bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abraham Maslow’s Notion of Self- Actualization in Philip Roth’s American Pastoral
Authors: Verma Manvi , Kaur Sukhvinder 
Published: October 2023

This article makes the argument more specifically on the humanistic psychology; a vibrant movement of the late 1950s; emphasizing the qualities, growth, need, creativity, and motivation of an individual. Philip Roth’s American Pastoral was an American classic, a novel of
American culture. It is not only a biography, but an intensive interpretation of the fall of American dream. The author demonstrates the American Pastoral from the humanistic point of view. This paper attempts to analyse the humanistic attitudes and values in the novel American Pastoral. The process from the basic to the being needs in the novel is being critically expressed within the framework of the humanistic psychology.
How to Achieve Profit Growth by Optimizing Operational Resources Based on Total Efficiency in Food and Beverage Companies in Indonesia
Authors: Suwardi  , Wibowo Kartiko Adi , Annisa Auliyana Yanuar 
Published: October 2023

This study aims to analyze resource optimization on the basis of total efficiency in achieving profit growth in manufacturing companies in Indonesia. Detailed investigations are empirically focused on external financing strategies and the effectiveness of asset management oriented on the basis of total efficiency to achieve profit growth.
This study uses a quantitative approach to the explanation of intermediation regression. With a total sample of 12 manufacturing companies in the national food and beverage sector for five years. Financial data analysis methods include descriptive analysis and inferential analysis.
The results of this study indicate that Profit Growth can only be significantly affected by Total Efficiency. Leverage is not able to significantly influence Total Efficiency, while Asset Management is able to significantly influence Total Efficiency. Intervening variable Total Efficiency is not able to mediate the relationship between Leverage on Profit Growth and Asset Management on Profit Growth.
The effect of anti-nerve growth factor monoclonal antibodies on the clinical signs of degenerative joint disease in cats
Authors: Seeley Lydia 
Published: October 2023

PICO Question
Are felinised anti-nerve growth factor monoclonal antibodies (frunevetmab) effective at reducing the clinical signs of pain and immobility in cats with degenerative joint disease when compared with no treatment?

Clinical bottom line
Category of research
Treatment.

Number and type of study designs reviewed
Three peer-reviewed randomised controlled trial treatment studies, two of which were pilot studies.

Strength of evidence
Moderate.

Outcomes reported
All three studies concluded that there was a statistical reduction in pain and an improvement in mobility in the groups administered frunevetmab, when compared to the groups administered the placebo.

Conclusion
There is moderate evidence suggesting that the administration of frunevetmab by injection led to a reduction in pain and an increase in mobility. Injections were given at day 0; day 0 and 28, or day 0, 28 and 56 depending on the study. Further research should be conducted to ensure repeatability, involving more objectively measured outcomes to reduce the reliance on subjective measures which are more likely to have associated bias.

How to apply this evidence in practice
The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources.
Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.
Öğretmenlerin Çocuklar İçin Felsefe (P4C) Eğitiminde Yaşadığı Sorunlar
Authors: KODAZ ÖCAL Nurten , AYBEK Birsel 
Published: October 2023

Çocuklar için felsefe üst düzey düşünme becerilerini geliştirme acısından önemli bir yaklaşım ve yöntemdir. Çocuklar için felsefeyi sınıflarında uygulayan öğretmenler, çocukların düşünme becerilerini geliştirdikleri, onları hayata hazırladığı, farklı fikirlere açık olmalarını sağladığı için felsefeyi önemli bulmakta ve öğrencilerinin gelecekte etkili bir vatandaş olmaları için bu uygulamaları sınıflarında yapmaktadırlar.
Öğretmenlerin çocuklar için felsefe uygulamalarına hazırlık ve uygulama aşamasında yaşadıkları sorunların belirlenmeye çalışıldığı bu çalışmaya farklı kademelerden 20 öğretmen katılmıştır. Nitel araştırma yönteminin kullanıldığı bu araştırmada öğretmenlerle görüşmeler gerçekleştirilmiş ve veriler içerik analizi ile çözümlenmiştir.
Araştırma sonucunda öğretmenlerin hazırlık aşamasında üst düzey düşünmeyi geliştirebilecek açık uçlu soruları hazırlama, uygun uyaran (hikaye, görsel, film vb.) ve tartışmaya konu olacak kavramı bulmada zorlandıkları görülmüştür. Öğretmenlerin okulların fiziki yapısı ile sınıfların kalabalık olmasından kaynaklı sorun yaşadıkları, çocuklar için felsefenin bir gereği olan çember düzenini oluşturamadıkları görülmüştür. Öğrencilerden kaynaklı ise ilgisiz olma, arkadaşlarını dinlememe, birbirlerinin fikirlerini sorgusuz kabul etme, motivasyon kaybı gibi durumlardan dolayı çocuklar için felsefe uygulamalarında sorunlar yaşadıkları tespit edilmiştir. Öğretmenler, bu sorunların başlangıçta yoğun olduğunu ancak zamanla sorunların üstesinden gelindiğini ifade etmişlerdir. Aynı zamanda öğretmenlerin öğretim programında Çocuklar için felsefeye uygun kazanım olmaması, öğretim programının bu tarz çalışmalara izin verecek esneklikte olmaması ve yoğun olması nedeniyle de sorunlar yaşadıkları belirlenmiştir. Çocuklar için felsefe öğrencilerin gelişimini desteklediği için bu uygulamalara yönelik eğitimleri Milli Eğitim Bakanlığı’nın hizmet içi eğitim olarak vermesinin gerekli olduğu görülmüştür.
GREK MİTOLOJİSİNDEKİ ÖGELERİN P4C UYGULAMALARINDA KULLANILABİLİRLİĞİ ÜZERİNE
Authors: HASANÇEBİ Arzu , NUYAN Elif 
Published: October 2023

Öz:
Bu makalede Çocuklar İçin Felsefe (P4C) uygulamalarında, Grek mitolojisindeki ögelerin birer uyaran olarak kullanılabilirliği tartışılacaktır. Lipman’ın geliştirmiş olduğu P4C pedagojisinin genel hedefi, eleştirel, sağduyulu ve etrafında olup bitenler karşısında bilinçli bireyler yetiştirmektir. Bugün dünyada altmıştan fazla ülkede uygulanan P4C eğitimi, çocukların daha küçük yaşlardan sorgulayıcı bir bakış açısı kazanmasını amaç edinmektedir. P4C uygulamaları, çocuklara doğrudan felsefe tarihi bilgisi aktarmadan, kavramlar üzerinde tartışabilmelerine imkan sunmaktadır. Geleneksel ve ezbere dayalı eğitim anlayışının dışına çıkılarak, çocukların başkalarını dinleyerek ve kendi argümanlarını kurarak iletişim becerilerinin gelişimine katkı sağlamaktadır. Uygulamalar sırasında çocukların düşünme becerilerini geliştirmek için kullanılan mateyaller uyaran olarak kabul edilmektedir. Düşünme sürecini harekete geçiren bu uyaranlar, hikaye, öykü, animasyon, afiş ya da kısa film gibi çeşitli malzemelerden oluşmaktadır. Grek mitolojisindeki hikayelerde anlatılan olayların ve kahramanların yaşantıları, P4C eğitiminin çocuklara tartıştırmak istediği değerler ve kavramlara zengin bir içerik sunmaktadır. Homeros anlatılarının ve Antik Yunan filozoflarının düşüncelerini açıklarken mitolojiye başvurmuş olması yadsınamaz. Mitolojik anlatıların Grek dünyasındaki yeri, hayati bir öneme sahiptir. Kendilerini ve evreni anlamlandırmaya çalışırken mitoslara başvurmuş olan Grekler, her ne kadar felsefenin doğuşuyla ilişkilenen, logosa geçişi gerçekleştirseler de tamamıyla mitoslardan kopmamışlardır. Hatta bugün bile sadece Grekler için günümüz dünyası için mitolojik kahramanlar, toplumsal yaşamın önemli bir parçasıdır. Edebiyat, sinema ve hatta bilimsel keşifler de bile Grek mitolojisine sıklıkla referanslar yapıldığını görmekteyiz. Bu açıdan, kavramsal düzeyde ontolojik, epistemolojik, estetik, etik veya politik tartışmaların birer destekçisi olarak mitoslara başvurulmuş olması şaşırtıcı değildir.

Anahtar Kelimeler: Felsefe, P4C, Mitos, Logos, Eleştirel düşünce, Grek mitolojisi
Parent-mediated interventions versus usual care in children with autism spectrum disorders. Protocol for a systematic review with meta-analysis and Trial Sequential Analysis
Authors: Conrad Charlotte Engberg , Ziegler Sonja Martha Teresa , Bilenberg Niels , Christiansen Jens , Fagerlund Birgitte , Hermann Rikke , Jeppesen Pia , Jørgensen Caroline Kamp , Thomsen Per Hove , Jakobsen Janus Christian , Lauritsen Marlene Briciet 
Published: October 2023

Abstract

Background
Autism spectrum disorder encompasses diverse patterns of social-communication and repetitive, restricted behaviours, and is associated with a higher risk of comorbid medical and psychiatric disorders. Various interventions have been developed to reduce the negative consequences of autism spectrum disorder and improve levels of functioning. Within different frameworks of interventions, there is increasing interest in parent-mediated interventions. This systematic review with meta-analysis aims to synthesise the current evidence of the effects, both positive and adverse, of parent-mediated interventions on younger children with autism spectrum disorder and their parents.
Methods
Electronic searches will be conducted in Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Latin American and Caribbean Health Sciences Literature (LILACS), American Psychological Association PsycInfo (PsycInfo), Science Citation Index Expanded (SCI-EXPANDED). Randomised clinical trials of parent-mediated interventions for children with autism and a control-group of usual care, waiting list or no treatment will be included. Two reviewers will independently screen, select and collect data. The methodological quality of the included studies will be evaluated using Cochrane methodology. The primary outcome will be autism symptom severity as measured by the Autism Diagnostic Observation Schedule (ADOS). Secondary outcomes will be adaptive functioning, adverse effects, child language, child socio-communicative symptoms, child´s quality of life and parental quality of life. The meta-analysis will be performed with Trial Sequential Analysis.
Discussion
This is the study protocol for a systematic review and meta-analysis of parent-mediated interventions versus usual care for children with autism spectrum disorder. The results of the review will inform clinicians and parents about the current evidence of the effects, both positive and adverse, of parent-mediated interventions on younger children with autism spectrum disorder and their parents, through improved methodology and the inclusion of new studies.
Protocol registration: PROSPERO 385188
Expression and Prognosis Analysis of TBX2 Subfamily in Human Lung Carcinoma
Authors: Mi Rui , Wang Qiubo , Liu Qingyang , Jiang Fengying , Ji Yuan 
Published: October 2023

Abstract
Purpose
Lung cancer has a high morbidity and mortality rate of all cancers worldwide. Therefore, there is an urgent need for reliable cancer markers for diagnosis and prognosis of patients with lung cancer.
Methods
In this study, we used the bioinformatics database to compare the expression of the TBX2 subfamily at the transcriptional and protein levels in non-small cell lung cancer. Then, to confirm our bioinformatics analysis above, we used western bloting to determine the expression of TBX2, TBX3, TBX4 and TBX5 in human lung squamous carcinoma cell lines. Besides, low expression of TBX2 subfamily predicted a poor prognosis of patients with lung cancer. Finally, The methylation database was used to explore the relationship between the low expression of TBX2 subfamily and methylation of gene promoter region.
Results
Our data showed a significant decrease of TBX2 subfamily expression in lung cancer tissues of several histological subtypes. Finally, the methylation of TBX2 subfamily members in the promoter region of NSCLC was significantly higher than that in normal tissues.
Conclusion
Our research provided sufficient evidence that TBX2 subfamily might play an inhibitory role in malignancy progression of lung cancer, which is promising to shed light on discovering a novel reliable cancer marker for prognosis of lung cancer patients.
Curriculum Implementation with a Plan: An Exploratory Analysis of Pre-service Teachers’ Application of Gagne’s Nine Events of Instruction
Authors: Mahama Inuusah 
Published: October 2023

Abstract

This study explored Ghanaian pre-service teachers’ application of Gagne’s instructional design. A sample of 135 pre-service teachers on internship at different pre-tertiary institutions participated by responding to Gagne’s nine events of instruction. The data were analysed descriptively (means/SD) and inferentially (MANOVA). The study revealed that pre-service teachers seem to be more aligned with traditional and less student-centred approaches. The findings suggest a lack of emphasis on strategies that promote active engagement, clear communication of objectives, building on prior knowledge, diverse content presentation, guidance and support, eliciting performance through practice, effective feedback, and enhancing retention and transfer. However, there were no substantial gender- or level-based differences in the application of the instructional model. Therefore, training programmes for teachers should be student-centred and highlight the benefits of connecting new information to familiar concepts for better comprehension.
An integrative single-cell multi-omics profiling of human pancreatic islets identifies T1D associated genes and regulatory signals
Authors: Chen Shuibing , Zhao Zeping , Albanus Ricardo D'Oliveira , Taylor Henry , Tang Xuming , Han Yuling , Orchard Peter , Varshney Arushi , Zhang Tuo , Manickam Nandini , Erdos Michael , Narisu Narisu , Taylor D. Leland , Saavedra Xiaxia , Zhong Aaron , Li Bo , Zhou Ting , Naji Ali , Liu Chengyang , Collins Francis , Parker Stephen 
Published: October 2023

Abstract
Genome wide association studies (GWAS) have identified over 100 signals associated with type 1 diabetes (T1D). However, translating any given T1D GWAS signal into mechanistic insights, such as causal variants, their target genes, and the specific cell types involved, has been challenging. Here, we present a comprehensive multi-omic integrative analysis of single-cell/nucleus resolution profiles of gene expression and chromatin accessibility in healthy and autoantibody+ (AAB+) human pancreatic islets, and islets under T1D-stimulating conditions. We nominate effector cell types for all T1D GWAS signals and the regulatory elements and genes for three independent T1D risk variants acting through β cells at the DLK1/MEG3, RASGRP1, and TOX loci. Subsequently, we validated the functional impact of these genes and regulatory regions using isogenic human embryonic stem cells (hESCs) and found that loss of RASGRP1 or DLK1, as well as disruption of their regulatory regions, led to increased β cell apoptosis. Furthermore, β cells derived from isogenic hESCs carrying the T1D risk allele of rs3783355 associated with DLK1 showed elevated β cell death. Through RNA-seq and ATAC-seq analyses, we identified five genes upregulated in both RASGRP1-/- and DLK1-/- β-like cells, four of which are associated with T1D. This integrative approach combining single-cell multi-omics, GWAS, and isogenic hPSC-derived β-like cells illuminates cell type context, genes, single nucleotide polymorphisms (SNPs), and regulatory elements underlying T1D-associated signals, providing insights into the biological functions and molecular mechanisms involved.
Good Statistical Practice - Good Clinical Practice for Statisticians
Authors: Stocken Deborah D , Mossop Helen , Armstrong Emma , Lewis Steff , Dutton Susan J , Peckitt Claire , Gamble Carrol , Brown Julia MB 
Published: October 2023

Abstract
Background Statisticians are fundamental in ensuring clinical research, including clinical trials, are conducted with quality, transparency, reproducibility and integrity. Good Clinical Practice (GCP) is an international quality standard for the conduct of clinical trials research. Statisticians are required to undertake training on GCP but existing training is generic and, crucially, does not cover statistical activities. This results in statisticians undertaking training mostly unrelated to their role and variation in awareness and implementation of relevant regulatory requirements with regards to statistical conduct. The need for role-relevant training is recognised by the NHS Health Research Authority and the Medicines and Healthcare products Regulatory Agency (MHRA).Methods The Good Statistical Practice (GCP for Statisticians) project was instigated by the UK Clinical Research Collaboration (UKCRC) Registered Clinical Trials Unit (CTU) Statisticians Operational Group and funded by the National Institute for Health and Care Research (NIHR), to develop materials to enable role-specific GCP training tailored to statisticians. Training materials have been developed based on MHRA GCP and cover legislation and guidance for best practice across all clinical trial processes with statistical involvement, incorporating existing UKCRC guidance on analysis plans, validation of statistical programming and data sharing. The training has been developed to include exercises and real-life scenarios to bridge the gap between theory and practice. Comprehensive feedback from pilot work with UKCRC CTU and NIHR Statisticians has been incorporated.Results An accessible, comprehensive, piloted training package has been developed tailored to statisticians working in clinical research, particularly the clinical trials arena. The training is freely available for national and international adoption.Conclusion All research staff should have training in GCP yet the training undertaken by most academic statisticians is generic and does not cover activities related to their role. The Good Statistical Practice (GCP for Statisticians) project has developed and extensively piloted new, role-specific, comprehensive, accessible GCP training tailored to statisticians working in clinical research, particularly the clinical trials arena. This role-specific training will encourage best practice, leading to transparent and reproducible statistical activity, as required by regulatory authorities and funders.
A Scan of Pleiotropic Immune Mediated Disease Genes Identifies Novel Determinants of Baseline FVIII Inhibitor Status in Hemophilia-A
Authors: Howard Tom , Almieda Marcio , Diego Vincent , Viel Kevin , Luu Bernadette , Haack Karin , Raja Rajalingam , Ameri Afshin , Chitlur Meera , Rydz Natalia , Lillicrap David , Watts Raymond , Kessler Craig , Ramsey Christopher , Dinh Long , Kim Benjamin , Powell Jerry , Peralta Juan , Bouls Ruayda , Abraham Shirley , Shen Yu-Min , Murillo Carlos , Mead Henry , Lehmann Paul , Fine Eli , Escobar Miguel , Kumar Satish , Williams-Blangero Sarah , Kasper Carol , Almasy Laura , Cole Shelley , Blangero John , Konkle Barbara 
Published: October 2023

Abstract
Hemophilia-A (HA) is caused by heterogeneous loss-of-function factor (F)VIII gene (F8)-mutations and deficiencies in plasma-FVIII-activity that impair intrinsic-pathway-mediated coagulation-amplification. The standard-of-care for severe-HA-patients is regular infusions of therapeutic-FVIII-proteins (tFVIIIs) but ~30% develop neutralizing-tFVIII-antibodies called “FVIII-inhibitors (FEIs)” and become refractory. We used the PATH study and ImmunoChip to scan immune-mediated-disease (IMD)-genes for novel and/or replicated genomic-sequence-variations associated with baseline-FEI-status while accounting for non-independence of data due to genetic-relatedness and F8-mutational-heterogeneity. The baseline-FEI-status of 450 North American PATH subjects—206 with black-African-ancestry and 244 with white-European-ancestry—was the dependent variable. The F8-mutation-data and a genetic-relatedness matrix were incorporated into a binary linear-mixed model of genetic association with baseline-FEI-status. We adopted a gene-centric-association-strategy to scan, as candidates, pleiotropic-IMD-genes implicated in the development of either ³2 autoimmune-/autoinflammatory-disorders (AADs) or ³1 AAD and FEIs. Baseline-FEI-status was significantly associated with SNPs assigned to NOS2A (rs117382854; p=3.2E-6) and B3GNT2 (rs10176009; p=5.1E-6), which have functions in anti-microbial-/-tumoral-immunity. Among IMD-genes implicated in FEI-risk previously, we identified strong associations with CTLA4 assigned SNPs (p=2.2E-5). The F8-mutation-effect underlies ~15% of the total heritability for baseline-FEI-status. Additive genetic heritability and SNPs in IMD-genes account for >50% of the patient-specific variability in baseline-FEI-status. Race is a significant determinant independent of F8‑mutation-effects and non-F8-genetics.
Therapeutic Intervention of Neuroinflammatory Alzheimer Disease Model by Inhibition of Classical Complement Pathway with the Use of Anti-C1r Loaded Exosomes
Authors: Richards Terjahna , Perron Jeanette C. , Patel Ketan , Wurpel John , Reznik Sandra E. , Schanne Francis 
Published: October 2023

Abstract

Alzheimer’s disease (AD) is a complex neurodegenerative disease associated with memory decline, cognitive impairment, amyloid plaque formation and tau tangles. Neuroinflammation has been shown to be a precursor to apparent amyloid plaque accumulation and subsequent synaptic loss and cognitive decline. In this study, the ability of a novel, small molecule, T-ALZ01, to inhibit neuroinflammatory processes was analyzed. T-ALZ01, an inhibitor of complement component C1r, demonstrated a significant reduction in the levels of the inflammatory cytokines, IL-6 and TNF-α in vitro. An LPS-induced animal model, whereby animals were injected intraperitoneally with 0.5 mg/kg LPS, was used to analyze the effect of T-ALZ01 on neuroinflammation in vivo. Moreover, exosomes (nanosized, endogenous extracellular vehicles) were used as drug delivery vehicles to facilitate intranasal administration of T-ALZ01 across the blood-brain barrier. T-ALZ01 demonstrated significant reduction in degenerating neurons and the activation of resident microglia and astrocytes, as well as inflammatory markers in vivo. This study demonstrates a significant use of small molecule complement inhibitors via exosome drug delivery as a possible therapeutic in disorders characterized by neuroinflammation, such AD.