bluuebunny/crossref_metadata_2025 huggingface dataset:
New medicines in primary care: perspectives and practices of healthcare professionals
Authors:   , Dankers Marloes
Published: July 2024

Rational use of new medicines is important, both in terms of quality of care and healthcare costs. We have studied the perspectives and practices of primary care healthcare professionals towards new medicines, divided into three subtopics: •Preferences of healthcare professionals for endpoints and cutoff values for clinical relevance in the evaluation of new medicines. Healthcare professionals are more strict than official organisations. A medicine that is considered clinically relevant by official organisations does therefore not necessarily reflect healthcare professionals’ perspectives on clinical relevance. •Factors influencing the decision to prescribe new medicines. The attitude of healthcare professionals towards new medicines is important, and the pharmaceutical industry tries to influence this attitude. •Prescription patterns of new medicines. Large variation between general practices exists. These differences cannot be explained by different patient or practice characteristics. We draw two important conclusions: 1.The uptake of new medicines in primary care is not easy to predict. Prescription patterns vary among new medicines, and the prescription of new medicines cannot be adequately explained by differences between patients and practices. No association between the prescription of different groups of new medicines exists. 2.Scientific evidence plays a limited role in the decision of healthcare providers to prescribe new medicines. Healthcare providers experience difficulties in interpreting and estimating realistic benefits and risks of new medicines. Individual attitudes of healthcare professionals are important in the decision to prescribe new medicines. The pharmaceutical industry influences decisions with various strategies.
Measuring the Level of Public Service Quality Using SERVQUAL Method in Gayungan Village, Surabaya City
Authors: Widianto Hendrawan , Zunaidi Rizqa Amelia
Published: July 2024

Kelurahan (village office) is the working area of lurah (village head), serving as a regional apparatus for developing economic facilities and public services. In this context, Gayungan Village has many problems arising from public opinion related to population registration, the need for correspondence, and the management of social assistance. Therefore, this research aimed to measure the level of public service quality as an evaluation material focused on tangibility, reliability, responsibility, assurance, and empathy dimensions. A quantitative analysis was adopted using service quality (servqual) method. The results showed that there was a discrepancy between expectations and reality in all dimensions. Tangibility, reliability, responsibility, assurance, and empathy dimensions obtained a gap value of -0.91, -1.06, -1.16, -1.04, and -0.88, respectively. Meanwhile, the improvement of public service quality should be carried out to appropriately meet the wishes and needs of the public.
PENDAMPINGAN MAHASISWA PROGRAM KAMPUS MENGAJAR ANGKATAN 7 DALAM UPAYA PENINGKATAN KEMAMPUAN LITERASI DAN NUMERASI DI SDN 3 REJOTANGAN KABUPATEN TULUNGAGUNG
Authors: Maskur Maskur , Prastika Aprilia Indi , Noormasari Audrey Berlian , Saputri Lina Gustaria Fillinanti Diah , Ammalyah Puput
Published: July 2024

The Campus Teaching Batch 7 program aims to improve students' literacy and numeracy skills through student mentoring at SDN 3 Rejotangan, Tulungagung Regency. This activity examines the effectiveness of the mentoring program in overcoming the problem of low student literacy and numeracy skills. The methods used are observation, interviews, and pre- and post-assistance tests to measure changes in students' abilities. The results show that there is a significant improvement in students' literacy and numeracy skills after receiving intensive assistance from students. This program also had a positive impact on students' learning motivation, as seen from the increased participation and enthusiasm of students in learning activities. The mentoring students acted as facilitators, providing interesting and relevant materials, and using interactive and fun learning methods. In addition, the collaboration between student assistants, teachers, and parents also supports the success of this program. Student assistance in the Teaching Campus Program Batch 7 is effective in improving students' literacy and numeracy skills at SDN 3 Rejotangan. Recommendations are given to develop similar programs in other schools to improve the quality of basic education in Indonesia.
Standards Information System for CLARIN centres and beyond
Authors: Ba´nski Piotr , Illig Eliza Margaretha
Published: July 2024

The present contribution describes features of the CLARIN Standards Information System that have been designed to assist data deposition centres in CLARIN. We also show what is needed and what has been done in order to go beyond the originally designated target, so as to provide service to sibling and descendant research infrastructures, of which DARIAH and Text+ are taken as examples. This paper is aimed primarily at representatives of research infrastructure nodes, responsible for preparing and sharing data deposition information about their centres or repositories. It assumes a degree of technical knowledge or experience in using the XML format and tools, the REST API, and version control systems.
Domain-Specific Languages for Epigraphy: the Case of ItAnt
Authors: Boschetti Federico , Rigobianco Luca , Quochi Valeria
Published: July 2024

This contribution illustrates how the definition of a Domain-Specific Language can support the activities of epigraphists and historical linguists. It presents and discusses a method and technological solution, based on Domain-Specific Languages, for facilitating scholars in digitally representing the available knowledge of archaic languages and cultures. This is achieved by increasing the human readability of the encoded data without sacrificing compliance with standard models and formats. The work is framed within the context of an Italian National collaborative research project devoted to the study of the languages and cultures of ancient Italy. The platform developed within this project offers an interesting use case and motivation for experimenting with Domain-Specific Languages for the creation of necessary digital critical editions of the inscriptions relevant for these languages. After explaining the definition process of the DSL grammar, we finally test the applicability of the DSL grammar to five example inscriptions in the Faliscan language.
MWE-Finder: An evaluation through three case studies
Authors: Kroon Martin , Odijk Jan
Published: July 2024

In this paper we showcase and evaluate MWE-Finder, a system that allows users to search for occurrences of an MWE in a large Dutch text corpus. To this end, we conduct three small case studies, and discuss the results in detail. We make use of the MWEs 0geen *+haan zal naar iets kraaien ‘no one will say anything about something’, iemand zal 0dat *+varken wassen ‘someone will deal with that problem’ and iemand zal iemand het hemd van het lijf vragen ‘someone will want to know all the ins and outs of something from someone’, which are all in canonical form following Odijk (2023) and Odijk and Kroon (2024).
The results show that MWE-Finder is very accurate in retrieving the target MWEs, reaching an accuracy of 93.7%, and an F1-score of 95.2%. The case studies additionally lay bare points of improvement of MWE-Finder, specifically concerning the enrichment of syntactic parses by making the object relation explicit in certain constructions.
UPAYA KEJAKSAAN MEMBERIKAN KEADILAN RESTORATIF TERHADAP TINDAK PIDANA
Authors: Svinarky Irene , Jamba Padrisan
Published: July 2024

Di dalam kehidupan manusia pasti ditemui kegiatan yang berkaitan dengan hukum baik yang sengaja dilakukan maupun yang tidak sengaja dilakukan. Apabila terjadi masalah hukum pidana, tidak semua yang diselesaikan sampai ke tahapan pengadilan, karena ada upaya hukum lain yang disebut dengan  Restorative Justice (RJ), baik di tingkat kepolisian ataupun kejaksaan. RJ ini disepakati untuk dilaksanakan, agar membantu masyarakat yang tersangkut masalah pidana dapat menyelesaiakan masalahnya tanpa harus menempuh proses panjang, tetapi yang perlu diingat tidak semua perkara pidana yang dapat diberikan rj. Oleh sebab itu, dengan keluarnya Perja No 15/2020, maka rj untuk perkara tertentu dapat membantu JPU dalam menghentikan penuntutan terhadap terdakwa. Tujuannya penelitian ini adalah: Untuk mengetahui upaya yang dilakukan oleh kejaksaan dalam memberikan rj terhadap tindak pidana yang dilakukan oleh masyarakat bermasalah. Penelitian ini dilakukan di Kejaksaan Kota Batam; Hasil penelitian yang penulis dapat bahas dalam upaya kejaksaan memberikan rj adalah: Kejaksaan memberikan rj kepada masyarakat dengan beberapa perkara saja yang sesuai dengan Perja Nomor 15/2020, karena tidak semua perkara yang dapat diberikan rj, namun pemberian rj ini juga menelaah beberapa faktor yang dapat dijadikan pertimbangan sesuai dengan aturan kejaksaan yang berlaku.
URGENSI PELAKSANAAN PERATURAN PEMERINTAH NO. 22 TAHUN 2021 KAITANNYA DENGAN PENGATURAN PENGELOLAAN LINGKUNGAN HIDUP DI KOTA BATAM
Authors: Ukas Ukas
Published: July 2024

Hukum Lingkungan, Bentuk Pengaturan, Pengelolaan dan Pemanfaatan lingkungan hidup baik berdasarkan UUPPLH secara umum pengaturannya secara khusus seperti Peraturan Pemerintah Nomor 22 Tahun 2021. memberikan manfaat dan atau pemanfaatan lingkungan hidup jika direncanakan penuh kebijakan yang ada. Berbicara dan memahami lingkungan hidup akan memberikan makana yang berbeda-beda berdasarkan sudut pandangan dari objek lingkungan hidup itu sendiri, namun tetap bermuara pada pengaturan, pengelolaan dan pemanfaatan lingkunga hidup. Pengelolaan lingkungan hidup itu dalam arti pengembangan yang akan datang perlunya memiliki  perencanaan dan atau direncanakan agar menjadi lingkungan yang berwawasan searah dengan pembangunan lingkungan itu sendiri. Benntuk pengelolaan lingkungan terpadu, perlindungan lingkungan, tujuan pengelolaan lingkungan hidup serta menciptakan mutu lingkungan yang lebih baik. Peraturan Pemerintah Nomor 22 Tahun 2021, mengikuti perkembangan pembangunan wawasan lingkungan dan dinamika perkembangan pembangunan ekonomi serta kemajemukan masyarakat. Harapan akan hak-hak masyarakat menikmati lingkungan yang bersih sehat merupakan tujuan akhir dari Peraturan Pemerintah tersebut.
Preliminary osteogenic and antibacterial investigations of wood derived antibiotic-loaded bone substitute for the treatment of infected bone defects
Authors: Salamanna Francesca , De Luca Angela , Vandenbulcke Filippo , Di Matteo Berardo , Kon Elizaveta , Grassi Alberto , Ballardini Alberto , Morozzi Giacomo , Raimondi Lavinia , Bellavia Daniele , Costa Viviana , Zaffagnini Stefano , Fini Milena , Giavaresi Gianluca
Published: July 2024

Introduction: The development of reliable treatments for infected or potentially infected bone loss resulting from open fractures and non-unions is extremely urgent, especially to reduce the prolonged courses of antimicrobial therapy to which affected patients are subjected. Numerous bone graft substitutes have been used over the years, but there are currently no effective solutions to treat critical bone loss, especially in the presence of infection. The present study evaluated the use of the biomorphic calcium phosphate bone scaffold b. Bone™, based on a next-generation resorbable biomimetic biomaterial, in bone reconstruction surgery in cases of infection.

Methods: Using an “in vitro 3D bone fracture model” to predict the behavior of this drug delivery system during critical bone loss at an infected (or potentially infected) site, the effects of scaffolds loaded with gentamicin or vancomycin on the viability and differentiation capacity of human mesenchymal stem cells (hMSCs) were evaluated.

Results: This scaffold, when loaded with gentamicin or vancomycin, exhibits a typical drug release curve that determines the inhibitory effects on the growth of Staphylococcus aureus, Enterococcus faecalis, and Escherichia coli, as well as relative biofilm formation.

Discussion: The study demonstrates that b.bone scaffolds can effectively address key challenges in orthopedic surgery and patient care by inhibiting bacterial growth and biofilm formation through rapid, potent antibiotic release, reducing the risk of treatment failure due to resistance, and providing a promising solution for bone infections and improved patient outcomes. Future studies could explore the combination of different antibiotics on these scaffolds for more tailored and effective treatments against post-traumatic osteomyelitis pathogens.
Unraveling the modulatory manner and function of circRNAs in the Asian honey bee larval guts
Authors: Gao Xuze , Zang He , Liu Xiaoyu , Guo Sijia , Ye Daoyou , Liu Zhitan , Jing Xin , Niu Qingsheng , Wu Ying , Lü Yang , Chen Dafu , Guo Rui
Published: July 2024

Circular RNAs (circRNAs) are a class of non-coding RNAs (ncRNAs) that can participate in biological processes such as gene expression, growth, and development. However, little has been explored about the function of circRNAs in the development of Apis cerana larval guts. By using our previously gained deep sequencing data from the guts of A. cerana worker larvae at 4-, 5-, and 6-day-old (Ac4, Ac5, and Ac6 groups), the expression pattern and regulatory role of circular RNAs (circRNAs) during the development process was comprehensively investigated, with a focus on differentially expressed circRNAs (DEcircRNAs) relevant to immunity pathways and developmental signaling pathways, followed by validation of the binding relationships among a key competing endogenous RNA (ceRNA) axis. Here, 224 (158) DEcircRNAs were detected in the Ac4 vs. Ac5 (Ac5 vs. Ac6) comparison group. It’s suggested that 172 (123) parental genes of DEcircRNAs were involved in 26 (20) GO terms such as developmental process and metabolic process and 138 (136) KEGG pathways like Hippo and Wnt signaling pathways. Additionally, ceRNA network analysis indicated that 21 (11) DEcircRNAs could target seven (three) DEmiRNAs, further targeting 324 (198) DEmRNAs. These DEmRNAs can be annotated to 33 (26) GO terms and 168 (200) KEGG pathways, including 12 (16) cellular and humoral immune pathways (endocytosis, lysosome, Jak-STAT, etc.) and 10 (nine) developmental signaling pathways (Hippo, mTOR, Hedgehog, etc.). Interestingly, DEcircRNAs in these two comparison groups could target the same ace-miR-6001-y, forming complex sub-networks. The results of PCR and Sanger sequencing confirmed the back-splicing sites within four randomly selected DEcircRNAs. RT-qPCR detection of these four DEcircRNAs verified the reliability of the used transcriptome data. The results of dual-luciferase reporter assay verified the binding relationships between novel_circ_001627 and ace-miR-6001-y and between ace-miR-6001-y and apterous-like. Our data demonstrated that DEcircRNAs were likely to modulate the developmental process of the A. cerana worker larval guts via regulation of parental gene transcription and ceRNA network, and novel_circ_001627/ace-miR-6001-y/apterous-like was a potential regulatory axis in the larval gut development. Findings from this work offer a basis and a candidate ceRNA axis for illustrating the circRNA-modulated mechanisms underlying the A. cerana larval guts.
First-principles study of the structure, magnetism, and electronic properties of the all-Heusler alloy Co2MnGe/CoTiMnGe(100) heterojunction
Authors: He Jianqiao , Huang Haishen , Wu Bo , Shen Guangxian , Zhou Tingyan , Gu Yuxin , Wen Lin , Zhang Qingqing
Published: July 2024

Based on first-principles calculations in the density functional theory, we systematically investigated the possible interface structure, magnetism, and electronic properties of the all-Heusler alloy Co2MnGe/CoTiMnGe(100) heterojunction. The calculation indicated that the Co2MnGe Heusler alloy is a half-metal with a magnetic moment of 4.97 μB. CoTiMnGe is a narrow-band gap semiconductor and may act as an ultra-sensitive photocatalyst. We cannot find an “ideal” spin-polarization of 100% in CoCo termination and MnGe termination. Due to the interface interaction, the direct magnetic hybridization or indirect RKKY exchange will be weakened, leading to an increase in the atomic magnetic moment of the interfacial layer. For eight possible heterojunction structures, the half-metallic gaps in the Co2MnGe bulk have been destroyed by the inevitable interface states. The spin-polarization value of 94.31% in the CoCo-TiGe-B heterojunction revealed that it is the most stable structure. It is feasible to search for high-performance magnetic tunnel junction by artificially constructing suitable all-Heusler alloy heterojunctions.
English as a lingua franca in interpreting and translation: a survey of practitioners
Authors: Albl-Mikasa Michaela , Ehrensberger-Dow Maureen , Gieshoff Anne Catherine , Hunziker Heeb Andrea
Published: July 2024

Over the last few decades, the English language has become prevalent throughout the world in the domains of international diplomacy, business, research, and technology and is becoming increasingly important in many other areas. Much research into the use of English as alingua francahas focused on its role in fostering communication across linguistic and cultural boundaries. Recently, however, concerns have been raised about the additional cognitive load that having to function in a non-native language can place on interlocutors. In an international survey, 883 professional language mediators (i.e., translators, conference interpreters, and community interpreters) provided details about their experiences dealing with the English produced by native vs. non-native speakers and identified features and difficulties associated with processing the respective input as well as their coping strategies. Although they acknowledged that both native and non-native speakers produce English that is difficult to deal with, the language mediators largely agreed that the latter were much more likely to do so, with vocabulary use, word choices, and sentence structures identified as particularly problematic. The main coping strategies for all three groups were to really concentrate on the message being conveyed, try to improve the formulation of it for the target audience, and intervene in the communication situation for clarification if possible. Self-regulation and reliance on information external to the situation were also mentioned as very important. Although almost half of the participants said that they preferred to work with native speaker produced output, many expressed no preference. The study results have important implications for various situations involving non-native speakers of the language being used for communication.
Application of optical coherence tomography in cardiovascular diseases: bibliometric and meta-analysis
Authors: Lian Wenjing , Chen Cong , Wang Jie , Li Jun , Liu Chao , Zhu Xueying
Published: July 2024

Significance

Since the advent of Optical Coherence Tomography (OCT) two decades ago, there has been substantial advancement in our understanding of intravascular biology. Identifying culprit lesion pathology through OCT could precipitate a paradigm shift in the treatment of patients with Acute Coronary Syndrome. Given the technical prowess of OCT in the realm of cardiology, bibliometric analysis can reveal trends and research focal points in the application of OCT for cardiovascular diseases. Concurrently, meta-analyses provide a more comprehensive evidentiary base, supporting the clinical efficacy of OCT-guided Percutaneous Coronary Intervention (PCI).

Design

This study employs a dual approach of Bibliometric and Meta-analysis.

Methods

Relevant literature from 2003 to 2023 was extracted from the Web of Science Core Collection (WoSCC) and analyzed using VOSviewer, CiteSpace, and R for publication patterns, countries, institutions, authors, and research hotspots. The study compares OCT-guided and coronary angiography-guided PCI in treating adult coronary artery disease through randomized controlled trials (RCTs) and observational studies. The study has been reported in the line with PRISMA and AMSTAR Guidelines.

Results

Adhering to inclusion and exclusion criteria, 310 publications were incorporated, demonstrating a continual rise in annual output. Chinese researchers contributed the most studies, while American research wielded greater influence. Analysis of trends indicated that research on OCT and angiography-guided PCI has become a focal topic in recent cohort studies and RCTs. In 11 RCTs (n = 5,277), OCT-guided PCI was not significantly associated with a reduction in the risk of Major Adverse Cardiac Events (MACE) (Odds ratio 0.84, 95% CI 0.65–1.10), cardiac death (0.61, 0.36–1.02), all-cause death (0.7, 0.49–1.02), myocardial infarction (MI) (0.88, 0.69–1.13), target lesion revascularization (TLR) (0.94, 0.7–1.27), target vessel revascularization (TVR) (1.04, 0.76–1.43), or stent thrombosis (0.72, 0.38–1.38). However, in 7 observational studies (n = 4,514), OCT-guided PCI was associated with a reduced risk of MACE (0.66, 0.48–0.91) and TLR (0.39, 0.22–0.68).

Conclusion

Our comprehensive review of OCT in cardiovascular disease literature from 2004 to 2023, encompassing country and institutional origins, authors, and publishing journals, suggests that OCT-guided PCI does not demonstrate significant clinical benefits in RCTs. Nevertheless, pooled results from observational studies indicate a reduction in MACE and TLR.
Numerical simulation method of the failure behavior of the UMo-Al monolithic fuel element
Authors: Zheng Zhifeng , Peng Shinian , Liu Yu , Wu Xiaoli , Sun Hongping , Xin Yong , Deng Jian
Published: July 2024

The UMo-Al monolithic fuel element has a special failure mode of blistering on the cladding surface under high temperature and high burn-up conditions. In order to provide an auxiliary means for the safety analysis and failure limit formulation of the fuel element, this study establishes a numerical simulation method of fuel failure behavior, considering the fracture behavior and the fission gas pressure acting on the cracks for the UMo-Al monolithic fuel element. Numerical simulation is based on ABAQUS software and the extended finite element method (XFEM) established by programming FORTRAN subroutines UMAT, UMATHT, and UAMP and using the thermo-mechanical sequential coupling method. Combined with Python to secondary develop ABAQUS with the FORTRAN subroutine, this study realizes the coupling of fission gas pressure load and crack propagation. This study obtained the failure threshold temperature, blistering height, area, and other blistering characteristics of the UMo-Al monolithic fuel element through numerical simulation of annealing experiments on L1P460 in RERTR-12. A comparison of the numerical simulation results with the RERTR-12 experiment shows that the method established in this study can effectively analyze blistering failures.
A new transient phenomenon caused by active current dynamics of grid-following converters during severe grid faults
Authors: Wu Chao , Huang Zhanqi , Wang Yong , Blaabjerg Frede
Published: July 2024

Existing transient stability analysis of grid-following (GFL) converters mainly focuses on the dynamics of the phase-locked loop (PLL), while current loop dynamics are usually neglected due to their faster response than PLL. However, this article reveals that active current may not be able to track its reference quickly during severe grid faults even with high current loop bandwidth, which leads to a non-negligible impact on the transient stability of GFL converters. Furthermore, this article discusses the intrinsic mechanism of why active current cannot track its reference quickly during severe grid faults and establishes a refined third-order transient synchronization model that offers a more accurate assessment of transient stability during severe grid faults than the conventional second-order model.
Estimation of water quality in Korattur Lake, Chennai, India, using Bayesian optimization and machine learning
Authors: Zeng Lingze
Published: July 2024

Assessing water quality becomes imperative to facilitate informed decision-making concerning the availability and accessibility of water resources in Korattur Lake, Chennai, India, which has been adversely affected by human actions. Although numerous state-of-the-art studies have made significant advancements in water quality classification, conventional methods for training machine learning model parameters still require substantial human and material resources. Hence, this study employs stochastic gradient descent (SGD), adaptive boosting (AdaBoosting), Perceptron, and artificial neural network algorithms to classify water quality categories as these well-established methods, combined with Bayesian optimization for hyperparameter tuning, provide a robust framework to demonstrate significant performance enhancements in water quality classification. The input features for model training from 2010 to 2019 comprise water parameters such as pH, phosphate, total dissolved solids (TDS), turbidity, nitrate, iron, chlorides, sodium, and chemical oxygen demand (COD). Bayesian optimization is employed to dynamically tune the hyperparameters of different machine learning algorithms and select the optimal algorithms with the best performance. Comparing the performance of different algorithms, AdaBoosting exhibits the highest performance in water quality level classification, as indicated by its superior accuracy (100%), precision (100%), recall (100%), and F1 score (100%). The top four important factors for water quality level classification are COD (0.684), phosphate (0.119), iron (0.112), and TDS (0.084). Additionally, variations or changes in phosphate levels are likely to coincide with similar variations in TDS levels.
Older age is associated with a distinct and marked reduction of functionality of both alloreactive CD4+ and CD8+ T cells
Authors: Litjens Nicolle H. R. , van der List Amy C. J. , Klepper Mariska , Reijerkerk Derek , Prevoo Fréderique , Betjes Michiel G. H.
Published: July 2024

Introduction

Older recipient age is associated with a significant decreased risk for rejection after kidney transplantation which is incompletely understood.

Methods

In a longitudinal study, circulating alloreactive T cells were assessed of young (≤45 years) and older (≥55 years) stable kidney transplant recipients. Alloreactive T-cells were identified by CD137-expression and phenotype, cytokine producing and proliferative capacity, were evaluated using multiparameter flowcytometry.

Results

The results show that before transplantation frequencies of alloreactive CD4+ and CD8+ T-cells in older KT-recipients are significantly higher and shifted towards an effector memory-phenotype. However, the frequency of polyfunctional (≥2 pro-inflammatory cytokines) CD4+ T-cells was significantly lower and less IL2 was produced. The frequency of polyfunctional alloreactive CD4+ T-cells and proliferation of alloreactive T-cells donor-specifically declined after transplantation reaching a nadir at 12 months after transplantation, irrespective of age. A striking difference was observed for the proliferative response of alloreactive CD8+ T-cells. This was not only lower in older compared to younger recipients but could also not be restored by exogenous IL2 or IL15 in the majority of older recipients while the response to polyclonal stimulation was unaffected.

Conclusion

In conclusion, older age is associated with a distinct and marked reduction of functionality of both alloreactive CD4+ and CD8+ T-cells.
Successfully treated with siltuximab and prednisone in a 7-year-old girl with DOCK8-deficiency presenting as recurrent wart-like lesions: a case report
Authors: Sun Zhe , Wei Ruoqu , Pan Chaolan , Ni Cheng , Zhang Xue , Guan Wenbin , Cheng Ruhong , Gu Yan , Yu Hong , He Kejun , Zhang Zhen , Yu Xia , Yao Zhirong
Published: July 2024

Dedicator of cytokinesis 8 (DOCK8) deficiency represents a primary immunodeficiency with a wide range of clinical symptoms, including recurrent infections, atopy, and increased malignancy risk. This study presents a case of a 6-year-old girl with DOCK8 deficiency, characterized by severe, treatment-resistant herpetic infections who was successfully treated with siltuximab and glucocorticoids. The successful use of siltuximab in achieving remission highlights the pivotal role of interleukin-6 (IL-6) in DOCK8 deficiency pathogenesis and suggests that IL-6 modulation can be critical in managing DOCK8 deficiency-related viral infections, which may inform future therapeutic strategies for DOCK8 deficiency and similar immunodeficiencies.
Assessment of water mass distribution and intrusions of circumpolar deep water in the Amundsen Sea based on the ocean reanalysis product FOAM-GLOSEA5v13
Authors: Li Ziang , Wang Chuning , Zhou Meng
Published: July 2024

The Amundsen Sea of West Antarctica is one of the regions of particularly interest to the oceanography community due to accelerated basal melting of its ice shelves. Quantitative estimates of the composition of water masses and their sources are essential for understanding the heat and salt budgets and the stability of ice shelves in this region. In this study, the water mass distributions on the Amundsen Sea continental shelf are estimated based on FOAM-GLOSEA5v13, a global oceanographic reanalysis product, using a modified statistical based optimal water mass analysis method. The reanalysis product effectively captures the signal of primary water masses, including the Winter Water (WW) and the Circumpolar Deep Water (CDW) below the Antarctic Summer Surface Water (SSW). The horizontal and vertical distributions and temporal evolution of three water mass endmembers (WW, CDW and DSW) and their mixing ratios are calculated, based on which an intrusion location detection method was established. Using the reanalysis product and intrusion detection method, all potential CDW intrusion sites along the shelf break are identified. Based on the reanalysis product, an intrusion site over the shelf break, away from major deep troughs was captured and confirmed by numerical particle tracking experiments.
The role of feeding as synchronizer of gut microbiota dynamics and its potential contribution to protein digestion in greater amberjack (Seriola dumerili)
Authors: Navarro-Guillén Carmen , Degré Lorentsen Eirik , Perera Erick , Yúfera Manuel , Bakke Ingrid , Vadstein Olav
Published: July 2024

Gut microbial communities are highly dynamic and respond to factors such as diet and host metabolism. However, there is limited information about how these responses can generate community dynamics at different time scales, such as circadian rhythms. The aim of the present study was to characterize variations along a daily cycle in the gut microbiota of fish on different feeding regimes. In addition, an estimation of the potential contribution of the gut bacterial community to the digestive process of the fish was assessed. The greater amberjack (Seriola dumerili) was used as experimental species, a promising species for Mediterranean aquaculture. Fish were randomly distributed in two different feeding regimes, in triplicate rearing tanks. Feeding regimes were continuous feeding and time-restricted feeding (three meals per day). Fish feces for RNA-based amplicon sequencing and bacterial proteolytic capacity were sampled along a 24h cycle. Time-restricted fed fish exhibited changes in the composition of the active bacterial community promoted by feeding, thus revealing two types of bacterial community profiles: “pre-feeding” and “active-feeder” profiles. Continuous-fed fish maintained an “active-feeder” community profile throughout the whole day. Bray-Curtis and Sørensen similarity indicated that differences in the composition between the two community profiles were mainly driven by the absence/presence of infrequent ASVs (amplicon variant sequences). The potential proteolytic bacterial activity tended to be higher before feeding. Thus, gut microbiota could be a key factor to understanding fish digestion, playing a role in interactions with host metabolism. In conclusion, our results suggest that feeding pattern and time of sampling are important parameters when assessing the microbiome’s contribution to host metabolism.
Prognostic and predictive role of YKL-40 in anal squamous cell carcinoma: a serological and tissue-based analysis in a multicentric cohort
Authors: Gambella Alessandro , Senetta Rebecca , Falco Enrico Costantino , Ricci Alessia Andrea , Mangherini Luca , Tampieri Cristian , Fissore Jessica , Orlando Giulia , Manetta Tilde , Mengozzi Giulio , Mistrangelo Massimiliano , Bertero Luca , Cassoni Paola
Published: July 2024

Introduction

Anal squamous cell carcinoma (ASC) is a rare gastrointestinal malignancy showing an increased incidence over the past decades. YKL-40 is an immune modulator and pro-angiogenetic factor that showed a promising prognostic and predictive potential in several malignancies, but limited data are available for ASC. This study aims to provide an extensive evaluation of the prognostic and predictive role of YKL-40 in a multicenter cohort of ASC patients.

Methods

We retrospectively retrieved 72 consecutive cases of ASC diagnosed between February 2011 and March 2021. Both serum and tissue protein expression of YKL-40 were assessed, the latter in ASC tumor cells and peritumor immune cells.

Results

Increased YKL-40 serum levels at the time of diagnosis were associated with older age (p = 0.035), presence of cardiovascular/metabolic comorbidities (p = 0.007), and death for any cause (p = 0.011). In addition, high serum levels of YKL-40 were associated with a poor prognosis (HR: 2.82, 95% CI: 1.01–7.84; p = 0.047). Protein expression of YKL-40 in ASC tumor cells was significantly associated with low tumor grade (p = 0.031), while the increased expression in peritumor immune cells was associated with a worse response of patients to chemoradiotherapy (p = 0.007). However, YKL-40 protein expression in ASC tumor cells or peritumor immune cells did not significantly impact patient overall survival.

Discussion

In conclusion, YKL-40 resulted a relevant prognostic (serum level) and predictive (tissue protein expression in peritumor immune cells) biomarker and can considerably improve ASC patient clinical management.
Tissue- and liquid-biopsy based NGS profiling in advanced non-small-cell lung cancer in a real-world setting: the IMMINENT study
Authors: Sposito Marco , Belluomini Lorenzo , Nocini Riccardo , Insolda Jessica , Scaglione Ilaria Mariangela , Menis Jessica , Simbolo Michele , Lugini Antonio , Buzzacchino Federica , Verderame Francesco , Spinnato Francesca , Aprile Giuseppe , Calvetti Lorenzo , Occhipinti Mario , Marinelli Daniele , Veccia Antonello , Lombardo Fiorella , Soto Parra Hector José , Ferraù Francesco , Savastano Clementina , Porta Camilla , Pradelli Lorenzo , Sicari Emilia , Castellani Silvia , Malapelle Umberto , Novello Silvia , Bria Emilio , Pilotto Sara , Milella Michele
Published: July 2024

Introduction

To date, for all non-small cell lung cancer (NSCLC) cases, it is recommended to test for driver alterations to identify actionable therapeutic targets. In this light, comprehensive genomic profiling (CGP) with next generation sequencing (NGS) has progressively gained increasing importance in clinical practice. Here, with the aim of assessing the distribution and the real-world frequency of gene alterations and their correlation with patient characteristics, we present the outcomes obtained using FoundationOne (F1CDx) and FoundationLiquid CDx (F1L/F1LCDx) NGS-based profiling in a nationwide initiative for advanced NSCLC patients.

Methods

F1CDx (324 genes) was used for tissue samples, and F1L (70 genes) or F1LCDx (324 genes) for liquid biopsy, aiming to explore the real-world occurrence of molecular alterations in aNSCLC and their relationship with patients’ characteristics.

Results

Overall, 232 advanced NSCLC patients from 11 Institutions were gathered [median age 63 years; never/former or current smokers 29.3/65.9%; adenocarcinoma/squamous 79.3/12.5%; F1CDx/F1L+F1LCDx 59.5/40.5%]. Alterations were found in 170 different genes. Median number of mutated genes per sample was 4 (IQR 3–6) and 2 (IQR 1–3) in the F1CDx and F1L/F1LCDx cohorts, respectively. TP53 (58%), KRAS (22%), CDKN2A/B (19%), and STK11 (17%) alterations were the most frequently detected. Actionability rates (tier I and II) were comparable: 36.2% F1CDx vs. 34% ctDNA NGS assays (29.5% and 40.9% F1L and F1LCDx, respectively). Alterations in KEAP1 were significantly associated with STK11 and KRAS, so as TP53 with RB1. Median tumor mutational burden was 6 (IQR 3–10) and was significantly higher in smokers. Median OS from metastatic diagnosis was 23 months (IQR 18.5–19.5) and significantly lower in patients harboring ≥3 gene mutations. Conditional three-year survival probabilities increased over time for patients profiled at initial diagnosis and exceeded those of individuals tested later in their clinical history after 12 months.

Conclusion

This study confirms that NGS-based molecular profiling of aNSCLC on tissue or blood samples offers valuable predictive and prognostic insights.
Therapeutic targeting of voltage-gated sodium channel NaV1.7 for cancer metastasis
Authors: Pukkanasut Piyasuda , Jaskula-Sztul Renata , Gomora Juan Carlos , Velu Sadanandan E.
Published: July 2024

This review focuses on the expression and function of voltage-gated sodium channel subtype NaV1.7 in various cancers and explores its impact on the metastasis driving cell functions such as proliferation, migration, and invasiveness. An overview of its structural characteristics, drug binding sites, inhibitors and their likely mechanisms of action are presented. Despite the lack of clarity on the precise mechanism by which NaV1.7 contributes to cancer progression and metastasis; many studies have suggested a connection between NaV1.7 and proteins involved in multiple signaling pathways such as PKA and EGF/EGFR-ERK1/2. Moreover, the functional activity of NaV1.7 appears to elevate the expression levels of MACC1 and NHE-1, which are controlled by p38 MAPK activity, HGF/c-MET signaling and c-Jun activity. This cascade potentially enhances the secretion of extracellular matrix proteases, such as MMPs which play critical roles in cell migration and invasion activities. Furthermore, the NaV1.7 activity may indirectly upregulate Rho GTPases Rac activity, which is critical for cytoskeleton reorganization, cell adhesion, and actin polymerization. The relationship between NaV1.7 and cancer progression has prompted researchers to investigate the therapeutic potential of targeting NaV1.7 using inhibitors. The positive outcome of such studies resulted in the discovery of several inhibitors with the ability to reduce cancer cell migration, invasion, and tumor growth underscoring the significance of NaV1.7 as a promising pharmacological target for attenuating cancer cell proliferation and metastasis. The research findings summarized in this review suggest that the regulation of NaV1.7 expression and function by small molecules and/or by genetic engineering is a viable approach to discover novel therapeutics for the prevention and treatment of metastasis of cancers with elevated NaV1.7 expression.
Case Report: Development of medication-related osteonecrosis of the jaw in a patient on long-term infliximab therapy
Authors: Oryniak Derek , Brown Meagan , Cholakis Lillie , Elgazzar Reda
Published: July 2024

Medication-Related Osteonecrosis of the Jaw (MRONJ) is a challenging and evolving aspect of Oral and Maxillofacial Surgery. In recent years, several medications apart from those traditionally associated with MRONJ such as bisphosphates (BPs) and Denosumab (DMB) have been implicated in bony necrosis of the jaw. This aim of this report is to demonstrate a significant case of bone necrosis following dental extractions on a patient being treated with infliximab therapy for Crohn's disease. Several cases in literature have reported MRONJ associated with infliximab but very few patients have developed as significant a form of the disease as seen in this report. Previous investigators have proposed pathophysiological pathways via which TNF-α inhibitors such as infliximab have a causative mechanism for MRONJ. When osteoclastic activity is restricted via these pathways, bone healing is impaired and MRONJ can occur. However, it remains a diagnostic challenge to differentiate between antiresorptive MRONJ and chronic osteomyelitis with bone necrosis in patients with acquired immunodeficiency. This case aims to illustrate why the antiresorptive effects of TNF-α inhibitors need to be considered as a possible primary driver of bone necrosis in such patients.
Leaf Area Index Estimation of Fully and Deficit Irrigated Alfalfa through Canopy Cover and Canopy Height
Authors: Cholula Uriel , Andrade Manuel A. , Solomon Juan K. Q.
Published: July 2024

In arid and semiarid regions, crop production has high irrigation water demands due to low precipitation. Efficient irrigation water management strategies can be developed using crop growth models to assess the effect of different irrigation management practices on crop productivity. The leaf area index (LAI) is an important growth parameter used in crop modeling. Measuring LAI requires specialized and expensive equipment not readily available for producers. Canopy cover (CC) and canopy height (CH) measurements, on the other hand, can be obtained with little effort using mobile devices and a ruler, respectively. The objective of this study was to determine the relationships between LAI, CC, and CH for fully and deficit-irrigated alfalfa (Medicago sativa L.). The LAI, CC, and CH measurements were obtained from an experiment conducted at the Valley Road Field Lab in Reno, Nevada, starting in the Fall of 2020. Three irrigation treatments were applied to two alfalfa varieties (Ladak II and Stratica): 100%, 80%, and 60% of full irrigation demands. Biweekly measurements of CC, CH, and LAI were collected during the growing seasons of 2021 and 2022. The dataset was randomly split into training and testing subsets. For the training subset, an exponential model and a simple linear regression (SLR) model were used to determine the individual relationship of CC and CH with LAI, respectively. Also, a multiple linear regression (MLR) model was implemented for the estimation of LAI with CC and CH as its predictors. The exponential model was fitted with a residual standard error (RSE) and coefficient of determination (R2) of 0.97 and 0.86, respectively. A lower performance was obtained for the SLR model (RSE = 1.03, R2 = 0.81). The MLR model (RSE = 0.82, R2 = 0.88) improved the performance achieved by the exponential and SLR models. The results of the testing indicated that the MLR performed better (RSE = 0.82, R2 = 0.88) than the exponential model (RSE = 0.97, R2 = 0.86) and the SLR model (RSE = 1.03, R2 = 0.82) in the estimation of LAI. The relationships obtained can be useful to estimate LAI when CC, CH, or both predictors are available and assist with the validation of data generated by crop growth models.
Complete Blood Count and Biochemistry Reference Intervals for Healthy Adult Donkeys in the United States
Authors: Goodrich Erin L. , Webb Julie L.
Published: July 2024

Previous hematologic and serum biochemistry reference interval (RI) values have been established for donkeys in various geographic regions, life-stages, or for specific donkey breeds. The last extensive investigation establishing RIs for adult donkeys in the United States (U.S.) was published over three decades ago. We aimed to establish updated robust RIs using a reference population of apparently healthy adult donkeys from across the U.S. Standard sized (n = 102), miniature (n = 17), and mammoth (n = 1) donkeys from four different states were enrolled, with 20% of the study population including donkeys captured directly from the wild in Death Valley National Park, CA. RIs were established in accordance with the American Society for Veterinary Clinical Pathology and Clinical Laboratory Standards Institute guidelines. The findings will assist practitioners with the interpretation of their complete blood count and biochemistry panel results in U.S. donkeys. This study also highlights a comparison of results for some important analytes in U.S. donkeys compared to U.S. horses and previously established donkey RIs.
A Literature Review on the Role of the Invasive Aedes albopictus in the Transmission of Avian Malaria Parasites
Authors: Veiga Jesús , Garrido Mario , Garrigós Marta , Chagas Carolina R. F. , Martínez-de la Puente Josué
Published: July 2024

The Asian tiger mosquito (Aedes albopictus) is an invasive mosquito species with a global distribution. This species has populations established in most continents, being considered one of the 100 most dangerous invasive species. Invasions of mosquitoes such as Ae. albopictus could facilitate local transmission of pathogens, impacting the epidemiology of some mosquito-borne diseases. Aedes albopictus is a vector of several pathogens affecting humans, including viruses such as dengue virus, Zika virus and Chikungunya virus, as well as parasites such as Dirofilaria. However, information about its competence for the transmission of parasites affecting wildlife, such as avian malaria parasites, is limited. In this literature review, we aim to explore the current knowledge about the relationships between Ae. albopictus and avian Plasmodium to understand the role of this mosquito species in avian malaria transmission. The prevalence of avian Plasmodium in field-collected Ae. albopictus is generally low, although studies have been conducted in a small proportion of the affected countries. In addition, the competence of Ae. albopictus for the transmission of avian malaria parasites has been only proved for certain Plasmodium morphospecies under laboratory conditions. Therefore, Ae. albopictus may play a minor role in avian Plasmodium transmission in the wild, likely due to its mammal-biased blood-feeding pattern and its reduced competence for the development of different avian Plasmodium. However, further studies considering other avian Plasmodium species and lineages circulating under natural conditions should be carried out to properly assess the vectorial role of Ae. albopictus for the Plasmodium species naturally circulating in its distribution range.
Statistical Analysis Applied to the Production of Mirto Liqueur
Authors: Addis Roberta , Mannu Alberto , Pintore Giorgio , Petretto Giacomo Luigi
Published: July 2024

Preparation of myrtle liqueur through ethanol-based extraction is a widely employed methodology. Nevertheless, optimization of existing processes is possible, especially through a modern statistical multivariate approach. In this context, a Design of Experiments (DoE) approach was used to quantitatively assess for the first time the effect of the time, ethanol concentration, temperature, and the ratio between the Myrtus communis berries’ weight and the extractant volume (v/w) on the amounts of anthocyanins, volatile compounds and dry residues in the liqueur. The kinetic profile relative to the volatile fraction variation during the process was described by gas chromatography (GC), while spectrophotometric analysis allowed quantification of the total anthocyanins and total polyphenols. Multiple response analysis showed that the maximum efficiencies in terms of the considered parameters (desirability function) were reached by setting the temperature to 25 °C and the ethanol percentage to 96% after 20 days of processing. Some hints as to the chemical instability and not negligible sensitivity of anthocyanins in relation to the experimental conditions for longer extraction times were also observed. The statistical model represents a novel tool for industrial production of myrtle liqueur.