limited therapeutic success and emphasizes the need for causal therapies.
Pancreatic colonization of fungi in the development of severe acute pancreatitis
Authors: Otsuka Yasuo , Kamata Ken , Minaga Kosuke , Watanabe Tomohiro , Kudo Masatoshi
Published: July 2022

Acute pancreatitis is a common emergent disorder, a significant population of which develops the life-threatening condition, called severe acute pancreatitis (SAP). It is generally accepted that bacterial infection is associated with the development and persistence of SAP. In addition to bacterial infection, recent clinical studies disclosed a high incidence of fungal infection in patients with SAP. Moreover, SAP patients with fungal infection exhibit a higher mortality rate than those without infection. Although these clinical studies support pathogenic roles played by fungal infection in SAP, beneficial effects of prophylactic anti-fungal therapy on SAP have not been proved. Here we summarize recent clinical findings as to the relationship between fungal infection and the development of SAP. In addition, we discuss molecular mechanisms accounting for the development of SAP in the presence of fungal infection.
Prosthesis-patient mismatch following transcatheter aortic valve replacement for degenerated transcatheter aortic valves: the TRANSIT-PPM international project
Authors: Testa Luca , Casenghi Matteo , Criscione Enrico , Van Mieghem Nicolas M. , Tchétché Didier , Asgar Anita W. , De Backer Ole , Latib Azeem , Reimers Bernhard , Stefanini Giulio , Trani Carlo , Giannini Francesco , Bartorelli Antonio , Wojakowski Wojtek , Dabrowski Maciej , Jagielak Dariusz , Banning Adrian P. , Kharbanda Rajesh , Moreno Raul , Schofer Joachim , Brinkmann Christina , van Royen Niels , Pinto Duane , Serra Antoni , Segev Amit , Giordano Arturo , Brambilla Nedy , Agnifili Mauro , Rubbio Antonio Popolo , Squillace Mattia , Oreglia Jacopo , Tanja Rudolph , McCabe James M. , Abizaid Alexander , Voskuil Michiel , Teles Rui , Zoccai Giuseppe Biondi , Sondergaard Lars , Bedogni Francesco
Published: July 2022

Background

A severe prosthesis-patient mismatch (PPM) is associated with adverse outcomes following transcatheter aortic valve replacement (TAVR) for de novo aortic stenosis or a failed surgical bioprosthesis. The impact of severe PPM in patients undergoing TAV-in-TAVR is unknown.

Aim

We sought to investigate the incidence and 1-year outcomes of different grades of PPM in patients undergoing TAV-in-TAVR.

Materials and methods

The TRANSIT-PPM is an international registry, including cases of degenerated TAVR treated with a second TAVR. PPM severity, as well as in-hospital, 30-day, and 1-year outcomes were defined according to the Valve Academic Research Consortium-3 (VARC-3) criteria.

Results

Among 28 centers, 155 patients were included. Severe PPM was found in 6.5% of patients, whereas moderate PPM was found in 14.2% of patients. The rate of severe PPM was higher in patients who underwent TAV-in-TAVR with a second supra-annular self-expanding (S-SE) TAVR (10%, p = 0.04). Specifically, the rate of severe PPM was significantly higher among cases of a SE TAVR implanted into a balloon-expandable (BE) device (19%, p = 0.003). At 1-year follow-up, the rate of all-cause mortality, and the rate of patients in the New York Heart Association (NYHA) class III/IV were significantly higher in the cohort of patients with severe PPM (p = 0.016 and p = 0.0001, respectively). Almost all the patients with a severe PPM after the first TAVR had a failed < 23 mm BE transcatheter heart valve (THV): the treatment with an S-SE resolved the severe PPM in the majority of the cases.

Conclusion

After TAV-in-TAVR, in a fifth of the cases, a moderate or severe PPM occurred. A severe PPM is associated with an increased 1-year all-cause mortality.

Clinical trial registration

[https://clinicaltrials.gov], identifier [NCT04500964].
Interprofessional education—situations of a university in Hong Kong and major hurdles to teachers and students
Authors: Li Joyce T. S. , Chau Janita P. C. , Wong Samuel Y. S , Lau Ann S. N. , Chan Wallace C. H. , Yip Peggy P. S. , Yang Yijian , Ku Fred K. T. , Sze Felix Y. B. , King Irwin K. C. , Lee Vivian W. Y.
Published: July 2022

Studies have provided evidence that Interprofessional Education (IPE) can improve learners’ attitudes, knowledge, skills, behaviors, and competency. Traditionally, IPE is commonly seen in the healthcare professional training in tertiary education. Aging is a global issue that requires more than just a single healthcare sector. It requires interdisciplinary collaboration and understanding to tackle the issues. Therefore, IPE is essential for nurturing university students to tackle the ever-changing global challenges. In addition, different hurdles can hinder IPE development. To have a better understanding of the feasibility, acceptance, and educational value of IPE in Hong Kong, we conducted a cross-sectional quantitative study. We invited teachers and students from a Hong Kong university to fill in an online survey that evaluated their understanding and participation in IPE, their attitude toward IPE, and the barriers to developing IPE from March to June 2020. Among the 37 academic staff and 572 students who completed the survey, 20 (54.1%) teachers and 422 (73.8%) students had never heard of IPE before, and 26 (70.3%) teachers and 510 (89.2%) students had never participated in any IPE activities. Major barriers reported by teachers included an increase in teaching load (72.9%), lack of administrative support (72.9%), lack of financial support and limited budget (67.5%), difficulty to make logistic arrangements (64.8%), and problems with academic schedules and calendars (62.1%). The survey findings revealed that despite the positive attitude of university teachers and students toward IPE, barriers that could hinder the development of IPE included heavy teaching and administrative load and logistic arrangement for classroom arrangement and academic scheduling involving multiple faculties.
Modulation of Autophagy in Adrenal Tumors
Authors: Sousa Diana , Pereira Sofia S. , Pignatelli Duarte
Published: July 2022

Adrenal masses are one of the most common tumors in humans. The majority are benign and non-functioning and therefore do not require immediate treatment. In contrast, the rare adrenal malignant tumors are often highly aggressive and with poor prognosis. Besides usually being detected in advanced stages, often already with metastases, one of the reasons of the unfavorable outcome of the patients with adrenal cancer is the absence of effective treatments. Autophagy is one of the intracellular pathways targeted by several classes of chemotherapeutics. Mitotane, the most commonly used drug for the treatment of adrenocortical carcinoma, was recently shown to also modulate autophagy. Autophagy is a continuous programmed cellular process which culminates with the degradation of cellular organelles and proteins. However, being a dynamic mechanism, understanding the autophagic flux can be highly complex. The role of autophagy in cancer has been described paradoxically: initially described as a tumor pro-survival mechanism, different studies have been showing that it may result in other outcomes, namely in tumor cell death. In adrenal tumors, this dual role of autophagy has also been addressed in recent years. Studies reported both induction and inhibition of autophagy as a treatment strategy of adrenal malignancies. Importantly, most of these studies were performed using cell lines. Consequently clinical studies are still required. In this review, we describe what is known about the role of autophagy modulation in treatment of adrenal tumors. We will also highlight the aspects that need further evaluation to understand the paradoxical role of autophagy in adrenal tumors.
Surface microbiota of Mediterranean loggerhead sea turtles unraveled by 16S and 18S amplicon sequencing
Authors: Kanjer Lucija , Filek Klara , Mucko Maja , Majewska Roksana , Gračan Romana , Trotta Adriana , Panagopoulou Aliki , Corrente Marialaura , Di Bello Antonio , Bosak Sunčica
Published: July 2022

The loggerhead sea turtle is considered a keystone species with a major ecological role in Mediterranean marine environment. As is the case with other wild reptiles, their outer microbiome is rarely studied. Although there are several studies on sea turtle’s macro-epibionts and endo-microbiota, there has been little research on epibiotic microbiota associated with turtle skin and carapace. Therefore we aimed to provide the identification of combined epibiotic eukaryotic, bacterial and archaeal microbiota on Mediterranean loggerhead sea turtles. In this study, we sampled skins and carapaces of 26 loggerheads from the Mediterranean Sea during 2018 and 2019. To investigate the overall microbial diversity and composition, amplicon sequencing of 16S and 18S rRNA genes was performed. We found that the Mediterranean loggerhead sea turtle epibiotic microbiota is a reservoir of a vast variety of microbial species. Microbial communities mostly varied by different locations and seas, while within bacterial communities’ significant difference was observed between sampled body sites (carapace vs. skin). In terms of relative abundance, Proteobacteria and Bacteroidota were the most represented phyla within prokaryotes, while Alveolata and Stramenopiles thrived among eukaryotes. This study, besides providing a first survey of microbial eukaryotes on loggerheads via metabarcoding, identifies fine differences within both bacterial and eukaryotic microbial communities that seem to reflect the host anatomy and habitat. Multi-domain epi-microbiome surveys provide additional layers of information that are complementary with previous morphological studies and enable better understanding of the biology and ecology of these vulnerable marine reptiles.
A novel signature to guide osteosarcoma prognosis and immune microenvironment: Cuproptosis-related lncRNA
Authors: Yang Mingyi , Zheng Haishi , Xu Ke , Yuan Qiling , Aihaiti Yirixaiti , Cai Yongsong , Xu Peng
Published: July 2022

Objective

Osteosarcoma (OS) is a common bone malignancy with poor prognosis. We aimed to investigate the relationship between cuproptosis-related lncRNAs (CRLncs) and the survival outcomes of patients with OS.

Methods

Transcriptome and clinical data of 86 patients with OS were downloaded from The Cancer Genome Atlas (TCGA). The GSE16088 dataset was downloaded from the Gene Expression Omnibus (GEO) database. The 10 cuproptosis-related genes (CRGs) were obtained from a recently published article on cuproptosis in Science. Combined analysis of OS transcriptome data and the GSE16088 dataset identified differentially expressed CRGs related to OS. Next, pathway enrichment analysis was performed. Co-expression analysis obtained CRLncs related to OS. Univariate COX regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were used to construct the risk prognostic model of CRLncs. The samples were divided evenly into training and test groups to verify the accuracy of the model. Risk curve, survival, receiver operating characteristic (ROC) curve, and independent prognostic analyses were performed. Next, principal component analysis (PCA) and t-distributed stochastic neighbor embedding (t-SNE) analysis were performed. Single-sample gene set enrichment analysis (ssGSEA) was used to explore the correlation between the risk prognostic models and OS immune microenvironment. Drug sensitivity analysis identified drugs with potential efficacy in OS. Real-time quantitative PCR, Western blotting, and immunohistochemistry analyses verified the expression of CRGs in OS. Real-time quantitative PCR was used to verify the expression of CRLncs in OS.

Results

Six CRLncs that can guide OS prognosis and immune microenvironment were obtained, including three high-risk CRLncs (AL645608.6, AL591767.1, and UNC5B-AS1) and three low-risk CRLncs (CARD8-AS1, AC098487.1, and AC005041.3). Immune cells such as B cells, macrophages, T-helper type 2 (Th2) cells, regulatory T cells (Treg), and immune functions such as APC co-inhibition, checkpoint, and T-cell co-inhibition were significantly downregulated in high-risk groups. In addition, we obtained four drugs with potential efficacy for OS: AUY922, bortezomib, lenalidomide, and Z.LLNle.CHO. The expression of LIPT1, DLAT, and FDX1 at both mRNA and protein levels was significantly elevated in OS cell lines compared with normal osteoblast hFOB1.19. The mRNA expression level of AL591767.1 was decreased in OS, and that of AL645608.6, CARD8-AS1, AC005041.3, AC098487.1, and UNC5B-AS1 was upregulated in OS.

Conclusion

CRLncs that can guide OS prognosis and the immune microenvironment and drugs that may have a potential curative effect on OS obtained in this study provide a theoretical basis for OS survival research and clinical decision-making.
Reactive oxygen species associated immunoregulation post influenza virus infection
Authors: Wang Lan , Cao Zheng , Wang Zi , Guo Jimin , Wen Jing
Published: July 2022

An appropriate level of reactive oxygen species (ROS) is necessary for cell proliferation, signaling transduction, and apoptosis due to their highly reactive character. ROS are generated through multiple metabolic pathways under a fine-tuned control between oxidant and antioxidant signaling. A growing number of evidence has proved their highly relevant role in modulating inflammation during influenza virus infection. As a network of biological process for protecting organism from invasion of pathogens, immune system can react and fight back through either innate immune system or adaptive immune system, or both. Herein, we provide a review about the mechanisms of ROS generation when encounter influenza virus infection, and how the imbalanced level of ROS influences the replication of virus. We also summarize the pathways used by both the innate and adaptive immune system to sense and attack the invaded virus and abnormal levels of ROS. We further review the limitation of current strategies and discuss the direction of future work.
Investigation of the causal etiology in a patient with T-B+NK+ immunodeficiency
Authors: Sertori Robert , Lin Jian-Xin , Martinez Esteban , Rana Sadhna , Sharo Andrew , Kazemian Majid , Sunderam Uma , Andrake Mark , Shinton Susan , Truong Billy , Dunbrack Roland M. , Liu Chengyu , Srinivasan Rajgopol , Brenner Steven E. , Seroogy Christine M. , Puck Jennifer M. , Leonard Warren J. , Wiest David L.
Published: July 2022

Newborn screening for severe combined immunodeficiency (SCID) has not only accelerated diagnosis and improved treatment for affected infants, but also led to identification of novel genes required for human T cell development. A male proband had SCID newborn screening showing very low T cell receptor excision circles (TRECs), a biomarker for thymic output of nascent T cells. He had persistent profound T lymphopenia, but normal numbers of B and natural killer (NK) cells. Despite an allogeneic hematopoietic stem cell transplant from his brother, he failed to develop normal T cells. Targeted resequencing excluded known SCID genes; however, whole exome sequencing (WES) of the proband and parents revealed a maternally inherited X-linked missense mutation in MED14 (MED14V763A), a component of the mediator complex. Morpholino (MO)-mediated loss of MED14 function attenuated T cell development in zebrafish. Moreover, this arrest was rescued by ectopic expression of cDNA encoding the wild type human MED14 ortholog, but not by MED14V763A, suggesting that the variant impaired MED14 function. Modeling of the equivalent mutation in mouse (Med14V769A) did not disrupt T cell development at baseline. However, repopulation of peripheral T cells upon competitive bone marrow transplantation was compromised, consistent with the incomplete T cell reconstitution experienced by the proband upon transplantation with bone marrow from his healthy male sibling, who was found to have the same MED14V763A variant. Suspecting that the variable phenotypic expression between the siblings was influenced by further mutation(s), we sought to identify genetic variants present only in the affected proband. Indeed, WES revealed a mutation in the L1 cell adhesion molecule (L1CAMQ498H); however, introducing that mutation in vivo in mice did not disrupt T cell development. Consequently, immunodeficiency in the proband may depend upon additional, unidentified gene variants.
microRNA-144/451 decreases dendritic cell bioactivity via targeting interferon-regulatory factor 5 to limit DSS-induced colitis
Authors: Lin Zhijie , Xie Xiaoyan , Gu Min , Chen Qian , Lu Guotao , Jia Xiaoqin , Xiao Weiming , Zhang Jun , Yu Duonan , Gong Weijuan
Published: July 2022

The microRNAs miR-144/451 are highly conserved miRNA that is strongly induced during erythropoiesis. Despite the biological functions of miR-144/451 have been extensively studied in erythropoiesis and tumorigenesis, few studies have been conducted in immune responses. In this study, we showed that miR-144/451-/- DCs exhibit increased activation. Mechanistically, the miR-144 directly targets the 3`-UTR of IRF5 and represses the expression of IRF5 in DCs. Ectopic expression of miR-144/451 by lentiviruses downregulates the levels of IRF5 and suppresses DCs function. In addition, knockdown of IRF5 by shRNA significantly inhibits activities of the miR-144/451-/- DCs. Expression of miR144/451 was decreased in DCs from both patients with IBD and mice with DSS-colitis compared with controls. Human PBMC derived DCs were downregulated expression of miR144/451 after LPS stimulation. In the DSS-induced colitis mice model, we showed that ablation of the miR-144/451 gene causes severe colitis, and their DCs from both periphery and MLN expressed higher co-stimulatory molecules and pro-inflammatory cytokines than wild-type mice. In addition, DCs isolated from miR-144/451-/- mice transfusion exacerbates mice colitis. In the bone marrow transplanted chimeric mice model, we show that miR-144/451-/- bone marrow transplantation deteriorated DSS-induced colitis. At last, we treat the mice with miR-144/451 delivered by chitosan nanoparticles revealing protective effects in DSS-induced colitis mice. Thus, our results reveal a novel miR144/451-IRF5 pathway in DCs that protects experimental colitis. The manipulation of miR-144/451 expression and DCs activation in IBD patients may be a novel therapeutic approach for the treatment of inflammatory diseases.
Case report: bullous pemphigoid development underlies dystrophic epidermolysis bullosa disease worsening
Authors: Di Zenzo Giovanni , Floriddia Giovanna , Rossi Sabrina , Mariotti Feliciana , Primerano Alessia , Condorelli Angelo Giuseppe , Didona Biagio , Castiglia Daniele
Published: July 2022

Autoimmune response to cutaneous basement membrane components superimposed on a genetic skin fragility disease, hereditary epidermolysis bullosa (EB), has been described, but its effects on disease course remain unclear. We report a 69-year-old individual with congenital skin fragility and acral trauma-induced blistering that had suddenly worsened with the onset of severe itch and diffuse spontaneous inflammatory blisters. Next-generation sequencing identified compound heterozygous null and missense COL7A1 mutations, allowing the diagnosis of recessive dystrophic EB. However, the patient’s clinical history prompted us to investigate whether he might have developed a pathological autoimmune response against basement membrane components. Tissue-bound and circulating IgG antibodies to the major bullous pemphigoid (BP) antigen, BP180, were detected in the patient’s skin and serum, respectively, consistent with a diagnosis of BP. Corticosteroid therapy was initiated resulting in remission of BP manifestations. EB patients presenting rapid disease worsening should be investigated for the development of a concomitant autoimmune blistering disease.
Mast cell tissue heterogeneity and specificity of immune cell recruitment
Authors: West Peter W. , Bulfone-Paus Silvia
Published: July 2022

Mast cells occupy a unique niche within tissues as long lived perpetrators of IgE mediated hypersensitivity and anaphylaxis, as well as other immune responses. However, mast cells are not identical in different tissues and the impact of this tissue heterogeneity on the interaction with other immune cells and on defined immune responses is still unclear. In this review, we synthesize the characteristics of mast cell heterogeneity in the gut and the skin. Furthermore, we attempt to connect mast cell heterogeneity with functional diversity by exploring differences in mast cell-induced immune cell recruitment in these two model organs. The differential expression of certain receptors on mast cells of different tissues, notably tissue-specific expression patterns of integrins, complement receptors and MRGPRX2, could indicate that tissue environment-dependent factors skew mast cell-immune cell interactions, for example by regulating the expression of these receptors.
Monoclonal antibodies effectively potentiate complement activation and phagocytosis of Staphylococcus epidermidis in neonatal human plasma
Authors: de Vor Lisanne , Beudeker Coco R. , Flier Anne , Scheepmaker Lisette M. , Aerts Piet C. , Vijlbrief Daniel C. , Bekker Mireille N. , Beurskens Frank J. , van Kessel Kok P. M. , de Haas Carla J. C. , Rooijakkers Suzan H. M. , van der Flier Michiel
Published: July 2022

Central line associated bloodstream infections (CLABSI) with Staphylococcus epidermidis are a major cause of morbidity in neonates, who have an increased risk of infection because of their immature immune system. As especially preterm neonates suffer from antibody deficiency, clinical studies into preventive therapies have thus far focused on antibody supplementation with pooled intravenous immunoglobulins from healthy donors (IVIG) but with little success. Here we study the potential of monoclonal antibodies (mAbs) against S. epidermidis to induce phagocytic killing by human neutrophils. Nine different mAbs recognizing Staphylococcal surface components were cloned and expressed as human IgG1s. In binding assays, clones rF1, CR5133 and CR6453 showed the strongest binding to S. epidermidis ATCC14990 and CR5133 and CR6453 bound the majority of clinical isolates from neonatal sepsis (19 out of 20). To study the immune-activating potential of rF1, CR5133 and CR6453, bacteria were opsonized with mAbs in the presence or absence of complement. We observed that activation of the complement system is essential to induce efficient phagocytosis of S. epidermidis. Complement activation and phagocytic killing could be enhanced by Fc-mutations that improve IgG1 hexamerization on cellular surfaces. Finally, we studied the ability of the mAbs to activate complement in r-Hirudin neonatal plasma conditions. We show that classical pathway complement activity in plasma isolated from neonatal cord blood is comparable to adult levels. Furthermore, mAbs could greatly enhance phagocytosis of S. epidermidis in neonatal plasma. Altogether, our findings provide insights that are crucial for optimizing anti-S. epidermidis mAbs as prophylactic agents for neonatal CLABSI.
The cancer-associated fibroblast-related signature predicts prognosis and indicates immune microenvironment infiltration in gastric cancer
Authors: Mak Tsz Kin , Li Xing , Huang Huaping , Wu Kaiming , Huang Zhijian , He Yulong , Zhang Changhua
Published: July 2022

Background

Gastric cancer (GC) is one of the most common cancers, with a wide range of symptoms and outcomes. Cancer-associated fibroblasts (CAFs) are newly identified in the tumor microenvironment (TME) and associated with GC progression, prognosis, and treatment response. A novel CAF-associated prognostic model is urgently needed to improve treatment strategies.

Methods

The detailed data of GC samples were downloaded from The Cancer Genome Atlas (TCGA), GSE62254, GSE26253, and GSE84437 datasets, then obtained 18 unique CAF-related genes from the research papers. Eight hundred eight individuals with GC were classified as TCGA or GSE84437 using consensus clustering by the selected CAF-related genes. The difference between the two subtypes revealed in this study was utilized to create the “CAF-related signature score” (CAFS-score) prognostic model and validated with the Gene Expression Omnibus (GEO) database.

Results

We identified two CAF subtypes characterized by high and low CAFS-score in this study. GC patients in the low CAFS-score group had a better OS than those in the high CAFS-score group, and the cancer-related malignant pathways were more active in the high CAFS-score group, compared to the low CAFS-score group. We found that there was more early TNM stage in the low CAFS-score subgroup, while there was more advanced TNM stage in the high CAFS-score subgroup. The expression of TMB was significantly higher in the low CAFS-score subgroup than in the high CAFS-score subgroup. A low CAFS-score was linked to increased microsatellite instability-high (MSI-H), mutation load, and immunological activation. Furthermore, the CAFS-score was linked to the cancer stem cell (CSC) index as well as chemotherapeutic treatment sensitivity. The patients in the high CAFS-score subgroup had significantly higher proportions of monocytes, M2 macrophages, and resting mast cells, while plasma cells and follicular helper T cells were more abundant in the low-risk subgroup. The CAFS-score was also highly correlated with the sensitivity of chemotherapeutic drugs. The low CAFS-score group was more likely to have an immune response and respond to immunotherapy. We developed a nomogram to improve the CAFS-clinical score’s usefulness.

Conclusion

The CAFS-score may have a significant role in the TME, clinicopathological characteristics, prognosis, CSC, MSI, and drug sensitivity, according to our investigation of CAFs in GC. We also analyzed the value of the CAFS-score in immune response and immunotherapy. This work provides a foundation for improving prognosis and responding to immunotherapy in patients with GC.
Air-Sea Trace Gas Fluxes: Direct and Indirect Measurements
Authors: Fairall Christopher W. , Yang Mingxi , Brumer Sophia E. , Blomquist Byron W. , Edson James B. , Zappa Christopher J. , Bariteau Ludovic , Pezoa Sergio , Bell Thomas G. , Saltzman Eric S.
Published: July 2022

The past decade has seen significant technological advance in the observation of trace gas fluxes over the open ocean, most notably CO2, but also an impressive list of other gases. Here we will emphasize flux observations from the air-side of the interface including both turbulent covariance (direct) and surface-layer similarity-based (indirect) bulk transfer velocity methods. Most applications of direct covariance observations have been from ships but recently work has intensified on buoy-based implementation. The principal use of direct methods is to quantify empirical coefficients in bulk estimates of the gas transfer velocity. Advances in direct measurements and some recent field programs that capture a considerable range of conditions with wind speeds exceeding 20 ms-1 are discussed. We use coincident direct flux measurements of CO2 and dimethylsulfide (DMS) to infer the scaling of interfacial viscous and bubble-mediated (whitecap driven) gas transfer mechanisms. This analysis suggests modest chemical enhancement of CO2 flux at low wind speed. We include some updates to the theoretical structure of bulk parameterizations (including chemical enhancement) as framed in the COAREG gas transfer algorithm.